Extraintestinal Manifestations Research Articles

Abdominal involvement as a primary manifestation of systemic or isolated gastrointestinal vasculitis

Systemic vasculitides can cause a wide variety of gastrointestinal manifestations (GI) ranging from mild and frequently nonspecific abdominal pains to potentially life-threatening bowel perforations. Vascular involvement in systemic vasculitides can affect any GI blood vessel, most commonly mesenteric, hepatic, or splenic arteries. Inflammatory changes affecting different layers of arterial vessel walls can lead to aneurysmatic dilatation or blood vessel occlusion with subsequent organ ischemia leading to mucosal ulcerations, GI bleeding, perforations, or bowel obstruction. While the presence of extraintestinal manifestations may aid in diagnosis, delays in making appropriate diagnoses and rapid initiation of glucocorticoid and immunosuppressive treatment can have detrimental consequences. Awareness of isolated gastrointestinal vasculitis is of particular importance as it frequently remains undiagnosed until end-stage organ damage becomes apparent. Vasculitis mimics such as vascular Ehlers-Danlos syndrome or fibromuscular dysplasia add another lay of complexity in approaching patients with suspected GI vasculitis and should always be carefully considered.

Not Your Typical Ulcerative Colitis Patient

Background: Extraintestinal manifestations (EIMs) of inflammatory bowel diseases (IBDs) are a common and debilitating feature of disease, occurring in up to 40% of patients with IBD. Despite the huge therapeutic progress of the last decade, one must not forget about the side effects that currently available medications might have and the challenges to both patient and physician. Case presentation: We present the case of a 33-year-old woman, that initially was admitted for diffuse abdominal pain, nausea and bloating. After careful investigation she was diagnosed with a drug induced acute pancreatitis, caused by sulfamethoxazole/trimethoprim taken for UTI. Further investigations established a diagnosis of ulcerative colitis. Initial treatment with mesalamine resulted in another acute pancreatitis event that required hospitalization. An anti-TNF therapy with infliximab was started with initial clinical remission but then she developed another adverse reaction, this time paradoxical psoriasis, while having an IBD flare. So, this begged the question, how do we treat a patient that had an adverse reaction to every prior treatment? Conclusion: Developing newer and newer therapies will bring also different possible adverse events that should be carefully diagnosed and managed.

Cholestyramine alleviates bone and muscle loss in irritable bowel syndrome via regulating bile acid metabolism.

Irritable bowel syndrome (IBS) is a widespread gastrointestinal disorder known for its multifaceted pathogenesis and varied extraintestinal manifestations, yet its implications for bone and muscle health are underexplored. Recent studies suggest a link between IBS and musculoskeletal disorders, but a comprehensive understanding remains elusive, especially concerning the role of bile acids (BAs) in this context. This study aimed to elucidate the potential contribution of IBS to bone and muscle deterioration via alterations in gut microbiota and BA profiles, hypothesizing that cholestyramine could counteract these adverse effects. We employed a mouse model to characterize IBS and analysed its impact on bone and muscle health. Our results revealed that IBS promotes bone and muscle loss, accompanied by microbial dysbiosis and elevated BAs. Administering cholestyramine significantly mitigated these effects, highlighting its therapeutic potential. This research not only confirms the critical role of BAs and gut microbiota in IBS-associated bone and muscle loss but also demonstrates the efficacy of cholestyramine in ameliorating these conditions, thereby contributing significantly to the field's understanding and offering a promising avenue for treatment.

The Natural History of Patients With Pre-Existing and De Novo Inflammatory Bowel Disease After Solid Organ Transplantation: EITOS Study of GETECCU.

