Jay A. Lieberman

Use of omalizumab in the treatment of food allergy and anaphylaxis.

Omalizumab is a humanized monoclonal anti-IgE antibody that is currently FDA-approved for allergic asthma. Given its mechanism of action, recent reports have suggested its possible clinical use for food allergy and some forms of anaphylaxis. Omalizumab exerts its action by binding to circulating IgE, reducing IgE receptor expression, and decreasing mediator release from mast cells and basophils. Clinical trials using omalizumab in patients with food allergy resulted in achieving tolerance to higher amounts of the allergen in some patients. When used as an adjunct therapy during immunotherapy trials in patients with food allergy and anaphylaxis, omalizumab allowed more rapid and higher doses of immunotherapy to be given. Omalizumab has also been reported to be effective in a few patients with idiopathic anaphylaxis and mast cell disorders. Large multi-center trials are needed to confirm the above findings, and to identify subsets of patients that would benefit the most from omalizumab.

Should we encourage allergen immunotherapy during pregnancy

Primary prevention of allergy is a laudable goal, but one that has unfortunately proven difficult to achieve. Many different strategies have been reported to date, but unequivocal supporting data for any single strategy does not exist. Any successful strategy must lead to immunomodulation and must be encountered very early on life, likely in utero. Reports of early bacterial and farm animal exposures lend supportive data to the concept of immune regulation via early fetal exposure, howeve attempts at clinical applications of this, such as probiotics has not been completely successful. One practical, clinical method for achieving a similar immune modulation to these exposures would be providing atopic women with allergy immunotherapy while pregnant (or perhaps even preconception). Allergy immunotherapy is associated with favorable immune modulation and some data suggest that these changes if produced in mother can influence the atopic status of offspring.

An analysis of anaphylaxis cases at a single pediatric emergency department during a 1-year period

BACKGROUND Case series of anaphylaxis can vary regarding causes, treatments, and follow-up of patients. Unfortunately, case series that are specific to the pediatric population are few. OBJECTIVE To describe confirmed cases of pediatric anaphylaxis in patients presenting to a pediatric hospital emergency department (ED). METHODS We identified all ED visits with the International Classification of Diseases, Ninth Revision (ICD-9) codes 995.XX (allergic reactions) and 989.5 (sting or venom reaction) for 1 calendar year (January 1, 2014, through December 31, 2014). Cases were reviewed by an allergist and an emergency medicine physician to identify true anaphylaxis cases using National Institute of Health/National Institute of Allergy and Infectious Diseases criteria. Any questionable or debatable cases were evaluated and adjudicated by a second allergist. RESULTS We identified 927 unique ED visits. Of these visits, 40 were determined to definitively meet anaphylaxis criteria. Median age of the patients was 6.5 years. A total of 70% of patients were male, and 80% were African American. Causes included foods (65%), venom or insect sting (12.5%), and medications (5%), and 17.5% were idiopathic. All patients had multiorgan involvement, with 98% having skin involvement, 78% having lower respiratory tract symptoms, and 40% having gastrointestinal symptoms. There were no deaths. Only 33% of patients received epinephrine at some point in their care. Only 12 patients were referred to an allergist, and only 4 of these were actually seen by an allergist. CONCLUSION At our center, foods are the most common trigger for pediatric anaphylaxis. Patients continue to be undertreated, and referral to an allergist from the ED is rare.

A randomized, double-blinded, placebo-controlled study of the use of viscous oral cromolyn sodium for the treatment of eosinophilic esophagitis

