More than just methylisothiazolinone: Retrospective analysis of patients with isothiazolinone allergy in North America, 2017-2020.

BACKGROUND: Isothiazolinones are a common cause of allergic contact dermatitis. OBJECTIVE: To examine the prevalence of positive patch test reactions to isothiazolinones from 2017-2020 and characterize isothiazolinone-allergic (Is+) patients compared with isothiazolinone nonallergic (Is-) patients. METHODS: Retrospective cross-sectional analysis of 9028 patients patch tested to methylchloroisothiazolinone (MCI)/methylisothiazolinone (MI) 0.02% aqueous, MI 0.2% aqueous, benzisothiazolinone (BIT) 0.1% petrolatum, and/or octylisothiazolinone (OIT) 0.025% petrolatum. Prevalence, reaction strength, concurrent reactions, clinical relevance, and source of allergens were tabulated. RESULTS: In total, 21.9% (1976/9028) of patients had a positive reaction to 1 or more isothiazolinones. Positivity to MI was 14.4% (1296/9012), MCI/MI was 10.0% (903/9017), BIT was 8.6% (777/9018), and OIT was 05% (49/9028). Compared with Is-, Is+ patients were more likely to have occupational skin disease (16.5% vs 10.3%, P <.001), primary hand dermatitis (30.2% vs 19.7%, P <.001), and be >40 years (73.1% vs 61.9%, P <.001). Positive patch test reactions to >1 isothiazolinone occurred in 44.1% (871/1976) of Is+ patients. Testing solely to MCI/MI would miss 47.3% (611/1292) of MI and 60.1% (466/776) of BIT allergic reactions. LIMITATIONS: Retrospective cross-sectional study design and lack of follow-up data. CONCLUSION: Sensitization to isothiazolinones is high and concurrent sensitization to multiple isothiazolinone allergens is common.

The use of social media platforms to discuss and educate the public on allergic contact dermatitis.

BACKGROUND: Social media platforms are increasingly used by patients to research and discuss medical problems. OBJECTIVE: The aim of this study was to identify by whom, how frequently, and in what manner allergic contact dermatitis (ACD) is discussed on social media sites. METHODS: Search terms "allergic contact dermatitis" and "contact dermatitis" were queried across Twitter, Instagram, Reddit, Facebook, YouTube, and Google search metrics. The frequency, content, and creators of the content were assessed. RESULTS: ACD content was identified on all platforms, generated by by patients, physicians, professional organizations, and companies. When comparing the volume of posts, more content was on Instagram than Twitter, particularly among patients. Patient support groups were identified on Facebook but not on Reddit. A formal analysis of YouTube videos found that the medical information presented in these videos was often of poor quality. CONCLUSIONS: Patch testing physicians should be aware that information on ACD exists across social media sites. While some content is generated by physicians, patients and industry groups also post and share material. Patch testing physicians should know that there is an opportunity to share ACD information, but they should also be aware that patients are posting and creating online support communities independent of physicians. HIGHLIGHTS: Online support communities exist for patients with ACD on Facebook. Online information is of lower quality, with a mean QUEST quality score of 7.4/28 on reviewed YouTube videos. Of the five social media sites reviewed, patients are most active on Instagram, Reddit, and Facebook. Approximately 9000 Google searches per month are conducted using contact dermatitis-related search terms. Differences in terminology exist between physicians and non-physicians. While the most popular hashtag term was "contact dermatitis", physicians disproportionately authored posts tagged with "allergic contact dermatitis."

The impact of dupilumab on patch testing and the prevalence of comorbid allergic contact dermatitis in recalcitrant atopic dermatitis: A retrospective chart review.

BACKGROUND: It is unclear whether the type 2 T helper cell-specific immunosuppressive action of dupilumab interferes with patch testing. OBJECTIVES: We sought to evaluate the reliability of patch testing on dupilumab and the contribution of allergic contact dermatitis (ACD) to complex dermatitis in patients with residual dermatitis on dupilumab. METHODS: This is a retrospective chart review of 48 patients with atopic dermatitis (AD) who were treated with dupilumab. We compare the results of patch tests performed before and after the initiation of dupilumab and the prevalence of comorbid ACD in patch-tested individuals. RESULTS: A minority of patch test reactions were "lost" on dupilumab (13/125; 10.4%). Five of 13 lost reactions occurred in individuals with documented immunodeficiency. Thirty-two of 35 patch-tested patients (91.4%) had comorbid ACD; 92.3% of individuals patch tested on dupilumab experienced further clinical improvement with allergen avoidance. LIMITATIONS: This is a nonrandomized study in a small cohort of patients. The clearance of dupilumab was assessed by subjective patient reports. CONCLUSIONS: Dupilumab does not appear to exert a dampening effect on patch test results. AD with comorbid ACD was highly prevalent and allergen avoidance resulted in significant improvement in residual dermatitis that had not resolved without dupilumab therapy.

