Patch testing hydroperoxides of limonene and linalool in consecutive patients-Results of the IVDK 2018-2020.

BACKGROUND: Hydroperoxides of limonene (Lim-OOHs) and linalool (Lin-OOHs) are potent contact sensitizers. OBJECTIVES: To investigate the prevalence of positive patch test (PT) reactions to Lim-OOHs and Lin-OOHs in consecutive patients, their demographic factors and concomitant reactions. METHODS: Between 7/2018 and 12/2020, Lim-OOHs 0.3% pet. and Lin-OOHs 1% pet. were patch tested in 5511 consecutive patients. We assessed PT reactivity and analysed data from patients with either positive or negative PTs to Lim-OOHs and Lin-OOHs. RESULTS: Positive PT results to Lim-OOHs (n = 170, 3.1%) and Lin-OOHs (n = 483, 8.8%) were frequent. Most of the positive reactions were weak (LimOOHs n = 134/LinOOHs n = 429), and even more frequently, doubtful (n = 252/n = 578) or irritant reactions (n = 81/n = 178) were documented. PT reactivity to Lim-OOHs and Lin-OOHs was increased in patients with irritant reactions to sodium lauryl sulphate (SLS). The proportion of leg dermatitis and concomitant positive reactions to fragrances and essential oils was increased in patients with reactivity to these hydroperoxides. CONCLUSION: The observed reaction pattern suggests that both test preparations display an irritant potential with an increased risk of false positive reactions. Preparations should be chemically monitored in order to reduce irritancy. Mindful interpretation of PT results and aimed patch testing of lower concentrations is recommended.

A negative breakdown test in a fragrance mix I-positive patient does not rule out contact allergy to its fragrance constituents.

BACKGROUND: In about half of the patients reacting positive to fragrance mix I (FM I), breakdown testing remains negative. This raises the question of whether the reaction to FM I is false-positive, or the breakdown test is false-negative. OBJECTIVES: To identify characteristics and sensitization patterns of patients positive to FM I, but not to its fragrance constituents. PATIENTS AND METHODS: Retrospective analysis of data from the Information Network of Departments of Dermatology (IVDK) between 2005 and 2019. Three patient groups were defined according to their reaction pattern: Group I, FM I positive and ≥1 single fragrance positive in the breakdown test (n = 1912); Group II, FM I positive and breakdown test negative (n = 1318); Group III, FM I negative (n = 19 790). RESULTS: Regarding the pattern of concomitant reactions to other fragrances, Group II had an intermediate position between Group I and Group III. In other respects (age and sex distribution, frequency of sensitization to non-fragrance baseline series allergens), Group II rather resembled Group I. CONCLUSIONS: Not every positive reaction to FM I in patients with negative breakdown tests is false-positive. There may be false-negative reactions to the single fragrance components when patch tested at 1% pet. Raising patch concentrations of some single fragrances is recommended.

The methylisothiazolinone epidemic goes along with changing patients' characteristics - After cosmetics, industrial applications are the focus.

BACKGROUND: Sensitization to methylisothiazolinone (MI) has seen an exceptional epidemic, mainly attributed to its use in cosmetics. OBJECTIVES: To trace the epidemic of MI allergy (2009-2018), and to analyze a possible change of patients' characteristics. METHODS: Informationsverbund Dermatologischer Kliniken-data of patients patch tested between 2009 and 2018 with MI (0.05% aq.) were analyzed concerning anamnestic items and sensitization frequencies. RESULTS: Overall, 4.9% reacted positive to MI. Comparing sensitization to MI in three periods (2009, 2013/14, and 2017/18), there was an increase to 7% in 2013 and a decrease to 3.4% in 2018. The MOAHLFA Index (M=Men, O=Occupational Dermatitis, A=Atopic Dermatitis, L=Leg Dermatitis, F=Face Dermatitis, A= Age > 40) for the period 2013/14 is characterized by a lower proportion of occupational dermatitis and a higher proportion of face dermatitis. The period 2017/18 is characterized by increases of occupational dermatitis and hand dermatitis, and a decrease of face dermatitis. Painters, personal care workers, and hairdressers were particularly affected. Sensitization in hairdressers and personal care workers (mostly cosmeticians) decreased after the peak in 2013/14, whereas sensitization to MI in painters continued to increase. CONCLUSIONS: After an unprecedented epidemic of MI allergy, mainly caused by its use in cosmetics, the continuous use of MI in industrial applications, for example, paints, and subsequent sensitization remain a matter of concern.