BACKGROUND There is a need for effective, nonsteroid pharmacologic therapies for eosinophilic esophagitis (EoE). Cromolyn sodium offers an option because mast cells have been implicated in the symptomatology of EoE and cromolyn has been shown to have some anti-eosinophilic properties. OBJECTIVE To evaluate the efficacy of cromolyn in decreasing esophageal eosinophilia in patients with EoE. Secondary outcomes included symptom improvement and adverse effects. METHODS We conducted a randomized, double-blinded, placebo-controlled trial of viscous oral cromolyn for EoE in pediatric patients. Subjects were randomized to 100 mg (2-11 years of age) or 200 mg (12-17 years of age) of cromolyn or placebo 4 times daily. The medications were mixed with powdered sugar at home to make them viscous. RESULTS Sixteen subjects (50% boys, median age 11.4 years) were enrolled. Nine were randomized to cromolyn and 7 were randomized to placebo. Cromolyn decreased the peak eosinophil count from 62.1 to 57.3 eosinophils per high-powered field (P = .78) and placebo decreased the peak eosinophil count from 87.0 to 71.3 eosinophils per high-powered field (P = .62) One subject randomized to cromolyn and none in the placebo arm had complete resolution of eosinophilia. Cromolyn decreased symptoms scores from a mean baseline score of 37.8 to a mean post-therapy score of 17.5, which was a 54% decrease (P = .04). Placebo decreased the symptom scores from a baseline score of 32.2 to a post-therapy score of 23.3, which was a 28% decrease (P = .05). CONCLUSION Cromolyn, when mixed into a viscous preparation, did not significantly decrease esophageal eosinophilia. However, it did decrease symptom scores (although not significantly more than placebo) and led to complete resolution in 1 subject.

Adult-onset food allergies

INSTRUCTIONS Credit can now be obtained, free for a limited time, by reading the review article and completing all activity components. Please note the instructions listed below: Review the target audience, learning objectives and all disclosures. Complete the pre-test. Read the article and reflect on all content as to how it may be applicable to your practice. Complete the post-test/evaluation and claim credit earned. At this time, physicians will have earned up to 1.0 AMA PRA Category 1 CreditTM. Minimum passing score on the post-test is 70%. Overall Purpose Participants will be able to demonstrate increased knowledge of the clinical treatment of allergy/asthma/immunology and how new information can be applied to their own practices. Learning Objectives At the conclusion of this activity, participants should be able to: Recognize which food allergies are likely to present initially in adulthood Describe sensitization patterns that lead to positive food allergy testing in adults Release Date: August 1, 2017 Expiration Date: July 31, 2019 Target Audience Physicians involved in providing patient care in the field of allergy/asthma/immunology Accreditation The American College of Allergy, Asthma & Immunology (ACAAI) is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians. Designation The American College of Allergy, Asthma & Immunology (ACAAI) designates this journal-based CME activity for a maximum of 1.0 AMA PRA Category 1 CreditTM. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Planning Committee Members Manish Ramesh, MD, PhD (Author) Jay Adam Lieberman, MD (Author) Jonathan A. Bernstein, MD (CME Subcommittee) Guha Krishnaswamy, MD (CME Subcommittee) John J. Oppenheimer, MD (CME Subcommittee, Associate Editor) Mitchell H. Grayson, MD (CME Series Editor, Deputy Editor) Gailen D. Marshall, Jr, MD, PhD (Editor-in-Chief) Disclosure Policy As required by the Accreditation Council for Continuing Medical Education (ACCME) and in accordance with the American College of Allergy, Asthma and Immunology (ACAAI) policy, all educational planners, presenters, instructors, moderators, authors, reviewers, and other individuals in a position to control or influence the content of an activity must disclose all relevant financial relationships with any

Adherence and systemic reaction rates to allergy immunotherapy among veterans.

Background Although allergen immunotherapy (AIT) is effective and safe, nonadherence is common. Limited data exist regarding adherence to ATT, factors that affect adherence, and systemic reactions associated with ATT among veteran populations. Objective To evaluate adherence to AIT and the prevalence of reactions secondary to AIT among patients at the Veterans Affairs Medical Center, Memphis, Tennessee. Methods A retrospective chart review was performed of veterans who received AIT at a single Veterans Affairs facility. Age, race, sex, the total number of shots, travel distance, a diagnosis of posttraumatic stress disorder (PTSD), and the number of severe adverse reactions were compared between the veterans who were adherent and veterans who were nonadherent. Results The overall adherence rate was 60.9%. Factors associated with adherence were a chart diagnosis of PTSD (293% [adherent group] versus 13.6% [nonadherent group]; p = 0.03) and home residence being a further distance from the facility (21.9 miles / 35.2 kilometers [adherent group] versus 18.0 miles/28.9 kilometers [nonadherentgroup]; p = 0.03). Patients who were adherent received an average of more total injections compared with patients who were nonadherent. Age, sex, race, and history of systemic reactions during AIT displayed no statistically significant differences between the groups. There were a total of 20 systemic reactions, and the systemic reaction rate was 0.2% per AIT encounter and 0.1% per injection. Conclusion AIT adherence and systemic reaction rates among veterans at our facility was comparable with similar studies. Adherence was associated with a chart diagnosis of PTSD and home residence that was further away from the clinic.

