Allergic Contact Dermatitis Research Articles

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

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 BIT has superseded MI in causing contact allergy, despite not being allowed for use in cosmetic products.

Adverse outcome pathway-based approach to reveal the mechanisms of skin sensitization and long-term aging effects of chlorothalonil

Chlorothalonil (CHT) is a widely used antifungal agent and is reported to be a sensitizer that can cause allergic contact dermatitis (ACD). ACD initiation is associated with various innate immune cell contributions and is usually accompanied by persistent inflammation, which is a potential contributing factor to skin damage. However, detailed information on the mechanisms by which CHT induces skin sensitization and damage is still insufficient. This study focused on investigating the possible sensitization process and mechanism of CHT and the adverse effects of repeated CHT exposure. CHT activates dendritic cells and promotes the proliferation of lymph cells in the skin sensitization phase, causing severe inflammation. Keratinocytes activate the NLRP3 inflammasome pathway to cause inflammation during CHT treatment, and macrophages also secrete inflammatory cytokines. In addition, CHT-induced inflammation triggered skin wrinkles, decreased epidermal thickness and decreased collagen. Cell experiments also showed that repeated exposure to CHT led to cell proliferation inhibition and senescence, and CHT-induced autophagy dysfunction was not only the reason for inflammation but also for senescence. This study defined the possible process through which CHT is involved in the skin sensitization phase and elucidated the mechanism of CHT-induced inflammation in innate immune responses. We also determined that repeated CHT exposure caused persistent inflammation, ultimately leading to skin aging.

Daily Supplementation with Bifidobacterium longum KACC91563 Alleviates Allergic Contact Dermatitis in an Animal Model.

Allergic contact dermatitis (ACD) is the most common chronic inflammatory skin disease (or immune-mediated disease), causing disruption to our psychological condition and life quality. In this study, the therapeutic properties of probiotic Bifidobacterium longum (B. longum) was investigated by using an ACD-induced animal model. For ACD induction, BALB/c mice ear and dorsal skin were sensitized with 240 µL of 1% (w/v) 2,4-dinitrochlorobenzene (DNCB) twice (3-day intervals). After a week of the first induction, the mice were re-sensitized by painting on their dorsal skin and ear with 0.4% (w/v) DNCB for a further three times (once per week). Before the ACD induction of 2 weeks and throughout the trial period, the BALB/c mice were supplemented daily with 1 mL of 1.0 × 109 CFU or 5.0 × 109 CFU B. longum using an intragastric gavage method. The ACD-induced mice without B. longum supplementation were used as a control. Results show that B. longum supplementation significantly alleviated ACD symptoms (e.g., ear swelling, epidermal damage) and immune response (e.g., reduced immune cell recruitment, serum IgE level, and cytokine production). The therapeutic efficiency of B. longum increased as the supplementation dose increased. Thus, daily supplementation with 5.0 × 109 CFU probiotic B. longum could be an effective method for the prevention and treatment of ACD.

Bioactivation of cinnamic alcohol in a reconstructed human epidermis model and evaluation of sensitizing potency of the identified metabolites.

