Allergic phenotype identified on allergen testing is associated with proton pump inhibitor nonresponse in eosinophilic esophagitis.

BACKGROUND AND AIM: Food/environmental allergens have been associated with eosinophilic esophagitis (EoE); however, the correlation between allergy profiles and disease responsiveness to proton pump inhibitor (PPI) therapy remains unclear. We aimed to assess the association between food/environmental allergies identified on allergen testing and histologic response to PPI in patients with treatment-naive EoE. METHODS: Adults with newly diagnosed EoE who underwent formal testing for food/environmental allergies at a tertiary center were included. All patients underwent twice-daily PPI for 8 weeks with subsequent repeat endoscopy and biopsy to assess histologic response. Patients with <15 eosinophils/hpf on post-PPI mucosal biopsies were classified as responders (PPI-r-EoE), while those with ≥15 eosinophils/hpf were nonresponders (PPI-nr-EoE). RESULTS: Sixty-one patients met inclusion criteria (21 PPI-r-EoE vs 40 PPI-nr-EoE). Demographic, clinical, and endoscopic finding variables were similar between groups. Positive food allergen test was more prevalent among PPI-nr-EoE patients (82.5% vs 42.9%, P = 0.003). On multivariable analysis, positive food allergen testing remained an independent predictor for PPI nonresponse (aOR 0.15, CI: 0.04-0.58, P = 0.0006). Positive environmental allergen testing was highly prevalent, with no significant differences between groups (77.5% vs 95.2%, P = 0.14). However, higher number of positive environmental allergens (23.3% [≥5 allergens] vs 73.3% [<5 allergens], P = 0.003) and specific aeroallergens correlated with PPI-nr-EoE. CONCLUSION: Positive food allergy testing and increased environmental allergens predicted lower likelihood of histologic response to PPI in EoE. Our findings support an allergic phenotype of EoE that may less likely respond to PPI therapy. Formal allergen testing may play a role in therapy selection and tailored management in EoE.

Pearls for practice from the 2022 joint task force drug allergy practice parameter.

PURPOSE OF REVIEW: To review updated recommendations in the 2022 Drug Allergy Practice Parameters for the evaluation and management of drug hypersensitivity reactions. RECENT FINDINGS: Adverse drug reactions have become increasingly prominent with the advent of new and emerging pharmacologic therapies. Hypersensitivity reactions encompass a significant proportion of adverse drug reactions and negatively impact both the individual patient and overall health system. Reactions are heterogeneous in presentation and may be immediate (onset of symptoms ≤6 h) or delayed (onset of symptoms >6 h to months) after drug exposure. The 2022 Drug Allergy Practice Parameter provides consensus-based statements for evaluation of hypersensitivity reactions to antibiotics, NSAIDs, cancer chemotherapies, immune checkpoint inhibitors, biologics, and excipients. In general, the guideline highlights the importance of patient history in elucidating the phenotype and severity of the index reaction. Drug challenge remains the gold standard for diagnosis and is increasingly favored over skin testing in patients with nonsevere, nonanaphylactic drug reaction histories. SUMMARY: The 2022 Drug Allergy Practice Parameter provides an updated framework for physicians to reference in clinical practice when managing patients with drug hypersensitivity reactions.

Overlapping Transcriptional Profile in Proton Pump Inhibitor Responsive and Nonresponsive Eosinophilic Esophagitis.

INTRODUCTION: We compared esophageal mucosal gene transcript expression in proton pump inhibitor (PPI) responsive (PPI-R) eosinophilic esophagitis (EoE), PPI nonresponsive (PPI-NR) EoE, and healthy controls. METHODS: Transcript expression in midesophagus biopsies was determined using NanoString and a custom panel of EoE-specific genes. The top upregulated and downregulated genes with ≥2-fold difference in expression and statistically significant ( P < 0.05) were identified. RESULTS: Nearly all the top upregulated (17 of 20) and downregulated (5 of 5) genes in EoE, compared with healthy controls, were shared between the PPI-R and PPI-NR groups. DISCUSSION: Esophageal mucosal transcript expressions are remarkably similar in PPI-R EoE and PPI-NR EoE compared with healthy controls.

