A Case Of Genital Ulcer Disease Biology Essay

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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

Syphilis

Genital Herpes

Chancroid

Donovanosis

Candidiasis

Genital Scabies

Non sexually transmitted causes

Drug eruptions

Traumatic

Contact dermatitis

Malignancy

Behcet's disease

Zoon's balanitis

Lichen planus

What are the drugs that can cause genital ulcer?

Drugs which can cause genital ulcer are:

Doxycycline

Sulfonamides

Carbamazepine

Phenytoin

Foscarnet

Topical Imiquimod

Topical 5 Fluorouracil

What are the ART drugs that can cause genital ulcers?

ART drugs which can cause genital ulcer are:

Lamivudine

Ritonavir

Saquinavir

Atazanavir

Zalcitabine

What are the differential diagnoses considered on history?

Based on history following diagnoses need consideration:

Genital Herpes

Syphilis

Chancroid

Donovanosis

Drug induced

STIs

Causuative Organism

Incubation Period

Chancroid

Haemophilus ducreyi

1 - 14 days.

Granuloma inguinale

Calymmatobacterium granulomatis (Klebsiella granulomatis)

3 days to 3 months

Lymphogranuloma venereum (LGV)

L1, L2, L3 serovars of Chlamydia trachomatis

3-12 days

Herpes genitalis

Herpes virus hominis type 1 and 2

3-7 days

Syphilis

Treponema pallidum

9-90 days

What are the common organisms causing genital ulcers & what are their incubation periods?

Examination

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:

Genital Herpes

Chancroid

Candidiasis

Drug induced genital ulcer

Primary Syphilis

What are the typical presentations of sexually transmitted genital ulcers?

Syphilis

Solitary

Punched out

Indurated

Painless

Non tender inguinal lymphadenopathy

Genital Herpes

Grouped vesicle

Erosions

Superficial ulcers

Painful

Tender inguinal lymphadenopathy

c) Donovanosis

Single / multiple

Indurated

Beefy red, rolled out margins

Bleeds on touch

Pseudobubo

d) Chancroid

Painful

Multiple

Purulent

Non indurated

Ragged undermined edges

Bubo

e) LGV

Painless

Transient

Solitary

Bubo

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:-

Bubonic Plague

Chancroid

LGV

What is a Pseudobubo?

Appearance of inguinal subcutaneous swelling in Granuloma inguinale infection is called a pseudobubo.

Investigations

Investigations revealed a normal haemogram and biochemical profile. His CD4 count was <50 cells/µl 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/ulcer 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?

Disease

Tests

Sensitivity

Specificity

Herpes virus

Tzanck smear

Culture

ELISA

<40%

60-70%

70-95%

-

-

94-100%

Primary syphilis

Secondary syphilis

Blood VDRL

Blood VDRL

74-87%

100%

98%

98%

H.ducreyi

Culture

Gram/Giemsa

PCR

75%

10-63%

98%

51-99%

99%

What are the newer FDA approved serological tests for Genital herpes?

Test

Comments

Herpes Select

HSV-1 and HSV-2 ELISA

The HSV-2 assay is 96-97% sensitive and 98% specific

HerpesSelect

HSV-1 and HSV-2 Immunoblot

Slightly higher sensitivity and specificity

Biokit HSV-2

Can be done from a finger prick

93% sensitive and 98% specific

Captia EIA

A new gG-based ELISA available for both HSV-1 and 2

What is the final diagnosis?

Genital herpes

AIDS in CDC category C - 3 / WHO Clinical Stage 4

Pulmonary tuberculosis

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

    or

Famciclovir 250 mg orally 3 times a day for 7-10 days

    or

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

    or

Famciclovir 125 mg orally twice daily for 5 days

    or

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

    or

Famiciclovir 250 mg orally twice a day

    or

Valacyclovir 500 mg orally once a day

    or

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?

AIDS

Drug resistance

ART

Mixed infection

Tuberculosis

Malignancy

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

Commentary

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.

Suggested reading

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.

"Venereal disease is the most formidable enemy of the human race; an enemy entrenched behind the strongest human passions and deepest social prejudice"

--- Sir William Osler

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