Alitretinoin and acitretin in severe chronic hand eczema; results from a retrospective daily practice study.

Acitretin has been used off-label for years to treat chronic hand eczema, but acitretin is less often prescribed as alitretinoïne was approved. This study evaluates both retinoids in a daily practice cohort of patients with severe chronic hand eczema in terms of drug survival and reasons for discontinuation. Patients using alitretinoin or acitretin between 01-01-1994 and 01-08-2015 were included in this retrospective daily practice study and analyzed by Kaplan-Meier drug survival curves. Potential determinants were analyzed by Cox regression analyses. Ninety-five patients were treated with alitretinoin and 109 patients with acitretin. The main reasons for discontinuation were adverse events and cleared hand eczema, 29.5 and 27.4% in alitretinoin versus 43.1 and 23.9% in acitretin. Patients with hyperkeratotic hand eczema had most often a good effect of treatment: 68.3% in alitretinoin and 50.7% in acitretin treatment. The drug survival rates of alitretinoin and acitretin after 12, 24, 36, and 52 weeks were 69.3, 45.1, 19.6, 7.0% and 74.3, 45.5, 33.8, 23.2%, respectively. Alitretinoin and acitretin are effective treatment options for patients with hand eczema. However, both treatments were more effective in patients with hyperkeratotic hand eczema. Fewer patients discontinued alitretinoin compared with acitretin due to adverse events.

The optimal patch test concentration for ascaridole as a sensitizing component of tea tree oil.

BACKGROUND: Tea tree oil is used as a natural remedy, but is also a popular ingredient in household and cosmetic products. Oxidation of tea tree oil results in degradation products, such as ascaridole, which may cause allergic contact dermatitis. OBJECTIVES: To identify the optimal patch test concentration for ascaridole, and to investigate the relationship between a positive reaction to ascaridole and a positive reaction to oxidized tea tree oil. PATIENTS/MATERIALS/METHODS: Three hundred and nineteen patients with eczema were patch tested with ascaridole 1%, 2%, and 5%, and 250 patients were patch tested with oxidized tea tree oil 5%. Readings were performed on D3 and D7 according to a patch test calibration protocol. RESULTS: With an increasing ascaridole test concentration, the frequency of positive reactions increased: ascaridole 1%, 1.4%; ascaridole 2%, 5.5%; and ascaridole 5%, 7.2%. However, the frequencies of irritant and doubtful reactions also increased, especially for ascaridole 5%. A positive reaction to ascaridole was related to a positive reaction to tea tree oil. CONCLUSIONS: This study is in support of ascaridole being a sensitizer. We recommend patch testing with ascaridole at 2%. The finding that every positive reaction to oxidized tea tree oil is accompanied by a positive reaction to ascaridole suggests that ascaridole might be a contact allergen in oxidized tea tree oil.

Occupational skin hazards and prevalence of occupational skin diseases in shoe manufacturing workers in Indonesia.

PURPOSE: Shoe manufacturing workers are exposed daily to an extensive range of potential physical and chemical occupational hazards. Shoe manufacturing in Indonesia is one of the industrial sectors that has shown sustained growth amongst the newly industrialized countries (NICs). In this study, we investigated the possible potential exposure of the workers to physical and occupational hazards and determined the prevalence of occupational skin diseases at a shoe manufacturing factory in Indonesia. METHODS: A cross-sectional study on the observation of the working process and an inventory and risk assessment of exposure to the chemicals used. Classification of chemicals as potential sensitizers/irritants and qualitative assessments of these chemicals were done. Workers were examined and interviewed using the Nordic Occupational Skin Questionnaire-2002/LONG. RESULTS: The risk of Occupational skin diseases (OSD) at the shoe factory was mainly related to the exposure of the workers' skin to potential physical and chemical hazards in hot and humid environmental conditions. From a total of 514 workers, 8.5 % reported current OSD and 4.8 % reported a history of OSD. Occupational skin diseases were diagnosed in 29 % of the workers by dermatologists and 7.6 % had an occupational contact dermatitis (OCD). Of the 39 workers with contact dermatitis, 33 consented to being patch tested, 14 (3 %) workers showed a positive results and considered as having an occupational allergic contact dermatitis (OACD) and 25 (4.9 %) had an occupational irritant contact dermatitis (OICD). CONCLUSION: We observed a repeated and prolonged exposure of the workers to numerous physical and chemical skin hazards at this factory.

