Kathon Research Articles

The dramatic increase in the rate of methylisothiazolinone contact allergy in Belgium: a multicentre study.

The rate of contact allergy and allergic contact dermatitis caused by methylisothiazolinone (MI) is dramatically increasing throughout Europe. To report on methylchloroisothiazolinone (MCI)/MI and MI allergy in Belgium. Between January 2010 and December 2012, the medical charts of 6599 patients of the Belgian Contact and Environmental Dermatitis Group were retrospectively reviewed for MCI/MI and MI sensitization by use of a standardized questionnaire. Available data on sensitization in 2081 patients tested in 2013 were also included. In 2012, the sensitization rate for MCI/MI had increased to 4.5% and that for MI to 6.0%; the latter showed a further increase to 7.2% in 2013. The people mainly affected were women with a median age of 49years with hand and/or facial dermatitis, most often resulting from the use of cosmetics. Simultaneous reactions to octylisothiazolinone were observed. A dramatic increase in the rate of contact allergy caused by MI in cosmetics is occurring in Belgium. Notwithstanding the recent recommendation to discontinue the use of MI in leave-on cosmetics, safer use concentrations should also be determined for rinse-off products. Close monitoring of MI sensitization in the near future will be necessary, and the highest test concentrations reported for MI and MCI/MI should be included in the baseline series.

Patch testing with methylchloroisothiazolinone/methylisothiazolinone 200 ppm aq. detects significantly more contact allergy than 100 ppm. A multicentre study within the European Environmental and Contact Dermatitis Research Group

Methylchloroisothiazolinone (MCI) and methylisothiazolinone (MI) are the active ingredients in commonly used preservative systems (e.g. Kathon CG(®)). MCI/MI is present in the European baseline patch test series at 100 ppm aq. Since 1986, 200 ppm (dose 0.006 mg/cm(2)) has been used in Sweden without causing skin irritation. Centres in Spain, the United Kingdom and Ireland have also used 200 ppm in their baseline series. To find the optimal patch test concentration for MCI/MI. MCI/MI 100 ppm aq. and MCI/MI 200 ppm aq. were simultaneously patch tested in 3300 consecutively tested dermatitis patients at eight European patch test clinics and one US patch test clinic. With the Finn Chambers(®) technique (diameter 8 mm), 15 µl was micropipetted on to the filter paper in the chamber. The corresponding volume for Van der Bend(®) chambers was 20 µl, and that for IQ Chambers(®) was 25 µl. Contact allergy to MCI/MI at 100 and 200 ppm was found in 1.2% and 2.1% of patients, respectively (p < 0.001). MCI/MI 200 ppm aq. (dose 0.006 mg/cm(2) ) diagnoses significantly more contact allergy than the presently used concentration of 100 ppm (dose 0.003 mg/cm(2)), without resulting in more adverse reactions. MCI/MI at 200 ppm should therefore be considered for inclusion in the European baseline test series.

Recommendation to increase the test concentration of methylchloroisothiazolinone/methylisothiazolinone in the European baseline patch test series – on behalf of the European Society of Contact Dermatitis and the European Environmental and Contact Dermatitis Research Group

Methylchloroisothiazolinone (MCI)/methylisothiazolinone (MI) in aqua is present in the European baseline patch test series at 100 ppm, whereas 200 ppm has been used in Sweden since 1986, in Spain in the late 1980s, and, in recent years, also in the United Kingdom and Ireland. With regard to MCI/MI, to investigate the data on contact allergy rates in dermatitis patients, the frequencies of allergic contact dermatitis in the same group, and adverse reactions, particularly patch test sensitization in tested dermatitis patients, and to find the optimal patch test concentration as dose in mg/cm(2) . We performed a survey of the literature found via the National Library of Medicine (PubMed, http://www.ncbi.nlm.nih.gov/pubmed, last accessed 20 February 2014). MCI/MI at 200 ppm aq. diagnosis substantially more contact allergy and allergic contact dermatitis, without any registered increase in patch test sensitization, than the presently used concentration of 100 ppm. MCI/MI at 200 ppm aq. is recommended to be included in the European baseline patch test series. To avoid patch test sensitization, a dose of 0.006 mg/cm(2) must not be exceeded, which means a volume of 15 µl for Finn Chambers(®) (Ø 8 mm).

Outbreak of contact sensitization to methylisothiazolinone: an analysis of French data from the REVIDAL-GERDA network.

