Evaluation of a novel 308-nm monochromatic excimer light delivery system in dermatology: a pilot study in different chronic localized dermatoses.

BACKGROUND: Recently, units have been developed that are capable of delivering large fluences of narrowband ultraviolet (UV) B selectively to cutaneous lesions within a reasonable time. OBJECTIVES: To analyse the efficacy of a novel nonlaser 308-nm monochromatic excimer light (MEL) delivery system in various dermatoses usually treated by narrowband UVB phototherapy. METHODS: Fifty-four patients with chronic and resistant localized dermatoses were enrolled in a prospective study: 17 with palmoplantar pustular psoriasis, seven with plaque-type psoriasis, four with nail psoriasis, eight with chronic atopic dermatitis of the hands, 10 with chronic nonatopic dermatitis of the hands and eight with alopecia areata. The 308-nm xenon chloride MEL delivery system (Excilite; DEKA, Florence, Italy) was used to produce an average incident dose rate of 50 mW cm(-2) at a tube-to-skin distance of 15 cm and with a maximum irradiating area of 512 cm2. The initial dose was based on multiples of a predetermined minimal erythema dose (MED), and subsequent doses were based on the response to treatment. Treatments were scheduled weekly for a maximum of 10 weeks. Clinical responses were evaluated using photographic documentation and (except for alopecia areata) clinical score. RESULTS: The MED ranged from 250 to 350 mJ cm(-2) (mean +/- SD 318.2 +/- 28.4). MEL at 308 nm was the most effective for palmoplantar pustular psoriasis with a mean improvement of 79% after a mean of 5.3 treatments and a mean dose of 11.8 MED per treatment. Plaque-type psoriasis was significantly less sensitive to treatment and nail psoriasis demonstrated no benefit from treatment. Chronic palmar atopic dermatitis was cleared in two patients and the mean improvement was 54% as compared with 46% in patients with chronic nonatopic dermatitis of the hands. Four complete regrowths among the eight patients with alopecia were observed after a mean of 5.1 treatments. The percentages of improvement had significantly decreased at the 6-month visit, and only four patients (24%) with palmoplantar pustular psoriasis still demonstrated a significant improvement. Common side-effects included intense erythema and, more rarely, blisters, but these were well tolerated. CONCLUSIONS: Our preliminary results confirm the efficacy of this novel 308-nm MEL delivery system, which appears to be effective and safe for palmoplantar pustular psoriasis. To a lesser extent, plaque-type psoriasis, chronic atopic and nonatopic dermatitis of the hands and alopecia may also benefit from this treatment.

[Risk factors for Abacavir-induced hypersensibility syndrome in the "real world"]. / Facteurs de risque de syndrome d'hypersensibilité à l'Abacavir en pratique clinique de routine.

UNLABELLED: Abacavir (ABC) is a generally well-tolerated NRTI. However, up to 5% of patients may develop hypersensitivity syndrome (HSS) within the first weeks of treatment. The objectives of this study were to describe the side effects of ABC, to evaluate the incidence of the ABC-HSS, and to identify the risk factors of HSS after first exposure to ABC in a cohort of patients followed up in a university HIV clinic. METHODS: The charts of all HIV-infected patients who started ABC between February 1998 and May 2002 were reviewed. HSS was defined as the onset, within 8 weeks of ABC initiation, of either a skin rash associated with at least one of the following symptoms (fever, gastrointestinal symptoms, respiratory symptoms, myalgia, malaise) or at least three of the above symptoms in the absence of rash. A multivariate logistic regression analysis was performed to identify risk factors of HSS. RESULTS: Of the 191 patients studied (134 M, 57 F, mean age 39 years), 53 (27.8%) presented with manifestations that were regarded as potential side-effects of ABC. Ten (5.2%) developed HSS, none of whom died. Two factors were independently associated with an increased risk of HSS: history of allergy to nevirapine (OR 8.1, 95% CI 1.6-40.5, p = 0.02), and being naïve to ART (OR 5.8, 95% CI 1.2-28.5, p = 0.04). CONCLUSION: This study "in the real world" confirms that the incidence of ABC-induced HSS is of about 5%. It also confirms that HSS occurs more frequently in patients with a history of allergy to nevirapine and in ART-naïve patients.