Identical twins with XLA requiring differing amounts of 20% subcutaneous immunoglobulin secondary to protein-losing enteropathy

First described by Bruton, congenital or X-linked agammaglobulinemia (XLA) is a genetic disorder in the BTK gene that affects the body’s ability to produce B cells. Because of the decrease or absence of B cells, patients are at risk for recurrent infection, typically due to bacteria. Over the last few decades, the prognosis of XLA has markedly improved because of timely diagnosis and treatment with immunoglobulin replacement therapy. Although patients with XLA typically do clinically well with weight-based immunoglobulin dosing, clinicians must factor in concurrent medical conditions that may require dose adjustments. In this case report, we highlight 2 genetically identical twins with XLA who also have protein-losing enteropathy. During their course, each has required differing doses of immunoglobulin despite similar weights, depending on whether they have active enteropathy flare. A set of 14-year-old identical twin boys has been followed from birth secondary to known XLA in an older male sibling. Both twins had done well on immunoglobulin infusion until approximately 4 years of age when they contracted cryptosporidium gastrointestinal (GI) infection after a trip to a waterpark. Both were treated with a course of nitazoxanide and recovered. Twin A later developed recurrent symptoms of abdominal pain, anorexia, and diarrhea a year after that reported infection. During these periods of active symptoms, Twin A was found to have low IgG levels despite normal weight-based dosing. Because of this, at age 6, Twin A underwent endoscopy with biopsies that revealed active duodenitis with infiltration of CD3þ T-lymphocytes. Interestingly, Twin B did not initially have complications after the initial cryptosporidium infection. However, at age 9, he started to develop increasing IgG requirements and then soon also developed symptoms of anorexia and weight loss. Endoscopy at that time revealed duodenitis with focally increased eosinophils and villus blunting along with focal ileitis. Tissue viral stains were negative. Since each twin’s diagnosis with this inflammatory infiltrate, they have been treated over the years with various doses of oral corticosteroids and azathioprine with clinical response. Over the past 2 years, both twins had done well clinically and therefore had been weaned off oral corticosteroids; Twin A remained on monotherapy with azathioprine because of some continued mild symptoms and Twin B was taken off azathioprine as he was asymptomatic. Both were maintained on the same weight-based weekly 20% subcutaneous immunoglobulin dosing, 4 g weekly, for a total of 533 mg/kg/month with the same product (Hizentra, CSL Behring, King of Prussia, Pa), with stable IgG levels. During this time of stability, both remained at the same weight (within 2 kg of each other), and maintained stable IgG levels, suggesting a similar metabolic IgG requirement. However, on recent routine follow-up, Twin B was found to have decreasing IgG levels (Twin A 1130 mg/dL, Twin B 751 mg/dL) without any GI symptoms. Despite increasing Twin B’s dose to 5 g weekly (666 mg/kg/month), the patient’s immunoglobulin level continued to decline (498 mg/dL). Because of concern that this drop was secondary to active enteropathy, fecal alpha-1 antitrypsin levels were measured and found to be significantly elevated in Twin B (75 mg/dL) and normal in Twin A (<20 mg/dL), confirming a protein-losing enteropathy and explaining the low immunoglobulin level despite increasing infusion dose. Twin B has since been restarted on prednisone (initial dose of 30 mg/day divided twice a day) and azathioprine, and his immunoglobulin infusion has been increased to 6 g weekly (800 mg/kg/month). With this, his serum IgG increased to 903 mg/dL. On this regimen, his IgG level has remained stable (range: 829-980 mg/dL) over the past 6 months, whereas his prednisone dose has been able to be weaned to 5 mg every other day and his IgG dose dropped back to 5 g weekly. In this case, we present identical twins with XLA who have required varying doses of IgG replacement therapy because of protein-losing enteropathy likely secondary to a postinfectious, inflammatory bowel-like disease. GI disorders are common in primary immunodeficiency diseases, with estimates of their prevalence ranging from 5% to 50% depending on the primary immunodeficiency. Compared with other antibody deficiencies, inflammatory GI complications are less reported in patients with XLA, because of the assumption that their intact T-cell function prevents these GI manifestations. Although patients with XLA commonly have GI complaints, it is usually secondary to infection, leading to chronic diarrhea and malabsorption. Infections are typically caused by Giardia lamblia, Salmonella, Campylobacter, Cryptosporidium, rotavirus, etc. Although our patients had a past cryptosporidium infection early in their childhood, the workup for their chronic symptoms did not reveal any active infection. In addition, their symptoms and protein-losing enteropathy both responded to prednisone and azathioprine. There is a known increased risk of inflammatory bowel disease (IBD) seen in other primary immunodeficiencies such as common variable immunodeficiency and chronic granulomatous disease, but rarely reported with XLA. Although some findings consistent with Crohn’s disease have been found in patients with XLA, the association between XLA and IBD has not been reported to date to the authors’ knowledge. The pathology in our patients