The preservative methylisothiazolinone (MI) is used in combination with methylchloroisothiazolinone (MCI), but the MCI/MI mixture has been identified as highly allergenic. MI is considered to be less allergenic, and since the mid-2000s has been widely used alone, but is now clearly identified as a contact allergen. The French Vigilance Network for Dermatology and Allergy of the Study and Research Group on Contact Dermatitis (REVIDAL-GERDA) added MI to its baseline patch testing series in 2010. To evaluate the change in the proportion of MI-positive tests in France between 2010 and 2012. We conducted a nationwide, multicentre, retrospective study of all MI-tested patients between 2010 and 2012. Sixteen centres participated in the study (7874 patients were tested). Patch tests were performed mainly at a concentration of MI 200 ppm aq. We observed a significant increase in the proportion of MI-positive tests in 2012 and 2011 as compared with 2010 (5.6%, 3.3%, and 1.5%, respectively; p < 0.001). We report a significant increase in the number of MI-positive tests. MI is confirmed to be a rapidly emerging allergen, as also observed in other European countries.

Methylisothiazolinone: second ‘epidemic’ of isothiazolinone sensitization

Isothiazolinones are used as biocides in a wide variety of products, such as cosmetics, detergents, and industrial products. In the 1980s, a formulation with methylchloroisothiazolinone (MCI) and methylisothiazolinone (MI) was responsible for an allergic contact dermatitis ‘epidemic’. To control this phenomenon, a maximum allowed dose was set. However in 2005, MI alone was introduced in cosmetics, and this was followed by a new ‘epidemic’ of sensitization to MI and MCI/MI (1). We performed a retrospective study, consulting the medical files of patch tested patients reactive to ISs, from 2005 to 2013. MCI/MI was tested at 100 ppm in water (TROLAB® patch test allergens, Almirall Hermal

Patch testing with serial dilutions of various isothiazolinones in patients hypersensitive to methylchloroisothiazolinone/methylisothiazolinone

In 2005, methylisothiazolinone (MI) on its own came into use as a preservative. Prior to that, MI was always present together with methylchloroisothiazolinone (MCI). Can the pattern of reactivity to the separate active ingredients in allergic patients tell us something about the primary sensitizer? To investigate the potential pattern of cross-reactivity between the isothiazolinones tested, and to find the minimal elicitation concentration for each chemical, in order to determine whether the primary sensitizer is MCI or MI. Patients reacting to MCI/MI and/or MI were additionally patch tested with MCI/MI, MCI, MI, 2-n-octyl-4-isothiazolin-3-one (OIT) and 4,5-dichloro-2-n-octyl-4-isothiazolin-3-one (dichloro-OIT) in serial dilutions. Three different groups of reactors were seen. One group did not react to MI; another group reacted to both MCI and MI, but had higher patch test reactivity to MCI; and a third group reacted to both MCI and MI with very similar patch test reactivity, but reacted more often to OIT and dichloro-OIT. Patch testing with the active ingredients of MCI/MI in serial dilutions could give information on the primary sensitizer.

Actualización en la dermatitis de contacto alérgica por metilcloroisotiazolinona/metilisotiazolinona y metilisotiazolinona

The combination of methylchloroisothiazolinone (MCI) and methylisothiazolinone (MI) is widely used as a preservative in cosmetics, household, and industrial products. Furthermore, MI at a concentration of 100ppm has been permitted in cosmetic products since 2005. Recently, a considerable increase in cases of contact dermatitis to both MCI and MI have been noted, and this warrants closer monitoring by relevant authorities and, probably, stricter legislation. In fact, MI at a test concentration of 2000ppm was recently included in the European baseline patch test series. The clinical manifestations of allergy to MCI/MI and MI are highly variable and diagnosis is often missed. In the standard patch test series of the Spanish Contact Dermatitis and Skin Allergy Research Group (GEIDAC), MCI/MI is tested at 100ppm, but at this concentration, up to 50% of cases might go undetected. Furthermore, our data indicate that MCI/MI at 200ppm would make it possible to diagnose more cases of contact allergy to MI. To improve the diagnosis of contact allergy to MCI/MI and MI, we believe that the test concentration of MCI/MI should be increased to 200ppm in the GEIDAC standard series and that MI should be added in the GEIDAC standard series.

