Syphilis & Genital Ulcerative Diseases Tom Barrett, MD Chief Medical Officer Howard Brown Health Center "The physician who knows syphilis knows medicine." Sir William Osler Syphilis • Syphilis is an infectious disease caused by the spirochete Treponema pallidum . It almost always is transmitted by sexual contact with infectious lesions, but it also can be transmitted in utero and via blood transfusion. • Syphilis has a myriad of presentations and can mimic many other infections and immune-mediated processes in it’s advanced stages. Hence, it has earned the nickname "the great imposter." WARNING • I HAVE PICTURES • Be thankful it is not 8am • You could be my mother and appear in slide decks The Facts • T pallidum is a fragile spiral bacterium 6-15 micrometers long by 0.25 micrometers in diameter. It can survive only briefly outside of the body; thus transmission almost always requires direct contact with the infectious lesion(s). • T pallidum penetrates abraded skin or intact mucous membranes easily and disseminates rapidly, although asymptomatically, via the blood vessels and lymphatics. • The prominent histologic features of the human response to the presence of T pallidum are vascular changes with associated endarteritis and periarteritis. Additionally, chronic infection can result in granulomatous lesions called gummas. • The initial lesion of primary syphilis develops at the site of transmission after an incubation period of 10-90 days, with a mean of about 21-28 days, and then heals spontaneously in 3-7 weeks after formation. Your average friendly spriochete Primary Syphilis • The chancre of primary syphilis usually begins as a single, painless papule that rapidly becomes eroded and indurated. The ulcer has a cartilaginous consistency at the edge and base. • Chancres may be found on the penis, anal canal, mouth, or external genitalia including the cervix and labia. • Atypical primary lesions are common and may manifest as a papular lesion without subsequent ulceration or induration. • The primary lesion usually is associated with regional lymphadenopathy that may be unilateral or bilateral. Inguinal adenitis is usually discrete, firm, mobile, and painless, without overlying skin changes. • Frequently solitary, may be multiple (Sometimes seen as "kissing" lesions on opposing skin surfaces, for example the labia.) • Patchy alopecia Primary symptoms disappear within a few weeks whether treated or not. If left untreated during the primary stage, about one-third will continue on to chronic stages. Differential? Secondary Syphilis • Develops about 4-10 weeks after the appearance of the primary lesion. • May include a localized or diffuse mucocutaneous rash and generalized nontender lymphadenopathy. The exanthem may be macular, papular, pustular, or mixed. • The most common systemic manifestations include malaise, fever, myalgias, and arthralgias, and rarely meningismus. • During secondary infection, the immune reaction is at its peak and antibody titers are high • Red papular lesions also may appear on the palms, soles, face, and scalp and may become necrotic. Patchy and nonpatchy alopecia may occur. In intertriginous areas, papules may coalesce to form highly infectious lesions called condylomata lata. Lesions usually progress from red, painful, and vesicular to "gun metal grey" as the rash resolves. • Mucous patches are superficial mucosal erosions, usually painless, that may develop on the tongue, oral mucosa, lips, vulva, vagina, and penis. • Other, less common, manifestations of secondary syphilis include gastrointestinal involvement, hepatitis, nephropathy, proctitis, arthritis, and optic neuritis. Symptomatic secondary syphilis usually resolves without treatment. The disease then enters a latent stage. Latent Syphilis • Latent syphilis is defined as syphilis characterized by seroreactivity without other evidence of disease. • Two types of latent syphilis: early latent and late latent. Up to 40% of untreated infections can develop into tertiary disease. Early Latent Syphilis • Early latent syphilis: Acquired syphilis within the last year and patient has: – a documented seroconversion or fourfold or greater increase in titer of a nontreponemal test or – unequivocal symptoms of secondary syphilis or – a sex partner documented to have primary, secondary, or early latent syphilis or – reactive nontreponemal and treponemal tests from a patient whose only possible exposure occurred within the previous 12 months. Late Latent Syphilis • When initial infection has occurred greater than 1 year previously, latent syphilis is classified as late latent. • The patient has no evidence of having acquired the disease within the preceding 12 months. Tertiary Syphilis • Symptomatic tertiary syphilis is the result of a