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39 years old serving soldier, resident of Belgaum, Karnataka, presented with the complaints of multiple painful ulcers over penis since one month duration. He initially noticed a red painful lesion over his penis, gradually increasing in size, with appearance of similar lesions on adjacent areas and overlying skin of penis, associated with scanty discharge.
There was no history of bleeding or pus discharge, fluid filled lesions, urinary symptoms or urethral discharge, local application of any drug prior to the onset of lesions, skin lesions, oral ulcers, joint pains or visual complaints. He denied h/o high risk sexual behaviour.
He was a known case of AIDS on immune surveillance & pulmonary tuberculosis on anti- retroviral therapy (ART) and anti tubercular therapy (ATT) respectively.
What is an ulcer?
An ulcer is defined as break in the continuity of the covering epithelium of skin or mucous membrane. It involves both epidermis and dermis and heals with scarring.
What is erosion?
Erosion constitutes a break in the continuity of epidermis which heals without scarring
What are the common causes of genital ulcers?
The common causes of genital ulcers are:
Sexually transmitted causes
Non sexually transmitted causes
What are the drugs that can cause genital ulcer?
Drugs which can cause genital ulcer are:
Topical 5 Fluorouracil
What are the ART drugs that can cause genital ulcers?
ART drugs which can cause genital ulcer are:
What are the differential diagnoses considered on history?
Based on history following diagnoses need consideration:
1 - 14 days.
Calymmatobacterium granulomatis (Klebsiella granulomatis)
3 days to 3 months
Lymphogranuloma venereum (LGV)
L1, L2, L3 serovars of Chlamydia trachomatis
Herpes virus hominis type 1 and 2
What are the common organisms causing genital ulcers & what are their incubation periods?
The vital parameters were normal. There was no pallor, icterus, cyanosis, clubbing. Lymphnodes: right axilla revealed multiple, mobile, non tender, non matted, lymph nodes in posterior & central group, largest- 1x2 cm. Bilateral inguinal lymphadenopathy- nodes were multiple, mobile, tender, firm, non matted, largest- 2x2 cm on left side. Systemic Examination was unremarkable.
Dermatological & Venereological examination revealed stained undergarments, prepuce was edematous. Multiple, polysized, coalescing ulcers and erosions round to oval in shape measuring from 2-3mm to 1.5 x 2 cm in size were present on glans penis, coronal sulcus and mucosal aspect of prepuce. In addition, there was a polycyclic ulcer over glans (Fig 1). The margins were well to ill defined with sloping edematous edges. The floor was covered with serous discharge & pale red granulation tissue. The base of ulcer was tender and non-indurated. There was no bleeding on touch. Scrotum, its contents & perineum were normal. Per-rectal examination did not reveal any abnormality.
Fig 1: Polyclyclic ulcer over the glans penis
What are the clinical possibilities?
Clinical possibilities are:
Drug induced genital ulcer
What are the typical presentations of sexually transmitted genital ulcers?
Non tender inguinal lymphadenopathy
Tender inguinal lymphadenopathy
Single / multiple
Beefy red, rolled out margins
Bleeds on touch
Ragged undermined edges
What is significant lymphadenopathy?
Significant lymphadenopathy region wise is:
Cervical lymph node > 1 cm
Axillary lymph node > 0.5 cm
Inguinal lymph node > 1.5 cm
What is a bubo?
A bubo (Greek boubôn, "groin") (plural form: buboes) is swelling of the lymph nodes
It is found in infections such as:-
What is a Pseudobubo?
Appearance of inguinal subcutaneous swelling in Granuloma inguinale infection is called a pseudobubo.
Investigations revealed a normal haemogram and biochemical profile. His CD4 count was <50 cells/Âµl and his viral load was one lakh copies/ml. Tzanck smear - revealed multinucleated giant cells, Anti HSV for IgG & IgM were negative. Gram stain of smear, 10% KOH mount from the lesion, and culture for H. ducreyi were negative. The swab for culture/sensitivity did not grow any organisms after 48 hrs. His blood VDRL was non-reactor and TPHA were negative.
How is a Tzanck smear performed?
Steps involved in preparation of Tzanck smear are as follows:
Gently scrape the vesicle/ulcerÂ base with No. 15 blade
Smear on a glass slide
Fix and add Giemsa stain for 1 minute
Observe under oil immersion microscope
What do you see in the Tzanck smear slide in Genital herpes?
Multinucleate giant cells (5-8 in number) arranged in 'jig-saw' puzzle appearance with intranuclear inclusion bodies.
