Presence Of 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.

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.

P989 Switching from intravenous to subcutaneous vedolizumab in patients with inflammatory bowel disease in clinical remission: a multicenter study from GETECCU

Abstract Background Despite the established use of intravenous (IV) vedolizumab for treating inflammatory bowel disease (IBD), there's growing interest in exploring the advantages of the novel subcutaneous (SC) administration route. However, comprehensive real-world evidence regarding the extended safety and effectiveness of this approach remains scarce. The aim of the study was to evaluate the effectiveness and safety of vedolizumab SC among IBD patients in clinical remission. Methods Multicenter, observational, retrospective study. IBD patients on IV vedolizumab treatment across 24 Spanish hospitals who were in clinical remission were given the option to switch to SC injections or continue with IV treatment. Data encompassing clinical disease activity (assessed through partial Mayo score, and Harvey-Bradshaw Index), biochemical markers (C-reactive protein and fecal calprotectin), adverse events and treatment persistence were retrospectively gathered from prospectively maintained clinical records at baseline, and at weeks 12, 24, and 48. Non-parametric tests were used for comparisons and Kaplan-Meier for survival. Results We identified 166 patients, with 19 excluded due to not being in clinical remission and 8 excluded due to absence of follow-up data, resulting in a final inclusion of 139 patients for analysis. Of these, 36 (25.9%) remained on IV vedolizumab, while 103 (74.1%) switched to SC vedolizumab. Both groups exhibited comparable demographic characteristics including age, gender, disease type, disease duration and extension, previous therapy, presence of extra intestinal manifestations and comorbidities (Table 1). However, there were differences in Crohn’s disease behavior among groups (p=0.013). There were not significant differences in clinical, biochemical and fecal calprotectin remission at week 12, 24 and 48 neither in the overall cohort nor assessing Crohn’s disease or ulcerative colitis separately (Figure 1). At the end of follow-up, median duration 47 weeks (29-49), persistence on the same formulation was 85%,1 (2.8%) patient on IV and 4 (3.9%) on SC withdrew the drug (p=0.810), 5 (4.8%) switched back to IV from SC. Adverse events were reported in 1 (2.8%) IV vs 11 (10.7%) SC vedolizumab (p=0.292), most of them being mild skin reactions to SC injection 3 (2.9%). Conclusion In our study we found that transitioning from IV to SC vedolizumab in patients with IBD in remission showed comparable effectiveness in maintaining disease remission. Switching to SC formulation appears safe with no new safety signals identified and most adverse events being mild.

P631 Effectiveness of Early Thiopurine Use in Korean Patients with Moderate-to-Severe Ulcerative Colitis: A Prospective Multicenter Cohort (MOSAIK) study

Abstract Background Thiopurines play an important role in the management of steroid-refractory steroid-dependent ulcerative colitis (UC). However, the effectiveness of the early use of thiopurines in UC remains controversial. Methods In this multicenter prospective cohort study, we divided patients with UC into those who underwent early (within 6 months of diagnosis) and late (6 months after diagnosis) thiopurine therapy to determine the effectiveness of early thiopurine treatment. The primary outcome was the cumulative rate of clinical relapse (Mayo score >2 points). Multivariate Cox proportional hazards regression was used to identify independent clinical factors associated with the outcomes. Results Overall, 333 patients with moderate-to-severe UC were included in the MOSAIK study. Of the 118 patients treated with thiopurines, 65 (55.1%) and 53 (44.9%) received thiopurine therapy within and after 6 months of diagnosis. The cumulative use rate of thiopurines was 38.96% at 3 years after diagnosis. The median initial dose of thiopurines was 0.7 mg/kg (0.3–2.0), and the median maintenance dose was 1.1 mg/kg (0.3–2.4). The cumulative rate of clinical relapse was not significantly different between patients who started thiopurine therapy within 6 months of diagnosis and those who started therapy 6 months after diagnosis during a 3–year period (p = 0.712). Multivariate analysis showed that the presence of extraintestinal manifestations (hazard ratio [HR]: 4.674, 95% CI: 1.210–18.061, p = 0.025) independently predicted an increased risk of clinical relapse. Conclusion Patients with UC who received early thiopurine therapy did not differ significantly in terms of clinical relapse compared with those who received late therapy.

P370 Quality of life in inflammatory bowel diseases – is the flare all that matters?

