Granulomas in acquired immunodeficiency syndrome-associated cutaneous Kaposi sarcoma: evidence for a role for Mycobacterium tuberculosis.

BACKGROUND: Co-lesional acquired immunodeficiency syndrome-associated cutaneous Kaposi sarcoma (AIDS-KS) and Mycobacterium tuberculosis-associated granulomatous inflammation are undocumented. METHOD: Retrospective appraisal of skin biopsies with co-lesional AIDS-KS and microscopic tuberculosis (TB). RESULTS: Sixteen biopsies from nine males and seven females form the study cohort. Histological assessment confirmed nodular and plaque KS in 12 and 4 cases each, respectively. Necrotizing, non-necrotizing and a combination of necrotizing and non-necrotizing granulomatous inflammation were present in nine, two and five biopsies each, respectively. The identification of acid fast bacilli on Ziehl-Neelsen staining and M. tuberculosis on polymerase chain reaction confirmed co-lesional TB in 15/16 biopsies. Co-lesional AIDS-KS and lichen scrofulosorum, hitherto undocumented, were confirmed in one biopsy. The histopathological findings served as a marker of human immunodeficiency virus (HIV) infection, visceral TB, therapeutic noncompliance and multidrug resistant pulmonary TB in nine, eight, five and one patient, respectively. M. tuberculosis was cultured from sputum or nodal tissue of all patients. CONCLUSION: Granulomatous inflammation in KS requires optimal histopathological and molecular investigation to confirm an M. tuberculosis origin. The cutaneous co-lesional occurrence of AIDS-KS and microscopic TB may serve as the sentinel clue to HIV infection, systemic TB, therapeutic noncompliance or multidrug resistant TB.

Molluscum-like cutaneous cryptococcosis: a histopathological and pathogenetic appraisal.

BACKGROUND: Molluscum-like cutaneous cryptococcosis (MLCC) is characterized by hypopigmented or skin-colored papules with central umbilication. The histomorphological nuances of Cryptococcus neoformans infection that effect mimicry of molluscum contagiosum are undocumented. This histopathological study was undertaken to assess the histopathological characteristics of MLCC and to determine potential evolutionary pathogenetic mechanisms and significance. METHODS: A 5-year retrospective re-appraisal of cutaneous cryptococcosis biopsies with a clinical molluscum-like appearance. RESULTS: All 26 specimens with a molluscum-like appearance showed a dome-shaped architecture with central invagination and dermal C. neoformans of varying size and shape, with capsular fragmentation; 20 biopsies had a paucireactive appearance and 6 combined granulomatous and paucireactive foci. Twenty, two and four biopsies showed transepidermal, transfollicular and combined transepidermal and transfollicular elimination (TFE) of fungi, necrobiotic collagen and debris through the central invagination, respectively. Subepithelial neutrophils and collagen necrobiosis were identified in 8 and 14 cases each, respectively. Varying sized and shaped yeasts, capsules of varying width, capsular fragmentation and collagen necrobiosis were ultrastructurally confirmed. CONCLUSION: Transepithelial and TFE of C. neoformans, necrobiotic collagen, inflammatory cells and cellular debris account for the morphological attributes of MLCC. The eliminatory process is a potential public health hazard, serving as a vehicle for C. neoformans transfer to the exterior.

Generic antiretroviral efficacy in AIDS-associated Kaposi's sarcoma in sub-Saharan Africa.

Generic antiretroviral drugs are pivotal in the implementation of WHO's '3 by 5' programme. However, clinical experience with generics in sub-Saharan Africa is insufficiently documented. We report on 50 patients with HIV-associated Kaposi's sarcoma treated with generic fixed-dose highly active antiretroviral therapy. At 52 weeks, 74% achieved an undetectable viral load of < 50 copies/ml, 86% achieved < 400 copies/ml, and a 3.1 log10 decline from baseline. Side-effects were minimal. The outcomes support the use of generic antiretroviral therapy.

A randomized controlled trial of highly active antiretroviral therapy versus highly active antiretroviral therapy and chemotherapy in therapy-naive patients with HIV-associated Kaposi sarcoma in South Africa.

