Atopic Comorbidities Research Articles

Upadacitinib for moderate-to-severe atopic dermatitis: stratified analysis from three randomized phase 3 trials by key baseline characteristics.

Atopic dermatitis (AD) is a heterogeneous inflammatory skin disease with different clinical phenotypes based on factors such as age, race, comorbidities, and clinical signs and symptoms. The effect of these factors on therapeutic responses in AD has only been scarcely studied and not for upadacitinib. Currently, there is no biomarker predicting response to upadacitinib. Evaluate the efficacy of the oral Janus kinase inhibitor upadacitinib across patient subgroups (baseline demographics, disease characteristics, and prior treatment) in patients with moderate-to-severe AD. Data from phase 3 studies (Measure Up 1, Measure Up 2, and AD Up) were utilized for this post hoc analysis. Adults and adolescents with moderate-to-severe AD were randomized to receive once daily oral upadacitinib 15 mg, upadacitinib 30 mg, or placebo; patients enrolled in the AD Up study received concomitant topical corticosteroids. Data from the Measure Up 1 and Measure Up 2 studies were integrated. A total of 2584 patients were randomized. A consistently greater proportion of patients achieved at least 75% improvement in the Eczema Area and Severity Index, a 0 or 1 on the validated Investigator Global Assessment for Atopic Dermatitis, and improvement in itch (including an achievement of a reduction of ≥4; and score of 0/1 in Worst Pruritus Numerical Rating Scale) with upadacitinib compared with placebo at week 16, regardless of age, sex, race, body mass index, AD severity, body surface area involvement, history of atopic comorbidities or asthma, or previous exposure to systemic therapy or cyclosporin. Upadacitinib had consistently high skin clearance rates and itch efficacy across subgroups of patients with moderate-to-severe AD through week 16. These results support upadacitinib as a suitable treatment option in a variety of patients. ClinicalTrials.gov Identifiers: NCT03569293 (Measure Up 1), NCT03607422 (Measure Up 2), and NCT03568318 (AD Up).

Genomic, Epigenomic, Transcriptomic, Proteomic and Metabolomic Approaches in Atopic Dermatitis.

Atopic dermatitis (AD) is a chronic inflammatory skin disease with a high prevalence in the developed countries. It is associated with atopic and non-atopic diseases, and its close correlation with atopic comorbidities has been genetically demonstrated. One of the main roles of genetic studies is to comprehend the defects of the cutaneous barrier due to filaggrin deficit and epidermal spongiosis. Recently, epigenetic studies started to analyze the influence of the environmental factors on gene expression. The epigenome is considered to be a superior second code that controls the genome, which includes alterations of the chromatin. The epigenetic changes do not alter the genetic code, however, changes in the chromatin structure could activate or inhibit the transcription process of certain genes and consequently, the translation process of the new mRNA into a polypeptide chain. In-depth analysis of the transcriptomic, metabolomic and proteomic studies allow to unravel detailed mechanisms that cause AD. The extracellular space and lipid metabolism are associated with AD that is independent of the filaggrin expression. On the other hand, around 45 proteins are considered as the principal components in the atopic skin. Moreover, genetic studies based on the disrupted cutaneous barrier can lead to the development of new treatments targeting the cutaneous barrier or cutaneous inflammation. Unfortunately, at present, there are no target therapies that focus on the epigenetic process of AD. However, in the future, miR-143 could be an important objective for new therapies, as it targets the miR-335:SOX axis, thereby restoring the miR-335 expression, and repairing the cutaneous barrier defects.

CO127 Atopic March and Comorbidities in Patients with Atopic Dermatitis in Colombia

To analyze the atopic march of atopic dermatitis (AD) in both children and adults and identify the risk factors associated with persistent clinical symptoms and associated atopic comorbidities.

Atopic dermatitis in children and adolescents seen at a general hospital in the City of Buenos Aires.

