Faculty Bibliography

INTRODUCTION/BACKGROUND:Atopic dermatitis (AD) is a chronic, relapsing disease that can start at any age and has a significant negative impact on quality of life, including a significant itch burden. Here we report the proportion of patients in a real-world study achieving a complete/almost complete resolution of itch, as measured by the Peak Pruritus Numeric Rating Scale (PP-NRS) and improvement in overall disease severity score (ODS), in patients aged ≥ 12 years with moderate-to-severe AD up to 3 years after commencing dupilumab treatment. METHODS:PROSE is an ongoing, prospective, observational, multicenter registry in the USA and Canada, collecting real-world data from patients aged ≥ 12 years with moderate-to-severe AD who initiated dupilumab in accordance with country-specific prescribing information. Assessments include patient-reported PP-NRS (range 0-10) and clinician-measured ODS score (range 0-4). RESULTS:A total of 857 patients were enrolled, of whom 42% were male and 6.4% were adolescents aged ≥ 12 to < 18 years. The mean [standard deviation (SD)] age was 40.1 (17.9) years, and the duration of AD was 17.4 (16.2) years. The subsequent mean (SD) duration of dupilumab treatment was 23.1 (13.7) months. The proportion of patients achieving complete/almost complete itch resolution (PP-NRS score of 0 or 1) improved consistently over time, from 2.7% (17/622) of patients at baseline to 56.3% (58/103) at 3 years. Additionally, by year 3, 65.1% (54/83) of patients had an ODS score of no/minimal disease (score of 0 or 1), versus 2.2% (19/852) at baseline. CONCLUSIONS:In this real-world setting of the PROSE registry, adult and adolescent patients with moderate-to-severe AD followed up for up to 3 years after the initiation of dupilumab treatment experienced sustained and substantial improvement in pruritus and ODS, using the stringent endpoints of PP-NRS 0 or 1 and ODS 0 or 1. TRIAL REGISTRATION/BACKGROUND:ClinicalTrials.gov identifier: NCT03428646.

Patch testing is the reference standard for the diagnosis of allergic contact dermatitis. Identification and avoidance of culprit allergens are essential in the treatment of this disease. Each year, new allergens are identified as emerging or important. The authors discuss allergens that are common, enduring, emergent, incompletely recognized, and controversial for the practicing allergist and dermatologist. This Clinical Management Review will encompass a review of fragrances, preservatives, rubber, acrylates, metals, and medications; their common sources of exposure; controversies in diagnosis and patch testing; management and how to avoid those allergens. This review will also include practical aspects of diagnosis and management and will provide resources that can be used as guidance for physicians and patients on nickel, methylchloroisothiazolinone/methylisothiazolinone, and fragrance, the most common allergens positive on patch testing.

BACKGROUND:Angioedema (AE) manifests with intermittent, localized, self-limiting swelling of the subcutaneous and/or submucosal tissue. AE is heterogeneous, can be hereditary or acquired, may occur only once or be recurrent, may exhibit wheals or not, and may be due to mast cell mediators, bradykinin, or other mechanisms. Several different taxonomic systems are currently used, making it difficult to compare the results of studies, develop multicenter collaboration, and harmonize AE treatment. OBJECTIVE:We developed a consensus on the definition, acronyms, nomenclature, and classification of AE (DANCE). METHODS:The initiative involved 91 experts from 35 countries and was endorsed by 53 scientific and medical societies, and patient organizations. A consensus was reached by online discussion and voting using the Delphi process over a period of 16 months (June 2021 to November 2022). RESULTS:The DANCE initiative resulted in an international consensus on the definition, classification, and terminology of AE. The new consensus classification features 5 types and endotypes of AE and a harmonized vocabulary of abbreviations/acronyms. CONCLUSION/CONCLUSIONS:The DANCE classification complements current clinical guidelines and expert consensus recommendations on the diagnostic assessment and treatment of AE. DANCE does not replace current clinical guidelines, and expert consensus algorithms and should not be misconstrued in a way that affects reimbursement of medicines prescribed by physicians using sound clinical judgment. We anticipate that this new AE taxonomy and nomenclature will harmonize and facilitate AE research and clinical studies, thereby improving patient care.

BACKGROUND:Response to abrocitinib treatment for moderate-to-severe atopic dermatitis (AD) has not been evaluated across racial and ethnic subpopulations. OBJECTIVE:To assess the efficacy and safety of abrocitinib on the basis of patient race, ethnicity, and Fitzpatrick skin type (FST). METHODS:Data were pooled post hoc from patients treated with abrocitinib 200 mg, 100 mg, or placebo in 3 monotherapy trials (NCT02780167, NCT03349060, and NCT03575871). Race and ethnicity were self-reported; FST was determined by study investigators. Evaluations through Week 12 include the following: (1) Investigator's Global Assessment of clear or almost-clear skin; (2) greater than or equal to 75% improvement in Eczema Area and Severity Index or SCORing AD; (3) a greater-than-or-equal-to 4-point improvement in Peak Pruritus Numerical Rating Scale score; (4) least squares mean changes in Dermatology Life Quality Index and Patient-Oriented Eczema Measure scores; and (5) treatment-emergent adverse events. RESULTS:The sample comprised 628 White, 204 Asian, and 83 Black patients; 37 were Hispanic or Latino; 624 had FST I to III and 320 had FST IV to VI. Treatment with either abrocitinib dose was associated with greater proportions of patients achieving Investigator's Global Assessment of clear or almost-clear skin, ≥ 75% improvement in Eczema Area and Severity Index, ≥ 75% improvement in SCORing AD, and a ≥ 4-point improvement in Peak Pruritus Numerical Rating Scale, or greater score changes from baseline in Dermatology Life Quality Index and Patient-Oriented Eczema Measure vs placebo regardless of race, ethnicity, or FST. Dose-response was most prominent in White patients. In Black patients, the effects of the 2 doses were similar. Treatment-emergent adverse events were more common in White and Black than in Asian patients. CONCLUSION:Abrocitinib was more efficacious than placebo across the racial and ethnic groups and ranges of phototypes analyzed. Studies with increased representation of populations of color are warranted to elucidate potential variations in response across diverse populations. TRIAL REGISTRATION:Clinicaltrials.gov Identifier: NCT02780167 (phase 2b), NCT03349060 (phase 3 MONO-1), and NCT03575871 (phase 3 MONO-2).

