Global warming and implications for epithelial barrier disruption and respiratory and dermatologic allergic diseases.

Global warming has direct and indirect effects, as well as short- and long-term impacts on the respiratory and skin barriers. Extreme temperature directly affects the airway epithelial barrier by disrupting the structural proteins and by triggering airway inflammation and hyperreactivity. It enhances tidal volume and respiratory rate by affecting the thermoregulatory system, causing specific airway resistance and reflex bronchoconstriction via activation of bronchopulmonary vagal C fibers and upregulation of transient receptor potential vanilloid (TRPV) 1 and TRPV4. Heat shock proteins are activated under heat stress and contribute to both epithelial barrier dysfunction and airway inflammation. Accordingly, the frequency and severity of allergic rhinitis and asthma have been increasing. Heat activates TRPV3 in keratinocytes, causing the secretion of inflammatory mediators and eventually pruritus. Exposure to air pollutants alters the expression of genes that control skin barrier integrity and triggers an immune response, increasing the incidence and prevalence of atopic dermatitis. There is evidence that extreme temperature, heavy rains and floods, air pollution, and wildfires increase atopic dermatitis flares. In this narrative review, focused on the last 3 years of literature, we explore the effects of global warming on respiratory and skin barrier and their clinical consequences.

Systemic treatments for atopic dermatitis (eczema): Systematic review and network meta-analysis of randomized trials.

BACKGROUND: Atopic dermatitis (AD) is an inflammatory skin condition with multiple systemic treatments and uncertainty regarding their comparative impact on AD outcomes. OBJECTIVE: We sought to systematically synthesize the benefits and harms of AD systemic treatments. METHODS: For the 2023 American Academy of Allergy, Asthma & Immunology and American College of Allergy, Asthma, and Immunology Joint Task Force on Practice Parameters AD guidelines, we searched MEDLINE, EMBASE, CENTRAL, Web of Science, and GREAT databases from inception to November 29, 2022, for randomized trials addressing systemic treatments and phototherapy for AD. Paired reviewers independently screened records, extracted data, and assessed risk of bias. Random-effects network meta-analyses addressed AD severity, itch, sleep, AD-related quality of life, flares, and harms. The Grading of Recommendations Assessment, Development and Evaluation approach informed certainty of evidence ratings. This review is registered in the Open Science Framework (https://osf.io/e5sna). RESULTS: The 149 included trials (28,686 patients with moderate-to-severe AD) evaluated 75 interventions. With high-certainty evidence, high-dose upadacitinib was among the most effective for 5 of 6 patient-important outcomes; high-dose abrocitinib and low-dose upadacitinib were among the most effective for 2 outcomes. These Janus kinase inhibitors were among the most harmful in increasing adverse events. With high-certainty evidence, dupilumab, lebrikizumab, and tralokinumab were of intermediate effectiveness and among the safest, modestly increasing conjunctivitis. Low-dose baricitinib was among the least effective. Efficacy and safety of azathioprine, oral corticosteroids, cyclosporine, methotrexate, mycophenolate, phototherapy, and many novel agents are less certain. CONCLUSIONS: Among individuals with moderate-to-severe AD, high-certainty evidence demonstrates that high-dose upadacitinib is among the most effective in addressing multiple patient-important outcomes, but also is among the most harmful. High-dose abrocitinib and low-dose upadacitinib are effective, but also among the most harmful. Dupilumab, lebrikizumab, and tralokinumab are of intermediate effectiveness and have favorable safety.

Dupilumab in children aged 6 months to younger than 6 years with uncontrolled atopic dermatitis: a randomised, double-blind, placebo-controlled, phase 3 trial.

