Approach to a genital ulcer

Genital ulcer
May be of infectious or non-infectious etiology Most are caused by sexually transmitted diseases

Infectious genital ulcer

Herpes simplex virus (HSV) Treponema pallidum (syphilis) Haemophilus ducreyi (chancroid) Chlamydia trachomatis serovars L1-3 (lymphogranuloma venereum; LGV) Klebsiella granulomatis (Granuloma inguinale; akaDonovanosis)

Non-infectious
fixed drug reactions Behets disease Neoplasm trauma

Epidemiology
A comprehensive evaluation of the patient with genital ulcers requires a thorough knowledge of the epidemiology of sexually transmitted pathogens in a given locale

Clinical Evaluation
Sexual history Medical history Symptoms Physical Examination

Sexual history
Gender of the sexual contacts (men, women, or both) Number of sexual contacts within the past month and past six months Sites of sexual contact (oral, genital, rectal) Use of barrier protection (consistent or inconsistent) Geographic location of the partner

Medical history
onset of risk relative to the onset of signs and symptoms (clue to IP) use of drugs (eg, methamphetamine) and/or heavy alcohol use, associated with an increase in high-risk behaviors past history of other STDs and prior HIV testing For noninfectious etiologies, a history of recurrent oral and genital lesions and uveitis may suggest Behets disease genital blisters and ulcerations that are associated with a particular medication may suggest fixed drug reaction

Symptoms
Painful versus painless
Painful - more typical of HSV and chancroid Painless- more typical of syphilis, LGV, and granuloma inguinale

Dysuria
dysuria may suggest a diagnosis of urethritis (eg, Chlamydia urethritis)

Constitutional symptoms
can be significant in primary clinical infection with HSV, secondary syphilis, and LGV

Recurrent episodes
history of recurrent ulcers would suggest HSV infection

Physical Examination
characteristics of the ulcer any associated lymphadenopathy

Characteristic of Ulcers
Classically, infection due to HSV or H. ducreyi (chancroid) presents as multiple ulcers, whereas syphilis usually presents as a single lesion Herpetic lesions begin as one or more grouped vesicles on an erythematous base The ulcers associated with chancroid begin as papules that go on to ulcerate The syphilitic chancre is classically a single, indurated, wellcircumscribed painless ulcer LGV often begins as a single papule or a shallow ulcer Granuloma inguinale can present as one or more nodular lesions that ulcerate. The ulcers, which slowly enlarge, are often friable and have raised, rolled margins

Lymphadenopathy
Inguinal lymphadenopathy is commonly seen with most genital ulcer-causing infections involving the genital tract The lymph nodes are often tender in patients with HSV, chancroid, and LGV Rubbery, non-tender nodes are often seen in late primary syphilis less common with granuloma inguinale
It is also important to assess whether the patient may have other findings to suggest c oncomitant STDs, such as urethral or cervical discharge (eg, gonorrhea, chlamydia), thrush (eg, HIV infection), or hepatomegaly (eg, hepatitis C or hepatitis B)

Herpes Simplex Virus

Genital herpes, primary: vulvar infection Multiple, extremely painful, punched-out, confluent, shallow ulcers on the edematous vulva and perineum. Micturition is often very painful. Associated inguinal lymphadenopathy is common. Systemic symptoms: Most individuals with primary infection are asymptomatic pain, itching, dysuria, vaginal or urethral discharge are common symptoms

Syphilis
A painless ulcer or chancre on the mucocutaneous site of inoculation (Ulcers are usually painless unless superinfected) Associated with regional lymphadenopathy Shortly after inoculation, syphilis becomes a systemic infection with characteristic secondary and tertiary stages

Primary syphilis: penile chancre A 28-year-old male with penile lesion for 7 days. Painless ulcer on distal penile shaft with smaller erosion on the glans.

Primary syphilis: chancre on scrotum A 25-year-old male with painful lesion on scrotum for 10 days

HAEMOPHILUS DUCREYI: CHANCROID

Characterised by a painful ulcer at the site of inoculation, usually on the external genitalia The development of suppurative regional lymphadenopathy

Chancroid: Painful ulcer with marked surrounding erythema and edema.

Chancroid Multiple, painful, punchedout ulcers with undermined borders on the vulva occurring after autoinoculation

Diagnosing A Genital Ulcer: A laboratory approach

All patients with genital ulcers should have a diagnostic evaluation for HSV and syphilis HSV- viral culture, polymerase chain reaction (PCR), direct fluorescent antibody (DFA), or Tzanck preparation Syphilis - indirectly via serologic testing (eg, VDRL, RPR) or directly through visualization of spirochetes by darkfield microscopy or direct immunofluorescence Chancroid Culture, gram-stain, PCR tesing lymphogranuloma venereum (LGV) serology, either microimmunofluorescence (MIF) or complement fixation (CF)

Lymphogranuloma Venereum
Lymphogranuloma venereum is a sexually transmitted disease caused by 3 serovars of Chlamydia trachomatis (L1,L2,L3) Endemic in West and East Africa, India, South East Asia and South America Risk factors includes:
Older age (median of 40 years old) White race Men engaging in MSM and having unprotected anal intercourse Co-infection with gonnorrhea

Pathogenesis
Lymphomagranuloma venereum (LGV) is acquired by direct contact with infected lesions , however transmission through contaminated fomites is possible LGV invades the submocosal connective tissues and lymphatic system After exposure, abrasion of the epithelium allows the organism to penetrate into the submucosal tissues where they are taken up by macrophages and carried to regional lymph nodes

 Clinical disease manifest in 3 stages

The first stage Usually appears 3-21 days after exposure Primary lesions appear at the site of inoculation and tends to be a small, painless papular lesion which may ulcerate Usually occurs at the coronal sulcus in men and the vulva, posterior vaginal wall and cervix for women

 The second stage

Occurs 2-6 weeks after primary infection Painful regional lymphadenopathy and systemic symptoms In men: the inguinal lymph nodes are affected and node enlargement on either side of the inguinal ligament produces the characteristic groove sign. In women: lymph drainage from the rectum and vagina results in pelvic lymphadenopathy. When deep lymph nodes are affected, lower abdominal and back pain may be present.