[Predictive factors of virological response to primary antiretroviral treatment]. / Facteurs prédictifs de la réponse virologique à un premier traitement antirétroviral.

OBJECTIVES: During 1999, first-line antiretroviral combinations for the treatment of HIV infections have diversified. The aim of our study was two-fold: define the factors associated with initial success and define the factors associated with virological rebound in patients in whom a primary antiretroviral therapy (ARV) had been initiated between 1999 and 2000. METHOD: We conducted a retrospective multicenter study regrouping 6 HIV clinics in the North-East of France. Data were Issued from the patients medical files. Primary success was defined as plasma HIV RNA viral load (VL<200 copies/ml within 6 Months of therapy and two consecutive VL<200 copies/ml. Virological rebound was defined as two consecutive VL>1000 copies/ml after primary success. Predictors of success were determined using multivariate logistic regression and SAS 8.2 software. RESULTS: Analysis concerned 123 patients, with 19% stage C when ARV was initiated. Their median CD4 and PVL values at baseline were 233/mm3 and 73,000 copies/ml respectively. The median duration of follow-up was of 20.7 Months [(mean (STD): 20.6 (6.7)]. Initial treatments were distributed as follows: 2 NRTI + 1NNRTI, n=66 (54%); 2 NRTI+1PI, n=44 (36%); 3 NRTI, n=13 (10%). Primary success was obtained in 100 (81,3%) patients. Among these, 6 (6%) developed secondary virologic failure. The absence of change in initial ARV treatment within first 4 Months, and good compliance to treatment were statistically associated with primary success in univariate (p values respectively: 0.004 and 0.04) and in multivariate analysis (p respectively: 0.009 and 0.03). The proportion of failure was higher in the patients with lower baseline CD4 levels lesser than 200/mm3 (p=0.09). CONCLUSION: In this cohort of patients, tolerance and compliance to the first regimen were associated to primary success. These results emphasize the role of compliance in primary success and reinforces need to work on compliance in such patients.

Anal human papillomavirus DNA screening by Hybrid Capture II in human immunodeficiency virus-positive patients with or without anal intercourse.

High risk human papillomaviruses (HPVs) have emerged as risk factors for anal carcinoma, of which incidence is higher in HIV-positive patients than in the general population. The aim of our study was to investigate the prevalence and risk factors for anal HPV infections in HIV-positive patients with or without history of anal intercourse. Fifty HIV 1-infected patients (36 men and 14 women) were tested at entry and followed-up every 3 months for one year for the presence of anal HPV DNA by the Hybrid Capture II trade mark assay. A series of 50 HIV-negative subjects matched for age and sex served as controls. At enrollment, anal HPV DNA was present in 29/50 HIV-positive patients (58 %) and in 3/50 control subjects (6 %). High risk (HR) HPV genotypes were detected in 20/50 HIV-positive patients (40 %) with no difference in homosexual men and other HIV-positive patients. Risk factors for HPV infection were CD4 + cell counts less than 500/microL (RR: 2.13 [95 % CI: 1.0-4.7]) and history of anogenital warts (RR: 2.36 [95 % CI: 1.2-4.6]). The HPV load was higher in patients with CD4+ < or = 500/microL than in patients with CD4 + > 500/microL (p < 0.04). During the follow-up, anal HR HPV DNA was repeatedly identified at high levels in 5 HIV-positive patients. There is some convincing evidence that HIV-positive patients with low CD4+ cells, whatever the routes of HIV transmission, have a high rate of anal HPV infection and might be at increased risk of developing anal neoplastic lesions. Identifying HR HPV infection might be warranted in immunosuppressed patients.

Nonspecific secretory immunity in HIV-infected patients with oral candidiasis.

