Association between HLA-C*04 and American cutaneous leishmaniasis in endemic region of southern Brazil.

Leishmaniasis is a parasitic infectious disease with global repercussions. American cutaneous leishmaniasis (ACL) is endemic in southern Brazil and its pathogenesis varies according to parasite species, immune response, and host genetics. In terms of immunogenetics, many host genes, including HLA (human leukocyte antigen), could be involved in susceptibility to and protection against ACL. Accordingly, the aim of this study was to investigate the association between HLA class I genes (HLA-A, -B, and -C) and ACL in an endemic region of southern Brazil. The allele frequencies of 186 patients diagnosed with ACL and 278 healthy individuals were compared. HLA class I (HLA-A, -B, and -C) typing was carried out by PCR-SSO using Luminex technology. The results revealed an association between the HLA-C*04 allele and the patient study group, in which it appeared more frequently than in the control group [21.5 vs 13.49% (P = 0.0016 and Pc = 0.0258; OR = 1.7560; 95%CI = 1.2227-2.5240)], thereby suggesting an increased susceptibility to ACL. Additional allelic groups such as HLA-A*02, HLA-B*35, HLA-B*45, HLA-C*01, and HLA-C*15 were also implicated; however, further investigation is necessary to confirm their association with ACL. Therefore, the results obtained in this study demonstrate the involvement of HLA class I genes in the susceptibility or resistance to ACL, with significant association between HLA-C*04 and ACL susceptibility.

[Differential diagnosis and management of balanitis]. / Differenzialdiagnose und Management der Balanitis.

Balanitis is a descriptive diagnosis for a heterogeneous group of infectious or inflammatory dermatoses which have to be differentiated from malignant conditions. Balanitis is caused not only by Candida spp. and bacterial infections, including anaerobic bacteria: viral infections, parasites and other sexually transmitted infections (STI) also have to be considered. Lichen planus, psoriasis and contact dermatitis can characteristically lead to inflammatory conditions of the glans penis. In addition to a complete skin examination, a thorough patient history with respect to topically applied products and sexual behavior is essential. Infections must be treated and the glans penis should be kept dry. It is important to ensure a balanced genital hygiene in patients. As a last resort therapeutic circumcision can be considered for most forms of chronic balanitis.

Tumor necrosis factor beta (TNF-ß) NcoI polymorphism is associated with multiple sclerosis in Caucasian patients from Southern Brazil independently from HLA-DRB1.

This study evaluated the association of tumor necrosis factor beta (TNF-ß) NcoI polymorphism with the presence of multiple sclerosis (MS), disability, and HLA-DRB1 alleles in 208 Brazilian MS patients. As controls, 147 healthy individuals were included. The disability was evaluated at baseline and 5-year follow-up using the Expanded Disability Status Scale (EDSS). The TNF-ß genotypes were determined using PCR and restriction fragment length polymorphism and serum TNF-α level was determined using enzyme-linked immunosorbent assay. Among the MS patients, 166 (79.8 %) were white, 39 (18.7 %) were brown, and three (1.4 %) were Asian descents (those were excluded from the further analysis). Among the 205 MS patients, 149 (72.6 %) presented remitting-relapsing MS. The baseline and 5-year follow-up EDSS ranged from 0.0 to 3.0 and from 1.0 to 5.7, respectively. The TNFB2/B2 genotype was associated with the presence of MS among the white patients (p = 0.0443). Brown patients presented higher disability (p = 0.0234) and higher TNF-α levels (p = 0.0463) than white patients. White and brown patients carrying TNFB2/B2 genotype exhibited higher TNF-α levels (p = 0.0354 and p = 0.0309, respectively) than those with other geotypes. Association between TNF-ß NcoI genotypes and HLA-DRB1 alleles was not observed among the MS patients (p > 0.05). Taken together, TNFB2 allele was associated with the presence of MS independently of HLA-DRB1 in white patients and the TNFB2/B2 genotype was associated with increased TNF-α levels in white and brown patients, which could be an important genetic factor candidate for the susceptibility and pathogenesis of MS.

Hypertension is associated with serologically active disease in patients with systemic lupus erythematosus: role of increased Th1/Th2 ratio and oxidative stress.