Limited data are available on the outcome of inflammatory bowel disease (IBD) in patients with solid organ transplantation (SOT). We describe the natural history of pre-existing IBD and de novo IBD after SOT. This was a retrospective, multicenter study that included patients with pre-existing IBD at the time of SOT and patients with de novo IBD after SOT. The primary outcome was IBD progression, defined by escalation of medical treatment, surgical therapy, or hospitalization due to refractory IBD. Risk factors were identified using multivariate Cox proportional hazard analysis. A total of 177 patients (106 pre-existing IBD and 71 de novo IBD) were included. Most patients with pre-existing IBD (92.5%) were in remission before SOT. During follow-up, 32% of patients with pre-existing IBD had disease progression, with a median time between SOT and IBD progression of 2.2 (interquartile range, 1.3-4.6) years. In the de novo cohort, 55% of patients had disease progression with a median time to flare of 1.9 (interquartile range, 0.8-3.9) years after diagnosis. In the pre-existing IBD cohort, active IBD at the time of SOT (hazard ratio, 1.80; 95% confidence interval, 1.14-2.84; P = .012) and the presence of extraintestinal manifestations (hazard ratio, 3.10; 95% confidence interval, 1.47-6.54; P = .003) were predictive factors for IBD progression. One-third of patients with pre-existing IBD and about half of patients with de novo IBD have disease progression after SOT. Active IBD at the time of SOT and the presence of extraintestinal manifestations were identified as risk factors for IBD progression.

Leaky gut, circulating immune complexes, arthralgia, and arthritis in IBD: coincidence or inevitability?

Most host-microbiota interactions occur within the intestinal barrier, which is essential for separating the intestinal epithelium from toxins, microorganisms, and antigens in the gut lumen. Gut inflammation allows pathogenic bacteria to enter the blood stream, forming immune complexes which may deposit on organs. Despite increased circulating immune complexes (CICs) in patients with inflammatory bowel disease (IBD) and discussions among IBD experts regarding their potential pathogenic role in extra-intestinal manifestations, this phenomenon is overlooked because definitive evidence demonstrating CIC-induced extra-intestinal manifestations in IBD animal models is lacking. However, clinical observations of elevated CICs in newly diagnosed, untreated patients with IBD have reignited research into their potential pathogenic implications. Musculoskeletal symptoms are the most prevalent extra-intestinal IBD manifestations. CICs are pivotal in various arthritis forms, including reactive, rheumatoid, and Lyme arthritis and systemic lupus erythematosus. Research indicates that intestinal barrier restoration during the pre-phase of arthritis could inhibit arthritis development. In the absence of animal models supporting extra-intestinal IBD manifestations, this paper aims to comprehensively explore the relationship between CICs and arthritis onset via a multifaceted analysis to offer a fresh perspective for further investigation and provide novel insights into the interplay between CICs and arthritis development in IBD.

Hot Topics on Nutrition in IBD

Inflammatory bowel diseases (IBD) affect primarily the bowel, but they are multisystemic diseases with a wide range of extraintestinal manifestations and complications. Nutritional imbalance occurs frequently in patients with IBD. The spectrum of malnutrition goes from undernutrition (low protein-caloric intake, disease-related malnutrition, micronutrient deficiencies) to overnutrition and obesity. The nutritional status of patients with IBD is increasingly recognized as a key aspect of the treatment and must be addressed in all patients. The screening and correction of the deficiencies should be individualized. Except for enteral nutrition in pediatric Crohn’s disease, no clinical evidence supports specific diets. Nevertheless, the role of personalized nutritional interventions as an adjunct therapy is well established. Compelling new data points to a key role of diet in gut inflammation directly or through modulation of intestinal microbiota. It will be of utmost importance to have well-designed longitudinal studies on dietary interventions alone or combined with current therapies. This review summarizes topics such as the spectrum of malnutrition, the evidence behind the concept of diet as an IBD cause, and the role of diet in IBD therapy.