Occupational Contact Dermatitis in Construction Workers: A Retrospective Analysis of the North American Contact Dermatitis Group Data, 2001-2020.

Background: Construction workers (CWs) are at risk for occupational contact dermatitis (CD) owing to workplace exposures. Objective: Determine the prevalence of occupational allergic CD and characterize common occupational allergens in CWs referred for patch testing in the United States and Canada. Methods: Retrospective cross-sectional analysis of patients patch tested by the North American Contact Dermatitis Group from 2001 to 2020. Results: Of 47,843 patch-tested patients, 681 (1.4%) were CWs. Compared with non-CWs, CWs were more likely to be male (91.0% vs 30.9%) have occupational skin disease (36.9% vs 11.4%) and have hand involvement (37.2% vs 22.5%) (all P < 0.0001). Of 681 CWs, 60.1% (411) had clinically relevant positive patch test reactions, and nearly 1/3 of CWs (128) had occupationally relevant reactions. Most common occupationally relevant allergens were potassium dichromate 0.25% pet. (30.5%, 39/128), bisphenol A epoxy resin 1% pet. (28.1%, 36/128), carba mix 3% pet. (14.8%, 19/128), cobalt (ii) chloride hexahydrate 1% pet. (14.1%, 18/128), and thiuram mix 1% pet. (14.1%, 18/128). Top sources of occupationally relevant allergens were cement/concrete/mortar (20.4%, 46/225), gloves (15.1%, 34/225), and coatings (paint/lacquer/shellac/varnish/stains) (9.8%, 22/225). Conclusions: Occupational CD in North American CWs is common. In this group, frequently identified etiological sources of occupational allergic CD included metals, epoxy resin, and rubber.

Allergic or Not: Final Interpretation of Doubtful Patch Test Reactions From the North American Contact Dermatitis Group, 2019-2020.

Background: Doubtful patch test reactions generally do not meet criterion for positivity in patch testing. However, the North American Contact Dermatitis Group (NACDG) allows for doubtful reactions to be coded with a final determination of "allergic/positive" based on the temporal pattern, appearance, known characteristics of the allergen, and/or other supportive patch test reactions. Objectives: To analyze NACDG data from the 2019-2020 patch test cycle to identify patterns in the interpretation and relevance of doubtful reactions. Methods: The frequency and proportions of doubtful reactions were tabulated and analyzed for patterns. Statistical analyses were limited to allergens with ≥30 doubtful reactions to ensure adequate sample size. Results: Of patch-tested patients, 31.9% (1315/4121) had ≥1 doubtful reaction. Of 2538 total doubtful reactions, 46% (n = 1167) had a final interpretation of "allergic/positive." The allergens with the highest proportion of doubtful reactions at the final visit were hydroperoxides of linalool 1% (4.5%), fragrance mix I 8.0% (3.9%), and cetrimonium chloride 0.5% (3.4%). Methylchloroisothiazolinone/methylisothiazolinone (MCI/MI) 0.02% (P < 0.001), MI 0.2% (P < 0.001), nickel sulfate hexahydrate 2.5% (P = 0.001), and neomycin sulfate 20.0% (P = 0.003) doubtful reactions were more likely to be interpreted as allergic than nonallergic. Methyldibromoglutaronitrile/phenoxyethanol 0.2% (P < 0.001), oleamidopropyl dimethylamine 0.1% (P < 0.001), formaldehyde 2.0% (P < 0.001), cetrimonium chloride 0.5% (P < 0.001), benzophenone-4 (sulisobenzone) 10% (P < 0.001), iodopropynyl butylcarbamate 0.5% (P < 0.001), cocamidopropyl betaine 1.0% (P = 0.002), and benzisothiazolinone 0.1% (P = 0.012) doubtful reactions were less likely to be interpreted as allergic. Of the 1167 doubtful reactions interpreted as allergic, 84.9% had current relevance. Conclusions: Doubtful reactions were common and approximately one half were coded with a final interpretation of "allergic/positive." Of those, most were clinically relevant. MCI/MI, MI, nickel, and neomycin were more likely to be interpreted as allergic.