BACKGROUND: Current systemic treatments for children younger than 6 years with moderate-to-severe atopic dermatitis that is uncontrolled with topical therapies might have suboptimal efficacy and safety. Dupilumab is approved for older children and adults with atopic dermatitis and for other type 2 inflammatory conditions. We aimed to evaluate efficacy and safety of dupilumab with concomitant low-potency topical corticosteroids in children aged 6 months to younger than 6 years with moderate-to-severe atopic dermatitis. METHODS: This randomised, double-blind, placebo-controlled, parallel-group, phase 3 trial was conducted in 31 hospitals, clinics, and academic institutions in Europe and North America. Eligible patients were aged 6 months to younger than 6 years, with moderate-to-severe atopic dermatitis (Investigator's Global Assessment [IGA] score 3-4) diagnosed according to consensus criteria of the American Academy of Dermatology, and an inadequate response to topical corticosteroids. Patients were randomly assigned (1:1) to subcutaneous placebo or dupilumab (bodyweight ≥5 kg to <15 kg: 200 mg; bodyweight ≥15 kg to <30 kg: 300 mg) every 4 weeks plus low-potency topical corticosteroids (hydrocortisone acetate 1% cream) for 16 weeks. Randomisation was stratified by age, baseline bodyweight, and region. Patient allocation was done via a central interactive web response system, and treatment allocation was masked. The primary endpoint at week 16 was the proportion of patients with IGA score 0-1 (clear or almost clear skin). The key secondary endpoint (coprimary endpoint for the EU and EU reference market) at week 16 was the proportion of patients with at least a 75% improvement from baseline in Eczema Area and Severity Index (EASI-75). Primary analyses were done in the full analysis set (ie, all randomly assigned patients, as randomly assigned) and safety analyses were done in all patients who received any study drug. This study was registered with ClinicalTrials.gov, NCT03346434. FINDINGS: Between June 30, 2020, and Feb 12, 2021, 197 patients were screened for eligibility, 162 of whom were randomly assigned to receive dupilumab (n=83) or placebo (n=79) plus topical corticosteroids. At week 16, significantly more patients in the dupilumab group than in the placebo group had IGA 0-1 (23 [28%] vs three [4%], difference 24% [95% CI 13-34]; p<0·0001) and EASI-75 (44 [53%] vs eight [11%], difference 42% [95% CI 29-55]; p<0·0001). Overall prevalence of adverse events was similar in the dupilumab group (53 [64%] of 83 patients) and placebo group (58 [74%] of 78 patients). Conjunctivitis incidence was higher in the dupilumab group (four [5%]) than the placebo group (none). No dupilumab-related adverse events were serious or led to treatment discontinuation. INTERPRETATION: Dupilumab significantly improved atopic dermatitis signs and symptoms versus placebo in children younger than 6 years. Dupilumab was well tolerated and showed an acceptable safety profile, similar to results in older children and adults. FUNDING: Sanofi and Regeneron Pharmaceuticals.

Mental health interventions for atopic dermatitis: knowledge gaps, pilot programmes and future directions.

Atopic dermatitis (AD) is associated with high levels of psychosocial burden, often resulting in poor mental health outcomes. Despite this association, few studies have evaluated the efficacy of mental health interventions within this population. Utilization of multidisciplinary and peer-led support, in addition to equipping patients with psychological tools, may be beneficial in improving mental health outcomes. Future research is needed to determine which interventions and formats are desired by, effective in and accessible to patients and caregivers with AD.

Polygenic prediction of atopic dermatitis improves with atopic training and filaggrin factors.

BACKGROUND: While numerous genetic loci associated with atopic dermatitis (AD) have been discovered, to date, work leveraging the combined burden of AD risk variants across the genome to predict disease risk has been limited. OBJECTIVES: This study aims to determine whether polygenic risk scores (PRSs) relying on genetic determinants for AD provide useful predictions for disease occurrence and severity. It also explicitly tests the value of including genome-wide association studies of related allergic phenotypes and known FLG loss-of-function (LOF) variants. METHODS: AD PRSs were constructed for 1619 European American individuals from the Atopic Dermatitis Research Network using an AD training dataset and an atopic training dataset including AD, childhood onset asthma, and general allergy. Additionally, whole genome sequencing data were used to explore genetic scoring specific to FLG LOF mutations. RESULTS: Genetic scores derived from the AD-only genome-wide association studies were predictive of AD cases (PRSAD: odds ratio [OR], 1.70; 95% CI, 1.49-1.93). Accuracy was first improved when PRSs were built off the larger atopy genome-wide association studies (PRSAD+: OR, 2.16; 95% CI, 1.89-2.47) and further improved when including FLG LOF mutations (PRSAD++: OR, 3.23; 95% CI, 2.57-4.07). Importantly, while all 3 PRSs correlated with AD severity, the best prediction was from PRSAD++, which distinguished individuals with severe AD from control subjects with OR of 3.86 (95% CI, 2.77-5.36). CONCLUSIONS: This study demonstrates how PRSs for AD that include genetic determinants across atopic phenotypes and FLG LOF variants may be a promising tool for identifying individuals at high risk for developing disease and specifically severe disease.

