Melanie A. Ruffner

Food Protein-induced Enterocolitis Syndrome: Insights from Review of a Large Referral Population

BACKGROUNDnFood protein-induced enterocolitis (FPIES) is a rare non-IgE mediated disease. Most studies have been limited in nature, with the largest cohort being 66 patients. The most common foods that have been reported are milk and soy.nnnOBJECTIVEnA retrospective chart review of patients seen in the Allergy Section at The Childrens Hospital of Philadelphia with International Classification of Diseases Ninth Revision code of 558.3 (Allergic Gastroenteritis and Colitis) between 2007 and 2012 was conducted to identify patients with suspected FPIES. Diagnosis of FPIES was confirmed based on meeting clinical criteria of delayed reaction with pronounced vomiting and/or diarrhea. Data regarding patient characteristics and features of their reactions were collected for analysis and comparison with existing studies.nnnRESULTSnA total of 462 cases were identified in our chart review. Patients had a similar demographic profile to the normal allergy patients seen in our clinic. The most common foods identified were milk (67%), soy (41%), rice (19%), oat (16%), and egg (11%). Patients had onset of FPIES to milk and soy around 7 months of age compared with 12 months of age for solid foods. FPIES reactions were identified to meats, tree nuts, peanuts, fruits, and vegetables; 70% of the patients reacted to one or two foods. Skin prick testing and atopy patch testing were not helpful in identifying the foods.nnnCONCLUSIONnFPIES reactions were seen more frequently than previously described. However, the presentation and clinical features were similar to previous reports. Milk- and soy-triggered FPIES were common, and 43.5% of patients who had a milk trigger reacted to soy. There is no laboratory test to identify foods that cause FPIES, and clinician-supervised oral food challenge is the only definitive test available.

Elevated expression of activated TH2 cells and milk-specific TH2 cells in milk-induced eosinophilic esophagitis

BACKGROUNDnEosinophilic esophagitis (EoE) is an allergic inflammatory disease that is triggered by food allergens and characterized by progressive esophageal dysfunction. Esophageal biopsy specimens are characterized by eosinophilia and expression of TH2 cytokines.nnnOBJECTIVEnTo ascertain whether TH2 cells can exist in the peripheral blood in patients with milk-induced EoE.nnnMETHODSnPeripheral blood mononuclear cells from 20 children with milk-induced EoE were collected during active EoE (EoE-A) while consuming milk and inactive EoE (EoE-I) while not consuming milk, and 8 healthy patients without EoE were used as controls. The samples were analyzed for T-cell phenotype, including intracellular cytokines before and after incubation with milk antigens and assessed by flow cytometry.nnnRESULTSnWe found a significant increase in CD4+ TH2 cells in the peripheral blood of patients with EoE-A compared with the controls. Furthermore, we observed a significant mean (SD) increase in the activation marker of CD154+ T cells (0.17% [0.047%]) in patients with EoE-A compared with control patients (0.034% [0.007%]) and EoE-I (0.025% [0.008]). These CD4+ T cells expressed significantly increase levels of TH2 cytokines (interleukins 4, 5, and 13) compared with the EoE-I and control groups. CD3+CD4+CD154+IL-5+ cells were significantly increased by milk antigens in both milk-induced EoE-A (0.050% [0.008%] to 0.079% [0.017%]) and EoE-I (0.0045% [0.002%] to 0.014% [0.008%]) compared with the controls (0.008% [0.003%] to 0.003% [0.001%]).nnnCONCLUSIONnOur findings indicate that in EoE peripheral T cells have specific activation to milk allergens.

Non–IgE-mediated food allergy syndromes

In contrast to IgE-mediated food allergies, diagnosis of the various non-IgE mediated food allergy syndromes can be challenging due to the overall lack of noninvasive confirmatory testing for these disorders. Many of the non-IgE food allergy syndromes are are diagnosed clinically, based on history and managed empirically with food avoidance. Therefore, it is essential for the practicing allergist to be familiar with the myriad presentations of non-IgE mediated food allergy. This review focuses on the presentation and management of the non-IgE mediated food allergy syndromes.

