Introduction: Improvement of small intestinal lesions is essential for achieving favorable long-term outcomes in patients with Crohn’s disease (CD); however, evidence regarding the efficacy of biologics for small bowel involvement remains limited. Risankizumab (RZB), a selective interleukin-23 (IL-23) p19 inhibitor, has shown efficacy in large randomized trials; however, data on its effect on small intestinal inflammation are limited. This study aimed to evaluate the real-world effectiveness of RZB on small intestinal lesions using balloon-assisted enteroscopy. Methods: We retrospectively analyzed 23 patients with CD who received RZB between July 2023 and January 2025. Clinical activity was assessed using the Harvey–Bradshaw Index (HBI), and serum biomarkers (albumin, C-reactive protein, and hemoglobin) were measured longitudinally. Endoscopic activity was evaluated using the Simple Endoscopic Score for CD (SES-CD) before treatment and at 28 weeks after treatment; paired endoscopic assessment was available in 16 patients. Results: At baseline, 10 patients had clinically active disease (HBI ≥4), and 13 were in clinical remission (HBI ≤3). In the active group, HBI and C-reactive protein levels significantly decreased after treatment, whereas hemoglobin and albumin concentrations increased during follow-up. Among the 16 patients who underwent paired endoscopic evaluation, both total and ileal SES-CD scores significantly decreased after 28 weeks of RZB therapy, demonstrating mucosal improvement in the small intestine. Notably, several patients who showed inadequate response to ustekinumab (UST) also exhibited endoscopic improvement after RZB treatment. Conclusions: RZB was effective in improving clinical and endoscopic disease activities, including small intestinal lesions, even in patients who were previously refractory to UST. Given the prognostic importance of small bowel inflammation, these findings highlight the potential of selective IL-23p19 inhibition as a valuable therapeutic option for patients with small bowel-dominant CD.

Background/Aim: Achieving both endoscopic and histological remission in ulcerative colitis (UC) is associated with improved clinical outcomes. There is a growing need for non-invasive methods to assess both remission states. This study investigates the utility of serum leucine-rich alpha-2 glycoprotein (LRG) as a biomarker for monitoring endoscopic and histological remission in patients with UC. Methods: Patients with UC who underwent colonoscopy from July 2020 to September 2021 at multiple centers in Japan were included to compare the accuracy of CRP and LRG in detecting endoscopic and histological remission. ROC curve analyses were performed and AUC values compared. Results: 412 patients were identified. The median values of CRP and LRG were 0.07 mg/dL and 12.2 μg/mL, respectively. Endoscopic remission, as defined as Mayo endoscopic sub-score of 0 or 1, was observed in 188 patients, and histological remission, as defined as Geboes score <3.1, was observed in 156 patients. The AUC values for CRP and LRG for detecting endoscopic remission were 0.68 and 0.76, respectively, and the AUC values for CRP and LRG for detecting histological remission were 0.70 and 0.76, respectively. In both cases, the AUC for LRG was significantly higher than that of CRP (P<0.0001). The optimal cutoff value of LRG for detecting histological remission was 13.4 μg/mL, with a sensitivity of 82% and a specificity of 58%. Conclusion: LRG is superior to CRP in detecting both endoscopic and histological remission in patients with UC.

Introduction: Long-term Crohn’s disease (CD) increases risk of cancer. However, data on the clinical characteristics and optimal endoscopic surveillance strategies for CD-associated cancers in Japan remain controversial. This study aimed to investigate the clinical characteristics, diagnostic methods, and treatment patterns of CD-associated cancers at our institution, and to consider strategies for effective surveillance in Japanese clinical practice. Methods: We retrospectively analyzed 21 patients with 26 CD-associated cancer locations treated at our hospital between August 2001 and March 2024, focusing on their clinical backgrounds, cancer characteristics, and endoscopic surveillance practices. Results: Anorectal cancer was the most common (61%), and 57% were stage II or higher at the time of diagnosis. There were 12 cases of fistula-associated cancer, with a median disease duration of 18.5 years, and 7 cases of stage II or higher. Targeted endoscopic biopsy established the diagnosis in 77%, often requiring multiple-site biopsies. Remission or mild endoscopic activity was observed in 75% (6/8) of stage 0–I patients, compared with 20% (2/10) of stage II–IV patients, suggesting a trend toward more advanced cancer with higher endoscopic activity (P = 0.03). Compared with non-anorectal cancers, 33% of anorectal cancers required four or more endoscopic biopsies for diagnosis, and this rate was significantly higher than that of non-anorectal cancers (P = 0.028). Conclusion: Anorectal cancer was the most common CD-associated cancer, and strictures and active inflammation made early diagnosis difficult. Annual surveillance with multiple-site biopsies of anal lesions was essential.