Anaphylaxis knowledge gaps and future research priorities: A consensus report.

BACKGROUND: Despite a better understanding of the epidemiology, pathogenesis, and management of patients with anaphylaxis, there remain knowledge gaps. Enumerating and prioritizing these gaps would allow limited scientific resources to be directed more effectively. OBJECTIVE: We sought to systematically describe and appraise anaphylaxis knowledge gaps and future research priorities based on their potential impact and feasibility. METHODS: We convened a 25-member multidisciplinary panel of anaphylaxis experts. Panelists formulated knowledge gaps/research priority statements in an anonymous electronic survey. Four anaphylaxis themed writing groups were formed to refine statements: (1) Population Science, (2) Basic and Translational Sciences, (3) Emergency Department Care/Acute Management, and (4) Long-Term Management Strategies and Prevention. Revised statements were incorporated into an anonymous electronic survey, and panelists were asked to rate the impact and feasibility of addressing statements on a continuous 0 to 100 scale. RESULTS: The panel generated 98 statements across the 4 anaphylaxis themes: Population Science (29), Basic and Translational Sciences (27), Emergency Department Care/Acute Management (24), and Long-Term Management Strategies and Prevention (18). Median scores for impact and feasibility ranged from 50.0 to 95.0 and from 40.0 to 90.0, respectively. Key statements based on median rating for impact/feasibility included the need to refine anaphylaxis diagnostic criteria, identify reliable diagnostic, predictive, and prognostic anaphylaxis bioassays, develop clinical prediction models to standardize postanaphylaxis observation periods and hospitalization criteria, and determine immunotherapy best practices. CONCLUSIONS: We identified and systematically appraised anaphylaxis knowledge gaps and future research priorities. This study reinforces the need to harmonize scientific pursuits to optimize the outcomes of patients with and at risk of anaphylaxis.

Severity grading system for acute allergic reactions: A multidisciplinary Delphi study.

BACKGROUND: There is no widely adopted severity grading system for acute allergic reactions, including anaphylactic and nonanaphylactic reactions, thus limiting the ability to optimize and standardize management practices and advance research. OBJECTIVE: The aim of this study was to develop a severity grading system for acute allergic reactions for use in clinical care and research. METHODS: From May to September 2020, we convened a 21-member multidisciplinary panel of allergy and emergency care experts; 9 members formed a writing group to critically appraise and assess the strengths and limitations of prior severity grading systems and develop the structure and content for an optimal severity grading system. The entire study panel then revised the grading system and sought consensus by utilizing Delphi methodology. RESULTS: The writing group recommended that an optimal grading system encompass the severity of acute allergic reactions on a continuum from mild allergic reactions to anaphylactic shock. Additionally, the severity grading system must be able to discriminate between clinically important differences in reaction severity to be relevant in research while also being intuitive and straightforward to apply in clinical care. Consensus was reached for all elements of the proposed severity grading system. CONCLUSION: We developed a consensus severity grading system for acute allergic reactions, including anaphylactic and nonanaphylactic reactions. Successful international validation, refinement, dissemination, and application of the grading system will improve communication among providers and patients about the severity of allergic reactions and will help advance future research.

Multiethnic genome-wide and HLA association study of total serum IgE level.

