Allergen Research Articles

Do hypoallergenic skincare products contain fewer potential contact allergens?

Personal care products (PCPs) commonly cause allergic contact dermatitis (ACD). Skincare companies often market their products as 'hypoallergenic'; however, this term is not regulated by industry standards. To determine whether PCPs marketed as hypoallergenic are truly less likely to precipitate ACD, we conducted a study of ingredients found in 'hypoallergenic PCPs' from two major UK retailers in 2022. Of 208 products meeting the inclusion criteria, 153 (73.6%) contained at least 1 allergen or related chemical from the British Society for Cutaneous Allergy baseline series, 21 (10.1%) had 2 potential allergens and 4 PCPs (1.9%) had 3 allergens. Cetearyl alcohol was the most common -allergen identified in leave-on PCPs and parabens in rinse-off products; fragrance was the most frequent related chemical found in 85 PCPs (40.1%). A high prevalence of common allergens was found in hypoallergenic PCPs, suggesting that dermatologists and consumers should be cautious of product ingredients.

Occupational allergic contact dermatitis: a case report

Abstract Allergic contact dermatitis is an inflammatory cutaneous reaction which occurs after immunological sensitization to the contact substance and clinically manifests with pruritic, erythematous, indurated, scaly plaques or cutaneous xerosis, thickening and scaling in case of chronic exposure. It is a T-cell mediated type IV reaction (delayed hypersensitivity response) and there have been discovered over 4000 contact allergens. As 30 percent of all occupational diseases involve cutaneous manifestations, irritant and contact dermatitis making up over 90 percent of instances of occupational skin diseases, the occupational doctor plays a key role in diagnosis and management of such patients. Prevention is the key in the treatment of this condition, thus recognizing the workplace risk factors, reducing antigen sources and providing appropriate protective equipment should be of utmost importance. Next, we present the case of a 48-year-old woman, who works as a technician in an aluminum manufacturing plant and who developed pruritic eczematous lesions located on the upper limbs, in order to review the risk factors and consequences of work-environmental exposure to allergens.

An Evaluation of the Presence of Contact Allergens in Over-the-Counter Scar Products.

An Evaluation of the Presence of Contact Allergens in Over-the-Counter Scar Products.

Metabolic re-programming of keratinocytes in response to contact allergens.

Allergic contact dermatitis (ACD) is a common skin disease caused by the recognition of haptens by the immune system. Keratinocytes play an important role in the initiation and facilitation of inflammatory responses in ACD. Immune responses are associated with major changes in metabolism. However, metabolic re-programming is not well studied in ACD; specifically, knowledge of metabolic alterations in structural cells is lacking. Metabolic re-programming in ACD was studied using publicly available transcriptome datasets. Primary pooled keratinocytes and a keratinocyte cell line (HaCaT) were stimulated with contact allergens, and inflammatory responses and expression of metabolic markers were measured by qPCR and flow cytometry, respectively. ACD is characterized by metabolic re-programming with a metabolic profile similar to atopic dermatitis. Exposure to contact allergens causes a wide array of metabolic alterations. Stimulation of keratinocytes with contact allergens induced inflammatory responses typical for ACD and was associated with an up-regulation of proteins representative for glucose uptake, fatty acid metabolism, oxidative phosphorylation and to some extent arginine biosynthesis. Changes in these metabolic pathways were also observed when comparing lesional with non-lesional contact dermatitis skin. ACD is, similarly to other inflammatory skin diseases, characterized by metabolic re-programming. Contact allergen exposure induces expression of a wide array of metabolic pathways, which is at least in part mediated through metabolic re-programming of keratinocytes.

Mass Spectrometry-Based Strategies for Assessing Human Exposure Using Hemoglobin Adductomics.

