Jonathan Spergel

Background Food allergies are common and are associated with substantial morbidity; the only approved treatment is oral immunotherapy for peanut allergy. Methods In this trial, we assessed whether omalizumab, a monoclonal anti-IgE antibody, would be effective and safe as monotherapy in patients with multiple food allergies. Persons 1 to 55 years of age who were allergic to peanuts and at least two other trial-specified foods (cashew, milk, egg, walnut, wheat, and hazelnut) were screened. Inclusion required a reaction to a food challenge of 100 mg or less of peanut protein and 300 mg or less of the two other foods. Participants were randomly assigned, in a 2:1 ratio, to receive omalizumab or placebo administered subcutaneously (with the dose based on weight and IgE levels) every 2 to 4 weeks for 16 to 20 weeks, after which the challenges were repeated. The primary end point was ingestion of peanut …

Food allergies affect an estimated 8% of the US population and have risen significantly in the past 20 years. 1 IgE− mediated reactions to food can range from simple urticaria to life-threatening anaphylaxis. The only treatment was the avoidance of the allergen and treatment of allergic reactions with epinephrine until 2020 when an oral immunotherapy (OIT) product (Palforzia [Stallergenes Greer, Boston, Massachusetts]) was approved for the treatment of peanut allergy. 2 There was no approved treatment by the US Food and Drug Administration for other foods or multiple foods until the recent approval of omalizumab for any food allergy for patients aged 1 year or older with the appropriate total IgE and weight. In the pivotal trial, Wood et al 3 reported in a randomized, placebo-controlled study that 67% of patients on omalizumab tolerated a single dose of 600 mg (1044 mg cumulative dose) or greater of peanut …

MethodsWe conducted a retrospective review of patients aged 4-8 years, treated with dupilumab and the age of measles, mumps, rubella (MMR) and varicella dose 2 vaccine administration (IRB 19-016617). Data extracted from electronic medical records included demographics, immunization administration, and dupilumab history.Results162 children were identified to be on dupilumab, of which 114 were included in final analyses. The average age of our population was 5.7 years and the average age of initiation of dupilumab was 4.7 years. Dupilumab was initiated for atopic dermatitis (AD)(n= 107), asthma (n= 5), eosinophilic esophagitis (EoE)(n= 1), and EoE+ asthma (n= 1).

MethodsWe systematically identified randomized controlled trials addressing topical treatments for AD from MEDLINE, EMBASE, CENTRAL, CINAHL, LILACS, ICTRP, and GREAT to July 8, 2023. We excluded split-body trials. We performed Bayesian random-effects network meta-analyses on AD severity, itch severity, sleep disturbance, AD-related quality of life, AD exacerbations, and harms. We used GRADE to rate certainty of evidence. A multidisciplinary panel including patient partners determined thresholds for patient-important benefits and harms.ResultsWe analyzed 235 trials enrolling 46,315 patients (pediatrics and adults) and evaluated 69 unique interventions over a median 4 weeks for induction and 16 weeks for maintenance (overall range 1–156). To gain AD control, pimecrolimus improved the most outcomes, while tacrolimus, moderatepotency corticosteroids, delgocitinib, and ruxolitinib had …

Eosinophilic esophagitis (EoE) is a chronic disease associated with type 2 inflammation. EoE usually requires long-term surveillance with esophagogastroduodenoscopy (EGD) and treatment with medications or elimination diets. In severe or untreated cases, fibrostenosis and esophageal stricture can occur. 1 The causes of EoEDeclaration of funding: BL Wright receives support from the NIH/NIAID (K23AI158813). J. Spergel receives support from the NIH/NIAID and the Consortium of Eosinophilic Gastrointestinal Disease Researchers (U54 AI117804). N. Wolfset receives support from an NIH T32 training grant (T32GM008562). MA Sacta receives support from the Gail B. Slap Department of Pediatrics Fellowship Award.

