Manifestations Of Inflammatory Bowel Disease Research Articles

Sulforaphane decreases oxidative stress and inhibits NLRP3 inflammasome activation in a mouse model of ulcerative colitis

Excessive oxidative stress and NLRP3 inflammasome activation are considered the main drivers of inflammatory bowel disease (IBD), and inhibition of inflammasomes ameliorates clinical symptoms and morphological manifestations of IBD. Herein, we examined the roles of NLRP3 activation in IBD and modulation of NLRP3 by sulforaphane (SFN), a compound with multiple pharmacological activities that is extracted from cruciferous plants. To simulate human IBD, we established a mouse colitis model by administering dextran sodium sulfate in the drinking water. SFN (25, 50 mg·kg−1·d−1, ig) or the positive control sulfasalazine (500 mg/kg, ig) was administered to colitis-affected mice for 7 days. Model mice displayed pathological alterations in colon tissue as well as classic symptoms of colitis beyond substantial tissue inflammation. Expression of NLRP3, ASC, and caspase-1 was significantly elevated in the colonic epithelium. The expression of NLRP3 inflammasomes led to activation of downstream proteins and increases in the cytokines IL-18 and IL-1β. SFN administration either fully or partially reversed these changes, thus restoring IL-18 and IL-1β, substantially inhibiting NLRP3 activation, and decreasing inflammation. SFN alleviated the inflammation induced by LPS and NLRP3 agonists in RAW264.7 cells by decreasing the levels of reactive oxygen species. In summary, our results revealed the pathological roles of oxidative stress and NLRP3 in colitis, and indicated that SFN might serve as a natural NLRP3 inhibitor, thereby providing a new strategy for alternative colitis treatment.

Liver Disease Associated with Inflammatory Bowel Disease

Inflammatory Bowel Disease (IBD) is a chronic condition characterized by persistent inflammation of the gastrointestinal tract, comprising ulcerative colitis (UC) and Crohn’s disease (CD). While the current global incidence of IBD exceeds 0.3% in Western nations, Indonesia reports a comparatively lower prevalence however with projections indicate a potential rise in incidence from 2020 to 2050. Hepatobiliary manifestation is one of the most common extraintestinal manifestations of IBD. Some of the liver disease associated with IBD had similar background immune response, inflammatory reaction, similar risk factor, or due to the treatment of IBD. Primary sclerosing cholangitis (PSC) has close association with IBD and both affect the prognostic and disease progression of each other. Non-alcoholic fatty liver disease (NAFLD) shares common metabolic risk factors. Several drugs used as the treatment of IBD might cause hepatic injury especially due to the long treatment duration of IBD. Hepatitis B reactivation is another concerning event found after prolonged used of immunosuppressive drugs of IBD. Therefore, close monitoring of liver function test periodically is a mandatory test to screen liver disease in IBD patients. Keyword: Inflammatory bowel disease, liver disease, autoimmune hepatitis, drug-induced liver injury

Cardiovascular disease: extraintestinal manifestation of inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a spectrum of diseases characterized by the interplay of the aberrant immune system, genetic factors, environmental factors, and intestinal microbiota, resulting in relapsing inflammation of the gastrointestinal tract. Underlying pro-inflammatory state and immune dysregulation act as a catalyst for increasing the likelihood of developing extraintestinal manifestations, including cardiovascular diseases (CVD) like atherosclerosis, pericarditis, myocarditis, venous and arterial thromboembolism, arrhythmias, despite a lower prevalence of classic CVD risk factors, like high body mass index or dyslipidemia compared to the general population. Chronic inflammation damages endothelium resulting in the recruitment of inflammatory cells, which induce cytotoxicity, lipoprotein oxidation, and matrix degradation, which increases the risk of atherosclerosis. Additionally, intestinal dysbiosis disrupts the intestinal mucosal barrier, releasing endotoxins and lipopolysaccharides into circulation, further exaggerating the atherosclerotic process. Abnormal collagen metabolism and alteration of nitric oxide-mediated vasodilation lead to blood pressure dysregulation in patients with IBD. Therefore, it is essential to make lifestyle modifications like smoking cessation, dietary changes, and increasing physical activity with adherence to medication to mitigate the risk of developing CVD in patients with IBD. This article reviews the potential links between IBD and the increased risk of CVD in such individuals.

