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Background: In contact dermatitis, it is crucial to understand and remember the outcome of patch testing. Unfortunately, many patients do not remember the results of their patch tests. Objectives: Our aim was to evaluate the effects of an intervention programme in which extensive information on specific contact allergy was provided, in individuals with positive patch test reactions. Methods: The study was designed as a randomized, investigator-blinded clinical trial. Participants with positive test reactions were randomized into two groups that received either standard information according to clinical routine or standard information and a reminder letter. Knowledge of contact allergies was evaluated using questionnaires 12 months after inclusion. Results: There were 184 adults included in the trial and the response rate at 1-year follow-up was 78% (143 of 184). Sixty-five per cent (45 of 69) in the intervention group and 54% (40 of 74) in the control group reported the correct name of the allergen (P = 0·23). Participants with several – as opposed to few – positive patch test reactions had difficulty in remembering the correct names of the allergens (P = 0·001). Moreover, the type of allergy had an influence on their ability to remember the name of the allergen correctly and their ability to make changes in lifestyle. Conclusions: The intervention performed did not significantly affect the participants’ ability to remember their contact allergy. To achieve better knowledge and changes in lifestyle, efforts to inform should concentrate on individuals with several positive patch test reactions, those with particular allergens, individuals over 60 years of age, and – concerning changes in lifestyle – males. (Less)

BACKGROUND Changing patterns of exposure lead to changes in the spectrum of contact allergy in the general population and in patients patch tested for suspected contact allergy. The main contact allergens (haptens) are assembled in the so-called 'baseline series'. OBJECTIVES To present the current spectrum of contact allergy to baseline series allergens, and its temporal development over the last 12 years, based on data collected by the 56 active departments of the trinational Information Network of Departments of Dermatology (IVDK). METHODS Patch-test data, along with core demographic and clinical information, subdivided into 4-year periods for all patients patch tested with the baseline series in the IVDK, were analysed descriptively. Moreover, log-binomial regression analysis addressed temporal trends of specific contact allergies, adjusted for potentially confounding factors. RESULTS Among the 125 436 patients tested with the German baseline series, the most common allergens were nickel (14·7%), fragrance mix I (8·1%), Myroxylon pereirae resin (7·5%) and cobalt (5·2%), with no conclusive trend. The rise and fall of contact allergy to methylchloroisothiazolinone/methylisothiazolinone (MI), following (self-) regulation in the European Union, reflected the MI contact allergy epidemic. Propolis showed a marked upward trend with a prevalence of 3·94% during the period 2015-2018. CONCLUSIONS Decreases in sensitization prevalence likely reflect reduced exposure, with some lag, as seen with hydroxyisohexyl 3-cyclohexene carboxaldehyde. If no (sufficient) decrease can be observed despite interventions, such as for nickel and chromium, affected subgroups should be identified and their causative exposures explored. Finally, increases such as that observed with propolis, certainly warrant targeted investigation of the exposures driving sensitization, and possibly intervention. What is already known about this topic? Contact allergy is prevalent in the general population. Surveillance based on clinical data offers timely information on trends concerning certain allergens or subgroups at risk. What does this study add? This analysis provides an update of the current contact allergy prevalence in Central Europe, including time trends. This study describes the demographic and clinical profile of patients tested from 2007 to 2018. This research identifies contact allergens that require (further) preventive efforts. Linked Comment: Schuttelaar. Br J Dermatol 2020; 183:800-801.

Background: In a European study on contact allergy in the general population, it was hypothesized that the combination of contact allergy to a fragrance together with a history indicating dermatitis at exposure, and thereafter subsequent avoidance of scented products, implied a diagnosis of allergic contact dermatitis. Objectives: The primary aim of this study was to validate this hypothesis and algorithm. The secondary aim was to investigate whether there was any association between the outcome of the repeated open application test (ROAT) and the patch test reactivity. Methods: In total, 109 patients with and without contact allergy to fragrance mix (FM) I were recruited. Volunteers from six European dermatology clinics participated in the study including a patch test and a ROAT. Results: Positive ROAT reactions were noted in 26 of the 44 volunteers with contact allergy to FM I. None of the volunteers reacted to the vehicle (P < 0·001). More individuals with a positive algorithm had positive ROATs than those with a negative algorithm. However, the difference was not statistically significant. The lower the patch test concentration eliciting a positive test reaction, the more likely a positive ROAT and the more likely that the positive ROAT appeared early during the investigative period. Conclusions: The algorithm used in this study was not substantiated in this ROAT set-up. The stronger the patch test reactivity the more likely was a positive ROAT and the more likely it was that the positive ROAT appeared early during the application period. What's already known about this topic?. To the best of our knowledge, a scientifically designed and conducted repeated open application test (ROAT) has never been performed before to validate a diagnosis of allergic contact dermatitis partly based on a questionnaire. What does this study add?. This is the largest controlled, randomized and blinded ROAT performed to date. Higher patch test reactivity to fragrance mix I indicated a greater likelihood of a positive ROAT. What are the clinical implications of this work?. Further refinement of the questions is required in order to diagnose allergic contact dermatitis from fragrances based on a questionnaire.

BACKGROUND Variables traditionally reported to influence the prognosis of occupational hand eczema (OHE) are atopic dermatitis (AD) and contact sensitization. However, recent studies indicate that lifestyle factors may be of major importance. OBJECTIVES To identify factors influencing the prognosis in a cohort of patients with recognized OHE. METHODS In this register-based cohort study, individuals with hand eczema recognized as occupational disease in the period January 2010-December 2011 were identified using files from Labor Market Insurance Denmark and included in the study. At baseline, information on sex, age, occupation, wet work, AD and contact sensitization was collected. In 2015 participants received a questionnaire with questions about lifestyle factors, current occupation and healing of OHE. RESULTS In total, 2703 patients received the questionnaire; 1491 responded to the question about healing of OHE and were included in the study. Altogether, 19·3% of patients reported complete healing at follow-up. Current tobacco smoking and a high level of stress were factors inversely associated with healing of hand eczema (P < 0·001 and P = 0·030, respectively), while a high level of exercise was significantly related to healing of eczema (P = 0·011). Change of profession was a favourable prognostic factor, while age, sex, AD, contact sensitization and education did not significantly influence prognosis. CONCLUSIONS Traditionally important risk factors such as AD and contact sensitization had no marked influence on prognosis, while lifestyle factors were of major importance. Our findings indicate that risk factors may vary over time, allowing for new perspectives on prevention. What's already known about this topic? Occupational hand eczema has a relapsing course and a poor overall prognosis. Atopic dermatitis and contact sensitization have previously been reported as risk factors for a poor prognosis. What does this study add? The results indicate that lifestyle factors are of importance for the prognosis of occupational hand eczema. Traditionally reported risk factors such as atopic dermatitis and contact sensitization do not currently influence prognosis.

