Frequent Extraintestinal Manifestations Research Articles

C-reactive Protein: An Inflammatory Biomarker and a Predictor of Neurodegenerative Disease in Patients With Inflammatory Bowel Disease?

Inflammatory bowel disease (IBD) refers to two chronic conditions of the digestive tract: ulcerative colitis (UC) and Crohn's disease (CD), representing a progressive inflammatory process that mainly occurs in the gut, with frequent extra-intestinal manifestations. Even if remission is periodically obtained for some patients, the histological activity and digestive symptoms may continue, maintaining a persistent systemic inflammation that could induce further extra-intestinal complications and contribute to the development of neurodegenerative disease. C-reactive protein (CRP) is an acute-phase reactant that is widely accepted as a dominant serum biomarker in IBD. CRP consequently activates the complement cascade, supports the release of pro-inflammatory cytokines, and the clearance of microbial pathogens. All these processes facilitate further processes, including atherosclerosis and hypercoagulability, alteration of the intestinal microbiota, and the increased permeability of the intestinal barrier for neurotoxic substances produced by gut microorganisms, due to the presence of a high level of lipopolysaccharides. For IBD, the connection between intestinal inflammation and central nervous system inflammation could be explained through the activity of the vagus nerve, a carrier of cytokines, CRP, and toxic materials to the brain, potentially inducing vascular lesions and damage of the glial vascular unit, with further risk for degeneration within the central nervous system. CRP is a key marker for IBD pathogenesis and is able to dissociate into its monomeric form, mCRP, on contact with activated cell and tissue components via the systemic circulation. We hypothesize that the chronic inflammatory process within IBD could initiate neuroinflammation and neurodegeneration, and therefore, further investigation of the significance of chronically raised plasma of CRP and mCRP in patients with IBD is warranted, as it may represent a critical predictive factor associated with a later neurodegenerative risk. Any future initiative aimed at pharmacologic modulation of CRP (e.g., blocking CRP-mCRP dissociation), could represent a new therapeutic approach protecting against intestinal inflammation and concomitantly reducing the risk of neuroinflammation, neurodegeneration, and cognitive decline.

Clinical Presentation and Spectrum of Gluten Symptomatology in Celiac Disease

Views on the clinical presentation and symptomatology of celiac disease have evolved alongside advances in disease detection and understanding of disease pathogenesis. While historically regarded a pediatric illness characterized by malabsorption, it is now better viewed as an immune illness of gluten-specific T cells with systemic manifestations affecting all ages. Its broad presentation, including frequent extraintestinal manifestations and asymptomatic disease, contributes to suboptimal disease detection. Adverse symptoms greatly impact patient quality of life and can result from chronic gluten exposure in untreated disease or those poorly responsive to the gluten free diet and can also present as acute symptoms after episodic gluten exposure. Functional gastrointestinal disease is a common comorbidity. Biomarkers like interleukin-2 that are highly sensitive and specific for celiac disease highlight a role for gluten-specific T cells in acute gluten symptomatology. A mechanistic understanding of symptoms will inform approaches to better measure and effectively treat them.

Lung Involvement in Patients with Ulcerative Colitis: Relationship between Exhaled Nitric Oxide and Lung Function.

Ulcerative colitis (UC) is characterized by immune system dysregulation with frequent extraintestinal manifestations, including airway involvement. A reduction in CO diffusing capacity and functional alterations in small airways have been described. An extended analysis of fractional exhaled nitric oxide (FeNO) may distinguish the sites of production, and the presence of small airway inflammation may be a useful, non-invasive marker for patient follow-up. The aim of our study was to compare the PFTs as well as FeNO and CANO values of UC patients with different clinical disease activities and healthy subjects to reveal lung function abnormalities and the presence of subclinical airway inflammation. We enrolled 42 adult outpatients at different clinical activity stages of UC (39 ± 13 years) and a healthy control group of 41 subjects (29 ± 3 years). C-reactive protein (CRP) and FeNO values at different flows (50,100, and 200 mL/s) were collected. All patients performed pulmonary function tests (PFTs) with static volumes and diffusing capacity (DLCO). FeNO and CANO values were significantly increased in UC patients when compared with controls (p = 0.0008 and p < 0.0001, respectively) and were proportional to disease activity (FeNO class 3: 28.1 ppb vs. classes 1-2: 7.7 ppb; CANO values class 3: 8.6 ppb vs. classes 1-2: 2.7 ppb (p < 0.0001)). TLC and DLCO were significantly reduced in severe (Mayo 3) UC patients (p = 0.010 and p = 0.003, respectively). The results of this study show significant lung functional abnormalities in UC patients and suggest the presence of airway inflammation directly correlated with disease activity, suggesting the need for an integrated approach in routine assessment.