Patch Testing With Nickel, Cobalt, and Chromium in Patients With Suspected Allergic Contact Dermatitis.

Background: Allergic contact dermatitis is frequently caused by metals, including multiple metals simultaneously. Objectives: To assess characteristics and associations of positive and clinically relevant patch test (PT) reactions with solitary and concurrent metal sensitization. Methods: A retrospective analysis of PT results for nickel, cobalt, and/or chromium from the North American Contact Dermatitis Group between 2001 and 2018 (n = 43,522). Results: 18.0% had a positive/allergic reaction to nickel sulfate hexahydrate, 7.3% to cobalt chloride hexahydrate, and 3.0% to potassium dichromate. 87.9% patients had a currently relevant reaction to 0, 9.4% to 1, and 2.7% to multiple metals tested. Patients with 1 versus no currently relevant reactions to metal were more likely to have a primary dermatitis site of trunk, feet, and ears; patients with currently relevant reactions to multiple metals had more dermatitis affecting the trunk and ears. Metal sources varied by co-reacting metal, especially for patients with cobalt and chromium allergy. Jewelry was the most commonly identified source of nickel and cobalt for both solitary and concurrent metal allergy. Conclusions: Sensitization to multiple metals occurred in 6% of patients. Allergen sources varied between patients with sensitivity to 1 metal versus those who had concurrent sensitivity to cobalt and/or chromium.

Nontraditional management of basal cell carcinoma.

This review discusses nontraditional modalities available for the treatment of basal cell carcinoma along with the existing evidence to support their respective uses in varying clinical situations. By definition, these modalities are nonsurgical, and in many cases, are not approved by the US Food and Drug Administration as treatments for basal cell carcinoma, including topical chemotherapies, photodynamic therapy, oral therapies, and complementary therapies. Nonetheless, as the population of patients with skin cancer increases at epidemic proportions, many of these modalities are, and will become, increasingly relevant in the dermatologist's armamentarium.

Patient-Centered Communication Tools for the Patch Test Clinic.

Patient-centered communication positively impacts the clinical encounter. Multiple strategies exist to improve communication between providers and their patients; the application and impact of these strategies have been studied in multiple specialties, though little exists regarding communication best practices in the patch test clinic. Because the procedural components of patch testing often span the course of an entire week, effective communication with patients during the patch testing visit is important for not only technical success, but also patient understanding and experience. In this study, we highlight the value of beginning the patch testing visit with clear introductions and agenda setting, improving patient understanding and engagement through methods such as teach backs and cycles of questions and answers that create patient-provider dialogue, and using communication techniques to make expressions of empathy. We provide detailed examples regarding the application of these techniques to the patch testing process, aimed at enhancing the patch testing experience and improving clinical outcomes. Our review exemplifies how dermatologists can leverage communication tools to improve patient satisfaction and outcomes during patch testing.

Patch Testing to Paraphenylenediamine: The North American Contact Dermatitis Group Experience (1994-2018).