Abstract Background Burden in inflammatory bowel diseases (IBD) is high and affects both physical and psychological status. Short inflammatory bowel disease questionnaire (SIBDQ) is a self-administered health-related quality of life questionnaire that evaluates social, bowel, emotional and systemic dimension. Our aim is to evaluate the impact of IBD status on patients’ daily life. Methods We analysed 82 patients diagnosed with Crohn’s disease or ulcerative colitis or that were admitted between March 2021 and April 2022 in Fundeni Clinical Institute, Bucharest. SIBDQ consists of ten questions, with score ranging from 10 (poor) to 70 (optimal). Patients completed SIBDQ and we assessed disease status and determined biological and clinical markers. Results 51% of patients were diagnosed with Crohn’s Disease. 79% were in clinical remission. The mean age was 39.53±12.9 years old and 52.4% were men. Mean illness duration was 8.03±7.18 years. Mean SIBDQ score was 50.25±14.51, with significantly higher scores in the remission subgroup (55.26±10.30 vs. 31.11±12.24, p<0.001) and it correlated with faecal calprotectin level (ρ=-0,502) and C-reactive protein level (ρ=- 0,531), without regard to disease type or sex. There were no correlations between SIBDQ score and Crohn’s disease or ulcerative colitis phenotype, duration since diagnosis, presence of extraintestinal manifestations or history of abdominal surgery related to IBD. Conclusion Patients with IBD flares have low quality of life and SIBDQ scores correlate with markers of disease severity, comparable to previously-published literature. Patients in clinical remission presented with higher SIBDQ scores, independently of IBD phenotype or previous surgery. Acute flares of IBD have a major impact on daily life, additional psychological and social support is needed in order to improve management.

P779 Long term efficacy of azathioprine monotherapy in patients with Inflammatory Bowel Disease

Abstract Background ECCO guidelines recommend monotherapy with azathioprine (AZA) as maintenance therapy of patients with inflammatory bowel disease (IBD) mainly in steroid-dependent disease. However, in the era of the new advanced treatments AZA is not considered as a preferable option, mainly because of the referred side effects and its use is limited in combination with biologic agents. Methods This is a retrospective observational study using data from the longitudinal, prospective IBD registry of University Hospital of Heraklion, Greece. Our aim was to study IBD patients who started on monotherapy with AZA, the profile of adverse effects they developed, the treatment persistence in monotherapy, as well as the possible related factors of treatment success [including age, gender, smoking status, body mass index, disease type, disease phenotype for Crohn’s disease (CD), history of IBD related surgery and the presence of extraintestinal manifestations]. Results Of 168 IBD patients treated with AZA, 89 (53%) were under AZA monotherapy [38 (43%) female, 67 (74%) CD, median age (IQR) 47 (32-56) years, mean (±SD) disease duration 17 (±8.4) years, median (IQR) time receiving AZA 72 (7-120) months]. Thirty (34%) patients continue their treatment till now (23 CD, 7 ulcerative colitis-UC), with a median time (IQR) of 108 (81-132) months. Of these, 18 (60%) (15 with CD and 3 with UC) present endoscopic remission and 11 (36%) (8 with CD, 3 with UC) mild endoscopic activity (based on SES-CD Score for CD and Mayo endoscopic score for UC). Of the 59 who discontinued, 33 (37%) experienced adverse events, 5 (5.5%) developed malignancy, 5 (5.5%) did not respond at baseline, 6 (6.5%) had loss of response (at a median of 91 months), 3 (3%) discontinued due to advanced age, 3 (3%) discontinued their medication on their own and 2 because of treatment de-escalation due to deep remission. Using logistic regression analysis, patients who responded to AZA monotherapy were patients without a history of IBD surgery or any extraintestinal manifestation, P=0.001 and 0.004, respectively. In the multivariate analysis, these associations remained statistically significant (P=0.01 and 0.006 respectively). Conclusion About one third of patients with IBD under AZA monotherapy experience long term response and about two thirds of them prolonged disease remission. Patients without either a history of IBD surgery or extraintestinal manifestations seem to respond better to AZA monotherapy.

P1197 ERAP2 genetic variant rs2248374 is linked to paradoxical skin reactions induced by TNF-alpha inhibitors in Romanian patients with Inflammatory Bowel Diseases