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.

Celiac Disease and Migraine Headaches: Current Knowledge and Future Directions

Background: Migraine headaches and celiac disease are widespread problems affecting millions of patients worldwide. Celiac disease is an autoimmune disease in which the consumption of gluten leads to the development of an abnormal immune response in the intestines and the atrophy of intestinal villi. The most characteristic clinical symptoms of celiac disease are gastrointestinal symptoms. Nevertheless, manifestations of the nervous system, including migraines, are also sometimes noted. A gluten-free diet is the only effective therapeutic approach for patients with celiac disease. It reduces symptoms and halts the progression of the disease. Neurological symptoms, including migraines, are frequent extraintestinal manifestations. In this study we aim to elaborate on current knowledge concerning both coexisting of migraines and celiac disease as well as effect of gluten free diet on headaches in patients with celiac disease, gluten intolerance and healthy individuals Results: Headaches, especially migraines, are more common in patients suffering from celiac disease. Numerous studies indicate that a gluten-free diet may help in the treatment of headaches and is also an effective way to stop the progression of celiac disease. Conclusion: Migraine headaches are quite common in patients with celiac disease, and a gluten-free diet may help alleviate them. The findings suggest the need for increased awareness of the co-occurrence of these two conditions. A gluten-free diet is the only effective treatment for celiac disease and can stop progression of the disease. Further research is needed to determine the potential benefits of such a diet in patients with gluten intolerance or healthy individuals.

Impact of Vedolizumab on Extraintestinal Manifestations in Inflammatory Bowel Disease: Results From a Descriptive, Retrospective, Real-world Study.

Patients with inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, may develop extraintestinal manifestations (EIMs). The EMOTIVE study aimed to analyze the effect of vedolizumab on EIMs in a real-world cohort of patients with IBD. This multicenter, descriptive, retrospective study was conducted in Belgium, Denmark, Israel, the Netherlands, and Switzerland in adults with moderately to severely active IBD and concurrent active EIMs at vedolizumab initiation (index date), with a ≥6-month follow-up after the index date. The primary endpoint was resolution of all EIMs within 6 months of vedolizumab initiation. In 99 eligible patients, the most frequent EIMs were arthralgia (69.7%), peripheral spondyloarthritis (21.2%), and axial spondyloarthritis (10.1%). Within 6 and 12 months of vedolizumab initiation, 19.2% and 25.3% of patients reported resolution of all EIMs, while 36.5% and 49.5% of all EIMs were reported to be improved (combination of resolution and partial response), respectively. Vedolizumab treatment persistence at 12 months was 82.8%. Adverse events were reported in 18.2% of patients, with the most frequent being arthralgia (4.0%). This real-world study showed resolution of all EIMs in up to one-fourth of patients with IBD and improvement in up to half of EIMs within 12 months of vedolizumab treatment. Overall, vedolizumab was effective on EIMs in patients with IBD and showed a good safety profile.

P866 Skin lesions among consecutive Inflammatory bowel disease patients in outpatient setting

Abstract Background It is well known that skin lesions may be frequent extraintestinal manifestations of inflammatory bowel diseases (IBD). During literature analysis we found out that there is an obvious lack of epidemiological data regarding this issue. Therefore, the aim of our study was to establish the prevalence of skin lesions among consecutive IBD patients in outpatient department. Methods Prospective study included out-patients with IBD who were managed in the hospital of Lithuanian University of Health Sciences from January to October of 2022. Patients completed the questionnaires including the demographic and the IBD data and history or present state of cutaneous lesions. We considered skin lesions related to IBD or its treatment if they were diagnosed following the diagnosis of IBD. Skin lesions which were reported before the diagnosis of IBD were considered as not related to IBD. Results 152 patients were included, mean age (MA) – 42.0±13.9 years. There were 88 (57.9%) males and 64 (42.1%) females. Ulcerative colitis (UC) was diagnosed in 110 (72.4%) patients, Crohn’s disease (CD) – in 42 (27.6%) patients. MA of UC patients was 42.3±13.6, CD – 41.1±14.9, p&amp;gt;0.05. In total, skin lesions were indicated by 65 (42.8%) subjects. According to our criteria, in 46 (30.3%; 95% CI: 23-38%) cases, skin lesions were considered as obviously related to IBD or its treatment. We further analyzed latter cases. Among UC patients, 32 (29.1%; 95% CI: 20-38%) had skin lesions related to IBD, among CD patients – 14 (33.3%; 95% CI: 18-48%), p&amp;gt;0.05. Erythema nodosum was diagnosed in 6 (3.9%) patients, pyoderma gangrenosum – 5 (3.3%), acne – 1 (0.7%), psoriasis – 9 (5.9%), vitiligo – 2 (1.3%), epidermolysis bullosa acquisita – 1 (0.7%), hemorrhagic vasculitis – 1 (0.7%), eczema – 9 (5.9%), allergic rash – 4 (2.6%). The comparison of different skin lesions among UC and CD patients is presented in table 1. Among the patients with UC proctitis, skin lesions were reported in 2 of 15 (13.3%) patients; among left-sided colitis – in 8 of 27 (29.6%); among pancolitis – in 22 of 67 (32.8%), p=0.03 between the groups of proctitis and pancolitis. Comparing the different forms of CD, skin lesions were reported in 3 of 15 (20.0%) patients with ileitis, 4 of 10 (40.0%) patients with colitis and 7 of 17 (41.2%) patients with ileocolitis; p&amp;gt;0.05 between different groups. Conclusion In our series the prevalence of skin lesions obviously related to IBD or its treatment is 30.3%. There were no differences in the prevalence of skin lesions between the UC and CD patients. The most common skin lesions in UC were psoriasis and skin eczema, in CD – erythema nodosum and skin eczema. Cutaneous lesions were significantly more prevalent in extensive UC compared to distal disease.

