Sunscreens Part 2: Regulation and Safety.

The second part of this CME article discusses sunscreen regulation and safety considerations for humans and the environment. First, we provide an overview of the history of the United States Food and Drug Administration's regulation of sunscreen. Recent Food and Drug Administration studies clearly demonstrate that organic ultraviolet filters are systemically absorbed during routine sunscreen use, but to date there is no evidence of associated negative health effects. We also review the current evidence of sunscreen's association with vitamin D levels and frontal fibrosing alopecia, and recent concerns regarding benzene contamination. Finally, we review the possible environmental effects of ultraviolet filters, particularly coral bleaching. While climate change has been shown to be the primary driver of coral bleaching, laboratory-based studies suggest that organic ultraviolet filters represent an additional contributing factor, which led several localities to ban certain organic filters.

Contact allergy to subcutaneous implantable cardioverter defibrillator in a child with Brugada syndrome.

Allergic reactions to components of cardiac implantable electronic devices are rare and often go undiagnosed, which can lead to a misdiagnosis of device infection. Contact allergy to subcutaneous implantable cardioverter defibrillator (S-ICD) is extremely rare. In this report, we present a case of cobalt-related contact allergy in a pediatric patient with Brugada syndrome who underwent S-ICD implantation.

The correlation between self-reported hand eczema and clinically based diagnosis in professional cleaners.

BACKGROUND: Most studies investigating the prevalence of hand eczema (HE) in professional cleaners use self-reported questionnaire-based data. However, no validation studies of self-reporting of HE among professional cleaners have previously been conducted. OBJECTIVES: To investigate (1) the point prevalence of self-reported HE, (2) the point prevalence of HE estimated by physical examination of the hands and (3) the sensitivity and specificity of self-reporting of HE compared with the diagnosis based on physical examination among professional cleaners. METHODS: Professional cleaners at three different hospitals in Region Zealand were invited to fill out a questionnaire. The point prevalence of self-reported HE was estimated based on questions from the Nordic Occupational Skin Questionnaire. After completing the questionnaire, each cleaner underwent a physical examination of the hands by a dermatologist on the same day. RESULTS: In total, 234 cleaners were invited to participate in the study, and 224 (response rate = 96.0%) agreed to take part. Based on the self-reported questionnaires, 5.3% (n = 12) of the cleaners had current HE. Based on an examination by a physician, 19.2% (n = 43) of the cleaners had current HE. The sensitivity of self-reported HE was found to be 28.0%, while the specificity was found to be 100.0%. The positive predictive value was found to be 100.0%, while the negative predictive value was 85.0%. CONCLUSION: The true point prevalence of HE among professional cleaners is underestimated when based on self-reporting.

Association between atopic disease and vaccination granulomas: A nested case-control study.

BACKGROUND: Vaccination granulomas are observed in 1% of all children vaccinated with an aluminium-adsorbed vaccine. Most children with granulomas also have aluminium contact allergy (CA). CA and atopic diseases are both highly prevalent among children and may be associated. OBJECTIVE: To investigate the association between vaccination granulomas and atopic dermatitis (AD), asthma and rhinitis in children. METHODS: We sourced a cohort of all Danish children born from 2009 to 2017 and conducted a nested case-control study, with cases defined as children with vaccination granulomas, matched to controls 1:10 on sex, socioeconomic class, gestational age and season of birth. All cases and controls were vaccinated with aluminium-adsorbed vaccines and followed until their second birthday. We used conditional logistic regression to estimate the odds ratios (ORs). RESULTS: The study included 2171 cases with vaccination granulomas, and 21 710 controls. Children with a diagnosis of AD had a significantly higher risk of a vaccination granuloma (OR 1.50, 95% confidence intervals [CI] 1.25-1.80). No significant association was found between granulomas and asthma or rhinitis. The association between granulomas and AD was even higher in an additional sensitivity-analysis, following the children until their fourth birthday (OR 2.71, 95% CI 2.36-3.11). CONCLUSION: AD was significantly associated with vaccination granulomas, but not with other atopic diseases, within both the first 2 and 4 years of life.

Contact allergens in African countries: A review of published patch test studies.

