THROMBOTIC THROMBOCYTOPENIC PURPURA - Rimini Varghese, MD; James N. Butera, MD
BASICS
DESCRIPTION
• An acute syndrome hallmarked by consumptive thrombocytopenia and microangiopathic hemolytic anemia with deposition of hyaline thrombi in arterioles, leading to ischemic multiorgan damage.
• Thrombotic thrombocytopenic purpura (TTP) syndrome is characterized by a pentad
- Thrombocytopenia
- Microangiopathic hemolytic anemia
- Renal insufficiency
- CNS symptoms
- Fever
EPIDEMIOLOGY
• Predominant age: Most common in patients 30-60 years old
• Predominant sex: Females > Males (2:1)
• Incidence ratio in blacks to non-blacks is 9:3
Incidence
11 cases/million/year
RISK FACTORS
• Pregnancy and oral contraceptives
• AIDS and early symptomatic HIV infection
• Autoimmune disease
- Antiphospholipid antibody syndrome
- Systemic lupus erythematosus
- Scleroderma
• Drug toxicity
- Cancer chemotherapy
Mitomycin C, gemcitabine
Bleomycin and cisplatin
Tacrolimus and cyclosporine
- Immune mediated
Quinine
Ticlopidine and clopidogrel
• Hematopoietic cell transplantation
Genetics
Mutation at the ADAMTS13 metalloproteinase gene locus on chromosome 9q34 has been described as the cause of familial TTP.
PATHOPHYSIOLOGY
• In TTP, the aggregating agent responsible for platelet thrombi is unusually large von Willebrand factor (ULvWF) multimers, which are far larger than those found in normal plasma.
• A metalloproteinase, ADAMTS13, which normally enzymatically cleaves the ULvWF multimers to prevent clumping within vessels is deficient, defective, or absent, allowing UlvWF to react with platlelets. This leads to endothelial cell damage and disseminated thrombi characteristic of TTP.
• Arterioles most often affected are in the brain, kidney, pancreas, heart, and adrenal glands.
- Lungs and liver are relatively spared.
ETIOLOGY
• In familial TTP, patients have very low or absent levels of ADAMTS13.
• In acquired idiopathic TTP, some studies have demonstrated IgG autoantibodies are made to the metalloproteinase ADAMTS13, to receptors on the surface of platelets, or to the surface of the endothelial cell (1)[A]. Trigger is unknown.
• Especially in those without ADAMSTS13 deficiency, endothelial injury, either directly from a drug/toxin or indirectly via platelet/neurophil activation, has been proposed as a cause of TTP.
- Drug-induced (see Risk Factors)
ASSOCIATED CONDITIONS
TTP and hemolytic-uremic syndrome (HUS) have very similar presentations and are often described as a continuum of the same pathophysiologic process, with some notable distinctions
• TTP generally presents with prominent neurologic symptoms and minimal renal involvement, whereas the opposite tends to be more characteristic of HUS.
• However, patients with HUS and TTP may have both prominent renal and neurologic manifestations, often making the distinction unclear.
• ADAMTS13 levels are diminished in adults with TTP but are normal in children diagnosed with HUS following infection with E. coli (particularly type O157:H7).
DIAGNOSIS
SIGNS AND SYMPTOMS
• Most commonly nonspecific
- Nausea, vomiting, weakness, abdominal pain, fatigue
• Related to thrombocytopenia
- Easy bruising, purpura or petechiae
- Epistaxis, menorrhagia
- Gastrointestinal bleeding
- Intracranial Hemorrhage
- Visual symptoms due to retinal hemorrhage
• Related to hemolytic anemia (microangiopathic hemolytic anemia [MAHA])
- Jaundice
• Related to end-organ ischemia
- Neurologic: CNS symptoms occur in 90%; presenting complaint in 60%
Often fluctuating symptoms
Headache
Altered mental status; spectrum runs from behavioral/personality changes to obtundation/stupor or coma
Seizures
History
• Generally acute onset of symptoms
• It is important to assess for cause or risk factors (see above).
• 58% of patients die within the 1st 48 hours without treatment.
• 90% mortality without treatment
• Patients often do not present with the classic presentation because the treatment is initiated before the pentad can develop.
Physical Exam
• Mental status/neurologic: Confusion, coma, stupor, weakness
• HEENT: Retinal hemorrhage, scleral icterus, epistaxis
• Abdomen/GI
- Nonspecific tenderness
• Skin: Jaundice, petechiae, purpura, ecchymoses
TESTS
Lab
• CBC/Reticulocyte count/peripheral smear
- Hemoglobin 10 g/dL
Average is 8-9 g/dL; 6 g/dL in 40%
- Platelets 25,000/mm3
Range 5,000-120,000/mm3
- Reticulocyte count increased
- Peripheral smear
Schistocytes (prominent)
Helmet cells, RBC fragments
Nucleated RBCs
Polychromasia
• Coagulation studies
- Normal in most; mild elevation in 15%
- Fibrinogen normal
• Coombs test: Negative direct Coombs test
• Electrolytes, BUN/creatinine: Mild elevation of BUN and creatinine (Creatinine 3)
• Liver function studies: Increased indirect bilirubin (hemolysis)
• LDH: 5-10 times normal
• Urinalysis
- Proteinuria, microscopic hematuria
- Positive dipstick for large blood but minimal RBCs on microscopic examination
• Haptoglobin decreased (hemolysis)
• EKG: Sinus tachycardia, heart block
• No utility of ADAMTS13 assay in diagnosis
Imaging
CT scan of the head: Often performed due to mental status changes to rule out possible intracranial hemorrhage or ischemic changes
Pathological Findings
Biopsy confirms the diagnosis, because diagnosis is made on clinical grounds and laboratory findings (2, 3)[A].
DIFFERENTIAL DIAGNOSIS
• HUS: (see "Associated Conditions")
• Antiphospholipid antibody syndrome: Prolonged PTT and presence of lupus anticoagulant
• Malignant hypertension: Diastolic >130, papilledema, retinal hemorrhages
• Pregnancy associated Preeclampsia/eclampsia or HELLP
- Low ATIII levels
• Disseminated intravascular coagulation
- Prolonged PT/PTT, low fibrinogen
- Low factor V and VIII
- Secondary to sepsis/shock or widely disseminated malignancy
• Idiopathic thrombocytopenic purpura
- No hemolysis, normal LDH and bilirubin
- Presence of anti-platelet antibodies
• Malignancy-associated microangiopathy
• Autoimmune hemolytic anemia: Positive direct Coombs test
• Sclerodermal kidney
TREATMENT
STABILIZATION
• ABCs, oxygen, IV access, telemetry
• Volume resuscitation if hypotensive/active bleeding
• Platelet transfusions may exacerbate end organ ischemia and should only be used in the setting of life-threatening hemorrhage (1, 4, 5)[B].
SPECIAL THERAPY
• In the absence of another apparent cause, the following dyad is sufficient to begin treatment for TTP while the workup proceeds (1)[B]
• Thrombocytopenia
- MAHA emergent plasma exchange transfusion (PET) (1, 4, 5)[A]
Cornerstone of treatment of classic TTP
Thought to replace a deficient or defective metalloproteinase and remove ULvWF and anti metalloproteinase antibodies.
1-1.5 plasma volumes/day should begin immediately and continue daily.
Continue daily until LDH, platelets, neurologic symptoms and renal function normalize (1,5)[A]
- Fresh frozen plasma: (1, 5)[A]
Temporary measure until plasma exchange transfusion can begin
MEDICATION (DRUGS)
First Line
• Utility of glucocorticoid therapy is still debated, with the majority of data derived from case series and clinical experience; British Guidelines recommend its use for all patients (6)[C]. In general, its use seems most beneficial in setting of exacerbation when PET is stopped, or in relapse after remission.
• Doses: Prednisone 1 mg/kg/d and taper once in remission (1, 6)[C] or methylprednisolone 1g IV per day for 3 days (6)[C]
Second Line
The following are used in refractory cases
• Rituxan (7)[C]
• Vincristine, cyclophosphamide, azathioprine
• IV immunoglobulin (IVIG)
SURGERY
Splenectomy is reserved severe, refractory cases; ambiguous results (5)[C].
FOLLOW-UP
• No maintenance therapy. After plasma exchange is discontinued, CBC and LDH should be frequently monitored. If testing remains normal, interval testing can be lengthened (2, 4)[C].
• Estimated 10-year relapse rate is 36%, and most often occur in patients with severe deficiency of ADAMTS13 activity.
• Promptly evaluate at manifestation of any symptoms of relapse (see "Signs and Symptoms") (8).
DISPOSITION
Issues for Referral
Nephrology or hematology for plasma exchange, cardiology for presence of significant heart block, neurosurgery for intracranial hemorrhage
PROGNOSIS
• Initial LDH and platelet counts are not predictive of the patient's response to treatment.
• Final platelet count and LDH or the length or intensity of treatment does not predict relapse.
- 30-day mortality is 10% in those who receive PET.
- 70% respond within 14 days; 90% within 28 days
COMPLICATIONS
• Central line infections and hemorrhage
• Citrate toxicity
• Hypersensitivity reactions to frequent plasma
REFERENCES
1. George JN. Clinical practice. Thrombotic thrombocytopenic purpura. N Engl J Med. 2006;354:1927.
2. Sadler JE, et al. Recent advances in thrombotic thrombocytopenic purpura. Hematology. 2004;407-421.
3. Rose BD, George JN. Causes of thrombotic thrombocytopenic purpura-hemolytic uremic syndrome in adults. Uptodate.com.
4. Yarranton H, Machin S. An update on the pathogenesis and management of acquired thrombotic thrombocytopenic purpura. Curr Opin Neurol. 2003;16:367-373.
5. Rose BD, George JN. Diagnosis of thrombotic thrombocytopenic purpura-hemolytic uremic syndrome in adults. Uptodate.com.
6. Allford SL, Hunt BJ, Rose P, Machin SJ. Guidelines on the diagnosis and management of the thrombotic microangiopathic haemolytic anaemias. Br J Haematol. 2003;120:556.
7. Darabi K, Berg AH. Rituximab can be combined with daily plasma exchange to achieve effective B-cell depletion and clinical improvement in acute autoimmune TTP. Am J Clin Pathol. 2006;125:592-597.
8. Ruggenenti P, Galbusera M, Cornejo RP, et al. Thrombotic thrombocytopenic purpura: Evidence that infusion rather than removal of plasma induces remission of the disease. Am J Kidney Dis. 1993;21:314.
Saturday, January 10, 2009
THROMBOANGIITIS OBLITERANS (BUERGER DISEASE)
THROMBOANGIITIS OBLITERANS (BUERGER DISEASE) - Rick Kellerman, MD
BASICS
DESCRIPTION
• Nonatherosclerotic segmental occlusion of small- and medium-sized arteries and veins caused by inflammatory changes in these vessels
• Primarily occurs in men who smoke
• System(s) Affected: Cardiovascular
• Synonym(s): Buerger disease
GENERAL PREVENTION
Never smoke.
EPIDEMIOLOGY
• Predominant age: 20-40 years
• Predominant sex: Male > Female (3:1). Increasing numbers of women are being diagnosed, possibly due to increased smoking.
Incidence
13 per 100,000 in U.S.
Prevalence
Among those with peripheral artery disease, prevalence ranges from 0.5-5.5% in Western Europe, to 45-63% in India, to 80% in Jews of Ashkenazi ancestry.
ALERT
Geriatric Considerations
Not common in this age group, but diagnosis in the elderly is increasing.
Pediatric Considerations
Not a problem in this age group
RISK FACTORS
• Smoking tobacco
• Occasional cases in users of smokeless tobacco and snuff
• Incidence higher in Israel, Middle East, Eastern Europe, Japan, India, Far East than in North America and Western Europe
• More common in countries with heavy tobacco use
Genetics
• Greater prevalence of HLA-A54, HLA-A9, and HLA-B5
• Familial cases reported rarely
ETIOLOGY
Postulated
• Smoking
• Genetic factors
• Autoimmune disorder with cell-mediated sensitivity to types I and III human collagens (both are normal constituents of blood vessels)
• Impaired peripheral endothelium-dependent vasodilation. Nonendothelium mechanisms of vasodilation are intact.
• Arsenic content of tobacco
• Chronic anaerobic periodontal infection
DIAGNOSIS
PRE HOSPITAL
• Point scoring systems may help clarify clinical diagnosis
• 1 set of criteria includes age 45; current or recent use of tobacco; distal extremity ischemia; exclusion of autoimmune and hypercoagulable disease
SIGNS AND SYMPTOMS
Symptoms tend to wax and wane in early disease and are often asymmetric. Symptoms may be gradual or have a sudden onset related to impaired vasculature. Usually more than 1 limb is involved.
History
• Coldness in feet and/or fingers
• Cold sensitivity
• Paresthesias (numbness, tingling, burning, hypoesthesia) of feet and/or fingers
• Intermittent claudication in arch of foot or leg (rarely hand, forearm)
• Persistent extremity pain (may be worse at rest); pain may be disabling
• Paroxysmal "electric shock" pain of ischemic neuropathy
• Migratory superficial phlebitis
Physical Exam
• Ulceration of digits
• Raynaud phenomenon
• Postural color changes: Pallor on elevation; rubor on dependency
• "Buerger color": Cyanosis of hands and feet
• Tender skin nodules on extremities
• Impaired distal pulses
• Proximal pulses normal; Allen test may be abnormal
• Foot edema
• Gangrene
TESTS
Lab
• Routine laboratory studies show no changes characteristic of this disorder.
• Autoantibodies to collagen and circulating immune complexes may be present, but are strictly for research purposes.
• Homocysteine may be elevated, but lacks specificity.
Imaging
• Doppler ultrasound (not specific)
• Arteriogram or digital-subtraction angiography
- Multiple areas of segmental occlusion of small to medium arteries of arms and legs
- "Skip" areas may be demonstrated.
- Numerous collateral vessels around occluded segments may give a characteristic corkscrew appearance
- Larger arteries are spared. More serious disease occurs distally.
- No apparent source of emboli
Diagnostic Procedures/Surgery
• History and physical examination
• Studies of nerve conduction velocity (to exclude neuropathy)
• Echocardiography (to exclude emboli)
Pathological Findings
• Segmental inflammatory thrombosis of both arteries and veins
• Histologic findings may vary between acute, intermediate, and chronic stages of the disease.
• Histologic sine qua non: Granulomas with collections of neutrophils in the organizing thrombus
- The vessel wall is relatively spared.
- Wall-sparing distinguishes thromboangiitis obliterans from arteriosclerosis and other systemic vasculitis, which show striking wall disruption.
• Acute lesions show occlusive, highly cellular inflammatory thrombi with less inflammation in vessel wall. Polymorphonuclear leukocytes, microabscesses, and multinucleated giant cells may be present.
• Intermediate lesions show organizing thrombus.
• Chronic lesions show recanalized thrombus and perivascular fibrosis.
DIFFERENTIAL DIAGNOSIS
• Peripheral neuropathy
• Peripheral atherosclerotic disease
• Arterial embolus and thrombosis
• Idiopathic peripheral thrombosis
• Hypercoagulable states
• Other causes of vasculitis
• Systemic lupus erythematosus
• Scleroderma
• Occupational trauma
• Repetitive trauma
• Cervical rib
• Livedo reticularis
• Raynaud disease
• Acrocyanosis
• Ergotism
• Frostbite
• Neurotrophic ulcers
• Reflex sympathetic dystrophy
• Metatarsalgia
• Gout
• Periarteritis nodosa
• Juvenile temporal arteritis with eosinophilia
• Polyarteritis
• Carpal tunnel syndrome
• Takayasu arteritis (young Japanese women)
• CREST syndrome (calcinosis, Raynaud phenomenon, poor esophageal mobility, sclerodactyly, telangiectasia)
TREATMENT
STABILIZATION
• Outpatient
• Inpatient if surgery needed for gangrene
• Inpatient for dorsal or lumbar sympathectomy if indicated
GENERAL MEASURES
• Stop smoking (mandatory).
• Protect against trauma (poor fitting shoes).
• Protect against infections.
• Protect against vasoconstriction from cold or drugs.
• Eliminate exposure to thermal damage.
• Eliminate exposure to chemical damage (iodine, carbolic acid, salicylic acid).
• Thrombolytic therapy of occlusive thrombus and angioplasty are experimental.
Diet
No restrictions
Activity
• Restricted by symptoms
• Use a bed cradle (nonheated) to prevent pressure from bed linens.
MEDICATION (DRUGS)
First Line
• Medications are not a substitute for discontinuing smoking.
• Antibiotics for infected digital ulcers and osteomyelitis
• Iloprost, a prostacyclin analog, promotes ulcer healing (available in Europe).
• Urokinase or streptokinase selectively infused into occluded artery
• Intramuscular endothelial growth factor gene therapy
• No form of medical treatment has been shown to be effective (including steroids, calcium channel blockers, reserpine, pentoxifylline, vasodilators, antiplatelet drugs, anticoagulants).
• Contraindications: Refer to manufacturer's literature.
• Precautions: Refer to manufacturer's literature.
• Significant possible interactions: Refer to manufacturer's literature.
Second Line
Calcium channel blocking agents, such as nifedipine, may allow vasodilatation, but have not been proven effective.
