Prevalence of dermatitis including allergic contact dermatitis from medical devices used by children and adults with Type 1 diabetes mellitus: A systematic review and questionnaire study.

Use of medical devices (MDs), that is, glucose sensors and insulin pumps, in patients with Type 1 diabetes mellitus (T1D) has proven an enormous advantage for disease control. Adverse skin reactions from these MDs may however hamper compliance. The objective of this study was to systematically review and analyse studies assessing the prevalence and incidence of dermatitis, including allergic contact dermatitis (ACD) related to MDs used in patients with T1D and to compare referral routes and the clinical investigation routines between clinics being part of the European Environmental and Contact Dermatitis Research Group (EECDRG). A systematic search of PubMed, EMBASE, CINAHL and Cochrane databases of full-text studies reporting incidence and prevalence of dermatitis in persons with T1D using MDs was conducted until December 2021. The Newcastle-Ottawa Scale was used to assess study quality. The inventory performed at EECRDG clinics focused on referral routes, patient numbers and the diagnostic process. Among the 3145 screened abstracts, 39 studies fulfilled the inclusion criteria. Sixteen studies included data on children only, 14 studies were on adults and nine studies reported data on both children and adults. Participants were exposed to a broad range of devices. Skin reactions were rarely specified. It was found that both the diagnostic process and referral routes differ in different centres. Further data on the prevalence of skin reactions related to MDs in individuals with T1D is needed and particularly studies where the skin reactions are correctly diagnosed. A correct diagnosis is delayed or hampered by the fact that, at present, the actual substances within the MDs are not declared, are changed without notice and the commercially available test materials are not adequately updated. Within Europe, routines for referral should be made more standardized to improve the diagnostic procedure when investigating patients with possible ACD from MDs.

A literature review and expert consensus statement on diagnostics in suspected metal implant allergy.

BACKGROUND: Although rare, allergic reactions to metal implants represent a diagnostic challenge in view of missing guidelines. OBJECTIVES: To develop an European expert consensus on characteristics of metal allergy reactions and the utility of various diagnostic tools in suspected metal implant allergy. METHODS: A nominal group technique (NGT) was applied to develop consensus statements. Initially an online literature database was created on a secure server to enable a comprehensive information. Twenty-three statements were formulated on potential aspects of metal implant allergy with a focus on diagnostics and grouped into five domains. For the consensus development, the panel of 12 experts initially did refine and reformulate those statements that were ambiguous or had unclear wording. By face-to-face (9/12) or virtual participation (3/12), an anonymous online voting was performed. RESULTS: Consensus (≥80% of agreement) was reached in 20/23 statements. The panel agreed that implant allergy despite being rare should be considered in case of persistent unexplained symptoms. It was, however, recommended to allow adequate time for resolution of symptoms associated with healing and integration of an implant. Obtaining questionnaire-aided standardized medical history and standardized scoring of patient outcomes was also considered an important step by all experts There was broad consensus regarding the utility/performance of patch testing with additional late reading. It was recognized that the lymphocyte transformation test (LTT) has to many limitations to be generally recommended. Prior to orthopaedic implant, allergy screening of patients without a history of potential allergy to implant components was not recommended. CONCLUSIONS: Using an expert consensus process, statements concerning allergy diagnostics in suspected metal implant allergy were created. Areas of nonconsensus were identified, stressing uncertainty among the experts around topics such as preoperative testing in assumed allergy, histological correlate of periimplant allergy and in vitro testing, which underscores the need for further research.

Allergic contact dermatitis caused by dipropylene glycol diacrylate in the Omnipod® insulin pump.

