Publications by authors named "Jonathan I Silverberg"

380 Publications

Lack of association between atopic dermatitis severity and worsening during pregnancy: a cross-sectional study.

J Am Acad Dermatol 2021 Oct 7. Epub 2021 Oct 7.

Department of Dermatology, George Washington School of Medicine, Washington, DC 20052. Electronic address:

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http://dx.doi.org/10.1016/j.jaad.2021.09.066DOI Listing
October 2021

Association of atopic dermatitis severity with menstrual worsening of disease in women: a cross-sectional study.

J Eur Acad Dermatol Venereol 2021 Oct 8. Epub 2021 Oct 8.

Department of Dermatology, George Washington School of Medicine, Washington, DC, 20052, USA.

Atopic dermatitis (AD) has many triggers[1, 2]. Previous studies found conflicting results about whether females experience menstrual worsening of AD.[3, 4] We explored associations of AD severity, AD worsening during menstruation and premenstrual syndrome (PMS). The study was approved by the Northwestern University institutional review board. Females (≥18 years) from the Northwestern Medicine eczema clinic who met Hanifin-Rajka AD criteria were serially recruited and completed self-administered electronic questionnaires (demographics, AD severity, history of PMS and AD worsening with menstruation) prior to encounters between 2014-2019 (>99% participation).
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http://dx.doi.org/10.1111/jdv.17730DOI Listing
October 2021

Dupilumab Provides Rapid and Sustained Clinically Meaningful Responses in Adults with Moderate-to-severe Atopic Dermatitis.

Acta Derm Venereol 2021 Oct 7. Epub 2021 Oct 7.

George Washington University School of Medicine of Health Sciences, Ross Hall, 300 Eye Street NW, Washington 20037, DC, USA.

Optimal management of atopic dermatitis requires a comprehensive assessment of response to treatment in order to inform therapeutic decisions. In a real-world setting, successful response to atopic dermatitis treatment is measured by sustained improvements in signs, symptoms, and quality of life. Post-hoc analyses of a 1-year, randomized, double-blinded, placebo-controlled trial (NCT02260986) of dupilumab with concomitant topical corticosteroid in 421 adults with moderate-to-severe atopic dermatitis (of whom 315/106 received placebo/dupilumab) was performed to assess the proportion of responders to dupilumab through a multidimensional composite endpoint. At 6-months, 80.2% of dupilumab-treated vs 40.0% placebo patients (p < 0.0001) achieved improvement in signs (Eczema Area and Severity ≤ 7), symptoms (worst itch score ≤ 4) or quality of life (Dermatology Life Quality Index ≤5), representative of minimal/clear atopic dermatitis. All 3 endpoints, indicative of no/minimal atopic dermatitis, were achieved by 44.3% of dupilumab-treated vs 10.2% placebo patients (p < 0.0001) and sustained through one year. Dupilumab treatment provided sustained clinically meaningful improvement in signs, symptoms and quality of life in adults with moderate-to-severe atopic dermatitis.
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http://dx.doi.org/10.2340/actadv.v101.307DOI Listing
October 2021

Olfactory dysfunction in children and adults post-COVID-19 infection in Brooklyn, New York.

Acta Paediatr 2021 Oct 1. Epub 2021 Oct 1.

Division of Infectious Diseases, Department of Pediatrics, State University of New York Downstate Medical Center, Brooklyn, NY, USA.

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http://dx.doi.org/10.1111/apa.16134DOI Listing
October 2021

Financial burden and impact of atopic dermatitis out-of-pocket healthcare expenses among black individuals in the United States.

Arch Dermatol Res 2021 Sep 27. Epub 2021 Sep 27.

Department of Dermatology, The George Washington University School of Medicine and Health Sciences, Washington, DC, 20037, USA.

Black race is associated with increased atopic dermatitis (AD) severity and healthcare resource utilization. However, the burden of out-of-pocket (OOP) expenses among black individuals with AD is not well understood. We sought to characterize the categories and impact of OOP healthcare expenses associated with AD management among black individuals. A 25-question voluntary online survey was administered to National Eczema Association members (N = 113,502). Inclusion criteria (US residents age ≥ 18 years; self-report of AD or primary caregivers of individuals with AD) was met by 77.3% (1118/1447) of respondents. Black individuals with AD were younger, had lower household income, Medicaid, urban residence, poor AD control and frequent skin infections (P ≤ 0.02). Blacks vs. non-blacks reported more OOP costs for prescription medications covered (74.2% vs. 63.6%, P = 0.04) and not covered (65.1% vs. 46.5%, P = 0.0004) by insurance, emergency room visits (22.1% vs. 11.8%, P = 0.005), and outpatient laboratory testing (33.3% vs. 21.8%, P = 0.01). Black race was associated with increased household financial impact from OOP expenses (P = 0.0009), and predictors of financial impact included minimally controlled AD (adjusted OR [95% CI] 13.88 [1.63-117.96], P = 0.02), systemic therapy (4.34 [1.63-11.54], 0.003), > $200 monthly OOP expenses (14.28 [3.42-59.60], P = 0.0003), and Medicaid (4.02 [1.15-14.07], P = 0.03). Blacks with Medicaid had higher odds of harmful financial impact (3.32 [1.77-6.24], P = 0.0002) than those of black race (1.81 [1.04-3.15], P = 0.04) or with Medicaid (1.39 [1.02-1.88], P = 0.04) alone. Black race is associated with increased OOP costs for AD and significant household financial impact. Targeted interventions are needed to address financial disparities in AD.
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http://dx.doi.org/10.1007/s00403-021-02282-3DOI Listing
September 2021

