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

BACKGROUND: Patch testing to multiple cross reactive allergens for allergic contact dermatitis (ACD) may not be necessary due to copositivity. OBJECTIVE: We evaluated the formaldehyde group allergens to determine the optimal, most cost-effective allergens to test. METHODS: A 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). RESULTS: 9832 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. LIMITATIONS: Data is from a single institution, and the cost-per-test was fixed to Medicare Part B in 2022. CONCLUSIONS: For diagnosing ACD, we recommend considering an optimized allergen selection algorithm.

Pediatric Patch Testing at Mayo Clinic Between 2016 and 2020.

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).

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.

Systematic Identification of Copositivity Groups in Standard Series Patch Testing Through Hierarchical Clustering.

Importance: Patients 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. Objective: To use patient data to systematically determine copositivity groups in the Mayo Clinic Standard Series. Design, Setting, and Participants: In 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 Measures: Copositivity 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. Results: Overall, 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 Relevance: This 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.

Trends in Patch Testing of Black Patients: The Mayo Clinic Decade Experience (January 1, 2011, to December 31, 2020).

Background: Trends in patch testing for allergic contact dermatitis (ACD) have not been well characterized in Black patients. Despite similar incidence of ACD in Black and White patients, there are differences in allergen profiles. Understanding patch testing trends in Black patients furthers knowledge that has considerable impact on the management of ACD in the Black population. Objective: The purpose of this study was to review the results of patch testing in Black patients at Mayo Clinic over a decade. Methods: We retrospectively reviewed the results of patch testing to the standard, extended standard, or hairdresser series in 149 Black patients seen at Mayo Clinic (Rochester, MN; Scottsdale, AZ; and Jacksonville, FL) from January 1, 2011, to December 31, 2020. Results: During the 10-year period, 149 Black patients (mean age, 49.2 years [SD, 17.1 years]; female 67.1%) were patch tested at Mayo Clinic to the standard, extended standard, or hairdresser series. Most common sites of dermatitis were generalized (30.9%), hands (18.8%), leg (16.8%), trunk (16.1%), and arm (14.8%). Overall, 109 patients (73.2%) had at least 1 positive reaction and 74 patients (50%) had 2 or more positive reactions. Overall, the 10 allergens with the highest reaction rates (from highest to lowest) identified in our study population were 4-amino-2-hyroxytoluene (33.3%), thimerosal (20.4%), nickel sulfate (18.9%), methylisothiazolinone (16.5%), methyldibromo glutaronitrile (13.4%), methyldibromo glutaronitrile/phenoxyethanol (12.5%), captan (12.5%), carmine (12.5%), methylchloroisothiazolinone/methylisothiazolinone (11.5%), and hydroperoxide of linalool 1% (11.3%). Conclusions: We describe patch test results in Black patients over a decade at Mayo Clinic. The top 10 allergens were preservatives, hair dyes, and fragrances. Differing patterns of allergens may occur in Black patients due to different patterns of exposures related to cultural practices.

Reevaluating Corticosteroid Classification Models in Patient Patch Testing.

Importance: Individuals with allergic contact dermatitis to one topical corticosteroid may also react to other corticosteroids. Corticosteroid classification models have been proposed to predict such copositivity, recommend representative screening corticosteroids, and guide allergen avoidance. Objective: To use patient data to determine copositivity patterns between corticosteroids and evaluate against previous corticosteroid classification models. Design, Setting, and Participants: This qualitative study included a retrospective analysis of the Mayo Clinic Contact Dermatitis Group corticosteroid patch test data from 2010 to 2019. Among patients undergoing patch testing with the Mayo Clinic's standard or steroid series who consented to research participation, 5637 patients were included in the analysis. Copositivity rates were determined between corticosteroids and analyzed by hierarchical clustering for comparison to previous classification models. Main Outcomes and Measures: The frequency of patch test positivity to each of the analyzed corticosteroids was noted and compared with previously published patch test positivity rates. Copositivity rates between each pair of corticosteroids were determined, and overall copositivity patterns were analyzed and evaluated against known steroid classes. Results: A total of 49 472 individual patches were applied to 5637 patients, testing 18 corticosteroids. Patch test positivity rates ranged between 0.3% and 4.7%. The fluocinonide positivity rate corresponded to the highest copositivity rate with other corticosteroids (mean [SD], 50.7% [26.1%]). Tixocortol-21-pivalate, 0.1%, and tixocortol-21-pivalate, 1%, positivity rates corresponded to the lowest copositivity rates (mean [SD], 4.1% [1.7%] and 3.6% [1.4%], respectively). Hierarchical clustering elucidated patterns that did not support previous corticosteroid classification models. Conclusions and Relevance: In this qualitative study, copositivity rates were variable between corticosteroids, and overall patch test positivity for allergy to topical corticosteroids was rare. Previously published corticosteroid classifications are not supported by real patient-derived data and may not be accurate in predicting corticosteroid copositivity.

