Acrylate Patch Testing for Allergic Contact Dermatitis Over 28 Years: Hierarchical Clustering for Subgroup Analysis and Computational Optimization for Patch Test Selection
Background: Acrylate allergy is rising, with many patients showing patch test positivity to multiple acrylates. Understanding acrylate sensitivity can guide avoidance and optimize screening. Objectives: To quantify acrylate patch test positivity, define subgroups using hierarchical clustering, and algorithmically optimize acrylate patch testing series. Methods: We conducted a retrospective review of 27 acrylate allergens patch tested at 3 Mayo Clinic sites (Arizona, Florida, Minnesota) from 1997 to 2024; 14 had ≥1% positivity. Pairwise copositivity rates were background-corrected and analyzed using hierarchical clustering, followed by computational optimization for patch test screening. Results: Among 17,148 patients, 90,818 tests yielded 1,557 positives (1.71%). Most frequent positive reactions were 2-hydroxyethyl acrylate 0.1% (HEA, 5.4%), 2-hydroxypropyl methacrylate 2% (HPMA, 5.0%), and 2-hydroxyethyl methacrylate 2% (HEMA, 4.6%). Clustering revealed 2 general subgroups, with ethyl cyanoacrylate 10% (ECA) showing minimal copositivity to other acrylates. Optimization analysis for screening showed that one allergen (HEMA) captured 49.4% of sensitized patients; 2 (HEMA + ECA) captured 72.2%. Four allergens, including HEMA, ECA, HEA, and diethylene glycol diacrylate 0.1% (DEGDA), captured >90%, and a 7-allergen series captured 100%, with no higher yield from additional acrylates in standard screening. Conclusions: Acrylate allergy is heterogeneous, comprising 2 subgroups, with cyanoacrylates co-reacting separately. Algorithm-guided series refinement improves diagnostic efficiency by prioritizing high-yield allergens for screening while minimizing unnecessary testing.
Evaluating Copositivity Patterns in Fragrance/Botanical Patch Testing through Hierarchical Clustering and Network Analysis
Abstract: Background: Fragrances/botanicals are ubiquitous allergens. Patients allergic to one fragrance/botanical are frequently sensitive to other fragrances/botanicals and are typically counseled to avoid all fragrances/botanicals. However, broad avoidance of all fragrances/botanicals may not be clinically necessary. Objectives: We examined copositivity patterns in fragrance/botanical patch testing. Methods: The Mayo Clinic patch test database was queried for pairwise copositivity rates for fragrances/botanicals between 1997 and 2022, representing a total of 43 allergens. Data analyzed included 4706 positive reactions out of 252,485 total patches applied to 15,864 patients. After background correction for general positivity, copositivity rates were organized through unsupervised hierarchical clustering to determine copositivity subgroups and then evaluated through network analysis. Results: After background correction, clustering revealed distinct copositivity subgroups: Fragrance Mix I– Myroxylon pereirae –limonene hydroperoxides–linalool hydroperoxides; Compositae Mix–sesquiterpene lactone–parthenolide; Fragrance Mix II–Lyral; lichen acid mix–treemoss extract; menthol– Mentha piperita ; narcissus–dandelion; and Santalum album –trans-anethole–tea tree–lemongrass–clove–turpentine– Rosa damascena – Lavandula – Geranium – Cananga odorata –neroli–bergamot. In addition, there were further isolated intergroup copositivity reactions seen in network analysis. Conclusions: Background correction followed by hierarchical clustering demonstrated the fragrance/botanical group can be divided into multiple copositivity subgroups. Combined with network analysis, patients with a positive patch test to one fragrance/botanical allergen may be preferentially guided to use specific other fragrances/botanicals.