Only few studies on contact allergy in African countries have been published. The aim of the present study was to provide an overview of the most common contact allergens identified by the use of patch tests in African countries based on a review of the existing literature. A total of twenty-four publications from eight African countries were initially identified by search in PubMed. The abstracts and method sections were screened, and 15 studies in which patch tests were actually used to identify the allergen causing the allergic contact dermatitis (ACD) were finally selected. Nickel, cobalt, chromium, fragrance mix and p-tert-butylphenol-formaldehyde resin were the dominating contact allergens responsible for 40%-90% of the positive patch test reactions. This study indicates that a targeted effort directed towards prevention, avoidance and regulation of reliably identified contact allergens could reduce the disease burden of ACD considerable in some African countries.

Contact sensitization to fragrance mix I and fragrance mix II among European dermatitis patients: A systematic review.

BACKGROUND: Fragrance substances are a frequent cause of contact allergy worldwide. Fragrance exposure varies by sex, age and possibly country, influenced by cosmetic availability, environmental conditions and cultural practices. OBJECTIVES: To systematically review and gather prevalence of sensitization to fragrance mix I (FM I) and fragrance mix II (FM II) in consecutively patch-tested European dermatitis patients. METHOD: A total of 4134 publications on patch test results of European dermatitis patients, published from 1981 to 2022, were systematically reviewed according to a previously registered and published PROSPERO protocol. RESULTS: Eighty-four eligible original articles were analysed. Overall prevalence of sensitization to fragrance mix I (FM I) was 6.81% (95% CI: 6.37-7.28), and FM II was 3.64% (95% CI: 3.3-4.01). Sensitization to FM I was most prevalent in Central and Eastern Europe and to FM II in Western Europe. No clear time trends were observed. Among paediatric dermatitis patients, sensitization prevalence for FM I and FM II was 4.09% (95% CI: 3.37-4.96) and 2.17% (95% CI: 1.53-3.07). CONCLUSION: The frequency of positive patch test results for both FMI and FMII remains high. Sensitization is also prevalent among children. Enhanced regulation and labelling of cosmetic products play a vital role in averting exposure and sensitization to fragrance allergens.

Gender differences in allergic contact dermatitis to common allergens.

BACKGROUND: Gender-based differences in skin structure, physiology, and allergen exposure can influence contact dermatitis development. OBJECTIVE: This study investigated the differences and trends in contact sensitizers, focusing on the top 10 allergens and personal care product (PCP) contact allergies from a gender perspective. METHODS: We conducted a retrospective chart review of 5998 patients undergoing patch testing at an occupational and contact dermatitis clinic in a Thai, university-based, tertiary referral hospital from January 2001 to December 2021. Patients' characteristics and patch test results were collected. RESULTS: Females had a higher positive patch test rate than males (71.8% vs. 65%, p < 0.001). However, males showed a greater prevalence of occupationally related allergic contact dermatitis (15.9%). Multivariate analysis revealed associations between being female and allergies to colophonium (aOR 1.46, 95% CI 1.07-1.99, p = 0.019), formaldehyde (aOR 1.97, 95% CI 1.17-13.31, p = 0.010), fragrance mix I (aOR 1.66, 95% CI 1.34-2.07, p < 0.001), MCI/MI (aOR 2.55, 95% CI 1.90-3.44, p < 0.001), neomycin (aOR 4.15, 95% CI 2.54-6.80, p < 0.001), and nickel (aOR 2.62, 95% CI 2.17-3.15, p < 0.001). Conversely, being male correlated with allergies to carba mix (aOR 0.51, 95% CI 0.41-0.64, p < 0.001), epoxy resin (aOR 0.26, 95% CI 0.14-0.47, p < 0.001), n-isopropyl-n-phenyl-4-phenylenediamine (aOR 0.41, 95% CI 0.20-0.83, p = 0.014), paraben mix (aOR 0.42, 95% CI 0.32-0.56, p < 0.001), and potassium dichromate (aOR 0.70, 95% CI 0.58-0.84, p < 0.001). Positive reactions to PCPs stood at 13% overall (males 17.1%, females 12.2%, p < 0.001). CONCLUSIONS: Gender plays a pivotal role in contact dermatitis. This work emphasises the importance of considering gender-specific factors when diagnosing and managing contact allergies.

Quality of patch testing patient's own material in patients with suspected occupational skin diseases throughout Germany: Interim results of the German Social Accident Insurance (DGUV) research project FB 317b.

