The prevalence and association between immune-mediated inflammatory disorders and inflammatory bowel disease

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While there is a clear link between IBDs and other immune-mediated inflammatory disorders (IMIDs), research into this relationship is limited, particularly in the Middle East. This study sought to determine the predictive factors and prevalence of IMIDs in IBDs patients at King Abdulaziz University Hospital in Saudi Arabia. Methods A single-center retrospective investigation was carried out on adult patients with confirmed IBDs. Between 2017 and 2022, the study was conducted at King Abdulaziz University Hospital in Jeddah, Saudi Arabia. Eligible patients over the age of 18 with verified IBDs diagnosis were found through the hospital's IBDs registry. Data on demographics, type of IBDs, disease duration, medications, extraintestinal manifestations (EIMs), and laboratory investigations were collected. The prevalence of IMIDs was examined, and multiple logistic regression analysis was done to discover predictors. Results A total of 172 patients were randomly selected, with a mean age of 37.33 years; 55.8% were women. Among them, 50.6% had IMIDs. Of the patients with IBDs, 57% had CD and 43% had UC. Patients with IMIDs had a shorter IBDs duration (10.06 years) compared to those without IMIDs (12.23 years, p < 0.05). Male sex was a positive predictor for IMIDs (Odds Ratio [OR]: 2.57), while erythema nodosum (OR: 4.75) and pyoderma gangrenosum (OR: 7.44) were protective. Conclusion The study revealed a significant prevalence of IMIDs among patients with IBDs, highlighting the need to recognize predictors for improved clinical management. 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F1000Research 2025, 14 :492 ( https://doi.org/10.12688/f1000research.160835.1 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. Close Copy Citation Details Export Export Citation Sciwheel EndNote Ref. Manager Bibtex ProCite Sente EXPORT Select a format first Track Share ▬ ✚ Research Article The prevalence and association between immune-mediated inflammatory disorders and inflammatory bowel disease [version 1; peer review: 2 approved with reservations] Assil F Ruckn https://orcid.org/0009-0000-5570-7490 1 , Mahmoud H Mosli 1-3 , Balsam K Osman 1 , [...] Rehal A Alalasi 1 , Jazmin A Alghamdi 1 , Sawsan M Alsiyoufi 1 , Rahaf Y Alam Aldeen 1 , Alhanouf A Alsharif 1 , Majed A Alsahafi 1-3 , Omar I Saadah 1,3,4 Assil F Ruckn https://orcid.org/0009-0000-5570-7490 1 , Mahmoud H Mosli 1-3 , [...] Balsam K Osman 1 , Rehal A Alalasi 1 , Jazmin A Alghamdi 1 , Sawsan M Alsiyoufi 1 , Rahaf Y Alam Aldeen 1 , Alhanouf A Alsharif 1 , Majed A Alsahafi 1-3 , Omar I Saadah 1,3,4 PUBLISHED 13 May 2025 Author details Author details 1 Faculty of Medicine, King Abdulaziz University, Jeddah, Makkah Province, Saudi Arabia 2 Department of Internal Medicine, King Abdulaziz University, Jeddah, Makkah Province, Saudi Arabia 3 Inflammatory Bowel Disease Research Group, King Abdulaziz University, Jeddah, Makkah Province, Saudi Arabia 4 Department of Pediatrics, Faculty of Medicine, King Abdulaziz University, Jeddah, Makkah Province, Saudi Arabia Assil F Ruckn Roles: Conceptualization, Data Curation, Funding Acquisition, Investigation, Methodology, Resources, Supervision, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing Mahmoud H Mosli Roles: Conceptualization, Data Curation, Formal Analysis, Methodology, Supervision, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing Balsam K Osman Roles: Conceptualization, Data Curation, Investigation, Methodology, Resources, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing Rehal A Alalasi Roles: Conceptualization, Data Curation, Investigation, Methodology, Resources, Writing – Original Draft Preparation, Writing – Review & Editing Jazmin A Alghamdi Roles: Conceptualization, Data Curation, Investigation, Methodology, Resources, Writing – Original Draft Preparation, Writing – Review & Editing Sawsan M Alsiyoufi Roles: Conceptualization, Data Curation, Investigation, Methodology, Resources, Writing – Original Draft Preparation, Writing – Review & Editing Rahaf Y Alam Aldeen Roles: Conceptualization, Data Curation, Investigation, Methodology, Resources, Writing – Original Draft Preparation, Writing – Review & Editing Alhanouf A Alsharif Roles: Conceptualization, Investigation, Methodology, Project Administration, Resources, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing Majed A Alsahafi Roles: Conceptualization, Data Curation, Project Administration, Resources, Supervision, Writing – Original Draft Preparation Omar I Saadah Roles: Conceptualization, Data Curation, Project Administration, Supervision, Validation OPEN PEER REVIEW DETAILS REVIEWER STATUS Abstract Background Inflammatory bowel diseases (IBDs), which includes ulcerative colitis (UC) and Crohn's disease (CD), are chronic immune-mediated inflammatory disorders. While there is a clear link between IBDs and other immune-mediated inflammatory disorders (IMIDs), research into this relationship is limited, particularly in the Middle East. This study sought to determine the predictive factors and prevalence of IMIDs in IBDs patients at King Abdulaziz University Hospital in Saudi Arabia. Methods A single-center retrospective investigation was carried out on adult patients with confirmed IBDs. Between 2017 and 2022, the study was conducted at King Abdulaziz University Hospital in Jeddah, Saudi Arabia. Eligible patients over the age of 18 with verified IBDs diagnosis were found through the hospital's IBDs registry. Data on demographics, type of IBDs, disease duration, medications, extraintestinal manifestations (EIMs), and laboratory investigations were collected. The prevalence of IMIDs was examined, and multiple logistic regression analysis was done to discover predictors. Results A total of 172 patients were randomly selected, with a mean age of 37.33 years; 55.8% were women. Among them, 50.6% had IMIDs. Of the patients with IBDs, 57% had CD and 43% had UC. Patients with IMIDs had a shorter IBDs duration (10.06 years) compared to those without IMIDs (12.23 years, p < 0.05). Male sex was a positive predictor for IMIDs (Odds Ratio [OR]: 2.57), while erythema nodosum (OR: 4.75) and pyoderma gangrenosum (OR: 7.44) were protective. Conclusion The study revealed a significant prevalence of IMIDs among patients with IBDs, highlighting the need to recognize predictors for improved clinical management. READ ALL READ LESS Keywords prevalence, association, IMIDs, IBDs, KAU, Saudi Corresponding Author(s) Mahmoud H Mosli ( [email protected] ) Close Corresponding author: Mahmoud H Mosli Competing interests: No competing interests were disclosed. Grant information: The author(s) declared that no grants were involved in supporting this work. Copyright: © 2025 Ruckn AF et al . This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. How to cite: Ruckn AF, Mosli MH, Osman BK et al. The prevalence and association between immune-mediated inflammatory disorders and inflammatory bowel disease [version 1; peer review: 2 approved with reservations] . F1000Research 2025, 14 :492 ( https://doi.org/10.12688/f1000research.160835.1 ) First published: 13 May 2025, 14 :492 ( https://doi.org/10.12688/f1000research.160835.1 ) Latest published: 13 May 2025, 14 :492 ( https://doi.org/10.12688/f1000research.160835.1 ) Introduction Inflammatory bowel disease (IBDs) refers to a set of chronic gastrointestinal inflammatory illnesses. The two most common types of IBD are ulcerative colitis ([UC]) and Crohn's disease ([CD]). CD can affect any part of the gastrointestinal system, but UC is limited to the large intestine ( Centers for Disease Control and Prevention, 2023 ). Immune-mediated inflammatory disorders ([IMIDs]) occur when the immune system fails to distinguish between normal and foreign cells, resulting in an attack on healthy cells and chronic inflammation, which is a common feature of IMIDs. There are about 80 different IMIDs that affect various body organs ( David et al., 2018 ). Notable IMIDs include rheumatoid arthritis (RA), systemic lupus erythematous (SLE), thyroid disorders, diabetes mellitus (DM), and coeliac disease. IBDs Bar Yehuda et al. (2019) are thought to be caused by an abnormal immune response to gut microbiota in those with genetic predispositions. There is a large overlap between the genetic changes found in several IMIDs ( Farh et al., 2015 ) and those with inflammatory bowel disease ( Criswell et al., 2005 ). That may explain why patients with IBDs are more likely to acquire other IMIDs ( Cotsapas et al., 2011 ; Vyse and Todd, 1996 ; Chun et al., 2017 ; Wilson et al., 2016 ; Halling et al., 2017 ). Disease classification at the time of diagnosis is critical since it offers important information about the disease's progression. These statistics are