Continuous usage of a hair dye product containing 2-methoxymethyl-para-phenylenediamine by hair-dye-allergic individuals.

BACKGROUND: Despite a positive patch test reaction to para-phenylenediamine (PPD) and/or toluene-2,5-diamine (PTD), many people attempt to continue dyeing their hair with products containing PPD or its derivatives. OBJECTIVES: Investigation of elicitation reactions among PPD/PTD-allergic individuals to hair dye products containing the less sensitizing PPD derivative 2-methoxymethyl (ME)-PPD. METHODS: Elicitation reactions were studied in 43 PPD/PTD-allergic individuals by a 45-min pretest with an ME-PPD-containing hair dye on their forearm. Upon a negative result this was followed by exposure to subsequent hair colour treatment(s). RESULTS: Overall, 38 of 43 PPD/PTD-allergic individuals did not develop an elicitation reaction during the pretest with ME-PPD-containing hair dye products, and were eligible for subsequent hair colour treatments. Of these 38 PPD/PTD-allergic individuals, 29 tolerated subsequent hair dyeing with ME-PPD-containing hair dye products, while seven showed mild and two showed moderate/marked allergic reactions upon the first hair colour treatment. CONCLUSIONS: Hair dye products with the less sensitizing ME-PPD were tolerated by 29 of 43 (67%) PPD/PTD-allergic individuals throughout continued hair dyeing with an average of nine treatments per year. Five individuals reacted upon pretesting, while only mild-to-moderate/marked skin reactions occurred upon hair dyeing in nine individuals who were not identified by the pretest. To our knowledge this is the first study among PPD/PTD-allergic individuals indicating that a negative 45-min pretest with a hair dye product helps to avoid severe allergic reactions.

Prevalence of contact allergy in the general population in different European regions.

BACKGROUND: Population-based studies about contact allergy are scarce. OBJECTIVES: To obtain reliable estimates of the prevalence of contact allergy in the general population in Europe. METHODS: A cross-sectional study of a random sample from the general population, aged 18-74 years, in five different European countries (Sweden, the Netherlands, Germany, Italy and Portugal). In total, 12 377 subjects were interviewed and a random sample (n = 3119) patch tested to TRUE Test panels 1-3 and Fragrance Mix (FM) II, hydroxyisohexyl 3-cyclohexene carboxaldehyde (HICC) and sesquiterpene lactone mix. A positive patch test reaction is considered as contact allergy. RESULTS: In total, 27·0% [95% confidence interval (CI) 25·5-28·5] had at least one positive reaction to an allergen of the European baseline series, with a significantly higher prevalence in women than in men. The highest age-standardized prevalences (≥ 1%) were found for nickel (14·5%, 95% CI 13·2-15·8), thiomersal (5·0%, 95% CI 4·2-5·8), cobalt (2·2%, 95% CI 1·7-2·7), FM II (1·9%, 95% CI 1·5-2·5), FM I (1·8%, 95% CI 1·4-2·3), HICC (1·4%, 95% CI 1·0-1·9), p-tert-butylphenol formaldehyde resin (1·3%, 95% CI 0·9-1·7) and para-phenylenediamine (1·0%, 95% CI 0·6-1·3). Only nickel and thiomersal showed a statistically significantly different prevalence for contact allergy among the different European populations. Subjects reporting contact dermatitis in their lifetime (age-standardized prevalence 15·1%, 95% CI 13·8-16·3) had an increased risk for contact allergy (odds ratio 1·9, 95% CI 1·5-2·5). The risk of having a contact allergy was not increased in those with atopic dermatitis (prevalence 7·6%, 95% CI 6·7-8·6; odds ratio 1·0, 95% CI 0·7-1·4). CONCLUSIONS: Contact allergy to at least one allergen of the European baseline series was diagnosed in more than one-quarter of the general European population. Therefore measures to improve the primary prevention of contact allergy have to be enforced.

Drug survival of cyclosporine in the treatment of hand eczema: a multicentre, daily use study.