Background Atopic dermatitis (AD) is characterized by an impaired skin barrier, which can allow enhanced penetration of allergens. It is not clear whether AD influences the risk of developing contact allergy. Objectives To examine the association between AD at preschool age and contact allergy at 16 years of age. Methods At 16 years of age, 2215 adolescents from the population-based cohort BAMSE were included. These adolescents had been followed with repeated questionnaires regarding AD throughout childhood, and contact allergy was assessed by skin patch test at 16 years. Results AD at preschool age was associated with contact allergy to at least one of the tested substances at 16 years of age among boys [adjusted odds ratio (OR) 1·51, 95% confidence interval (CI) 1·03-2·20] but not among girls (adjusted OR 0·77, 95% CI 0·54-1·10). AD at preschool age was not associated with contact allergy to nickel in either boys or girls. In contrast, AD at preschool age was associated with contact allergy to fragrance mix I (adjusted OR 3·10, 95% CI 1·66-5·80). This association was observed especially for AD at preschool age in combination with IgE sensitization to airborne or food allergens (adjusted OR 3·80, 95% CI 1·67-8·61). Conclusions The results suggest that AD in early childhood may be associated with contact allergy to fragrances, but not to nickel, in adolescence.

Background Earlier studies suggested an inverse association between contact allergy and psoriasis, although the results of clinical studies have been inconsistent. Gene expression studies in human contact allergy focusing on immune responses revealed nickel being an inducer of T helper (Th)1/Th17 and some Th22 immune polarization, whereas fragrances were found to promote a Th2-dominated immune activation. Objectives To investigate the epidemiological association between contact allergy and psoriasis in a large multicentre cohort and to analyse the sensitization profile to specific allergens in these patients. Methods Retrospective analysis of patch-tested patients from 56 departments of dermatology (1996-2015), including 2387 patients with psoriasis and 161 989 control patients. All patients with atopic dermatitis were excluded from both groups. Results The odds ratio (OR) for contact allergy was calculated to be 0·55 in patients with psoriasis (95% confidence interval 0·50-0·59). Logistic regression analyses with several independent variables indicated a 'protective effect' of having psoriasis for most allergens, independently of age, sex, affected body site and patch test indication. Fragrance mix II (OR 0·36) and lanolin alcohols (OR 0·38) were found to be among the least common allergens in patients with psoriasis. In contrast, the frequency of contact dermatitis to nickel was only marginally affected in patients with psoriasis compared with controls (OR 0·75). Conclusions The inverse association between psoriasis and allergic contact sensitization is likely to be not exclusively mediated by psoriasis itself. The polarization of the activated immune response by specific allergens may influence the occurrence and significance of contact allergies in underlying immune-mediated diseases, eventually even beyond the skin.

SummaryBackground Contact allergy to chloroprene rubber products is well known. Thiourea compounds are considered the cause of allergy. Diethylthiourea commonly occurs in this type of product and can decompose to the sensitizer ethyl isothiocyanate. Objectives To investigate the clinical importance of degradation products and metabolites from organic thioureas in contact allergy to chloroprene rubber with a focus on isothiocyanates and isocyanates. Methods Patients with contact allergy to diphenylthiourea were patch tested with phenyl isothiocyanate and phenyl isocyanate. Patients with known contact allergy to diethylthiourea were retested with diethylthiourea, while chemical analyses of their chloroprene rubber products were performed. The stability of diethylthiourea, diphenylthiourea and dibutylthiourea in patch-test preparations was investigated. Liquid chromatography/mass spectrometry and solid-phase microextraction/gas chromatography were used for determination of organic thioureas and isothiocyanates. Results All patients allergic to diphenylthiourea reacted to phenyl isothiocyanate, two of eight reacted to phenyl isocyanate and six of eight reacted to diphenylthiourea. Four patients allergic to diethylthiourea reacted at retest; diethylthiourea was detected in all chloroprene rubber samples, with levels of 2–1200 nmol cm−2. At 35 °C, ethyl isothiocyanate was emitted from all samples. Patch-test preparations of diethylthiourea, diphenylthiourea and dibutylthiourea all emitted the corresponding isothiocyanate, with diethylthiourea showing the highest rate of isothiocyanate emission. Conclusions Thiourea compounds are degraded to isothiocyanates, which are generally strong or extreme sensitizers, thus acting as prehaptens. This process occurs in both chloroprene rubber products and patch-test preparations. Positive reactions to phenyl isocyanate indicate cutaneous metabolism, as the only known source of exposure to phenyl isocyanate is through bioactivation of diphenylthiourea.

SummaryBackground For more than 30 years, fragrance mix I (FMI) has been the most important screening marker for fragrance contact allergy. Meanwhile, governmental and corporate initiatives have been implemented, aimed at reducing sensitization to fragrance allergens, including the single constituents of FMI. Objectives To examine trends in contact allergy to FMI from 1986 to 2015 in dermatitis patients, and test the hypothesis that sensitization to the fragrance screening marker has decreased within recent years. Methods Cross-sectional registry study on patch test results to FMI among consecutively tested dermatitis patients from a single university clinic across three 10-year periods. From 2006-2015, data on eczema location according to MOAHLFAA, clinical relevance of sensitization, and cosmetic exposures were available. Results Of 24,168 patients, 7.8% (95% CI: 7.4-8.1%) were sensitized to FMI. For women, a significant trend (p=0.004) was observed for an increase in sensitization to FMI across the three decades. From 2011-2015, the prevalence of contact allergy to FMI increased significantly for both women (8.0% versus 10.4%, p=0.002) and men (4.4% versus 7.3%, p=0.002) compared to the previous 5-year period. From 2006-2015, clinical relevance was established in 78.2% of FMI positive patients with no differences over time. An increase (28.6% versus 36.1%, p=0.05) in FMI positive patients suffering from facial dermatitis was observed for the period 2011-2015 compared to 2006-2010. Conclusions The prevalence of contact allergy to FMI has been increasing within recent years. No effect of previous preventive initiatives could be demonstrated. This article is protected by copyright. All rights reserved.

