Increased loss-of-function filaggrin gene mutation prevalence in atopic dermatitis patients across northern latitudes indicates genetic fitness: A systematic review and meta-analysis.

Loss-of-function (LoF) mutations in the filaggrin gene (FLG) constitute the strongest genetic risk for atopic dermatitis (AD). A latitude-dependent difference in the prevalence of LoF FLG mutations was systematically evaluated. A systematic review and meta-analysis were performed to estimate the prevalence of LoF FLG mutations in AD patients and the general population by geography and ethnicity. Risk of bias was assessed by Newcastle-Ottawa Scale and Jadad score. StatsDirect, version 3 software was used to calculate all outcomes. PubMed and EMBASE were searched until 9th December 2021. Studies were included if they contained data on the prevalence of LoF FLG mutations in AD patients or from the general population or associations between AD and LoF FLG mutations and were authored in English. Overall, 248 studies and 229 310 AD patients and individuals of the general population were included in the quantitative analysis. The prevalence of LoF FLG mutations was 19.1% (95% CI, 17.3-21.0) in AD patients and 5.8% (95% CI, 5.3-6.2) in the general population. There was a significant positive association between AD and LoF FLG mutations in all latitudes in the Northern hemisphere, but not in all ethnicities. The prevalence of LoF FLG mutations became gradually more prevalent in populations residing farther north of the Equator but was negligible in Middle Easterners and absent in most African populations. FLG LoF mutations are common and tend to increase with northern latitude, suggesting potential clinical implications for future AD management. The existence of possible genetic fitness from FLG LoF mutations remains unknown.

Patch Testing With Cobalt in Adults: A North American Contact Dermatitis Group Experience, 2001-2018.

Background: Cobalt is a recognized cause of allergic contact dermatitis (ACD); however, detailed information on patient characteristics, sites, and sources is lacking. Objective: The aim of the study is to assess trends in patch test reactions to cobalt and associated patient characteristics, common sources, and body sites affected. Methods: The study used a retrospective analysis of adult patients who were patch tested to cobalt by the North American Contact Dermatitis Group between 2001 and 2018 (n = 41,730). Results: Overall, 2986 (7.2%) and 1362 (3.3%) had allergic or currently relevant patch test reaction to cobalt, respectively. Patients with versus without an allergic patch test reaction to cobalt were more likely to be female, employed, have a history of eczema or asthma, be Black, Hispanic, or Asian, and have occupational-related dermatitis. The most commonly identified sources of cobalt in allergic patients included jewelry, belts, and cement, concrete, and mortar. Affected body site(s) varied by cobalt source among patients with currently relevant reactions. Occupational relevance was found in 16.9% of patients with positive reactions. Conclusions: Positive patch test reactions to cobalt were common. The most common body sites were the hands, and affected site varied by the source of cobalt.

Longitudinal Course of Sleep Disturbance and Relationship With Itch in Adult Atopic Dermatitis in Clinical Practice.

Background: Sleep disturbance (SD) is common in atopic dermatitis (AD). We examined the longitudinal course of SD and relationship with itch in AD patients. Methods: A prospective, dermatology practice-based study was performed (N = 1295) where patients were assessed at baseline and follow-up visits. Results: At baseline, 16.9% of the patients had severe SD based on Patient-Reported Outcomes Information System (PROMIS) SD T scores, 19.1% had difficulty falling asleep, 22.9% had difficulty staying asleep, and 34.2% had SD from AD. A total of 31.4% of the patients with difficulty staying asleep at baseline experienced persistent difficulties (for 3 follow-ups or more). Only 17.7% with baseline difficulty falling asleep had persistent disturbance. Despite significant fluctuation in sleep scores, SD generally improved over time. Of the patients facing baseline SD from AD, 31.5% experienced SD at the first visit, and only 12.3% experienced persistent SD at the second follow-up visit. Predictors of increased PROMIS sleep-related impairment T scores over time included baseline PROMIS sleep-related impairment T scores (0.74 [0.68-0.80]), having 3 to 6 nights of itch (2.22 [0.85-3.59]), and severe/very severe AD (4.40 [2.60-6.20]). Conclusions: A significant proportion of adult AD patients, particularly those with moderate-severe AD and frequent itch, had baseline SD. Although sleep scores generally improved over time, many patients experienced a fluctuating or persistent course.