BACKGROUND: Due to limited availability of commercial test preparations, patch testing patient's own material (POM) is of great importance to diagnose occupational allergic contact dermatitis. OBJECTIVES: To assess the quality of performance and documentation of patch testing with POM in patients with suspected occupational skin diseases (OSD) in Germany. METHODS: Retrospective-prospective analysis of protocols of patch tests with POM was conducted between 2013 and 2021 in patients with suspected OSD and submitted to statutory accident insurance institutions. Assessments were done by predefined criteria. RESULTS: Three thousand and four patch tests with POM from 460 patients were included. A full description of the POM was provided in 73.3% of all tests. The test concentration, test vehicle and pH value were documented in 74.3%, 70.5% and 42.2% of tests, for which the respective parameters were considered relevant. One hundred and sixty-one positive reactions to POM were documented. In 72%, sufficient patch testing with commercial test substances was conducted to investigate the positive reaction. In 30.4%, consecutive patch testing of all ingredients of the POM was done. CONCLUSIONS: The results not only show considerable shortcomings mainly in documentation but also to some extent performance of patch tests with POM in patients with suspected OSD in Germany.

Contact allergy to rubber accelerators in consecutively patch tested Danish eczema patients: A retrospective observational study from 1990 to 2019.

BACKGROUND: Rubber accelerators are used in the production of rubber gloves and may cause contact allergy. OBJECTIVES: To estimate long-term trend and prevalence of contact allergy to rubber accelerators for a 30-year period in Denmark, high-risk occupations, and exposures. METHODS: Data from all patients with contact dermatitis consecutively patch tested at the department of Skin and Allergy Gentofte hospital with the rubber accelerators from the European baseline series (EBS) from 1990 to 2019, were analysed. Further, patients under suspicion of rubber accelerator contact allergy were additionally patch-tested with rubber accelerators from the specialised rubber series from 2005 to 2019 and these were additional extracted. RESULTS: The overall prevalence of contact allergy to one or more of the rubber accelerators from the EBS series was 2.7% with a significant decline in the first 12-years, followed by a stable frequency in the past 18-years. Associations with occupational contact dermatitis, hand dermatitis, and leg/foot dermatitis were found. Wet-work occupations were most often affected and gloves the most frequent exposure. CONCLUSIONS: Contact allergy to one or more of the rubber accelerators from the EBS is frequent and has been unchanged for several decades, which calls for prevention.

Potassium dichromate sensitivity presenting as tefillin dermatitis: A retrospective cohort study.

BACKGROUND: Tefillin are a religious article worn by Jewish men during daily prayer. Tefillin dermatitis secondary to potassium dichromate sensitivity is recognised, but data remain sparse. OBJECTIVE: To investigate the prevalence and clinical characteristics of tefillin dermatitis. METHODS: Patients who underwent patch testing with the European baseline series in a tertiary dermatology clinic in 2009-2023 and were diagnosed with tefillin dermatitis were identified by file review and their clinical data recorded. RESULTS: Of 1679 consecutive male patients tested, 25 (1.49%) were diagnosed with tefillin dermatitis, accounting for 15.34% of all potassium-dichromate-positive patients (163/1679). Mean pre-symptomatic duration of tefillin use was 38 ± 16.9 years, and mean follow-up time, 3.1 ± 2.9 years. Patients presented with an eczematous rash on body areas in direct contact with the leather box or straps of the tefillin. An id reaction was noted in 32%, and sensitivity to other leather accessories, in 44%. Fourteen patients (56%) switched to chromate-free tefillin: symptoms resolved completely in 11 (79%) and partially in 2. LIMITATIONS: Retrospective cohort design. CONCLUSION: This is the largest study to date of tefillin dermatitis caused by sensitivity to potassium dichromate used in leather production. Prognosis after switching to chromate-free tefillin was good-to-excellent. Tefillin dermatitis may be more prevalent than previously thought.

Contact allergy to topical ophthalmic medications: A retrospective single-centre study of three decades.