BACKGROUND: Total serum IgE (tIgE) is an important intermediate phenotype of allergic disease. Whole genome genetic association studies across ancestries may identify important determinants of IgE. OBJECTIVE: We aimed to increase understanding of genetic variants affecting tIgE production across the ancestry and allergic disease spectrum by leveraging data from the National Heart, Lung and Blood Institute Trans-Omics for Precision Medicine program; the Consortium on Asthma among African-ancestry Populations in the Americas (CAAPA); and the Atopic Dermatitis Research Network (N = 21,901). METHODS: We performed genome-wide association within strata of study, disease, and ancestry groups, and we combined results via a meta-regression approach that models heterogeneity attributable to ancestry. We also tested for association between HLA alleles called from whole genome sequence data and tIgE, assessing replication of associations in HLA alleles called from genotype array data. RESULTS: We identified 6 loci at genome-wide significance (P < 5 × 10-9), including 4 loci previously reported as genome-wide significant for tIgE, as well as new regions in chr11q13.5 and chr15q22.2, which were also identified in prior genome-wide association studies of atopic dermatitis and asthma. In the HLA allele association study, HLA-A∗02:01 was associated with decreased tIgE level (Pdiscovery = 2 × 10-4; Preplication = 5 × 10-4; Pdiscovery+replication = 4 × 10-7), and HLA-DQB1∗03:02 was strongly associated with decreased tIgE level in Hispanic/Latino ancestry populations (PHispanic/Latino discovery+replication = 8 × 10-8). CONCLUSION: We performed the largest genome-wide association study and HLA association study of tIgE focused on ancestrally diverse populations and found several known tIgE and allergic disease loci that are relevant in non-European ancestry populations.

Whole genome sequencing identifies novel genetic mutations in patients with eczema herpeticum.

BACKGROUND: Eczema herpeticum (EH) is a rare complication of atopic dermatitis (AD) caused by disseminated herpes simplex virus (HSV) infection. The role of rare and/or deleterious genetic variants in disease etiology is largely unknown. This study aimed to identify genes that harbor damaging genetic variants associated with HSV infection in AD with a history of recurrent eczema herpeticum (ADEH+). METHODS: Whole genome sequencing (WGS) was performed on 49 recurrent ADEH+ (≥3 EH episodes), 491 AD without a history of eczema herpeticum (ADEH-) and 237 non-atopic control (NA) subjects. Variants were annotated, and a gene-based approach (SKAT-O) was used to identify genes harboring damaging genetic variants associated with ADEH+. Genes identified through WGS were studied for effects on HSV responses and keratinocyte differentiation. RESULTS: Eight genes were identified in the comparison of recurrent ADEH+to ADEH-and NA subjects: SIDT2, CLEC7A, GSTZ1, TPSG1, SP110, RBBP8NL, TRIM15, and FRMD3. Silencing SIDT2 and RBBP8NL in normal human primary keratinocytes (NHPKs) led to significantly increased HSV-1 replication. SIDT2-silenced NHPKs had decreased gene expression of IFNk and IL1b in response to HSV-1 infection. RBBP8NL-silenced NHPKs had decreased gene expression of IFNk, but increased IL1b. Additionally, silencing SIDT2 and RBBP8NL also inhibited gene expression of keratinocyte differentiation markers keratin 10 (KRT10) and loricrin (LOR). CONCLUSION: SIDT2 and RBBP8NL participate in keratinocyte's response to HSV-1 infection. SIDT2 and RBBP8NL also regulate expression of keratinocyte differentiation genes of KRT10 and LOR.

Improving patient education for atopic dermatitis: A randomized controlled trial of a caregiver handbook.

BACKGROUND/OBJECTIVES: Patient education is important to families' ability to manage and cope with pediatric atopic dermatitis (AD). We evaluated whether an educational handbook could improve AD symptoms, caregiver confidence in AD management skills, and AD-related quality of life. METHODS: Caregivers of children with AD ages 1 month to 16 years were randomly assigned to the intervention arm (handbook in addition to standard AD management) or the control arm (standard management alone). Caregivers completed self-report outcome questionnaires prior to a clinical visit for AD and at 3-month follow-up. RESULTS: 175 caregivers completed questionnaires at baseline and follow-up. AD symptoms measured by the Patient-Oriented Eczema Measure (POEM) improved in both the handbook and control arms. However, the decrease in the mean POEM score in the handbook arm (-4.4, 95% CI [-5.8, -3.0]) did not differ from that in the control arm (-3.4, 95% CI [-4.8, -2.03]; P = .343). Change in quality of life did not differ between study arms. Among caregivers attending a new patient visit for AD, mean confidence scores (measured from 0 to 100) increased more in the handbook arm (67 [95% CI {60, 74}] to 83 [95% CI {77, 88}]) relative to the control arm (74 [95% CI {65, 82}] to 75 [95% CI {67, 83}]; P = .012). The majority of caregivers rated the handbook as helpful in managing the child's AD. CONCLUSIONS: Despite an adequate sample size, the handbook did not improve AD symptoms more than standard management alone. The handbook improved confidence in management skills for families attending new patient visits for AD.

