TROPICAL SPRUE - Abdulrazak Abyad, MD, PhD, MBA, MPH, AGSF
BASICS
DESCRIPTION
Malabsorption syndrome of unknown or mutable etiology that occurs primarily in patients in the tropics and subtropics. Characteristics include protein malnutrition and folic acid anemia. Usual course is relapsing without treatment. Symptoms may appear years after leaving an endemic area.
• Endemic areas: Tropic regions only, Far East, India, Caribbean, and the Middle East. Distribution is sporadic.
• System(s) Affected: Gastrointestinal; Hemic; Lymphatic; Immunologic
EPIDEMIOLOGY
Predominant sex: Male = Female
Incidence
Unknown
RISK FACTORS
Parasitic infestation
ETIOLOGY
• Unknown
• Possible dietary deficiency
• Possible infectious agent
• Vitamin deficiency (folate), B12
• Food toxins (rancid fats)
• Toxigenic strains of coliform bacteria
DIAGNOSIS
SIGNS AND SYMPTOMS
• Fatigue
• Asthenia
• Weight loss
• Pallor
• Diarrhea
• Abdominal cramps
• Borborygmus
• Night blindness
• Stomatitis
• Glossitis
• Cheilosis
• Anorexia
• Steatorrhea
• Hyperkeratosis
• Edema
• Abdominal distension
• Hyperpigmentation
• Koilonychia
TESTS
Lab
• Megaloblastic anemia in 60% of cases
• Steatorrhea
• Decreased D-xylose
• Decreased serum iron
• Decreased calcium
• Decreased folic acid
• Decreased serum vitamin B12
• Decreased serum carotene
• Decreased cholesterol, albumin
• Deficiency of magnesium
• Deficiency of -tocopherol
Imaging
• Mild jejunal dilatation
• Jejunal fold coarsening
• Flocculation and segmentation of barium meal
Diagnostic Procedures/Surgery
• The presence of normal result on jejunal biopsy nearly excludes this diagnosis.
• Abnormal results on duodenal/jejunal biopsy: Not specific
• Malabsorption of at least 2 nutrients is considered essential for diagnosis.
• D-Xylose, fat, and radiolabeled vitamin B12 are used to test for absorptive capacity.
• Stool microscopy
• Imaging: Not specific
Pathological Findings
• Jejunal biopsy: Mild villous atrophy, increased villous crypts, mononuclear cell infiltration
• Patients may have chronic atrophic gastritis and nonspecific abnormalities of the colonic mucosa.
• Serum motilin and enteroglucagon levels are increased both while fasting and postprandially.
DIFFERENTIAL DIAGNOSIS
• Other causes of megaloblastic anemia
• Other malabsorption syndromes
• Celiac disease
• Inflammatory bowel disease
• Giardiasis
• Strongylosis
• Other infectious causes
- Coccidial isospora
- Capillaria philippinensis
- Cryptosporidium
TREATMENT
STABILIZATION
Outpatient
GENERAL MEASURES
• Replace deficiencies of elements (e.g., vitamin B12, folic acid)
• Control diarrhea
• Replace fluids and blood
Diet
No special diet (glutenfree diets do not improve this disease)
Activity
No restrictions, as tolerated
MEDICATION (DRUGS)
First Line
• Vitamin B12 1,000 ug SC for several days, then monthly thereafter for 6 months
• Folic acid 5 mg PO daily
• Tetracycline 250 mg q.i.d. for 1-2 months, then 1/2 doses for up to 6 months. Occasionally, longer course required
• Combination folic acid and B12 plus tetracycline or sulfonamide
• Contraindications: Allergy to tetracycline or oxytetracycline
• Precautions
- Use with caution in patients with intercurrent lupus, myasthenia gravis, or kidney or liver disease.
- Do not take medication with milk, antacids, or with iron preparations.
- Do not use tetracycline during pregnancy
- Do not use tetracycline in children 8 years.
• Significant possible interactions
- Antacids, anticoagulants, bismuth subsalicylate
- Oral contraceptives
- Lithium
Second Line
• Oxytetracycline
• Nonabsorbable sulfonamides
ALERT
Pediatric Considerations
Do not treat pediatric patients with tetracycline.
Pregnancy Considerations
Do not treat with tetracycline during pregnancy.
FOLLOW-UP
PROGNOSIS
• Good with appropriate treatment
• Recurrences do happen in native residents treated in the tropics.
COMPLICATIONS
• Malabsorption
• Relapse is possible if medication regimen is stopped too soon.
PATIENT MONITORING
As needed for symptoms
REFERENCES
1. Mandell GL, ed. Principles and Practice of Infectious Diseases. 5th ed. New York, NY: Churchill Livingstone; 2000.
2. Sleisenger MH, Fordtran JS, eds. Gastrointestinal and Liver Disease: Pathophysiology, Diagnosis, Management. 7th ed. Philadelphia, PA: WB Saunders; 2002.
MISCELLANEOUS
See also: Celiac disease; Diarrhea, chronic
Sunday, January 11, 2009
TROCHANTERIC BURSITIS
TROCHANTERIC BURSITIS - Matthew Pecci, MD
BASICS
DESCRIPTION
The trochanteric bursa is a fluid filled sac overlying the greater trochanter of the femur, and beneath the iliotibial band (IT band).
• Bursitis refers to inflammation of this bursa
GENERAL PREVENTION
• Maintain IT band, hip and low back flexibility
• Avoid direct trauma
EPIDEMIOLOGY
• More common in adults
• Common in runners
• Predominant age: All ages
• Predominant sex: Male = Female
RISK FACTORS
• Tight hip musculature
• Direct contusion
• Abnormal gait
- Leg length discrepancy
- Sacroiliac joint dysfunction
- Knee or hip osteoarthritis
- Abnormal foot mechanics (e.g., pes planus, overpronation)
PATHOPHYSIOLOGY
• Abnormal gait or poor muscle flexibility leads to friction on bursa causing inflammatory response
• Long-term
- Fibrosis and thickening of bursal sac due to chronic inflammatory process
ETIOLOGY
See "Risk Factors."
ASSOCIATED CONDITIONS
• Tight IT bands
• Leg length discrepancy
• Sacroillic (SI) joint dysfunction
• Osteoarthritis
• Pes planis
DIAGNOSIS
SIGNS AND SYMPTOMS
History
• Pain localized to the lateral aspect of the hip
- May radiate to groin or lateral thigh
- Worse when rising after prolonged sitting
- Exacerbated by prolonged walking or standing
- Worse with direct pressure over the greater trochanter. May not be able to lie on the affected side due to pain.
• Possible
- A fall landing directly on the affected hip
- Chronic low back pain
- Chronic leg/knee/ankle/hip pain
• Recent increase in running distance or intensity, or a change in running surfaces
Physical Exam
• Tenderness with direct palpation over the greater trochanter
• May have pain with extremes of internal and external rotation of hip
• May have pain with abduction of the hip against resistance
• May have a positive Ober test, which assesses IT band flexibility
• May have abnormal gait
• May have measurable leg length discrepancy
• May have positive Fabers test for SI joint dysfunction
• May have pes planus or overpronation
• Rarely has palpable fullness over the bursal sac
TESTS
Imaging
• Anteroposterior frog leg lateral of affected hip
• Consider lumbar spine x-rays if back pain thought to be a contributing factor
DIFFERENTIAL DIAGNOSIS
• IT band tendonitis
• Gluteus medius tendonitis/bursititis
• Osteoarthritis of hip
• Lumbo-sacral osteoarthritis/disc disease causing nerve root compression
• If associated trauma: Fracture of hip
• Stress reaction/fracture of femoral neck especially in female runners
• Septic bursitis/arthritis
TREATMENT
GENERAL MEASURES
Activity
• Minimize aggravating activities such as prolonged walking, or standing.
• Avoid lying on affected side.
• Runners
- May need to decrease distance and/or intensity of runs
- May need a period of cessation from running
- Avoid banked tracks or roads with excessive tilt.
Physical Therapy
• Ice
• Focus on achieving flexibility of hip musculature, particularly the IT band
• Address contributing factors
- Low back flexibility and strengthening
- If leg length discrepancy, may need heel lift
- If pes planis or overpronation, may need arch support, or custom orthotics
MEDICATION (DRUGS)
First Line
NSAIDs (1)[B]
• Naprosyn 500 mg PO b.i.d.
• Ibuprofen 800 mg PO t.i.d.
Second Line
Intra-bursal steroid injection (2,3)[B]
• 1 cc Dexamethasone 4 mg/cc or
• 1 cc Kenalog 40 mg/cc
SURGERY
• Rarely requires surgery
• Bursectomy
• Longitudinal release of the IT band (4)[B]
FOLLOW-UP
Four weeks post-treatment
PROGNOSIS
Depends on chronicity, with more acute cases having an excellent prognosis
COMPLICATIONS
Bursal thickening and fibrosis
REFERENCES
1. Browning KH. Hip and pelvis injuries in runners. The Physician and Sports Medicine. 2001;29.
2. Cardone DA, Tallia AF. Diagnostic and therapeutic injection of the hip and knee. Am Fam Physician. 2003;63;2147-2157.
3. Sheeb MI, et al. Evaluation of glucocorticosteroid injection for the treatment of trochanteric bursitis. J Rheumatol. 1996;23;2104-2106.
4. Anderson B. Trochanteric bursitis. UptoDate Online. 2006.
BASICS
DESCRIPTION
The trochanteric bursa is a fluid filled sac overlying the greater trochanter of the femur, and beneath the iliotibial band (IT band).
• Bursitis refers to inflammation of this bursa
GENERAL PREVENTION
• Maintain IT band, hip and low back flexibility
• Avoid direct trauma
EPIDEMIOLOGY
• More common in adults
• Common in runners
• Predominant age: All ages
• Predominant sex: Male = Female
RISK FACTORS
• Tight hip musculature
• Direct contusion
• Abnormal gait
- Leg length discrepancy
- Sacroiliac joint dysfunction
- Knee or hip osteoarthritis
- Abnormal foot mechanics (e.g., pes planus, overpronation)
PATHOPHYSIOLOGY
• Abnormal gait or poor muscle flexibility leads to friction on bursa causing inflammatory response
• Long-term
- Fibrosis and thickening of bursal sac due to chronic inflammatory process
ETIOLOGY
See "Risk Factors."
ASSOCIATED CONDITIONS
• Tight IT bands
• Leg length discrepancy
• Sacroillic (SI) joint dysfunction
• Osteoarthritis
• Pes planis
DIAGNOSIS
SIGNS AND SYMPTOMS
History
• Pain localized to the lateral aspect of the hip
- May radiate to groin or lateral thigh
- Worse when rising after prolonged sitting
- Exacerbated by prolonged walking or standing
- Worse with direct pressure over the greater trochanter. May not be able to lie on the affected side due to pain.
• Possible
- A fall landing directly on the affected hip
- Chronic low back pain
- Chronic leg/knee/ankle/hip pain
• Recent increase in running distance or intensity, or a change in running surfaces
Physical Exam
• Tenderness with direct palpation over the greater trochanter
• May have pain with extremes of internal and external rotation of hip
• May have pain with abduction of the hip against resistance
• May have a positive Ober test, which assesses IT band flexibility
• May have abnormal gait
• May have measurable leg length discrepancy
• May have positive Fabers test for SI joint dysfunction
• May have pes planus or overpronation
• Rarely has palpable fullness over the bursal sac
TESTS
Imaging
• Anteroposterior frog leg lateral of affected hip
• Consider lumbar spine x-rays if back pain thought to be a contributing factor
DIFFERENTIAL DIAGNOSIS
• IT band tendonitis
• Gluteus medius tendonitis/bursititis
• Osteoarthritis of hip
• Lumbo-sacral osteoarthritis/disc disease causing nerve root compression
• If associated trauma: Fracture of hip
• Stress reaction/fracture of femoral neck especially in female runners
• Septic bursitis/arthritis
TREATMENT
GENERAL MEASURES
Activity
• Minimize aggravating activities such as prolonged walking, or standing.
• Avoid lying on affected side.
• Runners
- May need to decrease distance and/or intensity of runs
- May need a period of cessation from running
- Avoid banked tracks or roads with excessive tilt.
Physical Therapy
• Ice
• Focus on achieving flexibility of hip musculature, particularly the IT band
• Address contributing factors
- Low back flexibility and strengthening
- If leg length discrepancy, may need heel lift
- If pes planis or overpronation, may need arch support, or custom orthotics
MEDICATION (DRUGS)
First Line
NSAIDs (1)[B]
• Naprosyn 500 mg PO b.i.d.
• Ibuprofen 800 mg PO t.i.d.
Second Line
Intra-bursal steroid injection (2,3)[B]
• 1 cc Dexamethasone 4 mg/cc or
• 1 cc Kenalog 40 mg/cc
SURGERY
• Rarely requires surgery
• Bursectomy
• Longitudinal release of the IT band (4)[B]
FOLLOW-UP
Four weeks post-treatment
PROGNOSIS
Depends on chronicity, with more acute cases having an excellent prognosis
COMPLICATIONS
Bursal thickening and fibrosis
REFERENCES
1. Browning KH. Hip and pelvis injuries in runners. The Physician and Sports Medicine. 2001;29.
2. Cardone DA, Tallia AF. Diagnostic and therapeutic injection of the hip and knee. Am Fam Physician. 2003;63;2147-2157.
3. Sheeb MI, et al. Evaluation of glucocorticosteroid injection for the treatment of trochanteric bursitis. J Rheumatol. 1996;23;2104-2106.
4. Anderson B. Trochanteric bursitis. UptoDate Online. 2006.
TRIGGER FINGER
TRIGGER FINGER - Alan M. Ehrlich, MD
BASICS
DESCRIPTION
A clicking, snapping, or locking of a finger or thumb after full flexion, with or without associated pain
GENERAL PREVENTION
Most cases are idiopathic, and no known prevention exists. No clear association with repetitive movements.
EPIDEMIOLOGY
• Predominant age: A childhood form that presents typically with thumb involvement in the 1st decade of life and an adult form that typically presents in the 5th and 6th decades of life
• Predominant sex: Female > Male (adult) (6:1); Female = Male (children)
Incidence
• 28/100,000/year in the general population
• Diabetics have 4 times the risk of the general population.
Prevalence
Lifetime prevalence in the general population is 2.8%
ALERT
Pediatric Considerations
• The thumb is more commonly involved with children.
• When children have a trigger finger instead of trigger thumb, surgery is often more complicated. Release of the A1 pulley alone is often insufficient, and other procedures may need to be done at the time of surgery.
RISK FACTORS
• Diabetes mellitus
• Rheumatoid arthritis
• Hypothyroidism
• Mucopolysaccharide disorders
• Amyloidosis
PATHOPHYSIOLOGY
• Narrowing of the flexor tendon sheath of the A1 pulley due to either thickening from inflammation or protein deposits. With prolonged inflammation, fibrocartilagenous metaplasia of the tendon sheath occurs.
• The flexor tendon may become distorted with a nodule formation, which can give rise to the triggering as the nodule has difficulty passing through the area of narrowing. Because flexors are stronger than extensors, the finger can get stuck in the flexed position.
ETIOLOGY
• Narrowing of the flexor tendon sheath due to either thickening from inflammation or protein deposits
• Most cases are idiopathic, and no known prevention exists.
• No clear association with repetitive movements
ASSOCIATED CONDITIONS
DeQuervain tenosynovitis, Carpal tunnel syndrome
Dupytren contracture, Diabetes mellitus
Rheumatoid arthritis, Hypothyroidism, Amyloidosis
DIAGNOSIS
PRE HOSPITAL
Diagnosis is based on clinical presentation
SIGNS AND SYMPTOMS
• History of clicking, snapping, or locking of a finger or thumb after full flexion, with or without associated pain.
• A palpable nodule may be present. Snapping or locking may be present, but are not necessary for the diagnosis
History
History of clicking, snapping, or locking of a finger or thumb after full flexion, with or without associated pain
Physical Exam
• A palpable nodule may be present.
• Snapping or locking may be present but are not necessary for the diagnosis
TESTS
None
Lab
None
Imaging
None
Diagnostic Procedures/Surgery
None
Pathological Findings
• Thickening of the A1 tendon sheath with fibrocartilagenous metaplasia
• Swelling or nodule formation of flexor tendon
TREATMENT
PRE-HOSPITAL
• Splinting the metacarpophalangeal (MCP) joint at 10-15 flexion for 6 weeks with the distal joints free to move has been effective. Splinting is more effective for treating fingers than thumbs (70% vs 50%). Less effective with severe symptoms, symptoms> 6 months, and multiple digits involved
• Long-acting corticosteroids may be injected up to 3 times to achieve relief of symptoms.
GENERAL MEASURES
• Splinting or steroid injection should be tried before surgery.
• Percutaneous release is usually preferred to open release.
Activity
Splinting of the affected digit to minimize flexion/extension of the MCP joint can lead to resolution of symptoms.
SPECIAL THERAPY
Physical Therapy
Physiotherapy has been used in the treatment of trigger digits in children.
MEDICATION (DRUGS)
First Line
Steroid injection of the tendon sheath or surrounding subcutaneous tissue
Second Line
NSAIDs may reduce pain and discomfort but have not been shown to improve the underlying cause. They do not reduce symptoms of snapping or locking.
SURGERY
• Percutaneous release of trigger finger has 90% success rate.
• Open surgery is an alternative to percutaneous release. Success rates are comparable to percutaneous release although complication rates may be higher
FOLLOW-UP
Follow up only needed if symptoms persist or if complications of surgery develop
DISPOSITION
Admission Criteria
Day surgery for trigger finger release
Discharge Criteria
Absence of complications
Issues for Referral
Refer to hand surgeon if not responding to splinting and/or steroid injections
PROGNOSIS
Prognosis for resolution of symptoms is excellent with either conservative or surgical intervention
COMPLICATIONS
• Complications from surgery include infection, bleeding, digital nerve inujury, and persistent pain.
• Injury to the A2 pulley may result in bowstringing which is a bulging of the flexor tendon in the palm with flexion. This can be associated with pain.
REFERENCES
1. Akhtar S, Bradley MJ, Quinton DN, Burke FD. Management and referral for trigger finger/thumb. BMJ. 2005;331:30-33.
2. Ryzewicz M, Wolf JN. Trigger digits: Principles, management, and complications. J Hand Surg. 2006;31A:135-146.
3. Moore JS. Flexor tendon entrapment of the digits (trigger finger and trigger thumb). J Occup Environ Med. 2000;42:5
4. Nimigan AS, Ross DC, Gan BS. Steroid injections in the management of trigger fingers. Am J Phys Med Rehabil. 2006;85:36-43.
5. Gilberts ECAM, Beekman WH, Stevens HJPD, Wereldsma JCJ. Prospective randomized trial of open versus percutaneous surgery for trigger digits. J Hand Surgery. 2001;26A:497-500
6. Cardon LJ, Ezaki M, Carter PR. Trigger finger in children. J Hand Surgery. 1999;24A:1156-1161.
7. Tordai P, Engkvist O. Trigger fingers in children. J Hand Surgery. 1999;24A:1162-1165.
BASICS
DESCRIPTION
A clicking, snapping, or locking of a finger or thumb after full flexion, with or without associated pain
GENERAL PREVENTION
Most cases are idiopathic, and no known prevention exists. No clear association with repetitive movements.
EPIDEMIOLOGY
• Predominant age: A childhood form that presents typically with thumb involvement in the 1st decade of life and an adult form that typically presents in the 5th and 6th decades of life
• Predominant sex: Female > Male (adult) (6:1); Female = Male (children)
Incidence
• 28/100,000/year in the general population
• Diabetics have 4 times the risk of the general population.
Prevalence
Lifetime prevalence in the general population is 2.8%
ALERT
Pediatric Considerations
• The thumb is more commonly involved with children.
• When children have a trigger finger instead of trigger thumb, surgery is often more complicated. Release of the A1 pulley alone is often insufficient, and other procedures may need to be done at the time of surgery.
RISK FACTORS
• Diabetes mellitus
• Rheumatoid arthritis
• Hypothyroidism
• Mucopolysaccharide disorders
• Amyloidosis
PATHOPHYSIOLOGY
• Narrowing of the flexor tendon sheath of the A1 pulley due to either thickening from inflammation or protein deposits. With prolonged inflammation, fibrocartilagenous metaplasia of the tendon sheath occurs.
• The flexor tendon may become distorted with a nodule formation, which can give rise to the triggering as the nodule has difficulty passing through the area of narrowing. Because flexors are stronger than extensors, the finger can get stuck in the flexed position.
ETIOLOGY
• Narrowing of the flexor tendon sheath due to either thickening from inflammation or protein deposits
• Most cases are idiopathic, and no known prevention exists.
• No clear association with repetitive movements
ASSOCIATED CONDITIONS
DeQuervain tenosynovitis, Carpal tunnel syndrome
Dupytren contracture, Diabetes mellitus
Rheumatoid arthritis, Hypothyroidism, Amyloidosis
DIAGNOSIS
PRE HOSPITAL
Diagnosis is based on clinical presentation
SIGNS AND SYMPTOMS
• History of clicking, snapping, or locking of a finger or thumb after full flexion, with or without associated pain.
• A palpable nodule may be present. Snapping or locking may be present, but are not necessary for the diagnosis
History
History of clicking, snapping, or locking of a finger or thumb after full flexion, with or without associated pain
Physical Exam
• A palpable nodule may be present.
• Snapping or locking may be present but are not necessary for the diagnosis
TESTS
None
Lab
None
Imaging
None
Diagnostic Procedures/Surgery
None
Pathological Findings
• Thickening of the A1 tendon sheath with fibrocartilagenous metaplasia
• Swelling or nodule formation of flexor tendon
TREATMENT
PRE-HOSPITAL
• Splinting the metacarpophalangeal (MCP) joint at 10-15 flexion for 6 weeks with the distal joints free to move has been effective. Splinting is more effective for treating fingers than thumbs (70% vs 50%). Less effective with severe symptoms, symptoms> 6 months, and multiple digits involved
• Long-acting corticosteroids may be injected up to 3 times to achieve relief of symptoms.
GENERAL MEASURES
• Splinting or steroid injection should be tried before surgery.
• Percutaneous release is usually preferred to open release.
Activity
Splinting of the affected digit to minimize flexion/extension of the MCP joint can lead to resolution of symptoms.
SPECIAL THERAPY
Physical Therapy
Physiotherapy has been used in the treatment of trigger digits in children.
MEDICATION (DRUGS)
First Line
Steroid injection of the tendon sheath or surrounding subcutaneous tissue
Second Line
NSAIDs may reduce pain and discomfort but have not been shown to improve the underlying cause. They do not reduce symptoms of snapping or locking.
SURGERY
• Percutaneous release of trigger finger has 90% success rate.
• Open surgery is an alternative to percutaneous release. Success rates are comparable to percutaneous release although complication rates may be higher
FOLLOW-UP
Follow up only needed if symptoms persist or if complications of surgery develop
DISPOSITION
Admission Criteria
Day surgery for trigger finger release
Discharge Criteria
Absence of complications
Issues for Referral
Refer to hand surgeon if not responding to splinting and/or steroid injections
PROGNOSIS
Prognosis for resolution of symptoms is excellent with either conservative or surgical intervention
COMPLICATIONS
• Complications from surgery include infection, bleeding, digital nerve inujury, and persistent pain.
• Injury to the A2 pulley may result in bowstringing which is a bulging of the flexor tendon in the palm with flexion. This can be associated with pain.
REFERENCES
1. Akhtar S, Bradley MJ, Quinton DN, Burke FD. Management and referral for trigger finger/thumb. BMJ. 2005;331:30-33.
2. Ryzewicz M, Wolf JN. Trigger digits: Principles, management, and complications. J Hand Surg. 2006;31A:135-146.
3. Moore JS. Flexor tendon entrapment of the digits (trigger finger and trigger thumb). J Occup Environ Med. 2000;42:5
4. Nimigan AS, Ross DC, Gan BS. Steroid injections in the management of trigger fingers. Am J Phys Med Rehabil. 2006;85:36-43.
5. Gilberts ECAM, Beekman WH, Stevens HJPD, Wereldsma JCJ. Prospective randomized trial of open versus percutaneous surgery for trigger digits. J Hand Surgery. 2001;26A:497-500
6. Cardon LJ, Ezaki M, Carter PR. Trigger finger in children. J Hand Surgery. 1999;24A:1156-1161.
7. Tordai P, Engkvist O. Trigger fingers in children. J Hand Surgery. 1999;24A:1162-1165.
TRIGEMINAL NEURALGIA
TRIGEMINAL NEURALGIA - Michael D. Perloff, MD, PhD
BASICS
DESCRIPTION
Disorder of sensory nucleus of 5th cranial nerve (trigeminal nerve), producing episodic, paroxysmal, severe, lancinating facial pain lasting seconds to minutes, followed by pain-free period in distribution of one or more of nerve divisions.
• Often precipitated by stimulation of well-defined, ipsilateral trigger zones, usually perioral, perinasal, and occasionally intraoral (e.g., washing, shaving)
• System(s) Affected: Nervous
• Synonym(s): Tic douloureux; Fothergill neuralgia; Trifacial neuralgia
EPIDEMIOLOGY
• Predominant age: Over age 50 years, incidence increases with age. (1,2)[A] Rare 35 years (consider another primary disease; see Etiology)
• Predominant sex: Female > Male (2:1)[1A]
Incidence
• 4.3/100 000/year (1)[A]
- 5.9/100 000/year for women (1)[A]
- 3.4/100 000/year for men (1)[A]
• >70, ~25.6/100 000/year (1)[A]
Prevalence
16/100,000 (1)[B]
ALERT
Pediatric Considerations
Unusual in childhood
RISK FACTORS
Unknown
ETIOLOGY
• Compression of trigeminal nerve by anomalous arteries or veins of posterior fossa, usually superior cerebral artery compressing trigeminal root, with cascade changes of sensory neurons occurring over days to weeks (2,3)
• Etiology classification
- Idiopathic
- Secondary: Cerebellopontine angle tumors (e.g., meningioma); tumors of 5th nerve (e.g., neuroma, vascular malformations), trauma, demyelinating disease (e.g., multiple sclerosis [MS])
ASSOCIATED CONDITIONS
• Sjogren syndrome
• Rheumatoid arthritis
• Chronic meningitis
• Facial migraine
• Acute polyneuropathy
• MS
• Hemifacial spasm
• Pretrigeminal neuralgia
• Charcot-Marie-tooth neuropathy
• Glossopharyngeal neuralgia
DIAGNOSIS
SIGNS AND SYMPTOMS
• Unilateral (rarely bilateral, unless secondary to MS)
• Symptoms rarely present at night
• Excruciating lip and/or gum and/or facial pain
• Paroxysmal facial pain
• Wincing, facial tic
• Pain elicited by tickle or touch
• Flushing
• Lacrimation
• Salivation
• Pain bursts several seconds to minutes, with refractory period after
• Slight right > left side preference (1)[C]
• 2nd-, 3rd-, 1st (rare) division trigeminal nerve most commonly affected (2,3)[A]
History
• Paroxysmal facial pain
• Pain elicited by tickle or touch
Physical Exam
All exam findings are typically negative due to paroxysmal nature of disorder
TESTS
Imaging
• MRI or CT scan: Neoplasm in cerebellopontine angle must be ruled out. Special MRA technique of collapsed MRA superimposed on routine spin echo T-1-weighted images
• No positive findings are significantly correlated with diagnosis (2,3)
Pathological Findings
• Trigeminal nerve: Inflammatory changes, demyelination, and degenerative changes (2)
• Trigeminal ganglion: Hypermyelination and microneuromata (3)
DIFFERENTIAL DIAGNOSIS
• Other forms of neuralgia usually have sensory loss. Presence of sensory loss nearly excludes diagnosis of trigeminal neuralgia (if younger patient, frequently MS).
• Neoplasia in cerebellopontine angle
• Vascular malformation of brain stem
• Demyelinating lesion (MS is diagnosed in 2-4% of patients with trigeminal neuralgia) (2)
• Vascular insult
• Migraine, cluster headache
• Giant cell arteritis
• Post-herpetic neuralgia
• Chronic meningitis
• Acute polyneuropathy
• Atypical odontalgia
• SUNCT syndrome (short-lasting, unilateral, neuralgiform pain with conjunctival injection)
TREATMENT
GENERAL MEASURES
• Outpatient
• Drug treatment is 1st approach. Invasive procedures for patients who cannot tolerate, or fail to respond to, or relapse after chronic, drug treatment
• Avoidance of stimulation (air, heat, cold) of trigger zones (lips, cheeks, gums)
Diet
No special diet
Activity
Full activity
SPECIAL THERAPY
Radiotherapy
Stereotactic radiosurgery has been shown to be effective after drug failure
• Minimal clinically effective dose: 70 Gy
• 75% of patients achieve complete relief within 3 months; by 3 years, 50% maintain complete relief (NNT = 2) (4)[B]
• Most common side effect: Sensory disturbance (corneal numbness)
Complementary and Alternative Medicine
Acupuncture, moxibustion (herb): Poor evidence
MEDICATION (DRUGS)
First Line
• Carbamazepine (Tegretol)
- Starting dose 100-200 mg b.i.d.; effective dose usually 200 mg q.i.d.; 1,200 mg/d maximum
- 70-90% of patients initially respond; by 3 years, 30% no longer helped (number needed to treat [NNT] = 1.8) (5)[A]
- Most common side effect: Sedation
• Contraindications: Monoamine oxidase (MAO) inhibitors, taken concurrently
• Precautions: Use with caution in the presence of liver disease.
• Significant possible interactions: Macrolide antibiotics, oral anticoagulants, anticonvulsants, tricyclics, oral contraceptives, steroids, digitalis, isonazid, monoamine oxidase (MAO) inhibitors, methyprylon nabilone, nizatidine, other H2 blockers, phenytoin, propoxyphene, benzodiazepines, calcium channel blockers
• Oxacarbazepine (Trileptal)
- Starting dose 150-300 mg b.i.d.; effective dose usually 375 mg b.i.d.; 1,200 mg/d maximum
- Efficacy similar to carbamazepine (5)[B]
- Faster, with less drowsiness and drug interactions than carbamazepine
- Decreases serum sodium
- Most common side effect: Sedation
Second Line
• Phenytoin (Dilantin)
- 300-400 mg/d (synergistic with carbamazepine)
- Potent P450 inducer (enhanced metabolism of many drugs)
- Various CNS side effects (sedation, ataxia)
• Baclofen (Lioresal)
- 10-80 mg/d; start at 5-10 mg t.i.d. with food (as adjunct with phenytoin or carbamazepine)
- Side effects: Drowsiness, weakness, nausea, vomiting
• Gabapentin (Neurontin)
- 100 mg t.i.d. or 300 mg at bedtime, increased up to 300-600 mg t.i.d.-q.i.d.
• Lamotrigine
- Titrate up to 200 mg b.i.d. (over weeks)
- 10% experience rash.
• Chlorphenesin carbamate (Maolate)
- 800-2,400 mg/d (as adjunct with phenytoin and/or carbamazepine)
- Side effect: Drowsiness
• Antidepressants: Amitriptyline, fluoxetine, trazodone
- Used especially with anticonvulsants
- Particularly effective for atypical forms of trigeminal neuralgia
• Clonazepam (Klonopin): Frequently causes drowsiness and ataxia
• Capsaicin cream, locally
• Botulinum toxin injection into zygomatic arch
• Valproic acid (Depakene, Depakote)
SURGERY
• Microvascular decompression of 5th cranial nerve at its entrance to (or exit from) brainstem
- 98% of patients achieve intial pain relief; by 33 months, 73% maintain complete relief (NNT 1.3) (6)[B]
- Surgical mortality across studies was ~1% (6)
- Most common side effect: Transient facial numbness and diplopia, headache, nausea, vomiting
- Mean hospital stay was ~5.4 days (6)[B]
• Peripheral-nerve ablation
- Radiofrequency thermocoagulation (possibly 90-97% partial or complete relief; recurrence rate unknown) (7)[C]
- Neurectomy
- Cryotherapy: High relapse rate
• 4% tetracaine dissolved in 0.5% bupivacaine nerve block (only a few case reports to date)
• Alcohol block or glycerol injection into trigeminal cistern: Unpredictable side effects (dysesthesia and anesthesia dolorosa); temporary relief
• Partial sensory rhizotomy
• Peripheral block or section of 5th nerve proximal to Gasserian ganglion
• Balloon compression of Gasserian ganglion (especially effective for 1st-division trigeminal neuralgia pain) (7)
FOLLOW-UP
PROGNOSIS
• 50-60% eventually fail pharmacological treatment (5B)
• Of those, relapse is seen in ~50% of stereotactic radiosurgeries and ~27% surgical microvascular decompressions (4,5)[B]
COMPLICATIONS
• Mental and physical sluggishness; dizziness with carbamazepine (5)
• Paresthesiae and corneal reflex loss with stereotactic radiosurgery (4)
• Surigical mortality and morbidity associated with microvascular decompression (6)
PATIENT MONITORING
• Carbamazepine and/or phenytoin serum levels
• If carbamazepine prescribed: CBC and platelets at baseline, then weekly for a month, then monthly for 4 months, then every 6-12 months if dose stable (regimens for monitoring vary)
• Reduce drugs after 4-6 weeks to determine whether condition is in remission; resume at previous dose if pain recurs. Withdraw drugs slowly after several months, again to check for remission or if lower dose of drugs can be tolerated.
REFERENCES
1. Manzoni GC, Torelli P. Epidemiology of typical and atypical craniofacial neuralgias. Neurol Sci. 2005; 26(Suppl 2):s65-s67.
2. Scrivani SJ, Mathews ES, Maciewicz RJ. Trigeminal neuralgia. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2005;100(5):527-538.
3. Nurmikko TJ, Eldridge PR. Trigeminal neuralgia-pathophysiology, diagnosis and current treatment. Br J Anaesth. 2001;87(1):117-132.
4. Lopez BC, Hamlyn PJ, Zakrzewska JM. Stereotactic radiosurgery for primary trigeminal neuralgia: State of the evidence and recommendations for future reports. J Neurol Neurosurg Psychiatry. 2004;75(7):1019-1024.
5. Beniczky S, Tajti J, Timea Varga E, Vecsei L. Evidence-based pharmacological treatment of neuropathic pain syndromes. J Neural Transm. 2005;112(6):735-749.
6. Ashkan K, Marsh H. Microvascular decompression for trigeminal neuralgia in the elderly: A review of the safety and efficacy. Neurosurgery. 2004;55(4):840-8; discussion 848-850.
7. Lopez BC, Hamlyn PJ, Zakrzewska JM. Systematic review of ablative neurosurgical techniques for the treatment of trigeminal neuralgia. Neurosurgery. 2004;54(4):973-82; discussion 982-983.
MISCELLANEOUS
See also: Headache, cluster; Migraine
BASICS
DESCRIPTION
Disorder of sensory nucleus of 5th cranial nerve (trigeminal nerve), producing episodic, paroxysmal, severe, lancinating facial pain lasting seconds to minutes, followed by pain-free period in distribution of one or more of nerve divisions.
• Often precipitated by stimulation of well-defined, ipsilateral trigger zones, usually perioral, perinasal, and occasionally intraoral (e.g., washing, shaving)
• System(s) Affected: Nervous
• Synonym(s): Tic douloureux; Fothergill neuralgia; Trifacial neuralgia
EPIDEMIOLOGY
• Predominant age: Over age 50 years, incidence increases with age. (1,2)[A] Rare 35 years (consider another primary disease; see Etiology)
• Predominant sex: Female > Male (2:1)[1A]
Incidence
• 4.3/100 000/year (1)[A]
- 5.9/100 000/year for women (1)[A]
- 3.4/100 000/year for men (1)[A]
• >70, ~25.6/100 000/year (1)[A]
Prevalence
16/100,000 (1)[B]
ALERT
Pediatric Considerations
Unusual in childhood
RISK FACTORS
Unknown
ETIOLOGY
• Compression of trigeminal nerve by anomalous arteries or veins of posterior fossa, usually superior cerebral artery compressing trigeminal root, with cascade changes of sensory neurons occurring over days to weeks (2,3)
• Etiology classification
- Idiopathic
- Secondary: Cerebellopontine angle tumors (e.g., meningioma); tumors of 5th nerve (e.g., neuroma, vascular malformations), trauma, demyelinating disease (e.g., multiple sclerosis [MS])
ASSOCIATED CONDITIONS
• Sjogren syndrome
• Rheumatoid arthritis
• Chronic meningitis
• Facial migraine
• Acute polyneuropathy
• MS
• Hemifacial spasm
• Pretrigeminal neuralgia
• Charcot-Marie-tooth neuropathy
• Glossopharyngeal neuralgia
DIAGNOSIS
SIGNS AND SYMPTOMS
• Unilateral (rarely bilateral, unless secondary to MS)
• Symptoms rarely present at night
• Excruciating lip and/or gum and/or facial pain
• Paroxysmal facial pain
• Wincing, facial tic
• Pain elicited by tickle or touch
• Flushing
• Lacrimation
• Salivation
• Pain bursts several seconds to minutes, with refractory period after
• Slight right > left side preference (1)[C]
• 2nd-, 3rd-, 1st (rare) division trigeminal nerve most commonly affected (2,3)[A]
History
• Paroxysmal facial pain
• Pain elicited by tickle or touch
Physical Exam
All exam findings are typically negative due to paroxysmal nature of disorder
TESTS
Imaging
• MRI or CT scan: Neoplasm in cerebellopontine angle must be ruled out. Special MRA technique of collapsed MRA superimposed on routine spin echo T-1-weighted images
• No positive findings are significantly correlated with diagnosis (2,3)
Pathological Findings
• Trigeminal nerve: Inflammatory changes, demyelination, and degenerative changes (2)
• Trigeminal ganglion: Hypermyelination and microneuromata (3)
DIFFERENTIAL DIAGNOSIS
• Other forms of neuralgia usually have sensory loss. Presence of sensory loss nearly excludes diagnosis of trigeminal neuralgia (if younger patient, frequently MS).
• Neoplasia in cerebellopontine angle
• Vascular malformation of brain stem
• Demyelinating lesion (MS is diagnosed in 2-4% of patients with trigeminal neuralgia) (2)
• Vascular insult
• Migraine, cluster headache
• Giant cell arteritis
• Post-herpetic neuralgia
• Chronic meningitis
• Acute polyneuropathy
• Atypical odontalgia
• SUNCT syndrome (short-lasting, unilateral, neuralgiform pain with conjunctival injection)
TREATMENT
GENERAL MEASURES
• Outpatient
• Drug treatment is 1st approach. Invasive procedures for patients who cannot tolerate, or fail to respond to, or relapse after chronic, drug treatment
• Avoidance of stimulation (air, heat, cold) of trigger zones (lips, cheeks, gums)
Diet
No special diet
Activity
Full activity
SPECIAL THERAPY
Radiotherapy
Stereotactic radiosurgery has been shown to be effective after drug failure
• Minimal clinically effective dose: 70 Gy
• 75% of patients achieve complete relief within 3 months; by 3 years, 50% maintain complete relief (NNT = 2) (4)[B]
• Most common side effect: Sensory disturbance (corneal numbness)
Complementary and Alternative Medicine
Acupuncture, moxibustion (herb): Poor evidence
MEDICATION (DRUGS)
First Line
• Carbamazepine (Tegretol)
- Starting dose 100-200 mg b.i.d.; effective dose usually 200 mg q.i.d.; 1,200 mg/d maximum
- 70-90% of patients initially respond; by 3 years, 30% no longer helped (number needed to treat [NNT] = 1.8) (5)[A]
- Most common side effect: Sedation
• Contraindications: Monoamine oxidase (MAO) inhibitors, taken concurrently
• Precautions: Use with caution in the presence of liver disease.
• Significant possible interactions: Macrolide antibiotics, oral anticoagulants, anticonvulsants, tricyclics, oral contraceptives, steroids, digitalis, isonazid, monoamine oxidase (MAO) inhibitors, methyprylon nabilone, nizatidine, other H2 blockers, phenytoin, propoxyphene, benzodiazepines, calcium channel blockers
• Oxacarbazepine (Trileptal)
- Starting dose 150-300 mg b.i.d.; effective dose usually 375 mg b.i.d.; 1,200 mg/d maximum
- Efficacy similar to carbamazepine (5)[B]
- Faster, with less drowsiness and drug interactions than carbamazepine
- Decreases serum sodium
- Most common side effect: Sedation
Second Line
• Phenytoin (Dilantin)
- 300-400 mg/d (synergistic with carbamazepine)
- Potent P450 inducer (enhanced metabolism of many drugs)
- Various CNS side effects (sedation, ataxia)
• Baclofen (Lioresal)
- 10-80 mg/d; start at 5-10 mg t.i.d. with food (as adjunct with phenytoin or carbamazepine)
- Side effects: Drowsiness, weakness, nausea, vomiting
• Gabapentin (Neurontin)
- 100 mg t.i.d. or 300 mg at bedtime, increased up to 300-600 mg t.i.d.-q.i.d.
• Lamotrigine
- Titrate up to 200 mg b.i.d. (over weeks)
- 10% experience rash.
