Classification of atopic hand eczema and the filaggrin mutations.

Hand eczema is a common disease with various risk factors of which atopic dermatitis is known to be one of the most important. Recently, two mutations in the gene coding for filaggrin, a protein important for the skin barrier, have repeatedly been shown to be associated with atopic dermatitis. Moreover, one study point towards an association between the filaggrin null alleles and the subgroup of patients having both hand eczema and atopic dermatitis. For the remainder of hand eczema patients, still unknown genetic risk factors exist. We propose that in future, classification of atopic hand eczema should distinguish between patients with and without the filaggrin null alleles and to further differentiate between associations with type I allergy, type IV allergy and exposure to irritants, respectively. Furthermore, we suggest future studies of atopic hand eczema to analyse for the filaggrin mutations. We believe this will increase the possibility of subgrouping this otherwise heterogenic disease and thereby enable a better phenotype-genotype characterization of hand eczema. This could improve the preventive initiatives, secure better information of patients about the prognosis for their disease, and possibly enable targeted treatment.

Clinical characteristics and consequences of hand eczema - an 8-year follow-up study of a population-based twin cohort.

BACKGROUND: Few population-based clinical follow-up studies on hand eczema are reported. OBJECTIVES: The aim of this study was to characterize clinical symptoms and to examine occupational and medical consequences as well as persistence of hand eczema in a population-based twin cohort. PATIENTS/METHODS: A total of 274 individuals with and without hand eczema were examined, patch tested, and interviewed in 1997-1998 and 2005-2006. Data on 188 individuals with hand eczema in 2005-2006 were analysed. RESULTS: Erythema and scaling were the most frequent symptoms, and fingers and palms were most often affected. Mean hand eczema severity index score in individuals with clinical symptoms was 12.0. Sick leave was reported by 12.4%; job change by 8.5%. Being in the lowest socio-economic group and atopic dermatitis were risk factors for sick leave [odds ratio (OR) = 5.6; 95% confidence interval (95% CI) 1.5-22.9 and OR = 2.9; 95% CI 1.0-8.1]. The majority (63.4%) had seen a doctor at least once, and atopic dermatitis was a risk factor for more than 1 visit (OR = 3.0; 95% CI 1.4-6.4). Duration of >10 years was a risk factor for persistence of symptoms, which was reported by 67.7%. CONCLUSIONS: The clinical picture and consequences of hand eczema vary; however, the majority experience chronic symptoms.

Retesting with the TRUE Test in a population-based twin cohort with hand eczema - allergies and persistence in an 8-year follow-up study.

Population-based studies on contact allergy with retesting of individuals are infrequently performed. Variable degrees of persistence are reported when individuals with contact allergy are retested with years in between. The patch test results of 270 individuals tested in 2005-2006 are presented and the pattern and frequency of sensitization discussed. Persistence when compared with patch test results from 1997-1998 is reported. 270 twin individuals with and without hand eczema underwent patch testing with the TRUE Test((R)) (Mekos Laboratories AS, Hilleroed, Denmark) in 1997-1998 and again in 2005-2006 as part of a larger study. In 2005-2006, a total of 74 (27.4%) of the 270 individuals had at least 1 positive patch test and 20 (7.4%) of the 270 had 2. The frequency in men and women was 9/90 (10%) and 65/180 (36.1%), respectively. The frequency of contact allergy in individuals with and without hand eczema was 59/185 (31.3%) and 15/85 (17.6%), respectively. The most prevalent contact allergies were to nickel, thiomersal, and fragrance mix I. All together, 74% of the positive reactions were reproduced. The frequency of contact allergy in this population-based cohort with hand eczema was comparable with previous reports. Persistence of contact allergy after many years was confirmed.

Heritability of hand eczema is not explained by comorbidity with atopic dermatitis.

Genetic factors have been shown to influence the risk of hand eczema, and may theoretically influence the frequency of eruptions as well as age at onset of the disease. However, the result may be confounded by atopic dermatitis, which is a major risk factor for development of hand eczema and is known to be influenced by genetic factors. In this study, the importance of genetic and environmental risk factors in the etiology of hand eczema, independent of atopic dermatitis, was investigated in a population-based twin cohort. In addition, any possible genetic influence on frequency of hand eczema eruptions and age at onset was explored. In all, 4,128 twin individuals (response rate 82%) answered a questionnaire on self-reported hand eczema. Similarity within twin pairs was estimated and quantitative genetic modelling performed. Controlling for age and atopic dermatitis, the effect of genetic risk factors was moderate and explained 41% of the variance in liability to develop hand eczema, leaving 59% of the variance to be caused by environmental factors. Genetic factors accounted for 31% of the variance in liability regarding frequency of eruptions. Environmental factors explained the variance in liability concerning age at onset.

