Nickel is the most frequent cause of contact allergy worldwide and has been studied extensively. This clinical review provides an updated overview of the epidemiology, exposure sources, methods for ...exposure quantification, skin deposition and penetration, immunology, diagnosis, thresholds for sensitization and elicitation, clinical pictures, prevention, and treatment. The implementation of a nickel regulation in Europe led to a decrease in the prevalence of nickel allergy, and changes in the clinical picture and disease severity. Nevertheless, the prevalences of nickel allergy in the European general population are approximately 8% to 19% in adults and 8% to 10% in children and adolescents, with a strong female predominance. Well‐known consumer items such as jewellery and metal in clothing are still the main causes of nickel allergy and dermatitis, although a wide range of items for both private and occupational use may cause dermatitis. Allergic nickel dermatitis may be localized to the nickel exposure site, be more widespread, or present as hand eczema. Today, efficient methods for exposure quantification exist, and new insights regarding associated risk factors and immunological mechanisms underlying the disease have been obtained. Nevertheless, questions remain in relation to the pathogenesis, the persistent high prevalence, and the treatment of severe cases.
The human repeated insult patch test (HRIPT) has a history of use in the fragrance industry as a component of safety evaluation, exclusively to confirm the absence of skin sensitization at a defined ...dose.
The aim of the study was to document the accumulated experience from more than 30 years of conducting HRIPTs.
A retrospective collation of HRIPT studies carried out to a consistent protocol was undertaken, with each study comprising a minimum of 100 volunteers.
The HRIPT outcomes from 154 studies on 134 substances using 16,512 volunteers were obtained. Most studies confirmed that at the selected induction/challenge dose, sensitization was not induced. In 0.12% of subjects (n = 20), there was induction of allergy. However, in the last 11 years, only 3 (0.03%) of 9854 subjects became sensitized, perhaps because of improved definition of a safe HRIPT dose from the local lymph node assay and other skin sensitization methodologies, as well as more rigorous application of the standard protocol after publication in 2008. This experience with HRIPTs demonstrates that de novo sensitization induction is rare and becoming rarer, but it plays an important role as an indicator that toxicological predictions from nonhuman test methods (in vivo and in vitro methods) can be imperfect.
Patch testing is an important diagnostic tool for the assessment of allergic contact dermatitis (ACD).
This study documents the North American Contact Dermatitis Group (NACDG) patch testing results ...from January 1, 2015, to February 28, 2017.
At 13 centers in North America, patients were tested in a standardized manner with a screening series of 70 allergens. Data were manually verified and entered into a central database. Descriptive frequencies were calculated, and trends were analyzed using χ test.
A total of 5597 patients were tested. There were 3725 patients (66.6%) who had at least 1 positive reaction, and 2798 patients (50.2%) were ultimately determined to have a primary diagnosis of ACD. A total of 572 patients (10.2%) had occupationally related skin disease. There were 10,983 positive allergic reactions. Nickel remained the most commonly detected allergen (17.5%). Methylisothiazolinone, which was added to the screening series for the 2013-2014 cycle, had the second highest positive reaction rate of allergens tested (13.4%). Compared with the previous reporting periods (2013-2014) and (2005-2014), positive reaction rates for the top 35 screening allergens statistically increased for only 1 allergen: hydroxyethyl methacrylate (3.4%; risk ratios, 1.24 confidence interval, 1.00-1.54 and 1.46 confidence interval, 1.23-1.73). Three newly added allergen preparations-ammonium persulfate (1.7%), chlorhexidine (0.8%), and hydroquinone (0.3%)-all had a reaction rate of less than 2%. Twenty-three percent of the tested patients had at least 1 relevant allergic reaction to an allergen not on the NACDG series; 12% of these were occupationally related. T.R.U.E. Test (SmartPractice Denmark, Hillerød, Denmark) would have hypothetically missed one quarter to almost 40% of reactions detected by the NACDG screening series.
These results confirm that the epidemic of sensitivity to methylisothiazolinone has continued in North America. Patch testing with allergens beyond a screening tray is necessary for a complete evaluation of occupational and nonoccupational ACD.
Cutaneous adverse events (CAE) from FreeStyle Libre include allergic contact dermatitis (ACD) caused by the allergen isobornyl acrylate (IBOA). We aim to report CAE from this glucose sensor, ACD to ...IBOA in particular, and the outcome of using barrier films as a prevention.
A monocentric, retrospective review of medical files from adult and pediatric patients with diabetes using Freestyle Libre, in the period between December 2016 and April 2019, was performed with a focus on CAE.
