Exploring Inflammatory Bowel Disease in Familial Mediterranean Fever Patients: Insights From a Retrospective Study

Exploring Inflammatory Bowel Disease in Familial Mediterranean Fever Patients: Insights From a Retrospective Study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Exploring Inflammatory Bowel Disease in Familial Mediterranean Fever Patients: Insights From a Retrospective Study Emine Nur Sunar Yayla, Deniz Gezgin Yıldırım, Hakan Öztürk, Sinan Sarı, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4960449/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background In light of the accepted association between familial Mediterranean fever (FMF) and inflammatory bowel disease (IBD), as well as the limited previous research on this subject, this study aimed to investigate the prevalence of IBD among individuals diagnosed with FMF and to explore the clinical features and genetic mutations present in FMF patients with IBD. Methods The study was conducted among patients diagnosed with FMF between 2006 and 2022. Patients diagnosed with IBD were included. Patient records were reviewed for demographic data, presenting symptoms and their duration, laboratory results at the time of initial diagnosis and during follow-up, colonoscopy findings, treatments administered, and post-treatment follow up colonoscopy results. Results Among 1176 patients diagnosed with FMF, 9 patients (0.76%) also diagnosed with IBD were included in the study. Genetic analysis showed that all patients had a detected MEFV gene mutation, with the M694V mutation being the most frequently observed. Approximately 44% of FMF and IBD patients exhibit homozygosity for the M694V mutation. Among 1122 FMF patients analyzed for MEFV gene mutations, 19% were homozygous for this variant. The frequency of the M694V homozygous mutation is higher in patients with both IBD and FMF compared to those with only FMF (p = 0.079). In the patients with IBD, diarrhea was the most common presenting complaint. Fever attacks accompanied by abdominal pain were observed in all patients. Further investigations through colonoscopy were conducted on 9 patients, revealing inflammation in the colonic mucosa in the majority (66%). All patients had been receiving colchicine. Methylprednisolone, mesalamine, azathioprine, tumor necrosis factor (TNF) inhibitors, and interleukin-1 (IL-1) inhibitors were among the treatments administered. Following the treatment, all patients experienced a reduction in symptoms, and acute phase reactants were found to be negative in all except one (6.6%). Conclusion The prevalence of IBD is increased in FMF patients with M694V homozygous mutation. Therefore, careful monitoring and thorough evaluation, including colonoscopies, are crucial for assessing IBD risk in these individuals. familial Mediterranean fever inflammatory bowel disease pediatric rheumatology MEFV gene mutation Background Familial Mediterranean fever (FMF) is the most common monogenic autoinflammatory disease, characterized by recurrent episodes of fever and serositis. Its prevalence in Turkey is considered to be 1/1000, and the carrier rate is 1/5 [ 1 – 4 ]. The MEFV gene responsible for FMF, located on the short arm of chromosome 16, encodes the pyrin protein with anti-inflammatory properties. Pyrin protein plays a crucial role in the natural immune response. It regulates the release of interleukin-1 (IL-1), leukocyte apoptosis, and blocks the nuclear factor-kappa B pathway [ 5 – 7 ]. More than 70 mutations have been identified in the MEFV gene, with the most common mutation being M694V [ 8 ]. Mutations in the MEFV gene lead to the activation of the IL-1 β pathway, causing a congenital immune disease. The inflammatory cycle is activated, resulting in severe inflammatory attacks [ 9 ]. Inflammatory bowel disease (IBD) is an immunologically mediated disorder involving chronic inflammation of the gastrointestinal tract, encompassing conditions such as Crohn's disease, ulcerative colitis, and indeterminate colitis [ 9 ]. The most common symptoms include abdominal pain, diarrhea, weight loss, and fever. While IBD can occur at any age, it is observed in 20–30% of cases during childhood and young adulthood. Although the etiology of the disease is not fully understood, it is believed to be multifactorial. In individuals with genetic predisposition, exposure to environmental triggers can lead to a dysregulated immune response, resulting in the breakdown of the mucosal barrier and the onset of the disease. The gene conferring susceptibility to ulcerative colitis is HLA-DRB1 and HLA-DQB, whereas the NOD2/CARD15 gene located on the 16th chromosome was identified in 2001 as being associated with Crohn's disease [ 10 ]. MEFV and NOD2/CARD15 genes, both located on the 16th chromosome, share structural similarities [ 8 , 10 , 11 ]. They play a crucial role in regulating apoptosis, cytokine release, and inflammation. Mutations in these genes can result in similar clinical manifestations such as abdominal pain, diarrhea, arthralgia, arthritis, and fever [ 12 – 14 ]. Although there are numerous studies supporting a potential relationship between FMF and IBD [ 15 – 17 ], there is still limited evidence available. In this study, we aimed to determine the clinical and demographic characteristics of patients diagnosed with both FMF and IBD, investigate the association between IBD and MEFV gene mutations, and to evaluate the prevalence of IBD in patients diagnosed with FMF. Methods Patients and definitions The study was conducted among patients aged 0–18 years diagnosed with FMF between 2006 and 2022 at the Department of Pediatric Rheumatology, Gazi University Faculty of Medicine. The diagnosis of FMF was established based on history, physical examination, laboratory findings, and genetic analysis results of MEFV gene mutations according to the Ankara 2008 criteria. The diagnosis of IBD diagnosis was based on clinical, serological, colonoscopic, and histopathological findings according to European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) guidelines. Patient records were retrospectively reviewed for demographic data, presenting symptoms and their duration, laboratory results at the time of initial diagnosis and during follow-up, colonoscopy findings, treatments administered, and post-treatment follow up colonoscopy results. Family history of IBD and FMF was queried and recorded. MEFV gene mutations in patients with IBD and FMF were compared with those with FMF only. Fisher's exact test was used to compare the frequency of MEFV gene mutations. Laboratory tests At the time of diagnosis, erythrocyte sedimentation rate, C-reactive protein and complete blood count was recorded. Genetic analysis of the MEFV gene was conducted for all patients. MEFV gene extraction was performed at the Nephrology and Tissue Laboratory at Gazi University Medical Faculty. The polymerase chain reaction (PCR) workup, revealed with the pyrosequencing DNA analysis system, targeted the 2-3-5-10 exons of the MEFV gene. Invasive procedures Colonoscopy under sedation was performed