Lipodystrophy in the patient with HIV: social, psychological, and treatment considerations.

Approximately 1.3 million people in the United States and an estimated 33.2 million worldwide are infected with HIV. In the past, HIV/AIDS was considered to be uniformly fatal. With the introduction of highly active antiretroviral therapy (HAART), HIV has become a chronic, manageable disease in countries that are able to provide this therapy. The preservation of lives has not been without complications. In these patients, metabolic and stereotypical body disfiguring fat changes have emerged and have been lumped under the term lipodystrophy. Lipoatrophy and fat accumulation are generally thought to be separate yet overlapping phenomena. The prevalence rates for lipoatrophy may be as high as 25% to 38%; estimates for fat accumulation vary widely (from 14%-63%). Far from being "purely cosmetic," these fat changes can have a profoundly negative social and psychological impact, causing patients to feel disfigured, isolated, and stigmatized. Further, lipodystrophy may also negatively impact compliance with HAART. While there is evidence that the use of new HIV medications can prevent the development of these fat changes, many patients already manifest fat abnormalities; switching HAART, especially after lipodystrophy has progressed, offers only limited benefit. In addition, many resource-poor nations continue to rely on older HAART out of necessity. Because of this, methods are needed to address disfiguring body shape changes. The authors review the prevalence of lipoatrophy and lipohypertrophy, focusing on the impact on patients as well as reviewing available treatment options.

Cutaneous manifestations of HIV in the era of highly active antiretroviral therapy: an institutional urban clinic experience.

BACKGROUND: Widespread introduction of highly active antiretroviral therapy (HAART) in the mid 1990s has altered the presentation of the cutaneous manifestations associated with HIV infection. OBJECTIVE: Our purpose was to evaluate the use of HAART on the prevalence and spectrum of cutaneous manifestations in HIV-infected patients. METHODS: A study of the initial visits of 897 HIV-infected patients at an urban dermatology clinic between 1996 and 2002 was performed. RESULTS: Folliculitis was the most common cutaneous disorder identified. Patients with CD4-positive cell counts less than 200 cells/mm3 had an increased prevalence of folliculitis and prurigo nodularis, whereas those with HIV viral loads higher than 55,000 copies/mL had a higher prevalence of idiopathic pruritus and candidiasis. Patients not receiving HAART had increased rates of folliculitis and prurigo nodularis. Patients receiving HAART had increased rates of photosensitivity and molluscum contagiosum. LIMITATIONS: This was a cross-sectional study in which temporality was unable to be determined. CONCLUSION: With ongoing therapeutic advancements, the cutaneous manifestations associated with HIV infection will continue to evolve.

DNA methylation in anal intraepithelial lesions and anal squamous cell carcinoma.

PURPOSE: Anal intraepithelial neoplasia is associated with human papillomavirus infection and may progress to invasive squamous cell carcinoma (SCC), which is increasing in immunocompromised patients. We hypothesize that anal intraepithelial neoplasia is associated with abnormal DNA methylation and that detection of these events may be used to improve screening programs. EXPERIMENTAL DESIGN: Seventy-six patients were identified who underwent anal cytology screening and subsequent biopsy at our institution between 1999 and 2004. The specimens from these patients included 184 anal biopsies [normal, n = 57; low-grade squamous intraepithelial lesion (LSIL), n = 74; high-grade squamous intraepithelial lesion (HSIL), n = 41; and invasive SCC, n = 12] and 37 residual liquid-based anal cytology specimens (normal, n = 11; LSIL, n = 12; HSIL, n = 14). The methylation status of the following genes was determined for each biopsy and cytology sample using real-time methylation-specific PCR: HIC1, RASSF1, RARB, CDKN2A, p14, TP73, APC, MLH1, MGMT, DAPK1, and IGSF4. RESULTS: Methylation-specific PCR analysis of biopsy samples revealed that DNA methylation was more common in SCC and HSIL than LSIL and normal mucosa. Specifically, methylation of IGSF4 and DAPK1 was prevalent in SCC (75% and 75% of cases, respectively) and HSIL (59% and 71%, respectively) but was absent in LSIL and normal biopsy samples. Methylation profiles of cytologic samples were similar to those found in the biopsy samples. CONCLUSIONS: Aberrant DNA methylation is a frequent event in anal HSIL and SCC. Methylation of IGSF4 and DAPK1 is specific for HSIL and SCC, and may serve as a useful molecular biomarker.

