Retrospective analysis of celiac disease in Yemen: Results of a multicenter screening between 2020 and 2024

Retrospective analysis of celiac disease in Yemen: Results of a multicenter screening between 2020 and 2024 | 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 Article Retrospective analysis of celiac disease in Yemen: Results of a multicenter screening between 2020 and 2024 Reem Alariqi, Wadee Abdullah Al-Shehari, Ameen M. Alwossabi, Ahmed Ahmed Al-Akwaa, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9475843/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 12 You are reading this latest preprint version Abstract Background Celiac disease (CD) is a chronic immune-mediated disorder triggered by gluten ingestion in genetically predisposed individuals. Despite increasing global awareness, CD remains underdiagnosed, particularly in developing countries such as Yemen, where epidemiological data are limited. Aim To assess the prevalence, demographic characteristics, and clinical manifestations of CD among patients in Yemen. Methods Retrospective descriptive cross-sectional study performed in Sana'a, Yemen, from January 2020 to December 2024. Patients of any age or gender with a confirmed diagnosis of Celiac Disease based on serological markers (Anti-tTG IgA) and/or intestinal biopsy according to the ESPGHAN 2020 guidelines. Results Out of 1,445 suspected cases, 131 were confirmed, yielding a prevalence of 9.1% . Females constituted the majority of cases (73%), and children aged ≤ 15 years represented the largest age group. The most common gastrointestinal symptoms were diarrhea (79%), abdominal pain (68%), and weight loss (43%). Extraintestinal manifestations were also prominent, particularly itchy rash (94%) and iron deficiency anemia (59%). Vitamin D deficiency (58%) and vitamin B12 deficiency (42%) were the most common; only about one-third of patients adhered to a gluten-free diet. Most cases were concentrated in urban areas, particularly Amanat Al-Asimah. Conclusion Celiac disease is a significant but often underdiagnosed health issue in Yemen. There is an urgent need for increased clinical awareness among healthcare providers and the implementation of standardized screening protocols, especially for high-risk groups Health sciences/Diseases Health sciences/Gastroenterology Health sciences/Health care Health sciences/Medical research Celiac disease Gluten-free diet Yemen. Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Introduction Celiac disease (CD) is a chronic immune-mediated systemic condition that primarily impacts the gastrointestinal tract (GIT) and has extensive repercussions on other organ systems, presenting a significant health issue. It is activated by the consumption of gluten, a protein present in wheat, barley, and rye, in genetically predisposed individuals [ 1 ]. Upon gluten consumption, these people's immune systems elicit an erroneous reaction that targets the small intestine [ 2 ]. This immune response damages the lining of the small intestine, particularly the villi, which are small, finger-like projections essential for nutrient absorption. The destruction and flattening of the villi significantly reduce the intestine's ability to absorb nutrients efficiently [ 3 ]. Most individuals with non-classical presentations exhibit gastrointestinal symptoms, such as recurrent mouth ulcers, altered bowel habits, and recurrent abdominal pain, as well as extraintestinal features like bone pain, short stature, iron deficiency anemia (IDA), and abnormal menstrual cycles [ 4 , 5 ]. The global seroprevalence of celiac disease, measured by specific antibodies, is estimated at 1.4%. It affects all ages and is more frequent in females (0.6%) than in males (0.4%), meaning that for every 1.5 females diagnosed, 1 male is diagnosed. Prevalence varies geographically: 0.4% in South America, 0.5% in Africa and North America, 0.6% in Asia, and 0.8% in Europe and Oceania [ 6 , 7 ]. Celiac disease (CD) is diagnosed by combining serum disease-specific antibodies with evidence of villous atrophy on small-intestinal biopsy. The only effective treatment for CD is a lifelong, strict gluten-free diet (GFD). Because CD has varied clinical presentations, many individuals remain undiagnosed and are at risk for late complications such as osteoporosis and intestinal tumors [ 8 ]. This study sought to provide a retrospective multicenter analysis from 2020 to 2024. The study aimed to determine the prevalence of confirmed celiac disease among patients referred to medical centers in Sana'a, based on Anti-tTG IgA seropositivity and in accordance with the diagnostic criteria for celiac disease in Yemen, as outlined by the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN). Furthermore, delineate gastrointestinal and extraintestinal clinical signs, investigate their correlation with age, gender, and marital status, and assess the geographic distribution and epidemiological pattern of celiac disease in Yemen. Methods Study setting: The study was conducted at the University of Science and Technology hospitals and the Basmat Hayat center, which includes records from many centers and hospitals in Yemen. Their data are documented, reliable, and easy to obtain. Study design and population This retrospective descriptive cross-sectional study was conducted in Sana'a, Yemen, from January 2020 to December 2024. All confirmed cases within this period were included, and patient data were collected retrospectively from medical records. The following data were collected from available patient medical records: age, gender, presence of intestinal symptoms (such as diarrhea, steatorrhea, and stomach discomfort), and extraintestinal manifestations (including dermatological, musculoskeletal, ophthalmic, oral, and gynecological problems, as well as anemia). Comorbidities were recorded, including diabetes mellitus. Laboratory analyses included tests for celiac disease (CD) antibodies, specifically IgA anti-tissue transglutaminase (IgA anti-TTG), as well as a complete blood count and iron levels. Inclusion Criteria : ​Individuals of any age or gender are eligible if they have a confirmed diagnosis of Celiac Disease. Diagnosis must be established using serological markers (anti-tTG IgA) according to the ESPGHAN 2020 guidelines. ​ Exclusion Criteria : ​1-Patients with incomplete clinical or laboratory data in their record ​2-Suspected cases that did not meet the definitive diagnostic criteria Statistical analysis: Epi Info Version 