Abstract Background The endoplasmic reticulum aminopeptidases (ERAPs) are responsible for trimming protein residues to optimal length for major histocompatibility complex class-1 mediated antigen presentation process. Genome-wide association studies have shown the influence of ERAP1 and ERAP2 genetic variants in disease susceptibility for autoimmune disorders. Their role in inflammatory bowel diseases (IBD) however remains obscure due to literature data paucity. The aim of this study was to evaluate the role of a single nucleotide polymorphism (SNP) rs2248374 (G/A) of ERAP2 gene in disease susceptibility and response to treatment in Romanian population with IBD. This SNP is of particular importance because the G allele produces a truncated ERAP2 transcript undergoing nonsense-mediated decay and therefore individuals with GG genotype have no functional ERAP2 enzyme. Methods The study involved 186 IBD patients (87/99 UC/CD, 91M/69F) and 150 healthy controls (77M/73F) all unrelated and of Romanian ethnicity. Extraintestinal manifestations (EIM) were documented in 43 IBD patients (19UC/24BC). Among patients with biological treatment against TNF-alpha (N=113) there were 31 (27.4%) primary non-responders and 13 (11.5%) with paradoxical skin reactions. All subjects were genotyped for ERAP2 rs2248374 (G/A) using TaqMan Allelic Discrimination Assay (C_25649529_10 Real-Time PCR System, Applied Biosystems by Thermo Fisher Scientific, USA). Association tests were performed with OpenEpi online software using Two by Two Table statistics. P-values (2-tail from Mid-P exact test) were considered significant if <0.05. Results Controls and patients were in Hardy-Weinberg equilibrium for the investigated SNP. No significant differences were observed in relation with the risk of disease or with the therapy response. The minor allele A frequency was significantly lower in IBD patients with paradoxical skin reactions (27%) versus patients without these manifestations (50%, p=0.02, OR 0.36). The genotype AA, responsible for full ERAP2 expression, had 0% frequency in the group with adverse skin reactions compared with 23.2% in patients without (p=0.04, OR 0.0). The GG genotype which is related with no ERAP2 protein expression was more frequent in the subgroup of patients with EIM (41.8%) than in patients without EIM (26.7%), showing a marginal association (p=0.06, OR 1.97). Conclusion Our results point to the fact that ERAP2 rs2248374 AA genotype exerts a protective effect over paradoxical skin reaction induced by TNF antagonist agents, and GG genotype shows marginal association with the presence of EIM in Romanian patients with IBD. We consider these results worthy of replication in larger cohorts of patients.

Extraintestinal Manifestations of Inflammatory Bowel Disease Are Associated With Increased Biologic Cycling.

Extraintestinal manifestations (EIMs) of inflammatory bowel disease (IBD) are a common, frequently debilitating complication of the disease. Biologics are indicated and often required in patients with EIMs to control disease; however, little is known about whether patients with EIMs cycle through more therapies than their counterparts without EIMs. To address this question, we performed a retrospective analysis of patients enrolled in the Study of Prospective Adult Research Cohort with IBD registry seen at our University Medical Center, on data from December 2016 to January 2021. Four hundred fifty-six participants with information on EIMs and biologic use available were included, and demographic and clinical characteristics were analyzed. Three hundred thirty-eight and 118 participants without and with EIMs were identified, respectively. Those with EIMs were likelier to have biologic exposure, and cycle through more biologics, both in univariate and multivariate analyses controlling for age, disease duration, sex, corticosteroid use, and IBD type (P-value = .006). In a subanalysis of patients with Crohn's disease (CD), EIMs were associated with increased biologic cycling in ileocolonic disease (P-value = .050). To our knowledge, this is the first study assessing biologic cycling in patients with EIMs. Our findings that patients with EIMs are likelier to cycle through biologics, particularly CD patients with ileocolonic disease, highlights the need for more research on which biologics may be most effective for specific subsets of IBD patients, including those with concurrent EIMs. The presence of EIMs is a marker of harder-to-treat IBD and may indicate earlier initiation of advanced therapies.

Prevalence of and Factors Associated With Extraintestinal Manifestations and Their Remission in Inflammatory Bowel Disease: The EXTRA-Intestinal Manifestation Prospective Study From the Groupe d'Etude Thérapeutique des Affections Inflammatoires du Tube Digestif.

Extraintestinal manifestations (EIMs) of inflammatory bowel disease (IBD) are challenging clinical situation. No prospective study assessed remission risk factors of EIMs. The aim of this study was to prospectively investigate the epidemiology, risk factors of EIM occurrence, and EIM remission in a large IBD cohort. We conducted a cross-sectional study in 30 French referral centers. Between May 2021 and June 2021, all consecutive patients attending to hospital appointment were systematically invited to fill out a questionnaire. A total of 1,971 consecutive patients with IBD were analyzed. There were 1,056 women (53.8%), and the median age of patients was 41 years (31-54). The median disease duration was 11 years (1-18). Overall, 544 (27.6%) had at least 1 EIM. In 20.2% of cases, patients had multiple EIMs. The most frequent EIMs were rheumatological (19%) and dermatological (10%) manifestations. Immunosuppressant treatment (odds ratio [OR] = 2.56; P < 0.001) was a risk factor of EIM, while the Montreal A3 classification (OR = 0.61, P = 0.023) and male gender (OR = 0.61, P < 0.001) were associated with a lower risk of EIM occurrence. IBD current clinical remission (OR = 2.42; P < 0.001) and smoking cessation (OR = 2.98; P < 0.001) were associated factors of EIM remission. Conversely, age at IBD diagnosis (OR = 0.98; P < 0.018) was associated with a lower risk of EIM remission. One quarter of patients had at least 1 EIM. Beyond factors associated with the presence of EIMs, patients with IBD current clinical remission and smoking cessation are more likely to achieve EIM remission, while increasing age at IBD diagnosis is associated with decreased chance of remission.

