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

BACKGROUND: Food 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. OBJECTIVE: We 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. METHODS: We 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. RESULTS: A 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. CONCLUSIONS: Our 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.

Successful treatment of recalcitrant chronic idiopathic urticaria with sulfasalazine.

BACKGROUND: Antihistamines are the standard treatment for chronic idiopathic urticaria (CIU). For patients whose urticaria is unresponsive to antihistamines, the treatment options are limited. During the previous decade, there have been several case reports demonstrating success with sulfasalazine therapy. In this article, we present a case series evaluating sulfasalazine therapy for antihistamine-unresponsive CIU. OBSERVATIONS: Nineteen patients with antihistamine-unresponsive CIU were treated with sulfasalazine between 2002 and 2005. During sulfasalazine therapy, 14 patients (74%) reported significant improvement, 4 patients (21%) reported minimal improvement but were not satisfied with their symptom relief, and 1 patient (5%) reported a worsening of symptoms. Of the 13 patients who required systemic steroids to control their urticaria, all were able to reduce or discontinue steroid use during sulfasalazine therapy. Although 7 patients (37%) had adverse effects (eg, nausea, headache, mild or transient leukopenia, and transaminitis) that were thought to be caused by the use of sulfasalazine, they all kept taking the drug. CONCLUSIONS: This case series demonstrates that sulfasalazine can be a successful and safe treatment option for patients with CIU who have not responded adequately to treatment with antihistamines. Sulfasalazine was steroid sparing in all subjects who were steroid dependent.

Eosinophilic esophagitis: clinical presentation in children.

Eosinophilic esophagitis (EoE) is increasing in western nations. Symptoms in infants and young children include feeding difficulties, failure to thrive, and gastroesophageal reflux. School-aged children may present with vomiting, abdominal pain, and regurgitation; adolescents and adults with dysphagia and food impaction. Delayed diagnosis increases risk of stricture formation. Children with untreated EoE have tissue changes resembling airway remodeling. Endoscopy does not always correlate. Management centers on food elimination. Approaches include skin prick and patch testing, removal of foods, or an amino acid formula diet. Long-term elimination diets can produce nutritional deficiencies and have poor adherence.

Basophil phenotypes in chronic idiopathic urticaria in relation to disease activity and autoantibodies.

Potentially pathogenic IgG autoantibodies to IgE or its receptor, Fc epsilonRIalpha, have been detected in approximately 40% of chronic idiopathic urticaria (CIU) patients. CIU patients' basophils display distinct altered Fc epsilonRIalpha-mediated degranulation. CIU patients with basophil histamine release in response to polyclonal goat anti-human IgE > or = 10% are classified as CIU responders (CIU-R) and < 10% are CIU non-responders (CIU-NR). We compared the presence of autoantibodies to basophil degranulation phenotypes and to disease status (active or inactive). Sera were collected from non-CIU subjects and CIU subjects who participated in a longitudinal study of disease severity and had defined basophil degranulation phenotypes. Immunoenzymetric assays (IEMA) quantified IgG anti-Fc epsilonRIalpha and anti-IgE. IgG anti-Fc epsilonRIalpha antibody was detected in 57% of CIU-R (n=35), 55% of CIU-NR (n=29), and 57% of non-CIU subjects (n=23), whereas IgG anti-IgE was present in 43% of CIU-R, 45% of CIU-NR, and 30% of non-CIU subjects. Both the autoantibody levels and the functional basophil phenotype remained stable in subjects with active disease (n=16), whereas there was an enhancement in basophil function as subjects evolved into a state of remission (n=6), which appears independent of the presence of autoantibody. IEMAs detected a similar frequency of autoantibodies in CIU-R, CIU-NR, and non-CIU subjects. Basophil function may be independent of IEMA-detected autoantibodies.

Immediate type I hypersensitivity response implicated in worsening injection site reactions to adalimumab.

BACKGROUND: Tumor necrosis factor (TNF) inhibitors such as adalimumab, etanercept, and infliximab play an increasingly important role in the management of a variety of chronic inflammatory disorders. With their increasing use, a wide spectrum of dermatological adverse effects, including injection site reactions and the development of dermatitis, have been recognized. Previous studies have implicated the role of the delayed-type hypersensitivity reaction in mediation of injection site reactions to etanercept. To our knowledge, there have been no published studies on immunologic mechanism of injection site reactions to adalimumab to date. OBSERVATIONS: We describe 2 patients with a history of worsening injection site reactions to adalimumab. Findings from skin testing in both patients were suggestive of an immediate type I hypersensitivity reaction to adalimumab. A histamine release assay performed on peripheral blood leukocytes from both patients demonstrated significant histamine release on exposure to adalimumab. Furthermore, passive transfer of serum from one of the allergic patients to basophils from a nonatopic, healthy donor sensitized those cells to release significant amounts of histamine with exposure to adalimumab. Conclusion This study demonstrates that an IgE-mediated immediate type I hypersensitivity reaction plays a role in the mediation of worsening injection site reactions in some patients receiving adalimumab.

Expression of activation markers on basophils in a controlled model of anaphylaxis.

BACKGROUND: Anaphylaxis has variable clinical presentations and lacks reliable biomarkers. Expression of activation markers on basophils has been useful in assessing sensitization in IgE-mediated diseases but has not been examined in vivo in anaphylaxis. OBJECTIVE: The study's goals were to assess the baseline expression of activation markers on basophils in individuals with a sting reaction history, the degree of change in expression of these markers after intentional sting challenge, and the relationship between in vitro and in vivo activation marker expression. METHODS: Patients allergic to insect venom were enrolled and grouped by clinical category defined by a history of a systemic or large local reaction and use of venom immunotherapy. Blood was collected before and after sting challenge. Enriched basophils were analyzed for activation marker expression. In select subjects, basophils were examined after in vitro stimulation with insect venom for activation marker expression and histamine release. RESULTS: Of 35 sting-challenge participants, 21 provided adequate samples for analysis. Pre-sting basophil CD63 expression was significantly higher in systemic reactors on immunotherapy. Following sting challenge, the rise in basophil CD69 expression and CD203c was significantly higher in systemic reactors on immunotherapy. Levels of activation markers on basophils were greater after in vitro venom stimulation than after in vivo challenge. CONCLUSION: Broader shifts in expression of basophil activation markers after in vivo challenge occurred among subjects with a history of in vivo systemic anaphylaxis despite venom immunotherapy. CLINICAL IMPLICATIONS: Basophil activation markers may be potential biomarkers for anaphylaxis.