UCLA Department of Medicine Clinical Insights

Rash in Syphilis: the great mimicker

A 32-year-old Caucasian male presented to his annual  preventive visit with a six-month history of a persistent, nonpruritic chest rash. He had been treated multiple times for presumed allergies and eczema with antihistamines, oral prednisone, and topical corticosteroids without improvement. The rash fluctuated in intensity without clear triggers. He also reported a painless, nonhealing lesion beneath his tongue following minor trauma.

Examination revealed a faint erythematous macular rash on the chest and upper arms, without palm or sole involvement, and a 5 mm white ulcer on the ventral tongue. Laboratory studies were unremarkable; however, sexually transmitted infection screening showed a reactive rapid plasma reagin (RPR) with positive treponemal testing (TP-PA) and a titer >1:1024. Other STI testing, including HIV, was negative.

He was treated with intramuscular penicillin G benzathine (2.4 million units). At six months, symptoms improved, and RPR declined to 1:128.

Discussion

Secondary syphilis remains a diagnostic challenge due to its variable and often nonspecific presentation. Despite longstanding recognition of Treponema pallidum infection [1], the secondary stage can mimic numerous dermatologic and systemic conditions, frequently leading to misdiagnosis as illustrated by this case. While a maculopapular rash involving the palms and soles is characteristic, it may be absent or subtle. Mucosal lesions, including oral involvement, can be mistaken for more common conditions or traumatic lesions, further complicating diagnosis.

Serologic testing adds another layer of complexity. Nontreponemal tests may be falsely negative in early infection prior to antibody development, and discordant results can occur in patients with

prior treated disease [2]. These factors necessitate careful interpretation and, in some cases, repeat testing.

In addition, given the known association with HIV coinfection [2], maintaining a high index of suspicion is critical. Early recognition of secondary syphilis through clinical awareness and appropriate testing is essential to prevent delayed treatment and ongoing transmission.

This case serves as a reminder that syphilis should remain an important consideration in the differential diagnosis particularly in patients with relevant risk factors or unusual dermatological and mucosal presentations.

References

1.     Rockwell DH, Yobs AR, Moore MB Jr.: The Tuskegee study of untreated syphilis; the 30th year of observation. Arch Intern Med. 1964, 114:792. 10.1001/archinte.1964.03860120104011

2.     Ratnam S: The laboratory diagnosis of syphilis. Can J Infect Dis Med Microbiol. 2005, 16:45. 10.1155/2005/597580