Snapshot A 41-year-old man presents to the clinic complaining of an intensely pruritic rash over his torso, back, and arms including his palms. He also describes being concerned about patchy hair loss on his scalp as well as the presence of warty growths on his penis. His sexual history is notable for frequent sexual encounters with both male and female partners without the use of condoms. Physical exam is significant for a diffuse, erythematous maculopapular rash, patchy alopecia on his scalp, wart-like white lesions on the base of his penis, and bilateral inguinal lymphadenopathy. VDRL and FTA-ABS were positive. Introduction Classification Treponema pallidum spirochete Associated conditions cardiovascular syphilis aneurysm formation neurosyphilis Epidemiology Demographics most common during years of peak sexual activity most new cases occur in men and women aged 20-29 years recent rise in syphilis cases among men who have sex with men (MSM) community Co-infection of syphilis with HIV is high Location genitourinary tract Risk factors unprotected sex IV drug use and needle-sharing ETIOLOGY Pathogenesis mechanism T. pallidum rapidly penetrates intact mucous membranes or dermal abrasions and enters the lymphatics and blood to cause systemic infection transmission intimate contact with infectious lesions (most common) blood transfusion transplacentally from infected mother to fetus Presentation Primary syphilis painless chancre indurated edge can visualize treponemes in fluid from chancre using dark-field microscopy Secondary syphilis disseminated disease diffuse, maculopapular rash that involves the palms and soles condylomata lata smooth, painless, wart-like white lesions on genitals lymphadenopathy patchy alopecia Tertiary syphilis gummas chronic granulomas aortitis from destruction of the vasa vasorum neurosyphilis tabes dorsalis Argyll Robertson pupil pupil constricts with accommodation but is not reactive to light other symptoms broad-based ataxia positive Romberg stroke without hypertension Congenital syphilis facial abnormalities rhagades (linear scars at angle of mouth) nasal discharge saddle nose notched Hutchinson teeth mulberry molars short maxilla saber shins sensorineural deafness Studies Labs nonspecific serologic testing VDRL (venereal disease research laboratory) can test in CSF with neurologic or otologic involvement of syphilis RPR (rapid plasma reagent) specific serologic testing FTA-ABS (fluorescent treponemal antibody-absorption) use to confirm diagnosis Microscopy dark-field microscopy visualize motile spirochetes Differential Herpes simplex virus painful genital vesicles and ulcers Haemophilus ducreyi painful genital ulcer with exudate Lymphogranuloma venereum buboes Klebsiella granulomatis beefy red ulcer that bleeds on contact Treatment Medical penicillin IM penicillin for primary or secondary syphilis and early latent syphilis IV penicillin G for late latent syphilis if allergic to penicillin, patient should be desensitized if patient is pregnant and allergic to penicillin, patient should be desensitized high risk of stillbirth, neonatal death, and mental retardation doxycycline an alternative for treating syphilis in pencillin-allergic patients ceftriaxone an alternative for tertiary syphilis in penicillin-allergic patients densensitization to penicillin can be attempted for tertiary syphilis but typically done in the intensive care setting under supervision of an allergy specialist Complications Jarisch-Herxheimer reaction flu-like syndrome after starting treatment for syphilis due to toxins released by killed T. pallidum symptomatic treatment (NSAIDs and acetaminophen) Complications of tertiary syphilis aortic insufficiency tabes dorsalis general paresis Prognosis Favorable prognosis for patients diagnosed with either primary or secondary syphilis 20% of untreated patients with tertiary syphilis die of the disease prognosis for tertiary syphilis depends on the extent of scarring and tissue damage with adequate treatment, 90% of patients with neurosyphilis have a favorable clinical recovery