Investigation of the effects of anti-TNF agents on hemoglobin levels in patients with inflammatory bowel disease.

Inflammatory bowel disease (IBD) is characterized by many clinical features. Anemia is 1 of the most frequent complications and/or extraintestinal manifestations of IBD. There are conflicting data regarding the relationship between changes in hemoglobin levels and disease prevalence in IBD patients with and without antitumor necrosis factor (antiTNF) therapy. In our study, we aimed to investigate the long-term effect of antiTNF agents on anemia in IBD.The records of IBD patients followed-up in our hospital between January 2011 and January 2021 were reviewed retrospectively. Demographic, clinical, endoscopic, radiological and medical treatment data of the patients were recorded. Complete blood count and laboratory markers of inflammation and disease activation, were recorded at the beginning and at the first year of treatment in all patients. The data of patients with and without antiTNF therapy were analyzed statistically. A total of 240 IBD patients who met the inclusion criteria were enrolled in the study. The number of patients with and without antiTNF therapy was 102 (42.5%) and 138 (57.5%), respectively. The change in all laboratory parameters between the beginning and the first year of treatment was statistically significant (P < .001) in all IBD patients with and without antiTNF therapy. The change in Hb level after 1 year of treatment was significantly different in patients with antiTNF therapy compared to those without therapy (3.00 ± 1.78 g/dL vs 1.19 ± 1.38 g/dL, P < .001). In the multiple regression analysis, male gender, antiTNF therapy, baseline Hb level and iron therapy were independent significant variables of hematopoietic response. This study showed that with appropriate treatment, hemoglobin levels of IBD patients with and without antiTNF therapy increased within 1 year, and the use of antiTNF agents in the treatment of IBD was an independent variable in correcting anemia.

Spondyloarthropathy in Inflammatory Bowel Disease: From Pathophysiology to Pharmacological Targets.

Spondyloarthritis (SpA) represents one of the most frequent extraintestinal manifestations of inflammatory bowel disease (IBD). Evidence of shared genetic and molecular pathways underlying both diseases is emerging, which has led to rational approaches when treating patients with concomitant diseases. Clinical efficacy of tumor necrosis factor (TNF) antagonists has been ascertained over the years, and they currently represent the cornerstone of treatment in patients with IBD and SpA, but the therapeutic armamentarium in these cases has been recently expanded. Evidence for vedolizumab is controversial, as it was associated both with improvement and development of arthralgias, while ustekinumab, the first anti-interleukin 12/23 (IL-12/23) approved for IBD, has demonstrated good efficacy, especially in peripheral arthritis, and more IL-23 inhibitors are being developed in IBD. Tofacitinib was the first Janus kinase (JAK) inhibitor to be approved in IBD, and as it demonstrated efficacy in treating ankylosing spondylitis, it may represent a good choice in axial arthritis, while more selective JAK inhibitors are yet to be approved. Unexpectedly, the first anti-IL17 that was studied in IBD (secukinumab) has shown not to be effective in treating IBD, and the role of anti-IL17 drugs in these diseases needs further investigation. Therefore, as availability of biologics and small molecules is increasing, their positioning in clinical practice is becoming more and more challenging, and multidisciplinary management needs to be implemented in both research and clinical settings in order to enhance early recognition of SpA in IBD patients, optimize treatment and ultimately improve the patients' quality of life.