critical for providing best medical treatment to patients. The Montreal classification system is used to categories individuals with IBDs based on the severity of the ailment and if it is associated with the development of IMIDs. This classification assesses the extent of disease and severity of symptoms with predictive value ( Monstad et al., 2014 ). A 2015 study of 17428 patients with IBDs and 17428 non-IBDs cases found that patients with IBDs had a higher prevalence of IMIDs than non-IBDs patients ( Wilson et al., 2016 ). Furthermore, a 2017 study of individuals with 20 distinct IMIDs discovered that they occurred more commonly in those with IBDs.10 Nonetheless, there have been few research examining the relationship between IBD and IMIDs among Middle Eastern and Persian Gulf populations. Thus, this study aimed to estimate the prevalence of IMIDs in patients with IBDs in Saudi Arabia. Methods A single-center retrospective analysis was carried out on adult patients with confirmed IBD, regardless of age, country, or gender, who were followed up at King Abdulaziz University Hospital in Jeddah, Saudi Arabia, from 2017 to 2022. The King Abdulaziz University ([KAU]) Inflammatory Bowel Disease Information System ([IBDIS]) registry was used to determine eligible patients. All patients over the age of 18 with a confirmed diagnosis of IBD using standard clinical, endoscopic, and histologic criteria were considered eligible. Sample size The sample size was calculated using a 95% CI and 80% power to detect a difference in the proportion of patients with IMIDs; if patients with IBD had a twofold increased risk of developing an IMID compared with the average risk of 10% in the general population, the minimum sample size of 102 patients was estimated using a sample size calculator algorithm. After estimating the sample size for this study, a random sample of eligible patients was obtained from the registry. A systematic random sample (interval sampling) methodology was used. In this procedure, the investigators pick individuals to be included in the sample based on a systematic rule, with the rule being to include the last patient from every ten patients ( Ahmed SK, 2024 ). All types of IMIDs searched within the registry using the International Classification of Diseases 10th Revision ([ICD-10]) coding are listed in extended data-Supplementary Table 1. Data collected using a predesigned data extraction sheet included patient demographics, type of IBD ([UC or CD]), duration of illness, medications, extraintestinal manifestations ([EIMs]) of IBD, complications, laboratory investigations including hemoglobin ([Hb]), white cell count ([WBC]), platelet count ([PLT]), C-reactive protein ([CRP]), albumin, aspartate aminotransferase ([AST]), alanine transaminase ([ALT]), total bilirubin, alkaline phosphatase [(ALP]), and outcomes ([for IMIDs]). The Montreal classification was used to classify patients with UC as follows. Regarding disease course, S0 denotes clinical remission or being asymptomatic, S1 denotes mild UC involving the passage of four or fewer stools/day ([with or without blood]), absence of any systemic illness, and conventional inflammatory markers such as erythrocyte sedimentation rate ([ESR]), S2 denotes moderate UC involving the passage of more than four stools/day, but with minimal UC signs of systemic toxicity, S3 denotes moderate UC involving the passage of more than four stools/day but minimal UC signs of systemic toxicity, S4 denotes severe UC involving the passage of at least six bloody stools/day, a pulse rate of at least 90 beats/minute, a body temperature of at least 37.5°C, hemoglobin of less than 10.5 g/100 ml, and ESR of at least 30 mm/hour. Regarding the extent of disease, E1 denotes ulcerative proctitis with involvement limited to the rectum ([proximal extent of inflammation is distal to the rectosigmoid junction]), E2 denotes left-sided UC ([distal UC]) reflecting involvement that is limited to the colon and rectum distal to the splenic flexure, and E3 denotes extensive UC ([pancolitis]) with involvement that extends proximal to the splenic flexure. Regarding age at diagnosis, A1 denotes 40 years. For CD, the Montreal classification categorizes patients according to location ([L1 = ileal; L2 = colonic; L3 = ileocolonic; L4 = isolated upper disease]), behavior ([B1 = non-stricturing, non-penetrating, B2 = stricturing, B3 = penetrating]), and age at the time of diagnosis ([A1 40 years]). Ethical considerations This work received ethical permission from the Research Ethics Committee of King Abdulaziz University Hospital in Jeddah, Saudi Arabia [Ethical permission Number: 441-23]. Date of approval: Monday, October 2, 2023. Statistical analysis Data were analyzed using SPSS software version 26. The chi-square test was used for qualitative data expressed as numbers and percentages to assess the association between the variables. Quantitative data are presented as mean and standard deviation ([mean (SD)]), and the Mann-Whitney test was used for non-parametric variables. Multiple logistic regression analysis calculated odds ratios ([OR]) at a 95% confidence interval ([CI]). Statistical significance was defined as a P -value < .05. Results Baseline characteristics Nine hundred and ten patients registered in the IBDIS database were screened for eligibility, and a random sample of 172 patients was selected for this study. The mean age of the patients was 37.33 ([11.03]) years; 55.8% were women, 72.1% had Saudi nationality, 44.2% were married, and 8.7% were smokers. The mean duration of IBD was 11.12 ([6.05]) years. Of the cohort, 57% had CD, and 43% had UC. Among the patients with UC, 54% had an S2 Montreal classification for severity, and 36.6% had an E3 Montreal classification for the extent of UC. Among the patients with CD, only 5.5% were > 40 years of age at diagnosis, 25.6% had an ileocolonic location, and 32% had a non-stricturing, non-penetrating lesion ([ Table 1 ]). The mean values of Hg, WBCs, platelet, Albumin, AST, ALT, Bilirubin, and ALP are shown in Table 2 . Of the patients with CD ([N = 98]), 64.2% had EIMs; the most common were arthralgia ([26.5%]) and erythema nodosum ([EN]) ([25.5%]). Regarding patients with UC ([N=74]), 63.5% had EIMs; arthralgia ([61.7%]) and EN ([36.1%]) were the most common. Half of the patients with CD had complications, such as osteoporosis ([42.8%]) and fistulas ([36.7%]). Of the patients with UC, 31% developed colon cancer and osteoporosis ([34.7%]). Table 1. Relationship between immune-mediated inflammatory disorders, patient demographics, and smoking status (N = 172). Variable Total Immune-mediated inflammatory disorders χ2 p-value No N (%) Yes N (%) Mean age (years) 37.33 ± 11.03 36.51 ± 16.55 38.14 ± 17.55 0.64 * 0.519 Sex Female 96 (55.8) 56 (65.9) 40 (46) 6.9 0.009 Male 76 (44.2) 29 (34.1) 47 (54) Nationality Non-Saudi 48 (27.9) 28 (32.9) 20 (23) 2.11 0.146 Saudi 124 (72.1) 57 (67.1) 67 (77) Marital status Single 96 (55.8) 52 (61.2) 44 (50.6) 1.95 0.162 Married 76 (44.2) 33 (38.8) 43 (49.4) Smoking status Non-smoker 157 (91.3) 81 (95.3) 76 (87.4) 3.4 0.065 Smoker 15 (8.7) 4 (4.7) 11 (12.6) N.B.: * = Mann-Whitney test. Table 2. Relationship between immune-mediated inflammatory disorders and IBD type, duration, Montreal classification for UC, age at diagnosis, location and behavior for CD, and laboratory results (N = 172). Variable Total N (%) Immune-mediated inflammatory disorders χ2 p-value No N (%) Yes N (%) Mean disease duration (years) 11.12 ± 6.05 12.23 ± 5.23 10.06 ± 6.6 3.18 * 0.001 IBD type CD 98 (57) 51 (60) 47 (54) 0.62 0.429 UC 74 (43) 34 (40) 40 (46) Ulcerative colitis Montreal classification Severity: (N = 74) S0 6 (8.1) 2 (2.4) 4 (4.6) 1.24 0.871 S1 12 (16.2) 5 (5.9) 7 (8) S2 40 (54) 19 (22.4) 21 (24.1) S3 16 (21.7) 8 (9.4) 8 (9.2) Extent (UC): (N =74) E1 20 (27) 11 (12.9) 9 (10.3) 3.3 0.507 E2 26 (35.1) 12 (14.1) 14 (16.1) E3 27 (36.6) 10 (11.8) 17 (19.5) No data 1 (1.3) 1 (1.2) 0 (0.0) Age of diagnosis: A1 - below 16 y 10 (13.5) 7 (8.2) 3 (3.4) A2 - between 17-40 y 41 (55.5) 18 (21.2) 23 (26.4) 3.4 0.32 A3 - above 40 y 23 (31 9 (10.6 14 (16.1) Crohn’s disease Age of diagnosis: A1 - 40 9 (5.2) 4 (4.7) 5 (5.7) Location: L1 - ileal 28 (16.3) 13 (15.3) 15 (17.2) L2 - colonic 25 (14.5) 18 (21.2) 7 (8) 5.97 0.113 L3 - ileocolonic 44 (25.6) 20 (23.5) 24 (27.6) Behavior: B1 - non stricturing, non-penetrating 55 (32) 27 (31.8) 28 (32.2) 1.12 0.772 B2 - stricturing 19 (11) 11 (12.9) 8 (9.2) B3 - penetrating 24 (14) 13 (15.3) 11 (12.6) Perianal diseases No 72 (73.5) 40 (47.1) 32 (36.8) 1.96 0.374 Yes 26 (26.5) 11 (12.9) 15 (17.2) Laboratory analysis Hemoglobin 11.74 ± 3.04 11.56 ± 3.42 11.92 ± 2.61 0.05* 0.958 WBCs 7.69 ± 3.93 7.11 ± 3.77 8.29 ± 4.03 2.11* 0.035 Platelets 317.71 ± 150.23 313.34 ± 163.61 322.23 135.83 0.82* 0.41 Albumin 36.9 ± 10.66 34.83 ± 11.79 39.04 ± 8.91 2.64 * 0.008 AST 25.4 ± 23.52 22.88 ± 