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Stem
A 26-year-old man presents to the sexual-health clinic with a 2-week history of a painless ulcer on the glans penis and, over the last 5 days, a diffuse, non-itchy coppery-red rash that has appeared on his trunk, palms and soles, with grey-white moist papules in the perianal region and painless grey patches on the tongue and buccal mucosa. He also reports low-grade fever, malaise and patchy hair loss from the scalp. He is sexually active with multiple male partners and does not consistently use condoms. He has not been tested for HIV.
On examination: temperature 37.9 degrees C, pulse 88/min, BP 118/72 mmHg. There is a single, clean-based, indurated (firm), painless ulcer (1.5 cm) on the glans with a raised border and clear serum exudate. There is bilateral, non-tender, rubbery inguinal lymphadenopathy. The rash is maculopapular, symmetric, and clearly involves the palms and soles; the perianal papules are broad, flat, moist and grey-white. The oral mucosa shows painless grey-white patches. There is patchy 'moth-eaten' alopecia of the scalp. There are no focal neurological signs, the pupils are equal and reactive, and there is no meningism.
Questions
a) What is the clinical diagnosis and the stage? Name the causative organism and one structural feature that explains its immune evasion. (2 marks)
This is secondary syphilis (with an overlapping healing primary chancre) caused by the spirochete Treponema pallidum subsp. pallidum. The constellation of a painless indurated chancre, a diffuse non-itchy maculopapular rash on the palms and soles, condylomata lata (the broad, flat, moist, grey-white perianal papules), mucous patches, generalised non-tender lymphadenopathy and moth-eaten alopecia is classic. A key structural feature that explains the organism's immune evasion and persistence is its outer membrane, which is hyposialylated and poor in transmembrane (surface-exposed) proteins — providing very few targets for antibody and complement, so it eludes humoral clearance. A second relevant feature is its periplasmic endoflagella, which drive the corkscrew (rotational) motility that allows it to penetrate mucosa and abraded skin and to disseminate systemically within hours of inoculation.
b) Outline the diagnostic strategy, including the two-tier serology, the role of dark-field microscopy, and the interpretation of a paradoxically NEGATIVE RPR in this patient. (3 marks)
Diagnostic strategy:
- Dark-field microscopy of the chancre exudate or a condyloma lata / mucous patch shows motile spirochaetes — the definitive test for early infectious lesions (limitation: not useful for oral/rectal lesions because of commensal spirochaetes). PCR of a lesion swab is an alternative where available.
- Two-tier serology is the cornerstone:
- Non-treponemal test (RPR or VDRL) — detects non-specific reagin antibodies; used for screening and to monitor disease activity and treatment response via the titre. A fourfold (two-dilution) change (e.g. 1:16 to 1:4) is clinically significant.
- Treponemal test (TPPA, FTA-ABS, or treponemal EIA) — detects specific anti-T. pallidum antibodies; used to confirm a reactive non-treponemal test; generally positive for life even after adequate treatment.
- If the RPR is paradoxically NEGATIVE in this patient, the explanation is the prozone phenomenon: very HIGH antibody titres (in high-spirochete-load secondary syphilis, and more often in HIV co-infection and pregnancy) interfere with the flocculation reaction, giving a false-negative screen. The action is to request dilution of the serum (e.g. 1:8, 1:16), which unmasks the true high titre; the treponemal test will usually be strongly positive.
Additional essential test: HIV serology (mandatory in every syphilis case because of the bidirectional synergy), hepatitis B and C serology.
c) State the definitive treatment for this patient, the dose, route and rationale, and the public-health action required. (3 marks)
Definitive treatment:
- Benzathine penicillin G 2.4 million units IM as a SINGLE dose (1.2 MU into each buttock). Rationale: penicillin is first-line for every stage of syphilis and has remained universally effective for over 70 years (no resistance documented); a single IM depot maintains treponemicidal levels for 2 to 3 weeks, sufficient for early disease. Primary, secondary and early latent syphilis all receive this single dose.
- Penicillin allergy (non-pregnant): doxycycline 100 mg PO twice daily for 14 days, or tetracycline 500 mg PO four times daily for 14 days, or ceftriaxone 1 to 2 g daily for 8 to 10 days (less evidence). Azithromycin is NOT recommended because of resistance.
Public-health action:
- Warn the patient about the Jarisch-Herxheimer reaction (fever, myalgia, rash exacerbation, hypotension within 2 to 24 hours of the first dose; self-limiting; NOT allergy; continue penicillin; paracetamol and fluids; especially important in pregnancy).
- Trace, test and treat sexual partners epidemiologically (those exposed within the previous 90 days receive benzathine penicillin G 2.4 MU IM single dose regardless of serology).
- Test for HIV (and re-test at 3 months to cover the seroconversion window); treat co-infections; vaccinate against hepatitis A and B.
- Advise sexual abstinence until lesions heal and treatment is complete.
- Notify public health (syphilis is a notifiable disease).
d) The patient returns 8 hours after treatment with fever (39 degrees C), rigors, myalgia and worsening of the rash, but NO urticaria, wheeze, lip swelling or stridor. What is the reaction, its mechanism, and your management? (1 mark)
This is the Jarisch-Herxheimer reaction. The mechanism is massive lipoprotein release from dying spirochaetes triggering a cytokine storm (TNF-alpha, IL-6, IL-8). It is self-limiting (resolves in 12 to 24 hours), is NOT a drug allergy (no urticaria/bronchospasm/angioedema), and penicillin must be continued. Management: reassure, give paracetamol 1 g and fluids, and observe for 24 hours — especially in pregnancy (fetal distress, preterm labour) and in cardiovascular/neurosyphilis (transient worsening of an aneurysm or neurology).
e) Name four late (tertiary or neurologic) complications of untreated syphilis, and state which single investigation is mandatory at the time of diagnosis in addition to syphilis serology. (1 mark)
Late complications:
- Gummas (granulomatous skin, bone and visceral lesions).
- Cardiovascular syphilis (ascending aortic aneurysm, aortic regurgitation, coronary ostial stenosis).
- Neurosyphilis — general paresis (dementia, grandiosity), tabes dorsalis (lancinating pains, sensory ataxia, positive Romberg, areflexia, Charcot joints), meningovascular stroke, Argyll Robertson pupil (accommodates but does not react to light).
- Ocular syphilis (uveitis, optic neuritis, visual loss) and otic syphilis (sensorineural deafness, vertigo).
- Also accept: congenital syphilis in a future pregnancy (stillbirth, hydrops, Hutchinson triad, saddle nose, saber shin).
The single mandatory investigation at diagnosis (in addition to syphilis serology) is an HIV test — because syphilis and HIV potentiate one another (the syphilitic chancre increases HIV acquisition and transmission several-fold), and HIV co-infection changes follow-up intensity and the threshold for CSF examination.