SURGERY
• Amputation
- For nonhealing ulcers, gangrene, or intractable pain
- Should preserve as much limb as possible
- Rarely required
• Omental autotransplantation has been successful in treating ulcers.
• Infrainguinal bypass
• In severe disease, a lumbar sympathectomy to increase blood supply to the skin
• Spinal cord stimulator
• Direct revascularization of distal arteries is not practical. Distal target vessel is usually not available.
FOLLOW-UP
PROGNOSIS
• Occasional remissions
• Unremitting progression if patient continues to smoke
• Death rare; normal survival curve
COMPLICATIONS
• Ulcerations
• Gangrene
• Need for amputation
• Rare occlusion of cerebral, coronary, renal, splenic, mesenteric, pulmonary, iliac arteries, and aorta
PATIENT MONITORING
Frequent history and physical examinations
REFERENCES
1. Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 16-1989. A 36-year-old man with peripheral vascular disease. N Engl J Med. 1989;320:1068-1076. (C)
2. Olin JW. Thromboangiitis obliterans (Buerger's disease). N Engl J Med. 2000;343:864-869. (C)
3. Olin JW, et al. The changing clinical spectrum of thromboangiitis obliterans (Buerger's disease). Circulation. 1990;82(Suppl):IV3-8.
4. Iwai T, Inoue Y, Umeda M, et al. Oral bacteria in the occluded arteries of patients with Buerger disease. J Vasc Surg. 2005;42:107. (C)
BASICS
DESCRIPTION
• Nonatherosclerotic segmental occlusion of small- and medium-sized arteries and veins caused by inflammatory changes in these vessels
• Primarily occurs in men who smoke
• System(s) Affected: Cardiovascular
• Synonym(s): Buerger disease
GENERAL PREVENTION
Never smoke.
EPIDEMIOLOGY
• Predominant age: 20-40 years
• Predominant sex: Male > Female (3:1). Increasing numbers of women are being diagnosed, possibly due to increased smoking.
Incidence
13 per 100,000 in U.S.
Prevalence
Among those with peripheral artery disease, prevalence ranges from 0.5-5.5% in Western Europe, to 45-63% in India, to 80% in Jews of Ashkenazi ancestry.
ALERT
Geriatric Considerations
Not common in this age group, but diagnosis in the elderly is increasing.
Pediatric Considerations
Not a problem in this age group
RISK FACTORS
• Smoking tobacco
• Occasional cases in users of smokeless tobacco and snuff
• Incidence higher in Israel, Middle East, Eastern Europe, Japan, India, Far East than in North America and Western Europe
• More common in countries with heavy tobacco use
Genetics
• Greater prevalence of HLA-A54, HLA-A9, and HLA-B5
• Familial cases reported rarely
ETIOLOGY
Postulated
• Smoking
• Genetic factors
• Autoimmune disorder with cell-mediated sensitivity to types I and III human collagens (both are normal constituents of blood vessels)
• Impaired peripheral endothelium-dependent vasodilation. Nonendothelium mechanisms of vasodilation are intact.
• Arsenic content of tobacco
• Chronic anaerobic periodontal infection
DIAGNOSIS
PRE HOSPITAL
• Point scoring systems may help clarify clinical diagnosis
• 1 set of criteria includes age 45; current or recent use of tobacco; distal extremity ischemia; exclusion of autoimmune and hypercoagulable disease
SIGNS AND SYMPTOMS
Symptoms tend to wax and wane in early disease and are often asymmetric. Symptoms may be gradual or have a sudden onset related to impaired vasculature. Usually more than 1 limb is involved.
History
• Coldness in feet and/or fingers
• Cold sensitivity
• Paresthesias (numbness, tingling, burning, hypoesthesia) of feet and/or fingers
• Intermittent claudication in arch of foot or leg (rarely hand, forearm)
• Persistent extremity pain (may be worse at rest); pain may be disabling
• Paroxysmal "electric shock" pain of ischemic neuropathy
• Migratory superficial phlebitis
Physical Exam
• Ulceration of digits
• Raynaud phenomenon
• Postural color changes: Pallor on elevation; rubor on dependency
• "Buerger color": Cyanosis of hands and feet
• Tender skin nodules on extremities
• Impaired distal pulses
• Proximal pulses normal; Allen test may be abnormal
• Foot edema
• Gangrene
TESTS
Lab
• Routine laboratory studies show no changes characteristic of this disorder.
• Autoantibodies to collagen and circulating immune complexes may be present, but are strictly for research purposes.
• Homocysteine may be elevated, but lacks specificity.
Imaging
• Doppler ultrasound (not specific)
• Arteriogram or digital-subtraction angiography
- Multiple areas of segmental occlusion of small to medium arteries of arms and legs
- "Skip" areas may be demonstrated.
- Numerous collateral vessels around occluded segments may give a characteristic corkscrew appearance
- Larger arteries are spared. More serious disease occurs distally.
- No apparent source of emboli
Diagnostic Procedures/Surgery
• History and physical examination
• Studies of nerve conduction velocity (to exclude neuropathy)
• Echocardiography (to exclude emboli)
Pathological Findings
• Segmental inflammatory thrombosis of both arteries and veins
• Histologic findings may vary between acute, intermediate, and chronic stages of the disease.
• Histologic sine qua non: Granulomas with collections of neutrophils in the organizing thrombus
- The vessel wall is relatively spared.
- Wall-sparing distinguishes thromboangiitis obliterans from arteriosclerosis and other systemic vasculitis, which show striking wall disruption.
• Acute lesions show occlusive, highly cellular inflammatory thrombi with less inflammation in vessel wall. Polymorphonuclear leukocytes, microabscesses, and multinucleated giant cells may be present.
• Intermediate lesions show organizing thrombus.
• Chronic lesions show recanalized thrombus and perivascular fibrosis.
DIFFERENTIAL DIAGNOSIS
• Peripheral neuropathy
• Peripheral atherosclerotic disease
• Arterial embolus and thrombosis
• Idiopathic peripheral thrombosis
• Hypercoagulable states
• Other causes of vasculitis
• Systemic lupus erythematosus
• Scleroderma
• Occupational trauma
• Repetitive trauma
• Cervical rib
• Livedo reticularis
• Raynaud disease
• Acrocyanosis
• Ergotism
• Frostbite
• Neurotrophic ulcers
• Reflex sympathetic dystrophy
• Metatarsalgia
• Gout
• Periarteritis nodosa
• Juvenile temporal arteritis with eosinophilia
• Polyarteritis
• Carpal tunnel syndrome
• Takayasu arteritis (young Japanese women)
• CREST syndrome (calcinosis, Raynaud phenomenon, poor esophageal mobility, sclerodactyly, telangiectasia)
TREATMENT
STABILIZATION
• Outpatient
• Inpatient if surgery needed for gangrene
• Inpatient for dorsal or lumbar sympathectomy if indicated
GENERAL MEASURES
• Stop smoking (mandatory).
• Protect against trauma (poor fitting shoes).
• Protect against infections.
• Protect against vasoconstriction from cold or drugs.
• Eliminate exposure to thermal damage.
• Eliminate exposure to chemical damage (iodine, carbolic acid, salicylic acid).
• Thrombolytic therapy of occlusive thrombus and angioplasty are experimental.
Diet
No restrictions
Activity
• Restricted by symptoms
• Use a bed cradle (nonheated) to prevent pressure from bed linens.
MEDICATION (DRUGS)
First Line
• Medications are not a substitute for discontinuing smoking.
• Antibiotics for infected digital ulcers and osteomyelitis
• Iloprost, a prostacyclin analog, promotes ulcer healing (available in Europe).
• Urokinase or streptokinase selectively infused into occluded artery
• Intramuscular endothelial growth factor gene therapy
• No form of medical treatment has been shown to be effective (including steroids, calcium channel blockers, reserpine, pentoxifylline, vasodilators, antiplatelet drugs, anticoagulants).
• Contraindications: Refer to manufacturer's literature.
• Precautions: Refer to manufacturer's literature.
• Significant possible interactions: Refer to manufacturer's literature.
Second Line
Calcium channel blocking agents, such as nifedipine, may allow vasodilatation, but have not been proven effective.
SURGERY
• Amputation
- For nonhealing ulcers, gangrene, or intractable pain
- Should preserve as much limb as possible
- Rarely required
• Omental autotransplantation has been successful in treating ulcers.
• Infrainguinal bypass
• In severe disease, a lumbar sympathectomy to increase blood supply to the skin
• Spinal cord stimulator
• Direct revascularization of distal arteries is not practical. Distal target vessel is usually not available.
FOLLOW-UP
PROGNOSIS
• Occasional remissions
• Unremitting progression if patient continues to smoke
• Death rare; normal survival curve
COMPLICATIONS
• Ulcerations
• Gangrene
• Need for amputation
• Rare occlusion of cerebral, coronary, renal, splenic, mesenteric, pulmonary, iliac arteries, and aorta
PATIENT MONITORING
Frequent history and physical examinations
REFERENCES
1. Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 16-1989. A 36-year-old man with peripheral vascular disease. N Engl J Med. 1989;320:1068-1076. (C)
2. Olin JW. Thromboangiitis obliterans (Buerger's disease). N Engl J Med. 2000;343:864-869. (C)
3. Olin JW, et al. The changing clinical spectrum of thromboangiitis obliterans (Buerger's disease). Circulation. 1990;82(Suppl):IV3-8.
4. Iwai T, Inoue Y, Umeda M, et al. Oral bacteria in the occluded arteries of patients with Buerger disease. J Vasc Surg. 2005;42:107. (C)
THORACIC OUTLET SYNDROME
THORACIC OUTLET SYNDROME - Frederico Milla, MD; Ruben Peralta, MD, FACS
BASICS
DESCRIPTION
• A constellation of symptoms that affect the head, neck, shoulders, and upper extremities, caused by compression of the neurovascular structures (i.e., brachial plexus and subclavian vessels) at the thoracic outlet
• Resulting from congenital bony, muscular, or tendon anomalies; posttraumatic, following clavicular or cervical spine injures; or idiopathic.
• Synonym(s): Scalenus anticus syndrome; Cervical rib syndrome; Costoclavicular syndrome; Thoracic outlet syndrome
ALERT
Pregnancy Considerations
Generalized tissue fluid accumulations and postural changes could aggravate symptoms.
EPIDEMIOLOGY
• Predominant age
- Neurologic type (95%): 20-60 years
- Venous type (4%):20-35 years
- Arterial type (1%; atherosclerosis): Young adult or >50
• Predominant sex
- Neurologic type: Female > Male (3.5:1)
- Venous type: Male > Female
- Arterial type: Male = Female
Incidence
3-80/1,000 population
RISK FACTORS
• Posttraumatic
• Exostosis of clavicle or first rib
• Postural abnormalities (e.g., drooping of shoulders, scoliosis)
• Body building, with increased muscular bulk in thoracic outlet area
• Rapid weight loss combined with vigorous physical exertion and/or exercise
• Occupational exposure
- Computer users
- Musicians
- Repetitive work involving shoulders, arms, hands
- Young thin females with long necks and drooping shoulders
ETIOLOGY
Compression of upper thoracic neurovasculature by
Cervical rib
Taut anomalous scalene muscles
Elongated C7 transverse process
Poor posture
Pancoast tumor
Atherosclerotic plaques within vessels
Subclavian muscle
Fibrous and ligamentous bands
Costocoracoid tendon
Callous bone formation from fractured clavicle or 1st rib
Aberrant tissue
Neck trauma
ASSOCIATED CONDITIONS
• Paget-von Schrotter syndrome: Thrombosis of subclavian vein
• Gilliatt-Sumner hand: Neurogenic atrophy of abductor pollicis brevis
DIAGNOSIS
SIGNS AND SYMPTOMS
• Neurologic type, upper plexus (C4-C7)
- Pain and paresthesias in head, neck, mandible, face, temporal area, upper back/chest, outer arm, and hand in a radial nerve distribution
- Occipital and orbital headache
• Neurologic type, lower plexus (C8-T1)
- Pain and paresthesias in axilla, inner arm, and hand in an ulnar nerve distribution, often nocturnal
- Hypothenar and interosseous muscle atrophy
• Venous type
- Arm claudication
- Cyanosis
- Swelling
- Distended arm veins
• Arterial type
- Digital vasospasm
- Thrombosis/embolism
- Aneurysm
- Gangrene
• Positive Adson maneuver (head rotation to the affected side with cervical extension then deep inhalation. Test is positive if paresthesias or if radial pulse not palpable during maneuver)
• Tenderness to percussion or palpation of supraclavicular area
• Worsening of symptoms with elevation of arm, overhead extension of arms, or with arms extended forward (e.g., driving a car, typing, carrying objects). Prompt disappearance of symptoms with arm returning to neutral position
• Morley test
- Brachial plexus compression test in the supraclavicular area from the scalene triangle
- A positive response is the reproduction of an aching sensation and typical localized paresthesia
• 1-minute Roos test
- A thoracic outlet shoulder girdle stress test
- Shoulders and arms are braced in a 90 abducted and externally rotated position; patient is required to clench and relax fists repetitively for 1 minute.
- A positive test reproduces the symptom.
TESTS
• Plethysmography with previously mentioned maneuvers.
• Doppler and duplex ultrasound if venous obstruction suspected
• Ulnar and median nerve conduction velocity studies (70 m/sec is abnormal)
• Venogram and arteriogram if presents with edematous changes in upper extremity
Imaging
• Radiograph (chest, C-spine, shoulders) may reveal elongated C7 transverse process or a cervical rib, Pancoast tumor, or healed clavicle fracture.
• Arteriogram or venogram, if arterial or venous obstruction, aneurysm, or emboli are suspected
• CT scan, if cord compression lesions (disc and/or tumor) are suspected
• Helical CT
• 3D MR angiography
Diagnostic Procedures/Surgery
• Thoracic outlet syndrome is a clinical diagnosis.
• Anterior scalene muscle injections are useful in confirming the diagnosis and in determining which patients may respond favorably to surgery.
DIFFERENTIAL DIAGNOSIS
• Cervical disk syndrome
• Carpal tunnel syndrome
• Orthopedic shoulder problems (shoulder strain, rotator cuff injury, tendinitis)
• Cervical spondylitis
• Ulnar nerve compression at elbow and hand
• Multiple sclerosis
• Spinal cord tumor or disease
• Angina pectoris
• Migraine
• Reflex sympathetic dystrophy
• C8 radiculopathies
TREATMENT
STABILIZATION
• Outpatient for conservative treatment
• Inpatient if surgery required
GENERAL MEASURES
• Conservative therapy
- If no vascular involvement is present and/or if no loss of function or lifestyle is present owing to severity of symptoms, conservative therapy may be undertaken for 2-3 months.
- Improvement can be expected in 60% of patients.
- Exercise program to promote shoulder muscle function
- Physical therapy for postural faults
- Cervical collar, traction
- Weight loss if axillary folds are causing compression
• Consultation with vascular surgeon or neurosurgeon if vascular or neurologic involvement is suspected.
Activity
• Light activity with arm and hand is encouraged.
• No straining or heavy activity for 3 months.
SPECIAL THERAPY
Physical Therapy
• Exercise program
• Postural correction
MEDICATION (DRUGS)
• Analgesics
• Muscle relaxants
• Antispasmodics
SURGERY
• Operative if vascular involvement is present and/or loss of function or lifestyle occurs secondary to severity of symptoms, and if conservative therapy fails after 2-3 months (1)[B].
• Resection of 1st rib or cervical ribs (transaxillary, supraclavicular, posterior approaches) (2)[B]
• Excision of adhesive bands via transaxillary approach
• Anterior scalenectomy
FOLLOW-UP
PROGNOSIS
• 60% improve with appropriate physiotherapy program.
• 90% have excellent or good early results with surgery (3)[B].
• 70-80% have no recurrence at 5 and 10 years.
COMPLICATIONS
• Postoperative shoulder, arm, hand pain, and paresthesias in 10%; usually responds to physiotherapy
• 1.5-2% of patients will have symptomatic recurrences 1 month-7 years postoperatively (usually within 3 months).
• 0.5-1% of patients have brachial plexus injury, probably owing to intraoperative traction
• Reoperation indicated for symptomatic recurrence with long posterior remnant of 1st rib (posterior approach) or with disrupted fibrous adhesions (transaxillary approach)
• Venous obstruction or arterial emboli; usually responds to thrombolytics
PATIENT MONITORING
Office follow-up visits, e.g., every 3 weeks
REFERENCES
1. Huang JH, Zager EL. Thoracic outlet syndrome. Neurosurgery. 2004;55:897-903.
2. Sanders RJ, Hammond SL. Management of cervical ribs and anomalous first ribs causing neurogenic thoracic outlet syndrome. J Vasc Surg. 2002;36:51-56.
3. Axelrod DA, Proctor MC, Geisser ME, et al. Outcomes after surgery for thoracic outlet syndrome. J Vasc Surg. 2001;33:1220-1225.
4. Mackinnon SE, Patterson GA, Novak CB. Thoracic outlet syndrome: A current overview. Semin Thoracic Cardiovasc Surg. 1996a;8:176-182.
5. Cooke RA. Thoracic outlet syndrome-aspects of diagnosis in the differential diagnosis of hand-arm vibration syndrome. Occupation Med. 2003;53:331-336
MISCELLANEOUS
2-3 months trial of physiotherapy is always indicated, except in presence of obvious bony abnormality.