• Chlorphenesin carbamate (Maolate)
- 800-2,400 mg/d (as adjunct with phenytoin and/or carbamazepine)
- Side effect: Drowsiness
• Antidepressants: Amitriptyline, fluoxetine, trazodone
- Used especially with anticonvulsants
- Particularly effective for atypical forms of trigeminal neuralgia
• Clonazepam (Klonopin): Frequently causes drowsiness and ataxia
• Capsaicin cream, locally
• Botulinum toxin injection into zygomatic arch
• Valproic acid (Depakene, Depakote)
SURGERY
• Microvascular decompression of 5th cranial nerve at its entrance to (or exit from) brainstem
- 98% of patients achieve intial pain relief; by 33 months, 73% maintain complete relief (NNT 1.3) (6)[B]
- Surgical mortality across studies was ~1% (6)
- Most common side effect: Transient facial numbness and diplopia, headache, nausea, vomiting
- Mean hospital stay was ~5.4 days (6)[B]
• Peripheral-nerve ablation
- Radiofrequency thermocoagulation (possibly 90-97% partial or complete relief; recurrence rate unknown) (7)[C]
- Neurectomy
- Cryotherapy: High relapse rate
• 4% tetracaine dissolved in 0.5% bupivacaine nerve block (only a few case reports to date)
• Alcohol block or glycerol injection into trigeminal cistern: Unpredictable side effects (dysesthesia and anesthesia dolorosa); temporary relief
• Partial sensory rhizotomy
• Peripheral block or section of 5th nerve proximal to Gasserian ganglion
• Balloon compression of Gasserian ganglion (especially effective for 1st-division trigeminal neuralgia pain) (7)
FOLLOW-UP
PROGNOSIS
• 50-60% eventually fail pharmacological treatment (5B)
• Of those, relapse is seen in ~50% of stereotactic radiosurgeries and ~27% surgical microvascular decompressions (4,5)[B]
COMPLICATIONS
• Mental and physical sluggishness; dizziness with carbamazepine (5)
• Paresthesiae and corneal reflex loss with stereotactic radiosurgery (4)
• Surigical mortality and morbidity associated with microvascular decompression (6)
PATIENT MONITORING
• Carbamazepine and/or phenytoin serum levels
• If carbamazepine prescribed: CBC and platelets at baseline, then weekly for a month, then monthly for 4 months, then every 6-12 months if dose stable (regimens for monitoring vary)
• Reduce drugs after 4-6 weeks to determine whether condition is in remission; resume at previous dose if pain recurs. Withdraw drugs slowly after several months, again to check for remission or if lower dose of drugs can be tolerated.
REFERENCES
1. Manzoni GC, Torelli P. Epidemiology of typical and atypical craniofacial neuralgias. Neurol Sci. 2005; 26(Suppl 2):s65-s67.
2. Scrivani SJ, Mathews ES, Maciewicz RJ. Trigeminal neuralgia. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2005;100(5):527-538.
3. Nurmikko TJ, Eldridge PR. Trigeminal neuralgia-pathophysiology, diagnosis and current treatment. Br J Anaesth. 2001;87(1):117-132.
4. Lopez BC, Hamlyn PJ, Zakrzewska JM. Stereotactic radiosurgery for primary trigeminal neuralgia: State of the evidence and recommendations for future reports. J Neurol Neurosurg Psychiatry. 2004;75(7):1019-1024.
5. Beniczky S, Tajti J, Timea Varga E, Vecsei L. Evidence-based pharmacological treatment of neuropathic pain syndromes. J Neural Transm. 2005;112(6):735-749.
6. Ashkan K, Marsh H. Microvascular decompression for trigeminal neuralgia in the elderly: A review of the safety and efficacy. Neurosurgery. 2004;55(4):840-8; discussion 848-850.
7. Lopez BC, Hamlyn PJ, Zakrzewska JM. Systematic review of ablative neurosurgical techniques for the treatment of trigeminal neuralgia. Neurosurgery. 2004;54(4):973-82; discussion 982-983.
MISCELLANEOUS
See also: Headache, cluster; Migraine
TRICHOMONIASIS
TRICHOMONIASIS - George R. Bergus, MD
BASICS
DESCRIPTION
Infection with Trichomonas vaginalis, a pear-shaped protozoan parasite that is a facultative anaerobe
• Found in men and women at genitourinary sites
• Incubation period: 3-28 days
• Transmission rarely seen in female children of infected women
• System(s) Affected: Renal/Urologic; Reproductive
• Synonym(s): Trick; Trichomonal urethritis
GENERAL PREVENTION
Practice safe sex by using condoms.
EPIDEMIOLOGY
• Makes up 10-25% of vaginal infections
• Predominant age: Young and middle-aged adults:
- Rare until onset of sexual activity
- Uncommon in prepubertal children; confirmed diagnosis should raise concern of sexual abuse
- Not uncommon in postmenopausal women; older people remain at risk
• Predominant sex: Both affected, but women more commonly symptomatic
Incidence
• First-time diagnosis: 300/100,000 women/year
• Any diagnosis: 600/100,000 women/year
• Among special populations
- Sexually active adult women in a family-planning clinic: 2,000/100,000
- Sexually active adult women in a sexually transmitted disease (STD) clinic: 35,000/100,000
RISK FACTORS
• Multiple sexual partners
• Trichomonas can be identified in 30-40% of the male sexual partners of infected women.
ETIOLOGY
Trichomonas vaginalis: Usually sexually transmitted, although a nonvenereal route is possible, as the organism survives for several hours in a moist environment.
ASSOCIATED CONDITIONS
Other STDs
DIAGNOSIS
SIGNS AND SYMPTOMS
• Female
- 40% of patients can be asymptomatic at the time of the diagnosis.
- Symptoms typically begin or worsen at the time of the menstrual period.
- Vaginal discharge: 75%; usually copious, and can be frothy; sometimes watery and pooling
- Vulvovaginal irritation: 50%
- Dysuria: 50%
- Vaginal odor: 10%
- "Strawberry cervix" from punctate hemorrhages: 5%
- Vaginal hyperemia
- Dyspareunia
- Suprapubic discomfort
- Cervical erosion
• Male
- Asymptomatic: 80%
- Symptomatic: 20%; urethral discharge, dysuria, epididymitis (rare)
TESTS
Lab
• Culture: Sensitivity >95% but takes 4-7 days
• Enzyme linked immunosorbent assay and direct fluorescent antibody tests: Sensitivity 80-90%
• Rapid diagnostic kits using polymerase chain reaction DNA probes: Sensitivity 97%, specificity 98%
• Female
- Wet prep: Sensitivity 60-70%, specificity 100%. Sensitivity reduced with loss of motility due to cooling, low inoculum size, and rapid scanning of the slide. Usually shows many more polymorphonuclear leukocytes (PMNs) than epithelial cells.
- Pap smear: Sensitivity 60%, specificity 99%
- The vaginal pH is >4.5 in 90% of women.
• Male: Wet prep and culture of urethral discharge after prostatic exam; sensitivity 50-80%
DIFFERENTIAL DIAGNOSIS
• Female: Vaginal candidiasis, bacterial vaginosis; cervical inflammation can lead to mistaken diagnosis of cervicitis
• Male: Chlamydia urethritis
TREATMENT
STABILIZATION
Outpatient
GENERAL MEASURES
Medication for both patient and partner(s)
Diet
Abstention from alcohol if metronidazole used for therapy
Activity
Sexual activity should not be resumed until patient and partner are both treated.
MEDICATION (DRUGS)
First Line
• Metronidazole
- Adult dose: 2 g at one time or 500 mg b.i.d. for 7 days
- Both routines effective in women, but one-time dose has higher failure rate in men
- All sexual partners need treatment.
• Contraindications: 1st trimester pregnancy or allergy to the antibiotic
• Precautions: Avoid metronidazole or reduce dosage in patients with liver failure
• Significant possible interactions: Ethanol, warfarin, disulfiram, phenobarbital
Second Line
• For treatment failure after first line metronidazole dose, the Centers for Disease Control and Prevention (CDC) recommends 2 g metronidazole daily for 3-5 days. If repeated failure, consider non-compliance, re-infection, or susceptibility testing through the CDC.
• Tinidazole: 2 g at one time (has enhanced activity and fewer side effects)
• Clotrimazole
- 100 mg vaginal tablets at bedtime for 14 days
- Cure rate: 20-25%, but will reduce symptoms in most women
• Alternatively, saline or vinegar douching can be tried.
ALERT
Pregnancy Considerations
• Do not use metronidazole in 1st trimester.
• Treatment of the infection during pregnancy does not prevent preterm labor.
FOLLOW-UP
PROGNOSIS
Good, but recurrent infection raises possibility of noncompliance with therapy, reinfection, or infection with resistant organism. If resistance suspected, try metronidazole 2 g daily for 3-5 days.
COMPLICATIONS
Recurrent infections.
PATIENT MONITORING
• Monitor target symptoms.
• No follow-up needed if symptoms resolve with treatment
REFERENCES
1. The Centers for Disease Control and Prevention (CDC). 2002 Sexually transmitted disease treatment guidelines. MMWR. 2002;51(RR-6):1-84.
2. Forna F, Gulmezogly AM. Interventions for treating trichomoniasis in women. Cochrane Database Syst Rev. 2003:CD000218.
3. Okun N, et al. Antibiotics for bacterial vaginosis or Trichomonas vaginalis in pregnancy: A systematic review. Obstet Gynecol. 2005;105(4):857-868.
4. Sobel JK. Vaginitis. N Engl J Med. 1997;337:1896-1903.
5. Klebanoft MA, et al. Failure of metronidazole to prevent preterm labor. N Engl J Med. 2001;345:487-493.
MISCELLANEOUS
See also: Abnormal pap smear; Vulvovaginitis, bacterial
BASICS
DESCRIPTION
Infection with Trichomonas vaginalis, a pear-shaped protozoan parasite that is a facultative anaerobe
• Found in men and women at genitourinary sites
• Incubation period: 3-28 days
• Transmission rarely seen in female children of infected women
• System(s) Affected: Renal/Urologic; Reproductive
• Synonym(s): Trick; Trichomonal urethritis
GENERAL PREVENTION
Practice safe sex by using condoms.
EPIDEMIOLOGY
• Makes up 10-25% of vaginal infections
• Predominant age: Young and middle-aged adults:
- Rare until onset of sexual activity
- Uncommon in prepubertal children; confirmed diagnosis should raise concern of sexual abuse
- Not uncommon in postmenopausal women; older people remain at risk
• Predominant sex: Both affected, but women more commonly symptomatic
Incidence
• First-time diagnosis: 300/100,000 women/year
• Any diagnosis: 600/100,000 women/year
• Among special populations
- Sexually active adult women in a family-planning clinic: 2,000/100,000
- Sexually active adult women in a sexually transmitted disease (STD) clinic: 35,000/100,000
RISK FACTORS
• Multiple sexual partners
• Trichomonas can be identified in 30-40% of the male sexual partners of infected women.
ETIOLOGY
Trichomonas vaginalis: Usually sexually transmitted, although a nonvenereal route is possible, as the organism survives for several hours in a moist environment.
ASSOCIATED CONDITIONS
Other STDs
DIAGNOSIS
SIGNS AND SYMPTOMS
• Female
- 40% of patients can be asymptomatic at the time of the diagnosis.
- Symptoms typically begin or worsen at the time of the menstrual period.
- Vaginal discharge: 75%; usually copious, and can be frothy; sometimes watery and pooling
- Vulvovaginal irritation: 50%
- Dysuria: 50%
- Vaginal odor: 10%
- "Strawberry cervix" from punctate hemorrhages: 5%
- Vaginal hyperemia
- Dyspareunia
- Suprapubic discomfort
- Cervical erosion
• Male
- Asymptomatic: 80%
- Symptomatic: 20%; urethral discharge, dysuria, epididymitis (rare)
TESTS
Lab
• Culture: Sensitivity >95% but takes 4-7 days
• Enzyme linked immunosorbent assay and direct fluorescent antibody tests: Sensitivity 80-90%
• Rapid diagnostic kits using polymerase chain reaction DNA probes: Sensitivity 97%, specificity 98%
• Female
- Wet prep: Sensitivity 60-70%, specificity 100%. Sensitivity reduced with loss of motility due to cooling, low inoculum size, and rapid scanning of the slide. Usually shows many more polymorphonuclear leukocytes (PMNs) than epithelial cells.
- Pap smear: Sensitivity 60%, specificity 99%
- The vaginal pH is >4.5 in 90% of women.
• Male: Wet prep and culture of urethral discharge after prostatic exam; sensitivity 50-80%
DIFFERENTIAL DIAGNOSIS
• Female: Vaginal candidiasis, bacterial vaginosis; cervical inflammation can lead to mistaken diagnosis of cervicitis
• Male: Chlamydia urethritis
TREATMENT
STABILIZATION
Outpatient
GENERAL MEASURES
Medication for both patient and partner(s)
Diet
Abstention from alcohol if metronidazole used for therapy
Activity
Sexual activity should not be resumed until patient and partner are both treated.
MEDICATION (DRUGS)
First Line
• Metronidazole
- Adult dose: 2 g at one time or 500 mg b.i.d. for 7 days
- Both routines effective in women, but one-time dose has higher failure rate in men
- All sexual partners need treatment.
• Contraindications: 1st trimester pregnancy or allergy to the antibiotic
• Precautions: Avoid metronidazole or reduce dosage in patients with liver failure
• Significant possible interactions: Ethanol, warfarin, disulfiram, phenobarbital
Second Line
• For treatment failure after first line metronidazole dose, the Centers for Disease Control and Prevention (CDC) recommends 2 g metronidazole daily for 3-5 days. If repeated failure, consider non-compliance, re-infection, or susceptibility testing through the CDC.
• Tinidazole: 2 g at one time (has enhanced activity and fewer side effects)
• Clotrimazole
- 100 mg vaginal tablets at bedtime for 14 days
- Cure rate: 20-25%, but will reduce symptoms in most women
• Alternatively, saline or vinegar douching can be tried.
ALERT
Pregnancy Considerations
• Do not use metronidazole in 1st trimester.
• Treatment of the infection during pregnancy does not prevent preterm labor.
FOLLOW-UP
PROGNOSIS
Good, but recurrent infection raises possibility of noncompliance with therapy, reinfection, or infection with resistant organism. If resistance suspected, try metronidazole 2 g daily for 3-5 days.
COMPLICATIONS
Recurrent infections.
PATIENT MONITORING
• Monitor target symptoms.
• No follow-up needed if symptoms resolve with treatment
REFERENCES
1. The Centers for Disease Control and Prevention (CDC). 2002 Sexually transmitted disease treatment guidelines. MMWR. 2002;51(RR-6):1-84.
2. Forna F, Gulmezogly AM. Interventions for treating trichomoniasis in women. Cochrane Database Syst Rev. 2003:CD000218.
3. Okun N, et al. Antibiotics for bacterial vaginosis or Trichomonas vaginalis in pregnancy: A systematic review. Obstet Gynecol. 2005;105(4):857-868.
4. Sobel JK. Vaginitis. N Engl J Med. 1997;337:1896-1903.
5. Klebanoft MA, et al. Failure of metronidazole to prevent preterm labor. N Engl J Med. 2001;345:487-493.
MISCELLANEOUS
See also: Abnormal pap smear; Vulvovaginitis, bacterial
TRICHINELLOSIS
TRICHINELLOSIS - Kenton I. Voorhees, MD, FAAFP
BASICS
DESCRIPTION
Trichinellosis is a parasitic disease that develops after ingesting infected pork or other meat containing viable cysts of Trichinella spiralis, a nematode, with rarer cases attributable to several different species of Trichinella. Cysts remain viable and can cause disease when infected meat is undercooked. Most common outbreaks are attributable to undercooked pork, homemade and commercial sausage, wild boar, bear, walrus, and other wild-animal meats. Horsemeat has become another important source in the European Union.
• Enteric phase: Phase I
- Cysts broken down by digestive acid and pepsin in stomach, freeing larvae, which develop into mature adult worms in upper to middle small intestine
- Takes about 1 week after ingestion; may last 3-5 weeks
• Systemic phase: Phase II
- Female worms then release newborn larvae that migrate through blood vessels and lymphatics to multiple organ systems
- Occurs 2-3 weeks after ingestion; may last for 2 months
• Muscular encystment phase: Phase III
- Larvae become encysted in striated skeletal and sometimes cardiac muscle, where they form a nurse cell that functions to nourish them and protect them from host immunity
- Complex can survive in humans up to 30 years
- Intramuscular cysts usually eventually calcify
• System(s) Affected: Gastrointestinal; Musculoskeletal
• Synonym(s): Trichinelliasis
ALERT
Pregnancy Considerations
Although not much information is available, 1 case has been reported of an infected woman 16 weeks pregnant who delivered a normal child without complications or evidence of problems.
GENERAL PREVENTION
• Avoid eating undercooked pork and game meat
• Prolonged freezing may be effective, but less so for wild-game meat
EPIDEMIOLOGY
• Predominant age: 20-49, although cases reported from all age groups
• Predominant sex: Male = Female
Incidence
• From 1997-2001, on average, 12 cases were reported annually in the United States. (1)
• Higher incidence in Alaska and northeastern United States
• Most mild cases probably undiagnosed, based on autopsy studies.
RISK FACTORS
• Access to wild game, homemade pork products, noncommercial sources of meat
• Eating pigs that were fed uncooked garbage
• Undercooking pork
• Eating inadequately cooked or frozen wild game
• Ethnic groups from Southeast Asia raising their own pork or favoring partially cooked pork products
• Residence in Alaska and northeastern United States
ETIOLOGY
Eating undercooked meat that is infected with viable Trichenella cysts
DIAGNOSIS
SIGNS AND SYMPTOMS
Signs and symptoms begin within 1 week of ingesting infected meat
• Common symptoms (can occur concurrently)
- Diarrhea: Mostly phase I
- Abdominal cramping: Mostly phase I
- Fever: Mostly phase II and III
- Myalgias: Mostly phase II and III
- Eosinophilia: Mostly phase II and III
- Periorbital edema: Mostly phase II and III
- Weakness: Mostly phase II and III
• Less common symptoms: Mostly phase II and III
- Conjunctivitis
- Subconjunctival hemorrhage
- Retinal hemorrhages
- Maculopapular rash
- Splinter hemorrhages
- Headache
- Photophobia
- Pneumonitis
- Tachycardia
- Heart failure
- Pericardial effusion
- CNS involvement
• Symptoms depend on number of ingested infective larvae and phase of parasitic invasion
- Light infections: 10 larvae per gram of muscle; usually asymptomatic
- Heavy infections: >50 larvae per gram of muscle; can be life threatening
- Skeletal muscle (gastrocnemius, masseter, diaphragm, biceps, lower back, extraocular muscles, jaw and neck) is most frequent site of symptoms due to larval migration; however, in severe cases myocardial damage, pulmonary infiltration, and focal neurologic damage can occur
History
A history of having eaten undercooked pork or wild game meat.
TESTS
Lab
• Serologic tests for T. spiralis, IgM, and IgG
• Enzyme linked immunosorbent assay IgM and IgG
• Bentonite flocculation after 3rd week for parasite-specific antibody
• Indirect immunofluorescence
• Complement fixation
• DNA testing: Random amplified polymorphic DNA, polymerase chain reaction
• Antibody levels
- Often not detectable until 3-5 weeks post infection, high false negative rate in phase I
- Peak 3rd month
- Remain detectable 2-3 years
• Antibody testing
- Testing 15-22% false negative in phase I
- Paired specimens helpful, 1-2 months apart; look for 4-fold increase in titer
• Eosinophilia (>600/mm3), with leukocytosis
• Increased creatine phosphate kinase
• Increased lactate dehydrogenase
• Hypergammaglobulinemia
• Elevated erythrocyte sedimentation rate (several weeks)
• Urinalysis may show myoglobinuria
• Drugs that may alter lab results: Rare increases in serum glutamic-oxaloacetic transaminase with thiabendazole
Imaging
• CT may help see calcified muscle cysts
• MRI may help in evaluation of neurologic complications
• Chest x-ray may detect patchy infiltrates
• Extremity x-ray may show calcified densities
Diagnostic Procedures/Surgery
Muscle biopsy of gastrocnemius or deltoid with 1 gram of muscle, including examination between compressed slides (higher detection rate)
Pathological Findings
Larvae on muscle biopsy (often gastrocnemius); absence of larvae does not exclude diagnosis; rarely find worm in stool
DIFFERENTIAL DIAGNOSIS
• Acute rheumatic fever
• Arthritis
• Angioedema
• Botulism
• Collagen vascular disease
• Dermatomyositis
• Encephalitis
• Eosinophilia-myalgia syndrome
• Gastroenteritis
• Idiopathic hypereosinophilic syndrome
• Idiopathic polymyositis
• Influenza
• Meningitis
• Pneumonitis
• Polyarteritis nodosa
• Polymyositis
• Typhoid fever
• Tuberculosis
TREATMENT
GENERAL MEASURES
• Outpatient unless complications such as cardiac, pulmonary, or neurological
• May call the centers for disease control and prevention (CDC) for appropriate diagnostic tests: (404) 639-3311
• Bedrest
• Antipyretics
• Analgesics
Diet
As tolerated
Activity
• As tolerated
• Bed rest may help muscular pain.
MEDICATION (DRUGS)
First Line
• For early intestinal phase (presenting in the 1st 1-2 weeks), to treat adult worms
- Mebendazole may be used 200-400 mg t.i.d. for 3 days, then 400-500 mg t.i.d. 10 days, adults and children > 2 years (2)[C]
- Albendazole: 400 mg b.i.d. for 8-14 days, adults and children > 2 years (2)[C]
- Pyrantel may be used 10-20 mg/kg body weight, repeated 2-3 days for pregnant women and children (3)[C]
- No drugs are very effective against larvae once they are encysted in muscle; however, they may halt further dissemination.
• Call the CDC for current dosage and recommendations (404) 639-3311.
• Severe cases: Corticosteroids, such as prednisone 40-60 mg/d for 3-5 days; taper as symptoms subside, particularly to help decrease inflammation when there are signs of myocarditis, neurologic disease, pulmonary insufficiency, or severe myositis
• Analgesics, NSAIDS, anti-pyretics may be helpful as needed
• Contraindications: Corticosteroids have been reported to be contraindicated in the intestinal phase, as they could prolong the phase.
• Precautions: Minimal experience exists with the use of medications in small children and in pregnancy. Mebendazole should not be given during the 1st trimester, and any medications should only be used if absolutely necessary.
• Significant possible interactions
- Carbamazepine or alcohol may decrease the effect of mebendazole.
- Cimetidine may increase the level of mebendazole.
Second Line
Thiabendazole: Used to be drug of choice at 25 mg/kg b.i.d. for 1 week, maximum dose 1.5 gm; replaced by the drugs previously mentioned because they have fewer side effects and are equally effective.
SURGERY
Pacemaker has been required on occasion for severe myocarditis
FOLLOW-UP
DISPOSITION
Admission Criteria
• Admit if cardiac, pulmonary or neurologic manifestations
• Pregnancy
PROGNOSIS
• Most infections are asymptomatic, short-lived, and generally have an uneventful recovery without medication.
• Prognosis good in most cases, although 5-10% of the cases can be severe.
• No clear evidence that chronic trichinosis exists.
• 1% of cases can be fatal, generally around 4th-8th week, as a result of cardiac failure or pneumonia
COMPLICATIONS
• Meningitis
• Subcortical infarcts
• Encephalitis
• Myocarditis with congestive heart failure
• Nephritis
• Glomerulonephritis
• Sinusitis
• Pneumonitis
• Ocular
• Prenancy: Abortion, premature delivery
• Death: Typically cardiac or thromboembolic events
PATIENT MONITORING
Monitor the patient for signs and symptoms of complications, such as cardiac, neurological, and pulmonary.
REFERENCES
1. Roy SL, et al. Trichinellosis surveillanceUnited States, 1997-2001. MMWR Surveill Summ. 2003;52(6):1-8.
2. Abramowicz M, ed. The Medical Letter on Drugs and Therapeutics. Drugs for Parasitic Infections. New Rochelle, NY: The Medical Letter, 2004
3. Kociecka W. Trichinellosis: Human disease, diagnosis and treatment. Vet Parisitol. 2000,93(3-4):365-383.
4. Dupouy-Camet J, et al. Opinion on the diagnosis and treatment of human trichinellosis. Expert Opin Pharmacother. 2002;3(8):1117-1130.
5. Bruschi F. New aspects of human trichinellosis: The impact of new Trichinella species. Postgrad Med J. 2002;78(915):15-22.
BASICS
DESCRIPTION
Trichinellosis is a parasitic disease that develops after ingesting infected pork or other meat containing viable cysts of Trichinella spiralis, a nematode, with rarer cases attributable to several different species of Trichinella. Cysts remain viable and can cause disease when infected meat is undercooked. Most common outbreaks are attributable to undercooked pork, homemade and commercial sausage, wild boar, bear, walrus, and other wild-animal meats. Horsemeat has become another important source in the European Union.
• Enteric phase: Phase I
- Cysts broken down by digestive acid and pepsin in stomach, freeing larvae, which develop into mature adult worms in upper to middle small intestine
- Takes about 1 week after ingestion; may last 3-5 weeks
• Systemic phase: Phase II
- Female worms then release newborn larvae that migrate through blood vessels and lymphatics to multiple organ systems
- Occurs 2-3 weeks after ingestion; may last for 2 months
• Muscular encystment phase: Phase III
- Larvae become encysted in striated skeletal and sometimes cardiac muscle, where they form a nurse cell that functions to nourish them and protect them from host immunity
- Complex can survive in humans up to 30 years
- Intramuscular cysts usually eventually calcify
• System(s) Affected: Gastrointestinal; Musculoskeletal
• Synonym(s): Trichinelliasis
ALERT
Pregnancy Considerations
Although not much information is available, 1 case has been reported of an infected woman 16 weeks pregnant who delivered a normal child without complications or evidence of problems.
GENERAL PREVENTION
• Avoid eating undercooked pork and game meat
• Prolonged freezing may be effective, but less so for wild-game meat
EPIDEMIOLOGY
• Predominant age: 20-49, although cases reported from all age groups
• Predominant sex: Male = Female
Incidence
• From 1997-2001, on average, 12 cases were reported annually in the United States. (1)
• Higher incidence in Alaska and northeastern United States
• Most mild cases probably undiagnosed, based on autopsy studies.
RISK FACTORS
• Access to wild game, homemade pork products, noncommercial sources of meat
• Eating pigs that were fed uncooked garbage
• Undercooking pork
• Eating inadequately cooked or frozen wild game
• Ethnic groups from Southeast Asia raising their own pork or favoring partially cooked pork products
• Residence in Alaska and northeastern United States
ETIOLOGY
Eating undercooked meat that is infected with viable Trichenella cysts
DIAGNOSIS
SIGNS AND SYMPTOMS
Signs and symptoms begin within 1 week of ingesting infected meat
• Common symptoms (can occur concurrently)
- Diarrhea: Mostly phase I
- Abdominal cramping: Mostly phase I
- Fever: Mostly phase II and III
- Myalgias: Mostly phase II and III
- Eosinophilia: Mostly phase II and III
- Periorbital edema: Mostly phase II and III
- Weakness: Mostly phase II and III
• Less common symptoms: Mostly phase II and III
- Conjunctivitis
- Subconjunctival hemorrhage
- Retinal hemorrhages
- Maculopapular rash
- Splinter hemorrhages
- Headache
- Photophobia
- Pneumonitis
- Tachycardia
- Heart failure
- Pericardial effusion
- CNS involvement
• Symptoms depend on number of ingested infective larvae and phase of parasitic invasion
- Light infections: 10 larvae per gram of muscle; usually asymptomatic
- Heavy infections: >50 larvae per gram of muscle; can be life threatening
- Skeletal muscle (gastrocnemius, masseter, diaphragm, biceps, lower back, extraocular muscles, jaw and neck) is most frequent site of symptoms due to larval migration; however, in severe cases myocardial damage, pulmonary infiltration, and focal neurologic damage can occur
History
A history of having eaten undercooked pork or wild game meat.
TESTS
Lab
• Serologic tests for T. spiralis, IgM, and IgG
• Enzyme linked immunosorbent assay IgM and IgG
• Bentonite flocculation after 3rd week for parasite-specific antibody
• Indirect immunofluorescence
• Complement fixation
• DNA testing: Random amplified polymorphic DNA, polymerase chain reaction
• Antibody levels
- Often not detectable until 3-5 weeks post infection, high false negative rate in phase I
- Peak 3rd month
- Remain detectable 2-3 years
• Antibody testing
- Testing 15-22% false negative in phase I
- Paired specimens helpful, 1-2 months apart; look for 4-fold increase in titer
• Eosinophilia (>600/mm3), with leukocytosis
• Increased creatine phosphate kinase
• Increased lactate dehydrogenase
• Hypergammaglobulinemia
• Elevated erythrocyte sedimentation rate (several weeks)
• Urinalysis may show myoglobinuria
• Drugs that may alter lab results: Rare increases in serum glutamic-oxaloacetic transaminase with thiabendazole
Imaging
• CT may help see calcified muscle cysts
• MRI may help in evaluation of neurologic complications
• Chest x-ray may detect patchy infiltrates
• Extremity x-ray may show calcified densities
Diagnostic Procedures/Surgery
Muscle biopsy of gastrocnemius or deltoid with 1 gram of muscle, including examination between compressed slides (higher detection rate)
Pathological Findings
Larvae on muscle biopsy (often gastrocnemius); absence of larvae does not exclude diagnosis; rarely find worm in stool
DIFFERENTIAL DIAGNOSIS
• Acute rheumatic fever
• Arthritis
• Angioedema
• Botulism
• Collagen vascular disease
• Dermatomyositis
• Encephalitis
• Eosinophilia-myalgia syndrome
• Gastroenteritis
• Idiopathic hypereosinophilic syndrome
• Idiopathic polymyositis
• Influenza
• Meningitis
• Pneumonitis
• Polyarteritis nodosa
• Polymyositis
• Typhoid fever
• Tuberculosis
TREATMENT
GENERAL MEASURES
• Outpatient unless complications such as cardiac, pulmonary, or neurological
• May call the centers for disease control and prevention (CDC) for appropriate diagnostic tests: (404) 639-3311
• Bedrest
• Antipyretics
• Analgesics
Diet
As tolerated
Activity
• As tolerated
• Bed rest may help muscular pain.
MEDICATION (DRUGS)
First Line
• For early intestinal phase (presenting in the 1st 1-2 weeks), to treat adult worms
- Mebendazole may be used 200-400 mg t.i.d. for 3 days, then 400-500 mg t.i.d. 10 days, adults and children > 2 years (2)[C]
- Albendazole: 400 mg b.i.d. for 8-14 days, adults and children > 2 years (2)[C]
- Pyrantel may be used 10-20 mg/kg body weight, repeated 2-3 days for pregnant women and children (3)[C]
- No drugs are very effective against larvae once they are encysted in muscle; however, they may halt further dissemination.
• Call the CDC for current dosage and recommendations (404) 639-3311.
• Severe cases: Corticosteroids, such as prednisone 40-60 mg/d for 3-5 days; taper as symptoms subside, particularly to help decrease inflammation when there are signs of myocarditis, neurologic disease, pulmonary insufficiency, or severe myositis
• Analgesics, NSAIDS, anti-pyretics may be helpful as needed
• Contraindications: Corticosteroids have been reported to be contraindicated in the intestinal phase, as they could prolong the phase.
• Precautions: Minimal experience exists with the use of medications in small children and in pregnancy. Mebendazole should not be given during the 1st trimester, and any medications should only be used if absolutely necessary.
• Significant possible interactions
- Carbamazepine or alcohol may decrease the effect of mebendazole.
- Cimetidine may increase the level of mebendazole.
Second Line
Thiabendazole: Used to be drug of choice at 25 mg/kg b.i.d. for 1 week, maximum dose 1.5 gm; replaced by the drugs previously mentioned because they have fewer side effects and are equally effective.
SURGERY
Pacemaker has been required on occasion for severe myocarditis
FOLLOW-UP
DISPOSITION
Admission Criteria
• Admit if cardiac, pulmonary or neurologic manifestations
• Pregnancy
PROGNOSIS
• Most infections are asymptomatic, short-lived, and generally have an uneventful recovery without medication.
• Prognosis good in most cases, although 5-10% of the cases can be severe.
• No clear evidence that chronic trichinosis exists.
• 1% of cases can be fatal, generally around 4th-8th week, as a result of cardiac failure or pneumonia
COMPLICATIONS
• Meningitis
• Subcortical infarcts
• Encephalitis
• Myocarditis with congestive heart failure
• Nephritis
• Glomerulonephritis
• Sinusitis
• Pneumonitis
• Ocular
• Prenancy: Abortion, premature delivery
• Death: Typically cardiac or thromboembolic events
PATIENT MONITORING
Monitor the patient for signs and symptoms of complications, such as cardiac, neurological, and pulmonary.
REFERENCES
1. Roy SL, et al. Trichinellosis surveillanceUnited States, 1997-2001. MMWR Surveill Summ. 2003;52(6):1-8.
2. Abramowicz M, ed. The Medical Letter on Drugs and Therapeutics. Drugs for Parasitic Infections. New Rochelle, NY: The Medical Letter, 2004
3. Kociecka W. Trichinellosis: Human disease, diagnosis and treatment. Vet Parisitol. 2000,93(3-4):365-383.
4. Dupouy-Camet J, et al. Opinion on the diagnosis and treatment of human trichinellosis. Expert Opin Pharmacother. 2002;3(8):1117-1130.
5. Bruschi F. New aspects of human trichinellosis: The impact of new Trichinella species. Postgrad Med J. 2002;78(915):15-22.
TRANSIENT ISCHEMIC ATTACK (TIA)
TRANSIENT ISCHEMIC ATTACK (TIA) - VladimirHachinski, MD, DSc; VivekJain, MD
BASICS
DESCRIPTION
Sudden onset of focal and transient (24 hours) neurological deficit due to brain ischemia
• System(s) Affected: Nervous
• Synonym(s): Mini-stroke
GENERAL PREVENTION
• Counseling toward cessation of smoking
• Strict control of medical risk factors (e.g., diabetes, hypertension, hyperlipidemia, cardiac disease)
• Antiplatelet therapy
• Angiotensin-converting enzyme inhibitors
• Statins
• Treat homocystinemia with vitamin B6, vitamin B12, and folic acid
• Anticoagulation when high risk of cardioembolism (e.g., atrial fibrillation)
EPIDEMIOLOGY
• Predominant age: Risk increases >45 years; highest in 7th and 8th decades
• Predominant sex: Male > Female (3:1)
Incidence
30/100,000
RISK FACTORS
• Hypertension
• Cardiac disease
• Smoking
• Diabetes
• Antiphospholipid antibodies
• Family history
• Hypercholesterolemia
• Atrial fibrillation
• Homocystinemia
Genetics
Inheritance is polygenic with tendency to clustering of risk factors within families
ETIOLOGY
• Carotid atherosclerotic disease with artery-to-artery thromboembolism
• Small, deep vessel disease associated with hypertension
• Cardiac
- Cardioembolism secondary to valvular (mitral valve) pathology
- Mural hypokinesias or akinesias with thrombosis (acute anterior myocardial infarctions or congestive cardiomyopathies)
- Cardiac arrhythmia (atrial fibrillation)
• Hypercoagulable states
- Antiphospholipid antibodies
- Deficiency of protein S, protein C
- Presence of antithrombin 3
- Oral contraceptives
- Associated with pregnancy and parturition
• Other causes
- Spontaneous and posttraumatic (e.g., chiropractic manipulation) arterial dissection
- Fibromuscular dysplasia
ALERT
Pediatric Considerations
• Cardiac (especially developmental abnormalities)
• Metabolic: Homocystinuria, Fabry disease
• Atrial fibrillation is frequent cause among the elderly
ASSOCIATED CONDITIONS
• Atrial fibrillation
• Other cardiac disease
DIAGNOSIS
SIGNS AND SYMPTOMS
• Carotid circulation (hemispheric): Monocular visual loss, hemiplegia, hemianesthesia, neglect, aphasia, visual field defects (less often: Headaches, seizures, amnesia, confusion)
• Vertebrobasilar (brainstem or cerebellar): Bilateral visual obscuration, diplopia, vertigo, ataxia, facial paresis, Horner syndrome, dysphagia, dysarthria; also headache, nausea, vomiting, and ataxia
TESTS
Lab
• International normalized ratio (INR) and partial thromboplastin time (PTT) (coumadin prolongs INR)
• Antiphospholipid antibodies
Imaging
• Duplex carotid ultrasonography
• ECG
• Angiography
- Cerebral
- Carotid arterial stenosis
• Transthoracic echocardiogram; if normal and cardiac source is suspected, follow with transesophageal echocardiogram
• Holter monitoring
• CT of head: Acute phase
• Brain MRI, include diffusion-weighted imaging
• MR angiography: Brain and blood vessels
• EEG, if suspecting seizure
DIFFERENTIAL DIAGNOSIS
• Migraine (hemiplegic)
• Focal seizure (Todd paralysis)
• Hypoglycemia
TREATMENT
GENERAL MEASURES
• Acute phase
- Outpatient for investigations
- Inpatient for surgery and high-risk groups
• Antithrombotic therapy
Diet
As appropriate to underlying medical problems (e.g., diabetic, low-fat, or low-salt diet)
Activity
No restrictions
MEDICATION (DRUGS)
First Line
• Enteric coated aspirin: 50-325 mg/d or
• Clopidogrel (Plavix): 75 mg/d
- Ticlopidine's descendent
- Has fewer side effects than Ticlopidine
- Shows slight advantage over aspirin
• Dipyridamole-aspirin (Aggrenox): 1 capsule PO b.i.d.
- Each capsule contains 200 mg extended-release dipyridamole and 25 mg immediate-release aspirin
- More efficacious than aspirin alone, but more costly
• Warfarin (INR-adjusted dose): For patients with atrial fibrillation and cardioembolic stroke
Second Line
• Ticlopidine (Ticlid): 250 mg PO b.i.d.; fallen out of favor due to unfavorable side-effect profile
• Contraindications
- Enteric coated aspirin: Active peptic ulcer disease, hypersensitivity to aspirin, previous bronchospastic reaction to aspirin or other NSAIDs
- Warfarin: Intolerance or allergy, dementia, liver disease, active bleeding, pregnancy, recent head injury
- Ticlopidine: Known hypersensitivity to the drug, presence of hematopoietic disorders, presence of hemostatic disorder, conditions associated with active bleeding, severe liver dysfunction
• Precautions
- Enteric coated aspirin: May aggravate pre-existing peptic ulcer disease; may worsen symptoms in some patients with asthma
- Warfarin: May cause poor balance, which can be dangerous for people with alcohol/drug problems or >80 years
- Clopidogrel and ticlopidine: TTP can occur
- Ticlopidine: 2.4% of patients develop neutropenia (0.8% severe), which is reversible with cessation of drug. Monitor blood counts every 2 weeks for first 3 months.
• Significant possible interactions
- Enteric coated aspirin: May potentiate effects of anticoagulants and sulfonylurea, hypoglycemic agents
- Warfarin: Aspirin, NSAIDs, antibiotics, tranquilizers
- Ticlopidine: Digoxin plasma levels decreased 15%, theophylline half-life increased from 8.6-12.2 hours
SURGERY
In medically fit patients with nondisabling stroke: Carotid endarterectomy
• Carotid artery stenosis 70-99%: Indicated on side ipsilateral to stroke
• Carotid artery stenosis 50-69%: Of modest benefit; depends on risk factors
• Carotid artery stenosis 50%: North American Symptomatic Carotid Endarterectomy Trial showed no benefit above medical therapy alone
FOLLOW-UP
PROGNOSIS
• The risk of stroke on the ipsilateral side within 1 year and cumulative thereafter is 5-20%.
• Frequency increases with addition of multiple risk factors and severity of carotid stenosis
• The major cause of death in the first 5 years is cardiac disease.
COMPLICATIONS
• Stroke
• Seizure
• Trauma if patient experiences sudden fall due to weakness
PATIENT MONITORING
Follow-up every 3 months for 1st year, then yearly
REFERENCES
1. Hachinski V. Stroke. Lancet. 1998;352(Suppl 3):S1-S30.
2. Hachinski V. Brain Attack: The Clinical Handbook. Guelph, Canada: Meducom International; 1999.
MISCELLANEOUS
See also: Stroke (Brain Attack)
BASICS
DESCRIPTION
Sudden onset of focal and transient (24 hours) neurological deficit due to brain ischemia
• System(s) Affected: Nervous
• Synonym(s): Mini-stroke
GENERAL PREVENTION
• Counseling toward cessation of smoking
• Strict control of medical risk factors (e.g., diabetes, hypertension, hyperlipidemia, cardiac disease)
• Antiplatelet therapy
• Angiotensin-converting enzyme inhibitors
• Statins
• Treat homocystinemia with vitamin B6, vitamin B12, and folic acid
• Anticoagulation when high risk of cardioembolism (e.g., atrial fibrillation)
EPIDEMIOLOGY
• Predominant age: Risk increases >45 years; highest in 7th and 8th decades
• Predominant sex: Male > Female (3:1)
Incidence
30/100,000
RISK FACTORS
• Hypertension
• Cardiac disease
• Smoking
• Diabetes
• Antiphospholipid antibodies
• Family history
• Hypercholesterolemia
• Atrial fibrillation
• Homocystinemia
Genetics
Inheritance is polygenic with tendency to clustering of risk factors within families
ETIOLOGY
• Carotid atherosclerotic disease with artery-to-artery thromboembolism
• Small, deep vessel disease associated with hypertension
• Cardiac
- Cardioembolism secondary to valvular (mitral valve) pathology
- Mural hypokinesias or akinesias with thrombosis (acute anterior myocardial infarctions or congestive cardiomyopathies)
- Cardiac arrhythmia (atrial fibrillation)
• Hypercoagulable states
- Antiphospholipid antibodies
- Deficiency of protein S, protein C
- Presence of antithrombin 3
- Oral contraceptives
- Associated with pregnancy and parturition
• Other causes
- Spontaneous and posttraumatic (e.g., chiropractic manipulation) arterial dissection
- Fibromuscular dysplasia
ALERT
Pediatric Considerations
• Cardiac (especially developmental abnormalities)
• Metabolic: Homocystinuria, Fabry disease
• Atrial fibrillation is frequent cause among the elderly
ASSOCIATED CONDITIONS
• Atrial fibrillation
• Other cardiac disease
DIAGNOSIS
SIGNS AND SYMPTOMS
• Carotid circulation (hemispheric): Monocular visual loss, hemiplegia, hemianesthesia, neglect, aphasia, visual field defects (less often: Headaches, seizures, amnesia, confusion)
• Vertebrobasilar (brainstem or cerebellar): Bilateral visual obscuration, diplopia, vertigo, ataxia, facial paresis, Horner syndrome, dysphagia, dysarthria; also headache, nausea, vomiting, and ataxia
TESTS
Lab
• International normalized ratio (INR) and partial thromboplastin time (PTT) (coumadin prolongs INR)
• Antiphospholipid antibodies
Imaging
• Duplex carotid ultrasonography
• ECG
• Angiography
- Cerebral
- Carotid arterial stenosis
• Transthoracic echocardiogram; if normal and cardiac source is suspected, follow with transesophageal echocardiogram
• Holter monitoring
• CT of head: Acute phase
• Brain MRI, include diffusion-weighted imaging
• MR angiography: Brain and blood vessels
• EEG, if suspecting seizure
DIFFERENTIAL DIAGNOSIS
• Migraine (hemiplegic)
• Focal seizure (Todd paralysis)
• Hypoglycemia
TREATMENT
GENERAL MEASURES
• Acute phase
- Outpatient for investigations
- Inpatient for surgery and high-risk groups
• Antithrombotic therapy
Diet
As appropriate to underlying medical problems (e.g., diabetic, low-fat, or low-salt diet)
Activity
No restrictions
MEDICATION (DRUGS)
First Line
• Enteric coated aspirin: 50-325 mg/d or
• Clopidogrel (Plavix): 75 mg/d
- Ticlopidine's descendent
- Has fewer side effects than Ticlopidine
- Shows slight advantage over aspirin
• Dipyridamole-aspirin (Aggrenox): 1 capsule PO b.i.d.