Patch Testing to Ethylhexylglycerin: The North American Contact Dermatitis Group Experience, 2013-2018.

Dermatitis 2021 Sep 27. Epub 2021 Sep 27.

From the Department of Dermatology, Park Nicollet Health Services Department of Dermatology, University of Minnesota Department of Dermatology, Minneapolis Veterans Affairs Medical Center University of Minnesota Medical School, Minneapolis Department of Dermatology, University of California San Francisco Department of Dermatology, Cleveland Clinic, OH Department of Dermatology, Dartmouth-Hitchcock Medical Center, Lebanon, NH Department of Dermatology, Duke University Medical Center, Durham, NC Department of Dermatology, The George Washington University School of Medicine and Health Sciences, Washington, DC Department of Dermatology, Columbia University Irving Medical School, New York, NY Associates in Dermatology, Fort Myers, FL Division of Dermatology, Sunnybrook Health Sciences Centre, University of Toronto, Ontario, Canada Department of Dermatology, University of Wisconsin School of Medicine and Public Health, Madison Division of Dermatology, Montreal General Hospital, McGill University, Quebec, Canada Division of Dermatology, University of Louisville, KY Division of Dermatology, University of Ottawa, Ontario, Canada Department of Dermatology, Keck School of Medicine, Los Angeles, CA.

Background: Ethylhexylglycerin (EHG) is a recently recognized contact allergen.

Objective: The aims of the study were to characterize individuals with positive patch test reactions to EHG and to analyze reaction strength, clinical relevance, and allergen sources.

Methods: This study was a retrospective analysis of the patients patch tested to EHG (5% petrolatum) by the North American Contact Dermatitis Group (2013-2018).

Results: Of 15,560 patients tested to EHG, 39 (0.25%) had positive (final interpretation of "allergic") reactions. Most were female (71.8%) and/or older than 40 years (76.9%). There were no statistically significant differences between age, sex, or atopic history when compared with EHG-negative patients. The most common anatomic sites of dermatitis were the face (28.2%) and scattered generalized distribution (25.6%). Most EHG-positive reactions were + (35.9%) or ++ (33.3%). Current clinical relevance was high (79.5%); none, however, were related to occupation. Personal care products were the most common source of exposure to EHG (59.0%).

Conclusions: Ethylhexylglycerin is a rare contact allergen; the positive frequency of 0.25% is similar to other low allergenic preservatives including parabens, benzyl alcohol, and phenoxyethanol. The patch test concentration of 5.0% seems to be nonirritating. Although relatively uncommon, EHG reactions were usually clinically relevant (79.5%), often because of moisturizers/lotions/creams.
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http://dx.doi.org/10.1097/DER.0000000000000709DOI Listing
September 2021

Iatrogenic Burden of Atopic Dermatitis.

Dermatitis 2021 Sep 27. Epub 2021 Sep 27.

From the Department of Dermatology, Feinberg School of Medicine at Northwestern University, Chicago, IL Department of Dermatology, The George Washington University School of Medicine and Health Sciences, Washington, DC.

Abstract: The management required for atopic dermatitis (AD) may worsen patient burden, thereby resulting in iatrogenic burden, that is, morbidity caused by medical treatment. We sought to describe the iatrogenic burden of AD and conducted a narrative review of key areas that clinicians can address to minimize it. Clinicians should think strategically about itch trigger avoidance, encourage slow incorporation of lifestyle changes, and emphasize step-up therapy when avoidance becomes too burdensome. Out-of-pocket treatment costs should be incorporated into shared decision making to balance affordability, preference, efficacy, and safety. Polypharmacy should be minimized by eliminating ineffective, nonevidence-based, and redundant therapies while appropriately stepping up to advanced therapy. Clinicians should take adequate time to communicate, the impact of AD on quality of life, and incorporate evidence-based guidelines. The multidimensional nature of AD requires a dynamic approach. Future guidelines should incorporate step-up, step-down, and maintenance approaches to reduce treatment burden and improve quality of life.
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http://dx.doi.org/10.1097/DER.0000000000000799DOI Listing
September 2021

Atopic dermatitis is not associated with SARS-CoV-2 outcomes.

Arch Dermatol Res 2021 Sep 17. Epub 2021 Sep 17.

