Atypical Blistering Manifestation of Secondary Syphilis: Case Report and Review of Reported Cases

Background/Objectives: Secondary syphilis typically presents with a non-pruritic maculopapular rash. However, vesicular and bullous manifestations are exceedingly rare in adults and may mimic autoimmune blistering diseases. The objective of this report is to describe atypical presentation of secondary syphilis with predominant vesiculobullous lesions and to emphasize the importance of including syphilis in the differential diagnosis of blistering skin diseases. Methods: We describe the case of a 46-year-old bisexual man with syphilis of unknown duration who presented with recurrent polymorphic skin eruptions, predominantly bullous and vesicular in nature. Clinical examination, serologic testing, and histopathologic evaluation were performed to establish the diagnosis. Results: Serologic tests confirmed active syphilis infection. A brief review of similar reported cases was conducted to highlight the clinical variability of vesiculobullous syphilis. Conclusions: Atypical vesiculobullous presentations of secondary syphilis pose significant diagnostic challenges and may be mistaken for autoimmune blistering disorders. Clinicians should maintain a high index of suspicion for syphilis in patients with polymorphic or blistering eruptions, particularly in those with risk factors for sexually transmitted infections. Awareness of these uncommon manifestations can facilitate timely diagnosis and appropriate treatment.