BACKGROUND: The prevalence of contact allergy to various ophthalmic medications appears to be rare; however, data on culprits, clinical relevance of sensitizations, and changes in frequency within recent decades are limited. OBJECTIVE: This study aimed to investigate the clinical relevance, risk factors, and prevalence of contact allergy to topical ophthalmic medications in patients suspected of allergic contact dermatitis to ophthalmic medication. METHODS: We retrospectively analysed patch test results and clinical data for 754 patients patch-tested with an ophthalmic medication series at our tertiary referral centre between January 1992 and December 2022. RESULTS: In total, 37.5% (283/754) of patch-tested patients had a contact allergy to at least one ophthalmic allergen, with 87.3% (247) being clinically relevant sensitization. Phenylephrine (31.8%, 192/604), povidone-iodine (29%, 27/93), and tobramycin (23%, 46/200) were the most important sensitizers. The incidence of contact allergies increased significantly in a linear manner (p = 0.008) from 20% to 44.1% within the study period. Male sex and age above 40 were risk factors for contact allergy to ophthalmic medication. CONCLUSIONS: One third of patch tested patients had allergic contact dermatitis to ophthalmic medication, particularly phenylephrine. Male sex and age above 40 years were independent risk factors and drove the linear increase in contact allergy to ophthalmic medications within the past 31 years.

Symmetrical drug-related intertriginous and flexural exanthema (SDRIFE) after administration of corticosteroids: Case series and review of literature.

BACKGROUND: Cutaneous manifestations of drug-induced type IV reactions vary widely, with symmetrical drug-related intertriginous and flexural exanthema (SDRIFE) being a less common presentation. Corticosteroids (CS), primarily known for their anti-inflammatory effects, rarely induce hypersensitivity reactions. OBJECTIVE: The aim of this case series is to report four cases of SDRIFE following systemic prednisolone therapy and to review existing CS classification proposals to better understand cross-reactivity of CS. PATIENTS/METHODS: Patients recruited at a German dermatology centre underwent allergologic evaluation including prick and patch testing with various CS. Positive cases underwent oral challenge testing with alternative agents. The classification systems of Coopman et al. and Baeck et al. were taken into account. DISCUSSION: Despite a paucity of literature, CS-induced type IV reactions do occur, including SDRIFE. Classification systems based on chemical structure provide insight into cross-reactivity patterns. Provocation tests with alternative CS highlight the complexity of managing CS hypersensitivity. CONCLUSION: SDRIFE may develop following systemic prednisolone therapy. Classification systems are helpful in understanding cross-reactivity and help in the selection of alternative preparations but are not always reliable. Individualised assessment is crucial for managing CS hypersensitivity, with consideration of alternative agents and emergency use of CS when necessary.

Analysis of preservatives and fragrances in topical medical devices: The need for more stringent regulation.

INTRODUCTION: Medical devices (MDs) have a long history of use, and come with regulatory frameworks to ensure user safety. Although topically applied MDs in the form of gels and creams might be used on damaged skin, their composition is often similar to that of cosmetic products applicable to intact skin, especially in terms of preservatives and fragrances. However, unlike cosmetics, these products are not subject to compound-specific restrictions when used in MDs. OBJECTIVE: This study aimed to identify and quantify preservatives and fragrances in topically applied MDs and assess their safety towards the Cosmetic Regulation (EC) 1223/2009. METHOD: Sixty-nine MDs available on the EU market were subjected to previously validated liquid chromatography tandem mass spectrometry (LC-MS/MS) and gas chromatography-mass spectrometry (GC-MS) methods to identify and quantify occurring preservatives and fragrances. RESULTS: Findings revealed that 32% of the examined MDs did not provide comprehensive ingredient lists, leaving users uninformed about potential risks associated with product use. Furthermore, 30% of these MDs would not meet safety standards for cosmetic products and, most significantly, 13% of the analysed samples contained ingredients that are prohibited in leave-on cosmetics. CONCLUSION: Results highlight the pressing demand for more stringent requirements regarding the labelling and composition of MDs to enhance patient safety. Improved regulation and transparency can mitigate potential risks associated with the use of topically applied MDs.

Contact allergy to acrylate-containing nail cosmetics: A retrospective 8-year study.

BACKGROUND: Over the last 10 years, allergic contact dermatitis (ACD) from acrylate-containing nail cosmetics (acrylic nails, gel nails, gel nail polish) has been reported repeatedly. OBJECTIVES: To investigate the frequency and clinical features of ACD in nail cosmetics in a university hospital in Amsterdam, The Netherlands. PATIENTS AND METHODS: A retrospective study in patients diagnosed with ACD from acrylate-containing nail cosmetics at the Amsterdam University Medical Centers between January 2015 and August 2023. RESULTS: Sixty-seven patients, all women, were diagnosed with ACD from nail cosmetics, representing 1.6% of all individuals and 2.3% of all women patch tested in this period. Sixty-five of sixty-seven (97%) subjects had a positive patch test to 2-hydroxyethyl methacrylate (HEMA). Forty-nine patients (73%) were consumers and 18 (27%) were professional nail stylists. The sites most frequently affected with dermatitis were the fingers (79%), hands (40%) and the head and/or neck. Avoidance of contact with acrylate-containing products resulted in complete clearing of dermatitis in 80% of patients. CONCLUSIONS: ACD from acrylate-containing nail cosmetics is frequent in women patch tested in Amsterdam. Nearly all were identified by a positive patch test to 2-hydroxyethyl methacrylate in the (meth)acrylate series or the European baseline series.