Recurrent and Sustained Viral Infections in Primary Immunodeficiencies

Viral infections are commonplace and often innocuous. Nevertheless, within the population of patients with primary immunodeficiencies (PIDDs), viral infections can be the feature that drives a diagnostic evaluation or can be the most significant morbidity for the patient. This review is focused on the viral complications of PIDDs. It will focus on respiratory viruses, the most common type of viral infection in the general population. Children and adults with an increased frequency or severity of respiratory viral infections are often referred for an immunologic evaluation. The classic teaching is to investigate humoral function in people with recurrent sinopulmonary infections, but this is often interpreted to mean recurrent bacterial infections. Recurrent or very severe viral infections may also be a harbinger of a primary immunodeficiency as well. This review will also cover persistent cutaneous viral infections, systemic infections, central nervous system infections, and gastrointestinal infections. In each case, the specific viral infections may drive a diagnostic evaluation that is specific for that type of virus. This review also discusses the management of these infections, which can become problematic in patients with PIDDs.

Variable immune deficiency related to deletion size in chromosome 22q11.2 deletion syndrome

The clinical features of 22q11.2 deletion syndrome include virtually every organ of the body. This review will focus on the immune system and the differences related to deletion breakpoints. A hypoplastic thymus was one of the first features described in this syndrome and low T cell counts, as a consequence of thymic hypoplasia, are the most commonly described immunologic feature. These are most prominently seen in early childhood and can be associated with increased persistence of viruses. Later in life, evidence of T cell exhaustion may be seen and secondary deficiencies of antibody function have been described. The relationship of the immunodeficiency to the deletion breakpoints has been understudied due to the infrequent analysis of people carrying smaller deletions. This manuscript will review the immune deficiency in 22q11.2 deletion syndrome and describe differences in the T cell counts related to the deletion breakpoints. Distal, non‐TBX1 inclusive deletions, were found to be associated with better T cell counts. Another new finding is the relative preservation of T cell counts in those patients with a 22q11.2 duplication.

Eosinophilic Esophagitis in Children

Purpose of ReviewEoE is a significant cause of gastrointestinal morbidity affecting 1:2000. Patients with EoE typically have multiple atopic comorbidities, and additionally, many patients with EoE can be controlled well with elimination diets. The purpose of this review is to summarize the care of pediatric eosinophilic esophagitis patients.Recent FindingsEoE represents a distinct clinical syndrome which is characterized by esophageal dysfunction and eosinophil-predominant inflammation of the esophageal mucosa. Patients with EoE can present with varying symptoms depending on their age; in this review, we review the presenting features of eosinophilic esophagitis in children as well as a diagnostic algorithm for EoE. The mucosal inflammation in EoE is driven by exposure to food antigens in many patients with EoE. Therefore, for the majority of patients, the mainstays of treatment remain food elimination diets or swallowed steroids.SummaryThis review summarizes the diagnostic approach to eosinophilic esophagitis (EoE) in pediatric patients, focusing on the importance of accurate diagnosis and selection of appropriate therapy.

Food Protein-Induced Enterocolitis Syndrome Food Challenges: Experience from a Large Referral Center

BACKGROUNDnFood protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated food allergy that is diagnosed based on clinical findings, but can be confirmed with oral food challenge (OFC). OFC is more often performed to assess the development of tolerance. Most studies describing OFCs in FPIES are limited in size.nnnOBJECTIVEnWe sought to describe our experience with OFCs using our FPIES protocol. Patients were given one-third of serving size with a 4-hour observation period, followed by home titration to full dose.nnnMETHODSnWe conducted a retrospective chart review of patients who underwent OFC via the FPIES protocol from 2014 to 2017. Data regarding the history of reaction, age at the time of challenge, and reactions during challenge or with home introduction were collected.nnnRESULTSnA total of 169 OFCs were completed under the FPIES protocol, in 119 patients to 19 different foods. Thirty challenges (18%) were positive, with 17 challenges (10%) during initial challenge and 13 (7.7%) during home dosing. Most reactions during initial challenge required intravenous fluids (IVF), but hypotension was uncommon. One hundred thirty-nine (82%) OFCs were negative with home introduction, indicating tolerance to the challenged foods. The mean age of passing a challenge to milk, soy, and grain was earlier than that of other solid foods.nnnCONCLUSIONSnOur data suggest that our FPIES OFC protocol is safe. Early administration of IVF may prevent the development of hypotension. It is difficult to stratify the risk of severe or delayed reaction based on patient characteristics, and more data are needed to identify those appropriate for home introduction.