on FMF patients with suspected IBD. Multiple biopsy samples were taken for histopathological examination during the procedure. Following examination of the biopsy samples by the pathologist the subjects who were diagnosed with IBD were included in the study. Ethics committee approval for the study was given by Gazi University Medical Faculty Clinical Research Ethics Committee with the article number of E-77082166-604.01.02-475052 and with the date of 07.10.2022. Results Among 1176 patients diagnosed with FMF, 9 patients (0.76%) also diagnosed with IBD were included in the study. Demographic and clinical characteristics of these 9 patients were examined. The majority of these patients were female (77%). Family history was present in 33% of the patients, with 1 having a family history of IBD and 2 having a family history of FMF. With the exception of Patients 3, 4, and 7, FMF was typically diagnosed at an earlier stage than IBD. Genetic analysis showed that all patients had a detected MEFV gene mutation, with the M694V mutation being the most frequently observed. A substantial proportion, approximately 44%, of FMF and IBD patients were found to exhibit homozygosity for the M694V mutation. Upon evaluating MEFV gene mutations across all FMF patients, data from 1122 individuals were analyzed, revealing that 213 of them (19%) were homozygous for the M694V variant. The frequency of the M694V homozygous mutation was higher in patients with both IBD and FMF compared to those with only FMF (p = 0.079). Demographic characteristics and detailed mutation analyses are summarized in Table 1 . Table 1 Demographic features of patients, genetic results and treatment modalities Patient Sex Family history Age at FMF diagnosis (months) Age at IBD diagnosis (months) Follow- up for FMF (months) MEFV genotype Treatment Need of surgery 1 Male + 5 8 23 M694V/M694V C, CS - 2 Female - 100 102 40 A744S/- C - 3 Female - 13 12 87 M694V/M694V C, CS, AZT - 4 Male - 167 165 11 A744S/M680I C, CS, M, AZT + 5 Female - 199 217 61 P369S/M694V C, M, AZT - 6 Female + 155 195 12 E148Q/P369S C, AZT, IL-1i - 7 Female + 25 11 153 M694V/M694V C, CS, M, AZT, IL-1i - 8 Female + 180 203 55 M694V/M694V C, TNFi - 9 Female + 22 25 33 M680I+/- C, CS, M, AZT, IL-1i - AZT: azathioprine; C: colchicine; CS: corticosteroid; FMF: familial Mediterranean fever; IBD: inflammatory bowel disease; IL-1i: interleukin 1 inhibitor; M: mesalazine; TNFi: tumor necrosis factor inhibitor In the patients with both IBD and FMF, diarrhea was the most common presenting complaint. All patients experienced fever attacks accompanied by abdominal pain. Additionally, rectal bleeding was noted in 77% of cases, periodic diarrhea in 44% and chronic diarrhea in 55%. Arthritis, oral ulcers, and weight loss were each observed in 44% of patients (Table 2 ). Table 2 Clinical characteristics of patients with FMF and IBD Patient Initial complaint FMF attack intervals, y Fever Abdominal pain Chronic diarrhea Periodic diarrhea Arthritis Rectal bleeding Oral ulcer Weight loss 1 Diarrhea 1 + + + - - + + - 2 Diarrhea 6 + + - + - + - - 3 Diarrhea 15 + + + - - + - + 4 Diarrhea 10 + + + - + + - + 5 Diarrhea 6 + + - + + - - - 6 Fever 4 + + - + - - + - 7 Diarrhea 4 + + + - - + + + 8 Arthritis 6 + + - + + + + - 9 Arthritis 12 + + + - + + - + FMF: familial Mediterranean fever; IBD: inflammatory bowel disease Further colonoscopic investigations were conducted on 9 patients, revealing inflammation in the colonic mucosa in the majority (66%). Notably, inflammation was also detected in the terminal ileum and jejunum in some cases. The colonoscopic and histopathologic characteristics of these findings are presented in Table 3 . Table 3 Colonoscopic views and biopsy results of patients with FMF and IBD Patient Disease location Colonoscopic view Colonoscopic biopsy Tanı 1 Colon Deep ulcers with a necrotic base and skip lesions Criptitis and chronic active inflammatory process accompanied by polymorphic leukocytes and eosinophils. IBD-U 2 Colon Complete loss of vascularity, apthous ulcers Chronic active inflammatory process accompanied by polymorphic leukocytes. UK 3 Colon Ulcers covered with lokalized white exudate and skip lesions Criptitis and mixed-type inflammation IBD-U 4 Colon Pancolitis, colectomy Criptitis and mixed-type inflammation UK 5 Terminal ileum Multiple ulcers with white exudate Chronic active ileitis Crohn 6 Terminal ileum, jejunum Aphthous ulcers Chronic active inflammatory process Crohn 7 Colon Skip pancolitis Surface ulcers and mixed-type inflammation IBD-U 8 Terminal ileum Deep necrotic ulcers Chronic active ileitis Crohn 9 Colon Deep ulcers with diffuse white exudate, pancolitis Ulcerative active colitis UK FMF: familial Mediterranean fever; IBD-U: inflammatory bowel disease-unclassified; UK: ulcerative colitis All patients had been receiving colchicine for FMF. Treatments administered included methylprednisolone, mesalamine, azathioprine, tumor necrosis factor (TNF) inhibitors, and IL-1 inhibitors. Only Patient 4 required surgical intervention and a total colectomy was performed (Table 1 ). Following treatment, all patients experienced a reduction in symptoms, and acute phase reactants were negative in all except Patient 9. In the follow-up colonoscopy of the Patient 9, minimal inflammatory changes were detected in the colonic mucosa. None of the bowel biopsies revealed any signs of amyloidosis and no patients had proteinuria during follow-up. Discussion Our investigation has elucidated an elevated prevalence of IBD within the cohort of FMF patients, underscoring an augmented occurrence in comparison to the general population. While existing literature extensively explores the coexistence of FMF in individuals with IBD, limited attention has been directed towards scrutinizing the prevalence of IBD among FMF patients. In our study, unlike previous studies, the presence of IBD was investigated in a large FMF cohort and these patients were analyzed in detail. In the study conducted by Yıldız et al., encompassing 686 FMF subjects, an IBD prevalence of 1.45% was established [ 18 ]. Similarly, another investigation involving 600 FMF patients revealed IBD in 1.16% of cases [ 19 ]. Within the scope of our own inquiry, this proportion was ascertained to be 0.76%. The prevalence of IBD in Turkey has been reported in the range of 6.6–44/100,000 in various studies [ 18 ]. Despite the potential onset of IBD at any age, the manifestation of symptoms typically occurs post-childhood, indicating a heightened rate compared to the general population [ 20 ]. Our study suggests a definitive association of this disease with FMF in the pediatric population. In Turkish population, the prevalence of FMF carrier status is known to be 14.8% [ 21 ]. According to a study conducted by the FMF research group, which included 2838 patients, FMF disease is observed at a rate of 1 in 1000 individuals. The most common mutations in Turkish individuals diagnosed with FMF are M694V (51.4%), followed by M680I (14.4%) and V726A (8.6%). The M694V homozygous mutation was detected at a rate of 