Background/Objectives: Paraphenylenediamine (PPD) is an aromatic amine dye that may cause allergic contact dermatitis. This study examines the epidemiology of allergic patch test reactions to PPD. Methods: This retrospective analysis characterizes individuals tested to PPD (1% petrolatum) by the North American Contact Dermatitis Group (1994-2018). Demographics and dermatitis site(s) were compared between PPD-allergic and PPD-negative patients. PPD reactions were analyzed by reaction strength, clinical relevance, occupational relatedness, and source as well as coreactivity with structurally related compounds. Results: Of 54,917 patients tested to PPD, 3095 (5.6%) had an allergic patch test reaction. Compared with PPD-negative patients, PPD-allergic patients had significantly greater odds of age >40 years (odds ratio [OR] 1.55 [95% confidence interval; CI 1.43-1.69]) and female gender (OR 1.52 [95% CI 1.41-1.66]), but lower odds of being White (OR 0.66 [95% CI 0.60-0.71]). The most common primary anatomic sites of dermatitis were face (25.5%), hands (21.9%), and scattered/generalized pattern (15.5%). Over half (55.3%) of PPD reactions were ++ or +++ at the final reading and 60.9% were currently relevant. Common exposure sources included hair dye (73.5%) and clothing/shoes/apparel (3.9%). Occupationally related reactions occurred in 8.3%, most commonly in hairdressers/cosmetologists (72.8%). The most common coreactions were benzocaine (11.3%), N-isopropyl-N'-phenyl-p-phenylenediamine (6.7%), disperse dye mix (6.5%), and black rubber mix (5.1%). Conclusions: The 24-year percentage of allergic reactions to PPD was 5.6%. PPD allergy was associated with female gender and age >40 years. PPD allergic patients were less likely to be White. Allergic reactions were usually clinically relevant and hair dye was the most frequently identified source.

Patch Test Results Among Older Adults: A Retrospective Analysis of the North American Contact Dermatitis Group Data (2009-2020).

Background: Allergic contact dermatitis (ACD) in older adults (OA) represents a significant health burden, but few studies examine the prevalence and characteristics of contact allergy and ACD in this population. Objective: To compare positive and clinically relevant patch test results in OA versus younger adults (YA) and children. Methods: Retrospective analysis of patch test results obtained in OA (≥65 years), YA (19-64 years), and children (≤18 years) by the North American Contact Dermatitis Group, 2009 to 2020. Results: Of 28,177 patients patch tested, 5366 (19.0%) were OA. OA were more likely to have a final primary diagnosis of ACD as compared with YA (50.8% vs 49.2%, P = 0.035) and children (44.6%, P < 0.0001). The primary site of dermatitis also differed by age group, with OA having a higher proportion of dermatitis affecting the trunk, scalp, anogenital region, and "under clothing," and a lower proportion of dermatitis affecting the face, lips, and feet. Limitations: Retrospective design, lack of follow-up, and referral population. Conclusion: OA were as likely and were statistically even more likely to have a final primary diagnosis of ACD compared with YA and children. Anatomic site of dermatitis also differed by age group. This underscores the need for patch testing in OA when ACD is suspected.

Patch Testing to Chlorhexidine Digluconate, 1% Aqueous: North American Contact Dermatitis Group Experience, 2015-2020.

Background: Chlorhexidine is an antiseptic that may cause allergic contact dermatitis. Objectives: To describe the epidemiology of chlorhexidine allergy and characterize positive patch test reactions. Methods: This retrospective study analyzed patients patch tested to chlorhexidine digluconate 1% aqueous by the North American Contact Dermatitis Group, 2015-2020. Results: Of 14,731 patients tested to chlorhexidine digluconate, 107 (0.7%) had an allergic reaction; of these, 56 (52.3%) reactions were currently clinically relevant. Most (59%) reactions were mild (+), followed by strong (++, 18.7%) and very strong (+++, 6.5%). Common primary dermatitis anatomic sites in chlorhexidine-positive patients were hands (26.4%), face (24.5%), and scattered/generalized distribution (17.9%). Compared with negative patients, chlorhexidine-positive patients were significantly more likely to have dermatitis involving the trunk (11.3% vs 5.1%; P = 0.0036). The most commonly identified source category was skin/health care products (n = 41, 38.3%). Only 11 (10.3%) chlorhexidine reactions were occupationally related; of these, 81.8% were in health care workers. Conclusions: Chlorhexidine digluconate allergy is uncommon, but often clinically relevant. Involvement of the hands, face, and scattered generalized patterns was frequent. Occupationally related reactions were found predominantly in health care workers.

North American Contact Dermatitis Group Patch Test Results: 2019-2020.