Psychological Interventions Are More Effective Than Educational Interventions at Improving Atopic Dermatitis Severity: A Systematic Review.

We determined which educational and/or psychological interventions were most effective in atopic dermatitis (AD). A systematic review of published studies evaluated the effectiveness of educational and/or psychological interventions in MEDLINE, Embase, SCOPUS, LILACS, Cochrane, China National Knowledge Infrastructure, Taiwan Electronic Periodical Services, and CiNii. Two reviewers conducted title/abstract, full-text review, and data extraction. Twenty-four prospective studies were included, including 20 randomized controlled trials. Educational (4/7 studies) and combined educational and psychological (5/6 studies) interventions reduced AD severity; psychological (10/11 studies) interventions showed the greatest benefit. The most commonly studied psychological intervention was habit reversal training (8/11 studies), which was most frequently incorporated in studies that reduced AD severity (8/10 studies). The most commonly studied educational interventions were education on AD triggers (7/7 studies) and skin care (7/7 studies); they were incorporated in all studies that reduced AD severity. Different psychological and/or educational interventions successfully reduced AD severity, especially habit reversal training.

Longitudinal Course of Sleep Disturbance and Relationship With Itch in Adult Atopic Dermatitis in Clinical Practice.

BACKGROUND: Sleep disturbance (SD) is common in atopic dermatitis (AD). We examined the longitudinal course of SD and relationship with itch in AD patients. METHODS: A prospective, dermatology practice-based study was performed (N = 1295) where patients were assessed at baseline and follow-up visits. RESULTS: At baseline, 16.9% of the patients had severe SD based on Patient-Reported Outcomes Information System (PROMIS) SD T scores, 19.1% had difficulty falling asleep, 22.9% had difficulty staying asleep, and 34.2% had SD from AD. A total of 31.4% of the patients with difficulty staying asleep at baseline experienced persistent difficulties (for 3 follow-ups or more). Only 17.7% with baseline difficulty falling asleep had persistent disturbance. Despite significant fluctuation in sleep scores, SD generally improved over time. Of the patients facing baseline SD from AD, 31.5% experienced SD at the first visit, and only 12.3% experienced persistent SD at the second follow-up visit. Predictors of increased PROMIS sleep-related impairment T scores over time included baseline PROMIS sleep-related impairment T scores (0.74 [0.68-0.80]), having 3 to 6 nights of itch (2.22 [0.85-3.59]), and severe/very severe AD (4.40 [2.60-6.20]). CONCLUSIONS: A significant proportion of adult AD patients, particularly those with moderate-severe AD and frequent itch, had baseline SD. Although sleep scores generally improved over time, many patients experienced a fluctuating or persistent course.

Epidemiology and Burden of Sleep Disturbances in Atopic Dermatitis in US Adults.

BACKGROUND: The relationship between atopic dermatitis (AD) severity, sleep disturbance (SD), and health-related outcomes is not fully elucidated. OBJECTIVE: The aim of the study was to determine the prevalence of SD in adult AD and its relationship with AD severity and health outcomes among the US population. METHODS: A cross-sectional, US population-based survey study of 2893 adults was performed. RESULTS: Among adults meeting the UK Diagnostic Criteria for AD, 255 (40.7%) reported 1 or more, 67 (11.1%) reported 3 to 4, and 57 (9.5%) reported 5 to 7 nights of SD in the past week; 475 (79.7%) reported at least some trouble sleeping in the past 3 days. Moderate and severe Patient-Oriented Scoring AD, Patient-Oriented Eczema Measure, and Numeric Rating Scale-itch and Numeric Rating Scale-skin pain scores were associated with more severe SD compared with those without AD. More frequent and severe SDs were associated with higher Dermatology Life Quality Index, lower 12-item Short-Form Health Survey, and higher Hospital Anxiety and Depression Scale (HADS) scores. Significant mediation by SD severity was observed between Patient-Oriented Eczema Measure and Numeric Rating Scale-itch with Dermatology Life Quality Index, 12-item Short-Form Health Survey physical and mental component scores, HADS-anxiety and HADS-depression scores, diagnosed anxiety, and heart disease. CONCLUSIONS: Atopic dermatitis and AD severity are associated with SDs. Sleep disturbances considerably impact quality of life and other health outcomes in adults with AD.

Mental Health Symptoms and Functional Impairment in Children With Atopic Dermatitis.