BackgroundLimited access to healthy foods, resulting from residence in neighborhoods with low-food access or from household food insecurity, is a public health concern. Contributions of these measures during pregnancy to birth outcomes remain understudied.ObjectivesWe examined associations between neighborhood food access and individual food insecurity during pregnancy with birth outcomes.MethodsWe used data from 53 cohorts participating in the nationwide Environmental Influences on Child Health Outcomes-Wide Cohort Study. Participant inclusion required a geocoded residential address or response to a food insecurity question during pregnancy and information on birth outcomes. Exposures include low-income-low-food-access (LILA, where the nearest supermarket is >0.5 miles for urban or >10 miles for rural areas) or low-income-low-vehicle-access (LILV, where few households have a vehicle …

BackgroundEosinophilic esophagitis (EoE) is characterized by persistent or relapsing allergic inflammation, and both clinical and histologic features of esophageal inflammation persist over time in most individuals. Mechanisms contributing to EoE relapse are not understood, and chronic EoE-directed therapy is therefore required to prevent long-term sequelae.ObjectiveWe investigated whether EoE patients in histologic remission have persistent dysregulation of esophageal gene expression.MethodsEsophageal biopsy samples from 51 pediatric and 52 adult subjects with EoE in histopathologic remission (<15 eosinophils per high-power field [eos/hpf]) and control (48 pediatric and 167 adult) subjects from multiple institutions were subjected to molecular profiling by the EoE diagnostic panel, which comprises a set of 94 esophageal transcripts differentially expressed in active EoE.ResultsDefining remission as <15 …

The 2023 anaphylaxis parameter focuses on updating and expanding our understanding of anaphylaxis and its treatment while providing new venues for shared decision making. Lack of a consensus definition remains an ongoing topic that highlights the need for research including validation of accepted criteria and expansion of how different triggers/allergens and age may affect severity and anaphylactic symptoms. 1 The expansion of criteria for infants, a population where anaphylaxis may not present similarly to older children and adults, is needed to increase diagnosis and prevent negative outcomes. 2 Overall, consensus criteria will be helpful not only to allergists but also to emergency department (ED) providers who are first responders in diagnosing and treating anaphylaxis. As multiple triggers can lead to anaphylaxis and administration of epinephrine does not diagnose anaphylaxis or provide clues to its …

MethodsWe conducted a retrospective chart review on all patients who underwent OFC over 3 years in a pediatric tertiary care center. SRs were defined as anaphylaxis requiring 2 or more doses of epinephrine, lower respiratory symptoms requiring albuterol, or cardiovascular or neurologic symptoms requiring intervention.Results2,507 (37%) of 6,790 OFCs reviewed were positive. The most commonly challenged foods were tree nuts (TN)(22.8%), peanut (20.3%), egg (15.1%), and baked egg (12.8%). There were 100 SRs (1.5%) of which 9% required PICU admission, 19% required Emergency Department (ED) monitoring, and 9% exclusively had a food protein-induced enterocolitis syndrome reaction. The most common foods triggering SRs were peanut (20%), TN (20%), egg (15%), and baked egg (14%). Interestingly, SRs were more common among positive OFC to pecan (19%) and pistachio (11.1%) compared …

MethodsPart A was a 16-week (W) placebo-controlled study; patients received weight-tiered, higher-or lower-exposure dupilumab, or placebo. In Part B, patients continued their dupilumab regimen, or switched from placebo to dupilumab (higher/lower exposure), to W52. This analysis includes patients receiving higher-exposure dupilumab or placebo.ResultsAt W16 (Part A), the dupilumab group had an improved proportion of patients achieving peak esophageal intraepithelial eosinophil count (PEC)≤ 6 eosinophils/high-power field (hpf)(least squares mean difference vs placebo [95% CI], 64.5%[48.19, 80.85], P< 0.0001), and PEC< 15 eosinophils/hpf (81.1%[68.07, 94.10], P< 0.0001). At W52 (Part B), 62.9% and 85.7% of dupilumab/dupilumab patients, and 52.9% and 64.7% of placebo/dupilumab patients, achieved PEC≤ 6 and< 15 eosinophils/hpf, respectively. At W16, the following improved with dupilumab vs …

