Faculty Bibliography

Rationale: Eczema is a chronic inflammatory skin disorder. We sought to evaluate efficacy and safety of TCM in humans and animal model of eczema.
Method(s): We retrospectively analyzed data of 28 patients with moderate-to-severe eczema who received TCM for at least 3 months in three cohorts based on eczema phenotype/endotype. Cohort #1 (n=10), ages 6 to 48 months, used topical steroids for at least 3 months prior to TCM with inadequate response. Cohort #2 (n=8), ages 2-40 years, had worsening eczema associated with sudden topical steroid withdrawal (TSW, n=8) at least 3 months prior to TCM. Cohort #3 had a very high total IgE (>5,000 kIU/L, n=10), ages 1-13 years. The TCM regimen included external herbal bath, cream, and oral tea. We also tested the TCM effects in a mouse model of eczema treated daily for 9 days.
Result(s): Following TCM treatment, cohort #1 showed reduced SCORAD and steroid use as early as one month (p<0.001) and close to zero by 6 months. Cohort #2 showed improved SCORAD (73.6%, p<0.001), and markedly decreased sleep disturbance (80%, p<0.001) as early as one month. Cohort #3 had markedly reduced total IgE from median 12,328 to 3,994 kIU/L after 6-24 months. TCM significantly reduced elevated blood eosinophils (p<0.05). No liver or kidney function abnormality was observed. Animal model of eczema showed distinctly reduced SCORAD, scratching scores, and skin eosinophil counts. TCM tea also showed dose dependent reduction of IgE, TNF-alpha and exotoxin production in vitro.
Conclusion(s): TCM is efficacious and safe in children and adults with steroid dependent-eczema.
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Rationale: With peanut allergy therapies under development, peanut-allergic children are completing clinical trials wishing to maintain desensitization. We describe our experience transitioning children to real food equivalents of peanut following trial completion.
Method(s): Children who completed peanut clinical trials with interest in continuing (post-oral immunotherapy [OIT]) or starting (post-epicutaneous immunotherapy [EPIT]) daily peanut ingestion were offered an oral food challenge (OFC) for the starting dose, which was determined based on study dose/eliciting dose during exit OFC. Dose-escalation to 2000 mg peanut protein was offered. The charts of post-study participants transitioned to daily peanut ingestion from May 2016-May 2019 were reviewed. Families without recent follow-up were contacted by telephone. This study was IRB approved.
Result(s): Twenty children (80% male; median age 7.6 years, range 4-15 years; n=5 post-EPIT, n=15 post-OIT) were transitioned to daily peanut ingestion. The median starting dose was 300 mg (post-EPIT: 100 mg [range 30-300 mg]; post-OIT: 400 mg [range 30-2000 mg]). Four participants started at 2000 mg; 11/16 dose-escalated. Thirteen participants reached a daily dose >1000 mg. Median follow-up was 1.7 years. Seventeen participants (85%) continued dosing for at least one year or were confirmed to currently actively dose if transitioned in the past year. Two participants discontinued due to side effects (gastrointestinal, hives, wheezing); one was lost to follow-up.
Conclusion(s): Most post-study children transitioned to daily peanut reached a maintenance dose of >1000 mg and continued dosing long-term with real food equivalents. This suggests that families are motivated to follow-through with daily peanut to maintain desensitization after study completion.
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It is well-established that food proteins, such as egg, soya, cow's milk and wheat, are detectable in breastmilk for many hours or days after ingestion. Exposure to these proteins is important to the process of developing tolerance but can also sometimes elicit IgE-mediated and non-IgE-mediated allergic symptoms in breastfed infants. Non-IgE-mediated allergy, outside of food protein-induced allergic proctocolitis and eosinophilic oesophagitis, is not well understood, leading to variations in the diagnosis and management thereof. A primary objective of the European Academy for Allergy and Clinical Immunology is to support breastfeeding in all infants, including those with food allergies. A Task Force was established, to explore the clinical spectrum of non-IgE-mediated allergies, and part of its objectives was to establish diagnosis and management of non-IgE-mediated allergies in breastfed infants. Eight questions were formulated using the Patient, Intervention, Comparison, Outcome (PICO) system and Scottish Intercollegiate Guideline Network (SIGN) criteria for data inclusion, and consensus was achieved on practice points through the Delphi method. This publication aims to provide a comprehensive overview on this topic with practice points for healthcare professionals.

Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated food allergy that manifests with projectile, repetitive emesis that can be followed by diarrhea and may be accompanied by lethargy, hypotonia, hypothermia, hypotension, and metabolic derangements. FPIES usually starts in infancy although onset at older ages is being increasingly recognized. FPIES is not rare, with the cumulative incidence of FPIES in infants estimated to be 0.015% to 0.7%, whereas the population prevalence in the US infants was 0.51%. FPIES diagnosis is challenging and might be missed because of later (1-4 hours) onset of symptoms after food ingestion, lack of typical allergic skin and respiratory symptoms, and food triggers that are perceived to be hypoallergenic. Diagnosis is based on the recognition of symptoms because there are no biomarkers of FPIES. The pathophysiology remains obscure although activation of the innate immune compartment has been detected. Management relies of avoidance of food triggers, treatment of accidental exposures, and periodic re-evaluations with supervised oral food challenges to monitor for resolution. There are no strategies to accelerate development of tolerance in FPIES. Here we review the most important current concepts in epidemiology, pathophysiology, diagnosis, and management of FPIES.