BackgroundDelayed-type hypersensitivity represents a significant clinical and public health challenge. Patients undergoing patch testing may exhibit positive reactions to more than one allergen. It is recognized that reactions to specific pairs of allergens are associated, reflecting a combination of exposure patterns and structural similarity.ObjectivesTo explore the influence of time of testing, age, sex and atopy status on allergen pair associations in a series of 45 110 consecutive patients tested over 30 years.MethodsPatch test records of all patients undergoing testing with a modified European baseline series between 1985 and 2014 were retrieved from a database at St John's Institute of Dermatology. Reactions were read on days 2 and 4. For each allergen it was recorded whether the allergen was tested and whether the result was positive or negative.ResultsThis is the largest reported study of patch test allergen pair relationships. Our analysis shows a high degree of variability in allergen pair associations. Rigorous statistical analysis reveals a large number of differences between groups, including a significant increase in the association between formaldehyde and multiple formaldehyde-releasing preservatives over the study period, in addition to pair associations with cobalt and formaldehyde-releasing preservatives. These were present to a significantly greater extent in men than in women.ConclusionsThese observations extend our understanding of cutaneous allergy, with implications for both clinical practice and mechanisms of cutaneous hypersensitivity.

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 4-3 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 riot develop an elicita Lion 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.

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.

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.

Summary 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.

Item does not contain fulltext BACKGROUND: Little is known about the impact of engineered nanoparticles (ENPs) on skin sensitization caused by chemicals. OBJECTIVES: We determined the ability of different ENPs (TiO2 , Ag and SiO2 ) and aged paint particles containing ENPs to modulate dermal sensitization by a known potent dermal sensitizer. METHODS: The fur of BALB/c mice in the area around the ears was cut with scissors 1 day prior to topical exposure to ENPs (0.4, 4 or 40 mg mL(-1) ), paint particles containing ENPs (4 mg mL(-1) ) or vehicle (day 0). On days 1, 2 and 3, the mice received dermal applications on the back of both ears of 2,4-dinitrochlorobenzene (DNCB) or vehicle. The stimulation index (SI) was calculated on day 6. RESULTS: Topical exposure to TiO2 , Ag or SiO2 ENPs, or aged paint particles followed by vehicle treatment as a control, did not influence the SI. When 4 mg mL(-1) TiO2 ENPs were applied prior to DNCB sensitization, we found an increased SI compared with vehicle-exposed mice prior to DNCB sensitization. Furthermore, an increased titanium concentration was found in the draining lymph node cells of this group. Topical exposure to Ag or SiO2 ENPs or aged paint particles prior to DNCB sensitization did not influence the SI. CONCLUSIONS: We have demonstrated that topical exposure to TiO2 ENPs increases chemical-induced dermal sensitization.

SummaryBackground The influence of filaggrin gene (FLG) mutations on early- vs. late-onset development of atopic dermatitis (AD), allergic contact dermatitis (ACD) and chronic irritant contact dermatitis (CICD) is not completely understood. Objectives To assess the association between FLG mutations and development of AD, ACD and CICD. Methods This study assessed 241 patients with AD. AD developed during infancy in 85 patients, during childhood in 79 patients (32 early and 47 late) and during adulthood in 77 patients. We also included 100 patients with ACD and 44 with CICD, as well as 164 healthy controls. Four prevalent FLG loss-of-function mutations were genotyped (R501X, 2282del4, R2447X and S3247X). Results The 2282del4 mutation was significantly associated with a greater risk of AD in the entire group [odds ratio (OR) 4·33, 95% confidence interval (CI) 1·26–14·96]. However, the 2282del4 mutation was associated only with AD that developed during infancy or in early childhood (≤ 8 years: OR 20·91, 95% CI 2·73–159·9), not with AD development in late childhood or adulthood (> 8 or > 18 years), or ACD or CICD. Similar associations were also observed for the combined 2282del4 or R501X genotype. Carriers of FLG mutations also experienced a longer duration of AD and required hospitalization more often. Conclusions FLG mutations are associated with only the early onset of AD, not late onset. Other factors should receive attention in patients with late-onset AD.

Summary Background Skin diseases are the most frequently recognized occupational diseases in Denmark. The prognosis for occupational contact dermatitis is often poor. Objectives To investigate the prognosis, assessed by eczema, job status and skin-related quality of life, among patients allergic to rubber chemicals and latex (ubiquitous allergens) and epoxy (nonubiquitous allergen), 2 years after recognition of occupational allergic contact dermatitis. Methods From a cohort of all patients recognized as having occupational dermatitis by the Danish National Board of Industrial Injuries in 2010, 199 patients with relevant rubber allergy (contact allergy to rubber chemicals or contact urticaria from latex) or epoxy allergy were identified. Follow-up consisted of a questionnaire covering current severity of eczema, employment, exposure and quality of life. Results The response rate was 75%. Clearance of eczema was reported by 11% of patients and 67% reported improvement. Overall 22% of patients with allergy to a nonubiquitous allergen had total clearance of eczema compared with 10% of cases allergic to ubiquitous allergens and 0% of those with contact urticaria (P = 0·116). Improvement was significantly more frequent in those who had changed jobs compared with those who had not (P = 0·01). Conclusions At follow-up, patients with contact urticaria had significantly poorer prognosis than those with contact allergy, and there was a trend towards a poorer prognosis for those with contact allergy to rubber chemicals than those with allergy to epoxy. A significant positive association between job change and improvement was found.

SummaryBackground Psoriasis is a common immune-mediated inflammatory disease that affects the skin and joints. The interleukin (IL)-23/IL-17A axis and IL-22 play key roles in the pathogenesis of psoriasis. IL-23-responsive innate lymphoid cells (ILCs) with a high capacity to produce IL-17 and/or IL-22 have recently been identified and associated with inflammatory bowel diseases. The occurrence and role of ILCs in human skin are poorly understood. Objectives To describe the prevalence of the different ILC subpopulations in skin from healthy controls and patients with psoriasis or allergy to nickel. Methods Skin biopsies were taken from healthy skin, nonlesional and lesional psoriatic skin, and nickel- and petrolatum-exposed skin from patients with contact allergy to nickel, and lymphocytes were isolated. The cells were stained and characterized by flow cytometry. Cytokine and ligand mRNA expression were measured by quantitative polymerase chain reaction. Results We found that members of the three groups of ILCs were present in human skin. Remarkably, the number and frequency of RORγt+CD56+ ILC3s, which are known to produce IL-22, were elevated in both nonlesional and lesional skin from patients with psoriasis compared with healthy skin and skin from patients with contact allergy to nickel. Furthermore, skin ILCs expressed high levels of the natural killer receptor NKG2D. NKG2D binds to stress-induced ligands, including major histocompatibility complex class I-related chain A, which we found to be strongly upregulated in lesional skin from patients with psoriasis. Conclusion These results show that ILCs are present in human skin and indicate that RORγt+CD56+ ILC3 may be involved in the pathogenesis of psoriasis.