Bone Alterations in Inflammatory Bowel Diseases: Role of Osteoprotegerin.

Metabolic bone disorders are one of the most frequent extra-intestinal manifestations in patients with inflammatory bowel diseases (IBD) that might result in an increase of skeletal fragility and risk of fracture. These disorders are a consequence of bone–gut crosstalk alterations, particularly due to inflammation, which involves the RANK-RANKL-Osteoprotegerin (OPG) pathway. This cross-sectional study investigates the role of serum OPG on bone health in IBD patients. In all patients, we carried out BMD measurements at the lumbar spine and femoral neck by the dual-energy X-ray absorptiometry (DXA), and evaluation of serum OPG, 25(OH)D, and PTH. We also divided all IBD patients into two groups: group 1 consisted of premenopausal women and men younger than 50 years old, while group 2 included postmenopausal women and men aged more than 50 years old. We enrolled 36 UC patients (51%), 34 CD patients (49%), and 70 healthy controls. IBD group mean age was 44 ± 17.3 years old, with a mean disease duration of 6 years. IBD patients had a mean value of OPG of 48.1 ± 26.64 pg/mL, while mean OPG in the control group was 61.35 ± 47.19 pg/mL (p < 0.05). In group 1, there was a correlation between BMD Z-scores at the lumbar spine and femoral neck and mean OPG levels in UC subjects (r = 0.47 and r = −0.21, respectively; p < 0.05), and only between Z-score at the lumbar spine and OPG level in the CD group (r = 0.83, p < 0.05). For the patients of group 2, we report a statistically significant correlation between T-score measured at the lumbar site in both UC and CD patients (r = −0.79 and r = 0.77, respectively; p < 0.05). In our study, we demonstrated serum OPG levels to be significantly decreased in IBD subjects compared to healthy age-matched individuals. However, according to our data, it seems that the measurement of serum OPG levels is not useful to better define metabolic bone disorders in IBD patients.

P263 Very early onset Inflammatory Bowel Diseases: Review of the Genoa-Messina joint clinical experience. Clinical history: Part I

Abstract Background Pediatric inflammatory bowel diseases (pIBD) have specific phenotypes compared to Inflammatory Bowel Diseases (IBD) in adults. The Very Early Onset-IBD (VEO-IBD) is considered a diagnosis of IBD in children before age 6 years old with 15% of prevalence. Methods The objective of this study was to compare the clinical and endoscopic features of VEO-IBD compared to pediatric IBD (diagnosis &amp;gt; 6 years old) also in terms of natural history and response to treatment. The VEO patients followed at the IBD-Centers of Messina and Gaslini were enrolled retrospectively. We compared the results of this population with what is reported in the literature in terms of clinical characteristics at onset (symptoms, age at onset, age at diagnosis), comorbidities, complications, associated immunodeficiencies, endoscopic models. Percentage comparison and chi-square test of data was performed. Results 74 VEO-IBD patients were enrolled. The onset is around 3 years, a predominantly colonic localization, inflammatory pattern. Positive family history for IBD in 8.1%. Histology is very nonspecific and is characterized above all by basal plasmacytosis (CD 68,4%; CU 72,7%) and hypereosinophilia (CD 36,8%; CU 40%). At diagnosis, IBD-U (= Unclassified) is prevalent (47,2%), the frequency of which will decrease over the years (3 years after onset, 32.4%), differentiating into CU and CD (table 1). The main clinical manifestations at onset are chronic diarrhea (CD 89,5%; CU 91%), blood in the stool and / or hematochezia (CD 78,9%; CU 96,4%; table 2). Sensitive onset tests for IBD are ESR, fecal calprotectin and iron deficiency anemia (positive respectively in CD 75-60-71,4%%; CU 58,8-84,6-66,7%). The most frequent extraintestinal manifestations are arthritis (CD 22,2%) and sclerosing cholangitis (CU 7,3%). To highlight the significant statistical association (p &amp;lt;0.05) between VEO-IBD and neuro / nephrological diseases (major renal malformations and nephropathies, autism and neuropsychiatric disorders; table 3). Among the most common complications are severe anemia (CD 31,6%; CU 42,6%), acute attack of severe colitis, malnutrition and fistulization. A monogenic form of VEO-IBD was found in 5.4% frequently linked to immunedeficiency, 2 cases required allogenic HSC transplantation (XIAP, WAS). Conclusion VEO-IBDs represent a challenge for the pediatric gastroenterologist. The clinical course is no more severe than pediatric inflammatory bowel diseases, with the exception of monogenic forms. A genetic association between nephro / neurological comorbidities and VEO-IBDs is likely, the genetics is still to be discovered. Further studies will be needed to define the best therapeutic and diagnostic approach for these diseases.