7.2 was used for data analysis. Frequency and proportion were used to summarize qualitative variables. Furthermore, for quantitative variables with normally distributed data, use the mean and standard deviation; otherwise, use the median with interquartile range (IQR). Results Prevalence and Annual distribution of celiac disease cases Among a total of 1,445 individuals suspected of having Celiac disease, 131 cases were confirmed through Anti-tTG Ab IgA. The Prevalence of confirmed Celiac disease was 9.1%. The distribution of confirmed Celiac disease by year in Yemen during the period 2020–2024 ranged from 11% to 27%, with the majority of cases reported in 2022 and 2023, accounting for 27% and 26%, respectively (see Fig. 1 ). Demographic characteristics Nearly two-thirds of the cases were female (73%), and most were children aged ≤ 15 years, followed by those aged 31–44 years. Additionally, 63% of cases were married, Table 1 Table 1 Sociodemographic characteristics of celiac patients, Yemen 2020–2024 (n = 131) Variable n (%) Gender: Female 95 (73%) Male 36 (27%) Age : Median (IQR)* ≤ 15 50 (38%) 16–30 31 (24%) 31–44 y 39 (30%) 45–60 y 10 (8%) > 60y 1 (1%) Marital status(n=) Single 30 (37%) Married 51(63%) *IQR: Interquartile range The median age (IQR) of Celiac was 25 (3–76 years), and over one-third of the cases were children (≤ 15 y), followed by those aged 31–44 years (Fig. 2 ). Clinical manifestations The most frequently observed gastrointestinal manifestations were diarrhea (79%), abdominal pain (68%), and weight loss (43%), as shown in Fig. 3 . Itchy Rash and Iron deficiency anemia were the most common extraintestinal manifestations, with 94% and 59%, respectively (Fig. 4 ). Table 2 Type of vitamin deficiency among celiac disease cases, n = 26 Type of vitamin deficiency N % Vitamin D3 15 58% Vitamin B12 11 42% Vitamin D deficiency and Vitamin B12 deficiency are relatively similar (58% and 42%, respectively) in celiac cases (Table 2 ). Only slightly more than one-third of cases were on a gluten - free diet, Fig. 5 Geographic distribution of cases Most cases were from Amanat Al Asimah (75), while Hadramawt, AL Mahwit, AL Jawf, and Raymah had the fewest cases (Fig. 6 ). Discussion This multicenter retrospective study gives insight into celiac disease (CD) in Yemen from 2020 to 2024. The observed prevalence of confirmed CD was 9.1%, much higher than the global average seroprevalence of about 1.4% and biopsy-confirmed prevalence of 0.6%. This likely reflects that the study focused on suspected or high-risk individuals rather than the general population. A recent meta-analysis found serological celiac disease (CeD) autoimmunity in 1.4% and biopsy-confirmed CeD in 0.6% globally [ 9 ]. However, the CeD frequency shows significant variability across countries. When compared with regional studies, the prevalence reported in this study is relatively consistent with findings from neighboring and similar populations—for example, studies in Saudi Arabia (11.5) [ 10 ]. A cross-sectional study in Egypt (2016–2018) found a celiac disease prevalence of 16.8% among children aged 2–18 years [ 11 ]. A population-based study conducted in Morocco examined all 550 individuals with Type 1 Diabetes Mellitus for Celiac Disease (CD), yielding a frequency of 10% [ 12 ].In Iran, the average study population was 2,058,545. Using a researcher-designed checklist and descriptive statistics, 113 celiac disease cases were diagnosed, with a mean age of 29.1 ± 16.6 years. The three-year prevalence was 5.49 per 100,000 individuals (95% CI: 5.17–5.82). Seventy percent of these patients (n = 78) were female [ 13 ]. The prevalence of celiac disease among Tunisian schoolchildren is approximately 1 in 157, which is comparable to the incidence observed in Europe [ 14 ]. A case-finding study at Sultan Qaboos University Hospital included 104 participants; 8 (7.7%) screened positive for celiac disease [ 15 ]. In contrast, lower prevalence rates have been documented in countries such as China, where the prevalence of CeD was estimated at approximately 0.27%, exhibiting significant diversity across the nation [ 16 ]. A hospital-based cross-sectional comparative study in India enrolled 460 children, with 230 in each group, with a mean age of 64.08 (SD 37.12) months. Twenty-one children (4.6%) tested positive for anti-tissue transglutaminase antibodies [ 17 ]. A multicenter Italian study found a 1.65% celiac disease prevalence in school-age children [ 18 ]. In contrast, a US study (2009–2014) reported a 0.7% prevalence among 22,277 children and adults [ 19 ]. The global variability in incidence is contingent upon multiple factors, reflecting geographic, genetic, dietary, and methodological differences. These variations highlight the influence of genetic predisposition (HLA-DQ2/DQ8), dietary gluten exposure, and s creening strategies on disease detection. A notable advantage of our procedure was the implementation of the latest ESPGHAN diagnostic recommendations [ 20 ], which require clear CeD serology and, in some cases, biopsy confirmation. This approach reduces both overestimation from studies that rely solely on CeD serology and underestimation from those that rely solely on biopsy confirmation. A five-year retrospective study in Yemen revealed that among 3,570 admissions at Al-Sabeen Hospital in Sana'a, the prevalence of CD was 3.4% (n = 120), with a female predominance of 58.3% (n = 70) and 70% (n = 84) diagnosed before the age of one year (mean age 12 ± 3.5 months) [ 21 ]. The annual distribution of cases in this study showed a peak during 2022 and 2023, followed by a slight decline in 2024. This trend may reflect increased awareness, improved diagnostic practices, or enhanced screening during those years. However, the decline observed in 2024 may indicate stabilization in case detection or potential inconsistencies in reporting, emphasizing the need for longer-term surveillance. Our investigation identified disparities in the frequency of CeD between western and southwestern Yemen. Comparable or even greater regional disparities have been documented in other nations. appears to be decelerating in recent years (from 26% in 2023 to 19% in 2024). Celiac Consistent with global literature, this study demonstrated a clear female predominance ( 73%), supporting the well-established observation that CD is more common in females. This may be attributed to hormonal, immunological, and behavioral factors, including greater healthcare-seeking behavior among