10.7% [ 22 ]. In contrast, M694V mutation is observed in healthy individuals at a rate of 3% [ 23 ]. In our investigation, the M694V mutation was identified in 5 patients (55%), M694V homozygous mutation in 4 patients (44%) and combined heterozygous mutation in 3 patients (33%) with FMF and IBD. These rates are notably higher compared to the FMF population [ 22 ]. It is also noteworthy that the prevalence of M694V homozygous mutation was 44% in the FMF and IBD group, compared to 19% in the entire FMF group in our study (p = 0.079). Due to the small sample size in the IBD and FMF group, we consider this difference to be statistically insignificant. Pediatric IBD in our country is reported to have an association with FMF in 21.1% of cases. In a study of 597 IBD patients, MEFV mutation was detected in 41.8% of the patients and 21.4% of patients with mutation were reported to have M694V homozygous mutation [ 16 ]. According to Uslu et al.'s study, MEFV gene mutations were detected in 25.7% of 33 patients with IBD. While the most prevalent mutation in IBD patients is M694V (10.6%), M694V mutation was identified in 43.7% and M694V homozygous mutation in 18.1% of IBD and FMF patients [ 10 ]. In another study involving 53 IBD patients, associated 26.4% of cases with FMF. Among these patients, M694V homozygous mutation was detected in half, and 14.3% exhibited K695R and M694V heterozygous mutations [ 15 ]. According to our study, M694V mutation is the most common mutation in FMF and IBD patients and the prevalence of IBD is increased in FMF patients with M694V homozygous mutation. In previous studies, diarrhea, abdominal pain, and rectal bleeding were reported as the most common symptoms in patients with coexisting FMF and IBD, in that order [ 15 ]. Similarly, our study also indicates that diarrhea is the most frequent complaint among patients with both FMF and IBD. Among the nine patients studied, four reported periodic diarrhea attacks, while five presented with chronic diarrhea. Rectal bleeding was observed in 77% of the patients. Those experiencing periodic diarrhea reported episodes with a frequency ranging from once a week to once every two months, with 4–6 attacks per day. These findings suggest that the presence of periodic or chronic diarrhea and rectal bleeding in FMF patients warrants careful evaluation for the potential coexistence of FMF and IBD. When colonoscopic examinations of patients with FMF and IBD were analyzed, colon involvement was observed in all 11 FMF patients who underwent colonoscopy in a study conducted in our country (17). In the study by Beşer et al., colitis was found in 9 (75%) of 12 FMF and IBD patients, pancolitis in 2 (16.6%) and ileocolitis in 1(8.3%) [ 8 ]. In our study, colonoscopy was performed in all 9 patients. Colon involvement was observed in 6 patients (66%) and terminal ileum involvement was observed in 3 patients. This distribution of gastrointestinal involvement emphasizes the predominance of colonic symptoms in FMF and IBD patients and reflects the findings of previous studies. All patients received colchicine treatment, with 8 colchicine-resistant cases additionally administered immunosuppressive therapies. Favorable outcomes were obtained in all patients except for the Patient 8, who exhibited ongoing minimal inflammatory changes in the colon mucosa during the follow-up colonoscopy. For IBD associated with FMF, it is recommended to administer treatments such as steroids, mesalamine, azathioprine, TNF inhibitors, in addition to colchicine, based on the type, involvement, and severity of IBD [ 8 ]. Our study has several limitations, notably its single-center and retrospective design. Despite these limitations, a significant strength of our research is the demonstration of the prevalence of IBD and the influence of the MEFV gene within a cohort of FMF patients. This comprehensive analysis will add valuable information to the understanding of the coexistence of FMF and IBD, potentially guiding future research and clinical management strategies. Conclusions In conclusion, our findings indicate an increased prevalence of IBD, particularly in FMF patients carrying the M694V homozygous mutation. Therefore, careful monitoring and thorough evaluation, including colonoscopy, are crucial for assessing IBD risk in these individuals. Abbreviations ESPGHAN European Society for Paediatric Gastroenterology,Hepatology and Nutrition FMF familial Mediterranean fever IBD inflammatory bowel disease IL-1 interleukin-1 TNF tumor necrosis factor Declarations Ethical approval Ethics committee approval for the study was given by Gazi University Medical Faculty Clinical Research Ethics Committee with the article number of E-77082166-604.01.02-475052 and with the date of 07.10.2022. Consent for publication Not applicable. Competing interests The authors declare that they have no competing interests Funding No specific funding was received from any bodies in the public, commercial or not-for-profit sectors to carry out the work described in this article. Author contributions Conceptualization, Y.E.N.; Writing – Original Draft Preparation, Y.E.N., Y.D.G., Ö.H.; Writing – Review & Editing,Y.E.N., Y.D.G., Ö.H., S.S., and S.O.; All the authors have read and agreed to the published version of the manuscript. Acknowledgements None. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4960449","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":346576280,"identity":"855a4db2-2c22-4ad9-b19a-3cb5f1be6a1f","order_by":0,"name":"Emine Nur Sunar Yayla","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA20lEQVRIiWNgGAWjYFAD9h4wxcNHvBaeMwwMB4AUG/FaJHLAWhgIauGX7jH7+LPtjrz5zLcHH3/MsZNhY2B++OgGHi2Sc84Yz+Zte2Y453ZessHBbclAh7EZG+fg0WJwI8eYmbHtMOMM6RwziYPbmIFaeNik8WmxB2ph/Nl22H6G5BmQlnrCWgwkcowZeNsOJ86Q4AFpOUxYi8SNtGJmnnOHk2fw5BgbnN12nIeNmYBf+Gckb2b8UXbYdgb7GcMHlduq7fnZmx8+xqcFC2AmTfkoGAWjYBSMAiwAAG+oQnWYHsS7AAAAAElFTkSuQmCC","orcid":"https://orcid.org/0000-0003-1646-2341","institution":"Ankara Etlik City Hospital","correspondingAuthor":true,"prefix":"","firstName":"Emine","middleName":"Nur Sunar","lastName":"Yayla","suffix":""},{"id":346576281,"identity":"4f4951ef-0b38-4eb6-9c8d-17bc1835f98a","order_by":1,"name":"Deniz Gezgin Yıldırım","email":"","orcid":"","institution":"Gazi University Faculty of Medicine: Gazi Universitesi Tip Fakultesi","correspondingAuthor":false,"prefix":"","firstName":"Deniz","middleName":"Gezgin","lastName":"Yıldırım","suffix":""},{"id":346576282,"identity":"c741c0ac-6f4c-43e5-8e95-bf1dd902ef6d","order_by":2,"name":"Hakan Öztürk","email":"","orcid":"","institution":"Gazi University Faculty of Medicine: Gazi Universitesi Tip Fakultesi","correspondingAuthor":false,"prefix":"","firstName":"Hakan","middleName":"","lastName":"Öztürk","suffix":""},{"id":346576283,"identity":"9342e0ee-496b-4bca-ae2d-51062709a215","order_by":3,"name":"Sinan Sarı","email":"","orcid":"","institution":"Gazi University Faculty of Medicine: Gazi Universitesi Tip Fakultesi","correspondingAuthor":false,"prefix":"","firstName":"Sinan","middleName":"","lastName":"Sarı","suffix":""},{"id":346576284,"identity":"8f547bdc-fa61-43c2-805f-bb3f1a29e464","order_by":4,"name":"Oğuz