Prevalence of Immunomodulator Use as Combination Therapy With Vedolizumab or Ustekinumab in Inflammatory Bowel Disease.

The benefit of adding an immunomodulator to vedolizumab and ustekinumab remains unclear and may compromise the safety of these biologics. We evaluated the prevalence and predictors of immunomodulator use with vedolizumab or ustekinumab in patients with inflammatory bowel disease in a large longitudinal cohort. Clinical information was ascertained from electronic medical records of patients enrolled in TARGET-IBD, a prospective longitudinal observational cohort of patients with inflammatory bowel disease (IBD) at 34 sites. The prevalence of immunomodulator use with vedolizumab, ustekinumab, and antitumor necrosis factor therapies and predictors of immunomodulator use with vedolizumab and ustekinumab were estimated. Rates of combination therapy were additionally stratified by time from drug approval. Four thousand thirty-nine adults with IBD were identified, of whom 18.8% were treated with vedolizumab and 13.0% were treated with ustekinumab. Combination therapy with vedolizumab and ustekinumab exceeded 30% (30.7% and 36.2%, respectively) and was more likely in those with perianal disease or previous biologic exposure. Age and presence of extraintestinal manifestations did not consistently predict the use of an immunomodulator. Combination therapy decreased in the years after drug approval. Combination therapy with vedolizumab or ustekinumab was common and was associated with perianal disease and greater exposure to other biologics, although the practice is decreasing with time. Further data are needed to determine the efficacy and safety of combination therapy in patients initiating vedolizumab or ustekinumab for IBD.

Natural History of Anal Ulcerations in Pediatric-Onset Crohn's Disease: Long-Term Follow-Up of a Population-Based Study.

Anal ulcerations are frequently observed in Crohn's disease (CD). However, their natural history remains poorly known, especially in pediatric-onset CD. All patients with a diagnosis of CD before the age of 17 years between 1988 and 2011 within the population-based registry EPIMAD were followed retrospectively until 2013. At diagnosis and during follow-up, the clinical and therapeutic features of perianal disease were recorded. An adjusted time-dependent Cox model was used to evaluate the risk of evolution of anal ulcerations toward suppurative lesions. Among the 1,005 included patients (females, 450 [44.8%]; median age at diagnosis 14.4 years [interquartile range 12.0-16.1]), 257 (25.6%) had an anal ulceration at diagnosis. Cumulative incidence of anal ulceration at 5 and 10 years from diagnosis was 38.4% (95% confidence interval [CI] 35.2-41.4) and 44.0% (95% CI 40.5-47.2), respectively. In multivariable analysis, the presence of extraintestinal manifestations (hazard ratio [HR] 1.46, 95% CI 1.19-1.80, P = 0.0003) and upper digestive location (HR 1.51, 95% CI 1.23-1.86, P < 0.0001) at diagnosis were associated with the occurrence of anal ulceration. Conversely, ileal location (L1) was associated with a lower risk of anal ulceration (L2 vs L1 HR 1.51, 95% CI 1.11-2.06, P = 0.0087; L3 vs L1 HR 1.42, 95% CI 1.08-1.85, P = 0.0116). The risk of fistulizing perianal CD (pCD) was doubled in patients with a history of anal ulceration (HR 2.00, 95% CI 1.45-2.74, P < 0.0001). Among the 352 patients with at least 1 episode of anal ulceration without history of fistulizing pCD, 82 (23.3%) developed fistulizing pCD after a median follow-up of 5.7 years (interquartile range 2.8-10.6). In these patients with anal ulceration, the diagnostic period (pre vs biologic era), exposure to immunosuppressants, and/or anti-tumor necrosis factor did not influence the risk of secondary anoperineal suppuration. Anal ulceration is frequent in pediatric-onset CD, with nearly half of patients presenting with at least 1 episode after 10 years of evolution. Fistulizing pCD is twice as frequent in patients with present or past anal ulceration.