Fifty-seven of 1,036 patients with diabetes (5.5%) were referred to our dermatology department because of CAE from FreeStyle Libre. Thirty-nine of 1,036 (3.8%) had ACD due to IBOA. Only two patients, of whom one sensitized to IBOA, had a benefit from using barrier films.
CAE occurred in 5.5% of FreeStyle Libre users, and 3.8% suffered from ACD due to IBOA. Barrier films had limited value in the prevention.
Summary
Background
Changing patterns of exposure lead to changes in the spectrum of contact allergy in the general population and in patients patch tested for suspected contact allergy. The main ...contact allergens (haptens) are assembled in the so‐called ‘baseline series’.
Objectives
To present the current spectrum of contact allergy to baseline series allergens, and its temporal development over the last 12 years, based on data collected by the 56 active departments of the trinational Information Network of Departments of Dermatology (IVDK).
Methods
Patch‐test data, along with core demographic and clinical information, subdivided into 4‐year periods for all patients patch tested with the baseline series in the IVDK, were analysed descriptively. Moreover, log‐binomial regression analysis addressed temporal trends of specific contact allergies, adjusted for potentially confounding factors.
Results
Among the 125 436 patients tested with the German baseline series, the most common allergens were nickel (14·7%), fragrance mix I (8·1%), Myroxylon pereirae resin (7·5%) and cobalt (5·2%), with no conclusive trend. The rise and fall of contact allergy to methylchloroisothiazolinone/methylisothiazolinone (MI), following (self‐) regulation in the European Union, reflected the MI contact allergy epidemic. Propolis showed a marked upward trend with a prevalence of 3·94% during the period 2015–2018.
Conclusions
Decreases in sensitization prevalence likely reflect reduced exposure, with some lag, as seen with hydroxyisohexyl 3‐cyclohexene carboxaldehyde. If no (sufficient) decrease can be observed despite interventions, such as for nickel and chromium, affected subgroups should be identified and their causative exposures explored. Finally, increases such as that observed with propolis, certainly warrant targeted investigation of the exposures driving sensitization, and possibly intervention.
What is already known about this topic?
Contact allergy is prevalent in the general population.
Surveillance based on clinical data offers timely information on trends concerning certain allergens or subgroups at risk.
What does this study add?
This analysis provides an update of the current contact allergy prevalence in Central Europe, including time trends.
This study describes the demographic and clinical profile of patients tested from 2007 to 2018.
This research identifies contact allergens that require (further) preventive efforts.
Linked Comment: Schuttelaar. Br J Dermatol 2020; 183:800–801.
What is already known about this topic?
Contact allergy is prevalent in the general population.
Surveillance based on clinical data offers timely information on trends concerning certain allergens or subgroups at risk.
What does this study add?
This analysis provides an update of the current contact allergy prevalence in Central Europe, including time trends.
This study describes the demographic and clinical profile of patients tested from 2007 to 2018.
This research identifies contact allergens that require (further) preventive efforts.
Linked Comment: Schuttelaar. Br J Dermatol 2020; 183:800–801.
Plain language summary available online
Respond to this article
Background
Contact allergy is a common condition and can severely interfere with daily life or professional activities. Due to changes in exposures, such as introduction of new substances, new ...products or formulations and regulatory intervention, the spectrum of contact sensitization changes.
Objective
To evaluate the current spectrum of contact allergy to allergens present in the European baseline series (EBS) across Europe.
Methods
Retrospective analysis of data collected by the European Surveillance System on Contact Allergies (ESSCA, www.essca-dc.org) in consecutively patch‐tested patients, 2013/14, in 46 departments in 12 European countries.
Results
Altogether, 31 689 patients were included in the analysis. Compared to a similar analysis in 2004, the prevalence of contact allergy to methylisothiazolinone went up to around 20% in several departments. In comparison, contact allergy to the metals nickel, cobalt and chromium remained largely stable, at 18.1%, 5.9% and 3.2%, respectively, similar to mostly unchanged prevalence with fragrance mix I, II and Myroxylon pereirae (balsam of Peru) at 7.3%, 3.8% and 5.3%, respectively. In the subgroup of departments diagnosing (mainly) patients with occupational contact dermatitis, the prevalence of work‐related contact allergies such as epoxy resin or rubber additives was found to be increased, compared to general dermatology departments.
Conclusion
Continuous surveillance of contact allergy based on network data offers the identification of time trends or persisting problems, and thus enables focussing in‐depth research (subgroup analyses, exposure analysis) on areas where it is needed.
Patch testing is an important diagnostic tool for assessment of allergic contact dermatitis (ACD).