Abnormal expression of MAPK, EGFR, CK17 and TGk in the skin lesions of chloracne patients exposed to dioxins.

OBJECTIVE: Chloracne is one of the most sensitive and specific hallmark of dioxin intoxication. Although its clinical features are clearly described, poor understanding of the molecular pathways of dioxin-induced chloracne hampers a rational approach to therapy. The aim of the present study was to investigate the role of EGFR, MAPK, CK17, and TGk in the pathogenesis of chloracne related to dioxin exposures. METHODS: Epidermal tissues of twelve chloracne patients exposed to dioxins were compared with tissues from 12 healthy controls. These skin tissues were obtained by punch biopsies. p-EGFR and p-MAPK were examined by immunofluorescence. The mRNA and protein levels of CK17 and TGk were examined by fluorescence in situ hybridization and immunohistochemistry, respectively. RESULTS: p-EGFR and p-MAPK were found in all chloracne tissues, whereas no expression was found in the controls. CK17 mRNA and protein were also found in all chloracne lesions, but none in controls (P=0.000). TGk mRNA and protein were detected in both groups, but the distribution was distinct. The positive signals in the controls were mainly in the stratum granulosum, while in the chloracne tissues, the positive signals were found more significantly in the stratum granulosum and stratum spinosum. CONCLUSIONS: The results demonstrate that in the human skin the activation of mitogen-activated protein kinase pathway and up-regulation of CK17 and TGK may play roles in the pathogenesis of chloracne related to dioxin exposures.

Relationship between formaldehyde and quaternium-15 contact allergy. Influence of strength of patch test reactions.

BACKGROUND: In groups of patients with formaldehyde allergy, many have positive patch tests to quaternium-15. Conversely, of patients allergic to quaternium-15, over half also react to formaldehyde. OBJECTIVES: To test our hypothesis that patients with stronger patch test reactions to formaldehyde are more likely to react to quaternium-15, attesting to the aetiological role for formaldehyde in such co-reactivity. METHODS: Retrospective analysis of all patients patch tested with formaldehyde and quaternium-15 in the European baseline series between 1994 and 2009 (TRUE test). RESULTS: In a group of 86 patients allergic to formaldehyde, 73% co-reacted to quaternium-15; in the subgroup of 70 women, the percentage was 83. In both groups, more reactions were observed to quaternium-15 in the patients with a ++ reaction compared to the patients with a + reaction to formaldehyde. Conversely, stronger reactions to quaternium-15 were significantly more often associated with formaldehyde sensitivity in a group of 107 patients reacting to quaternium-15 and a subgroup of 88 women. In men, such effects were not observed and only 5 of 16 (31%) men allergic to formaldehyde also reacted to quaternium-15. CONCLUSIONS: In women, but not in men, stronger reactions to formaldehyde lead to more positive quaternium-15 patch tests.

Formaldehyde-releasers: relationship to formaldehyde contact allergy. Part 2: Metalworking fluids and remainder.