women. Additionally, the disease was more frequently observed in children (≤ 15 years), followed by adults aged 31–44 years. This finding aligns with previous studies suggesting that CD often presents early in life but may also remain undiagnosed until adulthood [ 22 ]. Clinically, gastrointestinal manifestations such as diarrhea (79%), abdominal pain (68%), and weight loss (43%) were the most commonly reported symptoms. These findings are consistent with classical presentations of CD. However, the study also highlighted the high prevalence of extraintestinal manifestations, particularly itchy rash (94%) and iron deficiency anemia (59%), emphasizing the systemic nature of the disease. The high frequency of dermatological and hematological manifestations suggests that CD in Yemen may often present in non-classical forms, which can contribute to delayed diagnosis. Vitamin deficiencies were also common, particularly vitamin D (58%) and vitamin B12 (42%), reflecting the impact of intestinal malabsorption. These deficiencies are clinically significant, as they contribute to complications such as osteoporosis, anemia, and neurological disorders. One concerning finding was that only about one-third of patients adhered to a gluten-free diet (GFD). This low adherence rate may be due to limited availability, high cost, and lack of awareness regarding gluten-free products in Yemen. This highlights a major public health challenge and underscores the need for nutritional education and improved access to dietary alternatives. Geographically, most cases were concentrated in Amanat Al-Asimah, likely reflecting better access to diagnostic facilities rather than true disease distribution. The low number of cases reported in other governorates may indicate underdiagnosis and limited healthcare access, rather than a genuinely lower prevalence. Overall, this study is crucial for increasing awareness of this condition among general pediatricians and the general public. This understanding may help reduce complications from the disease, such as malnutrition, osteoporosis, lactose intolerance, depression, and intestinal lymphoma. The present research could inspire more nation-based studies. However, more research is needed to confirm these trends. The observation period may be too short, and the sample size may be too small to detect significant changes. In conclusion, celiac disease is a significant yet often underdiagnosed health issue in Yemen. This study finds a high prevalence of CeD (9.1%) and a greater impact among females. Clinical awareness among healthcare providers urgently needs improvement. Standardized screening for high-risk groups is also needed. Access to diagnostic tools and gluten-free food options should be improved. The current "case finding" strategy does not work well for CD diagnosis. Alternatives, such as school-based screening, should be considered to facilitate early diagnosis and prevent long-term complications. Future studies, especially prospective and population-based ones, are crucial for accurately determining the national prevalence and long-term outcomes of CD in Yemen. A major strength of this study is its multicenter design, which enabled data collection from diverse regions and clinical settings across Yemen over 4 years. This provides a more representative picture than single-center studies. However, the retrospective nature of the study introduces inherent limitations, such as potential inconsistencies in medical record-keeping and selection bias, as the screened population was primarily symptomatic or high-risk. Future multicenter research incorporating genetic testing is advised to improve our comprehension and management. Declarations Ethics Approval and Consent to Participate This study was conducted in accordance with the principles of the Declaration of Helsinki . Ethical approval was obtained from the Institutional Review Board ( IRB ) of Al-Razi University (approval number: AU-RB-2024-009, dated May 14, 2024). Given the retrospective nature of the research involving anonymized data collected during routine clinical care, the requirement for informed consent was waived by the ethics committee. Patient confidentiality was safeguarded throughout by anonymizing all data during collection and analysis, with no personal identifiers included in the research database. Consent for Publication Not applicable. Competing Interests The authors declare no conflicts of interest Author contributions RA: Investigation, Methodology, Project Administration, Writing – Review & Editing RA, WA: Conceptualization, Data Curation, Formal Analysis, Writing – Original Draft AmeenA, Ahmed A, AM: Investigation, Methodology, Project Administration, Writing – Review & Editing SA, MA, waka A ,SA: Conceptualization, Data Curation, Formal Analysis, Writing – Original Draft WA: Supervision, Validation, Visualization, Writing – Review & Editing WA: Writing – Review & Editing, Corresponding Author Funding None. Availability of Data Data are available from the corresponding author on request. Acknowledgements The authors thank the manager of the Science and Technology Hospital and the Basmat Hayat Center in Sana'a Governorate for providing data for this study. References Sapone, A. et al. Spectrum of gluten-related disorders: consensus on new nomenclature and classification. BMC Med. 10 , 13 (2012). Kim, S. 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Am. Coll. Gastroenterol. | ACG . 114 (10), 1587–1592 (2019). Singh, P. et al. Global Prevalence of Celiac Disease: Systematic Review and Meta-analysis. Clin. Gastroenterol. Hepatol. 16 (6), 823–836e2 (2018). Aljulifi, M. Z. et al. The prevalence of celiac disease in Saudi patients with type 1 diabetes mellitus. Ann. Saudi Med. 41 (2), 71–77 (2021). Eskander, A. et al. Prevalence of Celiac Disease in Children and Adolescents With Inflammatory Bowel Disease. Cureus 12 (8), e9977 (2020). Belhiba, O., Bousfiha, A. A. & Jennane, F. Prevalence of celiac disease in Moroccan children with type 1 diabetes mellitus: A 16-year cross-sectional study. Qatar Med. J. 2023 (4), 37 (2023). Janatolmakan, M. et al. Epidemiology of Celiac Disease in Western Iran during 2019–2021. Biomed Res Int, 2024: p. 1112812. (2024). Ben Hariz, M. et al. Prevalence of celiac disease in Tunisia: mass-screening study in schoolchildren. Eur. J. Gastroenterol. Hepatol. 