latent syphilis

**Definition & staging** - Syphilis is caused by the spirochete *Treponema pallidum* (subsp. *pallidum*). It is transmitted sexually, vertically (transplacentally), or rarely by blood. - Natural history: primary (painless chancre, ~3 weeks after exposure) → secondary (diffuse maculopapular rash including palms/soles, condylomata lata, mucous patches, generalized lymphadenopathy, fever) → latent → tertiary (in about one-third of untreated patients). - Latent syphilis follows resolution of secondary symptoms. It is defined by reactive serology with no clinical manifestations. - **Early latent:** infection acquired within the past 12 months. Evidence includes documented seroconversion, symptoms of primary or secondary syphilis within the past year, or a sexual partner with documented primary, secondary, or early latent syphilis. Relapses of secondary-stage lesions can occur and are infectious. - **Late latent:** infection >12 months ago. Also includes **latent syphilis of unknown duration**, which is managed as late latent. - Late latent syphilis is generally not sexually infectious. It can still be transmitted vertically in pregnancy.

**Diagnosis** - Nontreponemal tests (VDRL, RPR) detect antibodies to cardiolipin. They are used for screening and for monitoring treatment response, and titers fall after effective treatment. They can give false positives (mnemonic **VDRL**: Viruses [EBV, hepatitis], Drugs, Rheumatic fever/Rheumatoid arthritis, Lupus/Leprosy; also pregnancy, TB, and antiphospholipid syndrome). - Treponemal tests (FTA-ABS, TP-PA, EIA/CIA) are specific and usually stay positive for life. Either algorithm is used: traditional (RPR/VDRL first, then confirm with a treponemal test) or reverse sequence (treponemal EIA/CIA first, then RPR). - Latent syphilis is diagnosed when both tests are reactive, there are no signs or symptoms, and the exam is otherwise unremarkable. - Before labeling a patient latent, look for neurologic, ocular, or otic symptoms and for signs of tertiary disease. CSF exam (LP) is indicated if there are neurologic signs or symptoms, evidence of tertiary disease (aortitis, gumma), or treatment failure. Neurosyphilis can occur at any stage. - Test all patients with syphilis for HIV.

**Treatment** - **Early latent:** benzathine penicillin G 2.4 million units IM ×1. - **Late latent or unknown duration:** benzathine penicillin G 2.4 million units IM weekly ×3 (7.2 million units total). - Penicillin allergy: doxycycline is the usual alternative in non-pregnant patients (100 mg PO BID for 14 days for early latent, 28 days for late latent). **Pregnant patients must be desensitized and given penicillin.** - Neurosyphilis, ocular syphilis, and otosyphilis are treated with IV aqueous penicillin G for 10–14 days. - **Jarisch-Herxheimer reaction:** fever, myalgias, and headache within 24 hours of starting treatment. It is caused by cytokine release (TNF-α, IL-6, IL-8) from dying spirochetes. It is managed supportively (NSAIDs/antipyretics) and is not a penicillin allergy. It is more common in early syphilis. - Follow-up: repeat quantitative nontreponemal titers at 6, 12, and 24 months for latent disease. Treatment success is a ≥4-fold (2-dilution) decline. Failure is a sustained ≥4-fold rise or a failure to decline.

**High-yield associations** - Sequelae of untreated syphilis (tertiary): - Gummas (granulomatous lesions of skin, bone, or liver). - Cardiovascular syphilis: ascending aortic aneurysm and "tree-bark" calcification from vasa vasorum endarteritis, with aortic regurgitation. - Neurosyphilis: tabes dorsalis, Argyll Robertson pupil ("prostitute's pupil": accommodates but doesn't react), general paresis, meningovascular disease. - Congenital syphilis: Hutchinson teeth, saddle nose, mulberry molars, saber shins, interstitial keratitis, and sensorineural deafness (Hutchinson triad: notched teeth, interstitial keratitis, CN VIII deafness). Vertical transmission is possible during latent stages, so screen all pregnant women at the first prenatal visit. - Dark-field microscopy is not useful in latent syphilis because there are no lesions to sample. - Vignette clue: an asymptomatic patient with a positive screening RPR and positive FTA-ABS or TP-PA and no history of treatment. Duration is unknown, so give 3 weekly doses of penicillin G benzathine.