A novel variant in RUNX1 in a patient with refractory eosinophilic gastrointestinal disease and long-term clinical response to ketotifen

Background: Eosinophilic gastrointestinal disease (EGID) is an umbrella term for a heterogeneous group of disorders affecting the GI tract. In contrast to the relatively common eosinophilic esophagitis (EoE), eosinophilic gastroenteritis (EGE) remains poorly understood in terms of both its pathophysiology and genetic etiology, while treatment options remain limited. Aim: To expand the genotypic spectrum of EGE and describe our long-term experience of treatment with ketotifen. Methods: Case report of a patient with EGE followed by our team for over 27 years. Results: Our patient was diagnosed with EGE at the age of 4 years, accompanied by multiple other atopic manifestations and serum eosinophilia. He was later diagnosed with a heterozygous variant in RUNX1, a gene implicated in multi-lineage hematopoiesis, inhibition of Th2 polarization and T regulatory cell function. The patient has experienced long-term symptom improvement while treated with the mast cell stabilizing H1 antihistamine, ketotifen, with substantial symptomatic worsening after this agent was briefly stopped. Conclusion: We expand the genotypic spectrum of EGID etiology to include mutations in RUNX1, and suggest ketotifen as a viable option for patients with treatment-refractory EGE. Statement of novelty: This case reports on a possible novel genetic cause of EGID and describes long-term successful clinical management with ketotifen.