Clinical Characteristics of Crohn's Disease in a Cohort from Saudi Arabia.

Objective:In Saudi Arabia, there are limited studies on the clinical characteristics of patients specifically with Crohn's disease (CD). This study was conducted to describe the clinical characteristics of CD at a tertiary care center in Jeddah, Saudi Arabia.Methods:This retrospective study included all patients aged >14 years who had a definitive diagnosis of CD and were managed at King Abdulaziz University Hospital, Jeddah, Saudi Arabia, between 2012 and 2018. Data were collected for the following categories: clinical, laboratory, radiological, histological features at presentation, and disease-related complications.Results:The study included 245 newly diagnosed CD patients, aged 14–73 years (median: 26.3 years). All subjects presented with abdominal pain. Majority of the patients (59.7%) received a definitive diagnosis of CD >3 months after the onset of symptoms; 15.1% were initially suspected to have intestinal tuberculosis. Diarrhea and bleeding per rectum were reported in 60.8% and 49.7% of the patients, respectively. Sacroiliitis was the most frequent extraintestinal manifestations (11.4%). In terms of disease location, the terminal ileum (L1) was the most affected area (46.9%). Twenty-five patients had perianal disease, of which 40% had complex fistulae and 36% had perianal abscesses. The majority had hemoglobin levels >10 g/dl (74.1%), decreased serum iron (69.6%) and ferritin (50.5%) levels, and elevated erythrocyte sedimentation rate (68.2%) and C-reactive protein (82.2%).Conclusions:The majority of the patients in our cohort presented with the characteristic quartet of abdominal pain, weight loss, fever, and diarrhea. This study also found a significant number of patients with CD in Saudi Arabia experience diagnostic delay, which may contribute to disease morbidity and complications. These findings highlight the need for future studies to determine factors influencing this diagnostic delay.

P360 Aggressive Inflammatory Bowel Disease is associated to Hermansky-Pudlak Syndrome: Characterization of a Puerto Rican Cohort

Abstract Background Hermansky-Pudlak Syndrome (HPS), a rare autosomal recessive disorder, is the most common single-gene disorder in Puerto Rico. It is characterized by an aberrant biogenesis of lysosome-related organelles inducing oculocutaneous albinism, bleeding diathesis, and damage to other organs. Around 30% of patients with HPS develop granulomatous enterocolitis, a Crohn’s-like inflammatory bowel disease (IBD). The mutant HPS1 gene is associated with a more severe Early Onset IBD (EO-IBD). We wish to describe a group of patients with HPS-associated IBD. Methods Puerto Ricans with HPS and concomitant IBD were recruited in our IBD clinic for a prospective cohort study. After informed consent, demographic and medical data were collected from the patient and the medical record. Variables included sex, HPS genotype, age at the time of IBD diagnosis, IBD location and behavior according to Montreal and Paris Classification, surgical interventions, medications, and extra-intestinal manifestations (EIM). Descriptive analysis was performed calculating mean and standard deviations. This study is approved by the MSC IRB. Results 13 patients with HPS and IBD, 9 with confirmed genotype 1, were identified: 8 males and 5 females. The mean age at the time of IBD diagnosis was 22 ± 11 years. 6 were diagnosed at ≤ 16 y/o (A1), 6 were diagnosed between 17-40 years (A2) and 1 patient was in the range of EO-IBD (7 y/o). 9 patients had advanced penetrating behavior (B3) of which 7 had concomitant perianal involvement. Most patients (9) had a surgical intervention; 8 have an ostomy. The majority (10) are using biologics (4 with concurrent immunomodulators). The most frequent EIM was peripheral arthropathy seen in 45%. Conclusion HPS patients had a severe course of IBD, as shown by age at diagnosis, phenotype, the prevalence of perianal disease, surgery and use of biologics. In comparison to a database of 836 Puerto Ricans with non HPS Crohn’s Disease, those with HPS were more likely to have surgeries (69% vs 55%, P=.303) and use biologics (77% vs 43%, P=.015). Gastrointestinal symptoms including bleeding may be overlooked by the primary physician. Proactive vigilance in patients with HPS to make an early diagnosis of IBD and aggressive medical treatment may result in better outcomes for these patients.

