What is the most appropriate diagnostic test for a patient with a history of Mpox (Monkeypox) and recent high-risk sexual activities presenting with oropharyngeal and anal ulcers?

Diagnostic Testing for Oropharyngeal and Anal Ulcers in High-Risk Patient

The most appropriate diagnostic test is D) Serum Venereal Disease Research Laboratory test for secondary syphilis, as this patient's presentation of multiple oropharyngeal and anal ulcers following high-risk sexual contact is highly suggestive of secondary syphilis, which must be excluded first given its serious morbidity if untreated. 1

Clinical Reasoning

This 34-year-old transgender male presents with a classic constellation of findings that demands systematic evaluation:

• Multiple mucocutaneous ulcers (2 oropharyngeal + 3 anal) without vesicles
• Recent high-risk sexual exposure (condomless anal/oral intercourse with multiple partners)
• Geographic risk (recent travel to Spain, an area with endemic STIs)
• Systemic symptoms (headache, sore throat) suggesting disseminated infection 1

Why Syphilis Testing Takes Priority

Secondary syphilis is the most critical diagnosis to establish immediately because:

• Multiple ulcers in both oropharyngeal and anogenital sites are pathognomonic for secondary syphilis, which represents disseminated disease 1, 2
• The Infectious Diseases Society of America guidelines mandate that all patients presenting with genital or mucosal ulcers should be evaluated with a serologic test for syphilis 1
• Untreated syphilis progresses to tertiary disease with devastating neurologic and cardiovascular complications, directly impacting mortality and quality of life 1
• The patient is on PrEP, indicating ongoing HIV risk, and genital ulcers facilitate HIV transmission - syphilis co-infection dramatically increases this risk 1

Why Other Options Are Less Appropriate

Option C (Mpox PCR) is tempting given his history, but:

• His previous Mpox infection 5 months ago with complete resolution makes reinfection within this timeframe unlikely 3
• Mpox typically presents with vesiculopustular lesions progressing through defined stages (macules→papules→vesicles→pustules), not isolated ulcers 3, 4
• The median incubation period for Mpox is 7-10 days; his exposure was 2 weeks ago, and he would have presented with characteristic vesicles first 3
• While Mpox can cause ulcers, the absence of vesicular stage and presence of multiple sites simultaneously argues against this diagnosis 3

Option B (HIV rapid test) is important but not the priority:

• He is already on PrEP (emtricitabine/tenofovir), suggesting recent HIV testing
• HIV seroconversion typically takes 2-4 weeks; testing now (2 weeks post-exposure) may yield false-negative results
• While HIV testing should be performed, it doesn't explain his current ulcerative presentation 1

Option A (COVID-19 testing) is irrelevant:

• COVID-19 does not cause mucocutaneous ulcers
• His symptoms are not consistent with respiratory viral illness

Comprehensive Diagnostic Approach

After syphilis testing, this patient requires:

• HSV culture or PCR from ulcer base - HSV is the most common cause of genital ulcers in the US, and can cause severe proctitis in MSM 1, 5
• Testing for Chlamydia trachomatis and Neisseria gonorrhoeae from rectal and oropharyngeal sites - high-risk individuals require extragenital site evaluation 1
• HIV testing should be performed given high-risk exposure and facilitated transmission through ulcerative lesions 1
• Consider LGV serology if available, as invasive C. trachomatis serovars can cause proctitis with ulceration in MSM 1

Critical Clinical Pitfalls

• Up to 10% of patients with genital ulcers have HSV co-infected with T. pallidum - don't stop at one diagnosis 5, 2
• Even after complete evaluation, 25% of genital ulcers remain undiagnosed - empiric treatment may be necessary 1, 5, 6
• Clinical diagnosis alone is neither sensitive nor specific - laboratory confirmation is mandatory 1
• The patient's proctitis symptoms (perianal pain) suggest sexually acquired rectal infection requiring anoscopy if symptoms persist 1

Treatment Considerations Pending Results

While awaiting test results, empiric therapy should cover the most likely and serious pathogens. The CDC recommends treating for both gonorrhea and chlamydia in patients with anorectal symptoms and recent receptive anal intercourse, but syphilis treatment should be guided by serologic confirmation and staging 1