HIV prevalence in patients with herpes zoster

Introduction

Herpes zoster, due to reactivation of varicella-zoster virus infection, is associated with depression of immunity.[1] Herpes zoster has been reported in various immunodeficiency states, in lymphoma/leukaemia and other cancers, after organ transplantation, and during chemotherapy.[2],[3] Before the discovery of the human immunodeficiency virus (HIV), the development of herpes zoster was noted in homosexual men.[1],[5] Lately, results of sero-epidemiological studies have suggested that herpes zoster is associated with HIV infection.[6],[7]

The incubation period between HIV infection and the development of herpes zoster is, in most cases, several years,[8],[9] but due to continuous decline in immunity, herpes zoster may appear shortly after seroconversion.[10],[11] Assuming herpes zoster is a part of the clinical spectrum of HIV infection, we speculated that zoster might be a pointer to declining immunity, although lesser than it would be in full blown acquired immunodeficiency syndrome (AIDS). To test these hypotheses, we investigated the incidence of HIV seropositivity in men suffering from herpes zoster.

Materials and Methods

The study population included men with a diagnosis of herpes zoster who were seen in out patient clinic. All patients were then admitted in the Department of Dermatology and STD of a service hospital from Jan 1998 to Dec 1999. To determine the predictive value of herpes zoster for HIV infection during the above period, we requested physicians and medical officers who were working in out patient departments, internal medicine and ophthalmology to refer all patients with a history of herpes zoster, regardless of the presence or absence of other symptoms and signs or to refer patients when the herpes zoster occurred. None of these patients had HIV serology performed before they were enrolled in the study.

Patients who participated in this study gave informed consent. Patients with herpes zoster with previous diagnosis of AIDS related complex (ARC) or AIDS either in them or their wives were excluded from this study. Patients with underlying malignancies such as leukemia, Hodgkin′s disease, lymphomas or those receiving prolonged treatment with systemic corticosteroids for unrelated conditions were also not included in this study.

In addition to obtaining a detailed confidential questionnaire pertaining to sexual and drug history, a complete physical examination was done in all patients by one of the authors. The diagnosis of herpes zoster was made clinically. A history of or a presence of grouped vesicular dermatomal eruption was required. The diagnosis of herpes zoster was made on clinical grounds and usually confirmed by Tzanck smears when required.

Laboratory tests performed on patients with active herpes zoster infection included complete blood count with a differential cell count and routine examination of urine. Sera of all cases were tested for antibody to HIV by using a commercially available immunocomb test. An immunocomb test was considered seropositive if it was repeatedly reactive on two separate tests. Subsequently seropositivity was confirmed by Western blot assay.

Results

Out of 115 men suffering from herpes zoster, 11(9.5%) were found to be seropositive for HIV. None gave history of blood transfusion it the past and intravenous drug use. All had reportec with first episode of herpes zoster. Eleven of HI′ positive cases belonged to 21-40 years of age [Table - 1]. On the initial day of diagnosis of herpes zoster, our of 11 seropositive cases two patients had presented with weigh loss.

In the 11 seropositive patients with herpes zoster the dermatomal areas included trigeminal thoracic, thoracolumbar, and lumbosacral region.

Two cases had multiple cranial nerves involvement and one had disseminated herpes zoster [Table - 2].

Sexual behaviors

Out of 11 HIV seropositive case 9 (81.8%) were members of groups known to be at high risk for AIDS. They were heterosexual males who gave history of multiple sexual inter course with female commercial sex workers (CSW) 2 patients had one to three contacts and 7 men had four or more contacts. Analysis showed the being younger, staying away from home were significantly associated with having more number of sexual contacts. Two seropositive patients who were heterosexual males denied any contact with females known to be at high risk for AIDS [Table - 3]. None of the cases had used condom during sexual intercourse. Significant risk factors for inconsistent use of condom were complaint of lack of sexual pleasure during intercourse and higher number of sexual contacts.

None of the remaining 104 (90.5%) patients who were found to be seronegative for HIV at the time of their acute zoster infection were members of groups at high risk for AIDS. No risk factors could be identified for the seronegative patients who were all heterosexuals.

Complication

Of the 11 seropositive patients with herpes zoster 3 had resolution of skin lesions without complications. Of the remaining eight patients two had relatively minor complications including bacterial superinfection of the skin or conjuctivae that necessitated antibiotic therapy. Four patients had herpes zoster ophthalmicus with ocular complications. One patient had Ramsay Hunt syndrome with glossopharyngeal nerve involvement. 10 patients had post zoster scar formation. The clinical presentation of these patients are summarised in [Table - 4].

Discussion

Prior to the recognition of the current AI DS epidemic, herpes zoster had been most frequently seen in the elderly and among immunosuppressed patients.[12],[13] The clinical occurrence of localized zoster infection is believed to be the result of reactivation of a latent residual varicella-zoster virus (VZV) infection within a dorsal root ganglion in patients with previous varicella infection.