P667 Characterization of a large Hispanic cohort with Inflammatory Bowel Disease across a 25-year span

Abstract Background Inflammatory Bowel Disease (IBD) in Hispanics has increased, but characterization of this population is limited. We describe the demographic and clinical characteristics of a large Hispanic population with IBD and compare it among two periods, 1995- 2009 and 2010–2019. Methods The Registry of IBD has been recruiting patients with IBD continuously since 1995. Data is obtained from the subject and the medical record. This study includes 1365 Hispanics recruited between 1995 and 2019. Variables include age, gender, age at onset and diagnosis, IBD type, family history, smoking, extraintestinal manifestations (EIM), medications, and surgery for IBD. Descriptive statistics included frequency, median, mean, and standard deviation. SPSS software was used for comparison analysis utilizing Chi square and Fisher′s test. The protocol is approved by the IRB. Results 712 were males and 653 females. Crohn’s disease (CD) was more prevalent in males (479/836, 57.3%) and ulcerative colitis (UC) in females (288/517, 55.7%). The mean age at diagnosis was 34.1 + 15.4 for UC and 24.4 + 12 for CD (p&amp;lt;.001). History of smoking was infrequent (24.3%). Interval between onset of symptoms and diagnosis was 1.8 + 4.7 yrs. for UC and 2.5 + 5.3 yrs. for CD (p=.012). At recruitment, duration of disease was 7.4 + 8.4 yrs. for UC and 5.6 + 7.3 yrs. for CD (p&amp;lt;.001). Family history of IBD was present in 23% of CD and UC participants. The most frequent EIM was arthropathy in 37.9% and 25.9 % of UC and CD (p=.670), followed by skin manifestations in 13.2% and 18.9% respectively (p=.070). Aminosalicylates (94.9%) and corticosteroids (81.6%) were more frequent in UC, and immunomodulators (23%) and anti-TNF drugs (aTNF) (46.2%) in CD (p&amp;lt;.001). At the time of recruitment, 54.5% of CD and 23.7% of UC patients had previous surgery for IBD. Stratification of subjects into two groups by date of recruitment,1995–2009 and 2010–2019, showed similar ages at onset and diagnosis, but the time to diagnosis decreased for UC (2 vs 1.55 yrs.) and increased for CD (2.2 vs 2.6 yrs.) in the later interval. Medications varied between decades, with aTNF increasing markedly in CD and UC (p&amp;lt;.001) and aminosalicylates decreasing in CD (p&amp;lt;.001) in the later years. Surgery for UC decreased from 25.2% to 20.7%, whereas surgery for CD remained the same (52.2% vs 52.5%). Conclusion We describe a large cohort of Hispanics with IBD studied over two decades. Differences over time may reflect changes in disease phenotypes, environmental influences and the impact of physician awareness and new management guidelines and therapies. Further studies are needed to better characterize this population and explore outcomes.

P628 Risk Factors Associated with Extraintestinal Manifestations in Patients with Inflammatory Bowel Diseases

Abstract Background Risk factors associated with extraintestinal manifestations (EIMs) in patients with inflammatory bowel disease (IBD) have been evaluated mainly in retrospective studies. We aimed to determine risk factors associated with EIMs and to compare the frequency of EIMs between ulcerative colitis (UC) and Crohn’s disease (CD), based on retrospectively-prospectively collected data of a cohort of IBD patients followed in daily clinical practice. Methods Patients with biopsy-confirmed IBD aged 10–80 years old were included in the study. A comprehensive questionnaire was used to collect data on each site visit from July 2018 until March 2020. Logistic regression analysis and multivariable-adjusted models were used to examine risk factors associated with EIMs and chi-squared test was used to compare the frequency of EIMs between patients with UC and CD. Results 300 patients with IBD (180 with CD, 113 with UC, and 7 with indeterminate colitis) were evaluated. EIMs were observed in 49% of patients, with a 2-fold increased risk in CD (OR 2.31; 95% CI:1.37–3.89; P&amp;lt;.005). The musculoskeletal system was affected in 38% (43% in CD vs 29% in UC, OR 1.86; 95% CI:1.08–3.20; P&amp;lt;.05) with peripheral arthropathy being the most common manifestation (33% in CD vs 23% in UC, P=.095), followed by dermatological manifestations (13%), with a 4-fold increased risk of erythema nodosum in CD (11% vs 3% in UC, OR 3.95; 95% CI:1.12–13.93; P&amp;lt;.05). On univariate logistic regression analysis history of hospitalization for IBD, history of surgery for IBD, aphthous stomatitis, perianal disease, thyroiditis Hashimoto, age, use of thiopurines, and/or anti-TNF in the past were associated with increased risk of developing EIMs. A trend for increased risk of EIMs was found for family history of IBD in first-degree relatives (OR 2.47; 95% CI:0.91–6.74; P=.078) and fecal calprotectin above 250 μg/g (OR 2.22; 95% CI:0.90–5.47; P&amp;lt;.084). On multivariate analysis only aphthous stomatitis (OR 4.60; 95% CI:2.32–9.13; P&amp;lt;.001), perianal disease (OR 2.30; 95% CI:1.17–4.50; P&amp;lt;.05), thyroiditis Hashimoto (OR 2.82; 95% CI:1.03–7.74; P&amp;lt;.05) and age (2% increase in risk per year, OR 1.02; 95% CI:1.01–1.03; P&amp;lt;.05) were significant for EIMs. Conclusion In this retrospective/prospective study 49% of IBD patients developed EIMs with a 2-fold increased risk in CD. Musculoskeletal and dermatological manifestations were the most frequent EIMs. Aphthous stomatitis, perianal disease, thyroiditis Hashimoto and age were associated with increased risk of EIMs.

