An 11-year-old boy presented with slightly itchy skin eruption on his palms for the preceding 5 days. Examination revealed multiple circular plaques with central dusky coloration, bullae formation, and peripheral erythematous rings on his palms. The central bullae or dusky coloration with surrounding concentric rings resemble the appearance of a ‘target’. A few similar skin lesions were also seen on the other areas of his body. There was no mucosal lesion. Based on the distinctive clinical feature, a diagnosis of Herpes simplex-associated erythema multiforme (EM) was made (Fig. 1).

Fig.1 Erythema multiforme

Erythema multiforme is a cutaneous reaction pattern precipitated mainly by various infections and drugs. Herpes simplex virus (HSV) 1 and 2, adenovirus, measles, Mycoplasma, and Yersinia are considered important infectious cause of EM amongst others. Drugs like sulfonamides, penicillin, cephalosporin, and tetracycline may also precipitate EM. Rare causes of EM include malignancies and collagen vascular diseases. However, no underlying cause is found in a number of cases.

Other differential diagnoses that should be considered in the present case are: urticaria, hand foot and mouth disease (HFMD), fixed drug eruption (FDE), vasculitis, and urticarial vasculitis. In urticaria the central zone comprises of normal skin, lesions usually change within hours, associated with swelling, and lesions resolve and re-appear at different sites on daily basis. On the other hand, the central zone of EM is damaged skin, lesions are symmetrical, fixed (at least for some days), and all lesions usually appear within a few days. FDE may resemble EM, but usually the lesions are solitary or a few compared with multiple lesions of EM. FDE usually manifests as round or oval, sharply delineated erythematous plaque the center of which may blister or become necrotic. It gradually fades away with residual hyperpigmentation. Moreover, recurrent lesions usually appear at the same anatomical site. In HFMD, the characteristic rash consist of flat or raised erythematous lesions, sometimes with vesicles with a perilesional erythematous halo and are usually located on the palms, soles, knees and buttocks. The lesions on the palms and soles are characteristically elliptical in shape. Associated buccal mucosal lesions are usually present. Vasculitis or urticarial vasculitis may also mimic EM, but the target lesions are usually absent. Finally, histopathological examination of the lesional skin often helps to differentiate EM from other close mimickers.