Anna Nowak-Węgrzyn

Icahn School of Medicine at Mount Sinai, Borough of Manhattan, New York, United States

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Publications (50)287.07 Total impact

  • Elizabeth Feuille · Anna Nowak-Węgrzyn
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    ABSTRACT: Food protein-induced enterocolitis (FPIES), allergic proctocolitis (FPIAP), and enteropathy (FPE) are among a number of immune-mediated reactions to food that are thought to occur primarily via non-IgE-mediated pathways. All three are typically present in infancy and are triggered most commonly by cow's milk protein. The usual presenting features are vomiting with lethargy and dehydration in FPIES; bloody and mucous stools in FPIAP; and diarrhea with malabsorption and failure to thrive in FPE. Diagnosis is based on convincing history and resolution of symptoms with food avoidance; confirmatory diagnostic testing other than food challenge is lacking. The mainstay of management is avoidance of the suspected inciting food, with interval challenge to assess for resolution, which usually occurs in the first years of life. Studies published in the past few years clarify common presenting features, report additional culprit foods, address potential biomarkers, and suggest new management strategies.
    Current Allergy and Asthma Reports 08/2015; 15(8):546. DOI:10.1007/s11882-015-0546-9 · 2.45 Impact Factor
  • Anna Nowak-Węgrzyn · Yitzhak Katz · Sam Soheil Mehr · Sibylle Koletzko
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    ABSTRACT: Non-IgE-mediated gastrointestinal food-induced allergic disorders (non-IgE-GI-FAs) account for an unknown proportion of food allergies and include food protein-induced enterocolitis syndrome (FPIES), food protein-induced allergic proctocolitis (FPIAP), and food protein-induced enteropathy (FPE). Non-IgE-GI-FAs are separate clinical entities but have many overlapping clinical and histologic features among themselves and with eosinophilic gastroenteropathies. Over the past decade, FPIES has emerged as the most actively studied non-IgE-GI-FA, potentially because of acute and distinct clinical features. FPIAP remains among the common causes of rectal bleeding in infants, while classic infantile FPE is rarely diagnosed. The overall most common allergens are cow's milk and soy; in patients with FPIES, rice and oat are also common. The most prominent clinical features of FPIES are repetitive emesis, pallor, and lethargy; chronic FPIES can lead to failure to thrive. FPIAP manifests with bloody stools in well-appearing young breast-fed or formula-fed infants. Features of FPE are nonbloody diarrhea, malabsorption, protein-losing enteropathy, hypoalbuminemia, and failure to thrive. Non-IgE-GI-FAs have a favorable prognosis; the majority resolve by 1 year in patients with FPIAP, 1 to 3 years in patients with FPE, and 1 to 5 years in patients with FPIES, with significant differences regarding specific foods. There is an urgent need to better define the natural history of FPIES and the pathophysiology of non-IgE-GI-FAs to develop biomarkers and novel therapies. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
    The Journal of allergy and clinical immunology 05/2015; 135(5):1114-24. DOI:10.1016/j.jaci.2015.03.025 · 11.25 Impact Factor
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    ABSTRACT: Background: Modification of native peanut extracts could reduce adverse effects of peanut immunotherapy. Objective: We sought to compare native and chemically modified crude peanut extract (CPE) and major peanut allergens Ara h 2 and Ara h 6 in a mediator-release assay based on the rat basophilic leukemia (RBL) cell line transfected with human Fcε receptor. Methods: Native Ara h 2/6 was reduced and alkylated (RA), with or without additional glutaraldehyde treatment (RAGA). CPE was reduced and alkylated. Sera of subjects with peanut allergy (16 males; median age 7 years) were used for overnight RBL-passive sensitization. Cells were stimulated with 0.1 pg/mL to 10 μg/mL of peanut. β-N-acetylhexosaminidase release (NHR) was used as a marker of RBL degranulation, expressed as a percentage of total degranulation caused by Triton X. Results: Median peanut-specific immunoglobulin E was 233 kUA/L. Nineteen subjects were responders, NHR ≥ 10% in the mediator release assay. Responders had reduced NHR by RA and RAGA compared with the native Ara h 2/6. Modification resulted in a later onset of activation by 10- to 100-fold in concentration and a lowering of the maximum release. Modified RA-Ara h 2/6 and RAGA-Ara h 2/6 caused significantly lower maximum mediator release than native Ara h 2/6, at protein concentrations 0.1, 1, and 10 ng/mL (p < 0.001, < 0.001, and < 0.001, respectively, for RA; and < 0.001, 0.026, and 0.041, respectively, for RAGA). RA-CPE caused significantly lower maximum NHR than native CPE, at protein concentration 1 ng/mL (p < 0.001) and 10 ng/mL (p < 0.002). Responders had high rAra h 2 immunoglobulin E (mean, 61.1 kUA/L; p < 0.001) and higher NHR in mediator release assay to native Ara h 2/6 than CPE, which indicates that Ara h 2/6 were the most relevant peanut allergens in these responders. Conclusions: Chemical modification of purified native Ara h 2 and Ara h 6 reduced mediator release in an in vitro assay ∼100-fold, which indicates decreased allergenicity for further development of the alternative candidate for safe peanut immunotherapy.