OBJECTIVES: To determine whether disease activity verified by laboratorial parameters is associated with a higher frequency of hypertension in patients with systemic lupus erythematosus (SLE) without renal impairment and to investigate factors that could influence this hypertension. METHOD: This study included 102 controls, 70 patients with inactive SLE, and 53 patients with active SLE without renal impairment. We evaluated T helper type 1 (Th1)/Th2 lineage cytokines, nitric oxide (NO), insulin resistance (IR), and oxidative stress. RESULTS: Patients with active SLE had a higher probability of developing hypertension compared to controls [odds ratio (OR) 3.833, 95% confidence interval (CI) 1.806-8.137, p < 0.0003] and patients with inactive SLE (OR 2.215, 95% CI 1.032-4.752, p = 0.0394). Active SLE patients had a higher interleukin (IL)-12/IL-4 ratio (p < 0.05) than both controls and inactive SLE patients. Protein oxidation was significantly higher in patients with active SLE than in the control group and in patients with inactive SLE (p < 0.01 and p < 0.05, respectively). Multivariate analysis revealed an association between the presence of hypertension and he levels of glucose (p = 0.0276), insulin (p = 0.0498), hydroperoxides (p = 0.0221), IFN-γ (p = 0.0494), IL-17 (p = 0.0272), IL-12/IL-10 (p = 0.0373), IFN-γ/IL-10 (p = 0.0142), IFN-γ/IL-4 (p = 0.0320), and adiponectin (p = 0.0433). CONCLUSIONS: Patients with active SLE without renal impairment had an increased frequency of high blood pressure (43.4%) compared with patients with inactive SLE (25.7%) and controls (16.7%). Hypertension was associated with serologically active disease and was influenced by an increased Th1/Th2 ratio and oxidative stress.

Rare human skin infection with Corynebacterium ulcerans: transmission by a domestic cat.

Corynebacterium ulcerans is mainly known for its ability to cause animal infections. Some strains of C. ulcerans produce diphtheria toxin, which can cause life-threatening cardiopathies and neuropathies in humans. Human cutaneous C. ulcerans infection is a very rare disease that mimics classical cutaneous diphtheria. We present a very rare case of a C. ulcerans skin infection caused by a non-diphtheria toxin-producing strain of C. ulcerans that resolved after 3 weeks of therapy with amoxicillin-clavulanate. A pet cat was the probable source of infection. The presence of C. ulcerans in the mouth of the cat was confirmed by 16S rRNA gene analysis and the API Coryne system. In cases of human infection with potentially toxigenic corynebacteria, it is important to determine the species and examine the isolate for diphtheria toxin production. If toxigenicity is present, diphtheria antitoxin should be administered immediately. Carriers and potential infectious sources of C. ulcerans include not only domestic livestock but also pet animals. For the primary prevention of disease caused by diphtheria toxin-producing corynebacteria, vaccination with diphtheria toxoid is recommended.

Cream or foam in pedal skin care: towards the ideal vehicle for urea used against dry skin.

The aim of this study was to evaluate different urea-containing cosmetic preparations designed for foot care regarding skin occlusion. The primary aim was therefore to screen the short-term transepidermal water loss (TEWL) as a parameter for skin barrier function and skin occlusion and to characterize the relative role of the vehicle, i.e. cream or foam in the context of cosmetics containing urea in the 2-10% range addressing the cosmetic products urea 2% cream (GEHWOL FUSSKRAFT blau), petrolatum containing cream (GEHWOL med Schrundensalbe), urea 10% cream (GEHWOL med Lipidro-Crème), urea 10% foam (Allpresan Fuss Schaum) and vaseline (positive control) compared with an untreated area on the volar forearms of volunteers. Moreover, the short time (24 h) kinetics regarding the moisturizing effect of cream and foam formulations in diabetic patients were compared. The efficacy of a cream on reduction of skin thickness of hyperkeratotic skin in the heel region before and after a period of product application was also evaluated. In some of the trials, healthy individuals and in others, diabetic patients (type I and II) were enrolled. TEWL was determined before product application, as well as at given points of time thereafter. In this study, no excessive occlusion effects comparable with a blockage of the skin's natural water evaporation could be observed for any of the test products. To the extent to be expected, this was found neither for the cream products nor for the foam product. Slightly lowered TEWL values after application of the 10% urea cream can be interpreted as a beneficial effect in terms of an improved barrier function. Regarding skin moisture, the urea-containing cream formulation appeared equal or slightly superior to the foam formulation. The thickness of the horny layer was found reduced after application of 10 % urea-containing cream. At present it looks as if cream vehicles would still be vehicles of choice in general, when it comes to the formulation of skin care preparations for not only dry skin but also in the context of pedal skin care.

Evaluation of a particle gel immunoassay as a screening test for syphilis.

