Mucocutaneous manifestations in 150 HIV-infected Indian patients and their relationship with CD4 lymphocyte counts

INTRODUCTION

HIV infection leads to the progressive decline in cluster of differentiation (CD4+) T-lymphocyte counts, which have therefore been used to predict the stage of disease and hence guide management decisions. The laboratory determination of the CD4 count by flow cytometry is expensive and labour intensive. ¹ Lack of this facility in many centres necessitates dependence on clinical markers. HIV infection produces a panorama of mucocutaneous manifestations seen throughout the course of infection. Prevalences as high as 95% have been reported, ² though trends vary worldwide. ^3,4

Besides, skin can serve as a window to other systems. Hence, a thorough examination can guide to a diagnosis with severity or stage of affliction.

There are many studies pertaining to the mucocutaneous manifestations of HIV in western literature. Studies from India are few, and mostly from the southern part of the country. In view of the above scenario and the myriad mucocutaneous manifestations of HIV, the present study was carried out to determine the frequency of mucocutaneous manifestations in HIV/AIDS, to establish any association with CD4 counts and to highlight differences from previous studies.

MATERIAL AND METHODS

The present study was conducted in the outpatient and wards of the Department of Dermatology Venereology and Leprosy, Indira Gandhi Medical College, Shimla, over a period of one year from August 2007 to July 2008. A total of 150 HIV/AIDS patients (as per National AIDS Control Organisation guidelines), aged >12 years, enrolled at the antiretroviral therapy (ART) centre, Indira Gandhi Medical College, underwent a detailed physical examination with emphasis on mucocutaneous manifestations. All diagnoses were based on clinical criteria supplemented by laboratory procedures. CD4 counts were made by flow cytometry in the department of microbiology and most recent values were considered. Patients were divided into four groups according to the World Health Organization (WHO) immunological staging. The different mucocutaneous manifestations were analysed in relation to the CD4 counts. χ² test and Fischer's exact test were used for categorical variables as appropriate. Statistical software package, SPSS version 13.0 was used (SPSS Inc., Chicago, IL, USA). P values <0.05 were taken as significant.

RESULTS

A total of 150 HIV+ve cases were evaluated (79 women and 71 men). The mean duration of the disease from the time of diagnosis was 15.81 months. The mean age of patients was 35.4±15.3 years with 81.99% in 25–44 years age group. Ninety-six percent of the patients were married. Heterosexual contact was the commonest mode of transmission (96%). There was no case of transmission by intravenous drug abuse or homosexual contact. The majority of the women, 70 (88.6%), in the present study were housewives and drivers formed the largest group, 42 (59.15%), in men. More than half of the patients, 83 (55%), had only up to primary level of education. Fifty-nine (39.33%) patients had been on highly active antiretroviral therapy (HAART) for a mean duration of 6.22 months.

Mean CD4 count of the patients was 196.33 cells/mm³ (range 3–710 cells/mm³). Patients were distributed into WHO immunological groups on the bases of their CD4 counts (Table 1).

Mucocutaneous manifestations were seen in 96% of the individuals, 80–99% of the individuals in the different immunological groups. The maximum number of dermatoses per patient was eight, seen in one person in the severe immunosuppression group. Six patients had no mucocutaneous manifestations.

The mean number of dermatoses per patient was 2.9. The highest number of mean dermatoses, 3.29, was seen in individuals with severe immunosuppression (Table 1).

The frequency of infectious and non-infectious manifestations with mean CD4 counts and distribution across the WHO immunological groups is shown in Tables 2 and 3.

Other miscellaneous manifestations were facial dermatitis and polymorphous light eruption in four and two patients, respectively, and, acne, systemic sclerosis, Sweet's syndrome, leprosy, hidradenitis suppurativa, nummular eczema and irritant contact dermatitis in one patient each.

Patients were stratified into four groups according to the WHO immunological staging. There was a statistically significant association (P < 0.05) for candidiasis, scabies and paronychia in the infectious dermatoses group and oral pigmentation and diffuse hair loss in the non-infectious dermatoses group.

DISCUSSION

We examined 150 HIV patients over a one-year period. Women (79) and men (71) were present in comparable numbers. This was in contrast to other studies where men greatly outnumber women. ^5,6 The demographic profile reflected the attendance at the ART centre (the sole ART centre in the state at the time of the study) over the same period. In contrast to western studies where homosexual contact and intravenous drug abuse are one of the important modes of infection, we found no such case. ^4,5,7–10

Impairment of the skin immune system leads to microbial and malignant invasion and is believed to be responsible for the frequent occurrence of skin diseases. ¹¹

Dermatological manifestations at the time of examination were present in 96% of the patients. Studies have reported mucocutaneous manifestations in 40–95% of the patients. ^2,3,12–16 This high prevalence could be attributed to the severe immunosuppression, inclusion of mucosal findings and referral bias with the study setting in the department of dermatology. The mean number of mucocutaneous manifestations in the severe immunosuppression group, 3.29, was more than that in those without significant immunosuppression, 1.8. Patients with declining immunity (typified by CD4 counts) are more susceptible to infection. Also because of start of ART/other drugs for treatment or prophylaxis, these patients are exposed to cutaneous adverse effects of these drugs as well.