18.71 28.01± 27.51 0.42 * 0.671 ALT 27.82 ± 34.5 28.39 ± 39.48 27.22± 28.61 0.45 * 0.648 Bilirubin 16.69 ± 60.46 8.3 ± 6.7 25.29 ± 85.16 0.65 * 0.514 ALP 115.12 ± 114.29 98.73 ± 72.57 132.12 ± 144 1.13 * 0.357 N.B. * = Mann-Whitney test. ALP, alkaline phosphatase; ALT, alanine transaminase; AST, aspartate aminotransferase; CD, Crohn’s disease; IBD, inflammatory bowel disease; UC, ulcerative colitis; WBC, white blood cells. Study outcomes Of the total study cohort ([N = 172]), 87 ([50.6%]) patients had IMIDs other than IBD ([ Figure 1 ]). Among the patients with IMIDs, the most common disorders were DM type 1 ([31%]) and primary sclerosing cholangitis ([PSC]) ([24.1%]) ([ Figure 2 ]). The prevalence of IMID was significantly higher among male patients compared to female patients ([54% vs. 46%, respectively]); ([P < .05]) ([ Table 3 ]). The mean duration of disease was significantly shorter among patients with IMIDs ([10.06 (6.60) vs. 12.23 (5.23) years]) compared to those without IMIDs (P < .05). At the same time, IMID prevalence was significantly higher among patients with higher mean values of WBCs ([8.29 (4.03) vs. 7.11 (3.77)]) and serum albumin ([39.04 (8.91) vs. 34.83 (11.79)]) ( [P < .05]). The IMID prevalence was significantly lower among patients with CD with EIMs ([episcleritis, EN, or pyoderma gangrenosum [PG]]) (24.1% vs. 49.4%) ( [P < .05] ). Among patients with UC, the IMID prevalence was significantly lower among those with EN or aphthous stomatitis (1.1% vs. 18.8%) ([P < .05]). As for IBD complications, the IMID prevalence was substantially lower among patients with CD having fistulas (5.7% 15.3%) ([P < .05]) , while the IMID prevalence was significantly higher among patients with UC who developed colon cancer as a complication (8% vs. 1.2%) ([P < .05]) [ Table 3 ]. Figure 1. Percentage distribution of immune-mediated inflammatory disorders among studied patients (N = 172). Figure 2. Percentage distribution of type of immune-mediated inflammatory disorders among patients with IBD (N = 87). N.B.: Thyroid diseases = (Hashimoto’s thyroiditis /chronic lymphocytic thyroiditis/autoimmune thyroiditis). Table 3. Relationship between immune-mediated inflammatory disorders, extraintestinal manifestations, and disease complications for CD and UC (N = 172). Variable Total No. (%) Immune-mediated inflammatory disorders χ2 p-value No N (%) Yes N (%) Crohn’s disease (N = 98) Total extraintestinal manifestations (more than one answer was allowed) 63 (64.2) 42 (49.4) 21 (24.1) 11.83 0.001 Arthralgia (n = 1) 26 (26.5) 13 (15.3) 13 (14.9) 0.004 0.949 Aphthous stomatitis (n = 3) 17 (17.3) 12 (14.1) 5 (5.7) 3.38 0.066 Episcleritis (n = 4) 12 (12.2) 10 (11.8) 2 (2.3) 5.93 0.015 Erythema nodosum (n = 10) 25 (25.5) 21 (24.7) 4 (4.6) 13.99 <0.001 Pyoderma gangrenosum (n = 11) 19 (19.3) 15 (17.6) 4 (4.6) 7.45 0.006 Pancreatitis (n = 5) 1 (1) 1 (1.2) 0 (0.0) 1.03 0.31 Peritonitis (n = 6) 1 (1) 0 (0.0) 1 (1.1) 0.98 0.322 Demyelinating disease (n = 8) 1 (1) 0 (0.0) 1 (1.1) 0.98 0.322 Hepatic steatosis (n = 9) 1 (1) 1 (1.2) 0 (0.0) 1.03 0.31 Ulcerative colitis (N = 74) Total extraintestinal manifestations (More than one answer was allowed) 47 (63.5) 26 (30.6) 21 (24.1) 0.9 0.343 Arthralgia (n = 1) 29 (61.7) 11 (12.9) 18 (20.7) 1.84 0.175 Erythema nodosum (n = 10) 17 (36.1) 16 (18.8) 1 (1.1) 15.07 <0.001 Aphthous stomatitis (n = 3) /*6 (12.7) 6 (7.1) 0 (0.0) 6.36 0.012 Episcleritis (n = 4) 8 (17) 6 (7.1) 2 (2.3) 2.19 0.138 Pyoderma gangrenosum (n = 11) 11 (23.4) 8 (9.4) 3 (3.4) 2.55 0.11 Arthritis (n = 2) 2 (4.2) 0 (0.0) 2 (2.3) 1.97 0.17 Pancreatitis (n = 5) 2 (4.2) 2 (2.4) 0 (0.0) 2.07 0.15 Hepatic steatosis (n = 9) 1 (2.1) 0 (0.0) 1 (1.1) 0.98 0.322 Complications of Crohn’s disease (No.:98) 49 (50) 29 (34.1) 20 (23) 2.61 0.106 Type of complications of Crohn’s disease (N = 49) (More than one answer was allowed) Colon cancer (n = 1) 1 (2) 0 (0.0) 1 (1.1) 0.98 0.322 Venous Thrombo Embolism (n = 2) 6 (12.2) 3 (3.5) 3 (3.4) 0.001 0.977 Intestinal obstruction (n = 3) 6 (12.2) 1 (1.2) 5 (5.7) 2.66 0.102 Fistulas (n = 4) 18 (36.7) 13 (15.3) 5 (5.7) 4.18 0.041 Malnutrition (n = 8) 2 (4) 0 (0.0) 2 (2.3) 1.97 0.16 Osteoporosis (n = 11) 21 (42.8) 12 (14.1) 9 (10.3) 0.57 0.45 Perineal disease (n = 5) 10 (20.4) 7 (8.2) 3 (3.4) 1.79 0.18 Perforated bowel (n = 7) 3 (6.1) 2 (2.4) 1 (1.1) 0.36 0.547 Hernia (n = 12) 1 (2) 0 (0.0) 1 (1.1) 0.98 0.322 Complications of UC (n = 74) 23 (31) 8 (9.4) 15 (17.2) 2.27 0.131 Type of Complications of UC disease (n = 23) (More than one answer was allowed) Colon cancer (n = 1) 8 (34.7) 1 (1.2) 7 (8) 4.57 0.032 Venous Thrombo Embolism (n = 2) 4 (17.3) 2 (2.4) 2 (2.3) 0.001 0.981 Perforated bowel (n = 7) 1 (4.3) 0 (0.0) 1 (1.1) 0.98 0.322 Osteoporosis (n = 11) 8 (34.7) 3 (3.5) 5 (5.7) 0.47 0.49 Perineal disease (n = 5) 2 (8.6) 1 (1.2) 1 (1.1) 0.001 0.989 Malnutrition (n = 8) 1 (4.3) 0 (0.0) 1 (1.1) 0.98 0.322 The prevalence of IMID was significantly lower among patients treated with mesalazine (34.5% vs. 57.6%) ([P < .05]). In contrast, the IMID prevalence was substantially higher among patients who underwent surgery (34.5% vs. 25.9%) ([P < .05]) ([ Table 4 ]). Table 4. Relationship between immune-mediated inflammatory disorders and medications, nutritional support, surgery type, and outcome (N = 172). Variable Total N (%) Immune-mediated inflammatory disorders χ2 p-value No N (%) Yes N (%) Medications No 22 (12.8) 9 (10.6) 13 (14.9) 0.73 0.393 Yes 150 (87.2) 76 (89.4) 74 (85.1) Medications used Mesalazine 79 (45.9) 49 (57.6) 30 (34.5) 9.29 0.002 Azathioprine 62 (36) 34 (40) 28 (32.2) 1.13 0.286 Vedolizumab 11 (6.4) 5 (5.9) 6 (6.9) 0.07 0.786 Infliximab 28 (16.3) 12 (14.1) 16 (18.4) 0.57 0.448 Ustekinumab 3 (1.7) 1 (1.2) 2 (2.3) 0.31 0.574 Adalimumab 45 (26.2) 23 (27.1) 22 (25.3) 0.07 0.792 Corticosteroids 95 (55.6) 51 (60) 44 (51.2) 1.35 0.245 ASA 88 (51.5) 51 (60) 37 (42.5) 5.25 0.022 NSAIDS 50 (29.1) 22 (25.9) 28 (32.2) 0.82 0.363 Nutritional support 14 (8.1) 4 (4.7) 10 (11.5) 7.51 0.23 Normal diet 68 (39.5) 28 (32.9) 40 (46) Not applicable 90 (52.3) 53 (62.4) 37 (42.5) Nutritional support type (n = 14) Diabetic diet 3 (21.6) 1 (1.2) 2 (2.3) 4.27 0.113 Full liquid diet 1 (7.1) 1 (1.2) 0 (0.0) High potassium diet 1 (7.1) 0 (0.0) 1 (1.1) High potassium, Low fiber diet 1 (7.1) 1 (1.2) 1 (1.1) Low fat diet 2 (14.2) 1 (1.2) 1 (1.1) Low salt 2 (14.2) 0 (0.0) 2 (2.3) 3 (21.6) 0 (0.0) 3 (3.4) 1 (7.1) 1 (1.2) 0 (0.0) Surgery No 116 (67.4) 63 (74.1) 53 (60.9) 6.07 0.048 Yes 52 (30.2) 22 (25.9) 30 (34.5) Not applicable 4 (2.3) 0 (0.0) 4 (4.6) Dead 5 (2.9) 3 (3.5) 2 (2.3) 0.23 0.631 Alive 167 (97.1) 82 (96.5) 85 (97.7) Predictors of IMIDs According to multiple logistic regression analysis, male sex was a risk factor for IMID ([OR: 2.57, 95% CI = 1.08-6.08, P = .031 ]), while EN ([OR: 4.75, 95% CI = 1.28-6.01, P = .001 ]), or PG ([OR: 7.44, 95% CI = 1.46-17.95, P = .016 ]) as an EIM appeared to be significantly protective against developing any form of IMID ([ Table 5 ]). Table 5. Multivariate logistic regression analysis of risk factors of immune-mediated inflammatory disorders among studied IBD patients. Variable B Wald p-value Odds Ratio (CI:95%) Sex 0.94 4.63 0.031 2.57 (1.08-6.08) Duration of the disease 0.01 0.13 0.716 0.98 (0.91-1.06) Albumin 0.03 2.21 0.137 1.03 (0.99-1.07) Presence of any extraintestinal manifestations of Crohn’s disease 0.19 0.08 0.775 0.81 (0.2-3.21) Episcleritis 0.09 0.01 0.92 1.1 (0.16-.117) Erythema nodosum 2.69 10.1 0.001 4.75 (1.28-6.01) Pyoderma gangrenosum 2 5.83 0.016 7.44 (1.46-17.95) Aphthous stomatitis 0.12 1.34 0.846 0.19 (0.67-1.98) Fistulas 1.19 2.12 0.145 3.3 (0.66-6.53) Colon cancer 1.36 1.06 0.302 0.25 (0.1-3.4) Mesalazine 0.08 0.03 0.856 0.91 (0.35-2.34) ASA 0.39 0.64 0.422 0.67 (0.25-1.76) Surgery 0.31 0.37 0.539 1.36 (0.5-3.66) Discussion IBD, including UC and CD, are chronic IMIDs that cause recurring inflammation of the gastrointestinal tract because of the immune system attacking healthy cells. Shared genetic changes may aid in the coexistence of numerous IMIDs. This study sought to investigate the relationship between IMIDs and IBD. Our findings revealed a substantial relationship between IBD and IMIDs. Specifically, we discovered that roughly half of the patients with IBD ([50.6%]) had multiple IMIDs in addition to IBD ( Figure 1 ). Concerning specific IMIDs, our retrospective investigation found that T1DM was the most common in our sample, accounting for 31% of cases ([ Figure 2 ]). This finding is consistent with a prior study that included 47,325 IBD patients and proposed the existence of two possible pathways linking IBD and T1DM. These pathways include potential shared susceptibility genes like PTPN2 and changes in gut microbiota composition ( Halling et al., 2017 ; Bar Yehuda et al., 2019 ). Additionally, PSC was the second most common IMID found in our retrospective study, accounting for 24.1% ([ Figure 2 ]). The