Lebrikizumab Provides Rapid Clinical Responses Across All Eczema Area and Severity Index Body Regions and Clinical Signs in Adolescents and Adults with Moderate-to-Severe Atopic Dermatitis.

INTRODUCTION: Atopic dermatitis (AD) affects multiple areas of the body, some of which may be more refractory to treatment. We evaluated improvements in the Eczema Area and Severity Index (EASI) by body region and clinical signs for each body region in lebrikizumab-treated patients with moderate-to-severe AD. METHODS: ADvocate 1 and ADvocate 2 compared lebrikizumab 250 mg as monotherapy every 2 weeks versus placebo for 16 weeks. Efficacy measures included EASI, which rates the extent and severity of four clinical signs (erythema, edema/papulation, excoriation, lichenification) in four body regions (head/neck, upper extremities, trunk, lower extremities). Analyses are post hoc. RESULTS: Mean baseline EASI, body region EASI subscores, and the severity of clinical signs were consistent across both studies (EASI ranging from 16.0 to 72.0). At week 16 in both studies, patients treated with lebrikizumab showed significantly greater percent improvement in EASI across all body regions versus placebo (p ≤ 0.001), with improvements as early as week 2. In ADvocate 1, all clinical signs significantly improved across all body regions at week 16 with lebrikizumab (51.4-71.6% improvement) versus placebo (23.1-43.5%, p ≤ 0.001), with significant improvements as early as week 2 for all signs. Significant improvements for all clinical signs at week 16 were also seen in ADvocate 2 for lebrikizumab (53.5-75.6%) versus placebo (28.5-41.2%, p ≤ 0.001) and as early as week 2 for all body regions and signs except head/neck erythema and lower extremity erythema, edema/papulation, and lichenification, which showed significant improvement by week 4. CONCLUSIONS: Lebrikizumab as monotherapy consistently and rapidly reduced the extent of involvement and severity of AD in all EASI clinical signs and body regions, including the head and neck region and clinical sign of lichenification, compared with placebo. TRIAL REGISTRATION: ClinicalTrials.gov identifier: ADvocate 1 (NCT04146363) and ADvocate 2 (NCT04178967).

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.

Disease burden among patients with atopic dermatitis treated with systemic therapy for 4-12 months: results from the CorEvitas Atopic Dermatitis Registry.

BACKGROUND: Real-world data on the effectiveness of systemic therapy in atopic dermatitis (AD) are limited. METHODS: Adult patients with AD in the CorEvitas AD registry (2020-2021) who received systemic therapies for 4-12 months prior to enrollment were included based on disease severity: body surface area (BSA) 0%-9% and BSA ≥10%. Demographics, clinical characteristics, and outcomes were assessed using descriptive statistics. Pairwise effect sizes (ES) were used to compare BSA groups. RESULTS: The study included 308 patients (BSA 0%-9%: 246 [80%]; BSA ≥10%: 62 [20%]). Despite systemic therapy, both BSA groups reported the use of additional topical therapy and the presence of lesions at difficult locations. Moderate-to-severe AD (vIGA-AD®) was reported by 11% (BSA 0%-9%) and 66% (BSA ≥10%; ES = 0.56) of patients. Mean disease severity scores: total BSA (2% and 22%; ES = 3.59), EASI (1.1 and 11.1; ES = 2.60), and SCORAD (12.1 and 38.0; ES = 1.99). Mean scores for PROs: DLQI (3.7 and 7.5; ES = 0.75), and peak pruritus (2.2 and 4.5; ES = 0.81). Inadequate control of AD was seen in 27% and 53% of patients (ES = 0.23). CONCLUSIONS: Patients with AD experience a high disease burden despite systemic treatment for 4-12 months. This study provides potential evidence of suboptimal treatment and the need for additional effective treatment options for AD.

