A 45-year-old man presents with a long history of ulcers on the bottom of his feet. He recalls having a similar looking ulcer on the side of his penis when he was 19 years old for which he never sought treatment. The patient denies any fever, chills, or constitutional symptoms. He reports multiple sexual partners and a very promiscuous sexual history. He has also traveled extensively as a writer since he was 19. The patient is afebrile, and his vital signs are within normal limits. A rapid plasma reagin (RPR) test is positive, and the result of a Treponema pallidum particle agglutination (TP-PA) is pending. Which of the following findings would most likely be present in this patient?

Wide-based gait with a low step

A 24-year-old man presents with a painless genital ulcer for the past 2 weeks. He reports that he recently has been having unprotected sex with multiple partners. Past medical history is unremarkable. On physical examination, a single ulcer is present on the dorsal shaft of the penis which is circumscribed, indurated, and partially healed. There is moderate inguinal lymphadenopathy but no buboes. Which of the following tests would confirm the most likely diagnosis in this patient?

Perform a darkfield microscopic examination of a swab from the chancre

Swab the chancre and perform a saline wet mount

Fluorescent treponemal antibody absorption (FTA-ABS) test

Venereal Disease Research Laboratory (VDRL) test

A 25-year-old man presents with painless penile ulcer for 2 weeks. Physical examination reveals a firm, non-tender, clean-based ulcer with rolled edges. Dark-field microscopy of the lesion shows spirochetes. VDRL test is positive at 1:32 dilution. Which of the following is the most appropriate treatment?

Single dose of benzathine penicillin G 2.4 million units IM

Azithromycin 1g orally single dose

Three weekly doses of benzathine penicillin G 2.4 million units IM

Doxycycline 100 mg orally twice daily for 14 days

Ceftriaxone 250 mg IM single dose

A 28-year-old woman comes to the emergency department for a rash that began 3 days ago. She has low-grade fever and muscle aches. She has no history of serious illness and takes no medications. She has had 5 male sexual partners over the past year and uses condoms inconsistently. Her temperature is 38.1°C (100.6° F), pulse is 85/min, and blood pressure is 126/89 mm Hg. Examination shows a diffuse maculopapular rash that includes the palms and soles. The remainder of the examination shows no abnormalities. A venereal disease research laboratory (VDRL) test is positive. Which of the following is the next appropriate step in management?

Fluorescent treponemal antibody absorption test

A 3000-g (6.6-lb) female newborn is delivered at term to a 23-year-old primigravid woman. The mother has had no prenatal care. Immunization records are not available. Cardiac examination shows a continuous heart murmur. There are several bluish macules on the skin that do not blanch with pressure. Slit lamp examination shows cloudy lenses in both eyes. The newborn does not pass his auditory screening tests. Which of the following is the most likely diagnosis?

Congenital parvovirus infection

Congenital cytomegalovirus infection

A 28-year-old man presents with painless anal ulcer. Dark-field microscopy shows spirochetes. He is allergic to penicillin with history of anaphylaxis. Which of the following is the most appropriate treatment?

Doxycycline 100 mg orally twice daily for 14 days

Erythromycin 500 mg four times daily for 14 days

Penicillin desensitization followed by benzathine penicillin

Treponema pallidum for USMLE Step 2 CK: High-Yield Microbiology Lessons

Treponema pallidum - The Great Pretender

Spirochete causing syphilis; visualized by darkfield microscopy.
Primary: Painless chancre.
Secondary: Maculopapular rash (palms & soles), condylomata lata.
Tertiary: Gummas, aortitis, neurosyphilis (tabes dorsalis).
Congenital: Saber shins, Hutchinson teeth, saddle nose.
Treatment: Penicillin G.

⭐ Jarisch-Herxheimer reaction: flu-like syndrome (fever, chills, headache) after antibiotics are started for syphilis.

