Case 1 34 year old MSM, presented with h/o Genital ulcer of one week duration. Not painful. No discharge 27/01/2017 Sexually Transmitted Infections CMT Ulcerative STIs 2017 Dr.U.Y.Joshi. Consultant in Genitourinary Medicine and HIV Hull and East Yorkshire Case 1 contd Past Medical None significant Past STIs-None Allergic to Penicillin 27/01/2017 Case 1 contd Sexual History LSI 1/7 ago RMP of 3/12 , from Hull, Anal I&R, Oral I&R No condoms 2) 3/52 ago, CMP, ONS, from Leeds, Anal I&R, Oral I & R, No condoms 6 other sexual contacts in last 6/12 (none from abroad) Past H/O STI-none Past Medical –None significent Allergies-None 27/01/2017 Case 1 contd On Genital Examination Solitary ulcer with clear margins and raised edges, slightly tender but quite indurated (rigid edges) Bilateral Inguinal lymph nodes enlarged ,shotty but not tender. Perianal and Anal region- No abnormality detected No obvious skin rash seen 27/01/2017 Differential Diagnosis Herpes simplex Chancroid Trauma Provisional Diagnosis? Primary Chancre (Syphilis) Differential Diagnosis Differential Diagnosis Herpes simplex Chancroid Trauma Causes of Genital Ulcers Genital ulcer Disease(GUD) Sexually Transmitted Non Sexually Transmitted Infective Non Infective Genital Ulceration: Causes of Genital Ulcer/s STI Causes Herpes simplex virus (HSV) Primary Syphilis Chancroid Lymphogranuloma venereum (LGV) Donovanosis (granuloma inguinale) Genital Ulceration: Non STI causes Infective Non-Infective Herpes zoster Behcet’s disease Candidiasis Stevens-Johnson Mycobacterial ulcer Fixed drug eruption Amoebiasis Allergic or irritant contact dermatitis Tularaemia Erosive lichen planus Histoplasmosis Erosive lichen sclerosus Bullous eruption Carcinoma and Intraepithelial neoplasia Trauma e.g. zipper injury Apthosis Others Genital Ulceration: Causes and Investigations Syphilis in men Syphilis in women Usually appears in the: Usually appears in the: Coronal sulcus Vulva Glans Cervix Prepuce Mouth Cervical andAnus anal chancres may not be noticed by patients. There may be regional lymphadenopathy. Co- infection with HIV is common particularly in MSM Mouth Syphilis Caused by Treponema pallidum, a bacterial spirochete. Classically - a painless, indurated ulcer (chancre) with a clear moist base which exudes serum with pressure, seen in approximately 40% of cases. The majority however are non-classical; painful, soft and multiple. 27/01/2017 Primary chancre Cervix 27/01/2017 SYPHILIS (TONGUE) Chancroid 27/01/2017 27/01/2017 Investigations STI screen performed- inc First pass urine for neisseria gonorrhoeae and Chlamydia NAAT Serological tests for syphilis HIV and Hep B serology Swab from the genital lesion for multiplex PCR. ?Dark Field (Ground )Microscopy Dark Field(ground) Microscopy 27/01/2017 Investigations- Dark Field Microscopy(DFM) Use Polymerase Chain Reaction (PCR) (if available) • T. pallidum from the clinical lesion or as part of a multiplex PCR test for: • Herpes simplex virus (HSV) • T pallidum • Haemophilus ducreyi • Chlamydia trachomatis L1,2,3 serovars This is a more sensitive test than DFM but is currently not a Point-of-Care test Investigations -Serology Specific treponemal tests: Cardiolipin tests: Enzyme Immuno Assay (EIA) Rapid plasma reagin (RPR) EIA -IgM Venereal Disease Research Laboratory (VDRL) T. pallidum Particle Agglutination (TPPA) T. pallidum Pointhaemagglutination of care specific treponemal (TPHA) and cardiolipin tests are available but less sensitive than Linestandard Immuno serological Assay tests. (LIA) Investigations Serology Primary Syphilis In primary syphilis, the treponemal serology may intially be negative. The test becomes positive around the end of the first week after appearance of the chancre and it could be any one or a combination of tests If primary syphilis is suspected the EIA, EIA-IgM, TPPA or TPHA and RPR or VDRL should be requested. Investigations-Results Multiplex PCR Treponema pallidum Positive HSV and H.Ducrey-Negative Syphilis serology VDRL Positive 1:16 EIA Positive Serodia Particle -IgM Positive Investigations Results Hepatitis HBsAg –Negative HIV Antigen antibody Duo Test –Reactive Adv repeat STS and HIV serology for confirmation Treatment Treatment Early syphilis Penicillin is the treatment of choice. Other antibiotics can be used as shown in the table. Treatment options First line treatment Benzathine benzylpenicillin IM 2.4 M U X 1 Penicillin allergy Doxycyline 100mg bd PO14/7 Azithromycin 500mgod PO 10/7 Erythromycin 500mg qds PO 14/7 Ceftriaxone 500mg od IM 10/7 (if no anaphylaxis Consider desensitisation of patient if penicillin is required Parental treatment Amoxycillin 500mg tds po +probenecid 500mg qds po 14/7 declined As for penicillin allergy Early Infectious Syphilis Clinical Features of Secondary Syphilis I Clinical features appear 6-8 weeks after appearance of the chancre. Constitutional symptoms - low grade fever, malaise, anorexia and sore throat . Typically patients present with a generalised rash affecting