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Q1: A 24-year-old man presents with a single, painless, indurated ulcer on the glans penis with rubbery non-tender inguinal nodes. Discuss the diagnosis and its pathogen. (2 min)
This is primary syphilis. The painless, clean-based, indurated (firm, cartilaginous) ulcer with a raised border and non-tender rubbery regional lymphadenopathy is the classic chancre of primary syphilis, caused by the spirochete Treponema pallidum subsp. pallidum — a thin (0.1 to 0.2 micrometre wide), tightly coiled, motile spirochete with 6 to 14 spirals. Two structural features define the organism and its behaviour: its outer membrane is hyposialylated and poor in transmembrane proteins (the basis of its immune evasion and persistence — very few antibody targets on the surface), and its periplasmic endoflagella drive the corkscrew (rotational) motility that allows it to penetrate mucosa and abraded skin and to disseminate within hours. It cannot be cultured on artificial media, so diagnosis rests on dark-field microscopy of the chancre exudate (showing motile spirochaetes) and on two-tier serology. The chancre appears 9 to 90 days (average 21 days) after exposure and heals spontaneously in 3 to 6 weeks even without treatment — but the organism has already disseminated systemically, which is why treatment must be systemic and stage-based. The chancre must be differentiated from herpes (painful, multiple, vesicular), chancroid (painful, purulent, tender bubo), lymphogranuloma venereum (small ulcer then large bubo with groove sign) and granuloma inguinale (beefy red, Donovan bodies).
Q2: How would you confirm the diagnosis, and explain the two-tier serological strategy. (2 min)
Diagnosis is confirmed by two-tier serology, interpreted as a pair of test types. Non-treponemal tests (RPR, VDRL) detect non-specific reagin antibodies (anti-cardiolipin) and are used for screening and to monitor disease activity and treatment response via the titre — a fourfold (two-dilution) rise or fall is clinically significant (e.g. 1:16 to 1:4 after treatment). They can be false-positive (pregnancy, SLE, antiphospholipid, vaccination, malaria) and false-negative in the prozone (antibody excess in secondary syphilis — request serum dilution). Treponemal tests (TPPA, TPHA, FTA-ABS, treponemal EIA) detect specific anti-T. pallidum antibodies, are used to confirm a reactive non-treponemal test, and generally remain positive for life even after adequate treatment — so a positive treponemal with a negative non-treponemal could be past-treated disease OR very early primary syphilis (the treponemal becomes positive earlier than the non-treponemal). TPPA is the most sensitive and specific treponemal test. Dark-field microscopy of the chancre exudate confirms early infectious lesions by showing the motile spirochete directly. The two screening algorithms are the traditional (RPR first, then confirm with treponemal) and the reverse (treponemal EIA first, then RPR for activity), the latter catching more late/latent cases. HIV serology is mandatory at the time of diagnosis.
Q3: State the definitive treatment by stage, with doses, routes and rationale. (2 min)
Penicillin is first-line for every stage of syphilis — no resistance has ever been documented in over 70 years. Primary, secondary and early latent syphilis: benzathine penicillin G 2.4 million units IM as a single dose (1.2 MU into each buttock). Late latent, latent of unknown duration, and tertiary non-neuro (gummatous, cardiovascular): benzathine penicillin G 2.4 million units IM once weekly for 3 consecutive doses (7.2 MU total), and if any interval between doses exceeds 14 days, restart the course from the beginning. Neurosyphilis, ocular and otic syphilis: aqueous crystalline penicillin G 18 to 24 million units/day IV (3 to 4 million units every 4 hours or continuous infusion) for 10 to 14 days — because benzathine penicillin does NOT achieve treponemicidal levels in the CSF. The rationale is that benzathine penicillin forms a depot that releases drug slowly, maintaining treponemicidal levels for 2 to 3 weeks (sufficient for early disease), whereas established late disease needs a longer course and neurosyphilis needs IV penicillin for CSF penetration. Penicillin allergy (non-pregnant): doxycycline 100 mg twice daily for 14 days (early) or 28 days (late), or tetracycline 500 mg four times daily, or ceftriaxone 1 to 2 g daily for 8 to 10 days; azithromycin is NOT recommended (23S rRNA resistance). Follow-up: repeat RPR/VDRL at 6, 12 and 24 months; expect a fourfold fall by 6 to 12 months in early disease; treatment failure or re-infection if the titre does not fall fourfold or rises — re-evaluate (HIV, CSF, adherence, re-exposure) and re-treat.