association between IBD and PSC is well established, with a previous systematic review and meta-analysis conducted in 2021 revealing that patients with UC are 1.7 times more likely to develop PSC than those with CD ( Barberio et al., 2021 ). These findings should encourage clinicians who manage IBD patients to maintain a high level of clinical awareness and alertness in the face of the possibility of PSC co-occurrence. Careful and regular screening for PSC in this patient population is essential, since early and precise diagnosis is vital for avoiding significant consequences. Interestingly, our current findings indicate a higher likelihood of IMIDs in CD patients. This data is consistent with a recent study conducted in Switzerland, which found a preponderance of IMIDs among CD patients ( Wilson et al., 2019 ). These findings have significant implications for comprehensive management approaches, particularly for educating patients about the increased risk of developing additional IMIDs. Our study investigated the correlation between IMIDs and IBD severity using the Montreal classification. Contrary to previous research indicating heightened autoimmune disease severity in patients with multiple immune-mediated conditions ( Wilson et al., 2019 ), we found no statistically significant association between severe forms of IBD and the development of IMIDs ( Table 2 ). However, it is crucial to acknowledge that our methodology for assessing IBD severity is relatively rudimentary, and further investigation is needed to validate these preliminary findings. In our attempt to find predictors of IMID incidence among IBD patients, multiple logistic regression analysis found that male patients were more likely to have other IMIDs, as opposed to earlier research where female patients were more impacted by IMIDs ( Gjymishka et al., 2013 ). However, this disparity may be due to the small sample size from a single center. We also looked at the relationship between IMIDs and laboratory indicators such CRP, ESR, and total leukocyte count ([ Table 2 ]). The findings indicated no significant associations between CRP levels ([P = .199]) , ESR ([P = .321]) , total leukocyte count ([P = .234]) , and the presence of IMIDs in the study population. However, it is essential to note that these markers represent only a subset of potential predictors, and further investigation is warranted to explore additional markers or combinations for a more comprehensive assessment of immune-mediated inflammation. While prior research has mostly focused on the increased likelihood of developing IMIDs because of an increasing number of IBD-related symptoms ( Wilson et al., 2016 ), our study reveals a novel discovery on EIMs. We found that combining EN with UC and CD greatly reduced the formation of IMIDs ([P <.001]) ([ Table 3 ]). This study has significant clinical implications, implying that the existence of EIMs may indicate a more favorable disease course or a lower risk of extra immune-mediated problems in patients with UC and CD. Further research is needed to clarify the underlying mechanisms and explore potential therapeutic implications. Patients with concomitant IMIDs may have a more aggressive form of IBD that may account for the shorter mean duration of IBD than those without IMIDs. Individuals diagnosed with IMID before IBD exhibit a more aggressive pattern of IBD, according to another study ( Akiyama et al., 2022 ). According to García et al. (2020) , the existence of an IMID before IBD is not a reliable predictor of surgery. As a result, the IMID diagnostic date may predict IBD. Before being identified with IBD, people with IMID may require more rigorous treatment and closer monitoring to prevent surgery and improve their quality of life ( The 46th Annual Meeting of the European Society, 2020 ). Our findings demonstrated substantial relationships between treatment methods and the occurrence of IMIDs in IBD patients. We found a substantial decrease in IMID prevalence among patients treated with mesalazine ([P < .005]), indicating a potential preventive effect against IMID formation. However, additional prospective studies with bigger sample sizes and a controlled study design are required to validate and expand on these findings. The study's shortcomings include a small and potentially non-representative sample size and the retrospective nature of data collecting from electronic medical records. These issues may limit the findings' generalizability and induce bias due to poor recording, compromising their accuracy. Future research should use larger sample numbers and better data collection methods to improve dependability and develop more strong findings about the relationship between IBD and IMIDs. More research is needed to look into additional indicators or combinations for a more comprehensive assessment of immune-mediated inflammation, as well as to confirm the potential therapeutic applications of EIMs in patients with UC and CD. Conclusions This retrospective analysis demonstrates the increased risk of IBD patients having concomitant IMIDs. In our group, 50% of persons with IBD had concomitant IMIDs, with type 1 diabetes and PSC being the most frequent. Several variables have been associated to the onset of IMIDs, including male sex, shorter disease duration, specific laboratory results, and the occurrence of comorbidities. Patients treated with mesalazine, CD patients with EIMs, and UC patients with EN or aphthous stomatitis had considerably lower prevalences. These findings indicate protective factors and areas for further research into managing IMIDs in the setting of IBD. Ethics and consent This work received ethical permission from the Research Ethics Committee of King Abdulaziz University Hospital in Jeddah, Saudi Arabia [Ethical permission Number: 441-23]. Date of approval: Monday, October 2, 2023. This retrospective study utilized data from patient records for individuals who had previously provided informed consent for the use of their health information in research. Consent was obtained in accordance with ethical guidelines, and the study was conducted in compliance with applicable regulations to ensure the confidentiality and privacy of the participants. This is a retrospective study and consent was waived by ethical committee for this study. Data availability Underlying data Figshare: IBD DATA last.xlsx. Doi: https://doi.org/10.6084/m9.figshare.28184474 ( Ruckn, Assil (2025a) ) The project contains the following underlying data: • IBD DATA figshare 2.xlsx Data are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0). Extended data Figshare: supplementary table. Doi: https://doi.org/10.6084/m9.figshare.28255574.v1 ( Ruckn, Assil (2025b) ) This project contains the following extended data: • supplementary table.docx Supplementary Table represent all types of IMIDs searched within the registry using the International Classification of Diseases 10th Revision ([ICD-10]) coding. Data are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0). Acknowledgments The authors gratefully acknowledge the cooperation of the administrative staff of the study setting. 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Comments on this article Comments (0) Version 1 VERSION 1 PUBLISHED 13 May 2025 ADD YOUR COMMENT Comment Author details Author details 1 Faculty of Medicine, King Abdulaziz University, Jeddah, Makkah Province, Saudi Arabia 2 Department of Internal Medicine, King Abdulaziz University, Jeddah, Makkah Province, Saudi Arabia 3 Inflammatory Bowel Disease Research Group, King Abdulaziz University, Jeddah, Makkah Province, Saudi Arabia 4 Department of Pediatrics, Faculty of Medicine, King Abdulaziz University, Jeddah, Makkah Province, Saudi Arabia Assil F Ruckn Roles: Conceptualization, Data Curation, Funding Acquisition, Investigation, Methodology, Resources, Supervision, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing Mahmoud H Mosli Roles: Conceptualization, Data Curation, Formal Analysis, Methodology, Supervision, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing Balsam K Osman Roles: Conceptualization, Data Curation, Investigation, Methodology, Resources, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing Rehal A Alalasi Roles: Conceptualization, Data Curation, Investigation, Methodology, Resources, Writing – Original Draft Preparation, Writing – Review & Editing Jazmin A Alghamdi Roles: Conceptualization, Data Curation, Investigation, Methodology, Resources, Writing – Original Draft Preparation, Writing – Review & Editing Sawsan M Alsiyoufi Roles: Conceptualization, Data Curation, Investigation, Methodology, Resources, Writing – Original Draft Preparation, Writing – Review & Editing Rahaf Y Alam Aldeen Roles: Conceptualization, Data Curation, Investigation, Methodology, Resources, Writing – Original Draft Preparation, Writing – Review & Editing Alhanouf A Alsharif