Söylemezoğlu","email":"","orcid":"","institution":"Gazi University Faculty of Medicine: Gazi Universitesi Tip Fakultesi","correspondingAuthor":false,"prefix":"","firstName":"Oğuz","middleName":"","lastName":"Söylemezoğlu","suffix":""}],"badges":[],"createdAt":"2024-08-22 22:48:36","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4960449/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4960449/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":90033448,"identity":"92b0a653-5c68-4d7f-9c5a-83507f23f5f3","added_by":"auto","created_at":"2025-08-27 15:32:16","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":821111,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4960449/v1/20023b36-49ee-43e1-997c-7c274f17a887.pdf"}],"financialInterests":"","formattedTitle":"\u003cp\u003eExploring Inflammatory Bowel Disease in Familial Mediterranean Fever Patients: Insights From a Retrospective Study\u003c/p\u003e","fulltext":[{"header":"Background","content":"\u003cp\u003eFamilial Mediterranean fever (FMF) is the most common monogenic autoinflammatory disease, characterized by recurrent episodes of fever and serositis. Its prevalence in Turkey is considered to be 1/1000, and the carrier rate is 1/5 [\u003cspan additionalcitationids=\"CR2 CR3\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. The MEFV gene responsible for FMF, located on the short arm of chromosome 16, encodes the pyrin protein with anti-inflammatory properties. Pyrin protein plays a crucial role in the natural immune response. It regulates the release of interleukin-1 (IL-1), leukocyte apoptosis, and blocks the nuclear factor-kappa B pathway [\u003cspan additionalcitationids=\"CR6\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. More than 70 mutations have been identified in the \u003cem\u003eMEFV\u003c/em\u003e gene, with the most common mutation being M694V [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Mutations in the \u003cem\u003eMEFV\u003c/em\u003e gene lead to the activation of the IL-1 β pathway, causing a congenital immune disease. The inflammatory cycle is activated, resulting in severe inflammatory attacks [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eInflammatory bowel disease (IBD) is an immunologically mediated disorder involving chronic inflammation of the gastrointestinal tract, encompassing conditions such as Crohn's disease, ulcerative colitis, and indeterminate colitis [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. The most common symptoms include abdominal pain, diarrhea, weight loss, and fever. While IBD can occur at any age, it is observed in 20\u0026ndash;30% of cases during childhood and young adulthood. Although the etiology of the disease is not fully understood, it is believed to be multifactorial. In individuals with genetic predisposition, exposure to environmental triggers can lead to a dysregulated immune response, resulting in the breakdown of the mucosal barrier and the onset of the disease. The gene conferring susceptibility to ulcerative colitis is HLA-DRB1 and HLA-DQB, whereas the \u003cem\u003eNOD2/CARD15\u003c/em\u003e gene located on the 16th chromosome was identified in 2001 as being associated with Crohn's disease [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e \u003cp\u003e \u003cem\u003eMEFV\u003c/em\u003e and \u003cem\u003eNOD2/CARD15\u003c/em\u003e genes, both located on the 16th chromosome, share structural similarities [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. They play a crucial role in regulating apoptosis, cytokine release, and inflammation. Mutations in these genes can result in similar clinical manifestations such as abdominal pain, diarrhea, arthralgia, arthritis, and fever [\u003cspan additionalcitationids=\"CR13\" citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Although there are numerous studies supporting a potential relationship between FMF and IBD [\u003cspan additionalcitationids=\"CR16\" citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e], there is still limited evidence available.\u003c/p\u003e \u003cp\u003eIn this study, we aimed to determine the clinical and demographic characteristics of patients diagnosed with both FMF and IBD, investigate the association between IBD and \u003cem\u003eMEFV\u003c/em\u003e gene mutations, and to evaluate the prevalence of IBD in patients diagnosed with FMF.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003ePatients and definitions\u003c/h2\u003e \u003cp\u003eThe study was conducted among patients aged 0\u0026ndash;18 years diagnosed with FMF between 2006 and 2022 at the Department of Pediatric Rheumatology, Gazi University Faculty of Medicine. The diagnosis of FMF was established based on history, physical examination, laboratory findings, and genetic analysis results of \u003cem\u003eMEFV\u003c/em\u003e gene mutations according to the Ankara 2008 criteria. The diagnosis of IBD diagnosis was based on clinical, serological, colonoscopic, and histopathological findings according to European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) guidelines. Patient records were retrospectively reviewed for demographic data, presenting symptoms and their duration, laboratory results at the time of initial diagnosis and during follow-up, colonoscopy findings, treatments administered, and post-treatment follow up colonoscopy results. Family history of IBD and FMF was queried and recorded.\u003c/p\u003e \u003cp\u003e \u003cem\u003eMEFV\u003c/em\u003e gene mutations in patients with IBD and FMF were compared with those with FMF only. Fisher's exact test was used to compare the frequency of \u003cem\u003eMEFV\u003c/em\u003e gene mutations.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eLaboratory tests\u003c/h2\u003e \u003cp\u003eAt the time of diagnosis, erythrocyte sedimentation rate, C-reactive protein and complete blood count was recorded. Genetic analysis of the \u003cem\u003eMEFV\u003c/em\u003e gene was conducted for all patients. \u003cem\u003eMEFV\u003c/em\u003e gene extraction was performed at the Nephrology and Tissue Laboratory at Gazi University Medical Faculty. The polymerase chain reaction (PCR) workup, revealed with the pyrosequencing DNA analysis system, targeted the 2-3-5-10 exons of the \u003cem\u003eMEFV\u003c/em\u003e gene.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eInvasive procedures\u003c/h2\u003e \u003cp\u003eColonoscopy under sedation was performed on FMF patients with suspected IBD. Multiple biopsy samples were taken for histopathological examination during the procedure. Following examination of the biopsy samples by the pathologist the subjects who were diagnosed with IBD were included in the study.\u003c/p\u003e \u003cp\u003e Ethics committee approval for the study was given by Gazi University Medical Faculty Clinical Research Ethics Committee with the article number of E-77082166-604.01.02-475052 and with the date of 07.10.2022.