Background: Patch testing is an important diagnostic tool for assessment of allergic contact dermatitis (ACD). Objective: This study documents the North American Contact Dermatitis Group (NACDG) patch testing results from January 1, 2019, to December 31, 2020. Methods: At 13 centers in North America, patients were tested in a standardized manner with a screening series of 80 allergens, and, as indicated, supplemental allergens. Results: Overall, 4121 patients were tested; 2871 (69.7%) had at least 1 positive/allergic patch test reaction and 2095 patients (51.2%) had a primary diagnosis of ACD. The most commonly positive allergens were nickel (18.2%), methylisothiazolinone (MI) (13.8%), fragrance mix (FM) I (12.8%), hydroperoxides of linalool (HPL) (11.1%), and benzisothiazolinone (BIT) (10.4%). Compared with that of 2017-2018, prevalence of top 20 allergens statistically increased for FM I, HPL, BIT, propolis, and hydroperoxides of limonene (3.5%). For the first time, MI positivity did not increase between reporting periods. Approximately one-fifth of patients (20.3%) had ≥1 clinically relevant reaction(s) to allergens/substances not on the NACDG series. Conclusions: The epidemic of MI contact allergy in North America may have reached a plateau. Patch testing using a robust screening series, and supplemental allergens as indicated, is necessary for comprehensive evaluation of ACD.

Patch Testing With Benzophenone-3 and -4: The North American Contact Dermatitis Group Experience, 2013-2020.

Background: Benzophenone (BZP)-3 and BZP-4 are ultraviolet (UV) absorbers used in sunscreens and personal care products (PCPs) and may cause allergic contact dermatitis. Objective: To characterize positive patch test reactions to BZP-3 (10% in petrolatum [pet]) and BZP-4 (2% pet) in a screening allergen series. Methods: Retrospective analysis of patients tested to BZP-3 and BZP-4 was conducted by the North American Contact Dermatitis Group from 2013 to 2020. Results: Of 19,618 patients patch tested to BZP-3 and BZP-4, 103 (0.5%) and 323 (1.6%) had positive reactions, respectively: 413 (2.1%) reacted to at least 1 BZP (BZP-positive patient). As compared with BZP-negative patients, BZP-positive patients were significantly more likely to have a history of hay fever (39.3% vs 33.4%, P = 0.0134), history of atopic dermatitis (39.8% vs 30.7%, P = 0.0001), and facial involvement (37.4% vs 32.2%, P = 0.0272). Most reactions were currently clinically relevant (BZP-3: 90.4%; BZP-4: 65.8%). Common identified sources included PCPs and sunscreens. Coreactivity between BZP-3 and BZP-4 was low: 13.5% (14/104) of BZP-3-positive patients were allergic to BZP-4 and 4.3% (14/322) of BZP-4-positive patients were allergic to BZP-3. Conclusions: Eight-year prevalence of BZP positivity was 2.1%. Reactions were frequently clinically relevant and linked to PCPs and sunscreens.

Trends in the Prevalence of Methylchloroisothiazolinone/Methylisothiazolinone Contact Allergy in North America and Europe.

Importance: The common use of isothiazolinones as preservatives is a global cause of allergic contact dermatitis. Differences in allowable concentrations of methylisothiazolinone (MI) exist in Europe, Canada, and the US. Objective: To compare the prevalence of positive patch test reactions to the methylchloroisothiazolinone/methylisothiazolinone (MCI/MI) combination and MI alone in North America and Europe from 2009 to 2018. Design, Setting, and Participants: This retrospective analysis of North American Contact Dermatitis Group, European Surveillance System on Contact Allergies (ESSCA), and the Information Network of Departments of Dermatology (IVDK) databases included data from patients presenting for patch testing at referral patch test clinics in North America and Europe. Exposures: Patch tests to MCI/MI and MI. Main Outcomes and Measures: Prevalence of allergic contact dermatitis to MCI/MI and MI. Results: From 2009 to 2018, participating sites in North America and Europe patch tested a total of 226 161 individuals to MCI/MI and 118 779 to MI. In Europe, positivity to MCI/MI peaked during 2013 and 2014 at 7.6% (ESSCA) and 5.4% (IVDK) before decreasing to 4.4% (ESSCA) and 3.2% (IVDK) during 2017 and 2018. Positive reactions to MI were 5.5% (ESSCA) and 3.4% (IVDK) during 2017 and 2018. In North America, the frequency of positivity to MCI/MI increased steadily through the study period, reaching 10.8% for MCI/MI during 2017 and 2018. Positive reactions to MI were 15.0% during 2017 and 2018. Conclusions and Relevance: The study results suggest that in contrast to the continued increase in North America, isothiazolinone allergy is decreasing in Europe. This trend may coincide with earlier and more stringent government regulation of MI in Europe.