Patterns of simultaneous contact allergies in patients with contact sensitization to oxidised linalool and oxidised limonene.

BACKGROUND: Contact allergy rates of linalool and limonene hydroperoxides (HPs) have increased. OBJECTIVES: To demonstrate the patterns of simultaneous positive patch test (PT) reactions and prevalences of multiple contact allergies (MCAs) in patients with contact allergy to linalool and/or limonene HPs. METHODS: A retrospective analysis of consecutive dermatitis patients in 2015-2020 was performed. RESULTS: Of all 4192 patients, 1851 had at least one positive PT reaction. Of these, 410 (22.2%) had MCAs, significantly related to a higher age (p-value = 0.003). Patients with an exclusively positive reaction to linalool HPs but not limonene HPs were shown to have MCAs (p-value <0.001, odds ratio (95% confidence interval) = 4.15 (3.01-5.73)). Patients with simultaneous contact allergies to both linalool and limonene HPs had contact allergies to many other screening and fragrance allergens. CONCLUSIONS: Simultaneous positive PT reactions to allergens in baseline series and fragrances are common in patients with the HPs contact allergy, especially linalool HPs. The pattern of simultaneous PT reactions principally suggested the co-sensitization of the cosmetic allergens.

Frequency and clinical relevance of contact allergy in dental patients.

BACKGROUND: While many studies have reported on occupational allergic contact dermatitis amongst dental personnel, studies on the relevance of patch testing in dental patients are scarce. OBJECTIVES: To determine the frequency and clinical relevance of contact allergy in patients with intra- and perioral complaints. METHODS: A total of 360 patients with intra- and perioral complaints suspected of having a contact allergy were patch-tested with the dental allergen series, European Baseline Series, and extended Amsterdam Baseline Series at Amsterdam University Medical Centers between January 2015 and November 2021. RESULTS: A total of 285 patients (79.2%) had a positive patch test reaction for either one (18.6%) or multiple allergens (60.6%). Sodium tetrachloropalladate was the most sensitising allergen with 98 patients (27.2%) testing positive, followed by nickel sulphate (23.3%), methylisothiazolinone (15.6%), and fragrance mix I (14.2%). Clinical relevance was found in 68 of 208 patients (32.7%), with patients having one (15.4%) or multiple (17.3%) patch test reactions clinically relevant to their (peri)oral complaints. CONCLUSIONS: Clinically relevant patch test reactions were frequently seen in dental patients. Although this study provides us with a better understanding on the frequency and clinical relevance of contact allergy in dental patients, further studies are needed to confirm our results.

Declining frequency of sensitization to fragrance mixes I and II: IVDK-data of the years 2012-2021.

BACKGROUND: EU Commission Regulation 2017/1410 prohibits using atranol and chloroatranol, the main allergens in Evernia prunastri (oakmoss), and hydroxyisohexyl 3-cyclohexene carboxaldehyde (HICC) in cosmetic products. Oakmoss absolute is contained in fragrance mix (FM) I and HICC in FM II which are patch tested as screening mixtures in the baseline series. OBJECTIVE: To describe the time trends of reaction frequencies to both FMs as well as to their components in FM-positive patients. METHODS: Retrospective analysis of data from the Information Network of Departments of Dermatology (IVDK), 2012-2021. RESULTS: Positive reactions to FM I (FM II) declined from 9.1% (4.7%) in 2012 to 4.6% (3.0%) in 2021. Full breakdown tests were performed in 24% (FM I) and 31% (FM II), respectively, of the mix-positive patients. From this data, frequencies of sensitization to the 14 single fragrances of FM I and FM II were calculated. For the majority, a decline was noted from 2012/2013 to 2020/2021, for oakmoss absolute 1.9%-0.8% and for HICC 1.8%-0.9%. CONCLUSION: EU Commission Regulation 2017/1410 was an effective measure. However, our data have some limitations, possibly causing underestimation of sensitization frequencies to fragrances.