- Each capsule contains 200 mg extended-release dipyridamole and 25 mg immediate-release aspirin
- More efficacious than aspirin alone, but more costly
• Warfarin (INR-adjusted dose): For patients with atrial fibrillation and cardioembolic stroke
Second Line
• Ticlopidine (Ticlid): 250 mg PO b.i.d.; fallen out of favor due to unfavorable side-effect profile
• Contraindications
- Enteric coated aspirin: Active peptic ulcer disease, hypersensitivity to aspirin, previous bronchospastic reaction to aspirin or other NSAIDs
- Warfarin: Intolerance or allergy, dementia, liver disease, active bleeding, pregnancy, recent head injury
- Ticlopidine: Known hypersensitivity to the drug, presence of hematopoietic disorders, presence of hemostatic disorder, conditions associated with active bleeding, severe liver dysfunction
• Precautions
- Enteric coated aspirin: May aggravate pre-existing peptic ulcer disease; may worsen symptoms in some patients with asthma
- Warfarin: May cause poor balance, which can be dangerous for people with alcohol/drug problems or >80 years
- Clopidogrel and ticlopidine: TTP can occur
- Ticlopidine: 2.4% of patients develop neutropenia (0.8% severe), which is reversible with cessation of drug. Monitor blood counts every 2 weeks for first 3 months.
• Significant possible interactions
- Enteric coated aspirin: May potentiate effects of anticoagulants and sulfonylurea, hypoglycemic agents
- Warfarin: Aspirin, NSAIDs, antibiotics, tranquilizers
- Ticlopidine: Digoxin plasma levels decreased 15%, theophylline half-life increased from 8.6-12.2 hours
SURGERY
In medically fit patients with nondisabling stroke: Carotid endarterectomy
• Carotid artery stenosis 70-99%: Indicated on side ipsilateral to stroke
• Carotid artery stenosis 50-69%: Of modest benefit; depends on risk factors
• Carotid artery stenosis 50%: North American Symptomatic Carotid Endarterectomy Trial showed no benefit above medical therapy alone
FOLLOW-UP
PROGNOSIS
• The risk of stroke on the ipsilateral side within 1 year and cumulative thereafter is 5-20%.
• Frequency increases with addition of multiple risk factors and severity of carotid stenosis
• The major cause of death in the first 5 years is cardiac disease.
COMPLICATIONS
• Stroke
• Seizure
• Trauma if patient experiences sudden fall due to weakness
PATIENT MONITORING
Follow-up every 3 months for 1st year, then yearly
REFERENCES
1. Hachinski V. Stroke. Lancet. 1998;352(Suppl 3):S1-S30.
2. Hachinski V. Brain Attack: The Clinical Handbook. Guelph, Canada: Meducom International; 1999.
MISCELLANEOUS
See also: Stroke (Brain Attack)
TRANSFUSION REACTION
TRANSFUSION REACTION - Ruben Peralta, MD, FACS; Sarah Guzofski, MD
BASICS
DESCRIPTION
The transfusion of blood products can cause numerous serious complications, even death. Adverse reactions to blood products may occur by immune or non-immune mechanisms.
• Immune: Acute, febrile, allergic, transfusion-related acute lung injury (TRALI)
• Non-immune
- Acute: Circulatory overload, bacterial contamination, and other effects, including hyperkalemia, hypocalcemia, acidosis, coagulopathy, hypothermia
- Chronic: Viral infection (cytomegalovirus human T-cell leukemia virus, HTLV, HIV, hepatitis), hemosiderosis
ALERT
Pediatric Considerations
Reaction greater and outlook poorer in the very young
Geriatric Considerations
Higher risk of complications in the elderly
GENERAL PREVENTION
• Follow procedures for sample and blood labeling and patient identification. Two practitioners, and if possible, patient should verify that blood product and patient identity match. (1)[C]
• Obtain detailed history of patient's responses to previous transfusions
• Risk/benefit of any transfusion needs to favor benefit
• Autologous transfusion
• Use matched blood whenever possible; if not possible, thoroughly check universal blood for agglutination titer
• Observe patient closely during transfusion with serial vital signs
• Consider leukocyte-depleted blood in people with history of recurrent febrile reactions
• Avoid prophylactic antipyretics
• Use genotype-specific RBCs in sickle cell anemia
• Blood bank screening for bacteria and viruses
EPIDEMIOLOGY
• Frequency of immunologic reaction per unit of blood
- Allergic 1:100
- Febrile 1:100
- Delayed hemolytic 1:1600
- Acute hemolytic 1:50,000
- Fatal hemolytic reaction 1:500,000
• Infectious complications per unit of blood
- Hepatitis B 1:81,000
- HTLV-1 1:642,000
- Hepatitis C: 1:1,600,000
- HIV-1 1:2,000,000
RISK FACTORS
• Multiple blood transfusions
• Rh-negative mother
• Multiple pregnancies
Genetics
No known genetic pattern
ETIOLOGY
• Acute hemolytic transfusion reaction
- When ABO-incompatible blood is transfused, donor erythrocytes are destroyed by recipient's pre-formed antibodies causing intravascular hemolysis.
- Most commonly, when group O recipients receive non-group O blood; IgM antibodies to group A and B antigens fix complement and cause rapid hemolysis
- Often due to clerical error, misidentification of blood product or patient
• Febrile nonhemolytic transfusion reaction: Caused by recipient antibodies to leukocytes in unit of red cells, prevented by leukoreduction
• Anaphylactic: Reaction to a transfusion that contains plasma, theory that this is a reaction to IgA in donor blood in IgA-deficient patient has been called into question (2)[C]
• Urticarial: IgE antibodies in recipient react with allergen in donor's plasma
• Delayed reactions can occur in patients sensitized to an antigen by prior transfusions or pregnancy. It may be difficult to detect because antibody titer falls after initial sensitization, reaction 2-10 days after transfusion.
• TRALI: Begins with neutrophil adhesion to pulmonary endothelium, leading to endothelial damage and increased capillary permeability
ASSOCIATED CONDITIONS
• Disseminated intravascular coagulation
• Shock
• Acute renal failure
DIAGNOSIS
SIGNS AND SYMPTOMS
• Acute hemolytic transfusion reaction
- Anxiety
- Flushing
- Tachycardia
- Hypotension
- Chest, back, or flank pain
- Tachypnea
- Dyspnea
- Fever
- Chills
- NOTE: Symptoms masked in anesthetized patient, may see red-tinged urine
• Delayed (extravascular) hemolytic transfusion reaction
- Fever
- Anemia (2-14 days after transfusion)
- Jaundice
• TRALI: Range of symptoms from cough to life-threatening respiratory distress, can appear similar to acute respiratory distress syndrome
TESTS
Lab
Acute hemolytic transfusion reaction
• Positive direct antiglobulin test (Coombs)
• Plasma obtained 2-4 hours after lysis is red or pink, indicating free hemoglobin
• Elevated serum bilirubin (mild)
• Elevated lactate dehydrogenase
• Reduced serum haptoglobin
• Wine-colored urine indicating hemoglobinuria
• Additional lab tests for immune reactions, including blood bank incompatibility evaluation
• Tissue factor released from lysed RBCs can initiate disseminated intravascular coagulation; platelet count and coagulation studies should be monitored
• Monitor blood urea nitrogen, creatinine given risk of renal failure
DIFFERENTIAL DIAGNOSIS
Other causes of acute hemolysis
• Autoimmune diseases
• Hemoglobinopathies
• RBC enzyme defects
• Bacterial contamination of stored blood
TREATMENT
GENERAL MEASURES
• Follow hospital protocol for evaluation of transfusion reactions
• Stop transfusion immediately upon first sign of reaction
• IV normal saline to support blood pressure and adequate urine output, especially in DIC
• Avoid lactated Ringer's solution
• Repeat thorough evaluation of transfusion paperwork to rule out any clerical error (a common cause of an ABO-incompatible transfusion)
• Monitor vital signs.
• Recognize and treat disseminated intravascular coagulation if it occurs.
• Supportive therapy, maintain blood pressure using vasopressors in indicated airway
• For TRALI, patients may require ventilatory support. Use of corticosteroids and diuretics is controversial. (3)[C]
Diet
As tolerated
Activity
Bed rest
MEDICATION (DRUGS)
First Line
• Oxygen and ventilation support, as needed
• Epinephrine for anaphylaxis
• Corticosteroids may be helpful to reduce inflammation
• Normal saline and/or vasopressors to maintain systolic blood pressure
• Treat DIC if present, including supportive therapy and possibly heparin
• Diphenhydramine for urticarial reaction
FOLLOW-UP
PROGNOSIS
• Usual course: Acute
• Usually no harm if transfusion stopped at onset of manifestations
• TRALI: Can appear similar to acute respiratory distress syndrome but has a better prognosis; 10% mortality, generally self-limited with supportive care
COMPLICATIONS
• Uremia, oliguria, anuria
• Right heart failure
• Respiratory failure
• Multiorgan dysfunction syndrome
PATIENT MONITORING
Until hemolytic signs are gone
REFERENCES
1. Bryan S. Hemolytic transfusion reaction: Safeguards for practice. J Perianesth Nurs. 2002;17:399-403.
2. Gilstad CW. Anaphylactic transfusion reactions. Curr Opin Hematol. 2003;10:419-423.
3. Bux J. Transfusion-related acute lung injury (TRALI): A serious adverse event of blood transfusion. Vox Sanguinis. 2005;89(1);1-10.
4. Herbert PC, et al. Is a low transfusion threshold safe in critically ill patients with cardiovascular disease? Crit Care Med. 2001;29:227-234.
MISCELLANEOUS
Post-transfusion Purpura: Delayed thrombocytopenia (7-10 days after platelet transfusion), due to production of antibodies to donor or recipient platelets, more common in women. Treat with IV immunoglobulin or plasmapheresis. Avoid additional platelet transfusions, which may worsen thrombocytopenia
BASICS
DESCRIPTION
The transfusion of blood products can cause numerous serious complications, even death. Adverse reactions to blood products may occur by immune or non-immune mechanisms.
• Immune: Acute, febrile, allergic, transfusion-related acute lung injury (TRALI)
• Non-immune
- Acute: Circulatory overload, bacterial contamination, and other effects, including hyperkalemia, hypocalcemia, acidosis, coagulopathy, hypothermia
- Chronic: Viral infection (cytomegalovirus human T-cell leukemia virus, HTLV, HIV, hepatitis), hemosiderosis
ALERT
Pediatric Considerations
Reaction greater and outlook poorer in the very young
Geriatric Considerations
Higher risk of complications in the elderly
GENERAL PREVENTION
• Follow procedures for sample and blood labeling and patient identification. Two practitioners, and if possible, patient should verify that blood product and patient identity match. (1)[C]
• Obtain detailed history of patient's responses to previous transfusions
• Risk/benefit of any transfusion needs to favor benefit
• Autologous transfusion
• Use matched blood whenever possible; if not possible, thoroughly check universal blood for agglutination titer
• Observe patient closely during transfusion with serial vital signs
• Consider leukocyte-depleted blood in people with history of recurrent febrile reactions
• Avoid prophylactic antipyretics
• Use genotype-specific RBCs in sickle cell anemia
• Blood bank screening for bacteria and viruses
EPIDEMIOLOGY
• Frequency of immunologic reaction per unit of blood
- Allergic 1:100
- Febrile 1:100
- Delayed hemolytic 1:1600
- Acute hemolytic 1:50,000
- Fatal hemolytic reaction 1:500,000
• Infectious complications per unit of blood
- Hepatitis B 1:81,000
- HTLV-1 1:642,000
- Hepatitis C: 1:1,600,000
- HIV-1 1:2,000,000
RISK FACTORS
• Multiple blood transfusions
• Rh-negative mother
• Multiple pregnancies
Genetics
No known genetic pattern
ETIOLOGY
• Acute hemolytic transfusion reaction
- When ABO-incompatible blood is transfused, donor erythrocytes are destroyed by recipient's pre-formed antibodies causing intravascular hemolysis.
- Most commonly, when group O recipients receive non-group O blood; IgM antibodies to group A and B antigens fix complement and cause rapid hemolysis
- Often due to clerical error, misidentification of blood product or patient
• Febrile nonhemolytic transfusion reaction: Caused by recipient antibodies to leukocytes in unit of red cells, prevented by leukoreduction
• Anaphylactic: Reaction to a transfusion that contains plasma, theory that this is a reaction to IgA in donor blood in IgA-deficient patient has been called into question (2)[C]
• Urticarial: IgE antibodies in recipient react with allergen in donor's plasma
• Delayed reactions can occur in patients sensitized to an antigen by prior transfusions or pregnancy. It may be difficult to detect because antibody titer falls after initial sensitization, reaction 2-10 days after transfusion.
• TRALI: Begins with neutrophil adhesion to pulmonary endothelium, leading to endothelial damage and increased capillary permeability
ASSOCIATED CONDITIONS
• Disseminated intravascular coagulation
• Shock
• Acute renal failure
DIAGNOSIS
SIGNS AND SYMPTOMS
• Acute hemolytic transfusion reaction
- Anxiety
- Flushing
- Tachycardia
- Hypotension
- Chest, back, or flank pain
- Tachypnea
- Dyspnea
- Fever
- Chills
- NOTE: Symptoms masked in anesthetized patient, may see red-tinged urine
• Delayed (extravascular) hemolytic transfusion reaction
- Fever
- Anemia (2-14 days after transfusion)
- Jaundice
• TRALI: Range of symptoms from cough to life-threatening respiratory distress, can appear similar to acute respiratory distress syndrome
TESTS
Lab
Acute hemolytic transfusion reaction
• Positive direct antiglobulin test (Coombs)
• Plasma obtained 2-4 hours after lysis is red or pink, indicating free hemoglobin
• Elevated serum bilirubin (mild)
• Elevated lactate dehydrogenase
• Reduced serum haptoglobin
• Wine-colored urine indicating hemoglobinuria
• Additional lab tests for immune reactions, including blood bank incompatibility evaluation
• Tissue factor released from lysed RBCs can initiate disseminated intravascular coagulation; platelet count and coagulation studies should be monitored
• Monitor blood urea nitrogen, creatinine given risk of renal failure
DIFFERENTIAL DIAGNOSIS
Other causes of acute hemolysis
• Autoimmune diseases
• Hemoglobinopathies
• RBC enzyme defects
• Bacterial contamination of stored blood
TREATMENT
GENERAL MEASURES
• Follow hospital protocol for evaluation of transfusion reactions
• Stop transfusion immediately upon first sign of reaction
• IV normal saline to support blood pressure and adequate urine output, especially in DIC
• Avoid lactated Ringer's solution
• Repeat thorough evaluation of transfusion paperwork to rule out any clerical error (a common cause of an ABO-incompatible transfusion)
• Monitor vital signs.
• Recognize and treat disseminated intravascular coagulation if it occurs.
• Supportive therapy, maintain blood pressure using vasopressors in indicated airway
• For TRALI, patients may require ventilatory support. Use of corticosteroids and diuretics is controversial. (3)[C]
Diet
As tolerated
Activity
Bed rest
MEDICATION (DRUGS)
First Line
• Oxygen and ventilation support, as needed
• Epinephrine for anaphylaxis
• Corticosteroids may be helpful to reduce inflammation
• Normal saline and/or vasopressors to maintain systolic blood pressure
• Treat DIC if present, including supportive therapy and possibly heparin
• Diphenhydramine for urticarial reaction
FOLLOW-UP
PROGNOSIS
• Usual course: Acute
• Usually no harm if transfusion stopped at onset of manifestations
• TRALI: Can appear similar to acute respiratory distress syndrome but has a better prognosis; 10% mortality, generally self-limited with supportive care
COMPLICATIONS
• Uremia, oliguria, anuria
• Right heart failure
• Respiratory failure
• Multiorgan dysfunction syndrome
PATIENT MONITORING
Until hemolytic signs are gone
REFERENCES
1. Bryan S. Hemolytic transfusion reaction: Safeguards for practice. J Perianesth Nurs. 2002;17:399-403.
2. Gilstad CW. Anaphylactic transfusion reactions. Curr Opin Hematol. 2003;10:419-423.
3. Bux J. Transfusion-related acute lung injury (TRALI): A serious adverse event of blood transfusion. Vox Sanguinis. 2005;89(1);1-10.
4. Herbert PC, et al. Is a low transfusion threshold safe in critically ill patients with cardiovascular disease? Crit Care Med. 2001;29:227-234.
MISCELLANEOUS
Post-transfusion Purpura: Delayed thrombocytopenia (7-10 days after platelet transfusion), due to production of antibodies to donor or recipient platelets, more common in women. Treat with IV immunoglobulin or plasmapheresis. Avoid additional platelet transfusions, which may worsen thrombocytopenia
TRACHEITIS, BACTERIAL
TRACHEITIS, BACTERIAL - Bruce T. Vanderhoff, MD; Ramon F. Fakhoury, MD
BASICS
DESCRIPTION
Acute, potentially life-threatening infraglottic bacterial infection following a primary viral infection, usually parainfluenzae or influenza viruses
• Direct laryngoscopy reveals subglottic edema compounded by thick, purulent exudate in larynx, trachea, and bronchi, sometimes causing pseudomembranes.
• System(s) Affected: Pulmonary
• Synonym(s): Pseudomembranous croup; Membranous tracheitis
EPIDEMIOLOGY
• Predominant age: Mean age 54 months; range 3 weeks to 168 months. Infections in adolescents and adults have been reported.
• Predominant sex: Male > Female some studies have shown a ratio as high as 5:1; others, 1:1)
ALERT
Pediatric Considerations
Typically affects children ages 3-5 years.
Incidence
• True incidence unknown
• First cases described prior to 1950; resurgence of cases has been noted since 1979
• Fall/winter predominance
RISK FACTORS
• Periods of increased seasonal activity of respiratory viruses
• Case reports following adenoidectomy
Genetics
No known genetic predisposition
ETIOLOGY
• Staphylococcus aureus (most common pediatric cause): Consider methicillin resistance (MRSA)
• Haemophilus influenzae type b
• Streptococcus pyogenes/group A streptococcus
• Moraxella catarrhalis
• Peptostreptococcus
• Streptococcus pneumoniae
• Klebsiella pneumoniae
• Neisseria gonorrhea
ASSOCIATED CONDITIONS
Consider anatomic abnormalities or foreign body as well as recent pharyngeal or laryngeal surgery.
DIAGNOSIS
SIGNS AND SYMPTOMS
• Barking, "brassy" cough
• Inspiratory stridor
• Variable degree of respiratory distress
• Child is usually lying flat
• Fever >38C (100.4F)
• Toxic appearing
• Gradual progression of mild upper airway symptoms over 1 hour to 6 days to an acute, febrile phase of rapid respiratory decompensation
• Voice and cry usually normal
• Absence of drooling and dysphagia help distinguish it from epiglottitis.
• Does not respond to aerosolized epinephrine (unlike patients with croup)
• Subglottic edema
• If intubated for viral croup, premembranous tracheitis "web" can obstruct distal airway beyond endotracheal tube
TESTS
Rapid antigen tests are available for bacteria and viruses in some centers.
Lab
• Elevated WBC count with predominance of polymorphonuclear leukocytes
• Band cells often present
• Blood cultures usually negative
Imaging
• Anterior-posterior and lateral neck x-rays show subglottic and tracheal narrowing with haziness and radio-opaque linear or particulate densities (crusts)
• In patients with risk of acute respiratory obstruction, either do not obtain x-rays or monitor carefully.
• Often see pneumonic infiltrates
Diagnostic Procedures/Surgery
• Endoscopy is diagnostic and demonstrates severe inflammation of subglottic region and trachea with copious mucopurulent secretions and sloughed epithelium that separates from tracheal wall in sheets
• Obtain Gram stain, aerobic and anaerobic cultures of tracheal secretions
Pathological Findings
• Mucosal destruction and/or local immunodeficiency caused by viral infection may predispose to bacterial infection.
• Intense inflammation, sloughing of subglottic epithelium, and profuse mucopurulent secretions, which compromise airway and make airway management difficult
DIFFERENTIAL DIAGNOSIS
• Laryngotracheobronchitis (viral)
• Epiglottitis
• Foreign-body aspiration
• Retropharyngeal abscess
• Pneumonia
• Asthma
• Spasmodic croup
• Diphtheritic laryngitis
TREATMENT
GENERAL MEASURES
• Admission to ICU
• Constitutes true pediatric emergency
• Maintain airway: Often difficult due to copious secretions
• Hydration, humidification, antibiotics
• Endotracheal or nasotracheal intubation usually needed, especially in infants and children 4 years. Much less likely to need intubation if child >8 years. Advantage of intubation is ability to clear trachea and bronchi of secretions and pseudomembranes.
• Vigorous pulmonary toilet to clear airway of secretion
• Does not respond to epinephrine
ALERT
Pregnancy Considerations
Scrupulous hand washing is recommended for prevention.
Diet
Parenteral nutrition or nasogastric tube feeding if intubated; oral nutrition otherwise
Activity
Complete bed rest
MEDICATION (DRUGS)
First Line
• Nafcillin 150 mg/kg/d q.i.d. plus cefotaxime 150 mg/kg/d in 4-6 divided doses; maximum of 2 g q6h
• Vancomycin for MRSA
• Ceftriaxone 75 mg/kg/d b.i.d. plus ampicillin-sulbactam 300 mg/kg/d q.i.d.
• Best single drug choice: Ticarcillin-clavulanate 3.1 g IV q4-6h for adults, 150 mg/kg/d IV q12h for children (maximum 18-24 g/d)
• Does not respond to epinephrine
• Narrow regimen when pathogens and sensitivities available
• Contraindications: Refer to the manufacturer's literature for each drug.
• Precautions: Refer to the manufacturer's literature for each drug.
• Significant possible interactions: Refer to the manufacturer's literature for each drug.
Second Line
For patients with penicillin allergy: Clindamycin 40 mg/kg/d q.i.d. plus chloramphenicol 75 mg/kg/d q.i.d.
SURGERY
• Tracheotomy may be necessary
• Membrane may require surgical removal
FOLLOW-UP
PROGNOSIS
• With vigorous airway management with or without intubation for up to 7 days, complete recovery is expected.
• Cardiopulmonary arrest and death have occurred.
COMPLICATIONS
• Postintubation subglottic stenosis
• Cardiopulmonary arrest
• Pneumonia
• Toxic shock syndrome secondary to enterotoxin-producing staphylococci
PATIENT MONITORING
ICU care with cardiopulmonary monitoring
REFERENCES
1. Ang JY, Ezike E, Asmer BI, Antibacterial resistance. Indian J Pediatr. 2004;71:229-239.
2. Berhman RE, Kliegman RM, Jenson HB, eds. Nelson Textbook of Pediatrics. 16th ed. Philadelphia, PA: WB Saunders; 2000.
3. Bernstein T, Brilli R, Jacobs B. Is bacterial tracheitis changing? A 14-month experience in a pediatric intensive care unit. Clin Infect Dis. 1998;27:458-462.
4. Brook I. Aerobic and anaerobic microbiology of bacterial tracheitis in children. Clin Infect Dis. 1995;20(suppl 2):S222-S223.
5. Burns JA, Brown J, Ogle JW. Group A streptococcal tracheitis associated with toxic shock syndrome. Pediatr Infect Dis J. 1998;17:933-935.
6. Cunningham MJ. The old and new of acute laryngotracheal infections. Clinical Pediatr. 1992;31:56-64.
7. Eid NS, Jones VF. Bacterial tracheitis as a complication of tonsillectomy and adenoidectomy. J Pediatr. 1994;125:401-402.
MISCELLANEOUS
See also: Bronchiolitis; Common cold; Epiglottitis
BASICS
DESCRIPTION
Acute, potentially life-threatening infraglottic bacterial infection following a primary viral infection, usually parainfluenzae or influenza viruses
• Direct laryngoscopy reveals subglottic edema compounded by thick, purulent exudate in larynx, trachea, and bronchi, sometimes causing pseudomembranes.
• System(s) Affected: Pulmonary
• Synonym(s): Pseudomembranous croup; Membranous tracheitis
EPIDEMIOLOGY
• Predominant age: Mean age 54 months; range 3 weeks to 168 months. Infections in adolescents and adults have been reported.
• Predominant sex: Male > Female some studies have shown a ratio as high as 5:1; others, 1:1)
ALERT
Pediatric Considerations
Typically affects children ages 3-5 years.
Incidence
• True incidence unknown
• First cases described prior to 1950; resurgence of cases has been noted since 1979
• Fall/winter predominance
RISK FACTORS
• Periods of increased seasonal activity of respiratory viruses
• Case reports following adenoidectomy
Genetics
No known genetic predisposition
ETIOLOGY
• Staphylococcus aureus (most common pediatric cause): Consider methicillin resistance (MRSA)
• Haemophilus influenzae type b
• Streptococcus pyogenes/group A streptococcus
• Moraxella catarrhalis
• Peptostreptococcus
• Streptococcus pneumoniae
• Klebsiella pneumoniae
• Neisseria gonorrhea
ASSOCIATED CONDITIONS
Consider anatomic abnormalities or foreign body as well as recent pharyngeal or laryngeal surgery.
DIAGNOSIS
SIGNS AND SYMPTOMS
• Barking, "brassy" cough
• Inspiratory stridor
• Variable degree of respiratory distress
• Child is usually lying flat
• Fever >38C (100.4F)
• Toxic appearing
• Gradual progression of mild upper airway symptoms over 1 hour to 6 days to an acute, febrile phase of rapid respiratory decompensation
• Voice and cry usually normal
• Absence of drooling and dysphagia help distinguish it from epiglottitis.
• Does not respond to aerosolized epinephrine (unlike patients with croup)
• Subglottic edema
• If intubated for viral croup, premembranous tracheitis "web" can obstruct distal airway beyond endotracheal tube
TESTS
Rapid antigen tests are available for bacteria and viruses in some centers.
Lab
• Elevated WBC count with predominance of polymorphonuclear leukocytes
• Band cells often present
• Blood cultures usually negative
Imaging
• Anterior-posterior and lateral neck x-rays show subglottic and tracheal narrowing with haziness and radio-opaque linear or particulate densities (crusts)
• In patients with risk of acute respiratory obstruction, either do not obtain x-rays or monitor carefully.
• Often see pneumonic infiltrates
Diagnostic Procedures/Surgery
• Endoscopy is diagnostic and demonstrates severe inflammation of subglottic region and trachea with copious mucopurulent secretions and sloughed epithelium that separates from tracheal wall in sheets
• Obtain Gram stain, aerobic and anaerobic cultures of tracheal secretions
Pathological Findings
• Mucosal destruction and/or local immunodeficiency caused by viral infection may predispose to bacterial infection.
• Intense inflammation, sloughing of subglottic epithelium, and profuse mucopurulent secretions, which compromise airway and make airway management difficult
DIFFERENTIAL DIAGNOSIS
• Laryngotracheobronchitis (viral)
• Epiglottitis
• Foreign-body aspiration
• Retropharyngeal abscess
• Pneumonia
• Asthma
• Spasmodic croup
• Diphtheritic laryngitis
TREATMENT
GENERAL MEASURES
• Admission to ICU
• Constitutes true pediatric emergency
• Maintain airway: Often difficult due to copious secretions
• Hydration, humidification, antibiotics
• Endotracheal or nasotracheal intubation usually needed, especially in infants and children 4 years. Much less likely to need intubation if child >8 years. Advantage of intubation is ability to clear trachea and bronchi of secretions and pseudomembranes.
• Vigorous pulmonary toilet to clear airway of secretion
• Does not respond to epinephrine
ALERT
Pregnancy Considerations
Scrupulous hand washing is recommended for prevention.
Diet
Parenteral nutrition or nasogastric tube feeding if intubated; oral nutrition otherwise
Activity
Complete bed rest
MEDICATION (DRUGS)
First Line
• Nafcillin 150 mg/kg/d q.i.d. plus cefotaxime 150 mg/kg/d in 4-6 divided doses; maximum of 2 g q6h
• Vancomycin for MRSA
• Ceftriaxone 75 mg/kg/d b.i.d. plus ampicillin-sulbactam 300 mg/kg/d q.i.d.
• Best single drug choice: Ticarcillin-clavulanate 3.1 g IV q4-6h for adults, 150 mg/kg/d IV q12h for children (maximum 18-24 g/d)
• Does not respond to epinephrine
• Narrow regimen when pathogens and sensitivities available
• Contraindications: Refer to the manufacturer's literature for each drug.
• Precautions: Refer to the manufacturer's literature for each drug.
• Significant possible interactions: Refer to the manufacturer's literature for each drug.
Second Line
For patients with penicillin allergy: Clindamycin 40 mg/kg/d q.i.d. plus chloramphenicol 75 mg/kg/d q.i.d.
SURGERY
• Tracheotomy may be necessary
• Membrane may require surgical removal
FOLLOW-UP
PROGNOSIS
• With vigorous airway management with or without intubation for up to 7 days, complete recovery is expected.
• Cardiopulmonary arrest and death have occurred.
COMPLICATIONS
• Postintubation subglottic stenosis
• Cardiopulmonary arrest
• Pneumonia
• Toxic shock syndrome secondary to enterotoxin-producing staphylococci
PATIENT MONITORING
ICU care with cardiopulmonary monitoring
REFERENCES
1. Ang JY, Ezike E, Asmer BI, Antibacterial resistance. Indian J Pediatr. 2004;71:229-239.
2. Berhman RE, Kliegman RM, Jenson HB, eds. Nelson Textbook of Pediatrics. 16th ed. Philadelphia, PA: WB Saunders; 2000.
3. Bernstein T, Brilli R, Jacobs B. Is bacterial tracheitis changing? A 14-month experience in a pediatric intensive care unit. Clin Infect Dis. 1998;27:458-462.
4. Brook I. Aerobic and anaerobic microbiology of bacterial tracheitis in children. Clin Infect Dis. 1995;20(suppl 2):S222-S223.
5. Burns JA, Brown J, Ogle JW. Group A streptococcal tracheitis associated with toxic shock syndrome. Pediatr Infect Dis J. 1998;17:933-935.
6. Cunningham MJ. The old and new of acute laryngotracheal infections. Clinical Pediatr. 1992;31:56-64.
7. Eid NS, Jones VF. Bacterial tracheitis as a complication of tonsillectomy and adenoidectomy. J Pediatr. 1994;125:401-402.
MISCELLANEOUS
See also: Bronchiolitis; Common cold; Epiglottitis
TOXOPLASMOSIS
TOXOPLASMOSIS - William G. Gardner, MD, MACP
BASICS
DESCRIPTION
Infection with the protozoan parasite Toxoplasma gondii resulting in one of the following conditions
• Acute self-limited infection in immunocompetent persons
• Acute often symptomatic infection in immunocompromised persons
• Reactivation of latent infection in immunocompromised persons
• Congenital infection due to acute infection or reactivation of latent infection in the mother during pregnancy
ALERT
Pediatric Considerations
• Transmission to fetus in early pregnancy is less common but results in more severe disease
- Risk of perinatal death 5% if infected during 1st trimester
• The majority of infected children who are asymptomatic at birth eventually develop manifestations unless treated
• Early recognition and treatment of disease in the infant improves prognosis
Pregnancy Considerations
• Immunocompromised and HIV-infected women should undergo serologic testing in pregnancy
• Seronegative pregnant women should take precautions to avoid contact with cats, not eat raw or undercooked meat, and wash all fruits and vegetables carefully
GENERAL PREVENTION
Prevention important in seronegative pregnant women and immunodeficient patients
• Avoid eating raw or undercooked meat
• Wear gloves while handling, and wash hands after handling, raw meat
• Avoid contact with cat feces; wear gloves and wash hands immediately after changing cat litter
EPIDEMIOLOGY
• Predominant age: All ages
• Predominant sex: Male = Female
Incidence
• Incidence of congenital toxoplasmosis in the United States is 1/1,000-8,000 live births
• Affects ~4,000 newborns in the United States each year
Prevalence
• Overall 22.5% in the United States
• 15% among women of childbearing age
RISK FACTORS
• Immunocompromised patients, especially AIDS, lymphoma, high-dose corticosteroids
• Risk of transplacental transmission greatest during 3rd trimester, but disease more severe if acquired during 1st trimester
Genetics
Human leukocyte antigen DQ3 is a genetic marker of susceptibility to development of toxoplasma encephalitis in AIDS patients
ETIOLOGY
• Etiologic agent for each of the clinical syndromes is T. gondii.
• Transmission to humans
- Ingestion of raw or undercooked meat, food, or water containing tissue cysts or oocytes
- Transplacental to fetus from infected mother
- Blood product transfusion
- Solid organ transplantation
• Clinical syndromes
- Acute infection in immunocompetent host
- Acute or reactivation infection in immunocompromised host
- Congenital toxoplasmosis
- Ocular toxoplasmosis
• Not transmitted by breast feeding
DIAGNOSIS
SIGNS AND SYMPTOMS
• Congenital toxoplasmosis
- Clinical presentation varies widely
- No signs or symptoms of infection (67%)
- Classic triad uncommon: Chorioretinitis, hydrocephalus, cerebral calcifications
- Cerebrospinal fluid (CSF) pleocytosis and elevated protein (20%)
- Anemia, thrombocytopenia, jaundice at birth
- Microcephaly
- Mental retardation, seizures, visual defects, spasticity, other severe neurologic sequelae
• Ocular toxoplasmosis
- Chorioretinitis: Focal necrotizing retinitis
- Yellowish-white elevated cotton patch
- Congenital disease usually bilateral
- Acquired disease usually unilateral
- Symptoms include blurred vision, scotoma, pain, photophobia
• Acute toxoplasmosis: Immunocompetent host
- Approximately 80-90% are asymptomatic
- Cervical lymphadenopathy with discrete, usually nontender nodes 3 cm in diameter
- Fever, malaise, night sweats, myalgias
- Sore throat, maculopapular rash
- Visual disturbance due to chorioretinitis
- Hepatosplenomegaly, mesenteric, and retroperitoneal adenopathy
- Atypical lymphocytosis
- Most infected pregnant women are asymptomatic
• Acute toxoplasmosis: Immunocompromised host
- CNS disease (50%)
Encephalitis, meningoencephalitis, or mass lesions, hemiparesis, seizures, mental status changes, CSF with elevated protein, normal glucose, and mononuclear pleocytosis
- Chorioretinitis
- Myocarditis
- Pneumonia with high mortality rate
TESTS
Lab
• Lab diagnosis is made by polymerase chain reaction (PCR), histology, isolation, and indirect (serologic) methods
• PCR on blood, body fluids, and tissue
- Sensitive and specific
- Indicates current infection
• Direct demonstration of parasite in tissue or body fluid by histology or culture
• Serologic methods
- Does not distinguish time of infection
- IgG antibody is useful to indicate prior infection in immunocompromised persons and pregnant women; indicates risk for reactivation disease. If negative, indicates risk for acquiring; maternal antibodies persist in infants up to 1 year
- IgG avidity test: High avidity antibodies exclude recent infection
- IgM antibody may persist >1 year, so does not always indicate recent infection
- Absence of IgM antibody excludes infection
• Amniocentesis at 20-24 weeks in suspected congenital disease with PCR on amniotic fluid
• Amniotic fluid PCR before week 18 unreliable; isolation of toxoplasma from the placenta is diagnostic of a congenital infection.
• Newborn suspected of having congenital disease should have PCR testing on blood, CSF, and urine
• Several serologic tests used in diagnosis, some measuring IgM and other IgG antibodies
- The Sabin-Feldman dye test is a sensitive and specific neutralization test that measures the IgG antibodies and is a standard reference test for toxoplasmosis.
- Indirect fluorescent antibody test measures same antibodies as dye test. Titers parallel dye-test titers.
- IgM fluorescent antibody test detects IgM antibodies within 1st week of infection
• Double-sandwich IgM enzyme linked immunosorpent assay is more sensitive and specific than other IgM tests
- Negative results for IgM antibodies during the first 2 trimesters excludes a recently acquired infection.
Imaging
• Cerebral toxoplasmosis
- CT scan of head
- MRI scan of head
• Ultrasound of fetus at 20-24 weeks
Diagnostic Procedures/Surgery
• Lymph-node biopsy showing characteristic pathologic triad, as described subsequently
• Brain biopsy in CNS disease and demonstration of organisms by peroxidase-antiperoxidase technique
• Empiric therapy for CNS mass lesions in toxoplasma antibody-positive HIV patients with response on 2-week follow-up imaging study is presumptive evidence for a diagnosis.
Pathological Findings
Lymph-node histology shows triad of
• Reactive follicular hyperplasia
• Irregular clusters of epithelioid histiocytes on and blurring margins of germinal centers
• Distention of sinuses with monocytoid cells
DIFFERENTIAL DIAGNOSIS
• Congenital toxoplasmosis
- Other members of TORCH syndrome (rubella, cytomegalovirus, herpes simplex)
- Syphilis
- Listeria
- Other infectious encephalopathies
- Erythroblastosis fetalis
- Sepsis
• Ocular toxoplasmosis
- Tuberculosis
- Syphilis
- Leprosy
- Ocular histoplasmosis
• Acute toxoplasmosis (normal and immunocompromised)
- Lymphoma
- Infectious mononucleosis
- Cytomegalovirus
- Cat scratch disease
- Sarcoidosis
- Tuberculosis (TB)
- Tularemia
- Metastatic carcinoma
- Leukemia
• Toxoplasma encephalitis
- TB
- Fungal diseases
- Vasculitis
- Progressive multifocal leukoencephalopathy
- Brain abscess
- Tumor
- Herpes encephalitis
- CNS lymphoma
- Nocardia species
TREATMENT
STABILIZATION
• Outpatient for acquired disease in immunocompetent host and ocular toxoplasmosis
• Inpatient initially for CNS toxoplasmosis and acute disease in immunocompromised host
GENERAL MEASURES
Immunocompetent children and adults with toxoplasma lymphadenopathy usually require no treatment unless symptoms severe or prolonged
• If fetal infection add pyrimethamine, sulfadiazine, and leucovorin
• Infants with congenital toxoplasmosis should be treated for one year
Diet
No special diet
Activity
Level of activity dependent on organ systems involved and severity of disease
MEDICATION (DRUGS)
First Line
• Acute asymptomatic acquired infection in immunocompetent host requires no treatment
• Acute toxoplasmosis in pregnant woman
- Spiromycin 1 g t.i.d.
Without food
Continue until term
If documented fetal infection, after 18 weeks add pyrimethamine, sulfadiazine, and leucovorin
• Congenital toxoplasmosis
- Sulfadiazine 100 mg/kg/d plus
- Pyrimethamine 2 mg/kg/d for 2 days, then 1 mg/kg/d for 2-6 months, then same dose every Mon, Wed, and Friday plus
- Leucovorin (folinic acid) 10 mg 3 times a week while on pyrimethamine
- Treat for 1 year
• Ocular toxoplasmosis in adults
- Sulfadiazine 1-1.5 g/d plus
- Pyrimethamine loading dose 200 mg 1st day, then 50-75 mg/d plus
- Leucovorin 5-20 mg 3 times a week
- Treat 1-2 weeks after resolution of symptoms
• Toxoplasma encephalitis in AIDS patients
- Sulfadiazine 1-1.5 g q6h plus
- Pyrimethamine 200 mg 1st day then 50-75 mg/d plus
- Leucovorin10-20 mg/d
- Cilndamycin 600-1200 mg IV q6h plus pyrimethamine and leucovorin for those who cannot tolerate sulfonamide
- Treat for at least 6 weeks
- After acute treatment continue suppression therapy indefinitely
Sulfadiazine 500 mg q6h plus
Pyrimethamine 25-50 mg/d plus
Leucovorin 10 mg/d
• Contraindications: Known hypersensitivity to pyrimethamine or sulfadiazine (NOTE: Many HIV-positive patients have a sulfa sensitivity)
• Precautions
- Monitor for bone marrow toxicity
- Use with caution in patients with renal or hepatic dysfunction
- Adequate hydration is essential, because sulfadiazine is poorly soluble and may crystallize in the urine.