S3 Guidelines: Epicutaneous patch testing with contact allergens and drugs - Short version, Part 2.

Epicutaneous patch testing is the diagnostic standard for the detection of allergic contact dermatitis. The present guidelines are aimed at residents and board-certified physicians in the fields of dermatology and allergology as well as other medical specialties involved in establishing the indication for patch testing and its execution in patients with contact dermatitis and other forms of delayed-type hypersensitivity. The target audience also includes other health care providers and insurance funds. Based on a systematic literature search and a formal consensus process (S3), the guidelines were developed by dermatologists in collaboration with pediatricians, occupational medicine physicians, nursing staff as well as patient representatives. The systematic methodological approach and appraisal of evidence upon which the recommendations are based are outlined in a separate method report that also contains evidence tables. The guidelines address general aspects of patch testing as well as medicolegal issues. The recommendations given relate to topics such as the indication for patch testing, informed patient consent, as well as the choice of test substances, test chambers and test site, duration of exposure, reading times and interpretation of test reactions. Furthermore, recommendations are provided with respect to endogenous and exogenous factors, specific patient groups (children, pregnant women, immunosuppressed individuals) as well as possible risks and adverse events associated with patch testing using contact allergens.

S3 guidelines: Epicutaneous patch testing with contact allergens and drugs - Short version, Part 1.

Epicutaneous patch testing is the diagnostic standard for the detection of allergic contact dermatitis. The present guidelines are aimed at residents and board-certified physicians in the fields of dermatology and allergology as well as other medical specialties involved in establishing the indication for patch testing and its execution in patients with contact dermatitis and other forms of delayed-type hypersensitivity. The target audience also includes other health care providers and insurance funds. Based on a systematic literature search and a formal consensus process (S3), the guidelines were developed by dermatologists in collaboration with pediatricians, occupational medicine physicians, nursing staff as well as patient representatives. The systematic methodological approach and appraisal of evidence upon which the recommendations are based are outlined in a separate method report that also contains evidence tables. The guidelines address general aspects of patch testing as well as medicolegal issues. The recommendations given relate to topics such as the indication for patch testing, informed patient consent, as well as the choice of test substances, test chambers and test site, duration of exposure, reading times and interpretation of test reactions. Furthermore, recommendations are provided with respect to endogenous and exogenous factors, specific patient groups (children, pregnant women, immunosuppressed individuals) as well as possible risks and adverse events associated with patch testing using contact allergens. Note: This publication is part 1 of the short version of the S3 guidelines for "Epicutaneous patch testing using contact allergens and drugs" (registry no. 013 - 018; date: March 20, 2019; valid until December 31, 2021). Part 2 of the short version will be published in the next issue. The long version of these guidelines can be accessed at www.awmf.org. The method report is available as online publication (https://www.awmf.org/leitlinien/detail/ll/013-018.html) and contains the evidence tables in its appendix.

Skin sensitization quantitative risk assessment for occupational exposure of hairdressers to hair dye ingredients.