Contact Allergic Dermatitis Due to Kathon CG Contained in Ultrasound Gel

Contact Allergic Dermatitis Due to Kathon CG Contained in Ultrasound Gel

Méthylisothiazolinone : une épidémie de sensibilisation de contact. Expérience française

Preservatives are a class of allergens that is well represented in testing series. There are 5 preservatives in the TRUE test, 4 preservatives in the European series, and 13 in the North American Series.1–10 Methylchloroisothiazolinone/methylisothiozolinone (MCI/MI) (Kathon CG, Rohm and Haas, Spring House, PA) is a relatively new allergen that was introduced in 1980 in the United States. Its use rapidly increased until reports of contact allergy became an issue. Allowable levels of MCI/MI in products, sensitivity rates, and use rates vary by country. The overall incidence of sensitivity for this allergen, as reported by the North American Contact Dermatitis Group, is similar to other allergens in the preservative class.

Recommendation to include methylisothiazolinone in the European baseline patch test series – on behalf of the European Society of Contact Dermatitis and the European Environmental and Contact Dermatitis Research Group

Methylisothiazolinone (MI) is used as a preservative in occupational and household products, and cosmetics. It is a part of the preparation of methylchloroisothiazolinone (MCI)/MI, which is patch tested in water in the European baseline series. However, this preparation fails to detect a significant percentage of allergic contact reactions to MI. To investigate whether a separate test preparation with MI should be included in the European baseline series. Literature survey. In consecutively tested dermatitis patients, the contact allergy rate for MI varies between 0.6% and 6%, with a marked increase in recent years. The contact allergy rate for MI alone, not detected with MCI/MI, varies between 0% and 1.6%. Most cases are relevant, as shown by repeated open application test studies, and are mainly related to exposure from cosmetic products. Owing to the increase in contact allergy to MI not detected with MCI/MI, it is recommended that MI in water at 2000 ppm be included in the European baseline series. With the Finn Chamber(®) (diameter, 8 mm) technique, a volume of 15 µl should be applied, giving a dose of 60 µg/cm(2).

Methylisothiazolinone contact allergy – a growing epidemic

The prevalence of contact allergy to the isothiazolinone preservative methylchloroisothiazolinone (MCI) in combination with methylisothiazolinone (MI) and MI alone has increased in the last couple of years. To investigate the prevalence of contact allergy to MI, MCI/MI and benzisothiazolinone (BIT) among patch tested patients at Gentofte Hospital, as well as the use of MI in cosmetic products. Patients patch tested with either MI, MCI/MI or BIT from 2010 to 2012 were included in the study. The MOAHLFA index was registered in all patch tested patients, and relevant exposures were determined in patients with an isothiazolinone allergy. In a market survey, the ingredient labels of cosmetic products were investigated for MI content. The prevalence of MI and MCI/MI contact allergy increased significantly from 2010 to 2012: from 2.0% to 3.7% for MI (n = 2766), and from 1.0% to 2.4% for MCI/MI (n = 2802). MI-allergic patients had occupational, hand and face dermatitis significantly more often, and were aged > 40 years. Cosmetics were the most common substances causing relevant exposure found in both MCI/MI-allergic and MI-allergic patients. MI was found in 3.3% of cosmetics on the Danish retail market. The increase in MI contact allergy is alarming, and urgent action is needed.

Methylisothiazolinone

The preservative methylisothiazolinone (MI) is the American Contact Dermatitis Society Contact Allergen of the Year for 2013. Because the use of MI in cosmetics and toiletries in the United States rises, MI exposure also rises. Although it might seem likely that testing with methylchloroisothiazolinone (MCI)/MI would be adequate to pick up contact allergy to MI alone, the mix misses approximately 40% of allergy to MI, likely because of the low concentration of MI in the MCI/MI combination patch test. In Europe, several groups have documented frequency of allergy to this preservative of approximately 1.5%. The frequency of allergy to this preservative in the United States is unknown. If you are not testing for allergy to this preservative, you may be overlooking the importance of a very relevant preservative allergen that, to date, has managed to stay under the radar in the United States. This report reviews the background and reasons for adding MI to our routine screening patch testing series.