BACKGROUND: The impact of childhood atopic dermatitis (AD) on social and behavioral issues is not well understood. OBJECTIVE: This study sought to determine the prevalence and predictors of social and behavioral symptoms and functional impairment among US children with AD. METHODS: The 1996 to 2015 Medical Expenditure Panel Surveys were analyzed, including a representative, cross-sectional study of 2553 US children with AD. Behavioral and functional issues were examined using Columbia Impairment Scale (CIS) scores. RESULTS: Childhood AD was associated with behavioral and functional problems, particularly nervousness (odds ratio [OR], 1.18; 95% confidence interval [95% CI], 1.06-1.31), home behavior (OR, 1.18; 95% CI, 1.06-1.32), staying out of trouble (OR, 1.18; 95% confidence interval, 1.06-1.31), and relationships with other kids (OR, 1.17; 95% CI, 1.05-1.31) and with siblings (OR, 1.14; 95% CI, 1.02-1.28). Higher CIS scores were present in children with AD versus without AD (adjusted ß, 0.62; 95% CI, 0.22-1.02) and with psoriasis (adjusted ß, 0.86; 95% CI, 0.22-1.49). Among children with AD, higher CIS scores were notably associated with male sex, older age, lower household income, public insurance, and comorbid depression and anxiety. CONCLUSIONS: AD was associated with behavioral and functional impairment, similar to psoriasis and other common chronic conditions. There are significant sociodemographic differences in CIS scores.

Association of Atopic Dermatitis With Bacterial, Fungal, Viral, and Sexually Transmitted Skin Infections.

BACKGROUND: Atopic dermatitis (AD) is associated with altered skin barrier, microbiome, and immune dysregulation that may increase risk of skin infections. OBJECTIVE: The aim of the study was to determine whether AD is associated with skin infections and related outcomes. METHODS: Data from the 2006 to 2012 National Emergency Department Sample were analyzed, including an approximately 20% sample of all US emergency department (ED) visits (N = 198,102,435 adults or children). RESULTS: Skin infections were increased in ED visits of adults (7.14% vs 3.76%) and children (5.15% vs 2.48%) with AD. In multivariable logistic regression models, AD was associated with significantly higher odds of skin infection in adults (adjusted odds ratio [95% confidence interval] = 1.93 [1.89-1.97]) and children (2.23 [2.16-2.31]). Pediatric and adult AD were associated with significantly higher odds of carbuncle/furuncles, impetigo, cellulitis, erysipelas, methicillin-resistant and methicillin-sensitive Staphylococcus aureus infections, molluscum contagiosum, cutaneous warts, herpes simplex and zoster viruses, eczema herpeticum, dermatophytosis, and candidiasis of skin/nails and vulva/urogenitals. Adults with AD had significantly higher odds of genital warts (1.51 [1.36-1.52]) and herpes (1.23 [1.11-1.35]). Skin infections were associated with US $19 million excess annual costs of ED care in persons with AD. CONCLUSIONS: Atopic dermatitis patients had higher odds of multiple bacterial, viral, fungal, and sexually transmitted skin infections.

Lack of Association Between Dust Mite Sensitivity and Atopic Dermatitis.

BACKGROUND: Dust mites (DMs) play a role in type I respiratory allergy. Studies relating to DM irritant versus immune reactions are somewhat conflicting in atopic dermatitis (AD). OBJECTIVE: The aim of this study was to assess the diagnostic use of patch testing to DM in patients with AD and other dermatitides. METHODS: We performed a prospective study of 323 adults recruited in a patch testing clinic. Patch testing antigens were DM extract (0.01%, 0.1%, 1%, 10%, and 20% in petrolatum; Chemotechnique) and/or 200 index of reactivity in petrolatum (Stallergenes). Patches were placed and read at 48 hours with delayed readings after 72 to 168 hours. RESULTS: There was no association of DM positivity with AD, asthma, hay fever, or demographic factors. There was no association of DM positivity with the clinical diagnosis or phenotype. The number of positive (+, ++, and +++) and doubtful reactions to Chemotechnique DM extract increased with higher concentrations. Positive reactions to DM had a morphological appearance characterized by numerous discrete erythematous papules and, rarely, papulovesicles. Positive reactions to Stallergenes DM 200 IR were infrequent and all weak reactions, similar to DM 0.01%. CONCLUSIONS: Patch testing to DM does not seem to have clinical use for determining the etiology of dermatitis.