BASICS
DESCRIPTION
• A constellation of symptoms that affect the head, neck, shoulders, and upper extremities, caused by compression of the neurovascular structures (i.e., brachial plexus and subclavian vessels) at the thoracic outlet
• Resulting from congenital bony, muscular, or tendon anomalies; posttraumatic, following clavicular or cervical spine injures; or idiopathic.
• Synonym(s): Scalenus anticus syndrome; Cervical rib syndrome; Costoclavicular syndrome; Thoracic outlet syndrome
ALERT
Pregnancy Considerations
Generalized tissue fluid accumulations and postural changes could aggravate symptoms.
EPIDEMIOLOGY
• Predominant age
- Neurologic type (95%): 20-60 years
- Venous type (4%):20-35 years
- Arterial type (1%; atherosclerosis): Young adult or >50
• Predominant sex
- Neurologic type: Female > Male (3.5:1)
- Venous type: Male > Female
- Arterial type: Male = Female
Incidence
3-80/1,000 population
RISK FACTORS
• Posttraumatic
• Exostosis of clavicle or first rib
• Postural abnormalities (e.g., drooping of shoulders, scoliosis)
• Body building, with increased muscular bulk in thoracic outlet area
• Rapid weight loss combined with vigorous physical exertion and/or exercise
• Occupational exposure
- Computer users
- Musicians
- Repetitive work involving shoulders, arms, hands
- Young thin females with long necks and drooping shoulders
ETIOLOGY
Compression of upper thoracic neurovasculature by
Cervical rib
Taut anomalous scalene muscles
Elongated C7 transverse process
Poor posture
Pancoast tumor
Atherosclerotic plaques within vessels
Subclavian muscle
Fibrous and ligamentous bands
Costocoracoid tendon
Callous bone formation from fractured clavicle or 1st rib
Aberrant tissue
Neck trauma
ASSOCIATED CONDITIONS
• Paget-von Schrotter syndrome: Thrombosis of subclavian vein
• Gilliatt-Sumner hand: Neurogenic atrophy of abductor pollicis brevis
DIAGNOSIS
SIGNS AND SYMPTOMS
• Neurologic type, upper plexus (C4-C7)
- Pain and paresthesias in head, neck, mandible, face, temporal area, upper back/chest, outer arm, and hand in a radial nerve distribution
- Occipital and orbital headache
• Neurologic type, lower plexus (C8-T1)
- Pain and paresthesias in axilla, inner arm, and hand in an ulnar nerve distribution, often nocturnal
- Hypothenar and interosseous muscle atrophy
• Venous type
- Arm claudication
- Cyanosis
- Swelling
- Distended arm veins
• Arterial type
- Digital vasospasm
- Thrombosis/embolism
- Aneurysm
- Gangrene
• Positive Adson maneuver (head rotation to the affected side with cervical extension then deep inhalation. Test is positive if paresthesias or if radial pulse not palpable during maneuver)
• Tenderness to percussion or palpation of supraclavicular area
• Worsening of symptoms with elevation of arm, overhead extension of arms, or with arms extended forward (e.g., driving a car, typing, carrying objects). Prompt disappearance of symptoms with arm returning to neutral position
• Morley test
- Brachial plexus compression test in the supraclavicular area from the scalene triangle
- A positive response is the reproduction of an aching sensation and typical localized paresthesia
• 1-minute Roos test
- A thoracic outlet shoulder girdle stress test
- Shoulders and arms are braced in a 90 abducted and externally rotated position; patient is required to clench and relax fists repetitively for 1 minute.
- A positive test reproduces the symptom.
TESTS
• Plethysmography with previously mentioned maneuvers.
• Doppler and duplex ultrasound if venous obstruction suspected
• Ulnar and median nerve conduction velocity studies (70 m/sec is abnormal)
• Venogram and arteriogram if presents with edematous changes in upper extremity
Imaging
• Radiograph (chest, C-spine, shoulders) may reveal elongated C7 transverse process or a cervical rib, Pancoast tumor, or healed clavicle fracture.
• Arteriogram or venogram, if arterial or venous obstruction, aneurysm, or emboli are suspected
• CT scan, if cord compression lesions (disc and/or tumor) are suspected
• Helical CT
• 3D MR angiography
Diagnostic Procedures/Surgery
• Thoracic outlet syndrome is a clinical diagnosis.
• Anterior scalene muscle injections are useful in confirming the diagnosis and in determining which patients may respond favorably to surgery.
DIFFERENTIAL DIAGNOSIS
• Cervical disk syndrome
• Carpal tunnel syndrome
• Orthopedic shoulder problems (shoulder strain, rotator cuff injury, tendinitis)
• Cervical spondylitis
• Ulnar nerve compression at elbow and hand
• Multiple sclerosis
• Spinal cord tumor or disease
• Angina pectoris
• Migraine
• Reflex sympathetic dystrophy
• C8 radiculopathies
TREATMENT
STABILIZATION
• Outpatient for conservative treatment
• Inpatient if surgery required
GENERAL MEASURES
• Conservative therapy
- If no vascular involvement is present and/or if no loss of function or lifestyle is present owing to severity of symptoms, conservative therapy may be undertaken for 2-3 months.
- Improvement can be expected in 60% of patients.
- Exercise program to promote shoulder muscle function
- Physical therapy for postural faults
- Cervical collar, traction
- Weight loss if axillary folds are causing compression
• Consultation with vascular surgeon or neurosurgeon if vascular or neurologic involvement is suspected.
Activity
• Light activity with arm and hand is encouraged.
• No straining or heavy activity for 3 months.
SPECIAL THERAPY
Physical Therapy
• Exercise program
• Postural correction
MEDICATION (DRUGS)
• Analgesics
• Muscle relaxants
• Antispasmodics
SURGERY
• Operative if vascular involvement is present and/or loss of function or lifestyle occurs secondary to severity of symptoms, and if conservative therapy fails after 2-3 months (1)[B].
• Resection of 1st rib or cervical ribs (transaxillary, supraclavicular, posterior approaches) (2)[B]
• Excision of adhesive bands via transaxillary approach
• Anterior scalenectomy
FOLLOW-UP
PROGNOSIS
• 60% improve with appropriate physiotherapy program.
• 90% have excellent or good early results with surgery (3)[B].
• 70-80% have no recurrence at 5 and 10 years.
COMPLICATIONS
• Postoperative shoulder, arm, hand pain, and paresthesias in 10%; usually responds to physiotherapy
• 1.5-2% of patients will have symptomatic recurrences 1 month-7 years postoperatively (usually within 3 months).
• 0.5-1% of patients have brachial plexus injury, probably owing to intraoperative traction
• Reoperation indicated for symptomatic recurrence with long posterior remnant of 1st rib (posterior approach) or with disrupted fibrous adhesions (transaxillary approach)
• Venous obstruction or arterial emboli; usually responds to thrombolytics
PATIENT MONITORING
Office follow-up visits, e.g., every 3 weeks
REFERENCES
1. Huang JH, Zager EL. Thoracic outlet syndrome. Neurosurgery. 2004;55:897-903.
2. Sanders RJ, Hammond SL. Management of cervical ribs and anomalous first ribs causing neurogenic thoracic outlet syndrome. J Vasc Surg. 2002;36:51-56.
3. Axelrod DA, Proctor MC, Geisser ME, et al. Outcomes after surgery for thoracic outlet syndrome. J Vasc Surg. 2001;33:1220-1225.
4. Mackinnon SE, Patterson GA, Novak CB. Thoracic outlet syndrome: A current overview. Semin Thoracic Cardiovasc Surg. 1996a;8:176-182.
5. Cooke RA. Thoracic outlet syndrome-aspects of diagnosis in the differential diagnosis of hand-arm vibration syndrome. Occupation Med. 2003;53:331-336
MISCELLANEOUS
2-3 months trial of physiotherapy is always indicated, except in presence of obvious bony abnormality.
THALASSEMIA
THALASSEMIA - Herbert L. Muncie, Jr., MD
BASICS
DESCRIPTION
• A group of inherited disorders that affect the synthesis of adult hemoglobin tetramer (Hb A)
• -Thalassemia is due to a deficient synthesis of -globin, while -thalassemia is due to a deficient synthesis of -globin.
- The synthesis of the unaffected globin chain proceeds normally.
- This leads to inadequate hemoglobin and unbalanced accumulaton of goblin sythesis, which then results in hypochromic, microcytic red cells and hemolytic anemia.
• Thalassemia is prevalent in the Mediterranean region, the Middle East, Southeast Asia, and among ethnic groups originating from these areas.
• -Thalassemia is more common in persons of Mediterranean, African, or Southeast Asian descent, whereas -thalassemia is increased in patients of African and Southeast Asian descent.
• Types
- Thalassemia trait (- or -): Mild anemia with microcytosis and hypochromia. No transfusion therapy is needed.
- -Thalassemia intermedia: Milder form. Transfusion therapy may not be needed.
- -Thalassemia major: Severe anemia, growth retardation, hepatosplenomegaly, bone marrow expansion, and bone deformities. Transfusion therapy is necessary to sustain life.
• Varieties unique to Southeast Asians include hemoglobin H disease (a more severe form of -thalassemia) and hemoglobin E/-thalassemia, which often mimics -thalassemia major in its severity.
• System(s) Affected: Hematologic/Lymphatic/Immunologic; Cardiac; Hepatic
• Synonym(s): Mediterranean anemia; Hereditary leptocytosis; Thalassemia major and minor; Cooley anemia
ALERT
Pediatric Considerations
• Severe forms cause symptoms during early childhood and require treatment to sustain life.
• Newborns' cord blood or heel stick should be screened for hemoglobinopathies with hemoglobin electrophoresis or comparably accurate test. (1)[A]
Pregnancy Considerations
• Genetic counseling is advised for parents or other relatives of a child with thalassemia and for any individual with -thalassemia minor.
• During the first trimester, test chorionic-villus samples with polymerase chain reaction (PCR) technology to detect point mutations or deletions.
GENERAL PREVENTION
• Prenatal information
- Genetic counseling regarding partner selection and information on the availability of diagnostic tests in the event of pregnancy
• Complication prevention
- For offspring of adult thalassemia patients, evaluation for thalassemia by 1 year of age
- Severe forms
Avoid exposure to sick contacts.
Keep immunizations up-to-date, including pneumococcal vaccine and annual influenza vaccine.
- Prompt treatment of bacterial infections (after splenectomy, patients should maintain a supply of an appropriate antibiotic to take at the onset of symptoms of a bacterial infection.)
- Dental checkups every 6 months.
- Avoid activities that could increase the risk of bone fractures.
EPIDEMIOLOGY
• Predominant age: Symptoms start to appear 3-6 months after birth with severe form
• Predominant sex: Male = Female
Incidence
Occurs in 4.4/10,000 live births
Prevalence
• 1,000 patients in the United States are affected with -thalassemia major.
• The prevalence of thalassemia trait within the involved ethnic groups ranges from 5-30%.
RISK FACTORS
Family history
Genetics
• Inherited in an autosomal recessive pattern
• -Thalassemia results from deletion of one or more of the four genes responsible for -globin synthesis. Four-gene deletions results in fatal hydrops fetalis. Three-gene deletions results in hemoglobin H. Two-gene deletions is trait and one-gene deletion is a "silent" carrier state.
• -Thalassemia is caused by any of more than 200 point mutations and very rarely deletions.
• Significantly disparate phenotype with the same genotype is unexplained by variability of known loci
ETIOLOGY
Genetic
ASSOCIATED CONDITIONS
See Complications
DIAGNOSIS
SIGNS AND SYMPTOMS
Thalassemia trait has no signs or symptoms.
History
• Poor growth
• Inadequate food intake
• Fatigue
• Cholelithiasis
• Pathologic fractures
• Shortness of breath
Physical Exam
• Pallor
• Splenomegaly
• Jaundice
• Maxillary hyperplasia
• Dental malocclusion
TESTS
Special tests
• Bone marrow aspiration
• For children, calculate Mentzer index (MCV/RBC count)
- 13, thalassemia more likely
- >13, iron deficiency more likely. (2)
Lab
• Hemoglobin: Usual range 10.0-12.0 g/dL with thalassemia trait
• Hematocrit
- 28-40% in thalassemia trait
- May fall to 10% in -thalassemia major
• Peripheral blood
- Microcytosis
- Hypochromia
- High percentage of target cells
- Reticulocyte count elevated
• Hemoglobin electrophoresis
- In -thalassemia trait elevated Hb A2 levels
- In -thalassemia major or intermedia elevated Hb A2, elevated Hb F, reduced or absent Hb A1
- In -thalassemia, no recognizable electrophoretic pattern occurs.
Pathological Findings
• Bone marrow erythroid hyperplasia
• Iron deposits in heart muscle
• Hepatic siderosis
DIFFERENTIAL DIAGNOSIS
• Iron deficiency
• Other hemoglobinopathies
• Other hemolytic anemias
TREATMENT
• Outpatient for mild cases
• Inpatient for transfusion therapy
GENERAL MEASURES
• Mild cases require no therapy.
• Thalassemia intermedia: Normally no therapy necessary unless hemoglobin levels fall to a level that causes symptoms, then transfusion therapy may be needed
• Thalassemia major
- Maintain a mean hemoglobin level of at least 9.3 g/dL (1.4 mmol/L) with a regular transfusion schedule.
- Folate supplementation daily
- Treat bacterial infections promptly.
• Iron overload
- Patients receiving transfusion therapy increase total body iron 4 times over the normal amount.
- Therapy is iron chelation.
Diet
• Thalassemia minor requires no restrictions.
• -Thalassemia major
- Avoid iron-rich foods (red meats such as liver, and some cereals).
- Drinking tea may possibly help reduce iron absorption.
Activity
• Thalassemia minor requires no restrictions
• -Thalassemia major
- Avoid strenuous activities (e.g., football, soccer).
- Acceptable activity levels will be determined on an individual basis depending on severity of disorder.
MEDICATION (DRUGS)
• Antibiotics for bacterial infections
• Thalassemia intermedia
- Folic acid supplements
First Line
Thalassemia major
• Iron chelation with deferoxamine (Desferal)
- SC or continuous IV infusion (3)[C]
- Usually started before 5-8 years of age
Second Line
• Deferiprone, PO, acceptable alternative for patients unable to receive deferoxamine (3)[C]
• Contraindications to chelation therapy Refer to manufacturer's literature.
• Precautions with chelation therapy Refer to manufacturer's literature.
• Possible significant interactions with chelation therapy Refer to manufacturer's literature.
SURGERY
• Splenectomy
- May be needed if hypersplenism causes a marked increase in the transfusion requirement
- Defer surgery until patient is 4-6 years of age (due to increased infection risk).
- Administer polyvalent pneumococcal vaccine 1 month prior to splenectomy.
- Daily penicillin prophylaxis post splenectormy
• Bone marrow transplantation in childhood
- Only curative therapy and generally excellent outcome for low-risk patients
FOLLOW-UP
DISPOSITION
Issues for Referral
Thalassemia major usually requires hematology consult.
PROGNOSIS
• Outlook varies depending on type.
• Thalassemia minor patients live a normal life span.
• Thalassemia major patients live an average of 17 years and usually die by age 30.
• Iron overload causes most of the morbidity and mortality.
- Cardiac events are the primary cause of death.
- Effective iron chelation is improving longevity.
COMPLICATIONS
• Chronic hemolysis
• Susceptibility to infections after splenectomy
• Infections from blood transfusion
• Jaundice
• Leg ulcers
• Cholelithiasis
• Osteoporosis and low-trauma fractures
• Impaired growth rate
• Delayed or absent puberty
• Hypogonadism
• Hepatic siderosis
• Splenomegaly
• Cardiac disease from iron overload
• Thromboembolic phenomenon
• Aplastic and megaloblastic crises
PATIENT MONITORING
• For -thalassemia major, life-long monitoring is necessary because the therapy and disease progression have numerous potential complications.
• Thalassemia minor patients require no special follow-up.
REFERENCES
1. Andrews J, Wilson M. Screening for hemoglobinopathies. United States Preventive Services Task Force,1996;485-492.
2. Irwn JJ, Kirchner JT. Anemia in children. Am Fam Physician. 2001;64:1379-1386.
3. Rund D, Rachmilewitz E. -Thalassemia. N Engl J Med. 2005;353:1135-1146.
4. Dhaliwal G, Cornett PA, Tierney LM. Hemolytic anemia. Am Fam Physician. 2004;69:2599-2606.
BASICS
DESCRIPTION
• A group of inherited disorders that affect the synthesis of adult hemoglobin tetramer (Hb A)
• -Thalassemia is due to a deficient synthesis of -globin, while -thalassemia is due to a deficient synthesis of -globin.
- The synthesis of the unaffected globin chain proceeds normally.
- This leads to inadequate hemoglobin and unbalanced accumulaton of goblin sythesis, which then results in hypochromic, microcytic red cells and hemolytic anemia.
• Thalassemia is prevalent in the Mediterranean region, the Middle East, Southeast Asia, and among ethnic groups originating from these areas.
• -Thalassemia is more common in persons of Mediterranean, African, or Southeast Asian descent, whereas -thalassemia is increased in patients of African and Southeast Asian descent.
• Types
- Thalassemia trait (- or -): Mild anemia with microcytosis and hypochromia. No transfusion therapy is needed.