What are the other conditions where Tzanck smear can aid in the diagnosis?
Pemphigus group of diseases - acantholytic cells
Darier's disease - dyskeratotic cells
Herpes simplex, herpes zoster and chicken pox - multinucleate giant cells
What is the sensitivity & specificity of various diagnostic tests?
What are the newer FDA approved serological tests for Genital herpes?
HSV-1 and HSV-2 ELISA
The HSV-2 assay is 96-97% sensitive and 98% specific
HSV-1 and HSV-2 Immunoblot
Slightly higher sensitivity and specificity
Can be done from a finger prick
93% sensitive and 98% specific
A new gG-based ELISA available for both HSV-1 and 2
What is the final diagnosis?
AIDS in CDC category C - 3 / WHO Clinical Stage 4
What are the points in favour of Genital Herpes?
A history of multiple painful long standing ulcers in a HIV-positive individual and Tzanck smear showing multinucleated giant cells favor a diagnosis of genital herpes.
What are the treatment guidelines by WHO for first clinical episode of Genital herpes?
Acyclovir 400 mg orally 3 times a day for 7-10 days
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Famciclovir 250 mg orally 3 times a day for 7-10 days
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Valacyclovir 1 g orally twice a day for 7-10 days
What are the treatment guidelines by WHO for episodic therapy for recurrence?
Acyclovir 400 mg orally three times a day for 5 days
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Famciclovir 125 mg orally twice daily for 5 days
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Valacyclovir 1.0 g orally once a day for 5 day
What are the treatment guidelines by WHO for suppressive therapy?
Acyclovir 400 mg orally twice a day
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Famiciclovir 250 mg orally twice a day
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Valacyclovir 500 mg orally once a day
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Valacyclovir 1.0 g orally once a day
The patient was managed with tab Famciclovir 250 mg TDS for 10 days. Since he showed poor response the dose was increased to 500 mg TDS. ART and ATT were continued. Swelling over prepuce subsided, erosions healed well and the ulcers healed gradually.
What are the causes for persistence / resistant genital ulcer?
What are the complications of Genital herpes particularly in HIV patients?
The ulcers can be prolonged or severe and resistant to treatment. Systemic complications include aseptic meningitis, transverse myelitis, encephalitis, sacral radiculopathy, urinary incontinence, constipation. Dissemination can also cause hepatitis, pneumonitis, nephritis and monoarticular arthritis. The hematological complications include ITP, leucopenia, DIC.
How do you treat a resistant case of Genital herpes?
Oral Acyclovir 800 mg five times a day upto 6 weeks
Famciclovir 500 mg - 750 mg TDS for 3 to 6 weeks
Acyclovir IV 5 - 10 mg / kg 8 hrly
Acyclovir IV 1.5 - 2mg/kg/hr for 6 weeks administered with a Hickman's catheter
Cidofovir - IV 5 mg/kg IV once a week for three weeks and every other week for two months
Foscarnet IV 40 mg/kg 8 hourly
1% HPMPC cream
Genital herpes is a chronic, life-long viral infection. Two types of HSV have been identified, HSV-1 and HSV-2. The majority of cases of recurrent genital herpes are caused by HSV-2. Whether genital herpes is caused by HSV-1 or HSV-2 influences prognosis and counseling. Therefore, the clinical diagnosis of genital herpes should be confirmed by laboratory testing. Both virologic and type-specific serologic tests for HSV should be available in clinical settings that provide care for patients with STDs or those at risk for STDs. Immunocompromised patients might have prolonged or severe episodes of genital, perianal, or oral herpes. Lesions caused by HSV are common among HIV-infected patients and might be severe, painful, and atypical. HSV shedding is increased in HIV-infected persons. Whereas antiretroviral therapy reduces the severity and frequency of symptomatic genital herpes, frequent subclinical shedding still occurs. Suppressive or episodic therapy with oral antiviral agents is effective in decreasing the clinical manifestations of HSV among HIV-positive persons.
Bunker CB, Gotch F. AIDS and the Skin. In Burns DA, Breathnach SM, Cox NH, Griffiths CEM, editors. Rook's Textbook of Dermatology. Seventh ed. Oxford: Blackwell Science, 2004; 26.1 - 41.
2. Adriana RM, Stephen ES. Herpes simplex. In: Wolff K, Lowell AG, Stephen IK, Barbara A, Amy SP, David JL, editors. Fitzpatrick's Dermatology in General Medicine. Seventh ed. Mc Graw Hill, 2008; 1873-84.