Erythema multiforme is a disorder of the skin or mucous membranes consisting of either a mild, self-limited condition, known as erythema multiforme minor, or a severe, sometimes fatal multisystem form, known as erythema multiforme major, or Stevens-Johnson syndrome.

Toxic epidermal necrolysis is a potentially life-threatening exfoliative skin disease occurring as a severe skin reaction to a variety of causative factors. This condition may also be known as nonstaphylococcal scalded skin syndrome.

No cause of erythema multiforme may be identified in some cases. In other cases, the cause is suspected to be an immunologic reaction that occurs in response to infections, medications, physical agents, malignancy, pregnancy, or connective tissue diseases. It may occur as a result of an immune reaction, a hypersensitivity reaction to antigens, such as viruses, mycobacteria, or certain medications. Erythema multiforme may occur as a complication of herpes simplex infection. It may result from a herpesvirus-containing immune complex reaction to the herpes antigen, and occur 1 to 2 weeks after recurrences of herpes simplex.

Toxic epidermal necrolysis may result from various etiologic factors that may primarily include the intake of medications, such as sulfonamides, barbiturates, nonsteriodal anti-inflammatory drugs (NSAIDs), phenytoin, allopurinol, and penicillin. It may also occur secondary to infections (viral, bacterial, or fungal) in an immunosuppressed patient, neoplastic disease, chemical exposure, or graft-versus-host reactions. The condition may occur due to a reaction to antigenic material that causes a split in the epidermis with necrosis of much of the overlying epidermis. In some cases, the cause may be unclear due to the occurrence with serious diseases and drug treatment.

Manifestations of erythema multiforme include sudden onset of symmetrical, dark-red macules, papules, wheals, vesicles, bullae, or tubercles of the skin or mucous membranes. The condition appears on the distal portion of the extremities, including the palms of the hands and soles of the feet, and on the face. It may appear in successive eruptions of short duration. The skin lesions may appear in separate rings, concentric rings, disk-shaped patches, distributed elevations, or figured arrangements. Itching may also occur. Systemic manifestations may include malaise, arthralgia, and fever. The more severe form, Stevens-Johnson syndrome, presents with flu-like symptoms including fever, and is characterized by systemic as well as more severe skin and mucous membrane lesions with the bullae appearing on the oral mucosa, pharynx, anogenital region, and conjunctiva.

Manifestations of toxic epidermal necrolysis include painful, localized erythema that spreads rapidly. At the erythematous sites, blisters may occur, or the epidermis may peel off in large sheets with gentle touching or pulling. Systemic manifestations that may occur with the peeling of the dermis include malaise, chills, myalgias, and fever. Widespread areas of erosion, including all mucous membranes, occur within 24 to 72 hours. The areas of affected skin appear scalded, resembling second-degree burns.

Thorough history and physical examination are necessary to diagnose the conditions. Biopsy of the lesions may be done as a diagnostic measure.

In erythema multiforme, the target lesions may be diagnostic, and are recognized by a central, dark-red area, or a blister surrounded by a pale, edematous, round zone, that is also surrounded by a peripheral red rim. The lesions may show separation below the dermis in the blistering center of target lesions. The presence of vesicles and bullae may predict a more severe course. Immunofluorescence of biopsied lesions may show immunoglobulin and complement in the walls of the small dermal blood vessels.

Rapid diagnosis of toxic epidermal necrolysis is important so that the medication possibly causing the condition can be stopped immediately. Before widespread erythema and peeling off of the epidermis occur, it may be difficult to distinguish this condition from erythema multiforme major. Toxic epidermal necrolysis is thought to be a continuum of both forms of erythema multiforme. Ophthalmologic and urologic consultation may be required due to the adverse affects of the condition. This condition presents manifestations similar to staphylococcal scalded skin syndrome, and therefore the two must be differentiated by the age of the patient, the clinical setting, and the level of the epidermal split seen on biopsy.

In both conditions, if the cause is known, the patient should be treated accordingly, and the cause should be eliminated or avoided.

A simple case of erythema multiforme may require no treatment due to the self-limiting nature of the condition. However, in the severe form of the condition, Stevens-Johnson syndrome, systemic corticosteroids may be beneficial if used early. Intravenous (IV) fluids may be required if a patient has severe oral mucous membrane involvement. Topical anesthetics such as viscous lidocaine (Xylocaine) may help to decrease mouth discomfort. Acyclovir (Zovirax) may be administered orally or intravenously to treat primary or recurrent forms of herpes that may be causing the condition.

Patients with toxic epidermal necrolysis require hospitalization with close observation. Suspected medications should be discontinued immediately. The patient may need isolation to minimize the risk of infection. They may be treated as if severe burns existed, e.g., protecting the skin and affected areas from trauma and infection, and replacing fluid and electrolytes that may have been lost. Systemic corticosteroids may be successful in treatment of the condition if initiated early in the course of the disease. These medications work only to stop further immunologic injury to the skin. Close observation under well-controlled conditions is necessary due to the association of corticosteroids with many adverse effects.

Occurrences of erythema multiforme may last from 2 to 4 weeks, and recurrences are possible for several years. Some patients with severe mouth and throat lesions seem to acquire fatal respiratory infections if treated with systemic corticosteroids.

Toxic epidermal necrolysis is one of the few true dermatologic emergencies; and the mortality rate is high. Death may be caused by fluid and electrolyte imbalance and multi-organ complications, such as pneumonia, gastrointestinal (GI) bleeding, glomerulonephritis, hepatitis, or infection. Corticosteroids may increase the risk of sepsis, and therefore increase mortality rate. Septicemia is the most common cause of death, and usually occurs with pulmonary infections.

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For the purposes of this DC only, systemic therapy may consist of one or more of the following treatment agents: immunosuppressives, antihistamines, or sympathomimetics.