Cinnamic alcohol is a natural compound, widely used in fragrances, which can cause allergic contact dermatitis. Cinnamic alcohol lacks intrinsic reactivity and autoxidation or metabolic activation is necessary for it to act as a sensitizer. Bioactivation of cinnamic alcohol was explored using human liver microsomes, human liver S9 and SkinEthic™ Reconstructed Human Epidermis. A targeted multiple reaction monitoring mass spectrometry method was employed to study and quantify cinnamic alcohol along with eight potential phase I or phase II metabolites. The reconstructed human epidermis model, treated with cinnamic alcohol, was also analyzed with a non-targeted high-resolution mass spectrometry method to identify metabolites not included in the targeted method. Two metabolites identified with the targeted method, namely, pOH-cinnamic alcohol and pOH-cinnamic aldehyde, have not previously been identified in a metabolic in vitro system. Their reactivity toward biologically relevant nucleophiles was investigated and compared to their sensitizing potency in vivo in the murine local lymph node assay (LLNA). According to the LLNA, the pOH-cinnamic alcohol is non-sensitizing and pOH-cinnamic aldehyde is a moderate sensitizer. This makes pOH-cinnamic aldehyde less sensitizing than cinnamic aldehyde, which has been found to be a strong sensitizer in the LLNA. This difference in sensitizing potency was supported by the reactivity experiments. Cinnamic sulfate, previously proposed as a potential reactive metabolite of cinnamic alcohol, was not detected in any of the incubations. In addition, experiments examining the reactivity of cinnamic sulfate toward a model peptide revealed no evidence of adduct formation. The only additional metabolite that could be identified with the non-targeted method was a dioxolan derivative. Whether or not this metabolite, or one of its precursors, could contribute to the sensitizing potency of cinnamic alcohol would need further investigation. Cinnamic alcohol is one of the most common fragrance allergens and as it is more effective to patch test with the actual sensitizer than with the prohapten itself, it is important to identify metabolites with sensitizing potency. Further, improved knowledge of metabolic transformations occurring in the skin can improve prediction models for safety assessment of skin products.

Localized allergic contact dermatitis on skin flap: Unveiling immune privilege in non-immune privileged sites

Localized allergic contact dermatitis on skin flap: Unveiling immune privilege in non-immune privileged sites

Nine years of patch testing with isocyanates in a clinic of occupational dermatology.

Isocyanates are used as starting materials of polyurethane (PU) products. They are relatively important occupational skin sensitizers. To analyse results of a large isocyanate patch test series of 19 isocyanate test substances and 4,4'-diaminodiphenylmethane (MDA), a marker of 4,4'-diphenylmethane diisocyanate (MDI) hypersensitivity. Test files were screened for positive reactions in the isocyanate series. Patients with positive reactions were analysed for occupation, exposure and diagnosis. In 2010-2019, 53 patients had positive reactions in the series (16% of 338 patients tested). MDA, the well-established screening substance for MDI allergy, was positive in 30 patients, an in-house monomeric MDI test substance in 23 patients and 3 different polymeric MDI test substances in 19-21 patients. We diagnosed 16 cases of occupational allergic contact dermatitis (OACD) from MDI including 3 pipe reliners. Hexamethylene-1,6-diisocyanate (HDI) oligomers in paint hardeners caused 5 cases of OACD, more cases than 2,4-toluene diisocyanate (TDI; n = 3) and isophorone diisocyanate (IPDI; n = 1) put together. In contrast to previous studies, polymeric MDI test substances were not superior to a monomeric MDI. Pipe reliners may get sensitised not only by epoxy products and acrylates but also by MDI in hardeners of PU pipe coatings. HDI oligomers were the second most important causes of OACD after MDI.

Evaluation of atopic diseases in patients with allergic contact dermatitis.

Background: There is controversy on whether allergic contact dermatitis (ACD) is associated with atopy. Research on eczema and the risk of ACD is mixed, and there is sparse literature on other atopic conditions. Objective: Our study examined the prevalence of several atopic conditions, including allergic rhinitis, eczema, asthma, and food allergies in patients with ACD, and compared these to patients without ACD. Methods: We retrospectively reviewed adult patients ages ≥ 18 years with ACD (n = 162) with positive patch testing results and documented any history of atopy, including childhood eczema, asthma, allergic rhinitis, and immunoglobulin E-mediated food allergy. The prevalence of atopic conditions was compared between our ACD cohort and controls without ACD (n = 163) from our electronic medical records system (age and gender matched). Results: Among our patients with ACD, 53 (33%) had allergic rhinitis, 22 (14%) had childhood eczema, 32 (20%) had asthma, and 8 (5%) had food allergies. We observed that the odds of atopy overall (n = 76) in the ACD group compared with the control group were increased (odds ratio [OR] 1.88; p = 0.007). Allergic rhinitis was the highest risk factor (n = 53) with an OR of 12.64 (p < 0.001). Childhood eczema (n = 22) was also increased in the ACD group (OR 2.4; p = 0.026). The odds of asthma and food allergy in the ACD group were also increased; however, the difference was not statistically significant from the control group (OR 1.76 [p = 0.071] and OR 2.76 [p = 0.139], respectively). Conclusion: Patients with ACD had increased odds of eczema, allergic rhinitis, and atopic conditions overall. Asthma and food allergies were not found to have a statistically significant correlation. Larger studies that delve into atopic risk factors in ACD would be important to confirm these findings.