This real-world study assessed clinical characteristics and overall disease burden in adult patients with atopic dermatitis (AD) who were receiving systemic therapy for 4­12 months.Patients reported greater involvement of back and anterior trunk, and lesions at difficult locations. Irrespective of body surface area involvement, patients continued to experience inadequate control of AD, varied disease severity, and impact on quality of life.The study provides potential evidence of suboptimal treatment and the need for effective treatment options for the management of AD. Besides clinical outcomes, treating dermatologists and dermatology practitioners should include patient-reported outcomes in routine clinical care to determine the best treatment options for their patients.

Burden of adult atopic dermatitis and unmet needs with existing therapies.

OBJECTIVE: Patients with atopic dermatitis (AD) have low treatment satisfaction. In this study, we evaluated the humanistic burden, treatment satisfaction, and treatment expectations in patients with AD in the United States. METHODS: Adults with AD recruited through the National Eczema Association and clinical sites completed a web-based survey comprising the Patient-Oriented SCORing Atopic Dermatitis (PO-SCORAD), Dermatology Life Quality Index; Work Productivity and Activity Impairment Questionnaire-Atopic Dermatitis; Treatment Satisfaction Questionnaire for Medication (TSQM); and answered questions on healthcare provider (HCP) visits, treatment history, and treatment goals. Descriptive analyses were performed to compare participants by severity. RESULTS: Among 186 participants (mean [standard deviation] age 39.7 [15.3] years, 79.6% female), 26.9%, 44.6%, and 26.3% of the participants had mild, moderate, or severe AD, respectively, based on PO-SCORAD. Greater disease severity was associated with a greater impact on work and daily life, decreased TSQM scores, and increased HCP visits. Corticosteroid topical cream or ointment (53.8%) and oral antihistamines (31.2%) were most commonly used for the treatment of AD. Participants reported declining/stopping/changing AD treatment due to the potential for side effects or lack of efficacy. 'Leading normal lives' (28.0%) and 'being itch-free' (33.9%) were important treatment goals. CONCLUSIONS: Individuals with AD, especially severe disease, face a considerable humanistic burden even while using treatment.

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.

Hand and foot dermatitis in patients referred for patch testing: Analysis of North American Contact Dermatitis Group Data, 2001-2018.

BACKGROUND: Dermatitis localized to hands (HD), feet (FD), or both hands and feet (HFD) has multiple etiologies, including atopic dermatitis, irritant contact dermatitis, and allergic contact dermatitis. Unfortunately, little is known about clinical differences between patients with HD, FD, and HFD. OBJECTIVE: To characterize differences in demographics, etiology, and patch testing results among patients presenting with HD, FD, or HFD referred for patch testing. METHODS: A retrospective analysis of patients patch tested by the North American Contact Dermatitis Group between 2001 and 2018. RESULTS: Of 43,677 patients who were patch tested, 22.8% had HD, 2.9% had FD, and 3.7% had HFD. Allergic and currently relevant patch test reactions to ≥1 North American Contact Dermatitis Group screening allergen occurred in similar proportions in all 3 study groups. However, HD (18.0%) had higher proportions of occupationally relevant reactions than HFD (8.9%) or FD (4.0%). Nickel and fragrance mix I were in the top 5 currently relevant allergens for HD, FD, and HFD. Other top allergens, as well as allergen sources, differed between HD, FD, and HFD. LIMITATIONS: No data on HD or FD morphology or distribution. CONCLUSION: HD, FD, and HFD have several differences with respect to patient characteristics, etiologies, and clinically relevant allergens.

Contact Allergy to Topical Medicaments, Part 2: Steroids, Immunomodulators, and Anesthetics, Oh My!

Topical drugs are used to treat a variety of cutaneous and noncutaneous conditions. Direct application to the skin can result in adverse cutaneous effects, including allergic contact dermatitis (ACD). In part 2 of this series on topical medicament ACD, we focus on corticosteroids, immunomodulators, and anesthetics.

Shoe Allergens: A Retrospective Analysis of Cross-sectional Data From the North American Contact Dermatitis Group, 2005-2018.