Department of Dermatology, George Washington School of Medicine, Washington, DC, 20052, USA.

Atopic dermatitis is characterized by immune dysregulation, which may predispose toward worse COVID-19 outcomes. We conducted a retrospective cohort study to investigate the relationship of atopic dermatitis with COVID-19 symptom severity, hospitalization, length of hospital stay, requirement for oxygen therapy, long-term morbidity and mortality. Multivariable logistic regression models were constructed to examine the impact of atopic dermatitis (independent variable) on COVID-19 symptom severity, hospitalization, length of hospital stay, requirement for oxygen therapy, long-term morbidity and mortality (dependent variables). SARS-CoV-2 positive adult patients with diagnosed AD had similar odds of hospitalization (adjusted odds ratio [95% confidence interval]: 0.51 [0.20-1.35]), acute level of care at initial medical care (0.67 [0.35-1.30]), severe-critical SARS-CoV-2 (0.82 [0.29-2.30]), requirement of supplemental non-mechanical oxygen therapy (1.33 [0.50-3.58]), extended hospital stay (2.24 [0.36-13.85]), lingering COVID-19 symptoms (0.58 [0.06-5.31]) and COVID-19 death (0.002 [< 0.001- > 999]) compared to patients without AD. Our findings suggest AD is not an independent risk factor for COVID-19 severity or complications.
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http://dx.doi.org/10.1007/s00403-021-02276-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8447890PMC
September 2021

Impact and Associations of Atopic Dermatitis Out-of-Pocket Health Care Expenses in the United States.

Dermatitis 2021 Sep 27. Epub 2021 Sep 27.

From the Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, IL National Eczema Association, Novato, CA Department of Dermatology, George Washington University School of Medicine and Health Sciences, Washington, DC.

Background: Atopic dermatitis (AD) is associated with substantial financial cost, including increased out-of-pocket (OOP) expenses. Associations and impact of OOP costs are poorly understood.

Objective: The aim of the study was to characterize the impact and associations of OOP health care expenses for AD.

Methods: A 25-question online survey was administered to National Eczema Association members (N = 113,502). Inclusion criteria (US residents aged ≥18 years; self-reported AD or primary caregiver of individual with AD) were met by 77.3% (1118 of 1447).

Results: Respondents with monthly OOP expenses greater than $200 were more likely to have increased AD severity, flares, health care provider visits, prescription polypharmacy, use of step-up therapy, frequent skin infections, and poorer disease control (P < 0.005 for all). Respondents with OOP yearly expenditures greater than $1000 had similar associations and additionally increased rates of comorbid asthma, allergic rhinitis, and anxiety/depression (P < 0.005 for all). A total of 64.6% (n = 624) reported harmful household financial impact of OOP expenses. Predictors of harmful impact included severe AD (adjusted odds ratio [95% confidence interval], 2.62 [1.11-6.19], P = 0.04), comorbid asthma (1.42 [1.07-1.87], P = 0.03), 5 health care provider visits or more in a year (2.80 [1.62-4.82], P = 0.0007), greater than $200 OOP monthly expenditures (2.16 [1.45-3.22], 0.0006), and $1000 annual OOP expenditures or more (4.56 [3.31-6.27], P < 0.0001).

Conclusions: Out-of-pocket expenses for AD significantly impact household finances. Clinical interventions are needed to minimize OOP expenses while optimizing care outcomes.
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http://dx.doi.org/10.1097/DER.0000000000000795DOI Listing
September 2021

Association of obesity in early childhood with atopic dermatitis in late childhood and adolescence.

J Am Acad Dermatol 2021 Sep 3. Epub 2021 Sep 3.

Department of Dermatology, George Washington University School of Medicine and Health Sciences, DC; Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, IL. Electronic address:

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http://dx.doi.org/10.1016/j.jaad.2021.08.048DOI Listing
September 2021

Abrocitinib induction, randomized withdrawal, and retreatment in patients with moderate-to-severe atopic dermatitis: Results from the JAK1 Atopic Dermatitis Efficacy and Safety (JADE) REGIMEN phase 3 trial.

J Am Acad Dermatol 2021 Aug 17. Epub 2021 Aug 17.

Pfizer Inc, New York, New York. Electronic address:

Background: The heterogeneous course of moderate-to-severe atopic dermatitis necessitates treatment flexibility.

Objective: We evaluated the maintenance of abrocitinib-induced response with continuous abrocitinib treatment, dose reduction or withdrawal, and response to treatment reintroduction following flare (JAK1 Atopic Dermatitis Efficacy and Safety [JADE] REGIMEN: National Clinical Trial 03627767).

Methods: Patients with moderate-to-severe atopic dermatitis responding to open-label abrocitinib 200 mg monotherapy for 12 weeks were randomly assigned in a 1:1:1 ratio to blinded abrocitinib (200 or 100 mg) or placebo for 40 weeks. Patients experiencing flare received rescue treatment (abrocitinib 200 mg plus topical therapy).