Darkfield microscopy of Treponema pallidum spirochetes

Pathogenesis & Transmission - Stealth & Invasion

Transmission: Primarily sexual contact; enters via microscopic abrasions on skin or mucous membranes. Vertical (transplacental) transmission is also significant.
Invasion & Spread:
- Uses corkscrew motility (periplasmic endoflagella) to penetrate tissues.
- Spreads rapidly from the entry site via lymphatics and blood.

Treponema pallidum structure and flagellar motor

⭐ The bacterium is a "stealth pathogen"; its outer membrane has very few surface-exposed proteins (antigens), allowing it to evade the host immune response effectively.

Clinical Stages - A Multi-Act Drama

Primary (3-90 days post-exposure)
- Presents with a painless chancre (ulcer) at the inoculation site.
- Highly infectious; resolves in 3-6 weeks regardless of treatment.
Secondary (Weeks to 6 months post-chancre)
- Systemic symptoms: fever, lymphadenopathy, headache.
- Features diffuse maculopapular rash, condylomata lata (wart-like lesions).
⭐ The rash classically involves the palms and soles, a key diagnostic clue.
Latent (Asymptomatic)
- Serologically positive but no clinical signs.
- Early latent: < 1 year duration.
- Late latent: ≥ 1 year duration.
Tertiary (3-30 years post-infection)
- Gummas (granulomatous lesions) in skin, bone, liver.
- Cardiovascular syphilis (e.g., thoracic aortic aneurysm).
- Neurosyphilis (tabes dorsalis, Argyll Robertson pupils).

Congenital Syphilis - A Tragic Inheritance

Transmission: Primarily transplacental, especially from mothers with early-stage syphilis.
Clinical Manifestations:
- Early (<2 years): Profuse nasal discharge ("snuffles"), desquamating maculopapular rash on palms/soles, hepatosplenomegaly.
- Late (>2 years): Saber shins, saddle nose deformity.

⭐ Hutchinson's Triad: A classic late finding consisting of notched incisors, interstitial keratitis, and eighth nerve deafness.

Hutchinson's Triad in Congenital Syphilis

Diagnosis & Treatment - Unmasking & Eradicating

Direct Visualization
- Darkfield Microscopy: Gold standard for primary syphilis; visualizes live, motile spirochetes from chancre exudate.
- Not useful for oral/rectal lesions (commensal spirochetes).

Darkfield microscopy of Treponema pallidum spirochetes

Serology (Two-Step)
- Screening (Non-treponemal): RPR, VDRL. Detects antibodies to cardiolipin. Titers correlate with disease activity.
- Confirmatory (Treponemal): FTA-ABS, TP-PA. Detects antibodies specific to T. pallidum. Usually remain positive for life.

Treatment of Choice
- Penicillin G: Effective for all stages. Dosage and duration vary by stage.
- Primary/Secondary: Benzathine Penicillin G 2.4 million units IM x 1 dose.
- Tertiary/Latent: 2.4 million units IM weekly x 3 weeks.
- Neurosyphilis: Aqueous crystalline penicillin G IV.
- Allergies: Doxycycline or ceftriaxone (use with caution).

⭐ Jarisch-Herxheimer Reaction: An acute, self-limiting febrile reaction within 24 hours of treatment, caused by massive cytokine release from dying spirochetes. Presents with fever, chills, myalgias. Manage with NSAIDs.

High‑Yield Points - ⚡ Biggest Takeaways

Treponema pallidum is a spirochete, visualized by darkfield microscopy, not on Gram stain.

Primary syphilis presents with a painless chancre; Secondary with a rash on palms and soles and condylomata lata.

Tertiary syphilis involves gummas, aortitis, and neurosyphilis (tabes dorsalis).

Screen with nonspecific tests (VDRL/RPR); confirm with specific treponemal tests (FTA-ABS).

Penicillin G is the treatment for all stages; watch for the Jarisch-Herxheimer reaction.

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