Mast Cell Infiltration Is Associated With Persistent Symptoms and Endoscopic Abnormalities Despite Resolution of Eosinophilia in Pediatric Eosinophilic Esophagitis

• Published in: The American journal of gastroenterology Vol. 115; no. 2; pp. 224 - 233
• Main Authors: Bolton, Scott M., Kagalwalla, Amir F., Arva, Nicoleta C., Wang, Ming-Yu, Amsden, Katie, Melin-Aldana, Hector, Dellon, Evan S., Bryce, Paul J., Wershil, Barry K., Wechsler, Joshua B.
• Format: Journal Article
• Language: English
• Published: United States Wolters Kluwer 01.02.2020; Wolters Kluwer Health Medical Research, Lippincott Williams & Wilkins
• Subjects: Adolescent; Adrenal Cortex Hormones - therapeutic use; Autoimmune diseases; Biopsy; Blood diseases; Child; Child, Preschool; Children & youth; Demographics; Diet Therapy - methods; Disease; Edema; Edema - pathology; Endoscopy; Eosinophilic Esophagitis - pathology; Eosinophilic Esophagitis - physiopathology; Eosinophilic Esophagitis - therapy; Eosinophils - pathology; Esophageal diseases; Esophagoscopy; Esophagus; Exudates and Transudates; Female; Gastroenterology; Gastroesophageal reflux; Gastrointestinal diseases; Humans; Male; Mast Cells - pathology; Patients; Pediatrics; Statistical analysis; Steroids
• ISSN: 0002-9270; 1572-0241; 1572-0241
• DOI: 10.14309/ajg.0000000000000474

Mast cells (MCs) are increased in eosinophilic esophagitis (EoE). Endoscopic abnormalities, symptoms, and epithelial changes can persist after treatment despite a reduction of esophageal eosinophilia. It is unknown whether this could be due to persistent MC infiltration. We aimed to determine whether patients with histologically inactive (HI) EoE (defined as <15 eosinophils per high-powered field) with persistent symptoms, endoscopic, or epithelial abnormalities after treatment have increased MCs. Secondary analysis of prospective data from 93 children with EoE undergoing post-treatment endoscopy between 2011 and 2015. Thirty-five non-EoE controls were included. Immunohistochemistry for tryptase, an MC marker, was performed on mid and distal esophageal biopsies. Total and degranulated intraepithelial MCs per high-powered field (MC/hpf) were quantified. Symptoms and endoscopic findings were recorded at time of endoscopy. MC/hpf were compared between HI-EoE and control, and among HI-EoE based on endoscopic and histologic findings, and symptoms. Nine clinical remission (CR) patients were identified, with absence of endoscopic abnormalities and symptoms. MC/hpf were increased in HI-EoE compared with control (17 ± 11 vs 8 ± 6, P < 0.0). Patients with persistent endoscopic abnormalities had increased total (20 ± 12 vs 13 ± 10, P = 0.001) and degranulated (8 ± 6 vs 5 ± 4, P = 0.002) MC/hpf, with no difference in eosinophils. MC/hpf predicted furrowing (odds ratio = 1.06, P = 0.01) and rings (odds ratio = 1.05, P = 0.03) after controlling for treatment type, proton-pump inhibitor, eosinophils, and duration of therapy. Patients with persistent basal zone hyperplasia and dilated intercellular spaces had increased MC/hpf. Eosinophils were weakly correlated with MC/hpf in the mid (r = 0.30, P < 0.001) and distal (r = 0.29, P < 0.001) esophagus. Clinical remission patients had lower MC/hpf compared with patients with persistent symptoms and/or endoscopic abnormalities. MC density is increased in patients with endoscopic and epithelial abnormalities, as well as a few symptoms, despite resolution of esophageal eosinophilia after treatment. This association warrants further study to ascertain whether MCs play an eosinophil independent role in EoE.