BACKGROUND: Hand eczema is a common condition; it is often chronic and can be difficult to treat. Cyclosporine is used off-label to treat severe hand eczema; however, the evidence for this treatment is scarce. OBJECTIVE: To examine the drug survival of cyclosporine in a daily practice cohort of patients with chronic hand eczema. METHODS: This retrospective daily use study included hand eczema patients who were treated with cyclosporine between 01-06-1999 and 01-06-2014 in two Dutch university hospitals. Patient and treatment characteristics were retrospectively collected from medical charts. First treatment episodes were analysed by means of Kaplan-Meier drug survival curves. Possible determinants of drug survival were analysed by Cox regression models. Treatment effectiveness was analysed with a retrospective physician's global assessment. RESULTS: A total of 102 patients were treated with cyclosporine. The median drug survival rate was 0.86 years (10.3 months). The overall drug survival rate after 6 months, 1, 2 and 3 years were 61.7%, 45.2%, 18.6% and 13.9% respectively. Main reasons for discontinuation were adverse events, especially early in treatment, and ineffectiveness. After 3 months, a good response to treatment was recorded in 62.9% of the patients. CONCLUSION: Cyclosporine had a median drug survival of 10.3 months. Especially patients with recurrent vesicular hand eczema showed a good treatment response.

Assessment of the elicitation response in subjects weakly sensitized to p-phenylenediamine.

BACKGROUND: A 30-min application of a hair dye product containing 2% p-phenylenediamine (PPD) to subjects diagnostically graded +, showed that 12 of 18 reacted; eight of 18 with a true + and four of 18 with a doubtful (?+) response, whereas six of 18 did not react at all. In vitro skin-binding experiments showed that for diagnostic patch test conditions the measured exposure level (MEL) is more than 10-fold higher than the MEL for hair dyeing conditions. OBJECTIVE: To further analyse the limited elicitation response of the diagnostically + graded subjects to a PPD hair dye product, under standardized test conditions mimicking product usage, by varying exposure time and dose. METHODS: A hair dye model formulation containing 2% PPD, applied for 30, 45 and 60 min and a diagnostic PPD TRUE test(®) were applied to assess elicitation responses to increasing PPD exposure levels. Grading was performed according to International Contact Dermatitis Research Group guidelines. RESULTS: Six subjects were available for this follow-up study. One of six subjects responded with a + elicitation response to the hair dye model applied for 60 min. Four of the five remaining subjects elicited a + response to the PPD TRUE test(®) applied subsequently, while one of five responded doubtfully. CONCLUSIONS: Increasing the PPD exposure time twofold--resulting in a 5-6% increase of sensitivity of this hair dye model test--or further extending the exposure time 48-fold, was found sufficient to increase the MEL above the thresholds needed to elicit individuals with a + diagnostic PPD patch test who did not react to typical hair dye use conditions with a MEL of about 6·8 µg cm⁻². This analysis confirms that consideration of the MEL is a useful tool to better characterize thresholds of elicitation than consideration of the applied dose alone.

Cross-elicitation responses to 2-methoxymethyl-p-phenylenediamine under hair dye use conditions in p-phenylenediamine-allergic individuals.

BACKGROUND: The factors influencing elicitation responses in individuals allergic to p-phenylenediamine (PPD) in hair dyes are not well understood. OBJECTIVES: Investigation of the elicitation response to the new, less-sensitizing PPD alternative 2-methoxymethyl-p-phenylenediamine (ME-PPD) under simulated hair dye use conditions. METHODS: The cross-elicitation response to ME-PPD (2% in a hair dye test product for 30 min on forearm then rinsing) was analysed at days 2 and 3 in 30 PPD-allergic individuals with diagnostic patch test grades +, ++ or +++ according to the classification of the International Contact Dermatitis Research Group. RESULTS: Cross-reactivity to the ME-PPD-containing hair dye test product was elicited in nine of 30 subjects (30%), while 70% were negative. Cross-reactivity was elicited in two of four cases with grade +++, three of 10 with grade ++ and four of 16 with grade +. Under identical conditions, PPD was previously found to elicit a response in 21 of 27 PPD-allergic individuals. In 18 of these 21 individuals, either the strength of the cross-elicitation response to ME-PPD was decreased or no response occurred. CONCLUSIONS: Under simulated hair dye use conditions, a significantly lower degree of cross-elicitation to ME-PPD (30%) was observed than previously reported for PPD (32 of 38, 84%). Additionally, a decreased cross-elicitation strength was observed across all three patch test grades, likely reflecting the reduced skin-sensitization properties of ME-PPD. Consequently, careful dermatological evaluation is required to assess cross-reactivity to ME-PPD in patients allergic to hair dyes.

