Prevalence of Esophageal Eosinophilia, Eosinophilic Esophagitis, and Lymphocytic Gastritis in Children with Celiac Disease: A Saudi Tertiary Center Experience.

Background: Celiac disease (CD) is an immune-mediated enteropathy that has been associated with other immune-related gastrointestinal disorders, such as eosinophilic esophagitis (EoE) and lymphocytic gastritis (LG). To our knowledge, this is the first study in Saudi Arabia that has described such an association. Aim: To evaluate the prevalence of EoE and LG in children and adolescents with CD. Methods: This was a retrospective cross-sectional study of all pediatric patients (aged 0-18 years) with CD following up at King Abdulaziz University Hospital, between January, 2014, and December, 2021. The study examined clinical, demographic, endoscopic, and histopathological data. Results: Seventy-five patients with CD were included in the analysis. The median age was 12 years (range, 2-18 years). Male constituted 54.7% of the overall cohort (n = 41). The most common clinical symptoms were short stature (54.7%), weight loss (34.7%), abdominal pain (33.3%), abdominal distension (29.3%), anorexia (29.3%), diarrhea (24%), and vomiting (21.3%). The esophageal biopsy results reported were basal cell hyperplasia in 24 patients (32.9%), esophageal eosinophilia in 23 patients (31.5%), and EoE in 3 patients (4.1%). The gastric biopsy results were normal in 40 patients (53.3%). The most common abnormality was chronic inactive gastritis with no Helicobacter pylori (HP) infection (16%). LG was found in 3 patients (4%). Conclusions: The prevalence of EoE in this cohort of patients with CD was lower than the prevalence recorded in a number of other studies. Further studies are needed to determine the effects of a gluten-free diet (GFD) on EOE and LG.

Clinical and laboratory features of biliary atresia and patterns of management practices: Saudi national study (2000-2018).

BACKGROUND: We utilized the data from the Saudi national biliary atresia (BA) study (2000-2018) to describe the clinical, biochemical, imaging, and histopathological features of BA and the perioperative clinical practices among local pediatric gastroenterologists. METHODS: This is a retrospective, multicenter, nationwide study that included 10 tertiary care governmental hospitals including the four liver transplant (LT) centers in different regions across Saudi Arabia. RESULTS: BA was diagnosed in 204 infants (106 females; 10% preterm). The median age at referral was 65 days. Congenital anomalies were present in 68 patients (33%); 22 were splenic malformation (10.8%). The medians of laboratory investigations were total bilirubin (189 µmol/l), direct bilirubin (139 µmol/l), ALT (164 u/l), and GGT (472 u/l). The level of serum GGT was normal in 26 cases (12.7%). The ultrasound findings included hypoplastic or atrophic gall bladder (GB) (65%), normal GB (30%), and cord sign (5%). A HIDA scan was performed in 99 cases (48.52%). Magnetic resonance cholangiopancreatography (MRCP) was performed in 27 cases (13%). A total of 179 liver biopsies (88%) were obtained. The most common histopathologic findings were bile duct proliferation (92%), canalicular cholestasis (96%), bile plugs (84%), and portal fibrosis (95%). Cholangiography was performed in 139 cases (68%): operative in 122 (60%) and percutaneous in 17 (8%). A total of 143 children (70%) underwent Kasai portoenterostomy (KPE) at a median age of 70 days. After KPE, steroid was used in 37% of the cases and 100 cases (70%) were prescribed prophylactic antibiotics for variable duration (ranging between 3 and 12 months). CONCLUSION: Our data show marked variation in the diagnostic evaluation and perioperative management of BA cases among the different tertiary centers. There is a need to establish a national BA registry in Saudi Arabia aiming to standardize pre- and postoperative clinical practices. Additionally, normal serum GGT level, normal GB size on ultrasound, and being a premature baby should not preclude the diagnostic workup for BA.

Saudi consensus guidance for the management of inflammatory bowel disease during pregnancy.

ABSTRACT: The management of inflammatory bowel disease (IBD) in pregnant women is challenging and must be addressed on a patient-by-patient basis. Optimal patient management requires a multidisciplinary team and clear evidence-based recommendations that cater to this subset of patients. In this article, we provide concise guidelines and clinical care pathway for the management of IBD in pregnant women. Our recommendations were developed by a multidisciplinary working group that includes experts from the Saudi Ministry of Health in collaboration with the Saudi Gastroenterology Association and the Saudi Society of Clinical Pharmacology. All recommendations are based on up-to-date information following an extensive literature review. A total of 23 evidence-based expert opinion recommendations for the management of IBD in pregnant women are herein provided.