Results: Of 1233 patients, 798 responders to induction (64.7%) were randomly assigned. The flare probability during maintenance was 18.9%, 42.6%, and 80.9% with abrocitinib 200 mg, abrocitinib 100 mg, and placebo, respectively. Among patients with flare in the abrocitinib 200 mg, abrocitinib 100 mg, and placebo groups, 36.6%, 58.8%, and 81.6% regained investigator global assessment 0/1 response, respectively, and 55.0%, 74.5%, and 91.8% regained eczema area and severity index response, respectively, with rescue treatment. During maintenance, 63.2% and 54.0% of patients receiving abrocitinib 200 and 100 mg, respectively, experienced adverse events.

Limitations: The definition of protocol-defined flare was not established, limiting the generalizability of findings.

Conclusion: Induction treatment with abrocitinib was effective; most responders continuing abrocitinib did not flare. Rescue treatment with abrocitinib plus topical therapy effectively recaptured response.
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http://dx.doi.org/10.1016/j.jaad.2021.05.075DOI Listing
August 2021

Integrated Safety Analysis of Abrocitinib for the Treatment of Moderate-to-Severe Atopic Dermatitis From the Phase II and Phase III Clinical Trial Program.

Am J Clin Dermatol 2021 Sep 18;22(5):693-707. Epub 2021 Aug 18.

Pfizer Inc., Collegeville, PA, USA.

Background: Pivotal phase III studies demonstrated that abrocitinib, an oral, once-daily, JAK1-selective inhibitor, is effective treatment for moderate-to-severe atopic dermatitis (AD) as monotherapy and in combination with topical therapy.

Objective: The aim of this study was to evaluate the long-term safety of abrocitinib 200 mg and 100 mg in an integrated analysis of a phase IIb study, four phase III studies, and one long-term extension study.

Methods: Two cohorts were analyzed: a placebo-controlled cohort from 12- to 16-week studies and an all-abrocitinib cohort including patients who received one or more abrocitinib doses. Adverse events (AEs) of interest and laboratory data are reported.

Results: Total exposure in the all-abrocitinib cohort (n = 2856) was 1614 patient-years (PY); exposure was ≥ 24 weeks in 1248 patients and ≥ 48 weeks in 606 (maximum 108 weeks). In the placebo-controlled cohort (n = 1540), dose-related AEs (200 mg, 100 mg, placebo) were nausea (14.6%, 6.1%, 2.0%), headache (7.8%, 5.9%, 3.5%), and acne (4.7%, 1.6%, 0%). Platelet count was reduced transiently in a dose-dependent manner; 2/2718 patients (200-mg group) had confirmed platelet counts of < 50 × 10/mm at week 4. Incidence rates (IRs) were 2.33/100PY and 2.65/100 PY for serious infection, 4.34/100PY and 2.04/100PY for herpes zoster, and 11.83/100PY and 8.73/100PY for herpes simplex in the 200-mg and 100-mg groups, respectively. IRs for nonmelanoma skin cancer, other malignancies, and major adverse cardiovascular events were < 0.5/100PY for both doses. Five venous thromboembolism events occurred (IR 0.30/100PY), all in the 200-mg group. There were three deaths due to gastric carcinoma (diagnosed at day 43), sudden death, and COVID-19.

Conclusion: Abrocitinib, with proper patient and dose selection, has a manageable tolerability and longer-term safety profile appropriate for long-term use in patients with moderate-to-severe AD.

Trial Registries: ClinicalTrials.gov: NCT02780167, NCT03349060, NCT03575871, NCT03720470, NCT03627767, NCT03422822.
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http://dx.doi.org/10.1007/s40257-021-00618-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8370859PMC
September 2021

Patch Test Reactions Associated With Topical Medications: A Retrospective Analysis of the North American Contact Dermatitis Group Data (2001-2018).

Dermatitis 2021 Sep 1. Epub 2021 Sep 1.

From the Department of Dermatology, Park Nicollet Health Services Department of Dermatology, University of Minnesota Department of Dermatology, Minneapolis Veterans Affairs Medical Center University of Minnesota Medical School, Minneapolis Division of Dermatology, Sunnybrook Health Sciences Centre, University of Toronto, Ontario, Canada Department of Dermatology, Cleveland Clinic, OH Department of Dermatology, Duke University Medical Center, Durham, NC Associates in Dermatology, Fort Myers, FL Department of Dermatology, University of California San Francisco Department of Dermatology, Columbia University Irving Medical School, New York, NY Department of Dermatology, The George Washington University School of Medicine and Health Sciences, Washington, DC Division of Dermatology, CHU de Québec, Laval University, Canada Department of Dermatology, University of Wisconsin School of Medicine and Public Health, Madison Department of Dermatology, Dartmouth-Hitchcock Medical Center, Lebanon, NH Division of Dermatology, University of Louisville, KY Division of Dermatology, Montreal General Hospital, McGill University, Quebec, Canada Division of Dermatology, University of Ottawa, Ontario, Canada Department of Dermatology, University of Colorado, Boulder Department of Dermatology, Keck School of Medicine, Los Angeles, CA.