The incidence of OCD (occupational contact dermatitis) in different European Countries and USA ranges between 0.5 and 1.9 cases per 1000 workers per year. 1,2,3 OCD is lowering in the last 10-15 years, with incidence rate that varies between 1.2 to 0.56 cases per 1000 person-years from 1993 to 1996 in Germany 1,3 and from 0.29 to 0.1 cases per 1000 from 1997 to 2008 in a Czech study.4 Incidence of notified occupational skin diseases for health care workers (HCWs) was 3.1 cases per 1000 workers per year in USA, 1.5 in Bavaria, 1.5 in Denmark (only nurses), 0.4 in Northem Bavaria and 0.1-0.29 in Czech Republic.4 This article is protected by copyright. All rights reserved.

SummaryBackground Fragrance contact allergy is common and is currently screened for with the European baseline series fragrance markers: Fragrance Mix 1, Fragrance Mix 2, Myroxylon pereirae and hydroxyisohexyl 3-cyclohexene carboxaldehyde. Objectives To investigate the validity of patch testing with these fragrance markers in detecting fragrance allergy to 26 individual fragrance substances for which cosmetic ingredient labelling is mandatory in the European Union. Methods We conducted a retrospective review of the patch test records of all eczema patients who underwent testing with the European baseline series extended with the individual fragrance substances during the period 2015-2016. Results 359 patients (17.2%) reacted to one or more allergens from the labelled fragrance substance series and/or a fragrance marker from the European baseline series. The allergens that were positive with the greatest frequencies were oxidised linalool (154; 7.4%, 95% CI 6.3%-8.6%), oxidised limonene (89; 4.3%, 95% CI 3.4%-5.2%) and Evernia furfuracea (44; 2.1%, 95% CI 1.5%-2.8%). Of the 319 patients who reacted to any of the labelled fragrance substances, only 130 (40.8%) also reacted to a baseline series fragrance marker. The sensitivity of our history-taking for fragrance allergy was 25.7%. Conclusions With the evolving trends in fragrance allergy patch testing with Fragrance Mix 1, Fragrance Mix 2, Myroxylon pereirae and hydroxyisohexyl 3-cyclohexene carboxaldehyde are no longer sufficient for screening for fragrance allergy. This article is protected by copyright. All rights reserved.

Summary Background Allergic contact dermatitis (ACD) is a typical delayed-type hypersensitivity to sensitizing haptens mediated by T cells. Th1/Tc1 cells are currently considered to be the primary effectors in ACD. There is little information concerning the role played in ACD in humans by Th17/Tc17 cells, a recently defined subpopulation of effector T cells. Objectives In the present report we attempted to characterize Th17/Tc17 cells in the infiltrates of the skin in the elicitation phase of ACD. Methods Th17 as well as Th1/Th2 cytokine gene expression was examined by semiquantitative real-time polymerase chain reaction in paired samples of positive patch test biopsies and normal skin from 11 patients allergic to nine different allergens. The in situ characterization of interleukin (IL)-17-producing cells was carried out using anti-RORC and anti-T-cell subset antibodies by double immunofluorescence. Results Compared with normal paired skin samples, gene expression of transcription factor for human Th17 cells, RORC, and Th17-related cytokines IL-17A, IL-17F and IL-23 was significantly increased in positive patch test biopsies. The mRNA for interferon-γ and IL-4 was also increased. In the dermal infiltrates, about 20% of the infiltrating cells were IL-17-producing cells as they expressed RORC, and such RORC-expressing cells were detected in both CD4+ (∼30%) and CD8+ (∼20%) subsets. Conclusions This is the first demonstration of Th17/Tc17 cells in the elicitation phase of human ACD, showing that they are a regular participant in the immunopathology of this common allergic reaction regardless of the nature of the triggering allergen.

Summary Background The prevalence of contact allergy in the general population is nearly 20%. Objectives This study aimed to monitor the development of contact allergy to allergens from the TRUE-test (panels 1 and 2) between 1990 and 2006. Methods Two random samples of adults from the general population in Copenhagen, Denmark, were invited to participate in a general health examination including patch testing. In 1990 and 2006, we patch tested and questioned 543 and 3460 adult Danes. Patch test readings were performed on day 2 only. Results The overall prevalence decreased significantly from 15·5% in 1990 to 10·0% in 2006, mainly as a result of a decrease in thimerosal allergy from 3·4% to 0·8%. Furthermore, the prevalence of cobalt allergy and rubber-related allergens decreased from 1·1% to 0·2% and from 1·5% to 0·2%, respectively. Stratification by sex and age group revealed decreasing prevalences of contact allergy in all male age groups and in young and middle-aged female age groups (18–55 years) whereas increasing prevalences were observed among older women (56–69 years). The diverging trend observed in women was probably explained by a cohort effect due to a change in the prevalence of nickel allergy following the Danish regulation on nickel exposure. Conclusions Although the overall prevalence of contact allergy decreased in the general population, frequent contact allergens such as fragrance mix II and methyldibromo glutaronitrile were not tested. Thus, contact allergy remains prevalent in the general population.

Summary Background The pathogenesis of chronic hand eczema (CHE) is multifactorial and involves both endogenous predisposition and environmental triggers. Objectives Filaggrin is a structural protein of the cornified envelope and important for the formation of the epidermal skin barrier. The aim of this investigation was to evaluate the role of mutations in the filaggrin gene (FLG) in the development of CHE. Methods In total, 122 German patients with clearly defined CHE subtypes were screened for the FLG variants R501X and 2282del4 by polymerase chain reaction and restriction enzyme digest analysis. The prevalence of these variants in CHE patients was compared with that in 95 healthy individuals. Results Overall, allele frequency and the number of mutation carriers were similar in both the CHE and control groups. When classified according to clearly defined CHE subtypes, however, the nonfunctional FLG variants showed an association with CHE involving an aetiological combination of contact allergy and irritant factors [P = 0·04; P (exact test) = 0·06; P (difference in rates) = 0·09; 95% confidence interval (CI) 0–56·8)], or with excessive daily exposure to water and irritants [P = 0·003; P (difference in rates)