BACKGROUND: The optimal approach to HIV-associated Kaposi sarcoma (HIV-KS) in sub-Saharan Africa is unknown. With large-scale rollout of highly active antiretroviral therapy (HAART) in South Africa, we hypothesized that survival in HIV-KS would improve and administration of chemotherapy in addition to HAART would be feasible and improve KS-specific outcomes. METHODS: We conducted a randomized, controlled, open-label trial with intention-to-treat analysis. Treatment-naive patients from King Edward VIII Hospital, Durban, South Africa, a public-sector tertiary referral center, with HIV-KS, but no symptomatic visceral disease or fungating lesions requiring urgent chemotherapy, were randomized to HAART alone or HAART and chemotherapy (CXT). HAART arm received stavudine, lamivudine, and nevirapine (Triomune; CXT arm received Triomune plus bleomycin, doxorubicin, and vincristine every 3 weeks. When bleomycin, doxorubicin, and vincristine were not available, oral etoposide (50-100 mg for 1-21 days of a 28-day cycle) was substituted. Primary outcome was overall KS response using AIDS Clinical Trial Group criteria 12 months after HAART initiation. Secondary comparisons included time to response, progression-free survival, overall survival, adverse events, HIV control, CD4 reconstitution, adherence, and quality of life. RESULTS: Fifty-nine subjects were randomized to HAART and 53 to CXT; 12-month overall KS response was 39% in the HAART arm and 66% in the CXT arm (difference, 27%; 95% confidence interval, 9%-43%; P = 0.005). At 12 months, 77% were alive (no survival difference between arms; P = 0.49), 82% had HIV viral load <50 copies per milliliter without difference between the arms (P = 0.47); CD4 counts and quality-of-life measures improved in all patients. CONCLUSIONS: HAART with chemotherapy produced higher overall KS response over 12 months, whereas HAART alone provided similar improvement in survival and select measures of morbidity. In Africa, with high prevalence of HIV and human herpes virus-8 and limited resources, HAART alone provides important benefit in patients with HIV-KS.

Management of atopic dermatitis in adolescents and adults in South Africa.

OBJECTIVE: The guidelines for the management of atopic dermatitis in patients older than 18 years have been developed in an attempt to improve the outcomes of treatment of this condition in South Africa. This condition has a major impact on the quality of life of sufferers and it is expected that these guidelines, if implemented, will play a role in achieving this. RECOMMENDATIONS: All health care workers involved in the management of atopic dermatitis should take note of these guidelines and try to implement them in clinical practice as far as possible. All treatment methods and procedures not substantiated by evidence from the literature should be discontinued and avoided to decrease the financial burden of dermatitis treatment. VALIDATION: These guidelines were developed through general consensus by a group of five South African dermatologists, from evidence based on extensive literature review. Draft documents were made available for comment to the dermatology community as a whole, via the official website of the Dermatological Society of South Africa. They were also presented and discussed at the annual congress of the Dermatological Society of South Africa. All input from these sources, where appropriate, were then incorporated into these guidelines.

Tuberculids as sentinel lesions of tuberculous epididymo-orchitis.

BACKGROUND: Tuberculids are rarely associated with male genital tract tuberculosis (TB). Tuberculous epididymo-orchitis (TBEO) has been associated rarely with papulonecrotic tuberculid (PNT) but not with erythema induratum (EI) or the simultaneous occurrence of different tuberculids. METHODS: A retrospective assessment of tuberculids that occurred with underlying TBEO was carried out. RESULTS: Five patients, four with one and one with two skin biopsies, with clinical diagnoses of PNT (two), EI (one), impetigo (two) and calf ulcer (one), formed the study cohort. Histopathological evaluation confirmed PNT and EI in four and two skin biopsies, respectively. Two patients who returned for follow-up were commenced on anti-tuberculous therapy. All patients sought medical attention 3-34 months later for tender right-sided (two) and left-sided (three) testicular masses. Orchidectomy was undertaken following a poor clinical response to empirical treatment with trimethoprim sulfamethoxazole. Pathological examination of the testis and epididymis confirmed TBEO. The patients were initiated on anti-tuberculous therapy. There was dramatic healing of the skin lesions. CONCLUSION: Tuberculids are a sentinel cutaneous manifestation of visceral TB and a valuable external audit of treatment compliance and response. Heightened recognition of and more rigorous genitourinary tract investigation are necessary to identify occult or asymptomatic TBEO as the underlying cause of tuberculids.

Carraguard Vaginal Gel Safety in HIV-Positive Women and Men in South Africa.