Allergic Contact Dermatitis in Children With and Without Atopic Dermatitis

Prevalence and causes of allergic contact dermatitis (ACD) in children vary with time and geographical area. This study aimed to determine the relevant allergens causing ACD in children and the relation between ACD and atopic dermatitis (AD). A cohort study on 349 children (0-15 years old) patch tested over a 7-year period was conducted. Patch test results were positive for at least 1 allergen in 69.3% of patients and were relevant in 69.8%. The highest sensitization rate (76.7%) was observed in children who are 0 to 5 years old (n = 86, 64% females), followed by the group of 6- to 10-year olds (70%, n = 157, 47.8% females), whereas 62.3% of 11- to 15-year-old children (n = 106, 59.4%) were sensitized. The most frequent allergens were nickel (16.3%), cobalt (6.9%), Kathon CG (5.4%), potassium dichromate (5.1%), fragrance mix (4.3%), and neomycin (4.3%). Body areas mostly affected were upper limbs and hands (31%). Approximately one third of children also had AD. Allergic contact dermatitis was more widespread in children with AD. Patch tests resulted positive in 55.3% (50% relevant) of AD compared with 76.9% (77.5% relevant) of the children without AD. Sensitizers were similar to children without AD. Very young children showed a high rate of relevant positive patch test reactions to common haptens. Allergic contact dermatitis may easily coexist with AD.

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

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. To epidemiologically investigate the possible reasons for this development and to analyse concomitant reactions to MCI/MI and MI. A retrospective analysis of IVDK data from 2009 to 2011 was performed. 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. 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.

Contact Dermatitis in a Child from Methlychloroisothiazolinone and Methylisothiazolinone in Moist Wipes

Contact allergic reactions to methlychloroisothiazolinone/methylisothiazolinone also widely known as Kathon CG have been reported extensively reported. It is one of the most commonly used preservatives in rinse-off products, cosmetics, and others. Herein, a case of a 50-year-old girl is presented with chronic dermatitis in the anogenital area. The patient was patch tested and had positive reaction to Kathon CG. The detailed history taking revealed that the allergen was present in the moist cleaning wipes used instead of dry toilet paper. The presented case serves as a basis for a appraisal of the use of this preservative in wet wipes. In addition, the duration of the patch test protocol in children has also been discussed.

Methylchloroisothiazolinone/methylisothiazolinone contact sensitization: diverging trends in subgroups of IVDK patients in a period of 19 years

The preservative methylchloroisothiazolinone (MCI)/methylisothiazo- linone (MI) is an important allergen, and has thus been subject to regulation in some areas of exposure, mainly in cosmetics. To examine whether a decline in sensitization prevalence and intensity of elicitation (by the patch test) can be observed, either overall, or in certain subgroups defined by causative exposures. On the basis of long-term contact allergy surveillance data collected by the Information Network of Departments of Dermatology (www.ivkd.org), 1992-2010, in the course of 171 883 consultations, the time trend of (different grades of) positive patch test reactions to MCI/MI (0.01% aqua) was examined in an age-stratified analysis. The overall frequency of positive patch test reactions was 2.33% (95% confidence interval 2.26-2.4%). No significant overall trend of positive reactions or of the distribution of +, ++ and + + + reactions (p > 0.05) was observed, similarly to what was found for patients in whom cosmetics were recorded as causative exposure (p = 0.55). In contrast, in patients with occupational contact dermatitis who were < 40 years of age, a significant increase in prevalence, by 0.87 percentage points per decade, was identified (p = 0.018). Both applications of MCI/MI, cosmetic and industrial, should be the target of further preventive efforts.

Methylisothiazolinone contact allergy: a review

In the early 2000s the preservative methylisothiazolinone (MI) was released as an individual preservative for industrial products and, in 2005, it was permitted for use in cosmetic products. Up until then MI had been used only in combination with methylchloroisothiazolinone (MCI). MCI/MI is one of the most frequent causes of preservative contact allergy and early studies showed that both MI and MCI are sensitizers. The prevalence of MI contact allergy is already around 1·5% and sources of exposure are associated with occupation, cosmetic products or household products. Use of MI in industrial products is not restricted and cases of occupational contact allergy to MI, e.g. in painters, are reported. The frequency of use of MI in cosmetics is low, around 1%, while up to 16·5% of household products were preserved with MI. We found 19 (1·5%) out of 1272 cosmetic products labelled with MI, primarily rinse-off products, and analysed the concentration of MI by high-performance-liquid-chromatography the ultraviolet and mass spectrometry detection. The use concentration ranged between 2 and 100 ppm. Repeated exposure to MI showed that many patients allergic to MI reacted to 50 ppm which is half the maximum permitted concentration of MI in cosmetics. The recent cases and prevalence studies on MI contact allergy could be the first sign of an epidemic of MI contact allergy. The development in prevalence of MI contact allergy should be closely monitored by including MI in the European Baseline Series at 2000 ppm.