Halitosis: an underestimated but important extraintestinal manifestation in inflammatory bowel disease.

Halitosis: an underestimated but important extraintestinal manifestation in inflammatory bowel disease.

Halitosis: an underestimated but important extraintestinal manifestation in inflammatory bowel disease

Halitosis: an underestimated but important extraintestinal manifestation in inflammatory bowel disease

A systematic review and meta-analysis of extra-intestinal manifestation of inflammatory bowel disease in the Eastern Mediterranean Region (EMRO) countries.

Inflammatory bowel disease which is subgrouped mainly to ulcerative colitis and Crohn's disease is thought to be a multi-organ disease. Most organs can be involved in the disease course in addition to gastrointestinal tract involvement. In this systematic review we aimed to assess the prevalence of these manifestations in Eastern Mediterranean Regional Office (EMRO) countries. The present systematic review and meta-analysis study was performed according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guideline. Joanna Briggs Institute (JBI) Critical Appraisal Checklist was admired for the quality evaluation of the included studies. For determining the heterogeneity, we used Cochran test and I2 statistics. Finally, 12 studies were included in our study. Based on the results of our study the prevalence of arthritis in ulcerative colitis and Crohn's disease patients was 7.1% (95% CI: 2.6-18.2%) and 13.5% (95% CI: 2.6-47.3%), respectively. Prevalence of arthralgia in ulcerative colitis patients was 18.4% (95% CI: 14.3-23.3%). skin involvement prevalence was 9.9% (95% CI 4.7-19.6%) in inflammatory bowel disease (IBD) patients. ocular involvement prevalence was 7.2% (95% CI 17-25.8%) in IBD patients. PSC prevalence in ulcerative colitis and Crohn's disease patients was 3.5% (95% CI: 1.7-7.3%) and 2.7% (95% CI: 1.3-5.5%), respectively. Based on the results of this study arthralgia and arthritis were the most common extra-intestinal manifestation of IBD followed by dermatologic and ocular involvements. This extra-intestinal manifestation can challenge the patients' management and identifying their pattern is important during the disease course.

Sacroiliitis in inflammatory bowel disease.

This review summarizes the recent evidence regarding the epidemiology of inflammatory bowel disease (IBD) associated sacroiliitis, including the prevalence, pathogenesis, role of imaging, and therapeutic challenges. Sacroiliitis is an underappreciated musculoskeletal manifestation of IBD, a chronic inflammatory condition of the gut affecting the younger population. Untreated sacroiliitis can lead to joint destruction and chronic pain, further adding to morbidity in IBD patients. Recent publications suggest sacroiliitis can be detected on abdominal imaging obtained in IBD patients to study bowel disease, but only a small fraction of these patients were seen by rheumatologists. Early detection of IBD-associated sacroiliitis could be achieved by utilization of clinical screening tools in IBD clinics, careful examination of existing computed tomography and MRI studies, and timely referral to rheumatologist for further evaluation and treatment. Current treatment approaches for IBD and sacroiliitis include several targeted biologic therapies, but IBD-associated sacroiliitis has limited options, as these therapies may not overlap in both conditions. With the advances in imaging, sacroiliitis is an increasingly recognized comorbidity in IBD patients. Future studies focusing on this unique patient population will expand our understanding of complex pathophysiology of IBD-associated sacroiliitis and lead to identification of novel targeted therapies for this condition.