EMSY is increased and activates TSLP & CCL5 expression in eosinophilic esophagitis

Eosinophilic esophagitis (EoE) is a clinicopathologic disease characterized by an increased number of eosinophils (greater than or equal to 15 eosinophils per high powered field) in the esophageal mucosa, likely due to an immune or antigenic response (1). Specifically, there is an increased production of esophageal epithelial derived pro-inflammatory mediators such as Thymic Stromal Lymphopoietin (TSLP), Eotaxin 3 (CCL26), RANTES (CCL5), Calpain 14 (CAPN14), and interleukin (IL)-33 (2), which ultimately results in eosinophilic infiltration of the esophageal epithelium. TSLP is mainly secreted by epithelial cells and is a IL-7 like cytokine that is able to induce a strong T helper type 2 (Th2) inflammatory response (3). TSLP has been shown to play a crucial role in EoE pathogenesis (3). Similarly, IL-33 is an epithelial derived Th2 cell agonist and allergenic ligand that has been associated with EoE (4). Chemokine (C-C motif) ligand 5 (CCL5) is a cytokine that is known to contribute to several atopic and inflammatory eosinophilic diseases, including EoE. This article is protected by copyright. All rights reserved.

Complications Associated with Underweight Primary Immunodeficiency Patients: Prevalence and Associations Within the USIDNET Registry

PurposeThe point prevalence of underweight status and obesity in primary immunodeficiency disease (PID) is unknown, despite the described associations between PID and weight loss and failure to thrive. The goal of this study is to estimate the prevalence of underweight status and obesity in PID patients and to investigate the associations between abnormal body weight and complications of PID.MethodsUsing the US Immunodeficiency Network (USIDNET), we performed a retrospective analysis of 653 pediatric (age 2 to 20xa0years) and 514 adult (ageu2009>u200920) patient records with information on patient body mass index (BMI). Prevalence of underweight and obese status in PID patients was compared to data from the National Health and Nutrition Examination Survey (NHANES).ResultsAfter separating BMI data by year of entry to the database, we demonstrated that both adult and pediatric patients with PID had significantly higher prevalence of underweight patients in multiple years of analysis. Further examination of underweight patients by PID diagnosis revealed that underweight status in adults with CVID was associated with granulomatous disease as well as earlier age of CVID diagnosis. In the pediatric CVID cohort, underweight status was significantly associated with lymphopenia. Examination of obesity in pediatric and adult PID patients compared to NHANES database revealed only a single year when obesity in PID patients was significantly less prevalent. In other 2-year time intervals from 2005 to 2014, the prevalence of obesity was unchanged in children and adults.ConclusionsThese results quantify the prevalence of underweight status in PID in a North American population and demonstrate that whether as a result of weight loss or poor weight gain, underweight status is more prevalent in the PID population than in the general US population. The prevalence of obesity in PID patients was similar to that seen in the general population. This highlights the need for continued education on the association of low weight and PID.Clinical Trial RegistrationNCT01953016

A Review of Tertiary Referrals for Management of Pediatric Esophageal Eosinophilia

Background: Eosinophilic esophagitis is a chronic, immune-mediated disease characterized by symptoms of esophageal dysfunction and ≥15 eosinophils/high-powered field (eos/hpf). Proton pump inhibitor responsive esophageal eosinophilia (1) is an entity of esophageal eosinophilia that responds to PPI therapy and is thought to be clinically and histologically similar to EoE. Current guidelines suggest therapy with PPI prior to endoscopy and use of PPI as first line for esophageal eosinophilia. In order to gain a better understanding of community practice patterns and to try differentiate between these two entities, we sought to evaluate the clinical presentations, treatment and final diagnoses of patients presenting to our institution for second opinions of esophageal eosinophilia. Methods: A search of our electronic medical record yielded a list of patients presenting for a second opinion of esophageal eosinophilia. Charts were reviewed for clinical information. Results: A total of 187 charts were included. Patients ranged from 1-19 years old with 75% being male and 74% being Caucasian. Of the patients who had documentation of their medications at the time of initial endoscopy, 70% were not on any PPI prior to their endoscopy, and 94% were on <2 mg/kg/day. Of the 19 patients who had full response to PPI therapy and were diagnosed with PPI-REE, close to half had previously been treated with diet, steroids, or both. Patients with final diagnosis of EoE had significantly higher eos/hpf on initial endoscopy compared to those with diagnosis of PPI-REE (51.9 ± 30.6 v. 35.8 ± 16.4. p = 0.027), as well as higher likelihood of having IgE-mediated food allergy (79 v. 47%, p = 0.003). Conclusions: Diagnostic and therapeutic algorithms are needed for esophageal eosinophilia to prevent misdiagnosis and unnecessary procedures and therapies.