Assessment of subclinical myocardial dysfunctions in Egyptian children with celiac disease, a cross-sectional study

BackgroundCeliac disease (CD) is a chronic immune-mediated disorder with multiple extraintestinal manifestations. The increased incidence of cardiac morbidities in celiac patients highlights the importance of early detection of subclinical myocardial dysfunctions. In this study, we aimed to assess the cardiac functions and explore early subclinical myocardial dysfunctions in celiac patients by tissue Doppler imaging.ResultsA cross-sectional analytical study which included 42 celiac patients with CD and 36 age- and sex-matched controls. They were subjected to full medical history and examination and complete transthoracic echocardiography including tissue Doppler imaging to assess cardiac functions. Evidences of early subclinical systolic and diastolic dysfunctions were found in our patients; they had significantly lower tricuspid E/A ratio; lower S, E′, a′ in both ventricles; reduced mitral E′/a′ (2.13 ± 0.87, 2.94 ± 0.061 respectively, p < 0.001); and increased tricuspid E/e′ (6.09 ± 0.8, 4.15 ± 1.33 respectively, p < 0.001) compared to the controls. Biventricular MPI were within normal limits, yet with a significant difference from the control (p = 0.001). lower E′/a′ in the RV is significantly related to the extraintestinal manifestations (1.5 ± 0.48, 2.16 ± 0.71 respectively, p = 0.009).ConclusionChildren with CD had subclinical myocardial dysfunction especially in RV which is better detected by tissue Doppler imaging (TDI). These dysfunctions are increased with the presence of extraintestinal manifestations.

P155 Natural history of anal stricture in pediatric-onset Crohn’s disease: a two-decades population-based study

Abstract Background The natural history of anal stricture complicating pediatric-onset Crohn’s disease (CD) is poorly known. The aims of this study were: to determine in a population-based study the risk of anal stricture in pediatric-onset CD; to identify risk factors for anal stricture; and to evaluate the natural history of anal stricture at the population level. Methods All patients with a diagnosis of CD made before the age of 17 years between 1988 and 2011 in a population-based registry were followed retrospectively until 2013. A specific collection of additional data was performed in patients with anal stricture at diagnosis or during follow-up. Variables collected included: proctological examination, diagnostic management and treatment. Multivariate Cox models were used to identify factors associated with anal stricture. Results Among the 1,007 included CD patients (females, 451 (44.8%); median age at diagnosis 14.4 years (IQR, 12.0-16.1), median follow-up 8.8 years (IQR, 4.6-14.2)), only one (0.1%) had anal stricture at diagnosis while 26 (2.6%) presented anal stricture during follow-up. Cumulative incidence of anal stricture at 5 and 10 years after diagnosis was 0.6% (CI95%, 0.1-1.1) and 1.4% (CI95%, 0.5-2.3), respectively. Among the 27 patients with anal stricture, 25 (92.6%) had already at least one episode of anal ulceration or fistulizing perianal CD (pCD). In multivariable analysis, the presence of extra-intestinal manifestations (Hazard Ratio (HR) 2.2, CI95% 1.0-4.8, p=0.027), colonic location (L1 vs L3 HR 0.0 (-); L2 vs L3 HR 1.2, CI95% 0.6-2.7, p=0.006) and history of fistulizing pCD (HR 9.9, CI95% 4.3-22.8, p&amp;lt;0.0001) were significantly associated with anal stricture. Eleven (41%) patients needed at least one dilation. After a median follow-up of 16.9 years (IQR, 11.5-20.2), healing of anal stricture was observed only once. One patient (3.7%) presented an anal cancer 7 years after the diagnosis of anal stricture. Nine (33.3%) patients needed a stoma. Among them, 8 already had a fistulizing pCD and 4 needed an abdominoperineal amputation. Anal stricture was significantly associated with an increased risk of stoma (HR 5.8, CI95% 2.3-14.3), p=0.0002). Conclusion Anal stricture is a rare event in pediatric onset CD, occurring in 1.5% of patients over a 10 year-period after diagnosis. However, anal stricture had a negative impact on disease prognosis with a five-fold increase of the risk of stoma.