Atopic dermatitis (AD) is an inflammatory skin disease highly prevalent in pediatrics as per international studies. There is scarce information on the epidemiological characteristics of AD in the Argentine pediatric population. The objective of this study was to describe the prevalence and clinical characteristics of AD in a population of Argentine children seen at the Department of Pediatrics of a general hospital. Observational, cross-sectional study. Five hundred patients were randomly included; their mean age was 10 years (SD: 5); 50% (250) were female. A total of 24 had AD. The overall prevalence was 5% (95% confidence interval: 3-7) and 3/24 were severe forms. The most frequent atopic comorbidity was asthma. The prevalence of AD in our population is similar to that of other countries. Our study provides new data on the epidemiological characteristics of AD in our region.

Food allergy and infant feeding practices: Are they related?

BackgroundImmunoglobulin (Ig)E-mediated food allergy is a growing health problem affecting up to 10% of children. It is well-established that early introduction to peanuts and eggs from 4 months of age has a preventive effect. In contrast, there is no consensus about the effect of breastfeeding on food allergy development. ObjectiveTo evaluate the effect of breastfeeding and cows' milk formula (CMF) feeding on the development of IgE-mediated food allergy. MethodsInfants in the Cow's Milk Early Exposure Trial were followed for 12 months. The cohort was divided according to parental feeding preferences for the first 2 months of life: group 1: exclusive breastfeeding (EBF); group 2: breastfeeding with at least 1 daily meal of CMF; and group 3: feeding with CMF only. ResultsAmong a total of 1989 infants, 1071 were on EBF (53.8%), 616 were breastfed with addition of CMF (31%), and 302 were fed with CMF only (15.2%), from birth. By 12 months, 43 infants developed an IgE-mediated food allergy (2.2%); 31 in the EBF group (2.9%), 12 in the breastfeeding and CMF combined group (1.9%), and none in the CMF feeding-only group (P = .002). Family atopic comorbidity did not affect the results. ConclusionIn this prospective cohort, breastfed infants developed significantly higher rates of IgE-mediated food allergy during the first year of life. Perhaps the mechanism is related to compounds ingested by the mother and secreted in the breastmilk. Future larger cohorts should validate these results and offer the lactating mother recommendations. Trial RegistrationThe COMEET study and its derivatives were approved by the Ethics Committee of Meir Medical Center, IRB number 011-16-MMC. It was registered at the National Institutes of Health Clinical Trials Registry: NCT02785679.

Risk factors associated with safety of preschool peanut oral immunotherapy.

An understanding of how patient characteristics such as age, baseline peanut-specific IgE, and atopic comorbidities may influence potential safety outcomes during peanut oral immunotherapy (P-OIT) could aid in shared decision making between clinicians and patient families. This study explored the relationship between baseline patient characteristics and reactions during P-OIT using a large sample size to better understand potential risk factors influencing P-OIT safety. Data were obtained from the Food Allergy Immunotherapy (FAIT) registry, which collects real-world OIT data from community and academic allergy clinics across Canada. Multivariable logistic regression modeling was performed to examine the relationship between baseline patient characteristics and reactions during P-OIT. Multiple imputation was applied to reduce potential bias caused by missingness and to maximize the use of available information to preserve statistical power. Between April 2017 and June 2021, a total of 653 eligible patients initiated P-OIT. Multivariable regression analysis showed pre-OIT grade 2+ initial reaction (odds ratio [OR]= 1.33, 95% confidence interval [CI] 1.10, 1.61), allergic rhinitis (OR= 1.60, 95% CI 1.08, 2.38), older age (OR= 1.01, 95% CI 1.00, 1.02), and higher baseline peanut-specific IgE (OR= 1.02, 95% CI 1.02, 1.03) were associated with grade 2+ reaction during P-OIT after adjusting for potential risk factors. Our study identified several clinically important risk factors for grade 2+ reactions during P-OIT: pre-OIT grade 2+ initial reaction, allergic rhinitis, older age, and higher baseline peanut-specific IgE. These results highlight the need for individualized risk stratification for OIT.

