Results of the patch tests with European baseline series in children: Five years of experience from a single center in Turkey and a review of the literature

Background

Pediatric allergic contact dermatitis (ACD) is increasingly prevalent. Patch testing is the gold-standard diagnostic method.

Aims

Our study aimed to identify common contact-sensitizing allergens in Turkish children.

Patients/Methods

We retrospectively analyzed the patch test results and characteristics of 191 pediatric patients [114 (59.7%) females, 77 (40.3%) males], who received the diagnosis of allergic contact dermatitis between 2015 and 2019.

Results

The mean age of the patients was 12.2 years (range 4–18 years). Thirty-six (18.8%) of the patients in the study group had positive patch test outcomes with 56 positive allergens. Girls had a significantly higher rate of total positive patch test results than boys (75%/25%; p = 0.003, p < 0.05). The most frequent four allergens were nickel sulfate (n = 20, 10.4%), cobalt chloride (n = 6, 3.14%), p-phenylenediamine (n = 5, 2.61%), Methylchloroisothiazolinone/methylisothiazolinone (n = 5, 2.61%), respectively.

Conclusions

In our study, we discovered that in addition to the frequently encountered metal allergens such as nickel and cobalt, p-phenylenediamine and Methylchloroisothiazolinone/methylisothiazolinone sensitivities were frequent in the Turkish population. p-phenylenediamine sensitization can cause serious systemic dermatitis during the lifetime of children. We suggest that in Turkey personal care and hygiene products containing Methylchloroisothiazolinone/methylisothiazolinone should be legally regulated. Since childhood contact dermatitis may have an impact on the quality of life by influencing family and social life, suspected allergens should be detected as early as possible.     

Estudio descriptivo de la sensibilización a metilcloroisotiazolinona/metilisotiazolinona en una unidad de alergia cutánea

BackgroundMethylchloroisothiazolinone (MCI) and methylisothiazolinone (MI) are heterocyclic compounds used as preservatives in cosmetic and industrial products. They continue to be common allergens, causing positive patch test reactions in 2% to 4% of patients tested.Material and methodsWe searched the database at our skin allergy unit for all cases of sensitization to MCI/MI and MI diagnosed between January 1980 and March 2013.ResultsPatch tests were performed with MCI/MI in 8705 patients and with MI in 404 patients. In total, 222 patients (2.55%) were sensitized to MCI/MI and 21 (5.19%) were sensitized to MI. The incidence of MCI/MI cases peaked between 1998 and 2005 and again between 2009 and 2013. Of the 222 patients with MCI/MI sensitization, 142 were women (64%) and 49 were men (36%); the mean age was 43 years. The most frequently affected areas were the hands (54% of cases), the arms (36%), and the face (35%); 75.67% of cases were due to cosmetics and 2.25% were due to paint. Of the 21 patients with MI sensitization (mean age, 50 years), 12 were women (57%) and 9 were men (43%). The most common site of involvement in this group was the face (71% of cases), followed by the arms (38%) and the hands (29%). All the cases were due to cosmetics.ConclusionsOur data show that sensitization to the combination of MCI and MI and MI alone has increased in recent years. It would appear to be necessary to add MI to the baseline patch test series, although the test concentration has yet to be determined.     

Pruebas epicutáneas en pacientes con eczema perianal

Introduction and objectivesReports show that between 25% and 78% of patients with anogenital dermatitis have positive patch test results. Consequently, patch testing would appear to be warranted in patients presenting with eczema in the anogenital region. The objectives of the present study were to identify the most common allergens in patients with perianal eczema and to determine which allergen series are most useful for patch testing in patients with this condition.Material and methodsWe performed a retrospective review of patch test results in patients with only perianal eczema between 2001 and 2012.ResultsOf the 37 patients with perianal eczema, 16 had a positive reaction; methylchloroisothiazolinone/methylisothiazolinone was the main allergen involved. With the exception of 1 case of sensitization to gentamicin, all the positive results with present relevance were to allergens from the standard series of the Spanish Contact Dermatitis and Skin Allergy Research Group (GEIDAC) or to the patient's own products.ConclusionsIn our experience, methylchloroisothiazolinone/methylisothiazolinone is the main allergen involved in perianal eczema, and sensitization often results from using wet wipes. Patch testing in perianal eczema should be based on the GEIDAC standard series and the patient's own products.     