Cutaneous drug reactions associated with newer antiretroviral agents.

Skin is the most commonly affected organ in patients with HIV, and the incidence of cutaneous adverse reactions in persons infected with HIV versus those who are not infected is significantly higher. Cutaneous drug reactions contribute to increased morbidity and are often the cause of treatment nonadherence. Undoubtedly, the widespread use of highly active antiretroviral therapy has had a positive effect on the natural course of the disease; however, advances in HIV therapy will continue to increase the potential for cutaneous eruptions, further complicating the evaluation of skin manifestations that are so common in this disease. Distinguishing between cutaneous drug reactions and other cutaneous diseases associated with HIV infection can be challenging. Nevertheless, it is important for clinicians to be knowledgeable about the clinical characteristics and presentations of these reactions and to determine whether drug discontinuation is indicated.

Management options for facial lipoatrophy.

Lipoatrophy of the face, limbs, buttocks, and other subcutaneous tissue is increasingly recognized in HIV-infected patients. Although the pathogenesis of lipoatrophy and its association with metabolic abnormalities are becoming better understood with intense research efforts, there are very few treatment options, and the appearance of facial lipoatrophy can be devastating to patients. Treatment strategies include antiretroviral substitution, medications, and dermatologic and surgical interventions. Switching the HAART regimen produces only a modest effect. There are conflicting and generally disappointing data on the benefit of medications such as rosiglitazone. Surgical and dermatologic procedures are available for treatment of facial lipoatrophy, and several facial fillers have gained popularity as a means to restore the facial contour. Most are expensive, require multiple visits, and can produce scars. Temporary fillers require ongoing reapplication, and permanent fillers may sag if lipoatrophy progresses. All require a pure compound and expert technique and can be prohibitively expensive because these procedures are not generally covered by insurance. Prevention and early recognition of lipoatrophy and proper selection or early modification of antiretroviral treatment remain the best options.

Dermatologic diagnoses in the perianal area.

Perianal dermatosis can encompass lesions from benign eczematous processes to advanced malignancies. It is important for the colorectal surgeon to be able to distinguish common problems from more serious pathology. This article covers nonsexually transmitted diseases occurring in the intergluteal fold and perianal region. These include inflammatory dermatoses, bacterial and fungal infections, and other disease processes.

Clinical and epidemiologic characterization of photosensitivity in HIV-positive individuals.

BACKGROUND: An increased prevalence and severity of cutaneous photosensitivity has been recognized in association with human immunodeficiency virus (HIV) infection. However, this disorder remains poorly characterized in terms of its epidemiology, predisposing factors, clinical, and environmental associations. METHODS: To define the risk factors associated with the presence of photosensitivity among HIV-positive individuals, a cross-sectional study of 631 primary patient visits to an urban HIV Dermatology clinic between January 1997 and August 2001, inclusive, was conducted. A multivariate model was fit to estimate adjusted odds ratios for risk factors associated with photosensitivity diagnosis. Subsequently, a case-series of the patients with photosensitivity was reported. RESULTS: The overall prevalence of photosensitivity was 5.4%, while African-Americans (AA) exhibited a prevalence of 7.3%. In the multivariate model, using highly active anti-retroviral therapy (HAART) (OR=2.82, 95% CI: 1.13, 7.03) and being AA (OR=6.68, 95% CI: 1.56, 28.65) significantly increased the odds of photosensitivity. Patients with photosensitivity were more likely to present during periods of higher ultraviolet (UV) index (P=0.08). Two distinct clinical morphologies were noted: lichenoid and non-lichenoid, eczematous. Sub-morphologies in the non-lichenoid group were suggestive of differences in immunologic profile and estimated UV exposure. CONCLUSION: Photosensitivity associated with HIV infection is an increasingly recognized dermatologic condition with a heterogeneous clinical presentation. AA ethnicity and HAART were independent indicators for the diagnosis of photosensitivity, whereas CD4+ and UV exposure had non-significant associations. The subtleties in these and other clinical variables may directly aid in the recognition and diagnosis of this poorly characterized disorder.