Transition Readiness Into Adult Health Care in Children With Inflammatory Bowel Disease.

Background and aim Approximately 25% of inflammatory bowel disease (IBD) cases are diagnosed before the age of 18 years. Compared to adults, pediatric IBD is more aggressive and progresses rapidly. It is important to have a well-structured transition process in place when patients are transferred from pediatric to adult care. We aimed to evaluate the readiness of Saudi adolescents with IBD to be transitioned from pediatric to adult care using the Transition Readiness Assessment Questionnaire (TRAQ). Materials and methods This cross-sectional study was carried out at King Abdulaziz University Hospital (KAUH), Jeddah, Saudi Arabia, between January and December 2021. Pediatric patients aged between 12-18 with confirmed IBD were recruited. The mean TRAQ component and the overall scores were calculated and analyzed. Results A total of 54 patients with IBD were included. The overall mean TRAQ scores were moderately high (3.60±0.78), including high mean values for individual domains of the TRAQ. In terms of components of TRAQ, no significant differences between males and females were encountered; however, there was a trend for males having higher scores than females in tracking health issues (P=0.07). Patients older than 15 years had higher overall scores than younger patients (P=0.04). The level of child education was found to be the only independent variable that correlated with higher overall scores (P=0.005). Conclusions In this cohort of Saudi adolescents with IBD, patients showed moderately high overall mean TRAQ scores reflecting high readiness for transitioning. While males demonstrated a trend for higher scores compared to females in tracking health issues, patients older than 15 had higher total scores relative to younger patients. More studies are needed to examine the impact of better transition readiness on the long-term outcome of IBD.

Predictors of biliary atresia outcome: Saudi National Study (2000 - 2018).

Background: Outcomes in biliary atresia (BA) have been well-documented in large national cohorts from Europe, North America, and East Asia. Understanding the challenges that preclude success of the Kasai portoenterostomy (KPE) is the key to improve the overall outcomes of BA and implementing intervention strategies. Here, we analyzed the data from the Saudi national BA study (204 BA cases diagnosed between 2000 and 2018) to identify the prognostic factors of BA outcomes. Methods: One hundred and forty-three cases underwent KPE. Several prognostic factors (center case load, congenital anomalies, serum gamma-glutamyl transferase, use of steroids, ascending cholangitis post-operatively, and degree of portal fibrosis at time of KPE) were investigated and correlated with the primary outcomes of interest: 1) success of KPE (clearance of jaundice and total serum bilirubin <20 mmol/l after KPE), 2) survival with native liver (SNL), and 3) overall survival. Results: Use of steroids after KPE was associated with clearance of jaundice, 68% vs. 36.8% in the BA cases that did not receive steroids (P = 0.013; odds ratio 2.5) and a significantly better SNL rate at 2 - and 10-year of 62.22% and 57.77% vs. 39.47% and 31.57%, respectively (P = 0.01). A better 10-year SNL was observed in centers with caseload <1/year (group 1) as compared to centers that performed ≥1/year (group 2) [45.34% vs. 26.66%, respectively; P = 0.047]. On comparison of the 2 groups, cases in group 1 had KPE at significantly earlier age (median 59.5 vs. 75 days, P = 0.006) and received steroids after KPE more frequently than group 2 (69% vs. 31%, P < 0.001). None of the remaining prognostic variables were identified as being significantly related to BA outcome. Conclusion: Steroids use post-KPE predicted clearance of jaundice and better short- and long-term SNL. There is a need to establish a national BA registry in Saudi Arabia aiming to standardize the pre- and post-operative clinical practices and facilitate clinical and basic research to evaluate factors that influence BA outcome.

Protein structural insights into a rare PCSK9 gain-of-function variant (R496W) causing familial hypercholesterolemia in a Saudi family: whole exome sequencing and computational analysis.