An update of the risk assessment for methylchloroisothiazolinone/methylisothiazolinone (MCI/MI) with focus on rinse-off products

Methylchloroisothiazolinone/methylisothiazolinone (MCI/MI) has been widely used during the last 20 years for the preservation of aqueous systems in cosmetics, toiletries and in various industrial applications. MCI/MI has a broad spectrum of activity against fungi and bacteria at very low concentrations. The allergic contact potential of MCI/MI has been known for many years. This paper provides a review of pre-clinical and clinical experimental studies as well as experience from dermatology clinics worldwide. This forms the basis for an update of the risk assessment for the use of MCI/MI in rinse-off products. The scientific data indicate that the actual sensitization rate observed with a contact allergen is extremely dependent on dose and type of exposure. This review of the data leads to the conclusion that, under normal use conditions, within the current permitted/recommended use concentrations for MCI/MI of up to 15ppm, the risk of primary sensitization from the use of rinse-off products is negligible, and elicitation of allergic contact dermatitis in MCI/MI-sensitized individuals rare, after exposure to MCI/MI-preserved rinse-off products.     

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

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

Recent increase in allergic reactions to methylchloroisothiazolinone/methylisothiazolinone: is methylisothiazolinone the culprit?

Background. The frequency of sensitization to methylchloroisothiazolinone (MCI)/ methylisothiazolinone (MI) observed in the Information Network of Departments of Dermatology (IVDK) was constantly around 2.1% from 1998 to 2009. After that, it increased to 3.9% in 2011, paralleled by an increase in the frequency of allergic reactions to MI in the preservative series from 1.9% in 2009 to 4.4% in 2011. MI without MCI has increasingly been used as a preservative in cosmetics and skin care products in recent years. Objectives. To epidemiologically investigate the possible reasons for this development and to analyse concomitant reactions to MCI/MI and MI. Methods. A retrospective analysis of IVDK data from 2009 to 2011 was performed. Results. Stratified data analysis revealed pronounced increases in reactivity to MCI/MI and MI in females, face dermatitis patients, and patients tested because of suspected cosmetic intolerance. The proportion of MI‐positive patients among those reacting to MCI/MI increased from 43% to 59% between 2009 and 2011. Conclusion. More widespread consumer exposure has most likely led to the increase in primary sensitization to MI and subsequently to a rise in MCI/MI reactions resulting from immunological cross‐reactions. A reduction in the maximum use concentration of MI seems advisable. MI should be patch tested in the baseline series.     

Methylisothiazolinone,an emerging allergen in cosmetics?

Background: A few cases on primary sensitization by, and occupational contact dermatitis from, methylisothiazolinone in paints and glues have been published. In cosmetics, methylisothiazoline (MI) is permitted in a concentration of 100 p.p.m., while 15 p.p.m. for the mixture of methylchloroisothiazolinone and methylisothiazoline (MCI/MI). Objectives: To present cases of sensitization to, and allergic contact dermatitis from, cosmetic products containing methylisothiazolinone only. Patients, Materials, and Methods: Seven patients with suspected contact dermatitis – six of them with (peri‐)anal lesions and one with facial dermatitis – were patch tested with the baseline series, the own products exposed to, cosmetic ingredients, as well as with methylisothiazolinone 1000 p.p.m. and MCI/MI 200 p.p.m. Results: The patients with anal lesions had become sensitized by wipes for intimate hygiene, and one patient with facial dermatitis by a make‐up remover, all containing methylisothiazolinone only. Three out of seven cases would have been missed if only MCI/MI 100 p.p.m., as present in the baseline series, had been tested. Conclusion: The inclusion of methylisothiazolinone as a preservative in cosmetics might not represent the solution to the problem of allergic contact dermatitis from isothiazolinones, since it leads to primary sensitization.     

Sensitization to palladium chloride: a 10-year evaluation.