Prevalence of fragrance contact allergy in the general population of five European countries: a cross-sectional study.

BACKGROUND: Contact allergy to fragrances is assessed mostly in clinical populations of patients. Studies in the general population are scarce and vary in their methodology across countries. OBJECTIVES: To determine the prevalence of fragrance contact allergy in the European general population and to assess the clinical relevance of positive patch test reactions to different fragrances. METHODS: In five European countries (Germany, Italy, the Netherlands, Portugal and Sweden) a random sample from the general population aged 18-74 years was drawn. In total, 12 377 subjects were interviewed in this cross-sectional study and a random sample (n = 3119) was patch tested using the TRUE Test and Finn Chamber techniques. Patch test procedures were harmonized by mandatory training before the study and monitoring during the study. RESULTS: The highest prevalence for contact allergy of 2·6% [95% confidence interval (CI) 2·1-3·2] was found for fragrance mix (FM) I in petrolatum, with a high content of atranol and chloratranol, followed by 1·9% (95% CI 1·5-2·4) for FM II in petrolatum. The conservatively estimated prevalence of fragrance contact allergy was 1·9% (95% CI 1·5-2·5). This is defined as the existence of a positive patch test to FM I or FM II; any of their individual materials; Myroxylon pereirae; sesquiterpene lactones or 3- and 4-hydroxyisohexyl 3-cyclohexene carboxaldehyde that show clinical relevance, defined conservatively as lifetime avoidance of scented products and an itchy skin rash lasting > 3 days in a lifetime. Using the reported lifetime prevalence of any contact dermatitis instead of the lifetime prevalence of any itchy skin rash, the prevalence is 0·8% (95% CI 0·5-1·2). The prevalence rates of contact allergy to fragrances in women are about twice those in men. CONCLUSIONS: This study helps to identify targets for prevention of fragrance allergy.

Patch test results of hand eczema patients: relation to clinical types.

BACKGROUND: Allergic contact dermatitis is a well-known cause of hand eczema, although the influence of contact allergens on different clinical types of hand eczema remains still unclear. OBJECTIVE: To identify most common positive tested allergens among hand eczema patients and to define the relation between specific contact allergies and clinical types of hand eczema according to the guidelines of the Danish Contact Dermatitis Group (DCDG). METHODS: We included 1571 hand eczema subjects who were patch tested from 1 January 2002 to 31 December 2013. They were retrospectively classified according to the guidelines of the DCDG into six clinical types: recurrent vesicular hand eczema, chronic fissured hand eczema, hyperkeratotic palmar eczema, pulpitis, interdigital eczema and nummular hand eczema according to a newly developed flow chart. The prevalence of sensitizations and association with clinical type, atopic dermatitis, age and gender were studied. RESULTS: A total of 1395 subjects were classified into one of the six clinical types. The most frequently found clinical types were recurrent vesicular hand eczema (39.7%) and chronic fissured hand eczema (35.5%). Subjects with recurrent vesicular hand eczema were significantly more likely to have a contact allergy (OR 1.55), whereas subjects with hyperkeratotic palmar eczema and pulpitis were less likely to be sensitized (OR 0.51; OR 0.44). Overall, metals (nickel sulphate, cobalt chloride), fragrances and preservatives (methylchloroisothiazoline/methylisothiazoline, methyldibromoglutaronitrile) were the most frequent sensitizers in patients with hand eczema. This did not deviate in the different clinical types, although subjects with recurrent vesicular hand eczema were significantly more frequently sensitized to nickel sulphate and other allergens compared to other clinical types of hand eczema. CONCLUSION: In the diagnostic work up of hand eczema subjects with recurrent vesicular hand eczema should be patch tested, especially women of older age, although the need for patch testing in males with hyperkeratotic palmar eczema might be less imperative.