Biologics, Small Molecules and More in Inflammatory Bowel Disease: The Present and the Future

Inflammatory bowel disease (IBD) is a group of heterogeneous chronic inflammatory diseases of the gut presenting with intestinal and extraintestinal manifestations. Most cases fit in predominantly two types, namely, ulcerative colitis and Crohn’s disease. The incidence of IBD has been increasing steadily in the past three decades. Focused research has resulted in many therapeutic options. Biologics (derived from humans or animals) and small molecules have emerged as the cornerstone in the management of IBD and have become widely available. Currently, monoclonal antibodies against tumor necrosis factor-alpha (infliximab, adalimumab, certolizumab, and golimumab), integrins (vedolizumab and natalizumab), and interleukin (IL)-12 and IL-23 antagonists (ustekinumab), along with small molecules (tofacitinib), are approved for use. This article summarizes various aspects of these drugs, like clinical pharmacology, indications for use in IBD, safety in pregnancy and lactation, and the adverse effects profile based on the studies leading to their approval. This review also focuses on the recent advances and future perspectives specific to biologics in IBD.

Inflammatory Bowel Diseases and Non-Alcoholic Fatty Liver Disease: Piecing a Complex Puzzle Together.

Inflammatory bowel diseases (IBD), comprising Crohn's disease and ulcerative colitis, are systemic and multifaceted disorders which affect other organs in addition to the gastrointestinal tract in up to 50% of cases. Extraintestinal manifestations may present before or after IBD diagnosis and negatively impact the intestinal disease course and patients' quality of life, often requiring additional diagnostic evaluations or specific treatments. Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide. Current evidence shows an increased prevalence of NAFLD (and its more advanced stages, such as liver fibrosis and steatohepatitis) in IBD patients compared to the general population. Many different IBD-specific etiopathogenetic mechanisms have been hypothesized, including chronic inflammation, malabsorption, previous surgical interventions, changes in fecal microbiota, and drugs. However, the pathophysiological link between these two diseases is still poorly understood. In this review, we aim to provide a comprehensive overview of the potential mechanisms which have been investigated so far and highlight open issues still to be addressed for future studies.

Comprehensive Association Analyses of Extraintestinal Manifestations in Inflammatory Bowel Disease

Patients with inflammatory bowel disease (IBD) frequently develop extraintestinal manifestations (EIMs) that contribute substantially to morbidity. We assembled the largest multicohort data set to date to investigate the clinical, serologic, and genetic factors associated with EIM complications in IBD. Data were available in 12,083 unrelated European ancestry IBD cases with presence or absence of EIMs (eg, ankylosing spondylitis [ankylosing spondylitis and sacroiliitis], primary sclerosing cholangitis [PSC], peripheral arthritis, and skin and ocular manifestations) across 4 cohorts (Cedars-Sinai Medical Center, National Institute for Diabetes and Digestive and Kidney Diseases IBD Genetics Consortium, Sinai Helmsley Alliance for Research Excellence Consortium, and Risk Stratification and Identification of Immunogenetic and Microbial Markers of Rapid Disease Progression in Children with Crohn's Disease cohort). Clinical and serologic parameters were analyzed by means of univariable and multivariable regression analyses using a mixed-effects model. Within-case logistic regression was performed to assess genetic associations. Most EIMs occurred more commonly in female subjects (overall EIM: P= 9.0E-05, odds ratio [OR], 1.2; 95% CI, 1.1-1.4), with CD (especially colonic disease location; P= 9.8E-09, OR, 1.7; 95% CI, 1.4-2.0), and in subjects who required surgery (both CD and UC; P= 3.6E-19, OR, 1.7; 95% CI, 1.5-1.9). Smoking increased risk of EIMs except for PSC, where there was a "protective" effect. Multiple serologic associations were observed, including with PSC (anti-nuclear cytoplasmic antibody; IgG and IgA, anti-Saccharomyces cerevisiae antibodies; and anti-flagellin) and any EIM (anti-nuclear cytoplasmic antibody; IgG and IgA, anti-Saccharomyces cerevisiae antibodies; and anti-Pseudomonas fluorescens-associated sequence). We identified genome-wide significant associations within major histocompatibility complex (ankylosing spondylitis and sacroiliitis, P= 1.4E-15; OR, 2.5; 95% CI, 2.0-3.1; PSC, P= 2.7E-10; OR, 2.8; 95% CI, 2.0-3.8; ocular, P= 2E-08, OR, 3.6; 95% CI, 2.3-5.6; and overall EIM, P= 8.4E-09; OR, 2.2; 95% CI, 1.7-2.9) and CPEB4 (skin, P= 2.7E-08; OR, 1.5; 95% CI, 1.3-1.8). Genetic associations implicated tumor necrosis factor, JAK-STAT, and IL6 as potential targets for EIMs. Contrary to previous reports, only 2% of our subjects had multiple EIMs and most co-occurrences were negatively correlated. We have identified demographic, clinical, and genetic associations with EIMs that revealed underlying mechanisms and implicated novel and existing drug targets-important steps toward a more personalized approach to IBD management.

