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Several promising minimally invasive biomarkers for EoE have emerged; however, few are able to differentiate EoE from other atopic diseases.

Background: Food protein‐induced enterocolitis syndrome (FPIES) is a non-immunoglobulin E mediated food allergy that typically presents with repetitive emesis and may be associated with lethargy, marked pallor, hypotension, hypothermia, and/or diarrhea. Although many foods are known to cause FPIES, peanut-triggered FPIES is emerging due to changes in the feeding practice guidelines, which recommends early peanut introduction in infants. Objective: We aimed to characterize peanut-triggered acute FPIES cases in our pediatric population and to describe their attributes, treatment, and outcomes. We hypothesized that increases in the incidence of peanut-triggered FPIES coincided with implementation of the guidelines for early peanut introduction. Methods: A retrospective chart review was conducted of pediatric patients who presented to Phoenix Children’s Hospital Emergency Department and subspecialty clinics during a 6-year period (January 2013 to September 2019). Results: Thirty-three cases of patients with acute FPIES were identified, five of which were peanut triggered. In those patients with peanut-triggered FPIES, the median age for peanut introduction was 7 months (range, 5‐24 months). Two patients had positive peanut skin-prick test results. All five cases were identified in the past 2 years (2018 to 2019). No peanut-triggered reactions were documented in the preceding 4-year period (2013 to 2017). Conclusion: Peanut may be an emerging trigger of acute FPIES, coinciding with an earlier introduction of peanut in the infant diet after implementation of the new addendum guidelines for the prevention of peanut allergy. Oats and rice were the most common triggers of acute FPIES in our cohort. Further study will help clarify the significance and reproducibility of these findings.

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RATIONALE: Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is a rare condition caused by mutations in FOXP3 resulting in defective regulatory T-cells (T regs ). We report two siblings with clinical presentations suggestive of IPEX with a novel variant in FOXP3. METHODS:A 5-year-old male (proband) was evaluated for diarrhea since infancy, intermittent fevers and arthralgias. Fecal calprotectin was markedly elevated and a colonic biopsy revealed findings of nonspecific inflammatory colitis, responsive to high-dose steroids. Family history was notable for type 1 diabetes mellitus in a 14 year-old brother who was subsequently diagnosed with nonspecific inflammatory colitis. Targeted gene sequencing (Invitae, Illumina) was performed in the siblings and parents. FOXP3 expression was evaluated by flow cytometry in CD3 + CD4 + CD25 + T reg cells. In the proband, LRBA expression was assessed in monocytes, T, B and NK cells. Tr1 (CD3 + CD4 + CD45A -CD49b + LAG-3 -) and Tr1/Th3 (CD3 + CD4 + CD25 -CD127 + ) precursor cells were also evaluated. RESULTS: Sequence analysis for both siblings revealed familial variants of uncertain significance (VUS) in FOXP3 [c.1129C>G(p.His377Asp0)]. The proband also had 2 VUS in LRBA [c.3905C>T(p.Thr1302lle) and c.7675G>T(p.Ala2559Ser)]. The same LRBA variants were inherited in cis from the proband's unaffected father and LRBA protein expression was normal in all cells types analyzed. Both siblings had normal or increased percentages CD3 + CD4 + CD25 + FOXP3 + T regs cells. Tr1 and Tr1/Th3 precursor were normal (proband). CONCLUSIONS: These are the first reported cases of IPEX syndrome resulting from this novel FOXP3 variant. FOXP3 expression may be normal in patients with IPEX syndrome. Hematopoietic stem cell transplantation is being considered pending T regs suppression assays.

