Infectious Disease · Sexually Transmitted Infections
The facts most likely to be tested
Primary syphilis presents classically as a painless chancre with indurated borders and a clean base at the site of inoculation.
The causative organism is the spirochete *Treponema pallidum*, which is visualized via dark-field microscopy but cannot be cultured on standard media.
Regional nontender lymphadenopathy typically accompanies the primary lesion within one to two weeks of appearance.
Nontreponemal tests like RPR or VDRL are used for screening but may yield false-negative results in early primary syphilis due to a lack of antibody titer.
Confirmatory testing requires treponemal-specific assays such as FTA-ABS or TP-PA, which remain positive for life even after successful treatment.
The first-line treatment for primary syphilis is a single dose of intramuscular benzathine penicillin G.
Patients with a severe penicillin allergy should be treated with doxycycline for 14 days, provided they are not pregnant.
Vignette unlocked
A 24-year-old male presents to the clinic complaining of a sore on his penis that he noticed 10 days ago. He reports no pain, fever, or dysuria. Physical examination reveals a single, 1-cm painless ulcer with indurated, raised borders and a clean, non-purulent base on the coronal sulcus. Bilateral nontender inguinal lymphadenopathy is noted. He reports having unprotected sexual intercourse with a new partner three weeks ago.
What is the most appropriate next step in management?
Intramuscular benzathine penicillin G
The patient presents with the classic features of a primary syphilitic chancre; because the clinical presentation is highly suggestive, treatment should be initiated immediately with penicillin G, even if initial nontreponemal screening tests are negative.
Full handout
High yield triage
Etiology / Epidemiology
Caused by Treponema pallidum; transmitted via direct contact with infectious lesions. High-risk groups include MSM and those with unprotected sexual contact.
Clinical Manifestations
Presents as a painless chancre at the site of inoculation. Associated with painless regional lymphadenopathy.
Diagnosis
Darkfield microscopy is the gold standard. RPR/VDRL are screening tests; FTA-ABS is the confirmatory test.
Treatment
Benzathine penicillin G is the first-line treatment. Penicillin allergy requires desensitization.
Prognosis
High cure rate if treated early. 100% progression to secondary syphilis if left untreated.
Full handout
Epidemiology & Etiology
Caused by the spirochete Treponema pallidum. Transmission occurs through direct contact with an infectious lesion during sexual activity. Incidence is rising, particularly among MSM and patients with HIV coinfection.
Pertinent Anatomy
The primary lesion occurs at the site of inoculation, typically the genitalia, anus, or oropharynx. The organism rapidly disseminates via the lymphatic system and bloodstream shortly after initial infection.
Pathophysiology
The spirochete penetrates intact mucous membranes or microscopic skin abrasions. It induces a localized inflammatory response resulting in an indurated, ulcerated lesion known as a chancre. The host immune response eventually clears the primary lesion, but the organism persists and disseminates.
Clinical Manifestations
The hallmark is a painless chancre with indurated, raised borders and a clean base. Patients often present with painless, rubbery regional lymphadenopathy. Systemic symptoms like fever or malaise are rare in the primary stage but suggest progression to secondary syphilis.
Diagnosis
Darkfield microscopy of lesion exudate is the definitive diagnostic test. Serologic screening uses non-treponemal tests like RPR or VDRL, which must be confirmed with treponemal-specific tests like FTA-ABS or TP-PA.
Treatment
The treatment of choice is a single dose of Benzathine penicillin G 2.4 million units IM. Penicillin allergy mandates desensitization, as no other agent is considered curative for primary syphilis. Patients must be monitored with serial RPR titers to ensure a four-fold decline.
Prognosis
Primary syphilis is highly curable with appropriate antibiotic therapy. Failure to treat leads to secondary syphilis within weeks to months. Patients should be screened for other STIs, including HIV.
Differential Diagnosis
Chancroid: painful ulcer with purulent base
Herpes Simplex: painful grouped vesicles on erythematous base
Lymphogranuloma venereum: small, transient ulcer followed by painful inguinal buboes
Granuloma inguinale: beefy red, friable, painless ulcer
Behcet syndrome: recurrent oral/genital ulcers with uveitis