Primarily a disease of childhood varicella occurs in 90% children younger than 10 years of age. Among military recruits, mostly from ages 17 to 19 years, almost all recruits gave a positive history of varicella,[5] and the seronegativity rate was found to be 8.2%.[5]

Chickenpox is a disease of children. Herpes zoster occurs primarily in adults older than 5 years, although it can occur at any age.[1],[2],[3] By decades, the incidence of herpes zoster is 2.5/1000 persons affected per annum between the ages of 20 and 50 years, 5.09/1000 in those cases older than 80 years of age.[1] Overall each person who had a history of varicella experience an approximately 20% chance of acquiring herpes zoster in his lifetime. In our study all our patients with herpes zoster gave history of occurrence of varicella during their childhood. There is no evidence that herpes zoster can be directly acquired through contact with either varicella or zoster.[3] In our study none of our patients gave history of any contact with varicella or herpes zoster.

We found a high incidence of complications of herpes zoster among our patients who were found to be HIV seropositive. Although death due to zoster is likely to be exceedingly rare in HIV infected patients, zoster is an important cause of morbidity.[1]

Mild post herpetic pain was noticed in 5 HIV seropositive patients in our study. Glesby et al[4] have noticed that post herpetic neuralgia which was quite high in HIV seropositive patients as comparable with that (9%-14%) reported in population based studies of zoster in the pre-HIV infection era.[12]

A particularly high complication rate is seen with opthalmic zoster. Affecting 7% of all cases of zoster[13] in pre HIV era ophthalmic zoster is complicated by ocular disease in 20% to 70% of patients with HIV infection.[14],[15] All of our HIV seropositive cases having ophthalmic zoster had acute epithelial keratitis and one had oculomotor palsy.

One of our HIV seropositive patient had developed Ramsay Hunt syndrome involving facial, glossopharngeal and auditory nerves in combination with lesions of the external ear, tympanic membrane and anterior two thirds of tongue.

Motor paralysis from direct extension from the sensory ganglion to anterior horn cells occurs in 1 % to 5% of patients with zoster.[16] This paralysis usually occurs in the first 2 to 3 weeks after the onset of rash and can persist for several weeks. Localized motor deficiencies are found n up to 20% of patients with zoster involving the facial nerve.[16] In our study one case of herpes zoster involving trigeminal nerve had facial palsy and he was found to he HIV seropositive.

Although uncommon in immunocom-petent patients zoster had high risk of dissemination upto 40%,[9],[13] in immunocompromised persons and in HIV infections.[9] It is defined as more than 20 vesicles outside the primary and immediately adjacent dermatomes and cutaneous dissemination is followed by visceral (lungs, liver, brain) involvement in 15% of high risk patients. Occasionally, a few vesicles can be found remote from the primarily affected dermatome in 17 to 35% of immunocompetent patients. In our study one patient who was HIV seropositive had disseminated herpes zoster. None of the seronegative case had disseminated herpes zoster.

In a study of American homosexual men infected with HIV, the severity of zoster, the degree of pain, and infected lesions of cranial nerve and cervical dermatomes were associated with poor outcome of HIV related illness.[11] In our study, only the severity of the zoster pain was associated more in HIV seropositive men [Table - 4]. The occurrance of herpes zoster during the course of HIV infection has also been reported in the United States.[7],[15]

Our study has shown that a high percentage (9.5%) of apparently normal men with herpes zoster to be seropositive for HIV Desylva el al[17] from Mumbai have noted 22.5% of persons suffering from herpes zoster to be seropositive for HIV This high percentage may be due to increased promiscuity of men in Mumbai where the incidence of HIV infection is high among CSWs.[17] In a retrospective study Friedman-Kien et al[7] have found that 8% of HIV seropositive patients had prior herpes zoster. Buchbinder et al[10] have found that the incidence of herpes zoster per 1000 persons-year in HIV seropositive men was 29.4 cases and in HIV seronegative men 2.0 cases. Melbye et al[11] have estimated in 112 homosexual men suffering from herpes zoster that the cumulative incidence of AIDS of 22.8% within 2 years after herpes zoster, 45,5% within 4 years and an estimated 72.8% after 6 years.

This study as well as various studies from several workers[8],[10],[17],[18] have shown that patients with herpes zoster should be counseled about risk factors for HIV infection and when appropriate, offered HIV antibody testing.

The development of herpes zoster in otherwise asymptomatic individuals at high risk for HIV represent an early clinical sign that should alert the physician to consider the possibility of the impending development of an immune deficiency.[4],[7] In India, where diagnostic facilities are often limited, herpes zoster may be used as a sentinel event for estimating the number of HIV infected patients in a given population who will be requiring further screening tests for HIV.