Hemoglobin (Hb) adducts are widely used in human biomonitoring due to the high abundance of hemoglobin in human blood, its reactivity toward electrophiles, and adducted protein stability for up to 120 days. In the present paper, we compared three methods of analysis of hemoglobin adducts: mass spectrometry of derivatized N-terminal Val adducts, mass spectrometry of N-terminal adducted hemoglobin peptides, and limited proteolysis mass spectrometry . Blood from human donors was incubated with a selection of contact allergens and other electrophiles, after which hemoglobin was isolated and subjected to three analysis methods. We found that the FIRE method was able to detect and reliably quantify N-terminal adducts of acrylamide, acrylic acid, glycidic acid, and 2,3-epoxypropyl phenyl ether (PGE), but it was less efficient for 2-methyleneglutaronitrile (2-MGN) and failed to detect 1-chloro-2,4-dinitrobenzene (DNCB). By contrast, bottom-up proteomics was able to determine the presence of adducts from all six electrophiles at both the N-terminus and reactive hemoglobin side chains. Limited proteolysis mass spectrometry, studied for four contact allergens (three electrophiles and a metal salt), was able to determine the presence of covalent hemoglobin adducts with one of the three electrophiles (DNCB) and coordination complexation with the nickel salt. Together, these approaches represent complementary tools in the study of the hemoglobin adductome.

Contact allergy to medical devices

Abstract Background Medical devices are not subject to any legal obligation to declare ingredients. With an increasing number of available medical devices, increasing reports of contact allergies to these devices result in a more difficult, delayed or lack of diagnosis of the trigger. Methods Elaborate chemical methods, such as gas chromatography–mass spectroscopy, were able to detect novel contact allergens in medical devices. Results Diabetic patients requiring insulin benefit from sophisticated glucose sensor measurement systems and insulin pump systems, but are limited in their choices by the development of contact allergy. Potential contact allergens in medical adhesives, plasters, and wound dressings require extensive diagnostic testing. Contact allergic reactions to cardiac electronic implants are rare. The potential relevance of a contact allergic reaction to endoluminal stents to restenosis of the treated vascular territory is discussed. Contact dermatitis to medical gloves is usually due to the vulcanization accelerators. Mouth–nose protective or FFP2 mask-associated eczema is often irritant, very rarely allergic in origin. Conclusion With continued development of medical devices, new contact allergens are introduced. The declaration of their ingredients is necessary for rapid diagnosis and future prevention.

Orchestration of inflammation in contact allergy by innate immune and cellular stress responses

Abstract Background Inflammation is central to the initiation of immune responses and to the pathogenesis of many diseases such as allergic contact dermatitis (ACD). ACD is an inflammatory skin disease caused by low molecular weight organic chemicals and metal ions. The immune system plays a decisive role. After protein binding, the triggering chemicals act as contact allergens that are recognized by specific T cells. Before this can happen, however, the chemicals must trigger inflammation in the skin, without which the adaptive immune system in particular is not activated. Methods In recent years, the inflammatory mechanisms of contact allergy have been studied at the cellular and molecular level in vivo and in vitro. Results Contact allergens activate the innate immune system and additionally cellular stress responses, which in interaction are responsible for skin inflammation. In this context, inflammation is required for both initial sensitization and elicitation of ACD. Conclusion Skin inflammation in ACD is orchestrated by the interplay of the innate immune system and cellular stress responses.

Allergic Contact Dermatitis to Acrylates: A Study Among Manicurists and Clients

Summary The study aimеd to investigate the association between the professional environment and hypersensitivity reactions to various contact allergens, features of the clinical course, and types of allergic contact dermatitis (ACD) in 34 manicurists and ten service users. The analysis was based on the data on length of professional experience, localisation of rashes, clinical diagnoses and allergens, and the cause of positive reactions in epicutaneous testing. Pathological skin changes most often affected the upper limbs (hands, palms, fingers). As a diagnosis, the frequency of ACD was the highest – 79.4%, followed by that of dyshidrotic eczema (DE) – 17.6%, which also determines the highest percentage of dermatitis on the upper limbs (97%). Of the patients, 47.1% had a history of the disease for up to one year. For manicurists, the results of patch tests with the specialised MH-1000 series showed the highest frequency of positive reactions to 2-Hydroxyethyl methacrylate (2-HEMA) and 2-Hydroxypropyl methacrylate (2-HPMA) – 88.88% each, Ethylene glycol dimethacrylate (EGDMA) – 83.33% and 2-Hydroxyethyl acrylate (2-HEA) – 61.11%. After combining data for manicurists and clients, correlation analysis found a significant effect on the development of ACD to 2-HPMA (p=0.003) and EGDMA (p=0.005), as well as for hand dermatitis to 2-HEMA (p=0.05) and 2-HEA (p=0.044).