Fecal microbiota is associated with extraintestinal manifestations in inflammatory bowel disease

Introduction A large proportion of patients with inflammatory bowel disease (IBD) experience IBD-related inflammatory conditions outside of the gastrointestinal tract, termed extraintestinal manifestations (EIMs) which further decreases quality of life and, in extreme cases, can be life threatening. The pathogenesis of EIMs remains unknown, and although gut microbiota alterations are a well-known characteristic of patients with IBD, its relationship with EIMs remains sparsely investigated. This study aimed to compare the gut microbiota of patients with IBD with and without EIMs. Methods A total of 131 Danish patients with IBD were included in the study, of whom 86 had a history of EIMs (IBD-EIM) and 45 did not (IBD-C). Stool samples underwent 16S rRNA sequencing. Amplicon sequence variants (ASVs) were mapped to the Silva database. Diversity indices and distance matrices were compared between IBD-EIM and IBD-C. Differentially abundant ASVs were identified using a custom multiple model statistical analysis approach, and modules of co-associated bacteria were identified using sparse correlations for compositional data (SparCC) and related to patient EIM status. Results Patients with IBD and EIMs exhibited increased disease activity, body mass index, increased fecal calprotectin levels and circulating monocytes and neutrophils. Microbiologically, IBD-EIM exhibited lower fecal microbial diversity than IBD-C (Mann–Whitney’s test, p = .01) and distinct fecal microbiota composition (permutational multivariate analysis of variance; weighted UniFrac, R 2 = 0.018, p = .01). A total of 26 ASVs exhibited differential relative abundances between IBD-EIM and IBD-C, including decreased Agathobacter and Blautia and increased Eggerthella lenta in the IBD-EIM group. SparCC analysis identified 27 bacterial co-association modules, three of which were negatively related to EIM (logistic regression, p < .05) and included important health-associated bacteria, such as Agathobacter and Faecalibacterium. Conclusions The fecal microbiota in IBD patients with EIMs is distinct from that in IBD patients without EIM and could be important for EIM pathogenesis.

Risk relationship between inflammatory bowel disease and urolithiasis: A two-sample Mendelian randomization study.

The causal genetic relationship between common parenteral manifestations of inflammatory bowel disease (IBD) and urolithiasis remains unclear because their timing is difficult to determine. This study investigated the causal genetic association between IBD and urolithiasis using Mendelian randomization (MR) based on data from large population-based genome-wide association studies (GWASs). A two-sample MR analysis was performed to assess the potential relationship between IBD and urolithiasis. Specific single nucleotide polymorphism data were obtained from GWASs, including IBD (n = 59957) and its main subtypes, Crohn's disease (CD) (n = 40266) and ulcerative colitis (UC) (n = 45975). Summarized data on urolithiasis (n = 218792) were obtained from different GWAS studies. A random-effects model was analyzed using inverse-variance weighting, MR-Egger, and weighted medians. Genetic predisposition to IBD and the risk of urolithiasis were significantly associated [odds ratio (OR), 1.04 (95% confidence interval [CI], 1.00-.08), P = 0.01]. Consistently, the weighted median method yielded similar results [OR, 1.06 (95% CI, 1.00-1.12), P = 0.02]. The MR-Egger method also demonstrated comparable findings [OR, 1.02 (95% CI, 0.96-1.08), P = 0.45]. Both funnel plots and MR-Egger intercepts indicated no directional pleiotropic effects between IBD and urolithiasis. CD was strongly associated with it in its subtype analysis [OR, 1.04 (95% CI, 1.01-1.07), P = 0.01], and UC was also causally associated with urolithiasis, although the association was not significant [OR, 0.99 (95% CI, 0.95-1.03), P = 0.71]. A unidirectional positive causal correlation was identified between IBD and urolithiasis, with varying degrees of association observed among the different subtypes of IBD. Recognizing the increased incidence of urolithiasis in patients with IBD is crucial in clinical practice. Early detection and surveillance of IBD, improved patient awareness, adoption of preventive strategies, and promotion of collaborative efforts among healthcare providers regarding treatment methodologies are vital for improving patient outcomes.

Prevalence and clinical features of chronic uveitis in pediatric inflammatory bowel diseases: A nationwide study.