Background/objectives: Topical medications may lead to allergic contact dermatitis. This study characterized positive patch test reactions associated with medications in patients evaluated by the North American Contact Dermatitis Group (NACDG).

Methods: This study is a retrospective analysis of the NACDG data (2001-2018). Patients with at least 1 positive patch test reaction associated with a medication source were included. Allergens, reaction characteristics, clinical relevance, and source details were tabulated.

Results: Of 43,722 patients, 6374 (14.6%) had positive allergic patch test reactions associated with 1 or more topical medication sources. Patients with versus without allergic reactions to medications were more likely to be older than 40 years (P < 0.0001) and/or have primary sites of dermatitis on the legs, anal/genital region, or trunk (P < 0.0001). There were 8787 reactions to NACDG allergens; the most common were neomycin (29.4%), bacitracin (29.1%), propylene glycol 100% (10.6%), tixocortol-17-pivalate (10.0%), lidocaine (7.9%), budesonide (4.9%), and dibucaine (4.4%). Propylene glycol 100% was the most common inactive ingredient (10.6%). Current relevance was present in 61.0%. A total of 6.5% of the individuals with medication allergy would have had 1 or more positive patch test reactions missed if only tested to the NACDG screening series.

Conclusions: Positive patch test reactions associated with topical medications were common (14.6%), and most were clinically relevant. Patients with topical medication allergy were twice as likely to have anal/genital involvement. Active ingredients, especially neomycin, bacitracin, and tixocortol-17-pivalate, were frequent culprits.
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http://dx.doi.org/10.1097/DER.0000000000000777DOI Listing
September 2021

Upadacitinib plus topical corticosteroids in atopic dermatitis: Week 52 AD Up study results.

J Allergy Clin Immunol 2021 Aug 14. Epub 2021 Aug 14.

Translational Research in Inflammatory Skin Diseases, Institute for Health Services Research in Dermatology and Nursing, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Background: Primary (week 16) results from the ongoing phase 3, double-blind AD Up study (NCT03568318) demonstrate a positive benefit-risk profile for upadacitinib + topical corticosteroid (TCS) in patients with moderate-to-severe atopic dermatitis.

Objective: We evaluated the efficacy and safety of upadacitinib + TCS through 52 weeks.

Methods: Patients aged 12 to 75 years with chronic moderate-to-severe atopic dermatitis (≥10% of body surface area affected, Eczema Area and Severity Index [EASI] ≥16, Validated Investigator's Global Assessment for atopic dermatitis [vIGA-AD] ≥3, and Worst Pruritus Numerical Rating Scale [WP-NRS] score ≥4) were randomized 1:1:1 to once-daily upadacitinib 15 mg + TCS, upadacitinib 30 mg + TCS, or placebo (PBO) + TCS (rerandomized at week 16 to upadacitinib + TCS). Safety and efficacy, including proportion of patients experiencing ≥75% improvement in EASI (EASI-75), vIGA-AD of clear/almost clear with improvement ≥2 grades (vIGA-AD 0/1), and WP-NRS improvement ≥4, were assessed through week 52. Missing data were primarily handled by nonresponse imputation incorporating multiple imputation for missing values due to coronavirus disease 2019 (COVID-19).

Results: Of 901 patients, 300 were randomized to upadacitinib 15 mg + TCS, 297 to upadacitinib 30 mg + TCS, and 304 to PBO + TCS. For all end points, efficacy for upadacitinib 15 mg + TCS and upadacitinib 30 mg + TCS at week 16 was maintained through week 52. At week 52, the proportions of patients treated with upadacitinib 15 mg + TCS and upadacitinib 30 mg + TCS who experienced EASI-75 were 50.8% and 69.0%, respectively; 33.5% and 45.2%, respectively, experienced vIGA-AD 0/1; and 45.3% and 57.5%, respectively, experienced WP-NRS improvement ≥4. Upadacitinib + TCS was well tolerated through 52 weeks; no new important safety risks beyond the current label were observed. No deaths were reported; major adverse cardiovascular events and venous thromboembolic events were infrequent (≤0.2/100 patient-years).

Conclusions: Results through 52 weeks demonstrate long-term maintenance of efficacy and a favorable safety profile of upadacitinib + TCS in patients with moderate-to-severe AD.
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http://dx.doi.org/10.1016/j.jaci.2021.07.036DOI Listing
August 2021

Patch testing with ammonium persulfate: The North American Contact Dermatitis Group Experience, 2015-2018.

J Am Acad Dermatol 2021 Aug 11. Epub 2021 Aug 11.

Department of Dermatology, University of Colorado, Boulder, Colorado.

Background: Ammonium persulfate (APS), an oxidizing agent used in hair products, manufacturing, and pool/spa water, can cause skin reactions, including allergic contact dermatitis.