BACKGROUND: Palladium is increasingly used in industry, jewelry, and dentistry and is becoming more common since the European directive restricting the use of nickel in all products placed in direct and prolonged contact with the skin. OBJECTIVE: The role of palladium sensitization is still unclear, and the aim of our study is to evaluate the trend of sensitization in a contact dermatitis clinic population during a 10-year period. METHODS: We report our experience with 4,446 patients (3,077 female, 1,369 male; mean age, 40.1 +/-13.7 years) with suspected contact dermatitis patch-tested during the period of 1991 to 2000. RESULTS: A positive patch-test result to palladium chloride 1% was indicated in 236 patients (5.3%), with a higher percentage in females (6.7%) than in males (2.3%), and the sensitization to this metal has increased over the specified period, to a maximum in the year 2000 (9.7%). In the majority of cases, subjects were polysensitized (92.8%), but 7.2% of subjects were patch-test positive only to palladium. Of palladium-sensitized patients, 40.5% complained of hand dermatitis, 47.4% complained of body dermatitis, and 1.7% complained of burning mouth syndrome. Palladium sensitization is significantly related to female sex (OR = 3.08; 95% CI, 2.07-4.61) and to sensitization to other metals, with a maximum for nickel sulfate (OR = 32.9; 95% CI, 21.3-51.5). CONCLUSION: Sensitization to palladium is increasing by the year, reaching high values, but its role in reducing sensitization and symptoms is still unclear because of the frequent cosensitization with nickel and the low number of monosensitized patients with relevant sensitizations. We need to follow palladium sensitization in future years to verify an increase of sensitization due to the increasing use of this metal.     

Dermatitis alérgica de contacto por cosméticos

IntroductionContact dermatitis to cosmetics is a common problem in the general population, although its prevalence appears to be underestimated. We reviewed cases of allergic contact dermatitis to cosmetics diagnosed in our dermatology department over a 7-year period with a view to identifying the allergens responsible, the frequency of occurrence of these allergens, and the cosmetic products implicated.MethodsUsing the database of the skin allergy department, we undertook a search of all cases of allergic contact dermatitis to cosmetics diagnosed in our department from January 2000 through October 2007.ResultsIn this period, patch tests were carried out on 2,485 patients, of whom 740 were diagnosed with allergic contact dermatitis and the cause was cosmetics in 202 of these patients (170 women and 32 men), who accounted for 27.3 % of all cases. A total of 315 positive results were found for 46 different allergens. Allergens most often responsible for contact dermatitis in a cosmetics user were methylisothiazolinone (19 %), paraphenylenediamine (15.2 %), and fragrance mixtures (7.8 %). Acrylates were the most common allergens in cases of occupational disease. Half of the positive results were obtained with the standard battery of the Spanish Group for Research Into Dermatitis and Skin Allergies (GEIDAC). The cosmetic products most often implicated among cosmetics users were hair dyes (18.5 %), gels/soaps (15.7 %), and moisturizers (12.7 %).ConclusionMost patients affected were women. Preservatives, paraphenylenediamine, and fragrances were the most frequently detected cosmetic allergens, in line with previous reports in the literature. Finally, in order to detect new cosmetic allergens, cooperation between physicians and cosmetics producers is needed.     

Contact allergy to hairdressing allergens in female hairdressers and clients – current data from the IVDK, 2003–2006

Background: Hair cosmetics, in particular hair dyes, bleaches, and permanent wave solutions, contain a number of potential contact allergens. The pattern of exposure to these in hairdressers, clients and home‐users may change over time. Patients and Methods: Data on female patients who consulted centers of the Information Network of Departments of Dermatology (IVDK, http://www.ivdk.org ) between 01/2003 and 12/2006 was analyzed. Patients were divided into a) hair‐dressers, given they worked in this occupation and suffered from occupational skin disease (n = 480),and b) “clients”,who never worked as hairdressers, but in whom hair cosmetics were considered a potential cause of contact dermatitis (n = 780). Results: In hairdressers, the most important allergens were ammonium persulfate (21.7% positive),p‐toluenediamine (PTD,19.6% positive),p‐phenylenedi‐amine (PPD,18.1% positive) and, with decreasing time trend, glyceryl monothioglycolate (2005/2006 still 7.5% positive). Biocides must be regarded as important allergens in hairdressers, namely,(chloro) methylisothiazolinone and methyldibromoglutaronitrile. Clients, who were considerably older on average, had possibly been tested in a more aimed fashion, yielding (strikingly) higher sensitization prevalences to a number of allergens of oxidative hair dyes such as PPD or PTD. Conclusions: The continual analysis of sensitization prevalences in patients patch tested can identify areas needing in‐depth research and preventive intervention, such as avoiding the use of certain biocides in shampoo intended for professional use by hairdressers or further reducing the concentrations in oxidative hair dyes.     