BACKGROUND: Shoe contact allergy can be difficult to diagnose and manage. OBJECTIVE: The aim of the study was to characterize demographics, clinical characteristics, patch test results, and occupational data for the North American Contact Dermatitis Group patients with shoe contact allergy. METHODS: This is a retrospective study of 33,661 patients, patch tested from 2005 to 2018, with a shoe source, foot as 1 of 3 sites of dermatitis, and final primary diagnosis of allergic contact dermatitis. RESULTS: Three hundred fifty-two patients met the inclusion criteria. They were more likely to be male (odds ratio = 3.36, confidence interval = 2.71-4.17) and less likely to be older than 40 years (odds ratio = 0.49, confidence interval = 0.40-0.61) compared with others with positive patch test reactions. The most common relevant North American Contact Dermatitis Group screening allergens were potassium dichromate (29.8%), p-tert-butylphenol formaldehyde resin (20.1%), thiuram mix (13.3%), mixed dialkyl thioureas (12.6%), and carba mix (12%). A total of 29.8% (105/352) had positive patch test reactions to supplemental allergens, and 12.2% (43/352) only had reactions to supplemental allergens. CONCLUSIONS: Shoe contact allergy was more common in younger and male patients. Potassium dichromate and p-tert-butylphenol formaldehyde resin were the top shoe allergens. Testing supplemental allergens, personal care products, and shoe components should be part of a comprehensive evaluation of suspected shoe contact allergy.

Medical adhesive allergens: Retrospective analysis of cross-sectional data from the North American Contact Dermatitis Group, 2001-2018.

BACKGROUND: Identification of allergens causing medical adhesive contact allergy is difficult. OBJECTIVE: To characterize the demographics, clinical characteristics, patch test results, and occupational data for North American Contact Dermatitis Group patients with medical adhesive contact allergy. METHODS: A retrospective study of 43,722 North American Contact Dermatitis Group patients patch tested from 2001 to 2018 with medical adhesive (tapes/bandaids/adhesive aids/suture glue) sources, positive patch test results, and final primary diagnoses of allergic contact dermatitis. RESULTS: In total, 313 (0.7%) patients met the inclusion criteria. Compared with other patients with final primary diagnoses of allergic contact dermatitis, patients with a medical adhesive allergy were less likely to be male (odds ratio, 0.58; 95% CI, 0.45-0.77) and/or aged >40 years (odds ratio, 0.76; 95% CI, 0.60-0.96). The most common North American Contact Dermatitis Group screening series allergens were colophony (80.7%), balsam of Peru (3.9%), 2-hydroxyethyl methacrylate (2.7%), and carba mix (2.7%). One-fourth of the patients (79/313, 25.2%) had positive patch test reactions to supplemental allergens/materials, and 54 (17.3%) of the 313 patients only had reactions to supplemental allergens/materials. LIMITATIONS: Results of comprehensive patch testing may be prone to referral population selection bias and may not be representative of the general dermatology population. CONCLUSION: Colophony was the most common allergen. Supplemental allergens and materials should be tested in the evaluation of a suspected medical adhesive contact allergy.

Plant Dermatitis: More Than Just Poison Ivy.

Plants can cause allergic contact dermatitis (ACD), mechanical irritant contact dermatitis, chemical irritant contact dermatitis, light-mediated dermatitis, and pseudophytodermatitis. Allergic contact dermatitis to chemicals in the Toxicodendron genus, which includes poison ivy, poison oak, and poison sumac, is the most common cause of plant ACD; however, many other plants, such as Compositae, Alstroemeriaceae, and Rutaceae plants also are important causes of dermatitis. In individuals with recurrent ACD from plants other than Toxicodendron, patch testing can be used to identify the source of allergic reactions to plant species. This article provides an overview of the various plant dermatoses, common culprits of plant dermatitis, and diagnostic and therapeutic options for plant dermatoses.

Update on Contact Dermatitis and Patch Testing in Patients With Skin of Color.