Roles: Conceptualization, Investigation, Methodology, Project Administration, Resources, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing Majed A Alsahafi Roles: Conceptualization, Data Curation, Project Administration, Resources, Supervision, Writing – Original Draft Preparation Omar I Saadah Roles: Conceptualization, Data Curation, Project Administration, Supervision, Validation Competing interests No competing interests were disclosed. Grant information The author(s) declared that no grants were involved in supporting this work. Article Versions (1) version 1 Published: 13 May 2025, 14:492 https://doi.org/10.12688/f1000research.160835.1 Copyright © 2025 Ruckn AF et al . This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Download Export To Sciwheel Bibtex EndNote ProCite Ref. Manager (RIS) Sente metrics Views Downloads F1000Research - - PubMed Central info_outline Data from PMC are received and updated monthly. - - Citations open_in_new 0 open_in_new 0 open_in_new SEE MORE DETAILS CITE how to cite this article Ruckn AF, Mosli MH, Osman BK et al. The prevalence and association between immune-mediated inflammatory disorders and inflammatory bowel disease [version 1; peer review: 2 approved with reservations] . F1000Research 2025, 14 :492 ( https://doi.org/10.12688/f1000research.160835.1 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS track receive updates on this article Track an article to receive email alerts on any updates to this article. TRACK THIS ARTICLE Share Open Peer Review Current Reviewer Status: ? Key to Reviewer Statuses VIEW HIDE Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Version 1 VERSION 1 PUBLISHED 13 May 2025 Views 0 Cite How to cite this report: Poulsen GJ. Reviewer Report For: The prevalence and association between immune-mediated inflammatory disorders and inflammatory bowel disease [version 1; peer review: 2 approved with reservations] . F1000Research 2025, 14 :492 ( https://doi.org/10.5256/f1000research.176791.r421863 ) The direct URL for this report is: https://f1000research.com/articles/14-492/v1#referee-response-421863 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 08 Nov 2025 Gry Juul Poulsen , Aalborg University, Copenhagen, Denmark Approved with Reservations VIEWS 0 https://doi.org/10.5256/f1000research.176791.r421863 Many thanks for the opportunity to review this manuscript. This is a nice data source with detailed information about disease presentation and treatment. The results are very descriptive, but since there is no data on timing of measurement, it ... Continue reading READ ALL Many thanks for the opportunity to review this manuscript. This is a nice data source with detailed information about disease presentation and treatment. The results are very descriptive, but since there is no data on timing of measurement, it cannot be used to make any causal claims. Instead, the study presents disease profiles of IBD patients with and without IMIDS. Other limitations include small sample size, selected population and no background population to compare prevalence of IMIDs to. Relevance: Research has shown that comorbidity and complication profiles vary between countries, such as more perianal disease in East Asian IBD patients, and information about disease presentation and comorbidities in a Middle Eastern population is of importance, both for patients in the Middle East and for IBD patients of Middle Eastern background in other countries. Comments: Though few studies have looked at IBD in Middle Eastern and Persian Gulf populations, it would be nice with a few lines to summarize what is known about IBD in theses populations, especially since the authors have published several studies on the topic. The study is based on a single clinic which is a university hospital. How representative is this hospital for IBD patients in Saudi Arabia? Is there any chance that the hospital tends to treat more severe IBD patients or patients with a special disease profile? The study population consists of IBD patients in the registry, who were either dead or at data extraction date. The authors report a disease duration which I assume is the duration at date of data extraction. How was this calculated for patients who were dead at date of data extraction? A number of variables were coded from the electronic health records, but nothing is mentioned about the timing of these variables. Did the study only include data around the time of data extraction, or did it use whichever information was available, even if it was years before the data extraction? If a variable was reported at multiple time points, such as the lab measurements, which information was used? Likewise, is it possible based on the data source to say whether IMIDS were diagnosed before or after IBD diagnosis? If this study was to be replicated by another research group, they would need more information on the variables, such as ATC codes or similar for medication and more details on what is meant by “Nutrional support” and “surgery”. I am surprised that only one IBD patient had Rheumatoid arthritis. As I understand from the manuscript, electronic health records were searched based on the ICD-10 codes presented in the supplement. However, the supplement only gives the code M069 (Unspecified Rheumatoid arthritis) and not other codes that are used to code rheumatoid arthritis. I would suggest that the authors revise this code and potentially review the other IMID codes again. Tables 3 and 4 report EIMs, complications and other variables are reported with percentages among those who have any (e.g. percent with arthralgia within those with at least one EIM). The tables would be easier to read and more informative for the reader if these were the percentages within all IBD patients in the IMID/no IMID column. The multivariate logistic regression is problematic and not very informative. Primarily, because nothing is noted about timing on the variables, it is not clear whether some of the “predictors” are actually measured after the diagnosis of IMID were given. Secondly, though not described in the manuscript, it looks like the authors have included variables that were statistically significant in the Chi-square tests in the multivariate regression. Due to sample size, this method of selecting variables is rather arbitrary and lack interpretation. I suggest that you remove this analysis from the manuscript. Many of the conclusions in the study are overstated. For example, that the erythema nodosum and pyroderma gangrenosum were protective or that mesalazine could potentially have a preventive effect against IMID formation. Tables and figures: The tables and figures are messy and need editing. Overall, I would suggest omitting the chi-square and the Mann-Whitney test statistics since they provide little information. I have gone over the tables and figures: Figure 1 is very uninformative as it is and could easily be omitted. If kept, change the y-axis so that it starts at 0. Table 1: Include number of patients with and without IMID in header in head of table Table 2: Some of the percentages do not add up. For example, under the Montreal classification the percentages sums to 40.1% in the “No IMID” column and to 45.9% in the “IMID” column. This is a recurring problem throughout the table. In the “Total N” column the percentages sum to 100. Include number of patients with and without IMID in header of the table Some brackets “)” are missing. Did everybody have lab measurements? If not, please include number of individuals with lab measurements Table 3: What does (n=1) mean in the names of the EIM’s? For example Arthralgia (n=1)? Table 4: What does “not applicable” mean under surgery. There are apparently a few categories that lack descriptions. Nutritional support and vital status lack subheadings. Put “medications”, “nutritional support type” and “surgery” subheadings in bold. Is the work clearly and accurately presented and does it cite the current literature? Partly Is the study design appropriate and is the work technically sound? Partly Are sufficient details of methods and analysis provided to allow replication by others? Partly If applicable, is the statistical analysis and its interpretation appropriate? No Are all the source data underlying the results available to ensure full reproducibility? Yes Are the conclusions drawn adequately supported by the results? Partly Competing Interests: No competing interests were disclosed. Reviewer Expertise: Statistics, epidemiology, IBD I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Poulsen GJ. Reviewer Report For: The prevalence and association between immune-mediated inflammatory disorders and inflammatory bowel disease [version 1; peer review: 2 approved with reservations] . F1000Research 2025, 14 :492 ( https://doi.org/10.5256/f1000research.176791.r421863 ) The direct URL for this report is: https://f1000research.com/articles/14-492/v1#referee-response-421863 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Respond or Comment COMMENT ON THIS REPORT Views 0 Cite How to cite this report: Bertin L. Reviewer Report For: The prevalence and association between immune-mediated inflammatory disorders and inflammatory bowel disease [version 1; peer review: 2 approved with reservations] . F1000Research 2025, 14 :492 ( https://doi.org/10.5256/f1000research.176791.r385239 ) The direct URL for this report is: https://f1000research.com/articles/14-492/v1#referee-response-385239 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 28 May 2025 Luisa Bertin , University of Padua, Padua, Italy Approved with Reservations VIEWS 0 https://doi.org/10.5256/f1000research.176791.r385239 This retrospective single-center study examines the prevalence and predictive factors of immune-mediated inflammatory disorders (IMIDs) in 172 inflammatory bowel disease (IBD) patients at King Abdulaziz University Hospital, Saudi Arabia (2017-2022). The authors found that 50.6% of IBD patients had concomitant ... Continue reading READ ALL This retrospective single-center study examines the prevalence and predictive factors of immune-mediated inflammatory disorders (IMIDs) in 172 inflammatory bowel disease (IBD) patients at King Abdulaziz University Hospital, Saudi Arabia (2017-2022). The authors found that 50.6% of IBD patients had concomitant IMIDs, with Type 1 diabetes mellitus (31%) and primary sclerosing cholangitis (24.1%) being most common. Male sex emerged as a risk factor, while certain extraintestinal manifestations appeared protective. MAJOR CONCERNS 1. Methodological Issues - Sampling Bias The systematic sampling method described as "selecting the last patient from every ten patients" raises significant concerns about potential selection bias. This approach is poorly justified and could systematically exclude certain patient types or introduce temporal patterns that compromise the validity of prevalence estimates. The authors need to provide robust justification for why this specific sampling approach was chosen over true random sampling, or alternatively, demonstrate that their method doesn't introduce systematic bias. If the sampling method cannot be changed, this should be acknowledged as a major limitation that affects the generalizability of findings. 2. Sample Size Calculation Validity The sample size calculation assumes a 10% baseline IMID prevalence in the general population, but no supporting evidence is provided for this assumption in the Saudi Arabian context. This is problematic because IMID prevalence can vary significantly across different populations and geographic regions. The authors should provide epidemiological data supporting their baseline assumption or conduct sensitivity analyses using different baseline prevalences. Without proper justification, the study may be underpowered, leading to unreliable conclusions. 3. Statistical Analysis - Multiple Testing The authors perform numerous statistical comparisons throughout their analysis without applying appropriate corrections for multiple testing. This approach significantly increases the risk of Type I errors, meaning some of their significant findings may actually be false positives. They need to apply appropriate multiple testing corrections such as Bonferroni adjustment or false discovery rate control, then clearly state which results remain significant after correction. Any limitations in statistical power following these corrections should also be acknowledged. 4. Misinterpretation of "Protective" Factors The interpretation of erythema nodosum and pyoderma gangrenosum as "protective" factors against IMIDs is likely misleading and could lead to incorrect clinical interpretations. These associations more likely represent different disease phenotypes or diagnostic patterns rather than true protective mechanisms. The authors should reframe these findings as correlations rather than protective effects and discuss alternative explanations such as different disease phenotypes, diagnostic bias, or confounding factors. Causal language should be avoided when describing these associations. 5. Inadequate Methods Description Critical methodological details are missing from the manuscript, which limits both reproducibility and proper interpretation of results. The authors don't provide specific diagnostic criteria for each IMID studied, nor do they clarify the temporal relationship between IBD and IMID diagnoses. Additionally, data extraction procedures and validation methods are not adequately described. These details are essential for readers to understand exactly how the study was conducted and to enable replication by other researchers. MINOR CONCERNS 1. Presentation and Clarity Issues The manuscript would benefit from improved presentation quality throughout. Table 2 contains formatting inconsistencies and some variables are presented in ways that are difficult to interpret clearly. The figures could be higher resolution for better readability, and there's inconsistent presentation of statistical results, with some p-values shown as exact numbers while others are presented as inequalities. The terminology is also inconsistent, with "IBD" and "IBDs" used interchangeably throughout the manuscript. Standardizing these presentation elements would significantly improve the manuscript's clarity and professional appearance. 2. Literature Review Enhancement While the literature review is adequate, it could be strengthened by incorporating more recent comprehensive reviews and meta-analyses on IBD-IMID associations. The authors could better contextualize their findings within existing Middle Eastern literature and provide more detailed comparisons with findings from other populations. This would help readers understand how their results fit into the broader global picture of IBD and IMID relationships. 3. Discussion Expansion The limitations section is currently too brief and doesn't adequately address the implications of the single-center design or the retrospective nature of the study. The authors should expand this section to include all major methodological concerns and their potential impact on results. Additionally, the clinical implications could be discussed more thoroughly, with more specific recommendations for clinicians regarding screening practices and patient management. Cost-effectiveness considerations for implementing screening programs could also be valuable additions to the discussion. 4. Statistical Reporting Improvements The statistical reporting could be enhanced by providing better contextualization of effect sizes and including more detailed information about model assumptions and diagnostics. While odds ratios are provided, absolute risk differences would help clinicians better understand the practical significance of the findings. The authors should also report model diagnostics for their logistic regression analyses to demonstrate that statistical assumptions were met. 5. Data Presentation Enhancements Some aspects of data presentation could be clearer, particularly regarding denominators for percentage calculations and the handling of missing data. Laboratory reference ranges aren't provided, which makes it difficult to interpret the clinical significance of reported values. The authors should clarify all denominators used in percentage calculations, provide normal ranges for laboratory values, and describe patterns and methods for handling missing data throughout their analyses. This study addresses an important clinical question in an understudied population and has genuine potential to contribute valuable knowledge to our understanding of IMID prevalence in IBD patients. The research question is clinically relevant, and the findings could have meaningful implications for patient care in Middle Eastern populations where such data is limited. However, the major methodological concerns, particularly regarding the sampling methodology and statistical interpretation, must be addressed before this work can be considered suitable for publication. The authors should focus their revision efforts primarily on justifying or acknowledging the limitations of their sampling approach, correcting their statistical analysis for multiple comparisons, reframing their interpretation of "protective factors," and providing complete methodological details that would allow for study replication. Once these fundamental issues are resolved, this work could provide valuable insights that advance our understanding of the complex relationship between IBD and other immune-mediated inflammatory disorders. The clinical implications are potentially significant, and the geographic focus on Saudi Arabia fills an important gap in the literature. With appropriate revisions addressing the major concerns outlined above, this manuscript could make