    Allergy and Asthma Proceedings 05/2015; 36(3):185-191. DOI:10.2500/aap.2015.36.3840 · 3.35 Impact Factor
  • Anna Nowak-Węgrzyn
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    ABSTRACT: Non-IgE-mediated food allergic disorders account for up to 40% of milk protein allergy in infants and young children. We aim to review the recent literature and to provide an update on diagnosis and management of food protein-induced enterocolitis syndrome (FPIES) and food protein-induced allergic proctocolitis (FPIAP). The peer-reviewed articles indexed in PubMed have been reviewed. FPIES manifests in infants as profuse, repetitive vomiting and lethargy, often with diarrhea, leading to acute dehydration, or weight loss and failure to thrive, in chronic form. FPIES is caused most commonly by cow's milk (CM) and soy proteins; rice, oat, and other solid foods may also trigger FPIES. FPIES rarely occurs in the exclusively breastfed infants. FPIES is underrecognized; children are often mismanaged as having acute viral gastrointestinal illness, sepsis, or surgical disease, delaying diagnosis of FPIES for many months. Approximately 25% of children with FPIES develop food-specific IgE antibodies and some transition to immediate food allergy; IgE positivity is associated with a more protracted course. FPIES is a self-limiting condition, with most cases resolving by age three to five years. Ondansetron may be helpful in managing acute FPIES. FPIAP is a benign condition of bloody stools in a well-appearing infant, with usual onset between one and four weeks of age. Up to 60% of cases occur in exclusively breastfed infants and resolve with maternal elimination of CM and soy proteins. The majority of cases resolve by age 12 months. FPIES may transition to IgE-mediated food allergy in some patients; IgE positivity to the FPIES food is a marker of a more persistent disease. FPIAP is benign and resolves by age 12 months in most patients.
    Allergy and Asthma Proceedings 05/2015; 36(3):172-84. DOI:10.2500/aap.2015.36.3811 · 3.35 Impact Factor
  • 03/2015; 3(1):135-7. DOI:10.1016/j.jaip.2014.09.016
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    ABSTRACT: Cow's milk (CM) and hen's egg allergies are among the most common food allergies in children. With evidence of increasing food allergy prevalence and more persistent disease, it has become vital to improve the management of CM and egg allergies. The ability to tolerate baked milk or egg, such as in a cake or muffin, has been associated with an increased chance of tolerance development. Studies report that about 70% of CM- and egg-allergic children can tolerate baked milk or egg and that incorporating baked milk or egg into the diet is well tolerated. Being able to add baked milk or egg into the diet can also increase quality of life by expanding the diet, boosting nutrition, and promoting inclusion in social activities. There is some debate over how baked milk and egg should be introduced, at home or in a supervised setting. Anaphylaxis and treatment with epinephrine during baked milk or egg challenges have been reported. Study of potential biomarkers to predict tolerability of baked milk and egg, such as serum specific IgE levels and skin prick test wheal diameters, is ongoing. Many parents can reliably report that their CM- or egg-allergic child is already consuming baked goods without symptoms. However, for those who cannot report such tolerance, the most prudent approach is to perform a supervised oral food challenge to determine the tolerability of baked milk and egg. The purpose of this article was to review the pathophysiology, clinical data, and safety of baked milk and egg and provide a practical guide to managing CM allergy and/or egg allergy. Recipes for baked milk and egg challenges and guidance on how to add baked milk and egg if tolerated to the child's regular diet are provided. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
    02/2015; 3(1):13-23. DOI:10.1016/j.jaip.2014.10.001
  • Anna Nowak-Węgrzyn · Marion Groetch
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    ABSTRACT: Dietary intervention is a crucial component of food allergy management but can negatively impact nutrient intake. A comprehensive nutrition assessment with appropriate intervention is warranted in all children with food allergies to meet nutrient needs and optimize growth. Nutrition assessment may also be indicated in adults with food allergy. Frequently, an elimination diet is absolutely necessary to prevent potentially life-threatening anaphylaxis. Allergen elimination can also improve chronic symptoms, such as atopic dermatitis, when a food is proven to trigger symptoms. Allergen elimination goals are to prevent acute and chronic food-allergic reactions in the safest and least restrictive environment to supply a balanced diet that promotes health in children and adults. © 2015 S. Karger AG, Basel.