Update: enterogenic spondylarthritis

Spondylarthritis (SpA) is one of the most frequent extraintestinal manifestations of chronic inflammatory bowel disease (IBD). Several arthritogenic enterobacterial infections can induce sequelae such as reactive SpA. Studies on the gut-synovium axis in view of genetic, immunological, clinical and therapeutic aspects has made enterogenic SpA amodel disease of all forms of SpA. The same applies for investigating IBD, as subclinical gut inflammation seen in SpA patients has provided significant evidence for a better understanding of mucosa-associated early immune events in Crohn's disease (CD). This article summarizes the pathognomonic clinical features, diagnostic steps, differential diagnosis and current pathogenetic models of enterogenic SpA. Knowledge of pathogenetic contexts leads to concrete treatment recommendations. These vary individually depending on the underlying IBD, on the inflammatory intestinal or rheumatic activity and on the rheumatological manifestation pattern.

Ocular manifestations of inflammatory bowel diseases: an update for gastroenterologists.

Inflammatory bowel diseases (IBD), that includes ulcerative colitis and Crohn's disease, can affect not only the gastrointestinal tract but a wide spectrum of organs. The extra-intestinal manifestations (EIMs) are one of the most challenging aspect of IBD, playing a significant role for the lifetime care and the quality of life of patients. Ocular manifestations are the third most frequent EIMs, preceded by articular and dermatological ones. The aim of this narrative review is to describe the different types of ocular involvements, focusing on their clinical management. Uveitis and episcleritis are the most common ocular EIMs, differing for many aspects. Uveitis are unrelated with IBD activity and they even precede the onset of the intestinal disease, while episcleritis are common defined as a good mark of IBD activity. Pain is uncommon in most cases of episcleritis, while severe eye pain and photophobia are the most frequent onset of anterior uveitis. Less common but even more severe, are orbital pseudotumor or posterior segment involvement. Most of the ocular EIMs can be successfully treated with topic and oral steroids and the underlying therapy for IBD can reduce or cut out at all the recurrence of these manifestations. Symptoms are commonly not specific, in some cases being unnoticed for years leading to permanent ocular consequences. Cooperation between different specialists is crucial to avoid all the possible consequences of a non-treated EIMs, especially for ocular ones.

S3215 Hermansky-Pudlak-Associated IBD: Is It the Same? Description of a Puerto Rican Cohort

INTRODUCTION: Hermansky-Pudlak Syndrome (HPS) is the most common single gene disorder in Puerto Rico. It is a rare autosomal recessive disorder due to aberrant biogenesis of lysosome-related organelles leading to oculocutaneous albinism, bleeding diathesis, and involvement in other organs. About 30% of patients with HPS develop a form of Crohn’s-like inflammatory bowel disease (IBD), granulomatous enterocolitis. Whether this is a manifestation of HPS or true IBD is still in debate. We wish to describe a group of patients with HPS-associated IBD. METHODS: This is a prospective cohort study in which phenotypically identified patients with HPS and concomitant IBD are recruited. After informed consent, a questionnaire with demographic and medical data is administered through patient interview and record review is performed. The variables collected are sex, HPS genotype, age at the time of IBD diagnosis, comorbidities, IBD location and behavior according to Montreal Classification, surgical interventions, medications, and extra-intestinal manifestations (EIM). This study is approved by the IRB. RESULTS: Ten patients with HPS and concomitant IBD were identified in our clinics - 5 males and 5 females. HPS genotype in 9 showed 8 were HPS-1 and 1 was HPS-3. The mean age at the time of IBD diagnosis was 22 ± 10 years. Six were diagnosed between ages 17 and 40 years and 4 patients were diagnosed at ≤16 y/o. Seven patients had colonic involvement, 3 had ileocolonic involvement. Sixty percent of patients had an advanced penetrating behavior and 50% had perianal involvement. Six patients had some type of surgical intervention. Three patients were on both a biologic and an immunomodulator (IMM), 5 were on a biologic alone, 1 on IMM alone, and 1 without maintenance treatment. The most frequent EIM was anemia in 40% of patients. CONCLUSION: HPS patients had a severe course of IBD, as shown by phenotype, surgery, and use of biologics. A younger age at diagnosis and a higher than usual prevalence of perianal disease also predict a complicated course. Further studies are necessary to determine if HPS-associated IBD is related to the genetic defect and if this may result in a different clinical course than idiopathic IBD.