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eAmong 1176 patients diagnosed with FMF, 9 patients (0.76%) also diagnosed with IBD were included in the study. Demographic and clinical characteristics of these 9 patients were examined. The majority of these patients were female (77%). Family history was present in 33% of the patients, with 1 having a family history of IBD and 2 having a family history of FMF. With the exception of Patients 3, 4, and 7, FMF was typically diagnosed at an earlier stage than IBD. Genetic analysis showed that all patients had a detected \u003cem\u003eMEFV\u003c/em\u003e gene mutation, with the M694V mutation being the most frequently observed. A substantial proportion, approximately 44%, of FMF and IBD patients were found to exhibit homozygosity for the M694V mutation. Upon evaluating \u003cem\u003eMEFV gene\u003c/em\u003e mutations across all FMF patients, data from 1122 individuals were analyzed, revealing that 213 of them (19%) were homozygous for the M694V variant. The frequency of the M694V homozygous mutation was higher in patients with both IBD and FMF compared to those with only FMF (p\u0026thinsp;=\u0026thinsp;0.079). Demographic characteristics and detailed mutation analyses are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDemographic features of patients, genetic results and treatment modalities\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"9\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePatient\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSex\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFamily history\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eAge at FMF diagnosis (months)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eAge at IBD diagnosis (months)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eFollow- up for FMF (months)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cem\u003eMEFV\u003c/em\u003e genotype\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eTreatment\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNeed of surgery\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eM694V/M694V\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eC, CS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e102\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eA744S/-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e87\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eM694V/M694V\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eC, CS, AZT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e167\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e165\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eA744S/M680I\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eC, CS, M, AZT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e199\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e217\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e61\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eP369S/M694V\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eC, M, AZT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e155\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e195\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eE148Q/P369S\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eC, AZT, IL-1i\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e153\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eM694V/M694V\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eC, CS, M, AZT, IL-1i\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e180\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e203\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eM694V/M694V\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eC, TNFi\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eM680I+/-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eC, CS, M, AZT, IL-1i\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"9\"\u003eAZT: azathioprine; C: colchicine; CS: corticosteroid; FMF: familial Mediterranean fever; IBD: inflammatory bowel disease; IL-1i: interleukin 1 inhibitor; M: mesalazine; TNFi: tumor necrosis factor inhibitor\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eIn the patients with both IBD and FMF, diarrhea was the most common presenting complaint. All patients experienced fever attacks accompanied by abdominal pain. Additionally, rectal bleeding was noted in 77% of cases, periodic diarrhea in 44% and chronic diarrhea in 55%. Arthritis, oral ulcers, and weight loss were each observed in 44% of patients (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eClinical characteristics of patients with FMF and IBD\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"11\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePatient\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eInitial complaint\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFMF attack intervals, y\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eFever\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eAbdominal pain\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eChronic diarrhea\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003ePeriodic diarrhea\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eArthritis\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003eRectal bleeding\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c10\"\u003e \u003cp\u003eOral ulcer\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c11\"\u003e \u003cp\u003eWeight loss\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDiarrhea\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDiarrhea\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDiarrhea\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDiarrhea\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDiarrhea\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFever\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDiarrhea\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eArthritis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eArthritis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"11\"\u003eFMF: familial Mediterranean fever; IBD: inflammatory bowel disease\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eFurther colonoscopic investigations were conducted on 9 patients, revealing inflammation in the colonic mucosa in the majority (66%). Notably, inflammation was also detected in the terminal ileum and jejunum in some cases. The colonoscopic and histopathologic characteristics of these findings are presented in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eColonoscopic views and biopsy results of patients with FMF and IBD\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePatient\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDisease location\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eColonoscopic view\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eColonoscopic biopsy\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eTanı\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eColon\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eDeep ulcers with a necrotic base and skip lesions\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCriptitis and chronic active inflammatory process accompanied by polymorphic leukocytes and eosinophils.