Cost-effectiveness of patch testing allergens within the same group: A computational approach to optimize formaldehyde-related allergen selection

BackgroundPatch testing to multiple cross reactive allergens for allergic contact dermatitis (ACD) may not be necessary due to copositivity. ObjectiveWe evaluated the formaldehyde group allergens to determine the optimal, most cost-effective allergens to test. MethodsA retrospective analysis of Mayo Clinic (1997-2022) examined the well-established copositive formaldehyde group: Formaldehyde, Quaternium 15, Hexahydro-1,3,5-tris(2-hydroxyethyl)triazine, Diazolidinyl urea, Imidazolidinyl urea, Toluenesulphonamide formaldehyde resin, DMDM hydantoin, and Ethyleneurea melamine formaldehyde mix. Patch Optimization Platform (POP) identified which single formaldehyde-related allergen optimally captures patients with clinically relevant ACD. Next, POP determined the optimal additional 1, 2, 3, etc. allergens. Cost per patch test was $5.19 (Medicare 2022). Results9832 patients were tested to all listed allergens, with 830 having positive patch tests. POP determined that Quaternium 15 alone captures 53% of patients with ACD to the formaldehyde group; adding the optimal second allergen (Formaldehyde 1%) captures 78%; the optimal five top allergens capture over 94% of patients. The incremental cost-per-additional-diagnosis increased up to 44-fold as the number of allergens tested increased. LimitationsData is from a single institution, and the cost-per-test was fixed to Medicare Part B in 2022. ConclusionsFor diagnosing ACD, we recommend considering an optimized allergen selection algorithm.

Brazilian Peppertree: Watch Out for This Lesser-Known Relative of Poison Ivy.

Brazilian peppertree (Schinus terebinthifolia), a member of the Anacardiaceae family, has invaded territory throughout the world, including the southeastern and western United States. Similar to fellow family members poison ivy and poison oak, Brazilian peppertree causes allergic contact dermatitis (ACD) in susceptible individuals. As this pest increases its range, dermatologists living in endemic areas should familiarize themselves with Brazilian peppertree, its effects on the skin, and how to treat any associated ACD.

Supplemental Patch Testing Identifies Allergens Missed by Standard Screening Series.

Background: Supplemental patch testing is an adjunct to standard patch test screening series. Objective: To determine the demographics, characteristics, frequency, relevance, and interpretation of patch test reactions for supplemental patch testing. Methods: Retrospective study of patients tested 2017-2020 with North American Contact Dermatitis Group (NACDG) and supplemental screening series (Supplemental Series A [SSA], Supplemental Series B [SSB]). Demographics, characteristics, reaction strengths, relevance, and final interpretation were recorded. Results: Cohort included 791 patients; 73.5% female, 68.6% age >40 years. 74.1% were White, 15.2% Black, 5.7% Asian, and 1.5% Hispanic. The most common Dermatitis sites were scattered/generalized (27.2%), face (24.0%), and hands (23.5%). For 2017-2018 and 2019-2020, respectively, 82% (318/388) and 78.4% (316/403) had ≥1 "allergic" reaction. In addition, 13.5% (52/385) and 11.7% (47/403) had SSA reactions, and 38.1% (115/302) and 31.5% (101/321) had SSB reactions. In the 87 (2017-2018) and 99 (2019-2020) patients with negative NACDG testing, 17 (19.5%) and 12 (12.1%) had supplemental reactions. Of the 34 supplemental allergens with reaction frequency ≥1%, 58.8% (20/34) are not part of the American Contact Dermatitis Society 90 (2020) or NACDG 2021-2022 screening series. The highest frequency allergens from this group were dodecyl and octyl gallate, cinnamic alcohol, phenyl salicylate, hexahydro-1,3,5-tris-(2-hydroxyethyl) triazine, and abitol. Conclusions: Supplemental patch testing identifies additional relevant allergens in patients with suspected allergic contact Dermatitis.