Objective: To characterize positive patch test reactions to APS (2.5% petrolatum).

Methods: Retrospective analysis of patients tested to the North American Contact Dermatitis Group screening series from 2015 to 2018.

Results: Of 10,526 patients, 193 (1.8%) had positive patch test reactions to APS. Compared with APS-negative patients, APS-positive patients were significantly more likely to be male (43.2% vs 28.0%; P < .0001); have primary hand dermatitis (30.2% vs 22.0%; P = .0064), scattered generalized dermatitis (25.5% vs 17.9%; P = .0064), or trunk dermatitis (8.9% vs 4.9%; P = .0123); and have dermatitis that is occupationally related (22.2% vs 10.9%; P < .0001). More than half of the APS-positive reactions were currently relevant (57.0%); 19 (9.8%) were related to occupation, especially hairdressers (68.4%). Swimming pools/spas (23.3%) and hair care products (19.2%) were the most common sources of APS.

Limitations: Immediate reactions and follow-up testing were not captured.

Conclusion: The proportion of patients positive to APS was 1.8%. APS positivity was significantly associated with male sex and hand dermatitis. Swimming pool/spa chemicals were important sources of APS exposure.
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http://dx.doi.org/10.1016/j.jaad.2021.08.005DOI Listing
August 2021

Differences in Psychometric Properties of Clinician- and Patient-Reported Outcome Measures for Atopic Dermatitis by Race and Skin Tone: A Systematic Review.

J Invest Dermatol 2021 Aug 2. Epub 2021 Aug 2.

Department of Dermatology, School of Medicine and Health Sciences, George Washington University, Washington, District of Columbia, USA. Electronic address:

The psychometric validity and reliability of widely used atopic dermatitis (AD) outcome measures across different races and ethnicities are unclear. We describe the rates of reporting race, ethnicity, and skin tone in studies testing the psychometric properties of AD outcome measures and compare the psychometric analyses across race, ethnicity, and skin tone. We systematically reviewed MEDLINE and EMBASE for studies reporting psychometric properties of clinician-reported or patient-reported outcome measures in AD (International Prospective Register of Systematic Reviews: CRD42021239614). Overall, 16,100 nonduplicate articles were screened; 165 met inclusion criteria. Race and/or ethnicity were reported in 55 (33.3%) studies; of those, race was assessed by self-report in 10 studies (6.1%) or was unspecified in 45 (27.3%). A total of 16 studies (9.7%) evaluated psychometric property differences by race, and only five (4.4%) of those did not recognize it as a limitation. Properties assessed across race, ethnicity, or skin tone were differential item functioning, convergent validity feasibility, inter-rater reliability, intrarater reliability, test‒retest reliability, and known-groups validity. Multiple instruments demonstrated performance differences across ethnoracial groups. This review highlights the paucity of race/ethnicity consideration for psychometric property testing in AD outcome measurement instruments. More AD outcomes instruments should be validated in diverse populations.
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http://dx.doi.org/10.1016/j.jid.2021.06.033DOI Listing
August 2021

TH2 sensitization in the skin-gut-brain axis: How early-life Th2-mediated inflammation may negatively perpetuate developmental and psychologic abnormalities.

Pediatr Dermatol 2021 Aug 2. Epub 2021 Aug 2.

Department of Dermatology, Emory University School of Medicine, Atlanta, GA, USA.

We recently reported children with comorbid atopic dermatitis (AD), asthma, allergic rhinitis, and food allergies displaying a 2.7-fold increase in developmental delays. To this end, we hypothesize unregulated increases in T helper-2 (Th2)-driven inflammation, such as those seen in atopic diseases, can exert deleterious effects on the developing brain. Recognizing that available information is incomplete and that many potential associations are not firmly established, we speculate these effects underlie the association between Th2 sensitization and cognitive dysfunction in children. In this review, we explore the role of Th2 sensitization in the skin-gut-brain axis and explain how it can lead to reduced connectivity and transmission in the developing brain. With a focus on AD, we explore the association between Th2 sensitization and developmental abnormalities such as developmental delays, memory impairment, autism spectrum disorder (ASD), and epilepsy/seizures. As such, we review the available literature to examine the impact of increased IL-4 exposure in early life on the brain. We explore the possible association between Th2 sensitization and psychologic dysfunction such as attention-deficit/hyperactivity disorder (ADHD), depression, anxiety, and suicidal ideation. We also examine the impact that increased exposure to glucocorticoids and neurotrophins in early life exerts on the developing brain. Last, we discuss future directions for the advancement of our knowledge as a scientific community including possible interventions to reduce developmental and psychologic aberrations in children.
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http://dx.doi.org/10.1111/pde.14657DOI Listing
August 2021

Association of sleep disturbances with geriatric age in atopic dermatitis patients.

J Am Acad Dermatol 2021 Jul 29. Epub 2021 Jul 29.