- Watch for diarrhea especially if on clindamycin
• Significant possible interactions: Sulfonamides may increase
- Phenytoin (dilantin) levels
- Anticoagulant effect of warfarin (coumadin)
- Hypoglycemic effect of oral hypoglycemic agents
Second Line
• Clindamycin: 900-1,200 mg t.i.d. IV used for ocular and CNS toxoplasmosis alone and in combination with pyrimethamine. As effective as the sulfa + pyrimethamine, but fewer adverse effects.
• Corticosteroids (prednisone 1-2 mg/kg/d) added for macular chorioretinitis or CNS infection.
• Alternative atovaquone (mepron), azithromycin (zithromax), clarithromycin (biaxin), or dapsone plus pyrimethamine and leucovorin
• Trimethoprim/sulfamethoxazole appears to be equivalent to pyrimethamine/sulfadiazine in AIDS patients wih CNS disease
SURGERY
• Lymphnode biosy for presistantly enlarged lymphnodes to secure diagnosis
• Biopsy of brain lesion for diagnosis
FOLLOW-UP
DISPOSITION
Admission Criteria
• Acutely ill patients
• Neurologic abnormalities
Discharge Criteria
• Symptoms improving
• Taking oral medications
Issues for Referral
• Ophthalmologist if ocular disease
• Neurology consult for CNS disease
• Infectious diseases consult for systemic disease or HIV
PROGNOSIS
• Immunodeficient patients often relapse if treatment is stopped.
• Treatment may prevent the development of untoward sequelae in both symptomatic and asymptomatic infants with congenital toxoplasmosis.
COMPLICATIONS
• CNS toxoplasmosis: Seizure disorder or focal neurologic deficits
• Ocular toxoplasmosis: Partial or complete blindness
• Congenital toxoplasmosis: Multiple complications may occur, including
- Mental retardation
- Seizures
- Deafness and blindness
PATIENT MONITORING
• Follow-up visits every 2 weeks until stable, then every 1-3 months during therapy
• CBC weekly for 1st month, then every 2-4 weeks
• Renal and liver function tests monthly
REFERENCES
1. Benson CA, et al. Treating opportunistic infections among HIV infected adults and adolescents. Clin Infect Dis. 2005;40:S138-S140.
2. Mofenson LM, et al. Treating opportunistic infections among HIV-exposed and infected children. Clin Infect Dis. 2005;40:S6-S8.
3. Katkama C, et al. Pyrimethamine-clindamycin vs pyrimethamine-sulfadiazine in acute and long term therapy for toxoplasmic encephalitis in patients with AIDS. Clin Infect Dis. 1996;22:268.
4. Montoya JG, Liesenfeld O. Toxoplasmosis. Lancet. 2004;363:1965-1976.
BASICS
DESCRIPTION
Infection with the protozoan parasite Toxoplasma gondii resulting in one of the following conditions
• Acute self-limited infection in immunocompetent persons
• Acute often symptomatic infection in immunocompromised persons
• Reactivation of latent infection in immunocompromised persons
• Congenital infection due to acute infection or reactivation of latent infection in the mother during pregnancy
ALERT
Pediatric Considerations
• Transmission to fetus in early pregnancy is less common but results in more severe disease
- Risk of perinatal death 5% if infected during 1st trimester
• The majority of infected children who are asymptomatic at birth eventually develop manifestations unless treated
• Early recognition and treatment of disease in the infant improves prognosis
Pregnancy Considerations
• Immunocompromised and HIV-infected women should undergo serologic testing in pregnancy
• Seronegative pregnant women should take precautions to avoid contact with cats, not eat raw or undercooked meat, and wash all fruits and vegetables carefully
GENERAL PREVENTION
Prevention important in seronegative pregnant women and immunodeficient patients
• Avoid eating raw or undercooked meat
• Wear gloves while handling, and wash hands after handling, raw meat
• Avoid contact with cat feces; wear gloves and wash hands immediately after changing cat litter
EPIDEMIOLOGY
• Predominant age: All ages
• Predominant sex: Male = Female
Incidence
• Incidence of congenital toxoplasmosis in the United States is 1/1,000-8,000 live births
• Affects ~4,000 newborns in the United States each year
Prevalence
• Overall 22.5% in the United States
• 15% among women of childbearing age
RISK FACTORS
• Immunocompromised patients, especially AIDS, lymphoma, high-dose corticosteroids
• Risk of transplacental transmission greatest during 3rd trimester, but disease more severe if acquired during 1st trimester
Genetics
Human leukocyte antigen DQ3 is a genetic marker of susceptibility to development of toxoplasma encephalitis in AIDS patients
ETIOLOGY
• Etiologic agent for each of the clinical syndromes is T. gondii.
• Transmission to humans
- Ingestion of raw or undercooked meat, food, or water containing tissue cysts or oocytes
- Transplacental to fetus from infected mother
- Blood product transfusion
- Solid organ transplantation
• Clinical syndromes
- Acute infection in immunocompetent host
- Acute or reactivation infection in immunocompromised host
- Congenital toxoplasmosis
- Ocular toxoplasmosis
• Not transmitted by breast feeding
DIAGNOSIS
SIGNS AND SYMPTOMS
• Congenital toxoplasmosis
- Clinical presentation varies widely
- No signs or symptoms of infection (67%)
- Classic triad uncommon: Chorioretinitis, hydrocephalus, cerebral calcifications
- Cerebrospinal fluid (CSF) pleocytosis and elevated protein (20%)
- Anemia, thrombocytopenia, jaundice at birth
- Microcephaly
- Mental retardation, seizures, visual defects, spasticity, other severe neurologic sequelae
• Ocular toxoplasmosis
- Chorioretinitis: Focal necrotizing retinitis
- Yellowish-white elevated cotton patch
- Congenital disease usually bilateral
- Acquired disease usually unilateral
- Symptoms include blurred vision, scotoma, pain, photophobia
• Acute toxoplasmosis: Immunocompetent host
- Approximately 80-90% are asymptomatic
- Cervical lymphadenopathy with discrete, usually nontender nodes 3 cm in diameter
- Fever, malaise, night sweats, myalgias
- Sore throat, maculopapular rash
- Visual disturbance due to chorioretinitis
- Hepatosplenomegaly, mesenteric, and retroperitoneal adenopathy
- Atypical lymphocytosis
- Most infected pregnant women are asymptomatic
• Acute toxoplasmosis: Immunocompromised host
- CNS disease (50%)
Encephalitis, meningoencephalitis, or mass lesions, hemiparesis, seizures, mental status changes, CSF with elevated protein, normal glucose, and mononuclear pleocytosis
- Chorioretinitis
- Myocarditis
- Pneumonia with high mortality rate
TESTS
Lab
• Lab diagnosis is made by polymerase chain reaction (PCR), histology, isolation, and indirect (serologic) methods
• PCR on blood, body fluids, and tissue
- Sensitive and specific
- Indicates current infection
• Direct demonstration of parasite in tissue or body fluid by histology or culture
• Serologic methods
- Does not distinguish time of infection
- IgG antibody is useful to indicate prior infection in immunocompromised persons and pregnant women; indicates risk for reactivation disease. If negative, indicates risk for acquiring; maternal antibodies persist in infants up to 1 year
- IgG avidity test: High avidity antibodies exclude recent infection
- IgM antibody may persist >1 year, so does not always indicate recent infection
- Absence of IgM antibody excludes infection
• Amniocentesis at 20-24 weeks in suspected congenital disease with PCR on amniotic fluid
• Amniotic fluid PCR before week 18 unreliable; isolation of toxoplasma from the placenta is diagnostic of a congenital infection.
• Newborn suspected of having congenital disease should have PCR testing on blood, CSF, and urine
• Several serologic tests used in diagnosis, some measuring IgM and other IgG antibodies
- The Sabin-Feldman dye test is a sensitive and specific neutralization test that measures the IgG antibodies and is a standard reference test for toxoplasmosis.
- Indirect fluorescent antibody test measures same antibodies as dye test. Titers parallel dye-test titers.
- IgM fluorescent antibody test detects IgM antibodies within 1st week of infection
• Double-sandwich IgM enzyme linked immunosorpent assay is more sensitive and specific than other IgM tests
- Negative results for IgM antibodies during the first 2 trimesters excludes a recently acquired infection.
Imaging
• Cerebral toxoplasmosis
- CT scan of head
- MRI scan of head
• Ultrasound of fetus at 20-24 weeks
Diagnostic Procedures/Surgery
• Lymph-node biopsy showing characteristic pathologic triad, as described subsequently
• Brain biopsy in CNS disease and demonstration of organisms by peroxidase-antiperoxidase technique
• Empiric therapy for CNS mass lesions in toxoplasma antibody-positive HIV patients with response on 2-week follow-up imaging study is presumptive evidence for a diagnosis.
Pathological Findings
Lymph-node histology shows triad of
• Reactive follicular hyperplasia
• Irregular clusters of epithelioid histiocytes on and blurring margins of germinal centers
• Distention of sinuses with monocytoid cells
DIFFERENTIAL DIAGNOSIS
• Congenital toxoplasmosis
- Other members of TORCH syndrome (rubella, cytomegalovirus, herpes simplex)
- Syphilis
- Listeria
- Other infectious encephalopathies
- Erythroblastosis fetalis
- Sepsis
• Ocular toxoplasmosis
- Tuberculosis
- Syphilis
- Leprosy
- Ocular histoplasmosis
• Acute toxoplasmosis (normal and immunocompromised)
- Lymphoma
- Infectious mononucleosis
- Cytomegalovirus
- Cat scratch disease
- Sarcoidosis
- Tuberculosis (TB)
- Tularemia
- Metastatic carcinoma
- Leukemia
• Toxoplasma encephalitis
- TB
- Fungal diseases
- Vasculitis
- Progressive multifocal leukoencephalopathy
- Brain abscess
- Tumor
- Herpes encephalitis
- CNS lymphoma
- Nocardia species
TREATMENT
STABILIZATION
• Outpatient for acquired disease in immunocompetent host and ocular toxoplasmosis
• Inpatient initially for CNS toxoplasmosis and acute disease in immunocompromised host
GENERAL MEASURES
Immunocompetent children and adults with toxoplasma lymphadenopathy usually require no treatment unless symptoms severe or prolonged
• If fetal infection add pyrimethamine, sulfadiazine, and leucovorin
• Infants with congenital toxoplasmosis should be treated for one year
Diet
No special diet
Activity
Level of activity dependent on organ systems involved and severity of disease
MEDICATION (DRUGS)
First Line
• Acute asymptomatic acquired infection in immunocompetent host requires no treatment
• Acute toxoplasmosis in pregnant woman
- Spiromycin 1 g t.i.d.
Without food
Continue until term
If documented fetal infection, after 18 weeks add pyrimethamine, sulfadiazine, and leucovorin
• Congenital toxoplasmosis
- Sulfadiazine 100 mg/kg/d plus
- Pyrimethamine 2 mg/kg/d for 2 days, then 1 mg/kg/d for 2-6 months, then same dose every Mon, Wed, and Friday plus
- Leucovorin (folinic acid) 10 mg 3 times a week while on pyrimethamine
- Treat for 1 year
• Ocular toxoplasmosis in adults
- Sulfadiazine 1-1.5 g/d plus
- Pyrimethamine loading dose 200 mg 1st day, then 50-75 mg/d plus
- Leucovorin 5-20 mg 3 times a week
- Treat 1-2 weeks after resolution of symptoms
• Toxoplasma encephalitis in AIDS patients
- Sulfadiazine 1-1.5 g q6h plus
- Pyrimethamine 200 mg 1st day then 50-75 mg/d plus
- Leucovorin10-20 mg/d
- Cilndamycin 600-1200 mg IV q6h plus pyrimethamine and leucovorin for those who cannot tolerate sulfonamide
- Treat for at least 6 weeks
- After acute treatment continue suppression therapy indefinitely
Sulfadiazine 500 mg q6h plus
Pyrimethamine 25-50 mg/d plus
Leucovorin 10 mg/d
• Contraindications: Known hypersensitivity to pyrimethamine or sulfadiazine (NOTE: Many HIV-positive patients have a sulfa sensitivity)
• Precautions
- Monitor for bone marrow toxicity
- Use with caution in patients with renal or hepatic dysfunction
- Adequate hydration is essential, because sulfadiazine is poorly soluble and may crystallize in the urine.
- Watch for diarrhea especially if on clindamycin
• Significant possible interactions: Sulfonamides may increase
- Phenytoin (dilantin) levels
- Anticoagulant effect of warfarin (coumadin)
- Hypoglycemic effect of oral hypoglycemic agents
Second Line
• Clindamycin: 900-1,200 mg t.i.d. IV used for ocular and CNS toxoplasmosis alone and in combination with pyrimethamine. As effective as the sulfa + pyrimethamine, but fewer adverse effects.
• Corticosteroids (prednisone 1-2 mg/kg/d) added for macular chorioretinitis or CNS infection.
• Alternative atovaquone (mepron), azithromycin (zithromax), clarithromycin (biaxin), or dapsone plus pyrimethamine and leucovorin
• Trimethoprim/sulfamethoxazole appears to be equivalent to pyrimethamine/sulfadiazine in AIDS patients wih CNS disease
SURGERY
• Lymphnode biosy for presistantly enlarged lymphnodes to secure diagnosis
• Biopsy of brain lesion for diagnosis
FOLLOW-UP
DISPOSITION
Admission Criteria
• Acutely ill patients
• Neurologic abnormalities
Discharge Criteria
• Symptoms improving
• Taking oral medications
Issues for Referral
• Ophthalmologist if ocular disease
• Neurology consult for CNS disease
• Infectious diseases consult for systemic disease or HIV
PROGNOSIS
• Immunodeficient patients often relapse if treatment is stopped.
• Treatment may prevent the development of untoward sequelae in both symptomatic and asymptomatic infants with congenital toxoplasmosis.
COMPLICATIONS
• CNS toxoplasmosis: Seizure disorder or focal neurologic deficits
• Ocular toxoplasmosis: Partial or complete blindness
• Congenital toxoplasmosis: Multiple complications may occur, including
- Mental retardation
- Seizures
- Deafness and blindness
PATIENT MONITORING
• Follow-up visits every 2 weeks until stable, then every 1-3 months during therapy
• CBC weekly for 1st month, then every 2-4 weeks
• Renal and liver function tests monthly
REFERENCES
1. Benson CA, et al. Treating opportunistic infections among HIV infected adults and adolescents. Clin Infect Dis. 2005;40:S138-S140.
2. Mofenson LM, et al. Treating opportunistic infections among HIV-exposed and infected children. Clin Infect Dis. 2005;40:S6-S8.
3. Katkama C, et al. Pyrimethamine-clindamycin vs pyrimethamine-sulfadiazine in acute and long term therapy for toxoplasmic encephalitis in patients with AIDS. Clin Infect Dis. 1996;22:268.
4. Montoya JG, Liesenfeld O. Toxoplasmosis. Lancet. 2004;363:1965-1976.
TOXIC SHOCK SYNDROME (TSS)
TOXIC SHOCK SYNDROME (TSS) - Anthony W. Chow, MD
BASICS
DESCRIPTION
Acute multisystem illness associated with Staphylococcus aureus infections and characterized by sudden onset of high fever, peculiar skin rash with desquamation, and shock
• Menstrual: Associated with menstruation and tampon use
• Nonmenstrual: Associated with postoperative wounds and barrier contraception; more common than menstrual form
• Can occur in children, men, and women
• System(s) Affected: All organ systems can be affected, particularly: Cardiovascular/Pulmonary; Renal/Hepatic; Neurologic/Muscular; Endocrine/Metabolic; Skin/Exocrine
• Synonym(s): Staphylococcal scarlet fever
GENERAL PREVENTION
• Avoidance of continuous tampon use during menstruation
• Avoidance of super-absorbency tampons
• Frequent tampon changes during day
• Use of sanitary napkins at night
• Early medical attention to infected wounds
EPIDEMIOLOGY
• Predominant age: 30-60 years, but can occur in all ages
• Predominant sex: Female > Male (3:2)
Prevalence
Approximately 0.22-1.23 cases per 100,000 in the United States (1)
RISK FACTORS
• High
- Absence of antibody to TSS toxin-1 (TSST-1)
- Infection with S. aureus, which produces TSST-1
- Continuous use of super-absorbency tampons during menstruation
- Nasal surgery with packing
• Moderate
- Use of regular-absorbency tampons during menstruation
- Use of contraceptive sponge
• Low
- Alternating use of tampons and pads during menstruation
- Intrauterine contraceptive device
- Surgical-wound infections
- Early postpartum state
Genetics
No specific mode of inheritance is recognized.
ETIOLOGY
• S. aureus exotoxins, especially
- TSST-1
- Staphylococcal enterotoxins A, B, and C
- Other staphylococcal superantigens including enterotoxins D, E, and H
• Pediatric population: May occur as complication of chickenpox
• Geriatric population: Cellulitis or surgical-wound infections
• Pregnancy: Postpartum infections, especially post-cesarean section wound infection, or episiotomy infections
ASSOCIATED CONDITIONS
Staphylococcal infections
DIAGNOSIS
SIGNS AND SYMPTOMS
• Almost always present (>80%)
- Temperature >38.9C (>102F)
- Erythroderma
- Diffuse macular rash
- Skin desquamation a few days after rash appears
- Shock, orthostatic hypotension, or syncope
- Nausea or vomiting
• Commonly present (20-80%)
- Headache
- Confusion or agitation
- Acute respiratory distress syndrome
- Meningismus
- Pharyngeal erythema
- Vaginitis or vaginal discharge
- Conjunctivitis
- Periorbital edema
- Strawberry tongue
- Non-pitting edema
- Myalgia
- Oliguria
- Arthralgia
- Diarrhea
• Rarely present (20%)
- Arthritis
- Lymphadenopathy
- Hepatosplenomegaly
- Cardiomyopathy
- Pericarditis
- Photophobia
- Seizure
TESTS
Lab
• Microbiologic
- Isolation of S. aureus strains that produce TSST-1 or other toxins in a patient who does not have acute phase serum antibodies to these superantigens. (2)[B]
- Positive culture for S. aureus from vagina or surgical wound (>90%)
- Nasal or perineal carriage of S. aureus
- Positive blood culture for S. aureus (uncommon)
• Hematologic (50-90%)
- Granulocytosis with increased band forms
- Lymphopenia
- Normocytic, normochromic anemia
- Thrombocytopenia
- Coagulopathy
• Biochemical (50-90%)
- Hypoalbuminemia
- Abnormal electrolytes
- Hypocalcemia
- Hypomagnesemia
- Hypophosphatemia
- Increased serumglutamic-oxalcacetic transaminase
- Increased serumglutamic pyruric transaminase
- Increased creatine phosphokinase
- Increased blood urea nitrogen
- Increased serum creatinine
- Increased calcitonin
- Increased serum bilirubin
- Abnormal urine sediment
Imaging
No unusual or characteristic findings
Diagnostic Procedures/Surgery
No specific diagnostic test is currently available.
Pathological Findings
• Subepidermic cleavage plane in skin
• Minimal inflammatory reaction in tissues
• Lymphocyte depletion in lymph nodes
• Cervico-vaginal ulcerations
DIFFERENTIAL DIAGNOSIS
• Streptococcal scarlet fever
• Streptococcal TSS
- More often associated with severe pain and tenderness at a site of local trauma and infection, and more frequently accompanied by bacteremia
• Drug reactions
• Rocky Mountain spotted fever
• Leptospirosis
• Kawasaki disease
• Staphylococcal scalded-skin syndrome
• Meningococcal or possibly Gram-negative sepsis
• Measles, rubeola
TREATMENT
STABILIZATION
Inpatient, admission to intensive care for monitoring
GENERAL MEASURES
• Removal of tampon or other vaginal foreign bodies
• Removal of nasal packings
• Local wound care
• Fluid resuscitation
• Management of renal or cardiac insufficiency
• Mechanical ventilation if necessary
Diet
As tolerated
Activity
Bed rest throughout acute illness
MEDICATION (DRUGS)
First Line
• Treatment of shock or hypotension
- Fluid replacement
- Dopamine
- Steroids or naloxone have not been proven to be of value
• Eradication of S. aureus and inhibition of toxin production
• Oxacillin or nafcillin 100 mg/kg/d q4h (bactericidal against susceptible S. aureus, but may release more toxins by bacterial lysis) (3)[B]
• Clindamycin 25 mg/kg/d q8h (more efficacious than betalactams in suppressing in vitro production of TSST-1) (3)[B]
• Combination of clindamycin 25 mg/kg/d q8h plus oxacillin or nafcillin 100 mg/kg/d q4h (recommended for patients with deep-seated infections or bacteremia) (3)[B]
• Contraindications: Penicillin allergy
• Precautions
- Rash, diarrhea, seizures
- Reduce oxacillin dosage in patients with severe renal failure. It is not necessary to reduce the nafcillin dose for renal dysfunction.
• Significant possible interactions: See the manufacturer's profile of each drug.
Second Line
• Vancomycin: 30 mg/kg/d q6h for patients infected with methicillin-resistant S. aureus (MRSA)
• Linezolid: 10 mg/kg or 600 mg q12h for patients infected with MRSA
• Toxin neutralization
- Benefit in humans unproven, but animal and in vitro studies support this approach (4)[B]
- Immune globulin IV: 0.4 g/kg over 6 hours (5)[B]
SURGERY
• Surgical drainage of loculated infections
• Exploration and debridement of surgical wounds, which may not appear purulent or infected due to a decreased local inflammatory response in a patient with nonmenstrual TSS
FOLLOW-UP
PROGNOSIS
• Mortality: 3-9%
• Recurrence: 10-15%
COMPLICATIONS
• Common (>20%)
- Acute renal failure
- Adult respiratory distress syndrome
- Menorrhagia
- Alopecia
- Nail loss
• Rare (20%)
- Disseminated intravascular coagulation
- Ataxia, toxic encephalopathy
- Memory impairment
- Cardiomyopathy
- Protracted malaise
PATIENT MONITORING
• Admit to intensive care if in shock
• Daily vital signs until patient is afebrile and normotensive
REFERENCES
1. Hajjeh RA, et al. Toxic shock syndrome in the United States: Surveillance update, 1979-1996. Emerg Infect Dis. 1999;5:807-810.
2. Whiting JL, Rosten PM, Chow AW. Determination by Western blot (immunoblot) of seroconversions to toxic shock syndrome toxin 1 and enterotoxin A, B, or C during infection with TSS- and non-TSS- associated Staphylococcus aureus. Infect Immun. 1989;57:231-234.
3. Parsonnet J, Modern PA, Giacobbe KD. Effect of subinhibitory concentrations of antibiotics on production of TSST-1 [abstract 29], Program and Abstracts of the 32nd Meeting of the IDSA, Orlando. 1994:6A.
4. Barry W, et al. Intravenous immunoglobulin therapy for Toxic Shock Syndrome. JAMA. 1992;267:3315-3316.
5. Keller MA, Stiehm ER, Passive immunity in prevention and treatment of infectious diseases. Clin Microbiol Rev. 2000;13:602-614.
6. Darenberg J, et al. Intravenous immunoglobulin G therapy in streptococcal toxic shock syndrome: A European randomized double-blind, placebo-controlled trial. Clin Infect Dis. 2003;37:333-340.
BASICS
DESCRIPTION
Acute multisystem illness associated with Staphylococcus aureus infections and characterized by sudden onset of high fever, peculiar skin rash with desquamation, and shock
• Menstrual: Associated with menstruation and tampon use
• Nonmenstrual: Associated with postoperative wounds and barrier contraception; more common than menstrual form
• Can occur in children, men, and women
• System(s) Affected: All organ systems can be affected, particularly: Cardiovascular/Pulmonary; Renal/Hepatic; Neurologic/Muscular; Endocrine/Metabolic; Skin/Exocrine
• Synonym(s): Staphylococcal scarlet fever
GENERAL PREVENTION
• Avoidance of continuous tampon use during menstruation
• Avoidance of super-absorbency tampons
• Frequent tampon changes during day
• Use of sanitary napkins at night
• Early medical attention to infected wounds
EPIDEMIOLOGY
• Predominant age: 30-60 years, but can occur in all ages
• Predominant sex: Female > Male (3:2)
Prevalence
Approximately 0.22-1.23 cases per 100,000 in the United States (1)
RISK FACTORS
• High
- Absence of antibody to TSS toxin-1 (TSST-1)
- Infection with S. aureus, which produces TSST-1
- Continuous use of super-absorbency tampons during menstruation
- Nasal surgery with packing
• Moderate
- Use of regular-absorbency tampons during menstruation
- Use of contraceptive sponge
• Low
- Alternating use of tampons and pads during menstruation
- Intrauterine contraceptive device
- Surgical-wound infections
- Early postpartum state
Genetics
No specific mode of inheritance is recognized.
ETIOLOGY
• S. aureus exotoxins, especially
- TSST-1
- Staphylococcal enterotoxins A, B, and C
- Other staphylococcal superantigens including enterotoxins D, E, and H
• Pediatric population: May occur as complication of chickenpox
• Geriatric population: Cellulitis or surgical-wound infections
• Pregnancy: Postpartum infections, especially post-cesarean section wound infection, or episiotomy infections
ASSOCIATED CONDITIONS
Staphylococcal infections
DIAGNOSIS
SIGNS AND SYMPTOMS
• Almost always present (>80%)
- Temperature >38.9C (>102F)
- Erythroderma
- Diffuse macular rash
- Skin desquamation a few days after rash appears
- Shock, orthostatic hypotension, or syncope
- Nausea or vomiting
• Commonly present (20-80%)
- Headache
- Confusion or agitation
- Acute respiratory distress syndrome
- Meningismus
- Pharyngeal erythema
- Vaginitis or vaginal discharge
- Conjunctivitis
- Periorbital edema
- Strawberry tongue
- Non-pitting edema
- Myalgia
- Oliguria
- Arthralgia
- Diarrhea
• Rarely present (20%)
- Arthritis
- Lymphadenopathy
- Hepatosplenomegaly
- Cardiomyopathy
- Pericarditis
- Photophobia
- Seizure
TESTS
Lab
• Microbiologic
- Isolation of S. aureus strains that produce TSST-1 or other toxins in a patient who does not have acute phase serum antibodies to these superantigens. (2)[B]
- Positive culture for S. aureus from vagina or surgical wound (>90%)
- Nasal or perineal carriage of S. aureus
- Positive blood culture for S. aureus (uncommon)
• Hematologic (50-90%)
- Granulocytosis with increased band forms
- Lymphopenia
- Normocytic, normochromic anemia
- Thrombocytopenia
- Coagulopathy
• Biochemical (50-90%)
- Hypoalbuminemia
- Abnormal electrolytes
- Hypocalcemia
- Hypomagnesemia
- Hypophosphatemia
- Increased serumglutamic-oxalcacetic transaminase
- Increased serumglutamic pyruric transaminase
- Increased creatine phosphokinase
- Increased blood urea nitrogen
- Increased serum creatinine
- Increased calcitonin
- Increased serum bilirubin
- Abnormal urine sediment
Imaging
No unusual or characteristic findings
Diagnostic Procedures/Surgery
No specific diagnostic test is currently available.
Pathological Findings
• Subepidermic cleavage plane in skin
• Minimal inflammatory reaction in tissues
• Lymphocyte depletion in lymph nodes
• Cervico-vaginal ulcerations
DIFFERENTIAL DIAGNOSIS
• Streptococcal scarlet fever
• Streptococcal TSS
- More often associated with severe pain and tenderness at a site of local trauma and infection, and more frequently accompanied by bacteremia
• Drug reactions
• Rocky Mountain spotted fever
• Leptospirosis
• Kawasaki disease
• Staphylococcal scalded-skin syndrome
• Meningococcal or possibly Gram-negative sepsis
• Measles, rubeola
TREATMENT
STABILIZATION
Inpatient, admission to intensive care for monitoring
GENERAL MEASURES
• Removal of tampon or other vaginal foreign bodies
• Removal of nasal packings
• Local wound care
• Fluid resuscitation
• Management of renal or cardiac insufficiency
• Mechanical ventilation if necessary
Diet
As tolerated
Activity
Bed rest throughout acute illness
MEDICATION (DRUGS)
First Line
• Treatment of shock or hypotension
- Fluid replacement
- Dopamine
- Steroids or naloxone have not been proven to be of value
• Eradication of S. aureus and inhibition of toxin production
• Oxacillin or nafcillin 100 mg/kg/d q4h (bactericidal against susceptible S. aureus, but may release more toxins by bacterial lysis) (3)[B]
• Clindamycin 25 mg/kg/d q8h (more efficacious than betalactams in suppressing in vitro production of TSST-1) (3)[B]
• Combination of clindamycin 25 mg/kg/d q8h plus oxacillin or nafcillin 100 mg/kg/d q4h (recommended for patients with deep-seated infections or bacteremia) (3)[B]
• Contraindications: Penicillin allergy
• Precautions
- Rash, diarrhea, seizures
- Reduce oxacillin dosage in patients with severe renal failure. It is not necessary to reduce the nafcillin dose for renal dysfunction.
• Significant possible interactions: See the manufacturer's profile of each drug.
Second Line
• Vancomycin: 30 mg/kg/d q6h for patients infected with methicillin-resistant S. aureus (MRSA)
• Linezolid: 10 mg/kg or 600 mg q12h for patients infected with MRSA
• Toxin neutralization
- Benefit in humans unproven, but animal and in vitro studies support this approach (4)[B]
- Immune globulin IV: 0.4 g/kg over 6 hours (5)[B]
SURGERY
• Surgical drainage of loculated infections
• Exploration and debridement of surgical wounds, which may not appear purulent or infected due to a decreased local inflammatory response in a patient with nonmenstrual TSS
FOLLOW-UP
PROGNOSIS
• Mortality: 3-9%
• Recurrence: 10-15%
COMPLICATIONS
• Common (>20%)
- Acute renal failure
- Adult respiratory distress syndrome
- Menorrhagia
- Alopecia
- Nail loss
• Rare (20%)
- Disseminated intravascular coagulation
- Ataxia, toxic encephalopathy
- Memory impairment
- Cardiomyopathy
- Protracted malaise
PATIENT MONITORING
• Admit to intensive care if in shock
• Daily vital signs until patient is afebrile and normotensive
REFERENCES
1. Hajjeh RA, et al. Toxic shock syndrome in the United States: Surveillance update, 1979-1996. Emerg Infect Dis. 1999;5:807-810.
2. Whiting JL, Rosten PM, Chow AW. Determination by Western blot (immunoblot) of seroconversions to toxic shock syndrome toxin 1 and enterotoxin A, B, or C during infection with TSS- and non-TSS- associated Staphylococcus aureus. Infect Immun. 1989;57:231-234.
3. Parsonnet J, Modern PA, Giacobbe KD. Effect of subinhibitory concentrations of antibiotics on production of TSST-1 [abstract 29], Program and Abstracts of the 32nd Meeting of the IDSA, Orlando. 1994:6A.
4. Barry W, et al. Intravenous immunoglobulin therapy for Toxic Shock Syndrome. JAMA. 1992;267:3315-3316.
5. Keller MA, Stiehm ER, Passive immunity in prevention and treatment of infectious diseases. Clin Microbiol Rev. 2000;13:602-614.
6. Darenberg J, et al. Intravenous immunoglobulin G therapy in streptococcal toxic shock syndrome: A European randomized double-blind, placebo-controlled trial. Clin Infect Dis. 2003;37:333-340.
TORTICOLLIS
TORTICOLLIS - Mark L. Shatsky, DO
BASICS
DESCRIPTION
• Torticollis (L. tortus, twisted + collum, neck) used generically to describe a broad spectrum of disorders characterized by head tilt and rotation or involuntary movement.
• Adult spectrum includes
- Spasmodic torticollis (cervical dystonia; dystonia is a muscle contraction causing twisting and repetitive movements)
- Acute wryneck
• Childhood spectrum includes
- Congenital muscular torticollis; the most common cause of torticollis in 1st year of life. 3 types are described (1)
Most common: Sternocleidomastoid (SCM) tumor (fibromatosis colli)
Muscular torticollis: Tightness and no mass
Postural torticollis: No mass or tightness
- Acquired torticollis of childhood
• Other forms (oculogyric, gastroesophageal reflux, arthritis-related, scoliosis-related and hysterical torticollis) are not discussed here.
• Types
- Rotational (twisting)
- Anterocollis (flexion)
- Laterocollis (side bending)
- Retrocollis (extension)
• System(s) Affected: Musculoskeletal; Nervous
• Synonym(s): Adult acute: Wryneck; Congenital: Idiopathic generalized torticollis, sternocleidomastoid torticollis, neonatal torticollis; Spasmodic: Idiopathic cervical dystonia, focal dystonia, nuchal dystonia
GENERAL PREVENTION
No preventive measures known
EPIDEMIOLOGY
• By age
- Congenital muscular torticollis: Newborn and infants
- Acquired torticollis of childhood: 10 years
- Acute wryneck: 30-60 years
- Spasmodic torticollis: 30-50 years, mean age 40-43 years (2, 3)
• By gender
- Spasmodic torticollis: Female > Male (1.6:1) (2)
- Congenital muscular: Male > Female (3:2) (1)
Incidence
• Congenital: Up to 1:250 live births (1)
• Spasmodic: ~1:100,000
• Annual incidence for all focal dystonias combined 24:1,000,000 persons
Prevalence
• Prevalence for all focal dystonias combined: 295:1,000,000 persons
• No reliable evidence for acute wryneck and childhood acquired torticollis
RISK FACTORS
• Congenital muscular torticollis
- Intrauterine crowding
- Breech position in utero
- Ischemia or injury of muscle fibers during traumatic birth
• Acute wryneck
- Stress
- Unusual positioning of neck
- Localized exposure to cold
- Medication reaction
• Acquired torticollis of childhood
- Inflammation
- Neurologic disorder
- Optical disorder
- Rotatory force
• Spasmodic
- Family history of dystonia ~10% (2)
- Inflammation
- Neurologic disorder
- Optical disorder
- Rotatory force
- Link between spasmodic torticollis and psychological factors is unclear
Genetics
Some forms may have genetic basis (3)
ETIOLOGY
• Congenital muscular torticollis
- Prenatal or birth trauma
- Sternocleidomastoid may appear normal at birth, then swelling and tightness develop
• Acquired torticollis of childhood
- Onset of unilateral muscle pain, spasm and/or decreased range of motion without known trauma
- Look for underlying causes
• Acute wryneck
- Onset of unilateral muscle pain, spasm and/or decreased range of motion
- Precipitating factors include tension, stress, postural factors (work, sleep, lying while reading or watching TV, prolonged unusual positioning of neck), or localized exposure to cold (sleeping in draft, open car window)
- Medication reaction (amphetamines, cocaine, haloperidol, chlorpromazine, prochlorperazine, ketamine, etc.)
• Spasmodic torticollis
- Muscular damage from inflammatory disease (myositis, lymphadenitis)
- Cervical spine injuries
- Ocular disorder
- Organic CNS disorder
- Psychogenic
- Tumor
- Cervical spondylosis
- Vestibular dysfunction
ALERT
Pediatric Considerations Congenital
Associated with birth injury that, without treatment, becomes fibrous cord
If untreated, is associated with craniofacial deformities
Pregnancy Considerations
• Difficult delivery in congenital cases
• Associated with breech birth
ASSOCIATED CONDITIONS
• Congenital: Consider Klippel-Feil syndrome
• Acquired torticollis in childhood: Consider Klippel-Feil syndrome
• Spinal abnormalities
• Spasmodic: Consider psychiatric disorder
DIAGNOSIS
SIGNS AND SYMPTOMS
• Head tilt to affected side (80% right side); chin rotates to opposite side
• Intermittent painful spasms of sternocleidomastoid, trapezius, and other neck muscles
• Congenital: 1st sign at birth may be firm, nontender, palpable enlargement of sternocleidomastoid muscle (1, 4).
• Acquired in childhood: Unilateral neck stiffness, pain, or decreased range of motion
• Acute wryneck: Unilateral neck stiffness, pain, or decreased range of motion
• Spasmodic: Features include initial neck stiffness progressing to pain, head jerking, and neck spasms (2,3).
History
• Abnormal head posture
• Neck pain
• Neck mass or swelling
• Birth history
• Family history
• Medication history
• Trauma
Physical Exam
• Tenderness over cervical spine
• Neck mass, lymphadenopathy
• Craniofacial asymmetry (plagiocephaly)
• Range of motion for restrictions or pain; flexion (normal 45), extension (normal 55), rotation (normal 70), sidebending (normal 40)
• Phasic jerking or tremor of antagonist muscles
• Sensory tricks (geste antagoniste) such as touching face or chin reduces severity in most patients (pathognomonic for spasmodic torticollis) (3, 5).
• Ocular irregularities
• Spinal abnormality (short neck with low posterior hair line may indicate occipitocervical synostosis)
• Extremities: Check sensation, strength, reflexes, pulses
• Clicks/clunks/dislocation of hips
• Structural abnormalities of feet
TESTS
Imaging
• Radiographs to rule out spinal pathology
• Consider CT or MRI of cervical spine to aid in differential diagnosis, especially for acquired cases.
• Consider ultrasound and biopsy for congenital cases to rule out tumor.
DIFFERENTIAL DIAGNOSIS
• Osseous
- Atlantoaxial rotatory subluxation
- Atlanto-occipital subluxation
- Post-traumatic fracture or dislocation
- Cervical disk disorder
- Congenital scoliosis
- Klippel-Feil syndrome (congenital fusion of cervical vertebrae)
- Occipitocervical synostosis
- Grisel syndrome (unilateral or bilateral subluxation of C1 on C2, associated with infectious condition in the head or neck)
- Syringomyelia
- Arnold-Chiari malformation
• Nonosseous
- Myositis involving cervical muscles
- Soft-tissue trauma
- Neoplastic: Spinal cord tumor, acoustic neuroma, osteoblastoma, orbital tumor, fibromatosis, metastasis
- Infection: Upper respiratory tract infection, cervical lymph node abscess, epidural abscess, retropharyngeal abscess, vertebral osteomyelitis
- Vestibular disorders
- Essential head tremor
- Basal ganglia disease
- Cranial nerve palsy
- Psychiatric disorders
- Drug or toxin induced
- Down syndrome
- Sandifer syndrome (association of gastroesophageal reflux disease with spastic torticollis and dystonic body movements)
- Myasthenia gravis
TREATMENT
Issues for Referral
Specialty consultation as appropriate (neurologist, neurosurgeon, ophthalmologist, orthopedist, otolaryngologist)
GENERAL MEASURES
• Congenital
- Physical therapy and aggressive stretching program if started before age 3-6 months (1, 6)[B]
- Place TV/toys on opposite side of bed from rotational deformity (4)[B]
• Acquired in children
- Place TV on opposite side of bed from rotational deformity
• Acute wryneck
- Conservative management includes soft cervical collar, intermittent heat or ice, and/or bed rest
- Analgesics for temporary relief and to break pain/spasm cycle
- Benztropine reported to relieve acute muscle spasm
• Spasmodic
- Conservative management includes soft cervical collar, intermittent heat or ice, and/or bed rest
- Botulinum toxin type A or B is effective and safe for treating adults with cervical dystonia.
Diet
No special diet
Activity
No restrictions
Physical Therapy
If detected early, 90% of congenital muscular torticollis can be managed by stretching exercises performed by parents after receiving physical therapy instructions.
Complementary and Alternative Medicine
Evidence lacking for
Acupuncture
Behavior modification
Spinal manipulation
MEDICATION (DRUGS)
• Congenital muscular: Botulinum toxin type A effective in case series (1, 7)[C]
• Analgesics for temporary relief of pain
• Anticholinergics (benztropine, trihexyphenidyl) may relieve acute muscle spasm (3)[C].
• Diphenhydramine or diazepam for torticollis caused by medication (3)[C]
• Single injection cycle of botulinum toxin type A is effective and safe for treating adults with cervical dystonia (3)[B].
• Botulinum toxin type A and B injections may be more effective than anticholinergic drugs for cervical dystonia (3)[B].
• Patients with focal dystonia of unknown cause: Trial of carbidopa-levodopa (3)[C]
SURGERY
Congenital: Surgical release of involved muscle if physical therapy unsuccessful by 1 year of age (4)[C]
FOLLOW-UP
PROGNOSIS
• Congenital: Good for correctable pathology
- 50-70% resolve spontaneously by 1st year of life
• Child acquired: Good if underlying pathology is discovered
• Acute wryneck: Typically resolves in a few days to weeks
• Spasmodic: May wax and wane for years
COMPLICATIONS
• Facial asymmetry in congenital cases
• May have developmental dysplasia of hip in congenital cases
• Movement disorders
• Postural disorders
• Dental malocclusion
• Psychosocial: May have negative impact on quality of life
PATIENT MONITORING
• Periodic follow-up to assess progress
• Frequent assessment in acquired form
REFERENCES
1. Do TT. Congenital muscular torticollis: Current concepts and review. Curr Opin Pediatr. 2006;18(1):26-29.
2. Chan J, Brin MF, Fahn S. Idiopathic cervical dystonia: Clinical characteristics. Mov Disorder. 1991;6:119-126.
3. Tarsay D, Simon DK. Current concepts dystonia. N Engl J Med. 2006;355(8):818-829.
4. Epps HR, Salter RB. Orthopedic conditions of the cervical spine and shoulder. Pediatr Clin N Am. 1996;43(4):919-931.
5. Consky EA, Lang AE. Clinical assessments of patients with cervical dystonia. In: Jancovic J, Hallet M, eds. Therapy with Botulinum Toxin. New York: Marcel Dekker; 1994:211-237.
6. Demirbilek S, Atayurt HF. Congenital muscular torticollis and sternomastoid tumor: Results of nonoperative treatment. J Pediatr Surg. 1999;34(4):549-551.
7. Olexzek JL, Chang N, Apkon SD, Wilson PE. Botulinum toxin Type A in the treatment of children with congenital muscular torticollis. Am J Phys Med Rehabil. 2005;84(10):813-816.