Contact allergy in Indonesian patients with foot eczema attributed to shoes.

BACKGROUND: Shoe dermatitis is a form of contact dermatitis resulting from exposure to shoes. Allergens and types of shoes responsible may vary depending on manufacturing techniques, climatic conditions and indigenous traditions. This study focuses primarily on as yet unexplored shoe dermatitis cases in Indonesia. OBJECTIVE: To determine the prevalence of shoe dermatitis in the Dermatology outpatient clinic, Sardjito University Hospital, Yogyakarta, Indonesia over a period of 3 years and to identify the responsible allergens. METHODS: All patients meeting screening criteria for possible shoe contact dermatitis were patch tested with the European baseline series, shoe series and additional series based on earlier studies of Indonesian leather and shoe manufacturers; some were also patch tested with their own shoe materials and shoe extracts. RESULTS: Sixty-four (7.1%) of 903 patients with foot skin disorders were diagnosed with shoe dermatitis. Twenty-five (52.1%) of 48 patch-tested patients showed positive reactions to one or more allergens related to footwear. Sixteen patients were patch tested with their own shoe materials; 11 showed positive reactions. The most frequent relevant sensitizers were rubber allergens followed by preservatives, shoe adhesives and leather materials. CONCLUSION: Shoe dermatitis is common in Indonesia. Using three series of patch tests, we identified responsible allergens and patterns of sensitization in Indonesian shoe dermatitis patients.

Keratolysis exfoliativa (dyshidrosis lamellosa sicca): a distinct peeling entity.

BACKGROUND: Keratolysis exfoliativa (KE), also known as dyshidrosis lamellosa sicca, is a palmoplantar dermatosis characterized by air-filled blisters and collarette desquamation. It has been regarded as a subtype of dyshidrotic eczema, a fungal infection or a dermatophytid reaction. KE may also resemble acral peeling skin syndrome and localized epidermolysis bullosa simplex. Although KE is a common disorder, it is a rarely reported and is an under-recognized dermatosis. OBJECTIVES: To delineate the characteristic features of KE. METHODS: We investigated the clinical, immunohistopathological, ultrastructural and molecular features of KE. Patients were included from the clinical records. Additional diagnostic research consisted of mutation analysis of the candidate genes TGM5, KRT5, KRT14, FLG, SPINK6 and SPINK9. RESULTS: A total of 24 patients with KE were identified, six with familial and 18 with sporadic KE. Lesions consisted of air-filled blisters only on palmoplantar skin, followed by collarette and lamellar peeling. Both light microscopy and electron microscopy showed cleavage and partially degraded corneodesmosomes within the stratum corneum, whereas immunofluorescence microscopy showed normal expression of corneodesmosomal components. No mutations were found in TGM5, KRT5/14 and SPINK6/9. There was no clear link with atopy or with FLG mutations. CONCLUSIONS: Our study suggests premature corneodesmolysis as the main pathological mechanism of this palmoplantar skin disorder. We conclude that KE appears to be a distinct peeling entity.

Costs and cost-effectiveness analysis of treatment in children with eczema by nurse practitioner vs. dermatologist: results of a randomized, controlled trial and a review of international costs.