Eosinophilic esophagitis patients with multiple atopic conditions: Clinical characteristics and treatment response to topical steroids

BackgroundPatients with eosinophilic esophagitis (EoE) typically have concomitant atopic conditions, but whether there are differences in presentation or treatment response by the number of atopic diseases is unknown. ObjectiveTo determine whether patients with EoE having multiple atopic conditions have differences in presentation or response to topical corticosteroid (TCS) treatment. MethodsWe performed a retrospective cohort study of adults and children with newly diagnosed EoE. The total number of atopic comorbidities (allergic rhinitis, asthma, eczema, food allergy) was calculated. Patients with at least 2 atopic conditions other than allergic rhinitis were defined as having multiple atopic conditions and their baseline characteristics were compared with those with less than 2 atopic conditions. Histologic, symptom, and endoscopic responses to TCS treatment were also compared with bivariable and multivariable analyses. ResultsOf the 1020 patients with EoE having atopic disease information, 235 (23%) had 1 atopic comorbidity, 211 (21%) had 2, 113 (11%) had 3, and 34 (3%) had 4. At baseline, the 180 (18%) patients with 2 or more atopic diseases were younger and had more vomiting, less abdominal pain, more exudates and edema on endoscopy, and higher peak eosinophil counts. Among those treated with TCS, there was a trend toward better global symptom response in patients with less than 2 atopic conditions, but there was no difference in histologic or endoscopic response compared with those with 2 or more atopic conditions. ConclusionThere were differences in the initial presentation of EoE between those with and without multiple atopic conditions, but there were no major differences in histologic treatment response to corticosteroids by atopic status.

Atopic dermatitis: Correlation of distinct risk factors with age of onset in adulthood compared to childhood.

Atopic dermatitis (AD) has long been regarded as a primarily pediatric disease. However, there is growing evidence for a high rate of adult-onset AD. We aimed to characterize factors associated with adult-onset versus childhood-onset AD and controls. We analyzed cross-sectional data of the CK-CARE-ProRaD cohorts Bonn, Augsburg, Davos, Zürich of 736 adult patients stratified by age of AD onset (childhood-onset <18 years: 76.4% (subsets: 0 to 2; ≥2 to 6; ≥7 to 11; ≥12 to 18); adult-onset ≥18 years: 23.6% (subsets: ≥18 to 40; ≥41 to 60; ≥61) and 167 controls (91 atopic, 76 non-atopic)). We identified active smoking to be associated with adult-onset AD versus controls (adjusted Odds Ratio (aOR) = 5.54 [95% Confidence Interval: 1.06-29.01] vs. controlsnon-atopic , aOR = 4.03 [1.20-13.45] vs. controlsatopic ). Conjunctivitis showed a negative association versus controlsatopic (aOR = 0.36 [0.14-0.91]). Food allergy (aOR = 2.93 [1.44-5.96]), maternal food allergy (aOR = 9.43 [1.10-80.95]), palmar hyperlinearity (aOR = 2.11 [1.05-4.25]), and academic background (aOR = 2.14 [1.00-4.54]) increased the odds of childhood-onset AD versus controlsatopic . Shared AD-associated factors were maternal AD (4-34x), increased IgE (2-20x), atopic stigmata (2-3x) with varying effect sizes depending on AD onset and control group. Patients with adult-compared to childhood-onset had doubled odds of allergic rhinitis (aOR = 2.15 [1.12-4.13]), but reduced odds to feature multiple (3-4) atopic comorbidities (aOR = 0.34 [0.14-0.84]). Adult-onset AD, particularly onset ≥61 years, grouped mainly in clusters with low contributions of personal and familial atopy and high frequencies of physical inactivity, childhood-onset AD, particularly infant-onset, mainly in "high-atopic"-clusters. The identified associated factors suggest partly varying endo- and exogeneous mechanisms underlying adult-onset versus childhood-onset AD. Our findings might contribute to better assessment of the individual risk to develop AD throughout life and encourage prevention by non-smoking and physical activity as modifiable lifestyle factors.

High baseline prevalence of atopic comorbidities and medication use in children treated with allergy immunotherapy in the REAl-world effeCtiveness in allergy immunoTherapy (REACT) study.