Association between body mass index and age of disease onset with clinical outcomes in paediatric-onset Crohn’s Disease (CD): a UK nation-wide analyses using the NIHR-IBD BioResource

BackgroundThe evidence on the relationship between adiposity and disease outcomes in paediatric Crohn’s disease (CD) is limited and lacks consensus.AimTo investigate the relationship between (a) body mass index (BMI) and clinical CD outcomes (hospitalisation, surgery, disease behaviour, biologic use, extra-intestinal manifestations (EIMs)) and (b) the age of CD onset with clinical outcomes.DesignClinical outcomes were examined in CD patients diagnosed at age <17 years and enroled in the National Institute for Health Research IBD-UK BioResource at a median age of 24 years. All outcomes and BMI were recorded at the time of enrolment. Participants were categorised into normal (<25 kg/m2) and high (≥25 kg/m2) BMI. Age at disease diagnosis was categorised into pre-puberty/early puberty (<11 years), puberty (11–14 years) and post-puberty (15–17 years). Spearman rank correlation was used to test the associations between continuous variables and chi-square test to compare categorical variables.Results848 participants with CD were included (51.8% males) and median age at diagnosis was 14 years. Participants with high BMI experienced a greater frequency of EIMs (P = 0.05) than those with low BMI (1 type of EIM: 18.5% vs. 13.2%, respectively; ≥2 types of EIMs: 7.8% vs. 5.6%, respectively). Age at diagnosis and BMI showed weak correlations with corticosteroid use (ρ = 0.08, P = 0.03 and ρ = −0.09, P = 0.01; respectively). An early diagnosis (<11 years) was associated with higher occurrence of stenosing and penetrating disease behaviour (P = 0.01) and hospitalisations (P < 0.001).ConclusionsA higher BMI and an earlier age of disease onset are associated with worse CD clinical presentation.

Polyphenol-Rich Extract from 'Limoncella' Apple Variety Ameliorates Dinitrobenzene Sulfonic Acid-Induced Colitis and Linked Liver Damage.

Inflammatory bowel conditions can involve nearly all organ systems and induce pathological processes through increased oxidative stress, lipid peroxidation and disruption of the immune response. Patients with inflammatory bowel disease (IBD) are at high risk of having extra-intestinal manifestations, for example, in the hepatobiliary system. In 30% of patients with IBD, the blood values of liver enzymes, such as AST and ALT, are increased. Moreover, treatments for inflammatory bowel diseases may cause liver toxicity. Apple polyphenol extracts are widely acknowledged for their potential antioxidant effects, which help prevent damage from oxidative stress, reduce inflammation, provide protection to the liver, and enhance lipid metabolism. The aim of this study was to investigate whether the polyphenol apple extract from Malus domestica cv. 'Limoncella' (LAPE) may be an effective intervention for the treatment of IBD-induced hepatotoxicity. The LAPE was administrated in vivo by oral gavage (3-300 mg/kg) once a day for 3 consecutive days, starting 24 h after the induction of dinitro-benzenesulfonic acid (DNBS) colitis in mice. The results showed that LAPE significantly attenuated histological bowel injury, myeloperoxidase activity, tumor necrosis factor and interleukin (IL-1β) expressions. Furthermore, LAPE significantly improved the serum lipid peroxidation and liver injury in DNBS-induced colitis, as well as reduced the nuclear transcription factor-kappaB activation. In conclusion, these results suggest that LAPE, through its antioxidant and anti-inflammatory properties, could prevent liver damage induced by inflammatory bowel disease.

