Section 18. Drug Eruptions

Diagnosing drug eruptions has become a common experience to practitioners in all branches of modern medicine. The profusion of drugs now available, the continuous influx of new drugs, and the capability of drugs to cause actions different from or in addition to their pharmacologically desirable actions make adverse cutaneous reactions an inevitable fact of modern medical practice. The kinds of cutaneous reactions are varied. Exanthems (erythematous, morbilliform or maculopapular), urticaria, fixed drug eruptions, and erythema multiforme are the most common. Figure 18-1 is an urticarial reaction from Augmentin and Fig. 18-2 shows a morbilliform eruption from ampicillin. Constitutional symptoms of low-grade fever and malaise may be associated with such drug eruptions. Morbilliform eruptions from ampicillin are more frequently seen in children with infectious mononucleosis.

Drug eruptions may mimic nearly the entire range of dermatoses of other causes. One of the commonest forms is the exanthematic, whose lesions are usually erythematous and edematous. Common causes of drug eruptions include ampicillin, cephalosporins, semisynthetic penicillins, and barbiturates. We have just illustrated cases that were morbilliform. Illustrated here are cases clinically resembling erythema multiforme. Figure 18-3 resulted from a sulfonamide and Fig. 18-4 from a chloroquine (Plaquenil). Note again the tendency to universality and symmetry. Drug eruptions of the types so far illustrated may be uncomfortably pruritic and attended at their onset by prodromal malaise, but they are rarely serious and usually subside fairly quickly upon elimination of the causative drug and, on occasion, even in the face of continued administration of an absolutely required drug.

Another common type of adverse reaction to drugs is the so-called fixed drug eruption. The term fixed is intended to suggest that the cutaneous change, occurring for the first time in given sites (anywhere), recurs in those same sites upon subsequent and repeated administration. Upon subsequent provocation, new reactions in new sites may occur, but original sites always flare again. There are several drugs that are well known for their propensity to cause fixed drug eruptions, namely, phenolphthalein, salicylates, phenacetin, barbiturates, antipyrine, arsenicals, and gold salts. The clinical morphology of a fixed drug eruption is usually a roundish plaque that is palpably edematous and purplish. Sometimes fixed drug eruptions are bullous. Both illustrations here are of fixed drug eruptions caused by phenolphthalein.

This cutaneous change appeared after institution of treatment of an unrelated condition with an antihistamine. The proof of a drug as cause of an eruption is sometimes certain, on the basis of repeated experience, but often conjectural or circumstantial, especially in the case of newly introduced drugs. Proof by withdrawing a suspected drug and observing subsidence of the eruption and then reappearance upon resumption of the drug is usually not wise or safe practice.

Each of the anticonvulsant medications phenytoin (Dilantin), phenobarbital, and carbamazepine (Tegretol), as well as numerous other medications have been reported to cause this severe form of drug reaction. The mucocutaneous manifestations are strawberry tongue and a generalized scarlatiniform eruption that is followed by desquamation. The rash may also be purpuric. The presence of high fever, lymphadenopathy, and hepatosplenomegaly may give the false impression of an infectious disease. Elevations in blood urea nitrogen, liver enzymes, and peripheral eosinophil count may also be present.

The mechanisms of adverse reactions to drugs vary. Some, like the urticarial or eczematous, are clearly based on an allergic or immunologic mechanism; others are utterly obscure in mechanism. Such is the gingival hyperplasia caused by phenytoin. Since it occurs in almost all patients receiving the drug, all one can say is that the effect probably is within the normal pharmacologic action of the drug.

Iodides and bromides are drugs that can cause severe adverse cutaneous reactions, and of these, the worst are acneiform, furuncular, carbuncular, chancriform, pyodermatous, or granulomatous. Iodides and bromides are widely distributed, not only in foods and in the environment but also in proprietary and formally prescribed medicaments. These figures are of still relatively minor consequences of adverse reactions from the two halides, of which bromides are usually worse than iodides. Lesions like those of acne or folliculitis caused by an iodide are shown in Fig. 18-10. Figure 18-11 is a granulomatous reaction caused by a bromide. Another baleful characteristic of drug eruptions from halides is persistence and extension of reaction once it occurs. The reason for such persistence or extension, even when a known source of the offending drug is removed, is the wide dispersion of occult iodine or bromine salts in foods, in the environment, and indeed in the body's own chemistry. Iodine, for example, is a constituent of thyroid hormone.

This severe form of drug eruption begins with high fever. Patients develop a generalized redness and edema, followed by numerous pustules that are sterile and do not necessarily arise from hair follicles. The entire process resolves with generalized desquamation. Treatment consists of withdrawal of the causative medication (often a beta-lactam or macrolide antibiotic), and, sometimes, systemic corticosteroids. Rarely, AGEP may be the result of an antecedent infection and not a reaction to a drug.