Respiratory allergy, commonly manifesting as allergic rhinitis (AR) and asthma, is a chronic progressive disease that frequently starts in childhood. Allergy immunotherapy (AIT) is the only causal treatment for respiratory allergy with the potential to modify the underlying cause of allergy and, ultimately, prevent disease progression. This analysis aimed to determine if AIT is received sufficiently early to halt the progression of allergic disease, by characterizing the burden and progression of disease in children prior to AIT initiation in real-life clinical practice. The REAl-world effeCtiveness in allergy immunoTherapy (REACT) study was a large retrospective cohort study using German claims data between 2007 and 2017. Characteristics of two pre-defined AIT age cohorts from the REACT study - children (aged <18 years) and adults (aged ≥18 years) - were evaluated during the 1-year period before the first AIT prescription. For comparison, a control group of all subjects with a confirmed diagnosis of AR and without prescriptions for AIT was included. Burden of disease was assessed using diagnostic codes for atopic comorbidities [e.g., atopic dermatitis (AD), asthma, and acute allergic conjunctivitis] and non-atopic comorbidities (e.g., migraine, headache); medication use, recorded as prescriptions for symptom-relieving AR medication and reliever/controller medication for asthma, was also assessed. Data were analyzed descriptively, using summary statistics. Both children (n = 11,036) and adults (n = 30,037) showed a higher prevalence of atopic comorbidities and a greater drug burden prior to AIT initiation compared to AR patients not treated with AIT (n = 1,003,332). In the two age-specific AIT cohorts, children consistently showed the highest prevalence of atopic comorbidities compared to adults (AIT children, AIT adults - asthma: 41.4%, 34.5%; AD: 19.9%, 10.2%; acute allergic conjunctivitis: 13.6%, 10.2%). Generally, prescriptions per year for symptom-relieving AR and asthma treatments were also higher for children initiating AIT vs. adults (AIT children, AIT adults - AR prescriptions per subject: 1.72, 0.73; asthma prescriptions per subject: 1.42, 0.79). Children with AR who are offered AIT in real-life show considerable disease burden prior to initiation. As AIT may alleviate the burden and halt the progression of allergic disease, considering AIT earlier in the disease course may be warranted.

Recent insights into comorbidities in atopic dermatitis

ABSTRACT Introduction The relationship between atopic dermatitis and atopic diseases such as food allergies, asthma, and allergic rhinitis in terms of co-occurrence, underlying mechanisms, and therapy is well documented. There is increasing evidence that atopic dermatitis is associated with non-atopic comorbidities such as cardiac, autoimmune, and neuropsychological comorbidities, as well as cutaneous and extracutaneous infections, establishing atopic dermatitis as a systemic disease. Areas covered The authors reviewed evidence on atopic and non-atopic comorbidities of atopic dermatitis. A literature search was conducted in PubMed for peer-reviewed articles published until October 2022. Expert opinion Atopic and non-atopic diseases coexist with atopic dermatitis more often than would be expected by chance. The effect of biologics and small molecules on atopic and non-atopic comorbidities may contribute to a better understanding of the relationship between atopic dermatitis and its comorbidities. Their relationship needs to be explored further to dismantle the underlying mechanism and move toward an atopic dermatitis endotype-based therapeutic approach.

Prevalence and risk factors of atopic dermatitis in Chinese adults: a nationwide population-based cross-sectional study.

Prevalence and risk factors of atopic dermatitis in Chinese adults: a nationwide population-based cross-sectional study.

Pediatric chronic urticaria: Clinical and laboratory characteristics and factors linked to remission.

Chronic urticaria (CU) is defined as the occurrence of wheals/angioedema for ≥6 consecutive weeks. Until now, guidelines and publications addressing CU have focused mainly on adults. As a result, evidence and guidance in the pediatric population are scarce. This study aims to describe clinical and laboratory findings in pediatric CU and to determine factors associated with remission. 185 patients, 54% female, median age at onset of 8.8 years. Angioedema was present in almost half. The most common type of CU was chronic spontaneous urticaria (CSU) in 74%. At least one atopic comorbidity was found in almost a third (35%). In addition, 8% had an autoimmune disorder (exclusively in CSU) and 9% had a psychiatric condition. Basopenia was found in 67% and was more frequently associated with CSU. The basophil activation test (BAT) was positive in 40%. With regard to remission, being of male sex, angioedema absence, the absence of physical triggers, and eosinophil counts >0.51 × 109 /L were associated with shorter CU duration. Atopy is a common condition in pediatric CU. CSU is the most common type. Autoimmune comorbidities and basopenia were significantly more common in CSU. In addition, ours is one of the few studies, assessing BAT utility in the pediatric population, being positive in a relevant percentage (40%). BAT positivity was more frequent in CSU. Our results suggest that the absence of angioedema and physical triggers, male sex, and eosinophil counts >0.51 × 109 /L appear to be associated with a better prognosis in terms of remission.

