Syphilis

❓What❓

• STI caused by Treponema pallidum, a non-culturable spirochete visualizable by darkfield microscopy or Warthin-Starry silver staining

• Disease is staged (”early” “late”) due to unique immunologic response (i.e. despite apparent immune control of site of inoculation with resolution of primary chancre lesions, spirochetes then disseminate & lead to widespread clinical consequences)

❓Epidemiology❓

• Transmission: direct contact with infectious lesion — notably, with ↑ rates of transmission from “primary” lesions (i.e. chancre) than “secondary” lesions (e.g. mucous patches, condyloma lata) owing to lower spirochete burden in secondary stage lesions — or with recently active lesion (”early latent”)

• Risk Factors: due to stigma, older or married persons may not report new sexual encounters. Classic strong risk factors include IVDU & MSM

❓Presentation❓

• Primary = “Chancre”: papule develops at site of inoculation (painless > painful), which subsequently ulcerates with a raised margin & nonexudative base, & may be accompanied by regional lymphadenopathy. Chancres spontaneously heal within 3-6 weeks, even without treatment

• Secondary = Dissemination (~25%): patient may not have a history of chancre if primary lesion was asymptomatic & unnoticed. Secondary symptoms occur within weeks-months after date of inoculation

Reticuloendothelial 🔥 : fever, malaise, myalgias, weight loss, tender lymphadenopathy, splenomegaly

Dermatologic ✋ :

Diffuse lesions (symmetric maculopapular rash of palms/soles > pustular syphilis, pemphigus-like > lues maligna)

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Local lesions (discrete copper, red, or reddish-brown macules; condyloma lata representing local spread from chancre; “moth-eaten” alopecia)

Gastrointestinal 💩 : ulcerative proctocolitis (IBD mimicker), hepatitis (cholestatic > hepatocellular)

Renal 🧶 : secondary nephrotic syndrome due to membranous GN

Neurologic 🧠 : meningitis → stroke & cranial neuropathies; panuveitis; sensorineural hearing loss

• “Latent” = Asymptomatic: due to post-dissemination asymptomatic period, patients with late disease can present at any time, from 1 to 30 years after primary infection

• Tertiary = Mimicker (~25-40%):

❓Diagnosis❓

1. Both treponemal & nontreponemal serologies may be nonreactive in early primary
2. Both treponemal & nontreponemal serologies may be reactive to non-syphilis reasons
3. Treponemal antibodies: “once ⊕, always ⊕” (irrespective of treatment)
4. Nontreponemal antibodies may become nonreactive in treated patients, but also decline over time in absence of treatment

• Treponemal tests: TPPA, FTA-ABS, TP-EIA, CIA, MHA-TP. False ⊕ antibodies can be seen if exposure to other treponemes (yaws, pinta, bejel), other spirochetes (Lyme disease), severe gingivitis, or rarely autoimmune diseases

• Nontreponemal tests: RPR, VDRL. (Both detect reactivity to antigens synthesized from lecithin, cardiolipin, & cholesterol.) False ⊕ antibodies can be seen if exposure to other treponemes (yaws, pinta, bejel), viral infections (HIV), or rarely autoimmune diseases. False ⊖ possible if prozone effect

• Traditional = Silver staining: Warthin-Starry vs. Steiner staining only ~40% sensitive

• Modern = Immunostaining: anti-T. pallidum immunostain is ~70% sensitive

❓Treatment❓

• Penicillin!

📚 References 📚

• Syphilis: Epi, Pathophys (UpToDate)

• Stains & CD markers of Treponema pallidum

• Syphilitic Hepatitis: An Atypical Presentation of an Uncommon Disease

• Spiraling into a Distant Past

• Febrile Podcast “Sailor’s Salutation”

• Clinical, radiological, pathological and prognostic features of general paresis: a cohort study

• Tertiary syphilis and cardiovascular disease: the united triad: case report

• Treponema Pallidum: A Forgotten Pathogen With Major Cardiovascular Consequence

• Syphilitic bi-valvular endocarditis and myocarditis: modern tools applied to long-forgotten complications of a re-emerging disease

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Contact

Dx.atypia@gmail.com