Atypical Manifestations of Syphilis: A 10-Year Retrospective Study

Abstract

Background: The incidence of syphilis has increased in high-income countries in the past few decades, especially among men who have sex with men. In the present study, we aimed to analyze the correlations between atypical syphilis manifestations and the demographic, clinical, and laboratory features of patients and to review unusual presentations of syphilis reported in the literature. Methods: We conducted a retrospective analysis of 307 patients with syphilis diagnosed between 1 January 2013 and 31 October 2023 at the sexually transmitted infection (STI) centers of the University of Genoa and University of Foggia with both typical and atypical manifestations of disease. Results: In our series, atypical manifestations were detected in 25.8% of the patients, especially in the secondary stage of the disease. Lesions with annular morphology and lesions presenting as itchy erythematous scaly plaques with a psoriasiform appearance were the most common atypical presentations of secondary syphilis. A statistical analysis revealed that homosexual orientation, syphilis reinfection, and venereal disease research laboratory (VDRL) titers > 1:32 were correlated with atypical manifestations. Conclusions: Our study demonstrates that the spectrum of syphilis manifestations, in all the stages of the disease, is wide; atypical manifestations often pose diagnostic challenges, may delay the provision of appropriate treatment, and facilitate the spread of the infection.

Keywords: Follmann balanitis; TPHA; VDRL; atypical chancre; coinfections; neurosyphilis; psoriasiform syphilis; reinfection; sexual health; sexually transmitted diseases; syphilis.

Figure 1

Atypical manifestations of primary syphilis: (A) Follmann balanitis characterized by erythematous, concentric, rosette-like lesions on the balanopreputial sulcus, glans, and foreskin; (B) two identical chancres of the glans; (C) phagedenic chancre: chancre manifesting as an erythematous, infiltrated, and ulcerated plaque with an extensive loss of tissue involving the balanopreputial sulcus and the glans; superinfection by S. agalactiae was detected through a cutaneous swab on the lesion.

Figure 2

Atypical manifestations of secondary syphilis: (A) psoriasiform secondary syphilis—slightly infiltrated papules and plaques covered by thick adherent scales of the back; (B–D) annular secondary syphilis: erythematous slightly infiltrated macules with annular shapes on the trunk, upper limbs, and back; (E–G) scrotal and shaft penis eczema in a patient with typical lesions of secondary syphilis on the palms and soles.

Figure 3

Overlapping stages of primary and secondary syphilis: (A–C) concomitant presence of the right labial commissure chancre, psoriasiform exanthem of the trunk, and genital mucosal patches; (D,E) chancre of the upper lip, erythematous papules of the arm, and papulonodular lesions of the pubis.

Figure 4

(A,B) Malignant syphilis: multiple necrotic ulcerated papules in the genital area associated with erythematous macules and papules of the arms (patient 1); (C,D) isolated necrotic lesion of the back associated with mucosal patches of the perianal region (patient 2).