A Retrospective Review of Late Delayed Positive Patch Testing Greater Than Day 8 at Mayo Clinic From 2001 to 2020.

BACKGROUND: Patch tests are read between days 5 and 7, because most hypersensitivity reactions occur within 7 days. Later reactions can occur after day 8, which may be missed. OBJECTIVE: The aim of the study was to review all late delayed positive (LDP) reactions that have occurred after day 8 at Mayo Clinic from 2001 to 2020. METHODS: Mayo Clinic records were reviewed for patients who had patch test readings performed at greater than day 8. Late delayed positive reactions were defined as any patch tests that were initially negative from days 4 to 7 yet became positive after day 8. RESULTS: Two hundred seventy-four patients developed 439 LDPs to 89 allergens. Fourteen allergens had LDPs in at least 2% of patients: gold (gold sodium thiosulfate-3 concentrations, gold chloride, potassium dicyanoaurate), cobalt (cobalt sulfate, cobalt chloride hexahydrate), beryllium, palladium, acrylates (2-hydroxypropyl methacrylate, 2-hydroxyethyl methacrylate, 2-hydroxyethyl acrylate), dodecyl gallate, and gentamycin. Late delayed positive reactions to gold allergens were the most frequent reactions. Up to 90% of relevant gold allergen LDPs were positive by day 15. CONCLUSIONS: Positive patch test readings after day 8 are uncommon, but allergens most likely to be positive are metals (gold, cobalt, palladium, beryllium), acrylates, dodecyl gallate, and gentamycin. Gold allergens showed the highest LDP rates and relevance, with most reactions occurring by day 15.

Deep learning for dermatologists: Part II. Current applications.

Because of a convergence of the availability of large data sets, graphics-specific computer hardware, and important theoretical advancements, artificial intelligence has recently contributed to dramatic progress in medicine. One type of artificial intelligence known as deep learning has been particularly impactful for medical image analysis. Deep learning applications have shown promising results in dermatology and other specialties, including radiology, cardiology, and ophthalmology. The modern clinician will benefit from an understanding of the basic features of deep learning to effectively use new applications and to better gauge their utility and limitations. In this second article of a 2-part series, we review the existing and emerging clinical applications of deep learning in dermatology and discuss future opportunities and limitations. Part 1 of this series offered an introduction to the basic concepts of deep learning to facilitate effective communication between clinicians and technical experts.

Deep learning for dermatologists: Part I. Fundamental concepts.

Artificial intelligence is generating substantial interest in the field of medicine. One form of artificial intelligence, deep learning, has led to rapid advances in automated image analysis. In 2017, an algorithm demonstrated the ability to diagnose certain skin cancers from clinical photographs with the accuracy of an expert dermatologist. Subsequently, deep learning has been applied to a range of dermatology applications. Although experts will never be replaced by artificial intelligence, it will certainly affect the specialty of dermatology. In this first article of a 2-part series, the basic concepts of deep learning will be reviewed with the goal of laying the groundwork for effective communication between clinicians and technical colleagues. In part 2 of the series, the clinical applications of deep learning in dermatology will be reviewed and limitations and opportunities will be considered.

Seven Common Allergen Groups Causing Eyelid Dermatitis: Education and Avoidance Strategies.

OBJECTIVE: Eyelid dermatitis is most commonly attributed to allergic response. This retrospective clinical study identifies common allergens with eyelid involvement and addresses a literary gap by providing a clear approach for effective management of periorbital allergic contact dermatitis (ACD) recurrence. METHODS: Charts of 215 patients diagnosed with periorbital dermatitis who were patch tested with Mayo Clinic Standard Series, Extended Standard Series, and personal products from 2013 to 2017 were examined. Positive reaction rates for patients with eyelid involvement were compared to those without. Findings were also compared to North American Contact Dermatitis Group (NACDG) 2013-2014 and Mayo Clinic Contact Dermatitis Group (MCCDG) 2011-2015 general patch test populations. RESULTS: The 215 patients showed more common allergy to shellac, benzalkonium chloride, acrylates, and surfactants than the NACDG and MCCDG study populations. Periorbital ACD allergen groups eliciting the highest positive reaction rates were, in descending order: metals, shellac, preservatives, topical antibiotics, fragrances, acrylates, and surfactants. Of the corticosteroids, only tixocortol pivalate (the screening agent for prednisolone and fluorometholone) and budesonide elicited positive reactions. CONCLUSION: The top seven eyelid ACD allergen groups were identified. Avoidance of these allergens can be straightforward, with initial empiric counseling and free, online allergen avoidance programs. Patients who are unresponsive to avoidance should undergo patch testing.

