SFP Julsep 2005
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STI AND HIV/AIDS: ESSENTIALS FOR BEST PRACTICE - A HOLISTIC APPROACH UNIT NO. 4 SYNDROMIC APPROACH TO THE MANAGEMENT OF GENITAL ULCERS Dr Priya Sen ABSTRACT India, parts of South America and southern Africa. The main STIs which cause genital ulcerative disease include Lymphogranuloma venereum has been seen increasingly in genital herpes, primary syphilis, chancroid, Granuloma MSM who have had sexual contacts in Northern Europe. Of inguinale, and Lymphogranuloma venereum. Genital herpes significance is that GUD has been associated with an increased is the leading cause of genital ulcer disease worldwide. risk for HIV infection. Furthermore, more than one of these Primary syphilis is on an increasing incidence trend in diseases can be present in a patient who has genital ulcers. Singapore, whilst Chancroid is uncommon in Singapore, but still common in parts of India and South East Asia. A diagnosis based only on the patient’s medical history and physical DIAGNOSTIC APPROACH examination frequently is inaccurate. Therefore, all patients who have genital ulcers should be evaluated with a serologic A. Patient history: test for syphilis and a diagnostic evaluation for genital herpes. 1. Lesion history: prodrome, initial presentation (especially In settings where chancroid is prevalent, a test for presence of vesicles), duration of lesion, pain, other systemic Haemophilus ducreyi should also be performed. Even after symptoms, use of systemic or topical remedies, and any complete diagnostic evaluation, at least 25% of patients who history of similar symptoms in the past or partners with have genital ulcers have no laboratory-confirmed diagnosis. similar symptoms. 2. Medical history: HIV status, skin conditions, drug allergies, and medications. SFP2007; 33(2): 24-31 3. Sexual history: gender of partners, number of partners (new, anonymous, serodiscordant), venue for meeting partners, INTRODUCTION commercial sex exposure, partners with symptoms or signs, This topic will focus on genital ulcers caused by Sexually and partners with known HSV or recent syphilis diagnosis. Transmitted Infections (STIs). The main STIs which cause 4. Travel history. genital ulcerative disease include: P Genital herpes B. Physical exam: P Primary syphilis 1. Lesion: examine for appearance, distribution, number, size, P Chancroid induration, depth, and tenderness. P Granuloma inguinale 2. Genital exam: examine genital and perianal area for other P Lymphogranuloma venereum lesions. 3. Lymph node(s): note number and location of enlarged nodes, Non STD-related aetiologies size, tenderness, and presence of bubo. P Non-STD infectious causes of Genital Ulcer Disease (GUD): 4. General exam: thorough examination of oral cavity and skin Candidiasis/balanitis, scabies, common skin infections (e.g. of torso, palms and soles, and neurologic exam, including Staph). cranial nerves. P Non-infectious causes of GUD: aphthous ulcers, Behcet’s syndrome, fixed drug eruption, Reiter’s syndrome, trauma/ C. Laboratory testing abrasions. A diagnosis based only on the patient’s medical history and physical examination frequently is inaccurate. Therefore, all No aetiology is found in 20% to 50% of GUD cases, most patients who have genital ulcers should be evaluated with a likely related to the sensitivity of the laboratory tests (affected serologic test for syphilis and a diagnostic evaluation for genital by self-medication, duration of lesion and technology of the test). herpes. In settings where chancroid is prevalent, a test for Genital herpes is the leading cause of genital ulcer disease Haemophilus ducreyi should also be performed. Specific tests worldwide. Primary syphilis is on an increasing incidence trend for evaluation of genital ulcers include: in Singapore, whilst Chancroid is uncommon in Singapore, but P syphilis serology and either darkfield examination or direct still common in parts of India and South East Asia. Granuloma immunofluorescence test for T. pallidum, inguinale (Donovanosis) is rarely seen locally, but endemic in P culture or PCR test for HSV, and P culture for H. ducreyi. Other useful tests in the diagnosis of genital ulcer disease include: PRIYA SEN, Deputy Head, Department of STI Control, National P Type-specific serology testing for HSV-2. Might be helpful in Skin Centre identifying persons with genital herpes. SYNDROMIC APPROACH TO THE MANAGEMENT OF GENITAL ULCERS Table 1. Clinical Features of Common Genital Ulcers Genital Herpes Primary Syphilis Chancroid Aetiologic agent HSV-1 & HSV-2 T. pallidum H. ducreyi Incubation period 2-7 days 10-90 days (avg. 21 days) 3-10 days (avg. 4-7 days) Initial lesions Papule & vesicle* Papule Papule or pustule Presenting lesion Vesicles Chancre Ulcer/buboe Number and distribution