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eIBD-U\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eColon\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eComplete loss of vascularity, apthous ulcers\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eChronic active inflammatory process accompanied by polymorphic leukocytes.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eUK\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eColon\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eUlcers covered with lokalized white exudate and skip lesions\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCriptitis and mixed-type inflammation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eIBD-U\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eColon\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePancolitis, colectomy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCriptitis and mixed-type inflammation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eUK\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTerminal ileum\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMultiple ulcers with white exudate\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eChronic active ileitis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eCrohn\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTerminal ileum, jejunum\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAphthous ulcers\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eChronic active inflammatory process\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eCrohn\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eColon\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSkip pancolitis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSurface ulcers and mixed-type inflammation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eIBD-U\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTerminal ileum\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eDeep necrotic ulcers\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eChronic active ileitis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eCrohn\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eColon\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eDeep ulcers with diffuse white exudate, pancolitis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eUlcerative active colitis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eUK\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eFMF: familial Mediterranean fever; IBD-U: inflammatory bowel disease-unclassified; UK: ulcerative colitis\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eAll patients had been receiving colchicine for FMF. Treatments administered included methylprednisolone, mesalamine, azathioprine, tumor necrosis factor (TNF) inhibitors, and IL-1 inhibitors. Only Patient 4 required surgical intervention and a total colectomy was performed (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Following treatment, all patients experienced a reduction in symptoms, and acute phase reactants were negative in all except Patient 9. In the follow-up colonoscopy of the Patient 9, minimal inflammatory changes were detected in the colonic mucosa. None of the bowel biopsies revealed any signs of amyloidosis and no patients had proteinuria during follow-up.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eOur investigation has elucidated an elevated prevalence of IBD within the cohort of FMF patients, underscoring an augmented occurrence in comparison to the general population. While existing literature extensively explores the coexistence of FMF in individuals with IBD, limited attention has been directed towards scrutinizing the prevalence of IBD among FMF patients. In our study, unlike previous studies, the presence of IBD was investigated in a large FMF cohort and these patients were analyzed in detail.\u003c/p\u003e \u003cp\u003eIn the study conducted by Yıldız et al., encompassing 686 FMF subjects, an IBD prevalence of 1.45% was established [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Similarly, another investigation involving 600 FMF patients revealed IBD in 1.16% of cases [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Within the scope of our own inquiry, this proportion was ascertained to be 0.76%. The prevalence of IBD in Turkey has been reported in the range of 6.6\u0026ndash;44/100,000 in various studies [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Despite the potential onset of IBD at any age, the manifestation of symptoms typically occurs post-childhood, indicating a heightened rate compared to the general population [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Our study suggests a definitive association of this disease with FMF in the pediatric population.\u003c/p\u003e \u003cp\u003eIn Turkish population, the prevalence of FMF carrier status is known to be 14.8% [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. According to a study conducted by the FMF research group, which included 2838 patients, FMF disease is observed at a rate of 1 in 1000 individuals. The most common mutations in Turkish individuals diagnosed with FMF are M694V (51.4%), followed by M680I (14.4%) and V726A (8.6%). The M694V homozygous mutation was detected at a rate of 10.7% [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. In contrast, M694V mutation is observed in healthy individuals at a rate of 3% [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. In our investigation, the M694V mutation was identified in 5 patients (55%), M694V homozygous mutation in 4 patients (44%) and combined heterozygous mutation in 3 patients (33%) with FMF and IBD. These rates are notably higher compared to the FMF population [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. It is also noteworthy that the prevalence of M694V homozygous mutation was 44% in the FMF and IBD group, compared to 19% in the entire FMF group in our study (p\u0026thinsp;=\u0026thinsp;0.079). Due to the small sample size in the IBD and FMF group, we consider this difference to be statistically insignificant.\u003c/p\u003e \u003cp\u003ePediatric IBD in our country is reported to have an association with FMF in 21.1% of cases. In a study of 597 IBD patients, \u003cem\u003eMEFV\u003c/em\u003e mutation was detected in 41.8% of the patients and 21.4% of patients with mutation were reported to have M694V homozygous mutation [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. According to Uslu et al.'s study, \u003cem\u003eMEFV\u003c/em\u003e gene mutations were detected in 25.7% of 33 patients with IBD. While the most prevalent mutation in IBD patients is M694V (10.6%), M694V mutation was identified in 43.7% and M694V homozygous mutation in 18.1% of IBD and FMF patients [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. In another study involving 53 IBD patients, associated 26.4% of cases with FMF. Among these patients, M694V homozygous mutation was detected in half, and 14.3% exhibited K695R and M694V heterozygous mutations [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. According to our study, M694V mutation is the most common mutation in FMF and IBD patients and the prevalence of IBD is increased in FMF patients with M694V homozygous mutation.