Atopic comorbidities associated with granuloma annulare: A case-control study of the All of Us database

Atopic comorbidities associated with granuloma annulare: A case-control study of the All of Us database

The role of insomnia in the vulnerability to depressive and anxiety symptoms in atopic dermatitis adult patients

Atopic dermatitis (AD) is a common inflammatory chronic skin disease typically associated with atopic comorbidities and other non-atopic conditions such as sleep disturbances, and mood/anxiety disorders. A growing literature proposed a crucial role of sleep disturbances in the development of mental health problems in AD. We tested this assumption by mediation model analyses in adult AD patients.A total of 57 patients (mean age ± std. dev., 34.28 ± 13.07 years; 27 males; range 18–67 years) diagnosed with AD participated in a cross-sectional study. We evaluated self-perceived severity of AD, insomnia, depression, and anxiety symptoms using validated questionnaires: the Patient-Oriented Eczema Measure (POEM), the Insomnia Severity Index (ISI), the Beck Depression Inventory-second edition (BDI-II), and the Generalized Anxiety Disorder-7 scale (GAD-7), respectively. Two mediation models were performed, testing the mediation effect of insomnia symptoms on the relationship between AD severity and depression (model 1) and anxiety (model 2). AD symptoms, as expressed by POEM, were positively associated with insomnia, depression, and anxiety severity. Insomnia fully mediated the effect of AD severity on depression and anxiety. Specifically, insomnia accounted for 81.64% of the relationship between atopic eczema severity and depression, and for 81.84% of the effect of AD severity on anxiety symptoms. The present study proposed a critical role of insomnia in predisposing adult AD patients to experience depression and anxiety. Early interventions focused on treating sleep disturbances could indirectly be beneficial on mental health of patients with AD, counteracting the onset and exacerbation of anxiety and depression disorders.

Efficacy of Lebrikizumab in Patients With Atopic Dermatitis and Atopic Comorbidities: Pooled Results From Two Phase 3 Monotherapy Randomized, Double-Blind, Placebo-Controlled 16-Week Studies (ADvocate1 and ADvocate2)

Atopic comorbidities are common in patients with atopic dermatitis (AD). We evaluated lebrikizumab, a high-affinity monoclonal antibody targeting interleukin-13, in patients with AD with and without atopic comorbidities in 2 Phase 3, randomized, double-blind trials (ADvocate1 [NCT04146363] and ADvocate2 [NCT04178967]).

Dupilumab Efficacy in Children With Atopic Dermatitis Aged 6 Months to 5 Years With and Without Atopic Comorbidities

Atopic dermatitis (AD) is a chronic inflammatory systemic disease that frequently occurs with atopic comorbidities. Here, we evaluate the efficacy of dupilumab with concomitant topical corticosteroids (TCS) for moderate-to-severe AD in children with and without asthma, allergic rhinitis, and food allergies.

Racial and Ethnic Disparities in Allergen Immunotherapy Prescription for Allergic Rhinitis

Racial and ethnic differences exist in the severity of various atopic diseases including allergic rhinitis (AR). Patients of under-represented races and ethnicities may be subjected to disparate subcutaneous allergen immunotherapy (SCIT) prescription practices. To explore the racial and ethnic disparities in the use of SCIT among patients with AR. In this retrospective matched cohort study, we used the TriNetX US Collaborative Network, a multicenter electronic health record-based database to identify patients with AR 18 years and older. Patients were grouped according to their racial and ethnic identification. Study groups were matched for baseline demographics, atopic comorbidities, heart diseases and utilization of β-blockers, and angiotensin-converting enzyme inhibitors. The proportion of patients of under-represented racial and ethnic groups started on SCIT was contrasted to the non-Hispanic White cohort. We identified 1,038,000 patients with AR; the mean age (±standard deviation) at the index was 49.7 (±16.1) years, and 64.6% were female. Ethnicity information was available from 87.3% of patients, and the majority (92.3%) were non-Hispanic. Over a 3-year observation period, fewer Black patients (relative risk [RR], 0.40; 95% confidence interval [CI], 0.33-0.48) and Hispanic patients (RR, 0.80; 95% CI, 0.64-0.99) were started on SCIT compared with non-Hispanic White patients. The proportions of Asian patients who were initiated on SCIT tended to be lower when compared with non-Hispanic White patients (RR, 0.69; 95% CI, 0.47-1.009). In the United States, differences in SCIT prescription exist between Black and Hispanic patients relative to White patients. Barriers to treatment should be explored and mitigated.