19 (8), 687–694 (2007). Ambusaidi, S. et al. Prevalence of Coeliac Disease in Omani Adults with Iron Deficiency Anemia of Unknown Cause: Case-finding study. Sultan Qaboos Univ. Med. J. 22 (2), 262–267 (2022). Liang, C. P. et al. Celiac disease may be rare among children in South China. J. Int. Med. Res. 50 (2), 3000605221076923 (2022). Meena, M. et al. Prevalence and Predictors of Celiac Disease in Children With Constipation. Indian Pediatr. 61 (4), 331–336 (2024). Lionetti, E. et al. Prevalence and detection rate of celiac disease in Italy: Results of a SIGENP multicenter screening in school-age children. Dig. Liver Dis. 55 (5), 608–613 (2023). Unalp-Arida, A. et al. Lower Prevalence of Celiac Disease and Gluten-Related Disorders in Persons Living in Southern vs Northern Latitudes of the United States . Gastroenterology , 152 (8): p. (2017). 1922–1932.e2. Husby, S. et al. European Society for Pediatric Gastroenterology, Hepatology, and Nutrition guidelines for the diagnosis of coeliac disease. J. Pediatr. Gastroenterol. Nutr. 54 (1), 136–160 (2012). Alsofi, S. A. et al. Prevalence and Clinical Profile of Celiac Disease in Yemeni Children: A Five-Year Retrospective Study at Al-Sabeen Hospital. Cureus 17 (4), e82824 (2025). King, J. A. et al. Incidence of Celiac Disease Is Increasing Over Time: A Systematic Review and Meta-analysis. Am. J. Gastroenterol. 115 (4), 507–525 (2020). Additional Declarations No competing interests reported. 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6","display":"","copyAsset":false,"role":"figure","size":178298,"visible":true,"origin":"","legend":"\u003cp\u003eMap of distribution of celiac by governorates, Yemen.\u003c/p\u003e","description":"","filename":"6.png","url":"https://assets-eu.researchsquare.com/files/rs-9475843/v1/48fac5e2677e4a80b72ded2a.png"},{"id":109297296,"identity":"f101b33a-743d-460c-a148-be4b69d909b2","added_by":"auto","created_at":"2026-05-15 08:55:35","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":478191,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9475843/v1/09d2ad76-720c-4fb7-94b1-8f200ebb4130.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Retrospective analysis of celiac disease in Yemen: Results of a multicenter screening between 2020 and 2024","fulltext":[{"header":"Introduction","content":"\u003cp\u003eCeliac disease (CD) is a chronic immune-mediated systemic condition that primarily impacts the gastrointestinal tract (GIT) and has extensive repercussions on other organ systems, presenting a significant health issue. It is activated by the consumption of gluten, a protein present in wheat, barley, and rye, in genetically predisposed individuals [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Upon gluten consumption, these people's immune systems elicit an erroneous reaction that targets the small intestine [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThis immune response damages the lining of the small intestine, particularly the villi, which are small, finger-like projections essential for nutrient absorption. The destruction and flattening of the villi significantly reduce the intestine's ability to absorb nutrients efficiently [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Most individuals with non-classical presentations exhibit gastrointestinal symptoms, such as recurrent mouth ulcers, altered bowel habits, and recurrent abdominal pain, as well as extraintestinal features like bone pain, short stature, iron deficiency anemia (IDA), and abnormal menstrual cycles [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. The global seroprevalence of celiac disease, measured by specific antibodies, is estimated at 1.4%. It affects all ages and is more frequent in females (0.6%) than in males (0.4%), meaning that for every 1.5 females diagnosed, 1 male is diagnosed. Prevalence varies geographically: 0.4% in South America, 0.5% in Africa and North America, 0.6% in Asia, and 0.8% in Europe and Oceania [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eCeliac disease (CD) is diagnosed by combining serum disease-specific antibodies with evidence of villous atrophy on small-intestinal biopsy. The only effective treatment for CD is a lifelong, strict gluten-free diet (GFD). Because CD has varied clinical presentations, many individuals remain undiagnosed and are at risk for late complications such as osteoporosis and intestinal tumors [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThis study sought to provide a retrospective multicenter analysis from 2020 to 2024. The study aimed to determine the prevalence of confirmed celiac disease among patients referred to medical centers in Sana'a, based on Anti-tTG IgA seropositivity and in accordance with the diagnostic criteria for celiac disease in Yemen, as outlined by the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN). Furthermore, delineate gastrointestinal and extraintestinal clinical signs, investigate their correlation with age, gender, and marital status, and assess the geographic distribution and epidemiological pattern of celiac disease in Yemen.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy setting:\u003c/h2\u003e \u003cp\u003eThe study was conducted at the University of Science and Technology hospitals and the Basmat Hayat center, which includes records from many centers and hospitals in Yemen. Their data are documented, reliable, and easy to obtain.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eStudy design and population\u003c/h3\u003e\n\u003cp\u003eThis retrospective descriptive cross-sectional study was conducted in Sana'a, Yemen, from January 2020 to December 2024. All confirmed cases within this period were included, and patient data were collected retrospectively from medical records.\u003c/p\u003e \u003cp\u003eThe following data were collected from available patient medical records: age, gender, presence of intestinal symptoms (such as diarrhea, steatorrhea, and stomach discomfort), and extraintestinal manifestations (including dermatological, musculoskeletal, ophthalmic, oral, and gynecological problems, as well as anemia).\u003c/p\u003e \u003cp\u003eComorbidities were recorded, including diabetes mellitus. Laboratory analyses included tests for celiac disease (CD) antibodies, specifically IgA anti-tissue transglutaminase (IgA anti-TTG), as well as a complete blood count and iron levels.\u003c/p\u003e\n\u003cdiv class=\"Heading\"\u003e\u003cb\u003eInclusion Criteria\u003c/b\u003e:\u003c/div\u003e \u003cp\u003e​Individuals of any age or gender are eligible if they have a confirmed diagnosis of Celiac Disease. Diagnosis must be established using serological markers (anti-tTG IgA) according to the ESPGHAN 2020 guidelines.