Summary Background Patch test (PT) guidelines recommend classifying PT reactions based on morphological criteria only, i.e. irrespective of context information such as substance, concentration and vehicle. Objectives To analyse reclassification of PT reactions after revelation of context information subsequent to an initial blinded reading. Methods One hundred and twenty-two participants (experienced dermatologists and researchers) rated 20 digital images of different PT reactions twice, first blinded, then unblinded regarding substance, concentration and vehicle. Agreement between both ratings was quantified with Cohen’s kappa, and systematic differences statistically examined with tests for marginal homogeneity. Results Mostly, ratings remained stable, e.g. in > 90% of cases of images showing typical strong or extreme positive PT reactions. Reclassification was comparatively often observed in images depicting irritant reactions. Conversely, 16 of 122 participants re-rated doubtful reactions to thiuram mix and dichromate, respectively, as ‘allergic’ (weak or strong positive) after knowing the substance. Conclusions The considerable proportion of participants who choose an ‘allergic’ rating, despite a morphological presentation definitely not justifying this, points to a conceptual problem of the PT reading scale: the mixing up of morphological classification and interpretation. We therefore suggest amending the scale. Moreover, standardization of PT reading can be improved by continual PT training sessions.

Summary Background Hydroxyisohexyl 3-cyclohexene carboxaldehyde (HICC) is a synthetic fragrance ingredient. Case reports of allergy to HICC appeared in the 1980s, and HICC has recently been included in the European baseline series. Human elicitation dose–response studies performed with different allergens have shown a significant relationship between the patch-test threshold and the repeated open application test (ROAT) threshold, which mimics some real-life exposure situations. Fragrance ingredients are special as significant amounts of allergen may evaporate from the skin. Objectives The study aimed to investigate the relationship between elicitation threshold doses at the patch test and the ROAT, using HICC as the allergen. The expected evaporation rate was calculated. Materials and methods Seventeen HICC-allergic persons were tested with a dilution series of HICC in a patch test and a ROAT (duration up to 21 days). Seventeen persons with no HICC allergy were included as control group for the ROAT. Results The response frequency to the ROAT (in μg HICC cm−2 per application) was significantly higher than the response frequency to the patch test at one of the tested doses. Furthermore the response rate to the accumulated ROAT dose was significantly lower at half of the doses compared with the patch test. The evaporation rate of HICC was calculated to be 72% over a 24-h period. Conclusions The ROAT threshold in dose per area per application is lower than the patch test threshold; furthermore the accumulated ROAT threshold is higher than the patch test threshold, which can probably be explained by the evaporation of HICC from the skin in the open test.

Summary Background The prevalence of sensitization to fragrance mix (FM) I and Myroxylon pereirae (MP, balsam of Peru) has decreased in recent years among Danish women with dermatitis. Objectives This study investigated whether the decrease could be confirmed among women in the general population. Furthermore, it addressed the morbidity of FM I sensitization. Methods In 1990, 1998 and 2006, 4299 individuals aged 18–69 years (18–41 years only in 1998) completed a premailed questionnaire and were patch tested to FM I and MP. Data were analysed by logistic regression analyses and associations were expressed as odds ratios (ORs) with 95% confidence intervals (CIs). Results The prevalence of FM I and MP sensitization followed an inverted V-pattern among women aged 18–41 years (i.e. an increase from 1990 to 1998, followed by a decrease from 1998 to 2006). Logistic regression analyses showed that ‘medical consultation due to cosmetic dermatitis’ (OR 3·37, 95% CI 1·83–6·20) and ‘cosmetic dermatitis within the past 12 months’ (OR 3·53, CI 2·02–6·17) were significantly associated with sensitization to FM I. Conclusions In line with trends observed in Danish patients with dermatitis, our results supported a recent decrease in the prevalence of FM I and MP sensitization in Denmark. The study also showed that fragrance sensitization was associated with self-reported cosmetic dermatitis and use of health care related to cosmetic dermatitis.

Background Patch test reactivity to nickel varies over time. To what extent this variation is associated with fluctuations in the T-cell reactivity to nickel is not known. Objectives Our aim was to investigate the relationship between variation over time in the patch test and the systemic T-cell reactivity to nickel. Methods Patients (n = 15) with a history of contact allergy to nickel were subjected to three consecutive patch tests at 3-month intervals, utilizing NiSO4 at 10 concentrations ranging from 0.0032% to 12.5%. Prior to each patch test, blood mononuclear cells were analysed for T-cell reactivity to nickel by interleukin (IL)-4 and IL-13 enzyme-linked immunospot assay. Results Eleven patients reacted positively in all three patch tests, two patients reacted in one or two tests and two remained negative. All 13 positive patients displayed variability over time, in terms of the lowest dose of nickel to which they responded. Also the cytokine response to nickel varied over time but the patients' mean cytokine response was positively correlated with their mean patch test reactivity (r(s) = 0.70, P < 0.01 for IL-4; r(s) = 0.78, P < 0.001 for IL-13). However, although the changes over time in patch test reactivity and the cytokine responses to nickel displayed a similar pattern in many patients, there was no significant correlation between the individuals' variation over time in vivo and in vitro. Conclusions The overall magnitude of the T-cell reactivity to nickel and the patch test reactivity are closely associated but fluctuations in the systemic T-cell reactivity cannot be singled out as the major cause of longitudinal variability in nickel patch test reactivity.

We have recently found a correlation between contact allergy to gold sodium thiosulphate (GSTS) and gold concentration in the blood (B-Au) in a stented population: the higher the B-Au, the stronger the patch-test reaction. To further investigate the correlation between B-Au and patch-test reactivity to gold. In this provocation control cross-over trial of 24 patients with dermatitis with a known contact allergy to gold, the patients were randomized into two groups where one was topically provoked to gold (15 mg GSTS) and one to the control. All patients were simultaneously patch tested with GSTS in 10 aqueous dilutions (1.1 mg GSTS). Patch-test readings were performed and blood was drawn. After 6 weeks, the experiment was repeated and the group that had previously been provoked with gold was now provoked with the control and vice versa. B-Au was higher after gold provocation whereas no treatment effect was discerned for minimal eliciting concentration (MEC) or summarized test score (STS). Instead, significant differences in period effect were observed implying higher B-Au and STS and lower MEC on test occasion II. The most likely explanation is the increased B-Au and/or booster effect from test occasion I. There was a correlation between B-Au and MEC: the higher the B-Au, the lower the MEC. The correlation between B-Au and MEC indicates that the B-Au is of importance for the skin reactivity to gold.

