This study consisted of two phases. In the first phase, we recruited HIV-positive patients with PPE and performed a cross-sectional, descriptive study to determine the prevalence and etiology of PPE in HIV-positive patients. In the second phase, we recruited HIV-positive patients without PPE, and we compared them to the previously recruited HIV-positive patients with PPE to assess risk factors that may be associated with this skin disease.
The study was performed at the Government Hospital of Thoracic Medicine (GHTM), a tertiary care hospital in Chennai, India. GHTM is India's largest publicly supported HIV care and treatment facility center. GHTM has been providing HIV/AIDS care since 1990 and ARV therapy since 2004, and it is recognized for its care and treatment of people living with HIV and AIDS. An estimated 300–500 HIV-positive patients visit GHTM each day for HIV-related care, treatment, and counseling.
This study was carried out with approval from institutional review boards at the University of California, San Francisco (UCSF), and GHTM. All subjects were provided information from a trained study investigator about the methodology, information to be collected, potential risks, and purpose of the study in their preferred language (Tamil, English, or Telugu). After counseling and prior to enrollment, each patient provided written consent to be part of the study. Verbal consent was obtained for taking photographs and for clinical use as well as study purposes. All records were entered into a secure, electronic database (Epi Info v. 3.5.1 [Centers for Disease Control and Prevention]) for analysis.
Patient screening and enrollment were carried out over a 12-week period from April to June 2008. Known HIV-positive, ARV-naïve patients, 18 years of age and older, who were being evaluated by trained hospital staff at GHTM as part of standard HIV-related services, were queried regarding pruritic rash originating on extremities for a duration longer than one month. If they met these criteria, they were examined by an Indian-trained dermatologist for clinical confirmation of PPE and a 4.0 mm punch biopsy was taken from a skin lesion that both the patient and the dermatologist identified as the newest and most representative lesion of PPE. Specimens were prepared in New Delhi and sent to the All India Institute of Medical Sciences (AIIMS), New Delhi. Histologic slides were read by an Indian-trained dermatopathologist with previous experience in HIV dermatopathology, including PPE. The dermatopathologist was blinded to the on-site clinical diagnoses. Subjects included as cases were those who met clinical criteria for PPE with histologic confirmation. Histologic confirmation of PPE was defined as a moderately dense to dense, superficial and deep, perivascular and interstitial infiltrate of lymphocytes and eosinophils beneath the epidermis, consistent with “insect bite reaction.” Serial sections were examined to exclude a folliculocentric pathologic process, including EF.
Rash severity was evaluated using an objective “rash-severity scale” for PPE that was created for this study. Lesions that were limited to either the upper or lower extremities were described as “mild.” When both the upper and lower extremities were involved, the rash was categorized as “moderate” disease. A “severe” rash included lesions present on the extremities as well as the trunk. Lesions present all over the body, including the face, were defined as “very severe.”
In order to assess for potential risk factors, subjects meeting inclusion criteria were administered an oral and detailed questionnaire in their preferred language (Tamil, Telugu, or English) by trained clinicians. The questionnaire included items assessing the history of the rash, environmental and other types of exposures, and prior history of skin disorders ().
Questionnaire administered to all subjects in their preferred language
Routinely collected demographic and clinical data from the electronic THIS (TB and HIV Information System) database at GTHM were obtained for each subject with regard to immunologic status, which included WHO status, CD4 count, and date of HIV diagnosis. The THIS electronic patient database was implemented in 2001 at GHTM and collects routine and longitudinal data for patients during each visit to the facility using a unique patient identification number that is generated at the initial patient visit. This secure system stores and maintains patient data and can be accessed to inform patient care as well as to generate program-level reporting to the facility and other stakeholders.
To identify potential risk factors related to PPE, we recruited a control group, which included known HIV-positive, ARV-naïve patients older than 18 years of age, who did not have an active skin rash at the time of screening. Patients who reported experiencing skin lesions or pruritis, or who had any evidence of skin lesions on clinical exam, were excluded from this part of the study. Patient screening and enrollment were carried out over a one-week period in October 2008. After the same consent process as described in the “Part I” section was performed by trained hospital staff, the same questionnaire discussed in “Part I” was orally administered in the patient's preferred language ().
We performed statistical analysis using Epi Info version 3.5.1 and SPSS version 11.0 (SPSS Inc., Chicago, IL). Similar data were collected for both the PPE subjects and the control populations. Unique outcome measures included the histological characteristics of new pruritic lesions in the study population. Categorical variables such as gender, urban versus rural residence, occupation, treatment history, CD4 count, use of insect repellents, and environmental exposures were evaluated using the χ2 test (or the Fisher exact test when an expected value for a category was less than 5). The t-test was used to evaluate differences in age and the duration since HIV diagnosis. The Mann-Whitney test was used to compare non-normally distributed values such as CD4 cell count. A p-value of less than 0.05 was considered to be statistically significant.