Evaluation of the permanence of skin sensitization to allergens in patients with allergic contact dermatitis

BACKGROUND

Patch tests are an efficient method to confirm the etiological diagnosis of allergic contact dermatitis.

OBJECTIVES

1) To determine the permanence of results between two tests performed with an interval of at least one year, in patients with allergic contact dermatitis; 2) To compare the positive results according to rates of intensity; 3) To evaluate the permanence of sensitization according to each substance that was tested.

METHODS

Patients with previous diagnosis of allergic contact dermatitis, confirmed by patch tests carried out between the years 2005 and 2008, underwent new testing, using the same methodology, and data was compared.

RESULTS

A total of 1470 results of both tests on 49 patients were analyzed. The negative results remained in the second test in a rate of 96%, and 4% became positive (+) without relevance to the clinical history. Moreover, moderately (++) and strongly (+++) positive results were also maintained in, respectively, 86% and 100%. Nevertheless, weakly (+) positive results became negative in 65%. By ignoring all weakly (+) positive tests, the calculation of Kappa Index of Agreement Statistics between the two tests showed a value of 0.88.

CONCLUSION

Patch tests showed to be reliable for negative, moderately (++) positive and strongly (+++) positive results, by reproducing the same standard of individual response to allergens. However, for weakly (+) positive results, tests were not reliable.     

Contact allergy to preservatives. Analysis of IVDK data 1996-2009

Background Preservatives are well‐known and important contact allergens. Objectives To examine the frequency of sensitization to preservatives, including time trends. Methods Retrospective analysis of data on patch testing of preservatives contained in the standard series and special series collected by the IVDK during 1996–2009. Results Some 120 000 and 80 000 patients were tested with the baseline and the preservative series, respectively. Sensitization frequencies of the standard series allergens all ranged above 1%: methyldibromoglutaronitrile (MDBGN) 2·36–4·5%, methyl(chloro)isothiazolinone (MCI/MI) 2·22%, formaldehyde 1·54%, paraben mix 1·33% and Bronopol^® 1·25%. Regarding the special preservative series, 1·54% reacted positive to methylisothiazolinone (MI), and < 1% to the other preservatives. Concomitant reactions to formaldehyde in formaldehyde releasers ranged from 15% to almost 50%, and 67% of MI positives reacted to MCI/MI. As indicated by the MOAHLFA index, sensitization to MI, iodopropynylbutyl carbamate (IPBC) and quaternium 15 was associated more often with occupational dermatitis, whereas sensitization to imidazolidinyl urea and diazolidinyl urea was associated with face dermatitis, indicating cosmetic exposure. Epidemiologically relevant decreases (> 10%) were seen in chloroacetamide, benzyl alcohol and MDBGN. Epidemiologically relevant increases were noted in IPBC, sodium benzoate and MI. Conclusions Preservatives are still important contact allergens. The introduction of new preservatives should consider the specific characteristics of occupational and of nonoccupational (cosmetic, household) exposure, and preventive measures should aim equally at both areas.     

Contact allergy caused by methylisothiazolinone: the Belgian-French experience

The chemical Kathon CG®, a mixture of the preservatives methylchloroisothiazolinone (MCI) and methylisothiazolinone (MI), was the leading cause of a worldwide epidemic of contact-allergic reactions in the eighties. From 2000 on, MI alone became allowed in industrial products and in 2005 authorities gave a green light for its use in leave-on and rinse-off cosmetics up to a maximum concentration of 100 ppm (0.01%). Following initial occupational cases, a continuously increasing number of consumers sensitized to MI have been reported and both Belgian and French allergy groups decided to routinely test MI in their baseline series from 2010 onwards. Two multicenter studies, comprising 8,680 and 7,874 patients in Belgium and France respectively, both clearly show the rise in contact allergy caused by MI, with a spectacular sensitization rate of ~ 6.0% in 2012, even increasing to 7.0% in 2013. Mostly middle-aged women, presenting with facial-and/or hand dermatitis, were affected, although very young children were reported as well. Furthermore, the data confirmed that sensitization is primarily caused by cosmetics (mostly leave-on, but also rinse-off), household detergents and water-based paint. This unprecedented outbreak of contact sensitization to a preservative agent in Europe, and beyond, should have alerted the authorities much sooner and meanwhile the need for safer use concentrations of MI in cosmetics, detergents and industrial products is becoming more urgent every day.     

