Publications by authors named "Lynda C Schneider"

76 Publications

Effect of Dupilumab on Laboratory Parameters in Adolescents with Atopic Dermatitis: Results from a Randomized, Placebo-Controlled, Phase 3 Clinical Trial.

Am J Clin Dermatol 2021 Mar 3;22(2):243-255. Epub 2021 Mar 3.

Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA.

Background: Laboratory testing is typically required for patients with atopic dermatitis (AD) treated with systemic immunosuppressants. A previous analysis of laboratory outcomes in randomized, double-blinded, placebo-controlled clinical trials of dupilumab in adults with moderate-to-severe AD found no clinically important changes in hematologic, serum chemistry, and urinalysis parameters, supporting the use of dupilumab without routine laboratory monitoring.

Objective: The aim was to assess laboratory results in adolescents with moderate-to-severe AD treated with dupilumab in a phase 3, randomized, double-blind, placebo-controlled trial.

Methods: Adolescents aged ≥ 12 to < 18 years with moderate-to-severe AD were randomized 1:1:1 to subcutaneous dupilumab 200/300 mg every 2 weeks (q2w) (200 mg for patients < 60 kg at baseline; 300 mg for patients ≥ 60 kg at baseline); dupilumab 300 mg every 4 weeks (q4w); or placebo for 16 weeks. Laboratory evaluations included hematology, serum chemistry, and urinalysis parameters.

Results: Of 251 patients enrolled in the study, 250 received treatment and were included in the analysis. 4.7%, 2.4%, and 4.8% of patients receiving placebo, dupilumab 200/300 mg q2w, and dupilumab 300 mg q4w, respectively, had laboratory abnormalities reported as treatment-emergent adverse events, none of which prompted discontinuation of study treatment or study withdrawal. Mean eosinophil counts were elevated at baseline in all treatment groups. Patients in both dupilumab regimens, but not the placebo group, showed mild transient increases in mean eosinophil counts above baseline that returned to near-baseline values by week 16. Mean levels of lactate dehydrogenase trended towards the upper limit of normal at baseline and decreased with treatment; greater decreases were seen in dupilumab-treated patients than placebo-treated patients. There were no meaningful changes in other laboratory parameters, and none of the laboratory abnormalities were clinically significant.

Conclusion: No clinically meaningful changes in laboratory parameters were seen in adolescents, similar to that observed in adults. The findings of this study indicate no routine laboratory monitoring is required in this population prior to or during dupilumab treatment.

Trial Registration: ClinicalTrials.gov: NCT03054428. Video abstract: Effect of Dupilumab on Laboratory Parameters in Adolescents with Atopic Dermatitis: Results from a Randomized Placebo-Controlled Phase 3 Clinical Trial (MP4 175137 KB).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s40257-020-00583-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7973645PMC
March 2021

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

Allergy 2021 Feb 6. Epub 2021 Feb 6.

Division of Allergy and Clinical Immunology, Johns Hopkins University, Baltimore, MD, USA.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/all.14762DOI Listing
February 2021

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

Pediatr Dermatol 2021 Jan 24. Epub 2021 Jan 24.

Division of Immunology, Boston Children's Hospital, Boston, MA, USA.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/pde.14519DOI Listing
January 2021

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

J Allergy Clin Immunol 2021 Jan 19. Epub 2021 Jan 19.

Division of Allergy and Immunology, Icahn School of Medicine at Mount Sinai, New York, NY.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jaci.2021.01.003DOI Listing
January 2021

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

J Allergy Clin Immunol 2020 11 24;146(5):1089-1096. Epub 2020 Aug 24.

Division of Emergency Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jaci.2020.08.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006564PMC
November 2020

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

J Allergy Clin Immunol 2020 10 10;146(4):863-874. Epub 2020 Jul 10.

DBV Technologies, Montrouge, France; Division of Pediatric Allergy and Immunology, Icahn School of Medicine at Mount Sinai, New York, NY.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jaci.2020.06.028DOI Listing
October 2020

Nickel Allergic Contact Dermatitis: Identification, Treatment, and Prevention.

Pediatrics 2020 05;145(5)

Department of Pediatrics, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts.