Inflammatory bowel diseases (IBD) encompass a group of chronic inflammatory disorders primarily affecting the gastrointestinal tract but capable of impacting various organs, including the eye, with uveitis being the most common ocular condition. We assessed uveitis prevalence and clinical features in a nationwide cohort of pediatric IBD. Among 4229 cases, six patients (four Crohn's disease, one ulcerative colitis, and one unclassified IBD) were identified, resulting in an overall prevalence rate of 141.8 per 100,000 patients. Uveitis onset varied: two before IBD, two after, and two concomitantly. Symptomatic uveitis occurred in 2/6 patients, with anterior involvement in all cases. Median follow-up was 3 years (interquartile range [IQR]: 2-4.75 years). At the last follow-up, 5/6 patients exhibited quiescent IBD, while 4/6 had inactive uveitis. One patient had ocular complications. Uveitis is a rare but potentially complicating manifestation of pediatric IBD.

Protocolo diagnóstico y tratamiento del cuadro febril en el paciente con enfermedad inflamatoria intestinal

Fever is a common clinical manifestation of inflammatory bowel disease (IBD). Nevertheless, fever should not be systematically attributed to inflammation. There are multiple diseases that progress with fever and they may be masked by a flare-up of bowel inflammation. Therefore, a differential diagnosis is recommended. One of the main causes of febrile syndrome is infections. Patients with IBD are at increased risk for infections, in part because of immunosuppressive treatment. In addition, they are more susceptible to certain microorganisms, including enteropathogens such as Clostridioides difficile, and mycobacteria in patients receiving tumor necrosis factor alpha-inhibiting drugs. Second, neoplastic processes, both solid and hematological, can progress with fever, with the disease itself and the use of thiopurines being the main associated risk factors. Other causes of fever that should be considered are inflammatory or autoimmune disorders and drug fever. This protocol proposes an algorithm for the differential diagnosis of febrile illness in patients with IBD.

Manifestaciones extraintestinales y comorbilidades en la enfermedad inflamatoria intestinal

Inflammatory bowel disease (IBD) is a systemic disease that can affect different organs and systems in addition to the gastrointestinal tract, generating what are defined as extraintestinal manifestations (EIM) of IBD. This term encompasses a very heterogeneous group of diseases that are usually classified into four groups: classical (directly related to inflammatory activity in the extraintestinal area), systemic consequences of inflammatory activity, complications of treatments, and IBD-associated conditions. The pathophysiology is different for each of them, but they usually share an inflammatory underpinning related to the IBD itself. It is a frequent complication present in up to 50% of patients with IBD and up to 30%–40% of patients present with more than one EIM. It is essential to know these conditions in order to diagnose them early since, in many cases, they have a specific treatment and require a multidisciplinary approach according to the affected organs.

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.

WNT2B activates macrophages via NF-κB signaling pathway in inflammatory bowel disease.

Inflammation is a significant pathological manifestation of inflammatory bowel disease (IBD), yet its mechanism has remained unclear. Although WNT2B is enriched in the intestinal inflammatory tissue of IBD patients, the specific mechanism of WNT2B in the formation of intestinal inflammation remains unclear. This study was aimed to investigate whether macrophages expressing WNT2B can aggravate intestinal tissue inflammation. Samples were collected from both normal individuals and patients with IBD at multiple colon sites. Macrophages were identified using tissue immunofluorescence. IκB kinase (IKK)-interacting protein (IKIP), which interacts with WNT2B, was found by protein cross-linking and protein mass spectrometry. The expression of WNT2B, IKIP, the NF-κB pathway, and downstream molecules were analyzed. An acute colitis model of C57BL/6J mice was established using an adeno-associated virus (AAV)-mediated WNT2B knockdown system and 3% dextran sulfate sodium (DSS). The degree of intestinal inflammation in mice was assessed upon WNT2B knockdown in macrophages. Macrophages expressing WNT2B were found to be enriched in the colitis tissues of IBD patients. WNT2B in macrophages activated the NF-κB pathway and enhanced the expression of downstream inflammatory cytokines. By competitively binding IKIP, WNT2B reduced the binding of IKIP to IKKβ and promoted the activation of the NF-κB pathway. Using an AAV-mediated WNT2B knockdown system, WNT2B expression in intestinal macrophages was suppressed, leading to a reduction in intestinal inflammation. WNT2B activated the NF-κB pathway and enhanced the expression of downstream inflammatory cytokines by competitively binding to IKIP, potentially contributing to colon inflammatory injury in IBD.

