A Second Slice of FPIES: A Single-Center Reappraisal of Pediatric FPIES.

BACKGROUND: Food protein-induced enterocolitis syndrome (FPIES) is being increasingly recognized as a non-IgE-mediated food allergy; however, it remains unclear if and how the presentation, diagnosis, and management of this disease has changed in recent years. OBJECTIVE: To reappraise the FPIES cohort at a large US pediatric tertiary referral center. METHODS: We performed a retrospective chart review of pediatric patients with FPIES (International Classification of Diseases, Tenth Revision code K52.21) diagnosed in our allergy/immunology clinics between 2018 and 2022. RESULTS: There were 210 children diagnosed with FPIES. Most were White (73.8%), non-Hispanic (71.4%), and male (54.3%) with private insurance (77.6%). Cow's milk was the most common food trigger (35.2%), with the earliest median age of onset of 5 months. The atypical FPIES rate was 13.8%. FPIES was accurately diagnosed in 54.3% at the first medical contact. The oral food challenge pass rate was 73.5%. The rate of trigger resolution at 36 months was 77%. CONCLUSIONS: By comparing trends from a previous and current FPIES cohort, we were able to assess the potential impact of various guidelines and practice changes on the diagnosis and management of FPIES at our center. Milk and oat surpassed rice as the most common FPIES triggers; peanut and egg emerged as new FPIES triggers; there was a shorter time to diagnosis and an increased rate of atypical FPIES. Our findings reflect earlier recognition of FPIES and prompt allergy/immunology referral from community physicians, implementation of recent medical society guidelines for infant feeding practices, and growing clinical expertise of allergists at our center.

Heterozygous mutations in the C-terminal domain of COPA underlie a complex autoinflammatory syndrome.

Mutations in the N-terminal WD40 domain of coatomer protein complex subunit α (COPA) cause a type I interferonopathy, typically characterized by alveolar hemorrhage, arthritis, and nephritis. We described 3 heterozygous mutations in the C-terminal domain (CTD) of COPA (p.C1013S, p.R1058C, and p.R1142X) in 6 children from 3 unrelated families with a similar syndrome of autoinflammation and autoimmunity. We showed that these CTD COPA mutations disrupt the integrity and the function of coat protein complex I (COPI). In COPAR1142X and COPAR1058C fibroblasts, we demonstrated that COPI dysfunction causes both an anterograde ER-to-Golgi and a retrograde Golgi-to-ER trafficking defect. The disturbed intracellular trafficking resulted in a cGAS/STING-dependent upregulation of the type I IFN signaling in patients and patient-derived cell lines, albeit through a distinct molecular mechanism in comparison with mutations in the WD40 domain of COPA. We showed that CTD COPA mutations induce an activation of ER stress and NF-κB signaling in patient-derived primary cell lines. These results demonstrate the importance of the integrity of the CTD of COPA for COPI function and homeostatic intracellular trafficking, essential to ER homeostasis. CTD COPA mutations result in disease by increased ER stress, disturbed intracellular transport, and increased proinflammatory signaling.

Updates in food allergen immunotherapy.

PURPOSE OF REVIEW: Food allergies are on the rise. Though allergen avoidance and management of acute reactions have been the backbone of therapy, complete avoidance and timely acute care is often not feasible. Food allergen immunotherapy (FAIT) is a novel and evolving treatment option intended to induce desensitization and potential sustained unresponsiveness (SU) to food allergens. This review addresses the methods, mechanisms, efficacy, and adverse effects of oral immunotherapy (OIT), sublingual immunotherapy (SLIT), and epicutaneous immunotherapy (EPIT) for food allergens in the published literature. RECENT FINDINGS: Single FAIT has been most extensively studied in peanut, milk, and hen's egg allergic patients and has been successful in achieving desensitization in treated individuals through various modalities. Long-term data regarding SU is limited; however, current data suggests subsets of patients may be more likely to achieve SU compared to others. Other studies are actively assessing multifood AIT and novel FAIT protocols with adjunctive therapies. SUMMARY: Food allergy constitutes a prevalent problem with far-reaching consequences. The emergence of FAIT may mitigate the burden of food allergy. Current evidence is promising for specific allergens and pediatric patient populations. Future studies are needed to further assess efficacy between different modalities of immunotherapy for food allergens across an age continuum.

Implementation of a Night-Float Curriculum: Impact on Intern Confidence over Time.

OBJECTIVES: Formal nighttime education is becoming increasingly necessary as more internal medicine (IM) residency programs adopt night-float rotations (NFRs); however, the efficacy of an NFR curriculum throughout an academic year and which topics in an NFR curriculum increase trainee confidence are unknown. We implemented a 12-module, self-paced NFR curriculum for 76 postgraduate year-1 residents at an academic IM residency program. We evaluated the impact of this curriculum on postgraduate year-1 residents' clinical confidence, as well as longitudinal efficacy of the curriculum. METHODS: Night-float interns' (NFIs) clinical confidence regarding specific curricular topics was evaluated overall and during specific timeframes within the academic year. Pre- and post-NFR surveys using Likert scales for each topic were administered to NFIs from June 24, 2020 to March 2, 2021, representing 32 week-long NFR cycles. RESULTS: NFIs' pre- and postrotation confidence in managing clinical scenarios significantly improved for all 12 topics in the NFR curriculum. The NFR curriculum resulted most significantly in improved confidence during the first 4 months of the academic year, with 11 of 12 curricular topics reaching the threshold for statistical significance. Modules on altered mental status, hypotension, narrow-complex tachyarrhythmias, new fever, and sepsis and antibiotic escalation maintained their efficacy for the longest periods of time. CONCLUSIONS: It may be especially important to emphasize an NFR curriculum at the beginning of the academic year. IM residency programs also may wish to carefully consider that certain topics may maintain their efficacy throughout the year, whereas other topics should potentially be replaced with more complex modules as the academic year progresses.