Abstract
A 33-year-old man presented with a two-week history of an asymptomatic ulcer of the oropharynx and submandibular lymph nodes swelling. Laboratory examinations were normal, but serological tests revealed positivity for rapid plasma reagin, Treponema pallidum haemagglutination assay and anti-T. pallidum IgM antibodies. Since the patient denied any homosexual relationship, a biopsy of the lesion was performed, which confirmed primary syphilis. The patient received an intramuscular injection of Benzathine Penicillin G (2.4 MU) with complete resolution of the lesion. Extragenital chancres occur in at least 5% of patients with primary syphilis, and the oral mucosa is the most frequent location as a consequence of orogenital/oroanal contact with an infectious lesion. Because of their transient nature, these oral ulcerations are often underestimated by the patient or by any unsuspecting clinician. Health professionals should consider the recent sexual history of their patients and should be prepared to recognise oral and systemic manifestations of sexually transmitted infections.
Keywords
A previously healthy 33-year-old man presented with a two-week history of an asymptomatic lesion of the oral cavity. Examination revealed a well-demarcated grey–white plaque with central ulceration extending over the right pharyngopalatine arch. The bottom of the ulcer was cleansed and red coloured (Figure 1(a)). A right submandibular lymphadenopathy was appreciable: lymph nodes were small, tender, mobile and painless. Routine laboratory examinations were normal, and an HIV test was negative. Serological tests for syphilis revealed positivity for rapid plasma reagin (RPR) and Treponema pallidum haemagglutination assay (TPHA) with titres of 1:32 and 1:10,240, respectively. Anti-T. pallidum IgM antibodies were found by T. pallidum enzyme-linked immunosorbent assay (ELISA). Pharyngeal swab showed Staphylococcus aureus. At a careful investigation about sexual/social lifestyle, the patient denied having ever had homosexual sex or previous sexually transmitted infections (STIs). He reported that he had more than three heterosexual relationships in the last year and that he currently had a steady partner for three months. The serologic tests and the clinical presentation were suggestive for primary syphilis (PS), but we had no data about receptive oral sex; therefore, a biopsy of the lesion was performed to confirm the diagnosis. Histopathologic examination revealed infiltrates with lymphocytes, plasma cells, neutrophils and vascular dilatation with swollen endothelial cells. Immunohistochemical staining for T. pallidum revealed a large number of spirochetes (Figure 1(b)). It was performed on paraffin sections, using a rabbit polyclonal antibody (Serotec 1439-9406) at 1/2000 dilution, that is not only specific for Borrelia burgdorferi but also reacts with T. pallidum. A diagnosis of oropharynx PS was made, and the patient was treated with a single intramuscular injection of Benzathine Penicillin G (2.4 MU). The lesion completely resolved in four weeks.
(a) Well-delimited grey–white plaque with a central ulceration extending over the right pharyngopalatine arch. The bottom of the ulcer is cleansed and red coloured. (b) Immunohistochemical staining on paraffin sections, using a rabbit polyclonal antibody at 1/2000 dilution for Treponema pallidum, revealed a large number of spirochetes.
Discussion
The PS lesion is a red papule/nodule of varying size which tends to erode resulting in the chancre. This ulceration, typically painless, oval, with indurated borders and covered by a yellowish exudate, is located at the former contact site with the infectious lesion of a sexual partner, which is usually in the genital area. At least 5% of all primary chancres are extra-genital,1,2 and the mouth is the most frequent location (40–75%), 3 especially in men who have sex with men (MSM). 4 The primary chancre may also occur on anus, fingers, toes and nipples. 5
Because of their transient and painless nature, PS ulcerations are often underestimated by the patient or by any unsuspicious clinician.
In the mouth, PS can manifest as a solitary ulcer on the lips or, less commonly, the tongue, pharynx or tonsils with a simultaneous cervical lymphadenopathy.1,3
Differential diagnosis of oral PS includes trauma, infectious ulcers (chancroid, herpes simplex, tuberculosis, mycoses, Cytomegalovirus/Epstein Barr virus infections), autoimmune (pemphigus/pemphigoid, Behcet syndrome) or immune-related lesions (lichen planus, drug-related manifestations) and precancerous/cancerous ulcers (leukoplakia, squamous cell carcinoma, non-Hodgkin’s lymphoma).6–8
Oral lesions may be a feature of all stages of syphilis. As reported by Leuci et al., 9 35% of the patients with syphilitic oral manifestations (ulcers) have a primary stage of the disease. Oral manifestations are often detected in the syphilis secondary stage (56% of cases): they are ulcers in about 50% of cases but other non-specific lesions may occur (mucous patches, papules, plaques).3,9 These lesions are often associated with systemic/dermatological symptoms being rarely the only manifestation of the infection. 10 Oral involvement is also reported in tertiary syphilis (9% of cases) 9 as nodular/ulcerative lesions (gummas) that may affect the palate, tongue or tonsils with eventual bone destruction and/or palatal perforation. 10
Diagnosis of PS is based on a detailed analysis of the patient sexual/social lifestyles, a reasonable incubation period, clinical features and results of serological tests. 11 However, affected patients may have not yet a positive non-treponemal test, like RPR or Venereal Disease Research Laboratory. However, the specific tests for anti-T. pallidum IgG antibodies, like TPHA and ELISA, usually resulted positive earlier than the non-treponemal tests, and thus, they should be performed when the non-specific tests result negative but a diagnosis of PS is likely. 10
The definitive test is the demonstration of the spirochetes in the lesional tissue by dark field microscopy (DFM) and/or direct immunofluorescent assay (DFA). DFM allows for observation of the treponemes on a lesional sample through a dark field microscope: it allows an immediate diagnosis, but the differentiation between T. pallidum and other commensal Treponemes (like Treponema denticola) is not easy. 12 DFA identifies directly on tissue sections the treponemes conjugated with monoclonal fluorescein antibodies through a fluorescence microscope with the possibility to examine also materials potentially contaminated with commensal Treponemes. 13
A biopsy of the chancre is recommended in any questionable case.
In conclusion, we emphasise the importance of a continuous education of the sexually active population, especially MSM, to avoid risky behaviours for STIs, like unprotected oral sex.
Health professionals (dermatologists, otolaryngologists and dentists) should take from their patient a sexual history, and especially, non-experienced physicians should be alerted to recognise both oral and systemic manifestations of STIs.
Footnotes
Declaration of Conflicting Interests
The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The authors received no financial support for the research, authorship, and/or publication of this article.