- -Thalassemia intermedia: Milder form. Transfusion therapy may not be needed.
- -Thalassemia major: Severe anemia, growth retardation, hepatosplenomegaly, bone marrow expansion, and bone deformities. Transfusion therapy is necessary to sustain life.
• Varieties unique to Southeast Asians include hemoglobin H disease (a more severe form of -thalassemia) and hemoglobin E/-thalassemia, which often mimics -thalassemia major in its severity.
• System(s) Affected: Hematologic/Lymphatic/Immunologic; Cardiac; Hepatic
• Synonym(s): Mediterranean anemia; Hereditary leptocytosis; Thalassemia major and minor; Cooley anemia
ALERT
Pediatric Considerations
• Severe forms cause symptoms during early childhood and require treatment to sustain life.
• Newborns' cord blood or heel stick should be screened for hemoglobinopathies with hemoglobin electrophoresis or comparably accurate test. (1)[A]
Pregnancy Considerations
• Genetic counseling is advised for parents or other relatives of a child with thalassemia and for any individual with -thalassemia minor.
• During the first trimester, test chorionic-villus samples with polymerase chain reaction (PCR) technology to detect point mutations or deletions.
GENERAL PREVENTION
• Prenatal information
- Genetic counseling regarding partner selection and information on the availability of diagnostic tests in the event of pregnancy
• Complication prevention
- For offspring of adult thalassemia patients, evaluation for thalassemia by 1 year of age
- Severe forms
Avoid exposure to sick contacts.
Keep immunizations up-to-date, including pneumococcal vaccine and annual influenza vaccine.
- Prompt treatment of bacterial infections (after splenectomy, patients should maintain a supply of an appropriate antibiotic to take at the onset of symptoms of a bacterial infection.)
- Dental checkups every 6 months.
- Avoid activities that could increase the risk of bone fractures.
EPIDEMIOLOGY
• Predominant age: Symptoms start to appear 3-6 months after birth with severe form
• Predominant sex: Male = Female
Incidence
Occurs in 4.4/10,000 live births
Prevalence
• 1,000 patients in the United States are affected with -thalassemia major.
• The prevalence of thalassemia trait within the involved ethnic groups ranges from 5-30%.
RISK FACTORS
Family history
Genetics
• Inherited in an autosomal recessive pattern
• -Thalassemia results from deletion of one or more of the four genes responsible for -globin synthesis. Four-gene deletions results in fatal hydrops fetalis. Three-gene deletions results in hemoglobin H. Two-gene deletions is trait and one-gene deletion is a "silent" carrier state.
• -Thalassemia is caused by any of more than 200 point mutations and very rarely deletions.
• Significantly disparate phenotype with the same genotype is unexplained by variability of known loci
ETIOLOGY
Genetic
ASSOCIATED CONDITIONS
See Complications
DIAGNOSIS
SIGNS AND SYMPTOMS
Thalassemia trait has no signs or symptoms.
History
• Poor growth
• Inadequate food intake
• Fatigue
• Cholelithiasis
• Pathologic fractures
• Shortness of breath
Physical Exam
• Pallor
• Splenomegaly
• Jaundice
• Maxillary hyperplasia
• Dental malocclusion
TESTS
Special tests
• Bone marrow aspiration
• For children, calculate Mentzer index (MCV/RBC count)
- 13, thalassemia more likely
- >13, iron deficiency more likely. (2)
Lab
• Hemoglobin: Usual range 10.0-12.0 g/dL with thalassemia trait
• Hematocrit
- 28-40% in thalassemia trait
- May fall to 10% in -thalassemia major
• Peripheral blood
- Microcytosis
- Hypochromia
- High percentage of target cells
- Reticulocyte count elevated
• Hemoglobin electrophoresis
- In -thalassemia trait elevated Hb A2 levels
- In -thalassemia major or intermedia elevated Hb A2, elevated Hb F, reduced or absent Hb A1
- In -thalassemia, no recognizable electrophoretic pattern occurs.
Pathological Findings
• Bone marrow erythroid hyperplasia
• Iron deposits in heart muscle
• Hepatic siderosis
DIFFERENTIAL DIAGNOSIS
• Iron deficiency
• Other hemoglobinopathies
• Other hemolytic anemias
TREATMENT
• Outpatient for mild cases
• Inpatient for transfusion therapy
GENERAL MEASURES
• Mild cases require no therapy.
• Thalassemia intermedia: Normally no therapy necessary unless hemoglobin levels fall to a level that causes symptoms, then transfusion therapy may be needed
• Thalassemia major
- Maintain a mean hemoglobin level of at least 9.3 g/dL (1.4 mmol/L) with a regular transfusion schedule.
- Folate supplementation daily
- Treat bacterial infections promptly.
• Iron overload
- Patients receiving transfusion therapy increase total body iron 4 times over the normal amount.
- Therapy is iron chelation.
Diet
• Thalassemia minor requires no restrictions.
• -Thalassemia major
- Avoid iron-rich foods (red meats such as liver, and some cereals).
- Drinking tea may possibly help reduce iron absorption.
Activity
• Thalassemia minor requires no restrictions
• -Thalassemia major
- Avoid strenuous activities (e.g., football, soccer).
- Acceptable activity levels will be determined on an individual basis depending on severity of disorder.
MEDICATION (DRUGS)
• Antibiotics for bacterial infections
• Thalassemia intermedia
- Folic acid supplements
First Line
Thalassemia major
• Iron chelation with deferoxamine (Desferal)
- SC or continuous IV infusion (3)[C]
- Usually started before 5-8 years of age
Second Line
• Deferiprone, PO, acceptable alternative for patients unable to receive deferoxamine (3)[C]
• Contraindications to chelation therapy Refer to manufacturer's literature.
• Precautions with chelation therapy Refer to manufacturer's literature.
• Possible significant interactions with chelation therapy Refer to manufacturer's literature.
SURGERY
• Splenectomy
- May be needed if hypersplenism causes a marked increase in the transfusion requirement
- Defer surgery until patient is 4-6 years of age (due to increased infection risk).
- Administer polyvalent pneumococcal vaccine 1 month prior to splenectomy.
- Daily penicillin prophylaxis post splenectormy
• Bone marrow transplantation in childhood
- Only curative therapy and generally excellent outcome for low-risk patients
FOLLOW-UP
DISPOSITION
Issues for Referral
Thalassemia major usually requires hematology consult.
PROGNOSIS
• Outlook varies depending on type.
• Thalassemia minor patients live a normal life span.
• Thalassemia major patients live an average of 17 years and usually die by age 30.
• Iron overload causes most of the morbidity and mortality.
- Cardiac events are the primary cause of death.
- Effective iron chelation is improving longevity.
COMPLICATIONS
• Chronic hemolysis
• Susceptibility to infections after splenectomy
• Infections from blood transfusion
• Jaundice
• Leg ulcers
• Cholelithiasis
• Osteoporosis and low-trauma fractures
• Impaired growth rate
• Delayed or absent puberty
• Hypogonadism
• Hepatic siderosis
• Splenomegaly
• Cardiac disease from iron overload
• Thromboembolic phenomenon
• Aplastic and megaloblastic crises
PATIENT MONITORING
• For -thalassemia major, life-long monitoring is necessary because the therapy and disease progression have numerous potential complications.
• Thalassemia minor patients require no special follow-up.
REFERENCES
1. Andrews J, Wilson M. Screening for hemoglobinopathies. United States Preventive Services Task Force,1996;485-492.
2. Irwn JJ, Kirchner JT. Anemia in children. Am Fam Physician. 2001;64:1379-1386.
3. Rund D, Rachmilewitz E. -Thalassemia. N Engl J Med. 2005;353:1135-1146.
4. Dhaliwal G, Cornett PA, Tierney LM. Hemolytic anemia. Am Fam Physician. 2004;69:2599-2606.
TETRALOGY OF FALLOT
TETRALOGY OF FALLOT - Maya Roberts, BA; Mark R. Dambro, MD
BASICS
DESCRIPTION
• Large ventricular septal defect associated with right ventricular outflow obstruction (infundibular and/or valvular pulmonic stenosis), concentric right ventricular hypertrophy, and overriding aorta
• Pathophysiology depends primarily on severity of right ventricular outflow tract obstruction.
• Right and left ventricular pressures are generally equal.
• Right ventricular pressures are elevated with ventricular septal defect proximal to level of right ventricular obstruction.
• Right-to-left shunting predominates, resulting in varying degrees of arterial hemoglobin desaturation.
• System(s) Affected: Cardiovascular; Pulmonary
ALERT
Pediatric Considerations
Congenital disorder
Pregnancy Considerations
Pregnancy is usually well tolerated after successful surgical repair.
EPIDEMIOLOGY
• Predominant age: Newborn
• Predominant sex: Male > Female (slightly)
Incidence
• 5-10% of all congenital heart disease.
• Most common cardiac anomaly within 1st year of life requiring intervention.
Prevalence
In the US: 3.9/10,000 live births.
RISK FACTORS
• Predominately sporadic
• Increased incidence with increasing maternal age
Genetics
• Occasional familial occurrence, dominant mode of inheritance
• Reports of "incomplete penetrance" as asymptomatic mitral valve malpositioning in family members
ETIOLOGY
Unknown
ASSOCIATED CONDITIONS
• Stenotic pulmonary artery
• Patent ductus arteriosus
• Atrial septal defect
• Iron deficiency anemia
• 15% have extracardiac anomalies including Down syndrome, Alagille, DiGeorge, and velocardiofacial syndromes
DIAGNOSIS
SIGNS AND SYMPTOMS
• Presentation depends on the severity of pulmonic stenosis.
• "Pink" tetralogy of Fallot: Occurs in patients in whom mild right ventricular outflow tract obstruction results in left-to-right shunt (thus acyanotic)
• Cyanosis, particularly in the nail beds and lips, with severe right ventricular outflow tract obstruction (generally recognized early)
• Delayed development
• Retarded growth
• Clubbing and polycythemia in children secondary to hypoxia
• Exertional dyspnea, poor exercise tolerance
• Acute hypercyanotic episodes or "Tet spells" (caused by increased right-to-left shunt)
• Squatting position, typically following exertion and during "Tet spells" (reduces right-to-left shunting by increasing systemic vascular resistance)
• Normal arterial and jugular venous pulses
• Systolic thrill along the left sternal border
• Early systolic ejection sound (aortic)
• Single S2 (decreased P2)
• Crescendo-decrescendo systolic ejection murmur results from flow across narrowed right ventricular outflow tract.
• Continuous soft murmur of bronchial collateral vessels
• Retinal ischemia
• Right sided aortic arch: 25%
• Atrial septal defect: 15%
• Anomalous coronary arteries: 9%
TESTS
ECG
• Sinus rhythm in general; however, some may develop atrial fibrillation or flutter
• Right atrial enlargement and right ventricular hypertrophy
• Right axis deviation and right ventricular conduction abnormality may also be seen.
Imaging
• Chest radiograph
- Classic boot-shaped heart (coeur en sabot) with diminished pulmonary blood flow
- Prominent right ventricle
- Right-sided aortic arch and knob in 25% of patients
- Normal (or decreased) pulmonary vascularity in 50% of adults
• Transthoracic echocardiogram (occasionally transesophageal)
- 2-D images outline
Ventricular septal defect, atrial septum, right ventricular hypertrophy and extent and location of the infundibular obstruction.
Overriding aorta and assessment of pulmonic valve.
Coronary anatomy and peripheral branch pulmonic arteries.
- Doppler echocardiogram allows quantification of the outflow gradient.
- Color-flow Doppler mapping provides detailed assessment of the ventricular septal defect.
Diagnostic Procedures/Surgery
Cardiac catheterization
• Details anatomic structure
• Assesses pulmonary annulus size and pulmonary artery hypoplasia
• Assesses severity of right ventricular outflow obstruction
• Locates position of primary ventricular septal defect and its size, identifies possible additional ventricular septal defects
• Rules out coronary artery anomalies
• Balloon valvuloplasty to reduce pulmonary stenosis
Pathological Findings
• Anterior and cephalad deviation of the infundibular septum, resulting in malalignment with the muscular septum, creating a ventricular septal defect
• Malposition of the infundibular septum encroaching on the right ventricular outflow tract, resulting in an increased aortic root size
• Aortic root rotated into overriding position
DIFFERENTIAL DIAGNOSIS
• Fallot tetralogy with absent pulmonic valve
• Fallot tetralogy with absent pulmonary artery
• Pseudotruncus arteriosus
TREATMENT
STABILIZATION
Inpatient for diagnosis and surgery
GENERAL MEASURES
• Good dental hygiene
• Endocarditis prophylaxis
Diet
Salt restriction
Activity
As tolerated
MEDICATION (DRUGS)
No specific drug therapy in the absence of heart failure
SURGERY
• Total corrective surgical therapy includes patch closure of ventricular septal defect and pulmonary valvulotomy to relieve right ventricular outflow obstruction.
• Palliative surgical therapy (complete repair with a systemic-to-pulmonary shunt is the preferred modality of treatment).
- Blalock-Taussig shunt or modified shunt with Gore-Tex tubing: Subclavian to pulmonary artery
- Pott procedure (descending aorta to pulmonary artery and Waterston shunt (ascending aorta to pulmonary artery) no longer used because of high pulmonary blood flow and development of pulmonary hypertension
FOLLOW-UP
PROGNOSIS
Without surgery, survival was 40% at 3 years and 3% at 40 years. Surgical correction yields a survival of 92% at 10 years, 76% at 40 years.
COMPLICATIONS
• Postoperatively
- Residual right ventricular outflow obstruction
- Residual ventricular septal defect
- Chronic pulmonary regurgitation (with subsequent valve replacement occasionally required)
- Ventricular and atrial tachyarrhythmias
- Right bundle branch block (common)
- Left anterior hemiblock
- Infective bacterial endocarditis
- Hemoptysis
• Erythrocytosis secondary to chronic hypoxemia (increased risk for thrombosis, thrombotic cerebrovascular accident, and paradoxical emboli).
• Increased risk for brain abscess
• Acute gouty arthritis
• Infective endocarditis
• Delayed puberty
PATIENT MONITORING
• Postprocedure echocardiography suggested after 1 year
• Good dental hygiene and subacute bacterial endocarditis prophylaxis
• Regular follow-up assessment for patients not undergoing surgical correction
REFERENCES
1. Shinebourne E, Babu-Narayan S, Carvalho J. Tetralogy of Fallot: From fetus to adult. Heart. 2006;92:1353-1359.
2. Doyle T, Kavanaught-McHugh A, Graham T. Pathophysiology; clinical features; and diagnosis of tetralogy of Fallot overview of the management of tetralogy of Fallot. UpToDate. 2006.
3. Pham P, Silberbach M. What's new in pediatric cardiology. Pediatr Rev. 2004;25(11):381-387.
4. Ramaswamy P. Systemic to pulmonary artery shunting for palliation. eMedicine. 12 Dec, 2006
5. Braunwald E, ed. Heart Disease: A Textbook of Cardiovascular Medicine, 5th ed. Philadelphia: WB Saunders, 1996
6. Bertranou EG, Blackston EH, Hazelrig JB, et al. Life expectancy without surgery in tetralogy of Fallot. Am J Cardiol. 1978;42(3):458-466.
7. Liberthson R. Congenital Heart Disease: Diagnosis Management in Children and Adults. Boston: Little, Brown, and Company, 1989.
8. Perloff J. Clinical Recognition of Congenital Heart Disease, 4th ed. Philadelphia: WB Saunders, 1994.
BASICS
DESCRIPTION
• Large ventricular septal defect associated with right ventricular outflow obstruction (infundibular and/or valvular pulmonic stenosis), concentric right ventricular hypertrophy, and overriding aorta
• Pathophysiology depends primarily on severity of right ventricular outflow tract obstruction.
• Right and left ventricular pressures are generally equal.
• Right ventricular pressures are elevated with ventricular septal defect proximal to level of right ventricular obstruction.
• Right-to-left shunting predominates, resulting in varying degrees of arterial hemoglobin desaturation.
• System(s) Affected: Cardiovascular; Pulmonary
ALERT
Pediatric Considerations
Congenital disorder
Pregnancy Considerations
Pregnancy is usually well tolerated after successful surgical repair.
EPIDEMIOLOGY
• Predominant age: Newborn
• Predominant sex: Male > Female (slightly)
Incidence
• 5-10% of all congenital heart disease.
• Most common cardiac anomaly within 1st year of life requiring intervention.
Prevalence
In the US: 3.9/10,000 live births.
RISK FACTORS
• Predominately sporadic
• Increased incidence with increasing maternal age
Genetics
• Occasional familial occurrence, dominant mode of inheritance
• Reports of "incomplete penetrance" as asymptomatic mitral valve malpositioning in family members
ETIOLOGY
Unknown
ASSOCIATED CONDITIONS
• Stenotic pulmonary artery
• Patent ductus arteriosus
• Atrial septal defect
• Iron deficiency anemia
• 15% have extracardiac anomalies including Down syndrome, Alagille, DiGeorge, and velocardiofacial syndromes
DIAGNOSIS
SIGNS AND SYMPTOMS
• Presentation depends on the severity of pulmonic stenosis.
• "Pink" tetralogy of Fallot: Occurs in patients in whom mild right ventricular outflow tract obstruction results in left-to-right shunt (thus acyanotic)
• Cyanosis, particularly in the nail beds and lips, with severe right ventricular outflow tract obstruction (generally recognized early)
• Delayed development
• Retarded growth
• Clubbing and polycythemia in children secondary to hypoxia
• Exertional dyspnea, poor exercise tolerance
• Acute hypercyanotic episodes or "Tet spells" (caused by increased right-to-left shunt)
• Squatting position, typically following exertion and during "Tet spells" (reduces right-to-left shunting by increasing systemic vascular resistance)
• Normal arterial and jugular venous pulses
• Systolic thrill along the left sternal border
• Early systolic ejection sound (aortic)
• Single S2 (decreased P2)
• Crescendo-decrescendo systolic ejection murmur results from flow across narrowed right ventricular outflow tract.
• Continuous soft murmur of bronchial collateral vessels
• Retinal ischemia
• Right sided aortic arch: 25%
• Atrial septal defect: 15%
• Anomalous coronary arteries: 9%
TESTS
ECG
• Sinus rhythm in general; however, some may develop atrial fibrillation or flutter
• Right atrial enlargement and right ventricular hypertrophy
• Right axis deviation and right ventricular conduction abnormality may also be seen.
Imaging
• Chest radiograph
- Classic boot-shaped heart (coeur en sabot) with diminished pulmonary blood flow
- Prominent right ventricle
- Right-sided aortic arch and knob in 25% of patients
- Normal (or decreased) pulmonary vascularity in 50% of adults
• Transthoracic echocardiogram (occasionally transesophageal)
- 2-D images outline
Ventricular septal defect, atrial septum, right ventricular hypertrophy and extent and location of the infundibular obstruction.
Overriding aorta and assessment of pulmonic valve.
Coronary anatomy and peripheral branch pulmonic arteries.
- Doppler echocardiogram allows quantification of the outflow gradient.
- Color-flow Doppler mapping provides detailed assessment of the ventricular septal defect.
Diagnostic Procedures/Surgery
Cardiac catheterization
• Details anatomic structure
• Assesses pulmonary annulus size and pulmonary artery hypoplasia
• Assesses severity of right ventricular outflow obstruction
• Locates position of primary ventricular septal defect and its size, identifies possible additional ventricular septal defects
• Rules out coronary artery anomalies
• Balloon valvuloplasty to reduce pulmonary stenosis
Pathological Findings
• Anterior and cephalad deviation of the infundibular septum, resulting in malalignment with the muscular septum, creating a ventricular septal defect
• Malposition of the infundibular septum encroaching on the right ventricular outflow tract, resulting in an increased aortic root size
• Aortic root rotated into overriding position
DIFFERENTIAL DIAGNOSIS
• Fallot tetralogy with absent pulmonic valve
• Fallot tetralogy with absent pulmonary artery
• Pseudotruncus arteriosus
TREATMENT
STABILIZATION
Inpatient for diagnosis and surgery
GENERAL MEASURES
• Good dental hygiene
• Endocarditis prophylaxis
Diet
Salt restriction
Activity
As tolerated
MEDICATION (DRUGS)
No specific drug therapy in the absence of heart failure
SURGERY
• Total corrective surgical therapy includes patch closure of ventricular septal defect and pulmonary valvulotomy to relieve right ventricular outflow obstruction.
• Palliative surgical therapy (complete repair with a systemic-to-pulmonary shunt is the preferred modality of treatment).
- Blalock-Taussig shunt or modified shunt with Gore-Tex tubing: Subclavian to pulmonary artery
- Pott procedure (descending aorta to pulmonary artery and Waterston shunt (ascending aorta to pulmonary artery) no longer used because of high pulmonary blood flow and development of pulmonary hypertension
FOLLOW-UP
PROGNOSIS
Without surgery, survival was 40% at 3 years and 3% at 40 years. Surgical correction yields a survival of 92% at 10 years, 76% at 40 years.
COMPLICATIONS
• Postoperatively
- Residual right ventricular outflow obstruction
- Residual ventricular septal defect
- Chronic pulmonary regurgitation (with subsequent valve replacement occasionally required)
- Ventricular and atrial tachyarrhythmias
- Right bundle branch block (common)
- Left anterior hemiblock
- Infective bacterial endocarditis
- Hemoptysis
• Erythrocytosis secondary to chronic hypoxemia (increased risk for thrombosis, thrombotic cerebrovascular accident, and paradoxical emboli).
• Increased risk for brain abscess
• Acute gouty arthritis
• Infective endocarditis
• Delayed puberty
PATIENT MONITORING
• Postprocedure echocardiography suggested after 1 year
• Good dental hygiene and subacute bacterial endocarditis prophylaxis
• Regular follow-up assessment for patients not undergoing surgical correction
REFERENCES
1. Shinebourne E, Babu-Narayan S, Carvalho J. Tetralogy of Fallot: From fetus to adult. Heart. 2006;92:1353-1359.
2. Doyle T, Kavanaught-McHugh A, Graham T. Pathophysiology; clinical features; and diagnosis of tetralogy of Fallot overview of the management of tetralogy of Fallot. UpToDate. 2006.
3. Pham P, Silberbach M. What's new in pediatric cardiology. Pediatr Rev. 2004;25(11):381-387.
4. Ramaswamy P. Systemic to pulmonary artery shunting for palliation. eMedicine. 12 Dec, 2006
5. Braunwald E, ed. Heart Disease: A Textbook of Cardiovascular Medicine, 5th ed. Philadelphia: WB Saunders, 1996
6. Bertranou EG, Blackston EH, Hazelrig JB, et al. Life expectancy without surgery in tetralogy of Fallot. Am J Cardiol. 1978;42(3):458-466.
7. Liberthson R. Congenital Heart Disease: Diagnosis Management in Children and Adults. Boston: Little, Brown, and Company, 1989.
8. Perloff J. Clinical Recognition of Congenital Heart Disease, 4th ed. Philadelphia: WB Saunders, 1994.
TETANUS
TETANUS - Abdulrazak Abyad, MD, PhD, MBA, MPH, AGSF
BASICS
DESCRIPTION
• Severe illness characterized by intermittent tonic spasms of voluntary muscles
• Toxin enters the central nervous system along the peripheral nerves or is blood borne.
• Tetanospasmin binds at synapses and blocks inhibitors.
• Usual course is acute
• System(s) Affected: Nervous
• Synonym(s): Lockjaw
ALERT
Geriatric Considerations
Mortality high in elderly, and this group may not have adequate immunizations.
Pediatric Considerations
• Mortality high in young
• Infection may enter through umbilical cord.
Pregnancy Considerations
• Must treat vigorously despite pregnancy
• Infection may enter uterus postpartum.
• Tetanus toxoid probably safe, but few data available
GENERAL PREVENTION
• Active immunization with tetanus toxoid
• Wound debridement
• Passive immunization with tetanus immune globulin (TIG)
• Acellular vaccine
• Benzathine penicillin
• Penicillin G
• Erythromycin
EPIDEMIOLOGY
• Predominant age: >70% of cases in persons >50 years of age
• Predominant sex: Male = Female
Incidence
Rare
Prevalence
Rare
RISK FACTORS
• Burns
• Drug addiction (parenteral)
• Ear infection (with tympanic membrane perforation)
• Early postpartum with an infected uterus
• Exposure of open wounds to soil and animal feces
• Frostbite
• Newborn (umbilicus stump entry)
• Skin ulcers
• Surgical wounds
• Age >50 years
• Traumatic wound
ETIOLOGY
• Infection with Clostridium tetani
• Neurotoxin produced by C. tetani
• Tetanospasmin (an exotoxin)
DIAGNOSIS
SIGNS AND SYMPTOMS
• Arrhythmias
• Asphyxia
• Convulsions
• Cyanosis
• Drooling
• Dysphagia
• Fluctuating hypertension
• Hydrophobia
• Hyperhidrosis
• Hyperpyrexia
• Hyperreflexia
• Hypotension
• Irritability
• Low-grade fever
• Muscular rigidity
• Muscular spasticity
• Nuchal rigidity
• Opisthotonos
• Pain at wound site
• Painful tonic convulsions
• Risus sardonicus (fixed smile)
• Stiffness of the jaw
• Sudden bradycardia
• Sudden cardiac arrest
• Tachycardia
• Tingling at wound site
• Trismus
• Wound history (may be absent)
TESTS
• ECG: Supraventricular tachycardia
• Multifocal ventricular ectopia
• Bradycardia
• EEG sleeping pattern
• Culture of wound infrequently recovers C. tetani
Lab
• Polymorphonuclear leukocytosis
• Culture of C. tetani from wound (may not be positive even if tetanus is the problem)
DIFFERENTIAL DIAGNOSIS
• Dental abscess
• Subarachnoid hemorrhage
• Seizure disorder
• Meningoencephalitis
• Peritonsillar abscess
• Dystonic reaction to phenothiazines
• Hypocalcemic tetany
• Strychnine poisoning
• Alcohol withdrawal
TREATMENT
STABILIZATION
Intensive care
GENERAL MEASURES
• Wound excision
• Quiet observation
• Intubation
• IV hydration
• Catheterize the bladder.
• Prevent jarring of bed or drafts.
Diet
Nothing by mouth until well
Activity
Absolute bed rest with sedation
MEDICATION (DRUGS)
First Line
• Anticonvulsants
• Diazepam for muscle rigidity
• Pancuronium bromide (administered by anesthesiologist) plus ventilation
• Tetanus toxoid in a previously immunized patient
• TIG: 3,000-6,000 U IM. May infiltrate the area around the wound with a portion of the dose
• Penicillin G: 2 million U IV q6h. In a penicillin-allergic patient, use doxycycline 100 mg q12h, or clindamycin 150-300 mg IV q6h.
• Contraindications: Refer to the manufacturer's literature for each drug.
• Precautions
- Refer to the manufacturer's literature for each drug.
- Do not use TIG IV.
• Significant possible interactions: Refer to the manufacturer's literature for each drug.
Second Line
Equine tetanus antitoxin: 50,000 U IM, but only if TIG (human) is not available.
SURGERY
Tracheostomy if needed
FOLLOW-UP
PROGNOSIS
• 25-50% mortality
• Poor prognostic factors
- Form of tetanus
- Incubation period
- Onset period
- Patient's age
- Severity of symptoms
- Heart wound
• Recovery is complete if patient survives.
COMPLICATIONS
• Respiratory arrest
• Cardiac failure
• Pulmonary emboli
• Bacterial infection
• Dehydration
• Vertebral fractures
• Airway obstruction
• Anoxia
• Urinary retention
• Constipation
• Pneumonia
• Rhabdomyolysis
PATIENT MONITORING
Careful observation in intensive care
REFERENCES
1. Centers for Disease Control. Tetanus: United States 1981-1984. Morbid Mortal Weekly Rep. 1985;34:602.
2. Lugauer S, et al. Long-term clinical effectiveness of an acellular pertussis component vaccine and a whole cell pertussis component vaccine. Eur J Pediatr. 2002;161:142-146.
3. Mandell GL, ed. Principles and Practice of Infectious Diseases. 4th ed. New York: Churchill Livingstone; 1995.
4. von Behring E, Kitasato S. Uber das Zustandelkommen der Diphtherie-Immunitat und der Tetanus-Immunitat bei Thieren. Deutsch Med Wochenschr. 1890;16:1113.
BASICS
DESCRIPTION
• Severe illness characterized by intermittent tonic spasms of voluntary muscles
• Toxin enters the central nervous system along the peripheral nerves or is blood borne.
• Tetanospasmin binds at synapses and blocks inhibitors.
• Usual course is acute
• System(s) Affected: Nervous
• Synonym(s): Lockjaw
ALERT
Geriatric Considerations
Mortality high in elderly, and this group may not have adequate immunizations.
Pediatric Considerations
• Mortality high in young
• Infection may enter through umbilical cord.
Pregnancy Considerations
• Must treat vigorously despite pregnancy
• Infection may enter uterus postpartum.
• Tetanus toxoid probably safe, but few data available
GENERAL PREVENTION
• Active immunization with tetanus toxoid
• Wound debridement
• Passive immunization with tetanus immune globulin (TIG)
• Acellular vaccine
• Benzathine penicillin
• Penicillin G
• Erythromycin
EPIDEMIOLOGY
• Predominant age: >70% of cases in persons >50 years of age
• Predominant sex: Male = Female
Incidence
Rare
Prevalence
Rare
RISK FACTORS
• Burns
• Drug addiction (parenteral)
• Ear infection (with tympanic membrane perforation)
• Early postpartum with an infected uterus
• Exposure of open wounds to soil and animal feces
• Frostbite
• Newborn (umbilicus stump entry)
• Skin ulcers
• Surgical wounds
• Age >50 years
• Traumatic wound
ETIOLOGY
• Infection with Clostridium tetani
• Neurotoxin produced by C. tetani
• Tetanospasmin (an exotoxin)
DIAGNOSIS
SIGNS AND SYMPTOMS
• Arrhythmias
• Asphyxia
• Convulsions
• Cyanosis
• Drooling
• Dysphagia
• Fluctuating hypertension
• Hydrophobia
• Hyperhidrosis
• Hyperpyrexia
• Hyperreflexia
• Hypotension
• Irritability
• Low-grade fever
• Muscular rigidity
• Muscular spasticity
• Nuchal rigidity
• Opisthotonos
• Pain at wound site
• Painful tonic convulsions
• Risus sardonicus (fixed smile)
• Stiffness of the jaw
• Sudden bradycardia
• Sudden cardiac arrest
• Tachycardia
• Tingling at wound site
• Trismus
• Wound history (may be absent)
TESTS
• ECG: Supraventricular tachycardia
• Multifocal ventricular ectopia
• Bradycardia
• EEG sleeping pattern
• Culture of wound infrequently recovers C. tetani
Lab
• Polymorphonuclear leukocytosis
• Culture of C. tetani from wound (may not be positive even if tetanus is the problem)
DIFFERENTIAL DIAGNOSIS
• Dental abscess
• Subarachnoid hemorrhage
• Seizure disorder
• Meningoencephalitis
• Peritonsillar abscess
• Dystonic reaction to phenothiazines
• Hypocalcemic tetany
• Strychnine poisoning
• Alcohol withdrawal
TREATMENT
STABILIZATION
Intensive care
GENERAL MEASURES
• Wound excision
• Quiet observation
• Intubation
• IV hydration
• Catheterize the bladder.
• Prevent jarring of bed or drafts.
Diet
Nothing by mouth until well
Activity
Absolute bed rest with sedation
MEDICATION (DRUGS)
First Line
• Anticonvulsants
• Diazepam for muscle rigidity
• Pancuronium bromide (administered by anesthesiologist) plus ventilation
• Tetanus toxoid in a previously immunized patient
• TIG: 3,000-6,000 U IM. May infiltrate the area around the wound with a portion of the dose
• Penicillin G: 2 million U IV q6h. In a penicillin-allergic patient, use doxycycline 100 mg q12h, or clindamycin 150-300 mg IV q6h.
• Contraindications: Refer to the manufacturer's literature for each drug.
• Precautions
- Refer to the manufacturer's literature for each drug.
- Do not use TIG IV.
• Significant possible interactions: Refer to the manufacturer's literature for each drug.
Second Line
Equine tetanus antitoxin: 50,000 U IM, but only if TIG (human) is not available.
SURGERY
Tracheostomy if needed
FOLLOW-UP
PROGNOSIS
• 25-50% mortality
• Poor prognostic factors
- Form of tetanus
- Incubation period
- Onset period
- Patient's age
- Severity of symptoms
- Heart wound
• Recovery is complete if patient survives.
COMPLICATIONS
• Respiratory arrest
• Cardiac failure
• Pulmonary emboli
• Bacterial infection
• Dehydration
• Vertebral fractures
• Airway obstruction
• Anoxia
• Urinary retention
• Constipation
• Pneumonia
• Rhabdomyolysis
PATIENT MONITORING
Careful observation in intensive care
REFERENCES
1. Centers for Disease Control. Tetanus: United States 1981-1984. Morbid Mortal Weekly Rep. 1985;34:602.
2. Lugauer S, et al. Long-term clinical effectiveness of an acellular pertussis component vaccine and a whole cell pertussis component vaccine. Eur J Pediatr. 2002;161:142-146.
3. Mandell GL, ed. Principles and Practice of Infectious Diseases. 4th ed. New York: Churchill Livingstone; 1995.
4. von Behring E, Kitasato S. Uber das Zustandelkommen der Diphtherie-Immunitat und der Tetanus-Immunitat bei Thieren. Deutsch Med Wochenschr. 1890;16:1113.
TESTICULAR TORSION
TESTICULAR TORSION - Timothy L. Black, MD
BASICS
DESCRIPTION
• Twisting of testis and spermatic cord, resulting in acute ischemia
- Intravaginal torsion: Occurs within tunica vaginalis
- Extravaginal torsion: Involves twisting of testis, cord, and processus vaginalis (especially in newborns) and in undescended testes
• System(s) Affected: Reproductive
ALERT
Geriatric Considerations
Rare in this age group
Pediatric Considerations
Most common at age 14 years
EPIDEMIOLOGY
• Predominant age
- Occurs from newborn period to seventh decade
- Two thirds of cases occur in second decade, with peak at age 14 years. (1)[C]
- Second peak in neonates
• Predominant sex: Males only
Incidence
1:160 males
RISK FACTORS
• May be more common in winter
• Paraplegia
• Previous contralateral testicular torsion
Genetics
Unknown
ETIOLOGY
• Torsion is usually spontaneous and idiopathic.
