Extraintestinal Symptoms Research Articles

THE GUT MICROBIOME REGULATES EFFICACY OF SULFASALAZINE THERAPY FOR SPONDYLOARTHRITIS IN INFLAMMATORY BOWEL DISEASE

Joint inflammation, or spondyloarthritis (SpA), is the most common extra-intestinal manifestation of inflammatory bowel disease (IBD), but the specific role for therapies targeting SpA is not well defined. One of the earliest medications used for the treatment of IBD is sulfasalazine (SAS). SAS is a prodrug composed of two chemical moieties, the anti-inflammatory 5-aminosalicilate and the antibiotic sulfapyridine. The efficacy of SAS in peripheral arthritis is thought to depend on its “antibacterial” properties, however the impact of SAS on the IBD-SpA microbiome and how it may improve extra-intestinal symptoms is unknown. Therefore, our study aims to diagnostically evaluate the role for the fecal microbiome in clinical response to SAS therapy and identify microbial and immunologic therapeutic targets associated with clinical response.

ARTHRITIS AND ARTHRALGIA AS EXTRAINTESTINAL MANIFESTATIONS IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE TREATED WITH VEDOLIZUMAB: A META-ANALYSIS

Vedolizumab is a humanized gut selective drug that specifically targets α4β7 integrin and has been used successfully in the treatment of Inflammatory Bowel Disease (IBD). Although Vedolizumab is an effective treatment for IBD and acts specifically on the gastrointestinal system, some studies have reported extraintestinal manifestations as adverse events. One of the most frequently reported non-infectious adverse events is articular manifestations. However, it is difficult to know for sure whether the joint symptoms are due to the vedolizumab adverse event or due to extraintestinal symptoms of the disease itself.

Evaluating the Knowledge and Practice of Physicians Regarding Blastocystis hominis

Background: Blastocystis hominis is an enteric protozoan in humans and animals. This survey aimed to assess the knowledge and practice of physicians about B. hominis. Methods: This study was performed on physicians working in Ahvaz County, using a convenience sampling method from January to June 2020. Data were collected through face-to-face interviews and an electronic questionnaire. Descriptive statistics, including frequencies and percentages, were calculated for all variables. P-values < 0.05 were considered significant. Results: Our results showed that of the 352 physicians, 64.2% and 58.0% knew that B. hominis might cause abdominal pain and diarrhea, respectively, but their knowledge was poor about the possibility of extraintestinal clinical symptoms such as urticaria. Regarding the transmission route, 91.8% agreed that the fecal-oral route is the main mode of B. hominis transmission, but only 17.9% were aware of the role of host animals in its transmission. Furthermore, the physicians had poor knowledge of the need to treat symptomatic patients and resistance to metronidazole in some cases. More than two-thirds of the physicians (68%) had good practice treating infected immunocompromised patients but had poor practice treating symptomatic patients. Conclusions: This study emphasizes improving physicians’ knowledge of pathogenicity, clinical symptoms, and treating B. hominis. Since B. hominis is a common protozoan with pathogenic potential, we recommend training sessions for physicians to inform them of new findings about B. hominis.

Screening of celiac disease in children with growth failure

Celiac disease is a chronic enteropathy caused by intolerance to gluten. Its clinical spectrum is broad. Presentation of celiac disease varies from absence of symptoms to gastrointestinal (classic) and/or extraintestinal (non-classic) symptoms. Patients without symptoms may have latent or silent celiac disease. Because celiac disease can be atypical or even clinically silent, many patients remain undiagnosed and at risk for the long-term, sometimes serious complications of untreated celiac disease.The aim of this study is to determine the prevalence of celiac disease (CD) in children with growth failure and the diagnostic value of tissue-transglutaminase (TTG) IgA antibodies and IgA antigliadin antibodies (AGA) for celiac disease.Patients and Methods: A total of 104 children (43 male, 61 female) with growth failure without a specific etiology were studied. Extensive investigations had shown no abnormalities in any subject. Anthropometric parameters and IgA AGA and IgA TTG antibodies were evaluated in this study group. These antibodies were measured by enzyme-linked immunosorbent assay. All patients were referred for an endoscopic intestinal biopsy. The biopsy samples were classified according to revised Marsh criteria .Results: the prevalence of properly diagnosed CD among patients with growth failure in this study was 25.9% (27 of 104patients).Out of 104 patients 57 of them were positive upon screening with the serological tests. IgA -AGA, and IgA -TTG antibodies were found in 81.4% (n = 22 out of 27 with confirmed CD), and 88.8% (n = 24 out of 27 with confirmed CD) of patients with growth failure, respectively. Sensitivity,Specificity ,the positive predictive value (PPV),negative predictive value(NPV) for TTG antibodies were found to be 88.8%, 94.2%, 85.7%, and 94.7% for CD in the group of patients with growth filure in this study and for IgA AGA: sensitivity 81.4%, specificity 88.4%, positive predictive value( PPV) 75.8%, negative predictive value (NPV) 90.6% were found in this study.Conclusion: We conclude that the prevalence of celiac disease is high in patients with idiopathic growth failure and it is important to test all children with idiopathic growth failure for celiac disease by measuring serologic markers and performing an intestinal biopsy.