There has been an association between post solid organ transplant (SOT) hypogammaglobulinemia and infections, but the benefit of immunoglobulin (Ig) replacement has been less clear. We hypothesize that (1) only a subset of patients with post-SOT hypogammaglobulinemia have impaired antibody responses; (2) empiric Ig replacement before checking antibody responses may commit some patients to unnecessary therapy; and (3) patients with impaired antibody responses have fewer infections after replacement. METHODS: Epic Slicer Dicer was used to retrospectively identify patients with lung or kidney transplants evaluated by the Immunodeficiency Clinic at Johns Hopkins (2010-2019) for hypogammaglobulinemia (n5 59). Pneumococcal conjugate vaccine challenge titers to assess antibody responses were obtained. If titers revealed protection to fewer than 6/14 serotypes (cutoff 1.0 ug/ml) then patients were started on replacement. Data on severity, type, frequency of infections was collected. RESULTS: 27/36 SOT patients with hypogammaglobulinemia (median Ig level: 445 mg/dl, range: 199-634 mg/dl) had impaired antibody responses, and started replacement. They had a mean of 2.18 infections/year and median of 1 infection/year before replacement. After replacement they had a mean of 1.08 infections/year and median of 1 infection/year. 9/36 SOT patients with hypogammaglobulinemia (median Ig level: 458 mg/dl, range 354-511 mg/dl) had normal antibody responses and did not start replacement. They had a mean of 1.22 infections/year and median of 1 infection/year. CONCLUSIONS: Only a subset of patients with post-SOT hypogammaglobulinemia have evidence of impaired humoral response necessitating Ig replacement. This parameter can help identify patients who may benefit most from Ig replacement to reduce infectious complications.

RATIONALE: A systematic review may help identify promising minimally-invasive EoE biomarkers and remaining gaps in biomarker validation. METHODS: EMBASE, Ovid Medline, PubMed, and Web of Science were searched from inception to June 6, 2017. Studies were included if individuals in the study met the 2007 consensus definition for EoE diagnosis, used a minimally-invasive test of a biomarker defined as an objective measure of biological processes, pathogenic processes, or responses to therapeutic interventions, and included at least 1 control comparison. RESULTS: The search yielded 1,507 studies, 236 of which were reviewed at full text level, and 49 of which were included in the full text review (20 pediatric, 18 adult, 7 pediatric and adult, and 4 not stated). The majority (26 of 49) were reported since 2014. Thirty-six studies included normal controls, 8 analyzed separate atopic control groups, and 29 compared active and controlled EoE samples. Minimally invasive biomarkers were from blood (n541 studies), sponge/string (3), oral/throat swabs (2), breath (2), stool (2), and urine (2). The most commonly reported minimallyinvasive biomarkers were eosinophils (n517), cytokines/chemokines (13), eosinophil surface or intracellular markers (11), and eosinophil granule proteins (9). There were 23 studies that reported a significant difference for a biomarker comparing EoE to normal controls, 2 studies for comparing EoE to atopic controls, and 18 studies for comparing active and controlled EoE. CONCLUSIONS: Many promising minimally-invasive biomarkers for EoE have emerged for diagnosis and monitoring but only 8 performed separate atopic control analyses and only 2 of these found significant differences.

Background PFAPA (periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis) syndrome is diagnosed clinically. Adult-onset PFAPA syndrome is rare and often has a more diverse clinical presentation that its childhood counterpart. This is the first reported case of adult-onset PFAPA syndrome with complete response to lingual tonsillectomy. Case Summary A 41-year-old man was evaluated for periodic fevers associated with uvulitis, cervical lymphadenitis, pharyngitis, and lower extremity rash. He had a variable response to steroids and was intolerant of colchicine. Laboratory workup revealed intermittent elevation of erythrocyte sedimentation rate and C-reactive protein level. Computed tomography neck and laryngoscopy confirmed adenoidal and lingual tonsillar hypertrophy. He underwent adenoidectomy and lingual tonsillectomy with resolution of symptoms. Conclusions Hypertrophy of the remaining lymphoid structures within Waldeyer's ring may be associated with remote recurrence of PFAPA syndrome after tonsillectomy. Lingual tonsillectomy may be an alternative treatment strategy in select patients with PFAPA, prominent lingual hypertrophy, and incomplete response to steroids.