• History of trauma in 20% of patients
• One third have had prior episodic testicular pain.
• Contraction of cremasteric muscle or dartos may play a role and is stimulated by trauma, exercise, cold, and sexual stimulation.
• Possible alterations in testosterone levels during nocturnal sex response cycle; possible elevated testosterone levels in neonates
• Testis must have inadequate, incomplete, or absent fixation within scrotum.
• Torsion may occur in either clockwise or counter-clockwise direction. (2)[C]
DIAGNOSIS
SIGNS AND SYMPTOMS
• Scrotum is enlarged, red, edematous, and painful.
• The first symptom is pain (usually sudden, but may have a gradual onset, with subsequent increase in severity).
• Nausea and vomiting are common.
• Fever may occur, but is not typical.
• Testicle exquisitely tender
• Testis may be high in scrotum with a transverse lie.
• Absence of cremasteric reflex
History
• Acute onset of pain, often during period of inactivity
• Prior history of multiple episodes of testicular pain with spontaneous resolution may indicate intermittent testicular torsion. (1)
Physical Exam
Tender, swollen, erythematous testicle
TESTS
Lab
Urinalysis usually not helpful
Imaging
Doppler ultrasound may confirm testicular swelling, but is diagnostic by demonstrating lack of blood flow to the testicle.
Diagnostic Procedures/Surgery
• Doppler ultrasonic flow detection demonstrates absent or reduced blood flow with torsion, increased flow with inflammatory process (reliable only in first 12 hours). (2)[C]
• Radionuclide testicular scintigraphy with technetium-99m pertechnetate demonstrates absent/decreased vascularity in torsion, increased vascularity with inflammatory processes (including torsion of appendix testes).
• In boys with intermittent, recurrent testicular torsion, both Doppler ultrasound and radionuclide scintigraphy will be normal. (3)[C]
Pathological Findings
• Venous thrombosis
• Tissue edema and necrosis
• Arterial thrombosis
DIFFERENTIAL DIAGNOSIS
• Epididymo-orchitis
• Incarcerated/strangulated inguinal hernia
• Acute hydrocele
• Traumatic hematoma
• Idiopathic scrotal edema
• Torsion appendix testis
• Acute varicocele
• Testicular tumor
• Henoch-Schonlein purpura
• Scrotal abscess
• Leukemic infiltrate
TREATMENT
• Manual reduction: May be successful, facilitated by lidocaine 1% (plain) injection at level of external ring. Must always be followed by orchidopexy
• Surgical exploration via scrotal approach with detorsion, evaluation of testicular viability, orchidopexy of viable testicle, orchiectomy of nonviable testicle
• In boys with history of intermittent episodes of testicular pain, scrotal exploration warranted with testicular fixation if abnormal testicular attactments confirmed. (3)[C]
GENERAL MEASURES
Early examination crucial as necrosis of the testicle usually occurs after 6-8 hours
Diet
Regular
SURGERY
• Bilateral testicular fixation is recommended by many surgeons.
• At least 3- to 4-point fixation with nonabsorbable sutures between the tunica albuginea and the tunica vaginalis.
• Excision of window of tunica albuginea with suture to dartos fascia
• Any testis that is not clearly viable (and obvious) should be removed.
• Testes of questionalble viability which are preserved and pexed invariably atrophy.
• Requires general anesthesia
• Usually can be done as an outpatient
FOLLOW-UP
PROGNOSIS
• Testicular salvage is related directly to duration of torsion (85-97% if 6 hours, less than 10% if >24 hours).
• 80-94% may have depressed spermatogenesis related to duration of ischemic injury (possibly related to autoimmune-mediated injury).
• As many as 2/3 of salvaged testicles may atrophy in first 2-3 years after torsion.
COMPLICATIONS
• Possible testicular atrophy
• Abnormal spermatogenesis
• Infertility
PATIENT MONITORING
• Postoperative visit at 1-2 weeks
• Yearly visits until puberty, to evaluate for atrophy
REFERENCES
1. Van Glubeke E, et al. Acute scrotal pain in children: Results of 543 surgical explorations. Pediatr Surg Int. 1999;15:353-357.
2. Sessions AE, et al. Testicular torsion: Direction, degree, duration and disinformation. J Urol. 2003;169:663-665.
3. Eaton SH, et al. Intermittent testicular torsion: Diagnostic features and management outcomes. J Urol. 2005;174:1532-1535.
BASICS
DESCRIPTION
• Twisting of testis and spermatic cord, resulting in acute ischemia
- Intravaginal torsion: Occurs within tunica vaginalis
- Extravaginal torsion: Involves twisting of testis, cord, and processus vaginalis (especially in newborns) and in undescended testes
• System(s) Affected: Reproductive
ALERT
Geriatric Considerations
Rare in this age group
Pediatric Considerations
Most common at age 14 years
EPIDEMIOLOGY
• Predominant age
- Occurs from newborn period to seventh decade
- Two thirds of cases occur in second decade, with peak at age 14 years. (1)[C]
- Second peak in neonates
• Predominant sex: Males only
Incidence
1:160 males
RISK FACTORS
• May be more common in winter
• Paraplegia
• Previous contralateral testicular torsion
Genetics
Unknown
ETIOLOGY
• Torsion is usually spontaneous and idiopathic.
• History of trauma in 20% of patients
• One third have had prior episodic testicular pain.
• Contraction of cremasteric muscle or dartos may play a role and is stimulated by trauma, exercise, cold, and sexual stimulation.
• Possible alterations in testosterone levels during nocturnal sex response cycle; possible elevated testosterone levels in neonates
• Testis must have inadequate, incomplete, or absent fixation within scrotum.
• Torsion may occur in either clockwise or counter-clockwise direction. (2)[C]
DIAGNOSIS
SIGNS AND SYMPTOMS
• Scrotum is enlarged, red, edematous, and painful.
• The first symptom is pain (usually sudden, but may have a gradual onset, with subsequent increase in severity).
• Nausea and vomiting are common.
• Fever may occur, but is not typical.
• Testicle exquisitely tender
• Testis may be high in scrotum with a transverse lie.
• Absence of cremasteric reflex
History
• Acute onset of pain, often during period of inactivity
• Prior history of multiple episodes of testicular pain with spontaneous resolution may indicate intermittent testicular torsion. (1)
Physical Exam
Tender, swollen, erythematous testicle
TESTS
Lab
Urinalysis usually not helpful
Imaging
Doppler ultrasound may confirm testicular swelling, but is diagnostic by demonstrating lack of blood flow to the testicle.
Diagnostic Procedures/Surgery
• Doppler ultrasonic flow detection demonstrates absent or reduced blood flow with torsion, increased flow with inflammatory process (reliable only in first 12 hours). (2)[C]
• Radionuclide testicular scintigraphy with technetium-99m pertechnetate demonstrates absent/decreased vascularity in torsion, increased vascularity with inflammatory processes (including torsion of appendix testes).
• In boys with intermittent, recurrent testicular torsion, both Doppler ultrasound and radionuclide scintigraphy will be normal. (3)[C]
Pathological Findings
• Venous thrombosis
• Tissue edema and necrosis
• Arterial thrombosis
DIFFERENTIAL DIAGNOSIS
• Epididymo-orchitis
• Incarcerated/strangulated inguinal hernia
• Acute hydrocele
• Traumatic hematoma
• Idiopathic scrotal edema
• Torsion appendix testis
• Acute varicocele
• Testicular tumor
• Henoch-Schonlein purpura
• Scrotal abscess
• Leukemic infiltrate
TREATMENT
• Manual reduction: May be successful, facilitated by lidocaine 1% (plain) injection at level of external ring. Must always be followed by orchidopexy
• Surgical exploration via scrotal approach with detorsion, evaluation of testicular viability, orchidopexy of viable testicle, orchiectomy of nonviable testicle
• In boys with history of intermittent episodes of testicular pain, scrotal exploration warranted with testicular fixation if abnormal testicular attactments confirmed. (3)[C]
GENERAL MEASURES
Early examination crucial as necrosis of the testicle usually occurs after 6-8 hours
Diet
Regular
SURGERY
• Bilateral testicular fixation is recommended by many surgeons.
• At least 3- to 4-point fixation with nonabsorbable sutures between the tunica albuginea and the tunica vaginalis.
• Excision of window of tunica albuginea with suture to dartos fascia
• Any testis that is not clearly viable (and obvious) should be removed.
• Testes of questionalble viability which are preserved and pexed invariably atrophy.
• Requires general anesthesia
• Usually can be done as an outpatient
FOLLOW-UP
PROGNOSIS
• Testicular salvage is related directly to duration of torsion (85-97% if 6 hours, less than 10% if >24 hours).
• 80-94% may have depressed spermatogenesis related to duration of ischemic injury (possibly related to autoimmune-mediated injury).
• As many as 2/3 of salvaged testicles may atrophy in first 2-3 years after torsion.
COMPLICATIONS
• Possible testicular atrophy
• Abnormal spermatogenesis
• Infertility
PATIENT MONITORING
• Postoperative visit at 1-2 weeks
• Yearly visits until puberty, to evaluate for atrophy
REFERENCES
1. Van Glubeke E, et al. Acute scrotal pain in children: Results of 543 surgical explorations. Pediatr Surg Int. 1999;15:353-357.
2. Sessions AE, et al. Testicular torsion: Direction, degree, duration and disinformation. J Urol. 2003;169:663-665.
3. Eaton SH, et al. Intermittent testicular torsion: Diagnostic features and management outcomes. J Urol. 2005;174:1532-1535.
TESTICULAR MALIGNANCIES
TESTICULAR MALIGNANCIES - Eric Nelson, MD; Leonard G. Gomella, MD
BASICS
DESCRIPTION
Testicular cancer is relatively rare, but is the most common malignancy among 20- 34-year-old men. Fortunately, it is one of the most curable solid organ cancers (93% 5-year survival). Testicular neoplasms may arise from any testicular or adnexal cell component and are divided into germinal (90-95%) and nongerminal tumors (5-10%). The germinal tumors, discussed here, are further divided into seminomatous and nonseminomatous types (embryonal, teratoma, choriocarcinomas, yolk sac).
• Clinical staging (based on 1997 AJCC TNMS)
- Stage 0: Carcinoma in situ
- Stage Ia: Tumor limited to testis and epididymis without vascular/lymphatic invasion
- Stage Ib: Tumor limited to testis and epididymis with vascular/lymphatic invasion or tumor extending through the tunica albuginea with involvement of tunica vaginalis
- Stage Ic: Any tumor with elevated markers
- Stage IIa: Any tumor with lymph node mass/masses no more than 2 cm
- Stage IIb: Any tumor with lymph node mass/masses 2-5 cm
- Stage IIc: Any tumor with lymph node mass greater than 5 cm
- Stage IIIa: Any tumor/lymph node presence with evidence of nonregional nodal or pulmonary metastases
- Stage IIIb: Any tumor/lymph node presence with moderately elevated serum tumor markers
- Stage IIIc: Any tumor/lymph node presence with greatly elevated serum tumor markers
• System(s) Affected: Reproductive
ALERT
Pediatric Considerations
Rare (2% of all solid tumors in childhood)
EPIDEMIOLOGY
• Predominant age: Peak incidence: Age 20-40 years; smaller peaks between age 0-10 years and >60 years
• Predominant sex: Male only
Incidence
• 1-2% of all neoplasms in men
• Increased incidence in last 40 years with substantial differences among countries; etiology unclear
• In adults, 95% are Germ Cell Tumors (GCT); In children, 65% are GCTs. Half of GCTs are seminomas; half are nonseminomatous.
Prevalence
• 2.3-6.3 cases/year per 100,000 men (less common in African Americans0.9 cases/year per 100,000)
• Trimodal distribution: Predominant peak at 20-40 years; slight peak in children younger than 5 years; slight peak in men older than 60 years
• Seminoma rare before 10 years or after age 60 years, but most common histologic type overall
RISK FACTORS
• Crytporchidism: The only proven risk factor with 2.5- to 11-fold incidence increase
• Caucasian race: Especially Scandinavian and Swiss
• Family history
• Higher socioeconomic status
• Increased maternal hormones during pregnancy
• Infertility or abnormal semen parameters
• Preterm birth
• Testicular atrophy
• Trauma
Genetics
• Familial clustering observed
• All cases show chromosome 12 alteration (12p)
ETIOLOGY
Cryptorchidism increased risk
ASSOCIATED CONDITIONS
Weak association with testicular microlithiasis
DIAGNOSIS
SIGNS AND SYMPTOMS
History
In adults
• Testicular nodule/painless swelling (most common presentation)
• Dull ache/heavy sensation (30-40%)
• Hydrocele (10-20%)
• Acute pain (10%), especially with epididymitis/acute hemorrhage
• Gynecomastia (may or may not be due to elevated hormones) (5%)
• Enlargement of a small or atrophic testicle
• Infertility
• Symptoms due to metastases: Supraclavicular mass, respiratory symptoms (lung metastasis), low back pain (nerve root or psoas irritation), lower extremity swelling (iliac or caval thrombosis or obstruction), GI disturbances (retroduodenal metastasis), bone pain (skeletal metastasis)
• In children: Painless testicular mass most common; can be seen in association with torsion
TESTS
Lab
• Markers are useful in the following settings
- To diagnose and stage disease
- To monitor the therapeutic response
- To detect tumor recurrence
• Levels should be drawn pre- and postoperatively
• Elevated markers postorchiectomy generally indicates systemic metastases rather than tumor confined to retroperitoneal nodes.
• Half-life important to evaluate therapeutic responses
• Alpha-fetoprotein (AFP)
- Half-life 5-7 days
- Increased in yolk sac tumors, teratoma, embryonal carcinoma, or combined tumors
- Not increased in pure choriocarcinoma or pure seminoma
- Levels also increased with liver disease
• Human chorionic gonadotropin (hCG)
- Half-life 24-36 hours
- Increased in pure choriocarcinoma, but found in 5-10% pure seminomas
- Beta subunit measured; alpha subunit shared with FSH, LH, TSH
• Lactate dehydrogenase (LDH)
- Reflects "tumor burden"
- Too ubiquitous to be specific, but proven prognostic factor
• Placental alkaline phosphatase (PLAP) and Gamma-glutamyl-transpeptidase (GGTP): Individual sensitivities low, but simultaneous determinations revealed elevation of one or both in 80% of patients with active disease
• Drugs that may alter lab results
- AFP may be elevated with chemotherapy, anesthetics, antiepileptics, alcohol abuse
- hCG may be elevated by marijuana use.
• Disorders that may alter lab results
- AFP may be altered by liver damage by drugs (above), viral hepatitis, alcohol abuse, benign or malignant liver conditions
- hCG may be altered by hypogonadism and malignancies of pancreas, stomach, kidney, breast, and bladder.
Imaging
• Scrotal ultrasound is the gold standard for testicular imaging; any hypoechoic area within the tunica albuginea is markedly suspicious for testicular cancer; also used for patients with palpably normal testes and evidence of extragonadal metastases.
• For staging
- Chest x-ray: PA/Lat to assess lung parenchyma and mediastinal structures
- Chest CT: More sensitive than x-ray, but must have high index of suspicion because high incidence of false positives
- Abdomen/Pelvis CT: Most effective to identify retroperitoneal lymph node involvement; replaced IV urography and pedal lymphangiography; is excellent at identifying retrocrural nodes
- MRI: No real advantage over CT
- PET: No real advantage over CT
Diagnostic Procedures/Surgery
• Radical inguinal orchiectomy: Definitive procedure for pathologic diagnosis
• Transscrotal biopsy/orchiectomy contraindicated as lymphatic drainage violated and inguinal portion of spermatic cord left
• Open biopsy rarely done except in highly selected cases of pediatric tumors that may be benign
Pathological Findings
Basically, two different groups based on germinal versus nongerminal and seminomatous versus nonseminomatous types
DIFFERENTIAL DIAGNOSIS
• Epididymitis
• Hernia
• Hydrocele
• Hematoma
• Spermatocele
• Syphilitic gumma
• Varicocele
• In children: Epidermoid/dermoid cyst, paratesticular rhabdomysocarcoma, macroorchidism, torsion
TREATMENT
Inpatient and outpatient
GENERAL MEASURES
• Germ cell cancers are divided into seminoma and nonseminoma types for treatment planning.
• Tumors with a mixture of seminomatous and nonseminomatous components should be managed as nonseminoma.
• All patients should be treated on an intent-to-cure basis, even if metastatic.
• Surgery
- Radical inguinal orchiectomy for all patients
- Prosthesis can be inserted at this time.
• Pure seminoma
- General principles
Highly radiosensitive
Relatively slow growth of micrometastases
- Stage IS (carcinoma in situ): Chemotherapy
Spermatocytic: Age usually over 65 years; no adjuvant therapy
Typical and anaplasatic: If patient has risk factors (tumor >6 cm; vascular/lymphatic invasion), low-dose abdominal/pelvic radiation with single-agent chemotherapy with carboplatin. If no risk factors, follow with surveillance in a motivated patient.