Ocular manifestations of inflammatory bowel diseases: an update for gastroenterologists.

Inflammatory bowel diseases (IBD), that includes ulcerative colitis and Crohn's disease, can affect not only the gastrointestinal tract but a wide spectrum of organs. The extra-intestinal manifestations (EIMs) are one of the most challenging aspect of IBD, playing a significant role for the lifetime care and the quality of life of patients. Ocular manifestations are the third most frequent EIMs, preceded by articular and dermatological ones. The aim of this narrative review is to describe the different types of ocular involvements, focusing on their clinical management. Uveitis and episcleritis are the most common ocular EIMs, differing for many aspects. Uveitis are unrelated with IBD activity and they even precede the onset of the intestinal disease, while episcleritis are common defined as a good mark of IBD activity. Pain is uncommon in most cases of episcleritis, while severe eye pain and photophobia are the most frequent onset of anterior uveitis. Less common but even more severe, are orbital pseudotumor or posterior segment involvement. Most of the ocular EIMs can be successfully treated with topic and oral steroids and the underlying therapy for IBD can reduce or cut out at all the recurrence of these manifestations. Symptoms are commonly not specific, in some cases being unnoticed for years leading to permanent ocular consequences. Cooperation between different specialists is crucial to avoid all the possible consequences of a non-treated EIMs, especially for ocular ones.

INFLAMMATORY BOWEL DISEASE: CLINICAL FEATURES AND MANIFESTATIONS BEYOND THE BOWEL

Inflammatory bowel disease (IBD) encompasses a spectrum of diseases, with Crohn's disease (CD) and ulcerative colitis (UC) representing the two broadest subtypes of IBD. Multiple extraintestinal manifestations (EIMs) are more frequent in (IBD); 5% –50% of the patients might be affected. The most often implicated sites of manifestations are musculoskeletal and dermatological structures. However, while some symptoms like peripheral arthritis and erythema nodosum correlate with IBD progression, others have their own course of disease like axial arthropathy, gangrenosis of the pioderma and primary sclerosic cholangitis. This review would provide a summary of the most frequent EIMs and their prevalence.&#x0D; Peer Review History: &#x0D; Received 31 May 2020; Revised 7 June; Accepted 4 July, Available online 15 July 2020&#x0D; UJPR follows the most transparent and toughest ‘Advanced OPEN peer review’ system. The identity of the authors and, reviewers will be known to each other. This transparent process will help to eradicate any possible malicious/purposeful interference by any person (publishing staff, reviewer, editor, author, etc) during peer review. As a result of this unique system, all reviewers will get their due recognition and respect, once their names are published in the papers. We expect that, by publishing peer review reports with published papers, will be helpful to many authors for drafting their article according to the specifications. Auhors will remove any error of their article and they will improve their article(s) according to the previous reports displayed with published article(s). The main purpose of it is ‘to improve the quality of a candidate manuscript’. Our reviewers check the ‘strength and weakness of a manuscript honestly’. There will increase in the perfection, and transparency.&#x0D; Received file &#x0D; &#x0D; Average Peer review marks at initial stage: 5.5/10&#x0D; Average Peer review marks at publication stage: 7.0/10&#x0D; Reviewer(s) detail:&#x0D; Name: Dr. Md. Parwez Ahmad&#x0D; Affiliation: National Medical College, Birgunj, Nepal&#x0D; E-mail: parwezmedicine@gmail.com&#x0D; &#x0D; Name: Dr. George Zhu &#x0D; Affiliation: Tehran University of Medical Sciences, Tehran, Iran&#x0D; E-mail: sansan4240732@163.com&#x0D; &#x0D; Comments of reviewer(s): &#x0D; &#x0D;