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

The Prevalence of extraintestinal manifestations in Inflammatory Bowel Disease

INTRODUCTION: The term inflammatory bowel disease (IBD) refers to a chronic inflammatory disease of the gastrointestinal tract of unclear pathogenesis. IBD consists of ulcerative colitis (UC) and Crohn's disease (CD). The two most common manifestations of the disorder, both have a chronic course with episodes of acute activity. Their underlying pathogenesis and symptoms, however, are quite distinct. IBD has a multiple factor etiology involving genetics, immunological dysregulation and dysbiosis of the intestinal microbiome. The resulting chronic inflammation of the entire body is the cause of the symptoms and signs of the condition. Extraintestinal manifestations (EIM) occur in 5% to 50% of IBD patients over the course of their lifetime.&#x0D; PURPOSE: The aim of the study is to present the current state of knowledge about the prevalence of extraintestinal manifestations in Inflammatory Bowel Disease.&#x0D; MATERIALS AND METHOD: The available literature in PubMed was reviewed to write the article, using the keywords ,,inflammatory bowel disease”, ,,Crohn’s disease”, ,, ulcerative colitis”, ,,extraintestinal manifestations IBD”. &#x0D; CONCLUSION: Extraintestinal manifestations are evidence that IBD is not only confined to the intestine, these may involve many different organs other than the gut and may be more devastating than the IBD. Screening for EIM in these patients and prompt adequate treatment are essential. To adequately manage EIM and improve the quality of life of our patients, appropriate treatment regimens and therapies are required in a multidisciplinary team approach. Due to the lack of available dedicated diagnostic biomarkers for EIM, consideration of concomitant extraintestinal conditions in patients with inflammatory bowel disease might help in the selection and management of them. Clinicians caring for patients with IBD must be aware of these various systemic manifestations, as failure to diagnose and treat them early can result in significant morbidity.

Integrative Multiomics Profiling Unveils the Protective Function of Ulinastatin against Dextran Sulfate Sodium-Induced Colitis.

Ulcerative colitis is an inflammatory bowel disease with multiple pathogeneses. Here, we aimed to study the therapeutic role of ulinastatin (UTI), an anti-inflammatory bioagent, and its associated mechanisms in treating colitis. Dextran sulfate sodium was administrated to induce colitis in mice, and a subgroup of colitis mice was treated with UTI. The gut barrier defect and inflammatory manifestations of colitis were determined via histological and molecular experiments. In addition, transcriptomics, metagenomics, and metabolomics were employed to explore the possible mechanisms underlying the effects of UTI. We found that UTI significantly alleviated the inflammatory manifestations and intestinal barrier damage in the mice with colitis. Transcriptome sequencing revealed a correlation between the UTI treatment and JAK-STAT signaling pathway. UTI up-regulated the expression of SOCS1, which subsequently inhibited the phosphorylation of JAK2 and STAT3, thus limiting the action of inflammatory mediators. In addition, 16S rRNA sequencing illustrated that UTI maintained a more stable intestinal flora, protecting the gut from dysbiosis in colitis. Moreover, metabolomics analysis demonstrated that UTI indeed facilitated the production of some bile acids and short-chain fatty acids, which supported intestinal homeostasis. Our data provide evidence that UTI is effective in treating colitis and support the potential use of UTI treatment for patients with ulcerative colitis.