Prevalence of allergic contact dermatitis in children with and without atopic dermatitis: A multicenter retrospective case-control study.

As both allergic contact dermatitis and atopic dermatitis (AD) have similar clinical presentations and are characterized by spongiotic dermatitis on skin biopsy, many children with AD are not referred for patch testing and allergic contact dermatitis is underdiagnosed. To provide updated prevalence data of common contact allergens in children with and without AD. This is a retrospective case-control study using the Pediatric Allergic Contact Dermatitis Registry from 2018 to 2022. A total of 912 children were included (615 with AD and 297 without AD). Children with AD were more likely to have a longer history of dermatitis (4.1 vs 1.6years, P<.0001), have seen more providers (2.3 vs 2.1, P=.003), have greater than 1 positive patch test (PPT) result (P=.005), have a greater number of PPT results overall (2.3 vs 1.9, P=.012), and have a more generalized distribution of dermatitis (P=.001). PPT to bacitracin (P=.030), carba mix (P=.025), and cocamidopropyl betaine (P=.0007) were significantly increased in children with AD compared to those without AD. Technical variation between providers and potential for misclassification, selection, and recall biases. Children with AD are significantly more likely to have PPT reactions and should be referred for evaluation of allergic contact dermatitis and obtain patch testing.

Safety evaluation of the food enzyme subtilisin from the non-genetically modified Bacillus licheniformis strain NZYM-CX.

The food enzyme subtilisin (EC 3.4.21.62) is produced with the non-genetically modified Bacillus licheniformis strain NZYM-CX by Novozymes A/S. The production strain met the requirements for the qualified presumption of safety (QPS) approach. The food enzyme is intended to be used in eight food manufacturing processes: processing of cereals and other grains for the production of brewed products; processing of dairy products for the production of modified milk proteins and flavouring preparations; processing of plant- and fungal-derived products for the production of plant-based analogues of milk and milk products, protein hydrolysates and edible oils from algae; processing of meat and fish products for the production of protein hydrolysates; processing of yeast and yeast products. Since residual amounts of total organic solids (TOS) are removed in the production of edible oils from algae, dietary exposure was calculated only for the remaining seven food manufacturing processes. Exposure was estimated to be up to 2.393 mg TOS/kg body weight (bw) per day in European populations. As the production strain qualified for the QPS approach and no issues of concern arose from the production process of the food enzyme, the Panel considered that toxicological studies were unnecessary. A search for the similarity of the amino acid sequence of the food enzyme to known allergens was performed, and a total of 20 matches were found, 17 to respiratory allergens, two to food allergens (found in muskmelon and pomegranate) and one to a contact allergen. The Panel considered that the risk of allergic reactions upon dietary exposure to this food enzyme cannot be excluded, especially in individuals sensitised to muskmelon or pomegranate, but would not exceed the risk of consuming these foods. Based on the data provided, the Panel concluded that this food enzyme does not give rise to safety concerns under the intended conditions of use.

Contact Allergy in Atopic Patients

Summary Atopic dermatitis (AD) is a chronic inflammatory disease based on genetic and immune alterations and is part of the atopic symptom complex, including allergic rhinitis, allergic conjunctivitis, and bronchial asthma. A disturbed barrier function facilitates antigen penetration through the skin, with the subsequent development of allergic contact dermatitis (ACD). The gold standard for diagnosing ACD is epicutaneous (patch) testing, also applied to objectify contact sensitization in AD. This study aimed to determine the frequency of contact allergy (CA) among individuals with atopic history and the allergens that caused ACD in those cases. We studied 453 individuals tested in the period 2009-2022. Of these, a subpopulation of 189 individuals with atopic diathesis was identified. A retrospective analysis was used. Using clinical and allergological methods, we divided the tested patients according to sex, age, professional occupation, and areas of the body affected by dermatitis and identified the most common contact allergens that cause positive reactions and ACD. In conclusion, our results highlight the possibility of developing ACD in people with atopic diathesis. As far as we know, our study is the first one in Bulgaria to examine the frequency of contact sensitization in AD patients.