Q4: Discuss the complications of syphilis and which you must specifically not miss. (3 min)
Untreated syphilis progresses to tertiary disease in roughly one-third of patients, with three forms. Gummatous — granulomatous, paucibacillary nodules of skin, bone (skull, tibia, palate), and viscera, producing punched-out ulcers, pathological fracture and palate/nasal-septum perforation (saddle nose). Cardiovascular — T. pallidum seeds the vasa vasorum of the ascending aorta, producing obliterative endarteritis, medial necrosis, and an ascending aortic aneurysm (spares the aorta distal to the renal arteries; 'tree-bark' intima), aortic regurgitation and coronary ostial stenosis; manifests 15 to 30 years after infection and can rupture fatally. Neurosyphilis can occur at ANY stage — meningeal (headache, cranial nerve VII/VIII palsies, seizures), meningovascular (stroke in a young person, classically middle cerebral artery territory), general paresis (dementia, personality change, grandiosity, tremulous tongue, Argyll Robertson pupil), tabes dorsalis (lancinating lightning pains, sensory ataxia, positive Romberg, areflexia, loss of vibration and proprioception, Charcot joints), and ocular/otic syphilis (uveitis, optic neuritis, sensorineural deafness, vertigo). Congenital syphilis causes stillbirth, hydrops, 'snuffles', and the late stigmata (Hutchinson triad — notched peg-shaped incisors, interstitial keratitis, sensorineural deafness; saddle nose; saber shin; mulberry molars; Clutton joints). The Jarisch-Herxheimer reaction complicates the first treatment dose. What I must specifically not miss: (1) neurosyphilis and ocular/otic syphilis in a patient with any neurological or visual symptom — these require CSF examination and IV penicillin, NOT a single IM dose; missing them risks permanent blindness, deafness, dementia and stroke. (2) Syphilis in pregnancy — every positive serology in pregnancy must be treated the SAME DAY with penicillin (the only reliably effective drug; desensitise if allergic), because treatment before 16 to 20 weeks prevents virtually all congenital syphilis, whereas untreated maternal syphilis carries a 70 to 100 percent risk of fetal loss or congenital infection in primary/secondary disease. (3) The prozone phenomenon — a false-negative RPR in florid secondary syphilis. (4) HIV co-infection — test every patient.
Q5 (examiner's probe): How is congenital syphilis prevented, and how do you manage a penicillin-allergic pregnant woman with syphilis?
Prevention of congenital syphilis rests on universal serological screening of every pregnant woman at the first antenatal visit (with repeat screening at 28 weeks and at delivery in high-prevalence settings), and treatment of every positive case the SAME DAY with penicillin appropriate to the stage. The risk of vertical transmission is 70 to 100 percent in untreated primary/secondary maternal syphilis and falls to under 2 percent with adequate penicillin treatment completed at least 30 days before delivery; treatment before 16 to 20 weeks virtually eliminates congenital transmission because penicillin crosses the placenta and achieves treponemicidal levels in fetal serum and CSF. A pregnant woman with a history of penicillin allergy — even anaphylaxis — cannot be given doxycycline or tetracycline (teratogenic; tooth and bone effects in the fetus), and azithromycin is ineffective (resistance). The correct action is incremental desensitisation (oral or IV, starting at about 1 unit and doubling every 15 to 30 minutes to reach the full dose over about 4 hours) in a monitored setting, followed immediately by the stage-appropriate penicillin regimen. Desensitisation is temporary (re-sensitise for each course), but the risk of untreated syphilis (congenital syphilis, neurosyphilis) far exceeds the risk of a managed desensitisation. Fetal monitoring for the Jarisch-Herxheimer reaction is essential, since it can precipitate fetal distress, preterm labour and stillbirth. Congenital syphilis is a sentinel event that triggers review of maternal screening and treatment.