Persistent, refractory, and biphasic anaphylaxis: A multidisciplinary Delphi study.

BACKGROUND: The use of inconsistent definitions for anaphylaxis outcomes limits our understanding of the natural history and epidemiology of anaphylaxis, hindering clinical practice and research efforts. OBJECTIVE: Our aim was to develop consensus definitions for clinically relevant anaphylaxis outcomes by utilizing a multidisciplinary group of clinical and research experts in anaphylaxis. METHODS: Using Delphi methodology, we developed agenda topics and drafted questions to review during monthly conference calls. Through online surveys, a 19-member panel consisting of experts in allergy and/or immunology and emergency medicine rated their level of agreement with the appropriateness of statements on a scale of 1 to 9. A median value of 1.0 to 3.4 was considered inappropriate, a median value of 3.5 to 6.9 was considered uncertain, and a median value of 7.0 to 9.0 was considered appropriate. A disagreement index was then calculated, with values less than 1.0 categorized as "consensus reached." If consensus was not reached after the initial survey, subsequent surveys incorporating the aggregate de-identified responses from prior surveys were sent to panel members. This process was repeated until consensus was reached or 4 survey rounds had been completed, after which the question was categorized as "no consensus reached." RESULTS: The panel developed outcome definitions for persistent, refractory, and biphasic anaphylaxis, as well as for persistent and biphasic nonanaphylactic reactions. There was also consensus among panel members regarding the need to develop an anaphylaxis severity grading system. CONCLUSION: Dissemination and application of these definitions in clinical care and research will help standardize the terminology used to describe anaphylaxis outcomes and serve as the foundation for future research, including research aimed at development of an anaphylaxis severity grading system.

Long-term, open-label extension study of the efficacy and safety of epicutaneous immunotherapy for peanut allergy in children: PEOPLE 3-year results.

BACKGROUND: The PEPITES (Peanut EPIT Efficacy and Safety) trial, a 12-month randomized controlled study of children with peanut allergy and 4 to 11 years old, previously reported the safety and efficacy of epicutaneous immunotherapy (EPIT) for peanut allergy (250 µg, daily epicutaneous peanut protein; DBV712 250 µg). OBJECTIVE: We sought to assess interim safety and efficacy of an additional 2 years of EPIT from the ongoing (5-year treatment) PEOPLE (PEPITES Open-Label Extension) study. METHODS: Subjects who completed PEPITES were offered enrollment in PEOPLE. Following an additional 2 years of daily DBV712 250 µg, subjects who had received DBV712 250 µg in PEPITES underwent month-36 double-blind, placebo-controlled food challenge with an optional month-38 sustained unresponsiveness assessment. RESULTS: Of 213 eligible subjects who had received DBV712 250 µg in PEPITES, 198 (93%) entered PEOPLE, of whom 141 (71%) had assessable double-blind, placebo-controlled food challenge at month 36. At month 36, 51.8% of subjects (73 of 141) reached an eliciting dose of ≥1000 mg, compared with 40.4% (57 of 141) at month 12; 75.9% (107 of 141) demonstrated increased eliciting dose compared with baseline; and 13.5% (19 of 141) tolerated the full double-blind, placebo-controlled food challenge of 5444 mg. Median cumulative reactive dose increased from 144 to 944 mg. Eighteen subjects underwent an optional sustained unresponsiveness assessment; 14 of those (77.8%) maintained an eliciting dose of ≥1000 mg at month 38. Local patch-site skin reactions were common but decreased over time. There was no treatment-related epinephrine use in years 2 or 3. Compliance was high (96.9%), and withdrawals due to treatment-related adverse events were low (1%). CONCLUSIONS: These results demonstrate that daily EPIT treatment for peanut allergy beyond 1 year leads to continued response from a well-tolerated, simple-to-use regimen.

A clinical trial of intradermal and intramuscular seasonal influenza vaccination in patients with atopic dermatitis.