Occupational exposure of hairdressers to hair dyes has been associated with the development of allergic contact dermatitis (ACD) involving the hands. p-Phenylenediamine (PPD) and toluene-2,5-diamine (PTD) have been implicated as important occupational contact allergens. To conduct a quantitative risk assessment for the induction of contact sensitization to hair dyes in hairdressers, available data from hand rinsing studies following typical occupational exposure conditions to PPD, PTD and resorcinol were assessed. By accounting for wet work, uneven exposure and inter-individual variability for professionals, daily hand exposure concentrations were derived. Secondly, daily hand exposure was compared with the sensitization induction potency of the individual hair dye defined as the No Expected Sensitization Induction Levels (NESIL). For PPD and PTD hairdresser hand exposure levels were 2.7 and 5.9 fold below the individual NESIL. In contrast, hand exposure to resorcinol was 50 fold below the NESIL. Correspondingly, the risk assessment for PPD and PTD indicates that contact sensitization may occur, when skin protection and skin care are not rigorously applied. We conclude that awareness of health risks associated with occupational exposure to hair dyes, and of the importance of adequate protective measures, should be emphasized more fully during hairdresser education and training.

European Surveillance System on Contact Allergies (ESSCA): polysensitization, 2009-2014.

BACKGROUND: Polysensitization, defined as being allergic to three or more haptens from the European baseline series, is considered to reflect increased susceptibility to developing a contact allergy, and is likely to be associated with an impaired quality of life. OBJECTIVES: To evaluate the prevalences of polysensitization across Europe and to analyse factors associated with polysensitization. METHODS: Patch test data collected by the European Surveillance System on Contact Allergies (ESSCA; www.essca-dc.org) in consecutively patch tested patients from January 2009 to December 2014, comprising 11 countries and 57 departments, were retrospectively analysed. RESULTS: A total of 86 416 patients were available for analysis, showing a standardized prevalence of polysensitization of 7.02%, ranging from 12.7% (Austria) to 4.6% (Italy). Allergen pairs with the strongest association are reported for the total population, for South Europe, and for North/Central Europe. Overall, polysensitized patients showed a higher percentage of extreme (+++) positive patch test reactions than oligosensitized patients. Female sex, occupational dermatitis and age > 40 years were risk factors for polysensitization. CONCLUSIONS: The varying prevalences of polysensitization across Europe most likely reflect differences in patient characteristics and referral patterns between departments. Known risk factors for polysensitization are confirmed in a European dermatitis population.

Factors associated with p-phenylenediamine sensitization: data from the Information Network of Departments of Dermatology, 2008-2013.

BACKGROUND: Risk factors for p-phenylenediamine (PPD) sensitization include the use of hair dyes, the application of temporary black henna tattoos, working as a hairdresser, and, possibly, exposure to hair dye pretests. OBJECTIVES: To quantify the impact of these (putative) risk factors on PPD sensitization. METHODS: Six items related to PPD exposure were added to the routine Information Network of Departments of Dermatology questionnaire from 2008 to 2013. A retrospective analysis of data from 4314 patients tested with PPD 1% pet. was conducted. RESULTS: Of the PPD-positive patients (n = 271), 80% had their hair dyed, and, of these, 57% subsequently developed scalp dermatitis, whereas only 11% had had a henna tattoo. The self-administrated pretest with hair dye was performed by only a few patients, precluding a more detailed analysis. Hair dyeing [odds ratio (OR) 6.0; 95% confidence interval (CI): 3.9-9.4], henna tattoos (OR 2.4; 95%CI: 1.5-3.7) and being a hairdresser (OR 2.1; 95%CI: 1.3-3.2) increased the risk of PPD sensitization. Neither dyeing of own hair nor application of a temporary henna tattoo seemed to affect PPD sensitization in hairdressers. p-Aminoaryl compounds more often gave positive reactions in patients with henna tattoo. CONCLUSIONS: Hair dyeing is the major risk factor for PPD sensitization in this clinical setting, and application of a temporary black henna tattoo may also lead to (strong) PPD sensitization.

Differences in contents of organochlorine impurities do not influence responses to patch testing with Majantol®.