Trends in Patch Test Results With the Mayo Clinic Extended Standard Series: A 14-Year Retrospective Review (2010–2023)
Abstract: Background: Extended patch testing beyond the standard series is commonly performed in patients with allergic contact dermatitis. This broader testing allows for more precise and complete allergen identification, ultimately leading to improved clinical outcomes. Objective: To report the Mayo Clinic Contact Dermatitis Group (MCCDG) patch testing results using a custom extended series from 2010 to 2023. Methods: A retrospective review of patch testing results using the MCCDG extended standard series at the Mayo Clinic was conducted. Data from 2010 to 2023 were analyzed. Results: Patch testing with the extended standard series was performed in 3,767 unique patients, with a total of 3834 extended standard patch tests administered (81.8% in women, 18.2% in men). The top 5 allergens eliciting positive reactions were gold (I) sodium thiosulfate (10.4%), benzisothiazolinone (10.4%), carmine (9.4%), thimerosal (9.3%), and hydroperoxides of linalool (8.8%). Conclusions: The extended standard series expands the diagnostic scope for patients in whom the standard series incompletely identifies relevant allergens. Preservatives and fragrances remain among the most common sensitizers, emphasizing the need for ongoing allergen surveillance, periodic review, and updates to patch test series to enhance diagnostic accuracy and patient care.
Patch Testing in Solid Organ Transplant Recipients: Experience from a Tertiary Medical Center over 13 Years (2010–2022)
Abstract: Background: It is generally recommended that patients not be on immunosuppressive medications for patch testing, as these medications may suppress delayed-type hypersensitivity and lead to false negative results. There is a paucity of literature describing organ transplant recipients who underwent patch testing. Objective: The aim of this study is to examine patch testing results in solid organ transplant recipients over a 13-year period at our institution. Methods: We performed a retrospective analysis of patch test data from adult transplant recipients at our institution. Transplant patients who underwent patch testing were identified from a clinical patch test database, and a chart review was conducted. Results: Eighteen patients were included in the study. Patients had received kidney, liver, or heart transplants. Seven patients (38.9%) had at least one positive reaction. The highest reaction rates were seen with methylisothiazolinone (12.5%), methyldibromo glutaronitrile (12.5%), and benzalkonium chloride (10.0%). Limitations included small sample size, data from a tertiary referral center, and retrospective analysis. Conclusions: Liver and kidney transplant recipients displayed allergic reactions during patch testing. Patients may benefit from patch testing even if receiving immunosuppressive therapy, but some reactions may be falsely negative because of immunosuppression.
Pediatric Patch Testing at Mayo Clinic between 2016 and 2020
Abstract: Background: Allergic contact Dermatitis (ACD) is a common condition within the pediatric population. Patch testing is an important way to identify relevant allergens. Objective: To provide an update of the common contact allergens seen in children based on patch testing data at our institution from 2016 to 2020. Methods: We performed a retrospective analysis of patch test data from children aged 1–18 years from 2016 to 2020 at Mayo Clinic. Reaction rates were compared to the rates reported by the Pediatric Contact Dermatitis Registry (PCDR). Results: One hundred ninety-two children aged 1–18 were patch tested to various allergens. A total of 15,457 allergens were tested, with 291 positive tests. The top 5 allergens with highest positive reaction rates were hydroperoxides of linalool, hydroperoxides of limonene, methylisothiazolinone, nickel, and cobalt. Seven of the top 38 allergens with the highest reaction rates are not currently included in the Mayo Clinic Pediatric Patch Test Series, and 11 are not currently included in the Pediatric Baseline Series (as developed by the Pediatric Contact Dermatitis Workgroup). Conclusions: Patch testing is a useful tool to diagnose children with ACD. With new products and exposures, there is an opportunity to expand current pediatric patch testing series.