Coccidioidomycosis in patients with various inflammatory disorders treated with tumor necrosis factor α inhibitors.

Coccidioides fungi are found primarily in the southwestern United States and are the cause of coccidioidomycosis. Tumor necrosis factor α inhibitors (TNFIs) are therapies for autoimmune and inflammatory conditions; their association with coccidioidomycosis is not well characterized. We aimed to determine the prevalence and characteristics of coccidioidomycosis among TNFI recipients with different inflammatory disorders at a tertiary care center. We retrospectively reviewed the electronic health records of patients at our institution from April 4, 2010 to December 17, 2017, who received TNFIs (infliximab, etanercept, adalimumab, certolizumab pegol, or golimumab) and had positive culture, pathologic, and/or serologic results for coccidioidomycosis. Among 1770 patients identified who received TNFIs, 49 (2.8%) had proven or probable coccidioidomycosis. Of these 49, 28 (57%) were men, 47 (96%) were White, and 42 (86%) had pulmonary coccidioidomycosis. The most common TNFIs used were adalimumab, infliximab, and etanercept. Coccidioidomycosis was identified in 25 of 794 patients with rheumatologic disorders (3.1%), 18 of 783 patients with inflammatory bowel disease (IBD) (2.3%), and six of 193 patients with dermatologic disorders (3.1%) (P = .34). There was no difference in coccidioidal infections among recipients of any particular TNFI agents. A minority of patients (7/49, 14%) had an extrapulmonary infection, and the majority of these (6/7) had IBD. Our study shows a low prevalence of coccidioidomycosis in TNFI recipients, even within the Coccidioides-endemic area. Persons with IBD were disproportionately represented among those with extrapulmonary coccidioidomycosis. Treatment with azoles was effective. LAY SUMMARY: Among 1770 patients who received tumor necrosis factor α inhibitors, 49 (2.8%) had newly acquired coccidioidomycosis over a 7-year period. Dissemination occurred in 14.3%, but disproportionately among those with underlying inflammatory bowel disease. All patients recovered with medical management.

A Scalable Framework for Telehealth: The Mayo Clinic Center for Connected Care Response to the COVID-19 Pandemic.

Background: The Mayo Clinic Center for Connected Care has an established organizational framework for telehealth care delivery. It provides patients, consumers, care teams, and referring providers access to clinical knowledge through technologies and integrated practice models. Central to the framework are teams that support product management and operational functions. They work together across the asynchronous, synchronous video telemedicine, remote patient monitoring (RPM), and mobile core service lines. Methods: The organizational framework of the Center for Connected Care and Mayo Clinic telehealth response to the COVID-19 pandemic is described. Barriers to telehealth delivery that were addressed by the public health emergency are also reported. This report was deemed exempt from full review by the Mayo Clinic IRB. Results: After declaration of the COVID-19 pandemic, there was rapid growth in established telehealth offerings, including patient online services account creation, secure messaging, inpatient eConsults, express care online utilization, and video visits to home. Census for the RPM program for patients with chronic conditions remained stable; however, its framework was rapidly adapted to develop and implement a COVID-19 RPM service. In addition to this, other new telehealth and virtual care services were created to support the unique needs of patients with COVID-19 symptoms or disease and the health care workforce, including a digital COVID-19 self-assessment tool and video telemedicine solutions for ambulances, emergency departments, intensive care units, and designated medical-surgical units. Conclusion: Rapid growth, adoption, and sustainability of telehealth services through the COVID-19 pandemic were made possible by a scalable framework for telehealth and alignment of regulatory and reimbursement models.

Experiences of Health Care Providers Using a Mobile Medical Photography Application.