Department of Dermatology, George Washington University School of Medicine and Health Sciences, Washington, District of Columbia; Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois. Electronic address:

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http://dx.doi.org/10.1016/j.jaad.2021.07.039DOI Listing
July 2021

Age-related differences in patch testing results among children: Analysis of North American Contact Dermatitis Group Data, 2001-2018.

J Am Acad Dermatol 2021 Jul 24. Epub 2021 Jul 24.

Department of Dermatology, Pennsylvania State University, State College, Hershey, Pennsylvania.

Background: An updated understanding of allergic contact dermatitis is needed, particularly in children.

Objectives: To compare positive and clinically relevant reactions in children versus adults referred for patch testing.

Methods: Retrospective analysis of 1871 children and 41,699 adults from the North American Contact Dermatitis Group (NACDG) from 2001-2018.

Results: Both final diagnosis of allergic contact dermatitis (55.2% versus 57.3%; chi square, P = .0716) and prevalence of ≥ 1 currently relevant reaction to a NACDG screening allergen (49.2% vs 52.2%; P = .1178) were similar between children and adults. Currently in children, the most common relevant allergens were nickel sulfate (17.3%), hydroperoxides of linalool (7.8%), methylisothiazolinone (7.7%), cobalt chloride (7.0%), and fragrance mix I (4.9%). Approximately a fifth of children had a positive reaction to a non-NACDG allergen.

Conclusion: Over half of children referred for patch testing were diagnosed with allergic contact dermatitis. The most common relevant allergens in children were nickel sulfate, cobalt chloride, and hydroperoxides of linalool. Twenty percent of children had at least 1 positive reaction to allergens/substances not on the NACDG screening series, underscoring the need for comprehensive testing.
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http://dx.doi.org/10.1016/j.jaad.2021.07.030DOI Listing
July 2021

Association of Varying Clinical Manifestations and Positive Anti-SARS-CoV-2 IgG Antibodies: A Cross-Sectional Observational Study.

J Allergy Clin Immunol Pract 2021 09 15;9(9):3331-3338.e2. Epub 2021 Jul 15.

Department of Pathology, Johns Hopkins University, Baltimore, Md. Electronic address:

Background: The complex relationship between clinical manifestations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and individual immune responses is not fully elucidated.

Objective: To examine phenotypes of symptomatology and their relationship with positive anti-SARS-CoV-2 IgG antibody responses.

Methods: An observational study was performed of adults (≥18 years) from 5 US states. Participants completed an electronic survey and underwent testing to anti-SARS-CoV-2 nucleocapsid protein IgG antibody between May and July 2020. Latent class analysis was used to identify characteristic symptom clusters.

Results: Overall, 9507 adults (mean age, 39.6 ± 15.0 years) completed the survey; 6665 (70.1%) underwent antibody testing for anti-SARS-CoV-2 IgG. Positive SARS-CoV-2 antibodies were associated with self-reported positive SARS-CoV-2 nasal swab result (bivariable logistic regression; odds ratio [95% CI], 5.98 [4.83-7.41]), household with 6 or more members (1.27 [1.14-1.41]) and sick contact (3.65 [3.19-4.17]), and older age (50-69 years: 1.55 [1.37-1.76]; ≥70 years: 1.52 [1.16-1.99]), but inversely associated with female sex (0.61 [0.55-0.68]). Latent class analysis revealed 8 latent classes of symptoms. Latent classes 1 (all symptoms) and 4 (fever, cough, muscle ache, anosmia, dysgeusia, and headache) were associated with the highest proportion (62.0% and 57.4%) of positive antibodies, whereas classes 6 (fever, cough, muscle ache, headache) and 8 (anosmia, dysgeusia) had intermediate proportions (48.2% and 40.5%), and classes 3 (headache, diarrhea, stomach pain) and 7 (no symptoms) had the lowest proportion (7.8% and 8.5%) of positive antibodies.

Conclusions: SARS-CoV-2 infections manifest with substantial diversity of symptoms, which are associated with variable anti-SARS-CoV-2 IgG antibody responses. Prolonged fever, anosmia, and receiving supplemental oxygen therapy had strongest associations with positive SARS-CoV-2 IgG.
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http://dx.doi.org/10.1016/j.jaip.2021.06.046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8279919PMC
September 2021

Interventions to improve primary care provider management of atopic dermatitis: A systematic review.

Pediatr Dermatol 2021 Jul 14. Epub 2021 Jul 14.

Department of Dermatology, The George Washington University School of Medicine and Health Sciences, Washington, DC, USA.