Stasis Dermatitis: The Burden of Disease, Diagnosis, and Treatment.

Stasis dermatitis (SD), an inflammatory dermatosis occurring on the lower extremities, is a cutaneous manifestation of chronic venous insufficiency (CVI). SD is associated with a significant burden of disease. Symptoms such as pain, swelling, and itching can be debilitating for patients, leading to poor sleep, loss of mobility, and the inability to perform daily activities, and can interfere with work and leisure activities. Moreover, SD is a progressive disease with serious secondary complications such as ulcerations, which increase the patients' morbidity, reduce their quality of life, and increase health care burden. Challenges in diagnosing patients may have both short- and long-term sequalae for the patients due to unnecessary treatment and management. In addition, misdiagnosis may result in hospitalizations, placing additional burden on health care professionals in terms of time and financial burden on the health care system. Compression therapy and leg elevation represent the mainstay of treatment for CVI; however, it is also difficult to self-manage, which places a substantial burden on patients and caregivers. Moreover, compression therapy may cause discomfort and exacerbate itching. Subsequent nonadherence may result in disease progression that places additional burden on the physicians who manage these patients and the health care system in terms of resources required and costs incurred. A large proportion of patients with SD develop allergic contact dermatitis because of innate immune signals and altered skin barrier predisposing to sensitization to topical prescriptions, over-the-counter medications, and compression devices used to treat SD. Other than topical corticosteroids, there are no approved pharmacological options to treat inflammation in SD.

Agapanthus allergic contact dermatitis: A case report

Background: Agapanthus (Lily of the Nile) is a genus in the flowering plant family Amaryllidaceae. Contact dermatitis caused by flowering plants is common, but there are no reports of contact dermatitis caused by this plant, Agapanthus. Case Illustration: An 82-year-old Japanese man had cultivated Agapanthus in his home garden. After breaking the stem of the leaf while wearing shorts, he noticed erythematous rashes on the thighs. The patch test of the leaf stem sap “as is” showed mildly positive, with erythematous papules. Discussion: The patch test confirmed the allergic contact dermatitis of Agapanthus with leaf stem sap. There are many well-known flowering plants, like lilies, daisies, jasmine, orchids so on, that can cause contact dermatitis. To date, many people fold Agapanthus flowers and decorate them at home, so far, this plant should also be added to the causative plant for contact dermatitis. Conclusion: To the best of our knowledge, there are no reports of contact dermatitis caused by this plant. Agapanthus contact dermatitis will need to be brought to people’s attention.

Treatment of Allergies to Fur Animals.

Allergy to fur animals is becoming an increasingly common clinical problem in everyday medical practice. Depending on the route of exposure to the allergen, patients present with many, often non-specific symptoms. The most common illnesses among people with allergies to the above-mentioned allergens are as follows: allergic rhinitis, allergic conjunctivitis, atopic bronchial asthma, food allergy, allergic contact dermatitis, and sometimes anaphylactic shock. In recent years, there has been a change in the holistic approach to the treatment of allergy patients. The method of treatment should be tailored to a specific patient, taking into account his or her predispositions, economic possibilities, and therapeutic goals. The article describes the main methods of treating allergies, focusing primarily on allergies to fur animals. Allergy treatment always requires great care, and qualification for specific types of therapy should be preceded by a thorough and accurate diagnosis.