Usefulness of Skin-Prick Tests in Children With Hand Eczema: Comparison With Their Use in Childhood and Adult Eczema

Background Hand eczema is not uncommon in children but it is rarely studied using skin-prick tests. Few reports have addressed their usefulness in children and none has specifically analyzed their use in children with hand eczema. Material and methods We performed a retrospective study of all children up to 16 years of age with hand eczema who were assessed in the Department of Dermatology at Hospital General Universitario in Alicante, Spain with the standard GEIDAC panel over a 5-year period. We compared the epidemiologic data and results of skin-prick tests in this group with those obtained in children with eczema at any site and in adults with hand eczema. Results The study included a total of 1695 patients: 141 (8.3%) children and 1533 (91.7%) adults. Hand eczema was diagnosed in 496 (31.9%) adults and 32 (22.7%) children. Positive results were obtained in skin-prick tests in 50% of children with hand eczema compared with 37.6% of children with eczema at any site and 50.6% of adults with hand eczema. The current relevance of the positive allergens found in children with hand eczema (76.2%) was greater than that observed in children with eczema at any site (61%) or in adults with hand eczema (43%). The most common allergens in children with hand eczema were kathon CG and fragrance mix I, whereas in the other 2 groups metals were the most common. The most common final diagnosis in children with hand eczema was allergic contact dermatitis (34.3%), which proved to be more common than atopic dermatitis. Conclusions We recommend the use of skin-prick tests in all children with chronic hand eczema.

Extreme patch test reactivity to p-phenylenediamine but not to other allergens in children

According to clinical impression, extreme patch test reactions (+++) to p-phenylenediamine (PPD) are not uncommon in children. To investigate the patch test reactivity in children (aged 1-14 years) in comparison with other age groups and other allergens. A retrospective analysis was performed of data from the German Information Network of Departments of Dermatology, including all patients consecutively patch tested between 1994 and 2004 with PPD, and, for comparison, nickel, fragrance mix I, and methylchloroisothiazolinone (MCI)/methylisothiazolinone (MI). The distribution of +, ++ and +++ grades of positive reactions among those with a positive reaction were analysed in five age strata. We found a strikingly higher proportion of +++ reactions to PPD in children than in all other age groups (p < 0.001). No such difference was observed for the other allergens. The main suspected exposures associated with extreme reactions to PPD in children were hair dyes and 'henna tattoos'. The high proportion of extreme patch test reactions to PPD, but not to other important allergens, in children reflects intense sensitization, probably because of a high induction dose from PPD-containing 'henna tattoos'. In children with a history of contact allergy to 'henna tattoos' or hair dyes, the standard patch test concentration of PPD 1% should be drastically reduced.

Utilidad de las pruebas epicutáneas en el eczema de manos en niños: estudio comparativo con el eczema en la edad pediátrica y con el eczema de manos en adultos

Background Hand eczema is not uncommon in children but it is rarely studied using skin-prick tests. Few reports have addressed their usefulness in children and none has specifically analyzed their use in children with hand eczema. Material and methods We performed a retrospective study of all children up to 16 years of age with hand eczema who were assessed in the Department of Dermatology at Hospital General Universitario in Alicante, Spain with the standard GEIDAC panel over a 5-year period. We compared the epidemiologic data and results of skin-prick tests in this group with those obtained in children with eczema at any site and in adults with hand eczema. Results The study included a total of 1695 patients: 141 (8.3%) children and 1533 (91.7%) adults. Hand eczema was diagnosed in 496 (31.9%) adults and 32 (22.7%) children. Positive results were obtained in skin-prick tests in 50% of children with hand eczema compared with 37.6% of children with eczema at any site and 50.6% of adults with hand eczema. The current relevance of the positive allergens found in children with hand eczema (76.2%) was greater than that observed in children with eczema at any site (61%) or in adults with hand eczema (43%). The most common allergens in children with hand eczema were kathon CG and fragrance mix I, whereas in the other 2 groups metals were the most common. The most common final diagnosis in children with hand eczema was allergic contact dermatitis (34.3%), which proved to be more common than atopic dermatitis. Conclusions We recommend the use of skin-prick tests in all children with chronic hand eczema.