\u003c/p\u003e \u003cp\u003eIn previous studies, diarrhea, abdominal pain, and rectal bleeding were reported as the most common symptoms in patients with coexisting FMF and IBD, in that order [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Similarly, our study also indicates that diarrhea is the most frequent complaint among patients with both FMF and IBD. Among the nine patients studied, four reported periodic diarrhea attacks, while five presented with chronic diarrhea. Rectal bleeding was observed in 77% of the patients. Those experiencing periodic diarrhea reported episodes with a frequency ranging from once a week to once every two months, with 4\u0026ndash;6 attacks per day. These findings suggest that the presence of periodic or chronic diarrhea and rectal bleeding in FMF patients warrants careful evaluation for the potential coexistence of FMF and IBD.\u003c/p\u003e \u003cp\u003eWhen colonoscopic examinations of patients with FMF and IBD were analyzed, colon involvement was observed in all 11 FMF patients who underwent colonoscopy in a study conducted in our country (17). In the study by Beşer et al., colitis was found in 9 (75%) of 12 FMF and IBD patients, pancolitis in 2 (16.6%) and ileocolitis in 1(8.3%) [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. In our study, colonoscopy was performed in all 9 patients. Colon involvement was observed in 6 patients (66%) and terminal ileum involvement was observed in 3 patients. This distribution of gastrointestinal involvement emphasizes the predominance of colonic symptoms in FMF and IBD patients and reflects the findings of previous studies.\u003c/p\u003e \u003cp\u003eAll patients received colchicine treatment, with 8 colchicine-resistant cases additionally administered immunosuppressive therapies. Favorable outcomes were obtained in all patients except for the Patient 8, who exhibited ongoing minimal inflammatory changes in the colon mucosa during the follow-up colonoscopy. For IBD associated with FMF, it is recommended to administer treatments such as steroids, mesalamine, azathioprine, TNF inhibitors, in addition to colchicine, based on the type, involvement, and severity of IBD [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eOur study has several limitations, notably its single-center and retrospective design. Despite these limitations, a significant strength of our research is the demonstration of the prevalence of IBD and the influence of the MEFV gene within a cohort of FMF patients. This comprehensive analysis will add valuable information to the understanding of the coexistence of FMF and IBD, potentially guiding future research and clinical management strategies.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eIn conclusion, our findings indicate an increased prevalence of IBD, particularly in FMF patients carrying the M694V homozygous mutation. Therefore, careful monitoring and thorough evaluation, including colonoscopy, are crucial for assessing IBD risk in these individuals.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eESPGHAN\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eEuropean Society for Paediatric Gastroenterology,Hepatology and Nutrition\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eFMF\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003efamilial Mediterranean fever\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eIBD\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003einflammatory bowel disease\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eIL-1\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003einterleukin-1\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eTNF\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003etumor necrosis factor\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003ch2\u003eEthical approval\u003c/strong\u003e \u003cp\u003eEthics committee approval for the study was given by Gazi University Medical Faculty Clinical Research Ethics Committee with the article number of E-77082166-604.01.02-475052 and with the date of 07.10.2022.\u003c/p\u003e\u003ch2\u003eConsent for publication\u003c/strong\u003e \u003cp\u003eNot applicable.\u003c/p\u003e \u003ch2\u003eCompeting interests\u003c/strong\u003e \u003cp\u003eThe authors declare that they have no competing interests\u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003eNo specific funding was received from any bodies in the public, commercial or not-for-profit sectors to carry out the work described in this article.\u003c/p\u003e\u003ch2\u003eAuthor contributions\u003c/h2\u003e \u003cp\u003eConceptualization, Y.E.N.; Writing \u0026ndash; Original Draft Preparation, Y.E.N., Y.D.G., \u0026Ouml;.H.; Writing \u0026ndash; Review \u0026amp; Editing,Y.E.N., Y.D.G., \u0026Ouml;.H., S.S., and S.O.; All the authors have read and agreed to the published version of the manuscript.\u003c/p\u003e\u003ch2\u003eAcknowledgements\u003c/h2\u003e \u003cp\u003eNone.\u003c/p\u003e\u003ch2\u003eData availability\u003c/h2\u003e \u003cp\u003eThe datasets used and/or analyzed in the current study are available from the corresponding author upon reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eOzen S. Familial Mediterranean fever: revisiting an ancient disease. Eur J Pediatrics. 2003;162:449\u0026ndash;54.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOzen S, Aktay N, Lainka E, Duzova A, Bakkaloglu A, Kallinich T. Disease severity in children and adolescents with familial Mediterranean fever: a comparative study to explore environmental effects on a monogenic disease. Ann Rheum Dis. 2009;68(2):246\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOzen S, Hoffman HM, Frenkel J, Kastner D. Familial Mediterranean fever (FMF) and beyond: a new horizon. Fourth International Congress on the Systemic Autoinflammatory Diseases held in Bethesda, USA, 6\u0026ndash;10 November 2005. Annals of the rheumatic diseases. 2006;65(7):961-4.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLivneh A, Langevitz P, Zemer D, Zaks N, Kees S, Lidar T, et al. Criteria for the diagnosis of familial Mediterranean fever. Arthr Rhuem. 1997;40(10):1879\u0026ndash;85.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBen-Chetrit E, Backenroth R. Amyloidosis induced, end stage renal disease in patients with familial Mediterranean fever is highly associated with point mutations in the MEFV gene. Ann Rheum Dis. 2001;60(2):146\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eConsortium FF, Bernot A, Clepet C, Dasilva C, Devaud C, Petit J-L, et al. A candidate gene for familial Mediterranean fever. Nat Genet. 1997;17(1):25\u0026ndash;31.