Background: Eosinophilic esophagitis (EoE) is a chronic, immune-mediated inflammatory disease affecting the esophagus, characterized by esophageal dysfunction, dysphagia, and tissue remodeling, leading to significant impairment in quality of life. The pathogenesis of EoE involves a complex interplay of genetic, environmental, and immunological factors. Although the disease is strongly associated with type 2 immune responses, emerging evidence suggests that B cells and antibody responses, particularly IgG4, also play a crucial role in disease development and progression. Summary: This review explores the pathogenesis of EoE with a focus on the role of B cells, plasma cells, and antibodies. Epithelial barrier dysfunction is a pivotal factor in EoE, influenced by genetic predisposition, environmental triggers, and immune responses. The impaired barrier allows for antigen penetration, triggering type 2 immune responses, and chronic inflammation. Elevated levels of IgG4 in esophageal tissues and their potential to drive inflammation and tissue remodeling are highlighted. Animal models and clinical studies provide insights into the involvement of B cells and antibodies in EoE, suggesting that these components may contribute to the chronic inflammatory state and disease severity. Key Messages: B cells are increasingly recognized for their role in EoE, particularly through their production of antibodies and cytokines that contribute to the inflammatory milieu. EoE is primarily driven by type 2 immune responses involving cytokines such as IL-4, IL-5, and IL-13, which promote eosinophil recruitment and chronic inflammation. Regulatory B cells, which produce anti-inflammatory cytokines such as IL-10 and IL-35, may play a role in modulating immune responses in EoE and contribute to the production of IgG4 antibodies. Elevated levels of IgG4 in esophageal tissues of EoE patients are linked to chronic inflammation and tissue remodeling, suggesting a potential role in disease pathogenesis. Further studies are needed to elucidate the specific mechanisms by which B cells and antibodies contribute to EoE.

Since the late 1990s, eosinophilic esophagitis (EoE) became a known disease characterized by eosinophilic infiltration into the esophagus accompanied by esophageal symptoms. Over the past 2 decades, there has been an exponential increase in the understanding of the epidemiology and pathogenesis of disease leading to new therapies. Despite this, we still have significant knowledge gaps in our clinical care. Despite a plethora of knowledge gained about EoE over the last 3 decades, medical care of EoE continues to struggle with uncertainties. Presently, we lack available methods to predict who is at risk of complications or who will be refractory to therapy. There is only a paucity of data about how to maintain long-term control of inflammation, and we have yet to develop clinically applicable biomarkers to predict clinical phenotypes (i.e., those who will recur while on therapy). This review focuses on a few of the common limitations in current care of EoE: (1) diagnosis, (2) accurate food antigen testing, (3) prediction of clinically relevant phenotypes, (4) maintenance and surveillance strategies, (5) optimal disease endpoints, and (6) need for less invasive monitoring. Despite rapid increase in our comprehension of EoE, patients continue to have unmet needs. However, with the continued rapidity of investigation, many of these current deficiencies are being addressed and will likely be resolved in the future.

Introduction: Eosinophilic colitis (EoC) is an immune-mediated disorder characterized by chronic colitis with significant eosinophilic infiltration. Diagnosing EoC is sometimes challenging due to more common disorders associated with colonic eosinophilia like inflammatory bowel disease (IBD). This study aimed to examine the prevalence and clinical features of patients who were initially diagnosed with IBD and later found to have EoC (IBD-EoC) and to identify the clinical factors facilitating a definitive EoC diagnosis. Methods: Medical records of patients with eosinophilic gastrointestinal diseases (EGIDs) were retrospectively reviewed and subsequently analyzed for the cases of IBD-EoC. Clinical characteristics were compared between patients with IBD-EoC and those initially diagnosed with EoC (definitive EoC). Results: Among 42 patients with EGIDs, 4 were diagnosed with EoC. Two of them were definitive EoC, while the remaining 2 were initially diagnosed with IBD (IBD-EoC), representing 0.64% of patients with IBD. Unlike in patients with definitive EoC, the endoscopic findings atypically suggestive of IBD and the possibility of EoC were not communicated between the endoscopists and the pathologists in patients with IBD-EoC. The absence of mucosal eosinophil count in the initial histologic report further delayed the diagnosis of EoC. Treatment failure with 5-ASA prompted the reassessment of endoscopic and histologic findings, leading to the revised diagnosis of EoC. The presence of peripheral blood eosinophilia facilitated the initial diagnosis with EoC in patients with definitive EoC. Conclusion: Proactive communication between endoscopists and pathologists is crucial for diagnosing EoC.