Results of patch testing 2-hydroxyethyl methacrylate (HEMA) in the European baseline series: A 4-year retrospective study.

BACKGROUND: 2-Hydroxyethyl methacrylate (HEMA) was added to the European baseline series (EBS) in 2019. Few recent data are available on the frequency and relevance of positive reactions to this hapten. OBJECTIVES: To investigate the frequency and relevance of positive patch tests to HEMA in the EBS in a university hospital in Amsterdam, The Netherlands. PATIENTS AND METHODS: Retrospective study in patients with positive patch tests to HEMA investigated between June 2019 and August 2023. RESULTS: Of 2927 consecutive patients, 88 (79 women and 9 men; 3.0%) had a positive reaction to HEMA. The prevalence in women was 3.9%, in men 1.0%. Forty-three (49%) reactions were judged to be of current clinical relevance and 21 (24%) of past relevance. In this group of 64 patients with relevant reactions, 18 (28%) had occupational contact with (meth)acrylate-containing products, of who 11 (61%) were nail stylists. In 46 patients with non-occupational allergic contact dermatitis, 31 (67%) had allergic reactions to nail cosmetics. Glues and glue-containing products accounted for 22% of the materials causing allergic contact dermatitis and dental products for 8%. CONCLUSIONS: Allergic reactions to HEMA are very frequent in women investigated in Amsterdam. Nearly two thirds of cases were caused by nail cosmetics.

Current frequency of contact allergy to isothiazolinones (methyl-, benz- and octylisothiazolinone) across Europe.

BACKGROUND: The use of methylisothiazolinone (MI) as a preservative in cosmetic products caused an alarming increase in MI contact allergy across Europe in the 2010s. This was followed by regulations of use with a total ban on leave-on (implemented in 2017) and reduced use concentrations in rinse-off cosmetics (2018). OBJECTIVE: To follow-up on the prevalence of contact allergy to MI and the related benzisothiazolinone (BIT) and octylisothiazolinone (OIT) in consecutively patch-tested patients in Europe. METHODS: A cross-sectional audit following the design of two previous audits on MI contact allergy from 1 May 2022 to 31 October 2022 included all patients patch tested with the European baseline series, including or supplemented with MI, BIT and OIT across 10 departments in eight European countries. RESULTS: A total of 2554 patients were consecutively patch tested with the three isothiazolinones during the study period. The prevalence of MI and BIT contact allergy was 2.9% (95% confidence interval [CI]: 2.3%-3.7%; range 1.1%-5.8%) and 3.1% (95% CI: 2.4%-3.9%; range 0.0%-6.6%), respectively; that of OIT was 0.7% (95% CI: 0.4%-1.1%; range 0%-3.2%). Rinse-off cosmetic (73.3%) and leave-on cosmetic products (13.3%) were still associated with eliciting allergic contact dermatitis to MI. CONCLUSION: We confirmed a positive impact of regulatory measures on the prevalence of MI contact allergy in Europe, which halved compared to 2015. However, our data suggest that consumers may still be exposed to older cosmetic products containing MI. BIT has superseded MI in causing contact allergy, despite not being allowed for use in cosmetic products.

Increasing non-cosmetic exposure and sensitization to isothiazolinones require action for prevention: Review.

Frequent use of methylchloroisothiazolinone/methylisothiazolinone (MCI/MI) and MI in cosmetic products has been the main cause of widespread sensitization and allergic contact dermatitis to these preservatives (biocides). Their use in non-cosmetic products is also an important source of sensitization. Less is known about sensitization rates and use of benzisothiazolinone (BIT), octylisothiazolinone (OIT), and dichlorooctylisothiazolinone (DCOIT), which have never been permitted in cosmetic products in Europe. BIT and OIT have occasionally been routinely patch-tested. These preservatives are often used together in chemical products and articles. In this study, we review the occurrence of contact allergy to MI, BIT, OIT, and DCOIT over time, based on concomitant patch testing in large studies, and case reports. We review EU legislations, and we discuss the role of industry, regulators, and dermatology in prevention of sensitization and protection of health. The frequency of contact allergy to MI, BIT, and OIT has increased. The frequency of contact allergy to DCOIT is not known because it has seldom been patch-tested. Label information on isothiazolinones in chemical products and articles, irrespective of concentration, is required for assessment of relevance, information to patients, and avoidance of exposure and allergic contact dermatitis.