BACKGROUND: In a randomized, controlled trial (RCT) on childhood eczema we reported that substituting nurse practitioners (NPs) for dermatologists resulted in similar outcomes of eczema severity and in the quality of life, and higher patient satisfaction. OBJECTIVES: To determine costs and cost-effectiveness of care provided by NPs vs. dermatologists and to compare our results with those in studies from other countries. METHODS: We estimated the healthcare costs, family costs and the costs in other sectors alongside the RCT. All the costs were linked to quality of life [Infants' Dermatitis Quality of Life Index (IDQOL), Children's Dermatology Life Quality Index (CDLQI)] and to patient satisfaction (Client Satisfaction Questionnaire-8) to determine the incremental cost-effectiveness ratio (ICER). We also examined all the reported studies on the costs of childhood eczema. RESULTS: The mean annual healthcare costs, family costs and costs in other sectors were €658, €302 and €21, respectively, in the NP group and €801, €608 and €0·93, respectively, in the dermatologist group. The ICER in the NP group compared with the dermatologist group indicated €925 and €751 savings per one point less improvement in IDQOL and CDLQI, respectively, and €251 savings per one point more satisfaction in the NP group at 12 months. The mean annual healthcare costs and family costs varied considerably in the six identified studies. CONCLUSIONS: Substituting NPs for dermatologists is both cost-saving and cost-effective. The treatment of choice is that provided by the NPs as it is similarly effective to treatment provided by a dermatologist with a higher parent satisfaction. International comparisons are difficult because the types of costs determined, the units and unit prices, and eczema severity all differ between studies.

Pharmacokinetics, efficacy and safety of alitretinoin in moderate or severe chronic hand eczema.

BACKGROUND: Recent studies have found that alitretinoin can induce clinically significant responses in subjects with severe chronic hand eczema (CHE) unresponsive to topical corticosteroids. AIMS: To assess the pharmacokinetics (PK), efficacy and safety of alitretinoin 10 or 30 mg once daily. METHODS: This was a randomized, double-blind study, which enrolled 32 subjects aged 18-75 years with CHE unresponsive to potent topical corticosteroids. Subjects received alitretinoin 10 mg (n = 16) or 30 mg (n = 16) once daily for 12 or 24 weeks. Standard PK variables [area under the curve (AUC) of plasma concentration vs. time, maximum plasma concentration (C(max)), time to maximum plasma concentration (t(max)), elimination half-life (t(1/2)), total systemic clearance (CL/F) and volume of distribution (Vd/F)] were determined for alitretinoin and metabolites. Efficacy was assessed using the Physician's Global Assessment (PGA) scale. RESULTS: Chronic administration of alitretinoin for up to 24 weeks did not result in accumulation or time-dependent changes in the disposition of alitretinoin. Exposure was found to be proportional to dose. Systemic exposure (AUC) to alitretinoin was proportional to dose for 10 and 30 mg alitretinoin; 62.8% of subjects achieved clear/almost clear hands in the 30 mg group and 12.5% in the 10 mg group. Alitretinoin was well tolerated. CONCLUSIONS: Chronic administration of alitretinoin for 12-24 weeks did not lead to accumulation or time-dependent changes in drug exposure. Alitretinoin was effective and well tolerated in the treatment of subjects with moderate or severe CHE unresponsive to potent topical corticosteroids.

A randomized controlled trial in children with eczema: nurse practitioner vs. dermatologist.