P280 Quality of life in military patients with Inflammatory Bowel Disease

Abstract Background Inflammatory Bowel Disease (IBD), represented by Crohn's disease (CD) and Ulcerative Colitis (UC), are chronic conditions that can impair quality of life (HRQOL). Active military personnel are particularly at risk, given the strain of their work and military missions. The aim of our study was to evaluate the HRQOL of active military patients with IBD and to search for factors related to its alteration. Methods This was a prospective cross-sectional study, over a period of 5 months [February 2022 - June 2022], including male military patients that were still serving. The HRQOL of these patients was assessed by the IBD-Disk, which is a visual scale that consists of 10 items (Abdominal pain, diarrhea, social behavior, education and work, sleep, energy, emotions, body image, sexual activity, joint pain). It is validated for the assessment of HRQOL in IBD patients. Each dimension is scored from 0 to 10, with a total score of 0 to 100. The higher the score, the more impaired the HRQOL. The overall IBD-Disk score was considered impaired if it was higher than 40. Results We included 30 patients. The most represented age range was from 31 to 40 years. Ten patients were smokers. Twenty-four patients had CD and 6 had UC. The majority of CD was isolated ileal (n=16) with an upper gastrointestinal tract involvement in one patient and anoperineal manifestations in 5 patients. UC was distal in 3 patients and extensive in the other 3. Nine patients had extra-intestinal involvement, principally rheumatological (n=8). The mean overall IBD-Disk score was 21.6 [6 - 66]. We noted that CD was associated with the alteration of the dimensions related to urgent stools (p=0.001), social life (0.002) and sleep (p=0.004). The presence of anoperineal lesions during CD was associated with impairment of the social (p=0.002) and energy (p=0.006) dimensions. The presence of extra-intestinal manifestations was associated with elevated social dimension score (p=0.002). Azathioprine treatment was associated with impaired sleep dimension (p=0.048). Patients with a disease that had been evolving for more than 5 years had an alteration in the dimension related to urgent stools (diarrhea) (p=0.036), energy (p=0.048) as well as the dimension of sexual life (p=0.042). History of hospitalization for IBD was associated with impaired body image (p=0.030). History of surgical resection was associated with impaired energy (p=0.029), sexuality (p=0.015) and overall quality of life (p=0.02). Conclusion In our active military patients, HRQOL was not impaired overall, but several factors, related to severe forms, were associated with lower HRQOL.

P561 Risk of stoma formation in patients with Crohn’s perianal fistulas over a two decades period. A cohort study from a tertiary referral center.

Abstract Background Optimal management of perianal Crohn’s disease (pCD) consists of combined medical (preferentially anti-TNF) and surgical treatment. However, it is still unclear if this has improved outcomes. This study aimed to described outcome and prognosis of pCD patients at a referral center over almost two decades. Methods All pCD patients referred for active perianal fistulas between 2000-2018 at our center were considered eligible for this retrospective study. Patients were divided into two groups according to the date of pCD diagnosis: period A (2000-2006) and period B (2006-2018). The complement of Kaplan-Meier estimates were used to visualize the time since pCD diagnosis until temporary and definitive fecal diversion. Clinically important outcomes such as need for temporary or permanent fecal diversion, and factors associated to these outcomes were evaluated by Cox regressions models. Results A total of 336 patients with active pCD were identified. The mean interval between the diagnosis of CD and the perineal fistulizing disease was 4.9 years (+-7.64). Mean follow up was 10.83 years (SD ± 4.5). The two groups were similar for demographic and clinical characteristics, except for the cumulative exposure to biologicals prior to pCD diagnosis [27.8% vs 46.9% in period A and B, respectively (p&amp;lt;0.001)]. (Table 1) The risk for temporary and definitive fecal diversion was higher for group B, at 5- [temporary stoma: 10.8 CI (6.7%-17.3%) vs 27.3% CI (21.1%-34.9%), p&amp;lt;0.001; definitive stoma: 0.7% CI (0.1%-4.8%) vs 13.1% CI (8.7%-19.5%), p=0.002] and 10-years follow-up [temporary stoma: 23.3% CI (17%-31.5%) vs 39.0% CI (31.1%-48.1%), p&amp;lt;0.001; definitive stoma: 11.7% CI (7.2%-18.7%) vs 19.9% CI (13.9-28.0%), p=0.002], respectively. (Figure 1 and Figure 2). At multivariate analysis, the presence of extraintestinal manifestations [HR 2.55 CI (1.40-4.62)], B2 stricturing disease [HR 4.43 CI (1.46-13.4)], B3 penetrating disease [HR 7.10 CI (2.37-21.27)], and diagnosis of pCD diagnosis after 2006 (period B) [HR 2.20 CI (1.16-4.17)], were independent risk factors for need for permanent ileostomy. (Table 2) Conclusion This retrospective analysis spanning almost twenty years shows that prognosis of CD patients affected by anal fistulas remains poor and has not much changed over time, despite the introduction of biologicals and new surgical techniques. The observed increase in definitive fecal diversion in more recent years can be partially explained by referral bias and/or a more aggressive clinical management of the most severe cases. Extraintestinal manifestations and synchronous complicated luminal disease increased the risk of definitive stoma in the long-term.

Linear Growth Impairment in Patients With Pediatric Inflammatory Bowel Disease.