Buccal and digestive tract opportunistic infections occur frequently in patients infected by HIV. In this study, we measured lysozyme (Lz), lactoferrin (Lf), total IgA (T-IgA), and secretory IgA (S-IgA) levels to investigate nonspecific secretory immunity in HIV-infected patients with oral candidiasis. Serum, saliva, and stool samples were analyzed by time-resolved immunofluorometric assay for Lz and Lf levels and by enzyme-linked immunosorbent assay for T-IgA and S-IgA levels. Mean salivary Lf and T-IgA levels (66.50 mg/L and 0.10 g/L, respectively) and mean fecal Lf, T-IgA, and S-IgA outputs (0.87, 54.0, and 43.6 mg/d, respectively) were significantly higher in HIV-infected patients with oropharyngeal candidiasis than in HIV-infected patients without oropharyngeal candidiasis and healthy subjects. There was a modification in the molecular form rate, with a high increase in S-IgA and monomeric IgA transudation from the plasmatic compartment into salivary and digestive fluids and an increase in salivary Lf local synthesis by polymorphonuclear neutrophils. HIV infection appears to be associated with dysregulation of some of the nonspecific immune factors at the mucosal surface. Despite high saliva concentrations and high intestinal output, innate immunity was not able to stop yeast expansion in HIV-infected patients.

Evaluation of internal transcribed spacer region of ribosomal DNA sequence analysis for molecular characterization of Candida albicans and Candida dubliniensis isolates from HIV-infected patients.

Molecular typing systems have been needed to study Candida colonization in HIV-infected patients, particularly for investigating virulence and fluconazole resistance. Three methods--electrophoretic karyotyping (EK), detection of restriction fragment length polymorphisms (RFLP) and randomly amplified polymorphic DNA analysis (RAPD)--have been most frequently used. In this study, comparative sequence analysis of the internal transcribed spacer (ITS) region of rDNA was evaluated for delineation of Candida isolates from 14 HIV-infected patients. EK, ITS sequence analysis, RFLP and RAPD resulted in 11, 10, 9 and 8 DNA genotypes, respectively, from 39 Candida albicans isolates. The 10 genotypes observed using ITS sequence analysis were defined by six variation sites in the sequence. Molecular typing of sequential oral isolates showed the persistence of the same genotype of C. albicans in nine patients, and genotype variation in one patient. EK and RAPD showed that another patient was co-infected by two distinct genotypes and ITS analysis identified one of the two genotypes as Candida dubliniensis. Comparative ITS sequence analysis is a quick and reproducible method that provides clear and objective results, and it also identifies C. dubliniensis. The discriminatory power of this new typing approach could be improved by concomitant analysis of other DNA polymorphic sequences.

Increased serum and salivary immunoglobulins against Candida albicans in HIV-infected patients with oral candidiasis.

The aim of this study was to explore anti-Candida albicans systemic and mucosal humoral responses against Candida virulence antigens such as somatic antigen and secreted aspartic proteases (Saps) in HIV-infected patients with oral candidiasis. Twenty-eight subjects were included in the study: 11 HIV-positive patients without oral candidiasis (group A), 6 HIV-positive patients with oral candidiasis (group B) and 11 HIV-negative healthy controls (group C). Total IgA, IgG and IgM concentrations and antibodies to C. albicans (somatic antigen, Sap1, Sap6) were measured in serum and saliva. We developed a time-resolved immunofluorometric assay with biotin and europium-labeled streptavidin for this purpose. Salivary total IgA, IgG and IgM concentrations were higher in group B. IgA, IgG and IgM anti-C. albicans antibodies (against somatic antigen, Sap1, Sap6) were higher in saliva and serum from patients from group B compared with patients from group A and controls. Our results suggest that, in oral candidiasis, HIV-infected patients have a high mucosal response, specifically directed against C. albicans virulence antigens, such as somatic antigen, Sap1 and Sap6.

[Oncogenic human papillomaviruses in extra-genital Bowen disease revealed by in situ hybridization]. / Papillomavirus humains oncogènes révélés par technique d'hybridation in situ dans la maladie de Bowen extra-génitale.