INDOLENT SYSTEMIC MASTOCYTOSIS MASQUERADING AS CHRONIC ANEMIA IN ULCERATIVE COLITIS: A CASE STUDY

Abstract BACKGROUND Anemia is a frequent systemic/extra-intestinal manifestation of inflammatory bowel disease (IBD). It has a complex multifactorial etiology which suppresses erythropoiesis due to pro-inflammatory mediators, myelosuppression, iron and micronutrient deficiency. It significantly impacts quality of life (QoL) and increases hospitalizations, length of hospital stays and mortality rates. It Is commonly thought to arise as a consequence of IBD or it’s related therapy. Current strategies are aimed at correction of anemia with low priority towards identifying a specific cause. Here, we represent a case of UC with chronic anemia secondary to systemic mastocytosis (SM). CASE A 41 y/o female with UC presents to the outpatient clinic with complaints of fatigue. Further questioning revealed a baseline of 1-2 formed bowel movements per day. She did not report any hematochezia or weight loss. She was managed on 300 mg of vedolizumab every 4 weeks. Prior failure to medications includes anti-tumor necrosis factor inhibitors and tofacitinib. Labs were consistent with albumin 4.5 mg/dL and CRP &amp;lt; 1 mg/dL. Iron studies revealed low iron, TIBC and ferritin levels. Fecal calprotectin measurements were not available due to patient non-compliance. Patient (Pt) was thought to have experienced a UC flare and colonoscopy was recommended. Colonoscopy was unrevealing with no sign of active disease on examination (Mayo Endo 0). Pt was referred to hematology where she underwent a bone marrow biopsy revealing multifocal dense infiltrates of mast cells (≥15 mast cells in aggregates) expressing CD2+ and CD 25+ with 25% showing atypical morphology in bone marrow biopsies. KIT D816V mutation was also positive. The serum tryptase level in this pt was 47.1ug/L. She was then placed on anti-histamines, proton pump inhibitors and steroid therapy. CONCLUSION SM is a clonal disorder of MC that infiltrates one or more organs. It almost always involves the bone marrow. Gastrointestinal (GI) symptoms are present in up to 80% patients. These symptoms are secondary to systemic effects of MC mediators. Incidence of SM in UC has never been established. SM has been shown to mimic Crohn’s disease and is difficult to differentiate based on clinical and endoscopic features. Furthermore, little is known regarding histopathological features of GI involvement in SM. The presence of chronic anemia despite adequate therapy in a clinically/endoscopically inactive UC patient should raise suspicion of other pathologic causes of anemia. Our case highlights the importance of diagnosing the specific cause of anemia in IBD as it may lead to inaccurate clinical judgements of disease flares leading to undue alteration in therapy.

HERMANSKY-PUDLAK SYNDROME-ASSOCIATED INFLAMMATORY BOWEL DISEASE: A SYSTEMATIC REVIEW ON CLINICAL MANIFESTATIONS AND INVESTIGATIONS INTO OPTIMAL MANAGEMENT