Systemic allergic contact dermatitis to palladium, platinum, and titanium: mechanisms, clinical manifestations, prevalence, and therapeutic approaches.

Contact dermatitis (CD) is an inflammatory skin disease of eczema that is elicited by chemicals or metal ions that have toxic effects without eliciting a T-cell response (contact elicitation) or by small reactive chemicals that modify proteins and induce innate and adaptive immune responses (contact allergens). The clinical condition is characterized by localized skin rash, pruritus, redness, swelling, and lesions, which are mainly detected by patch tests and lymphocyte stimulation. Heavy metals such as palladium (Pd), platinum (Pt), and titanium (Ti) are ubiquitous in our environment. These heavy metals have shown CD effects as allergic agents. Immunological responses result from the interaction of cytokines and T cells. Occupational metal CD accounts for most cases of work-related cutaneous disorders. In this systematic review, the allergic effects of heavy metals, including Pd, Pt, and Ti, and the mechanisms, clinical manifestations, prevalence, and therapeutic approaches are discussed in detail. Furthermore, the therapeutic approaches introduced to treat CD, including corticosteroids, topical calcineurin inhibitors, systemic immunosuppressive agents, phototherapy, and antihistamines, can be effective in the treatment of these diseases in the future. Ultimately, the insights identified could lead to improved therapeutic and diagnostic pathways.

Assessment of Contact Allergens in "Hypoallergenic" Athletic Shoes by Mass Spectrometry.

Background: Identification of athletic shoes for patients with contact allergy is difficult. Company reports of allergen content are often incorrect. Objectives: To determine whether chemical analysis of 4 athletic shoes, previously reported to be free of the most common contact allergens, contain quantifiable allergen levels. Methods: Samples from the uppers and insoles of 4 shoes believed to be free of common allergens were assessed by mass spectrometry. A total of 4 rubber accelerators and 2 adhesives were directly quantified and additional 7 rubber accelerators were assessed using semiquantitative measures. Results: Aside from carbamates (assayed as 59 ppm zinc in insoles) in SeaVee's Sixty-Six sneakers, para-tertiarybutylphenol formaldehyde resin (PTBFR) (assayed as 7.6 ppm paratertiary butylphenol or 4-tertiary butylphenol [4TBP] in uppers) in Allbirds Tree Runners and rosin (assayed as 628 ppm sodium abietate in uppers) and carbamates (24 ppm zinc in uppers) in Saucony Jazz sneakers, these shoes had low levels of all allergens assayed in this study. Tom's Carlo sneakers contained rosin (127 ppm sodium abietate in insoles), PTBFR (6.5 ppm 4TBP in uppers), and carbamates (112 ppm sodium abietate in insoles) but had low levels of all other assayed allergens. Conclusions: Although identifying allergen-free shoes is challenging, the results of this analysis will help patch testing physicians recommend athletic shoes to patients with specific allergies.

Need for new strategies to improve the recall and avoidance rates of contact allergens: A retrospective cohort study from Turkey.

Previous studies reported a low-to-moderate benefit from patch testing regarding allergen recall and avoidance. To determine the allergen recall and avoidance rates of patients with allergic contact dermatitis (ACD) in Turkey. This was a retrospective cohort study based on a phone questionnaire of 465 patients diagnosed with ACD from major allergen groups, that is, metals, preservatives, rubber, fragrances (ubiquitous allergens) and hair dye/black henna, topical drug and resins (nonubiquitous allergens), at our tertiary referral centre between 1996 and 2018. Among 176 responders, allergen groups were remembered better (53.4%) than the individual allergens (36.9%). Age <40 years and keeping the allergy pass had a significantly positive impact on the recall rate of methylchloroisothiazolinone/methylisothiazolinone and nickel, particularly non-occupational nickel allergy from metal jewellery in females, respectively. Exacerbations of ACD (56.3%) were mainly due to reexposures to ubiquitous allergens. 42.9% of patients with occupational ACD changed or quit their job, most of them being construction workers and hairdressers, showing a high share (83.3%) of benefit. The overall rates of allergen recall and avoidance were moderate. New strategies are needed to improve the recall and avoidance rates of contact allergens, such as increased use of allergy pass, smartphone applications and legal precautions.

