Introduction

Coexistence of bile acid diarrhoea (BAD) and microscopic colitis (MC) has been described (1), and treating this with sequestrants could reduce the need for budesonide. Fasting plasma 7α-hydroxy-4-cholesten-3-one (C4) values >46 ng/mL are specific for BAD but sensitivity is only 47% (37-57%) compared with tauroselcholic [75-Se]
acid (SeHCAT) retention <10% (2). C4 values between 33 and 46 are in a diagnostic grey zone. Budesonide directly affects the bile acid homeostasis making the temporal relation between treatment and testing important. Fortunately, unlike SeHCAT testing, C4 may be sampled immediately when a patient presents with a flare of MC.

Aims & Methods

To assess the prevalence of coexisting BAD in patients with active MC.
Consequtive patients with MC and a flare fulfilling the Hjortswang diarrhoea criteria (≥3 stools or ≥1 watery stool per day) and a negative test for infectious diarrhoea were included. Patients were treated with budesonide 9 mg once daily for 6 weeks. Clinical assessment, Bristol stool charts, and fasting C4 were obtained at baseline, during the last treatment week and 4 weeks after end of treatment. Remission was defined as a daily mean of <1 watery bowel movement and <3 total bowel movements [EudraCT: 2019-002762-12].

Results

49 patients were included; 26 (53%) with collagenous colitis. Mean age was 60 (range 55-70) years, 22% current smoker, none on NSAIDs. Six (12%; 95%CI: 5–25%) of 49 patients had BAD diagnosed by C4. Another 3 patients had grey zone C4 values. Mean C4 did not change during budesonide treatment, 22 and 23 ng/mL at baseline and at week 6, respectively. SeHCAT was performed outside the study in 26 patients of whom 3 had retention of <10% and 6 of <15%. The mean total number of stools per day declined from baseline 7.9 to 1.9 and watery stools from 3.7 to 0.3 during budesonide treatment. Remission was obtained in 45. Twenty-nine had relapsed four weeks after end of budesonide treatment, 5 of 6 (83%; 95%CI: 36–100%) with MC and BAD, and 24 of 43 (56%; 95%CI: 40–71%) with MC and not BAD.

Conclusion

During an inflammatory flare of MC, 12% (5–25%) had C4-defined BAD. However, C4 only identifies about half of patients with BAD compared with the diagnostic gold standard SeHCAT, meaning about 25% of patients with MC could have coexisting BAD. Screening for BAD may have merit in MC patients with relapse of diarrhoea after budesonide treatment.

References

1 Bjørnbak C, Engel PJH, Nielsen PL, Munck LK. Microscopic colitis: clinical findings, topography, and persistence of histopathological subgroups. Aliment Pharmacol Ther. 2011, 34: 1225-34.
2. Borup C, Vinter-Jensen L, Jørgensen SPG, Wildt S, Graff J, Gregersen T, Zaremba A, Andersen TB, Nøjgaard C, Timm HB, Lamazière A, Rainteau D, Hansen SH, Rumessen JJ, Munck LK. Prospective comparison of diagnostic tests for bile acid diarrhoea. Aliment Pharmacol Ther. 2024; 59: 39-50.

Disclosure

Budesonide was donated for study use by Tillotts Pharma as an unrestricted scientific grant. Tillotts Pharma had no influence on the planning, conduct, or reporting of the study.

Introduction

Eosinophilic esophagitis (EoE) presents with varying histologic extents, yet the impact of comorbidities on eosinophilic distribution and the implications on disease progression and treatment response remains poorly understood.^1,2 This study aimed to investigate the prevalence of different EoE extents and their impact on disease progression and treatment response within a multicenter cohort.

Aims & Methods

Clinical, endoscopic, and histologic data from adult EoE patients actively followed up at four Italian referral centers from October 2022 to October 2023 were retrospectively collected. The primary endpoint was to assess the prevalence of different EoE histologic extents (proximal, distal, diffuse) based on the presence of a pathological eosinophilic infiltrate (³15 Eo/HPF) and evaluate their association with comorbidities (atopic diseases, gastroesophageal reflux disease), clinical characteristics, endoscopic features. The secondary objective was to compare treatment responses among different histologic extents of EoE.