Metastatic crohn’s disease in a child: rare extraintestinal manifestation

Extraintestinal manifestations occur in every second child with Crohn’s disease, can affect any organ system, and determine the type of therapy and prognosis of the disease. The skin is the most frequent “target organ” of all extraintestinal manifestations, the spectrum of skin lesions is extremely clinically and pathogenically heterogeneous. Metastatic Crohn’s disease (MBC) is a rare extraintestinal manifestation of the disease, approaches to the diagnosis and management of which are not standardized in either adults or children. The most frequent description of MBC in the literature is skin damage, although interstitial lung damage, bone and muscle damage, and ENT organs, could be destructive. MCD lesions vary in morphology and can arise anywhere on the skin, rarely undergo reverse development, require special approaches to therapy. The primary diagnosis of such elements is extremely difficult, often delated, biopsy is required for a definitive diagnosis - the detection of epithelioid granuloma and its elements outside the gastrointestinal tract. Therapeutic approaches to MCD are not standardized now, they are carried out according to the protocols of CD management, and the effect of the use of oral steroids, a-TNFa drugs is shown. A case of metastatic Crohn’s disease in a 16-year-old teenager with an unusual localization - the nasal septum is described. The destructive nature of the lesion with the formation of perforation of the nasal septum determined the difficult path of differential diagnosis with Wegener’s granulomatosis. Morphological examination of the biopsy of the nasal mucosa revealed epithelioid cells of sarcoid-like granuloma. Systemic glucocorticosteroids use (GCS) led to epithelialization of the nasal septum defect and a decrease in the activity of CD in the intestine mucosa.

Ustekinumab in the Treatment of Inflammatory Bowel Diseases: Evolving Paradigms.

Inflammatory bowel diseases, comprising Crohn's disease (CD) and ulcerative colitis (UC), are chronic, relapsing, and remitting immune-mediated inflammatory diseases affecting the gastrointestinal tract. Ustekinumab (UST) is a monoclonal antibody that blocks the p40 subunit of the anti-interleukin (IL) 12/23. Pivotal trials (CERTIFI and UNITI-IM for CD, UNIFI for UC) established the efficacy of UST for the induction and maintenance of remission in both CD and UC, with the most favorable results in naïve patients to biologics. In recent years, a wealth of 'real-world' data has emerged supporting positive clinical, endoscopic, and histological outcomes in patients treated with UST, as well as reassuring safety data. More recently, the results of the first head-to-head trials of UST and tumor necrosis factor (TNF) antagonists were reported. Moreover, a number of studies exploring the role of UST in specific clinical settings, such as perianal CD, postoperative complications and recurrence, extraintestinal manifestations, chronic antibiotic-refractory pouchitis, and pregnancy, were reported. This review explores the results reported to date on UST, including those from pivotal trials, real-world data, and emerging studies regarding therapeutic drug monitoring and immunogenicity. The safety profile of UST was also reviewed.

An Unusual Case of Widespread, Pruritic Metastatic Crohn’s

Patients suffering from Crohn’s disease often present with skin symptoms, mainly in the perianal area. We here report on a patient with widespread granulomatous skin lesions covering a large body surface. Histology findings together with the clinical presentation led to the diagnosis of “metastatic” Crohn’s disease. This case report is interesting due to the diagnostic challenges this type of skin manifestation presented. Of note, the Crohn’s disease (CD) affecting the Gastro Intestinal (GI) tract presented less severe than the skin symptoms. Extraintestinal manifestations and co-morbidities of Crohn’s disease are often challenging and require interdisciplinary management. We here describe an unusual case of metastatic Crohn’s Disease.