Most atopic dermatitis (AD) patients are managed by primary care providers (PCPs). PCP discomfort diagnosing and managing AD leads to suboptimal patient outcomes. In order to determine the efficacy of interventions aimed at improving PCP management of AD, a systematic literature review was performed for interventions to improve primary care management of AD. PubMed, MEDLINE, Embase, Scopus, LILACS, Cochrane, GREAT, and CINAHL were searched from database origin to February 24, 2020. Two reviewers independently performed the title/abstract and full-text review, and data extraction. Overall, 3009 non-duplicate articles were screened; 145 full-text articles were assessed. Thirteen studies met inclusion criteria, including 8 randomized controlled trials, 2 cohorts, 2 qualitative studies, and 1 unspecified design. Seven interventions (53.8%) significantly improved PCP knowledge/ability and/or a patient outcome, including patients consulting with a dermatology-trained nurse, pairing clinical education with expert consultation, pairing trainees with clinical mentors, giving clinicians a treatment guide, pairing clinical education with a treatment guide, and providing an eczema action plan. Studies had moderate-high risk-of-bias, moderate quality, and heterogeneous designs. There are few studies published and little evidence supporting the efficacy of interventions aimed at improving primary care management of AD. Further research is required to develop and implement effective interventions to improve primary care management of AD.
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http://dx.doi.org/10.1111/pde.14667DOI Listing
July 2021

Factors impacting vaccine hesitancy toward Coronavirus disease-19 (COVID-19) vaccination in Brooklyn, New York.

Hum Vaccin Immunother 2021 Jul 9:1-2. Epub 2021 Jul 9.

Department of Pediatrics, Division of Infectious Diseases, State University of New York Downstate Medical Center, Brooklyn, NY, USA.

The Coronavirus disease-2019 (COVID-19) pandemic led to the development of several candidate vaccines. However, current research suggests that the potential of successful vaccines is tempered by vaccine skepticism or hesitancy. If vaccine efficacy is 80%, then the herd immunity required from vaccination is about 75-90%. The aim of the current study was to study factors impacting COVID-19 vaccine hesitancy in a representative sample of adults (age≥18 years) in a COVID-19 hotspot COVID-19: coronavirus disease-19.
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http://dx.doi.org/10.1080/21645515.2021.1948786DOI Listing
July 2021

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

Dermatitis 2021 Jul 7. Epub 2021 Jul 7.

From the Departments of Dermatology Biostatistics and Bioinformatics, Duke University Medical Center, Durham, NC Department of Dermatology, Minneapolis Veterans Affairs Medical Center; Department of Dermatology, University of Minnesota, Minneapolis Division of Dermatology, Sunnybrook Health Sciences Centre, University of Toronto, Ontario, Canada Department of Dermatology, George Washington University School of Medicine and Health Sciences, Washington, DC Department of Dermatology, Cleveland Clinic Lerner College of Medicine, OH Department of Dermatology, Columbia University Irving Medical Center, New York, NY Division of Dermatology, University of Louisville, KY Department of Dermatology, University of California Medical School, San Francisco Department of Dermatology, University of Wisconsin School of Medicine and Public Health, Madison Division of Dermatology, University of Ottawa, The Ottawa Hospital, Ontario, Canada Department of Dermatology, Dartmouth Hitchcock Medical Center, Lebanon, NH Division of Dermatology, McGill University Health Centre, Montreal General Hospital, Quebec, Canada Department of Dermatology, Keck School of Medicine, University of Southern California, Los Angeles.

Differences in consumer product availability, distribution, and use may lead to national differences in contact sensitization frequencies.

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.
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http://dx.doi.org/10.1097/DER.0000000000000701DOI Listing
July 2021

Patch Testing With Tocopherol and Tocopherol Acetate: The North American Contact Dermatitis Group Experience, 2001 to 2016.

Dermatitis 2021 Sep-Oct 01;32(5):308-318

Department of Dermatology, University of Wisconsin School of Medicine and Public Health, Madison.

Background: Vitamin E (tocopherol) a naturally occurring mixture of antioxidants commonly used in topical skin care products, may cause allergic contact dermatitis.

Objective: The aim of this study was to characterize positive patch test reactions to tocopherol and tocopherol acetate.

Methods: This is a retrospective analysis of North American Contact Dermatitis Group patch test data to tocopherols (dl-α-tocopherol 100% and/or dl-α-tocopherol acetate 100%) from 2001 to 2016.

Results: Of the 38,699 patients patch tested to tocopherol and/or tocopherol acetate, 349 (0.9%) had positive reactions; of these, 87.6% were currently relevant. Most (51.4%) were weak (+) and/or not related to occupation (99.1%). Compared with tocopherol-negative patients, tocopherol-positive individuals were more likely to be female (72.5% vs 67.2%, P = 0.0355), have a final primary diagnosis of allergic contact dermatitis (74.2% vs 52.6%, P < 0.0001), and have dermatitis in a scattered generalized distribution (23.8% vs 18.2%, P = 0.0072); they were also less likely to have hand involvement (16.6% vs 22.3%, P = 0.0064). The most common source of tocopherol was personal care products, especially moisturizers.

Conclusions: Positive patch test reactions to tocopherols were relatively rare given their widespread use. When positive, current clinical relevance was high. Tocopherol-positive patients were more likely to be female and presented with dermatitis on the face or in a scattered generalized pattern.
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http://dx.doi.org/10.1097/DER.0000000000000706DOI Listing
July 2021
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