BACKGROUND: Antibody responses to the inactivated seasonal influenza vaccine in patients with atopic dermatitis (AD) have not been carefully characterized. OBJECTIVE: The primary objective of this study was to compare antibody responses to intradermal vaccination in participants with moderate/severe AD with those in nonatopic participants. Secondary objectives were to evaluate the effect of route of administration, Staphylococcus aureus skin colonization, and disease severity on vaccine response. METHODS: This was an open-label study conducted in the 2012-2013 influenza season at 5 US clinical sites. A total of 360 participants with moderate/severe AD or nonatopic subjects were assessed for eligibility, 347 of whom received intradermal or intramuscular vaccination per label and were followed for 28 days after vaccination. The primary outcome was the difference in the proportion of participants achieving seroprotection (hemagglutination-inhibition antibody titer ≥1:40 on day 28 after vaccination). RESULTS: Seroprotection rates for influenza B, H1N1, and H3N2 were not different (1) between participants with AD and nonatopic participants receiving intradermal vaccination and (2) between AD participants receiving intradermal and intramuscular vaccination. After intradermal, but not intramuscular, vaccination, participants with AD with S aureus colonization experienced (1) lower seroprotection and seroconversion rates and lower hemagglutination-inhibition antibody titer geometric mean fold increase against influenza B and (2) lower seroconversion rates against influenza H1N1 than noncolonized participants with AD. CONCLUSION: Participants with AD colonized with S aureus exhibited a reduced immune response to influenza vaccination compared with noncolonized participants after intradermal but not intramuscular vaccination. Because most patients with AD are colonized with S aureus, intramuscular influenza vaccination should be given preference in these patients.

Omalizumab facilitates rapid oral desensitization for peanut allergy.

BACKGROUND: Peanut oral immunotherapy is a promising approach to peanut allergy, but reactions are frequent, and some patients cannot be desensitized. The anti-IgE medication omalizumab (Xolair; Genentech, South San Francisco, Calif) might allow more rapid peanut updosing and decrease reactions. OBJECTIVE: We sought to evaluate whether omalizumab facilitated rapid peanut desensitization in highly allergic patients. METHODS: Thirty-seven subjects were randomized to omalizumab (n = 29) or placebo (n = 8). After 12 weeks of treatment, subjects underwent a rapid 1-day desensitization of up to 250 mg of peanut protein, followed by weekly increases up to 2000 mg. Omalizumab was then discontinued, and subjects continued on 2000 mg of peanut protein. Subjects underwent an open challenge to 4000 mg of peanut protein 12 weeks after stopping study drug. If tolerated, subjects continued on 4000 mg of peanut protein daily. RESULTS: The median peanut dose tolerated on the initial desensitization day was 250 mg for omalizumab-treated subjects versus 22.5 mg for placebo-treated subject. Subsequently, 23 (79%) of 29 subjects randomized to omalizumab tolerated 2000 mg of peanut protein 6 weeks after stopping omalizumab versus 1 (12%) of 8 receiving placebo (P < .01). Twenty-three subjects receiving omalizumab versus 1 subject receiving placebo passed the 4000-mg food challenge. Overall reaction rates were not significantly lower in omalizumab-treated versus placebo-treated subjects (odds ratio, 0.57; P = .15), although omalizumab-treated subjects were exposed to much higher peanut doses. CONCLUSION: Omalizumab allows subjects with peanut allergy to be rapidly desensitized over as little as 8 weeks of peanut oral immunotherapy. In the majority of subjects, this desensitization is sustained after omalizumab is discontinued. Additional studies will help clarify which patients would benefit most from this approach.

Addendum guidelines for the prevention of peanut allergy in the United States: Report of the National Institute of Allergy and Infectious Diseases-sponsored expert panel.

BACKGROUND: Food allergy is an important public health problem because it affects children and adults, can be severe and even life-threatening, and may be increasing in prevalence. Beginning in 2008, the National Institute of Allergy and Infectious Diseases, working with other organizations and advocacy groups, led the development of the first clinical guidelines for the diagnosis and management of food allergy. A recent landmark clinical trial and other emerging data suggest that peanut allergy can be prevented through introduction of peanut-containing foods beginning in infancy. OBJECTIVES: Prompted by these findings, along with 25 professional organizations, federal agencies, and patient advocacy groups, the National Institute of Allergy and Infectious Diseases facilitated development of addendum guidelines to specifically address the prevention of peanut allergy. RESULTS: The addendum provides 3 separate guidelines for infants at various risk levels for the development of peanut allergy and is intended for use by a wide variety of health care providers. Topics addressed include the definition of risk categories, appropriate use of testing (specific IgE measurement, skin prick tests, and oral food challenges), and the timing and approaches for introduction of peanut-containing foods in the health care provider's office or at home. The addendum guidelines provide the background, rationale, and strength of evidence for each recommendation. CONCLUSIONS: Guidelines have been developed for early introduction of peanut-containing foods into the diets of infants at various risk levels for peanut allergy.