Results

149 patients were included (median age: 37 years [IQR 25-51], 38.2% males). Proximal EoE was observed in 8.1% (12/149), distal EoE in 27.5% (41/149), and diffuse EoE in 64.4% (96/149) of patients. In proximal-EoE, male patients were significantly more prevalent (91.7% vs. 68.3% distal-EoE vs. 55.5% diffuse-EoE, P=0.03). No significant differences were found in the rate of autoimmune comorbidities (8.3%, 14.6% distal-EoE, 10.4% diffuse-EoE; P=0.8). Only allergic rhinitis was significantly more prevalent in the distal and diffuse-EoE groups compared to the proximal group (33.3% vs. 72.5% vs. 61.5%, P=0.049). The prevalence of asthma, atopic dermatitis, oral allergy syndrome, and gastroesophageal reflux disease was similar among the three EoE extent groups. Endoscopic inflammatory features at diagnosis were significantly more prevalent in the proximal-EoE group, compared to the distal and diffuse-EoE groups (91.7% vs 53.8% vs 66%; P=0.05). Endoscopic fibrotic features at diagnosis were similar between all the groups (proximal-EoE 50%, distal 42.5%, and diffuse-EoE 51.1%; P=0.6) The clinical response after first-line therapy was comparable in all groups (75.0%, 70.7%, and 69.8%, P=0.93) and proton pump inhibitors were the most frequently prescribed therapy (77.8%). The endoscopic fibrotic remission rate after first-line therapy was higher in the proximal-EoE compared to the distal and diffuse-EoE groups (100.0% vs. 35.7% vs. 13.8%, P=0.0001).

Conclusion

In adult patients with EoE, an increasing proximal-to-distal gradient of esophageal eosinophilic infiltrate was observed. There was no clear correlation between the histologic extent of EoE and comorbidities, development of fibrosis, and response to treatment.

References

1. Ghoz H, Stancampiano FF, Valery JR, et al. Extent of eosinophilic esophagitis predicts response to treatment. Endosc Int Open 2021;9:E1234-e1242.
2. Godat A, Mueller R, Schenker D, et al. Eosinophil Distribution in Eosinophilic Esophagitis and its Impact on Disease Activity and Response to Treatment. Clin Gastroenterol Hepatol 2023.

Clinical Case Summary

A 77-year-old man underwent liver transplantation in 2008 due to alcoholic cirrhosis associated with hemochromatosis, and was taking tacrolimus and mycophenolate mofetil since that.
He was admitted in the Emergency Department in February 2023 with right upper quadrant abdominal pain and diarrhea for one week. Abdominal computed tomography(CT) showed ileal thickening. Laboratory tests revealed leukocytosis(19,000 leukocytes/mm3) and elevated C-reactive protein(16 mg/dL). Acute gastroenteritis was assumed and he was discharged on metronidazole with clinical improvement. One month later, he returned to the Emergency Department with abdominal pain for two days. CT revealed concentric wall thickening of the last ileal loop and a probable enteromesenteric fistula. He was admitted for further evaluation. Colonoscopy revealed deep mucosal ulceration of the terminal ileum. After colonoscopy, his abdominal pain worsened, so he repeated the abdominal CT, which showed a new organized collection in the right flank measuring 63 mm and small gas bubbles of pneumoperitoneum in the right upper quadrant. He underwent ileocecal resection with terminal ileostomy, and the histopathological evaluation revealed a neoplasm composed of atypical lymphoid proliferation, with positive immunohistochemistry for CD45, CD20, CD79a, BCL2, and BCL6, compatible with diffuse large B-cell lymphoma. After staging and exclusion of distant disease, the patient was proposed for chemotherapy following reduction of immunosuppression.
The clinical presentation of Inflammatory Bowel Disease can be quite heterogeneous and several pathologies can mimic its clinical, endoscopic, and/or histological findings. This case illustrates the importance of considering the diagnosis of small bowel lymphoma as a differential diagnosis of Crohn's disease, especially in elderly patients with risk factors, such as chronic immunosuppression.