primary syphilis

Primary syphilis results from direct contact with an infectious lesion during sexual activity, allowing Treponema pallidum (a spirochete) to enter through microabrasions in skin or mucosa. The organism replicates locally, producing a chancre—a painless, indurated ulcer with a clean base—usually on the genitals, anus, or oral mucosa. Histologically, the lesion shows endarteritis obliterans with plasma cell infiltration, a hallmark of treponemal infection. Regional lymphadenopathy is typically firm, nontender, and bilateral. Because the chancre is painless and may occur in areas not easily visible (e.g., cervix, rectum), it often goes unnoticed, facilitating further transmission. Diagnosis is made via darkfield microscopy of exudate showing motile spirochetes, or serologic testing using nontreponemal tests (RPR, VDRL) and treponemal-specific tests (FTA-ABS, TPPA) for confirmation. Nontreponemal tests may be falsely negative early due to the prozone phenomenon, and titers correlate with disease activity. If untreated, the lesion heals spontaneously, but the infection progresses to secondary syphilis (disseminated disease with rash, condyloma lata, systemic symptoms) weeks to months later, and can eventually latent and tertiary stages (gummas, neurosyphilis, cardiovascular syphilis) if untreated. Treatment is a single intramuscular dose of benzathine penicillin G, which is curative in primary and secondary syphilis. Key USMLE associations: chancre = painless ulcer (compare to painful chancroid caused by Haemophilus ducreyi), darkfield microscopy for diagnosis, and Jarisch-Herxheimer reaction (acute febrile reaction) after treatment initiation due to release of lipopolysaccharide-like substances from dying spirochetes.