We have reviewed formaldehyde-releasers used in metalworking fluids (MWFs) in this and a previous part of a two-part article. These biocides do not appear to be frequent or important sensitizers. Even in highly selected patient groups of metalworkers, mean prevalence rates of sensitivity are low: 0.2% for Tris(hydroxymethyl)nitromethane, 1.6% for tris(N-hydroxyethyl)hexahydrotriazine, 1.9% for Bioban P-1487 and Bioban CS-1246, and 2.8% for Bioban CS-1135. In the case of the Biobans, many reactions may have been irritant. Only N,N'-methylenebis(5-methyloxazolidine) has a fairly high mean score of 4.0% in metalworkers. With the exception of Bioban P-1487, there is a clear relationship between positive patch test reactions to the releasers and formaldehyde sensitivity: 40-70% of reactions to releasers occur in patients sensitive to formaldehyde and may therefore be caused by formaldehyde allergy. There is a lack of reliable data on the clinical relevance of contact allergy to the formaldehyde releasers in MWF. In most studies, no data on relevance were provided and in those that did, relevance was often found for a (very small) minority of the reactions only. Also discussed here are the formaldehyde-releasers MDM hydantoin, methenamine, N-methylolchloracetamide, paraformaldehyde, and Preventol D2.

Formaldehyde-releasers: relationship to formaldehyde contact allergy. Metalworking fluids and remainder. Part 1.

This is part of a series of review articles on formaldehyde-releasers and their relationship to formaldehyde contact allergy. Formaldehyde-releasers used in metalworking fluids (MWF) and a group of releasers not presented in previous articles are discussed. Here, in Part 1 of the article, there is a short overview of the composition and functions of MWF, the function of biocides in them, and adverse reactions to MWF. In addition, the releasers in MWF that have caused contact allergy are presented with CAS, synonyms, molecular formula, chemical structure, applications, patch test studies, and amount of formaldehyde released by them. In Part 2 of the article, the relationship between formaldehyde-releasers used in MWF and formaldehyde contact allergy is discussed as are data on miscellaneous releasers not previously presented, followed by a discussion of Parts 1 and 2 of the article.

Formaldehyde-releasers: relationship to formaldehyde contact allergy. Formaldehyde-releasers in clothes: durable press chemical finishes. Part 1.

This is one of a series of review articles on formaldehyde-releasers and their relationship to formaldehyde contact allergy and in this paper formaldehyde-releasers used as durable press chemical finishes (DPCF) in textiles are discussed. The literature on allergy to DPCF since 1980 is presented in two parts. Part 1 (this article) presents a short historical overview of the problems with formaldehyde in clothes and discusses the chemistry of durable press chemical finishes, legislation in various countries, and studies on the amount of formaldehyde present in clothes. In addition, the DPCF that have caused contact allergy are presented with CAS, synonyms, molecular formula, chemical structure, applications, and patch test studies. In the forthcoming part 2, the frequency of sensitization to DPCF, occupational contact sensitization, relevance of patch test reactions, and relationship to formaldehyde contact allergy will be reviewed, followed by a discussion of both parts of the article together.

Formaldehyde-releasers: relationship to formaldehyde contact allergy. Part 2. Formaldehyde-releasers in clothes: durable press chemical finishes.

This is the second part of a review article on formaldehyde-releasers used as durable press chemical finishes (DPCF) in textiles. The early finishes contained large amounts of free formaldehyde, which led to many cases of allergic contact dermatitis to clothes in the 1950s and 1960s. Currently, most finishes are based on modified dimethylol dihydroxyethyleneurea, which releases less formaldehyde. Nevertheless, recent studies in the United States and Israel have identified patients reacting to DPCF, considered to have allergic contact reactions to clothes, either from formaldehyde released by the DPCF therein or from the DPCF per se (in patients negative to formaldehyde). However, all studies had some weaknesses in design or interpretation and in not a single case has the clinical relevance been proven. The amount of free formaldehyde in most garments will likely be below the threshold for the elicitation of dermatitis for all but the most sensitive patients. The amount of free cyclized urea DPCF in clothes is unlikely to be high enough to cause sensitization. Patch test reactions to formaldehyde-releasing DPCF will in most cases represent a reaction to formaldehyde released from the test material.

Formaldehyde-releasers in cosmetics: relationship to formaldehyde contact allergy. Part 1. Characterization, frequency and relevance of sensitization, and frequency of use in cosmetics.