Characteristics of Litigations Involving Contact Dermatitis: An Exploratory Analysis.

Background: Contact dermatitis (CD) is one of the most common skin disorders, occurring in >20% of patients worldwide. Estimated cost burden for CD in the United States approaches $1 billion annually. Objective: To describe characteristics of litigation among patients with CD. Methods: Westlaw legal database for U.S. lawsuits was queried for lawsuits between the years 1983 and 2021 containing the keywords "dermatitis or eczema." Each lawsuit associated with CD was analyzed by plaintiff demographics, verdict, prosecution reason, payouts, and allergen implicated. Results: Of 98 cases, 61 met the inclusion criteria. Verdicts issued favored plaintiffs (42.6%) more than defendants (32.8%) with the remaining cases decided through settlements. If payout occurred, the mean was $246,310 (standard deviation [SD] = $798,536), the median was $20,000 (Q1 = $8,500, Q3 = $88,725, interquartile range = $80,225). The top reason for litigation was toxic exposure (n = 38, 62.2%), and common contact allergens associated with lawsuits were latex (n = 4, 20%), surgical tape (n = 4, 20%), and beauty products (n = 4, 20%). Conclusion: Common allergens associated with lawsuits include latex, surgical tape, and beauty products. Most CD cases adjudicated in the United States since 1983 are associated with toxic exposures.

2-Hydroxyethyl methacrylate (HEMA): A clinical review of contact allergy and allergic contact dermatitis-Part 1. Introduction, epidemiology, case series and case reports.

2-Hydroxyethyl methacrylate (HEMA) has been increasingly recognised as a contact allergen and was added to the European baseline series in 2019. In this article (2 parts), the results of an extensive literature review of the clinical aspects of contact allergy/allergic contact dermatitis to HEMA are presented. In part 1, the epidemiology of HEMA contact allergy is discussed and detailed information on published case series and case reports presented. HEMA is an important cause of contact allergy/allergic contact dermatitis in North America and Europe with recent prevalences of >3% in the USA + Canada and 1.5%-3.7% in Europe. Currently, most cases are caused by nail cosmetics, both in consumers and professional nail stylists. In our literature review, we have found 24 studies presenting case series of patients with allergic contact dermatitis attributed to HEMA and 168 case reports. However, the presence of HEMA in the products causing ACD was established in only a minority. Part 2 will discuss cross- and co-sensitisation, and other skin reactions to HEMA, will assess whether HEMA is the most frequent (meth)acrylate allergen and how sensitive HEMA as a screening agent is, investigate the presence of HEMA in commercial products and provide practical information on patch testing procedures.

Nickel Sensitivity in Patients With Irritable Bowel Syndrome.

Nickel (Ni) is the most common contact allergen in the population. We aimed to investigate whether there is a relationship between Ni sensitivity and irritable bowel syndrome (IBS) in our study. This study was conducted in 50 patients with IBS who were followed up between March 2018 and July 2018, and 40 healthy people as a control group in a single center with a dermatology department. European standard contact allergen series Ni preparate and corticosteroid pomace were applied to the back region of the study subjects. The evaluation was performed at 48, 72, and 96 hours according to the scheme proposed by the International Contact Dermatitis Research Group (ICDRG). Those who reacted at 72 hours were considered to have Ni allergy. Results: The female/male ratio was 24/26 and 18/22 in the patient and control groups, respectively. The mean ages of the patient and control groups were 42.82 (±10.65) and 39.77 (±11.21) years, respectively. Ni sensitivity was present in 40% of the patient group and 17.5% of the control group (p=0.03). We believe that the presence of Ni sensitivity is important in the pathogenesis of IBS disease. In our study, Ni sensitivity was found to be quite high in IBS patients compared to the normal population.