OBJECTIVE: To understand the ways in which providers use a mobile photography application integrated with the electronic health record (EHR) to facilitate clinical care, and the process outcomes that result from the application's use. METHODS: An e-mail survey was sent on November 13, 2017, to 1,463 health care providers at Mayo Clinic who had used an internally developed, EHR-integrated medical photography application. RESULTS: The survey was completed by 712 (49%) providers. Providers reported using the application on approximately 1 in 7 days spent in clinical practice. Median provider satisfaction with the use of the application (0-100 scale; higher numbers indicate favorable response) was 94 (interquartile range [IQR]: 74-100). Although the use for store-and-forward telemedicine was reported (22% often or frequently used the application to send photographs to a specialist for advice), the most common use was for clinical documentation (65% often or frequently used the application to supplement text-based notes with photographs, and 71% often or frequently used the application to take photographs for reference by a colleague who may see the patient in the future). Of the health care providers, 36% indicated that the application's use often or frequently expedited treatment. DISCUSSION: Health care providers reported using a mobile point-of-care medical photography application regularly in clinical practice and were generally satisfied with the application. CONCLUSION: Point-of-care medical photography using a secure mobile, EHR-integrated application has potential to become a new standard of care for clinical documentation and may facilitate continuity across the continuum of care with multiple providers who see a patient.

The Final Patch Test Read: Day 5 or Day >7?

BACKGROUND: A major question in patch testing is when to perform the final reading. Our current standard practice is to place patches on day 1, remove them on day 3, and perform readings on days 3 and 5. For certain allergens, another reading is performed sometime from days 7 to 14≥. OBJECTIVES: The aim of the study was to identify allergens with positive reactions on day 5 that were negative on day 7 or later and allergens with negative reactions on day 5 that were subsequently positive on day 7 or later. METHODS: We reviewed records of patients who underwent patch testing from January 2007 to December 2016 at Mayo Clinic with readings on day 5 and day 7 or later. CONCLUSIONS: In total, 131 allergens had positive reactions on day 5 that were negative on day 7 or later, and 58 allergens had negative reactions on day 5 that were positive on day 7 or later. Twenty-five allergens had significantly higher reaction rates on day 5 than day 7 or later. Our standard practice is to perform readings on days 3 and 5 and on days 3, 5, and 7 or later for series containing metals. Readings on days 3, 5, and 7 or later should also be considered for acrylates.

The policy dimensions, regulatory landscape, and market characteristics of teledermatology in the United States.

The COVID-19 pandemic has spurred healthcare systems across the world to rapidly redesign their models of care delivery. As such, this pandemic has accelerated the adoption of teledermatology in the United States. However, it remains unknown whether this momentum will be maintained after the pandemic. The future of teledermatology in the United States will be significantly influenced by a complex set of policy, legal, and regulatory frameworks. An understanding of these frameworks will help dermatologists more effectively adopt and implement teledermatology platforms. In this article, we review the current state of teledermatology in the United States, including policy dimensions, the regulatory landscape, market characteristics, and future directions.

The Utility of Screening for Coccidioidomycosis in Recipients of Inhibitors of Tumor Necrosis Factor α.

BACKGROUND: Tumor necrosis factor α inhibitors (TNFi) are commonly used to treat immune-mediated disorders, but they are associated with an increased risk of mycobacterial and fungal infections. We compared the outcomes of TNFi recipients screened for asymptomatic coccidioidomycosis with those of unscreened patients to compare the development of symptomatic coccidioidomycosis and to describe its outcomes for patients with abnormal coccidioidal screenings. METHODS: We searched electronic health records from 4 September 2010 through 26 September 2016 for all patients receiving a TNFi for dermatologic, rheumatologic, or gastroenterologic diagnoses, then categorized patients by whether or not they had undergone coccidioidal serologic testing for screening or diagnostic purposes. RESULTS: A total of 2793 patients had a TNFi prescribed. Of those, 1951 met the inclusion criteria: 1025/1951 (52.5%) never had coccidioidal screening; 925/1951 (47.4%) had serologic screening either before beginning TNFi therapy or annually, or both after beginning a TNFi. Symptomatic coccidioidomycosis developed in 35/1025 (3.4%) unscreened patients. Of those screened, 861/925 (93.1%) had negative serologic tests, of which 11/861 (1.3%) subsequently developed symptomatic coccidioidomycosis; 36/925 (3.9%) had coccidioidomycosis at screening (7, probable infection; 11, possible infection; 18, asymptomatic seropositive result); and 17 had only positive findings for immunoglobulin M antibodies and did not meet the definition for coccidioidomycosis. The unscreened cohort was more likely to have symptomatic coccidioidomycosis than the screened cohort (35/1025 vs 11/861, P < .01). CONCLUSIONS: Screening for asymptomatic coccidioidomycosis within a Coccidioides-endemic area allowed for identifying and managing asymptomatic coccidioidomycosis before patients began TNFi therapy. Less symptomatic infection developed in the screened than the unscreened cohort.