IntroductionLinear growth impairment (LGI) is one of the complications of pediatric inflammatory bowel disease (IBD). This study aimed to assess the linear growth of patients with pediatric IBD and to detect the frequency and the possible risk factors of LGI.MethodsA retrospective cross-sectional review of medical records of patients with pediatric IBD was conducted in the pediatrics department, Salmaniya Medical Complex, Bahrain, from 1984 to 2019. Demographic and anthropometric data were gathered. World Health Organization (WHO) standards and references were used to define LGI. According to WHO, stunting and severe stunting were defined as length/height for age of <-2 standard deviations and <-3 standard deviations from age and sex-specific reference means, respectively. To determine the possible risk factors for LGI, stunted patients were compared with normal height patients in regard to demographic data, clinical presentations, and treatment used.ResultsOut of 130 patients with pediatric IBD, 88 (67.7%) had anthropometric data available. Fifty-five (62.5%) were males. Forty-seven (53.4%) had Crohn’s disease and 41 (46.6%) had ulcerative colitis. The mean age at presentation was 10.7±3.8 years. The median age at the time of growth measurement was 14.2 (interquartile range=12.1-24.4) years. Fifteen (17%) patients were stunted, and seven (46.7%) of those stunted patients were severely stunted. Weight at presentation was lower in stunted patients (21.6±5.9 kilograms) compared to normal height patients (31±13.4 kilogram) (p=0.048). Sex, delivery type, birth weight, height at presentation, age at presentation, age at growth measurements, IBD type, disease duration, presence of extraintestinal manifestations, and prednisolone and biologic therapy use were not significant factors of stunting.ConclusionPatients with pediatric IBD have a high prevalence of LGI compared to the general population. Low weight at disease presentation is the only significant risk factor for LGI. This might indicate that IBD as a disease by itself is having the main negative impact on linear growth.

Mimics of Crohn's Disease.

Crohn's disease is a chronic inflammatory disease that can affect any portion of the gastrointestinal tract. Associated symptoms can vary based on the severity of disease, extent of involvement, presence of extraintestinal manifestations, and development of complications. Diagnosis is based on a constellation of findings. Many diseases can mimic Crohn's disease and lead to diagnostic conundrums. These include entities associated with the gastrointestinal luminal tract, vascular disease, autoimmune processes, various infections, malignancies and complications, drug- or treatment-induced conditions, and genetic diseases. Careful consideration of possible causes is necessary to establish the correct diagnosis.

MEFV Mutations in IBD Patients: A Systematic Review and Meta- analysis.

Several studies have suggested that mutations in MEFV, the gene responsible for familial Mediterranean fever (FMF), are frequently detected in inflammatory bowel disease (IBD) patients. We aimed to provide further evidence regarding a potential correlation between MEFV gene mutations and IBD by identifying all relevant studies and analyzing their results. EMBASE, PubMed/MEDLINE, and Google Scholar were used to identify all studies that published until January 2021 and reported MEFV mutation patterns in patients with ulcerative colitis (UC), Crohn's disease (CD) and indeterminate colitis (IC) with or without a control group. The Newcastle-Ottawa quality assessment scale was used to appraise the quality of the included studies. Thirteen observational studies, including 937 patients and 977 controls, were analyzed. MEFV mutation rate in IBD patients was 0.238 (95%CI: 0.209-0.270; I 2 =95%); MEFV mutated alleles were more frequent in IBD patients when compared with controls (p=0.03 for UC, p=0.01 for CD and IC). Subgroup analysis indicated that MEFV mutations were increased in patients with IC when compared with UC and CD (I 2 =91%, p<0.001). Patients with extra-intestinal manifestations and pancolitis had 2.57 (95%CI 1.07-6.14; p=0.03) and 2.02 (95%CI: 1.01-4.04, P=0.049) odds ratios to carry MEFV mutant genotypes, respectively. Exon 10 mutations had the most serious impact. No source of heterogeneity was detected. MEFV mutations are common in IBD and are linked with the presence of extra-intestinal manifestations and pancolitis. Further research to assess the clinical significance and evolutionary significance of MEFV mutations in IBD patients is warranted.