Background Dupilumab is approved in Canada for eosinophilic esophagitis (EoE) in patients (pts) aged ≥12 years who weigh ≥40 kg; no treatments are approved for pts aged ampersand:003C12 years. Aims The Phase 3 EoE KIDS trial evaluated dupilumab efficacy and safety vs placebo (PBO) in pts aged 1–ampersand:003C12 years with EoE. Methods Part A was a 16-week (W) PBO-controlled study; pts were randomized 2:2:1:1 to weight-tiered dupilumab on a higher-exposure (HE) or lower-exposure (LE) regimen, or PBO (2 groups) to W16. In Part B, pts continued dupilumab, or switched from PBO to dupilumab (HE/LE), to W52. Results At W16 (Part A), the HE dupilumab group had an improved proportion of pts achieving peak esophageal intraepithelial eosinophil count (PEC) ≤6 eosinophils/high-power field (hpf) vs PBO (67.6 …

Cow's milk allergy is rare in exclusively breastfed infants. To support the continuation of breastfeeding an infant after diagnosis with a cow's milk allergy, it is critical to examine the evidence for and against any form of cow's milk elimination diet for lactating mothers. In this narrative review, we highlight the lack of high-quality evidence, hence subsequent controversy, regarding whether the minuscule quantities of cow's milk proteins detectable in human milk cause infant cow's milk allergy symptoms. Current clinical practice recommendations advise a 2–4 week trial of maternal cow's milk dietary elimination for: a) IgE-mediated cow's milk allergy only if the infant is symptomatic on breastfeeding alone; b) non-IgE-mediated associated symptoms only if the history and examination strongly suggest cow's milk allergy; and c) infants with moderate to severe eczema/atopic dermatitis, unresponsive to topical steroids and …

The Oath of Maimonides reminds us of the goal and ideals of physicians, and states “May the love for my art actuate me at all time; may neither avarice nor miserliness, nor thirst for glory, or a great reputation engages my mind; for the enemies of truth and philanthropy could easily deceive me and make me forgetful of my lofty aim of doing good to Thy children. May I never see in the patient anything but a fellow creature in pain.” 1 Unfortunately, our “fellow creatures” continue to be in great pain as war and terrorism continue, with these episodes becoming more common, numerous, and affecting larger swaths of people. The recent acts of terrorism (at the time of this writing) by Hamas in Israel resulting in the deaths of hundreds of innocent partygoers at a music festival and families in their homes, along with brazen acts of hostage-taking of both the elderly and children, are tragic and inexcusable. The indiscriminate …

MethodsClinical data were collected on 788 patients undergoing standardized OIT to 1-5 foods from September 2019 to July 2023. Patients with persistent enteric symptoms (ie nausea, vomiting, change in appetite, dysphagia, weight loss) not responsive to dose modification and pretreatment with anti-histamines were referred to Gastroenterology (GI) in the Center of Pediatric Eosinophilic Disorders at the Children’s Hospital of Philadelphia.ResultsSeventy patients were referred to GI for persistent enteric symptoms, 15 underwent an endoscopy (EGD), 6 were diagnosed with EoE. EoE patients had similar characteristics than those without (non-EoE): 66% were male, 12.6 (1-24) years old, 50% received multiple foods OIT. EoE patients compared to non-EoE had more often dysphagia (50% vs 17%, p< 0.05) and reduced appetite (50% vs 5%, p< 0.05), whereas had similar rates of abdominal pain (50% in both groups …

MethodsIn an open label pilot study, EoE patients aged 6 to 25 were treated with dupilumab and conventional EoE therapies followed by standardized reintroduction of EoE-causal foods. Peripheral blood mononuclear cells from subjects isolated before (baseline) and after dupilumab therapy and food reintroduction were cultured in the presence or absence of milk proteins or tetanus toxoid prior to evaluation by flow cytometry. Memory T cell (CD45RO+ CD4+) proliferation and IL4 production in response to milk stimulation were evaluated and normalized to tetanus toxoid responses (expressed as a ratio of P1 milk/P1 tetanus and IL4 milk/IL4 tetanus). Patients with inadequate T cell responses to tetanus, and patients with high non-specific background, were excluded from analysis.ResultsWe observed a decrease in the ratio of P1 milk/P1 tetanus during treatment with dupilumab compared with baseline (baseline: n …