Nickel is a ubiquitous metal added to jewelry and metallic substances for its hardening properties and because it is inexpensive. Estimates suggest that at least 1.1 million children in the United States are sensitized to nickel. Nickel allergic contact dermatitis (Ni-ACD) is the most common cutaneous delayed-type hypersensitivity reaction worldwide. The incidence among children tested has almost quadrupled over the past 3 decades. The associated morbidities include itch, discomfort, school absence, and reduced quality of life. In adulthood, individuals with Ni-ACD may have severe disabling hand eczema. The increasing rate of Ni-ACD in children has been postulated to result from early and frequent exposure to metals with high amounts of nickel release (eg, as occurs with ear piercing or with products used daily in childhood such as toys, belt buckles, and electronics).To reduce exposure to metal sources with high nickel release by prolonged and direct contact with human skin, Denmark and the European Union legislated a directive several decades ago with the goal of reducing high nickel release and the incidence of Ni-ACD. Since then, there has been a global reduction in incidence of Ni-ACD in population-based studies of adults and studies of children and young adults being tested for allergic contact dermatitis. These data point to nickel exposure as a trigger for elicitation of Ni-ACD and, further, provide evidence that legislation can have a favorable effect on the economic and medical health of a population.This policy statement reviews the epidemiology, history, and appearances of Ni-ACD. Examples of sources of high nickel release are discussed to highlight how difficult it is to avoid this metal in modern daily lives. Treatments are outlined, and avoidance strategies are presented. Long-term epidemiological interventions are addressed. Advocacy for smarter nickel use is reviewed. The American Academy of Pediatrics supports US legislation that advances safety standards (as modeled by the European Union) that protect children from early and prolonged skin exposure to high-nickel-releasing items. Our final aim for this article is to aid the pediatric community in developing nickel-avoidance strategies on both individual and global levels.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1542/peds.2020-0628DOI Listing
May 2020

Replicated methylation changes associated with eczema herpeticum and allergic response.

Clin Epigenetics 2019 08 23;11(1):122. Epub 2019 Aug 23.

University of Colorado, Denver, CO, USA.

Background: Although epigenetic mechanisms are important risk factors for allergic disease, few studies have evaluated DNA methylation differences associated with atopic dermatitis (AD), and none has focused on AD with eczema herpeticum (ADEH+). We will determine how methylation varies in AD individuals with/without EH and associated traits. We modeled differences in genome-wide DNA methylation in whole blood cells from 90 ADEH+, 83 ADEH-, and 84 non-atopic, healthy control subjects, replicating in 36 ADEH+, 53 ADEH-, and 55 non-atopic healthy control subjects. We adjusted for cell-type composition in our models and used genome-wide and candidate-gene approaches.

Results: We replicated one CpG which was significantly differentially methylated by severity, with suggestive replication at four others showing differential methylation by phenotype or severity. Not adjusting for eosinophil content, we identified 490 significantly differentially methylated CpGs (ADEH+ vs healthy controls, genome-wide). Many of these associated with severity measures, especially eosinophil count (431/490 sites).

Conclusions: We identified a CpG in IL4 associated with serum tIgE levels, supporting a role for Th2 immune mediating mechanisms in AD. Changes in eosinophil level, a measure of disease severity, are associated with methylation changes, providing a potential mechanism for phenotypic changes in immune response-related traits.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13148-019-0714-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6706929PMC
August 2019

Identification of children with anaphylaxis at low risk of receiving acute inpatient therapies.

PLoS One 2019 7;14(2):e0211949. Epub 2019 Feb 7.

Division of Emergency Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.

Objective: Opportunity exists to reduce unnecessary hospitalizations for children with anaphylaxis given wide variation in admission rates across U.S. emergency departments (EDs). We sought to identify children hospitalized with anaphylaxis at low risk of receiving epinephrine and other acute inpatient therapies, as these patients may be candidates for ED discharge rather than inpatient hospitalization.

Methods: We conducted a single-center retrospective cohort study of children 1-21 years of age hospitalized with anaphylaxis from 2009 to 2016. Acute inpatient therapies included intramuscular (IM) or racemic epinephrine, bronchodilators, fluid boluses, vasopressors, non-invasive ventilation, or intubation. We derived age-specific (pre-verbal [<36 months] vs. verbal [≥ 36 months]) prediction rules using recursive partitioning to identify children at low risk of receiving acute inpatient therapies.