BACKGROUND: Cases of allergic contact dermatitis (ACD) caused by isobornyl acrylate (IBOA) in the Omnipod® insulin pump have previously been reported. OBJECTIVES: To present three cases of patients with ACD caused by a new allergen in the pump, and results from chemical analyses. METHODS: Omnipod pumps from different batches were analysed by gas chromatography-mass spectrometry. Aimed testing, with the department's medical device (MD) series and substances identified in the pump including dipropylene glycol diacrylate (DPGDA) at 0·01% and 0·1% in petrolatum (pet.), was performed. Patch testing also included extracts from the device, the adhesive patch as is, and allergens from baseline series. RESULTS: All patients tested positive to 0·1% DPGDA in pet., and two patients additionally to a 0·01% concentration. DPGDA was found in extracts of the Omnipod pumps brought by the patients. An Omnipod pump from an earlier batch contained tripropylene glycol diacrylate, IBOA, N,N-dimethylacrylamide, di(ethylene glycol)ethyl ether acrylate (DEGEA) but no DPGDA. One of the patients reacted positively to all of these allergens except DEGEA, which was not tested. CONCLUSIONS: When suspecting ACD to MDs, DPGDA at 0·1% in pet. should be tested. The contents of Omnipod have changed over time. Patch testing with updated test series and relevance assessment of positive reactions is a delicate task. Children, with lifelong use of MDs, risk contracting many allergies with potential cross-allergies. A question should be raised as to whether these low molecular weight acrylates should be used at all in devices constantly worn on the skin.

Continuous glucose monitoring systems give contact dermatitis in children and adults despite efforts of providing less 'allergy- prone' devices: investigation and advice hampered by insufficient material for optimized patch test investigations.

BACKGROUND: Medical devices are increasingly being reported to cause contact allergic dermatitis reactions. OBJECTIVE: Review of patients with diabetes type I referred for suspected allergic contact dermatitis to insulin pump or glucose sensor systems. METHOD: We have reviewed 11 referred diabetes mellitus patients investigated for allergic contact dermatitis reactions to medical devices and specifically Dexcom G6® . Extracts from the medical devices were analysed. RESULTS: The majority of patients was children, the majority had relevant allergies and particularly allergy to isobornyl acrylate which was also found in the glucose sensor system Dexcom G6® . CONCLUSIONS: The following case reports bring in focus the fact that patients sensitized through use of one medical device and being advised the use of another, or find another product for a while useful, are not by necessity free from future episodes of allergic contact dermatitis. The case reports emphasize the need for collaboration since it is impossible for even well-equipped laboratories to properly investigate the medical devices when information on the substances used in production is not uniform and complete and material to investigate are scarce. The importance of adequate patch test series and testing with own material and furthermore the importance to re-analyse medical devices and re-analyse test data are emphasized.

Validation of questionnaire algorithm based on repeated open application testing with the constituents of fragrance mix II: the EDEN Fragrance Study.

BACKGROUND: In a European study on contact allergy in the general population, it has been 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/algorithm. The secondary aim was to investigate whether there was any association between the outcome of the recent repeated open application test (ROAT) and the patch test reactivity. METHODS: One hundred nine subjects with and without contact allergy to fragrance mix II (FM II) were recruited. Volunteers from six European dermatology clinics participated in the study including a patch test and a ROAT. RESULTS: Twenty-four positive ROAT reactions were noted in total including 20 of those 32 with contact allergy to FM II. None of the volunteers reacted to the vehicle (P < 0.001). More individuals with a positive algorithm had positive ROATs when compared with those with a negative algorithm. However, the difference was not statistically significant (P = 0.12). The lower the patch test concentration eliciting a positive test reaction, the more likely was 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 validated but it was indicated in this ROAT setup. 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.

Validation of a questionnaire algorithm based on repeated open application testing with the constituents of fragrance mix I.

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.

Hand strength and dexterity in individuals with hand eczema.

