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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. 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. 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. 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. Sanofi and Regeneron Pharmaceuticals

Atopic dermatitis is a chronic inflammatory disease characterized by intense pruritus and dry, inflamed skin. An impaired skin barrier and a dysregulated immune response to a variety of triggers are key factors in the complex pathophysiological mechanism of this disease. The predominant early immunologic response in atopic dermatitis includes type 2 helper T (Th2) cells, innate lymphoid cells, and keratinocytes that produce the type 2 cytokines, such as thymic stromal lymphopoietin (TSLP, a major promoter of atopy) and interleukins 4, 13, and 31. 1 Interleukins 4 and 13 and TSLP inhibit the differentiation of keratinocytes and thereby reduce the production of . . .

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. 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. 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%). 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.

The American Academy of Allergy, Asthma and Immunology (AAAAI)/American College of Allergy, Asthma and Immunology (ACAAI) Joint Task Force on Practice Parameters updated guidelines for managing atopic dermatitis (eczema). Table 1 summarizes recommendations relevant to family physicians.

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.

The tumor necrosis factor receptor family member TACI (transmembrane activator and calcium-modulator and cyclophilin ligand interactor) mediates isotype switching in B cells. We found that 4 of 19 unrelated individuals with common variable immunodeficiency (CVID) and 1 of 16 individuals with IgA deficiency (IgAD) had a missense mutation in one allele of TNFRSF13B (encoding TACI). One of the four individuals with CVID had a single nucleotide insertion in the other TNFRSF13B allele. None of these mutations were present in 50 healthy subjects. TNFRSF13B mutations cosegregated with the phenotype of CVID or IgAD in family members of four index individuals that we studied. B cells from individuals with TACI mutations expressed TACI but did not produce IgG and IgA in response to the TACI ligand APRIL, probably reflecting impaired isotype switching. These results suggest that TACI mutations can result in CVID and IgAD.

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 6vz_jLtTkCJ6tzGx5HdiGv 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)

Introduction Patients with atopic dermatitis (AD) are uniquely susceptible to a number of serious viral skin complications, including eczema herpeticum (EH), caused by herpes simplex virus. This study explored the associations between biomarkers of epithelial barrier dysfunction, type 2 immunity, Staphylococcus aureus infection, and S. aureus -specific immunoglobulin responses in a cohort of AD subjects with and without a history of EH (EH+ and EH−, respectively). Methods A total of 112 subjects with AD (56 EH+, 56 EH−), matched by age and AD severity, were selected from a registry of over 3000 AD subjects. Logistic regression was used to test the association between history of S. aureus skin infection and history of EH, while controlling for a number of confounders. Results Compared to those without a history of S. aureus skin infection, subjects with a history of S. aureus skin infection were found to have more than sixfold increased odds of having a history of EH (6.60, 95% confidence interval [CI]: 2.00–21.83), after adjusting for history of other viral skin infections (molluscum contagiosum virus, human papillomavirus), serum total IgE, and IgG against the S. aureus virulence factor SE l X. Conclusions These findings indicate an important relationship between S. aureus skin infections and EH.

Injections of TNX-901 may provide protection after ingestion of peanut. Peanut allergy is characterized by symptoms and signs after ingestion that may include nausea, vomiting, diarrhea, abdominal pain, urticaria, angioedema, bronchospasm, hypotension, loss of consciousness, and death. 1 , 2 Although data from animals demonstrate that allergic reactions are mediated by antigen-specific IgE bound to high-affinity receptors for IgE (FcεRIs) on mast cells and basophils, 3 , 4 non-IgE pathways for anaphylaxis exist, at least in mice, 5 , 6 and direct clinical evidence of IgE involvement in peanut allergy in humans is lacking. Approximately 1.5 million people in the United States have peanut allergy, 7 , 8 50 to 100 of whom die each year from unintended . . .

Food allergy is a major public health problem affecting nearly 10 % of children in most industrialized countries. Unfortunately, there are no effective therapies for food allergy, relegating patients to simply avoid the offending foods and treat reactions that occur on accidental exposure. Recently however, studies suggest that food immunotherapy may provide a promising new approach to food allergy, particularly using the oral form of immunotherapy (OIT). Enthusiasm for this approach though must be tempered because of the significant allergic reactions that often occur with OIT that tends to limit its use to patients with less severe disease. On the other hand, recent studies suggest that concomitant treatment of patients with omalizumab (anti-IgE monoclonal antibody) during the updosing phase of OIT may greatly reduce the allergic reactions associated with OIT, even in high-risk patients. This combined method may provide a novel approach to successfully and rapidly treat a large fraction of patients with high-risk food allergy.