Could syphilis be involved in the patient's symptoms?

Could Syphilis Be Involved?

Yes, syphilis should be strongly considered in the differential diagnosis for any patient presenting with unexplained ulcers, rashes, neurologic symptoms, cardiovascular manifestations, or systemic illness, particularly in sexually active individuals. 1

Clinical Presentations That Should Trigger Syphilis Consideration

Primary Syphilis

• Look for a painless ulcer (chancre) at the site of infection with regional lymphadenopathy, typically appearing 10-90 days after exposure 1, 2
• Important caveat: The classic "single painless chancre" teaching is outdated—primary syphilitic lesions may be multiple, painful, and atypical, especially in HIV-infected individuals 3, 1
• The chancre may be missed or absent entirely, particularly in women or with oral/rectal lesions 1
• Darkfield microscopy or direct fluorescent antibody testing of lesion exudate provides definitive diagnosis during this stage 1, 4

Secondary Syphilis

• Constitutional symptoms mimicking acute HIV infection: fever, malaise, lymphadenopathy, headache 1
• Diffuse rash that characteristically involves palms and soles 2, 5
• Mucocutaneous lesions including condyloma lata (genital/perineal warts) 3, 5
• Nodular presentations can occur, particularly in HIV-positive patients 6
• Patchy alopecia, mucous patches in the mouth, and generalized lymphadenopathy 5

Latent Syphilis

• Positive serologic tests without any clinical manifestations 1
• Early latent: infection acquired within the preceding 12 months 3
• Late latent: infection occurred more than 1 year previously 3
• Latent syphilis of unknown duration: when timing cannot be established, particularly in patients aged 13-35 years with nontreponemal titer ≥32 3

Tertiary Syphilis

• Occurs in approximately 25% of untreated patients after 3-12 years of latency 1
• Cardiovascular manifestations: aortitis, aortic aneurysm, aortic regurgitation 3, 1
• Gummatous lesions: inflammatory lesions of skin, bone, or any organ system 3, 1
• Late benign syphilis: granulomatous lesions that can involve upper/lower respiratory tracts, mouth, eye, abdominal organs 3

Neurosyphilis (Can Occur at ANY Stage)

• Critical point: Neurosyphilis can develop at any stage of syphilis, not just late disease 3, 1
• Neurologic symptoms: meningitis, cranial nerve palsies, stroke, altered mental status 2, 5
• Ocular involvement: uveitis, optic neuritis, vision changes 3, 1
• Auditory symptoms: hearing loss, tinnitus 6
• CSF findings: reactive VDRL in CSF is diagnostic; elevated protein or leukocyte count with negative VDRL is probable neurosyphilis 3

High-Risk Populations Requiring Heightened Suspicion

• Men who have sex with men (MSM): comprised 32.7% of all males with primary and secondary syphilis in 2023 2
• People with HIV: increased risk of atypical presentations, multiple lesions, and accelerated disease progression 1, 6
• Individuals engaging in condomless sex with multiple partners 2
• Pregnant women: critical to identify due to risk of congenital syphilis and stillbirth 3, 2
• Persons with history of sexually transmitted infections 3
• Methamphetamine users and those meeting partners online 3

Diagnostic Approach

Serologic Testing Algorithm

• Screen with nontreponemal tests (RPR or VDRL) and confirm with treponemal tests (FTA-ABS or TP-PA) 1, 5
• A fourfold change in nontreponemal titer is clinically significant for monitoring disease activity 1
• Important consideration: The reverse sequence algorithm (treponemal test first) is increasingly used, but complete endpoint titers must always be reported—laboratories reporting titers as ">1:32" without specifying the actual titer make patient management impossible 3

When to Perform CSF Examination

• Any neurologic, ocular, or auditory symptoms 3, 1, 6
• Tertiary syphilis manifestations 7
• Treatment failure (failure of nontreponemal titers to decline fourfold within 6 months) 6, 7
• Very high RPR titers in HIV-positive patients 6
• Late syphilis with clinical manifestations requires CSF analysis to exclude neurosyphilis 3

HIV Testing Mandate

• All patients diagnosed with syphilis must be tested for HIV 3, 1
• In high HIV prevalence areas, retest HIV-negative patients with primary syphilis after 3 months 3

Treatment Implications

Standard Treatment

• Primary/secondary/early latent syphilis: Benzathine penicillin G 2.4 million units IM single dose 1, 8, 2
• Late latent or unknown duration: Benzathine penicillin G 2.4 million units IM weekly × 3 doses 1
• Neurosyphilis: Aqueous crystalline penicillin G 18-24 million units IV daily for 10-14 days 1, 6

Penicillin Allergy

• For early syphilis: Doxycycline 100 mg PO twice daily for 14 days 1, 9, 7
• For late latent syphilis: Doxycycline 100 mg PO twice daily for 28 days 1, 9
• For pregnant women and neurosyphilis: Penicillin desensitization is mandatory—no alternatives are acceptable 1, 7

Common Pitfalls to Avoid

• Don't dismiss syphilis because the lesion is painful or multiple—atypical presentations are increasingly common 3
• Don't skip CSF examination in patients with neurologic, ocular, or auditory symptoms—neurosyphilis can occur at any stage 3, 6
• Don't accept incomplete nontreponemal titers from laboratories—endpoint titers are essential for management 3
• Don't forget that oral lesions may harbor T. pallidum even without visible symptoms—serologic screening is crucial in at-risk patients 3
• Don't overlook syphilis in pregnant women—up to 40% of fetuses with in-utero exposure are stillborn or die in infancy 2