BACKGROUND: Patients with hand eczema often describe symptoms such as pain, clumsiness and difficulty flexing their fingers, thus impairing the function of the hand. OBJECTIVE: The aim of this study was to investigate whether hand eczema is associated with a measurable impairment of hand strength and dexterity. We also studied the relationship between hand function and the ability to perform activities of daily living (ADL), pain level and quality of life measured with the Dermatology Life Quality Index (DLQI). METHODS: Twenty-one participants with ongoing hand eczema were examined with well-established methods for measuring hand grip strength, pinch strength and dexterity. A questionnaire was designed to investigate perceived ability to perform ADL. The participants were also asked to grade their current pain level, and the DLQI was used to assess the participants' quality of life. A group of 12 participants was reinvestigated when healed. RESULTS: The participants demonstrated a significant improvement in all functional tests when healed. There was a strong correlation between ADL and both dexterity and hand grip strength. There was also a strong correlation between ADL and pain. All participants reported some difficulty performing ADL. CONCLUSIONS: Our results suggest that ongoing hand eczema may lead to a measurable decrease of strength and dexterity of the hand, leading to an impairment of the ability to perform ADL and consequently to a poorer quality of life.

The epidemic of methylisothiazolinone contact allergy in Europe: follow-up on changing exposures.

BACKGROUND: Methylisothiazolinone (MI) has caused an unprecedented epidemic of contact allergy in Europe and elsewhere. Subsequently, regulatory action has been taken, at least in Europe, aiming at reducing risk of MI sensitization. OBJECTIVE: To follow-up on the prevalence of contact allergy to MI in consecutively patch tested patients and assess the spectrum of products containing MI or methylchloroisothiazolinone (MCI)/MI in patients positive to MI which elicited current allergic contact dermatitis. METHODS: A cross-sectional survey was performed in 2016 and 2017, including all adult patients patch tested with the baseline series (including MI 0.2% aq.) between 1 May and 31 October at 14 centres in 11 European countries. Patients with positive reactions (+ to +++) to MI were further examined regarding history, clinical characteristics and eliciting products, which were categorized into 34 types and 4 classes (leave-on, rinse-off, household, occupational). The results were compared with the reference year 2015. RESULTS: A total of 317 patients, n = 202 of 4278 tested in 2016 (4.72%) and n = 115 of 3879 tested in 2017 (2.96%), had positive reactions to MI; the previous result from 2015 was 5.97% (P < 0.0001). The share of currently relevant contact allergy among all positive reactions declined significantly as well (P = 0.0032). Concerning product classes, a relative decline of leave-on and a relative increase of rinse-off and household products was noted. CONCLUSION: The prevalence of MI contact allergy decreased by 50% from 2015 to 2017. As a consequence of regulation, the share of cosmetics products (leave-on in particular) eliciting allergic contact dermatitis is decreasing. The chosen method of analysing causative products in sensitized patients has proven useful to monitor effects of intervention.

The role of the dermatologist in the immune-mediated/allergic diseases - position statement of the EADV task force on contact dermatitis, EADV task force on occupational skin diseases, UEMS-EBDV subcommission allergology and European Dermatology Forum.

BACKGROUND: The members of the Task Force on Contact Dermatitis and the Task Force on Occupational Dermatoses of the European Academy of Dermatology and Venereology (EADV), of the European Dermatology Forum (EDF), and the members of the UEMS Section of Dermatology-Venereology (UEMS-EBDV) we want to vindicate the fundamental role that the specialist in Dermatology has in the diagnosis and management of Immuno-mediated /allergic Diseases. OBJECTIVE: In disagreement with the blueprint paper of the UEMS section of Allergology (2013), in which dermatologists are excluded from one of their core activities it was decided to write this consensus paper. DISCUSSION: The skin occupies a crucial place in the broad spectrum of allergic diseases; there is no other organ with such a multitude of different clinical conditions mediated by so many pathogenetic immune mechanisms. Subsequently, dermatologists play a fundamental role in the management of immune-mediated diseases including among others contact dermatitis, atopic dermatitis, urticaria and angioedema or cutaneous adverse drug, food and arthropod reactions. The essential role of dermatology in the diagnostic, therapeutic and preventive management of immune mediated /allergic diseases which is crucial for patient management is justified from both the academic and professional point of view. CONCLUSION: Based on the best care of the patient with cutaneous immune allergic disease a multidisciplinary approach is desirable and the dermatologist has a pivotal role in patient management. Be so good and no one will not ignore you, dermatologist. Ideally Dermatology should be governed according the following Henry Ford statement: "Arriving together is the beginning; keeping together is progress; working together is success."