Multiple*, may coalesce. Usually one Single or multiple of lesions Bilateral in primary; unilateral in recurrent. Diameter 1-2 mm 5-15 mm Variable Edges Erythematous Sharply demarcated, elevated, round, or oval Undermined, ragged, irregular Depth Superficial Superficial or deep Excavated, deep Base Serous, erythematous, nonvascular Smooth, non-purulent, relatively Necrotic, generally purulent, nonvascular bleeds easily Induration None Usually present None Pain Common, often with prodrome Uncommon* Common, severe of tingling* Lymphadenopathy Usually present in primary infection, Firm, non-tender, bilateral Tender, may suppurate, usually and absent in recurrences unilateral Source: Adapted from Ballard (in K Holmes) *Useful in differential diagnosis P Biopsy of genital ulcers. Might be helpful in identifying the Clinical features cause of ulcers that are unusual or that do not respond to First episode genital herpes may either be primary or non- initial therapy. primary. Primary genital herpes is defined as infection occurring P HIV testing. Should be performed on all patients who have in persons with no prior exposure to either HSV 1 or 2. Non- genital ulcers caused by T. pallidum or H. ducreyi, and should primary genital herpes is defined as first genital episode in be strongly considered for those who have genital ulcers persons who have evidence of prior HSV infection at another caused by HSV. body site with either HSV type 1 or 2. First episode genital herpes is often severe, presenting with Clinicians often have to treat patients before test results are multiple grouped vesicles, which rupture easily leaving painful available because early treatment decreases the possibility of erosions and ulcers. In the male, the lesions occur mainly on ongoing transmission and because successful treatment of the prepuce and sub-preputial areas of the penis; in females, on genital herpes depends on prompt initiation of therapy. The the vulva, vagina and cervix. Healing of uncomplicated lesions clinician should treat based on the most likely diagnosis, on take 2 to 4 weeks. the basis of clinical presentation and epidemiologic Recurrent attacks are less severe than the first episode. circumstances. In some instances, treatment must be Groups of vesicles or erosions develop on a single anatomical initiated for additional conditions because of diagnostic site, and these usually heal within 10 days. Recurrences averages uncertainty. Even after complete diagnostic evaluation, at 5 to 8 attacks a year and are more frequent during the first 2 least 25% of patients who have genital ulcers have no years of infection. Genital herpes caused by HSV 1 generally laboratory-confirmed diagnosis. recurs infrequently. The majority of persons with HSV infection have mild, often unrecognised or sub-clinical disease and are unaware of the HERPES SIMPLEX VIRUS INFECTION infection. They may nevertheless shed the virus intermittently in the genital tract and thus transmit the infection to their Definition partners unknowingly. Genital herpes is caused by the DNA Herpes simplex virus (HSV), usually HSV type 2. However, type 1 infections are Laboratory investigations also possible. Transmission of the virus can occur through genital P Tzanck smear/test: Demonstrates giant cells from lesions; to genital, mouth to genital, genital to anal, and mouth to anal not sensitive and only provides presumptive evidence of contact. infection by a herpes virus. SYNDROMIC APPROACH TO THE MANAGEMENT OF GENITAL ULCERS P Viral isolation in cell culture: Sensitive and specific; sensitivity 2. Valacyclovir 500 mg orally bid or 1000 mg orally once a day declines as lesions heal; viral typing possible. for 5 days P HSV antigen detection: By DFA or EIA techniques; or insensitive, viral typing not possible; but economical and 3. Famciclovir 125 mg orally bid for 5 days or 1 g bid orally for quick. 1 day P PCR detection of viral nucleic acid: Highest sensitivity; viral typing possible; but expensive and not widely available. Suppressive treatment [Ib, A] P Type-specific serological tests (TSST): Based on recombinant 1. Acyclovir 400 mg orally bid type-specific glycoproteins gG1 (HSV 1) and gG2 (HSV or 2). Good sensitivity and specificity and are useful in certain 2. Valacyclovir 500 mg orally od clinical situations, e.g. confirming diagnosis of genital herpes, or counselling of sexual partners of infected persons, detection 3. Valacyclovir 1000 mg orally od (for > 10 recurrences in 1 of unrecognised infection and for seroepidemiological year) studies. Examples of these tests are HerpeSelect 1 and 2 or ELISA (Focus Technologies, USA) and Immunoblot test kits. 4. Famciclovir 250 mg orally bid Physicians should stop treatment after 9 to 12 months to see if Treatment recurrence rate warrants continued prophylaxis.