    Progress in allergy 01/2015; 101:209-20. DOI:10.1159/000373904
  • Stephanie Albin · Anna Nowak-Węgrzyn
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    ABSTRACT: This article presents an overview of potential treatments of food allergy, with an emphasis on various forms of immunotherapy (including oral immunotherapy, sublingual immunotherapy, epicutaneous immunotherapy, immunotherapy with modified food antigens, and immunotherapy with a recombinant peanut vaccine). Allergen nonspecific treatments, such as Chinese herbal formulas, probiotics/prebiotics, helminths, monoclonal antibodies, and toll-like receptor agonists, are also summarized. Copyright © 2015 Elsevier Inc. All rights reserved.
    Immunology and Allergy Clinics of North America 11/2014; 35(1). DOI:10.1016/j.iac.2014.09.011 · 2.22 Impact Factor
  • Anna Nowak-Węgrzyn · Laura A Czerkies · Barbara Collins · José M Saavedra
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    ABSTRACT: The American Academy of Pediatrics (AAP) defined a formula as hypoallergenic if it ensures with 95% confidence that 90% of infants with confirmed cow's milk allergy (CMA) will not react with defined symptoms under double-blind, placebo-controlled conditions. This study's objective was to determine whether a new amino acid-based formula (AAF) meets the AAP hypoallergenicity criteria. Methods. Children with CMA were randomized to double-blind placebo-controlled food challenges (DBPCFC) with a new AAF and a commercial AAF in crossover fashion followed by an at-home open challenge with the new AAF. Allergic reactions were assessed using a scoring system. Results. Thirty-three subjects completed DBPCFCs with both formulas without acute allergic reactions. The lower bound 95% confidence interval for hypoallergenicity was 91.3%. No unusual stool patterns, allergic symptoms, or signs of intolerance were reported during the open challenge.
    Clinical Pediatrics 11/2014; 54(3). DOI:10.1177/0009922814557785 · 1.26 Impact Factor
  • Nikhil R Menon · Anna Nowak-Węgrzyn
    Pediatrics 11/2014; 134 Suppl 3(Supplement):S164-5. DOI:10.1542/peds.2014-1817BBB · 5.30 Impact Factor
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    ABSTRACT: Background: Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated food allergy. FPIES diagnosis is frequently delayed because of the absence of classic allergic symptoms and lack of biomarkers. Objective: We sought to characterize the clinical features and resolution of FPIES in patients evaluated in our practice. Methods: Subjects 6 months to 45 years of age with FPIES were prospectively recruited for oral food challenges (OFCs). Medical records were searched to identify the subjects who did not participate in OFCs. Results: Among 160 subjects, 54% were male; median age at diagnosis was 15 months. We performed 180 OFCs to 15 foods in 82 subjects; 30% of the study population had FPIES confirmed based on OFC results. The most common foods were cow's milk (44%), soy (41%), rice (22.5%), and oat (16%). The majority (65%) reacted to 1 food, 26% reacted to 2 foods, and 9% reacted to 3 or more foods. The majority were atopic, and 39% had IgE sensitization to another food. Thirty-nine (24%) subjects had positive specific IgE levels to the food inducing FPIES. Among children with specific IgE to cow's milk, 41% changed from a milk FPIES to an IgE-mediated phenotype over time. The median age when tolerance was established was 4.7 years for rice, 4 years for oat, and 6.7 years for soy. Median age when milk tolerance was established for subjects with undetectable milk-specific IgE levels was 5.1 years, whereas none of the subjects with detectable milk-specific IgE became tolerant to milk during the study (P = .003). Conclusion: FPIES typically resolves by age 5 years. Milk FPIES, especially with detectable food-specific IgE, can have a protracted course and eventually transition to acute reactions.
