Contact allergy to methyldibromo glutaronitrile--data from a 'front line' network

The preservative methyldibromo glutaronitrile (MDBGN) has caused an epidemic of contact allergy in Europe. However, most data concerning contact allergy comes from hospital departments of dermatology. As a part of the primary health care sector, Danish dermatologists in private practice provide the front line of care for patients with skin diseases. Data from this source may therefore better reflect trends in the general population than material from hospital departments of dermatology. In this study, the frequency of MDBGN allergy and the characteristics of patients seen by dermatologists in private practice were studied. In 1 year, 2146 patients were patch tested by the participating dermatologists from 4 clinics in various parts of Denmark. 5% (110) had positive patch tests to MDBGN, with no difference between the sexes. After adjustment was made for other background variables, multivariate analysis using logistic regression showed a significant association between hand eczema and MDBGN allergy (OR 2.5, P < 0.001). In 53 cases (52.4%), the patch test reaction to MDBGN was judged to be of current relevance. Creams and lotions accounted for 31% of the identified causative products and liquid soaps for 23%. It is concluded that contact allergy to MDBGN is frequent among patients seen by dermatologists in private practice. This is consistent with results from hospital departments of dermatology in Europe and indicates a general trend and ongoing epidemic in the general population. The significant relationship between hand eczema and MDBGN allergy is of concern, and the finding that wash-off products, especially liquid soaps, play a significant role in MDBGN allergy calls for a revision of the safety assessment of MDBGN in wash-off products.     

Deodorants: an experimental provocation study with isoeugenol

Axillary dermatitis is common and overrepresented in people with contact allergy to fragrances. Many people suspect their deodorants to be the incriminating products. In order to investigate the significance of isoeugenol in deodorants for the development of axillary dermatitis when used by people with and without contact allergy to isoeugenol, patch tests with deodorants and ethanol solutions with isoeugenol, as well as repeated open application tests (ROAT) with roll-on deodorants with and without isoeugenol at various concentrations, were performed in 35 dermatitis patients, 10 without and 25 with contact allergy to isoeugenol. A positive ROAT was observed only in patients hypersensitive to isoeugenol (P<0.001) and only in the axilla to which the deodorants containing isoeugenol had been applied (P<0.001). Deodorants containing isoeugenol in the concentration range of 0.0063-0.2% used 2 times daily on healthy skin can thus elicit axillary dermatitis within a few weeks in people with contact allergy to isoeugenol.     

A new, recurrent mutation of GJB3 (Cx31) in erythrokeratodermia variabilis

BACKGROUND: Erythrokeratodermia variabilis (EKV) is an autosomal dominant or recessive genodermatosis characterized by the coexistence of randomly occurring, transient, erythematous patches and hyperkeratosis of the skin. The disorder has been mapped to chromosome 1p35.1 but is genetically heterogeneous. EKV may be caused by pathogenic mutations in one of two neighbouring connexin genes, GJB3 and GJB4, encoding the gap junction proteins Cx31 and Cx30.3, respectively. Twelve distinct mutations identified to date cluster either at the cytoplasmic amino-terminus or in the four transmembrane domains. OBJECTIVES: To report a large family with EKV and an unrelated sporadic case. METHODS: DNA amplification and mutation analysis, followed by denaturing high-performance liquid chromatography to confirm the segregation of the mutations in the two families with EKV. RESULTS: A novel, recurrent GJB3 mutation (625C-->T; L209F) was identified in the family with EKV and in the unrelated sporadic case. CONCLUSIONS: This mutation is the first to affect a conserved residue in the cytoplasmic carboxy-terminus of any connexin gene with a cutaneous phenotype, emphasizing its structural and/or functional importance.     

Combined effects of irritants and allergens. Synergistic effects of nickel and sodium lauryl sulfate in nickel- sensitized individuals

Knowledge of the combined effects of irritants and allergens is of interest with respect to accurate risk assessment. The threshold for elicitation of allergic contact dermatitis in previously sensitized individuals may theoretically be markedly influenced by the simultaneous presence of irritants and allergens. Combined exposures have, however, only been studied infrequently. In the present study, the combined effect of an irritant and an allergen was evaluated in a dose-response designed experimental study. 20 nickel-sensitized subjects were exposed to patch testing with varying concentrations of NiCl2 (nickel chloride) and sodium lauryl sulfate (SLS) alone and in combination. Evaluation of skin reactions was performed by colorimetry, measurement of transepidermal water loss and clinical evaluation, and the data were analyzed by logistic dose-response models. A synergistic effect was found of combined exposure to NiCl2 and SLS, as compared to each of the substances applied separately, as evaluated by colorimetry and clinical scoring. This means that the effect produced by the combined exposure was substantially greater than the effect produced by either of the substances alone. A synergistic effect of combined exposure on skin barrier impairment was not found, since the barrier function is significantly influenced by SLS-exposure only and not by NiCl2. Concentration limits are used by industry and government agencies to protect consumers. The present results clearly illustrate that elicitation thresholds and concentration limits may be influenced considerably by combined exposure to allergens and irritants.     

