Histopathologic features of exanthematous drug eruptions of the macular and papular type

Although exanthematous drug eruptions of the macular and papular type are common and often cause diagnostic problems, histopathologic features are not precisely defined in the literature. We present the first prospective histopathologic study of maculopapular drug eruption in 48 patients in whom the diagnosis had been made on the basis of clinical examination, history of a known offending drug, and follow-up. Because more than 1 biopsy was taken in 11 patients, 60 biopsy specimens could be examined. The most consistent epidermal features were mild spongiosis mainly of the lower layers (97% of biopsies), some hyperplasia (72%), a few lymphocytes (82%), and neutrophils (32%). The dermoepidermal junction revealed discrete vacuolization (97%), scattered lymphocytes (75%), and rare necrotic keratinocytes (32%). All cases showed a dermal perivascular inflammatory infiltrate that was superficial only in 72% of biopsies and superficial and deep in 28% of biopsies. An interstitial infiltrate in the papillary dermis could be found in 93%, more often patchy than lichenoid. In general, the perivascular infiltrate was mild and composed of lymphocytes (100%), eosinophils (60%), and neutrophils (50%). In the papillary dermis, neutrophils often outnumbered the eosinophils. Another feature were the clusters of neutrophils (38%) and eosinophils (20%) in the lumina of dilated, otherwise normal, blood vessels. Rashes induced by anticonvulsants and anxiolytics were characterized by predominance of neutrophils and largish lymphocytes. Edema of the papillary dermis was encountered frequently (85%), whereas wiry collagen bundles were an exceptional finding. In conclusion, our study defined a constellation of histopathologic findings highly suggestive of the diagnosis of exanthematous drug eruption of the macular and papular type.