Results of Patch Testing to Botanicals: Review of the Mayo Clinic Experience over 2 Decades (1997–2017)
Abstract: Background: Botanicals are increasingly incorporated into skincare products. Although allergic contact dermatitis due to botanicals is recognized, data describing the prevalence of positive patch tests to botanicals are sparse. Objective: To report the Mayo Clinic experience of patch testing to selected botanical products in the standard, extended standard, fragrance, and plant series. Methods: IRB-approved retrospective study of the Mayo Clinic experience with patch testing to botanicals from 1997 to 2017. Results: In total, 12,169 people were patch tested to botanicals in the standard, extended standard, fragrance, and plant series; 4032 were men and 8137 were women. The mean age of the population tested was 54 (standard deviation 17.7) years. Almost 11% (1320/12,169) of the patch-tested population exhibited positive reactions to at least 1 botanical agent. Myroxylon pereirae resin 25% was the most common positive allergen in the series. Patients who had positive reactions to at least 1 botanical agent were more (19.8%) likely to have a positive reaction to at least 1 additional botanical than those patients who did not have any positive tests. Most patients presented with generalized involvement (334) or involvement of the hands (284) or face (232). Conclusion: Physicians should be aware of the high prevalence of allergic contact dermatitis and patch test positivity associated with botanical products.
B-138 Skewed Demographics of Patient Population Contributes to Selection Biases in Clinical Study Population
Abstract Background The racial, ethnic and sex compositions of a study population may impact the clinical performance of a biomarker. In a prospective clinical study to evaluate biomarkers for asthmatic and allergic conditions in a large medical center in the upper Midwest, a largely White-alone patient population was encountered. Using several outreach strategies, potential eligible patients were contacted to enroll in a biomarker clinical study and to provide blood specimens. The patient demographics between the eligible candidates and the enrolled participants were compared. The analysis was carried out to understand the likelihood of enrollment in different race, ethnicity, and sex groups; and to identify factors that contribute to selection biases in enrolled cohorts. Methods Patients with eligible asthma and allergic conditions were selected based on relevant diagnostic codes in their electronic medical records, verified by clinical research coordinator. In accordance with Institutional Review Board approval, eligible patients were contacted via their electronic healthcare portal or with a phone call. The study information was also posted in an internal classified ad as an additional outreach strategy. Interested participants were then contacted a second time to complete consent. Upon consent, participants were considered as “enrolled”. Demographics information including sex, race, ethnicity, and age were de-identified for comparison analysis. Results Among all eligible patients, a disproportionally low representation of Blacks, Asians, and Hispanics (“non-White” groups) was observed, relative to regional demographics (22.2% non-White groups, 2021 census) and higher asthma and allergy prevalence in the non-White groups. In eligible adult patients (>18 years old) with asthma, only 13.4% were from non-White racial and ethnic groups. In eligible pediatric asthma patients, a larger proportion at 24.1% were from American Indian, Asian, Black, or Hispanic groups. In patients with allergic conditions, 10.3% of the adult patients were from non-White only groups, compared to 21.9% in pediatric patients. Among all eligible patients, White-alone patients were more likely to enroll in the study compared to their counterparts from non-White groups, further skewing the racial and ethnic distribution in the enrolled cohorts. As a result, less than 10% of enrolled adult patients were from non-White background in both allergy and asthma cohorts. Among the enrolled pediatric asthma and allergy patients, 16.9% and 10.3% respectively were from non-White groups. We also identified sex and age dependent enrollment behavior across different study cohorts. In adult groups, there were more female eligible patients (allergy: 66.7% female; asthma: 66.7% female) than male patients. Female adult patients were significantly more likely to participate, thus constituting 79.6% and 75.8% of the enrolled allergy and asthma cohorts. In the pediatric groups, male patients represented a larger share of eligible patients (allergy: 58.6%; asthma 64.7%). Female pediatric patients were still more likely to participate in the study. Hence, male and female enrolled patients were closer to equal distribution (allergy: 50.0% male; asthma 59.7% male). Conclusion The non-even distribution of demographics in eligible patients contributed to biased distribution in enrolled patients. Existing outreach approaches were not effective in reversing enrollment rates in underrepresented racial and ethnic groups.
