Clinical features and management of severe dermatological reactions to drugs

Cutaneous adverse drug reactions are a frequent occurrence and have been reported in more than 2% of hospitalised patients. Among the most commonly involved drugs are sulphonamides, penicillins, anticonvulsants and non-steroidal anti-inflammatory drugs. Two groups of mechanisms are involved in the pathogenesis of drug reactions: immunological, with all 4 types of hypersensitivity reactions described; and non-immunological, accounting for at least 75% of all drug reactions. Besides minor skin reactions like urticaria, maculopapular rash, fixed eruptions or erythema nodosum, which are generally self-limited, severe life-threatening manifestations also occur. Erythema multiforme is secondary to drugs in half the cases; the minor form is characterised by typical target and iris lesions and is usually benign. However, a much more severe condition, erythema multiforme major or Stevens-Johnson syndrome, is associated with mucosal, ocular and visceral involvement, and carries a mortality of 5 to 15% if untreated. Toxic epidermal necrolysis, which could represent an even more dramatic form of the same disease, is characterised by severe widespread erythema, blisters and loss of skin in sheets, with denudation of more than 10% of the body surface area. This entity is frequently due to drugs. Mortality is 25 to 70%, and 90% of the survivors will have sequelae. Exfoliative dermatitis is an erythematous scaling disease often produced by drugs and carrying significant mortality. Photodermatitis may at times present with severe eczematous features. For clinical and epidemiological reasons it is important to try to identify the culprit drug following an approach based on previous experience with the drug, timing of events, patient reaction to dechallenge, patient reaction to rechallenge (if feasible), alternative aetiological candidates, and drug concentration or evidence of overdose. Management of severe skin reactions to drugs should require admission to a burn unit, where patients should be placed in warmed air-fluidised beds, receive excellent nursing care, analgesics and tranquillisers. Peeling necrotic epidermis should be removed and denuded dermis covered with biological grafts or synthetic dressings. Fluid balance must be adequately maintained; nutritional support and careful monitoring of early signs of skin infections is mandatory to ensure immediate antimicrobial treatment. Ocular care must be excellent to avoid serious sight-threatening sequelae. Steroids are presently not recommended. With these therapeutic modalities, morbidity and mortality can be markedly decreased.