An evaluation of dose/unit area and time as key factors influencing the elicitation capacity of methylchloroisothiazolinone/methylisothiazolinone (MCI/MI) in MCI/MI-allergic patients.

Methylchloroisothiazolinone and methylisothiazolinone (MCI/MI) contact allergy affects 1-3% of patch-tested patients in European centres. The aim of the present study was to evaluate the importance of the factors--time and concentration (dose/per unit area)--in the elicitation capacity by means of a repeated open application test (ROAT) experimental design. The study was designed as a double-blind, placebo-controlled, dose-response ROAT preceded by a diagnostic patch testing. 25 subjects with confirmed MCI/MI allergy and 10 healthy, non-MCI/MI allergic control subjects were exposed to 0.025 microg/cm2 (2 p.p.m.) of MCI/MI/unit area of the skin for 4 weeks. After a wash-out period of at least 4 weeks, the subjects were exposed to 0.094 microg/cm2 (7.5 p.p.m.) of MCI/MI/unit area of the skin for 4 weeks. The study showed the importance of both time and exposure in the elicitation process. It demonstrated that the elicitation threshold for MCI/MI is expected to be in the proximity of 0.025 microg/cm2 although it was not possible to establish a definitive elicitation threshold for MCI/MI in this study.

Cross-reactivity between thiurams.

Retesting with an allergen at a site with previous allergic contact dermatitis has been shown to enhance reactivity. It has been suggested that retesting with a cross-reactive allergen will also induce hyperreactivity. Concurrent sensitization to more than 1 thiuram is common, but whether this is due to concomitant primary sensitization or cross-reactivity is uncertain. The aim of this study was to investigate the use of retesting to distinguish between concomitant sensitization and cross-reactivity in the rubber chemicals tetraethylthiuram disulphide (TETD) and tetramethylthiuram disulphide (TMTD). There was a non-significant trend towards enhanced reactivity for both TETD and TMTD when testing in an area with previous allergic contact dermatitis due to TETD. Cross-reactivity between the 2 chemicals is likely, but a definite conclusion from this pilot study is not possible.

Allergic contact dermatitis from allyl isothiocyanate in a Danish cohort of 259 selected patients.

Allyl isothiocyanate is present in many plants. Allergic contact dermatitis from allyl isothiocyanate is well known but infrequently reported. The aim of this study was to investigate the prevalence of contact allergy to allyl isothiocyanate in patients with suspected contact dermatitis from vegetables and food. 259 such patients were tested at the Department of Dermatology, Gentofte Hospital, Denmark, from 1994 to 2003. Only 2 patients (0.8%) had a positive reaction (+) to allyl isothiocyanate and 43 patients (16.6%) had a ?+ reaction. One of the patients with a positive reaction provided samples of margarine, salad cream, oil and mayonnaise. These were analysed with high-performance liquid chromatography, and a moderate concentration of allyl isothiocyanate (2.5 ppm) was detected in the sample of margarine. This patient was a professional sandwich maker presenting with fingertip dermatitis mimicking 'tulip fingers' or allergic contact dermatitis from garlic and onions. In conclusion, allergic contact dermatitis from allyl isothiocyanate occurs in only a limited number of cases, despite frequent exposure. The large number of ?+ reactions raises the question as to whether the recommended patch test concentration is too low.

Tenofovir treatment in an unselected cohort of highly antiretroviral experienced HIV positive patients.

The aim of the present study was to explore the treatment effect of tenofovir as implemented in clinical practice. Data are presented on 34 patients. 11 patients had tenofovir added to a stable anti-retroviral treatment (ART) and 23 patients had drugs other than tenofovir. CD4 counts, HIV-RNA levels and genotypic resistance were determined at baseline and after 3 and 6 months. After initiation of tenofovir treatment, a mean decrease in HIV-RNA for all 34 patients was observed (-0.43 log1o copies/ml (+/- 1.22) and -0.49 log10 copies/ml (+/- 1.36) after 3 and 6 months, respectively, (p = 0.045)). However, the effect of tenofovir on HIV-RNA in the group of patients who had tenofovir added to a stable ART was limited, and the decrease in HIV-RNA was significantly higher in patients who had drugs other than tenofovir changed as well (p = 0.004 and p = 0.03 after 3 and 6 months, respectively). After initiation of tenofovir treatment, no significant increases in CD4 count were observed. All new NRTI-associated mutations could be explained by the background treatment. In conclusion, we observed a significant decrease in HIV-RNA only when tenofovir was prescribed, in conjunction with other anti-retroviral drugs, to patients on a failing highly active antiretroviral drug regimen (HAART).