 The lymph nodes are mobile and discrete, but with progressive inflammation they become fixed and suppurative with bubo formation (abscess) . Buboes, enlarged fluctuant nodes, may spontaneously rupture or form chronically draining sinuses. Hematogenous dissemination may occur and one may experience nonspecific constitutional symptoms (LOA, LOW, vomitting, myalgia, fever) or, less commonly, present with meningoencephalitis, pneumonitis, arthritis or hepatitis.

 The third stage

marked by subsequent scarring and fibrosis of affected tissue and results in lymphatic obstruction and genital oedema lead to severely disfiguring conditions such as thickening and fibrosis of the labia in women (esthiomene) and distortion of the penis in men. Regional spread of LGV to the pelvis in women may cause salpingitis, pelvic adhesions and infertility.

Diagnosis
Histopathology
Biopsy of primary lesion reveals non specific ulceration with granulation tissue and endothelial swelling
Biopsy of affected lymph node would reveal suppurative granulomatous inflammation

Diagnosis
The diagnosis of LGV is difficult. Serological Assay
Complement fixation is the mostly used Titer of 1:64 or greater provides a probable diagnosis Titer of below 1:16 generally excludes acute LGV

Immunoflurescence
More specific but less sensitive Titer of 1:256 of greater provides a probable diagnosis

Treatment
Treatment First Line Second Line Third Line Drugs Oral Doxycycline Oral Erythromycin Oral Azithromycin Course 100 BD for 3 weeks 500mg QID for 3 weeks 1g/ounce weekly for 3 weeks

Surgery is often required in late stages and includes aspiration of buboes through intact skin (direct incision has a high risk of fistula formation), rectal stricture dilatation, recto-vaginal fistula repair, genital reconstruction, and colostomy.

Granuloma inguinale
It is caused by the Gram-negative pleomorphic bacterium Klebsiella granulomatis. Presents as a painless genital ulcer that bleeds easily

 Endemic in tropical and subtropical regions such as Papua New Guinea and India. Prevalence of granuloma inguinale is highest among adults aged 2040 years. Believed to be sexually transmitted because of its predominance in sexually active persons, especially those with multiple sexual partners or contact with prostitutes,

Pathogenesis
K. granulomatis invades epidermal and dermal tissues causing local inflammation On histopathology, large mononuclear cells containing inclusion bodies (Donovan bodies) are characteristic. The associated epithelial changes include ulceration, microabscesses, acanthosis, irregular elongation of the rete pegs and pseudoepitheliomatous hyperplasia. Untreated lesions may become hyperkeratotic. The dermal layer exhibits inflammatory changes, with a dense cellular infiltrate and varying degrees of fibrosis and edema.

Clinical features
The initial lesion of granuloma inguinale (GI) is a small firm papule at the site of infection which appears after an incubation period of 350 days. This typically erodes to form a painless ulcer The ulcer is granulomatous and beefy-red with a nonpurulent base and bleeds readily when manipulated. Occasionally the ulcers may become necrotic and foul smelling with significant tissue destruction.

Clinical Features
Multiple lesions may develop on opposing surfaces or along skin folds. In men: ulcers are generally found at the coronal sulcus and are more common in uncircumcised men. In women: the labia minora and fourchette are most commonly affected but lesion may appear in the upper genital tract, including the cervix. Therefore, vaginal bleeding or discharge, pelvic inflammatory disease or a pelvic mass are not uncommon presentations.

Clinical Features
Abscess formation in the groin mimics lymphadenitis (pseudobuboes), but the lymph nodes themselves are rarely involved. The typical clinical picture may be altered if the genital lesions become secondarily infected, resulting in pain, purulent exudate and tender lymphadenopathy

Without treatment, GI is slowly progressive, often resulting in soft tissue destruction and extensive scarring

Diagnosis
The diagnosis is made clinically and with the presence of intracellular Donovan bodies seen within large mononuclear cells on smear or biopsy A smear is obtained firstly by removing debris found at the base of the ulcer with a cotton swab A second swab is used to scrape the surface of the ulcer without causing bleeding The tissue is then spread onto a slide , air dried and stained with Giemsa stain .

 Donovan bodies are identified as darkly staining, intracellular , ovoid organism with/without a capsule. The smear may be negative if the lesion is early, sclerotic or secondarily infected. In such case, histologic diagnosis is required

Treatment
Treatment regimens are empiric. Currently recommended regimens include:
Oral azithromycin 1 g followed by 500 mg daily, Oral doxycycline 100 mg twice daily, Oral ciprofloxacin 750 mg twice daily or erythromycin 500 mg four times daily. Oral Bactrim

Duration of therapy has not been established but a minimum of 3 weeks or until all lesions have completely resolved is recommended.