Background We hypothesized that a nurse practitioner would improve the quality of life of a child with eczema more than a dermatologist because of a structured intervention and more consultation time. Objectives To compare the level of care by nurse practitioners with that by dermatologists in children with eczema. Methods New referrals aged < or = 16 years with a diagnosis of eczema were recruited. In a randomized, parallel-group study with a follow-up period of 1 year, 160 participants were randomized either to conventional care from a dermatologist or to care from a nurse practitioner. The primary outcome measure was change in quality of life at 12 months, as assessed by the Infants' Dermatitis Quality of Life Index (IDQOL) for children aged < or = 4 years, and by the illustrated version of the Children's Dermatology Life Quality Index (CDLQI) for children aged 4-16 years. Secondary outcomes were changes in IDQOL and CDLQI at 4 and 8 months, family impact of childhood atopic dermatitis (Dermatitis Family Impact Questionnaire, DFI), eczema severity (objective SCORAD) and patient satisfaction (Client Satisfaction Questionnaire-8, CSQ-8) at 4, 8 and 12 months. Results The mean IDQOL in the dermatologist group improved significantly from 11.6 [SD 8.1; 95% confidence interval (CI) 9.0-14.2] at the baseline to 5.6 (SD 3.9; 95% CI 4.3-7.0) at 12 months with a mean change from the baseline of -6.5 (SD 6.6; 95% CI -14.2 to -8.9; P < 0.001). The mean IDQOL in the nurse practitioner group improved significantly from 10.7 (SD 4.9; 95% CI 9.1-12.3) at baseline to 5.7 (SD 5.4; 95% CI 4.0-7.5) at 12 months with a mean change from the baseline of -4.9 (SD 5.5; 95% CI -6.8 to -3.0; P < 0.001). The between-groups difference was (-)1.7 (95% CI -4.6 to 1.2; P = 0.26). The mean CDLQI in the dermatologist group improved significantly from 12.1 (SD 6.3; 95% CI 9.9-14.2) at baseline to 5.6 (SD 4.2; 95% CI 4.2-7.1) at 12 months with a mean change from the baseline of -5.9 (SD 6.0; 95% CI -8.0 to -3.9; P < 0.001). The mean CDLQI in the nurse practitioner group improved significantly from 10.0 (SD 4.4; 95% CI 8.5-11.4) at the baseline to 4.9 (SD 3.5; 95% CI 3.7-6.1) at 12 months with a mean change from the baseline of -5.2 (SD 4.0; 95% CI -6.6 to -3.8; P < 0.001). The between-groups difference was (-)0.7 (95% CI -3.3 to 1.7; P = 0.55). The between-groups comparison was not significant for the IDQOL and the CDLQI at baseline or 4, 8 and 12 months. Both treatment groups showed significant improvement in DFI and objective SCORAD at 12 months. The between-groups comparison was not significant at baseline or 4, 8 and 12 months. Significantly higher satisfaction levels were observed at 4, 8 and 12 months in the nurse practitioner group. Conclusions The level of care provided by a nurse practitioner in terms of the improvement in the eczema severity and the quality of life outcomes was comparable with that provided by a dermatologist. In addition, the parents were more satisfied with the care that was provided by a nurse practitioner.

Elicitation of the immune response to p-phenylenediamine in allergic patients: the role of dose and exposure time.

BACKGROUND: Usage of hair dye products containing p-phenylenediamine (PPD) is a concern for PPD-allergic individuals. OBJECTIVES: The present study investigates the role of dose and exposure time on elicitation of allergic contact dermatitis under conditions of permanent hair dyeing. METHODS: Elicitation responses after application of a typical hair dye product containing 2% PPD for 30 min followed by rinsing were analysed in 38 PPD-allergic individuals with a documented history of hair dye-related allergy. Skin binding experiments in vitro were performed to distinguish the dose available for elicitation from the dose applied. RESULTS: A positive reaction was elicited in 20 of 20 patients with grades ++ to +++ and 12 of 18 with grade + according to the classification of the International Contact Dermatitis Research Group. Under conditions of diagnostic patch testing (48 h exposure), the dose available for elicitation is more than 10-fold higher compared with the dose available for hair dyeing (30-min exposure, rinsing of product). CONCLUSIONS: This investigation demonstrates that under simulated hair dye use conditions the actual exposure to PPD is more than an order of magnitude lower than under diagnostic patch testing, although sufficient to elicit a clearly noticeable reaction in 84% of PPD patch test-positive individuals.

Comparators, study duration, outcome measures and sponsorship in therapeutic trials of psoriasis: update of the EDEN Psoriasis Survey 2001-2006.

BACKGROUND: Several new therapeutic options for psoriasis have been tested in clinical trials in recent years. Choice of comparator, study duration and outcome measures are critical for interpreting application of trial results to clinical practice. OBJECTIVES: We examined whether these trial aspects have changed substantially in recent years in comparison with the past. METHODS: A systematic search and evaluation of all randomized controlled trials (RCTs) for psoriasis published from January 2001 up to December 2006 in 14 leading medical and dermatological journals, compared with those published from 1977 to 2000. RESULTS: There were 140 RCTs of psoriasis in the period 2001-2006 and 249 in the period 1977-2000. The proportion of placebo-controlled studies increased from 44.6% to 69.3%. The median study duration increased from 7 weeks to 12 weeks. The proportion of studies adopting the Psoriasis Area and Severity Index score as an outcome increased from 30.6% to 57.7%, while the number of studies incorporating a quality of life measure increased from only one (0.4%) to 12 studies (7.7%). The proportion of studies sponsored by pharmaceutical companies increased from 61.0% to 73.7%. CONCLUSIONS: Despite the increased number of new options, the number of head-to-head comparative trials has decreased and most trials focus on short-term effects, probably reflecting the increased influence of industrial sponsorship on the research agenda.

