A 23-year-old female resident of an AIDS hospice in Ho Chi Minh City had a chronic ulcer on her left hand (Fig. 1). The lesion started on the tip of the third finger and over the course of 1 year slowly progressed to include the ventral palm. On examination, the ulcer was well circumscribed with mild surrounding edema and tenderness. There was no bleeding or purulence. Sensation in the unaffected areas was normal. Motor function of the hand was normal. She had similar lesions on her buttocks, which had also appeared around the same time as the finger ulcer. She had been diagnosed as HIV positive 3 years earlier. CD4 testing was not available, and she had never taken antiretroviral medications. The patient had no history of fever, weight loss, cough, or other systemic symptoms except for intermittent diarrhea. She was single and had previously sold seafood in a local market, which involved regularly handling live fish.
What is your diagnosis?
Differential diagnosis: Cutaneous tuberculosis or atypical mycobacterium, cutaneous fungal infection, herpes simplex virus (HSV), varicella-zoster virus, malignancy, bacterial infection.
Diagnosis: Herpes simplex virus infection
Complete blood count and liver function tests were within normal limits. VDRL was negative. The pathology reading on a biopsy performed at local hospital was reported as "nonspecific inflammation" with negative acid-fast bacillus and fungal stains. The patient had taken multiple courses of antibiotic and antifungal medications without improvement.
The patient was treated empirically with acyclovir 200 mg 5 times a day, and within 2 weeks, the ulcers had almost completely healed (Fig. 2). After 4 weeks of treatment, the dose of acyclovir was reduced to 200 mg 3 times a day. Three months later, the patient left the hospice and was lost to follow-up.
The diagnosis of HSV infection can usually be made by viral culture or direct fluorescent antibody testing. A Tzanck preparation from direct smear of the lesion can help to narrow the differential to herpesviruses. Polymerase chain reaction for HSV DNA is sensitive, but the test has not been FDA cleared for use on genital lesions.1 Serological testing for HSV antibodies is available, but only the newer glycoprotein G-based type-specific assays can differentiate between HSV-1 and HSV-2. Testing for HSV was not available in Vietnam at the time this patient was treated. A presumptive diagnosis of a herpesvirus infection was made based on the rapid response of the ulcer to treatment with acyclovir.
More than 80% of adults in Asia have evidence of previous HSV-1 infection by antibody testing.2 The prevalence of HSV-2 infection is lower in Asian countries than in African and western nations.3 There are little data on HSV infection rates in Vietnam, but 1 study of female sex workers in 3 Mekong Delta provinces showed HSV-2 antibody prevalence rates of 30% to 33%.4
Atypical presentations of herpes are not uncommon in immunocompromised patients.4 Ulcers can appear in single or multiple locations and are more likely to become chronic and extensive. Herpes simplex virus lesions in the HIV-infected patient can usually be treated with acyclovir, although acyclovir-resistant HSV has been reported.5,6 Severe or disseminated HSV infections may require treatment with high-dose intravenous acyclovir.
In the immunocompromised patient, chronic ulcers may be due to infectious causes (bacterial, mycobacterial, fungal, or viral) or noninfectious causes such as malignancy. Opportunistic infections of the hand due to Cryptococcus and Candida have been reported.6 Ulcers can also become secondarily infected with bacteria, making the underlying primary etiology more difficult to diagnose.
Varicella-zoster virus is another herpesvirus that can cause skin disease in immunocompromised hosts. The lesions usually appear as clusters of vesicles localized to one or more dermatomes, but can coalesce into large ulcers or become disseminated. Varicella-zoster virus may also respond to treatment with acyclovir, but generally requires higher doses than are used for treatment of HSV disease.
This patient had a history of regular live fish exposure, occasionally associated with bacterial infections such as Erysipelothrix rhusiopathiae or Mycobacterium marinum. In this case, the acid-fast bacillus stain on the biopsy was negative, and the diagnosis of HSV infection was made by the rapid and complete response to an empiric trial of acyclovir.
Initial management of ulcerative diseases in HIV patients should include microbiological evaluation of the lesion. Biopsy may be indicated when microbiological evaluation is nondiagnostic. In resource-limited settings where laboratory capabilities are limited, however, empiric treatment of chronic ulcers with antiviral medication active against HSV may be both diagnostic and curative.
1. Centers for Disease Control and Prevention. Sexually transmitted disease treatment guidelines 2006. MMWR
. 2006;55(no. RR-11):1-94.
2. Smith JS, Robinson NJ. Age-specific prevalence of infection with herpes simplex virus types 2 and 1: a global review. J Infect Dis.
3. Weiss H. Epidemiology of herpes simplex virus type 2 infection in the developing world. Herpes.
4. O'Farrell N, Thuong NV, Nghia KV, et al. HSV-2 antibodies in female sex workers in Vietnam. Int J STD AIDS.
5. Severson JL, Tyring SK. Relation between herpes simplex virus and human immunodeficiency virus infections. Arch Dermatol.
6. Wynn SW, Elhassan BT, Gonzalez MH. Infections of the hand in the immunocompromised host. J Am Soc Surg Hand.