palms and soles. A. The rash can be itchy in about 10% of patients B. Scaly (psoriasiform), annular or hyper or hypopigmented. C. Hypertrophic papules occurring in warm moist areas such as the anus, vulva, medial aspect of thighs, underside of breast and armpits result in flat warty lesions known as condylomata lata. These are the most infectious lesions and are often mistaken for anogenital warts. D. The primary lesion may still be present and should also be looked for. 27/01/2017 HIV Serology Screening test by EIA Antigen/Antibody (Duo) Test. May become reactive by 6 weeks. (Lab still advises to repeat after 3months from the time of the last risk) Confirmation of positive test by Western Blot Method. Offer pretest discussion for high risk clients Diagnosis in HIV-positive persons with Early syphilis More likely to have multiple, large and deep genital ulcers and The risk of neurological complications may be higher with early syphilis. However, the clinical features in HIV-positive and negative individuals with early syphilis are often similar. In a minority of cases, serology may be unreliable: Tendency for the RPR/VDRL titre to be lower in primary and statistically significantly higher in secondary syphilis Although lower or false-negative titres have been reported Syphilis in HIV positive individuals - Treatment Treatment as appropriate for the stage of syphilis infection ie HIV positive individuals to be given same treatment as it is for HIV negative individuals Investigations Serology Secondary and early latent syphilis In secondary and early latent syphilis, all the tests will be positive. EIA is usually the test performed, if positive, it will be confirmed by TPPA or TPHA and at the same time the RPR or VDRL will be performed to assess activity. The Laboratory should be informed of the possibility of secondary syphilis so that the serum is diluted if the cardiolipin test is initially negative. TREATMENT OF EARLY SYPHILIS - PRIMARY, SECONDARY AND EARLY LATENT < 2 YEARS OF ONSET OF INFECTION First Line Regimens for adult males and non- pregnant/non-breastfeeding females Benzathine Penicillin G 2.4 MU IM single dose or Procaine Penicillin G 600,000 units IM daily x 10 days Partner Notification About 50% of sexual partners will be infected. In primary syphilis, sexual partners within the last three months before the chancre appear should be checked and treated. In secondary or early latent syphilis partners in the last two years may need to be checked depending on the sexual history. All partners should be given epidemiological treatment for syphilis at the initial visit as for EIS. Jarisch–Herxheimer Reaction: An acute febrile illness with headache, myalgia, chills andrigours and resolving within 24 hours. Common in early syphilis but is usually not important unless there is neurological or ophthalmic involvement or in pregnancy when it may cause fetal distress and premature labour. Learning Points Be aware of return of Syphilis infection in the developed world. Careful history taking is paramount inc sexual orientation, sexual practices, allergies and past STIs. Under take appropriate clinical examination. Appropriate documentation of clinical findings is critical. 27/01/2017 22 year old female complaining of : Vulval soreness and dysuria – 2 days. Unable to pass water. How would you proceed? History: Noticed sores this morning, extremely painful. Feels unwell and rundown What diagnostic test/s would you carry out? What tests would you carry out? HSV Culture /NAAT Other tests? Treatment Aciclovir -400 mgs 3 times daily for five days Analgesics Herpes Simplex Virus Genital infection What treatment would you offer? Genital Herpes Treatment Aciclovir -400 mgs 3 times daily for five days Analgesics Diagnosis-HSV Viral Culture? NAAT testing HSV Serology? HSV Diagnosis HSV DNA by PCR HSV DNA detection by polymerase chain reaction (PCR) increases HSV detection rates by 11-71% compared with virus culture. PCR-based methods allow less stringent conditions for sample storage and transport than virus culture New real-time PCR assays are rapid and highly specific. Real-time PCR is recommended as the preferred diagnostic method for genital herpes Treatment of Genital Herpes Primary Attack - Oral Therapy superior to topical Aciclovir Dose 200 mgs x 5 x 5 Famciclovir Dose 250 mgs x 3 x 5 Valaciclovir Dose 500 mgs x 2 x 5 Oral Therpay: Speeds the rate of healing Shortens the duration lessens the severity of symptoms decreases the duration of viral shedding Recurrent Genital Herpes Usually of shorter duration and lesser severity May precipitate with physical or mental stress Prodromal symptoms of tingling Usually heal within a week Symptoms more severe in females than males. Psychological impact quite high Recurrent genital herpes Suppressive treatment indicated if Recurrences frequent- 4 or more recurrences per year Affecting sexual relationship/social life Aciclovir 400mgs twice daily for at least 6 months –un interrupted .