In this part of a series of review articles on formaldehyde-releasers and their relationship to formaldehyde contact allergy, formaldehyde-releasers in cosmetics are discussed. In this first part of the article, key data are presented including frequency of sensitization and of their use in cosmetics. In Europe, low frequencies of sensitization have been observed to all releasers: 2-bromo-2-nitropropane-1,3-diol 0.4-1.2%, diazolidinyl urea 0.5-1.4%, imidazolidinyl urea 0.3-1.4%, quaternium-15 0.6-1.9% (for DMDM hydantoin no recent data are available). All releasers score (far) higher prevalences in the USA; the possible explanations for this are discussed. The relevance of positive patch test reactions has been insufficiently investigated. In the USA, approximately 20% of cosmetics and personal care products (stay-on products: 17%, rinse-off products 27%) contain a formaldehyde-releaser. The use of quaternium-15 is decreasing. For Europe, there are no comparable recent data available. In the second part of the article, the patch test relationship of the releasers in cosmetics to formaldehyde contact allergy will be reviewed and it will be assessed whether products preserved with formaldehyde-releasers may contain enough free formaldehyde to pose a threat to individuals who have contact allergy to formaldehyde.

Formaldehyde-releasers in cosmetics: relationship to formaldehyde contact allergy. Part 2. Patch test relationship to formaldehyde contact allergy, experimental provocation tests, amount of formaldehyde released, and assessment of risk to consumers allergic to formaldehyde.

This is the second part of an article on formaldehyde-releasers in cosmetics. The patch test relationship between the releasers in cosmetics to formaldehyde contact allergy is reviewed and it is assessed whether products preserved with formaldehyde-releasers may contain enough free formaldehyde to pose a threat to individuals with contact allergy to formaldehyde. There is a clear relationship between positive patch test reactions to formaldehyde-releasers and formaldehyde contact allergy: 15% of all reactions to 2-bromo-2-nitropropane-1,3-diol and 40-60% of the reactions to the other releasers are caused by a reaction to the formaldehyde in the test material. There is only fragmented data on the amount of free formaldehyde in cosmetics preserved with formaldehyde donors. However, all releasers (with the exception of 2-bromo-2-nitropropane-1,3-diol, for which adequate data are lacking) can, in the right circumstances of concentration and product composition, release >200 p.p.m. formaldehyde, which may result in allergic contact dermatitis. Whether this is actually the case in any particular product cannot be determined from the ingredient labelling. Therefore, we recommend advising patients allergic to formaldehyde to avoid leave-on cosmetics preserved with quaternium-15, diazolidinyl urea, DMDM hydantoin, or imidazolidinyl urea, acknowledging that many would tolerate some products.

No increased risk of cancer after coal tar treatment in patients with psoriasis or eczema.

Coal tar is an effective treatment for psoriasis and eczema, but it contains several carcinogenic compounds. Occupational and animal studies have shown an increased risk of cancer after exposure to coal tar. Many dermatologists have abandoned this treatment for safety reasons, although the risk of cancer after coal tar in dermatological practice is unclear. This large cohort study included 13,200 patients with psoriasis and eczema. Information on skin disease and treatment, risk factors, and cancer occurrence was retrieved from medical files, questionnaires, and medical registries. Proportional hazards regression was used to evaluate differences in cancer risk by treatment modality. Patients treated with coal tar were compared with a reference category of patients treated with dermatocorticosteroids (assumed to carry no increased cancer risk). The median exposure to coal tar ointments was 6 months (range 1-300 months). Coal tar did not increase the risk of non-skin malignancies (hazard ratio (HR) 0.92; 95% confidence interval (CI) 0.78-1.09), or the risk of skin cancer (HR 1.09; 95% CI 0.69-1.72). This study has sufficient power to show that coal tar treatment is not associated with an increased risk of cancer. These results indicate that coal tar can be maintained as a safe treatment in dermatological practice.