8. Alper BS. Torticollis. DynaMed. Available from: http://www.DynamicMedical.com. Accessed Sept 4, 2006.
BASICS
DESCRIPTION
• Torticollis (L. tortus, twisted + collum, neck) used generically to describe a broad spectrum of disorders characterized by head tilt and rotation or involuntary movement.
• Adult spectrum includes
- Spasmodic torticollis (cervical dystonia; dystonia is a muscle contraction causing twisting and repetitive movements)
- Acute wryneck
• Childhood spectrum includes
- Congenital muscular torticollis; the most common cause of torticollis in 1st year of life. 3 types are described (1)
Most common: Sternocleidomastoid (SCM) tumor (fibromatosis colli)
Muscular torticollis: Tightness and no mass
Postural torticollis: No mass or tightness
- Acquired torticollis of childhood
• Other forms (oculogyric, gastroesophageal reflux, arthritis-related, scoliosis-related and hysterical torticollis) are not discussed here.
• Types
- Rotational (twisting)
- Anterocollis (flexion)
- Laterocollis (side bending)
- Retrocollis (extension)
• System(s) Affected: Musculoskeletal; Nervous
• Synonym(s): Adult acute: Wryneck; Congenital: Idiopathic generalized torticollis, sternocleidomastoid torticollis, neonatal torticollis; Spasmodic: Idiopathic cervical dystonia, focal dystonia, nuchal dystonia
GENERAL PREVENTION
No preventive measures known
EPIDEMIOLOGY
• By age
- Congenital muscular torticollis: Newborn and infants
- Acquired torticollis of childhood: 10 years
- Acute wryneck: 30-60 years
- Spasmodic torticollis: 30-50 years, mean age 40-43 years (2, 3)
• By gender
- Spasmodic torticollis: Female > Male (1.6:1) (2)
- Congenital muscular: Male > Female (3:2) (1)
Incidence
• Congenital: Up to 1:250 live births (1)
• Spasmodic: ~1:100,000
• Annual incidence for all focal dystonias combined 24:1,000,000 persons
Prevalence
• Prevalence for all focal dystonias combined: 295:1,000,000 persons
• No reliable evidence for acute wryneck and childhood acquired torticollis
RISK FACTORS
• Congenital muscular torticollis
- Intrauterine crowding
- Breech position in utero
- Ischemia or injury of muscle fibers during traumatic birth
• Acute wryneck
- Stress
- Unusual positioning of neck
- Localized exposure to cold
- Medication reaction
• Acquired torticollis of childhood
- Inflammation
- Neurologic disorder
- Optical disorder
- Rotatory force
• Spasmodic
- Family history of dystonia ~10% (2)
- Inflammation
- Neurologic disorder
- Optical disorder
- Rotatory force
- Link between spasmodic torticollis and psychological factors is unclear
Genetics
Some forms may have genetic basis (3)
ETIOLOGY
• Congenital muscular torticollis
- Prenatal or birth trauma
- Sternocleidomastoid may appear normal at birth, then swelling and tightness develop
• Acquired torticollis of childhood
- Onset of unilateral muscle pain, spasm and/or decreased range of motion without known trauma
- Look for underlying causes
• Acute wryneck
- Onset of unilateral muscle pain, spasm and/or decreased range of motion
- Precipitating factors include tension, stress, postural factors (work, sleep, lying while reading or watching TV, prolonged unusual positioning of neck), or localized exposure to cold (sleeping in draft, open car window)
- Medication reaction (amphetamines, cocaine, haloperidol, chlorpromazine, prochlorperazine, ketamine, etc.)
• Spasmodic torticollis
- Muscular damage from inflammatory disease (myositis, lymphadenitis)
- Cervical spine injuries
- Ocular disorder
- Organic CNS disorder
- Psychogenic
- Tumor
- Cervical spondylosis
- Vestibular dysfunction
ALERT
Pediatric Considerations Congenital
Associated with birth injury that, without treatment, becomes fibrous cord
If untreated, is associated with craniofacial deformities
Pregnancy Considerations
• Difficult delivery in congenital cases
• Associated with breech birth
ASSOCIATED CONDITIONS
• Congenital: Consider Klippel-Feil syndrome
• Acquired torticollis in childhood: Consider Klippel-Feil syndrome
• Spinal abnormalities
• Spasmodic: Consider psychiatric disorder
DIAGNOSIS
SIGNS AND SYMPTOMS
• Head tilt to affected side (80% right side); chin rotates to opposite side
• Intermittent painful spasms of sternocleidomastoid, trapezius, and other neck muscles
• Congenital: 1st sign at birth may be firm, nontender, palpable enlargement of sternocleidomastoid muscle (1, 4).
• Acquired in childhood: Unilateral neck stiffness, pain, or decreased range of motion
• Acute wryneck: Unilateral neck stiffness, pain, or decreased range of motion
• Spasmodic: Features include initial neck stiffness progressing to pain, head jerking, and neck spasms (2,3).
History
• Abnormal head posture
• Neck pain
• Neck mass or swelling
• Birth history
• Family history
• Medication history
• Trauma
Physical Exam
• Tenderness over cervical spine
• Neck mass, lymphadenopathy
• Craniofacial asymmetry (plagiocephaly)
• Range of motion for restrictions or pain; flexion (normal 45), extension (normal 55), rotation (normal 70), sidebending (normal 40)
• Phasic jerking or tremor of antagonist muscles
• Sensory tricks (geste antagoniste) such as touching face or chin reduces severity in most patients (pathognomonic for spasmodic torticollis) (3, 5).
• Ocular irregularities
• Spinal abnormality (short neck with low posterior hair line may indicate occipitocervical synostosis)
• Extremities: Check sensation, strength, reflexes, pulses
• Clicks/clunks/dislocation of hips
• Structural abnormalities of feet
TESTS
Imaging
• Radiographs to rule out spinal pathology
• Consider CT or MRI of cervical spine to aid in differential diagnosis, especially for acquired cases.
• Consider ultrasound and biopsy for congenital cases to rule out tumor.
DIFFERENTIAL DIAGNOSIS
• Osseous
- Atlantoaxial rotatory subluxation
- Atlanto-occipital subluxation
- Post-traumatic fracture or dislocation
- Cervical disk disorder
- Congenital scoliosis
- Klippel-Feil syndrome (congenital fusion of cervical vertebrae)
- Occipitocervical synostosis
- Grisel syndrome (unilateral or bilateral subluxation of C1 on C2, associated with infectious condition in the head or neck)
- Syringomyelia
- Arnold-Chiari malformation
• Nonosseous
- Myositis involving cervical muscles
- Soft-tissue trauma
- Neoplastic: Spinal cord tumor, acoustic neuroma, osteoblastoma, orbital tumor, fibromatosis, metastasis
- Infection: Upper respiratory tract infection, cervical lymph node abscess, epidural abscess, retropharyngeal abscess, vertebral osteomyelitis
- Vestibular disorders
- Essential head tremor
- Basal ganglia disease
- Cranial nerve palsy
- Psychiatric disorders
- Drug or toxin induced
- Down syndrome
- Sandifer syndrome (association of gastroesophageal reflux disease with spastic torticollis and dystonic body movements)
- Myasthenia gravis
TREATMENT
Issues for Referral
Specialty consultation as appropriate (neurologist, neurosurgeon, ophthalmologist, orthopedist, otolaryngologist)
GENERAL MEASURES
• Congenital
- Physical therapy and aggressive stretching program if started before age 3-6 months (1, 6)[B]
- Place TV/toys on opposite side of bed from rotational deformity (4)[B]
• Acquired in children
- Place TV on opposite side of bed from rotational deformity
• Acute wryneck
- Conservative management includes soft cervical collar, intermittent heat or ice, and/or bed rest
- Analgesics for temporary relief and to break pain/spasm cycle
- Benztropine reported to relieve acute muscle spasm
• Spasmodic
- Conservative management includes soft cervical collar, intermittent heat or ice, and/or bed rest
- Botulinum toxin type A or B is effective and safe for treating adults with cervical dystonia.
Diet
No special diet
Activity
No restrictions
Physical Therapy
If detected early, 90% of congenital muscular torticollis can be managed by stretching exercises performed by parents after receiving physical therapy instructions.
Complementary and Alternative Medicine
Evidence lacking for
Acupuncture
Behavior modification
Spinal manipulation
MEDICATION (DRUGS)
• Congenital muscular: Botulinum toxin type A effective in case series (1, 7)[C]
• Analgesics for temporary relief of pain
• Anticholinergics (benztropine, trihexyphenidyl) may relieve acute muscle spasm (3)[C].
• Diphenhydramine or diazepam for torticollis caused by medication (3)[C]
• Single injection cycle of botulinum toxin type A is effective and safe for treating adults with cervical dystonia (3)[B].
• Botulinum toxin type A and B injections may be more effective than anticholinergic drugs for cervical dystonia (3)[B].
• Patients with focal dystonia of unknown cause: Trial of carbidopa-levodopa (3)[C]
SURGERY
Congenital: Surgical release of involved muscle if physical therapy unsuccessful by 1 year of age (4)[C]
FOLLOW-UP
PROGNOSIS
• Congenital: Good for correctable pathology
- 50-70% resolve spontaneously by 1st year of life
• Child acquired: Good if underlying pathology is discovered
• Acute wryneck: Typically resolves in a few days to weeks
• Spasmodic: May wax and wane for years
COMPLICATIONS
• Facial asymmetry in congenital cases
• May have developmental dysplasia of hip in congenital cases
• Movement disorders
• Postural disorders
• Dental malocclusion
• Psychosocial: May have negative impact on quality of life
PATIENT MONITORING
• Periodic follow-up to assess progress
• Frequent assessment in acquired form
REFERENCES
1. Do TT. Congenital muscular torticollis: Current concepts and review. Curr Opin Pediatr. 2006;18(1):26-29.
2. Chan J, Brin MF, Fahn S. Idiopathic cervical dystonia: Clinical characteristics. Mov Disorder. 1991;6:119-126.
3. Tarsay D, Simon DK. Current concepts dystonia. N Engl J Med. 2006;355(8):818-829.
4. Epps HR, Salter RB. Orthopedic conditions of the cervical spine and shoulder. Pediatr Clin N Am. 1996;43(4):919-931.
5. Consky EA, Lang AE. Clinical assessments of patients with cervical dystonia. In: Jancovic J, Hallet M, eds. Therapy with Botulinum Toxin. New York: Marcel Dekker; 1994:211-237.
6. Demirbilek S, Atayurt HF. Congenital muscular torticollis and sternomastoid tumor: Results of nonoperative treatment. J Pediatr Surg. 1999;34(4):549-551.
7. Olexzek JL, Chang N, Apkon SD, Wilson PE. Botulinum toxin Type A in the treatment of children with congenital muscular torticollis. Am J Phys Med Rehabil. 2005;84(10):813-816.
8. Alper BS. Torticollis. DynaMed. Available from: http://www.DynamicMedical.com. Accessed Sept 4, 2006.
TOURETTE SYNDROME
TOURETTE SYNDROME - Cheryl A. Wehler, MD
BASICS
DESCRIPTION
• Tourette syndrome (TS) is a childhood onset neurobehavioral disorder characterized by the presence of multiple motor and at least 1 phonic tics (see "Physical Exam") (1).
- Tics are sudden, brief, repetitive, stereotyped motor movements (motor tics) or sounds produced by moving air through the nose, mouth, or throat (phonic tics).
- Tics tend to occur in bouts.
- Tics can be simple or complex; motor tics precede vocal tics, and simple tics precede complex tics.
- Tics often are preceded by sensory symptoms, especially a compulsion to move; patients are able to suppress their tics but voluntary suppression is associated with an inner tension that results in more forceful tics when suppression ceases.
• System(s) Affected: Nervous
EPIDEMIOLOGY
• Predominant age
- By definition, TS onset is in 1st 2 decades
- In TS, simple motor tics typically begin at age 5-6 years (phonic tics usually appear a few years later), and reach peak severity between 10 and 12 years.
- 1/2 to 3/4 of children with TS experience a substantial decrease in tics by late adolescence or early adulthood.
• Predominant sex: Male > Female (3-4:1)
• Predominant race/ethnicity: Clinically heterogeneous disorder, but main characteristics independent of culture
Prevalence
Prevalence of TS estimated at 1-10:1000 children and adolescents
RISK FACTORS
• Inherited developmental disorder; frequency and severity of tics exacerbated by environmental factors
• Morbid risk for TS among relatives range between 9.8% and 15%; 1st-degree relatives of individuals with TS have a 10- to 100-fold increased risk of developing TS compared with general population.
Genetics
• Genetic predisposition, frequent familial history of tic disorders and OCD
• Precise pattern of transmission and identification of genes are unknown; recent studies suggest polygenic inheritance with evidence for a locus on chromosome 17q; sequence variants in SLITRK1 gene on chromosome 13q also are associated with TS.
• Higher concordance in monozygotic compared to dizygotic twins; wide range of phenotypes
ETIOLOGY
• Abnormality of basal ganglia development
• Mechanism uncertain; probably involves dysfunction of basal ganglia-thalamo-cortical circuits likely involving decreased inhibitory output from the basal ganglia, which results in an imbalance of inhibition and excitation in the motor cortex.
• Research suggests that abnormalities of dopamine neurotransmission, most likely in the ventral striatum, play a primary role in the pathophysiology.
ASSOCIATED CONDITIONS
• Most common comorbid conditions are ADHD, OCD (symptoms peak later than tics), and depression
• Impairments of visual perception, sleep disorders, restless leg syndrome, and migraine headaches higher than in general population
• Disruptive behavior problems, aggression, anxiety disorders, social difficulties, and/or learning problems
DIAGNOSIS
Often retrospective; no sensitive and specific diagnostic tests for TS
SIGNS AND SYMPTOMS
• Motor and vocal tics are the clinical hallmark
• Tics fluctuate in type, frequency, and anatomic distribution over time
• Multiple motor tics such as facial grimacing, blinking, head or neck jerking, tongue protruding, sniffing, touching
• Vocal tics such as grunts, snorts, throat clearing, barking, yelling, hiccupping
• Tics are exacerbated by anticipation, emotional upset, anxiety, or fatigue.
• Tics subside when patient is concentrating or absorbed in activities.
• Motor and vocal tics may persist during all stages of sleep, especially light sleep.
History
Diagnosis of TS is based on history and clinical presentation (i.e., observation of tics with or without presence of coexisting disorders).
Physical Exam
• Typically normal; blink reflex abnormalities may be observed.
• Motor and vocal tics are diagnostic sine qua non of TS.
• No clinical measures known to reliably predict children who will continue to express tics in adulthood; severity of tics in late childhood is associated with future tic severity.
• DSM criteria
- A. Both multiple motor and 1 vocal tics have been present at some time during the illness, although not necessarily concurrently.
- B. These may appear simultaneously or at different periods during the illness. The tics occur many times a day (usually in bouts) nearly every day or intermittently throughout a period of >1 year, with no tic-free period of >3 consecutive months.
- C. The anatomic location, number, frequency, complexity, type, and severity of tics change over time.
- D. Onset before age 18 years.
- E. The tics are not due to the direct physiologic effects of a substance (e.g., stimulants) or a general medical condition (e.g., Huntington disease or post-viral encephalitis).
TESTS
Lab
• No definitive laboratory tests for diagnosis of TS.
• TSH should be measured because of association of tics with hyperthyroidism
Imaging
• No useful imaging studies available for diagnosis of TS.
• EEG shows nonspecific abnormalities; useful only to differentiate tics from epilepsy.
Pathological Findings
• Smaller caudate volumes in TS patients
• Striatal dopaminergic terminals are increased, as is striatal dopamine transporter (DAT) density.
DIFFERENTIAL DIAGNOSIS
• Chronic motor or vocal tic disorder
• Transient tic disorder
• Tic disorder not otherwise specified
• Huntington disease
• Stroke
• Lesch-Nyhan syndrome
• Wilson disease
• Sydenham's chorea
• Multiple sclerosis
• Post-viral encephalitis
• Head injury
• Drug effects (e.g., dopamine agonists)
TREATMENT
GENERAL MEASURES
• Neurologic and psychiatric evaluation for diagnosis of primary disorder and comorbid psychiatric conditions (especially ADHD, OCD, and depression)
• Educate patient, family, teachers, and friends to Identify and address psychosocial stressors and environmental triggers.
• Many patients require no treatment for tics; patient should play active role in treatment decisions.
• No cure for tics: Treatment is purely symptomatic, and multimodal treatment usually is indicated.
• TS clusters with several comorbidities; each disorder must be evaluated for associated functional impairment, because patients often are more disabled by their psychiatric conditions than tics; choice of initial treatment largely depends on worst symptoms (tics, obsessions, impulsivity).
• Monotherapy at low doses is preferred to polytherapy.
• Taper medications known to exacerbate tics (e.g., dopamine agonists).
Diet
No restrictions
Activity
No restrictions, encourage exercise and activities
SPECIAL THERAPY
Behavioral treatment of tics
• Habit reversal training (HRT) provides a viable tic-suppression treatment (2)[A].
- HRT is equally effective for motor and vocal tics.
MEDICATION (DRUGS)
First Line
-Adrenergic medications
• Clonidine is a first-line agent for tic suppression; an 2-adrenergic receptor agonist, it is drug of choice (3)[A].
- Ameliorate both tics and ADHD (4)[A]
- Efficacious and safe in children with average dose of 0.3 mg/d
- Clonidine causes sedation and hypotension, but not EKG abnormalities.
• Guanfacine, also an 2-adrenergic receptor agonist, is useful in controlling tics and ADHD at 0.5-1.5 mg b.i.d. (5)[A].
- Guanfacine is less sedating and has a longer duration of action.
Second Line
• Dopamine receptor antagonists
- Typical antipsychotics (e.g., haloperidol 0.5-5 mg at bedtime; pimozide 1-8 mg at bedtime; and chlorpromazine) (3)[A]
- Atypical antipsychotics (e.g., risperidone 0.5-3 mg b.i.d.; olanzapine and quetiapine) (6)[A]
- Only haloperidol, pimozide, and risperidone proven effective in controlled studies
- Olanzapine (5-20 mg/d) also has been shown to reduce tics and aggression.
- No controlled trials evaluating clozapine for TS treatment; does not cause tardive dyskinesia, but risk of agranulocytosis necessitates weekly CBCs for 6 months, and monthly CBCs thereafter.
- Shared side effects include sedation, weight gain, anxiety, orthostatic hypotension, restlessness, extrapyramidal movements, Parkinsonism, tardive dyskinesia, lowered seizure threshold (especially clozapine), and QTc prolongation (especially pimozide).
Haloperidol used in range of 0.5-4 mg at bedtime
Pimozide is dosed at 1-8 mg at bedtime; must be given under EKG monitoring because of risk of cardiac arrhythmias.
Risperidone 1-2 mg b.i.d. or t.i.d.; causes tardive dyskinesia at doses exceeding 6 mg/d.
EKG abnormalities are common and dose-dependent with olanzapine, clozapine, haloperidol.
Typical neuroleptics (e.g., haloperidol and pimozide) are more prone to cause extrapyramidal side effects.
Atypical antipsychotics (e.g., olanzapine and risperidone) are less likely to result in extrapyramidal side effects (e.g., akathisia) but may be associated with metabolic abnormalities such as weight gain, diabetes, hypertriglyceridemia, and dyslipidemia.
Use of risperidone in TS is associated with dysphoria and depression (6)[A].
• Benzodiazepines
- Better tolerated than neuroleptics, but less efficacious
- Side effects include sedation, weight gain, irritability, oppositional behavior, mood changes, and cognitive impairment
• Presynaptic dopamine-depleting agents
- Tetrabenazine (not yet available in U.S.) is very effective for tic control but has some side effects associated with postsynaptic dopamine blockade.
• Miscellaneous medications
- Botulinum toxin injections may be used for severe dystonic tics.
• Treatment of ADHD in patients with tics
- Stimulants such as methylphenidate and dextroamphetamine are most effective and safe treatments of ADHD (7)[A].
Comorbid tic disorder is not a serious contraindication as previously held; exacerbation of tics is neither clinically significant nor common (7)[A].
Guanfacine or clonidine is safe and effective for ADHD treatment (5)[A].
• Treatment of OCD in patients with tics
- Selective serotonin reuptake inhibitors (SSRIs) are most effective and safe; the 1st-line treatment of OCD (8)[A].
Comorbid tic disorder not a contraindication; exacerbation of tics neither clinically significant nor common.
Side effects of SSRIs include gastrointestinal distress, agitation, sexual dysfunction, akathisia, and headache.
Some risk of suicidality noted with SSRIs and other antidepressants.
Clomipramine, a tricyclic antidepressant, is also effective in reducing OC behaviors.
It can be used in place of SSRIs in patients refractory to that treatment or to augment SSRI treatment in partial responders.
Clomipramine side effects include weight gain, dry mouth, constipation, and lowering of seizure threshold.
EKG changes including QTc interval prolongation and tachycardia are the more serious side effects of clomipramine and require monitoring.
Other effective augmentation agents include atypical neuroleptics, such as clonazepam or buspirone.
SURGERY
Thalamic ablation and deep brain stimulation (DBS) have been used experimentally for tic reduction.
FOLLOW-UP
PROGNOSIS
In 1/2-2/3 of children with TS, severity of tics attenuate during adolescence, often remitting completely by early adulthood. However, OCD symptoms tend to increase during this same period in many individuals.
PATIENT MONITORING
Observe for associated psychiatric disorders.
REFERENCES
1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR), 4th ed. Washington, DC: American Psychiatric Association; 2000.
2. Wilhelm S, Deckersbach T, Coffey BJ, et al. Habit reversal versus supportive psychotherapy for Tourette's disorder: a randomized controlled trial. Am J Psychiatry. 2003;160(6):1175-1177.
3. Scahill L, Erenberg G, Berlin CM, et al. Contemporary assessment and pharmacotherapy of Tourette syndrome. NeuroRx. 2006;3(2):192-206.
4. Tourette Syndrome Study Group. Treatment of ADHD in children with tics: a randomized controlled trial. Neurology. 2002;58(4):527-536.
5. Scahill L, Chappell OB, Kim YS, et al. A placebo-controlled study of guanfacine in the treatment of children with tic disorders and attention deficit hyperactivity disorder. Am J Psychiatry. 2001;158(7):1067-1074.
6. Dion Y, Annable L, Stat D, et al. Risperidone in the treatment of Tourette syndrome: a double-blind, placebo-controlled trial. J Clin Psychopharmacol. 2002;22(1):31-39.
7. Spencer T, Biederman, J, Wilens, T, et al. A large, double-blind, randomized clinical trial of methylphenidate in the treatment of adults with attention-deficit/hyperactivity disorder. Biolog Psychiatry. 2005;57(5):456-463.
8. Eapen V, MM Robertson. Co-morbid obsessive-compulsive disorder and Tourette syndrome. CNS Drugs. 2000;13(3):173-183.
BASICS
DESCRIPTION
• Tourette syndrome (TS) is a childhood onset neurobehavioral disorder characterized by the presence of multiple motor and at least 1 phonic tics (see "Physical Exam") (1).
- Tics are sudden, brief, repetitive, stereotyped motor movements (motor tics) or sounds produced by moving air through the nose, mouth, or throat (phonic tics).
- Tics tend to occur in bouts.
- Tics can be simple or complex; motor tics precede vocal tics, and simple tics precede complex tics.
- Tics often are preceded by sensory symptoms, especially a compulsion to move; patients are able to suppress their tics but voluntary suppression is associated with an inner tension that results in more forceful tics when suppression ceases.
• System(s) Affected: Nervous
EPIDEMIOLOGY
• Predominant age
- By definition, TS onset is in 1st 2 decades
- In TS, simple motor tics typically begin at age 5-6 years (phonic tics usually appear a few years later), and reach peak severity between 10 and 12 years.
- 1/2 to 3/4 of children with TS experience a substantial decrease in tics by late adolescence or early adulthood.
• Predominant sex: Male > Female (3-4:1)
• Predominant race/ethnicity: Clinically heterogeneous disorder, but main characteristics independent of culture
Prevalence
Prevalence of TS estimated at 1-10:1000 children and adolescents
RISK FACTORS
• Inherited developmental disorder; frequency and severity of tics exacerbated by environmental factors
• Morbid risk for TS among relatives range between 9.8% and 15%; 1st-degree relatives of individuals with TS have a 10- to 100-fold increased risk of developing TS compared with general population.
Genetics
• Genetic predisposition, frequent familial history of tic disorders and OCD
• Precise pattern of transmission and identification of genes are unknown; recent studies suggest polygenic inheritance with evidence for a locus on chromosome 17q; sequence variants in SLITRK1 gene on chromosome 13q also are associated with TS.
• Higher concordance in monozygotic compared to dizygotic twins; wide range of phenotypes
ETIOLOGY
• Abnormality of basal ganglia development
• Mechanism uncertain; probably involves dysfunction of basal ganglia-thalamo-cortical circuits likely involving decreased inhibitory output from the basal ganglia, which results in an imbalance of inhibition and excitation in the motor cortex.
• Research suggests that abnormalities of dopamine neurotransmission, most likely in the ventral striatum, play a primary role in the pathophysiology.
ASSOCIATED CONDITIONS
• Most common comorbid conditions are ADHD, OCD (symptoms peak later than tics), and depression
• Impairments of visual perception, sleep disorders, restless leg syndrome, and migraine headaches higher than in general population
• Disruptive behavior problems, aggression, anxiety disorders, social difficulties, and/or learning problems
DIAGNOSIS
Often retrospective; no sensitive and specific diagnostic tests for TS
SIGNS AND SYMPTOMS
• Motor and vocal tics are the clinical hallmark
• Tics fluctuate in type, frequency, and anatomic distribution over time
• Multiple motor tics such as facial grimacing, blinking, head or neck jerking, tongue protruding, sniffing, touching
• Vocal tics such as grunts, snorts, throat clearing, barking, yelling, hiccupping
• Tics are exacerbated by anticipation, emotional upset, anxiety, or fatigue.
• Tics subside when patient is concentrating or absorbed in activities.
• Motor and vocal tics may persist during all stages of sleep, especially light sleep.
History
Diagnosis of TS is based on history and clinical presentation (i.e., observation of tics with or without presence of coexisting disorders).
Physical Exam
• Typically normal; blink reflex abnormalities may be observed.
• Motor and vocal tics are diagnostic sine qua non of TS.
• No clinical measures known to reliably predict children who will continue to express tics in adulthood; severity of tics in late childhood is associated with future tic severity.
• DSM criteria
- A. Both multiple motor and 1 vocal tics have been present at some time during the illness, although not necessarily concurrently.
- B. These may appear simultaneously or at different periods during the illness. The tics occur many times a day (usually in bouts) nearly every day or intermittently throughout a period of >1 year, with no tic-free period of >3 consecutive months.
- C. The anatomic location, number, frequency, complexity, type, and severity of tics change over time.
- D. Onset before age 18 years.
- E. The tics are not due to the direct physiologic effects of a substance (e.g., stimulants) or a general medical condition (e.g., Huntington disease or post-viral encephalitis).
TESTS
Lab
• No definitive laboratory tests for diagnosis of TS.
• TSH should be measured because of association of tics with hyperthyroidism
Imaging
• No useful imaging studies available for diagnosis of TS.
• EEG shows nonspecific abnormalities; useful only to differentiate tics from epilepsy.
Pathological Findings
• Smaller caudate volumes in TS patients
• Striatal dopaminergic terminals are increased, as is striatal dopamine transporter (DAT) density.
DIFFERENTIAL DIAGNOSIS
• Chronic motor or vocal tic disorder
• Transient tic disorder
• Tic disorder not otherwise specified
• Huntington disease
• Stroke
• Lesch-Nyhan syndrome
• Wilson disease
• Sydenham's chorea
• Multiple sclerosis
• Post-viral encephalitis
• Head injury
• Drug effects (e.g., dopamine agonists)
TREATMENT
GENERAL MEASURES
• Neurologic and psychiatric evaluation for diagnosis of primary disorder and comorbid psychiatric conditions (especially ADHD, OCD, and depression)
• Educate patient, family, teachers, and friends to Identify and address psychosocial stressors and environmental triggers.
• Many patients require no treatment for tics; patient should play active role in treatment decisions.
• No cure for tics: Treatment is purely symptomatic, and multimodal treatment usually is indicated.
• TS clusters with several comorbidities; each disorder must be evaluated for associated functional impairment, because patients often are more disabled by their psychiatric conditions than tics; choice of initial treatment largely depends on worst symptoms (tics, obsessions, impulsivity).
• Monotherapy at low doses is preferred to polytherapy.
• Taper medications known to exacerbate tics (e.g., dopamine agonists).
Diet
No restrictions
Activity
No restrictions, encourage exercise and activities
SPECIAL THERAPY
Behavioral treatment of tics
• Habit reversal training (HRT) provides a viable tic-suppression treatment (2)[A].
- HRT is equally effective for motor and vocal tics.
MEDICATION (DRUGS)
First Line
-Adrenergic medications
• Clonidine is a first-line agent for tic suppression; an 2-adrenergic receptor agonist, it is drug of choice (3)[A].
- Ameliorate both tics and ADHD (4)[A]
- Efficacious and safe in children with average dose of 0.3 mg/d
- Clonidine causes sedation and hypotension, but not EKG abnormalities.
• Guanfacine, also an 2-adrenergic receptor agonist, is useful in controlling tics and ADHD at 0.5-1.5 mg b.i.d. (5)[A].
- Guanfacine is less sedating and has a longer duration of action.
Second Line
• Dopamine receptor antagonists
- Typical antipsychotics (e.g., haloperidol 0.5-5 mg at bedtime; pimozide 1-8 mg at bedtime; and chlorpromazine) (3)[A]
- Atypical antipsychotics (e.g., risperidone 0.5-3 mg b.i.d.; olanzapine and quetiapine) (6)[A]
- Only haloperidol, pimozide, and risperidone proven effective in controlled studies
- Olanzapine (5-20 mg/d) also has been shown to reduce tics and aggression.
- No controlled trials evaluating clozapine for TS treatment; does not cause tardive dyskinesia, but risk of agranulocytosis necessitates weekly CBCs for 6 months, and monthly CBCs thereafter.
- Shared side effects include sedation, weight gain, anxiety, orthostatic hypotension, restlessness, extrapyramidal movements, Parkinsonism, tardive dyskinesia, lowered seizure threshold (especially clozapine), and QTc prolongation (especially pimozide).
Haloperidol used in range of 0.5-4 mg at bedtime
Pimozide is dosed at 1-8 mg at bedtime; must be given under EKG monitoring because of risk of cardiac arrhythmias.
Risperidone 1-2 mg b.i.d. or t.i.d.; causes tardive dyskinesia at doses exceeding 6 mg/d.
EKG abnormalities are common and dose-dependent with olanzapine, clozapine, haloperidol.
Typical neuroleptics (e.g., haloperidol and pimozide) are more prone to cause extrapyramidal side effects.
Atypical antipsychotics (e.g., olanzapine and risperidone) are less likely to result in extrapyramidal side effects (e.g., akathisia) but may be associated with metabolic abnormalities such as weight gain, diabetes, hypertriglyceridemia, and dyslipidemia.
Use of risperidone in TS is associated with dysphoria and depression (6)[A].
• Benzodiazepines
- Better tolerated than neuroleptics, but less efficacious
- Side effects include sedation, weight gain, irritability, oppositional behavior, mood changes, and cognitive impairment
• Presynaptic dopamine-depleting agents
- Tetrabenazine (not yet available in U.S.) is very effective for tic control but has some side effects associated with postsynaptic dopamine blockade.
• Miscellaneous medications
- Botulinum toxin injections may be used for severe dystonic tics.
• Treatment of ADHD in patients with tics
- Stimulants such as methylphenidate and dextroamphetamine are most effective and safe treatments of ADHD (7)[A].
Comorbid tic disorder is not a serious contraindication as previously held; exacerbation of tics is neither clinically significant nor common (7)[A].
Guanfacine or clonidine is safe and effective for ADHD treatment (5)[A].
• Treatment of OCD in patients with tics
- Selective serotonin reuptake inhibitors (SSRIs) are most effective and safe; the 1st-line treatment of OCD (8)[A].
Comorbid tic disorder not a contraindication; exacerbation of tics neither clinically significant nor common.
Side effects of SSRIs include gastrointestinal distress, agitation, sexual dysfunction, akathisia, and headache.
Some risk of suicidality noted with SSRIs and other antidepressants.
Clomipramine, a tricyclic antidepressant, is also effective in reducing OC behaviors.
It can be used in place of SSRIs in patients refractory to that treatment or to augment SSRI treatment in partial responders.
Clomipramine side effects include weight gain, dry mouth, constipation, and lowering of seizure threshold.
EKG changes including QTc interval prolongation and tachycardia are the more serious side effects of clomipramine and require monitoring.
Other effective augmentation agents include atypical neuroleptics, such as clonazepam or buspirone.
SURGERY
Thalamic ablation and deep brain stimulation (DBS) have been used experimentally for tic reduction.
FOLLOW-UP
PROGNOSIS
In 1/2-2/3 of children with TS, severity of tics attenuate during adolescence, often remitting completely by early adulthood. However, OCD symptoms tend to increase during this same period in many individuals.
PATIENT MONITORING
Observe for associated psychiatric disorders.
REFERENCES
1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR), 4th ed. Washington, DC: American Psychiatric Association; 2000.
2. Wilhelm S, Deckersbach T, Coffey BJ, et al. Habit reversal versus supportive psychotherapy for Tourette's disorder: a randomized controlled trial. Am J Psychiatry. 2003;160(6):1175-1177.
3. Scahill L, Erenberg G, Berlin CM, et al. Contemporary assessment and pharmacotherapy of Tourette syndrome. NeuroRx. 2006;3(2):192-206.
4. Tourette Syndrome Study Group. Treatment of ADHD in children with tics: a randomized controlled trial. Neurology. 2002;58(4):527-536.
5. Scahill L, Chappell OB, Kim YS, et al. A placebo-controlled study of guanfacine in the treatment of children with tic disorders and attention deficit hyperactivity disorder. Am J Psychiatry. 2001;158(7):1067-1074.
6. Dion Y, Annable L, Stat D, et al. Risperidone in the treatment of Tourette syndrome: a double-blind, placebo-controlled trial. J Clin Psychopharmacol. 2002;22(1):31-39.
7. Spencer T, Biederman, J, Wilens, T, et al. A large, double-blind, randomized clinical trial of methylphenidate in the treatment of adults with attention-deficit/hyperactivity disorder. Biolog Psychiatry. 2005;57(5):456-463.
8. Eapen V, MM Robertson. Co-morbid obsessive-compulsive disorder and Tourette syndrome. CNS Drugs. 2000;13(3):173-183.
TINNITUS
TINNITUS - David M. Holmes, MD
BASICS
DESCRIPTION
Tinnitus is derived from the Latin word tinnire meaning "to ring." Tinnitus is the perception of sound in the absence of an acoustic stimulus. The sound may be of a buzzing, ringing, roaring, chirping, whistling or hissing quality.
• Subjective tinnitus can be heard only by the patient.
• Objective tinnitus can be heard through a stethoscope placed on the head and neck near the patient's ear.
• Tinnitus >6 months is chronic.
GENERAL PREVENTION
• Avoid prolonged exposure to loud noises.
• Wear hearing protection when loud noises can't be avoided, such as when using a lawn mower, power tools, guns, and machinery.
• Avoid overuse of ototoxic medications.
EPIDEMIOLOGY
• Predominant age: 40-70 years old (prevalence increases with age)
• Predominant sex: Males > Females (due to males traditionally having greater noise exposure in military, occupational, and recreational activities). 27% of males and 15% of females 45 yrs experience tinnitus.
Incidence
About 50 million people in United States have tinnitus. About 12 million people seek medical attention.
Prevalence
• Affects up to 17% of general population in the United States
• 25% of people with chronic tinnitus consider it to be a significant problem.
• 4% of people with tinnitus experience impairment in their day-to-day functional abilities.
RISK FACTORS
• Advanced age
• Renal impairment
• Hepatic impairment
• Pregnancy
• Hearing loss
• Excessive noise exposure
• Use of ototoxic medications
Genetics
There appears to be a genetic predisposition, but a tinnitus gene has not yet been discovered. Genes have been identified for temporal mandibular joint (TMJ) dysfunction, Meniere's Disease, acoustic neuroma and a few rare causes of hearing loss.
PATHOPHYSIOLOGY
• Moderate sounds cause tiny movements of the stereocilia, which are attached to hair cells in the cochlea. This triggers neuronal transmission in the 8th cranial nerve. Loud sounds (85 decibels) cause stereocilia to bend more than they should. Hair cells that respond to higher-frequency sounds are located at the base of the cochlea and are the first to be damaged. This causes high-pitched ringing. If loud noise exposure is excessive, then stereocilia cannot recover and permanent damage occurs. This results in hearing loss and possibly tinnitus.
• Other causes of hearing loss or damage to the auditory system can also cause tinnitus.
ETIOLOGY
• Subjective Tinnitus
- "My AAAA NOISE PAIN"
Medications and heavy Metals that cause or exacerbate tinnitus: Aspirin, aminoglycosides, benzodiazepines, calcium channel blockers, chloroquine, cisplatin, erythromycin, fluoroquinolones, lead, lidocaine, loop diurectics, mercury, methotrexate, NSAIDs, proton pump inhibitors, quinine, sertraline, tetracycline, tricyclic antidepressants (TCAs), valproate, vancomycin
Meniere disease (estimated 1% prevalence in the United States) or other forms of endolymphatic hydrops (abnormally high inner ear pressure)
Acoustic trauma (one-time exposure to very loud noise)
Aging-related hearing loss (presbycusis)
Anemia
Arterial problems (high blood pressure [HTN], arteriosclerosis, cerebral aneurysm, cerebrovascular accident [CVA])
Noise-induced hearing loss
Otosclerosis and Osteogenesis Imperfecta
Infections (otitis media/externa, meningitis, lyme disease, neurosyphillis, rubella) and Impaction (cerumen)
Sclerosis (multiple sclerosis)
Endocrine (diabetes mellitus, hypothyroid, hyperthyroid)
Psychogenic (depression, anxiety, fibromyalgia, psychosis)
Automimmune disease of inner ear
Injury (head and neck) and Idiopathic
Neoplasms (acoustic neuroma or cholesteatoma)
• Objective Tinnitus ( 1% of all cases of tinnitus) "CAGED PETS"
- Vascular abnormalities
Carotid stenosis
A-V shunt/fistula (congenital and acquired)
Glomus jugulare
Existing stapedial artery
Dehiscent jugular bulb or a vascular loop
- Mechanical abnormalities
Palatal myoclonus
Eustachian tube is abnormally patent
Temporo-mandibular joint disorder
Stapedial muscle spasticity
ASSOCIATED CONDITIONS
• Hearing loss (approx. 90% of chronic tinnitus is associated with sensorineural hearing loss) (5)
- Causes of sensorineural hearing loss: Loud noise, presbycusis, ototoxic medications, Meniere disease, acoustic neuroma
- Causes of conductive hearing loss: Cerumen, ear infection/effusion, trauma, tumor
• TMJ dysfunction
• Depression, anxiety, insomnia, fibromyalgia
DIAGNOSIS
SIGNS AND SYMPTOMS
• Onset and duration: Gradual (presbycusis), sudden (recent loud noise exposure)
• Location: Unilateral (cerumen impaction, otitis media), unilateral plus hearing loss (acoustic neuroma, CVA)
• Pattern: Continuous (hearing loss), episodic (Meniere disease), pulsatile (vascular)
• Pitch: Low-pitch, rumbling (Meniere disease), high-pitched (sensorineural hearing loss)
• Severity: Use 1-10 scale (10 = most severe), Visual Analog Scale, Tinnitus Severity Index, or Tinnitus Handicap Inventory
• Excerbated by fatigue, stress, noise exposure, medications
• Alleviated by lying down with head in dependent position (patent eustachian tube), medications, masking sounds (e.g., water running)
Other Associated Signs and Symptoms
• Hearing loss
• Sudden hearing loss in one ear that progresses to the other ear (autoimmune)
• Ear pain
• Sinus congestion, allergies
• Vertigo (Meniere disease)
• Vestibular disturbances
• Facial muscle paralysis (cholesteatoma)
• High blood pressure
• Symptoms of hyper or hypo-thryoidism
• Symptoms of hyperglycemia
• Symptoms of depression or anxiety
• Insomnia
• Difficulty concentrating
• Suicidal thoughts
History
• Noise exposure >85 dB (normal traffic = 85 dB)
• Upper respiratory infection, ear infection
• Otalgia
• Otorrhea
• Head trauma
• Surgery
• Family history of hearing loss or tinnitus
• Hearing history: Type of hearing loss (congenital, sensorineural, conductive, or mixed)
• Medical history: Hypo/hyperthyroidism, HTN, diabetes mellitus, arteriosclerosis, autoimmune disorders
• Medications
• Exposure to heavy metals (lead or mercury)
• Psychosocial history: Employment, recreational activities, insomnia, anxiety, depression, obsessive compulsive disorder, psychosis, fibromyalgia
Physical Exam
• Otoscopy: Otitis media/externa, cerumen
• Auscultation close to ear for objective tinnitus
• Auscultation of blood vessels in the neck (bruits, venous hum)
• Tinnitus of venous origin is suppressed by compression of ipsilateral jugular vein
• Examine temporal mandibular joint
• Air and bone conduction testing with 512 or 1024 Hz tuning fork (Weber and Rinne tests)
• Neurological exam: Romberg test, Dix-Hallpike maneuver (if patient has vertigo), gait testing, cranial nerves
• Test hearing
• Refer to audiologist for complete evaluation.