Impact of inflammatory bowel disease on the risk of acute coronary syndrome: A Swedish Nationwide Cohort Study.

There are conflicting data on the risk of acute coronary syndrome (ACS) in patients with inflammatory bowel disease (IBD). Only a few previous reports include patients diagnosed during the last decade. To assess and compare the risk of ACS between patients with IBD and the general population. In this cohort study, we used nationwide registers to identify patients diagnosed with IBD in Sweden 2003-2021. Every patient was matched by birth year, sex, calendar year and area of residence with up to 10 general population comparators. The primary outcome was incident ACS. We used semi-parametric Cox proportional hazard models to estimate hazard ratios (HRs). We identified 76,517 patients with IBD (Crohn's disease [CD], N = 22,732; ulcerative colitis [UC], N = 42,194 and IBD-unclassified, N = 11,591) and 757,141 comparators. During a median follow-up of 8 years, 2546 patients with IBD (37.5/10,000 person-years) were diagnosed with ACS compared with 19,598 (28.0/10,000 person-years) among comparators (HR 1.30; 95% confidence interval 1.24-1.35) after adjustments for confounding factors, and approximately one extra case of ACS in 100 IBD patients followed for 10 years. The highest HRs for ACS were in patients with elderly onset IBD (≥60 years) and among patients with CD or UC with extra-intestinal manifestations. No increased HRs were observed in patients diagnosed with IBD before the age of 40. In this contemporary cohort of patients with IBD, exposed to modern IBD care, there was an increased risk for ACS compared with individuals from the general population.

Navigating the Gut-Cardiac Axis: Understanding Cardiovascular Complications in Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) presents a complex interplay of chronic inflammation in the gastrointestinal tract and is associated with various extraintestinal manifestations, including cardiovascular complications (CVCs). IBD patients face an elevated risk of CVCs, including coronary artery disease, heart failure, arrhythmias, stroke, peripheral artery disease, venous thromboembolism, and mesenteric ischemia, necessitating comprehensive cardiovascular risk assessment and management. The intricate interplay between chronic inflammation, genetic predisposition, environmental factors, and immune dysregulation likely contributes to the development of CVCs in IBD patients. While the exact mechanisms linking IBD and CVCs remain speculative, potential pathways may involve shared inflammatory pathways, endothelial dysfunction, dysbiosis of the gut microbiome, and traditional cardiovascular risk factors exacerbated by the chronic inflammatory state. Moreover, IBD medications, particularly corticosteroids, may impact cardiovascular health by inducing hypertension, insulin resistance, and dyslipidemia, further amplifying the overall CVC risk. Lifestyle factors such as smoking, obesity, and dietary habits may also exacerbate cardiovascular risks in individuals with IBD. Lifestyle modifications, including smoking cessation, adoption of a heart-healthy diet, regular exercise, and optimization of traditional cardiovascular risk factors, play a fundamental role in mitigating CVC risk. Emerging preventive strategies targeting inflammation modulation and gut microbiome interventions hold promise for future interventions, although further research is warranted to elucidate their efficacy and safety profiles in the context of IBD. Continued interdisciplinary collaboration, advanced research methodologies, and innovative interventions are essential to address the growing burden of CVCs in individuals living with IBD and to improve their long-term cardiovascular outcomes.