Wet work exposure and hand eczema among healthcare workers: a cross-sectional study.

BACKGROUND: Hand eczema is more common in healthcare workers than in the general population. Hands are subject to changing occupational exposures as a result of mandatory hygiene regulations for healthcare workers. OBJECTIVES: To describe exposure to hygiene procedures and investigate the associations between occupational hand washing, use of nonsterile gloves and hand disinfectant, and self-reported hand eczema. METHODS: This was a cross-sectional study; an electronic questionnaire was distributed to 28 762 hospital employees in southern Sweden. Nurses, assistant nurses or physicians constituted the group of healthcare workers analysed. Adjustments were made for sex, age, wet work at home, lifestyle factors and atopic dermatitis. RESULTS: In total, 12 288 (43%) responded, including 9051 healthcare workers. In this group the 1-year prevalence of self-reported hand eczema was 21%. On a daily basis, 30% reported hand washing with soap > 20 times at work, 45% used hand disinfectants > 50 times and 54% wore nonsterile gloves for > 2 h. After adjustment for confounding factors, a dose-dependent association with self-reported hand eczema was found for the daily number of hand washes with soap at work and time working with disposable gloves but not for alcoholic disinfectant use. Hand washing outside work was not associated with self-reported hand eczema in the adjusted multivariate analysis. CONCLUSIONS: In this study, we found a higher 1-year prevalence of self-reported hand eczema among Swedish healthcare workers than reported in the general population. Hand washing with soap and use of disposable gloves were associated with the occurrence of self-reported hand eczema in a dose-dependent way. Use of hand disinfectant was not associated with self-reported hand eczema.

Prevalence of skin disease in a population-based sample of adults from five European countries.

BACKGROUND: There is a lack of prevalence data on skin diseases in the general adult population; most studies have been carried out in small, national or consecutive clinical samples. OBJECTIVES: To determine the prevalence of common skin disease in the general European population and to assess differences in the characteristics of treatment between countries. METHODS: A random sample consisting of 12 377 participants aged 18-74 years was drawn from the general population of five European countries (Germany, Italy, the Netherlands, Portugal and Sweden). This was a cross-sectional study and all participants were interviewed using a standardized questionnaire that assessed the occurrence of 10 common skin diseases during lifetime, past year and past month. If a skin disease was reported, we additionally assessed who performed the diagnosis and treatment, and whether drugs had been prescribed. RESULTS: The most common skin disease was warts (41·3%), followed by acne (19·2%) and contact dermatitis (15·0%). In general, women were more often affected by skin diseases compared with men; only skin cancer had a slightly higher prevalence in men. The prevalence of skin diseases in northern countries (Germany, the Netherlands and Sweden) was generally higher than in the southern countries (Italy and Portugal). In the Netherlands the treatment of skin diseases was less often performed by a dermatologist compared with the other countries. CONCLUSIONS: The prevalence estimates reported in this study are derived from a representative sample of the general population. Data assessment was performed comprehensively across countries, thus country-specific prevalence estimates are comparable.

Skincare products containing low concentrations of formaldehyde detected by the chromotropic acid method cannot be safely used in formaldehyde-allergic patients.