CD100 boosts the inflammatory response in the challenge phase of allergic contact dermatitis in mice.

Allergic contact dermatitis (ACD) is an inflammatory disease with a complex pathophysiology in which epidermal-resident memory CD8+ T (TRM ) cells play a key role. The mechanisms involved in the activation of CD8+ TRM cells during allergic flare-up responses are not understood. The expression of CD100 and its ligand Plexin B2 on CD8+ TRM cells and keratinocytes before and after allergen exposure was determined by flow cytometry and RT-qPCR. The role of CD100 in the inflammatory response during the challenge phase of ACD was determined in a model of ACD in CD100 knockout and wild-type mice. We show that CD8+ TRM cells express CD100 during homeostatic conditions and up-regulate it following re-exposure of allergen-experienced skin to the experimental contact allergen 1-fluoro-2,4-dinitrobenzene (DNFB). Furthermore, Plexin B2 is up-regulated on keratinocytes following exposure to some contact allergens. We show that loss of CD100 results in a reduced inflammatory response to DNFB with impaired production of IFNγ, IL-17A, CXCL1, CXCL2, CXCL5, and IL-1β and decreased recruitment of neutrophils to the epidermis. Our study demonstrates that CD100 is expressed on CD8+ TRM cells and is required for full activation of CD8+ TRM cells and the flare-up response of ACD.

IgE-Mediated and Non-IgE-Mediated Fish Allergy in Pediatric Age: A Holistic Approach-A Consensus by Diagnostic Commission of the Italian Society of Pediatric Allergy and Immunology.

Fish is one of the "big nine" foods triggering allergic reactions. For this reason, fish allergens must be accurately specified on food labels. Fish allergy affects less than 1% of the world population, but a higher prevalence is observed in pediatric cohorts, up to 7%. Parvalbumin is the main fish allergen found in the muscles. In childhood, sensitization to fish allergens occurs most frequently through the ingestion of fish, rarely transcutaneously or by inhalation. Fish allergy symptoms usually appear within two hours of the allergen contact. The diagnosis begins with the collection of the history. If it is suggestive of fish allergy, prick tests or the measurement of serum-specific IgE should be performed to confirm the suspicion. The oral food challenge is the gold standard for the diagnosis. It is not recommended in case of a severe allergic reaction. It is important to make a differential diagnosis with anisakiasis or scombroid poisoning, which have overlapping clinical features but differ in pathogenesis. Traditionally, managing fish allergy involves avoiding the triggering species (sometimes all bony fish species) and requires an action plan for accidental exposures. The present review will analyze IgE- and non-IgE-mediated fish allergy in children from epidemiology, pathogenesis to clinical features. Moreover, clinical management will be addressed with a particular focus on potential nutritional deficiencies.

Analysis of Contact Allergens in Polyvinyl Chloride Examination Gloves in the United States.

Background: Polyvinyl chloride (PVC) gloves are recommended as a safe alternative for patients with rubber accelerator allergy. However, allergic contact dermatitis to other chemicals in PVC gloves has been reported. Objective: To analyze single-use PVC medical examination gloves in the United States for the presence of potential contact allergens. Methods: Using liquid chromatography-mass spectrometry, 20 unique PVC gloves were analyzed in triplicate for 6 chemicals: benzisothiazolinone, bisphenol A, mono(2-ethylhexyl) maleate, tricresyl phosphate, triphenyl phosphate, and triphenyl phosphite. Results: All 20 PVC gloves contained detectable quantities of benzisothiazolinone (range, 0.001-1.48 parts per million [ppm]), bisphenol A (0.01-0.11 ppm), triphenyl phosphate (0.01-2.11 ppm), and triphenyl phosphite (0.001-0.22 ppm). Eighteen (90%) gloves contained mono(2-ethylhexyl) maleate (0.001-0.14 ppm) and 3 (15%) contained tricresyl phosphate (0.001-0.002 ppm). Conclusions: Known allergens were present in all 20 PVC gloves. However, the detected levels were mostly low and their relationship with sensitization and elicitation thresholds requires further study.