Results: During the study period 665 children were hospitalized for anaphylaxis, of whom 108 (16.2%) received acute inpatient therapies. The prediction rule for patients < 36 months (no wheezing, no cardiac involvement [hypotension or wide pulse pressure]) had a sensitivity of 90.5% (CI 69.6-98.8%) and a negative predictive value of 98.3% (CI 94.1-99.8%) for identifying children at low risk of receipt of acute inpatient therapies during hospitalization. For children ≥ 36 months, the prediction rule (no wheezing, no cardiac involvement, presence of gastrointestinal symptoms) had a sensitivity of 90.8% (CI 82.7-96.0%) and a negative predictive value of 92.4% (CI 85.6-96.7%).

Conclusions: We derived age specific prediction rules for children hospitalized with anaphylaxis at low risk of receiving epinephrine and other acute inpatient therapies. These children may be candidates for ED discharge rather than inpatient hospitalization.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0211949PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6366886PMC
November 2019

Immunoglobulin E blockade during food allergen ingestion enhances the induction of inhibitory immunoglobulin G antibodies.

Ann Allergy Asthma Immunol 2019 02 4;122(2):213-215. Epub 2018 Nov 4.

Division of Immunology, Department of Pediatrics, Boston Children's Hospital, Boston, Massachusetts; Department of Pediatrics, Harvard Medical School, Boston, Massachusetts. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.anai.2018.10.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6360101PMC
February 2019

Photocleavage-based affinity purification of biomarkers from serum: Application to multiplex allergy testing.

PLoS One 2018 1;13(2):e0191987. Epub 2018 Feb 1.

AmberGen, Incorporated, Watertown, Massachusetts, United States of America.

Multiplex serological immunoassays, such as implemented on microarray or microsphere-based platforms, provide greater information content and higher throughput, while lowering the cost and blood volume required. These features are particularly attractive in pediatric food allergy testing to facilitate high throughput multi-allergen analysis from finger- or heel-stick collected blood. However, the miniaturization and microfluidics necessary for creating multiplex assays make them highly susceptible to the "matrix effect" caused by interference from non-target agents in serum and other biofluids. Such interference can result in lower sensitivity, specificity, reproducibility and quantitative accuracy. These problems have in large part prevented wide-spread implementation of multiplex immunoassays in clinical laboratories. We report the development of a novel method to eliminate the matrix effect by utilizing photocleavable capture antibodies to purify and concentrate blood-based biomarkers (a process termed PC-PURE) prior to detection in a multiplex immunoassay. To evaluate this approach, it was applied to blood-based allergy testing. Patient total IgE was purified and enriched using PC-PURE followed by multiplex microsphere-based detection of allergen-specific IgEs (termed the AllerBead assay). AllerBead was formatted to detect the eight most common pediatric food allergens: milk, soy, wheat, egg, peanuts, tree nuts, fin fish and shellfish, which account for >90% of all pediatric food allergies. 205 serum samples obtained from Boston Children's Hospital were evaluated. When PC-PURE was employed with AllerBead, excellent agreement was obtained with the standard, non-multiplex, ImmunoCAP® assay (average sensitivity above published negative predictive cutoffs = 96% and average Pearson r = 0.90; average specificity = 97%). In contrast, poor ImmunoCAP®-correlation was observed when PC-PURE was not utilized (average sensitivity above published negative predictive cutoffs = 59% and average Pearson r = 0.61; average specificity = 97%). This approach should be adaptable to improve a wide range of multiplex immunoassays such as in cancer, infectious disease and autoimmune disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0191987PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5794080PMC
March 2018

Systemic Reactions in Pediatric Patients Receiving Standardized Allergen Subcutaneous Immunotherapy with and without Seasonal Dose Adjustment.

J Allergy Clin Immunol Pract 2018 Sep - Oct;6(5):1711-1716.e4. Epub 2018 Jan 12.

Division of Immunology, Boston Children's Hospital, Department of Pediatrics Harvard Medical School, Boston, Mass. Electronic address:

Background: The 2003 Joint Task Force on Practice Parameters recommended standardizing allergen subcutaneous immunotherapy (SCIT). Data from longitudinal surveillance survey in North America reported a systemic reaction (SR) rate of 0.1% to 0.2% of injection visits. The rate of SR to standardized SCIT in pediatric patients has not been well evaluated.

Objective: The objective of this study was to evaluate the rate of SRs to standardized SCIT in pediatric patients aged 5 to 18 years in a single tertiary care center in the United States.

