Stevens-Johnson syndrome
Stevens-Johnson syndrome (SJS) is a severe hypersensitivity reaction characterized by a painful rash, skin sloughing, and mucous membrane disruption, often triggered by certain medications or infections. This condition typically begins with symptoms resembling an upper respiratory infection, including fever, sore throat, and body aches, which then progress to a flat, red rash that can develop into blisters. The syndrome can affect various parts of the body, including the skin, eyes, and gastrointestinal tract, potentially leading to life-threatening complications.
The condition is classified based on the extent of skin involvement, with SJS defined as less than 10% skin detachment, while toxic epidermal necrolysis (TEN) involves more than 30%. Most cases are drug-induced, with common triggers including antibiotics, anticonvulsants, and NSAIDs, though some cases remain idiopathic. Diagnosis is confirmed through a skin biopsy, and treatment focuses on discontinuing the offending drug, managing symptoms, and preventing complications, as no universally effective drug treatments exist. While some therapies have shown promise, rigorous scientific validation is still needed.
Stevens-Johnson syndrome
ALSO KNOWN AS: Toxic epidermal necrolysis; erythema multiforme
ANATOMY OR SYSTEM AFFECTED: Abdomen, back, breasts, eyes, feet, gastrointestinal system, genitals, hands, head, immune system, knees, legs, lungs, neck, nose, reproductive system, respiratory system, urinary system
DEFINITION: A severe immune response-mediated hypersensitivity reaction to particular drugs or infections that causes a rash, sloughing of the skin, and the disruption of mucous membranes
CAUSES: Hypersensitivity to infections and drugs
SYMPTOMS: Fever, headache, cough, rash, blistering
DURATION: Lasts minimum of two to three weeks; rashes last one to six weeks; convalescence can be very long
TREATMENTS: Discontinuation of offending drug, intravenous fluids and salts, symptom management, treatment of secondary infections
Causes and Symptoms
Stevens-Johnson syndrome begins with a nonspecific upper respiratory tract infection or after the consumption of a particular drug. The early symptoms last for one to fourteen days and consist of fever, sore throat, headache, cough, body aches, and sometimes and diarrhea. Subsequently, a flat, red rash (erythema multiforme) breaks out over the face and that later spreads to the rest of the body. Painful blisters form in the center of the rash, and the skin around the blisters is quite loose and rubs off easily. Patients have a headache, fever, weakness (malaise), and a cough that produces thick, pus-filled material.
Blisters can form on the mucous membranes that line the mouth (preventing the patient from eating or drinking), throat, genitals, eyes, and anus. If the urinary tract is involved, then the patient will not be able to urinate. Eye involvement causes the eyes to swell and fill with pus so that they seal shut. Blisters on the surface of the eyes (corneas) can scar them. Lesions in the respiratory tract restrict breathing, and tissue sloughing can cause respiratory collapse. Sores in the digestive tract can cause and narrowing of the esophagus. The open, skinless sores are also susceptible to infections.
Stevens-Johnson syndrome is classified according to the percentage of the skin affected. If 10 percent or less of the body surface area detaches, then the patient has Stevens-Johnson syndrome. If 10 to 30 percent of the skin detaches, then the patient has overlapping Stevens-Johnson syndrome/toxic epidermal necrolysis (TEN). If more than 30 percent of the skin is detached, then the patient has TEN.
Drug reactions cause most cases of Stevens-Johnson syndrome. The drugs that may trigger it include antibiotics, such as penicillin, ciprofloxacin, and sulfa drugs; anticonvulsant drugs, such as phenytoin, carbamazepine, and barbiturates; nonsteroidal anti-inflammatory drugs (NSAIDs); the antigout drug allopurinol; the narcolepsy treatment modafinil (Provigil); anti-Human immunodeficiency virus (HIV) drugs; diuretics; and topical ocular medications. Viral, bacterial, fungal, and protozoan infections can also cause the disease, as can various types of cancers. Between one-quarter and one-half of all cases of Stevens-Johnson syndrome are idiopathic, which means that there is no discernible cause. There is also a genetic basis for this disorder.
Diagnosis requires a skin biopsy, which shows extensive cell death, detachment of the upper layer of the skin (epidermis) from the middle layer of the skin (dermis), and of the skin with particular called lymphocytes.
The large amount of skin loss in TEN is similar to a severe burn and is life-threatening. Water and salts leak through the denuded areas and can produce organ failure. Infection at the damaged areas is also a major cause of death in TEN patients.
Treatment and Therapy
The most important therapeutic step is to discontinue all drugs suspected of triggering the disease. Management of symptoms is also essential. Mouthwashes can treat oral lesions and allow intake, which, when coupled with the intravenous replacement of fluid and salts, can prevent dehydration and electrolyte imbalance. Skin lesions are treated as burns. Topical anesthetics can reduce pain, and denuded skin areas are covered with saline compresses. Any that develops must be rapidly identified and treated.
There is no universally accepted drug treatment for Stevens-Johnson syndrome. Oral corticosteroids appear to help during the first few days, but not after that. In advanced cases of TEN, corticosteroids increase the incidence of complications. Intravenous delivery of antibodies (immunoglobulins) against the Fas ligand that mediates cell death has helped small groups of TEN patients, but this treatment has not been systematically evaluated. Also, drugs that down-regulate the have been used, but too little data exists to evaluate their properly.
Perspective and Prospects
Stevens-Johnson syndrome was first described in 1922 by Albert Mason Stevens and Frank Chambliss Johnson. They encountered two young boys who showed of the mucous lining of the cheeks, pus-filled eyes, and the generalized skin blisters that are now commonly associated with the disease. Stevens and Johnson originally thought that the boys suffered from a type of unknown infectious disease. Bernard Thomas named the condition in 1950. The condition gained public attention in 2010 when it contributed to the death of former professional basketball player Manute Bol.
No treatment for Stevens-Johnson syndrome provides consistent benefits to patients in systematic studies. Nevertheless, several treatments have shown promise in small studies. For example, intravenous treatments, skin grafts, the antitransplant drug cyclosporine, and a blood filtration procedure called plasmapheresis have successfully treated small groups of patients with few complications and little mortality. However, until larger, double-blind, placebo-based studies establish the efficacy of these treatments, they will remain experimental.
Bibliography
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