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: Benzathine penicillin G 2.4 million units IM in a single dose

www.cdc.gov/std/treatment/2006 Treatment of Syphilis

• Late Latent Syphilis or Latent Syphilis of Unknown Duration:

Benzathine penicillin G 7.2 million units total, administered as 3 doses of 2.4 million units IM each at 1-week intervals

www.cdc.gov/std/treatment/2006 Treatment of Syphilis

• Neurosyphilis:

Aqueous crystalline penicillin G 18–24 million units per day, administered as 3–4 million units IV every 4 hours or continuous infusion, for 10–14 days – Followed by Benzathine penicillin 2.4 million units IM every week for three weeks

www.cdc.gov/std/treatment/2006 Syphilis Treatment in Pregnancy • Regimen in Pregnancy: Treatment during pregnancy should be the penicillin regimen appropriate for the stage of syphilis

www.cdc.gov/std/treatment/2006 Syphilis Treatment in Pregnancy • During the second half of pregnancy, syphilis management may be facilitated by a sonographic fetal evaluation for congenital syphilis, but this evaluation should not delay therapy. Sonographic signs of fetal or placental syphilis (i.e., hepatomegaly, ascites, hydrops, or a thickened placenta) indicate a greater risk for fetal treatment failure. Evidence is insufficient to recommend specific regimens for these situations. • Women treated for syphilis during the second half of pregnancy are at risk for premature labor and/or fetal distress, if the treatment precipitates the Jarisch- Herxheimer reaction. www.cdc.gov/std/treatment/2006 PCN Allergic Patients

• No proven alternatives to penicillin are available for treating neurosyphilis, congenital syphilis, or syphilis in pregnant women. Penicillin also is recommended for use, whenever possible, in HIV-infected patients • Doxycycline can be used as alternative in primary and secondary syphilis treatment. Syphilis and HIV

• All patients who have syphilis should be offered testing for HIV infection. • All patients who have syphilis should be offered testing for HIV infection. •• AllAll patientspatients whowho havehave syphilissyphilis shouldshould bebe offeredoffered testingtesting forfor HIVHIV infection.infection. Syphilis and HIV Truth or Dare:

Do all HIV+ patients with syphilis require:

Benzathine penicillin G 7.2 million units total, administered as 3 doses of 2.4 million units IM at 1-week intervals Syphilis and HIV • Compared with HIV-negative patients, HIV- positive patients who have early syphilis might be at increased risk for neurologic complications and might have higher rates of treatment failure with currently recommended regimens. The magnitude of these risks is not defined precisely but is likely minimal. No treatment regimens for syphilis have been demonstrated to be more effective in preventing neurosyphilis in HIV- infected patients than the syphilis regimens recommended for HIV-negative patients.

www.cdc.gov/std/treatment/2006 Syphilis and HIV • HIV-infected persons should be evaluated clinically and serologically for treatment failure at 3, 6, 9, 12, and 24 months after therapy. • Although of unproven benefit, some specialists recommend a CSF examination 6 months after therapy. • HIV-infected persons who meet the criteria for treatment failure (i.e., signs or symptoms that persist or recur or persons who have fourfold increase in nontreponemal test titer) should be managed in the same manner as HIV-negative patients (i.e., a CSF examination and re-treatment). • CSF examination and re-treatment also should be strongly considered for persons whose nontreponemal test titers do not decrease fourfold within 6–12 months of therapy. • The majority of specialists would re-treat patients with benzathine penicillin G administered as 3 doses of 2.4 million units IM each at weekly intervals, if CSF examinations are normal. www.cdc.gov/std/treatment/2006 The Clinical Presentation of Syphilis in HIV-Infected Men who have Sex with Men (MSM) in an Urban Clinic