- Stage IIa and IIb: Radiation; chemotherapy if involved nodes close to kidney
- Stage IIc and III: Cisplatin-based chemotherapy; if residual mass: Observe if desmoplastic; if mass >3 cm and well-delineated: Do surgical resection; if histology positive: Do salvage chemotherapy
• Nonseminomatous germ cell tumors
- Stage IS: Chemotherapy with bleomycin, etoposide, cisplatin (BEP) (3 cycles)
- Stage I: If risk factors (T2, embryonal >40%, vascular/lymphatic invasion) absent, can do surveillance in motivated patient; if risk factors present or unreliable patient, do modified (template) RPLND and primary chemo with 3 cycles BEP. Then observe for N0-N1; for N2, give adjuvant chemotherapy, BEP
- Stage IIa, IIb: Bilateral RPLND and chemotherapy with BEP 3 cycles. If minimal nodal involvement (2 cm), no adjuvant chemo; if nodal involvement (>2 cm), give adjuvant chemo and BEP (2 cycles).
- Stage IIc, III: For good-risk disease, chemotherapy with BEP 3 cycles. RPLND if residual retroperitoneal mass. Salvage chemotherapy for recurrent disease after chemo, RPLND, or persistently elevated tumor markers. For poor-risk disease, primary chemotherapy with ifosfamide and possible bone marrow transplant; salvage chemo if poor response. "Desperation surgery" for tumor unresponsive to salvage chemo.
Diet
No special diet
Activity
As tolerated
SPECIAL THERAPY
Radiotherapy
Selective cases of seminoma
MEDICATION (DRUGS)
First Line
• Commonly used chemotherapeutic agents include BEP. Other regimens include vinblastine which has greater toxicity.
• Salvage chemotherapy includes vinblastine, ifosfamide, and cisplatin.
• Precautions
- Cisplatin: Nephrotoxicity, ototoxicity, neurotoxicity
- Etoposide: Marrow suppression, leukemia
- Cyclophosphamide/ifosfamide: Hemorrhagic cystitis (prevent with Mesna)
- Bleomycin: Pulmonary fibrosis
- Vincristine: Marrow suppression, neuromuscular toxicity
- Carboplatin: Ototoxicity
- Taxol: Neuropathy
• Refer to the manufacturer's literature for each drug.
Second Line
Ondansetron (Zofran), dronabinol (Marinol), metoclopramide (Reglan), and others for nausea control
SURGERY
• All patients receive radical orchiectomy for diagnosis and excellent local control.
• Retroperperitoneal lymph node dissection (open or laparoscopic) based on treatment algorithm
FOLLOW-UP
PROGNOSIS
• More than 90% of patients with newly diagnosed GCT are cured.
• Seminoma has a cure rate greater than 90% (near 100% for low-stage disease).
• For nonseminomatous tumors, cure rate is >95% in stages I and II; it is approximately 70% with chemotherapy and resection of residual disease in stages III and IV.
COMPLICATIONS
• Orchiectomy: Intrascrotal hematoma, retroperitoneal hematoma
• RPLND: Intraoperative hemorrhage, lymphocele, loss of seminal emission/infertility
• Radiation: Radiation enteritis, nephritis
PATIENT MONITORING
• Intensity and details of follow-up are evolving.
• General guidelines below
- For seminomatous tumors
Clinical examination/tumor markers and CXR: At one month; every 3 months for 2 years; then every 6 months until 5 years
Pelvic CT at years 1, 2, and 5 (every 6 months if abnormal post-treatment CT)
- For nonseminomatous tumors
Clinical examination/tumor markers and CXR: Every 2 months for first year; every 3 months for second year; then every 6 months until 5 years
Pelvic CT at 3, 6, 9, 12, 24 months for surveillance and only when clinically indicated for postchemotherapy patients
REFERENCES
1. Gori S, et al. Germ cell tumours of the testis. Crit Rev Oncol Hematol. 2005;53:141-164.
2. Gosse ON, et al. Testicular tumours (nonseminomatous). BJU Int. 2004;94:1196-1201.
3. Huyghe E, et al. Increasing incidence of testicular cancer worldwide: A review. J Urol. 2003;170:5-11.
4. Richie JP. In: Walsh PC, et al. eds. Campbell's Urology. Philadelphia, PA: W.B. Saunders Co.; 2002.
BASICS
DESCRIPTION
Testicular cancer is relatively rare, but is the most common malignancy among 20- 34-year-old men. Fortunately, it is one of the most curable solid organ cancers (93% 5-year survival). Testicular neoplasms may arise from any testicular or adnexal cell component and are divided into germinal (90-95%) and nongerminal tumors (5-10%). The germinal tumors, discussed here, are further divided into seminomatous and nonseminomatous types (embryonal, teratoma, choriocarcinomas, yolk sac).
• Clinical staging (based on 1997 AJCC TNMS)
- Stage 0: Carcinoma in situ
- Stage Ia: Tumor limited to testis and epididymis without vascular/lymphatic invasion
- Stage Ib: Tumor limited to testis and epididymis with vascular/lymphatic invasion or tumor extending through the tunica albuginea with involvement of tunica vaginalis
- Stage Ic: Any tumor with elevated markers
- Stage IIa: Any tumor with lymph node mass/masses no more than 2 cm
- Stage IIb: Any tumor with lymph node mass/masses 2-5 cm
- Stage IIc: Any tumor with lymph node mass greater than 5 cm
- Stage IIIa: Any tumor/lymph node presence with evidence of nonregional nodal or pulmonary metastases
- Stage IIIb: Any tumor/lymph node presence with moderately elevated serum tumor markers
- Stage IIIc: Any tumor/lymph node presence with greatly elevated serum tumor markers
• System(s) Affected: Reproductive
ALERT
Pediatric Considerations
Rare (2% of all solid tumors in childhood)
EPIDEMIOLOGY
• Predominant age: Peak incidence: Age 20-40 years; smaller peaks between age 0-10 years and >60 years
• Predominant sex: Male only
Incidence
• 1-2% of all neoplasms in men
• Increased incidence in last 40 years with substantial differences among countries; etiology unclear
• In adults, 95% are Germ Cell Tumors (GCT); In children, 65% are GCTs. Half of GCTs are seminomas; half are nonseminomatous.
Prevalence
• 2.3-6.3 cases/year per 100,000 men (less common in African Americans0.9 cases/year per 100,000)
• Trimodal distribution: Predominant peak at 20-40 years; slight peak in children younger than 5 years; slight peak in men older than 60 years
• Seminoma rare before 10 years or after age 60 years, but most common histologic type overall
RISK FACTORS
• Crytporchidism: The only proven risk factor with 2.5- to 11-fold incidence increase
• Caucasian race: Especially Scandinavian and Swiss
• Family history
• Higher socioeconomic status
• Increased maternal hormones during pregnancy
• Infertility or abnormal semen parameters
• Preterm birth
• Testicular atrophy
• Trauma
Genetics
• Familial clustering observed
• All cases show chromosome 12 alteration (12p)
ETIOLOGY
Cryptorchidism increased risk
ASSOCIATED CONDITIONS
Weak association with testicular microlithiasis
DIAGNOSIS
SIGNS AND SYMPTOMS
History
In adults
• Testicular nodule/painless swelling (most common presentation)
• Dull ache/heavy sensation (30-40%)
• Hydrocele (10-20%)
• Acute pain (10%), especially with epididymitis/acute hemorrhage
• Gynecomastia (may or may not be due to elevated hormones) (5%)
• Enlargement of a small or atrophic testicle
• Infertility
• Symptoms due to metastases: Supraclavicular mass, respiratory symptoms (lung metastasis), low back pain (nerve root or psoas irritation), lower extremity swelling (iliac or caval thrombosis or obstruction), GI disturbances (retroduodenal metastasis), bone pain (skeletal metastasis)
• In children: Painless testicular mass most common; can be seen in association with torsion
TESTS
Lab
• Markers are useful in the following settings
- To diagnose and stage disease
- To monitor the therapeutic response
- To detect tumor recurrence
• Levels should be drawn pre- and postoperatively
• Elevated markers postorchiectomy generally indicates systemic metastases rather than tumor confined to retroperitoneal nodes.
• Half-life important to evaluate therapeutic responses
• Alpha-fetoprotein (AFP)
- Half-life 5-7 days
- Increased in yolk sac tumors, teratoma, embryonal carcinoma, or combined tumors
- Not increased in pure choriocarcinoma or pure seminoma
- Levels also increased with liver disease
• Human chorionic gonadotropin (hCG)
- Half-life 24-36 hours
- Increased in pure choriocarcinoma, but found in 5-10% pure seminomas
- Beta subunit measured; alpha subunit shared with FSH, LH, TSH
• Lactate dehydrogenase (LDH)
- Reflects "tumor burden"
- Too ubiquitous to be specific, but proven prognostic factor
• Placental alkaline phosphatase (PLAP) and Gamma-glutamyl-transpeptidase (GGTP): Individual sensitivities low, but simultaneous determinations revealed elevation of one or both in 80% of patients with active disease
• Drugs that may alter lab results
- AFP may be elevated with chemotherapy, anesthetics, antiepileptics, alcohol abuse
- hCG may be elevated by marijuana use.
• Disorders that may alter lab results
- AFP may be altered by liver damage by drugs (above), viral hepatitis, alcohol abuse, benign or malignant liver conditions
- hCG may be altered by hypogonadism and malignancies of pancreas, stomach, kidney, breast, and bladder.
Imaging
• Scrotal ultrasound is the gold standard for testicular imaging; any hypoechoic area within the tunica albuginea is markedly suspicious for testicular cancer; also used for patients with palpably normal testes and evidence of extragonadal metastases.
• For staging
- Chest x-ray: PA/Lat to assess lung parenchyma and mediastinal structures
- Chest CT: More sensitive than x-ray, but must have high index of suspicion because high incidence of false positives
- Abdomen/Pelvis CT: Most effective to identify retroperitoneal lymph node involvement; replaced IV urography and pedal lymphangiography; is excellent at identifying retrocrural nodes
- MRI: No real advantage over CT
- PET: No real advantage over CT
Diagnostic Procedures/Surgery
• Radical inguinal orchiectomy: Definitive procedure for pathologic diagnosis
• Transscrotal biopsy/orchiectomy contraindicated as lymphatic drainage violated and inguinal portion of spermatic cord left
• Open biopsy rarely done except in highly selected cases of pediatric tumors that may be benign
Pathological Findings
Basically, two different groups based on germinal versus nongerminal and seminomatous versus nonseminomatous types
DIFFERENTIAL DIAGNOSIS
• Epididymitis
• Hernia
• Hydrocele
• Hematoma
• Spermatocele
• Syphilitic gumma
• Varicocele
• In children: Epidermoid/dermoid cyst, paratesticular rhabdomysocarcoma, macroorchidism, torsion
TREATMENT
Inpatient and outpatient
GENERAL MEASURES
• Germ cell cancers are divided into seminoma and nonseminoma types for treatment planning.
• Tumors with a mixture of seminomatous and nonseminomatous components should be managed as nonseminoma.
• All patients should be treated on an intent-to-cure basis, even if metastatic.
• Surgery
- Radical inguinal orchiectomy for all patients
- Prosthesis can be inserted at this time.
• Pure seminoma
- General principles
Highly radiosensitive
Relatively slow growth of micrometastases
- Stage IS (carcinoma in situ): Chemotherapy
Spermatocytic: Age usually over 65 years; no adjuvant therapy
Typical and anaplasatic: If patient has risk factors (tumor >6 cm; vascular/lymphatic invasion), low-dose abdominal/pelvic radiation with single-agent chemotherapy with carboplatin. If no risk factors, follow with surveillance in a motivated patient.
- Stage IIa and IIb: Radiation; chemotherapy if involved nodes close to kidney
- Stage IIc and III: Cisplatin-based chemotherapy; if residual mass: Observe if desmoplastic; if mass >3 cm and well-delineated: Do surgical resection; if histology positive: Do salvage chemotherapy
• Nonseminomatous germ cell tumors
- Stage IS: Chemotherapy with bleomycin, etoposide, cisplatin (BEP) (3 cycles)
- Stage I: If risk factors (T2, embryonal >40%, vascular/lymphatic invasion) absent, can do surveillance in motivated patient; if risk factors present or unreliable patient, do modified (template) RPLND and primary chemo with 3 cycles BEP. Then observe for N0-N1; for N2, give adjuvant chemotherapy, BEP
- Stage IIa, IIb: Bilateral RPLND and chemotherapy with BEP 3 cycles. If minimal nodal involvement (2 cm), no adjuvant chemo; if nodal involvement (>2 cm), give adjuvant chemo and BEP (2 cycles).
- Stage IIc, III: For good-risk disease, chemotherapy with BEP 3 cycles. RPLND if residual retroperitoneal mass. Salvage chemotherapy for recurrent disease after chemo, RPLND, or persistently elevated tumor markers. For poor-risk disease, primary chemotherapy with ifosfamide and possible bone marrow transplant; salvage chemo if poor response. "Desperation surgery" for tumor unresponsive to salvage chemo.
Diet
No special diet
Activity
As tolerated
SPECIAL THERAPY
Radiotherapy
Selective cases of seminoma
MEDICATION (DRUGS)
First Line
• Commonly used chemotherapeutic agents include BEP. Other regimens include vinblastine which has greater toxicity.
• Salvage chemotherapy includes vinblastine, ifosfamide, and cisplatin.
• Precautions
- Cisplatin: Nephrotoxicity, ototoxicity, neurotoxicity
- Etoposide: Marrow suppression, leukemia
- Cyclophosphamide/ifosfamide: Hemorrhagic cystitis (prevent with Mesna)
- Bleomycin: Pulmonary fibrosis
- Vincristine: Marrow suppression, neuromuscular toxicity
- Carboplatin: Ototoxicity
- Taxol: Neuropathy
• Refer to the manufacturer's literature for each drug.
Second Line
Ondansetron (Zofran), dronabinol (Marinol), metoclopramide (Reglan), and others for nausea control
SURGERY
• All patients receive radical orchiectomy for diagnosis and excellent local control.
• Retroperperitoneal lymph node dissection (open or laparoscopic) based on treatment algorithm
FOLLOW-UP
PROGNOSIS
• More than 90% of patients with newly diagnosed GCT are cured.
• Seminoma has a cure rate greater than 90% (near 100% for low-stage disease).
• For nonseminomatous tumors, cure rate is >95% in stages I and II; it is approximately 70% with chemotherapy and resection of residual disease in stages III and IV.
COMPLICATIONS
• Orchiectomy: Intrascrotal hematoma, retroperitoneal hematoma
• RPLND: Intraoperative hemorrhage, lymphocele, loss of seminal emission/infertility
• Radiation: Radiation enteritis, nephritis
PATIENT MONITORING
• Intensity and details of follow-up are evolving.
• General guidelines below
- For seminomatous tumors
Clinical examination/tumor markers and CXR: At one month; every 3 months for 2 years; then every 6 months until 5 years
Pelvic CT at years 1, 2, and 5 (every 6 months if abnormal post-treatment CT)
- For nonseminomatous tumors
Clinical examination/tumor markers and CXR: Every 2 months for first year; every 3 months for second year; then every 6 months until 5 years
Pelvic CT at 3, 6, 9, 12, 24 months for surveillance and only when clinically indicated for postchemotherapy patients
REFERENCES
1. Gori S, et al. Germ cell tumours of the testis. Crit Rev Oncol Hematol. 2005;53:141-164.
2. Gosse ON, et al. Testicular tumours (nonseminomatous). BJU Int. 2004;94:1196-1201.
3. Huyghe E, et al. Increasing incidence of testicular cancer worldwide: A review. J Urol. 2003;170:5-11.
4. Richie JP. In: Walsh PC, et al. eds. Campbell's Urology. Philadelphia, PA: W.B. Saunders Co.; 2002.
TENDINITIS
TENDINITIS - Mathew J. Devine, DO; Matthew J. Fleig, MD; E. James Swenson, MD
BASICS
DESCRIPTION
• Inflammation of a tendon and/or tendinous sheath
• System(s) Affected: Musculoskeletal
ALERT
• The term tendinopathy has replaced the term tendinitis as a generic descriptor of clinical conditions associated with pain, swelling, and impaired performance in and around tendons arising from overuse.
- The labels "tendinitis" and "tendinosis" are reserved for the condition after histological examination is performed. (1)
• Tendinopathies can be subdivided into the following categories
- Tendinitis: Acute inflammation of the tendon
- Tendinosis: Chronic degeneration of the tendon. Can also be related to partial tendon rupture.
- Tenosynovitis: Inflammation of the tendon sheath
• Common sites of overuse tendon injuries
- Knee: Patella or "jumper's knee," medial plica, and pes anserine
- Shoulder: Rotator cuff muscles
- Ankle: Achilles and posterior tibialis
- Hip: Hamstring muscles and iliotibial tract
- Elbow: Lateral epicondylitis or "tennis elbow," medial epicondylitis or "golfer's or thrower's elbow," and triceps (2)
GENERAL PREVENTION
For prevention of future injuries, the following have been shown to be useful
• Pre-participation screening, warm-up sessions, core and supporting muscle strengthening, safe environment, protective equipment using braces or taping, and health education
EPIDEMIOLOGY
• Predominant age: Rotator cuff, Achilles tendon, and patellar injuries are more common in adolescent and in middle-aged groups.
