Toxic epidermal necrolysis and Stevens–Johnson syndrome

Management Strategy

The causative drug should be quickly identified and discontinued. In general, drugs introduced 4–28 days before the onset of symptoms must be considered as suspects. The most common drugs causing SJS/TEN are antibacterial sulfonamides (including cotrimoxazole, sulfasalazine, and dapsone), allopurinol, antiepileptics of the aromatic amines family (carbamazepine, oxcarbazepine, phenobarbital, and phenytoin), lamotrigine, non-steroidal antiinflammatory drugs (NSAIDs) of the oxicam family, and nevirapine.

Extensive epidermal loss in SJS/TEN is accompanied by numerous systemic involvements, many of which may be life-threatening such as respiratory failure. Therefore, the patient should be managed in a center of reference, i.e., a specialist dermatology department, intensive care or burn unit, for critical care management and specialist nursing delivery. Supportive therapy is critical, including fluid replacement, maintaining a warm environment, nutritional support, analgesia, organ support (when necessary), surveillance for infection, and appropriate dressings. Fluid replacement requirements depend on the extent of involvement of the skin and may be 5–7 L in the first 24 hours. The ambient temperature should be raised to 28–32°C. Nutritional support may require nasogastric tube feeding (except in case of severe esophageal involvement) until the oral mucosa has healed. Analgesia with opiates is often necessary. Infection surveillance includes taking skin swabs or skin cultures from lesional skin throughout the acute phase and sending these for bacteriology. Administration of prophylactic antibiotics is not recommended, as it may favor skin colonization (particularly with Candida albicans ) and promote resistance. All lines should be checked daily for signs of infection and changed at least every 3 days, and the tips of all discarded lines and catheters sent for culture. If signs of sepsis develop, including rising or falling temperature, rigors, hypotension, fall in urine output, or deterioration of respiratory status, diabetic control, or level of consciousness, initial antibiotic therapy can be guided by the results of skin samples, then adapted to results of blood and/or urine cultures. Blisters should be decompressed by piercing and expression of tissue fluid. Blister roofs and detached epidermis must be left in situ to act as a biologic dressing.

Ophthalmologic review should be obtained as soon as possible from admission to minimize the risk of long-term severe ocular sequelae resulting from conjunctival scarring and corneal ulcerations. Regular instillation of an ocular lubricant without preservatives, and/or topical vitamin A, is recommended. The efficacy of topical steroids is controversial. Topical antibiotics are not recommended. Separation of conjunctival adhesions must be carried out daily by an ophthalmologist or ophthalmically trained nurse.

Oral and nasal debris should be removed regularly. Analgesic and antiseptic mouthwashes must be used frequently.

Tracheal and bronchial involvement is a marker of disease severity and thus must be closely investigated. Respiratory failure can occur, requiring mechanical ventilation.

The cornerstone of the management of SJS/TEN is supportive care in the center used to treat the disease. Macrolides are indicated in cases triggered by Mycoplasma pneumoniae . To date, the efficacy of immunomodulatory agents at the acute phase of the disease remains debatable. Systemic steroids and ciclosporin are the most controversial.

Systemic corticosteroids : several reports suggest that they may increase morbidity and mortality, usually by increasing the risk of sepsis. Conversely, a number of case reports and case studies advocate the use of high-dose corticosteroids at the early stage. Recently, a large epidemiological Japanese study did not show any benefit of systemic steroids on the in-hospital mortality (see below). However, in cases of lupus or dermatomyositis-related TEN, corticosteroids may be used as part of the auto-immune trigger/component accordingly.

Ciclosporin: a French prospective trial and several retrospective case series showed benefits in terms of mortality at the acute phase. However, these results were not confirmed in a large monocenter French study using propensity scores (see later).

Several other potential disease-modifying treatments, especially intravenous immunoglobulin (IVIG) and anti-TNF agents ( especially etanercept ), have been reported in small numbers of patients, but there is currently no strong evidence base for recommending any specific intervention other than supportive care.

Survivors of SJS/TEN should lifelong avoid exposure to the culprit drug and related compounds.

Established SJS/TEN can usually be diagnosed clinically. Biopsy for histology and direct immunofluorescence of an affected area of skin can exclude conditions such as staphylococcal scalded skin syndrome, linear immunoglobulin A (IgA) bullous dermatosis, and paraneoplastic pemphigus.