BACKGROUND: Recent trends in Western Europe show an increase in sexually transmitted infections. Surveillance data in Switzerland confirm this rising trend. Notifications of syphilis cases nearly doubled in the year 2002 and almost tripled in 2003. This trend necessitates an early correct diagnosis making reliable screening tests mandatory. MATERIALS AND METHODS: In the presented study a particle gel immunoassay (ID-PaGIA syphilis antibody test, Diamed) using recombinant treponemal antigens TpN15, TpN17 and TpN47 was evaluated as a screening test in comparison to the currently used Treponema pallidum particle agglutination test (Serodia-TPPA, Fujirebio). Serum samples were obtained from a cross-sectional sero-epidemiological study among men who have sex with men. Samples were tested with the PaGia and the TPPA. In the case of equivocal results a titrated TPPA of an external laboratory was used as a confirmation test. RESULTS: In total 650 serum samples (48 seropositive patients, 602 negative) were evaluated. The PaGIA showed a sensitivity of 0.89 (43/48) and the TPPA of 0.83 (40/48). This difference was not statistically relevant (p = 0.4). The particle gel assay showed a significantly higher specificity (1.0) compared to the TPPA (0.98) (p = 0.004). CONCLUSION: The PaGIA showed a sensitivity comparable to that of other treponemal tests with an even better specificity. Advantages of the PaGIA are the fast reaction time of only 20 min and the simplicity of the procedure with minimal technical equipment.

[Conventional and molecular diagnosis of cutaneous mycoses]. / Konventionelle und molekulare Diagnostik bei Dermatomykosen.

The clinical presentation of fungal infections of the skin, hair, and nails is varied and sometimes presents a confusing clinical picture. The main objective is to rapidly institute diagnostic measures to avoid delays in therapy with potential expansion of the infection. A variety of laboratory tests are required. Classical methods are based on microscopy, different culture procedures, and histologic examination. Genotypic approaches to detection and identification of fungal pathogens have become very rapid and sensitive, making them additional options for routine diagnosis.

[Working hours and job satisfaction among physicians in hospitals and general practice in Munich. Results of an anonymous questionnaire]. / Arbeitszeit und Arbeitszufriedenheit angestellter und beamteter Arzte in München. Ergebnisse einer anonymen Befragung.

PURPOSE: In autumn 2004 the local association of physicians (Arztlicher Kreis- und Bezirksverband München) performed a survey among employed physicians in Munich on working hours and working conditions. The aim of the study was to assess the extent to which the German law on working hours is actually implemented in employed physicians, and to obtain information about their work satisfaction. METHODS: A questionnaire was sent to all employed physicians in hospitals and medical practices. Participants were asked to give anonymous information and send it back per mail. RESULTS: In total, 2450 out of 5461 physicians took part in the survey. 45% reported that their working hours do not meet the German law on working hours of 1994. 44.4% stated that overtime is not fully recognized by their employers. 43.5% think the job would become more attractive if the law was implemented. 63.3% expect an income loss with the implementation. 53.7% are thinking about quitting their job. For 59.9% the burden of long working hours is an important reason for this. Women are more likely to be given a limited employment contract than men, and their overtime is more rarely recognized in full. CONCLUSION: Many employed physicians in Munich are dissatisfied with their job. The high burden of long working hours is a main reason for this.

The association of the HLA in patients with schizophrenia, schizoaffective disorder, and in their biological relatives.

To determine the association of the HLA in 50 patients with schizophrenia, schizoaffective disorder, 48 healthy controls, 41 biological relatives without psychiatric disease, and 48 biological relatives with mood disorder, the HLA genotype at the class I and class II were determined. The subjects were interviewed by structured diagnostic criteria categorized according to DSM-IV, axis I, (SCID-IV). Significant positive association was found with HLA-B.15 in patients, family with humor disorder and without mental disorder (p=0.003) and negative association of the HLA-B.35 in relatives without psychiatric disease (p=0.03). The HLA-B.15 frequency was significantly increased in a subgroup of patients with age at onset in the early 20s, lower educational achievement, occupational disability, chronically ill, more paranoid type. These findings suggest the existence of some involvement of an immunogenetic mechanism in a subgroup of schizophrenic, schizoaffective patients, and biological relatives.

The prevalence of positive reactions in the atopy patch test with aeroallergens and food allergens in subjects with atopic eczema: a European multicenter study.

