Drug-induced skin disease

Abstract

Drug-induced cutaneous reactions encompass a wide variety of rashes that depend in part on route of administration (e.g., contact versus systemic) as well as type of cutaneous response and molecular mechanism underlying the reaction. One such reaction is a type IV immunologic reaction (delayed hypersensitivity) manifest as contact dermatitis and commonly elicited by drugs such as antihistamines, antibiotic ointments, local anesthetics, and paraben esters in cosmetic creams and lotions. A generalized eruption of this sort will occasionally occur with systemic administration of a drug to someone previously sensitized by topical application. Systemic administration of agents can cause nonspecific pruritus or maculopapular eruptions that resemble visual exanthems. The pathogenesis is unclear and no immune mechanism has been demonstrated. If the drug is continued, exfoliative dermatitis can result. Other types of reactions are urticarial in nature and include acute urticaria/angioedema, erythema multiforme (bullous and nonbullous), Stevens-Johnson syndrome, urticaria in association with serum sickness-like reactions, and urticaria associated with anaphylactoid reactions. In many of these, an allergic reaction in which there is an immunoglobulin (Ig) E-dependent release of mediators in the skin causes hives or swelling. In others, circulating immune complexes may be present, often involving IgG antibody complexed with drug and complement fixation; hives may then be caused by anaphylatoxin release or a concomitant IgE-mediated reaction. In some instances, a cellular reaction may augment the aforementioned inflammatory reactions, perhaps as part of a late-phase reaction or a true delayed hypersensitivity component. Major offenders involved in such reactions are antibiotics such as penicillin and sulfa, barbiturates, anticonvulsants, and phenothiazines. Urticarial reactions to aspirin and other nonsteroidal anti-inflammatory drugs are in general nonimmunologic. Other types of cutaneous reactions to drugs include erythema nodosum, fixed drug eruptions, purpura (thrombocytopenic or nonthrombocytopenic), phototoxic and photoallergic reactions, and exfoliative dermatitis or toxic epidermal necrolysis. Phototoxic reactions are nonimmunologic, occur on first exposure, and depend on the light absorption spectrum of the drug. Photoallergic reactions resemble contact dermatitis but involve a delayed hypersensitivity reaction to an antigen formed by interaction of the drug with light and binding of the altered drug (hapten) to a cutaneous protein to form a complete antigen. Exfoliative dermatitis or toxic epidermal necrolysis can be severe sequalae of maculopapular eruptions in which the drug is continued or can be severe erythema multiforme-like reactions and are potentially fatal. Superinfection with group 2 staphylococcus may be contributory in some cases. Finally, cases of physically induced allergy such as dermatographism have been reported after drug reactions.