Endoscopic Features and Eosinophil Density Are Associated with Food Impaction in Adults with Esophageal Eosinophilia.

BACKGROUND AND AIMS: Food impaction has been described in both eosinophilic esophagitis and proton pump inhibitor-responsive esophageal eosinophilia. The association between endoscopic/histologic features of esophageal eosinophilia and food impaction remains unclear. We aimed to identify clinical, endoscopic, and histologic findings associated with a history of food impaction in esophageal eosinophilia. METHODS: This was a retrospective cohort study of adult esophageal eosinophilia patients at a tertiary center in 6/2005-10/2014. Only patients with ≥15 eosinophils/high-power field on mucosal biopsies were included. Demographics, comorbidities, symptoms, endoscopic/histologic findings on initial endoscopy, and history of food impaction were reviewed. Statistical analyses were performed using Fisher's exact test (univariate) and forward stepwise logistic regression (multivariate). RESULTS: 400 patients (42 ± 14 years, 61 % male) were included, with 78 (20 %) having food impaction history. On univariate analyses, rings (62 vs 42 %, p = 0.003), erosions (12 vs 5 %, p = 0.03), eosinophil density on biopsy (40 [IQR = 30-50] vs 30 [IQR = 15-50], p = 0.004), and dysphagia (88 vs 62 %, p < 0.0001) were more prevalent among patients with food impaction history, while heartburn (10 vs 33 %, p < 0.0001) and abdominal pain (1 vs 12 %, p = 0.002) were less common. On multivariate analysis, rings (OR 2.6, p = 0.002), erosions (OR 3.2, p = 0.02), and eosinophil density (ß-coefficient = 0.01, p = 0.04) remained associated with food impaction. CONCLUSIONS: Findings of rings and erosions on endoscopy and increased eosinophil density on histology were independently associated with a history of food impaction in adult esophageal eosinophilia patients. Food impaction may result from both active inflammation (erosions and increased eosinophil density) and chronic fibrostenotic changes (rings).

Desensitizations for chemotherapy and monoclonal antibodies: indications and outcomes.

Acute infusion reactions to both chemotherapeutic agents and humanized monoclonal antibodies can occur, which may limit therapeutic options for treatment of malignancies and chronic inflammatory diseases. Many of these acute infusion reactions are consistent with a type I hypersensitivity reaction, including anaphylaxis. If a patient experiences a significant acute infusion reaction, often the recommendation is to discontinue the medication and find an alternative agent. However, the "second-line" agent may be more toxic or inferior. If the reaction is likely a type I or type IV hypersensitivity reaction, one option is to undergo desensitization to the offending drug. Drug desensitization is the process of readministering a needed drug in incremental doses over hours or days until a full therapeutic dose is tolerated. This article will review the current literature on indications and outcomes for drug desensitization in the management of allergy to either chemotherapeutic agents or monoclonal antibodies.

First-trimester sex hormone binding globulin and subsequent gestational diabetes mellitus.

OBJECTIVE: We sought to examine the association between early pregnancy levels of sex hormone binding globulin and subsequent gestational diabetes mellitus, an association that has not been studied previously. STUDY DESIGN: We conducted a nested case-control study of 44 patients with gestational diabetes mellitus and 94 women with negative third-trimester screening for gestational diabetes mellitus. Sex hormone binding globulin levels were measured from serum samples that had been collected in the first trimester, and clinical data were ascertained from prospectively collected electronic medical records. RESULTS: Compared with women without gestational diabetes mellitus, first-trimester sex hormone binding globulin levels were lower among women in whom gestational diabetes mellitus subsequently developed (187 +/- 82 nmol/L vs 233 +/- 92 nmol/L, P <.01). In logistic regression analysis that was adjusted for body mass index, age, race, smoking, blood pressure, serum testosterone and estradiol levels, and gestational age at serum collection, sex hormone binding globulin levels remained independently associated with subsequent gestational diabetes mellitus. For every 50-nmol/L increase in sex hormone binding globulin, the odds of gestational diabetes mellitus fell by 31% (odds ratio, 0.69; 95% CI: 0.48, 0.99). CONCLUSION: Sex hormone binding globulin offers a potential early marker to target women who are at risk for gestational diabetes mellitus.