Pimecrolimus identifies a common genomic anti-inflammatory profile,is clinically highly effective in psoriasis and is well tolerated

The ascomycin macrolactam pimecrolimus is a novel inflammatory cytokine release inhibitor that so far has not been administered systemically to humans. In this phase I/II randomized double-blind, placebo-controlled, multiple rising dose proof of concept study psoriasis patients were treated with oral pimecrolimus or placebo. Gene profiling identified a common genomic profile with a downregulation of genes associated with inflammation but no changes in gene expression linked to drug-related side-effects. A steady state of pimecrolimus was reached after 5-10 d, Cmax, and area under the curve (0-24) was 54.5 ng per ml and 589.9 ng h per ml, respectively, at steady state at the highest dose. There was clear clinical efficacy in patients receiving 20 mg pimecrolimus twice daily and 30 mg twice daily with a reduction of Psoriasis Area and Severity Index by 60% and 75%, respectively. Histopatho logically and immunopathologically there was a reversion of the psoriatic phenotype towards normal. There were no notable clinical, laboratory, kidney function, or immunologic side-effects. We conclude that pimecrolimus taken orally is highly effective in a concentration-dependent manner in patients with psoriasis and on a short-term basis it is well tolerated and this is confirmed by its pharmacogenomic profile. The latter also indicates that pimecrolimus should be equally effective in other inflammatory skin diseases.     

Are anti-Chlamydia pneumoniae antibodies prognosis indicators for peripartum cardiomyopathy?

BACKGROUND: The authors recently pointed out an epidemiological relation between specific anti-Chlamydia pneumoniae antibodies and peripartum cardiomyopathy in Niamey (Republic of Niger). DESIGN: In this work, they studied the prognosis value of such specific antibodies. METHODS: The serological status for specific IgG, IgA and IgM anti-C. pneumoniae antibodies of 50 African women (age, mean+/-SD = 30.2 +/- 7 years) hospitalized in Niamey, with peripartum cardiomyopathy, was determined at the time of diagnosis. The diagnosis was categorized as 'complete remission' (13 patients, age = 29.3 +/- 6.5 years, observation delay = 27 months), 'incomplete remission' (27 patients, age = 30.7 +/- 7.6 years, observation delay = 14 months) and 'deceased' (10 patients, age = 30.3 +/- 6.2 years, observation delay = 13 months). The control group comprised 27 African women (age = 25.2 +/- 4.6 years), living in the same area. The Mann-Whitney and Fisher's exact tests were used for the statistical comparison. RESULTS: The dilution of IgG specific anti-C. pneumoniae antibodies was higher (P = 0.047) in the 'incomplete remission' compared with 'complete remission'. The dilution of IgA specific anti-C. pneumoniae antibodies was higher (P = 0.033) in the patients with a severe evolution ('deceased' + 'incomplete remission') compared with 'complete remission'. There was no significant difference between patients in 'complete remission' compared with 'controls'. CONCLUSIONS: At the time of peripartum cardiomyopathy diagnosis the specific IgG and IgA anti-C. pneumoniae antibodies are of prognosis value: a high dilution is more often associated with a poor prognosis. This is the first identified prognosis factor during the precocious evolution of peripartum cardiomyopathy.     

The prevalence and etiology of elevated aminotransferase levels in the United States

Chronic liver disease is a major cause of morbidity and mortality in the United States. Although often used to detect liver disease, the prevalence and etiology of elevated aminotransferases are unknown.We analyzed data on adults ages 17 yr and older (N = 15,676) from the Third National Health and Nutrition Examination Survey (1988-1994). Participants were classified as having elevated aminotransferase levels if either aspartate aminotransferase or alanine aminotransferase was elevated above normal. Aminotransferase elevation was classified as "explained" if there was laboratory evidence of hepatitis B or C infection, iron overload, or if there was a history of alcohol consumption. Analyses were weighted to provide national estimates.The prevalence of aminotransferase elevation in the United States was 7.9%. Aminotransferase elevation was more common in men compared to women (9.3% vs 6.6%, p = 0.002), in Mexican Americans (14.9%) and non-Hispanic blacks (8.1%) compared to non-Hispanic whites (7.1%, p < 0.001). High alcohol consumption, hepatitis B or C infection and high transferrin saturation were found in only 31.0% of cases. Aminotransferase elevation was unexplained in the majority (69.0%). In both men and women, unexplained aminotransferase elevation was significantly associated with higher body mass index, waist circumference, triglycerides, fasting insulin, and lower HDL; and with type 2 diabetes and hypertension in women (all p < 0.05).Aminotransferase elevation was common in the United States, and the majority could not be unexplained by alcohol consumption, viral hepatitis or hemochromatosis. Unexplained aminotransferase elevation was strongly associated with adiposity and other features of the metabolic syndrome, and thus may represent nonalcoholic fatty liver disease.     

Recently Graduated Medical Students Lack Exposure to and Comfort with Chronic Liver Diseases

Digestive Diseases and Sciences - The prevalence of chronic liver disease (CLD) is rising, but it remains unclear if medical school curricula are emphasizing CLD to reflect its growing...