Understanding fibrosis in eosinophilic esophagitis: Are we there yet?

Eosinophilic esophagitis (EoE) is an immune/antigen‐mediated, progressive fibrostenotic disease characterized by symptoms of esophageal dysfunction and abnormal eosinophilic infiltration in the esophagus. Despite current treatment modalities of dietary antigen elimination or topical corticosteroids, a subset of patients do not have clinical or histologic response. Even with resolution of superficial epithelial eosinophilia, patients may still have progressive subepithelial fibrosis, which may lead to esophageal strictures over time. Histologic identification of subepithelial fibrosis requires deep esophageal biopsies, which are not routinely obtained. Herein, we review the challenges in diagnosing and treating fibrosis in EoE. We propose the novel concept of vitamin D supplementation to treat fibrosis in EoE through downregulation of profibrotic mediator, transforming growth factor‐beta.

The changing face of anaphylaxis in adults and adolescents

BACKGROUND Our institution has published serial studies of adults and adolescents with anaphylactic events. The first series was published in 1993 and the last was published in 2006. It was our perception that the nature of anaphylactic episodes had changed over the 2 decades since the last review. OBJECTIVE To determine whether the etiologies and presentations of anaphylaxis have changed during the past decade in our population. METHODS Patient charts were identified based on International Classification of Diseases, Ninth Revision codes for anaphylactic shock. Charts identified were analyzed for clinical symptoms reported, comorbidities, etiology, investigative testing, and subsequent treatment. These cases were categorized as definitive, probable, or idiopathic based on history and results from testing, similar to our prior reports. RESULTS We identified 281 possible cases, of which 218 met criteria for anaphylaxis. Of these cases, median age was 42 years (range 9-78) and 64% were female. In the review of cases, 85 (39%) were determined to have a definitive etiology, 57 were determined to have a probable etiology (26%), and 76 (35%) were idiopathic. Interestingly, of those with a definitive cause, the most common etiology identified was galactose-α-1,3-galactose, accounting for 28 cases (33%). Foods were the second leading cause, accounting for 24 cases (28%). CONCLUSION In this follow-up report on anaphylaxis etiology from a single center, the most common etiology was galactose-α-1,3-galactose. This differs greatly from prior reports from our center. Interestingly, the percentage of cases attributed to idiopathic anaphylaxis decreased from 59% in our previous report to 35% in the present report, which could largely be explained by the number of galactose-α-1,3-galactose cases.

Autoimmune Features of Wiskott-Aldrich Syndrome: A Case Report

Diffuse alveolar hemorrhage in a pediatric patient requires urgent and aggressive therapy. Here we report a young child with Wiskott-Aldrich syndrome and antiplatelet antibody manifesting as recurrent pulmonary hemorrhage due to pauci-immune capillaritis that was successfully treated with rituximab.