Familial hypercholesterolemia (FH) is a globally underdiagnosed genetic condition associated with premature cardiovascular death. The genetic etiology data on Arab FH patients is scarce. Therefore, this study aimed to identify the genetic basis of FH in a Saudi family using whole exome sequencing (WES) and multidimensional bioinformatic analysis. Our WES findings revealed a rare heterozygous gain-of-function variant (R496W) in the exon 9 of the PCSK9 gene as a causal factor for FH in this family. This variant was absent in healthy relatives of the proband and 200 healthy normolipidemic controls from Saudi Arabia. Furthermore, this variant has not been previously reported in various regional and global population genomic variant databases. Interestingly, this variant is classified as "likely pathogenic" (PP5) based on the variant interpretation guidelines of the American College of Medical Genetics (ACMG). Computational functional characterization suggested that this variant could destabilize the native PCSK9 protein and alter its secondary and tertiary structural features. In addition, this variant was predicted to negatively influence its ligand-binding ability with LDLR and Alirocumab antibody molecules. This rare PCSK9 (R496W) variant is likely to expand our understanding of the genetic basis of FH in Saudi Arabia. This study also provides computational structural insights into the genotype-protein phenotype relationship of PCSK9 pathogenic variants and contributes to the development of personalized medicine for FH patients in the future.

Rare variant burden analysis from exomes of three consanguineous families reveals LILRB1 and PRSS3 as potential key proteins in inflammatory bowel disease pathogenesis.

Background: Inflammatory bowel disease (IBD) is a chronic autoimmune disorder characterized by severe inflammation and mucosal destruction of the intestine. The specific, complex molecular processes underlying IBD pathogenesis are not well understood. Therefore, this study is aimed at identifying and uncovering the role of key genetic factors in IBD. Method: The whole exome sequences (WESs) of three consanguineous Saudi families having many siblings with IBD were analyzed to discover the causal genetic defect. Then, we used a combination of artificial intelligence approaches, such as functional enrichment analysis using immune pathways and a set of computational functional validation tools for gene expression, immune cell expression analyses, phenotype aggregation, and the system biology of innate immunity, to highlight potential IBD genes that play an important role in its pathobiology. Results: Our findings have shown a causal group of extremely rare variants in the LILRB1 (Q53L, Y99N, W351G, D365A, and Q376H) and PRSS3 (F4L and V25I) genes in IBD-affected siblings. Findings from amino acids in conserved domains, tertiary-level structural deviations, and stability analysis have confirmed that these variants have a negative impact on structural features in the corresponding proteins. Intensive computational structural analysis shows that both genes have very high expression in the gastrointestinal tract and immune organs and are involved in a variety of innate immune system pathways. Since the innate immune system detects microbial infections, any defect in this system could lead to immune functional impairment contributing to IBD. Conclusion: The present study proposes a novel strategy for unraveling the complex genetic architecture of IBD by integrating WES data of familial cases, with computational analysis.

Incidence and clinical characteristics of pediatric inflammatory bowel disease in Oman.

Background: Pediatric inflammatory bowel disease (PIBD) has been documented all over the world, and there is now a large body of clinical, pathological, and treatment knowledge and protocols in place in many countries. There is currently limited knowledge on the prevalence and pathology of PIBD in Omani population. The aim of this study is to report the incidence and clinical features of PIBD in Oman. Methods: This was a retrospective, cross-sectional, multicenter study carried out on all children <13 years of age between January 1, 2010 and December 31, 2021. Results: Fifty-one children were identified, 22 males (43.1%) and 29 females (56.9%), who were mostly from the Muscat region of Oman. The median incidence in the country was 0.57 (confidence interval [CI]: 0.31-0.64) per 105 children for inflammatory bowel disease (IBD), 0.18 (CI: 0.07-0.38) per 105 children for ulcerative colitis (UC), and 0.19 (CI: 0.12-0.33) per 105 children for Crohn's disease (CD). There was a significant increase in the incidence of all PIBD types after the year 2015. Bloody diarrhea was the most common symptom, followed by abdominal pain. Perianal disease affected nine children (40.9%) with CD. Conclusion: The incidence of PIBD in Oman is lower than in some neighboring Gulf countries but similar to that of Saudi Arabia. An alarming upward trend was noted from the year 2015. Large-scale population-based studies are required to investigate the possible causes of this increasing incidence.

Inflammatory bowel disease in the elderly: A focus on disease characteristics and treatment patterns.