Allergic contact dermatitis (ACD) is a common dermatologic condition that presents with unique features in patients with skin of color (SOC). Additionally, the types of allergens that most frequently cause ACD vary in Black and White patients and are attributed to cultural differences between these 2 groups. Similarly, accurate patch testing in the SOC demographic requires an understanding of the morphologic differences between a positive patch test result in darker skin types compared to lighter skin types. Knowledge of these differences is essential to effectively diagnose and evaluate patients with ACD. There are identifiable disparities in duration of dermatitis affecting patients with ACD who live more than 50 miles from a patch testing center as well as those who live in impoverished areas. Dermatologists should be aware of these factors that impact patient care in appreciable ways so they are better prepared to serve these populations.

Contact Allergy in Canada Versus United States: Analysis of the North American Contact Dermatitis Group Data 2005-2016.

OBJECTIVE: The aim of the study was to describe the differences in contact allergy between the United States (US) and Canada. METHODS: This is a retrospective cross-sectional analysis of the North American Contact Dermatitis Group data from 2005 to 2016. Frequencies of demographics, clinical characteristics, positive reactions, trends, and occupations were calculated. RESULTS: A total of 28,640 patients underwent patch testing. At least 1 positive patch test was observed in 18,599 patients (US, 11,641 [66.5%]; Canada, 6958 [62.5%]). When comparing the 2 groups, US positive reactions were more likely to occur in male patients (odds ratio [OR] = 1.40, 95% confidence interval [CI] = 1.31-1.49), older than 40 years (OR = 1.30, 95% CI = 1.22-1.38), Black (OR = 2.67, 95% CI = 2.24-3.19) or Hispanic race (OR = 3.53, 95% CI = 2.61-4.78), and/or patients with scattered generalized dermatitis (OR = 1.96, 95% CI = 1.80-2.13). They were less likely to occur in patients with eczema (OR = 0.61, 95% CI = 0.57-0.65) and Asian race (OR = 0.50, 95% CI = 0.44-0.56). Nickel (US, 16.0%; Canada, 22.4%) and methylisothiazolinone (US, 13.4%; Canada, 11.0%) were the top allergens. The third most frequent was neomycin (US, 11.7%) and fragrance mix I (Canada, 10.2%). CONCLUSIONS: National differences in allergen prevalence and trends exist in North America.

Acetophenone Azine: The 2021 American Contact Dermatitis Society Allergen of the Year.

The American Contact Dermatitis Society chose acetophenone azine (AA) as the 2021 Allergen of the Year. Acetophenone azine is an emerging contact allergen that often is associated with the use of sports equipment and footwear. The pattern of dermatitis initially starts locally at the site of contact but can develop into a generalized dermatitis. Strong suspicion is necessary to diagnose AA allergy, and patch testing should be completed with AA and to potentially relevant sports equipment and/or shoes. Acetophenone azine is not yet available as a commercial patch-test preparation, but the optimal concentration is 0.1% in acetone or petrolatum. This column serves as an introduction to AA as an emerging allergen and highlights diagnosis, management, and patch testing for AA contact allergy.

Contact Dermatitis of the Hands: Is It Irritant or Allergic?

Hand contact dermatitis is common, and irritant contact dermatitis (ICD) is more likely than allergic contact dermatitis (ACD) in both occupational and nonoccupational settings. Irritant contact dermatitis can have acute and chronic presentations, and hand hygiene products can contribute. The most common relevant hand contact allergens in North American patch test populations are methylisothiazolinone (MI), nickel, formaldehyde, quaternium-15, and fragrance mix I. In health care workers, rubber accelerators often are relevant as potential contact allergens. Clinically, it can be difficult to differentiate between ICD and ACD, and patch testing often is required for definitive diagnosis. When patch testing is indicated, supplemental allergen series in addition to a screening series often are needed. Management of hand contact dermatitis requires gentle skin care, avoidance of irritants and/ or allergens when appropriate, and prescription topical or systemic therapies or phototherapy when indicated.

Contact allergy to nickel: still #1 after all these years.