CD05 Consort allergic contact dermatitis to occupational acrylates

CD05 Consort allergic contact dermatitis to occupational acrylates

CD13 Effect of ciclosporin on serum inflammatory cytokines in patients with allergic contact dermatitis due to the weed Parthenium: a preliminary study

CD13 Effect of ciclosporin on serum inflammatory cytokines in patients with allergic contact dermatitis due to the weed <i>Parthenium:</i> a preliminary study

CD03 Watch out! Allergic contact dermatitis to acrylates in a smart watch

CD03 Watch out! Allergic contact dermatitis to acrylates in a smart watch

CD07 Let the games begin! Paediatric facial allergic contact dermatitis secondary to a gaming virtual reality headset

CD07 Let the games begin! Paediatric facial allergic contact dermatitis secondary to a gaming virtual reality headset

Allergic Contact Dermatitis to Lidocaine and Sodium Metabisulfite.

Allergic Contact Dermatitis to Lidocaine and Sodium Metabisulfite.

Characterization of Pediatric Patch Testing: A Retrospective Review, 2020-2023.

Background: Recent evidence shows similar rates of allergic contact dermatitis (ACD) among children and adults despite children accounting for less than 10% of patch testing subjects. With a need for in-depth analyses of pediatric ACD, we herein characterize a pediatric cohort at a large North American patch testing center. Methods: A retrospective chart review was conducted for 135 patients ages 1-17 years who underwent patch testing from July 2020 from August 2023. Data were stratified by age 1-5, 6-11, and 12-17 years. Significance-Prevalence Index Numbers (SPIN) were calculated. Results: A total of 86% were sensitized, 40% had a relevant reaction, and positivity rates were equal between males and females. Top allergens by SPIN differed with age, but overall were linalool hydroperoxides (SPIN = 11.01), propylene glycol (10.30), limonene hydroperoxides (10.27), fragrance mix I (5.62), and lanolin (4.90). In total, 14% of the top allergens were not represented on the North American Contact Dermatitis Group standard series. Of those tested to personal products, 45% had positive reactions and 72% of which were relevant. Conclusions: Emulsifiers and fragrances were the most relevant allergen categories, with the impact of emulsifiers not previously reported. ACD may affect males and females equally in this population. Supplemental allergens and personal products tested "as-is" contribute to conclusive pediatric patch testing.

Sucrose Solution Ingestion Exacerbates Dinitrofluorobenzene-Induced Allergic Contact Dermatitis in Rats.

Allergic dermatitis is a skin disease with growing prevalence worldwide that has been associated with diets high in fats and sugars. Regular consumption of sucrose-containing beverages may increase the risk for several health problems, including allergic diseases and particularly asthma, but the association between sucrose consumption and allergic dermatitis is understudied. We investigated the effects of sucrose solution intake on allergic contact dermatitis in rats and found early exacerbation of 2,4-dinitrofluorobenzene (DNFB)-induced disease symptoms and altered composition of the gut microbiota after 14 d of intake. The levels of short-chain fatty acids-produced by fermentation by the intestinal microbiota-were not affected in the cecal contents and feces but decreased in the blood; this effect was especially notable for acetate. To restore blood acetate concentrations, triacetin was mixed with a 10% sucrose solution and fed to the rat model. This strategy prevented the early exacerbation of DNFB-induced symptoms. The decreased absorption of short-chain fatty acids from the intestinal lumen was not linked to the decreased expression of short-chain fatty acid transporters in the small intestine; instead, the mechanism involves a reduction in the sodium concentration in the intestinal lumen due to increased expression of sodium-glucose transporter 1 (SGLT1).