This study documents the North American Contact Dermatitis Group (NACDG) patch testing results from ...January 1, 2019, to December 31, 2020.
At 13 centers in North America, patients were tested in a standardized manner with a screening series of 80 allergens, and, as indicated, supplemental allergens.
Overall, 4121 patients were tested; 2871 (69.7%) had at least 1 positive/allergic patch test reaction and 2095 patients (51.2%) had a primary diagnosis of ACD. The most commonly positive allergens were nickel (18.2%), methylisothiazolinone (MI) (13.8%), fragrance mix (FM) I (12.8%), hydroperoxides of linalool (HPL) (11.1%), and benzisothiazolinone (BIT) (10.4%). Compared with that of 2017-2018, prevalence of top 20 allergens statistically increased for FM I, HPL, BIT, propolis, and hydroperoxides of limonene (3.5%). For the first time, MI positivity did not increase between reporting periods. Approximately one-fifth of patients (20.3%) had ≥1 clinically relevant reaction(s) to allergens/substances not on the NACDG series.
The epidemic of MI contact allergy in North America may have reached a plateau. Patch testing using a robust screening series, and supplemental allergens as indicated, is necessary for comprehensive evaluation of ACD.
Allergic contact dermatitis (ACD) from isothiazolinones has frequently been described in the literature. Following an epidemic of sensitization to methylchloroisothiazolinone/methylisothiazolinone ...(MCI/MI) in the 1980s, and more recently to MI, the Scientific Committee on Consumer Safety of the European Commission banned their use in leave‐on products, while restricting that in rinse‐off cosmetics. Despite a decreasing prevalence of ACD from MCI/MI and MI, cases caused by occupational exposure and non‐cosmetic isothiazolinone sources are on the rise. Moreover, sensitization to newer and lesser known isothiazolinones has been reported. This paper reviews the epidemiology of contact allergy to different isothiazolinones, clinical presentation of isothiazolinone‐induced ACD, most relevant sensitization sources and potential cross‐reactions between isothiazolinone derivatives. It also provides an update on recent legislative measures.
Adverse outcome pathways (AOPs) offer a pathway-based toxicological framework to support hazard assessment and regulatory decision-making. However, little has been discussed about the scientific ...confidence needed, or how complete a pathway should be, before use in a specific regulatory application. Here we review four case studies to explore the degree of scientific confidence and extent of completeness (in terms of causal events) that is required for an AOP to be useful for a specific purpose in a regulatory application: (i) Membrane disruption (Narcosis) leading to respiratory failure (low confidence), (ii) Hepatocellular proliferation leading to cancer (partial pathway, moderate confidence), (iii) Covalent binding to proteins leading to skin sensitization (high confidence), and (iv) Aromatase inhibition leading to reproductive dysfunction in fish (high confidence). Partially complete AOPs with unknown molecular initiating events, such as 'Hepatocellular proliferation leading to cancer', were found to be valuable. We demonstrate that scientific confidence in these pathways can be increased though the use of unconventional information (eg, computational identification of potential initiators). AOPs at all levels of confidence can contribute to specific uses. A significant statistical or quantitative relationship between events and/or the adverse outcome relationships is a common characteristic of AOPs, both incomplete and complete, that have specific regulatory uses. For AOPs to be useful in a regulatory context they must be at least as useful as the tools that regulators currently possess, or the techniques currently employed by regulators.
To cite this article: Martin SF, Esser PR, Weber FC, Jakob T, Freudenberg MA, Schmidt M, Goebeler M. Invited review for the journal allergy mechanisms of chemical‐induced innate immunity in allergic ...contact dermatitis. Allergy 2011; 66: 1152–1163.
Allergic contact dermatitis (ACD) is one of the most prevalent occupational skin diseases and causes severe and long‐lasting health problems in the case of chronification. It is initiated by an innate inflammatory immune response to skin contact with low molecular weight chemicals that results in the priming of chemical‐specific, skin‐homing CD8+ Tc1/Tc17 and CD4+ Th1/Th17 cells. Following this sensitization step, T lymphocytes infiltrate the inflamed skin upon challenge with the same chemical. The T cells then exert cytotoxic function and secrete inflammatory mediators to produce an eczematous skin reaction. The recent characterization of the mechanisms underlying the innate inflammatory response has revealed that contact allergens activate innate effector mechanisms and signalling pathways that are also involved in anti‐infectious immunity. This emerging analogy implies infection as a potential trigger or amplifier of the sensitization to contact allergens. Moreover, new mechanistic insights into the induction of ACD identify potential targets for preventive and therapeutic intervention. We summarize here the latest findings in this area of research.
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