Background: As the population ages, the number of elderly inflammatory bowel disease (IBD) patients is expected to increase. The clinical features and therapeutic options for young and old patients may differ, as elderly IBD patients are likely to have different comorbidities and disease characteristics. The goal of this study was to examine the clinical aspects and therapeutic choices for elderly Saudi IBD patients. Methods: We conducted a retrospective study aimed at describing the demographic, clinical, and management characteristics of IBD in elderly patients (≥60 years) who followed up at King Abdulaziz University Hospital (KAUH), Jeddah, Saudi Arabia. The data was extracted from the KAUH inflammatory bowel disease information system (IBDIS) registry. The primary outcome was to describe disease characteristics in accordance with the Montréal classification and the secondary outcomes were to describe treatment patterns and identify significant clinical associations. Results: Our data were collected from 76 patients who fulfilled the study inclusion criteria. Females outnumbered males (53.9% vs 46.1%) and the mean age was 51.5 ± 9.7 years. Essential hypertension (26.3%) was the most common comorbidity followed by diabetes mellitus (23.6%), and malignant neoplasms (9.21%). More than half of the patients with Crohn's disease (CD) had disease onset after forty years of age. The most common form of disease distribution was ileocolonic disease (64.7%). Less than 17% of patients had a penetrating disease phenotype. About 88 percent of patients with UC presented >40 years of age. Approximately, half of the cohort had left-sided ulcerative colitis (UC) (48%), followed by pancolitis (40%). The most prescribed medication class for IBD was 5-aminosalicylic acid (5-ASA) derivatives (56.58%) followed by corticosteroids and immunosuppressive drugs. Conclusions: In Saudi Arabia, age-specific concerns including comorbidities and polypharmacy remain the major challenges in the management of elderly IBD patients.

The use of therapeutic drug monitoring for early identification of vedolizumab response in Saudi Arabian patients with inflammatory bowel disease.

Vedolizumab is a humanized monoclonal antibody used to treat moderate-to-severe inflammatory bowel disease (IBD). The aim of the study was to assess the effectiveness of the induction of vedolizumab trough level in predicting short-term (week 14) clinical outcomes, and covariates that affect the response in Saudi Arabian patients. This prospective, real-life study included a total of 16 patients (4 Crohn's disease (CD) and 12 ulcerative colitis (UC)) with a confirmed diagnosis of IBD and generally naïve to receiving vedolizumab therapy. Using ELISA assay, vedolizumab induction trough and peak levels were measured at weeks 0, 2, and 6. The follow-up assessment was at week 14, where clinical outcomes were measured using the partial Mayo score for UC, and the CD activity score (CDAI), and Harvey Bradshaw index (HBI) for CD. At week 14, 9 patients (52.9%) out of 16 patients demonstrated response to therapy; clinical remission was reported in 5 patients (29.4%), and in 4 cases a clinical response was noted (23.5%). Clinical remission at week 14 was linked significantly with week 6 median vedolizumab levels in responders (25.1 µg/ml 95% CI: 16.5-42.9) compared to non-responders (7.7 µg/ml, 95% CI: 4.6-10.6) (P = 0.002). Receiver operator curve analysis at week 6 identified a cut-off > 8.00 µg/mL for short-term clinical remission. Also, at week 14, BMI significantly correlated with week 6 vedolizumab trough levels (P = 0.02). No other covariates correlated with drug levels at any time point examined. Week 6 early vedolizumab trough level measurements in IBD patients predicted short-term week 14 clinical remission.

Composition of the gut microbiota in patients with inflammatory bowel disease in Saudi Arabia: A pilot study.

Conclusions: The results of this study provide an overview of the variations in microbiota diversity present in Saudi IBD patients compared to healthy controls. Results: The key finding was three negative bacterial biomarkers, Paraprevotellaceae, the Muribaculaceae families of Bacteroidetes phylum, and the Leuconostocaceae family of Firmicutes phylum, which had a higher relative abundance in healthy individuals compared to IBD patients. It was also found that primary microbiota signatures at certain genera and species levels, including Prevotella copri, Bifidobacterium adolescentis, Ruminococcus callidus, Coprococcus sp., Ruminococcus gnavus, Dorea formicigenerans, Leuconostoc, Dialister, Catenibacterium, Eubacterium biforme, and Lactobacillus mucosae, were absent in almost all IBD patients, while Veillonella dispar was absent in all healthy individuals. Methods: After obtaining an informed consent, fecal samples were collected from 11 participants with IBD (patients) and 10 healthy individuals (controls). The bacterial components of the microbial population were identified by next-generation sequencing of partial 16S rRNA. Statistically significant dissimilarities were observed between samples for all metrics. Background: Inflammatory bowel disease (IBD) is a chronic intestinal inflammatory condition attributed to a complex interaction between imbalances in the gut microbiome, environmental conditions, and a deregulated immune response. The aim of the study was to investigate the composition of the gut microbiome of Saudi patients with IBD.

