The challenging diagnosis of seronegative oral syphilis in an hiv-infected patient

Background In people living with HIV/syphilis-coinfection, overlapping of clinical stages and misleading anti-treponemal serologic tests have been described. This is the report of serological (false-negative) non-reactive, polymerase chain reaction (PCR)-confirmed syphilis in an HIV-infected patient. Case Description An HIV-infected male patient, 28-years-old, receiving antiretrovirals (TDF/FTC/DTG) with therapeutic success (CD4: 667 cells/mm3, undetectable HIV-plasma viral load), was referred to our Oral Pathology & Medicine Service in Mexico City. A 3-month asymptomatic ulcerated lesion on the right side of the soft palate and anterior pillar, with granular appearance, irregular borders, and measuring 2 to 3 cm in diameter, was observed. A painless, right cervical lymph node was present. A quantitative serum Venereal Disease Research Laboratory (VDRL) assay was nonreactive (serum was diluted 6-fold to rule out a prozone phenomenon and remained negative). Histopathologic analysis revealed an intense mixed inflammatory infiltrate; differential diagnosis included secondary syphilis, lymphoproliferative disorder, and deep mycotic infection. The immunohistochemistry (IHC) for T. pallidum was negative. DNA extraction was performed, and the T. pallidum gene polA was amplified by PCR; as a consequence, the patient received benzathine-penicillin G (2.4 million units) single dose. VDRL and treponemal FTA-abs were done twice, with negative results. A new biopsy revealed positive IHC-T. pallidum. Two months later, a mucous patch appeared on the tonsillar pillar, with histopathologic features of secondary syphilis and positivity for IHC-T. pallidum. VDRL and FTA-abs assays remained non-reactive. Oral lesions resolved after 3 doses of benzathine-penicillin G. Conclusions In absence of serological evidence, the diagnosis of oral syphilis is a challenge. PCR and IHC may represent supplementary helpful diagnostic tools.