The most common mucocutaneous manifestation seen was candidiasis (35.33%), followed by seborrhoeic dermatitis (31.33%), oral pigmentation (29.33%), xerosis/ichthyosis (22.67%), pyodermas (22%), periodontitis (17.33%), nail pigmentation (16.67%), loss of lunula (15.33%), superficial fungal infection (14.67), diffuse hair loss (14%), herpes simplex virus infection (14%) and human papillomavirus infection (14%).

Most of the manifestations in our study population were comparable to previous western and Indian studies though a few points need to be highlighted.

Nail and oral pigmentary changes were one of the highlights of the study. Oral pigmentation was seen as blue black patches over the tongue, buccal mucosa, palate and other mucosal surfaces. Nail pigmentation was seen predominantly as longitudinal blue black bands. Munoz Perez et al. ⁷ and Zancanaro et al. ⁵ reported very low incidences compared with those seen in our study. These changes have rarely been reported by other western authors. Though, Cribier et al. ¹⁷ reported nail pigmentation in 14% of their study cohort. Criton et al. ¹⁸ from India reported pigmentary bands in the nail in 25% of their patients and related it to the presence of tuberculosis in all the patients. In our patients only 10 of the 25 were co-infected with tuberculosis and only four were on a zidovudine-based regimen. Only one patient with oral pigmentation was on a zidovudine-based regimen. Cutaneous pigmentary changes have been reported similarly in low incidences in American and East European populations but higher incidences have been reported in other Asian studies. ^5–7,19,20

Alopecia has been reported in previous studies in the range of 3–10%. ^3,6,7,13,21 We observed a higher percentage (14%) of patients having diffuse hair loss. Plausible explanation being the severe degree of immunosuppression and other associated chronic comorbid conditions. The association across the WHO immunological stages was statistically significant (P = 0.016).

Trichomegaly, characterized by elongated eyelashes, was seen in 9 (6%) patients. Though mentioned in literature, reference to the same has not been made in western and Indian studies. ^22,23 None of these patients was on a zidovudine-based regimen. All except two patients were in the severe immunosuppression group.

Premature complete greying of hair was seen in one patient.

Four patients had subcutaneous fungal infections, of which two had disseminated lesions. Cultures revealed Alternaria sp. and Trichophyton rubrum in one each. Histopathology supported the diagnosis of a fungal infection in the other two. Alternaria sp. was isolated from the skin biopsy specimen and nail culture of the same patient. This has been described previously in immunocompromised patients. ^24,25

One patient was diagnosed as borderline tuberculoid leprosy while on HAART at a CD4+ cell count of 139 cells/mm³. There was no evidence of reaction.

The frequency of pruritic papular eruptions reported in our study was significantly lower than that in western literature. ^6,7,13,16 Regional variations could be one explanation for the same. Another pruritic eruption, scabies, was reportedly higher in our study. ^4,7,19 Similar differences were also seen comparing other Indian studies. ^3,12,14,26

Reported incidences of psoriasis in western studies range from 2% to 4%, ^4,7,19 Very high incidences have been reported from Asia. ^2,6,20 We saw a single patient in psoriatic erythroderma with deforming arthritis of hands and feet. Institutution of HAART showed a dramatic response with the patient becoming ambulatory within the first week of treatment.

Sweet's syndrome was diagnosed in one female patient (fulfilling clinical criteria). She had presented with a sudden eruption of erythematous plaques over the face, hands and upper back with pseudovesiculation and associated fever. Histopathological examination showed findings suggestive of Sweet's syndrome. Though a rare association it has been reported in the literature. ²⁷

Incidences of xerosis/ichthyosis, pyodermas and molluscum contagiosum reported in our study were higher than that in previous Indian studies. ^{3,12,14,18,28,29}

Cutaneous neoplasms were not seen in the present study. Kaposi's sarcoma has been reported at high incidences in western literature though Indian reports are rare. ^4,9,10,26 The absence of homosexual individuals together with a low prevalence of human herpes virus 8 in Indians may explain the apparent absence in our study.

Western studies on cutaneous manifestations in HIV have been carried out in populations where the mode of transmission is predominantly homosexual or through intravenous drug abuse. Extrapolating those findings to Indian patients where up to 85% of the transmission is through heterosexual contact would be inappropriate. Regional disease patterns further compound the differences. Hence an active attempt should be made to evaluate these differences and define regional patterns that will guide clinicians to better patient diagnosis and management. Our study is one small step in that direction, where some such differences have been highlighted. Clinicians should pay heed to subtle manifestations like pigmentary changes and hair changes that may hint of a severe underlying immunosuppression.