INTRODUCTION

Reactivated latent varicella zoster virus from the dorsal root ganglia causes herpes zoster. Latency is a state in which the viral genome is present in a non-replicating stage in an infected cell, and a good knowledge of the mechanisms of latency can help in developing effective therapies for VZV infections of the nervous system. Many mechanisms, such as downregulating the expression of MHC class I and class II on the surface of virus-infected cells, help the virus to escape from the immune system of the host [1].

Herpes zoster (HZ) usually begins with a prodrome of symptoms such as pain, paresthesia, pruritus, tingling, etc., which can lead to misdiagnosis in many patients. It begins with painful grouped vesicles on an erythematous base along the dermatomal pattern. Edematous and erythematous papules, sometimes plaques, may precede the vesicles. Any cutaneous site may be affected, with the trunk representing the most common location [2].

Atypical presentations such as bullous variants, multi-dermatomal involvement, and disseminated variants are not uncommon, especially in immunocompromised individuals [3]. Although HZ usually occurs once in life, the recurrence rate may be about 4–5%. Complications occur in 13–40% of cases. The most frequent is post-herpetic neuralgia (PHN), whose incidence, affected by different definitions and by the age of the patients observed, is generally estimated between 10–20% of cases of HZ (up to 30% in the elderly). Generally, 80% of all PHN cases occur in individuals over 50 years of age [4–7].

Various studies show an increased occurrence of herpes zoster in human immunodeficiency virus (HIV) infected patients. In HIV patients, the age of onset for herpes zoster is lower, and it tends to be more severe with more complications [8,9].

Diagnosis is usually clinical, with a good history and the typical grouped vesicular rash along the dermatomes. Tzanck smear done from the vesicles shows multinucleated giant cells and acantholytic cells. Serological testing may be needed in atypical presentations [10].

Herpes zoster is associated with various immunosuppressive diseases such as diabetes, cancer, tuberculosis, and patients on immunosuppressive medications. Herpes zoster may present as an immune reconstitution disease, and many studies have shown increased incidence of stroke following herpes zoster [11,12].

HIV is a major public health problem, with more than 39 million lives affected so far. Many people are still unaware of their infection, which may lead to complications and death. Early detection, proper treatment, and preventive measures help in reducing HIV transmission, and unnecessary complications can be prevented, thereby improving the quality of life of those patients. Therefore, the present study was conducted to explore the demographic profile of herpes zoster, to determine the HIV seropositivity in herpes zoster patients, and to assess the CD4 count in HIV-positive herpes zoster cases. This may help and save many lives from unnecessary complications.

MATERIALS AND METHODS

A cross-sectional study was conducted on 120 patients with herpes zoster attending the Dermatology Outpatient Department at the Regional Institute of Medical Sciences, Imphal, Manipur, for 24 months from September 2015 to August 2017. All patients presenting with herpes zoster within the age group of 13–91 years were included, and those on immunosuppressive therapy, pregnancy, and lactation were excluded. A proforma was filled, and general physical examination, relevant systemic, and clinical examination were performed after obtaining informed consent. Laboratory tests, viz. Tzanck smear, blood for the serological test of HIV was done. The presence of HIV infection was confirmed as per the National AIDS Control Organization (NACO) guidelines. Diagnosis of clinically suspected cases was done with three ER (ELISA Rapid) HIV test kits. Analysis was done with IBM SPSS Statistics 21 for Windows (IBM Corp. 1995, 2012). Results on continuous measurements were presented as mean ± SD (min–max), and results on categorical measurements were presented as numbers (%). Chi-squared/Fisher’s exact test was used to find the significance of the study parameters on a categorical scale between two or more groups, and a p-value < 0.05 was considered statistically significant.

RESULTS

The study included 120 patients with herpes zoster. The mean age of the study group was 53.97 years. The majority belonged to age group 41–60 years (40%), followed by 21–40 years (28.3%) and 61–80 years (20.8%).

Out of the 120 patients with herpes zoster, 15 (12.5%) were tested HIV positive; more than half of them (8 cases; 53.3%) were in age group 20–40 years.

The majority of the patients were females (62.5%).