Combining anti-IgE with oral immunotherapy.

Food allergy is a significant medical problem that affects up to 8% of children in developed countries. At present, there are no curative therapies available in routine practice and management of food allergy involves strict allergen avoidance, education, and prompt treatment upon accidental exposure. Oral immunotherapy (OIT) is an efficacious experimental approach to food allergy and has been shown to provide a substantial benefit in terms of allergen desensitization. However, OIT is associated with high rates of allergic reactions, and the period of protection offered by OIT appears to be limited and highly variable. Recurrence of allergen sensitivity after a period of treatment discontinuation is commonly observed. With the aim of overcoming these limitations of OIT, several trials have studied omalizumab (anti-IgE monoclonal antibody) as an adjuvant treatment for patients undergoing OIT. Results from these trials have shown that the addition of omalizumab to OIT leads to a significant decrease in the frequency and severity of reactions, which allows for an increase in the threshold of tolerance to food allergens. This review provides a summary of the current literature and addresses some of the key questions that remain regarding the use of omalizumab in conjunction with OIT.

Addendum guidelines for the prevention of peanut allergy in the United States: Report of the National Institute of Allergy and Infectious Diseases-sponsored expert panel.

BACKGROUND: Food allergy is an important public health problem because it affects children and adults, can be severe and even life-threatening, and may be increasing in prevalence. Beginning in 2008, the National Institute of Allergy and Infectious Diseases, working with other organizations and advocacy groups, led the development of the first clinical guidelines for the diagnosis and management of food allergy. A recent landmark clinical trial and other emerging data suggest that peanut allergy can be prevented through introduction of peanut-containing foods beginning in infancy. OBJECTIVES: Prompted by these findings, along with 25 professional organizations, federal agencies, and patient advocacy groups, the National Institute of Allergy and Infectious Diseases facilitated development of addendum guidelines to specifically address the prevention of peanut allergy. RESULTS: The addendum provides 3 separate guidelines for infants at various risk levels for the development of peanut allergy and is intended for use by a wide variety of health care providers. Topics addressed include the definition of risk categories, appropriate use of testing (specific IgE measurement, skin prick tests, and oral food challenges), and the timing and approaches for introduction of peanut-containing foods in the health care provider's office or at home. The addendum guidelines provide the background, rationale, and strength of evidence for each recommendation. CONCLUSIONS: Guidelines have been developed for early introduction of peanut-containing foods into the diets of infants at various risk levels for peanut allergy.

Addendum Guidelines for the Prevention of Peanut Allergy in the United States: Report of the National Institute of Allergy and Infectious Diseases-Sponsored Expert Panel.

BACKGROUND: Food allergy is an important public health problem because it affects children and adults, can be severe and even life-threatening, and may be increasing in prevalence. Beginning in 2008, the National Institute of Allergy and Infectious Diseases, working with other organizations and advocacy groups, led the development of the first clinical guidelines for the diagnosis and management of food allergy. A recent landmark clinical trial and other emerging data suggest that peanut allergy can be prevented through introduction of peanut-containing foods beginning in infancy. OBJECTIVES: Prompted by these findings, along with 25 professional organizations, federal agencies, and patient advocacy groups, the National Institute of Allergy and Infectious Diseases facilitated development of addendum guidelines to specifically address the prevention of peanut allergy. RESULTS: The addendum provides three separate guidelines for infants at various risk levels for the development of peanut allergy and is intended for use by a wide variety of health care providers. Topics addressed include the definition of risk categories, appropriate use of testing (specific IgE measurement, skin prick tests, and oral food challenges), and the timing and approaches for introduction of peanut-containing foods in the health care provider's office or at home. The addendum guidelines provide the background, rationale, and strength of evidence for each recommendation. CONCLUSIONS: Guidelines have been developed for early introduction of peanut-containing foods into the diets of infants at various risk levels for peanut allergy.