BACKGROUND: Formaldehyde is a well-known contact sensitizer. Formaldehyde releasers are widely used preservatives in skincare products. It has been found that formaldehyde at concentrations allowed by the European Cosmetics Directive can cause allergic contact dermatitis. However, we still lack information on whether formaldehyde at low concentrations affects dermatitis in formaldehyde-allergic individuals. OBJECTIVES: To study the effects of low concentrations of formaldehyde on irritant contact dermatitis in formaldehyde-allergic individuals. METHODS: Fifteen formaldehyde-allergic individuals and a control group of 12 individuals without contact allergy to formaldehyde and formaldehyde releasers were included in the study. The individuals performed the repeated open application test (ROAT) during 4 weeks with four different moisturizers releasing formaldehyde in concentrations that had been determined as > 40, 20-40, 2·5-10 and 0 p.p.m. by the chromotropic acid (CA) spot test. Dimethyloldimethylhydantoin was used as a formaldehyde releaser in the moisturizers. The ROAT was performed on areas of experimentally induced sodium lauryl sulfate dermatitis. The study was double blind, controlled and randomized. RESULTS: Nine of the 15 formaldehyde-allergic individuals had reappearance or worsening of dermatitis on the areas that were treated with moisturizers containing formaldehyde. No such reactions were observed in the control group (P < 0·001) or for the moisturizers without formaldehyde in the formaldehyde-allergic individuals (P < 0·001). CONCLUSIONS: Our results demonstrate that the low concentrations of formaldehyde often found in skincare products by the CA method are sufficient to worsen an existing dermatitis in formaldehyde-allergic individuals.

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

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

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

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

Preservatives in cosmetics in the Israeli market conform well to the EU legislation.

BACKGROUND: Preservatives are important and frequent skin sensitizers, found in a wide range of products for personal and occupational use. According to the European legislation, some cosmetic ingredients are restricted in terms of quantity and a detailed list of ingredients must be present on the product or packaging. OBJECTIVES: To examine the use of preservatives in common cosmetics on the Israeli market. MATERIALS/METHODS: Sixty different Israeli brand cosmetics, including shampoos, liquid soaps, body creams and hand creams were randomly selected. Ingredient labels were examined. The products were investigated by the chromotropic acid method for release of formaldehyde and by high performance liquid chromatography for the presence of formaldehyde, DMDM hydantoin and methylchloroisothiazolinone/methylisothiazolinone (MCI/MI) and MI content. RESULTS: All products but one contained a detailed list of ingredients printed on the package. According to labelling, the most prevalent preservatives in Israeli shampoos and liquid soaps were DMDM hydantoin and MCI/MI. Hand creams and body creams contained mainly parabens but also iodopropynyl butylcarbamate, phenoxyethanol and DMDM hydantoin. Formaldehyde in doses from 4 to 429 ppm, and DMDM hydantoin were detected in 38 and 16 (63% and 27%) of the products, respectively. MCI/MI was detected in 11 (18%) of the products, with highest prevalence in rinse- off products (55%). Excluding one hand cream which measured 106 ppm MI, the amount of formaldehyde, DMDM hydantoin, MCI/MI and MI was within the allowed concentrations by the European directive in all cases. CONCLUSIONS: In Israel, adaptation of the European directive prevails, as shown by the measurements we performed on randomly selected products.

Development of a clinical score system for the diagnosis of photoallergic contact dermatitis using a consensus process: item selection and reliability.