BACKGROUND: The association between mucosal oncogenic human papillomaviruses (HPV) and bowenoid papulosis or genital Bowen's disease is well documented. In contrast this association with extra-genital Bowen's disease is poorly studied. The aim of this study was to detect oncogenic (16/18, 31/33/51) and non oncogenic (8/11) mucosal HPV using a in situ hybridization method in 28 skin biopsy specimens of extra-genital Bowen's disease. PATIENTS AND METHODS: Twenty-eight cases of extra-genital Bowen's disease seen in the period 1990-96 in the Dermatology department were included: 19 women and 9 men (mean age: 72 years). Bowen's disease locations were: hands and feet (8 cases), limbs (11 cases), face (8 cases), trunk (1 case). Blinded histopathologic examination confirmed the diagnosis of Bowen's disease and signs of HPV infection (koilocytosis). In situ hybridization was performed using three biotinylated probes detecting HPV types 6/11, 16/18, 31/33/51. RESULTS: Oncogenic HPV genoma was detected in 8 skin samples (28.6 p. 100). In all these cases, 16/18 probe was positive and in two cases, both 16/18 and 31/33/51 probes were positive; 4/8 Bowen's diseases of the extremities were positive for HPV. Koilocytes were found in 6/8 of skin samples with positive HPV detection. DISCUSSION: Mucosal oncogenic HPV are detected by in situ hybridization in 28.6 p. 100 of extra-genital Bowen's disease. In situ hybridization is an easier technique than Southern-Blot hybridization which is the gold standard. Five studies reported similar results and three studies reported different results that we discuss. A precise understanding of oncogenic HPV implication in the development of extra-genital Bowen's disease could lead to the development of new therapeutic strategies (topical cidofovir or imiquimod).

Longitudinal study of anti-Candida albicans mucosal immunity against aspartic proteinases in HIV-infected patients.

Oropharyngeal candidiasis (OPC), mainly caused by Candida albicans, is commonly observed in HIV-infected patients. Secreted aspartic proteinases (Saps) are virulent agents involved in adherence to the mucosal surface and in tissue invasion. The immune secretory response to these agents was investigated in 15 HIV-infected patients, during oral yeast colonization and episodes of oropharyngeal candidiasis (OPC), in a 1-year longitudinal study. We developed an avidin-biotin-amplified immunofluorometric assay for the detection of specific immunoglobulins G, A, and M against somatic, Sap2 and Sap6 antigens. We report increases in anti-somatic, anti-Sap2, and anti-Sap6 salivary antibodies in patients with OPC. Over the 1-year period, not only OPC episodes but also variations in yeast colonization levels were correlated with variations in salivary anti-Sap6 antibody levels. Our results show the ability of HIV-infected patients to produce high levels of salivary antibodies; however, these antibodies were not efficient in limiting candidal infection, probably because of cellular cooperation deficiency and the enhanced virulence of the infecting strain.

Hepatitis C virus co-infection is a negative prognostic factor for clinical evolution in human immunodeficiency virus-positive patients.

A longitudinal study of human immunodeficiency virus (HIV)-infected individuals followed-up in 13 centres was performed to assess the influence of hepatitis C virus (HCV) on the clinical and immunological evolution of HIV-infected patients. Eight-hundred and twelve HIV-infected patients with known HIV acquisition date, 89 co-infected with HCV, were included in the cohort. Clinical progression was defined as: 30% decrease of Karnofsky's index; and/or 20% body weight loss; and/or acquired immune deficiency syndrome (AIDS)-defining illness; and/or death (except by accident, suicide, or overdose). Immunological progression was defined as a decrease of initial CD4 count to below 200 mm(-3). If immunological progression was not statistically different between groups (P=0.25), clinical progression was significantly faster in HCV-HIV co-infected patients in univariate (P=0.02) and multivariable survival analysis (hazard ratio=1.63, P=0.03). This argues for active management of hepatitis C chronic infection among HCV-HIV co-infected patients.

[Papillomavirus-induced anogenital lesions in 121 HIV seropositive men. Clinical, histological, viral study, and evolution]. / Lésions anogénitales à papillomavirus chez 121 hommes séropositifs pour le VIH. Etude clinique, histologique, virale, et évolution.