Summary Background Contact sensitization to fragrance mix (FM) I and Myroxylon pereirae (MP) is common among European patients with dermatitis. Recently, FM II was included in the European baseline series as an additional marker of fragrance sensitization. Objectives This literature review aims to assess the prevalence of fragrance sensitization in the general population, and to suggest how future population-based studies and questionnaires should be constructed, better to assess the prevalence and burden of fragrance sensitization. This is of relevance as it is often difficult to establish causality in biological systems. Methods A systematic review of the literature was carried out by searching Pubmed-Medline, Biosis and contact dermatitis textbooks. Results Nineteen studies were identified, of which 13 were performed among adults. Sample sizes varied between 82 and 2545 tested subjects, and 11 648 subjects were tested in total. The median prevalence of FM and MP sensitization among adults was 2·3% (women, 1·7%; men, 1·3%) and 1·1% (women, 1·4%; men, 0%), respectively. Conclusions Based on the reliability of patch test data from the general population and exposure data obtained from patients with dermatitis, the prevalence and burden of fragrance sensitization in the general population is significant.

Summary Background Periorbital dermatitis is common and frequently recalcitrant to treatment. Due to the exposed and visible location, patients often suffer severely from periorbital dermatitis. Objectives To determine the frequency and causes of periorbital dermatitis including contact sensitizers. Methods We investigated two cohorts of patients (Erlangen and IVDK without Erlangen) between 1999 and 2004. Results The differences between the two cohorts with periorbital dermatitis [Department of Dermatology at University Hospital Erlangen (n = 88) and the German Information Network of Departments of Dermatology (IVDK) collective (n = 2035)] were determined by the MOAHLFA (male, occupational dermatosis, atopic eczema, hand dermatitis, leg dermatitis, facial dermatitis, age ≥ 40 years) index. Statistically significant factors for periocular eczema are female sex, atopic skin diathesis and age ≥ 40 years. In both cohorts allergic contact dermatitis was the main cause of periorbital eczema (Erlangen 44·3%, IVDK 31·6%), followed by periorbital atopic dermatitis (Erlangen 25%, IVDK 14·1%), airborne dermatitis (Erlangen 10·2%, IVDK 1·9%), irritant contact dermatitis (Erlangen 9·1%, IVDK 7·6%), periorbital rosacea (Erlangen 4·5%, IVDK 2·2%), allergic conjunctivitis (Erlangen 2·3%, IVDK included in ‘others’) and psoriasis (Erlangen 2·3%, IVDK included in ‘others’). The most relevant allergens/allergen sources inducing periorbital eczema were consumers’ products (facial cream, eye shadow and ophthalmic therapeutics) (31%), fragrance mix (19%), balsam of Peru (10%), thiomersal (10%) and neomycin sulphate (8%); 12·5% of patients with allergic periocular dermatitis could be exclusively elucidated by testing patients’ own products. Conclusions Our data demonstrate the multiplicity of causes for periorbital eczematous disease manifestation, which requires patch testing of standard trays as well as consumers’ products to elucidate the relevant contact sensitization.

Summary Background Fluctuating irritability of the skin induced by low ambient temperature and humidity may compromise the reproducibility of patch testing. Objectives To assess the impact of temperature and absolute humidity at the time of patch testing on the occurrence of irritant or doubtful (IR/?), weak positive (+) and (strong) positive (++/+++) reactions, respectively, among 12 allergens included in the German Standard Series. Methods Analysis of clinical data collected in the surveillance network IVDK (http://www.ivdk.org) between January 1993 and December 2001 (n = 73 691 patients) combined with meteorological data obtained by the national services in Germany and Austria. Multinomial logistic regression analysis was used to estimate the risk associated with temperature, absolute humidity and vapour pressure, respectively, adjusted for sex, age, atopic dermatitis and duration of patch test application. Results For low temperature and humidity, a relevant increase of IR/? reaction frequency was observed in the cases of paraben mix and (chloro-) methylisothiazolinone. Both IR/? and + reactions were significantly increased with respect to the allergens fragrance mix, oil of turpentine, methyldibromo glutaronitrile + phenoxyethanol and particularly formaldehyde, while ++/+++ reactions were hardly affected by weather conditions. Conclusions The observed increase of IR/? reactions may be due to epidermal barrier function impairment. The impact of dry/cold weather on + reactions in terms of possibly false-positive reactions is restricted to few allergens. In the case of + reactions of unknown relevance, a re-test under warm conditions or verification tests such as the repeated open application test or the provocative use test may be recommendable.

Summary Background In 2004 a U.K.-based company developed and marketed a patch test kit (Colourstart®; Trichocare, Ridgmont, Beds, U.K.) for use by hairdressers. It is intended to assess whether clients have a ‘problem with hair dye’ and promotes itself as the ‘only practical solution to sensitivity testing’. However, a patient presented with a hair dye reaction that had not been detected while using this patch test system. Objectives To assess the Colourstart® system in the next seven consecutive patients presenting with a history of adverse reactions to hair dyes. Methods The Colourstart® system was tested in parallel with commercially available hair dye patch test reagents, where applicable. Results Only three of seven patients allergic to p-phenylenediamine were detected using this system and one patient allergic to toluene-2,5-diamine sulphate was not detected using this system. Conclusions The results raise concerns about the sensitivity of this kit for consumer protection, but also wider questions about the regulation, use and interpretation of ‘home diagnostic patch test kits’ in general.

Summary Background The rapidly increasing level of contact allergy to methyldibromoglutaronitrile (MDBGN) in Europe is of concern. In April 2003, the EU Commission prohibited the use of MDBGN in leave-on cosmetic products, such as creams and lotions, until a level of safe use can be defined. Industry risk assessment has indicated that such a safe level could be 50–100 p.p.m. Objectives To determine whether 50 p.p.m. or 100 p.p.m. could be tolerated by MDBGN-sensitized individuals, and to evaluate if the risk for elicitation of MDBGN allergy is higher for a leave-on product with a high lipid content than for a product with a low lipid content. Methods Eighteen volunteers with contact allergy to MDBGN and 10 healthy controls were exposed to repeated open application tests (ROATs) with two moisturizers with a high and a low lipid content, respectively, both containing MDBGN at a concentration of 50 p.p.m. The ROATs were performed on the left and the right side of the neck for 14 days, or until a positive reaction was seen. If a positive reaction did not develop within the first 14 days, two analogous moisturizers containing 100 p.p.m. MDBGN were applied for a further 14 days. Clinical assessments were done on days 2, 3, 7, 14, 21 and 28 or when a reaction developed. Results Eleven of 18 (61%) subjects developed dermatitis on the test area, of whom 10 developed a positive reaction to the 50 p.p.m. moisturizer, seven having a positive reaction on day 2 or 3. Reactions to the low-lipid moisturizer were the more frequent. All participants used more of the low-lipid moisturizer than the high-lipid moisturizer. The controls all had negative ROATs. Conclusions Even 50 p.p.m. cannot be regarded as a safe concentration for use and the prohibition of MDBGN is scientifically well founded.