Association between TNFA-308 G/A polymorphism and sensitization to para-phenylenediamine: a case-control study.

BACKGROUND: Para-phenylenediamine (PPD) and related chemicals are common contact sensitizers, frequently causing allergic contact dermatitis (ACD). The cytokine tumor necrosis factor-alpha (TNF-alpha) plays a key role in contact sensitization. METHODS: In this case-control study, we evaluated the distribution of variations in the regulatory region of the gene for TNF-alpha (TNFA-308 G/A) in 181 Caucasian individuals with a history of ACD and sensitization to PPD and 161 individuals with no history of sensitization to PPD. RESULTS: The frequency of GA or AA TNFA genotypes was significantly higher in individuals sensitized to PPD than in age- and gender-matched controls giving an odds ratio (OR) of 2.16 (95% confidence interval, CI: 1.35-3.47; P = 0.0016). This relation was even more pronounced when restricting cases to females over 45 years (OR = 3.71; 95% CI: 1.65-8.31; P = 0.0017) vs younger females (less than or equal to 45 years; OR = 2.41; 95% CI: 1.03-5.65; P = 0.044) or males (OR = 1.05; 95% CI: 0.449-2.47; P = 1.0). In addition, a logistic regression model revealed a significant effect for TNFA-308 AA and AG vs GG genotype (point estimate = 2.152; 95% Wald CI: 1.332-3.477). CONCLUSIONS: These findings suggest a possible role for the TNFA-308 genetic polymorphism as a susceptibility factor for chemically induced ACD.

Para-phenylenediamine and allergic sensitization: risk modification by N-acetyltransferase 1 and 2 genotypes.

BACKGROUND: Para-phenylenediamine (PPD) is a common contact sensitizer causing allergic contact dermatitis, a major skin problem. As PPD may need activation to become immunogenic, the balance between activation and/or detoxification processes may influence an individual's susceptibility. PPD is acetylated and the metabolites do not activate dendritic-like cells and T cells of PPD-sensitized individuals. OBJECTIVES: To investigate whether PPD can be acetylated in vitro by the two N-acetyltransferases 1 (NAT1) and 2 (NAT2). Based on the assumption that N-acetylation by NAT1 or NAT2 is a detoxification reaction with respect to sensitization, we examined whether NAT1 and NAT2 genotypes are different between PPD-sensitized individuals and matched controls. METHODS: Genotyping for NAT1 and NAT2 polymorphisms was performed in 147 PPD-sensitized individuals and 200 age- and gender-matched controls. Results Both PPD and monoacetyl-PPD were N-acetylated in vitro by recombinant human NAT1 and to a lesser extent by NAT2. Genotyping for NAT1*3, NAT1*4, NAT1*10, NAT1*11 and NAT1*14 showed that genotypes containing the rapid acetylator NAT1*10 allele were under-represented in PPD-sensitized cases (adjusted odds ratio 0.72, 95% confidence interval 0.45-1.16). For NAT2, NAT2*4, NAT2*5AB, NAT2*5C, NAT2*6A and NAT2*7B alleles were genotyped. Individuals homozygous for the rapid acetylator allele NAT2*4 were under-represented in cases compared with controls (4.3% vs. 9.4%), but this trend was not significant. CONCLUSIONS: With respect to data indicating that NAT1 but not NAT2 is present in human skin, we conclude that NAT1 genotypes containing the rapid acetylator NAT1*10 allele are potentially associated with reduced susceptibility to PPD sensitization.