• Predominant sex: Male = Female
• Overuse injuries are more common in high risk populations; athletes and geriatric populations
Pediatric Considerations
Tendons in children tend to be stronger than the epiphyseal plate. Therefore, consider growth plate, avulsion fractures versus overuse apophysitis following trauma in children. (2)
Prevalence
Tendinopathy is commonly seen.
RISK FACTORS
• Extrinsic factors
- Training errors (most common)
- Footwear and equipment (2nd most common)
- Training surfaces
- Environmental conditions
• Intrinsic factors
- Malalignment
- Limb length discrepancy
- Muscular imbalance
- Muscular insufficiency
PATHOPHYSIOLOGY
• Overuse injuries involve incomplete and disorganized repair mechanisms. These result in a defective "repaired" tendon which lacks extra cellular tissue organization and has decreased strength making the tendon more susceptible to further injury. (1)
• Healing response of an acute tendon injury has a triphasic response of inflammation, proliferation, and maturation.
ETIOLOGY
• Increased repetitive stress and force on the tendon cause an increased risk of injury. Over time with intrinsic and extrinsic factors listed above tendinopathies can develop.
• Etiologic causes are still unknown and have only been theorized. (3)
ASSOCIATED CONDITIONS
• Bursitis (common)
• Arthritis
DIAGNOSIS
SIGNS AND SYMPTOMS
• Pain at the specific point of the affected tendon is the most common symptom.
• Reproducible pain on muscle group activity
• Thickening of tendon(s) involved
• Decreased active range of motion of the muscle group involved
ALERT
• Excessive post-traumatic tension or pain in lower extremity, should consider urgent care for acute compartment syndrome
• With excessive swelling in traumatic injury, must also consider tendon rupture
History
• In general population, history of repetitive use with onset of pain in area of muscle origin or insertions
• History of overuse or overtraining in the case of an athlete
Physical Exam
• Precise physical exam is key to the diagnosis.
• Palpable pain over muscle tendon unit
• Warmth and redness in acute tendinopathies
• Note asymmetry and tendon thickness in chronic tendinopathies.
• Pain may limit range of motion.
TESTS
• Full musculoskeletal exam
• Neurological exam as needed
Lab
If arthritis suspected-ANA, sed rate
Imaging
• Imaging only to be used as adjunct as needed
• Ultrasound: Can measure tendon width, water content within the tendon and peritendon, and collagen integrity.
- Abnormal tendons on sonogram have the following findings: Increased tendon diameter, focal hypoechoic intratendinous areas, localized tendon swelling and thickening, collagen discontinuity, and tendon sheath swelling of calcifications. (4)
• MRI
- Indicated only in specific causes
- Reveals tendon thickening and increased signal of tendons
- Areas of mucoid degeneration seen as high intensity on T1- and T2- weighted images
• Areas of increased signal on MRI need to be correlated with clinical pathology because these could represent asymptomatic areas of degeneration.
• MRI is unreliable in changes of paratendinitis.
Pathological Findings
• Tendinitis: Symptomatic degeneration of the tendon with an inflammatory response
• Tendinosis: Intratendinous degeneration. Common findings are collagen disorientation, fiber separation with increased mucoid ground substance
• Paratendinitis: Inflammation of the outer layer of the tendon alone
• Paratendinitis with tendinosis: Paratendinitis with intratendinous degeneration
DIFFERENTIAL DIAGNOSIS
• Knee
- Patellofemoral pain syndrome: Lateral tracking of patella causing irritation and abrasion of the cartilage of the patella resulting in pain
- Exertional compartment syndrome: A reversible ischemia secondary to a noncompliant osseofascial compartment that is unresponsive to the expansion of muscle volume that occurs with exercise. (1) Most common in anterior compartment of lower extremities
- Stress fractures: Partial or complete bone fracture from repeated force lower than the force required to fracture the bone in a single loading. Most common areas are the tibia, metatarsals, and the fibula. (1)[A]
• Shoulder
- Bursitis: Often is present with a tendinopathy
- Frozen shoulder
- Arthritis: An inflammation within a specific joint of the body. Should be differentiated from tendinopathy, which is isolated to the muscle insertion site and not within the joint spaces
- Cervical radiculopathy
• Ankle
- Rupture: Achilles rupture is uncommon and is not a cause of tendinitis.
- Sprains: In acute sprains, tendinitis can develop if too much stress is placed on noninjured musculature.
• Hip
- Stress fracture: With excessive pain on internal rotation of hip, place the patient on crutches until femoral fracture is ruled out.
Pediatric Considerations
• Osgood-Schlatter lesion (common)
• Sever's disease: Calcaneal apophysitis
• Pelvic apophysitis
• Little league elbow/Little league shoulder
TREATMENT
STABILIZATION
Avoid extrinsic factors.
GENERAL MEASURES
Treat as outpatient
Diet
No special diets recommended
Activity
During acute phase: Rest of tendon involved
SPECIAL THERAPY
Cryotherapy
Icing very beneficial in treatment (A)
Physical Therapy
Muscle strengthening and intrinsic factor recognition is critical to continue healing process. Patient progress should be monitored with pain threshold. If pain continues, then the activity needs to be decreased.
Radiotherapy
Current research shows no benefit using laser therapy or other radiotherapies. (3)[C]
Complementary and Alternative Medicine
Orthotics: OTC or prescription as needed
MEDICATION (DRUGS)
First Line
NSAIDs provide good analgesic effects.
• Piroxicam (Feldene): 10-20 mg/d
• Naprosyn: OTC; 500 mg b.i.d. with food
• Ibuprophen: OTC: Up to 800 mg t.i.d. with food
Second Line
Corticosteroids
• Medrol dose pack (PO)
• Injectable
- Methylprednisolone (Depo-medrol): 40 mg used with 1 or 2% lidocaine (Xylocaine) 4-6 cc
- Contraindication: Tendons should never be injected with local anesthetic and/or cortisone to allow participation in an athletic event. This can lead to complete rupture of the tendon.
• Topical: Research in progress
ALERT
• Recently, some of the COX-2 inhibitors have been removed from the market. Current literature supports the use of Celecoxib for tendinopathy in individuals without cardiovascular risk.
• Contraindication: Do not use NSAIDs in patient with recent history of GI bleed or ulcer.
• Precautions: Compare medications for any drug interactions. See manufacturer's profile of each drug.
• Use caution with renal disease.
• A rare side effect of fluoroquinolones has been tendon rupture and tendinopathy. (3)[A]
SURGERY
• For chronic tendinopathy, surgical treatment is an option if conservative treatment fails after 4-6 months. Patellar tendinitis most commonly operated on. (3)
• Long-standing tendinopathies are associated with poorer surgical outcomes.
FOLLOW-UP
• Advise patient of susceptibility of exacerbation of injury up to 3 weeks after resolution of symptoms with increased activity.
• Treatment plans vary on site of injury.
• Most plans include rest, medications, cryotherapy, and physical therapy.
DISPOSITION
Most individuals recover to full strength and normal activity.
Issues for Referral
Orthopedics/Sports medicine referral in cases of highly competitive athlete, continued pain greater than 4 weeks, radiological finding of avulsion/stress fractures, or uncertainty of diagnosis.
PROGNOSIS
Symptoms usually subside with rest and proper therapy. Most tendinopathies improve without any major complications.
COMPLICATIONS
Exacerbation of pain in affected area
REFERENCES
1. Wilder RP, Sethi S. Overuse injuries: Tendinopathies, stress fractures, compartment syndrome, and shin splints. Clin Sports Med. 2004;23:55-81.
2. Maffulli N, et al. Types and epidemiology of tendinopathy. Clin Sports Med. 2003;22:675-693.
3. Sharma P, Maffulli N. Tendon injury and tendinopathy: Healing and repair. J Bone Joint Surg. 2005;87:187-202.
4. Warden S, Brukner P. Patellar tendinopathy. Clin Sports Med. 2003;22:743-760.
5. Cook JL, Purdam CR. Rehabilitation of lower limb tendinopathies. Clin Sports Med. 2003;22:777-789.
BASICS
DESCRIPTION
• Inflammation of a tendon and/or tendinous sheath
• System(s) Affected: Musculoskeletal
ALERT
• The term tendinopathy has replaced the term tendinitis as a generic descriptor of clinical conditions associated with pain, swelling, and impaired performance in and around tendons arising from overuse.
- The labels "tendinitis" and "tendinosis" are reserved for the condition after histological examination is performed. (1)
• Tendinopathies can be subdivided into the following categories
- Tendinitis: Acute inflammation of the tendon
- Tendinosis: Chronic degeneration of the tendon. Can also be related to partial tendon rupture.
- Tenosynovitis: Inflammation of the tendon sheath
• Common sites of overuse tendon injuries
- Knee: Patella or "jumper's knee," medial plica, and pes anserine
- Shoulder: Rotator cuff muscles
- Ankle: Achilles and posterior tibialis
- Hip: Hamstring muscles and iliotibial tract
- Elbow: Lateral epicondylitis or "tennis elbow," medial epicondylitis or "golfer's or thrower's elbow," and triceps (2)
GENERAL PREVENTION
For prevention of future injuries, the following have been shown to be useful
• Pre-participation screening, warm-up sessions, core and supporting muscle strengthening, safe environment, protective equipment using braces or taping, and health education
EPIDEMIOLOGY
• Predominant age: Rotator cuff, Achilles tendon, and patellar injuries are more common in adolescent and in middle-aged groups.
• Predominant sex: Male = Female
• Overuse injuries are more common in high risk populations; athletes and geriatric populations
Pediatric Considerations
Tendons in children tend to be stronger than the epiphyseal plate. Therefore, consider growth plate, avulsion fractures versus overuse apophysitis following trauma in children. (2)
Prevalence
Tendinopathy is commonly seen.
RISK FACTORS
• Extrinsic factors
- Training errors (most common)
- Footwear and equipment (2nd most common)
- Training surfaces
- Environmental conditions
• Intrinsic factors
- Malalignment
- Limb length discrepancy
- Muscular imbalance
- Muscular insufficiency
PATHOPHYSIOLOGY
• Overuse injuries involve incomplete and disorganized repair mechanisms. These result in a defective "repaired" tendon which lacks extra cellular tissue organization and has decreased strength making the tendon more susceptible to further injury. (1)
• Healing response of an acute tendon injury has a triphasic response of inflammation, proliferation, and maturation.
ETIOLOGY
• Increased repetitive stress and force on the tendon cause an increased risk of injury. Over time with intrinsic and extrinsic factors listed above tendinopathies can develop.
• Etiologic causes are still unknown and have only been theorized. (3)
ASSOCIATED CONDITIONS
• Bursitis (common)
• Arthritis
DIAGNOSIS
SIGNS AND SYMPTOMS
• Pain at the specific point of the affected tendon is the most common symptom.
• Reproducible pain on muscle group activity
• Thickening of tendon(s) involved
• Decreased active range of motion of the muscle group involved
ALERT
• Excessive post-traumatic tension or pain in lower extremity, should consider urgent care for acute compartment syndrome
• With excessive swelling in traumatic injury, must also consider tendon rupture
History
• In general population, history of repetitive use with onset of pain in area of muscle origin or insertions
• History of overuse or overtraining in the case of an athlete
Physical Exam
• Precise physical exam is key to the diagnosis.
• Palpable pain over muscle tendon unit
• Warmth and redness in acute tendinopathies
• Note asymmetry and tendon thickness in chronic tendinopathies.
• Pain may limit range of motion.
TESTS
• Full musculoskeletal exam
• Neurological exam as needed
Lab
If arthritis suspected-ANA, sed rate
Imaging
• Imaging only to be used as adjunct as needed
• Ultrasound: Can measure tendon width, water content within the tendon and peritendon, and collagen integrity.
- Abnormal tendons on sonogram have the following findings: Increased tendon diameter, focal hypoechoic intratendinous areas, localized tendon swelling and thickening, collagen discontinuity, and tendon sheath swelling of calcifications. (4)
• MRI
- Indicated only in specific causes
- Reveals tendon thickening and increased signal of tendons
- Areas of mucoid degeneration seen as high intensity on T1- and T2- weighted images
• Areas of increased signal on MRI need to be correlated with clinical pathology because these could represent asymptomatic areas of degeneration.
• MRI is unreliable in changes of paratendinitis.
Pathological Findings
• Tendinitis: Symptomatic degeneration of the tendon with an inflammatory response
• Tendinosis: Intratendinous degeneration. Common findings are collagen disorientation, fiber separation with increased mucoid ground substance
• Paratendinitis: Inflammation of the outer layer of the tendon alone
• Paratendinitis with tendinosis: Paratendinitis with intratendinous degeneration
DIFFERENTIAL DIAGNOSIS
• Knee
- Patellofemoral pain syndrome: Lateral tracking of patella causing irritation and abrasion of the cartilage of the patella resulting in pain
- Exertional compartment syndrome: A reversible ischemia secondary to a noncompliant osseofascial compartment that is unresponsive to the expansion of muscle volume that occurs with exercise. (1) Most common in anterior compartment of lower extremities
- Stress fractures: Partial or complete bone fracture from repeated force lower than the force required to fracture the bone in a single loading. Most common areas are the tibia, metatarsals, and the fibula. (1)[A]
• Shoulder
- Bursitis: Often is present with a tendinopathy
- Frozen shoulder
- Arthritis: An inflammation within a specific joint of the body. Should be differentiated from tendinopathy, which is isolated to the muscle insertion site and not within the joint spaces
- Cervical radiculopathy
• Ankle
- Rupture: Achilles rupture is uncommon and is not a cause of tendinitis.
- Sprains: In acute sprains, tendinitis can develop if too much stress is placed on noninjured musculature.
• Hip
- Stress fracture: With excessive pain on internal rotation of hip, place the patient on crutches until femoral fracture is ruled out.
Pediatric Considerations
• Osgood-Schlatter lesion (common)
• Sever's disease: Calcaneal apophysitis
• Pelvic apophysitis
• Little league elbow/Little league shoulder
TREATMENT
STABILIZATION
Avoid extrinsic factors.
GENERAL MEASURES
Treat as outpatient
Diet
No special diets recommended
Activity
During acute phase: Rest of tendon involved
SPECIAL THERAPY
Cryotherapy
Icing very beneficial in treatment (A)
Physical Therapy
Muscle strengthening and intrinsic factor recognition is critical to continue healing process. Patient progress should be monitored with pain threshold. If pain continues, then the activity needs to be decreased.
Radiotherapy
Current research shows no benefit using laser therapy or other radiotherapies. (3)[C]
Complementary and Alternative Medicine
Orthotics: OTC or prescription as needed
MEDICATION (DRUGS)
First Line
NSAIDs provide good analgesic effects.
• Piroxicam (Feldene): 10-20 mg/d
• Naprosyn: OTC; 500 mg b.i.d. with food
• Ibuprophen: OTC: Up to 800 mg t.i.d. with food
Second Line
Corticosteroids
• Medrol dose pack (PO)
• Injectable
- Methylprednisolone (Depo-medrol): 40 mg used with 1 or 2% lidocaine (Xylocaine) 4-6 cc
- Contraindication: Tendons should never be injected with local anesthetic and/or cortisone to allow participation in an athletic event. This can lead to complete rupture of the tendon.
• Topical: Research in progress
ALERT
• Recently, some of the COX-2 inhibitors have been removed from the market. Current literature supports the use of Celecoxib for tendinopathy in individuals without cardiovascular risk.
• Contraindication: Do not use NSAIDs in patient with recent history of GI bleed or ulcer.
• Precautions: Compare medications for any drug interactions. See manufacturer's profile of each drug.
• Use caution with renal disease.
• A rare side effect of fluoroquinolones has been tendon rupture and tendinopathy. (3)[A]
SURGERY
• For chronic tendinopathy, surgical treatment is an option if conservative treatment fails after 4-6 months. Patellar tendinitis most commonly operated on. (3)
• Long-standing tendinopathies are associated with poorer surgical outcomes.
FOLLOW-UP
• Advise patient of susceptibility of exacerbation of injury up to 3 weeks after resolution of symptoms with increased activity.
• Treatment plans vary on site of injury.
• Most plans include rest, medications, cryotherapy, and physical therapy.
DISPOSITION
Most individuals recover to full strength and normal activity.
Issues for Referral
Orthopedics/Sports medicine referral in cases of highly competitive athlete, continued pain greater than 4 weeks, radiological finding of avulsion/stress fractures, or uncertainty of diagnosis.
PROGNOSIS
Symptoms usually subside with rest and proper therapy. Most tendinopathies improve without any major complications.
COMPLICATIONS
Exacerbation of pain in affected area
REFERENCES
1. Wilder RP, Sethi S. Overuse injuries: Tendinopathies, stress fractures, compartment syndrome, and shin splints. Clin Sports Med. 2004;23:55-81.
2. Maffulli N, et al. Types and epidemiology of tendinopathy. Clin Sports Med. 2003;22:675-693.
3. Sharma P, Maffulli N. Tendon injury and tendinopathy: Healing and repair. J Bone Joint Surg. 2005;87:187-202.
4. Warden S, Brukner P. Patellar tendinopathy. Clin Sports Med. 2003;22:743-760.
5. Cook JL, Purdam CR. Rehabilitation of lower limb tendinopathies. Clin Sports Med. 2003;22:777-789.