Nickel is ubiquitous in our daily environment and remains the most common cause of contact allergy worldwide. Regulation of nickel release exists in Europe but unfortunately continues to be absent in the United States. Nickel contact allergy most often is associated with earrings and other jewelry; however, novel exposures to nickel through diet and electronic devices and other materials also occur. Once diagnosed, allergen avoidance is key for improvement of symptoms.

Contact dermatitis associated with preservatives: Retrospective analysis of North American Contact Dermatitis Group data, 1994 through 2016.

BACKGROUND: Preservatives are often necessary components of commercial products. Large-scale North American studies on preservative allergy are limited. OBJECTIVE: To evaluate demographics, positive patch test reactions (PPTRs), clinical relevance, and trends for preservatives tested by the North American Contact Dermatitis Group. METHODS: We conducted a retrospective cross-sectional analysis of North American Contact Dermatitis Group patch testing results of preservatives from 1994 through 2016. RESULTS: A total of 50,799 patients were tested; 11,338 (22.3%) had a PPTR to at least 1 preservative. The most frequent reactions were to methylisothiazolinone 0.2% aqueous (aq) (12.2%), formaldehyde 2% aq (7.8%), formaldehyde 1% aq (7.8%), quaternium-15 2% petrolatum (pet) (7.7%), and methyldibromo glutaronitrile/phenoxyethanol 2% pet (5.1%). Paraben mix 12% pet (1%), iodopropynyl butylcarbamate 0.1% pet (0.4%), benzyl alcohol 1% pet (0.3%), and phenoxyethanol 1% pet (0.2%) had the lowest PPTRs. Linear regression analysis of preservatives tested showed that only methylchloroisothiazolinone/methylisothiazolinone 0.01% aq (parameter estimate, 0.42; 95% CI, 0.17-0.66; P < .005) had a significant increase in PPTRs over time. LIMITATIONS: Collected variables are dependent on clinical judgment. Results may be prone to referral selection bias. CONCLUSIONS: This large North American study provides insight on preservative PPTRs and trends from 1994 through 2016.

Contact Allergy to Topical Medicaments, Part 1: A Double-edged Sword.

Topical drugs are used to treat a variety of cutaneous and noncutaneous conditions. Direct application to the skin can result in adverse cutaneous effects, including allergic contact dermatitis (ACD). In this article, we review medicament ACD with a focus on acne and rosacea medications, antimicrobials, antihistamines, and topical pain preparations.

Fragrance- and Botanical-Related Allergy and Associated Concomitant Reactions: A Retrospective Analysis of the North American Contact Dermatitis Group Data 2007-2016.

IMPORTANCE: When fragrance- and botanical-related (F/BR) allergy is identified, concomitant reaction (CR) frequencies can help direct avoidance recommendations. OBJECTIVE: This study aimed to determine the CR rates for F/BR allergens. DESIGN: A retrospective cross-sectional analysis of the North American Contact Dermatitis Group data 2007-2016 was conducted. Frequencies of demographics, positive reactions, strength of reactions, trends, and CR rates were calculated. RESULTS: A total of 5504 (22.7%) of 24,246 patients had F/BR allergic reactions. The F/BR-sensitive patients were more likely to be female, older than age 40 years, and White and have face, leg, or anal/genital dermatitis. Top allergens included fragrance mix I (FMI, 10.6%), Myroxylon pereirae (balsam of Peru [BOP], 8%), and fragrance mix II (FMII, 4.9%). There were increasing trends for FMI, FMII, cinnamic aldehyde, and Compositae mix and decreasing trends for BOP and propolis. When patients were positive to any F/BR allergen, they were likely to be positive to FMI, FMII, and BOP. Concomitant reactions were bidirectional between multiple fragrance allergens and propolis, colophony, and Compositae mix. CONCLUSIONS: Concomitant reactions were identified between fragrances, between fragrances and BR allergens, and between BR allergens and fragrances. If CRs of greater than 10% suggest cross-reactivity, then all patients with fragrance sensitivity should avoid BR allergens and vice versa.