Out of the fifteen HIV-positive cases in the study, the majority of the patients (11 cases; 73.3%) had a CD4 count of more than 500 cells/mm³, followed by 3 (20%) with a CD4 count of 250–500 cells/mm³ and one (6.7%) had a CD4 count of 100–250 cells/mm³.

The thoracic dermatome was involved in the majority of the patients (63 cases; 52.5%) (Fig. 1a), followed by cranial nerve involvement in 21 (17.5%) and cervical nerve in 20 (16.7%) patients. The thoracic dermatome was the most affected dermatome in 8 (53.3%) and 55 (52.4%) cases of HIV-positive and HIV-negative patients, respectively. Cranial nerves were the second most commonly affected in HIV-positive patients (5; 33.3%) (Fig. 1b), as compared to HIV-negative patients, where cervical nerves were the second most commonly affected, in 19 patients (18.1%).

Figure 1: (a) Multiple grouped vesicles with pustules along the right first and second thoracic dermatomes. (b) Multiple grouped vesicles with crusting and necrosis along the right V2 division of the trigeminal nerve in an HIV-positive child.

Out of the 120 cases in our study, 86 cases (71.6%) had single dermatome involvement and 34 (28.3%) had multi-dermatome involvement. Single dermatomal involvement was observed in 82 (78.1%) of the HIV-negative cases and 4 (26.7%) of the HIV-positive cases, whereas the majority of the HIV-positive (11; 73.3%) patients had multi-dermatomal involvement as compared to only 23 (21.9%) of HIV-negative cases. The multi-dermatomal involvement in HIV-positive patients compared to HIV-negative cases was statistically significant, with a p-value of < 0.01 (Table 1).

Table 1: Number of affected dermatomes based on HIV status.

Out of 17 diabetic cases with herpes zoster in the study, 13 (76.5%) diabetic cases had multi-dermatome involvement, and only 4 (23.5%) had single dermatome involvement.

Thirteen (10.8%) out of the 120 patients had post-herpetic neuralgia (PHN), following HZ infection. Out of 15 HIV-positive cases, 7 (46.7%) developed PHN, while 8 (53.3%) did not. Among 105 HIV-negative patients, 99 (94.3%) did not develop PHN. PHN was much higher in HIV-positive than in HIV-negative cases, and this finding was statistically significant (p-value < 0.01) (Table 2).

Table 2: Distribution of patients based on post-herpetic neuralgia according to HIV status.

Out of 17 diabetic cases with herpes zoster, only 4 (23.5%) developed PHN.

Hypertension (28; 23.3%) was the most common comorbidity associated, followed by diabetes (17; 14.2%). Rheumatoid arthritis was associated in 4 (3.3%) patients. Several patients had chronic renal failure and cancer (2.5% each), and 2 patients had tuberculosis (1.7%).

The most common complication following herpes zoster infection in our study was secondary infection (in 14 cases; 11.7%), followed by PHN in 13 (10.8%) cases. Dyspigmentation was noted in 9 (7.5%) patients, and scar/keloid and ocular complications in 5 (4.2%) and 4 (3.3%) patients, respectively. Forty-five (37.5%) cases in the study had complications following herpes zoster infection.

DISCUSSION

In this study, the majority of the patients (48; 40%) were between 40 and 60 years of age with a mean age of 53.97 years, which was similar to findings of Babamahmoodi et al. [13] (56.3 ± 20 years), and Chung et al. [14] with 51 ± 16.5 years. Our result was in contrast to the study by Cebrián-Cuenca et al. [15], where the mean age was 61.1 years, and to a study by Smetana et al. [16], where the majority of the patients were above 70 years of age.

Among the HIV-positive cases in our study, the majority (8; 53.3%) were in the age group of 20–40 years, with a mean age of onset of 28.8 years. This finding was comparable to studies by Naveen et al. [17] and Abdalla et al. [18]. Many studies conclude that herpes zoster is common in the older age group, whereas in immunocompromised patients, it may present in an early age [8].

In our study, there was a female preponderance, with a male-to-female ratio of 1:1.66. Out of the 120 patients included in the study, 75 (62.5%) were females, similarly to findings by Cebrián-Cuenca et al. [15] and Costache et al. [23]. This was, however, in contrast to studies by Gebo et al. [19] and Usha et al. [20], where male preponderance was noted.