Methods: A retrospective chart review was conducted in 2 groups: group 1 started SCIT within a period extending from January 2009 to June 2012, whereas group 2 started SCIT within a period extending from January 2013 to June 2016. The protocol was modified in group 2 such that updosing and maintenance doses were adjusted in the spring for tree and grass pollen and in the fall for weed pollen.

Results: There were a total of 128 patients in group 1 and 118 patients in group 2. The rate of SR was 0.429% in group 1 and 0.364% in group 2, which was not significant. There was no difference in the severity of SR in the 2 groups with no-fatal or near-fatal SR noted. Asthma was a significant risk factor in the younger age subgroup aged 5 to 11 years.

Conclusions: Standardized SCIT appears to be associated with an SR rate of 0.429% to 0.364% of visits in pediatric patients. Protocol modification did not lead to a significant drop in SR. Larger multicenter studies are required to further evaluate the rate of SRs from standardized SCIT.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jaip.2017.11.040DOI Listing
November 2019

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

JAMA 2017 11;318(18):1798-1809

Hôpital Necker, Enfants Malades, Paris, France.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jama.2017.16591DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5820709PMC
November 2017

Combining anti-IgE with oral immunotherapy.

Pediatr Allergy Immunol 2017 Nov 7;28(7):619-627. Epub 2017 Sep 7.

Sean N. Parker Center for Allergy and Asthma Research at Stanford University, Stanford, CA, USA.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/pai.12767DOI Listing
November 2017

Reducing Hospitalization Rates for Children With Anaphylaxis.

Pediatrics 2017 Jun;139(6)

Divisions of Emergency Medicine and.

Background And Objectives: Most children with anaphylaxis in the emergency department (ED) are hospitalized. Opportunities exist to safely reduce the hospitalization rate for children with anaphylaxis by decreasing unnecessary hospitalizations. A quality improvement (QI) intervention was conducted to improve care and reduce hospitalization rates for children with anaphylaxis.

Methods: We used the Model for Improvement and began with development and implementation in 2011 of a locally developed evidence-based guideline based on national recommendations for the management of anaphylaxis. Guideline adoption and adherence were supported by interval reminders and feedback to providers. Patients from 2008 to 2014 diagnosed with anaphylaxis were identified, and statistical process control methods were used to evaluate change in hospitalization rates over time. The balancing measure was any return visit to the ED within 72 hours. To control for secular trends, hospitalization rates for anaphylaxis at 34 US children's hospitals over the same time period were analyzed.

Results: Over the study period, there were 1169 visits for children with anaphylaxis, of which 731 (62%) occurred after the QI implementation. The proportion of children hospitalized decreased from 54% to 36%, with no increase in the 72-hour ED revisit rate. The hospitalization rate across 34 other US pediatric hospitals remained static at 52% over the study period.

Conclusions: We safely reduced unnecessary hospitalizations for children with anaphylaxis and sustained the change over 3 years by using a QI initiative that included evidence-based guideline development and implementation, reinforced by provider reminders and structured feedback.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1542/peds.2016-4114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5470504PMC
June 2017

Ditching the Itch with Anti-Type 2 Cytokine Therapies for Atopic Dermatitis.

N Engl J Med 2017 03;376(9):878-879

From the Division of Immunology, Boston Children's Hospital, Boston.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1056/NEJMe1616072DOI Listing
March 2017

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

J Allergy Clin Immunol 2017 May 13;139(5):1575-1582.e8. Epub 2017 Feb 13.

University of Colorado Denver, Aurora, Colo.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jaci.2016.12.952DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5786280PMC
May 2017

Addendum guidelines for the prevention of peanut allergy in the United States.

JAAPA 2017 Mar;30(3):1-5

In the Division of Allergy, Immunology, and Transplantation at the National Institute of Allergy and Infectious Diseases in Bethesda, Md., Alkis Togias is the chief of the Allergy, Asthma, and Airway Biology Branch (AAABB), Susan F. Cooper is a health specialist in the Office of Program Planning and Scientific information, Marshall Plaut is the chief of the Food Allergy, Atopic Dermatitis and Allergic Mechanisms Section in AAABB, and Daniel Rotrosen is division director. The affiliations of the other authors are listed in Table 2. The authors have disclosed no potential conflicts of interest, financial or otherwise. This work was written by employees of the National Institutes of Health and the expert panelists reviewed, edited, and approved the work, which is in the public domain in the United States.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/01.JAA.0000512231.15808.66DOI Listing
March 2017

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.