OBJECTIVE: To assess the safety of the candidate microbicide Carraguard gel in HIV-positive women and men. DESIGN: A randomized, placebo-controlled, triple-blinded clinical trial of Carraguard gel when applied vaginally once per day for 14 intermenstrual days by sexually abstinent and sexually active HIV-positive women; and when applied directly to the penis once per day for 7 days by sexually abstinent HIV-positive men. METHODS: In each cohort (n = 20 per cohort), participants were randomized to Carraguard, methylcellulose placebo, or no product (1:1:1). In addition to traditional microbicide trial safety endpoints, the effects of microbicide use on vaginal shedding of HIV-1 RNA and markers of genital inflammation, epithelial sloughing, and microhemorrhage were also explored. RESULTS: Gel compliance was high in both gel-use groups in the 3 cohorts. Carraguard use was not associated with abnormal genital findings, other abnormal clinical findings, markers of genital inflammation, epithelial sloughing or microhemorrhage, or self-reported symptoms in women and men, or with abnormal vaginal flora or genital shedding of HIV-1 RNA in women. Adverse events were mostly mild, not attributed to gel use, and similarly distributed between groups. CONCLUSIONS: Once-daily use of Carraguard for 7 to 14 days appeared to be safe in HIV-positive women and men.

Lymphedematous HIV-associated Kaposi's sarcoma.

BACKGROUND: Advanced Kaposi's sarcoma is frequently associated with chronic lymphedema (cLO). The histopathological features of lymphedematous HIV-associated KS (KS) are poorly documented and the co-existence of fibroma-like nodules in lymphedematous KS is under-recognized. The aims of this study were to assess the clinicopathological spectrum and diagnostic difficulties associated with lymphedematous KS and to highlight the clinicopathological profile of fibroma-like nodules. In addition, the pathogenesis of fibroma-like nodules and cLO is revisited. MATERIALS AND METHODS: Prospective 17-month clinicopathological study of all biopsies from patients with lymphedematous KS. RESULTS: Seventy-four biopsies, the majority from the lower limbs, from 41 patients were evaluated. Nineteen, 14, five and three patients had one, two, three or four biopsies each, respectively. In 14 biopsies, there was poor clinicopathological correlation of KS stage. Exclusive lesional KS (patch, plaque, nodule or lymphangioma-like) was identified in 29 biopsies; 23 and eight biopsies demonstrated KS or fibroma-like morphology and the adjacent dermis demonstrated cLO. There was variable intratumoral and peritumoral venous compression and lymphatic dilatation. Fourteen biopsies demonstrated cLO exclusively. Smaller fibroma-like nodules lacked KS spindle cells, whereas >5 mm nodules demonstrated focal KS spindle cell proliferation and aggregation on extensive sectioning. The subcutis of 42 biopsies demonstrated variable fibrosis, hemosiderin deposits, lymphocytes, plasma cells, KS, interstitial granular material and pools of lymph fluid. Subcutaneous abscesses were identified in six biopsies. All biopsies had variable epidermal features of cLO. CONCLUSIONS: cLO influences clinicopathological correlation of KS stage and may also mask the presence of KS and the co-existence of subcutaneous abscesses. Smaller fibroma-like nodules are hypothesized to be a manifestation of cLO that have the potential to acquire the characteristics of KS. Lymphatic and venous obstruction, protein-rich interstitial fluid, tissue hemosiderin and subcutaneous infection are hypothesized to play a combined role in the evolution and perpetuation of cLO.

Tinea capitis in Kwa-Zulu Natal, South Africa.

Tinea capitis is the most common dermatophyte infection in children. The hair involvement can be classified as endothrix, ectothrix, or favus, and the clinical appearance is variable. The goal of this study was to determine the demography, etiology, and clinical patterns of tinea capitis in South Africa. A prospective, cross-sectional study was conducted over a 1-year period. All cases were classified clinically and subject to Wood light examination, microscopy, and culture. One hundred patients were studied. The male:female ratio was 1.4:1. The mean age was 4.6 years (range 1-11 years). Trichophyton violaceum was isolated in 90% of positive cultures. Wood light was positive in one patient with Microsporum gypseum. The most common clinical variety was the "black dot" type, seen in 50% of patients. Twenty percent of the children presented with more than one clinical type simultaneously. We concluded that the most common cause of tinea capitis in South Africa is T. violaceum. The presentation is variable.