BackgroundGuidance addressing atopic dermatitis (AD) management, last issued in 2012 by the American Academy of Allergy, Asthma and Immunology/American College of Allergy, Asthma and Immunology Joint Task Force, requires updating as a result of new treatments and improved guideline and evidence synthesis methodology.ObjectiveTo produce evidence-based guidelines that support patients, clinicians, and other decision-makers in the optimal treatment of AD.MethodsA multidisciplinary guideline panel consisting of patients and caregivers, AD experts (dermatology and allergy/immunology), primary care practitioners (family medicine, pediatrics, internal medicine), and allied health professionals (psychology, pharmacy, nursing) convened, prioritized equity, diversity, and inclusiveness, and implemented management strategies to minimize influence of conflicts of interest. The Evidence in Allergy Group …

Eosinophilic esophagitis (EoE) is a multifactorial food allergy of the esophagus that was first recognized as a distinct entity in the 1990s and can be diagnosed at any age. Initial detection of EoE is complicated by its variable clinical presentations across the ages, ranging from failure to thrive in infancy to frank food impaction in adulthood. These differences have prompted discussions about whether EoE is truly a single disease entity or, alternatively, a collection of distinct disease states that differ between children and adults. Here, we consider current insights into the phenotypic (ie clinical, endoscopic) and endotypic (ie molecular, transcriptomic) features of EoE, which suggest that EoE is a complex disease associated with progressive phenotypes spanning childhood to adulthood as well as a heterogenous collection of genetic and molecular endotypes.Notable differences exist in the clinical presentation of EoE in …

The incidence and prevalence of eosinophilic esophagitis (EoEs) has increased dramatically since its first description in 1978. With our additional understanding of the disease, EoE is now considered a non-IgE mediated food allergy with Type 2 (T2) predominant signature with cow's milk being the most common trigger food. Other allergens can lead to T2 inflammation including wheat and egg being the next most common foods. Aeroallergens can also trigger disease in a small population of patients. Treatment with dietary elimination or pharmacologic treatments treating T2 inflammation have shown both clinical and histologic improvements.

MethodsUsing the American Academy of Pediatrics multi-state (27 states) Comparative Effectiveness Research through Collaborative Electronic Reporting electronic health record database, we identified children with IgE-FA, defined as having≥ 2 corresponding diagnosis codes separated by≥ 6 months,≥ 1 epinephrine autoinjector prescription, and≥ 1 food allergen. Subjects were observed for≥ 1 year. We determined the cumulative incidence of IgE-FA and individual food allergies during the periods 09/01/2012–08/31/2015 (pre-LEAP) and 09/01/2015–08/31/2018 (post-LEAP).ResultsThe cumulative incidences of IgE-FA in the pre-LEAP (median age 1.5 years) and post-LEAP (median age 1.3 years) cohorts were 1.29%(n= 966 of 74,250 subjects) and 1.49%(n= 927 of 61,487 subjects), respectively. The top 5 food allergens (and cumulative incidences pre-LEAP vs. post-LEAP) in both the pre-LEAP and post …

MethodsInclusion criteria: EoE unresponsive to≥ 8 weeks of proton pump inhibitors (PPIs), baseline peak intraepithelial eosinophil count (PEC)≥ 15/high-power field (hpf). Exclusion criteria: weight< 5kg/≥ 60kg, eosinophilic gastroenteritis, swallowed topical corticosteroids (STCs)< 8 weeks pre-baseline.Results102 children enrolled (female 24%, white 82%, Black/African-American 11%). Mean (standard deviation [SD]) age was 7.1 (3.1) yrs. 98% had atopic/allergic comorbidities (food allergy 81%, allergic rhinitis 77%, asthma 55%), with 89% having≥ 2, and 78%≥ 3. Mean (SD) EoE duration was 4.1 (2.8) yrs; onset age was 3.7 (2.7) yrs. 80% had received prior STCs, 82% were on elimination diets, and 48% were taking PPIs at randomization. Patients had EoE symptoms/signs on> 50% of days in the 14-days pre-baseline (mean [SD], symptoms: 0.51 [0.39]; signs: 0.54 [0.37]). Baseline histology/endoscopy mean …