J Pediatr Nurs 2017 Jan - Feb;32:91-98

Departments of Medicine and Pediatrics, Harvard Medical School, Boston, MA.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.pedn.2016.12.006DOI Listing
September 2017

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.

Ann Allergy Asthma Immunol 2017 02 5;118(2):166-173.e7. Epub 2017 Jan 5.

Departments of Medicine and Pediatrics, Harvard Medical School, Boston, Mass.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.anai.2016.10.004DOI Listing
February 2017

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.

J Allergy Clin Immunol 2017 Jan;139(1):29-44

Departments of Medicine and Pediatrics, Harvard Medical School, Boston, Mass.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jaci.2016.10.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5226648PMC
January 2017

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.

Pediatr Dermatol 2017 Jan;34(1):e1-e21

The Departments of Medicine and Pediatrics, Harvard Medical School, Boston, Massachusetts.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/pde.13093DOI Listing
January 2017

Omalizumab facilitates rapid oral desensitization for peanut allergy.

J Allergy Clin Immunol 2017 Mar 5;139(3):873-881.e8. Epub 2016 Sep 5.

Division of Immunology, Boston Children's Hospital, Boston, Mass. Electronic address:

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jaci.2016.08.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5369605PMC
March 2017

Multidisciplinary interventions in the management of atopic dermatitis.

J Allergy Clin Immunol 2016 08;138(2):325-34

Allergy Program, Division of Immunology, Boston Children's Hospital, Boston, Mass; Harvard Medical School, Boston, Mass.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jaci.2016.04.003DOI Listing
August 2016

Implementation of a Standardized Clinical Assessment and Management Plan (SCAMP) for Food Challenges.

J Allergy Clin Immunol Pract 2017 Mar - Apr;5(2):335-344.e3. Epub 2016 Jun 30.

Division of Immunology, Boston Children's Hospital, Boston, Mass; Department of Pediatrics, Harvard Medical School, Boston, Mass. Electronic address:

Background: Oral food challenges (OFCs) are routinely used to confirm ongoing food allergy. Serum-specific IgE (sIgE) and skin prick testing (SPT) are imperfect predictors of which patients will pass OFCs.

Objective: The objective of this study was to describe the design and implementation of a Standardized Clinical Assessment and Management Plan (SCAMP) to study and iteratively improve sIgE and SPT thresholds to determine when and where to conduct OFCs for patients.

Methods: Allergists consulted recommended sIgE and SPT thresholds when ordering challenges although diversions were permitted. Criteria were iteratively improved after periodic analyses of challenge outcome and diversions.

Results: Over 3 years, allergists ordered 2368 food challenges for 1580 patients with histories of IgE-mediated reactions to food: 1386 in an outpatient clinic and 945 in a higher resource infusion center. Reactions to challenge were observed in 13% of clinic and 23% of infusion center challenges. Six patients challenged in clinic required treatment with epinephrine compared with 22 in the infusion center. The need for epinephrine was more common in patients with asthma-5% of asthmatic patients required epinephrine compared with 1% of nonasthmatic patients (P < .01). Recommended sIgE and SPT thresholds were incrementally changed and, using the control chart methodology, a significant decrease was noted in the proportion of challenges ordered in the higher resource location.

Conclusions: By setting and continually refining sIgE and SPT recommendations using the SCAMP method, allergists can better determine the risk of severe reaction and triage patients to the appropriate setting for an OFC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jaip.2016.05.021DOI Listing
November 2017

Ovomucoid specific immunoglobulin E as a predictor of tolerance to cooked egg.

Allergy Rhinol (Providence) 2015 Jan;6(3):198-204

Department of Medicine, Division of Immunology, Boston Children's Hospital, Boston, Massachusetts, USA.

Background: Ovomucoid is the dominant allergen in hen's egg. Although several studies evaluated the utility of ovomucoid specific immunoglobulin E (sIgE) levels in predicting baked (e.g., muffin or cupcake) or raw egg food challenge outcomes, studies that evaluated ovomucoid sIgE as a predictor of cooked egg (e.g., scrambled or hard boiled) challenge outcomes are limited.

Objective: To determine the relation of ovomucoid sIgE levels with cooked egg food challenge outcomes.

Methods: A retrospective review of 44 children who underwent cooked egg food challenge and who had the ovomucoid sIgE level measured.

