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Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) 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 disorders are diagnosed and treated. Mortality can be as high as 7.5% in children and 20 to 25% in adults.
SJS and 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, severity, or both of these disorders may be higher in bone-marrow transplant recipients, in Pneumocystis jirovecii–infected HIV patients, in patients with SLE, and in patients with other chronic rheumatologic diseases.
Etiology
Drugs precipitate over 50% of SJS cases and up to 95% of TEN cases. The most common drug causes include
Cases that are not caused by drugs are attributed to
Rarely, a cause cannot be identified.
Pathophysiology
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 receptor that induces apoptosis) and its ligand, particularly a soluble form of Fas ligand released from mononuclear cells. Recent findings suggest that granulysin released from cytotoxic T cells and natural killer cells might play a role in keratinocyte death.
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 macules 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 (eg, phimosis, 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 in SJS and early TEN includes erythema multiforme, viral exanthems, and drug rash; and, in later stages of TEN, paraneoplastic pemphigus, toxic shock syndrome, exfoliative erythroderma, and thermal burn. In children, TEN is less common and must be distinguished from staphylococcal scalded skin syndrome.
Prognosis
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 of infection, multiorgan failure, and death. With early therapy, survival rates approach 90%. The severity-of-illness score for TEN (see Table 2: Hypersensitivity and Inflammatory Disorders: Severity-of-Illness Score for Toxic Epidermal Necrolysis (SCORTEN) ) systematically scores 7 independent risk factors within the first 24 h of presentation to the hospital to determine the mortality rate for a particular patient.
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Table 2
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| Severity-of-Illness Score for Toxic Epidermal Necrolysis (SCORTEN) |
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Risk Factor*
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Score
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0
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1
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Age
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< 40 yr
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≥ 40 yr
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Associated cancer
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No
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Yes
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Heart rate (beats/min)
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< 120
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≥ 120
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Serum BUN (mg/dL)
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≤ 28
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> 28
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Detached or compromised body surface
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< 10%
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≥ 10%
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Serum bicarbonate (mEq/L)
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≤ 20
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≥ 20
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Serum glucose (mg/dL)
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≤ 250
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> 250
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*More risk factors indicate a higher score and a higher mortality rate (%) as follows:
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0–1 = 3.2% (CI: 0.1 to 16.7)
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2 = 12.1% (CI: 5.4 to 22.5)
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3 = 35.3% (CI: 19.8 to 53.5)
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4 = 58.3% (CI: 36.6 to 77.9)
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≥ 5 =
> 90% (CI: 55.5 to 99.8)
CI = confidence interval.
Data from Bastuji-Garin S, Fouchard N, Bertocchi M, et al: SCORTEN: A severity-of-illness score for toxic epidermal necrolysis. Journal of Investigative Dermatology 115:149–153, 2000.
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Treatment
Treatment is most successful when SJS or TEN is recognized early and treated in an inpatient dermatologic or ICU setting; treatment in a burn unit may be needed for severe disease. Ophthalmology consultation is mandatory for patients with ocular involvement. Drugs should be stopped immediately. Patients are isolated to minimize exposure to infection and are given fluids, electrolytes, blood products, and nutritional supplements as needed. Skin care includes prompt treatment of secondary bacterial infections. Prophylactic antibiotics are controversial.
Drug treatment of STS and TEN is controversial. High-dose systemic corticosteroids (eg, methylprednisolone 80 to 200 mg IV or prednisone 80 mg 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. Cyclosporine (3 to 5 mg/kg po once/day) inhibits CD8 cells and has been shown to decrease the duration of active disease by 2 to 3 days in some instances. 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. Despite some remarkable results using high-dose IVIG for TEN, clinical trials involving small cohorts have reported conflicting results.
Last full review/revision October 2009 by Wingfield E. Rehmus, MD, MPH
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