BACKGROUND: Photoallergic contact dermatitis (PACD) is an uncommon condition, and there is a lack of validated criteria for its diagnosis. OBJECTIVE: To identify a set of relevant criteria to be considered when suspecting a diagnosis of PACD and to assess the reproducibility of these criteria. METHODS: This was a diagnostic item selection and reliability study performed between July 2012 and October 2012. A panel of seven recognized experts was invited to consecutive rounds of a Delphi survey and to a conclusive face-to-face meeting with the aim of obtaining an agreement on criteria for the diagnosis of PACD. The panel was also provided with a series of 16 reports of suspected PACDs to be classified according to a five-point likelihood scale. Identified criteria with the weights attributed by experts were used to develop a score system for the diagnosis of PACD. Consensus was measured by calculating the Intraclass Correlation Coefficient (ICC). The performance of the score system was evaluated in terms of overall classification accuracy. RESULTS: Seven criteria were identified by experts as relevant for the diagnosis of PACD. The criteria were related to the type of skin lesions, accompanying symptoms, skin area involved, general medical history, modality of exposure to the culprit substance, history of exposure to the sun or other light sources and photopatch test results. Experts reached a moderate agreement on PACD cases classification, with ICC = 0.69 (95% Confidence Interval, CI, 0.50-0.86). The score system enabled discrimination of probable and definite PACD cases from possible and unlikely or excluded ones, with a nearly perfect agreement being observed between the score system classification and judgment by experts. CONCLUSION: A diagnostic score was proposed. The score should receive a comprehensive validation on a larger series of cases and with multiple evaluators.

Immune responses to hair dyes containing toluene-2,5-diamine.

BACKGROUND: Toluene-2,5-diamine (PTD) is the most frequently used dye in oxidative hair dyes on the Scandinavian market. However, little is known about immune responses to PTD-containing oxidative hair dyes. OBJECTIVES: To study immune responses induced by PTD-containing hair dyes in mice. METHODS: Immune responses against two different permanent hair dye products containing 1·60% (w/w) and 0·48% (w/w) PTD within the colour gel, and various concentrations of pure PTD were studied. The local inflammatory response was measured by ear swelling and cell infiltration, and T- and B-cell infiltration and proliferation was determined in the draining lymph nodes. RESULTS: Concentration-dependent immune responses were seen to PTD both in the skin and draining lymph nodes. The hair dye containing 1·60% PTD induced strong local inflammation and caused T- and B-cell infiltration and proliferation as well as an increased number of regulatory T cells in the draining lymph nodes. In contrast, the hair dye containing 0·48% PTD induced skin inflammation but only minor responses in the draining lymph nodes. CONCLUSIONS: Consumer-available PTD-containing permanent hair dyes can be potent immune activators inducing both pro- and anti-inflammatory responses. The outcome of the response is dependent on allergen dose, amount of additional allergens and exposure regime.

Update to RIFM fragrance ingredient safety assessment, 4-hexen-1-ol, 5-methyl-2-(1-methylethenyl)-, CAS registry number 58461-27-1.

4-Hexen-1-ol, 5-methyl-2-(1-methylethenyl)- was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, photoirritation/photoallergenicity, skin sensitization, and environmental safety. Data show that 4-hexen-1-ol, 5-methyl-2-(1-methylethenyl)- is not genotoxic. The repeated dose, reproductive, and local respiratory toxicity endpoints were evaluated using the Threshold of Toxicological Concern (TTC) for a Cramer Class I material, and the exposure to 4-hexen-1-ol, 5-methyl-2-(1-methylethenyl)- is below the TTC (0.03 mg/kg/day, 0.03 mg/kg/day, and 1.4 mg/day, respectively). Data from read-across analog 3-methylbut-3-en-1-ol (CAS # 763-32-6) show that there are no safety concerns for 4-hexen-1-ol, 5-methyl-2-(1-methylethenyl)- for skin sensitization under the current declared levels of use. The photoirritation/photoallergenicity endpoints were evaluated based on ultraviolet/visible (UV/Vis) spectra; 4-hexen-1-ol, 5-methyl-2-(1-methylethenyl)- is not expected to be photoirritating/photoallergenic. The environmental endpoints were evaluated; 4-hexen-1-ol, 5-methyl-2-(1-methylethenyl)- was found not to be Persistent, Bioaccumulative, and Toxic (PBT) as per the International Fragrance Association (IFRA) Environmental Standards, and its risk quotients, based on its current volume of use (VoU) in Europe and North America (i.e., Predicted Environmental Concentration/Predicted No Effect Concentration [PEC/PNEC]), are <1.