Multidisciplinary interventions in the management of atopic dermatitis.

Atopic dermatitis (AD) is the most common pediatric skin disease. AD has a significant effect on patient and family quality of life caused by intense pruritus, sleep disruption, dietary and nutritional concerns, and psychological stress associated with the disease and its management. Multidisciplinary approaches to AD care have been developed in appreciation of the complex interplay among biological, psychological, behavioral, and dietary factors that affect disease control and the wide range of knowledge, skills, and support that patients and families require to effectively manage and cope with this condition. Common components of multidisciplinary treatment approaches include medical evaluation and management by an AD specialist, education and nursing care, psychological and behavioral support, and nutritional assessment and guidance. Models of care include both clinical programs and structured educational groups provided as adjuncts to standard clinical care. Available evidence suggests beneficial effects of multidisciplinary interventions in improving disease severity and quality of life, particularly for patients with moderate-to-severe disease. Additional research is needed to identify the best candidates for the various multidisciplinary approaches and evaluate the cost-effectiveness of these programs.

Effect of Varying Doses of Epicutaneous Immunotherapy vs Placebo on Reaction to Peanut Protein Exposure Among Patients With Peanut Sensitivity: A Randomized Clinical Trial.

Importance: Epicutaneous immunotherapy may have potential for treating peanut allergy but has been assessed only in preclinical and early human trials. Objective: To determine the optimal dose, adverse events (AEs), and efficacy of a peanut patch for peanut allergy treatment. Design, Setting, and Participants: Phase 2b double-blind, placebo-controlled, dose-ranging trial of a peanut patch in peanut-allergic patients (6-55 years) from 22 centers, with a 2-year, open-label extension (July 31, 2012-July 31, 2014; extension completed September 29, 2016). Patients (n = 221) had peanut sensitivity and positive double-blind, placebo-controlled food challenges to an eliciting dose of 300 mg or less of peanut protein. Interventions: Randomly assigned patients (1:1:1:1) received an epicutaneous peanut patch containing 50 µg (n = 53), 100 µg (n = 56), or 250 µg (n = 56) of peanut protein or a placebo patch (n = 56). Following daily patch application for 12 months, patients underwent a double-blind, placebo-controlled food challenge to establish changes in eliciting dose. Main Outcomes and Measures: The primary efficacy end point was percentage of treatment responders (eliciting dose: ≥10-times increase and/or reaching ≥1000 mg of peanut protein) in each group vs placebo patch after 12 months. Secondary end points included percentage of responders by age strata and treatment-emergent adverse events (TEAEs). Results: Of 221 patients randomized (median age, 11 years [quartile 1, quartile 3: 8, 16]; 37.6% female), 93.7% completed the trial. A significant absolute difference in response rates was observed at month 12 between the 250-µg (n = 28; 50.0%) and placebo (n = 14; 25.0%) patches (difference, 25.0%; 95% CI, 7.7%-42.3%; P = .01). No significant difference was seen between the placebo patch vs the 100-µg patch. Because of statistical testing hierarchical rules, the 50-µg patch was not compared with placebo. Interaction by age group was only significant for the 250-µg patch (P = .04). In the 6- to 11-year stratum, the response rate difference between the 250-µg (n = 15; 53.6%) and placebo (n = 6; 19.4%) patches was 34.2% (95% CI, 11.1%-57.3%; P = .008); adolescents/adults showed no difference between the 250-µg (n = 13; 46.4%) and placebo (n = 8; 32.0%) patches: 14.4% (95% CI, -11.6% to 40.4%; P = .40). No dose-related serious AEs were observed. The percentage of patients with 1 or more TEAEs (largely local skin reactions) was similar across all groups in year 1: 50-µg patch = 100%, 100-µg patch = 98.2%, 250-µg patch = 100%, and placebo patch = 92.9%. The overall median adherence was 97.6% after 1 year; the dropout rate for treatment-related AEs was 0.9%. Conclusions and Relevance: In this dose-ranging trial of peanut-allergic patients, the 250-µg peanut patch resulted in significant treatment response vs placebo patch following 12 months of therapy. These findings warrant a phase 3 trial. Trial Registration: clinicaltrials.gov Identifier: NCT01675882.