BACKGROUND:Abrocitinib, an oral, once-daily Janus kinase 1-selective inhibitor, improved itch severity, sleep, and work productivity versus placebo in patients with moderate-to-severe atopic dermatitis. OBJECTIVE:The aim of this study was to investigate relationships among itch, sleep, and work productivity in the phase III JADE MONO-2 clinical trial. METHODS:A repeated-measures longitudinal model was used to examine relationships between itch (using the Peak Pruritus Numerical Rating Scale [PP-NRS] or Nighttime Itch Scale [NTIS]) and sleep disturbance/loss (using the Patient-Oriented Eczema Measure sleep item and SCORing AD Sleep Loss Visual Analog Scale) and, separately, between itch and work productivity (using the Work Productivity and Activity Impairment-Atopic Dermatitis Version 2.0 questionnaire). Mediation modelling was used to investigate the effect of treatment (abrocitinib vs placebo) on work impairment via improvements in itch and sleep. RESULTS:The relationships between itch/sleep and itch/work productivity were approximately linear. PP-NRS scores of 0, 4-6, and 10 were associated with 0 days, 3-4 days, and 7 days per week of disturbed sleep, respectively. PP-NRS or NTIS scores of 0-1, 4-5, and 10 were associated with 0-10%, 20-30%, and >50% overall work impairment, respectively. Seventy-five percent of the effect of abrocitinib on reducing work impairment was indirectly mediated by improvement in itch, followed by sleep. CONCLUSION/CONCLUSIONS:These results quantitatively demonstrate that reducing itch severity is associated with improvements in sleep and work productivity. Empirical evidence for the mechanism of action of abrocitinib showed that itch severity is improved, which reduces sleep loss/sleep disruption and, in turn, improves work productivity. CLINICAL TRIAL REGISTRATION/BACKGROUND:NCT03575871.

Atopic dermatitis (AD) and food allergies are more prevalent and more severe in people with skin of color than White individuals. The American College of Allergy, Asthma, and Immunology (ACAAI) sought to understand the effects of racial disparities among patients with skin of color with AD and food allergies. The ACAAI surveyed its members (N = 200 completed), conducted interviews with health care providers and advocacy leaders, and hosted a roundtable to explore the challenges of diagnosis and management of AD and food allergies in people with skin of color and to discuss potential solutions. Most of the survey respondents (68%) agreed that racial disparities make it difficult for people with skin of color to receive adequate treatment for AD and food allergies. The interviews and roundtable identified access to care, burden of costs, policies and infrastructure that limit access to safe foods and patient education, and inadequate research involving people with skin of color as obstacles to care. Proposed solutions included identifying ways to recruit more people with skin of color into clinical trials and medical school, educating health care providers about diagnosis and treating AD and food allergy in people with skin of color, improving access to safe foods, creating and disseminating culturally appropriate materials for patients, and working toward longer appointment times for patients who need them. Challenges in AD and food allergy in persons with skin of color were identified by the ACAAI members. Solutions to these challenges were proposed to inspire actions to mitigate racial disparities in AD and food allergy.

Rationale: Carrying a penicillin allergy label is associated with increased healthcare costs and adverse events. De-labeling a penicillin allergy can optimize antimicrobial stewardship and improve patient care.
Method(s): We performed an IRB-approved retrospective study of patients over 11 years-old, who were de-labeled of penicillin allergy (negative skin testing and aminopenicillin oral challenge) in our clinic between May 2019 and May 2022. Patients had their penicillin allergy removed from our electronic medical record (EMR) and were given a wallet card denoting results. A letter with fax confirmation of receipt was sent to both primary care physician and pharmacy. EMR review and phone interviews with patients and pharmacies were subsequently conducted to determine penicillin allergy status and antibiotic prescribing patterns.
Result(s): A total of 78 charts were reviewed: 68 underwent phone interviews, 9 were lost to follow up, and 1 was deceased. From these charts, 77 (99%) remained de-labeled in our EMR, whereas 24 (31%) had an active penicillin allergy listed in their pharmacy. Out of 68 patients interviewed, 66 (97%) recalled a negative penicillin allergy result, 30 (44%) took penicillins since de-labeling, 31 (46%) were not prescribed penicillins, 4 (6%) avoided penicillins, while 3 (4%) reported unknown antibiotic use.
Conclusion(s): This study demonstrates that our pencillin de-labeling protocol is effective in maintaining a non-allergic status and allowing for subsequent penicillin administration. However, the discrepancy in allergy records between our EMR and patients' pharmacies exemplifies the need to identify barriers in universally de-labeling patients.
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