Clinical Presentations and Diagnosis Delays N = 118

Symptoms N (%) N (%) delay in Median delay in days diagnosis Generalized rash 70 (59) 16 (23) 25 Rash – palms and 44 (37) 4 (9) 7 soles Sore throat 25 (21) 14 (56) 44 Cervical LAD 23 (19) 12 (52) 56 Subjective fever 18 (15) 7 (39) 42 Inguinal LAD 13 (11) 6 (46) 36 Chancre 13 (11) 6 (46) 73 Mouth ulcers 13 (11) 9 (69) 78 Asymptomatic + RPR 9 (8) - -

The presentation of syphilis in this NYC population was characterized by a wide range of symptoms that were not always recognized as syphilis. What Is It? Syphilis Mimics

Herpes

• Nationwide 45 million people aged 12 and older (1 out of 5 of the total adolescent and adult population) are infected with HSV-2. • It is more common in women (1 out of 4) than in men (1 out of 5). • HSV-2 infection is also more common in areas of high socio-economic disadvantage. • HSV-type 1 • HSV-type 2

Chancroid

• Haemophilus ducreyi (a small gram-negative rod organism) which occurs mainly in developing countries, especially the African, Asian and Latin American nations. • Chancroid is a bacterial disease causing painful, irregularly shaped sores, but is a localized infection which can be treated and cured and has no long- term effects.

• The size can vary from 1-2 millimeters to several centimeters but is usually 1-2 centimeters in diameter. • The shape can be irregular , oval, or round

• Unlike the chancre of syphilis: the chancroid ulcer edge is soft the ulcer changes shape when the edges are squeezed

Granuloma inguinale aka Donovanosis

• caused by the bacteria Calymmatobacterium granulomatis. • commonly found in tropical and subtropical, but it occurs on occasion in the United States, typically in the Southeast. • approximately 100 cases/yr in the US. • spread through vaginal or anal intercourse, rarely via oral sex. Granuloma inguinale aka Donovanosis • 50% of infected men and women have lesions in the anal area. Appears as small, beefy-red bumps in genital or anal area. • The skin gradually wears away, bumps turn into raised, beefy-red, velvety nodules. Usually painless, but bleed easily if injured. • Tissue damage may spread to the inguinal folds. Genitals and surrounding skin has a loss of skin color. primary lesion chronic lesion Lymphogranuloma inguinale

• Lymphogranuloma inguinale : aka : • Lymphogranuloma venereum (LGV) – Nicholas-Favre Disease – Sixth Venereal Disease – Tropical Bubo • Lymphogranuloma inguinale is an infection of the lymph tissue in the genital area caused by a strain of Chlamydia trachomatis, the bacterium that produces Nongonococcal Urethritis (NGU). • The disease occurs most often in • Africa • Central America • South America • Southeast Asia • The Caribbean • Lymphogranuloma inguinale infects an average of about 250-400 people a year in the United States. Symptoms Lymphogranuloma inguinale

• Lymphogranuloma inguinale has three stages: • Stage 1

– A small, painless sore similar to a pimple, blister/lesion/soft bump occurring at the point where the bacterium entered the body (usually the penis or vagina) that often goes unnoticed – Some people do not experience this and if they do healing is usually rapid without scarring – The infection then spreads to the lymph nodes in the groin area and from there to the surrounding tissue, where it causes painful swelling closest to the point of infection – Discharge from the penis or vagina from 3-30 days after exposure Symptoms Lymphogranuloma inguinale

• Stage 2 (1-2 weeks after initial Symptoms Lymphogranuloma inguinale toms appear) – Inflammation and swelling of lymph nodes and surrounding tissue – Lymph nodes closest to the infection continue to swell until a pus-filled bulge is created, called a bubo – Throbbing pain and fever • The buboes can : – Grow very big, until the skin covering them turns blue – Open through the skin, drain continuously and remain open (about 30% of cases) – Can become infected by other bacteria Symptoms Lymphogranuloma inguinale • Stage 3 – lymphatic obstruction – chronic edema – strictures – fibrosis Partner Notification

• Important part of preventing continued spread • Prevent disease progression in patients who may not have symptoms once infected • Help identify patients at need for treatment of other STIs: HIV, gonorrhea, chlamydia, etc. The END, yahoo!!!!!