Outcomes of Endoscopic Closure of Respiratory Esophageal Fistula in Children Using the Esophageal Approach: A Case Series.

Repository-esophageal fistula (REF) in children includes congenital or acquired tracheoesophageal fistula (TEF) and pleuro-esophageal fistula (PEF). TEF is a well-known congenital anomaly that is managed surgically. Recurrent tracheoesophageal fistula (rTEF) occurring after surgical repair of TEF is not an uncommon complication and most of the time requires repeat surgery. The aim of this paper is to report the outcomes of endoscopic closure of REF in children in Oman. This is a retrospective case series describing the endoscopic closure of REF in children in the Royal Hospital (RH), Oman. Five cases were identified with one of them having acquired PEF while the rest had rTEF. All children had esophageal endoscopic closure of the esophageal fistula using endoclips, cauterization, and glue injection. The patient who had PEF had successful closure of the fistula and only one out of four with rTEF had successful endoscopic closure. Esophageal endoscopic approach is unsatisfactory in the closure of rTEF but could be effective in the closure of inflammatory PEF. An esophageal approach for the closure of rTEF may need to be consolidated with simultaneous bronchoscopic closure.

Multimorbidity among inflammatory bowel disease patients in a tertiary care center: a retrospective study.

BACKGROUND AND OBJECTIVES: Inflammatory bowel disease (IBD) is a chronic systemic inflammatory condition that debilitate the quality of life. Multimorbidity, a concept only beginning to emerge in IBD, is defined as two or more comorbidities present in the same individual. Notably, we used the term multimorbidity to refer to two or more comorbidities excluding IBD. Multimorbidity is linked to decreased quality of life, poorer disease outcomes, increased hospitalizations, healthcare costs and polypharmacy complications. We aim to estimate the prevalence of multimorbidity and to explore its effect on IBD patients. METHODS: We retrospectively reviewed all IBD patients registered in a validated web-based registry since February 2018. Data on patient demographics, comorbidities, IBD and extraintestinal complications were obtained. We analyzed the date using univariate, bivariate and multivariable analysis. RESULTS: Among 767 IBD patients, 54.6% had Crohn's disease (CD), 41.9% had ulcerative colitis (UC) and 3.5% had IBD unclassified. The median age at diagnosis was 22 years (IQR: 15-29). Males compromised 50.2% of patients. According to the Montréal IBD classification, most UC patients had moderate UC (47.8%) while most CD patients had non-stricturing non-penetrating CD (49.8%). Overall, 10.3% IBD patients had multimorbidity and 23.9% had at least one comorbidity. The most common comorbidity was diabetes mellitus (4.9%) followed by essential hypertension (4%) and iron deficiency anemia (3%). Female gender (P = 0.008) and UC (P = 0.005) were more likely to have multimorbidity. Multimorbid IBD patients were more likely to develop thrombosis than non-multimorbid peers (16.7% vs. 1.6%; P < 0.001). Higher age at diagnosis (OR = 1.04, 95%CI: 1.01-1.07) and having a history of thrombosis (OR = 7.82, 95% CI: 2.67-22.92) are associated with increased risk of multimorbidity. CONCLUSION: Multimorbidity is not uncommon among IBD patients, especially females diagnosed with UC. Our findings indicate that future studies are needed to explore the effects of multimorbidity on IBD patients.

Saudi Arabia consensus guidance for the diagnosis and management of adults with inflammatory bowel disease.

Optimal management of inflammatory bowel disease (IBD) relies on a clear understanding and tailoring evidence-based interventions by clinicians in partnership with patients. This article provides concise guidelines for the management of IBD in adults, based on the most up-to-date information at the time of writing and will be regularly updated. These guidelines were developed by the Saudi Ministry of Health in collaboration with the Saudi Gastroenterology Association and the Saudi Society of Clinical Pharmacy. After an extensive literature review, 78 evidence-and expert opinion-based recommendations for diagnosing and treating ulcerative colitis and Crohn's disease in adults were proposed and further refined by a voting process. The consensus guidelines include the finally agreed on statements with their level of evidence covering different aspects of IBD diagnosis and treatment.

Granulomatous hepatitis in a Saudi child with IL2RA defect: a case report and literature review.