TESTS
• Audiometry
• Tympanometry
• Auditory Brainstem Response (to diagnose retrocochlear pathology such as acoustic neuroma)
• Electrocochleography (to diagnose endolymptic hydrops)
• Electronystagmography (to diagnose vestibular disorders)
Lab
• Western blot immunoassay for HIV, renal failure, anaphylaxis, double strand DNA
• Thyroid-stimulating hormone, free T4
• Glucose
• Lipid profile
• CBC
Imaging
• Gadolinium-enhanced MRI (if tinnitus is continuous)
• Contrast-enhanced CT or MRI (if tinnitus is pulsatile)
• Sonography, angiography, or MRA (to asses vascular abnormalities in the neck)
• SPECT may be more sensitive than CT, MRI or magnetic resonance angiography and it identifies dynamic changes within the brain at the neurotransmitter level
DIFFERENTIAL DIAGNOSIS
Auditory hallucinations
TREATMENT
GENERAL MEASURES
• Teat the underlying cause
• Discharge and continue ototoxic medications, if possible
• Use a combination of measures. (5)[B]
• Management depends on tinnitus severity and how it affects the patient's quality of life.
• Anxiety, insomnia, and depression may exacerbate tinnitus, which may in turn exacerbate the anxiety, insomnia, and/or depression. Treat these conditions to stop this vicious cycle. (5)[B]
• Hearing aids/cochlear implants (7)[C]
• Hearing protection for loud noise exposure (5)[A]
• Refer patients to a comprehensive tinnitus management program (audiologist) (5)[B]
Diet
Normal
SPECIAL THERAPY
• Tinnitus retraining therapy and masking: Counseling and wearable low-level, broad-band noise generators. It may require 1-2 yrs of therapy. Significant improvement has been reported in up to 80% of patients with high-pitched tinnitus. (7) However, clinical evidence concluded masking devices have unknown effectiveness. (6)
• Acoustic therapy: Listening to relaxing music or other sounds through head phones when the environment is too quiet. (5)[B]
• Biofeedback and stress reduction: Relaxation technique that helps people manage stress by changing the body's reaction to it. This in turn helps reduce the severity of the tinnitus. (7)[B]
• Psychotherapy: May reduce severity (5)[B]
Complementary and Alternative Medicine
• Acupuncture (unknown effectiveness) (6)
• Hypnosis (unknown effectiveness) (6)
• Low-power laser to mastoid bone (unknown effectiveness) (6)
• Ginko biloba, melatonin, lecithin, (all are ineffective) (6)
MEDICATION (DRUGS)
First Line First Line (Likely to be effective)
• TCAs such as Amitriptyline (50 mg qhs X 1 wk followed by 100 mg at bedtime) (3,6)[A]
• Antiepileptics
• Baclofen
• Benzodiazepines
• Cinnarizine
• Hyperbaric oxygen
• Nicotinamide
• Zinc
SURGERY
• Otosclerosis: Stapedectomy surgery with implantation of ossicular prostheses (5)[C]
• Severe Meniere disease or other forms of endolympahtic hydrops that are not alleviated with medications: Installation of endolyphatic shunt, labyrinthectomy, or vetibular neurectomy (5)[C]
• Auditory neoplasms: Surgical resection or radiation (5)[C]
FOLLOW-UP
DISPOSITION
Admission Criteria
Hospitalization is rarely indicated
Issues for Referral
• Audiologist for complete evaluation/therapy
• Otolaryngologist, neurologist, or neurosurgeon, depending on etiology
PROGNOSIS
Most cases of chronic tinnitus cannot be cured (due to association with irreversible sensorinerual hearing loss). Therefore, focus is on managing the tinnitus and reducing its severity, not curing it. (5)
REFERENCES
1. Adams PF, Hendershot GE, Marano MA. Current estimates from the National Health Interview Survey, 1996. Hyattsville, MD: National Center for Health Statistics, 1999.
2. Bayar N, et al. Efficacy of amitriptyline in the treatment of subjective tinnitus. J Otolaryngol. 2001;30:300-303.
3. Crummer RW, Hassan GA. Diagnostic approach to tinnitus. Am Fam Physician. 2004;69:1:121-126.
4. Folmer RL, Martin WH, Shi Y. Tinnitus: Questions to reveal the cause, answers to provide relief. J Fam Prac. 2004;53:7.
5. Waddell A, Canter R. Tinnitus. Clinical Evidence. 2003;10:634-643.
ADDITIONAL READING
Review references above and Web sites below.
BASICS
DESCRIPTION
Tinnitus is derived from the Latin word tinnire meaning "to ring." Tinnitus is the perception of sound in the absence of an acoustic stimulus. The sound may be of a buzzing, ringing, roaring, chirping, whistling or hissing quality.
• Subjective tinnitus can be heard only by the patient.
• Objective tinnitus can be heard through a stethoscope placed on the head and neck near the patient's ear.
• Tinnitus >6 months is chronic.
GENERAL PREVENTION
• Avoid prolonged exposure to loud noises.
• Wear hearing protection when loud noises can't be avoided, such as when using a lawn mower, power tools, guns, and machinery.
• Avoid overuse of ototoxic medications.
EPIDEMIOLOGY
• Predominant age: 40-70 years old (prevalence increases with age)
• Predominant sex: Males > Females (due to males traditionally having greater noise exposure in military, occupational, and recreational activities). 27% of males and 15% of females 45 yrs experience tinnitus.
Incidence
About 50 million people in United States have tinnitus. About 12 million people seek medical attention.
Prevalence
• Affects up to 17% of general population in the United States
• 25% of people with chronic tinnitus consider it to be a significant problem.
• 4% of people with tinnitus experience impairment in their day-to-day functional abilities.
RISK FACTORS
• Advanced age
• Renal impairment
• Hepatic impairment
• Pregnancy
• Hearing loss
• Excessive noise exposure
• Use of ototoxic medications
Genetics
There appears to be a genetic predisposition, but a tinnitus gene has not yet been discovered. Genes have been identified for temporal mandibular joint (TMJ) dysfunction, Meniere's Disease, acoustic neuroma and a few rare causes of hearing loss.
PATHOPHYSIOLOGY
• Moderate sounds cause tiny movements of the stereocilia, which are attached to hair cells in the cochlea. This triggers neuronal transmission in the 8th cranial nerve. Loud sounds (85 decibels) cause stereocilia to bend more than they should. Hair cells that respond to higher-frequency sounds are located at the base of the cochlea and are the first to be damaged. This causes high-pitched ringing. If loud noise exposure is excessive, then stereocilia cannot recover and permanent damage occurs. This results in hearing loss and possibly tinnitus.
• Other causes of hearing loss or damage to the auditory system can also cause tinnitus.
ETIOLOGY
• Subjective Tinnitus
- "My AAAA NOISE PAIN"
Medications and heavy Metals that cause or exacerbate tinnitus: Aspirin, aminoglycosides, benzodiazepines, calcium channel blockers, chloroquine, cisplatin, erythromycin, fluoroquinolones, lead, lidocaine, loop diurectics, mercury, methotrexate, NSAIDs, proton pump inhibitors, quinine, sertraline, tetracycline, tricyclic antidepressants (TCAs), valproate, vancomycin
Meniere disease (estimated 1% prevalence in the United States) or other forms of endolymphatic hydrops (abnormally high inner ear pressure)
Acoustic trauma (one-time exposure to very loud noise)
Aging-related hearing loss (presbycusis)
Anemia
Arterial problems (high blood pressure [HTN], arteriosclerosis, cerebral aneurysm, cerebrovascular accident [CVA])
Noise-induced hearing loss
Otosclerosis and Osteogenesis Imperfecta
Infections (otitis media/externa, meningitis, lyme disease, neurosyphillis, rubella) and Impaction (cerumen)
Sclerosis (multiple sclerosis)
Endocrine (diabetes mellitus, hypothyroid, hyperthyroid)
Psychogenic (depression, anxiety, fibromyalgia, psychosis)
Automimmune disease of inner ear
Injury (head and neck) and Idiopathic
Neoplasms (acoustic neuroma or cholesteatoma)
• Objective Tinnitus ( 1% of all cases of tinnitus) "CAGED PETS"
- Vascular abnormalities
Carotid stenosis
A-V shunt/fistula (congenital and acquired)
Glomus jugulare
Existing stapedial artery
Dehiscent jugular bulb or a vascular loop
- Mechanical abnormalities
Palatal myoclonus
Eustachian tube is abnormally patent
Temporo-mandibular joint disorder
Stapedial muscle spasticity
ASSOCIATED CONDITIONS
• Hearing loss (approx. 90% of chronic tinnitus is associated with sensorineural hearing loss) (5)
- Causes of sensorineural hearing loss: Loud noise, presbycusis, ototoxic medications, Meniere disease, acoustic neuroma
- Causes of conductive hearing loss: Cerumen, ear infection/effusion, trauma, tumor
• TMJ dysfunction
• Depression, anxiety, insomnia, fibromyalgia
DIAGNOSIS
SIGNS AND SYMPTOMS
• Onset and duration: Gradual (presbycusis), sudden (recent loud noise exposure)
• Location: Unilateral (cerumen impaction, otitis media), unilateral plus hearing loss (acoustic neuroma, CVA)
• Pattern: Continuous (hearing loss), episodic (Meniere disease), pulsatile (vascular)
• Pitch: Low-pitch, rumbling (Meniere disease), high-pitched (sensorineural hearing loss)
• Severity: Use 1-10 scale (10 = most severe), Visual Analog Scale, Tinnitus Severity Index, or Tinnitus Handicap Inventory
• Excerbated by fatigue, stress, noise exposure, medications
• Alleviated by lying down with head in dependent position (patent eustachian tube), medications, masking sounds (e.g., water running)
Other Associated Signs and Symptoms
• Hearing loss
• Sudden hearing loss in one ear that progresses to the other ear (autoimmune)
• Ear pain
• Sinus congestion, allergies
• Vertigo (Meniere disease)
• Vestibular disturbances
• Facial muscle paralysis (cholesteatoma)
• High blood pressure
• Symptoms of hyper or hypo-thryoidism
• Symptoms of hyperglycemia
• Symptoms of depression or anxiety
• Insomnia
• Difficulty concentrating
• Suicidal thoughts
History
• Noise exposure >85 dB (normal traffic = 85 dB)
• Upper respiratory infection, ear infection
• Otalgia
• Otorrhea
• Head trauma
• Surgery
• Family history of hearing loss or tinnitus
• Hearing history: Type of hearing loss (congenital, sensorineural, conductive, or mixed)
• Medical history: Hypo/hyperthyroidism, HTN, diabetes mellitus, arteriosclerosis, autoimmune disorders
• Medications
• Exposure to heavy metals (lead or mercury)
• Psychosocial history: Employment, recreational activities, insomnia, anxiety, depression, obsessive compulsive disorder, psychosis, fibromyalgia
Physical Exam
• Otoscopy: Otitis media/externa, cerumen
• Auscultation close to ear for objective tinnitus
• Auscultation of blood vessels in the neck (bruits, venous hum)
• Tinnitus of venous origin is suppressed by compression of ipsilateral jugular vein
• Examine temporal mandibular joint
• Air and bone conduction testing with 512 or 1024 Hz tuning fork (Weber and Rinne tests)
• Neurological exam: Romberg test, Dix-Hallpike maneuver (if patient has vertigo), gait testing, cranial nerves
• Test hearing
• Refer to audiologist for complete evaluation.
TESTS
• Audiometry
• Tympanometry
• Auditory Brainstem Response (to diagnose retrocochlear pathology such as acoustic neuroma)
• Electrocochleography (to diagnose endolymptic hydrops)
• Electronystagmography (to diagnose vestibular disorders)
Lab
• Western blot immunoassay for HIV, renal failure, anaphylaxis, double strand DNA
• Thyroid-stimulating hormone, free T4
• Glucose
• Lipid profile
• CBC
Imaging
• Gadolinium-enhanced MRI (if tinnitus is continuous)
• Contrast-enhanced CT or MRI (if tinnitus is pulsatile)
• Sonography, angiography, or MRA (to asses vascular abnormalities in the neck)
• SPECT may be more sensitive than CT, MRI or magnetic resonance angiography and it identifies dynamic changes within the brain at the neurotransmitter level
DIFFERENTIAL DIAGNOSIS
Auditory hallucinations
TREATMENT
GENERAL MEASURES
• Teat the underlying cause
• Discharge and continue ototoxic medications, if possible
• Use a combination of measures. (5)[B]
• Management depends on tinnitus severity and how it affects the patient's quality of life.
• Anxiety, insomnia, and depression may exacerbate tinnitus, which may in turn exacerbate the anxiety, insomnia, and/or depression. Treat these conditions to stop this vicious cycle. (5)[B]
• Hearing aids/cochlear implants (7)[C]
• Hearing protection for loud noise exposure (5)[A]
• Refer patients to a comprehensive tinnitus management program (audiologist) (5)[B]
Diet
Normal
SPECIAL THERAPY
• Tinnitus retraining therapy and masking: Counseling and wearable low-level, broad-band noise generators. It may require 1-2 yrs of therapy. Significant improvement has been reported in up to 80% of patients with high-pitched tinnitus. (7) However, clinical evidence concluded masking devices have unknown effectiveness. (6)
• Acoustic therapy: Listening to relaxing music or other sounds through head phones when the environment is too quiet. (5)[B]
• Biofeedback and stress reduction: Relaxation technique that helps people manage stress by changing the body's reaction to it. This in turn helps reduce the severity of the tinnitus. (7)[B]
• Psychotherapy: May reduce severity (5)[B]
Complementary and Alternative Medicine
• Acupuncture (unknown effectiveness) (6)
• Hypnosis (unknown effectiveness) (6)
• Low-power laser to mastoid bone (unknown effectiveness) (6)
• Ginko biloba, melatonin, lecithin, (all are ineffective) (6)
MEDICATION (DRUGS)
First Line First Line (Likely to be effective)
• TCAs such as Amitriptyline (50 mg qhs X 1 wk followed by 100 mg at bedtime) (3,6)[A]
• Antiepileptics
• Baclofen
• Benzodiazepines
• Cinnarizine
• Hyperbaric oxygen
• Nicotinamide
• Zinc
SURGERY
• Otosclerosis: Stapedectomy surgery with implantation of ossicular prostheses (5)[C]
• Severe Meniere disease or other forms of endolympahtic hydrops that are not alleviated with medications: Installation of endolyphatic shunt, labyrinthectomy, or vetibular neurectomy (5)[C]
• Auditory neoplasms: Surgical resection or radiation (5)[C]
FOLLOW-UP
DISPOSITION
Admission Criteria
Hospitalization is rarely indicated
Issues for Referral
• Audiologist for complete evaluation/therapy
• Otolaryngologist, neurologist, or neurosurgeon, depending on etiology
PROGNOSIS
Most cases of chronic tinnitus cannot be cured (due to association with irreversible sensorinerual hearing loss). Therefore, focus is on managing the tinnitus and reducing its severity, not curing it. (5)
REFERENCES
1. Adams PF, Hendershot GE, Marano MA. Current estimates from the National Health Interview Survey, 1996. Hyattsville, MD: National Center for Health Statistics, 1999.
2. Bayar N, et al. Efficacy of amitriptyline in the treatment of subjective tinnitus. J Otolaryngol. 2001;30:300-303.
3. Crummer RW, Hassan GA. Diagnostic approach to tinnitus. Am Fam Physician. 2004;69:1:121-126.
4. Folmer RL, Martin WH, Shi Y. Tinnitus: Questions to reveal the cause, answers to provide relief. J Fam Prac. 2004;53:7.
5. Waddell A, Canter R. Tinnitus. Clinical Evidence. 2003;10:634-643.
ADDITIONAL READING
Review references above and Web sites below.
TINEA VERSICOLOR
TINEA VERSICOLOR - Elisabeth L. Backer, MD
BASICS
DESCRIPTION
• Common superficial mycosis with variety/changing shades of colors. Macules usually hypopigmented, light brown or salmon colored. Fine scale often apparent.
• System(s) Affected: Skin/Exocrine
• Synonym(s): Pityriasis versicolor
EPIDEMIOLOGY
• Predominant age: Teenagers and young adults
• Predominant sex: Male = Female
Prevalence
Common
ALERT
Pregnancy Considerations
Usually occurs after puberty (except in tropical areas). Facial lesions are more common in children.
Geriatric Considerations
Not common in geriatric population
RISK FACTORS
• Hot, humid weather
• Use of oils
• Hyperhydrosis
• HIV infection/immunosuppression (1)[C]
• High cortisol levels (Cushings, prolonged steroid administration)
• Pregnancy
• Malnutrition
• Oral contarceptives
Genetics
No known genetic pattern
ETIOLOGY
• Saprophytic yeast: Pityrosporum orbiculare (also known as Pityropsporum ovale, Malassezia furfur or Malassezia ovalis)
• Variations in skin lipid formation
DIAGNOSIS
SIGNS AND SYMPTOMS
• Color
- Sun-exposed areas: Lesions usually white
- Covered areas: Lesions often brown or red-brown
• Distribution (sebum-rich areas): Chest, shoulders, back (also face and intertriginous areas)
• Appearance: Small individual lesions that frequently coalesce
• Scale: Fine, more visible with scraping
• Pruritus (mild)
• More prominent in summer
• Periodic recurrence
TESTS
Wood's lamp: Golden fluorescence or pigment changes
Lab
• Direct microscopy of scales with 10% potassium hydroxide preparation to visualize hyphae and spores
• Routine lab not usually necessary
Pathological Findings
• Short, stubby, or Y-shaped hyphae
• Small, round spores in clusters on hyphae
DIFFERENTIAL DIAGNOSIS
Other skin diseases with discolored macules and plaques, including
• Pityriasis alba/rosea
• Vitiligo
• Seborrheic dermatitis
• Nummular eczema
• Secondary syphilis
TREATMENT
GENERAL MEASURES
• Outpatient
• Apply prescribed topical medications to affected parts with cotton balls.
• Repeat treatment each spring prior to sun exposure.
Diet
No special diet
Activity
No restrictions
MEDICATION (DRUGS)
First Line
• Ketoconazole 2% shampoo applied to damp skin and left on for 5 minutes for 1-3 days or
• Selenium sulfide shampoo 2.5% (Selsun)
- Allowed to dry for 10 minutes prior to showering: Daily for 1 week or
- Allowed to remain on body for 12-24 hours prior to showering: Once a week for 4 weeks or
• Clotrimazole topical (Lotrimin) b.i.d. for 2-4 weeks, or
• Miconazole (Micatin, Monistat) b.i.d. for 2-4 weeks, or
• Ketoconazole 2% (Nizoral) cream b.i.d. for 2-4 weeks, or
• Terbinafine (Lamisil) 1% solution b.i.d. for 1 week or
• Terbinafine (Lamisil DermGel) once daily for 1 week
• Cure rates of topical anti-yeast preparations typically 70-80%. (2,3)[C] Healing continues post active treatment. Resumption of even pigmentation may take months.
• Contraindications: Ketoconazole contraindicated in pregnancy
Second Line
• Use for extensive disease or non-responders
• Ketoconazole (rarely needed and has significant adverse reactions) 400 mg in single dose or 200 mg/d for 1 week. Cure rate >90% (4)[C]
• Itraconazole 200 mg/d for 1 week. Cure rate >90% (5)[C]
• Ketoconazole shampoo can be used weekly for maintenance.
• Sulfur-salicylic acid (Sebulex) soap or shampoo can be used chronically for prophylaxis.
FOLLOW-UP
PROGNOSIS
• Duration of lesions months/years
• Recurs almost routinely
COMPLICATIONS
None expected
PATIENT MONITORING
• Recheck and treat again each spring prior to tanning season.
• Avoid skin oils.
• Suntanning accentuates lesions.
REFERENCES
1. Gulec AT, et al. Superficial fungal infections in 102 renal transplant recipients. J Am Acad Dermatol. 2003;49:187.
2. Lange DS, et al. Ketoconazole 2% shampoo in the treatment of tinea versicolor. J Am Acad Dermatol. 1998;39:944.
3. del Pacio et al. Randomized comparative trial of itraconazole and selenium shampoo for the treatment of P. versicolor. Rev Infect Dis. 1987;9(Suppl 1):S121.
4. Goodless, DR, et al. Ketoconazole in the treatment of Pityriasis Versicolor: International review of clinical trials. DICP. 1991;25:395.
5. Kose, O, et al. Comparison of single 400 mg dose versus a 7 day 200 mg daily dose of itraconazole in the treatment of tinea versicolor. J Derm Treat. 2002;13:77.
6. Habif TP. Clinical Dermatology, Third edition. 1996.
7. Faergemann J. Pityriasis versicolor. Semin Dermatol. 1993;12:276.
8. Drake LA, et al., and the Guidelines/Outcomes Committee of the American Academy of Dermatology. Guidelines of care for superficial mycotic infections of the skin: Pityriasis (tinea) versicolor. J Amer Acad Dermatol. 1996; 34(2 pt 1):287-289.
9. Lynch PJ. Dermatology for the House Officer. 3rd ed. Baltimore, MD: Williams Wilkins; 1994.
10. Savin R. Diagnosis and treatment of tinea versicolor. J Fam Pract. 1996;43:127.
BASICS
DESCRIPTION
• Common superficial mycosis with variety/changing shades of colors. Macules usually hypopigmented, light brown or salmon colored. Fine scale often apparent.
• System(s) Affected: Skin/Exocrine
• Synonym(s): Pityriasis versicolor
EPIDEMIOLOGY
• Predominant age: Teenagers and young adults
• Predominant sex: Male = Female
Prevalence
Common
ALERT
Pregnancy Considerations
Usually occurs after puberty (except in tropical areas). Facial lesions are more common in children.
Geriatric Considerations
Not common in geriatric population
RISK FACTORS
• Hot, humid weather
• Use of oils
• Hyperhydrosis
• HIV infection/immunosuppression (1)[C]
• High cortisol levels (Cushings, prolonged steroid administration)
• Pregnancy
• Malnutrition
• Oral contarceptives
Genetics
No known genetic pattern
ETIOLOGY
• Saprophytic yeast: Pityrosporum orbiculare (also known as Pityropsporum ovale, Malassezia furfur or Malassezia ovalis)
• Variations in skin lipid formation
DIAGNOSIS
SIGNS AND SYMPTOMS
• Color
- Sun-exposed areas: Lesions usually white
- Covered areas: Lesions often brown or red-brown
• Distribution (sebum-rich areas): Chest, shoulders, back (also face and intertriginous areas)
• Appearance: Small individual lesions that frequently coalesce
• Scale: Fine, more visible with scraping
• Pruritus (mild)
• More prominent in summer
• Periodic recurrence
TESTS
Wood's lamp: Golden fluorescence or pigment changes
Lab
• Direct microscopy of scales with 10% potassium hydroxide preparation to visualize hyphae and spores
• Routine lab not usually necessary
Pathological Findings
• Short, stubby, or Y-shaped hyphae
• Small, round spores in clusters on hyphae
DIFFERENTIAL DIAGNOSIS
Other skin diseases with discolored macules and plaques, including
• Pityriasis alba/rosea
• Vitiligo
• Seborrheic dermatitis
• Nummular eczema
• Secondary syphilis
TREATMENT
GENERAL MEASURES
• Outpatient
• Apply prescribed topical medications to affected parts with cotton balls.
• Repeat treatment each spring prior to sun exposure.
Diet
No special diet
Activity
No restrictions
MEDICATION (DRUGS)
First Line
• Ketoconazole 2% shampoo applied to damp skin and left on for 5 minutes for 1-3 days or
• Selenium sulfide shampoo 2.5% (Selsun)
- Allowed to dry for 10 minutes prior to showering: Daily for 1 week or
- Allowed to remain on body for 12-24 hours prior to showering: Once a week for 4 weeks or
• Clotrimazole topical (Lotrimin) b.i.d. for 2-4 weeks, or
• Miconazole (Micatin, Monistat) b.i.d. for 2-4 weeks, or
• Ketoconazole 2% (Nizoral) cream b.i.d. for 2-4 weeks, or
• Terbinafine (Lamisil) 1% solution b.i.d. for 1 week or
• Terbinafine (Lamisil DermGel) once daily for 1 week
• Cure rates of topical anti-yeast preparations typically 70-80%. (2,3)[C] Healing continues post active treatment. Resumption of even pigmentation may take months.
• Contraindications: Ketoconazole contraindicated in pregnancy
Second Line
• Use for extensive disease or non-responders
• Ketoconazole (rarely needed and has significant adverse reactions) 400 mg in single dose or 200 mg/d for 1 week. Cure rate >90% (4)[C]
• Itraconazole 200 mg/d for 1 week. Cure rate >90% (5)[C]
• Ketoconazole shampoo can be used weekly for maintenance.
• Sulfur-salicylic acid (Sebulex) soap or shampoo can be used chronically for prophylaxis.
FOLLOW-UP
PROGNOSIS
• Duration of lesions months/years
• Recurs almost routinely
COMPLICATIONS
None expected
PATIENT MONITORING
• Recheck and treat again each spring prior to tanning season.
• Avoid skin oils.
• Suntanning accentuates lesions.
REFERENCES
1. Gulec AT, et al. Superficial fungal infections in 102 renal transplant recipients. J Am Acad Dermatol. 2003;49:187.
2. Lange DS, et al. Ketoconazole 2% shampoo in the treatment of tinea versicolor. J Am Acad Dermatol. 1998;39:944.
3. del Pacio et al. Randomized comparative trial of itraconazole and selenium shampoo for the treatment of P. versicolor. Rev Infect Dis. 1987;9(Suppl 1):S121.
4. Goodless, DR, et al. Ketoconazole in the treatment of Pityriasis Versicolor: International review of clinical trials. DICP. 1991;25:395.
5. Kose, O, et al. Comparison of single 400 mg dose versus a 7 day 200 mg daily dose of itraconazole in the treatment of tinea versicolor. J Derm Treat. 2002;13:77.
6. Habif TP. Clinical Dermatology, Third edition. 1996.
7. Faergemann J. Pityriasis versicolor. Semin Dermatol. 1993;12:276.
8. Drake LA, et al., and the Guidelines/Outcomes Committee of the American Academy of Dermatology. Guidelines of care for superficial mycotic infections of the skin: Pityriasis (tinea) versicolor. J Amer Acad Dermatol. 1996; 34(2 pt 1):287-289.
9. Lynch PJ. Dermatology for the House Officer. 3rd ed. Baltimore, MD: Williams Wilkins; 1994.
10. Savin R. Diagnosis and treatment of tinea versicolor. J Fam Pract. 1996;43:127.
TINEA CRURIS
TINEA CRURIS - Elizabeth L. Backer, MD
BASICS
DESCRIPTION
• Superficial fungal infection of groin area
• Most common cause in North America: Trichophyton rubrum (rare cases caused by Epidermophyton floccosum and Trichophyton mentagrophytes)
• Characterized by development of well-marginated, erythematous, half-moon-shaped plaques in crural folds that spread to upper thighs
• Advancing border is well defined, often with fine scaling and sometimes vesicular eruptions.
• Lesions are usually bilateral and do not include scrotum or penis (unlike Candida infections), but may migrate to perineum, perianal area, gluteal cleft, and onto buttocks in chronic/progressive cases
• System(s) Affected: Skin/Exocrine
• Synonym(s): Jock itch; Ringworm
GENERAL PREVENTION
Avoidance of risk factors
EPIDEMIOLOGY
• Predominant age: Any age, but rare in children
• Predominant sex: Male > Female
Incidence
Common
ALERT
Pediatric Considerations
Rare prior to puberty
Geriatric Considerations
More common in geriatric population, due to increase in risk factors
Pregnancy Considerations
Rare in pregnancy
RISK FACTORS
• Summer months and/or increased sweating
• Wearing wet clothing
• Wearing multiple layers of clothing
• Depression of cell-mediated immune response (e.g., individuals with atopy or AIDS)
• Obesity
ETIOLOGY
• Source of infection usually the patient's own tinea pedis.
• Most common causative dermatophyte is Trichophyton rubrum
• Rare cases caused by Epidermophyton floccosum and Trichophyton mentagrophytes
ASSOCIATED CONDITIONS
Tinea pedis
DIAGNOSIS
SIGNS AND SYMPTOMS
• Lesions may be asymptomatic, but more frequently are quite pruritic.
• Acute inflammation may result from wearing occlusive clothing.
• Chronic scratching may result in an eczematous appearance.
• Previous application of topical steroids may alter appearance, causing a more extensive eruption with irregular borders and erythematous papules. This modified form is called tinea incognito (1)[C].
TESTS
Wood's lamp exam reveals no fluorescence.
Lab
• Fungal culture using Sabouraud's dextrose agar or dermatophyte test medium
• Potassium hydroxide preparation of skin scrapings from dermatophyte leading border shows translucent, branching, rod-shaped hyphae
Pathological Findings
Skin biopsy showing fungal hyphae in epidermis
DIFFERENTIAL DIAGNOSIS
• Intertrigo: Inflammatory process of moist opposed skin folds, often including infection with bacteria, yeast, and fungi. Painful longitudinal fissures occur in creases of skin folds.
• Erythrasma: Diffuse brown, scaly, noninflammatory plaque with irregular borders, often involving groin. Caused by bacterial infection with Corynebacterium minutissimum. Fluoresces coral-red with Wood's lamp.
• Seborrheic dermatitis of groin
• Psoriasis of groin
• Candidiasis of groin
• Acanthosis nigricans
TREATMENT
STABILIZATION
Outpatient
GENERAL MEASURES
• Avoid predisposing conditions such as hot baths and tight-fitting clothing (boxer shorts better than briefs) (2)[C].
• Keep area as dry as possible (talcum/powders may be beneficial) (2)[C].
• Topical steroid preparations should not be used (see "Tinea incognito") (1)[C].
Diet
No restrictions
Activity
Full activity
MEDICATION (DRUGS)
First Line
Topical azole antifungal compounds (3)[C]:
• Econazole (Spectazole), ketoconazole (Nizoral), usually applied b.i.d. for 2-3 weeks
• Terbinafine (Lamisil) is an OTC compound; can be applied once daily or b.i.d. for 1-2 weeks
• Butenafine (Mentax): Applied once daily for 2 weeks; also very effective
Second Line
• Oral antifungal agents are effective, but not indicated in uncomplicated tinea cruris. If topical therapy fails, consult a dermatologist for possible oral therapy. Griseofulvin can be given 500 mg/d PO for 1-2 weeks.
• The following oral regimens have been reported in medical literature as being effective, but currently are not specifically approved by the FDA for tinea cruris
- Oral terbinafine (Lamisil) 250 mg/d for 1 week
- Oral itraconazole (Sporanox) 100 mg b.i.d. once and repeated 1 week later
- Oral fluconazole (Diflucan) 150 mg once per week for 4 weeks
• Topical terbinafine 1% solution has recently been studied and appears effective as a once-daily application for 1 week.
• Contraindications: Oral itraconazole (Sporanox) is contraindicated with astemizole (Hismanal), triazolam (Halcion), lovastatin (Mevacor), simvastatin (Zocor). But pravastatin (Pravachol) can be given with itraconazole. These compounds should not be given during pregnancy.
FOLLOW-UP
PROGNOSIS
Excellent prognosis for cure with therapy
COMPLICATIONS
Secondary bacterial infection
PATIENT MONITORING
Liver function testing prior to therapy and at regular intervals during course of therapy for patients requiring oral terbinafine, fluconazole, itraconazole, and griseofulvin
REFERENCES
1. Smith ES, et al. Nondermatologists are more likely to prescribe antifungal/corticosteroid products. J Am Acad Dermatol. 1998;39:43.
2. Akinwale SO. Personal hygiene as an alternative to griseofulvin in the treatment of tinea cruris. Afr J Med Sci. 2000;29:41.
3. Bonifaz A, et al. Comparative study between terbinafine 1% emulsion-gel versus ketoconazole 2% cream in tinea cruris and corporis. Eur J Derm. 2000;10:107.
4. www.uptodate.com
MISCELLANEOUS
See also: Acanthosis nigricans
BASICS
DESCRIPTION
• Superficial fungal infection of groin area
• Most common cause in North America: Trichophyton rubrum (rare cases caused by Epidermophyton floccosum and Trichophyton mentagrophytes)
• Characterized by development of well-marginated, erythematous, half-moon-shaped plaques in crural folds that spread to upper thighs
• Advancing border is well defined, often with fine scaling and sometimes vesicular eruptions.
• Lesions are usually bilateral and do not include scrotum or penis (unlike Candida infections), but may migrate to perineum, perianal area, gluteal cleft, and onto buttocks in chronic/progressive cases
• System(s) Affected: Skin/Exocrine
• Synonym(s): Jock itch; Ringworm
GENERAL PREVENTION
Avoidance of risk factors
EPIDEMIOLOGY
• Predominant age: Any age, but rare in children
• Predominant sex: Male > Female
Incidence
Common
ALERT
Pediatric Considerations
Rare prior to puberty
Geriatric Considerations
More common in geriatric population, due to increase in risk factors
Pregnancy Considerations
Rare in pregnancy
RISK FACTORS
• Summer months and/or increased sweating
• Wearing wet clothing
• Wearing multiple layers of clothing
• Depression of cell-mediated immune response (e.g., individuals with atopy or AIDS)
• Obesity
ETIOLOGY
• Source of infection usually the patient's own tinea pedis.
• Most common causative dermatophyte is Trichophyton rubrum
• Rare cases caused by Epidermophyton floccosum and Trichophyton mentagrophytes
ASSOCIATED CONDITIONS
Tinea pedis
DIAGNOSIS
SIGNS AND SYMPTOMS
• Lesions may be asymptomatic, but more frequently are quite pruritic.
• Acute inflammation may result from wearing occlusive clothing.
• Chronic scratching may result in an eczematous appearance.
• Previous application of topical steroids may alter appearance, causing a more extensive eruption with irregular borders and erythematous papules. This modified form is called tinea incognito (1)[C].
TESTS
Wood's lamp exam reveals no fluorescence.
Lab
• Fungal culture using Sabouraud's dextrose agar or dermatophyte test medium
• Potassium hydroxide preparation of skin scrapings from dermatophyte leading border shows translucent, branching, rod-shaped hyphae
Pathological Findings
Skin biopsy showing fungal hyphae in epidermis
DIFFERENTIAL DIAGNOSIS
• Intertrigo: Inflammatory process of moist opposed skin folds, often including infection with bacteria, yeast, and fungi. Painful longitudinal fissures occur in creases of skin folds.
• Erythrasma: Diffuse brown, scaly, noninflammatory plaque with irregular borders, often involving groin. Caused by bacterial infection with Corynebacterium minutissimum. Fluoresces coral-red with Wood's lamp.
• Seborrheic dermatitis of groin
• Psoriasis of groin
• Candidiasis of groin
• Acanthosis nigricans
TREATMENT
STABILIZATION
Outpatient
GENERAL MEASURES
• Avoid predisposing conditions such as hot baths and tight-fitting clothing (boxer shorts better than briefs) (2)[C].
• Keep area as dry as possible (talcum/powders may be beneficial) (2)[C].
• Topical steroid preparations should not be used (see "Tinea incognito") (1)[C].
Diet
No restrictions
Activity
Full activity
MEDICATION (DRUGS)
First Line
Topical azole antifungal compounds (3)[C]:
• Econazole (Spectazole), ketoconazole (Nizoral), usually applied b.i.d. for 2-3 weeks
• Terbinafine (Lamisil) is an OTC compound; can be applied once daily or b.i.d. for 1-2 weeks
• Butenafine (Mentax): Applied once daily for 2 weeks; also very effective
Second Line
• Oral antifungal agents are effective, but not indicated in uncomplicated tinea cruris. If topical therapy fails, consult a dermatologist for possible oral therapy. Griseofulvin can be given 500 mg/d PO for 1-2 weeks.
• The following oral regimens have been reported in medical literature as being effective, but currently are not specifically approved by the FDA for tinea cruris
- Oral terbinafine (Lamisil) 250 mg/d for 1 week
- Oral itraconazole (Sporanox) 100 mg b.i.d. once and repeated 1 week later
- Oral fluconazole (Diflucan) 150 mg once per week for 4 weeks
• Topical terbinafine 1% solution has recently been studied and appears effective as a once-daily application for 1 week.
• Contraindications: Oral itraconazole (Sporanox) is contraindicated with astemizole (Hismanal), triazolam (Halcion), lovastatin (Mevacor), simvastatin (Zocor). But pravastatin (Pravachol) can be given with itraconazole. These compounds should not be given during pregnancy.
FOLLOW-UP
PROGNOSIS
Excellent prognosis for cure with therapy
COMPLICATIONS
Secondary bacterial infection
PATIENT MONITORING
Liver function testing prior to therapy and at regular intervals during course of therapy for patients requiring oral terbinafine, fluconazole, itraconazole, and griseofulvin
REFERENCES
1. Smith ES, et al. Nondermatologists are more likely to prescribe antifungal/corticosteroid products. J Am Acad Dermatol. 1998;39:43.
2. Akinwale SO. Personal hygiene as an alternative to griseofulvin in the treatment of tinea cruris. Afr J Med Sci. 2000;29:41.
3. Bonifaz A, et al. Comparative study between terbinafine 1% emulsion-gel versus ketoconazole 2% cream in tinea cruris and corporis. Eur J Derm. 2000;10:107.
4. www.uptodate.com
MISCELLANEOUS
See also: Acanthosis nigricans
TINEA PEDIS
TINEA PEDIS - Elizabeth L. Backer, MD
BASICS
DESCRIPTION
• Superficial infection of feet caused by dermatophytes. Most common dermatophyte infection encountered in clinical practice.
• 2 clinical forms: Acute and chronic
• System(s) Affected: Skin/Exocrine
• Synonym(s): Athlete's foot
GENERAL PREVENTION
• Good personal hygiene
• Wearing rubber or wooden sandals in community showers or bathing places
• Careful drying between toes after showering or bathing. (Blow drying feet with hair dryer may be more effective than drying with towel.)
• Changing socks and shoes frequently
• Applying drying or dusting powder
• Applying topical antiperspirants
• Putting on socks before underwear, to prevent infection from spreading to groin
EPIDEMIOLOGY
• Predominant age: 20-50 years, although can occur at any age
• Predominant sex: Male > Female
Prevalence
~4% of population
ALERT
Pediatric Considerations
Rare in younger children; common in teens
Geriatric Considerations
Elderly are more susceptible to outbreaks because of immunocompromise and impaired perfusion of distal extremities.
RISK FACTORS
• Hot, humid weather
• Occlusive/tight-fitting footwear
• Immunosuppressed patients
• Prolonged application of topical steroids
Genetics
No known genetic pattern
ETIOLOGY
• Trichophyton mentagrophytes (acute)
• Trichophyton rubrum (chronic)
• Trichophyton tonsurans
• Epidermophyton floccosum
ASSOCIATED CONDITIONS
• Hyperhidrosis
• Onychomycosis
• Tinea manum/cruris/corporis
DIAGNOSIS
SIGNS AND SYMPTOMS
• Acute form: Self-limited, intermittent, recurrent vesicular/bullous lesions between toes or on soles
• Chronic form: Most common; slowly progressive pruritic erythematous lesions between toes; interdigital fissures opaque white scales with extension onto soles, sides/dorsum of feet (moccasin distribution)
• Other features: Strong odor, hyperkeratosis, maceration, ulceration
• May be associated with onychomycosis and other tinea infections.
TESTS
Wood's lamp exam will not fluoresce unless complicated by another fungus, which is very uncommon; M. furfur (yellow to white), coryne bacterium (red), or Microsporum (blue green).
Lab
• Direct microscopic examination (potassium hydroxide)
• Culture (Sabouraud's medium)
Pathological Findings
• Potassium hydroxide preparation: Septate and branched mycelia
• Culture: Dermatophyte
DIFFERENTIAL DIAGNOSIS
• Interdigital type: Erythrasma, impetigo, pitted keratolysis, candida intertrigo
• Moccasin type: Psoriasis vulgaris, eczematous dermatitis, pitted keratolysis
• Inflammatory/bullous type: Impetigo, allergic contact dermatitis, dyshidrotic eczema, bullous disease
TREATMENT
STABILIZATION
Outpatient
GENERAL MEASURES
• Treatment is generally with topical antifungal medications for up to 4 weeks (1)[A].
• Soak with aluminum chloride 30% or aluminum subacetate for 20 minutes b.i.d.
• Careful removal of dead/thickened skin after soaking or bathing
• Chronic or extensive disease or nail involvement requires oral antifungal medication, systemic therapy.
Diet
No restrictions
Activity
Avoid sweating feet
MEDICATION (DRUGS)
First Line
• Acute treatment
- Aluminum acetate soak (Burow's solution; Domeboro, 1 pack to 1 quart warm water)
- Antifungal cream of choice b.i.d. after soaks.
• Chronic treatment
- Antifungal cream b.i.d. (1)[A]
- May try systemic antifungal therapy (consider if concomitant onychomycosis or after failed topical treatment)
• Systemic antifungals (2)[A]
- Itraconazole (Sporanox) 200 mg PO b.i.d. for 14 days (cure rate >90%)
- Terbinafine (Lamisil) 250 mg PO daily for 14 days
• If concomitant onychomycosis
- Itraconazole 200 mg PO b.i.d. for 1st week of month for 3 months. Monitoring liver function testing is recommended.
- Terbinafine 250 mg PO daily for 12 weeks, or pulse dosing: 500 mg PO daily for 1st week of month for 3 months. Not recommended if creatinine clearance 50 mL/min.
• Contraindications: Itraconazole, pregnancy category C
• Precautions: All systemic antifungal drugs may have potential hepatotoxicity.
• Significant possible interactions: Itraconazole requires gastric acid for absorption; effectiveness is reduced with antacids, H2 blockers, proton pump inhibitors, etc. Take with acidic beverage such as soda if on antacids.