\u003c/p\u003e \u003cp\u003e​ \u003cb\u003eExclusion Criteria\u003c/b\u003e:\u003c/p\u003e \u003cp\u003e​1-Patients with incomplete clinical or laboratory data in their record\u003c/p\u003e \u003cp\u003e​2-Suspected cases that did not meet the definitive diagnostic criteria\u003c/p\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis:\u003c/h2\u003e \u003cp\u003eEpi Info Version 7.2 was used for data analysis. Frequency and proportion were used to summarize qualitative variables. Furthermore, for quantitative variables with normally distributed data, use the mean and standard deviation; otherwise, use the median with interquartile range (IQR).\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003ePrevalence and Annual distribution of celiac disease cases\u003c/h2\u003e \u003cp\u003eAmong a total of 1,445 individuals suspected of having Celiac disease, 131 cases were confirmed through Anti-tTG Ab IgA. The Prevalence of confirmed Celiac disease was 9.1%.\u003c/p\u003e \u003cp\u003eThe distribution of confirmed Celiac disease by year in Yemen during the period 2020\u0026ndash;2024 ranged from 11% to 27%, with the majority of cases reported in 2022 and 2023, accounting for 27% and 26%, respectively (see Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eDemographic characteristics\u003c/h3\u003e\n\u003cp\u003eNearly two-thirds of the cases were female (73%), and most were children aged\u0026thinsp;\u0026le;\u0026thinsp;15 years, followed by those aged 31\u0026ndash;44 years. Additionally, 63% of cases were married, 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\u003eSociodemographic characteristics of celiac patients, Yemen 2020\u0026ndash;2024 (n\u0026thinsp;=\u0026thinsp;131)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\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 \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003en (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGender:\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e95 (73%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e36 (27%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge\u003c/b\u003e:\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMedian (IQR)*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026le;\u0026thinsp;15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e50 (38%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e16\u0026ndash;30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e31 (24%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e31\u0026ndash;44 y\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e39 (30%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e45\u0026ndash;60 y\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10 (8%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;60y\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (1%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMarital status(n=)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSingle\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e30 (37%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMarried\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e51(63%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"2\"\u003e*IQR: Interquartile range\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe median age (IQR) of Celiac was 25 (3\u0026ndash;76 years), and over one-third of the cases were children (\u0026le;\u0026thinsp;15 y), followed by those aged 31\u0026ndash;44 years (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e\n\u003ch3\u003eClinical manifestations\u003c/h3\u003e\n\u003cp\u003eThe most frequently observed gastrointestinal manifestations were diarrhea (79%), abdominal pain (68%), and weight loss (43%), as shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eItchy Rash and Iron deficiency anemia were the most common extraintestinal manifestations, with 94% and 59%, respectively (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\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\u003eType of vitamin deficiency among celiac disease cases, n\u0026thinsp;=\u0026thinsp;26\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eType of vitamin deficiency\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eN\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e%\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVitamin D3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e58%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVitamin B12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e42%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eVitamin D deficiency and Vitamin B12 deficiency are relatively similar (58% and 42%, respectively) in celiac cases (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eOnly slightly more than one-third of cases were on a gluten - free diet, Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eGeographic distribution of cases\u003c/h2\u003e \u003cp\u003eMost cases were from Amanat Al Asimah (75), while Hadramawt, AL Mahwit, AL Jawf, and Raymah had the fewest cases (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis multicenter retrospective study gives insight into celiac disease (CD) in Yemen from 2020 to 2024. The observed prevalence of confirmed CD was 9.1%, much higher than the global average seroprevalence of about 1.4% and biopsy-confirmed prevalence of 0.6%. This likely reflects that the study focused on suspected or high-risk individuals rather than the general population. A recent meta-analysis found serological celiac disease (CeD) autoimmunity in 1.4% and biopsy-confirmed CeD in 0.6% globally [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. However, the CeD frequency shows significant variability across countries. When compared with regional studies, the prevalence reported in this study is relatively consistent with findings from neighboring and similar populations\u0026mdash;for example, studies in Saudi Arabia (11.5) [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. A cross-sectional study in Egypt (2016\u0026ndash;2018) found a celiac disease prevalence of 16.8% among children aged 2\u0026ndash;18 years [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. A population-based study conducted in Morocco examined all 550 individuals with Type 1 Diabetes Mellitus for Celiac Disease (CD), yielding a frequency of 10% [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e].In Iran, the average