Introduction

Celiac disease (CD) is an autoimmune disorder triggered by gluten ingestion, leading to intestinal villous atrophy. While a gluten-free diet (GFD) is the mainstay of treatment, some patients exhibit persistent villous atrophy (pVA) on follow-up biopsies. This raises concerns about the long-term health consequences of pVA in CD patients adhering to GFD.

Aims & Methods

Objectives: To evaluate the association between pVA and long-term outcomes in CD patients.

Results

We collected 151 patients with CD. Approximately 24.5% of patients had pVA. Patients with pVA exhibited a significantly higher risk of complications (HR 7.61, 95% CI 3.18 to 17.64, p<0.001). Overall, during follow-up, 9 patients (5.96%) developed a complication (three refractory CD, one B-cell lymphoma, three persistence of malabsorption symptoms and two ulcerative jejuno-ileitis). Over these 9, 7 patients had a pVA.
While most patients adhered to GFD, 35.1% still had persistent VA at follow-up.

Conclusion

This study demonstrates that persistent villous atrophy in CD patients following GFD is associated with increased risk of complications. It also shows the effectiveness of the 5-point scoring system, in stratifying CD patients by risk of pVA. The system accurately identified high-risk patients with a significantly higher prevalence of pVA. It can also help identify these individuals who, despite a lack of current symptoms, may still be at higher risk for future complications so it can be used in clinical practice to personalized follow-up modalities.

References

Rossi A, Lohi J, Mustalahti K, et al. Persistent villous atrophy predicts development of complications and mortality in adult patients with coeliac disease: a multicentre longitudinal cohort study and development of a score to identify high-risk patients [Internet]. BMJ Gut. 2023;72(11):2095-2105. Available from: https://gut.bmj.com/content/72/11/2095

Introduction

In recent years, eosinophilic gastrointestinal disorders (EGIDs) have attracted attention due to an increase in their incidence. Although many reports have focused on eosinophilic esophagitis (EoE), there are relatively few reports of eosinophilic enteritis (EoN), which causes eosinophil infiltration of the small intestine. In addition, although the diagnostic criteria for EGID also specify that the number of eosinophils infiltrating the gastrointestinal tract other than the esophagus should be 20 or more, the small intestine has not been clearly defined. Furthermore, not even normal eosinophils have been clearly defined for the small intestine, it is necessary to establish the clinical features of EoN. using double-balloon Enteroscopy (DBE) to differentiate it from other small intestinal diseases such as IBD and IBS, which cause similar symptoms of EoN. Accordingly, we examined both the extent of eosinophilic infiltration in the small intestine using DBE and the associated clinical background in cases which EoN was suspected.

Aims & Methods

Patients who underwent DBE for examination of the small intestine at our hospital from January 2021 to December 2024 and had a biopsy from the small intestine were included. Biopsies were taken from 1 or more of the duodenum, upper jejunum, lower jejunum, upper ileum, lower ileum, or terminal ileum, and the number of eosinophils per 1HPF was counted. By using a × 40 objective and × 10 oculars the number of eosinophils per high power field (EOS / HPF) in up to two HPFs was counted in each biopsy specimens. Five patients who visited our hospital with abdominal symptoms, were suspected of EoN, and underwent DBE‑guided small‑intestinal biopsy revealing more than 50 eosinophils per high‑power field, after other diseases had been ruled out, were classified into the EoN group. (3 males and 2 females, mean age 58.3 years). The non-EoN group (7 males and 6 females, mean age 48.4 years) consisted of 14 patients who underwent small intestinal biopsy by DBE for other reasons during the study period, and the number of eosinophil infiltration in the small intestinal mucosa and clinical background were compared.

Results

All five patients in the EoN group presented to our hospital with a chief complaint of abdominal pain and diarrhea and four cases showed edema of the small intestine on CT. All five had an elevated peripheral blood eosinophil count (median 13%). In contrast, the non-EoN group showed no increase with a median of 2.4%. In total, 80 small intestine biopsy specimens were obtained from 18 patients using DBE, 25 specimens in the EoN group and 55 specimens in the non-EoN group. The median eosinophil count in the EoN group was 77 (15-213), which was elevated and significantly higher than the 23 (3-111) in the non-EoN group. (P < 0.01)(Table 1)(Figure 1)
Table 1. Characteristics of patients and biopsy specimens

Conclusion

Small intestinal biopsy using DBE may be useful for the diagnosis of EoN, as eosinophil counts are significantly increased in the small intestine in patients with suspected EoN.

Introduction

Upadacitinib has shown to be more effective than placebo for treating extraintestinal manifestations (EIM) in post-hoc analyses. However, real-world data on the effectiveness of upadacitinib in patients with inflammatory bowel disease (IBD) and EIMs are lacking.

Aims & Methods

A multicenter, retrospective and observational study was conducted at 19 Spanish hospitals. Patients with IBD and active EIMs when initiating upadacitinib were eligible. The primary outcome was EIM improvement at weeks 8-12. The EIM assessment was based on the physician's subjective evaluation and categorized into clinical remission, partial response, nonresponse and worsening. EIM improvement was defined as either clinical remission or partial response. Axial arthropathy, peripheral arthropathy, pyoderma gangrenosum, erythema nodosum, sweet syndrome, aphthous stomatitis, uveitis, episcleritis, primary sclerosing cholangitis and bronchiectasis were considered. In patient experiencing >1 EIM, all had to be resolved or improved to be considered. If not, the worst outcome was recorded. Patients’ visits were scheduled at weeks 0, 8-12, and 6 months. Multivariate analysis was performed to find factors associated with EIM improvement at w8-12.

Results

A total of 160 patients were included, 120 patients with Crohn’s Disease (75.6%), 90 females (56.3%) with a median age of 46.6 years (IQR 37.9-56.7). Upadacitinib was initiated in one hundred twenty-six (78.8%) patients due to EIMs and luminal activity and 35 patients (21.3%) exclusively due to EIMs. All patients were bio-experienced with 84 patients previously treated with ≥3 biologics (52.5%). Baseline EIMs assessment was for at least 1 EIM in 107 patients (66.9%), 42 patients presented 2 EIMs (26.3%) while 11 patients (6.9%) experienced ≥ 3 EIMs.
At w8-12, 99 patients (61.9%) achieved EIM improvement, 40 patients (25 %) clinical remission, 58 patients (36.9%) partial response, 58 patients (36.5 %) nonresponse and worsening in 3 patients. Patients initiating Upadacitinib due to exclusively active EIMs was associated with EIM improvement at weeks 8-12 (OR 2.99 95% CI 1.06-8.42; p=0.04). IBD clinical remission at w8-12 was achieved in 75 patients (61%).
Evaluation at 6 months was available for 103 patients, 73 patients (70.9%) presented EIM improvement, 41 patients (39.8%) clinical remission, 32 patients (31.1%) partial response, 20 patients (19.4%) nonresponse and 10 patients (9.7%) worsening. IBD clinical remission at 6 months was achieved in 51 patients (62.2%).
During the follow-up, Upadacitinib was ceased in 27 patients (16.9%). Adverse events were detected in 39 patients (24.3%) and 7 patients (4.4%) experienced worsening of previous inactive EIMs.

Conclusion

Upadacitinib was highly effective in the short term for treating bio-experienced patients with active EIMs, particularly for patients without luminal activity

Disclosure

No conflict