Second Line
• Systemic antifungals
- Fluconazole 150 mg, 1 tablet every week for 1-4 weeks. (Noted in 1997 Sanford Guide: 70% cure; however, not an FDA-approved indication)
- Griseofulvin 660-750 mg/d for 21 days
• Contraindications: Griseofulvin
- Patients with porphyria, hepatocellular failure
- Patients with history of hypersensitivity to griseofulvin
• Precautions: Griseofulvin
- Should be used only in severe cases
- Periodic monitoring of organ-system functioning, including renal, hepatic, and hematopoietic
- Possible photosensitivity reactions
- Lupus erythematosus, lupuslike syndromes, or exacerbation of existing lupus erythematosus have been reported.
• Significant possible interactions: Griseofulvin
- Decreases activity of warfarin-type anticoagulants
- Barbiturates usually depress griseofulvin activity.
- May potentiate effect of alcohol, producing such effects as tachycardia and flush.
FOLLOW-UP
PROGNOSIS
• Control, but not complete cure.
• Infections tend to be chronic with exacerbations (e.g., in hot weather).
COMPLICATIONS
• Secondary bacterial infections (portal of entry for streptococcal infections, producing lymphangitis/cellulitis)
• Eczematoid changes
PATIENT MONITORING
As needed
REFERENCES
1. Crawford F, et al. Athlete's foot and fungally infected toe nails. Clin Evid. 2000;4:939.
2. Bell-Syer SE, et al. Oral treatments for fungal infections of the skin of the foot. Cochrane Database Syst Rev. 2002;CD003584.
3. www.uptodate.com.
MISCELLANEOUS
See also: Dermatitis, Contact, Dyshidrosis
BASICS
DESCRIPTION
• Superficial infection of feet caused by dermatophytes. Most common dermatophyte infection encountered in clinical practice.
• 2 clinical forms: Acute and chronic
• System(s) Affected: Skin/Exocrine
• Synonym(s): Athlete's foot
GENERAL PREVENTION
• Good personal hygiene
• Wearing rubber or wooden sandals in community showers or bathing places
• Careful drying between toes after showering or bathing. (Blow drying feet with hair dryer may be more effective than drying with towel.)
• Changing socks and shoes frequently
• Applying drying or dusting powder
• Applying topical antiperspirants
• Putting on socks before underwear, to prevent infection from spreading to groin
EPIDEMIOLOGY
• Predominant age: 20-50 years, although can occur at any age
• Predominant sex: Male > Female
Prevalence
~4% of population
ALERT
Pediatric Considerations
Rare in younger children; common in teens
Geriatric Considerations
Elderly are more susceptible to outbreaks because of immunocompromise and impaired perfusion of distal extremities.
RISK FACTORS
• Hot, humid weather
• Occlusive/tight-fitting footwear
• Immunosuppressed patients
• Prolonged application of topical steroids
Genetics
No known genetic pattern
ETIOLOGY
• Trichophyton mentagrophytes (acute)
• Trichophyton rubrum (chronic)
• Trichophyton tonsurans
• Epidermophyton floccosum
ASSOCIATED CONDITIONS
• Hyperhidrosis
• Onychomycosis
• Tinea manum/cruris/corporis
DIAGNOSIS
SIGNS AND SYMPTOMS
• Acute form: Self-limited, intermittent, recurrent vesicular/bullous lesions between toes or on soles
• Chronic form: Most common; slowly progressive pruritic erythematous lesions between toes; interdigital fissures opaque white scales with extension onto soles, sides/dorsum of feet (moccasin distribution)
• Other features: Strong odor, hyperkeratosis, maceration, ulceration
• May be associated with onychomycosis and other tinea infections.
TESTS
Wood's lamp exam will not fluoresce unless complicated by another fungus, which is very uncommon; M. furfur (yellow to white), coryne bacterium (red), or Microsporum (blue green).
Lab
• Direct microscopic examination (potassium hydroxide)
• Culture (Sabouraud's medium)
Pathological Findings
• Potassium hydroxide preparation: Septate and branched mycelia
• Culture: Dermatophyte
DIFFERENTIAL DIAGNOSIS
• Interdigital type: Erythrasma, impetigo, pitted keratolysis, candida intertrigo
• Moccasin type: Psoriasis vulgaris, eczematous dermatitis, pitted keratolysis
• Inflammatory/bullous type: Impetigo, allergic contact dermatitis, dyshidrotic eczema, bullous disease
TREATMENT
STABILIZATION
Outpatient
GENERAL MEASURES
• Treatment is generally with topical antifungal medications for up to 4 weeks (1)[A].
• Soak with aluminum chloride 30% or aluminum subacetate for 20 minutes b.i.d.
• Careful removal of dead/thickened skin after soaking or bathing
• Chronic or extensive disease or nail involvement requires oral antifungal medication, systemic therapy.
Diet
No restrictions
Activity
Avoid sweating feet
MEDICATION (DRUGS)
First Line
• Acute treatment
- Aluminum acetate soak (Burow's solution; Domeboro, 1 pack to 1 quart warm water)
- Antifungal cream of choice b.i.d. after soaks.
• Chronic treatment
- Antifungal cream b.i.d. (1)[A]
- May try systemic antifungal therapy (consider if concomitant onychomycosis or after failed topical treatment)
• Systemic antifungals (2)[A]
- Itraconazole (Sporanox) 200 mg PO b.i.d. for 14 days (cure rate >90%)
- Terbinafine (Lamisil) 250 mg PO daily for 14 days
• If concomitant onychomycosis
- Itraconazole 200 mg PO b.i.d. for 1st week of month for 3 months. Monitoring liver function testing is recommended.
- Terbinafine 250 mg PO daily for 12 weeks, or pulse dosing: 500 mg PO daily for 1st week of month for 3 months. Not recommended if creatinine clearance 50 mL/min.
• Contraindications: Itraconazole, pregnancy category C
• Precautions: All systemic antifungal drugs may have potential hepatotoxicity.
• Significant possible interactions: Itraconazole requires gastric acid for absorption; effectiveness is reduced with antacids, H2 blockers, proton pump inhibitors, etc. Take with acidic beverage such as soda if on antacids.
Second Line
• Systemic antifungals
- Fluconazole 150 mg, 1 tablet every week for 1-4 weeks. (Noted in 1997 Sanford Guide: 70% cure; however, not an FDA-approved indication)
- Griseofulvin 660-750 mg/d for 21 days
• Contraindications: Griseofulvin
- Patients with porphyria, hepatocellular failure
- Patients with history of hypersensitivity to griseofulvin
• Precautions: Griseofulvin
- Should be used only in severe cases
- Periodic monitoring of organ-system functioning, including renal, hepatic, and hematopoietic
- Possible photosensitivity reactions
- Lupus erythematosus, lupuslike syndromes, or exacerbation of existing lupus erythematosus have been reported.
• Significant possible interactions: Griseofulvin
- Decreases activity of warfarin-type anticoagulants
- Barbiturates usually depress griseofulvin activity.
- May potentiate effect of alcohol, producing such effects as tachycardia and flush.
FOLLOW-UP
PROGNOSIS
• Control, but not complete cure.
• Infections tend to be chronic with exacerbations (e.g., in hot weather).
COMPLICATIONS
• Secondary bacterial infections (portal of entry for streptococcal infections, producing lymphangitis/cellulitis)
• Eczematoid changes
PATIENT MONITORING
As needed
REFERENCES
1. Crawford F, et al. Athlete's foot and fungally infected toe nails. Clin Evid. 2000;4:939.
2. Bell-Syer SE, et al. Oral treatments for fungal infections of the skin of the foot. Cochrane Database Syst Rev. 2002;CD003584.
3. www.uptodate.com.
MISCELLANEOUS
See also: Dermatitis, Contact, Dyshidrosis
TINEA CORPORIS
TINEA CORPORIS - Elizabeth L. Backer, MD
BASICS
DESCRIPTION
• Scaling, pruritic plaques characterized by a sharply defined annular pattern with peripheral activity and central clearing
• Ringlike shaped lesions (hence called ringworm)
• Papules and occasionally pustules/vesicles present at border, and less commonly in center
• Affects face, trunk, and extremities
• Zoophilic infections are acquired from animals.
• Anthropophilic infections are acquired from personal contact (e.g., wrestling) (1)[C] or fomites.
• System(s) Affected: Skin/Exocrine
• Synonym(s): Ringworm; Tinea circinata
GENERAL PREVENTION
• Avoid contact with suspicious lesions
• Some evidence for using fluconazole or itraconazole in suppressive doses in wrestlers to prevent outbreaks during competitive season (2)[C].]
EPIDEMIOLOGY
• Predominant age: All ages
• Predominant sex: Male = Female
Incidence
Fairly common
RISK FACTORS
• Warm climates
• Direct contact with an active lesion on a human, an animal, or rarely from soil
• Working with animals
• Immunosuppression (such as in diabetes and HIV, or with prolonged use of topical steroids)
Genetics
Evidence suggests a genetic susceptibility in some people.
ETIOLOGY
• Fungal infection due to dermatophyte (e.g., Trichophyton rubrum [most common])
• Microsporum canis often results in multiple lesions.
ASSOCIATED CONDITIONS
Other tinea infections such as tinea pedis, cruris, capitis, barbae, and manus
DIAGNOSIS
SIGNS AND SYMPTOMS
• Characteristic rash and pruritus
• Scaling plaques that are circular/ovale, bright red, sharply marginated, occurring singly or in groups of 3-4 (lesions may run together)
• Each plaque is 5 cm in diameter.
• Plaques are solid, but annular forms occur.
• Occasional hyperpigmentation
TESTS
• Tinea corporis does not fluoresce under Wood's lamp.
• Culture on Sabouraud's medium: Sample by scraping or vigorous rubbing of a cotton swab on the lesion, then rolling/rubbing it on the medium.
Lab
• Potassium hydroxide preparation of skin scrapings
• Fungal culture may be obtained, but not generally necessary
Diagnostic Procedures/Surgery
Skin scraping
• Use No. 15 blade and place several small scrapings of the active border on glass slide with coverslip.
• Apply 10-20% potassium hydroxide and heat gently without boiling.
• Let stand for 5 minutes and examine for septate, branching hyphae
- Use lowered condenser and dim light to enhance contrast.
- Hyphae may be accentuated with a commercial fungal stain or a drop of blue ink.
Pathological Findings
Branching hyphae with septa on potassium hydroxide preparation
DIFFERENTIAL DIAGNOSIS
• Pityriasis rosea
• Eczema (nummular)
• Contact dermatitis
• Syphilis
• Psoriasis
• Subacute lupus erythematosus
• Erythema annulare
• Erythema multiforme
• Erythema migrans
TREATMENT
STABILIZATION
Outpatient
GENERAL MEASURES
Proper hygiene
Diet
Unrestricted diet
Activity
Avoid contact sports (e.g., wrestling) temporarily while starting treatment.
MEDICATION (DRUGS)
• Topical antifungal creams: (3, 4)[C]
- Miconazole (Monistat-Derm) or clotrimazole (Lotrimin, Mycelex) applied b.i.d. for 2 weeks. Also ketoconazole (Nizoral) applied daily for 2 weeks.
- To prevent relapse, use for 1 week after resolution.
- Also econazole (Spectazole) and allylamines, such as naftifine (Naftin, Lamisil)
- For added benefit, wash with antifungal shampoo ketoconazole (Nizoral shampoo) prior to use of cream.
• For resistant, extensive, and/or invasive infections, or in immunocompromised patients, oral agents are recommended
- Oral ultramicrosize griseofulvin (e.g., Gris-PEG) 7 mg/kg/d in children >2 years of age; 375 mg/d in adults for 4 weeks
- Oral itraconazole, in lieu of ketoconazole: Less toxic and fewer drug side effects. Although not indicated, itraconazole (Sporanox) is effective at 200 mg/d for 7-14 days.
• Terbinafine (Lamisil) 250 mg/d for 1-2 weeks
• Fluconazole (Diflucan) 150-300 mg (1 dose weekly for 2-4 weeks)
• Contraindications: Known hypersensitivity to agent
• Precautions: Terbinafinegastrointestinal side effects; rare hepatotoxicity and hematologic changes
• Griseofulvin induces hepatic enzymes that metabolize warfarin and other drugs.
FOLLOW-UP
PROGNOSIS
Resolution without sequelae in 1-2 weeks of therapy
COMPLICATIONS
• Bacterial superinfection
• Generalized, invasive dermatophyte infection
PATIENT MONITORING
Necessary for invasive disease or prolonged treatment with oral ketoconazole
REFERENCES
1. Adams BB, et al. Tinea corporis gladiatorum. J Am Acad Dermatol 2002;47:286.
2. Kohl TD, Martin DC, Nemeth R, et al. Fluconazole for the prevention and treatment of tinea gladiatorum. Pediatr Infect Dis J 2000;19(8):717-722.
3. Bonifaz A, et al. Comparative study between terbinafine 1% emulsion-gel versus ketoconazole 2% cream in tinea cruris and tinea corporis. Eur J Dermatol 2000;10:107.
4. Kohl TD, et al. Comparison of topical and oral treatments for tinea gladiatorum. Clin J Sport Med 1999;9:161.
5. www.uptodate.com
MISCELLANEOUS
See also: Tinea capitis, Tinea cruris, Tinea pedis
BASICS
DESCRIPTION
• Scaling, pruritic plaques characterized by a sharply defined annular pattern with peripheral activity and central clearing
• Ringlike shaped lesions (hence called ringworm)
• Papules and occasionally pustules/vesicles present at border, and less commonly in center
• Affects face, trunk, and extremities
• Zoophilic infections are acquired from animals.
• Anthropophilic infections are acquired from personal contact (e.g., wrestling) (1)[C] or fomites.
• System(s) Affected: Skin/Exocrine
• Synonym(s): Ringworm; Tinea circinata
GENERAL PREVENTION
• Avoid contact with suspicious lesions
• Some evidence for using fluconazole or itraconazole in suppressive doses in wrestlers to prevent outbreaks during competitive season (2)[C].]
EPIDEMIOLOGY
• Predominant age: All ages
• Predominant sex: Male = Female
Incidence
Fairly common
RISK FACTORS
• Warm climates
• Direct contact with an active lesion on a human, an animal, or rarely from soil
• Working with animals
• Immunosuppression (such as in diabetes and HIV, or with prolonged use of topical steroids)
Genetics
Evidence suggests a genetic susceptibility in some people.
ETIOLOGY
• Fungal infection due to dermatophyte (e.g., Trichophyton rubrum [most common])
• Microsporum canis often results in multiple lesions.
ASSOCIATED CONDITIONS
Other tinea infections such as tinea pedis, cruris, capitis, barbae, and manus
DIAGNOSIS
SIGNS AND SYMPTOMS
• Characteristic rash and pruritus
• Scaling plaques that are circular/ovale, bright red, sharply marginated, occurring singly or in groups of 3-4 (lesions may run together)
• Each plaque is 5 cm in diameter.
• Plaques are solid, but annular forms occur.
• Occasional hyperpigmentation
TESTS
• Tinea corporis does not fluoresce under Wood's lamp.
• Culture on Sabouraud's medium: Sample by scraping or vigorous rubbing of a cotton swab on the lesion, then rolling/rubbing it on the medium.
Lab
• Potassium hydroxide preparation of skin scrapings
• Fungal culture may be obtained, but not generally necessary
Diagnostic Procedures/Surgery
Skin scraping
• Use No. 15 blade and place several small scrapings of the active border on glass slide with coverslip.
• Apply 10-20% potassium hydroxide and heat gently without boiling.
• Let stand for 5 minutes and examine for septate, branching hyphae
- Use lowered condenser and dim light to enhance contrast.
- Hyphae may be accentuated with a commercial fungal stain or a drop of blue ink.
Pathological Findings
Branching hyphae with septa on potassium hydroxide preparation
DIFFERENTIAL DIAGNOSIS
• Pityriasis rosea
• Eczema (nummular)
• Contact dermatitis
• Syphilis
• Psoriasis
• Subacute lupus erythematosus
• Erythema annulare
• Erythema multiforme
• Erythema migrans
TREATMENT
STABILIZATION
Outpatient
GENERAL MEASURES
Proper hygiene
Diet
Unrestricted diet
Activity
Avoid contact sports (e.g., wrestling) temporarily while starting treatment.
MEDICATION (DRUGS)
• Topical antifungal creams: (3, 4)[C]
- Miconazole (Monistat-Derm) or clotrimazole (Lotrimin, Mycelex) applied b.i.d. for 2 weeks. Also ketoconazole (Nizoral) applied daily for 2 weeks.
- To prevent relapse, use for 1 week after resolution.
- Also econazole (Spectazole) and allylamines, such as naftifine (Naftin, Lamisil)
- For added benefit, wash with antifungal shampoo ketoconazole (Nizoral shampoo) prior to use of cream.
• For resistant, extensive, and/or invasive infections, or in immunocompromised patients, oral agents are recommended
- Oral ultramicrosize griseofulvin (e.g., Gris-PEG) 7 mg/kg/d in children >2 years of age; 375 mg/d in adults for 4 weeks
- Oral itraconazole, in lieu of ketoconazole: Less toxic and fewer drug side effects. Although not indicated, itraconazole (Sporanox) is effective at 200 mg/d for 7-14 days.
• Terbinafine (Lamisil) 250 mg/d for 1-2 weeks
• Fluconazole (Diflucan) 150-300 mg (1 dose weekly for 2-4 weeks)
• Contraindications: Known hypersensitivity to agent
• Precautions: Terbinafinegastrointestinal side effects; rare hepatotoxicity and hematologic changes
• Griseofulvin induces hepatic enzymes that metabolize warfarin and other drugs.
FOLLOW-UP
PROGNOSIS
Resolution without sequelae in 1-2 weeks of therapy
COMPLICATIONS
• Bacterial superinfection
• Generalized, invasive dermatophyte infection
PATIENT MONITORING
Necessary for invasive disease or prolonged treatment with oral ketoconazole
REFERENCES
1. Adams BB, et al. Tinea corporis gladiatorum. J Am Acad Dermatol 2002;47:286.
2. Kohl TD, Martin DC, Nemeth R, et al. Fluconazole for the prevention and treatment of tinea gladiatorum. Pediatr Infect Dis J 2000;19(8):717-722.
3. Bonifaz A, et al. Comparative study between terbinafine 1% emulsion-gel versus ketoconazole 2% cream in tinea cruris and tinea corporis. Eur J Dermatol 2000;10:107.
4. Kohl TD, et al. Comparison of topical and oral treatments for tinea gladiatorum. Clin J Sport Med 1999;9:161.
5. www.uptodate.com
MISCELLANEOUS
See also: Tinea capitis, Tinea cruris, Tinea pedis
TINEA CAPITIS
TINEA CAPITIS - George R. Bergus, MD
BASICS
DESCRIPTION
• A fungal infection of the scalp and hair; often called "ringworm"
• Infection results from contact with infected persons or animals.
• Contagious and may become epidemic
• Affected areas of the scalp can show characteristic black dots resulting from broken hairs.
• System(s) Affected: Skin/Exocrine
• Synonym(s): Scalp ringworm
GENERAL PREVENTION
• Good personal hygiene
• Don't share headwear.
• Identification and treatment of infected individuals and household pets
EPIDEMIOLOGY
• Predominant age: Children, particularly ages 3-9 years. Adult infection is rare.
• Predominant sex: Male = Female
Incidence
Although still common, incidence and prevalence have dropped markedly over the past 30 years.
ALERT
Pediatric Considerations
Highest incidence in this age group
RISK FACTORS
• Day care centers or schools
• Living in confined quarters
• Poor hygiene
• Immunosuppression
ETIOLOGY
• 90% Trichophyton tonsurans
• 10% Microsporum species (canis, audouinii, gypseum)
DIAGNOSIS
SIGNS AND SYMPTOMS
• Infection commonly begins with round patches of scale (alopecia less common).
• Frequently, infection will take on the patterns of chronic scaling with little inflammation or marked inflammation and alopecia.
• Less frequently, patients will present with multiple patches of alopecia and characteristic black-dot pattern of broken hairs.
• Extreme inflammation results in kerion (exudative pustular nodulation).
TESTS
Viewed under a Wood lamp, the 10% of infections caused by Microsporum species will fluoresce a light green. 90% of tinea capitis infections, those caused by Trichophyton, will not fluoresce.
Lab
• Microscopy of a Potassium hydroxide preparation of hairs from affected area can show arthrospores that appear within hair shafts.
• Fungal culture of hairs from affected areas allows the infection to be confirmed and the causative organism to be identified.
Pathological Findings
• Chronic inflammation
• Superficial infection producing lesions with follicular pustules, abscess
• Hyphae in follicles, keratin of skin
DIFFERENTIAL DIAGNOSIS
• Psoriasis and seborrhea dermatitis are most often confused with tinea capitis.
• Pyoderma
• Alopecia areata and trichotillomania
• Aphasia cutis congenita
TREATMENT
Outpatient
GENERAL MEASURES
• Careful hand washing
• Launder towels, clothing, headwear of infected individual
• Check other family members
Diet
No special diet, except persons treated with griseofulvin should not be on a restricted-fat diet.
Activity
No restrictions
MEDICATION (DRUGS)
First Line
• Griseofulvin (Fulvicin P/G, Fulvicin U/F, Gris-PEG)(1,2A for Trichophyton and Microsporum)
- Microsized preparation
- Available in 125-mg, 250-mg, and 500-mg tablets and 125-mg/5-mL suspension
- Standard dose for griseofulvin used in trials is 125 mg/d in patients weighing 10-20 kg; 250 mg/d for 20-40 kg, and 500 mg/d > 40 kg taken b.i.d. or as a single daily for 6-12 weeks
• Oral terbinafine (Lamisil)(1A for Trichophyton) standard dosing for terbinafine is 62.5 mg/d in patients weighing 10-20 kg; 125 mg/d for 20-40 kg, and 250 mg/d > 40 kg for 2-4 weeks
• Itraconazole (Sporanox) (2A for Microsporum)
- Matches griseofulvin in treatment and is better tolerated
- 3-5 mg/kg/d, but most studies have used 100 mg/d for 6 weeks in children >2 years of age
• Contraindications
- Griseofulvin is contraindicated in patients with porphyria because of increased risk of hepatotoxicity.
• Precautions
- Griseofulvin: Headache in up to 10% of patients initially, but generally resolves after 1st week of treatment. Abdominal bloating, dyspepsia, and diarrhea also common. Hypersensitivity and liver toxicity rare. The manufacturer recommends monitoring liver functions while on griseofulvin.
- Terbinafin: Gastrointestinal symptoms (including diarrhea, dyspepsia, and abdominal pain), liver test abnormalities, and taste disturbances. In general, the adverse events were mild and transient
- Itraconazole: Nausea, vomiting, diarrhea, headache, dizziness, abnormal hepatic function tests, rare significant liver toxicity
• Significant possible interactions
- Griseofulvin accentuates the effect of alcohol and increases the metabolism of warfarin and oral contraceptives.
- Terbinafine clearance is increasedby rifampin, decreased by cimetidine.
Second Line
If kerion is present, prednisone 1 mg/kg/d can be added to antifungal therapy for 5-10 days. (3)[C]
ALERT
Pregnancy Considerations
Oral antifungals are contraindicated in pregnancy.
FOLLOW-UP
PROGNOSIS
• Without treatment, lesions will usually heal spontaneously in 6 months.
• Lesions with marked inflammation will resolve spontaneously much more rapidly but are more likely to leave scarring
COMPLICATIONS
Permanent scarring and hair loss from kerion
PATIENT MONITORING
• Recheck after 2 weeks of therapy to document improvement and after the 6-week course of therapy
• Patients might need liver function monitoringsee medication precautions
REFERENCES
1. Fuller LC, et al. A randomized comparison of 4 weeks of terbinafine vs. 8 weeks of griseofulvin for the treatment of tinea capitis. Br J Dermatol. 2001;144(2):321-327.
2. Gupta AK, et al. Therapeutic options for the treatment of tinea capitis caused by Trichophyton species: Griseofulvin versus the new oral antifungal agents, terbinafine, itraconazole, and fluconazole. Pediatr Dermatol. 2001;18:433-438.
3. Hussain I, et al. A randomized, comparative trial of treatment of kerion celsi with griseofulvin plus oral prednisolone vs. griseofulvin alone. Med Mycol. 1999;37(2):97-99.
4. Fuller LC, et al. Diagnosis and management of scalp ringworm. BMJ. 2003;326(7388):539-541.
5. Friedlander SF. The evolving role of itraconazole, fluconazole and terbinafine in the treatment of tinea capitis. Pediatr Infect Dis J. 1999;18:205-210.
6. Friedlander SF, et al. Terbinafine in the treatment of Trichophyton tinea capitis. Pediatrics. 2002;109:602-607.
7. Temple ME. Pharmacotherapy of tinea capitis. J Amer Board Fam Pract. 1999;12:236-242.
MISCELLANEOUS
See also: Alopecia; Tinea corporis
BASICS
DESCRIPTION
• A fungal infection of the scalp and hair; often called "ringworm"
• Infection results from contact with infected persons or animals.
• Contagious and may become epidemic
• Affected areas of the scalp can show characteristic black dots resulting from broken hairs.
• System(s) Affected: Skin/Exocrine
• Synonym(s): Scalp ringworm
GENERAL PREVENTION
• Good personal hygiene
• Don't share headwear.
• Identification and treatment of infected individuals and household pets
EPIDEMIOLOGY
• Predominant age: Children, particularly ages 3-9 years. Adult infection is rare.
• Predominant sex: Male = Female
Incidence
Although still common, incidence and prevalence have dropped markedly over the past 30 years.
ALERT
Pediatric Considerations
Highest incidence in this age group
RISK FACTORS
• Day care centers or schools
• Living in confined quarters
• Poor hygiene
• Immunosuppression
ETIOLOGY
• 90% Trichophyton tonsurans
• 10% Microsporum species (canis, audouinii, gypseum)
DIAGNOSIS
SIGNS AND SYMPTOMS
• Infection commonly begins with round patches of scale (alopecia less common).
• Frequently, infection will take on the patterns of chronic scaling with little inflammation or marked inflammation and alopecia.
• Less frequently, patients will present with multiple patches of alopecia and characteristic black-dot pattern of broken hairs.
• Extreme inflammation results in kerion (exudative pustular nodulation).
TESTS
Viewed under a Wood lamp, the 10% of infections caused by Microsporum species will fluoresce a light green. 90% of tinea capitis infections, those caused by Trichophyton, will not fluoresce.
Lab
• Microscopy of a Potassium hydroxide preparation of hairs from affected area can show arthrospores that appear within hair shafts.
• Fungal culture of hairs from affected areas allows the infection to be confirmed and the causative organism to be identified.
Pathological Findings
• Chronic inflammation
• Superficial infection producing lesions with follicular pustules, abscess
• Hyphae in follicles, keratin of skin
DIFFERENTIAL DIAGNOSIS
• Psoriasis and seborrhea dermatitis are most often confused with tinea capitis.
• Pyoderma
• Alopecia areata and trichotillomania
• Aphasia cutis congenita
TREATMENT
Outpatient
GENERAL MEASURES
• Careful hand washing
• Launder towels, clothing, headwear of infected individual
• Check other family members
Diet
No special diet, except persons treated with griseofulvin should not be on a restricted-fat diet.
Activity
No restrictions
MEDICATION (DRUGS)
First Line
• Griseofulvin (Fulvicin P/G, Fulvicin U/F, Gris-PEG)(1,2A for Trichophyton and Microsporum)
- Microsized preparation
- Available in 125-mg, 250-mg, and 500-mg tablets and 125-mg/5-mL suspension
- Standard dose for griseofulvin used in trials is 125 mg/d in patients weighing 10-20 kg; 250 mg/d for 20-40 kg, and 500 mg/d > 40 kg taken b.i.d. or as a single daily for 6-12 weeks
• Oral terbinafine (Lamisil)(1A for Trichophyton) standard dosing for terbinafine is 62.5 mg/d in patients weighing 10-20 kg; 125 mg/d for 20-40 kg, and 250 mg/d > 40 kg for 2-4 weeks
• Itraconazole (Sporanox) (2A for Microsporum)
- Matches griseofulvin in treatment and is better tolerated
- 3-5 mg/kg/d, but most studies have used 100 mg/d for 6 weeks in children >2 years of age
• Contraindications
- Griseofulvin is contraindicated in patients with porphyria because of increased risk of hepatotoxicity.
• Precautions
- Griseofulvin: Headache in up to 10% of patients initially, but generally resolves after 1st week of treatment. Abdominal bloating, dyspepsia, and diarrhea also common. Hypersensitivity and liver toxicity rare. The manufacturer recommends monitoring liver functions while on griseofulvin.
- Terbinafin: Gastrointestinal symptoms (including diarrhea, dyspepsia, and abdominal pain), liver test abnormalities, and taste disturbances. In general, the adverse events were mild and transient
- Itraconazole: Nausea, vomiting, diarrhea, headache, dizziness, abnormal hepatic function tests, rare significant liver toxicity
• Significant possible interactions
- Griseofulvin accentuates the effect of alcohol and increases the metabolism of warfarin and oral contraceptives.
- Terbinafine clearance is increasedby rifampin, decreased by cimetidine.
Second Line
If kerion is present, prednisone 1 mg/kg/d can be added to antifungal therapy for 5-10 days. (3)[C]
ALERT
Pregnancy Considerations
Oral antifungals are contraindicated in pregnancy.
FOLLOW-UP
PROGNOSIS
• Without treatment, lesions will usually heal spontaneously in 6 months.
• Lesions with marked inflammation will resolve spontaneously much more rapidly but are more likely to leave scarring
COMPLICATIONS
Permanent scarring and hair loss from kerion
PATIENT MONITORING
• Recheck after 2 weeks of therapy to document improvement and after the 6-week course of therapy
• Patients might need liver function monitoringsee medication precautions
REFERENCES
1. Fuller LC, et al. A randomized comparison of 4 weeks of terbinafine vs. 8 weeks of griseofulvin for the treatment of tinea capitis. Br J Dermatol. 2001;144(2):321-327.
2. Gupta AK, et al. Therapeutic options for the treatment of tinea capitis caused by Trichophyton species: Griseofulvin versus the new oral antifungal agents, terbinafine, itraconazole, and fluconazole. Pediatr Dermatol. 2001;18:433-438.
3. Hussain I, et al. A randomized, comparative trial of treatment of kerion celsi with griseofulvin plus oral prednisolone vs. griseofulvin alone. Med Mycol. 1999;37(2):97-99.
4. Fuller LC, et al. Diagnosis and management of scalp ringworm. BMJ. 2003;326(7388):539-541.
5. Friedlander SF. The evolving role of itraconazole, fluconazole and terbinafine in the treatment of tinea capitis. Pediatr Infect Dis J. 1999;18:205-210.
6. Friedlander SF, et al. Terbinafine in the treatment of Trichophyton tinea capitis. Pediatrics. 2002;109:602-607.
7. Temple ME. Pharmacotherapy of tinea capitis. J Amer Board Fam Pract. 1999;12:236-242.
MISCELLANEOUS
See also: Alopecia; Tinea corporis
THYROIDITIS
THYROIDITIS - Richard P. Levy, MD
BASICS
DESCRIPTION
Variety of inflammatory thyroid disorders that can cause thyroid enlargement and thyroid atrophy; may lead to hypothyroidism or hyperthyroidism; complete resolution can occur (1)[B]
• Hashimoto disease
- Most common form
- Autoimmune disease, often presenting as asymptomatic diffuse goiter
- Often first detected after thyroid atrophy and hypothyroidism have occurred
- Can present as hyperthyroidism (Hashitoxicosis)
• Granulomatous thyroiditis (subacute)
- Probably related to viral infection
- Usually presents with thyroid pain, which may be severe
- Involves 1 or both thyroid lobes
- Accompanied by hyperthyroidism, followed by phase of mild hypothyroidism, then by permanent resolution to normal
• "Silent" thyroiditis
- Characterized by lack of pain
- One form is characterized by spontaneously resolving hypothyroidism and/or hyperthyroidism often associated with pregnancy. (2)[B]
- Another form has characteristics of granulomatous thyroiditis without the pain.
• Rare forms
- Suppurative: Due to bacterial infection of thyroid
- Radiation-induced: Due to ingested radionuclides or external irradiation
- Riedel: Dense infiltration of fibrous tissue into thyroid gland and surrounding structures; cause unknown
• Other forms
- Lymphocytic thyroiditis
- Postpartum onset of goiter and/or hypothyroidism that may resolve spontaneously
• System(s) Affected: Endocrine/Metabolic
ALERT
Pregnancy Considerations
• Avoid radioisotope scanning.
• Avoid hypothyroidism.
• Minimize use of antithyroid drugs. (3)[B]
EPIDEMIOLOGY
• Incidence/prevalence not known definitively
• Lymphocytic thyroiditis incidence increases with age, probably up to 10% > age 65
• Granulomatous thyroiditis is much less common and has an epidemic pattern.
• Predominant age: All ages, but predominantly postpuberty
• Predominant sex: Female > Male
RISK FACTORS
• Hashimoto disease
- Positive family history of thyroid disease or other autoimmume disease
- Preceding autoimmune diseases, including type I diabetes, primary adrenal insufficiency, rheumatoid arthritis, pregnancy/delivery
• Granulomatous thyroiditis
- Recent viral respiratory infection
- Other known cases in community
ETIOLOGY
• Hashimoto disease
- Autoimmune response of thyroid tissue
- Genetic susceptibility
• Granulomatous thyroiditis
- Chronic inflammatory response of thyroid tissue
- Preceding infection with any of a variety of viruses
ASSOCIATED CONDITIONS
Hashimoto disease: Other autoimmune diseases including
• Type I diabetes
• Primary adrenal insufficiency
• Premature ovarian failure
DIAGNOSIS
SIGNS AND SYMPTOMS
• Lymphocytic thyroiditis
- Insidious onset of goiter, often detected incidentally
- Slow onset of hypothyroidism
- Association with other autoimmune diseases
• Granulomatous thyroiditis
- Pain, tenderness, and enlargement of one or both thyroid lobes
- Malaise, fever
- Mild to moderate symptoms of hyperthyroidism
- History of recent respiratory infection
TESTS
Lab
• Hashimoto disease
- Elevated antithyroid antibodies (especially high titers of anti-thyroid peroxidase antibodies)
- Free thyroxine index 5 (normal 4.5-12) with thyroid-stimulating (TSH) >5 ug/dL (normal 0.5 to 5 ug/dL)
- Thyroid radioactive iodine uptake variable with scintiscan showing patchy distribution of radioiodine
- Positive cytopathology of fine needle aspirate or positive formal biopsy
• Granulomatous thyroiditis
- Elevated erythrocyte sedimentation rate
- Normal or moderately elevated WBC without a granulocyte shift to band forms
- Free thyroxine index >12, TSH undetectable, radioactive iodine uptake 5% in 24 hours (often nil) early in course
- Free thyroxine index 4.5 with radioactive iodine uptake above normal (>35% in 24 hours in the United States) late in course
• Immunometric assays
• CBC with differential count
• Drugs that may alter lab results
- Thyroid
- Corticosteroids
- Iodine-containing drugs and contrast media
- Lithium
- Amiodarone
• Disorders that may alter lab results
- Iodine deficiency
- Nonthyroidal illness
Imaging
• Thyroid radioiodine uptake and scan in granulomatous thyroiditis
• Ultrasonography if hemorrhage into thyroid cyst suspected
Diagnostic Procedures/Surgery
Needle biopsy in confusing cases
Pathological Findings
• Hashimoto disease
- Lymphocytic infiltration
- Oxyphilic changes in follicular cells
- Fibrosis
- Thyroid atrophy
• Granulomatous thyroiditis
- Giant cells
- Mononuclear cell infiltrate
DIFFERENTIAL DIAGNOSIS
• Hashimoto disease
- Simple goiter
- Iodine-deficient goiter (especially in endemic areas)
- Early Graves disease
- Lithium-induced goiter
• Granulomatous thyroiditis
- Infections of oropharynx and trachea
- Hemorrhage into a thyroid cyst
- Subacute systemic illness
- Suppurative thyroiditis
TREATMENT
GENERAL MEASURES
• Outpatient
• Analgesics for pain
• Corticosteroids for severe granulomatous thyroiditis
Diet
No special diet
Activity
Fully active
MEDICATION (DRUGS)
First Line
• Hashimoto disease
- If hypothyroid or goitrous: Levothyroxine (Synthroid, Levoxyl); generic may not be bioavailable; begin with 25 or 50 ug/d and titrate to TSH suppression to lower limit of assay normal range
- If thyrotoxic and symptomatic: Propylthiouracil and propranolol
• Granulomatous thyroiditis
- Pain: Analgesics, (e.g., codeine)
- Symptomatic hyperthyroidism: Propranolol 40 mg q6h
- Symptomatic hypothyroid phase: Levothyroxine 80 ug/100 Ibs (45.5 kg) body weight per day
- Severe symptoms: Prednisone once daily in lowest effective dose
• Maintenance: Optimal levothyroxine dose can be established by measuring TSH at 6- to 8-week intervals until the TSH is at a lower level of normal for the assay used
• Contraindications
- Propylthiouracil: Allergy or hypersensitivity to analgesics/narcotics
- Propranolol: Insulin therapy, asthma
- Prednisone: Adverse reactions
- Levothyroxine: None
• Precautions: Reduce doses of corticosteroids, propranolol, and narcotics as soon as feasible
• Significant possible interactions: Sucralfate (Carafate) and iron preparations may decrease levothyroxine availability
Second Line
Methimazole for propylthiouracil
FOLLOW-UP
PROGNOSIS
• Hashimoto disease: Persistent goiter, eventual thyroid failure
• Granulomatous thyroiditis: Eventual return to normal over weeks or months; remission may be slower in elderly
COMPLICATIONS
Treatment-induced hypothyroidism or hyperthyroidism
PATIENT MONITORING
• Hashimoto disease: Repeat thyroid function tests every 3-12 months
• Granulomatous thyroiditis: Repeat thyroid function tests every 3-6 weeks until permanently euthyroid and check every 6-12 months
REFERENCES
1. Burman KD. Thyroiditis. Wellesley, MA: UpToDate; 2004.
2. Muller AF, Drexhage HA, Berghout A. Postpartum thyroiditis and autoimmune thyroiditis in women of childbearing age: Recent insights and consequences for antenatal and postnatal care. Endocr Rev. 2001;22:605-630.
3. StagnaroGreen A. Recognizing, understanding, and treating postpartum thyroiditis. Endocrinol Metab Clin North Am. 2000;29:417-430.
MISCELLANEOUS
See also: Hyperthyroidism; Hypothyroidism, adult
BASICS
DESCRIPTION
Variety of inflammatory thyroid disorders that can cause thyroid enlargement and thyroid atrophy; may lead to hypothyroidism or hyperthyroidism; complete resolution can occur (1)[B]
• Hashimoto disease
- Most common form
- Autoimmune disease, often presenting as asymptomatic diffuse goiter
- Often first detected after thyroid atrophy and hypothyroidism have occurred
- Can present as hyperthyroidism (Hashitoxicosis)
• Granulomatous thyroiditis (subacute)
- Probably related to viral infection
- Usually presents with thyroid pain, which may be severe
- Involves 1 or both thyroid lobes
- Accompanied by hyperthyroidism, followed by phase of mild hypothyroidism, then by permanent resolution to normal
• "Silent" thyroiditis
- Characterized by lack of pain
- One form is characterized by spontaneously resolving hypothyroidism and/or hyperthyroidism often associated with pregnancy. (2)[B]
- Another form has characteristics of granulomatous thyroiditis without the pain.
• Rare forms
- Suppurative: Due to bacterial infection of thyroid
- Radiation-induced: Due to ingested radionuclides or external irradiation
- Riedel: Dense infiltration of fibrous tissue into thyroid gland and surrounding structures; cause unknown
• Other forms
- Lymphocytic thyroiditis
- Postpartum onset of goiter and/or hypothyroidism that may resolve spontaneously
• System(s) Affected: Endocrine/Metabolic
ALERT
Pregnancy Considerations
• Avoid radioisotope scanning.
• Avoid hypothyroidism.
• Minimize use of antithyroid drugs. (3)[B]
EPIDEMIOLOGY
• Incidence/prevalence not known definitively
• Lymphocytic thyroiditis incidence increases with age, probably up to 10% > age 65
• Granulomatous thyroiditis is much less common and has an epidemic pattern.
