Syphilis and Treponematosis

Syphilis is caused by Treponema pallidum subspecies pallidum, a spirochete, and progresses through distinct clinical stages if untreated.

The broader treponematoses share the same genus but cause non-venereal disease through direct skin contact rather than sexual transmission, and are geographically and clinically distinct: yaws (T. pallidum subspecies pertenue, tropical regions), bejel/endemic syphilis (T. pallidum subspecies endemicum, arid regions), and pinta (T. carateum, Central and South America), all of which share serological cross-reactivity with venereal syphilis, an important consideration when interpreting positive serology in someone from an endemic region without a sexual exposure history.

• Primary syphilis: a single, classically painless, indurated ulcer (chancre) with a clean base, appearing 2 to 3 weeks after exposure at the site of inoculation, healing spontaneously over 3 to 6 weeks even without treatment; regional lymphadenopathy, also typically non-tender, accompanies it
• Secondary syphilis (weeks to a few months after the primary chancre, reflecting hematogenous dissemination): a generalized maculopapular rash characteristically involving the palms and soles (a distinguishing feature from most other exanthems), generalized lymphadenopathy, mucous patches, condylomata lata (broad, moist, wart-like plaques in warm, moist areas), patchy alopecia, and constitutional symptoms (fever, malaise, headache)
• Latent syphilis: no clinical features, detected only serologically; subdivided into early latent (infection within the preceding 12 months, or 24 months per some definitions) and late latent (or of unknown duration), a distinction with treatment implications
• Tertiary syphilis (years to decades after untreated infection, now uncommon given widespread earlier treatment): gummatous disease (destructive granulomatous lesions in skin, bone, or viscera), cardiovascular syphilis (aortitis, aortic aneurysm, aortic regurgitation), and neurosyphilis, which can occur at any stage, not only tertiary disease, presenting with meningitis, cranial nerve palsies, tabes dorsalis (dorsal column degeneration causing sensory ataxia and lightning pains), or general paresis (progressive dementia with personality change)
• Congenital syphilis from untreated maternal infection causes stillbirth, and, in surviving infants, early features (hepatosplenomegaly, rash, snuffles) or late features (Hutchinson's teeth, saddle nose, saber shins, interstitial keratitis)

• Non-treponemal tests (RPR or VDRL) are used for screening and monitoring treatment response, since titres fall predictably with successful treatment and rise with relapse or reinfection; can give false positives (pregnancy, autoimmune disease, other infections)
• Treponemal tests (TPPA, TPHA, or treponemal EIA/CLIA) confirm the diagnosis and, once positive, generally remain positive for life regardless of treatment, so cannot be used to monitor treatment response or distinguish active from previously treated infection
• Modern screening algorithms increasingly start with a treponemal test (reverse algorithm), confirmed by a non-treponemal test if positive
• Dark field microscopy of exudate from a primary chancre, where available, allows direct visualization and rapid diagnosis before serology becomes positive
• Neurosyphilis is diagnosed by CSF analysis (lymphocytic pleocytosis, elevated protein, and a reactive CSF-VDRL, which is highly specific but insensitive; a negative CSF-VDRL does not exclude neurosyphilis if clinical suspicion is high)

• Primary, secondary, and early latent syphilis: benzathine penicillin G 2.4 million units IM as a single dose
• Late latent syphilis (or latent of unknown duration), and tertiary (gummatous or cardiovascular) syphilis: benzathine penicillin G 2.4 million units IM once weekly for 3 consecutive weeks
• Neurosyphilis (including ocular and otic syphilis): IV aqueous crystalline penicillin G 18 to 24 million units/day, given as 3 to 4 million units IV every 4 hours (or continuous infusion), for 10 to 14 days
• Penicillin allergy: doxycycline 100 mg PO bd for 14 days (early syphilis) or 28 days (late latent/tertiary) is the standard alternative; penicillin desensitization followed by standard penicillin treatment is required in pregnancy, given penicillin remains the only reliably effective treatment for preventing congenital syphilis and doxycycline is contraindicated in pregnancy
• Jarisch-Herxheimer reaction: an acute febrile reaction with myalgia, headache, and worsening of skin lesions, occurring within hours of the first treatment dose from a rapid inflammatory response to spirochete lysis, managed with antipyretics and reassurance, distinct from a true penicillin allergic reaction; can precipitate premature labor if it occurs during pregnancy treatment, warranting appropriate monitoring
• Serological follow up: repeat non-treponemal titres at 6 and 12 months (early syphilis) to confirm an adequate fourfold decline confirming treatment response; longer follow up (6, 12, and 24 months) for late latent disease
• Sexual partners are notified and tested based on the stage of infection and estimated exposure window (3 months for primary, 6 months for secondary, 1 year for early latent)

Referral: sexual health/infectious disease services for all confirmed syphilis; neurology and lumbar puncture for suspected neurosyphilis; cardiology for suspected cardiovascular syphilis; obstetrics for management in pregnancy.