BACKGROUND: The atopy patch test (APT) was proposed to evaluate IgE-mediated sensitizations in patients with atopic eczema (AE). OBJECTIVE: The prevalence and agreement with clinical history and specific IgE (sIgE) of positive APT reactions was investigated in six European countries using a standardized method. METHODS: A total of 314 patients with AE in remission were tested in 12 study centers on clinically uninvolved, non-abraded back skin with 200 index of reactivity (IR)/g of house dust mite Dermatophagoides pteronyssinus, cat dander, grass, and birch pollen allergen extracts with defined major allergen contents in petrolatum. Extracts of egg white, celery and wheat flour with defined protein content were also patch tested. APT values were evaluated at 24, 48, and 72 h according to the European Task Force on Atopic Dermatitis (ETFAD) guidelines. In addition, skin-prick test (SPT) and sIgE and a detailed history on allergen-induced eczema flares were obtained. RESULTS: Previous eczema flares, after contact with specific allergens, were reported in 1% (celery) to 34% (D. pteronyssinus) of patients. The frequency of clear-cut positive APT reactions ranged from 39% with D. pteronyssinus to 9% with celery. All ETFAD intensities occured after 48 and 72 h. Positive SPT (16-57%) and elevated sIgE (19-59%) results were more frequent. Clear-cut positive APT with all SPT and sIgE testing negative was seen in 7% of the patients, whereas a positive APT without SPT or sIgE for the respective allergen was seen in 17% of the patients. APT, SPT and sIgE results showed significant agreement with history for grass pollen and egg white (two-sided Pr > /Z/ < or = 0.01). In addition, SPT and sIgE showed significant agreement with history for the other aeroallergens. With regard to clinical history, the APT had a higher specificity (64-91% depending on the allergen) than SPT (50-85%) or sIgE (52-85%). Positive APT were associated with longer duration of eczema flares and showed regional differences. In 10 non-atopic controls, no positive APT reaction was seen. CONCLUSION: Aeroallergens and food allergens are able to elicit eczematous skin reactions after epicutaneous application. As no gold standard for aeroallergen provocation in AE exists, the relevance of aeroallergens for AE flares may be evaluated by APT in addition to SPT and sIgE. The data may contribute to the international standardization of the APT.

[Adverse chemotherapy effects on skin and mucous membranes]. / Chemotherapie-Nebenwirkungen an Haut und Schleimhäuten.

Mucocutaneous side effects of chemotherapeutic agents are frequent, especially alopecia and stomatitis. The latter can be dose limiting or can endanger the patient in case of secondary infection. Nail changes and hyperpigmentation are cosmetically disturbing. For the diagnosis of the acral erythrodysesthesia syndrome and the neutrophilic eccrine hidradenitis knowledge of the clinical presentation is required. Interaction of chemotherapeutic agents with radiotherapy or UV light can aggravate or cause skin changes like the radiation recall. Despite the completely different mode of action of new substances or immunotherapeutic agents like monoclonal antibodies the same range of side effects can be observed.

[Skin manifestations of diseases of the gastrointestinal tract]. / Hautveränderungen bei Erkrankungen des Magen-Darmtraktes.

Diseases of the gut frequently show skin symptoms. These can give first and important clues in regard to diagnosis. In general the etiology can be divided into genetic disorders, chronic inflammation, drug reaction, infectious diseases or related to malignancy. In genetic disorders increasing knowledge about the involved genes is available, allowing prenatal diagnosis and screening of clinically not affected family members. Especially in cancer prone syndromes early diagnosis and preventive treatment is crucial. Inflammatory bowel diseases show a high prevalence, therefore necessitating the knowledge of skin complications such as pyoderma gangrenosum, Sweet syndrome and erythema nodosum. Gastrointestinal malignancies may metastasize into the skin or may produce typical paraneoplastic changes.

Peripheral blood mononuclear cells from IgE- and non-IgE-associated allergic atopic eczema/dermatitis syndrome (AEDS) demonstrate increased capacity of generating interleukin-13 but differ in their potential of synthesizing interferon-gamma.