• Predominant age: All ages, but predominantly postpuberty
• Predominant sex: Female > Male
RISK FACTORS
• Hashimoto disease
- Positive family history of thyroid disease or other autoimmume disease
- Preceding autoimmune diseases, including type I diabetes, primary adrenal insufficiency, rheumatoid arthritis, pregnancy/delivery
• Granulomatous thyroiditis
- Recent viral respiratory infection
- Other known cases in community
ETIOLOGY
• Hashimoto disease
- Autoimmune response of thyroid tissue
- Genetic susceptibility
• Granulomatous thyroiditis
- Chronic inflammatory response of thyroid tissue
- Preceding infection with any of a variety of viruses
ASSOCIATED CONDITIONS
Hashimoto disease: Other autoimmune diseases including
• Type I diabetes
• Primary adrenal insufficiency
• Premature ovarian failure
DIAGNOSIS
SIGNS AND SYMPTOMS
• Lymphocytic thyroiditis
- Insidious onset of goiter, often detected incidentally
- Slow onset of hypothyroidism
- Association with other autoimmune diseases
• Granulomatous thyroiditis
- Pain, tenderness, and enlargement of one or both thyroid lobes
- Malaise, fever
- Mild to moderate symptoms of hyperthyroidism
- History of recent respiratory infection
TESTS
Lab
• Hashimoto disease
- Elevated antithyroid antibodies (especially high titers of anti-thyroid peroxidase antibodies)
- Free thyroxine index 5 (normal 4.5-12) with thyroid-stimulating (TSH) >5 ug/dL (normal 0.5 to 5 ug/dL)
- Thyroid radioactive iodine uptake variable with scintiscan showing patchy distribution of radioiodine
- Positive cytopathology of fine needle aspirate or positive formal biopsy
• Granulomatous thyroiditis
- Elevated erythrocyte sedimentation rate
- Normal or moderately elevated WBC without a granulocyte shift to band forms
- Free thyroxine index >12, TSH undetectable, radioactive iodine uptake 5% in 24 hours (often nil) early in course
- Free thyroxine index 4.5 with radioactive iodine uptake above normal (>35% in 24 hours in the United States) late in course
• Immunometric assays
• CBC with differential count
• Drugs that may alter lab results
- Thyroid
- Corticosteroids
- Iodine-containing drugs and contrast media
- Lithium
- Amiodarone
• Disorders that may alter lab results
- Iodine deficiency
- Nonthyroidal illness
Imaging
• Thyroid radioiodine uptake and scan in granulomatous thyroiditis
• Ultrasonography if hemorrhage into thyroid cyst suspected
Diagnostic Procedures/Surgery
Needle biopsy in confusing cases
Pathological Findings
• Hashimoto disease
- Lymphocytic infiltration
- Oxyphilic changes in follicular cells
- Fibrosis
- Thyroid atrophy
• Granulomatous thyroiditis
- Giant cells
- Mononuclear cell infiltrate
DIFFERENTIAL DIAGNOSIS
• Hashimoto disease
- Simple goiter
- Iodine-deficient goiter (especially in endemic areas)
- Early Graves disease
- Lithium-induced goiter
• Granulomatous thyroiditis
- Infections of oropharynx and trachea
- Hemorrhage into a thyroid cyst
- Subacute systemic illness
- Suppurative thyroiditis
TREATMENT
GENERAL MEASURES
• Outpatient
• Analgesics for pain
• Corticosteroids for severe granulomatous thyroiditis
Diet
No special diet
Activity
Fully active
MEDICATION (DRUGS)
First Line
• Hashimoto disease
- If hypothyroid or goitrous: Levothyroxine (Synthroid, Levoxyl); generic may not be bioavailable; begin with 25 or 50 ug/d and titrate to TSH suppression to lower limit of assay normal range
- If thyrotoxic and symptomatic: Propylthiouracil and propranolol
• Granulomatous thyroiditis
- Pain: Analgesics, (e.g., codeine)
- Symptomatic hyperthyroidism: Propranolol 40 mg q6h
- Symptomatic hypothyroid phase: Levothyroxine 80 ug/100 Ibs (45.5 kg) body weight per day
- Severe symptoms: Prednisone once daily in lowest effective dose
• Maintenance: Optimal levothyroxine dose can be established by measuring TSH at 6- to 8-week intervals until the TSH is at a lower level of normal for the assay used
• Contraindications
- Propylthiouracil: Allergy or hypersensitivity to analgesics/narcotics
- Propranolol: Insulin therapy, asthma
- Prednisone: Adverse reactions
- Levothyroxine: None
• Precautions: Reduce doses of corticosteroids, propranolol, and narcotics as soon as feasible
• Significant possible interactions: Sucralfate (Carafate) and iron preparations may decrease levothyroxine availability
Second Line
Methimazole for propylthiouracil
FOLLOW-UP
PROGNOSIS
• Hashimoto disease: Persistent goiter, eventual thyroid failure
• Granulomatous thyroiditis: Eventual return to normal over weeks or months; remission may be slower in elderly
COMPLICATIONS
Treatment-induced hypothyroidism or hyperthyroidism
PATIENT MONITORING
• Hashimoto disease: Repeat thyroid function tests every 3-12 months
• Granulomatous thyroiditis: Repeat thyroid function tests every 3-6 weeks until permanently euthyroid and check every 6-12 months
REFERENCES
1. Burman KD. Thyroiditis. Wellesley, MA: UpToDate; 2004.
2. Muller AF, Drexhage HA, Berghout A. Postpartum thyroiditis and autoimmune thyroiditis in women of childbearing age: Recent insights and consequences for antenatal and postnatal care. Endocr Rev. 2001;22:605-630.
3. StagnaroGreen A. Recognizing, understanding, and treating postpartum thyroiditis. Endocrinol Metab Clin North Am. 2000;29:417-430.
MISCELLANEOUS
See also: Hyperthyroidism; Hypothyroidism, adult
THYROIDITIS
THYROIDITIS - Richard P. Levy, MD
BASICS
DESCRIPTION
Variety of inflammatory thyroid disorders that can cause thyroid enlargement and thyroid atrophy; may lead to hypothyroidism or hyperthyroidism; complete resolution can occur (1)[B]
• Hashimoto disease
- Most common form
- Autoimmune disease, often presenting as asymptomatic diffuse goiter
- Often first detected after thyroid atrophy and hypothyroidism have occurred
- Can present as hyperthyroidism (Hashitoxicosis)
• Granulomatous thyroiditis (subacute)
- Probably related to viral infection
- Usually presents with thyroid pain, which may be severe
- Involves 1 or both thyroid lobes
- Accompanied by hyperthyroidism, followed by phase of mild hypothyroidism, then by permanent resolution to normal
• "Silent" thyroiditis
- Characterized by lack of pain
- One form is characterized by spontaneously resolving hypothyroidism and/or hyperthyroidism often associated with pregnancy. (2)[B]
- Another form has characteristics of granulomatous thyroiditis without the pain.
• Rare forms
- Suppurative: Due to bacterial infection of thyroid
- Radiation-induced: Due to ingested radionuclides or external irradiation
- Riedel: Dense infiltration of fibrous tissue into thyroid gland and surrounding structures; cause unknown
• Other forms
- Lymphocytic thyroiditis
- Postpartum onset of goiter and/or hypothyroidism that may resolve spontaneously
• System(s) Affected: Endocrine/Metabolic
ALERT
Pregnancy Considerations
• Avoid radioisotope scanning.
• Avoid hypothyroidism.
• Minimize use of antithyroid drugs. (3)[B]
EPIDEMIOLOGY
• Incidence/prevalence not known definitively
• Lymphocytic thyroiditis incidence increases with age, probably up to 10% > age 65
• Granulomatous thyroiditis is much less common and has an epidemic pattern.
• Predominant age: All ages, but predominantly postpuberty
• Predominant sex: Female > Male
RISK FACTORS
• Hashimoto disease
- Positive family history of thyroid disease or other autoimmume disease
- Preceding autoimmune diseases, including type I diabetes, primary adrenal insufficiency, rheumatoid arthritis, pregnancy/delivery
• Granulomatous thyroiditis
- Recent viral respiratory infection
- Other known cases in community
ETIOLOGY
• Hashimoto disease
- Autoimmune response of thyroid tissue
- Genetic susceptibility
• Granulomatous thyroiditis
- Chronic inflammatory response of thyroid tissue
- Preceding infection with any of a variety of viruses
ASSOCIATED CONDITIONS
Hashimoto disease: Other autoimmune diseases including
• Type I diabetes
• Primary adrenal insufficiency
• Premature ovarian failure
DIAGNOSIS
SIGNS AND SYMPTOMS
• Lymphocytic thyroiditis
- Insidious onset of goiter, often detected incidentally
- Slow onset of hypothyroidism
- Association with other autoimmune diseases
• Granulomatous thyroiditis
- Pain, tenderness, and enlargement of one or both thyroid lobes
- Malaise, fever
- Mild to moderate symptoms of hyperthyroidism
- History of recent respiratory infection
TESTS
Lab
• Hashimoto disease
- Elevated antithyroid antibodies (especially high titers of anti-thyroid peroxidase antibodies)
- Free thyroxine index 5 (normal 4.5-12) with thyroid-stimulating (TSH) >5 ug/dL (normal 0.5 to 5 ug/dL)
- Thyroid radioactive iodine uptake variable with scintiscan showing patchy distribution of radioiodine
- Positive cytopathology of fine needle aspirate or positive formal biopsy
• Granulomatous thyroiditis
- Elevated erythrocyte sedimentation rate
- Normal or moderately elevated WBC without a granulocyte shift to band forms
- Free thyroxine index >12, TSH undetectable, radioactive iodine uptake 5% in 24 hours (often nil) early in course
- Free thyroxine index 4.5 with radioactive iodine uptake above normal (>35% in 24 hours in the United States) late in course
• Immunometric assays
• CBC with differential count
• Drugs that may alter lab results
- Thyroid
- Corticosteroids
- Iodine-containing drugs and contrast media
- Lithium
- Amiodarone
• Disorders that may alter lab results
- Iodine deficiency
- Nonthyroidal illness
Imaging
• Thyroid radioiodine uptake and scan in granulomatous thyroiditis
• Ultrasonography if hemorrhage into thyroid cyst suspected
Diagnostic Procedures/Surgery
Needle biopsy in confusing cases
Pathological Findings
• Hashimoto disease
- Lymphocytic infiltration
- Oxyphilic changes in follicular cells
- Fibrosis
- Thyroid atrophy
• Granulomatous thyroiditis
- Giant cells
- Mononuclear cell infiltrate
DIFFERENTIAL DIAGNOSIS
• Hashimoto disease
- Simple goiter
- Iodine-deficient goiter (especially in endemic areas)
- Early Graves disease
- Lithium-induced goiter
• Granulomatous thyroiditis
- Infections of oropharynx and trachea
- Hemorrhage into a thyroid cyst
- Subacute systemic illness
- Suppurative thyroiditis
TREATMENT
GENERAL MEASURES
• Outpatient
• Analgesics for pain
• Corticosteroids for severe granulomatous thyroiditis
Diet
No special diet
Activity
Fully active
MEDICATION (DRUGS)
First Line
• Hashimoto disease
- If hypothyroid or goitrous: Levothyroxine (Synthroid, Levoxyl); generic may not be bioavailable; begin with 25 or 50 ug/d and titrate to TSH suppression to lower limit of assay normal range
- If thyrotoxic and symptomatic: Propylthiouracil and propranolol
• Granulomatous thyroiditis
- Pain: Analgesics, (e.g., codeine)
- Symptomatic hyperthyroidism: Propranolol 40 mg q6h
- Symptomatic hypothyroid phase: Levothyroxine 80 ug/100 Ibs (45.5 kg) body weight per day
- Severe symptoms: Prednisone once daily in lowest effective dose
• Maintenance: Optimal levothyroxine dose can be established by measuring TSH at 6- to 8-week intervals until the TSH is at a lower level of normal for the assay used
• Contraindications
- Propylthiouracil: Allergy or hypersensitivity to analgesics/narcotics
- Propranolol: Insulin therapy, asthma
- Prednisone: Adverse reactions
- Levothyroxine: None
• Precautions: Reduce doses of corticosteroids, propranolol, and narcotics as soon as feasible
• Significant possible interactions: Sucralfate (Carafate) and iron preparations may decrease levothyroxine availability
Second Line
Methimazole for propylthiouracil
FOLLOW-UP
PROGNOSIS
• Hashimoto disease: Persistent goiter, eventual thyroid failure
• Granulomatous thyroiditis: Eventual return to normal over weeks or months; remission may be slower in elderly
COMPLICATIONS
Treatment-induced hypothyroidism or hyperthyroidism
PATIENT MONITORING
• Hashimoto disease: Repeat thyroid function tests every 3-12 months
• Granulomatous thyroiditis: Repeat thyroid function tests every 3-6 weeks until permanently euthyroid and check every 6-12 months
REFERENCES
1. Burman KD. Thyroiditis. Wellesley, MA: UpToDate; 2004.
2. Muller AF, Drexhage HA, Berghout A. Postpartum thyroiditis and autoimmune thyroiditis in women of childbearing age: Recent insights and consequences for antenatal and postnatal care. Endocr Rev. 2001;22:605-630.
3. StagnaroGreen A. Recognizing, understanding, and treating postpartum thyroiditis. Endocrinol Metab Clin North Am. 2000;29:417-430.
MISCELLANEOUS
See also: Hyperthyroidism; Hypothyroidism, adult
BASICS
DESCRIPTION
Variety of inflammatory thyroid disorders that can cause thyroid enlargement and thyroid atrophy; may lead to hypothyroidism or hyperthyroidism; complete resolution can occur (1)[B]
• Hashimoto disease
- Most common form
- Autoimmune disease, often presenting as asymptomatic diffuse goiter
- Often first detected after thyroid atrophy and hypothyroidism have occurred
- Can present as hyperthyroidism (Hashitoxicosis)
• Granulomatous thyroiditis (subacute)
- Probably related to viral infection
- Usually presents with thyroid pain, which may be severe
- Involves 1 or both thyroid lobes
- Accompanied by hyperthyroidism, followed by phase of mild hypothyroidism, then by permanent resolution to normal
• "Silent" thyroiditis
- Characterized by lack of pain
- One form is characterized by spontaneously resolving hypothyroidism and/or hyperthyroidism often associated with pregnancy. (2)[B]
- Another form has characteristics of granulomatous thyroiditis without the pain.
• Rare forms
- Suppurative: Due to bacterial infection of thyroid
- Radiation-induced: Due to ingested radionuclides or external irradiation
- Riedel: Dense infiltration of fibrous tissue into thyroid gland and surrounding structures; cause unknown
• Other forms
- Lymphocytic thyroiditis
- Postpartum onset of goiter and/or hypothyroidism that may resolve spontaneously
• System(s) Affected: Endocrine/Metabolic
ALERT
Pregnancy Considerations
• Avoid radioisotope scanning.
• Avoid hypothyroidism.
• Minimize use of antithyroid drugs. (3)[B]
EPIDEMIOLOGY
• Incidence/prevalence not known definitively
• Lymphocytic thyroiditis incidence increases with age, probably up to 10% > age 65
• Granulomatous thyroiditis is much less common and has an epidemic pattern.
• Predominant age: All ages, but predominantly postpuberty
• Predominant sex: Female > Male
RISK FACTORS
• Hashimoto disease
- Positive family history of thyroid disease or other autoimmume disease
- Preceding autoimmune diseases, including type I diabetes, primary adrenal insufficiency, rheumatoid arthritis, pregnancy/delivery
• Granulomatous thyroiditis
- Recent viral respiratory infection
- Other known cases in community
ETIOLOGY
• Hashimoto disease
- Autoimmune response of thyroid tissue
- Genetic susceptibility
• Granulomatous thyroiditis
- Chronic inflammatory response of thyroid tissue
- Preceding infection with any of a variety of viruses
ASSOCIATED CONDITIONS
Hashimoto disease: Other autoimmune diseases including
• Type I diabetes
• Primary adrenal insufficiency
• Premature ovarian failure
DIAGNOSIS
SIGNS AND SYMPTOMS
• Lymphocytic thyroiditis
- Insidious onset of goiter, often detected incidentally
- Slow onset of hypothyroidism
- Association with other autoimmune diseases
• Granulomatous thyroiditis
- Pain, tenderness, and enlargement of one or both thyroid lobes
- Malaise, fever
- Mild to moderate symptoms of hyperthyroidism
- History of recent respiratory infection
TESTS
Lab
• Hashimoto disease
- Elevated antithyroid antibodies (especially high titers of anti-thyroid peroxidase antibodies)
- Free thyroxine index 5 (normal 4.5-12) with thyroid-stimulating (TSH) >5 ug/dL (normal 0.5 to 5 ug/dL)
- Thyroid radioactive iodine uptake variable with scintiscan showing patchy distribution of radioiodine
- Positive cytopathology of fine needle aspirate or positive formal biopsy
• Granulomatous thyroiditis
- Elevated erythrocyte sedimentation rate
- Normal or moderately elevated WBC without a granulocyte shift to band forms
- Free thyroxine index >12, TSH undetectable, radioactive iodine uptake 5% in 24 hours (often nil) early in course
- Free thyroxine index 4.5 with radioactive iodine uptake above normal (>35% in 24 hours in the United States) late in course
• Immunometric assays
• CBC with differential count
• Drugs that may alter lab results
- Thyroid
- Corticosteroids
- Iodine-containing drugs and contrast media
- Lithium
- Amiodarone
• Disorders that may alter lab results
- Iodine deficiency
- Nonthyroidal illness
Imaging
• Thyroid radioiodine uptake and scan in granulomatous thyroiditis
• Ultrasonography if hemorrhage into thyroid cyst suspected
Diagnostic Procedures/Surgery
Needle biopsy in confusing cases
Pathological Findings
• Hashimoto disease
- Lymphocytic infiltration
- Oxyphilic changes in follicular cells
- Fibrosis
- Thyroid atrophy
• Granulomatous thyroiditis
- Giant cells
- Mononuclear cell infiltrate
DIFFERENTIAL DIAGNOSIS
• Hashimoto disease
- Simple goiter
- Iodine-deficient goiter (especially in endemic areas)
- Early Graves disease
- Lithium-induced goiter
• Granulomatous thyroiditis
- Infections of oropharynx and trachea
- Hemorrhage into a thyroid cyst
- Subacute systemic illness
- Suppurative thyroiditis
TREATMENT
GENERAL MEASURES
• Outpatient
• Analgesics for pain
• Corticosteroids for severe granulomatous thyroiditis
Diet
No special diet
Activity
Fully active
MEDICATION (DRUGS)
First Line
• Hashimoto disease
- If hypothyroid or goitrous: Levothyroxine (Synthroid, Levoxyl); generic may not be bioavailable; begin with 25 or 50 ug/d and titrate to TSH suppression to lower limit of assay normal range
- If thyrotoxic and symptomatic: Propylthiouracil and propranolol
• Granulomatous thyroiditis
- Pain: Analgesics, (e.g., codeine)
- Symptomatic hyperthyroidism: Propranolol 40 mg q6h
- Symptomatic hypothyroid phase: Levothyroxine 80 ug/100 Ibs (45.5 kg) body weight per day
- Severe symptoms: Prednisone once daily in lowest effective dose
• Maintenance: Optimal levothyroxine dose can be established by measuring TSH at 6- to 8-week intervals until the TSH is at a lower level of normal for the assay used
• Contraindications
- Propylthiouracil: Allergy or hypersensitivity to analgesics/narcotics
- Propranolol: Insulin therapy, asthma
- Prednisone: Adverse reactions
- Levothyroxine: None
• Precautions: Reduce doses of corticosteroids, propranolol, and narcotics as soon as feasible
• Significant possible interactions: Sucralfate (Carafate) and iron preparations may decrease levothyroxine availability
Second Line
Methimazole for propylthiouracil
FOLLOW-UP
PROGNOSIS
• Hashimoto disease: Persistent goiter, eventual thyroid failure
• Granulomatous thyroiditis: Eventual return to normal over weeks or months; remission may be slower in elderly
COMPLICATIONS
Treatment-induced hypothyroidism or hyperthyroidism
PATIENT MONITORING
• Hashimoto disease: Repeat thyroid function tests every 3-12 months
• Granulomatous thyroiditis: Repeat thyroid function tests every 3-6 weeks until permanently euthyroid and check every 6-12 months
REFERENCES
1. Burman KD. Thyroiditis. Wellesley, MA: UpToDate; 2004.
2. Muller AF, Drexhage HA, Berghout A. Postpartum thyroiditis and autoimmune thyroiditis in women of childbearing age: Recent insights and consequences for antenatal and postnatal care. Endocr Rev. 2001;22:605-630.
3. StagnaroGreen A. Recognizing, understanding, and treating postpartum thyroiditis. Endocrinol Metab Clin North Am. 2000;29:417-430.
MISCELLANEOUS
See also: Hyperthyroidism; Hypothyroidism, adult
THYROID MALIGNANT NEOPLASIA
THYROID MALIGNANT NEOPLASIA - James P. Miller, MD; Timothy L. Black, MD
BASICS
DESCRIPTION
Autologous growth of thyroid nodules with potential for metastases
• Papillary carcinoma
- Most common variety, 60-70% of thyroid tumors
- May be associated with radiation exposure
- Tumor contains psammoma bodies
- Metastasizes by lymphatic route (30% at time of diagnosis)
- Multicentric
• Follicular carcinoma
- 10-20% of thyroid tumors
- Incidence has been decreasing since the addition of dietary iodine.
- Occurs usually in females >40 years of age
- Metastasizes by the hematogenous route
• Hurthle cell carcinoma
- Usually in patients >60 years of age
- Radioresistant
- Composed of distinct large eosinophilic cells with abundant cytoplasmic mitochondria
• Medullary carcinoma (MTC)
- Arises from parafollicular cells, C-cells
- 2-5% of all thyroid tumors
- 25-35% are associated with multiple endocrine neoplasia syndromes, which can be familial or sporadic.
- Calcitonin is a chemical marker.
• Anaplastic carcinoma
- 3% of thyroid tumors
- Usually in patients >60 years of age
• Other: Lymphoma, sarcoma, or metastatic (renal, breast, or lung)
• System(s) Affected: Endocrine/Metabolic
• Synonym(s): Follicular carcinoma of the thyroid; Papillary carcinoma of the thyroid; Hurthle cell carcinoma of the thyroid; Anaplastic cell carcinoma of the thyroid
ALERT
Geriatric Considerations
Risk of malignancy increases over age 60.
Pediatric Considerations
>60% of thyroid nodules are malignant.
GENERAL PREVENTION
• Physical exam in high-risk group
• Calcium infusion or pentagastrin stimulation test in high-risk multiple endocrine neoplasia patients
EPIDEMIOLOGY
• Predominant age: Usually > 40 years of age
• Predominant sex: Female > Male (2.6:1)
Incidence
• 10/100,000/yr in United States
• 6 deaths/1,000,000/yr in United States
RISK FACTORS
• Family history
• Neck irradiation (6-2,000 rads): Papillary carcinoma
• Iodine deficiency: Follicular carcinoma
• Multiple endocrine neoplasia syndrome: Medullary carcinoma
• Previous history of less than a total thyroidectomy for malignancy: Anaplastic carcinoma
Genetics
• Medullary: Autosomal dominant with multiple endocrine neoplasia syndrome
• BRAF mutation
• RET oncogene
ETIOLOGY
Unknown
ASSOCIATED CONDITIONS
Medullary carcinoma: Pheochromocytoma, hyperparathyroidism, ganglioneuroma of the gastrointestinal tract, neuromata of mucosal membranes
DIAGNOSIS
SIGNS AND SYMPTOMS
History
• Change in voice
• Positive family history
• Neck mass
• Dysphagia
• Dyspnea
Physical Exam
• Neck mass, if fixed suggest advanced disease
• Cervical adenopathy
TESTS
• Medullary carcinoma: Calcitonin level (normal is 30 pg/mL [300 ng/L]), Pentagastrin stimulation test
• Thyroglobulin level (TG): Postoperative tumor marker
• DNA content of tumors from biopsy specimen; diploid content has a better prognosis
Lab
Thyroid function tests usually normal
Imaging
• Thyroid scan: Cold nodules are more suspicious of malignancy.
• Ultrasound: Solid mass is more suspicious of malignancy
• CT and MRI can be useful to evaluate large substernal masses and recurrent soft tissue masses.
• 18F-FDG positron emission tomography scan can help if the cytology is inconclusive. Helpful with recurrent disease when patient has negative I131scan and an elevated TG level (1)[C]
Diagnostic Procedures/Surgery
• Fine-needle aspiration
• Surgical biopsy/excision
• Laryngoscopy, if vocal cord paralysis is suspected
Pathological Findings
• Papillary: Psammoma bodies, anaplastic epithelial papillae
• Follicular: Anaplastic epithelial cords with follicles
• Hurthle cell: Large eosinophilic cells with granular cytoplasm
• Medullary: Large amounts of amyloid stroma
• Anaplastic: Small cell and giant cell undifferentiated tumors
DIFFERENTIAL DIAGNOSIS
• Multinodular goiter
• Thyroid adenoma
• Thyroglossal duct cyst
• Thyroiditis
• Thyroid cyst
• Ectopic thyroid
• Dermoid cyst
TREATMENT
Inpatient
GENERAL MEASURES
Diet
Avoid iodine deficiency.
Activity
As tolerated
SPECIAL THERAPY
Radiotherapy
• I131thyroid remnant ablation
• External beam radiation for advanced disease
MEDICATION (DRUGS)
• Postoperatively will require thyroid replacement to suppress serum thyroid-stimulating hormone (TSH) level
- Levothyroxine (T4, Synthroid) 100-200 ug/d or
- Liothyronine (T3, Cytomel) 50-100 ug/d
• Significant possible interactions
- Amphetamines
- Anticoagulants
- Tricyclic antidepressants
- Antidiabetic medications
- Aspirin
- Barbiturates
- -Adrenergic blockers
- Cholestyramine
- Colestipol
- Oral contraceptives
- Digitalis preparation
- Ephedrine
- Estrogens
- Methylphenidate
- Phenytoin
SURGERY
• Papillary carcinoma: Lobectomy with isthmectomy (if lesion 1.5 cm) or total thyroidectomy and removal of suspicious lymph nodes
• Follicular carcinoma and Hurthle cell: Total thyroidectomy and removal of suspicious lymph nodes
• Medullary carcinoma: Total thyroidectomy with central node dissection. Unilateral or bilateral modified radical neck dissection if lateral nodes are histologically positive
• Anaplastic carcinoma: Aggressive en bloc thyroidectomy; tracheostomy often required
FOLLOW-UP
PROGNOSIS
• Papillary carcinoma: Overall mortality 3-8%
• Follicular carcinoma: Overall 80% 5-year survival rate, 77% 10-year survival rate. Histologically microinvasive tumors parallel papillary tumor results, whereas grossly invasive tumors do far worse.
• Hurthle cell carcinoma: 93% 5-year survival rate and 83% survival rate overall. Grossly invasive tumorssurvival is 25%.
• Medullary carcinoma: Negative nodes 90% 5-year survival rate and 85% 10-year survival rate; with positive nodes 65% 5-year survival rate and 40% 10-year survival rate
• Anaplastic carcinoma: Survival unexpected
COMPLICATIONS
Recurrence of tumor
PATIENT MONITORING
• Thyroid scan at 6 weeks and administration of iodine-131 for any visible uptake evidence of residual thyroid tissue (after total thyroidectomy) or lymph node disease is treated with radioactive iodine
• At 6 months and then yearly, the patient should have a thyroid scan and chest radiograph.
• Papillary and follicular: A thyroglobulin level should be done yearly. rhTSH stimulated thyroglobulin level may be more sensitive. (2,3)[B]
• Medullary: Calcitonin level should be done yearly with pentagastrin stimulation.
• The thyroid scan and thyroglobulin level should be done with the patient in the hypothyroid state induced by 6-week withdrawal of levothyroxine or 2- to 3-week withdrawal of liothyronine.
REFERENCES
1. Wang W, et al. Prognostic value of [18F]-Fluorodeoxyglucose positron emission tomographic scanning in patients with thyroid cancer. J Clin Endocrinol Metab. 2000;85:1107-1113.
2. Blamey S, et al. Using recombinant Human TSH for the diagnosis of recurrent thyroid cancer. ANZ Journal of Surg. 2005;75:10-20.
3. Haugen BR, et al. A comparison of recombinant human thyrotropin and thyroid hormone withdrawal for the detection of thyroid remnant or cancer. J Clin Endocrinol Metab. 1999;84:3877-3885.
4. www.thyroidmanager.org/chapter18/18-nodu-cancer.htm
5. Gagel RF, Goepfert H, Callender RL. Changing concepts in the pathogenesis and management of thyroid carcinoma. CA Cancer J Clin. 1996;46:261-283.
BASICS
DESCRIPTION
Autologous growth of thyroid nodules with potential for metastases
• Papillary carcinoma
- Most common variety, 60-70% of thyroid tumors
- May be associated with radiation exposure
- Tumor contains psammoma bodies
- Metastasizes by lymphatic route (30% at time of diagnosis)
- Multicentric
• Follicular carcinoma
- 10-20% of thyroid tumors
- Incidence has been decreasing since the addition of dietary iodine.
- Occurs usually in females >40 years of age
- Metastasizes by the hematogenous route
• Hurthle cell carcinoma
- Usually in patients >60 years of age
- Radioresistant
- Composed of distinct large eosinophilic cells with abundant cytoplasmic mitochondria
• Medullary carcinoma (MTC)
- Arises from parafollicular cells, C-cells
- 2-5% of all thyroid tumors
- 25-35% are associated with multiple endocrine neoplasia syndromes, which can be familial or sporadic.
- Calcitonin is a chemical marker.
• Anaplastic carcinoma
- 3% of thyroid tumors
- Usually in patients >60 years of age
• Other: Lymphoma, sarcoma, or metastatic (renal, breast, or lung)
• System(s) Affected: Endocrine/Metabolic
• Synonym(s): Follicular carcinoma of the thyroid; Papillary carcinoma of the thyroid; Hurthle cell carcinoma of the thyroid; Anaplastic cell carcinoma of the thyroid
ALERT
Geriatric Considerations
Risk of malignancy increases over age 60.
Pediatric Considerations
>60% of thyroid nodules are malignant.
GENERAL PREVENTION
• Physical exam in high-risk group
• Calcium infusion or pentagastrin stimulation test in high-risk multiple endocrine neoplasia patients
EPIDEMIOLOGY
• Predominant age: Usually > 40 years of age
• Predominant sex: Female > Male (2.6:1)
Incidence
• 10/100,000/yr in United States
• 6 deaths/1,000,000/yr in United States
RISK FACTORS
• Family history
• Neck irradiation (6-2,000 rads): Papillary carcinoma
• Iodine deficiency: Follicular carcinoma
• Multiple endocrine neoplasia syndrome: Medullary carcinoma
• Previous history of less than a total thyroidectomy for malignancy: Anaplastic carcinoma
Genetics
• Medullary: Autosomal dominant with multiple endocrine neoplasia syndrome
• BRAF mutation
• RET oncogene
ETIOLOGY
Unknown
ASSOCIATED CONDITIONS
Medullary carcinoma: Pheochromocytoma, hyperparathyroidism, ganglioneuroma of the gastrointestinal tract, neuromata of mucosal membranes
DIAGNOSIS
SIGNS AND SYMPTOMS
History
• Change in voice
• Positive family history
• Neck mass
• Dysphagia
• Dyspnea
Physical Exam
• Neck mass, if fixed suggest advanced disease
• Cervical adenopathy
TESTS
• Medullary carcinoma: Calcitonin level (normal is 30 pg/mL [300 ng/L]), Pentagastrin stimulation test
• Thyroglobulin level (TG): Postoperative tumor marker
• DNA content of tumors from biopsy specimen; diploid content has a better prognosis
Lab
Thyroid function tests usually normal
Imaging
• Thyroid scan: Cold nodules are more suspicious of malignancy.
• Ultrasound: Solid mass is more suspicious of malignancy
• CT and MRI can be useful to evaluate large substernal masses and recurrent soft tissue masses.
• 18F-FDG positron emission tomography scan can help if the cytology is inconclusive. Helpful with recurrent disease when patient has negative I131scan and an elevated TG level (1)[C]
Diagnostic Procedures/Surgery
• Fine-needle aspiration
• Surgical biopsy/excision
• Laryngoscopy, if vocal cord paralysis is suspected
Pathological Findings
• Papillary: Psammoma bodies, anaplastic epithelial papillae
• Follicular: Anaplastic epithelial cords with follicles
• Hurthle cell: Large eosinophilic cells with granular cytoplasm
• Medullary: Large amounts of amyloid stroma
• Anaplastic: Small cell and giant cell undifferentiated tumors
DIFFERENTIAL DIAGNOSIS
• Multinodular goiter
• Thyroid adenoma
• Thyroglossal duct cyst
• Thyroiditis
• Thyroid cyst
• Ectopic thyroid
• Dermoid cyst
TREATMENT
Inpatient
GENERAL MEASURES
Diet
Avoid iodine deficiency.
Activity
As tolerated
SPECIAL THERAPY
Radiotherapy
• I131thyroid remnant ablation
• External beam radiation for advanced disease
MEDICATION (DRUGS)
• Postoperatively will require thyroid replacement to suppress serum thyroid-stimulating hormone (TSH) level
- Levothyroxine (T4, Synthroid) 100-200 ug/d or
- Liothyronine (T3, Cytomel) 50-100 ug/d
• Significant possible interactions
- Amphetamines
- Anticoagulants
- Tricyclic antidepressants
- Antidiabetic medications
- Aspirin
- Barbiturates
- -Adrenergic blockers
- Cholestyramine
- Colestipol
- Oral contraceptives
- Digitalis preparation
- Ephedrine
- Estrogens
- Methylphenidate
- Phenytoin
SURGERY
• Papillary carcinoma: Lobectomy with isthmectomy (if lesion 1.5 cm) or total thyroidectomy and removal of suspicious lymph nodes
• Follicular carcinoma and Hurthle cell: Total thyroidectomy and removal of suspicious lymph nodes
• Medullary carcinoma: Total thyroidectomy with central node dissection. Unilateral or bilateral modified radical neck dissection if lateral nodes are histologically positive
• Anaplastic carcinoma: Aggressive en bloc thyroidectomy; tracheostomy often required
FOLLOW-UP
PROGNOSIS
• Papillary carcinoma: Overall mortality 3-8%
• Follicular carcinoma: Overall 80% 5-year survival rate, 77% 10-year survival rate. Histologically microinvasive tumors parallel papillary tumor results, whereas grossly invasive tumors do far worse.
• Hurthle cell carcinoma: 93% 5-year survival rate and 83% survival rate overall. Grossly invasive tumorssurvival is 25%.
• Medullary carcinoma: Negative nodes 90% 5-year survival rate and 85% 10-year survival rate; with positive nodes 65% 5-year survival rate and 40% 10-year survival rate
• Anaplastic carcinoma: Survival unexpected
COMPLICATIONS
Recurrence of tumor
PATIENT MONITORING
• Thyroid scan at 6 weeks and administration of iodine-131 for any visible uptake evidence of residual thyroid tissue (after total thyroidectomy) or lymph node disease is treated with radioactive iodine
• At 6 months and then yearly, the patient should have a thyroid scan and chest radiograph.
• Papillary and follicular: A thyroglobulin level should be done yearly. rhTSH stimulated thyroglobulin level may be more sensitive. (2,3)[B]
• Medullary: Calcitonin level should be done yearly with pentagastrin stimulation.
• The thyroid scan and thyroglobulin level should be done with the patient in the hypothyroid state induced by 6-week withdrawal of levothyroxine or 2- to 3-week withdrawal of liothyronine.
REFERENCES
1. Wang W, et al. Prognostic value of [18F]-Fluorodeoxyglucose positron emission tomographic scanning in patients with thyroid cancer. J Clin Endocrinol Metab. 2000;85:1107-1113.
2. Blamey S, et al. Using recombinant Human TSH for the diagnosis of recurrent thyroid cancer. ANZ Journal of Surg. 2005;75:10-20.
3. Haugen BR, et al. A comparison of recombinant human thyrotropin and thyroid hormone withdrawal for the detection of thyroid remnant or cancer. J Clin Endocrinol Metab. 1999;84:3877-3885.
4. www.thyroidmanager.org/chapter18/18-nodu-cancer.htm
5. Gagel RF, Goepfert H, Callender RL. Changing concepts in the pathogenesis and management of thyroid carcinoma. CA Cancer J Clin. 1996;46:261-283.
THYROGLOSSAL DUCT CYST
THYROGLOSSAL DUCT CYST - Maryellen Antonetti, MPH, PA-C, RN
BASICS
DESCRIPTION
• Persistence of thyroglossal duct or remnant with fluid accumulation (cyst) following embryologic thyroid descent in the neck
• Usually midline, single, smooth, and mobile
• Reported to be the most common congenital thyroid malformation seen on ultrasound.
• System(s) Affected: Endocrine/Metabolic; Skin/Exocrine
EPIDEMIOLOGY
• Predominant age: 50% 10 years, 65% 20 years
• Predominant sex: Male = Female
RISK FACTORS
None
Genetics
Familial inheritance is rare, with dominance being the most common.
ETIOLOGY
Failure of the thyroglossal duct to obliterate after descent of the thyroid in the 6th gestational week
DIAGNOSIS
SIGNS AND SYMPTOMS
History
• Swelling
• Pain
• Redness
• Palpable neck mass
Physical Exam
• Midline neck mass
• Nontender, unless infected
• Rises in the neck with tongue protrusion and swallowing
• 80% juxtaposed to the hyoid bone
• Palpate cervical and supraclavicular nodes
• Doppler to evaluate vascularity
TESTS
Lab
Thyroid stimulating hormone
Imaging
• Ultrasound
• Thyroid scan if midline ectopic thyroid or thyroid nodule is suspected
• Small roll under shoulders allows exposure of neck in infants.
Diagnostic Procedures/Surgery
If infected, may need initial drainage before definitive resection
Pathological Findings
• Cyst lined with stratified squamous or pseudostratified ciliated columnar epithelium
• Thyroid tissue seen in 10-45% of cysts
• Reports show traces of the thyroglossal duct located near the hyoid bone, superior to thyroid isthmus or lingually.
DIFFERENTIAL DIAGNOSIS
• Ectopic midline thyroid
• Dermoid cyst
• Thyroid adenoma of isthmus or pyramidal lobe
• Lymphadenitis
• Cervical thymic cyst
TREATMENT
Outpatient surgery under general anesthesia
GENERAL MEASURES
Diet
Unrestricted
Activity
Unrestricted
MEDICATION (DRUGS)
None. All thyroglossal duct cysts should be surgically removed.
SURGERY
• Once diagnosed, the excision can be done using the Sistrunk procedure. This requires removal of the center portion of the hyoid bone to minimize recurrence.
• If the cyst is infected, it should be initially treated (antibiotics and local heat) and/or drained. After resolution of the inflammation, excision should be performed (1,2)[C].
FOLLOW-UP
DISPOSITION
Admission Criteria
Drainage of abscess
PROGNOSIS
Resolution with resection (5% recurrence using the Sistrunk procedure)
COMPLICATIONS
• Infection and malignant degeneration may occur if cyst is not excised.
• Reports demonstrate that the location of such masses (lingual) can cause not only various respiratory problems but also infant death.
• Wide local excision is a valuable extension of the Sistrunk operation for the management of recurrent disease (4)[A].
PATIENT MONITORING
One to 2 weeks after drainage or resection
REFERENCES
1. Ostlie DJ, et al. Thyroglossal duct infections and surgical outcomes. J Pediatr Surg. 2004;39:396-399.
2. Kaselas CH, et al. Thyroglossal duct cyst's inflammation. When do we operate? Pediatr Surg Int. 2005;21:991-993.
3. Schader I, et al. Hereditary duct cyst. Pediatric Surg Int. 2005;21(7):593-594.
4. Patel NN, Hartley BEJ, Howard DJ. Management of thyroglossal tract disease after failed Sistrunk's procedure. J Laryngol Otol. 2003;117(9):710-712.[A]
BASICS
DESCRIPTION
• Persistence of thyroglossal duct or remnant with fluid accumulation (cyst) following embryologic thyroid descent in the neck
• Usually midline, single, smooth, and mobile
• Reported to be the most common congenital thyroid malformation seen on ultrasound.
• System(s) Affected: Endocrine/Metabolic; Skin/Exocrine
EPIDEMIOLOGY
• Predominant age: 50% 10 years, 65% 20 years
• Predominant sex: Male = Female
RISK FACTORS
None
Genetics
Familial inheritance is rare, with dominance being the most common.
ETIOLOGY
Failure of the thyroglossal duct to obliterate after descent of the thyroid in the 6th gestational week
DIAGNOSIS
SIGNS AND SYMPTOMS
History
• Swelling
• Pain
• Redness
• Palpable neck mass
Physical Exam
• Midline neck mass
• Nontender, unless infected
• Rises in the neck with tongue protrusion and swallowing
• 80% juxtaposed to the hyoid bone
• Palpate cervical and supraclavicular nodes
• Doppler to evaluate vascularity
TESTS
Lab
Thyroid stimulating hormone
Imaging
• Ultrasound
• Thyroid scan if midline ectopic thyroid or thyroid nodule is suspected
• Small roll under shoulders allows exposure of neck in infants.
Diagnostic Procedures/Surgery
If infected, may need initial drainage before definitive resection
Pathological Findings
• Cyst lined with stratified squamous or pseudostratified ciliated columnar epithelium
• Thyroid tissue seen in 10-45% of cysts
• Reports show traces of the thyroglossal duct located near the hyoid bone, superior to thyroid isthmus or lingually.
DIFFERENTIAL DIAGNOSIS
• Ectopic midline thyroid
• Dermoid cyst
• Thyroid adenoma of isthmus or pyramidal lobe
• Lymphadenitis
• Cervical thymic cyst
TREATMENT
Outpatient surgery under general anesthesia
GENERAL MEASURES
Diet
Unrestricted
Activity
Unrestricted
MEDICATION (DRUGS)
None. All thyroglossal duct cysts should be surgically removed.
SURGERY
• Once diagnosed, the excision can be done using the Sistrunk procedure. This requires removal of the center portion of the hyoid bone to minimize recurrence.
• If the cyst is infected, it should be initially treated (antibiotics and local heat) and/or drained. After resolution of the inflammation, excision should be performed (1,2)[C].
FOLLOW-UP
DISPOSITION
Admission Criteria
Drainage of abscess
PROGNOSIS
Resolution with resection (5% recurrence using the Sistrunk procedure)
COMPLICATIONS
• Infection and malignant degeneration may occur if cyst is not excised.
• Reports demonstrate that the location of such masses (lingual) can cause not only various respiratory problems but also infant death.
• Wide local excision is a valuable extension of the Sistrunk operation for the management of recurrent disease (4)[A].
PATIENT MONITORING
One to 2 weeks after drainage or resection
REFERENCES
1. Ostlie DJ, et al. Thyroglossal duct infections and surgical outcomes. J Pediatr Surg. 2004;39:396-399.
2. Kaselas CH, et al. Thyroglossal duct cyst's inflammation. When do we operate? Pediatr Surg Int. 2005;21:991-993.
3. Schader I, et al. Hereditary duct cyst. Pediatric Surg Int. 2005;21(7):593-594.
4. Patel NN, Hartley BEJ, Howard DJ. Management of thyroglossal tract disease after failed Sistrunk's procedure. J Laryngol Otol. 2003;117(9):710-712.[A]