Preservatives sensitivity in Israel: a 10-year overview (1995-2004)

This study presents a 10-year survey of 2285 patients tested to common preservatives in northern Israel. The demographic and clinical data were analysed using a revised MOAHLFA index. Patch testing was based on the International Contact Dermatitis Research Group (ICDRG) guidelines. 411 (18%) patients were found to have positive reactions to 1 or more preservatives. The most frequent allergens tested positively were thimerosal, methylchloroisothiazolinone/methylisothiazolinone (MCI/MI), and formaldehyde. The reactions to MCI/MI remained stable around 1.7% throughout the years 1995-1998, with a significant increase to 3.7%-4% (P = 0.029) during 1999-2004. The reactions to formaldehyde remained low around 0.3% until 1999; however, a considerable increase throughout the years 2000-2004 was noted, with rates of 1.5%-1.9% (P = 0.028). The sensitivity rates for parabens, quaternium-15, imidazolidinylurea, and diazolidinylurea were low and unchanged, mostly under 0.5%. As for methyldibromoglutaronitrile (MDBGN), sensitivity rates around 2% were detected for the years 1996 and throughout 2000-2004. Overall, this extensive survey showed a concerning increase in the sensitivity rates for MCI/MI, formaldehyde, and MDBGN.     

Contact dermatitis to methylisothiazolinone

Methylisothiazolinone (MI) is a preservative found in cosmetic and industrial products. Contact dermatitis caused by either methylchloroisothiazolinone/methylisothiazolinone (MCI/MI or Kathon CG) or MI has shown increasing frequency. The latter is preferably detected through epicutaneous testing with aqueous MI 2000 ppm, which is not included in the Brazilian standard tray. We describe a series of 23 patients tested using it and our standard tray. A case with negative reaction to MCI/MI and positive to MI is emphasized.     

Outcome of a second patch test reading of TRUE Tests® on D6/7

Background. Two readings of patch test reactions are recommended. Objectives. To evaluate the outcome of a second patch test reading of TRUE Test® allergens on D6/7 in relation to negative or doubtful reactions on D3/4. Methods. This was a retrospective investigation of patch test data from January 1992 to October 2011 from consecutive eczema patients tested with the TRUE Test® panels. Results. In the period of nearly 20 years, a total of 9997 patients were tested. The total number of positive reactions to the 29 allergens was 6509; 4.4% were positive on D6/7 and negative on D3/4; and 9.1% were positive on D6/7 after a doubtful (?+) reaction on D3/4. Neomycin was the most frequent allergen giving delayed positive reactions (57%), followed by budesonide (42%) and hydrocortisone‐17‐butyrate (31%). Conclusion. A total of 4.4% of positive TRUE Test® reactions would be missed, and 9.1% might be missed, if only one reading was performed on D3/4. The results emphasize that many doubtful reactions at D3/4 may develop into positive reactions at a later reading. This may have important implications for evaluation of the clinical relevance of the test result.     

Another look at seasonal variation in patch test results. A multifactorial analysis of surveillance data of the IVDK. Information Network of Departments of Dermatology

There is conflicting evidence concerning seasonal variability of patch test results and no evidence concerning the influence of season on weak-positive, possibly false-positive, irritant reactions, which was analysed in the present study. Data collected in the German Information Network of Departments of Dermatology (IVDK) 1992 to 1997 were combined with external environmental data on temperature and absolute humidity in Germany, and bivariate as well as logistic regression analyses performed concerning the association between reactivity to selected allergens and air temperature and absolute humidity on the respective days of patch testing. Between 39,239 and 41,629 patients had been tested with the 4 allergens considered here. Only formaldehyde exhibited a distinct increase in questionable or irritant as well as weak-positive reactions associated with dry, cold weather. Methylchloroisothiazolinone/methylisothiazolinone and lanolin alcohol showed only a weak, and epoxy resin no, association with climatic conditions. The results indicate that weak-positive reactions, at least to formaldehyde as a prototype of an allergen which is at the same time a marginal irritant, may sometimes be irritant rather than allergic. Patients showing these should be re-tested to improve the poor reproducibilty observed with this allergen.