BACKGROUND: A subgroup of patients with allergic atopic eczema/dermatitis syndrome (AEDS) are known to have normal total and specific IgE levels and negative skin prick tests towards common environmental allergens. This form of the disease has been termed non-IgE-associated allergic AEDS. Although allergic mechanisms appear to be important, the pathogenesis of both IgE- and non-IgE-associated forms of the disease is unknown. METHODS: We have compared the cytokine production pattern of peripheral blood mononuclear cells (PBMC) from IgE-associated AEDS, non-IgE-associated AEDS, and normal control individuals. PBMC were stimulated with anti-CD3 and/or anti-CD28 monoclonal antibodies (mAb) and cytokine production was measured by immunoassays in supernatants of 24-h cultures. RESULTS: Compared to healthy subjects and non-IgE-associated AEDS patients, stimulated PBMC from IgE-associated AEDS patients produced less interferon (IFN)-gamma. However, stimulated PBMC from both IgE-associated AEDS and non-IgE-associated AEDS patients produced more interleukin (IL)-13 than PBMC from control individuals. Moreover, IL-5 production was significantly increased in non-IgE-associated AEDS but not in IgE-associated AEDS patients. CONCLUSIONS: The underlying mechanism leading to increased differentiation of T helper (Th) 2 cells may involve a deficient capacity in producing IFN-gamma in IgE-associated AEDS but not in non-IgE-associated AEDS patients. IL-13 may be a key cytokine in the pathogenesis of both allergic forms of AEDS.

Galli-Galli disease: an unrecognized entity or an acantholytic variant of Dowling-Degos disease?

Galli-Galli disease is an inherited disease characterized by slowly progressive and disfiguring reticulate hyperpigmentation of the flexures, clinically and histopathologically diagnostic for Dowling-Degos disease, but also associated with suprabasal, nondyskeratotic acantholysis. A few patients exhibiting these features have been described, mainly in the non-English-language literature, which suggests that Galli-Galli disease is not an entity of its own, as originally thought, but is an acantholytic variant of Dowling-Degos disease. We report a typical case of Galli-Galli disease, which supports this concept.

Influence of weather and climate on subjective symptom intensity in atopic eczema.

The frequent clinical observation that the course of atopic eczema, a skin disease involving a disturbed cutaneous barrier function, is influenced by climate and weather motivated us to analyse these relationships biometrically. In the Swiss high-mountain area of Davos the intensity of itching experienced by patients with atopic eczema was evaluated and compared to 15 single meteorological variables recorded daily during an entire 7-year observation period. By means of univariate analyses and multiple regressions, itch intensity was found to be correlated with some meteorological variables. A clear-cut inverse correlation exists with air temperature (coefficient of correlation: -0.235, P < 0.001), but the effects of water vapour pressure, air pressure and hours of sunshine are less pronounced. The results show that itching in atopic eczema is significantly dependent on meteorological conditions. The data suggest that, in patients with atopic eczema, a certain range of thermo-hygric atmospheric conditions with a balance of heat and water loss on the skin surface is essential for the skin to feel comfortable.

Food intake of patients with atopic dermatitis.

There is only restricted information about the nutritional behavior of adult patients with atopic dermatitis (AD). Our purpose was to evaluate the food intake in a series of patients with AD with particular consideration of self-reported food intolerance. Particular attention was paid to the risks of nutrient deficiencies. We examined the intake of 28 food items in 116 AD patients with a food-frequency questionnaire (FFQ). For each food item the cohort was divided in two groups according to whether symptoms were reported or not (symptomatic vs. asymptomatic). We found in a series of food items a significant lower food intake among symptomatic patients. Significantly lower intakes were reported by symptomatic patients for dairy products, fish, egg, pork, oranges, non-specified fruits, apples, kiwis, green or red peppers, peanuts and hazelnuts. We concluded that in symptomatic AD patients supplementation with specific nutrients might become mandatory. This is particularly pertinent for calcium, iodine, vitamin C and n-3 fatty acids.

Immunohistochemical characterization of the perivascular infiltrate cells in tissues adjacent to stainless steel implants compared with titanium implants.

Metallic orthopaedics implants are composed of elements that are known to be skin sensitizers in the general population. In this study, we analyzed the cells of perivascular infiltration in the tissue adjacent to titanium (n = 23) and steel (n = 8) implants after explantation of the metals by immunohistochemical methods. The following panel of monoclonal antibodies were used as parameters: CD 1a (Langerhans cells), CD 4 (T-helper cells), CD 8 (T-suppressor cells), CD 11c (monocytes and macrophages), CD 45 RO (memory cells), CD 45 RA (naive cells), eosinophil cationic proteins (ECP), neutrophil elastase, and HLA-DR. The number of perivascular total cells did not differ significantly. All cells were identified in both metal subgroups, but a statistical difference was not seen in the above-mentioned parameters. We conclude that sensitization to metals is possible in the tissue adjacent to steel and titanium implants, because all cells which play an important role in allergic delayed-type hypersensitivity (type IV) reactions are present. This phenomenon may be called a 'pre-sensitization' phase, because no sensitization or allergic reactions were seen in our cases. Second, in the present study, a statistical difference was not seen in the number of infiltrate cells in the tissue adjacent to steel compared with titanium implants.