    Journal of Allergy and Clinical Immunology 05/2014; 134(2). DOI:10.1016/j.jaci.2014.04.008 · 11.25 Impact Factor
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    Elizabeth Feuille · Anna Nowak-Węgrzyn
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    ABSTRACT: Food protein-induced enterocolitis syndrome (FPIES) is a poorly understood non-IgE-mediated food hypersensitivity, primarily affecting infants and toddlers. There are few data regarding pathophysiology of FPIES that suggest local intestinal imbalance between TNF-α and TGF-β. Patients frequently present with multiple reactions, which are characterized by projectile, repetitive emesis, dehydration, lethargy, and failure to thrive. Despite the severity of presentation, the diagnosis is frequently delayed, and patients often undergo extensive and invasive evaluation prior to reaching the diagnosis. Reviews published in the last year provide a general approach to diagnosis and management of FPIES and aim to increase awareness and understanding of FPIES among general pediatricians. Multicenter studies are necessary to reevaluate and modify the oral food challenge criteria. Research on the pathophysiology of FPIES reactions is necessary to provide insight into the evidence-based approach to diagnosis and management of FPIES. Registries are needed to understand the phenotype, triggers, and prevalence of FPIES.
    Current Opinion in Allergy and Clinical Immunology 03/2014; 14(3). DOI:10.1097/ACI.0000000000000055 · 3.66 Impact Factor
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    ABSTRACT: SLIT (sublingual immunotherapy) is a therapeutic method aiming at producing allergen-specific tolerance of the immune system to a gradually increasing dose of an allergen that is administered sublingually. SLIT initiates similar immune mechanisms as does subcutaneous immunotherapy (SCIT). The aim of the study at this position is to update the current knowledge on sublingual immunotherapy. Randomized double-blind, placebo-controlled (RDBPC) studies that compared both immunotherapy forms point to an advantage of SCIT over SLIT in decreasing symptoms of asthma and allergic rhinitis, a comparable effect of both the methods on immune parameters (sIgE, IL-10) and upper respiratory tract inflammations and an advantage of SCIT over SLIT with respect to lower respiratory tract inflammations as based on provocation tests. At present, there are no grounds for recommending SLIT in food allergy. In view of the high safety profile and absence of anxiety-provoking infections, SLIT may be the method that is more often selected in children as compared to adults. On the other hand, immune mechanisms and results of clinical trials provide an argument for preferential employment of SCIT in adults. It should be borne in mind, however, that SLIT is effective if a good quality vaccine with a high allergen dose, is employed for at least three years. National and international reports indicate the necessity of conducting further clinical trials, especially including a direct comparison between SCIT and SLIT with respect to effectiveness and safety.
    01/2014; 1(1):30–37. DOI:10.1016/j.alergo.2014.03.002
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    ABSTRACT: Decreased serum food-specific IgA antibodies have been associated with allergic disease in cross-sectional, case-control studies. The purpose of this study was to prospectively compare egg-white-(EW)-specific IgA and IgA2 levels between egg-allergic children and children tolerating egg. Seventeen egg-allergic children were followed prospectively. Total IgA, EW-specific IgA, and EW-specific IgA2 levels were measured in their sera with a sensitive ELISA. As negative controls were used children with no previous history of egg allergy. Egg-allergic children with or without concomitant milk allergy were evaluated as additional controls with measurement of casein-specific IgA. After 2.5 ± 0.9 yrs, nine out of the 17 allergic children became tolerant and eight remained allergic to baked egg. Baseline EW-specific IgA2 levels were significantly lower in the egg-allergic subjects (median 23.9 ng/ml) compared with the negative control subjects (99.4 ng/ml) and increased significantly by 28% over the study time period in eight out of the nine allergic children that became tolerant to baked egg. There was no significant change over time in EW-specific IgA in any of the study groups. Non-milk-allergic subjects with concomitant egg allergy had almost threefold higher casein-specific IgA levels than the milk- and egg-allergic subjects (p = 0.025). These results suggest a potential role for allergen-specific IgA2 antibodies in the induction of food tolerance. Furthermore, they support the hypothesis that immature or impaired production of allergen-specific IgA2 may be associated with the pathophysiology of food allergy, a defect that seems to be selective for the culprit allergen.
