Neurosyphilis as the Primary Venereal Disease Causing This Symptom Constellation
Among sexually transmitted infections, neurosyphilis is the only venereal disease that can cause the combination of profuse sweating (diaphoresis), cognitive dysfunction, fatigue, and weight gain, though weight gain is not a typical feature. 1
Clinical Presentation of Neurosyphilis
Neurosyphilis can occur at any stage of syphilis and presents with cognitive dysfunction as a hallmark neurological manifestation. 1 The CDC guidelines specifically list cognitive dysfunction as clinical evidence of neurologic involvement requiring CSF examination 1.
Key Neurological Features:
- Cognitive dysfunction is a well-documented presentation of neurosyphilis, ranging from mild deficits to dementia 1, 2
- Motor or sensory deficits, cranial nerve palsies, and meningeal signs commonly occur 1
- Constitutional symptoms including fatigue are present, particularly in secondary syphilis which can mimic acute HIV infection 1
- Diaphoresis (profuse sweating) occurs as part of the systemic manifestations of secondary syphilis 3
Important Caveat About Weight Gain:
Weight gain is NOT a typical manifestation of syphilis at any stage. 3 The classic presentation involves weight loss and constitutional symptoms rather than weight gain. If a patient presents with this constellation including weight gain, consider:
- Concurrent endocrine disorders (hypothyroidism)
- HIV coinfection with metabolic complications
- Other systemic conditions mimicking or coexisting with syphilis
Diagnostic Approach
Any patient with cognitive dysfunction and risk factors for sexually transmitted infections requires CSF examination to evaluate for neurosyphilis. 1
Mandatory CSF Examination Criteria:
- Neurologic signs or symptoms (including cognitive dysfunction) 1
- Ophthalmic or auditory symptoms 1
- HIV coinfection 1
- Serum nontreponemal titer ≥1:32 1
- Treatment failure 1
Serological Testing Algorithm:
- Screen with nontreponemal tests (VDRL, RPR) followed by treponemal confirmation (FTA-ABS, TP-PA) 1, 4
- Negative blood VDRL makes neurosyphilis highly unlikely (p<0.01), and lumbar puncture may not be necessary in this scenario 5
- All patients with syphilis must be tested for HIV 1
Treatment Protocol
For confirmed neurosyphilis, treat with aqueous crystalline penicillin G 18-24 million units per day IV, administered as 3-4 million units every 4 hours or continuous infusion, for 10-14 days. 1, 4
Alternative Regimen (if compliance assured):
- Procaine penicillin 2.4 million units IM once daily PLUS
- Probenecid 500 mg orally four times daily, both for 10-14 days 1
Post-Treatment Consideration:
Some specialists add benzathine penicillin 2.4 million units IM weekly for 3 weeks after completing neurosyphilis treatment to provide comparable total duration. 1
Critical Clinical Pitfalls
HIV coinfection may accelerate syphilis progression and make clinical lesions more apparent. 1, 4 HIV-infected patients with neurosyphilis require the same treatment regimen but warrant closer monitoring 1.
Secondary syphilis can mimic acute HIV infection with constitutional symptoms, CSF abnormalities, and lymphocytic pleocytosis, making differentiation challenging 1. Both conditions should be tested simultaneously in at-risk patients.
Penicillin allergy in neurosyphilis patients requires desensitization - there are no acceptable alternative antibiotics for neurosyphilis treatment 4, 6. Doxycycline and tetracycline alternatives only apply to non-neurological latent syphilis after CSF examination excludes neurosyphilis 1, 6.
Follow-Up Requirements
If CSF pleocytosis was present initially, repeat CSF examination every 6 months until cell count normalizes. 1 The leukocyte count is the most sensitive measure of treatment effectiveness 1.
Treatment failure is indicated by: failure of CSF cell count to decrease after 6 months or failure to normalize by 2 years 1.