a meaningful contribution to the field. Is the work clearly and accurately presented and does it cite the current literature? Partly Is the study design appropriate and is the work technically sound? Partly Are sufficient details of methods and analysis provided to allow replication by others? Partly If applicable, is the statistical analysis and its interpretation appropriate? Partly Are all the source data underlying the results available to ensure full reproducibility? Yes Are the conclusions drawn adequately supported by the results? Partly Competing Interests: No competing interests were disclosed. Reviewer Expertise: IBD I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Bertin L. Reviewer Report For: The prevalence and association between immune-mediated inflammatory disorders and inflammatory bowel disease [version 1; peer review: 2 approved with reservations] . F1000Research 2025, 14 :492 ( https://doi.org/10.5256/f1000research.176791.r385239 ) The direct URL for this report is: https://f1000research.com/articles/14-492/v1#referee-response-385239 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Respond or Comment COMMENT ON THIS REPORT Comments on this article Comments (0) Version 1 VERSION 1 PUBLISHED 13 May 2025 ADD YOUR COMMENT Comment keyboard_arrow_left keyboard_arrow_right Open Peer Review Reviewer Status info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Reviewer Reports Invited Reviewers 1 2 Version 1 13 May 25 read read Luisa Bertin , University of Padua, Padua, Italy Gry Juul Poulsen , Aalborg University, Copenhagen, Denmark Comments on this article All Comments (0) Add a comment Sign up for content alerts Sign Up You are now signed up to receive this alert Browse by related subjects keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2025 Poulsen G. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 08 Nov 2025 | for Version 1 Gry Juul Poulsen , Aalborg University, Copenhagen, Denmark 0 Views copyright © 2025 Poulsen G. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (0) Approved With Reservations info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Many thanks for the opportunity to review this manuscript. This is a nice data source with detailed information about disease presentation and treatment. The results are very descriptive, but since there is no data on timing of measurement, it cannot be used to make any causal claims. Instead, the study presents disease profiles of IBD patients with and without IMIDS. Other limitations include small sample size, selected population and no background population to compare prevalence of IMIDs to. Relevance: Research has shown that comorbidity and complication profiles vary between countries, such as more perianal disease in East Asian IBD patients, and information about disease presentation and comorbidities in a Middle Eastern population is of importance, both for patients in the Middle East and for IBD patients of Middle Eastern background in other countries. Comments: Though few studies have looked at IBD in Middle Eastern and Persian Gulf populations, it would be nice with a few lines to summarize what is known about IBD in theses populations, especially since the authors have published several studies on the topic. The study is based on a single clinic which is a university hospital. How representative is this hospital for IBD patients in Saudi Arabia? Is there any chance that the hospital tends to treat more severe IBD patients or patients with a special disease profile? The study population consists of IBD patients in the registry, who were either dead or at data extraction date. The authors report a disease duration which I assume is the duration at date of data extraction. How was this calculated for patients who were dead at date of data extraction? A number of variables were coded from the electronic health records, but nothing is mentioned about the timing of these variables. Did the study only include data around the time of data extraction, or did it use whichever information was available, even if it was years before the data extraction? If a variable was reported at multiple time points, such as the lab measurements, which information was used? Likewise, is it possible based on the data source to say whether IMIDS were diagnosed before or after IBD diagnosis? If this study was to be replicated by another research group, they would need more information on the variables, such as ATC codes or similar for medication and more details on what is meant by “Nutrional support” and “surgery”. I am surprised that only one IBD patient had Rheumatoid arthritis. As I understand from the manuscript, electronic health records were searched based on the ICD-10 codes presented in the supplement. However, the supplement only gives the code M069 (Unspecified Rheumatoid arthritis) and not other codes that are used to code rheumatoid arthritis. I would suggest that the authors revise this code and potentially review the other IMID codes again. Tables 3 and 4 report EIMs, complications and other variables are reported with percentages among those who have any (e.g. percent with arthralgia within those with at least one EIM). The tables would be easier to read and more informative for the reader if these were the percentages within all IBD patients in the IMID/no IMID column. The multivariate logistic regression is problematic and not very informative. Primarily, because nothing is noted about timing on the variables, it is not clear whether some of the “predictors” are actually measured after the diagnosis of IMID were given. Secondly, though not described in the manuscript, it looks like the authors have included variables that were statistically significant in the Chi-square tests in the multivariate regression. Due to sample size, this method of selecting variables is rather arbitrary and lack interpretation. I suggest that you remove this analysis from the manuscript. Many of the conclusions in the study are overstated. For example, that the erythema nodosum and pyroderma gangrenosum were protective or that mesalazine could potentially have a preventive effect against IMID formation. Tables and figures: The tables and figures are messy and need editing. Overall, I would suggest omitting the chi-square and the Mann-Whitney test statistics since they provide little information. I have gone over the tables and figures: Figure 1 is very uninformative as it is and could easily be omitted. If kept, change the y-axis so that it starts at 0. Table 1: Include number of patients with and without IMID in header in head of table Table 2: Some of the percentages do not add up. For example, under the Montreal classification the percentages sums to 40.1% in the “No IMID” column and to 45.9% in the “IMID” column. This is a recurring problem throughout the table. In the “Total N” column the percentages sum to 100. Include number of patients with and without IMID in header of the table Some brackets “)” are missing. Did everybody have lab measurements? If not, please include number of individuals with lab measurements Table 3: What does (n=1) mean in the names of the EIM’s? For example Arthralgia (n=1)? Table 4: What does “not applicable” mean under surgery. There are apparently a few categories that lack descriptions. Nutritional support and vital status lack subheadings. Put “medications”, “nutritional support type” and “surgery” subheadings in bold. Is the work clearly and accurately presented and does it cite the current literature? Partly Is the study design appropriate and is the work technically sound? Partly Are sufficient details of methods and analysis provided to allow replication by others? Partly If applicable, is the statistical analysis and its interpretation appropriate? No Are all the source data underlying the results available to ensure full reproducibility? Yes Are the conclusions drawn adequately supported by the results? Partly Competing Interests No competing interests were disclosed. Reviewer Expertise Statistics, epidemiology, IBD I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. reply Respond to this report Responses (0) Poulsen GJ. Peer Review Report For: The prevalence and association between immune-mediated inflammatory disorders and inflammatory bowel disease [version 1; peer review: 2 approved with reservations] . F1000Research 2025, 14 :492 ( https://doi.org/10.5256/f1000research.176791.r421863) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/14-492/v1#referee-response-421863 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2025 Bertin L. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 28 May 2025 | for Version 1 Luisa Bertin , University of Padua, Padua, Italy 0 Views copyright © 2025 Bertin L. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (0) Approved With Reservations info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions This retrospective single-center study examines the prevalence and predictive factors of immune-mediated inflammatory disorders (IMIDs) in 172 inflammatory bowel disease (IBD) patients at King Abdulaziz University Hospital, Saudi Arabia (2017-2022). The authors found that 50.6% of IBD patients had concomitant IMIDs, with Type 1 diabetes mellitus (31%) and primary sclerosing cholangitis (24.1%) being most common. Male sex emerged as a risk factor, while certain extraintestinal manifestations appeared protective. MAJOR CONCERNS 1. Methodological Issues - Sampling Bias The systematic sampling method described as "selecting the last patient from every ten patients" raises significant concerns about potential selection bias. This approach is poorly justified and could systematically exclude certain patient types or introduce temporal patterns that compromise the validity of prevalence estimates. The authors need to provide robust justification for why this specific sampling approach was chosen over true random sampling, or alternatively, demonstrate that their method doesn't introduce systematic bias. If the sampling method cannot be changed, this should be acknowledged as a major limitation that affects the generalizability of findings. 2. Sample Size Calculation Validity The sample size calculation assumes a 10% baseline IMID prevalence in the general population, but no supporting evidence is provided for this assumption in the Saudi Arabian context. This is problematic because IMID prevalence can vary significantly across different populations and geographic regions. The authors should provide epidemiological data supporting their baseline assumption or conduct sensitivity analyses using different baseline prevalences. Without proper justification, the study may be underpowered, leading to unreliable conclusions. 3. Statistical Analysis - Multiple Testing The authors perform numerous statistical comparisons throughout their analysis without applying appropriate corrections for multiple testing. This approach significantly increases the risk of Type I errors, meaning some of their significant findings may actually be false positives. They need to apply appropriate multiple testing corrections such as Bonferroni adjustment or false discovery rate control, then clearly state which results remain significant after correction. Any limitations in statistical power following these corrections should also be acknowledged. 4. Misinterpretation of "Protective" Factors The interpretation of erythema nodosum and pyoderma gangrenosum as "protective" factors against IMIDs is likely misleading and could lead to incorrect clinical interpretations. These associations more likely represent different disease phenotypes or diagnostic patterns rather than true protective mechanisms. The authors should reframe these findings as correlations rather than protective effects and discuss alternative explanations such as different disease phenotypes, diagnostic bias, or confounding factors. Causal language should be avoided when describing these associations. 5. Inadequate Methods Description Critical methodological details are missing from the manuscript, which limits both reproducibility and proper interpretation of results. The authors don't provide specific diagnostic criteria for each IMID studied, nor do they clarify the temporal relationship between IBD and IMID diagnoses. Additionally, data extraction procedures and validation methods are not adequately described. These details are essential for readers to understand exactly how the study was conducted and to enable replication by other researchers. MINOR CONCERNS 1. Presentation and Clarity Issues The manuscript would benefit from improved presentation quality throughout. Table 2 contains formatting inconsistencies and some variables are presented in ways that are difficult to interpret clearly. The figures could be higher resolution for better readability, and there's inconsistent presentation of statistical results, with some p-values shown as exact numbers while others are presented as inequalities. The terminology is also inconsistent, with "IBD" and "IBDs" used interchangeably throughout the manuscript. Standardizing these presentation elements would significantly improve the manuscript's clarity and professional appearance. 2. Literature Review Enhancement While the literature review is adequate, it could be strengthened by incorporating more recent comprehensive reviews and meta-analyses on IBD-IMID associations. The authors could better contextualize their findings within existing Middle Eastern literature and provide more detailed comparisons with findings from other populations. This would help readers understand how their results fit into the broader global picture of IBD and IMID relationships. 3. Discussion Expansion The limitations section is currently too brief and doesn't adequately address the implications of the single-center design or the retrospective nature of the study. The authors should expand this section to include all major methodological concerns and their potential impact on results. Additionally, the clinical implications could be discussed more thoroughly, with more specific recommendations for clinicians regarding screening practices and patient management. Cost-effectiveness considerations for implementing screening programs could also be valuable additions to the discussion. 4. Statistical Reporting Improvements The statistical reporting could be enhanced by providing better contextualization of effect sizes and including more detailed information about model assumptions and diagnostics. While odds ratios are provided, absolute risk differences would help clinicians better understand the practical significance of the findings. The authors should also report model diagnostics for their logistic regression analyses to demonstrate that statistical assumptions were met. 5. Data Presentation Enhancements Some aspects of data presentation could be clearer, particularly regarding denominators for percentage calculations and the handling of missing data. Laboratory reference ranges aren't provided, which makes it difficult to interpret the clinical significance of reported values. The authors should clarify all denominators used in percentage calculations, provide normal ranges for laboratory values, and describe patterns and methods for handling missing data throughout their analyses. This study addresses an important clinical question in an understudied population and has genuine potential to contribute valuable knowledge to our understanding of IMID prevalence in IBD patients. The research question is clinically relevant, and the findings could have meaningful implications for patient care in Middle Eastern populations where such data is limited. However, the major methodological concerns, particularly regarding the sampling methodology and statistical interpretation, must be addressed before this work can be considered suitable for publication. The authors should focus their revision efforts primarily on justifying or acknowledging the limitations of their sampling approach, correcting their statistical analysis for multiple comparisons, reframing their interpretation of "protective factors," and providing complete methodological details that would allow for study replication. Once these fundamental issues are resolved, this work could provide valuable insights that advance our understanding of the complex relationship between IBD and other immune-mediated inflammatory disorders. The clinical implications are potentially significant, and the geographic focus on Saudi Arabia fills an important gap in the literature. With appropriate revisions addressing the major concerns outlined above, this manuscript could make a meaningful contribution to the field. Is the work clearly and accurately presented and does it cite the current literature? Partly Is the study design appropriate and is the work technically sound? Partly Are sufficient details of methods and analysis provided to allow replication by others? Partly If applicable, is the statistical analysis and its interpretation appropriate? Partly Are all the source data underlying the results available to ensure full reproducibility? Yes Are the conclusions drawn adequately supported by the results? Partly Competing Interests No competing interests were disclosed. Reviewer Expertise IBD I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. reply Respond to this report Responses (0) Bertin L. Peer Review Report For: The prevalence and association between immune-mediated inflammatory disorders and inflammatory bowel disease [version 1; peer review: 2 approved with reservations] . F1000Research 2025, 14 :492 ( https://doi.org/10.5256/f1000research.176791.r385239) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. 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