Interleukin-2 receptor alpha (IL2RA) defect (OMIM- # 606367) is an immune disease where affected patients are vulnerable to developing recurrent microbial infections in addition to lymphadenopathy and dermatological manifestations. This condition is known to be caused by pathogenic variants in the IL2RA gene, which are inherited in an autosomal recessive fashion. In this case report, we present a patient with IL2RA defect from Saudi Arabia who presented with chronic diarrhea, poor weight gain, mild villous atrophy, malnutrition, hepatomegaly, nonspecific inflammation, and an eczematous skin rash. His genetic analysis revealed a novel, homozygous, and likely pathogenic variant, that is, c.504 C>A (Cys168Ter), located in the exon 4of the IL2RA gene, which was inherited from his parents in an autosomal recessive mode of inheritance. This variant produces a 272-amino-acid shorter IL2RA protein chain, which most likely becomes degraded in the cytosol. Thus, we assume that the c.504 C>A is a null allele that abolishes the synthesis of IL2RA, malforms the IL-2 receptor complex, and eventually causes immunodeficiency manifestations. To our knowledge, this is the first time a person with IL2RA defect has shown signs of granulomatous hepatitis on a liver biopsy.

The Epidemiology and Outcome of Biliary Atresia: Saudi Arabian National Study (2000-2018).

Background: The epidemiology and outcomes of biliary atresia (BA) have been well-documented in national cohorts from two main ethnicities, namely, the Asian Orientals and Caucasians, with incidence ranging from 1 in 5,000 to 1 in 9,000 live births in East Asia and 1 in 15,000 to 19,000 live births in Europe and North America. Objective: We report the first nationwide BA study outside North America, Europe, and East Asia to describe the epidemiology and outcomes of BA in Saudi Arabia. Methods: A national database of BA cases diagnosed between 2000 and 2018 was analyzed. We assessed clearance of jaundice (bilirubin <20 µmol/L) in all cases that underwent Kasai portoenterostomy (KPE). We then estimated survival using the Kaplan-Meier method with endpoints of liver transplantation (LT), death, or survival with native liver (SNL). Results: BA was diagnosed in 204 infants (106 females; 10% pre-term). The incidence of BA was 1 in 44,365, or 2.254 in 100,000 live births (range, 0.5-4 in 100,000). Polysplenia was diagnosed in 22 cases (11%). The median age at referral was 65 days. A total of 146 children (71.5%) underwent KPE at a median age of 70 days. Clearance of jaundice was achieved in 66 of the 146 (45%) infants. The 10-year SNL after KPE was 25.5%, and the overall 10-year estimated survival was 72.5%. The Kaplan-Meier survival curves for patients undergoing KPE at the age of <60, 61-90, and >90 days showed a SNL rate at 51.6, 33, and 12.5%, respectively, at 5 years (P < 0.001). The 2-, 5-, and 10-year post-LT survival rates were 92.5, 90.6, and 90%, respectively. Undergoing an initial KPE did not impact negatively on the overall LT survival rate when compared to BA cases that underwent primary LT (P = 0.88). Conclusion: The incidence rate of BA in Saudi Arabia is lower than the incidence reported elsewhere. Late referral of BA cases remains a problem in Saudi Arabia; as a result, the SNL rate was lower than reported by other national registries. Hence, national policies devoted to timely referral and earlier age at KPE are needed.

Oral health-related quality of life in children with celiac disease.

PURPOSE: There is limited knowledge about oral health-related quality of life (OHRQoL) in children with celiac disease (CD). This study aimed to assess OHRQoL in children with CD compared to healthy controls. METHODS: This case-control study included children with CD and healthy controls. Three scales were used to assess OHRQoL in different age groups: 6-7 years, 8-10 years, and 11-14 years. The OHRQoL scores were compared between cases and controls to examine the possible associations between OHRQoL and demographics, socioeconomic status, and oral health. RESULTS: Overall, 104 children with CD and 104 healthy children (controls) were included. The mean age was 10.67 ± 2.39 years in CD patients and 10.69 ± 2.36 in controls (P = 0.971). Male and female children constituted 50% of each group. Children with CD had significantly higher OHRQoL scores than controls (P = 0.003). Low education levels of parents of children with CD and a higher number of siblings in controls were associated with high OHRQoL scores (P = 0.002, P < 0.020, and P = 0.010, respectively). Recurrent aphthous stomatitis (RAS) increased the OHRQoL scores by 7.5 on average (P = 0.016). CONCLUSION: Children with CD had poor OHRQoL compared with healthy controls. Poor OHRQoL in children with CD was associated with RAS and with lower parental income and education. RAS was an independent predictor of poor OHRQoL in children with CD.