study population was 2,058,545. Using a researcher-designed checklist and descriptive statistics, 113 celiac disease cases were diagnosed, with a mean age of 29.1\u0026thinsp;\u0026plusmn;\u0026thinsp;16.6 years. The three-year prevalence was 5.49 per 100,000 individuals (95% CI: 5.17\u0026ndash;5.82). Seventy percent of these patients (n\u0026thinsp;=\u0026thinsp;78) were female [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. The prevalence of celiac disease among Tunisian schoolchildren is approximately 1 in 157, which is comparable to the incidence observed in Europe [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. A case-finding study at Sultan Qaboos University Hospital included 104 participants; 8 (7.7%) screened positive for celiac disease [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. In contrast, lower prevalence rates have been documented in countries such as China, where the prevalence of CeD was estimated at approximately 0.27%, exhibiting significant diversity across the nation [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. A hospital-based cross-sectional comparative study in India enrolled 460 children, with 230 in each group, with a mean age of 64.08 (SD 37.12) months. Twenty-one children (4.6%) tested positive for anti-tissue transglutaminase antibodies [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. A multicenter Italian study found a 1.65% celiac disease prevalence in school-age children [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. In contrast, a US study (2009\u0026ndash;2014) reported a 0.7% prevalence among 22,277 children and adults [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. The global variability in incidence is contingent upon multiple factors, reflecting geographic, genetic, dietary, and methodological differences. These variations highlight the influence of genetic predisposition (HLA-DQ2/DQ8), dietary gluten exposure, and \u003cb\u003es\u003c/b\u003ecreening strategies on disease detection. A notable advantage of our procedure was the implementation of the latest ESPGHAN diagnostic recommendations [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e], which require clear CeD serology and, in some cases, biopsy confirmation. This approach reduces both overestimation from studies that rely solely on CeD serology and underestimation from those that rely solely on biopsy confirmation. A five-year retrospective study in Yemen revealed that among 3,570 admissions at Al-Sabeen Hospital in Sana'a, the prevalence of CD was 3.4% (n\u0026thinsp;=\u0026thinsp;120), with a female predominance of 58.3% (n\u0026thinsp;=\u0026thinsp;70) and 70% (n\u0026thinsp;=\u0026thinsp;84) diagnosed before the age of one year (mean age 12\u0026thinsp;\u0026plusmn;\u0026thinsp;3.5 months) [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. The annual distribution of cases in this study showed \u003cb\u003ea\u003c/b\u003e peak during 2022 and 2023, followed by a slight decline in 2024. This trend may reflect increased awareness, improved diagnostic practices, or enhanced screening during those years. However, the decline observed in 2024 may indicate stabilization in case detection or potential inconsistencies in reporting, emphasizing the need for longer-term surveillance. Our investigation identified disparities in the frequency of CeD between western and southwestern Yemen. Comparable or even greater regional disparities have been documented in other nations. appears to be decelerating in recent years (from 26% in 2023 to 19% in 2024). Celiac Consistent with global literature, this study demonstrated a clear female predominance \u003cb\u003e(\u003c/b\u003e73%), supporting the well-established observation that CD is more common in females. This may be attributed to hormonal, immunological, and behavioral factors, including greater healthcare-seeking behavior among women. Additionally, the disease was more frequently observed in children (\u0026le;\u0026thinsp;15 years), followed by adults aged 31\u0026ndash;44 years. This finding aligns with previous studies suggesting that CD often presents early in life but may also remain undiagnosed until adulthood [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eClinically, gastrointestinal manifestations such as diarrhea (79%), abdominal pain (68%), and weight loss (43%) were the most commonly reported symptoms. These findings are consistent with classical presentations of CD. However, the study also highlighted the high prevalence of extraintestinal manifestations, particularly itchy rash (94%) and iron deficiency anemia (59%), emphasizing the systemic nature of the disease. The high frequency of dermatological and hematological manifestations suggests that CD in Yemen may often present in non-classical forms, which can contribute to delayed diagnosis.\u003c/p\u003e \u003cp\u003eVitamin deficiencies were also common, particularly vitamin D (58%) and vitamin B12 (42%), reflecting the impact of intestinal malabsorption. These deficiencies are clinically significant, as they contribute to complications such as osteoporosis, anemia, and neurological disorders. One concerning finding was that only about one-third of patients adhered to a gluten-free diet (GFD). This low adherence rate may be due to limited availability, high cost, and lack of awareness regarding gluten-free products in Yemen. This highlights a major public health challenge and underscores the need for nutritional education and improved access to dietary alternatives. Geographically, most cases were concentrated in Amanat Al-Asimah, likely reflecting better access to diagnostic facilities rather than true disease distribution. The low number of cases reported in other governorates may indicate underdiagnosis and limited healthcare access, rather than a genuinely lower prevalence. Overall, this study is crucial for increasing awareness of this condition among general pediatricians and the general public. This understanding may help reduce complications from the disease, such as malnutrition, osteoporosis, lactose intolerance, depression, and intestinal lymphoma. The present research could inspire more nation-based studies. However, more research is needed to confirm these trends. The observation period may be too short, and the sample size may be too small to detect significant changes.