OBJECTIVE: To determine the prevalence of the Human Papillomavirus (HPV) in Human Immunodeficiency Virus (HIV) infected men, using clinical examination and molecular hybridization in situ. PATIENTS AND METHODS: From May 1995 to May 1997 we studied the prevalence, clinical and histological characteristics, the types and the evolution of the HPV lesions among 121 HIV-infected men. The HPV DNA was determined by molecular hybridization in situ, using biotinylated probes which recognized HPV types 6/11, 16/18 and 31/33/35 in 79 p. 100 (5/19) of the patients (17 biopsies). RESULTS: Sixteen per cent (19/121) of the patients are HPV infected: genital warts in 37 p. 100 (7/19), anal warts in 37 p. 100 (7/19), and ano-genital warts in 26 p. 100 (5/19) of the patients. In every case of anal codyloma, intracanalar lesions were found. In 47 p. 100 (9/19) of the cases, histological exam showed an intra-epithelial neoplasia. The HPV types 6/11, 16/18 and 31/33/51 were positive in 53 p. 100 (9/17), 35 p. 100 (6/17) and 35 p. 100 (6/17) biopsies respectively. High-risk types of HPV have been noted in 71 p. 100 (12/17) of the biopsies. The evolution of the clinical lesions was: recovering in 47 p. 100 (9/19) of the patients (after 3 months of treatment), recurrence in 16 p. 100 (3/19) of the anal warts (after 1 to 3 months of treatment), stabilization in 16 p. 100 (3/19) of the genital warts (after 6 months of treatment) and extension in 11 p. 100 (2/19) of the anogenital warts (after 3 months of treatment). CONCLUSION: The high prevalence of condyloma and dysplasia emphasizes the importance of the anogenital exam in HIV-positive patients. In case of anal lesions, anuscopy and biopsy are required. We insist on the need to closely follow these patients with HPV lesions in order to adapt treatment. Anal cytology and HPV-DNA detection by Hybrid Capture Assay, should be developed for screening and prevention of the malignant transformation of HPV lesions in this population.

Cutaneous reaction to ultraviolet irradiation in human-immunodeficiency-virus-infected patients. A case-control study.

BACKGROUND: HIV-infected patients, like renal transplant recipients, are at increased risk of developing skin cancer in photoexposed areas. Previous studies demonstrated that prolonged ultraviolet (UV)-induced erythema and a decreased and delayed tanning could be correlated with an increased risk of skin cancers. OBJECTIVE: As HIV-infected patients are at an increased risk of developing skin cancers, we aimed to assess the cutaneous response to UV irradiation in these patients. METHODS: Twelve HIV-infected patients and 12 healthy volunteers were included in a prospective case-control study. No patient or volunteer had a history of skin cancer or photodermatosis. The minimal erythemal dose (MED) was determined using a solar simulator UV source, and, then, each subject underwent an exposure of 6 MED. The erythemal and pigmentation responses were studied using a visual scale and a tristimulus colorimeter over a 4-week period. RESULTS: We failed to demonstrate any significant differences between HIV-infected patients and controls for erythema and delayed pigmentation. No difference was found for MED between the two groups although most HIV-infected patients received potentially photosensitive drugs. CONCLUSIONS: Our results suggest that, as a group, the HIV-infected patients without a history of photosensitivity or skin cancer did not demonstrate a greater susceptibility to intense UV irradiation in terms of erythema and pigmentation induced by intense UV exposition.

Porphyria cutanea tarda associated with human immunodeficiency virus infection.

Since 1987, about 60 cases of porphyria cutanea tarda (PCT) associated with human immunodeficiency virus (HIV) have been reported. The respective roles of HIV and toxic hepatic factor in PCT remain unclear. We report 10 new cases and analyse the following toxic hepatic factors: hepatitis C and B, alcoholism, drugs. The route of HIV transmission to these 10 men were: IV drugs abuse (3), homo/bisexuality (4), heterosexuality (1), and unknown (2). When PCT was diagnosed, their average age was 38 years (29-54) and the HIV-infection had been established for 4.8 years (0.33-9). Seven men had HIV-related symptoms and a CD4+ lymphocyte count below 200/mm3. Cutaneous signs and urinary porphyrin count were characteristic. Alcohol abuse was present in 8/10 patients. AST, ALT and/or gamma GT were high in 9/10 patients; 5/10 patients had HCV antibodies (4 were HCV-PCR positive). HBs antigenemia was negative among the 5/8 patients with HBV antibodies; 10/10 patients took prescribed hepatotoxic drugs. Our series confirms the presence of toxic hepatic factors in PCT of HIV-positive patients. Hepatitis C, alcoholism and hepatotoxic drug consumption seem to be triggers for the appearance of PCT in HIV-positive patients.