Introduction: Moderate-to-severe ulcerative colitis (UC) is commonly treated with oral corticosteroids. However, in cases of oral corticosteroid failure, no clear consensus exists on whether to transition to intravenous corticosteroids (IVCS) or initiate advanced therapies. The aim of this study was to evaluate whether responsiveness to oral corticosteroids is associated with differences in the efficacy of IVCS. Methods: This multicenter cohort study (conducted at 10 facilities) included patients with moderate-to-severe UC who were transitioned to IVCS after failure of oral corticosteroid therapy. The patients were categorized into the partial responder and nonresponder groups based on their response to oral corticosteroids, as measured by improvements in their PRO-2 scores. The primary outcome was clinical remission at day 30, defined as a total PRO-2 score ≤1 with a rectal bleeding subscore of 0. Logistic regression was used to estimate the odds ratio (OR) of achieving clinical remission. Results: A total of 123 patients with UC were included, with 41 and 82 patients in the partial responder and nonresponder groups, respectively. Clinical remission at day 30 was achieved in 41.4% of the partial responders and 18.3% of the nonresponders (multivariable-adjusted OR, 0.35 [95% CI: 0.15–0.83]; p = 0.017). The nonresponder group had a higher risk of requiring advanced therapies within 90 days than the partial responder group (multivariable-adjusted OR, 2.48 [95% CI: 1.09–5.66]; p = 0.030). Conclusions: In patients with UC and oral corticosteroid failure, responsiveness to oral corticosteroids may be associated with differences in IVCS efficacy.

Introduction: Upadacitinib (UPA), a Janus kinase inhibitor approved for the treatment of Crohn’s disease (CD), has demonstrated high efficacy in clinical trials; however, real-world data on its outcomes remain limited. This study evaluated UPA outcomes in patients with CD in a real-world setting. Methods: We retrospectively analyzed patients who initiated UPA treatment between June 2023 and June 2024. The primary endpoints were clinical response and remission at 12 and 54 weeks. The secondary endpoints included changes in the C-reactive protein (CRP) levels, serum albumin levels, and perianal fistula response. Results: Thirteen patients (mean age, 32.0 years; 92.3% male; mean disease duration, 114.1 months) were included. At baseline, three (23.1%) patients used oral corticosteroids, and 11 (84.6%) had undergone prior biologic therapy, with nine (81.8%) exposed to anti-tumor necrosis factor-alpha antibodies. The mean follow-up period was 53.1 weeks, and the 54-week continuation rate was 83.3%. The clinical response rates were 46.2% and 53.8%, and the remission rates were 69.2% and 84.6% at 12 and 54 weeks, respectively. The mean Crohn’s Disease Activity Index scores decreased from 226.8 at baseline to 73.7 at 54 weeks, and the average CRP and albumin levels improved correspondingly. Among the 7 patients (53.8%) with draining perianal fistulas, six (85.7%) achieved cessation of pus discharge by week 8 (mean, 4.4 weeks). No significant adverse events were observed. Conclusion: UPA appears to be an effective treatment for CD and may facilitate the early resolution of perianal fistulas, supporting its role in managing perianal disease.

Introduction: De novo inflammatory bowel disease (IBD) is a rare but clinically significant complication after solid organ transplantation (SOT), with incidence higher than that in the general population. Its pathogenesis, diagnostic challenges, and optimal management remain poorly defined. We describe 6 cases of de novo IBD following liver or heart transplantation and evaluate therapeutic outcomes with selective biologics targeting the IL-23 pathway. Methods: Six SOT recipients (3 liver, 3 heart) developed new-onset ulcerative colitis-type (UC-type, n = 3) or Crohn’s disease-like (CD-like, n = 3) IBD after a median of 47.5 months post-transplantation. None had pre-transplant intestinal symptoms; colonoscopy was negative before transplantation in 2 UC-type cases. Alternative etiologies – including cytomegalovirus colitis, drug-induced colitis, and post-transplant lymphoproliferative disorder – were rigorously excluded. Treatments included systemic corticosteroids, mirikizumab, ustekinumab, or risankizumab. Median follow-up was 15.6 months. Results: Corticosteroids induced remission in 2 UC-type cases, while one steroid-refractory UC-type case and all CD-like cases achieved clinical improvement and endoscopic response or remission with IL-23-targeted biologics. No opportunistic infections, severe biologic-related adverse events, or graft rejection were observed. Conclusions: De novo IBD emerged years after SOT, with variable phenotypes despite baseline immunosuppression. IL-23 pathway inhibitors demonstrated favorable efficacy and safety in this vulnerable population, representing a promising strategy warranting further prospective evaluation.

Karger Publishers and the editors of Inflammatory Intestinal Diseases would like to thank the reviewers for their ongoing support in reviewing manuscripts for our Journal in 2025. This year we have chosen not to disclose the names of our reviewers to preserve the principle of anonymity inherent to the single-blind peer-review we follow. Even so, this should not be in our way to sincerely thank all contributing reviewers who have volunteered their time, effort, and expertise in benefit of the quality of the manuscripts we received and published in 2025. Individual reviewers can still claim their personal “Certificate of Review” via the Journal’s manuscript submission system.