BACKGROUND: Majantol® [2,2-dimethyl-3-(3-methylphenyl)propan-1-ol; CAS no. 103694-68-4] has been identified as a contact allergen in humans, despite negative animal tests. Hence impurities, specifically organochlorines, in Majantol® might have been the reason for positive patch test reactions in the past. OBJECTIVES: To assess elicitation via patch testing with a standard market-quality version of Majantol® ('normal') with a normal content of organochlorine impurities, as compared with an ultra-purified version of Majantol® ('pure'), without detectable organochlorine impurities. METHODS: Between 1 October 2013 and 31 December 2014, two different Majantol® patch test preparations of the above-mentioned quality were tested 5% pet. in parallel in the 'monitor series', that is, together with the baseline series, in 8005 consecutive patients from 33 departments of dermatology of the Information Network of Departments of Dermatology (IVDK). RESULTS: Fifty-three of 7740 [0.69% (95%CI: 0.51-0.87)] patch tested patients reacted to at least one Majantol® preparation. The majority (n = 32) (60.4%) reacted to both preparations, 13 (24.5%) reacted to the 'normal' version only, and 8 (15.1%) reacted to the 'pure' version only. There was good concordance between results [Cohen's kappa 0.75 (95%CI: 0.65-0.85)], and there was no significant difference in frequency or intensity between the two preparations. More doubtful or irritant reactions than positive reactions were observed, and> 80% of all positive reactions were weak positive. CONCLUSION: Organochlorine impurities are very probably not the cause of allergic reactions to Majantol®.

Contact allergy to ingredients of topical medications: results of the European Surveillance System on Contact Allergies (ESSCA), 2009-2012.

PURPOSE: The aim of this study was to give an overview of the prevalence of contact allergy to active ingredients and excipients of topical medications across Europe. METHODS: Retrospective analysis of data collected by the European Surveillance System on Contact Allergies (www.essca-dc.org) with substances applied to consecutively patch tested patients, 2009-2012, in 54 departments in 12 European countries. RESULTS: In view of the varying composition of the baseline series used in the previously mentioned departments and countries, between 58 833 (lanolin alcohols) and 16 498 patients (sodium metabisulfite) were patch tested with the topical agents covered in this study. Among these, positive (allergic) reactions were most commonly observed to sodium metabisulfite (3.12% positive), followed by propolis (2.48%), Compositae mix (1.73%), lanolin alcohols (1.65%) and caine mix III (benzocaine, cinchocaine and tetracaine; 1.27%). CONCLUSIONS: Several of the substances warrant routine screening for contact allergy, i.e. patch testing in a baseline series. However, in view of a vast number of other topical agents, additional patch testing with the suspect topical drug preparations (including natural remedies and cosmetics) is warranted. In the event of a positive test to the (pharmaceutical) product, single ingredients should be tested individually to precisely identify the hapten(s). Copyright © 2016 John Wiley & Sons, Ltd.

A variant of the CXCL11 gene may influence susceptibility to contact allergy, particularly in polysensitized patients.

BACKGROUND: Hereditary factors may influence individual susceptibility to contact allergy. OBJECTIVES: To investigate genetic variants with impacts on early inflammatory reactions and T cell functions that possibly increase the risk of contact allergy. PATIENTS AND METHODS: Three hundred and seventy two patients undergoing patch testing were recruited from the Information Network of Departments of Dermatology (IVDK). Of these, 133 were monosensitized and 239 were polysensitized, defined as reacting to three or more unrelated sensitizers. Within the polysensitized individuals, a subgroup with at least one particularly strong patch test reaction (strong reactors; n = 194) was considered. Three hundred and forty-seven blood bank donors served as controls. Fifteen genetic variants in 13 genes were analysed. RESULTS: The homozygous variant CXCL11 AA genotype (rs6817952) was significantly more frequent among polysensitized patients (10 of 239 = 4.2%; p = 0.0048; odds ratio 7.49; 95%CI: 1.7-36.1) than among monosensitized patients (2.2%) and in the control group (0.6%). None of the remaining genetic variants investigated were characterized by similarly strong associations. However, the significance was lost after correction for multiple comparisons. CONCLUSIONS: The homozygous variant CXCL11 genotype is associated with an increased risk of contact allergy. To confirm this exploratory finding, further independent studies are needed.