Letter to the Editor

Prevalence of eosinophilic colitis and the diagnoses associated with colonic eosinophilia

Eosinophilic gastrointestinal disorders (EGIDs) refer to a rare group of chronic immune-mediated diseases of the tubular gastrointestinal tract, characterized clinically by gastrointestinal dysfunction and symptoms, and histologically by eosinophil-predominant immune response with unknown etiology. They include eosinophilic esophagitis (EoE), gastritis (EoG), enteritis (EoN) and colitis (EoC) based on sites involved according the latest International Consensus Recommendations for Eosinophilic Gastrointestinal Disease Nomenclature (2022 ICR-EGID Nomenclature). EoE is the most well-studied entity of EGIDs with established diagnostic criteria, 3 endotypes (OMEGA study), histology scoring system (EoEHSS), randomized clinical trials (SOFEED study), and non-IgE-mediated hypersensitive reaction as its presumed pathogenesis. Non-esophageal gastrointestinal disorders (Non-EoE EGIDs), although reported more than four decades earlier than EoE, are however less well-understood. The rarity of these diseases, heterogeneous clinical presentations, broad differential diagnosis, and most importantly, the lack of a consensus on diagnostic criteria and clinical management have all contributed to an incomplete understanding of these diseases. This review focuses on diagnosis of Non-EoE EGIDs and discusses several challenges we face in daily practice from a pathologist perspective.

Colonic eosinophilia, an enigmatic finding often referred to as eosinophilic colitis (EoC), is a poorly understood condition. Whether EoC is a distinct disease or a colonic manifestation of eosinophilic gastrointestinal diseases (EGIDs) or inflammatory bowel disease (IBD) is undetermined.

Subjects with EoC (n = 27) and controls (normal [NL, n = 20], Crohn’s disease [CD, n = 14]) were enrolled across sites associated with the Consortium of Eosinophilic Gastrointestinal Disease Researchers. EoC was diagnosed as colonic eosinophilia (ascending ≥100, descending ≥85, sigmoid ≥65 eosinophils/high-power field) with related symptoms. Colon biopsies were subjected to RNA sequencing. Associations between gene expression and histologic features were analyzed with Spearman correlation; operational pathways and cellular constituents were computationally derived.

We identified 987 differentially expressed genes (EoC transcriptome) between EoC and NL (>1.5-fold change, P < .05). Colonic eosinophil count correlated with 31% of EoC transcriptome, most notably with CCL11 and CLC (r = 0.78 and 0.77, P < .0001). Among EoC and other EGIDs, there was minimal transcriptomic overlap and minimal evidence of a strong allergic type 2 immune response in EoC compared with other EGIDs. Decreased cell cycle and increased apoptosis in EoC compared with NL were identified by functional enrichment analysis and immunostaining using Ki-67 and cleaved caspase-3. Pericryptal circumferential eosinophil collars were associated with the EoC transcriptome (P < .001). EoC transcriptome–based scores were reversible with disease remission and differentiated EoC from IBD, even after controlling for colonic eosinophil levels (P < .0001).

We established EoC transcriptomic profiles, identified mechanistic pathways, and integrated findings with parallel IBD and EGID data. These findings establish EoC as a distinct disease compared with other EGIDs and IBD, thereby providing a basis for improving diagnosis and treatment.

La colitis eosinofílica primaria (CEoP) es una enfermedad inflamatoria causada por infiltración de eosinófilos en la mucosa del colon, sin otras posibles causas identificadas, que se caracteriza por dolor abdominal y diarrea. Su prevalencia se desconoce.

Conocer la prevalencia de CEoP en pacientes con diarrea crónica y en aquellos con criterios clínicos del síndrome del intestino irritable con predominio de diarrea (SII-D).

Todos los pacientes con diarrea crónica no inflamatoria, atendidos en forma consecutiva durante una década, fueron estudiados mediante colonoscopia con toma sistemática de biopsias. Se excluyeron aquellos con enfermedad orgánica conocida o descompensada, con datos de alarma, estudios de investigación limitada anormales y factores asociados a eosinofilia. Del grupo general, se seleccionaron aquellos con criterios clínicos de SII-D (Roma III). Colitis eosinofílica se definió como la presencia de > 35 eosinófilos/100 células epiteliales por campo en cualquiera de los segmentos.

Fueron atendidos 683 pacientes. Se incluyeron 545 enfermos (361 mujeres), entre quienes se detectaron 22 casos de CEoP, para una prevalencia del 4.0%. Trescientos cuarenta y tres sujetos tenían criterios de SII-D (223 mujeres), entre los que se detectaron 16 casos de CEoP, para una prevalencia del 4.7%. La colonoscopia fue normal o casi normal en todos los casos detectados.

La prevalencia de CEoP fue del 4.0% de los enfermos con diarrea crónica y del 4.7% en aquellos con SII-D. La eosinofilia periférica parece ser la principal característica clínica distintiva, pero la toma sistemática de biopsias es indispensable para establecer el diagnóstico.

Primary eosinophilic colitis (PEC) is an inflammatory disease caused by the infiltration of eosinophils into the mucosa of the colon, determined after having ruled out other possible causes. It is characterized by abdominal pain and diarrhea and its prevalence is unknown.

To know the prevalence of PEC in patients with chronic diarrhea and in those with clinical criteria for diarrhea-predominant irritable bowel syndrome (IBS-D).

All patients with chronic noninflammatory diarrhea that were consecutively seen over a decade were studied through colonoscopy, with systematic biopsy. Patients with a known or decompensated organic disease, alarm features, abnormal minimal laboratory test results, and factors associated with eosinophilia were excluded. Patients with the clinical criteria for IBS-D (Rome III) were selected from the general group. Eosinophilic colitis was defined as the presence of > 35 eosinophils/100 epithelial cells per field in any of the segments.

From the 683 patients seen, a total of 545 patients (361 women) were included in the study. Twenty-two cases of PEC were detected, resulting in a prevalence of 4.0%. A total of 343 patients had IBS-D criteria (223 women), with 16 cases of PEC detected, for a prevalence of 4.7%. Colonoscopy was normal, or almost normal, in all the PEC cases detected.

The prevalence of PEC was 4.0% in the patients with chronic diarrhea and 4.7% in the patients with IBS-D. Peripheral eosinophilia appeared to be the main distinctive clinical characteristic, but systematic biopsy was essential for making the diagnosis.