Treatment of Hydroxyurea-Induced Ulcers With Timolol
ImportancePatients are frequently copositive for multiple allergens simultaneously, either due to chemical similarity or simultaneous sensitization. A better understanding of copositivity groups would help guide contact avoidance.ObjectiveTo use patient data to systematically determine copositivity groups in the Mayo Clinic Standard Series.Design, Setting, and ParticipantsIn this retrospective cross-sectional analysis, the Mayo Clinic patch test database was queried for pairwise copositivity rates in the 80 allergen Mayo Clinic Standard Series between 2012 and 2021. Data were collected from 3 tertiary care sites of the Mayo Clinic Contact Dermatitis Group and a total of 5943 patients were included, comprising all patients undergoing patch testing to the Mayo Clinic Standard Series allergens.Main Outcomes and MeasuresCopositivity rates between every 2 allergens in the 80-allergen Mayo Clinic Standard Series were estimated. After background correction, copositivity rates were analyzed using unsupervised hierarchical clustering to systematically identify copositivity groups in an unbiased manner.ResultsOverall, 394 921 total patches were applied to 5943 patients (4164 [70.1%] women, 1776 [29.9%] men, with a mean [SD] age of 52.3 [18.8] years ), comprising 9545 positive reactions. After background correction based on overall positivity rates, hierarchical clustering revealed distinct copositivity groups. Many were supported by prior literature, including formaldehyde releasers, cobalt-nickel-potassium dichromate, acrylates, 3-dimethylaminopropylamine-amidoamine-oleamidopropyl dimethylamine, alkyl glucosides, budesonide-hydrocortisone-17-butyrate, certain fragrances, compositae-sesquiterpene lactone mix, mercapto mix-mercaptobenzothiazole, carba mix-thiuram mix, and disperse orange-p-phenylenediamine. However, novel associations were also found, including glutaraldehyde-sorbitan sesquioleate, benzalkonium chloride-neomycin-bacitracin, bronopol-methylchloroisothiazolinone-methylisothiazolinone, and benzoic acid-iodopropynyl butylcarbamate.Conclusions and RelevanceThis retrospective cross-sectional analysis found that copositivity rates varied between allergens; allergens with extremely high positivity rates demonstrated nonspecific copositivity to multiple other allergens. Background correction based on positivity rates followed by hierarchical clustering confirmed prior known copositivity groups, contaminants and/or excipients leading to copositivity, and novel associations to guide contact avoidance.
Trends in Patch Testing with the Mayo Clinic Standard Series, 2017–2021
Background: Patch testing to a standard series is used to identify culprit allergens in patients with contact dermatitis. The reaction rates evolve over time based on trends in cutaneous exposures by the general population. Objective: The aim of this study was to analyze the patch test results of the Mayo Clinic standard series in patients tested from 2017 to 2021. Methods: The patch test reactions of standard series allergens tested from 2017 to 2021 were retrospectively reviewed and compared with the results of our prior report from 2011 to 2015 as well as the North American Contact Dermatitis Group (NACDG) report from 2017 to 2018. Results: Of 2667 patients tested, 1683 (63.1%) had at least 1 positive reaction. The 15 allergens with the highest reaction rates were hydroperoxides of linalool 1%, nickel (II) sulfate hexahydrate, methylisothiazolinone, Myroxylon pereirae resin, hydroperoxides of linalool 0.5%, methyldibromo glutaronitrile, neomycin sulfate, cobalt (II) chloride hexahydrate, fragrance mix I, benzalkonium chloride, bacitracin, hydroperoxides of limonene, methylchloroisothiazolinone/methylisothiazolinone, p-phenylenediamine, and textile dye mix. Twelve (80%) of these allergens were also in the top 15 of the most recent NACDG report. Conclusions: Hydroperoxides of linalool and hydroperoxides of limonene are new allergens that have been added to our standard series. These are associated with high reaction rates.