Summary Background Iodopropynyl butylcarbamate (IPBC) is a new preservative in medical and cosmetic leave-on products. Although cases of allergic contact dermatitis to IPBC have been reported, it is not known whether the usual test concentration of 0·1% is appropriate for screening tests with IPBC. Objectives To determine the concentration of IPBC that should be used in screening patch tests. Methods An analysis was made of data filed by 26 centres of dermatology on patch tests performed with one or two concentrations of IPBC (0·1%, 0·2%, 0·3% or 0·5%) in 8106 unselected patients. Criteria used to determine the best test concentration of IPBC were the reaction index, the positivity ratio, the rate of crescendo reactions, and the relations between IPBC reactions and the MOAHLFA index irritant reactions to sodium lauryl sulphate (SLS), and allergic reactions to other contact allergens including preservatives. Results IPBC 0·1%, 0·2%, 0·3% and 0·5% yielded 0·5%, 0·8%, 1·3% and 1·7% positive reactions, but this increase was accompanied by an even greater increase in doubtful and irritant reactions. These figures and the other criteria examined suggested the range of suitable test concentrations of IPBC to lie between 0·2% and 0·3%. A detailed analysis of MOAHLFA indices and of associations between reactions to IPBC and reactions to other allergens and to SLS showed that most of the positive reactions to IPBC 0·2% can be assumed to be allergic ones and that with IPBC 0·2% fewer false-positive reactions can be expected than with IPBC 0·3%. Conclusions Patch testing with IPBC 0·2% is suggested for patients with eczema possibly related to preservatives.

Summary Background Sensitization to topical treatments used in leg ulcers is common. Questioning and patch testing are used to identify causative drugs or dressings. Objectives To study the current frequency of sensitization in our centre, to analyse previously published studies, and to compare sensitization in recent years with studies published before 1990. Methods A retrospective study was undertaken of all patients admitted with leg ulcers in 2001 and 2002. Of the files of 235 patients with leg ulcers reviewed, we identified 106 patients (group A) who had been patch tested in our institution between 2001 and 2002 with the European standard series and an additional series. The frequency of sensitization was compared with an earlier unpublished retrospective study in our centre of 36 leg ulcer patients tested in 1988 (group B), with a group of unselected contact dermatitis patients tested between 1 January 1997 and 31 December 2000 in our centre (group C), and with results published in the literature. We performed a computerized database search of MEDLINE and compared results obtained in recent years with those obtained before 1990 to obtain evidence of changing trends. Results Seventy-five per cent of the 106 patients had at least one positive reaction, and 57% had two or more positive reactions. Balsam of Peru was positive in 40% of cases, followed by lanolin (21%), fragrance mix (18%), trichlocarban (13%), colophony (11%), Cetavlon® (cetrimide cream) (9%) and neomycin (9%). Thirty-five of the 36 group B patients had at least one positive reaction. Lanolin was the most frequent (31%), followed by balsam of Peru (22%), Cetavlon® (19%), colophony (14%), terebenthene (14%), quinoline mix (11%) and benzocaine (8%). Two hundred and eighty-six of 526 patients of group C were positive in at least one test (54·4%). Three allergens gave a sensitization rate >10%: balsam of Peru (12·5%), fragrance mix (15·2%) and nickel sulphate (21·1%). Review of the literature and calculation of sensitization rates in a pool of 3043 patients extracted from 24 series, plus our own, showed persistence of high sensitization rates and a significant (8·5%) increase in sensitization between the two periods compared. There was a decrease in sensitivity to lanolin, constant sensitization to aminoglycosides, a slight increase in sensitivity to thiuram mix and glucocorticoids, and a marked increase in sensitivity to balsam of Peru in France. Newer topical treatments and dressings showed very low rates of sensitivity with the exception of hydrogels. Conclusions Despite warnings, sensitization to topical treatments for leg ulcers is still frequent and, moreover, continues to increase, some variations reflecting local nursing practices and variations in topical treatment available. Although a decrease in sensitization rate with lanolin has been observed throughout the world, no decrease in sensitization rate has been demonstrated with aminoglycosides, and sensitization to glucocorticoids, thiuram mix and new products (hydrogels) is now increasingly being reported.

Summary Background Allergic contact dermatitis (ACD) is pathogenetically dependent on cell-mediated immune responses mediated by type 1 T lymphocytes. Atopic dermatitis (AD), in contrast, occurs as a result of sustained activation of type 2 subsets of T cells. Although atopic patients may become sensitized to various contact allergens, little is known about the influence of atopy on delayed-type hypersensitivity. Objectives To investigate the in vitro responses of peripheral blood mononuclear cells (PBMC) to nickel stimulation in groups of atopic and nonatopic patients with patch test-verified nickel ACD. Methods Ten nonatopic patients with nickel ACD, 10 patients with nickel ACD and concomitant AD, 10 patients with AD but with no contact allergy, and 10 healthy persons participated in the study. PBMC were cultured in the presence or absence of nickel sulphate, phytohaemagglutinin (PHA) or tetanus toxoid (TT). [3H]thymidine incorporation was used to measure the rate of antigen-induced DNA synthesis and enzyme-linked immunosorbent assay was used to measure the production of interleukin (IL)-2 (type 1 cytokine) and IL-5 (type 2 cytokine). Results Nickel-stimulated PBMC of nickel-allergic patients with AD proliferated significantly less and secreted significantly lower amounts of IL-2 than cells of nonatopic nickel-allergic patients. IL-5 production was also lower in the former group, although the difference was nonsignificant. Moreover, neither the nickel-specific DNA synthesis nor the cytokine production by PBMC of atopic nickel-allergic patients differed significantly from those of healthy control persons and AD patients without contact allergy. Proliferative and secretory responses of PBMC to PHA or TT stimulation differed nonsignificantly between the groups. Nickel-induced IL-2 production correlated well with IL-5 production in nickel-allergic patients regardless of their atopic status. Conclusions Our results indicate that PBMC of nickel-allergic patients with concomitant AD are characterized by impaired in vitro proliferative and secretory responses to the contact allergen nickel but not to the mitogen PHA or the recall antigen TT. The type 2 cytokine IL-5 may play a role in the development of ACD.

