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Syphilis (mechanism of disease)

This is a flowchart on syphilis, covering the etiology, pathophysiology, and manifestations, including that for the Jarisch-Herxheimer reaction. ADDITIONAL TAGS: Risk factors / SDOH Cell / tissue damage Structural factors Syphilis Medicine / iatrogenic Infectious / microbial Biochem / metabolic Immunology / inflammation Signs / symptoms Tests / imaging / labs Environmental, toxin Neurology pathology Flow physiology Pathophysiology Etiology Manifestations Treponema pallidum: gram-neg; spiral-shaped bacteria; spirochete family Sexual contact (via small mucocutaneous lesions) during direct vaginal, anal, oral contact Transmission via … Vertical (from mother to child) during pregnancy or birth Blood transfusion or organ donations (rare) Spirochetes disseminate systematically via the lymphatic system and the bloodstream within hours Treponema bacteria is highly contagious during stages I and II Treponemes cause obliterating endarteritis at entry site Primary syphilis: Primary lesion (chancre): Typically starts out as a solitary, raised papule,usually on the genitals (90-95%) → painless, firm ulcer with indurated borders and smooth base → resolves spontaneously within 3-6 weeks without scarring Ischemic death of sensory vasa nervorum Nontender regional lymphadenopathy Painless Inflammatory reaction: endarteritis (+/- obliterating → ischemia, necrosis) and perivascular inflammatory infiltrates (type IV hypersen.) Nontender regional lymphadenopathy Fever, fatigue, myalgia, headache Polymorphic rash: typically disseminated, nonpruritic macular or papular rash; involves trunk, extremities, palms, soles; reddish-brown or copper-colored; heals within 6 months; +/- recurrence Condylomata lata: broad-based, wart-like, smooth, white papular erosions; painless; located in anogenital regions, intertriginous folds, on oral mucosa Secondary syphilis: Latent syphilis: seropositive but no clinical symptoms; can last months, years, or for life Aortitis, syphilitic mesaortitis Gumma: destructive lesions with necrotic center; tends to ulcerate; affects any organ Tertiary syphilis: Gumma in CNS is neurosyphilis: Treponema-induced vasculitis of vasa vasorum of large vessels Vessel wall atrophy Ascending aortic aneurysm (thoracic aortic aneurysm); aortic root dilation and insufficiency Perivascular inflammatory infiltrate that consists mainly of monocytes → destructive granulomas Immunosuppression Coinfection with HIV Acute meningeal syphilis: symptoms of acute meningitis (but aseptic) → neck stiffness, nausea Meningovascular syphilis: subacute stroke, cranial neuropathies Argyll Robertson pupil: bilateral miosis; pupils accommodate but do not react to direct or indirect light Tabes dorsalis: demyelination of dorsal columns and DRG: impaired proprioception → progressive sensory broad-based ataxia (+ Romberg); absent deep tendon reflexes; loss of sensation in the lower extremities; sharp, shooting pain in the legs and the abdomen; Charcot joint Most often seen if treatment begins in the early phases of the secondary stage Acute, transient, systemic reaction to bacterial endotoxin-like substances and pyrogens that are released after initiation of antibiotic therapy Jarisch-Herxheimer reaction: Antibiotics Flu-like: fever, chills, headache, myalgia Tachypnea, hypotension, tachycardia Self-limiting within 12–24 hours