Takayasu arteritis after COVID-19 infection in a 26-year-old female patient with Crohn's disease

Extraintestinal manifestations, e.g. of the skin, joints or liver, are frequently found in Crohn's disease. We report about a 26-year-old female patient with longstanding Crohn's disease, who was admitted to our hospital with suspicion of an acute attack with suggestive symptoms and increased significantly inflammatory parameters. Shortly before, symptomatic COVID-19 disease (SARS-CoV-2 variant omicron) had been made. Comprehensive endoscopic and imaging diagnostics ruled out active Crohn's disease. However, inflammatory thickening of the aortic arch was seen, and a diagnosis of Takayasu arteritis (type II b) was made. Steroid therapy resulted in a rapid and sustained improvement of clinical symptoms. The occurrence of Takayasu arteritis is extremely rare outside Japan. An coincidence has been described in chronic inflammatory bowel diseases and is discussed as a possible extraintestinal manifestation. The occurrence of immune-mediated disease after COVID-19 disease has been described and may be triggered by the infection. Patients with inflammatory bowel disease may represent a special risk population.

Latest Treatment Perspectives for IBD-related Arthritis - a review

Introduction: IBD-related arthritis (spondyloarthropathy) is the most common extraintestinal manifestation (EIM) of inflammatory bowel disease (IBD) and is often considered a formidable clinical challenge. Emergence of TNFα-antagonists has revolutionised the clinical approach to management of IBD-related arthritis and remains the mainstay of the therapy. However, its use presents several limitations, underscoring the need for new treatment modalities. Recently, new agents have been approved for the management of IBD, although their influence on IBD-related arthritis has been scarcely investigated. Aim of the Study: The aim of the study was to collect and analyse current literature regarding the efficacy of new agents used for treating IBD-related arthritis. Methods and Materials: Extensive research was conducted using the PubMed, ScienceDirect database and Google Scholar, with the primary focus on literature from the past 5 years. Firstly, potential novel treatment options for IBD-related arthritis were obtained. The names of the drugs were juxtaposed with terms related to “IBD-related arthritis” to gather data regarding their efficacy in said condition. Additionally, references from selected articles were included in the analysis. Results: Emerging treatment options show promising results in achieving remission of IBD-related arthritis. However, our study revealed research gap as the current literature lacks large-scale, prospective studies that assess the efficacy of the aforementioned agents in achieving a resolution of IBD-related arthritis. Therefore, the results of our study encourage further research, with special emphasis on large-scale randomised controlled trials.

A242 EPIDEMIOLOGICAL ASPECTS, RISK FACTORS, AND CUMULATIVE PREVALENCE OF EXTRAINTESTINAL MANIFESTATIONS IN INFLAMMATORY BOWEL DISEASE: RESULTS FROM A 7,150 PATIENTS’ COHORT IN A TERTIARY CARE CENTER

