Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN)

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.

The exact mechanism of Stevens-Johnson syndrome and toxic epidermal necrolysis is unknown; however, one theory holds that altered drug metabolism (eg, failure to clear reactive metabolites) in some patients triggers a T-cell–mediated cytotoxic reaction to drug antigens in keratinocytes. CD8+ T cells have been identified as important mediators of blister formation.

Findings suggest that granulysin released from cytotoxic T cells and natural killer cells might play a role in keratinocyte death; granulysin concentration in blister fluid correlates with severity of disease. Interleukin-15 has also been found to be increased in patients with SJS/TEN and has been found to increase granulysin production. Another theory is that interactions between Fas (a cell-surface receptor that induces apoptosis) and its ligand, particularly a soluble form of Fas ligand released from mononuclear cells, lead to cell death and blister formation. A genetic predisposition for SJS/TEN has been suggested.

Within 1 to 3 weeks after the start of the offending drug, patients develop a prodrome of malaise, fever, headache, cough, and keratoconjunctivitis. 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. The palms and soles may be involved. Skin, mucosal, and eye pain are common. In some cases, diffuse erythema is the first skin abnormality of toxic epidermal necrolysis.

In severe cases of toxic epidermal necrolysis, large sheets of epithelium slide off the entire body at pressure points (Nikolsky sign), exposing weepy, painful, and erythematous skin. Painful oral crusts and erosions, keratoconjunctivitis, and genital problems (eg, urethritis, 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 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 Stevens-Johnson syndrome (SJS) and early toxic epidermal necrolysis (TEN) includes erythema multiforme Erythema Multiforme Erythema multiforme is an inflammatory reaction, characterized by target or iris skin lesions. Oral mucosa may be involved. Diagnosis is clinical. Lesions spontaneously resolve but frequently... read more , viral exanthems, and other drug rashes; SJS/TEN can usually be differentiated clinically as the disorder evolves and is characterized by significant pain and skin sloughing. In later stages of TEN, differential diagnosis includes the following:

In children, TEN is less common and must be distinguished from staphylococcal scalded skin syndrome Staphylococcal Scalded Skin Syndrome Staphylococcal scalded skin syndrome is an acute epidermolysis caused by a staphylococcal toxin. Infants and children are most susceptible. Symptoms are widespread bullae with epidermal sloughing... read more . Characteristics of staphylococcal scalded skin syndrome usually include sparing of mucous membranes, absence of risk factors for TEN (eg, drug history), and clinical suspicion of staphylococcal infection.

Severe toxic epidermal necrolysis 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 toxic epidermal necrolysis Severity-of-Illness Score for Toxic Epidermal Necrolysis (SCORTEN) systematically scores 7 independent risk factors within the first 24 hours of presentation to the hospital to determine the mortality rate for a particular patient.

Treatment is most successful when Stevens-Johnson syndrome and toxic epidermal necrolysis are recognized early and treated in an inpatient dermatologic or intensive care unit setting; treatment in a burn unit Treatment Burns are injuries of skin or other tissue caused by thermal, radiation, chemical, or electrical contact. Burns are classified by depth (superficial and deep partial-thickness, and full-thickness)... read more may be needed for severe disease. Ophthalmology consultation and specialized eye care are mandatory for patients with ocular involvement. Potentially causative 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 and daily wound care as for severe burns. Prophylactic systemic antibiotics are controversial and often avoided.

Drug treatment of Stevens-Johnson syndrome and toxic epidermal necrolysis is controversial. Cyclosporine (3 to 5 mg/kg orally once/day) inhibits CD8 cells and has been shown to decrease the duration of active disease by 2 to 3 days in some instances and possibly decrease mortality. The use of systemic corticosteroids remains controversial. Many experts thought systemic corticosteroids increased mortality because of increased rates of infection and the risk of masking sepsis. However, some reports show improved outcomes with early corticosteroid therapy.

Plasmapheresis Plasmapheresis Apheresis refers to the process of separating the cellular and soluble components of blood using a machine. Apheresis is often done on donors where whole blood is centrifuged to obtain individual... read more can remove reactive drug metabolites or antibodies and can be considered. Early high-dose IVIG 2.7 g/kg over 3 days blocks antibodies and Fas ligand. However, despite some remarkable initial results using high-dose IVIG for toxic epidermal necrolysis, further clinical trials involving small cohorts have reported conflicting results, and a retrospective analysis has suggested no improvement or even higher than expected mortality (1 Treatment reference Stevens-Johnson syndrome and toxic epidermal necrolysis are severe cutaneous hypersensitivity reactions. Drugs, especially sulfa drugs, antiseizure drugs, and antibiotics, are the most common... read more ).

The TNF-alpha inhibitors infliximab and etanercept can help reduce inflammation.

Thalidomide has also been tested but increases mortality and is now contraindicated.