Abstract Hermansky-Pudlak Syndrome (HPS) is a rare autosomal condition resulting from a mutation in 1 of at least 7 different genes leading to the triad of tyrosine-positive oculocutaneous albinism, platelet dysfunction leading to prolonged bleeding time, and ceroid lipofuscin within the reticuloendothelial system. The latter of these can result in systemic derangements including renal failure, pulmonary fibrosis, cardiomyopathy, and a disabling granulomatous colitis. This colitis is a unique type of inflammatory bowel disease (IBD) with complications such as intestinal fistulization, ileitis, enterocolitis and perianal disease. There is data to suggest that HPS colitis is due to the development of classical IBD. However, optimal management remains undetermined. Our systematic review aims to analyze the clinical presentation behind HPS colitis, endoscopic versus histopathological findings, and ultimate treatment plans required for optimal management of this disease among HPS genotypes. A comprehensive literature review was conducted on patients with HPS and its associated colitis manifestations from inception to August 2023. Analyses on patient demographics, clinical presentation, HPS genotype, endoscopic versus histopathological findings, medical versus surgical interventions were thoroughly performed. Six cohort studies on HPS patients with coexisting colitis were identified. A total of 84 patients comprised these studies with mean age 32 +/- 9.65. Racial breakdowns were 68% Puerto Rican, 23% white, 4% Indian, 2% Mexican, 1% Honduran, and 1% African American. 59 patients had the HPS-1 genotype, 8 with HPS-3, 3 with HPS-4, and 1 with HPS-6. The most common presenting symptoms were hematochezia (37%), diarrhea (23%), abdominal pain (16%), and constipation (10%). Endoscopic evaluation showed normal gross findings in 65% of cases and abnormalities in only 35%. However, IBD-associated histopathological positivity was more prevalent with the most common findings being granulomas (33%), macrophages without colitis (19%), macrophages with colitis (15%), and lymphoid aggregates (10%). Medical therapy was initiated in 48 cases with the most common medications being steroids (46%), followed by anti-TNFa agents (40%), and immunomodulators (35%). 28 cases required surgical intervention with the most common operation performed being a (subtotal) colectomy and ileostomy. There were scattered cases of laparoscopic loop ileostomies, total colectomies, and proctocolectomies too. Interestingly, 10 patients received no intervention whatsoever. HPS-associated colitis is a debilitating condition that remarkably resembles IBD. There is no consensus on optimal therapy and many patients ultimately require operative intervention. The HPS-1 gene appears to be highly prevalent in this condition and younger patients are more affected, however more research is needed.

P398 The Burden of Psychiatric Manifestations in Inflammatory Bowel Diseases: A Systematic Review with Meta-analysis

Abstract Background Psychiatric manifestation in individuals with inflammatory bowel disease (IBD) has been the subject of extensive research, but uncertainties remain regarding its precise magnitude, its impact on intestinal disease, and the whole burden of psychiatric manifestations.This systematic review aims to synthesize available evidence on the prevalence and impact of psychiatric disorders in patients with IBD. Methods A systematic search of PubMed/MEDLINE, EMBASE, and SCOPUS databases was performed to identify relevant studies published between January 2010 and January 2023. Cross-sectional, case-control, cohort, registry, and population studies that addressed the prevalence of depression, anxiety, bipolar disorder, and schizophrenia in patients with IBDs and that met the specific inclusion criteria were selected. A meta-analysis to assess the strength of association between IBD and selected psychiatric disorders was also performed. Data extraction and quality assessment were performed. Results The search yielded a total of 3209 articles. 193 met the inclusion criteria, but only 26 studies provided the complete data for the analysis (Table 1). Overall, the prevalence of psychiatric comorbidities was found to be significantly higher in IBD compared with the general population. The analysis revealed a moderate but significant association between IBD and depression, with a pooled odds ratio (OR) of 1.42 (95%CI 1.33-1.52). (Fig.1) Also, anxiety emerged as a prevalent comorbidity in IBD with a pooled OR of 1.3 (95%CI =1.22-1.44). Evidence on the relationship between bipolar disorders and IBD was limited and mixed, with a pooled OR of 1.64 (95%CI=1.20-2.24), despite a substantial heterogeneity (I2=94.01%). Only three studies examined the association between schizophrenia and IBD, providing widely heterogeneous results, with an inconclusive OR (p= 0,73), estimated at 0.93 (95%CI=0.62-1.39). Conclusion This systematic review with meta-analysis highlights that patients with IBD, both CD and UC, frequently experience psychiatric comorbidities such as depression, anxiety, bipolar disorders, and, to a lesser extent, schizophrenia. These disorders are more prevalent in IBD patients than in the general population. Depression and anxiety are particularly prevalent. Bipolar disorder is still an underexplored area in the context of IBD. Data on the relationship between schizophrenia and IBD is sparse and inconclusive and requires further research. Given the high prevalence of psychiatric comorbidities in IBD patients, the results of this systematic review underscore the need for a deeper understanding of these associations and early identification and tailored interventions for mental health in patients with IBD to improve their quality of life.