Infectious Disease · Sexually Transmitted Infections

Syphilis (Secondary)

USMLE2PANCE
7

Bets

The facts most likely to be tested

1

Secondary syphilis presents with a diffuse maculopapular rash that characteristically involves the palms and soles.

Confidence:
2

Patients frequently exhibit generalized lymphadenopathy and systemic symptoms including fever, malaise, and sore throat.

Confidence:
3

Condylomata lata are highly infectious, flat-topped, wart-like, moist lesions found in intertriginous areas.

Confidence:
4

The diagnosis is confirmed via nontreponemal screening tests (RPR or VDRL) followed by treponemal-specific confirmatory testing (FTA-ABS or TP-PA).

Confidence:
5

Jarisch-Herxheimer reaction is an acute febrile response occurring within 24 hours of initiating antibiotic therapy due to the rapid lysis of spirochetes.

Confidence:
6

The first-line treatment for secondary syphilis is a single dose of intramuscular benzathine penicillin G.

Confidence:
7

Patchy alopecia (moth-eaten appearance) and mucous patches in the oral cavity are classic, high-yield physical exam findings.

Confidence:

Vignette unlocked

A 26-year-old male presents to the clinic complaining of a non-pruritic rash that started on his trunk and spread to his extremities over the last two weeks. Physical examination reveals a diffuse, copper-colored maculopapular rash involving the palms and soles. He also has generalized lymphadenopathy and several flat, moist, gray-white plaques in the perianal region. He reports a painless genital ulcer that resolved spontaneously six weeks ago.

What is the most appropriate treatment for this patient?

+Reveal answer

Intramuscular benzathine penicillin G

The patient's presentation of a palmoplantar rash and condylomata lata is diagnostic of secondary syphilis, which is treated with a single dose of intramuscular benzathine penicillin G.

Mo

Depth

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High yield triage

Etiology / Epidemiology

Caused by Treponema pallidum; transmitted via direct contact with infectious lesions in unprotected sexual activity.

Clinical Manifestations

Diffuse maculopapular rash involving palms and soles; condyloma lata.

Diagnosis

RPR or VDRL screening followed by FTA-ABS or TP-PA confirmatory testing.

Treatment

Benzathine penicillin G 2.4 million units IM once; penicillin allergy requires desensitization.

Prognosis

High cure rate; monitor for Jarisch-Herxheimer reaction within 24 hours of treatment.

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Epidemiology & Etiology

Caused by the spirochete Treponema pallidum. Primarily affects sexually active adults with multiple partners or history of STIs. Incidence is rising globally, particularly among MSM populations.

Pertinent Anatomy

Systemic hematogenous dissemination allows the spirochete to colonize the skin, mucous membranes, and lymph nodes. Involvement of the palms and soles is a hallmark of systemic spread.

Pathophysiology

Occurs 4–10 weeks after primary chancre. The spirochete undergoes hematogenous dissemination throughout the body. Immune complex deposition leads to the characteristic mucocutaneous lesions and systemic symptoms.

Clinical Manifestations

Presents with a diffuse, symmetric maculopapular rash that classically involves the palms and soles. Patients exhibit condyloma lata (flat, wart-like, highly infectious lesions) and generalized lymphadenopathy. Systemic symptoms include fever, malaise, and alopecia (moth-eaten alopecia). Red flags include signs of neurosyphilis like cranial nerve palsies or meningitis.

Diagnosis

Screening requires non-treponemal tests (RPR or VDRL), which may be falsely negative in the prozone phenomenon. Confirmatory testing is mandatory using treponemal-specific assays like FTA-ABS or TP-PA. A four-fold rise in non-treponemal titers indicates active infection or reinfection.

Treatment

The first-line treatment is Benzathine penicillin G 2.4 million units IM in a single dose. Penicillin allergy is a major barrier; in non-pregnant patients, doxycycline is an alternative, but desensitization is preferred. Patients must be monitored for the Jarisch-Herxheimer reaction, an acute febrile response to spirochete lysis.

Prognosis

Prognosis is excellent with appropriate antibiotic therapy. Patients must be followed with serial RPR titers at 6 and 12 months to ensure a four-fold decline. Failure to decline suggests treatment failure or reinfection.

Differential Diagnosis

Pityriasis rosea: spares palms and soles

Rocky Mountain Spotted Fever: rash starts on wrists/ankles and moves centrally

Condyloma acuminata: caused by HPV, typically cauliflower-like rather than flat

Drug eruption: lacks systemic lymphadenopathy and classic distribution

Hand-foot-and-mouth disease: associated with oral vesicles and fever