A case of macular rash misleading to drug eruption in secondary syphilis

Dear Editor, Although some multiforme skin eruptions occur in secondary syphilis, it is difficult to distinguish between common cutaneous macular rash such as drug eruption and a mild erythematous rash with nonspecific eruption in syphilis infection. Moreover, the drug eruption type of rash was reported as a rare condition of secondary syphilis. We report a case of mild secondary syphilis misdiagnosed as a drug eruption. A 45-year-old Japanese man had a three-month history of visiting a sex establishment. One month later, he noticed erythema of the glans, and azithromycin (1000 mg; single dose) was prescribed at the local clinic. Five days following drug administration, erythema of the whole body appeared without itch and fever appeared and the patient was prescribed oral steroids and antiallergic agents for 10 days. However, he experienced no improvement and was referred to our department. Light erythema of 2–3 cm was scattered on the extremities and trunk (Fig. 1a–c), and a 5-mm induration was observed on the glans (Fig. 1d). No skin rash was observed on the palms. Blood tests showed no abnormalities other than fluorescent treponemal antibody absorption IgG/IgM and Treponema pallidum hemagglutinin test (1:5120, 1:20, and 1:200, respectively), and there was no evidence of viral or bacterial infection. Skin biopsy of the trunk revealed edema at the superficial dermis and mild lymphocyte infiltration around the blood vessels and adnexa (Fig. 1e, f). Immunostaining test did not detect Treponema. Within a few days of treatment with amoxicillin (750 mg/day), skin eruption improved, and amoxicillin was continued for ten weeks. Oral challenge test and drug-induced lymphocyte stimulation test for azithromycin were negative. This case could have been secondary syphilis as syphilitic roseola or papular syphilide; however, these eruptions were too mild to be specific for syphilis. Azithromycin may contribute to the alleviation of syphilitic rash. Had there appeared a rash on the palms, which is characteristically observed with syphilitic roseola, syphilis could have been early diagnosed. Pathological diagnosis was also difficult, because when Alessi et al. evaluated tissues samples from macular rash, spirochetes were difficult to detect, and plasma cell infiltration was inconspicuous. Trevelyan et al. reported a similar rash that presented as widespread maculopapular rash. The syphilitic macular rash, which is most readily observed after 8 weeks