Efficacy and safety of peanut epicutaneous immunotherapy in patients with atopic comorbidities.

Co-occurring atopic conditions are common in children with peanut allergy. As such, it is important to examine the safety and efficacy of epicutaneous immunotherapy with Viaskin Peanut 250 μg patch (VP250) in peanut-allergic children with these conditions. We sought to compare efficacy and safety of VP250 versus placebo in peanut-allergic children with/withoutongoing atopic conditions at baseline, includingasthma, atopic dermatitis/eczema, or concomitant food allergy. A subgroup analysis of peanut-allergic children aged 4 to 11 years enrolled in PEPITES (12 months) and REALISE (6 months) randomized, placebo-controlled, phase 3 trials was conducted. The efficacy outcome measure was the difference in prespecified responder rate between placebo and VP250 groups at month 12 based on eliciting dose of peanut protein using double-blind, placebo-controlled food challenge in PEPITES. Safety profiles were evaluated by baseline concomitant disease subgroup in all randomized subjects who received 1 or more dose of the study drug in PEPITES and REALISE pooled data. Responder rates were significantly (P< .05, all comparisons) greater with VP250 compared with placebo treatment regardless of whether subjects had other atopic conditions. Safety and tolerability profiles were generally similar across subgroups, with no new safety concerns detected. Atrend for both higher responder rates and rates of local reactions was observed in subjects with baseline atopic dermatitis versus those without. In subjects with concomitant food allergy at baseline, higher rates of treatment-emergent adverse events, but not study discontinuations or overall rates of anaphylaxis, were observed. The results support the safety and efficacy of VP250 for treating peanut-allergic children with or without concomitant atopic conditions.

Allergic Comorbidities Influence Dupilumab Therapy Persistence in Patients with Asthma and CRSwNP

Dupilumab is a monoclonal antibody against IL-4Ra, approved for treatment of multiple atopic diseases, including asthma and chronic rhinosinusitis with nasal polyposis (CRSwNP). Dupilumab clinical trials showed low discontinuation rates. As dupilumab targets key mechanisms implicated in multiple atopic comorbidities, there exists a need to understand how allergic comorbidities affect dupilumab persistence when prescribed for indications of asthma and CRSwNP.

Assessing Disparities in the Prevalence of Atopic Comorbidities Among Food-Allergic Children

Previous studies have reported that Black children with food allergy (FA) have higher risk of atopic comorbidities than White children. Our study sought to understand if disparities in the prevalence of atopic comorbidities among children with FA are driven by individual and community-level socioeconomic status (SES). We analyzed data from a prospective, multicenter cohort investigating the natural history of pediatric atopy: the Food Allergy Outcomes Related to White and African American Racial Differences (FORWARD) study. A validated, multicomponent area deprivation index (ADI) percentile score was tabulated by the census block group for each subject's home address. The association of ADI with atopic comorbidities in FA was assessed via multivariable regression analysis. Of the 700 children in this study, the mean ADI was 37.7 (95% confidence interval: 35.6-39.7). The mean ADI was higher in children with asthma (43.3) compared with those without asthma (31.8), which remained significant after adjusting for race (P < .0001). Children with allergic rhinitis (AR) had a higher mean ADI (39.1) compared with those without (33.4) (P= .008). ADI was associated with secondhand smoking, parents' education, and household income. Black children had a higher risk for asthma after adjusting for ADI and SES-related factors. The independent association of ADI with asthma and AR, regardless of race, suggests a role of neighborhood-level socioeconomic deprivation in the development of these conditions among children with FA. Black children with FA remained at higher risk for asthma after adjusting for SES-related variables, which can indicate an independent risk for asthma in these children.