Complex Inheritance of Rare Missense Variants in PAK2, TAP2, and PLCL1 Genes in a Consanguineous Arab Family With Multiple Autoimmune Diseases Including Celiac Disease.

Background: Autoimmune diseases (AIDs) share a common molecular etiology and often present overlapping clinical presentations. Thus, this study aims to explore the complex molecular basis of AID by whole exome sequencing and computational biology analysis. Methods: Molecular screening of the consanguineous AID family and the computational biology characterization of the potential variants were performed. The potential variants were searched against the exome data of 100 healthy individuals and 30 celiac disease patients. Result: A complex inheritance pattern of PAK2 (V43A), TAP2 (F468Y), and PLCL1 (V473I) genetic variants was observed in the three probands of the AID family. The PAK2 variant (V43A) is a novel one, but TAP2 (F468Y) and PLCL1 (V473I) variants are extremely rare in local Arab (SGHP and GME) and global (gnomAD) databases. All these variants were localized in functional domains, except for the PAK2 variant (V43A) and were predicted to alter the structural (secondary structure elements, folding, active site confirmation, stability, and solvent accessibility) and functional (gene expression) features. Therefore, it is reasonable to postulate that the dysregulation of PAK2, TAP2, and PLCL1 genes is likely to elicit autoimmune reactions by altering antigen processing and presentation, T cell receptor signaling, and immunodeficiency pathways. Conclusion: Our findings highlight the importance of exploring the alternate inheritance patterns in families presenting complex autoimmune diseases, where classical genetic models often fail to explain their molecular basis. These findings may have potential implications for developing personalized therapies for complex disease patients.

Human papillomavirus bowel colonization in inflammatory bowel disease: A comparative case control study.

Background and Aims: Although much of the research on the plausible environmental triggers for inflammatory bowel disease (IBD) has focused on bacterial pathogens, the relationship between bowel colonization with human papillomavirus (HPV) and IBD has not been previously explored. In this study, we aimed to investigate the association between HPV ileocolonic colonization and IBD. Patients and Methods: We performed a cross-sectional study involving consecutive patients with established IBD who were referred for endoscopic evaluation. During endoscopy, mucosal biopsies were obtained from the most inflamed colonic or ileal segments in cases and from the rectosigmoid region for controls. A hybrid capture assay was used to detect tissue HPV. The prevalence of HPV colonization was determined for cases and controls and was compared using Fisher's exact test. Results: A total of 201 patients, including 104 patients with IBD and 97 non-IBD controls, were prospectively included. Females comprised 55.5% of the study participants (58% vs. 55.2% for controls, P = 0.94). Fifty-seven (54.8%) patients had ulcerative colitis, and 45 (43.2%) had Crohn's disease. The mean age was 43.2 +-18.2 years. Endoscopically active disease was documented in 56 cases (56%). HPV colonization was detected in four (4.1% subjects in controls vs. none in the cases, P = 0.05). Conclusions: There was no evidence of HPV ileocolonic colonization in this cohort of patients with IBD, regardless of disease activity. HPV colonization does not appear to be linked to IBD diagnosis or disease severity.

Case Report: Dubin-Johnson Syndrome Presenting With Infantile Cholestasis: An Overlooked Diagnosis in an Extended Family.

Dubin-Johnson syndrome (DJS) is an often-missed diagnosis of neonatal cholestasis. We report two patients with DJS, who presented with neonatal cholestasis. The first patient underwent extensive investigations for infantile cholestasis with no definitive etiology reached; the diagnosis of DJS was missed until the age of 14 years old. The diagnosis was confirmed genetically with c.2273G > T, p.G758V mutation in exon 18 of the ABCC2 gene. The 2nd patient is a 7-day-old baby, the son of the 1st patient who gave birth to him at the age of 21 years old. He was diagnosed with DJS at the age of 2 weeks based on normal clinical and laboratory workup apart from direct hyperbilirubinemia. He had the same mutation as his mother in homozygous status. The husband was heterozygous for the same mutation. DJS is one of the often-missed differential diagnoses of neonatal cholestasis. It should be suspected in patients of infantile cholestasis, who have an, otherwise, normal physical examination, and laboratory investigations to avoid unnecessary lengthy, invasive, and expensive workups.