\u003c/p\u003e \u003cp\u003eIn conclusion, celiac disease is a significant yet often underdiagnosed health issue in Yemen. This study finds a high prevalence of CeD (9.1%) and a greater impact among females. Clinical awareness among healthcare providers urgently needs improvement. Standardized screening for high-risk groups is also needed. Access to diagnostic tools and gluten-free food options should be improved. The current \"case finding\" strategy does not work well for CD diagnosis. Alternatives, such as school-based screening, should be considered to facilitate early diagnosis and prevent long-term complications. Future studies, especially prospective and population-based ones, are crucial for accurately determining the national prevalence and long-term outcomes of CD in Yemen.\u003c/p\u003e \u003cp\u003eA major strength of this study is its multicenter design, which enabled data collection from diverse regions and clinical settings across Yemen over 4 years. This provides a more representative picture than single-center studies. However, the retrospective nature of the study introduces inherent limitations, such as potential inconsistencies in medical record-keeping and selection bias, as the screened population was primarily symptomatic or high-risk. Future multicenter research incorporating genetic testing is advised to improve our comprehension and management.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics Approval and Consent to Participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was conducted in accordance with the principles of the Declaration of \u003cstrong\u003eHelsinki\u003c/strong\u003e. Ethical approval was obtained from the Institutional Review Board ( \u003cstrong\u003eIRB\u003c/strong\u003e ) of Al-Razi University (approval number: AU-RB-2024-009, dated May 14, 2024). Given the retrospective nature of the research involving anonymized data collected during routine clinical care, the requirement for informed consent was waived by the ethics committee. Patient confidentiality was safeguarded throughout by anonymizing all data during collection and analysis, with no personal identifiers included in the research database.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for Publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no conflicts of interest\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eRA: Investigation, Methodology, Project Administration, Writing \u0026ndash; Review \u0026amp; Editing\u003c/p\u003e\n\u003cp\u003eRA, WA: Conceptualization, Data Curation, Formal Analysis, Writing \u0026ndash; Original Draft\u003c/p\u003e\n\u003cp\u003eAmeenA, Ahmed A, AM: Investigation, Methodology, Project Administration, Writing \u0026ndash; Review \u0026amp; Editing\u003c/p\u003e\n\u003cp\u003eSA, MA, waka A ,SA: Conceptualization, Data Curation, Formal Analysis, Writing \u0026ndash; Original Draft\u003c/p\u003e\n\u003cp\u003eWA: Supervision, Validation, Visualization, Writing \u0026ndash; Review \u0026amp; Editing\u003c/p\u003e\n\u003cp\u003eWA: Writing \u0026ndash; Review \u0026amp; Editing, Corresponding Author\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of Data\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData are available from the corresponding author on request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors thank the manager of the Science and Technology Hospital and the Basmat Hayat Center in Sana\u0026apos;a Governorate for providing data for this study.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eSapone, A. et al. 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Hepatol.\u003c/em\u003e \u003cb\u003e16\u003c/b\u003e (6), 823\u0026ndash;836 (2018). e2.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBrown, N. K. et al. A Clinician's Guide to Celiac Disease HLA Genetics. \u003cem\u003eOfficial J. Am. Coll. Gastroenterol. | ACG\u003c/em\u003e. \u003cb\u003e114\u003c/b\u003e (10), 1587\u0026ndash;1592 (2019).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSingh, P. et al. Global Prevalence of Celiac Disease: Systematic Review and Meta-analysis. \u003cem\u003eClin. Gastroenterol. Hepatol.\u003c/em\u003e \u003cb\u003e16\u003c/b\u003e (6), 823\u0026ndash;836e2 (2018).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAljulifi, M. Z. et al. The prevalence of celiac disease in Saudi patients with type 1 diabetes mellitus. \u003cem\u003eAnn. Saudi Med.\u003c/em\u003e \u003cb\u003e41\u003c/b\u003e (2), 71\u0026ndash;77 (2021).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEskander, A. et al. Prevalence of Celiac Disease in Children and Adolescents With Inflammatory Bowel Disease. \u003cem\u003eCureus\u003c/em\u003e \u003cb\u003e12\u003c/b\u003e (8), e9977 (2020).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBelhiba, O., Bousfiha, A. A. \u0026amp; Jennane, F. Prevalence of celiac disease in Moroccan children with type 1 diabetes mellitus: A 16-year cross-sectional study. \u003cem\u003eQatar Med. J.\u003c/em\u003e \u003cb\u003e2023\u003c/b\u003e (4), 37 (2023).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJanatolmakan, M. et al. \u003cem\u003eEpidemiology of Celiac Disease in Western Iran during 2019\u0026ndash;2021.\u003c/em\u003e Biomed Res Int, 2024: p. 1112812. (2024).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBen Hariz, M. et al. Prevalence of celiac disease in Tunisia: mass-screening study in schoolchildren. \u003cem\u003eEur. J. Gastroenterol. Hepatol.\u003c/em\u003e \u003cb\u003e19\u003c/b\u003e (8), 687\u0026ndash;694 (2007).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAmbusaidi, S. et al. Prevalence of Coeliac Disease in Omani Adults with Iron Deficiency Anemia of Unknown Cause: Case-finding study. \u003cem\u003eSultan Qaboos Univ. Med. J.\u003c/em\u003e \u003cb\u003e22\u003c/b\u003e (2), 262\u0026ndash;267 (2022).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLiang, C. P. et al. Celiac disease may be rare among children in South China. \u003cem\u003eJ. Int. Med. Res.\u003c/em\u003e \u003cb\u003e50\u003c/b\u003e (2), 3000605221076923 (2022).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMeena, M. et al. Prevalence and Predictors of Celiac Disease in Children With Constipation. \u003cem\u003eIndian Pediatr.\u003c/em\u003e \u003cb\u003e61\u003c/b\u003e (4), 331\u0026ndash;336 (2024).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLionetti, E. et al. Prevalence and detection rate of celiac disease in Italy: Results of a SIGENP multicenter screening in school-age children. \u003cem\u003eDig. Liver Dis.\u003c/em\u003e \u003cb\u003e55\u003c/b\u003e (5), 608\u0026ndash;613 (2023).