Drug Eruptions

Our practical approach to drug eruptions has nine steps. The first step is to establish a morphological diagnosis. Drugs may cause all kinds of elementary lesions. They may be localized or generalized. Their course is acute or chronic. The most common morphological type is maculopapular rash; and the second, urticaria. The second step is to exclude causes other than drugs. For example, if there is a maculopapular rash, measles, rubella and scarlet fever should be excluded. The third step is to take a detailed history giving a special emphasis on the temporal relationship between the occurrence of the rash and the intakes of the drugs. If a rash is an allergic reaction, a period of sensitization is required. If a drug is used for the first time, such a rash usually develops only after a several weeks of the usage. However, if the patient has been sensitized previously, the allergic reaction develops just after the exposure. The time interval between the intake of a drug, which is capable to cause the rash, and the occurrence of the rash is minutes to hours for urticaria, and hours to days for maculopapular rash. The fourth step is to look at lists of drugs and their reactions, and at lists of rashes and their causes. The fifth step is to stop intakes of drugs. Elimination is the real treatment of drug eruptions. All drugs other than those with a vital importance should not be used no more until the rash disappears. The sixth step is to relieve symptoms. Symptomatic treatment varies according to the morphological diagnosis. The seventh step is to do skin tests with drugs, which might be the cause of the rash. However, both false-positive and false-negative results are common. The eighth step is to re-challenge giving very small doses of the possible causative drugs of the rash and increasing the doses gradually. Provocation should be done, only if the drugs are vital. The patient should be hospitalized, if the rash has a potential to threaten the life. The ninth step is to forbid further intakes of the causative drug. If it has not been determined precisely, all possible causative drugs should be prohibited. Prohibition may be done comprehensively to include also chemically related drugs.

Fixed drug eruption is characterized by nummular erythematous macules leaving post-inflammatory hyperpigmentation and recurring at the same site after each intake of the causative drug. In its active phase, there may be edema or even blisters. The glans penis is a common location for fixed drug eruption. If erosions develop on the glans penis, fixed drug eruption should be differentiated from syphilis.

Erythema multiforme is characterized by erythematous macules, papules or small plaques preferably located in the acral and periorificial areas. These lesions usually are round and are composed of concentric rings showing various hues of red. The so-called target or iris lesions are almost pathognomonic for erythema multiforme. Blistering may also develop. If blisters predominate and mucosal involvement is severe, Stevens-Johnson syndrome is the case. If the causative drug is not stopped and supportive treatment is not appropriate, this syndrome may lead to blindness and even to death. Erythema multiforme may also be preceded by herpes simplex. Post-herpetic erythema multiforme usually has a recurrent course and is usually milder than drug-induced erythema multiforme.

Toxic epidermal necrolysis is characterized by widespread large blisters and erosions as well speckled erythematous macules (targetoid lesions). It is the most severe end of the spectrum of erythema multiforme. Its most important complications are fluid-electrolyte imbalance and sepsis. Death is common, even if an intensive care is done.

Prof. Dr. Varol Lütfü AKSUNGUR