Ashkan Rezazadeh Ardabili

Background: Early pathological observations consistently highlighted the involvement of the intestinal lymphatic system in Crohn’s disease (CD), although this remains underappreciated in current conceptual models of disease pathogenesis. This narrative review synthesizes evidence supporting lymphatic dysfunction as a key contributor of CD pathogenesis, and discusses its therapeutic potential. Methods: We searched PubMed to identify relevant studies on lymphatic biology in CD, including pathological, clinical, and experimental data. Results: Lymphatic obstruction, lymphangitis, and lymphangiectasia are early, widespread features of CD; structural remodeling coexists with compensatory lymphangiogenesis, suggesting a bidirectional relationship in which lymphatic dysfunction both drives and is sustained by intestinal inflammation. Peyer’s patches, closely integrated with the lymphatic network, may represent a portal of entry for luminal pathogens. CD susceptibility genes impair microbial handling at this interface, potentially enabling translocation into the lymphatics, endothelial injury, and the granulomatous lymphangitis hallmark of CD. Experimental models reinforce this framework: pathogens such as Yersinia or norovirus can induce lymphangitis preceding overt intestinal inflammation. Metastatic cutaneous CD, a rare extraintestinal manifestation involving lymphatic vessels characterized by granulomatous dermal inflammation at sites anatomically discontinuous from the gut, may provide a unique window into lymphatic pathology independent of the intestinal microbiome. Conclusions: These observations support an alternative view of CD in which intestinal lymphatic dysfunction plays an under-recognized role in both promoting and sustaining inflammation. This framework may explain disease features (patchy distribution, transmural inflammation, mesenteric hypertrophy) and positions the lymphatic system as a therapeutic target to restore drainage and modulate immune-lymphatic crosstalk.

Introduction: Despite numerous studies on surgical outcomes in Crohn’s disease (CD), global evidence remains fragmented, with limited synthesis of data on international surgical trends, regional variations and comparative outcomes. This systematic review aims to evaluate the rates of CD-related surgeries in the biologic era and to identify evidence gaps to inform future surgical strategies. Methods and analysis: A comprehensive search will be conducted in MEDLINE, Embase, and CINAHL from 9 February 2015 to 10 February 2025. A combination of controlled vocabulary and free-text terms related to surgical interventions and CD will be used to identify relevant literature. Studies eligible for inclusion include observational studies and randomised controlled trials (RCTs). The primary outcome is overall surgical rates in CD. Secondary outcomes include emergency versus elective surgery, minimally invasive vs conventional approaches, disease duration prior to surgery, permanent stoma formation rates, reconstruction approach and postoperative complications. Both adult and paediatric populations are considered. The risk of bias will be assessed independently by reviewers using appropriate tools. Meta-analyses or narrative synthesis will be conducted based on study heterogeneity, with subgroup and sensitivity analyses to explore regional, temporal and methodological variability. Ethics and dissemination: This protocol does not require ethical approval, as it involves secondary data analysis. Findings will be disseminated via peer-reviewed journal publications and relevant conferences. PROSPERO registration: CRD420251006137

Background: In light of the growing number of treatment options, the benefit-risk balance of IBD drugs is increasingly important in clinical decision-making. Post-marketing surveillance studies are pivotal to assess infection risk, yet mainly focus on severe infections. This study aimed to assess the incidence and risk factors associated with mild, moderate, and severe infections in IBD patients. Methods: We previously developed and validated a Patient-Reported Infections Questionnaire (PRIQ) which accurately assesses 15 infection categories with a 3-month recall period. The current prospective, multicentre, observational cohort study was performed between June 1, 2020 and July 1, 2021, enrolling consecutive IBD patients using myIBDcoach. Incidence rates (IR) were calculated for all infections and negative binomial regression was utilized to identify risk factors for infections over time. Results: In total, 629 IBD patients (n=346 CD, n=283 UC, 58.3% female) were included, completing 2397 PRIQs during 573.8 person-years (PY) of follow-up. This resulted in 991 reported infections and an overall IR of 172.7 per 100PY, predominantly characterized by mild (IR 117.5 per 100PY) and moderate (IR 50.9 per 100PY) infections. Risk factors significantly associated with increased overall infection rates included female sex, higher comorbidity burden, smoking, and specific treatments, such as steroids, immunomodulators, anti-TNF agents, and JAK-inhibitors, with steroids doubling infection risk (IRR 2.02). Conclusion: Mild and moderate infections are common among IBD patients and are particularly associated with both patient characteristics and specific immunosuppressive treatments. These findings emphasize the need for vigilant monitoring, especially for patients at higher infection risk, and allow for more personalized advice on benefit-risk of IBD treatments.

LINKED CONTENT: This article is linked to Aliu et al papers. To view these articles, visit https://doi.org/10.1111/apt.17988 and https://doi.org/10.1111/apt.18027.

Summary: Background: Persistent gastrointestinal symptoms are prevalent in adult patients with inflammatory bowel disease (IBD), even when endoscopic remission is reached. These symptoms can have profound negative effects on the quality of life of affected patients and can be difficult to treat. They may be caused by IBD‐related complications or comorbid disorders, but they can also be explained by irritable bowel syndrome (IBS)‐like symptoms.Aims: To provide a practical step‐by‐step guide to diagnose and treat persistent gastrointestinal symptoms in patients with IBD in remission via a personalised approach.Methods: We scrutinised relevant literature on causes, diagnostics and treatment of persistent gastrointestinal symptoms (abdominal pain or discomfort, bloating, abdominal distension, diarrhoea, constipation and faecal incontinence) in patients with IBD in remission.Results: A graphical practical guide for several steps in diagnosing, identifying potential triggers and adequate treatment of persistent gastrointestinal symptoms in IBD in remission is provided based on supporting literature. The first part of this review focuses on the diagnostic and treatment approaches for potential IBD‐related complications and comorbidities. The second part describes the approach to IBS‐like symptoms in IBD in remission.Conclusions: Persistent gastrointestinal symptoms in IBD in remission can be traced back to potential pathophysiological mechanisms in individual patients and can be treated adequately. For both IBD‐related complications and comorbidities and IBS‐like symptoms in IBD in remission, pharmacological, dietary, lifestyle or psychological treatments can be effective. A systematic and personalised approach is required to reduce the burden for patients, healthcare systems, and society.

LINKED CONTENT: This article is linked to Everhov et al paper. To view this article, visit https://doi.org/10.1111/apt.17675

Summary: Background: Abdominal pain is highly prevalent in patients with inflammatory bowel disease (IBD) in remission, but the aetiology is incompletely understood.Aim: To investigate the association of clinical, lifestyle and psychosocial factors with abdominal pain in patients with IBD in remission.Methods: We performed a prospective multicentre study enrolling consecutive patients with IBD. Data were collected between 1 January 2020 and 1 July 2021, using myIBDcoach, an established remote monitoring platform for IBD. Chronic abdominal pain in IBD in remission (IBDremissionPain+) was defined as abdominal pain score ≥3 (0–10 NRS) on ≥1/3 of all assessments, combined with faecal calprotectin remissionPain+ patients were characterised by female sex, younger age, higher BMI, and shorter disease duration. They reported more often or higher levels of stress, fatigue, depressive and anxiety symptoms, and life events (all p < 0.001). In the multivariable analysis, sex, disease entity, fatigue, depressive symptoms and life events were associated with abdominal pain over time (all p < 0.05).Conclusion: In this cohort of patients with IBD in remission, abdominal pain was common and associated with psychosocial factors. A more holistic treatment approach for patients with IBD suffering from abdominal pain may improve quality of care and subjective wellbeing.