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Stevens-Johnson
syndrome and toxic epidermal necrolysis are severe cutaneous hypersensitivity
reactions. Drugs, especially sulfa drugs, antiepileptics, and antibiotics,
are the most common causes. Macules rapidly spread and coalesce,
leading to epidermal blistering, necrosis, and sloughing. Diagnosis
is usually obvious by appearance of initial lesions and clinical
syndrome. Treatment is supportive care; corticosteroids, cyclophosphamide,
and other drugs may be tried. Prognosis depends on how early the
syndromes are diagnosed and treated; mortality may reach 40%.
Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are clinically similar except for their distribution. By one commonly accepted definition, changes affect < 10% of body surface area in SJS and > 30% of body surface area in TEN; involvement of 15 to 30% of body surface area is considered SJS-TEN overlap.
The disorders affect between 1 and 5 people/million. Incidence and/or severity of both disorders may be higher in bone-marrow transplant recipients, in Pneumocystis jiroveci (formerly P. carinii)–infected HIV patients, and in patients with SLE.
Etiology
and Pathophysiology
Drugs precipitate over 50% of SJS cases and up to 95% of TEN cases. Sulfa drugs (eg, co-trimoxazole, sulfasalazine ), antiepileptics (eg, phenytoin , carbamazepine , phenobarbital , valproate ), antibiotics (eg, aminopenicillins, quinolones, cephalosporins), and miscellaneous individual drugs (eg, piroxicam , allopurinol , chlormezanone) are most often implicated. Cases that are not due to drugs are attributed to infection (mostly with Mycoplasma pneumoniae), vaccination, and graft-vs-host disease. Rarely, a cause cannot be identified.
Exact mechanism is unknown; however, one theory holds that altered drug metabolism in some patients causes formation of reactive metabolites that bind to and alter cell proteins, triggering a T-cell–mediated cytotoxic reaction to drug antigens in keratinocytes. Another possible mechanism involves interactions between Fas, a cell-surface death receptor, and its ligand.
Symptoms and Signs
Within 1 to 3 wk after the start of the offending drug, patients develop a prodrome of malaise, fever, headache, cough, and conjunctivitis. Macules, often in a “target” configuration, then appear suddenly, usually on the face, neck, and upper trunk. These simultaneously appear elsewhere on the body, coalesce into large flaccid bullae, and slough over a period of 1 to 3 days. Nails and eyebrows may be lost along with epithelium.
In severe cases of TEN, large sheets of epithelium slide off the entire body at pressure points (Nikolsky's sign), exposing weepy, painful, and erythematous skin. Painful oral crusts and erosions, keratoconjunctivitis, and genital problems (such as phimosis and vaginal synechiae) accompany skin sloughing in up to 90% of cases. Bronchial epithelium may also slough, causing cough, dyspnea, pneumonia, pulmonary edema, and hypoxemia. Glomerulonephritis and hepatitis may develop.
Diagnosis
Diagnosis is often obvious from appearance of lesions and rapid progression of symptoms. Histologic examination of sloughed skin shows necrotic epithelium, a distinguishing feature. Differential diagnosis includes, in SJS and early TEN, erythema multiforme, viral exanthems, and drug rash; and, in later stages of TEN, paraneoplastic pemphigus, toxic shock/toxic strep syndrome, exfoliative erythroderma, and thermal burn. In children, TEN is less common and must be distinguished from the staphylococcal scalded skin syndrome.
Prognosis
and Treatment
Severe TEN is similar to extensive burns; patients are acutely ill, may be unable to eat or open their eyes, and suffer massive fluid and electrolyte losses. They are at high risk for infection, multiorgan failure, and death. With early therapy, survival rates approach 90%.
Treatment is most successful when SJS-TEN is recognized early and treated in an inpatient dermatologic or ICU setting; burn units may be indicated for severe disease. Ophthalmology consultation is essential. Drugs should be discontinued immediately. Patients are isolated to minimize exposure to infection and are repleted aggressively with fluids, electrolytes, blood products, and nutritional supplements as needed. Skin care includes prompt treatment of secondary bacterial infections. Prophylactic antibiotics are controversial.
Treatment of STS/TEN is controversial. High-dose systemic corticosteroids (eg, 80 to 200 mg methylprednisolone IV or 80 mg prednisone po once/day for 7 to 10 days or until progression stops) or cyclophosphamide (300 mg IV q 24 h for 7 days or until significant improvement) can be given to inhibit T-cell–mediated cytolysis. However, corticosteroids are controversial and are thought by some to increase mortality. Plasmapheresis can remove reactive drug metabolites or antibodies. Early high-dose IV immune globulin (IVIG) 2.7 g/kg over 3 days blocks antibodies and Fas ligand, an apoptosis-inducing protein. Despite some remarkable results using high-dose IVIG for TEN, clinical trials involving small cohorts have reported conflicting results.
Last full review/revision November 2005
Content last modified November 2005
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