Out of the 120 patients with herpes zoster with unknown HIV status included in this study, 15 (12.5%) were found to be HIV positive, which was in concordance with studies by Kar et al. [21], Dubey et al. [22] and Abdalla et al. [18], where HIV positivity was seen in 9.5%, 13.04%, and 15%, respectively. This finding was in contrast to studies by Usha et al. [20] and Naveen et al. [17], where HIV-positive cases were 32% and 37.7%, respectively. In a study by Costache et al^. [23], HIV positivity was very low in herpes zoster patients (4%). This difference in different studies could be due to differences in HIV prevalence in different regions.

The majority of the HIV-positive patients in our study (73.3%) had a CD4 count of more than 500 cells/mm³, followed by 20% with a CD4 count of 250–500 cells/mm³ and 6.7% with 100–250 cells/mm³. Shearer et al. [24] in a study on HIV-positive patients on ART found a mean CD4 count of 100 cells/mm³. This contrasting result may be because, in our study, we included patients whose HIV status was unknown on presentation, in contrast to Shearer et al. [24], where the cases were of herpes zoster with HIV on ART.

The majority of the patients had involvement of the thoracic dermatome (52.5%), followed by cranial nerves (17.5%), cervical nerves (16.7%), and 13.3% had lumbo-sacral nerve involvement. This finding was comparable with similar studies by Naveen et al. [17], where the thoracic dermatome was most commonly involved, in 46.6%, followed by cranial nerves in 18.8%. The involvement of the thoracic dermatome was much higher (87.5%) in a study by Usha et al. [20]. In a study by Babamahmoodi et al. [13], 59% had head and neck involvement, and 37% had thoracic involvement. In both HIV-positive and HIV-negative cases in the present study, the thoracic dermatome was the most commonly involved. The second most common dermatome in HIV-positive patients was cranial nerves (33.3%), and the cervical nerves in HIV-negative patients (18.1%). Onunu et al. [25] had similar findings, where cranial nerve involvement was higher in HIV-positive individuals. In a study by Abdalla et al. [18], it was also found that 67% of HIV-positive individuals had involvement of the head region.

In this study, 71.6% had single dermatomal involvement, which conformed with studies done by Dubey et al. [22] and Naveen et al. [17]. Our finding was in contrast to a study by Usha et al. [20], where 42% of cases had multi-dermatome involvement; this could be because of the higher percentage of HIV-positive patients in that study. Multi-dermatomal involvement was seen in 73.3% of the HIV-positive patients in this study. The higher incidence of multi-dermatomal involvement in HIV-positive cases as compared to HIV-negative individuals was statistically significant (p-value < 0.01). This finding was similar to the study by Usha et al. [20]. Out of 15 diabetic patients, 76.5% had multi-dermatome involvement. This higher incidence of multi-dermatomal involvement in HIV and diabetic patients was because both groups were immunocompromised, therefore unable to localize the infection to a single dermatome.

Out of 120 patients, post-herpetic neuralgia (PHN) was seen in 10.8% of the patients, while 46.7% of the HIV-positive patients had PHN. This higher incidence of PHN in HIV-positive cases as compared to HIV-negative cases was statistically significant (p-value < 0.01). Similarly to our study, 12% of patients developed PHN in the study by Usha et al. [20]. Our result was comparable to Kar et al. [21], where PHN in HIV-positive cases was noted in 63.6% of cases.

In the present study, 47.5% of patients had one or more co-morbidities, among which hypertension was seen in 23.3%, diabetes mellitus in 14.2%, rheumatoid arthritis in 3.3%, chronic renal failure and cancer in 2.5% each, and tuberculosis in 1.7%.

The most common complication noted in the present study was secondary infection (11.7%), followed by PHN in 10.8%, dyspigmentation in 7.5%, and scar formation and ocular complications in 4.2% each.

The limitations of this study were the small sample size and short study period.

CONCLUSION

Herpes zoster in the younger age group with multi-dermatomal involvement warrants HIV testing. Patients with early and severe involvement should be routinely screened for HIV, which may help in early diagnosis and in preventing complications related to HIV.

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