P208 Enthesopathies in patients with inflammatory bowel diseases

Abstract Background Background. The aim of study was to evaluate the enthesis in patients with inflammatory bowel diseases (IBD) and to assess the involvement of enthesis in different IBD behavior. Methods Methods. 95 IBD pts were prospectively enrolled into the study: 55 pts with ulcerative colitis (UC) and 40 - with Crohn’s disease (CD). The average duration of the disease was 48 (12; 102) months in UC, and 42 (18; 87) months in CD. The severity of UC exacerbation was assessed by the Mayo index, in CD – by Harvey-Bradshaw index. In UC, moderate and severe exacerbation was revealed in 40 pts (73%), in CD - in 17 (43%). Among 95 pts with IBD, extraintestinal manifestations occurred in 67 pts (71%), of which 34 (62%) pts with UC and 33 (82%) pts with CD. 70 enthesis were evaluated clinically and by US in each pt. The clinical examination included tenderness of enthesis, US examination with power Doppler detected inflammatory (hypoechogenicity of enthesis, thickening of enthesis, presence of vascularization) and structural (erosion, enthesophyte) changes in enthesis. Fisher’s exact test, Spearman’s coefficient and binary logistic regression to determine the odds ratio (OR) were used to calculate differences. Results Results. The duration of IBD course directly correlated with the number of tender entheses (SR = 0.24; p = 0.017), as well as the number of enthesophytes (SR = 0.20; p = 0.044). The severity of IBD exacerbation and enthesis involvement didn’t have statistically significant correlation. However, the inflammatory lesions of entheses (the number of erosions with vascularization) correlated with CRP level (SR = 0.25; p = 0.01). We also identified a relationship between the presence of extraintestinal manifestations and the enthesis involvement: for example, the presence of at least one extraintestinal manifestation increased the likelihood of detecting erosions by 4.77 times (95% CI 1.6–13.9, p = 0.003). The presence of joint pain increased the likelihood of detecting erosions of entheses by 3.37 times (95% CI 1.18–9.65, p = 0.02). Clinical signs of musculoskeletal system involvement (tenderness of enthesises on palpation) significantly increased the frequency of enthesitis, including vascularized enthesitis (p = 0.01). Conclusion Conclusion. In IBD pts with long disease duration and the presence of extraintestinal manifestations, structural (erosion, enthesophytes) changes in enthesis were observed significantly more often. The frequency of entheses erosions was higher in the presence of pain in the joints, and the number of erosions with vascularization with an increase in laboratory markers of inflammation (CRP).

DOP04 Inflammatory Bowel Disease (IBD) and Solid Organ Transplantation. Natural history of pre-existing and de novo IBD patients. (EITOS study of GETECCU)

Abstract Background Limited data is available of the outcome of inflammatory bowel disease (IBD) in patients with solid organ transplantation (SOT). The aim of our study was to describe the natural history of pre-existing IBD and de novo IBD after SOT. Methods A retrospective, observational, multi-centre, nationwide study was designed. IBD patients with SOT were included. We identified two separate cohorts: (1) patients with pre-existing IBD at the time of SOT and (2) patients without IBD at the time of SOT (de novo IBD). The primary outcome was IBD progression, defined by the escalation of medical treatment, surgical therapy for medically refractory IBD or IBD-related hospitalization during follow-up. Risk factors were identified using multivariate Cox proportional hazard analysis. Results A total of 177 patients (106 pre-existing IBD and 71 de novo IBD) from 31 centres were included. Baseline characteristics are shown in Table 1. Eighty-six patients with IBD and SOT underwent liver transplantation, while 82 required renal, 4 lung, 3 heart, 1 liver/kidney and 1 pancreas/kidney transplantation. Pre-existing IBD patients were followed-up over a median of 4.8 years (range 2.6–9.4). At the time of SOT, 61 patients (59.8%) were not under maintenance treatment or were treated with 5-aminosalicylates, 10 (9.8%) were on immunosuppressive therapy and 31 (30.4%) were receiving biological agents, of which 8 were on combo therapy. At the moment of SOT, only 8 patients (7.5%) had moderate IBD activity whereas the remaining patients were in remission. During follow-up 33.7% of patients with pre-existing IBD had disease progression, with a median time between SOT and IBD progression of 2.2 years (range 1.3–4.6). No differences between Crohn′s disease and ulcerative colitis were found (Figure 1). The median time of follow-up in de novo IBD group was 5.1 years (range 2.1–8.2). In this cohort, 55.9% of patients had disease progression during follow-up (Figure 2), with a median time to flare of 1.9 years (range 0.8–3.9) from diagnosis. In pre-existing IBD cohort, multivariate Cox-regression analysis identified active IBD at the time of SOT (HR=1.80; 95%CI: 1.14–2.84; p=0.012) and the presence of extraintestinal manifestations (HR=3.10; 95%CI: 1.47–6.54; p=0.003) as predictive factors of IBD progression after SOT. Conclusion One third of patients with pre-existing IBD have disease progression, needing medical therapy escalation, surgery or hospitalization after SOT. Active IBD at the time of SOT and the presence of extraintestinal manifestations were identified as risk factors for disease progression. In de novo IBD cohort, about half of patients showed disease progression during follow-up.