Abstract Background Canada is among the countries with a high burden of inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC). Extraintestinal manifestations (EIMs) incorporate a spectrum of systemic IBD-accompanying conditions that are associated with a poorer quality of life, higher disease activity, and increased need for IBD-related surgery and treatment escalation. Aims We aimed to establish the all-time and cumulative prevalence of EIMs in a large cohort of IBD patients and assess the risk factors associated with EIMs in IBD. Methods We conducted a retrospective cohort study of 7,150 IBD patients followed at the Division of Gastroenterology, University of Alberta, diagnosed between 1954–2022, with 159,026 person-years follow-up. Data were obtained via manual chart review, from electronic medical records and administrative reporting systems. The EIMs included ophthalmological, musculoskeletal, urogenital, hepatobiliary, dermatological, and pulmonary. Univariate and multivariate logistic regression models and cumulative prevalence curves with the Kaplan-Meier analysis were used. Results Data of 3,910 CD and 3,240 UC patients (50.3% females, median age 48.0 (range 17-98 y.o.)) were analyzed. Over one-third of IBD patients (34.0%) had at least one EIM. The EIMs prevalence did not differ significantly between CD and UC (34.8% vs. 33.0%; p=0.112). In CD patients, the most common EIM was scleritis/episcleritis (10.9%), followed by nephrolithiasis (10.1%) and axial spondyloarthritis (7.3%). The UC patients most frequently had scleritis/episcleritis (10.3%), primary sclerosing cholangitis (8.4%) and nephrolithiasis (7.8%). In CD patients, age at diagnosis ≥40 y.o. (OR 1.77, 95%CI 1.33-2.37), disease duration ≥20 years (OR 2.28, 95%CI 1.62-3.21) and C-reactive protein≥8.0 mg/L (OR 1.46, 95%CI 1.01-2.12) were independent risk factors for EIMs (Fig.1a). Among UC patients, the following EIM risk factors were identified: disease duration ≥20 years (OR 1.63, 95%CI 1.19-2.22), obesity (OR 1.40, 95%CI 1.04-1.89), vitamin B12 deficiency (OR 1.64, 95%CI 1.12-2.40), and need for IBD surgery (OR 1.63, 95%CI 1.13-2.34) (Fig.1b). Cumulative probability of EIMs in CD vs. UC was 8% vs. 12%, at 10 years, 27% vs. 38% at 20 years, and 51% vs. 59% at 30 years since diagnosis (Log-rank, pampersand:003C0.001) (Fig.1c). Conclusions Over one-third of IBD patients have at least one EIM and their pattern and cumulative prevalence varies substantially between CD and UC. It is important to be aware of the EIMs’ risk factors to recognize them early and provide adequate management aiming to decrease morbidity and mortality and improve the quality of life of IBD patients. Fig. 1a. Associations between demographic, phenotypic and clinical IBD features and EIMs among CD patients - results of the multivariate logistic regression analysis. Fig. 1b. Associations between demographic, phenotypic and clinical IBD features and EIMs among UC patients - results of the multivariate logistic regression analysis. Fig 1c. Cumulative prevalence of EIMs in CD (grey line) vs. UC (pink line). Funding Agencies None

A236 THE EFFECTIVENESS AND SAFETY OF DUAL ADVANCED THERAPIES IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE: A CASE-SERIES

Abstract Background Patients with inflammatory bowel disease (IBD) refractory to medical therapy and patients with IBD and concurrent extra-intestinal manifestations (EIMs) pose a challenge within gastroenterology. The small number of approved agents for IBD limits therapeutic options for this population. Utilizing a combination of newer biologic therapies with favourable safety profiles may provide a safe and efficacious option for treating patients with refractory disease or patients with well-controlled IBD but uncontrolled EIMs. Aims The aim of our study was to assess the safety and efficacy of dual advanced therapies for patients with IBD. Methods Patients at London Health Sciences Centre and St. Joseph’s Healthcare Centre on dual advanced therapies for inflammatory bowel disease were retrospectively assessed for a minimum period of 12 months. Major bacterial infection, adverse events, endoscopic, histologic, and clinical remission of IBD, and remission of EIMs of IBD were assessed. Results Five patients with Crohn’s disease receiving dual advanced therapies were identified. Stricturing Crohn’s disease was the predominant phenotype in 80% of the patients. One patient had perianal fistulizing disease. Dual therapy was initiated for concurrent management of EIMs in 80% of patients (enteropathic arthritis in 2 patients, spondyloarthritis in 2 patients, rheumatoid arthritis in 1 patient) and for refractory IBD in one patient. The majority of patients were on a combination of a tumour-necrosis-factor inhibitor and vedolizumab. Other advanced therapies included JAK inhibitors and ustekinumab. The patients were predominantly female (80%) and age at diagnosis was ampersand:003C50 years old in 80% of patients. No adverse events or major bacterial infections were observed during dual therapy. At the end of follow-up, all 5 patients were in clinical remission of their IBD and 4 patients demonstrated endoscopic remission. Only 60% of patients had remission of their EIMs within the follow-up period. Conclusions Our findings suggest that dual advanced therapies are safe and may represent a long-term treatment option for complicated patients with IBD. Funding Agencies None