Colophony is not used as a fragrance ingredient. However, colophony is a well-established marker of fragrance contact allergy(2-4) . Colophony was therefore included as a fragrance allergy marker in our recent paper in BJD on contact allergy in the general population (prevalence 1.0%; 95%-CI 0.6%-1.3%)(5) . When including colophony as a fragrance marker in the article on fragrance contact allergy(1) together with fragrance mix I (FM I) in the True test containing an evernia prunastri (oak moss) with a high content of atranol and chloratranol or fragrance mix II (FM II) or any of the individual materials in either FM I or FM II or Myroxylon pereirae (MP) or sesquiterpene lactones, some information in table 5 of this article(1) change slightly according to the numbers given here: This article is protected by copyright. All rights reserved. (Less)

Background Delayed-type hypersensitivity reactions to nickel (Ni2+) in humans are associated with increased production of both T helper (Th) 1- and Th2-like cytokines. Cytokine responses to the major group of contact allergens, i.e. organic compounds, have been less extensively studied. We have investigated here the cytokine production induced by a mixture of methylchloroisothiazolinone (MCI) and methylisothiazolinone (MI), the active ingredients in common preservatives that are capable of eliciting allergic contact dermatitis. Objective To characterize the immune response induced by MCI/MI in terms of the production of Th1- and Th2-like cytokines in peripheral blood mononuclear cells (PBMC) from allergic and non-allergic subjects. Methods Ten subjects with a history of contact allergy to MCI/MI and nine age-matched non-allergic volunteers participated. Their actual status was confirmed by patch testing. PBMC were cultured in the presence or absence of MCI/MI; cell proliferation was measured employing [H-3]thymidine incorporation; and the number of cytokine-producing cells was determined using the enzyme-linked immunospot (ELISpot) assay and the levels of soluble cytokines in culture media by the enzyme-linked immunosorbent assay (ELISA). Results The proliferative response of PBMC to MCI/MI was significantly greater in the case of the allergic group than for the non-allergic group, as was the production of interleukin (IL)-2 and IL-13 (as determined by ELISpot and/or ELISA). PBMC from three of the allergic individuals with increased production of IL-2 and IL-13 responded to MCI/MI with elevated numbers of cells producing IL-4 and IL-5. The increases in the production of IL-2, IL-4, IL-5 and IL-13 were positively correlated. Conclusion MCI/MI elicited concomitant production of both Th1- and Th2-like cytokines by PBMC from subjects with contact allergy to these substances. This finding indicates that the organic compounds MCI/MI elicit a mixed Th1- and Th2-type of response, similar to that elicited by the metal ion Ni2+ in Ni2+-sensitized individuals. (Less)

Summary Background The most likely age of sensitization to fragrance chemicals is unknown. Objectives To investigate the frequency of allergy to the 8% fragrance mix (FM) in each decade of life in patients undergoing patch testing for the investigation of skin symptoms. Methods Patients (n = 23 846; 14 104 female and 9742 male) underwent patch testing to a standard series between 1 January 1984 and 31 December 1998. All data were recorded on a computerized database. Results We found that 8·4% of females and 6·4% of males were allergic to the FM. The frequency of fragrance allergy was low in the first two decades of life (2·5–3·4%). It gradually increased in females after the age of 20 years to peak in the 60s at 14·4% of those tested, with a decline to 11·6% in the 80s. The prevalence in males rose more slowly and peaked at 13·7% in the 70s, declining to 10·8% in the 80s. The youngest patients sensitized were aged 2 years. Conclusions These findings support the hypothesis that allergy to fragrance results from a combination of repeated environmental exposure and age-related susceptibility factors.

SummaryBackground Mechlorethamine is frequently used in the treatment of cutaneous lymphoma, but its application is limited in 30–80% of cases because of cutaneous intolerance. Reducing the concentration to avoid this side-effect has been only modestly successful. Objectives To investigate whether a shorter application period could reduce the frequency of intolerance. Methods In an open prospective study in 39 patients with cutaneous T-cell lymphoma or parapsoriasis, mechlorethamine was applied according to the usual practices of the participating physicians (number of weekly applications, treatment confined to lesions or performed over the entire body) and then washed off after 1 h in all cases. Results Cutaneous intolerance was observed in 19 of 39 patients (49%). Six of these patients showed allergic contact dermatitis to mechlorethamine after a mean period of 9·3 weeks, while the other 13 developed irritant contact dermatitis after a longer period. Cutaneous intolerance did not differ significantly according to the number of applications per week or the extent of body area treated. The therapeutic response rate was 69%, and no difference in therapeutic efficacy was noted between daily and intermittent applications. Conclusions Comparison with published studies showed no significant difference in the number of cases of cutaneous intolerance after short-term application, although their occurrence was delayed. Therapeutic response was decreased appreciably by short-term application as compared with results in the literature.

Patients with suspected allergic contact dermatitis still have to undergo patch testing for a correct diagnosis. As this has several disadvantages there is a need for additional methods, preferentially those that can be performed in vitro. Objectives To investigate the possibility of diagnosing contact allergy to nickel (Ni2+) using the enzyme-linked immunospot (ELISpot) assay that allows the analysis of cytokines at a single-cell level in ex vivo activated peripheral blood mononuclear cells (PBMC).Eleven female patients and nine age- and sex-matched healthy volunteers participated in the study. All patients had a history of nickel allergy and a positive patch test reaction to NiSO4, while the controls' test was negative. PBMC were cultured in the presence or absence of NiCl2. Cell proliferation was measured with [3H]thymidine incorporation, and the number of cytokine-producing cells analysed with the ELISpot assay.The proliferative response of PBMC to Ni2+, expressed as stimulation index, was significantly higher in the nickel-allergic patients than in the control group. Using the ELISpot assay, we found that PBMC from nickel-allergic individuals responded to Ni2+ with significantly greater production of interleukin (IL)-4, IL-5, IL-13 and interferon-gamma, but not IL-12, compared with the healthy controls. The number of IL-4- and IL-5-producing cells correlated with the number of IL-13-producing cells in the nickel-allergic patients, but Ni2+-induced PBMC proliferation did not correlate with the number of cytokine-producing cells for any of the cytokines tested.Our results indicate that the ELISpot assay could be a tool in the discrimination between nickel-allergic and non-allergic individuals.