Oral food challenges are an integral part of an allergist's practice and are used to evaluate the presence or absence of allergic reactivity to foods. A work group within the Adverse Reactions to Foods Committee of the American Academy of Allergy, Asthma & Immunology was formed to update a previously published oral food challenge report. The intention of this document was to supplement the previous publication with additional focus on safety, treatment of IgE-mediated allergic reactions, guidance for challenges in infants and adults, psychosocial considerations for children and families participating in an oral food challenge, specific guidance for baked milk or baked egg challenges, masking agents and validated blinding recipes for common food allergens, and recommendations for conducting and interpreting challenges in patients with suspected food protein-induced enterocolitis syndrome. Tables and figures within the report and an extensive online appendix detail age-specific portion sizes, appropriate timing for antihistamine discontinuation, serum and skin test result interpretation, written consents, and instructional handouts that may be used in clinical practice.

PURPOSE OF REVIEW/OBJECTIVE:To critically appraise the recent most relevant studies in the rapidly advancing field of food oral and sublingual immunotherapy. RECENT FINDINGS/RESULTS:Food allergen-specific immunotherapy via oral (OIT) and sublingual route (SLIT) increases the threshold of reactivity to peanut, cow's milk, egg, wheat, and many other foods in the majority of the treated individuals. This desensitized state is contingent upon the continued ingestion of the maintenance doses of the food. Permanent oral tolerance is achievable in a smaller subset of the treated individuals. The optimal duration of therapy has not been firmly established but is likely dependent on the phenotype (severity and persistence). Efficacy of food-OIT is superior compared with SLIT, whereas the safety of OIT is less favorable. Standardization of treatment protocols, maintenance dosing, duration of therapy, target populations and harmonization of the outcomes are top priorities at this stage. SUMMARY/CONCLUSIONS:OIT and SLIT represent two different routes of food allergen-specific immunotherapy. Although significant progress has been made in the last decade, both treatment modalities are still in the very early stages of development and further investigations are necessary to optimize the protocols and improve safety while maximizing efficacy.

Exopalaemon modestus (EM) is a shrimp delicacy that could cause food allergy, the major allergen of EM is Exo m 1. The amino acid (AA) sequence, IgE-binding epitopes and allergenic peptides in gastrointestinal (GI) digests of Exo m 1, and their effects on basophil function were investigated. Exo m 1 has an AA-sequence of high similarity with other shrimp tropomyosins, while not 100% matching. The IgE-binding epitopes of Exo m 1 are epitope 1 (43-59, VHNLQKRMQQLENDLDS), epitope 2 (85-105, VAALNRRIQLLEEDLERSEER), epitope 3 (131-164, ENRSLSDEERMDALENQLKEARFLAEEADRKYDE), epitope 4 (187-201, ESKIVELEEELRVVG) and epitope 5 (243-280, ERSVQKLQKEVDRLEDELVNEKEKYKSITDELDQTFSE). Among the thirty-three peptides of Exo m 1 identified in GI digests, two were highly recognized by IgE, twenty-four moderately or weakly bound IgE, and seven had no IgE-reactivities. These IgE-binding epitopes and GI digestion induced-allergenic peptides could activate basophil degranulation, and CD63 and CD203c expression, they could be potential peptide-based immunotherapy for shrimp allergic individuals.

Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated food allergy that has been well-characterized clinically, yet it is still poorly understood. Acute FPIES is characterized by vomiting 1-4 h and/or diarrhea within 24 h after ingestion of a culprit food. Chronic FPIES is the result of chronic exposure to an offending food that can result in chronic watery diarrhea, intermittent vomiting, and failure to thrive. FPIES typically presents in infancy and self-resolves by school age in most patients. Adult-onset FPIES is rare, but it has been reported. Cow's milk and soy are the most common triggering foods in infants in the US, and as solids are introduced in the diet, FPIES reactions to grains (rice, oat) increase in prevalence. Variability in common trigger foods exists depending on the geographical origin-for example, fish is a frequent trigger in Spanish and Italian patients. Heavy reliance on a detailed history is required for the diagnosis as physical exam findings, laboratory tests, and/or imaging studies are suggestive and not specific for FPIES. Oral food challenges remain the gold standard for confirming diagnosis, and the challenge protocol may be for an individual depending on risk of reaction, prior reaction severity, and positive-specific IgE status. The recent development of diagnostic criteria in 2017 will serve to increase recognition of the disorder and allow for early implementation of management strategies. Acute management during reactions includes IV hydration, anti-emetics, and IV corticosteroids. Reaction prevention strategies include strict food avoidance until the physician deems a food reintroduction challenge clinically appropriate. Future efforts in FPIES research should be aimed at elucidating the underlying disease mechanisms and possible treatment targets.