chronic, progressive inflammatory process that eventually produces clinical symptoms years to decades after the initial infection. • Gummatous syphilis • Cardiovascular syphilis • Neurosyphilis. – Syphilitic meningitis – Meningovascular syphilis – Parenchymatous neurosyphilis Patients present with ataxia, incontinence, paresthesias, and loss of position, vibratory, pain, and temperature sensations. Paresis and dementia, with changes in personality and intellect, may develop. • Tertiary Syphilis • Gummatous syphilis: manifests as coalescent granulomatous lesions that usually affect skin, bone, and mucous membranes, but may involve any organ system. The lesions often cause local destruction of the affected organ system. • Cardiovascular syphilis: results from endarteritis of the aorta, subsequent medial necrosis, aortitis, and aneurysm formation. Other large arteries may be affected as well. Tertiary Syphilis • Neurosyphilis may be asymptomatic or symptomatic. In asymptomatic neurosyphilis, no signs or symptoms are present, but cerebral spinal fluid (CSF) abnormalities are demonstrable, including possible pleocytosis, elevated protein, decreased glucose, or a reactive CSF Venereal Disease Research Laboratory (VDRL) test. • Symptomatic neurosyphilis may manifest as syphilitic meningitis, meningovascular syphilis, or parenchymatous neurosyphilis. – Syphilitic meningitis usually develops within several years of initial infection, and patients present with typical symptoms of meningitis, including headache, nausea and vomiting, and photophobia, but are typically afebrile. Patients may exhibit cranial nerve abnormalities. – Meningovascular syphilis manifests 5-10 years after infection and is the result of endarteritis, which affects small blood vessels of the meninges, brain, and spinal cord. Patients may present with CNS vascular insufficiency or outright stroke. – Parenchymatous neurosyphilis results from direct parenchymal CNS invasion by T pallidum and is usually a late development (15-20 years after primary infection). Diagnosis • T pallidum cannot be cultivated in vitro and is too small to be seen under the light microscope. Therefore, direct visualization of the organism by darkfield microscopy, immunofluorescent staining, or serologic testing is necessary for diagnosis of syphilis. – Darkfield microscopic diagnosis of oral lesions should be avoided because of the difficulty in distinguishing T pallidum morphologically from Treponema macrodentium and Treponema microdentium, 2 nonpathologic treponemes found in the mouths of healthy individuals. – A positive darkfield examination is the only means of making an absolute diagnosis of syphilis. • A negative darkfield examination does not rule out the diagnosis, and the lesion should be reexamined the following day. • Question: Who here has done a darkfield exam or could perform one today in their office? Diagnosis • The nontreponemal tests, VDRL and rapid plasma reagent (RPR), are antilipoidal antibodies seen in other disease states, pregnancy, and occasionally after vaccination. They are nonspecific and cannot rule in disease. These tests have sensitivities approaching 80% in patients with symptomatic primary syphilis and virtually 100% in patients with secondary syphilis. – A positive VDRL/RPR should be quantified and titers followed at regular intervals after treatment. As such, its value is in response to treatment. However, it does not correlate with symptom resolution. – Most patients have nonreactive nontreponemal tests within several years after successful treatment for syphilis, but a significant number have persistently positive tests, the so-called serofast reaction. – Patients with a reactive VDRL or RPR should have the result confirmed by specific treponemal testing. FTA-ABS and or EIA. • Tertiary syphilis – Serology is used in the diagnosis. – Evaluation of neurosyphilis requires a lumbar puncture (LP) and evaluation of the CSF. – The CDC currently recommends LP only if the patient is seroreactive and HIV positive, has symptoms of neurosyphilis, or is receiving treatment for neurosyphilis. Neuro-Syphilis Diagnosis • Positive LP: – Elevated CSF WBC >5WBC/mm3 or >10-20 WBC/mm3 in HIV positive patient – CSF protein > 40mg/dl – Reactive CSF VDRL (50% may be false negative) • If VDRL is false negative, other labs may help determine likelihood of Neuro-syphilis • Use clinical judgment Conundrums Diagnosis RPR Automated enzyme FTA-ABS immunoassay (EIA) EIA + + + - + + + - - - - + Conundrums Diagnosis RPR Automated enzyme FTA-ABS immunoassay (EIA ) Syphilis + + + Syphilis - + + (early primary) False positive + - - ??????????? - - + Treatment of Syphilis Primary and Secondary Syphilis: Benzathine penicillin G 2.4 million units IM in a single dose Early Latent Syphilis: