Dermatitis®

It is still unclear whether patients with atopic dermatitis (AD) have an increased risk of developing rheumatoid arthritis (RA).

We aimed to investigate the association between AD and risk of RA using systematic review and meta-analysis.

We searched Medline and EMBASE up to April 2021 using search strategy, including terms for “atopic dermatitis” and “rheumatoid arthritis.” Eligible cohort study must compare the incidence of RA between patients with AD and comparators without AD. Eligible case-control study must recruit cases with RA and controls without RA. Then, the study must compare the prevalence of AD between the groups. Point estimates with standard errors from each study were combined using the generic inverse variance method.

The meta-analysis found that AD patients had a significantly higher risk of incident RA than individuals without AD with a pooled odds ratio (OR) of 1.30 (95% confidence interval [CI], 1.17–1.44; I², 48%). Subgroup analysis revealed a significantly higher risk of RA in cohort study subgroup (pooled OR, 1.37; 95% CI, 1.25–1.50; I², 63%) but not case-control study subgroup (pooled OR, 0.99; 95% CI, 0.77–1.28; I², 10%).

This study found a significantly higher risk of incident RA among AD patients.

Atopic dermatitis (AD) in the elderly has been poorly investigated, although its incidence is gradually increasing mainly in industrialized countries. Age-specific factors in older patients must be considered when selecting treatment options.

To evaluate the efficacy and tolerability of dupilumab in treating elderly patients with severe AD.

This was a retrospective, multicenter study involving 26 elderly patients (age, ≥65 years) with severe AD who were treated with dupilumab for at least 16 weeks. Absolute and percentage frequencies were used to evaluate qualitative variables and mean and SD for quantitative ones. For Eczema Area and Severity Index (EASI), Pruritus Numeric Rating Scale (NRS), and Dermatology Life Quality Index (DLQI), the median was also calculated. Wilcoxon test was used to evaluate the variations in EASI, Pruritus NRS, and DLQI observed between the 2 examinations.

After 4 months of therapy, the majority of patients showed a significant improvement in EASI (64.4%), Pruritus NRS (58.2%), and DLQI (44.9%). Only 11% of patients reported mild or moderate conjunctivitis.

To the best of our knowledge, this is the first study concerning the use of dupilumab in the elderly with severe AD. Our data show the effectiveness of dupilumab in this particular population with a lower percentage of conjunctivitis than observed in studies on adults and also excellent control of itching. Only larger, controlled case studies will be able to clarify whether the dosage or frequency of administration of dupilumab in these patients should be different from the protocol used for adults.

Itch is a complex and burdensome symptom in atopic dermatitis (AD). Severity of scratching/excoriation (SCORAD-scratch) has been found to be a valid measure of itch in AD. However, little is known about the longitudinal course of scratching/excoriations in AD.

A prospective, dermatology practice–based study was performed of adults with AD (N = 399). The patients were assessed at baseline and approximately 6, 12, 18, and 24 months.

Severity of excoriations correlated best with the Numerical Rating Scale–worst itch (Spearman correlation, ρ = 0.50), followed by a Patient-Reported Outcome Measurement Information System Itch Questionnaire–scratching behavior T score (ρ = 0.48), Numerical Rating Scale–average itch (ρ = 0.41), relative frequency of itch (ρ = 0.36), and frequency of itch from eczema (ρ = 0.29, all P < 0.0001). Scratching severity showed good reliability (intraclass correlation coefficient range = 0.62–0.69). Overall, 30.6% and 5.5% had moderate (2) or severe (3) SCORAD-scratch scores. Among patients with baseline moderate (2) or severe (3) SCORAD-scratch scores, 18.9% and 13.6% continued to have moderate or severe scores at 1 or more follow-up visits. In repeated-measures regression models, persistent SCORAD-scratch scores were associated with baseline severity of excoriations (adjusted β [95% confidence interval] = 0.51 [0.37 to 0.65]), Medicaid insurance (−0.35 [−0.65 to −0.04]), and Eczema Area and Severity Index scores (0.03 [0.02 to 0.04]).

Adult AD patients had a heterogeneous longitudinal course with fluctuating severity of excoriations.

The burden of illness associated with atopic dermatitis (AD) is significant and multidimensional, especially in those with moderate to severe disease.

Our objective was to evaluate the disease burden of patients with AD in relation to psychological distress, sleep disturbance, and alcohol misuse.

Patients with AD, attending 2 tertiary referral centers in Dublin, Ireland, were recruited. A series of validated questionnaires were used including the Patient-Oriented Eczema Measure, Dermatology Life Quality Index (DLQI), Center for Epidemiologic Studies–Depression Scale, Quality of Life in Atopic Dermatitis Questionnaire, Alcohol Use Disorders Identification Test, and Pittsburgh Sleep Quality Index. The Eczema Area and Severity Index was calculated contemporaneously with the questionnaire completion.

One hundred patients completed the questionnaire, of whom 52% were female. Sixty-three percent of patients experienced impaired quality of life as measured by the DLQI. Higher DLQI scores correlated with decreasing age (r = 0.3277, P < 0.0009). Thirty percent were found to be at risk of clinical depression, and higher Center for Epidemiologic Studies–Depression Scale scores correlated with a younger age and eczema severity. Sleep disturbance was greater in those at risk of depression (mean = 10.40 vs 5.79, P < 0.0001). Patients with moderate to severe AD were more likely to score higher on the Alcohol Use Disorders Identification Test, and 25% met the criteria for alcohol use disorder. In relation to sleep, 73% of patients scored higher than 5 on the Pittsburgh Sleep Quality Index, which signifies poor sleep quality.

Patients with AD endure a significant burden on health with regard to mental well-being, alcohol use, and sleep quality. Clinicians should consider screening patients for these comorbidities.

Itch, the most bothersome symptom in atopic dermatitis, is largely mediated by pruritogenic cytokines via Janus kinase 1 signaling in cutaneous sensory neurons.

The aims of the study were to assess the magnitude and rapidity of itch relief with the Janus kinase 1 selective inhibitor abrocitinib and to evaluate the extent to which the effect of abrocitinib on itch relief is independent of overall disease improvement.

Pooled data from 1 phase 2b (NCT02780167) and 2 phase 3 (NCT03349060, NCT03575871) double-blind, randomized, placebo-controlled monotherapy trials in moderate to severe atopic dermatitis (N = 942) were analyzed.

Abrocitinib produced significant and clinically meaningful itch relief versus placebo from week 2 through week 12 (end of treatment) that was associated with marked sleep and quality-of-life improvements. Mean percentage reductions in itch scores 24 hours after the first dose were greater for both abrocitinib doses (200 and 100 mg) versus placebo. Itch improvement occurred regardless of baseline itch severity, sex, race, body mass index, or Investigator Global Assessment response, suggesting that abrocitinib-associated itch relief is at least partially independent of overall disease improvement.

Abrocitinib showed a rapid and profound antipruritic effect, partially independent of improvement in overall disease.

The burden of coronavirus disease 2019 (COVID-19) among patients with atopic dermatitis (AD) is poorly understood.

The aims of the study were to characterize a large cohort of COVID-19–positive adult patients with AD and to identify predictors of COVID-19–associated hospitalization and mortality.

A population-based nested case-control study was performed. Multivariable logistic regression was used to evaluate odds ratios and 95% confidence intervals of predictors for COVID-19–associated hospitalization and mortality.

Of 78,073 adult patients with AD, 3618 (4.6%) tested positive for COVID-19. Subclinical COVID-19 infection occurred in 3368 (93.1%) of COVID-19–positive patients, whereas 123 (3.4%), 46 (1.3%), 55 (1.5%), and 26 (0.7%) patients developed a mild, moderate, severe, and critical disease, respectively. Altogether, 250 patients (6.0%) were hospitalized, and 40 patients (1.1%) died because of COVID-19 complications. Coronavirus disease 2019–associated hospitalization was independently associated with the intake of extended courses of systemic corticosteroids (adjusted odds ratio, 1.96; 95% confidence interval, 1.23–3.14; P = 0.005). None of AD-related variables independently predicted COVID-19–associated mortality. The presence of comorbid metabolic syndrome, chronic obstructive pulmonary disease, chronic renal failure, and depression projected both COVID-19–associated hospitalization and mortality.

Prolonged systemic corticosteroids during the pandemic are associated with increased odds of COVID-19–associated hospitalization and should be avoided in patients with AD.

Moderate-to-severe atopic dermatitis (AD) is inadequately controlled with current treatments for many patients. Abrocitinib is an oral Janus kinase 1 selective inhibitor under investigation for the treatment of AD.

The aim of the study was to evaluate patient-reported outcomes in a phase 2b study of abrocitinib in adults with moderate-to-severe AD inadequately controlled by topical therapy (NCT02780167).

Patients (N = 267) were randomly assigned 1:1:1:1:1 to 12-week, once-daily abrocitinib (200, 100, 30, 10 mg) or placebo. Patient-reported outcomes included pruritus numeric rating scale (average), Patient Global Assessment, Patient-Oriented Eczema Measure, Pruritus and Symptoms Assessment for AD, Dermatology Life Quality Index, and Hospital Anxiety and Depression Scale (HADS).

Abrocitinib 200 or 100 mg resulted in significantly greater improvements from baseline versus placebo in peak pruritus numeric rating scale (by days 2 and 3, respectively), Patient-Oriented Eczema Measure, Pruritus and Symptoms Assessment for AD, Dermatology Life Quality Index, and HADS (200 mg only, by week 1 or 2), and proportions of the patients with Patient Global Assessment clear/almost clear with 2-point or greater improvement (by weeks 1 and 4, respectively) that continued through week 12 (except HADS).

Abrocitinib treatment resulted in rapid (2 days to 2 weeks) and persistent improvements in AD symptoms and impacts in moderate-to-severe disease.

Atopic dermatitis (AD) is associated with considerable financial cost. However, the full burden of out-of-pocket (OOP) expenses is not well understood.

We sought to characterize the OOP health care expenses associated with AD management.

A 25-question voluntary online survey was administered to National Eczema Association members worldwide (n = 113,502). Inclusion criteria (US residents age ≥18 years who either self-reported had AD or were primary caregivers of individuals with AD) were met by 77.3% (1118/1447) of respondents.

Respondents reported OOP expenses in 3 categories: (1) health care providers and prescriptions, including health care provider visit deductibles (68.7% [686]), prescription co-pays (64.3% [635]), and prescriptions not covered by insurance (48.6% [468]); (2) nonprescription health care products, including moisturizers (94.3% [934]), hygiene products (85.0% [824], allergy medications (75.1% [715]), itch relievers (68.25% [647]), dietary supplements (52.2% [491]), and sleep aids (37.0% [336]); and (3) complementary approaches, including cleaning products (74.7% [732]), clothing/bedding (44.8% [430]), alternative medications (19.0% [180]), and adjunctive therapies (15.9% [150]). The median annual AD OOP expense was US $600 (range, US $0–$200,000), with 41.9% (364) reporting expenditures US $1000 or greater.

Out-of-pocket expenses place a significant financial burden on individuals with AD. Additional studies are needed to better understand associations and impact of OOP costs.

Tape-strips are a minimally invasive approach to characterize skin biomarkers in atopic dermatitis (AD). However, they have not yet been used for tracking gene expression changes with systemic treatment.

The aim of the study was to evaluate gene expression changes and therapeutic response biomarkers in AD patients before and after dupilumab (interleukin 4Rα antibody) treatment using tape-strips to obtain epidermal tissue for analysis.

Lesional and nonlesional tape-stripped skin was sampled from 18 AD patients before and after dupilumab treatment and from 17 healthy subjects and analyzed by RNA-seq.

At baseline, we detected 6745 and 4859 differentially expressed genes between lesional and nonlesional skin versus normal, respectively, whereas 841 and 977 genes were differentially expressed after treatment, respectively (fold change >1.5 and false discovery rate <0.05). Tape-strips captured significant modulation with dupilumab in key AD immune (eg, C-C motif chemokine ligand 13 [CCL13], CCL17, CCL18) and barrier (eg, periplakin, FA2H) biomarkers. Changes in biomarkers (CCL20, interleukin 34, FABP7) were also significantly correlated with clinical disease improvements (Eczema Area and Severity Index; R > 0.5 or R < −0.4, P < 0.05).

This real-life study represents the first comprehensive RNA-seq molecular profiling of tape-strips from moderate to severe AD patients after dupilumab therapy. Analysis of tape strip specimens detected significant gene expression changes in key AD biomarkers with dupilumab treatment, suggesting that this approach may be useful to monitor therapeutic responses in inflammatory skin diseases.

Pain is a frequent symptom of atopic dermatitis (AD).

The aims of the study were to evaluate the effects of dupilumab on pain/discomfort in AD and to determine whether pain correlates with other outcomes.

This was a post hoc analysis of 5 randomized, placebo-controlled clinical trials in which adults with chronic AD received placebo or dupilumab 300 mg every 2 weeks or once weekly with and without topical corticosteroids. Proportions of patients with no pain/discomfort on this dimension of the 5-dimension EuroQoL (EQ-5D) at week 16 (all trials) and week 52 (CHRONOS) were compared between placebo and dupilumab. Correlations were evaluated between pain/discomfort and signs and symptoms of AD.

Among 2632 evaluated patients, 72.9% to 83.1% reported at least moderate pain/discomfort at baseline. Higher proportions treated with dupilumab reported no pain/discomfort at week 16 relative to placebo; risk differences ranged from 22.3% (95% confidence interval = 11.5%–33.1%) to 42.2% (95% confidence interval = 26.6%–57.8%, all P ≤ 0.0001), with similar effects observed at week 52. Correlations at baseline of pain/discomfort with signs and symptoms of AD were low to moderate.

Pain/discomfort, present in a substantial proportion of patients with moderate-to-severe AD, was significantly reduced by dupilumab treatment. Given the low-to-moderate correlations with other AD symptoms at baseline, pain likely represents a distinct AD symptom.

Trial Registration: ClinicalTrials.gov identifiers NCT01859988, NCT02277743, NCT02277769, NCT02260986, and NCT02755649.