Results: Thirty-six of 44 children (81.8%) passed cooked egg challenge. The ovomucoid sIgE level predicted cooked egg challenge outcome (passed median, <0.35 kU/L [range, <0.35-0.64 kU/L]; failed median, 0.40 kU/L [range, <0.35-3.13 kU/L]; p = 0.004). Ovomucoid sIgE levels correlated with egg white (EW) sIgE levels (Spearman correlation coefficient, 0.588; p < 0.001). Receiver operating characteristic curve analysis of ovomucoid and EW sIgE demonstrated areas under the curve of 0.711 and 0.766, respectively. No significant difference was observed among those immunologic parameters in their abilities to predict cooked egg challenge outcome (p = 0.559).

Conclusion: The ovomucoid sIgE level may be helpful in predicting cooked egg challenge outcomes. However, our study did not support a role for ovomucoid sIgE replacing EW sIgE testing in evaluating egg allergy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2500/ar.2015.6.0135DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5391491PMC
January 2015

Targeted deep sequencing identifies rare loss-of-function variants in IFNGR1 for risk of atopic dermatitis complicated by eczema herpeticum.

J Allergy Clin Immunol 2015 Dec 3;136(6):1591-1600. Epub 2015 Sep 3.

Department of Pediatrics, National Jewish Health, 1400 Jackson St, Denver, CO.

Background: A subset of atopic dermatitis is associated with increased susceptibility to eczema herpeticum (ADEH+). We previously reported that common single nucleotide polymorphisms (SNPs) in the IFN-γ (IFNG) and IFN-γ receptor 1 (IFNGR1) genes were associated with the ADEH+ phenotype.

Objective: We sought to interrogate the role of rare variants in interferon pathway genes for the risk of ADEH+.

Methods: We performed targeted sequencing of interferon pathway genes (IFNG, IFNGR1, IFNAR1, and IL12RB1) in 228 European American patients with AD selected according to their eczema herpeticum status, and severity was measured by using the Eczema Area and Severity Index. Replication genotyping was performed in independent samples of 219 European American and 333 African American subjects. Functional investigation of loss-of-function variants was conducted by using site-directed mutagenesis.

Results: We identified 494 single nucleotide variants encompassing 105 kb of sequence, including 145 common, 349 (70.6%) rare (minor allele frequency <5%), and 86 (17.4%) novel variants, of which 2.8% were coding synonymous, 93.3% were noncoding (64.6% intronic), and 3.8% were missense. We identified 6 rare IFNGR1 missense variants, including 3 damaging variants (Val14Met [V14M], Val61Ile, and Tyr397Cys [Y397C]) conferring a higher risk for ADEH+ (P = .031). Variants V14M and Y397C were confirmed to be deleterious, leading to partial IFNGR1 deficiency. Seven common IFNGR1 SNPs, along with common protective haplotypes (2-7 SNPs), conferred a reduced risk of ADEH+ (P = .015-.002 and P = .0015-.0004, respectively), and both SNP and haplotype associations were replicated in an independent African American sample (P = .004-.0001 and P = .001-.0001, respectively).

Conclusion: Our results provide evidence that both genetic variants in the gene encoding IFNGR1 are implicated in susceptibility to the ADEH+ phenotype.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jaci.2015.06.047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4679503PMC
December 2015

A Review of Multidisciplinary Interventions in Atopic Dermatitis.

J Clin Med 2015 May 21;4(5):1156-70. Epub 2015 May 21.

Division of Immunology, Boston Children's Hospital, 300 Longwood Ave, Boston, MA 02115, USA.

Multidisciplinary interventions have been developed for patients with atopic dermatitis (AD) and their families, with the aim of improving outcomes such as disease control, adherence, and quality of life. We reviewed the content of different multidisciplinary approaches to intervention for AD and evidence for their impact on key outcome measures. We also provided data from our multidisciplinary outpatient program for pediatric AD. Studies included in the review suggest benefits of multidisciplinary interventions as models of treatment or adjuncts to standard medical care, with a positive impact on outcomes including disease severity and itching/scratching. There were limitations to existing studies, including heterogeneous methods used to assess quality of life outcomes across studies and lack of controlled studies assessing the outcome of clinical care programs. Further research will be useful in assessing the impact of multidisciplinary interventions on important outcomes such as treatment adherence and sleep, identifying the elements of multidisciplinary interventions that are most critical for improved outcomes, and identifying the best candidates for multidisciplinary intervention approaches.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/jcm4051156DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4470222PMC
May 2015