    Pediatric Allergy and Immunology 10/2013; 25(1). DOI:10.1111/pai.12143 · 3.86 Impact Factor
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    ABSTRACT: Children with food allergy have been shown to have increased small intestinal permeability (IP) following ingestion of the offending food as well as during elimination diets. We investigated IP in asymptomatic food allergic children during an elimination diet to identify clinical characteristics associated with altered IP. Urinary recovery ratios of lactulose and mannitol (L/M) were determined 5 h following ingestion of 7.5 g of lactulose and 2 g of mannitol in 131 cow's milk and egg allergic children. An L/M ratio of ≥0.025 was considered abnormal based upon previously established laboratory internal references. A chart review was conducted to assess the clinical characteristics of these patients. A total of 50 (38%) of the 131 children (median 6.7, range 4.8-8.9 yr; 66.2% male) with food allergy had elevated IP while asymptomatic on strict elimination diets. Age and height negatively correlated with IP. However, in the regression model analysis, abnormal IP was associated with shorter stature independently of age. Otherwise, food allergic patients with increased IP were comparable in gender, nutritional status, age of onset of food allergy, history of reactions, atopic diseases, and family history of food allergies to those with normal IP. Elevated IP was found in about one-third of asymptomatic food allergic children on elimination diets and was associated with shorter stature. Our results suggest that increased IP may be an intrinsic trait in a subset of food allergic children. However, large, prospective studies are necessary to determine the role of impaired intestinal barrier in food allergy.
    Pediatric Allergy and Immunology 08/2013; 24(6). DOI:10.1111/pai.12106 · 3.86 Impact Factor
  • Kirsi M. Järvinen · Anna Nowak-Węgrzyn
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    ABSTRACT: Food protein-induced enterocolitis syndrome (FPIES) is a non–IgE-mediated gastrointestinal food hypersensitivity that manifests as profuse, repetitive vomiting, often with diarrhea, leading to acute dehydration and lethargy or weight loss and failure to thrive if chronic. FPIES is elicited most commonly by milk and soy proteins; however, rice, oat, and other solid foods may also elicit FPIES. Certain FPIES features overlap with food protein-induced enteropathy and proctocolitis, whereas others overlap with anaphylaxis. FPIES is not well recognized among pediatricians and emergency department physicians; the affected children are often mismanaged as having acute viral gastrointestinal illness, sepsis, or surgical disease, delaying diagnosis of FPIES for many months. The aim of this review is to provide case-driven presentation of the features of FPIES. Although randomized clinical trials on management options are missing, the relevant current literature and authors' experience are reviewed in detail.
    07/2013; 1(4):317–322.e4. DOI:10.1016/j.jaip.2013.04.004
  • 07/2013; 1(4):418-421.e2. DOI:10.1016/j.jaip.2013.04.012
  • Stephanie A Leonard · Anna Nowak-Węgrzyn
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    ABSTRACT: PURPOSE OF REVIEW: To provide an overview of clinical manifestations, diagnosis and pathophysiology of food protein-induced enterocolitis syndrome (FPIES), an under-recognized and often misdiagnosed nonimmunoglobulin E-mediated food hypersensitivity. This review will highlight updates on natural history and clinical management. RECENT FINDINGS: The main developments in FPIES involve epidemiology, common presentation and variants thereof, and natural history. Improved understanding and recognition of FPIES have influenced changes in clinical management. SUMMARY: A large prospective population-based study reported cow's milk-FPIES cumulative incidence to be 0.34% by 1 year of age; immunoglobulin E-mediated cow's milk allergy was 0.5%. A case report has suggested that FPIES pathophysiology involves Th2 activation, and a shift away from Th2 signalling may be associated with resolution. Appreciation of the frequent incidence of multiple food-FPIES has influenced anticipatory guidance. Two case reports have described FPIES to food proteins in maternal breast milk. The threshold dose for FPIES reactivity may decrease with successive episodes. Reports from different populations indicate that children may outgrow FPIES sooner than previously thought.
    Current opinion in pediatrics 10/2012; 24(6). DOI:10.1097/MOP.0b013e3283599ca1 · 2.74 Impact Factor
  • Annals of allergy, asthma & immunology: official publication of the American College of Allergy, Asthma, & Immunology 09/2012; 109(3):221-2. DOI:10.1016/j.anai.2012.06.020 · 2.75 Impact Factor
  • The Journal of allergy and clinical immunology 08/2012; 131(1). DOI:10.1016/j.jaci.2012.06.049 · 11.25 Impact Factor

Publication Stats

790 Citations
287.07 Total Impact Points

Institutions

  • 2010–2015
    • Icahn School of Medicine at Mount Sinai
      • • Department of Pediatrics
      • • Division of Allergy and Immunology
      Borough of Manhattan, New York, United States
  • 2014
    • Gracie Square Hospital, New York, NY
      New York City, New York, United States
  • 2012
    • Rady Children's Hospital
      San Diego, California, United States
  • 2011
    • University of Western Australia
      • School of Paediatrics and Child Health
      Perth, Western Australia, Australia