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eUnalp-Arida, A. et al. \u003cem\u003eLower Prevalence of Celiac Disease and Gluten-Related Disorders in Persons Living in Southern vs Northern Latitudes of the United States\u003c/em\u003e. \u003cem\u003eGastroenterology\u003c/em\u003e, \u003cb\u003e152\u003c/b\u003e(8): p. (2017). 1922\u0026ndash;1932.e2.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHusby, S. et al. European Society for Pediatric Gastroenterology, Hepatology, and Nutrition guidelines for the diagnosis of coeliac disease. \u003cem\u003eJ. Pediatr. Gastroenterol. Nutr.\u003c/em\u003e \u003cb\u003e54\u003c/b\u003e (1), 136\u0026ndash;160 (2012).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAlsofi, S. A. et al. Prevalence and Clinical Profile of Celiac Disease in Yemeni Children: A Five-Year Retrospective Study at Al-Sabeen Hospital. \u003cem\u003eCureus\u003c/em\u003e \u003cb\u003e17\u003c/b\u003e (4), e82824 (2025).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKing, J. A. et al. Incidence of Celiac Disease Is Increasing Over Time: A Systematic Review and Meta-analysis. \u003cem\u003eAm. J. Gastroenterol.\u003c/em\u003e \u003cb\u003e115\u003c/b\u003e (4), 507\u0026ndash;525 (2020).\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Celiac disease, Gluten-free diet, Yemen.","lastPublishedDoi":"10.21203/rs.3.rs-9475843/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9475843/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eCeliac disease (CD) is a chronic immune-mediated disorder triggered by gluten ingestion in genetically predisposed individuals. Despite increasing global awareness, CD remains underdiagnosed, particularly in developing countries such as Yemen, where epidemiological data are limited.\u003c/p\u003e\u003ch2\u003eAim\u003c/h2\u003e \u003cp\u003eTo assess the prevalence, demographic characteristics, and clinical manifestations of CD among patients in Yemen.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eRetrospective descriptive cross-sectional study performed in Sana'a, Yemen, from January 2020 to December 2024. Patients of any age or gender with a confirmed diagnosis of Celiac Disease based on serological markers (Anti-tTG IgA) and/or intestinal biopsy according to the ESPGHAN 2020 guidelines.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eOut of 1,445 suspected cases, 131 were confirmed, yielding a prevalence of \u003cb\u003e9.1%\u003c/b\u003e. Females constituted the majority of cases (73%), and children aged\u0026thinsp;\u0026le;\u0026thinsp;15 years represented the largest age group. The most common gastrointestinal symptoms were diarrhea (79%), abdominal pain (68%), and weight loss (43%). Extraintestinal manifestations were also prominent, particularly itchy rash (94%) and iron deficiency anemia (59%). Vitamin D deficiency (58%) and vitamin B12 deficiency (42%) were the most common; only about one-third of patients adhered to a gluten-free diet. Most cases were concentrated in urban areas, particularly Amanat Al-Asimah.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eCeliac disease is a significant but often underdiagnosed health issue in Yemen. There is an urgent need for increased clinical awareness among healthcare providers and the implementation of standardized screening protocols, especially for high-risk groups\u003c/p\u003e","manuscriptTitle":"Retrospective analysis of celiac disease in Yemen: Results of a multicenter screening between 2020 and 2024","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-05-15 02:32:58","doi":"10.21203/rs.3.rs-9475843/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2026-05-18T07:31:27+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"135014171120142907482540892692647501532","date":"2026-05-07T17:35:33+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"196499435488643899186859883614316151851","date":"2026-05-07T16:55:26+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"35106654114122037081405656607265584826","date":"2026-05-06T16:07:51+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"110691254748032741042590273994368964680","date":"2026-05-06T06:29:45+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"286592664947845972718737821010388979099","date":"2026-05-06T00:15:57+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"194864212521690207410906808376605307631","date":"2026-05-05T14:56:57+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-05-05T14:52:45+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-04-27T14:07:47+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-04-21T14:16:28+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-04-21T14:15:36+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2026-04-20T18:52:14+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"fb41032e-1ab3-4417-9ab2-744f72fd5efd","owner":[],"postedDate":"May 15th, 2026","published":true,"recentEditorialEvents":[{"type":"editorInvitedReview","content":"","date":"2026-05-18T07:31:27+00:00","index":122,"fulltext":""},{"type":"reviewerAgreed","content":"135014171120142907482540892692647501532","date":"2026-05-07T17:35:33+00:00","index":121,"fulltext":""},{"type":"reviewerAgreed","content":"196499435488643899186859883614316151851","date":"2026-05-07T16:55:26+00:00","index":120,"fulltext":""},{"type":"reviewerAgreed","content":"35106654114122037081405656607265584826","date":"2026-05-06T16:07:51+00:00","index":118,"fulltext":""},{"type":"reviewerAgreed","content":"110691254748032741042590273994368964680","date":"2026-05-06T06:29:45+00:00","index":116,"fulltext":""},{"type":"reviewerAgreed","content":"286592664947845972718737821010388979099","date":"2026-05-06T00:15:57+00:00","index":114,"fulltext":""},{"type":"reviewerAgreed","content":"194864212521690207410906808376605307631","date":"2026-05-05T14:56:57+00:00","index":107,"fulltext":""},{"type":"reviewersInvited","content":"64","date":"2026-05-05T14:52:45+00:00","index":"","fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[{"id":67738709,"name":"Health sciences/Diseases"},{"id":67738710,"name":"Health sciences/Gastroenterology"},{"id":67738711,"name":"Health sciences/Health care"},{"id":67738712,"name":"Health sciences/Medical research"}],"tags":[],"updatedAt":"2026-05-15T02:32:59+00:00","versionOfRecord":[],"versionCreatedAt":"2026-05-15 02:32:58","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9475843","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9475843","identity":"rs-9475843","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}