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eConsortium IF. Ancient missense mutations in a new member of the RoRet gene family are likely to cause familial Mediterranean fever. Cell. 1997;90(4):797\u0026ndash;807.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBeser \u0026Ouml;F, Kasap\u0026ccedil;opur \u0026Ouml;, \u0026Ccedil;okugras F\u0026Ccedil;, Kutlu T, Arsoy N, Erkan T. Association of inflammatory bowel disease with familial Mediterranean fever in Turkish children. J Pediatr Gastroenterol Nutr. 2013;56(5):498\u0026ndash;502.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChae JJ, Wood G, Masters SL, Richard K, Park G, Smith BJ et al. The B30. 2 domain of pyrin, the familial Mediterranean fever protein, interacts directly with caspase-1 to modulate IL-1β production. Proceedings of the National Academy of Sciences. 2006;103(26):9982-7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eUslu N, Y\u0026uuml;ce A, Demir H, Saltik-Temizel IN, Usta Y, Yilmaz E, et al. The association of inflammatory bowel disease and Mediterranean fever gene (MEFV) mutations in Turkish children. Dig Dis Sci. 2010;55:3488\u0026ndash;94.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOgura Y, Bonen DK, Inohara N, Nicolae DL, Chen FF, Ramos R, et al. A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease. Nature. 2001;411(6837):603\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAyaz N, \u0026Ouml;zen S, Bilginer Y, Erg\u0026uuml;ven M, Taşkıran E, Yılmaz E, et al. MEFV mutations in systemic onset juvenile idiopathic arthritis. Rheumatology. 2009;48(1):23\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYurtcu E, Gokcan H, Yilmaz U, Sahin FI. Detection of MEFV gene mutations in patients with inflammatory bowel disease. Genetic Test Mol Biomarkers. 2009;13(1):87\u0026ndash;90.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSari S, Egritas O, Dalgic B. The familial Mediterranean fever (MEFV) gene may be a modifier factor of inflammatory bowel disease in infancy. Eur J Pediatrics. 2008;167:391\u0026ndash;3.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBeşer \u0026Ouml;F, \u0026Ccedil;okuğraş F\u0026Ccedil;, Kutlu T, Ergin\u0026ouml;z E, G\u0026uuml;lc\u0026uuml; D, Kasap\u0026ccedil;opur \u0026Ouml;, et al. Association of familial Mediterranean fever in Turkish children with inflammatory bowel disease. Turkish Archives Pediatrics/T\u0026uuml;rk Pediatri Arşivi. 2014;49(3):198.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eUrgancı N, Ozgenc F, Kuloğlu Z, Y\u0026uuml;ksekkaya H, Sarı S, Erkan T, et al. Familial Mediterranean fever mutation analysis in pediatric patients with inflammatory bowel disease: A multicenter study. Turkish J Gastroenterol. 2021;32(3):248.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGurkan OE, Dalgic B. Gastrointestinal mucosal involvement without amyloidosis in children with familial Mediterranean fever. 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Familial Mediterranean fever gene mutation frequencies in a sample Turkish population. Clin Exp Rheumatol. 2016;34(6 Suppl 102):97\u0026ndash;100.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTunca M, Ozdogan H, Kasapcopur O, Yalcinkaya F, Tutar E, Topaloglu R, et al. Familial Mediterranean fever (FMF) in Turkey: results of a nationwide multicenter study. Med (Baltim). 2005;84(1):1\u0026ndash;11.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYilmaz E, Ozen S, Balcı B, Duzova A, Topaloglu R, Besbas N, et al. Mutation frequency of familial Mediterranean fever and evidence for a high carrier rate in the Turkish population. Eur J Hum Genet. 2001;9(7):553\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":true,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"familial Mediterranean fever, inflammatory bowel disease, pediatric rheumatology, MEFV gene mutation","lastPublishedDoi":"10.21203/rs.3.rs-4960449/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4960449/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eIn light of the accepted association between familial Mediterranean fever (FMF) and inflammatory bowel disease (IBD), as well as the limited previous research on this subject, this study aimed to investigate the prevalence of IBD among individuals diagnosed with FMF and to explore the clinical features and genetic mutations present in FMF patients with IBD.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThe study was conducted among patients diagnosed with FMF between 2006 and 2022. Patients diagnosed with IBD were included. Patient records were reviewed for demographic data, presenting symptoms and their duration, laboratory results at the time of initial diagnosis and during follow-up, colonoscopy findings, treatments administered, and post-treatment follow up colonoscopy results.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eAmong 1176 patients diagnosed with FMF, 9 patients (0.76%) also diagnosed with IBD were included in the study. Genetic analysis showed that all patients had a detected \u003cem\u003eMEFV\u003c/em\u003e gene mutation, with the M694V mutation being the most frequently observed. Approximately 44% of FMF and IBD patients exhibit homozygosity for the M694V mutation. Among 1122 FMF patients analyzed for \u003cem\u003eMEFV\u003c/em\u003e gene mutations, 19% were homozygous for this variant. The frequency of the M694V homozygous mutation is higher in patients with both IBD and FMF compared to those with only FMF (p\u0026thinsp;=\u0026thinsp;0.079). In the patients with IBD, diarrhea was the most common presenting complaint. Fever attacks accompanied by abdominal pain were observed in all patients. Further investigations through colonoscopy were conducted on 9 patients, revealing inflammation in the colonic mucosa in the majority (66%). All patients had been receiving colchicine. Methylprednisolone, mesalamine, azathioprine, tumor necrosis factor (TNF) inhibitors, and interleukin-1 (IL-1) inhibitors were among the treatments administered. Following the treatment, all patients experienced a reduction in symptoms, and acute phase reactants were found to be negative in all except one (6.6%).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eThe prevalence of IBD is increased in FMF patients with M694V homozygous mutation. Therefore, careful monitoring and thorough evaluation, including colonoscopies, are crucial for assessing IBD risk in these individuals.\u003c/p\u003e","manuscriptTitle":"Exploring Inflammatory Bowel Disease in Familial Mediterranean Fever Patients: Insights From a Retrospective Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-09-27 11:57:26","doi":"10.21203/rs.3.rs-4960449/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"024ec94d-0414-4ab2-b8f7-e19c27c2eeb4","owner":[],"postedDate":"September 27th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-08-27T15:24:05+00:00","versionOfRecord":[],"versionCreatedAt":"2024-09-27 11:57:26","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4960449","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4960449","identity":"rs-4960449","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}