Iron Deficiency Anemia in Colorectal Cancer Patients: Is Preoperative Intravenous Iron Infusion Indicated? A Narrative Review of the Literature.

Iron deficiency anemia is the most common extraintestinal symptom in patients with colorectal cancer (CRC). Inflammation associated with malignancy leads to functional iron deficiency via the hepcidin pathway, whereas chronic blood loss causes absolute iron deficiency and depletion of iron stores. The assessment and treatment of preoperative anemia is of great importance in patients with CRC, since published data have consistently shown that preoperative anemia is associated with increased need for perioperative blood transfusions and more postoperative complications. Recent studies have documented mixed results regarding the preoperative intravenous iron administration in anemic CRC patients in terms of efficacy for anemia correction, cost-effectiveness, need for transfusions and risk for postoperative complications.

Fecal Calprotectin in Self-Reported Milk Intolerance: Not Only Lactose Intolerance

The hypothesis is that inflammatory/allergic conditions should be considered in self-reported milk intolerance (SRMI) patients who test negative and/or are asymptomatic at Lactose Hydrogen Breath Test (LHBT). We analyzed fecal calprotectin (FCP) values in SRMI patients to investigate the frequency of a "positive" intestinal inflammation marker and its correlation with lactose tolerance/intolerance. Data from 329 SRMI patients were retrospectively analyzed; according to the positive/negative results (maldigester/digester) and the presence/absence of symptoms reported during LHBT (intolerant/tolerant), patients were divided into: 'lactose tolerants' (n. 104), 'maldigesters/intolerants' (n. 187), 'digesters/intolerants' (n. 38). FCP values were analyzed in all three subgroups. A percentage of SRMI patients complained of constipation (>15%), extraintestinal symptoms (>30% including anemia), multiple food hypersensitivity (7.6%) and had intraepithelial lymphocytic infiltration at duodenal biopsy (>50%). Over 50.0% showed FCP values above the normal limit. Lactose tolerants and maldigesters/intolerants had higher positivity frequencies (p < 0.0001, for both) and absolute values (p = 0.04, for maldigesters/intolerants) of FCP compared to digesters/intolerants. FCP was not useful to differentiate tolerant from intolerant subjects (AUC 0.58). Our data suggest the existence of an allergic/inflammatory pathogenetic mechanism in a subset of SRMI subjects. FCP results are in keeping with this hypothesis, even if they cannot differentiate lactose tolerant from intolerant patients.

P763 Role of quality of life in patients with Inflammatory Bowel Disease

Abstract Background Complaints like diarrhea, incontinence, frequent hospitalizations etc. can affect quality of life (QoL) in IBD patients (IBDP). QoL plays a central role in patient care. We investigated in which aspects patients with high quality of life (HQL) differ from patients with low quality of life (LQL). Methods This study was based on an anonymous questionnaire. IBDP of specialized outpatient clinics in three hospitals in Germany participated. Using questions about IBD/ lifestyle, disease activity (Harvey-Bradshaw-Index (HBI)/ Partial Mayo Score (PMS)) and psychological tests (Hospital Anxiety and Depression Scale (HADS), State-Trait-Anxiety Inventory (STAI), Social Support Questionnaire (F-SozU), Complaints-list (BL-R'), NEO-Five-Factor Inventory (NEO-FFI), differences between IBDP with HQL (SIBDQ≥50) vs. LQL (SIBDQ&amp;lt;50) were investigated. Results Overall, 103 (36%) patients had LQL and 183 (64%) had HQL. In general, LQL patients are more likely to be female (p=0.013), to worry about course of disease (p&amp;lt;0.001), to engage in irregular or no exercise (p=0.044), to have anal discomfort (p&amp;lt;0.001), to have extraintestinal symptoms, such as joint (p&amp;lt;0.001) or eye (p=0.004) disorders, and they are more likely to be taking cortisone (p&amp;lt;0.001).Furthermore LQL patients have higher number of general complaints (p&amp;lt;0.001) and are more often in active state of disease (HBI/CAI) (p&amp;lt;0.001 / p&amp;lt;0.001) or have higher disease activity than HQL patients. LQL patients rated the effect of their current medication poorer (p&amp;lt;0.001).Investigation of psychological parameters showed that LQL patients had higher scores on depression scale (p&amp;lt;0.001) and anxiety scale (p&amp;lt;0.001) of HADS-D. Both trait anxiety (p&amp;lt;0.001) and state anxiety (p&amp;lt;0.001) of STAI are significantly higher in LQL patients and they experience less social support (p=0.011). LQL patients are particularly likely to exhibit the personality trait neuroticism (p&amp;lt;0.001) in NEO-FFI, whereas HQL patients exhibit extraversion (p&amp;lt;0.001) and conscientiousness (p=0.007). Conclusion IBD patients with LQL differ from IBD patients with HQL in several factors. Inter alia, concerning disease in terms of higher disease activity, poorer effect of medication and additional extraintestinal manifestations. But also in terms of psychological factors such as anxiousness, depressiveness, and regarding extend of social support. By paying attention to and working on these factors affecting QOL physician and IBD-patient may improve this very important therapeutic goal together.

Self-reported prevalence of fructan food hypersensitivity in university students from the State of Mexico

To determine the self-reported prevalence of fructans food hypersensitivity in a sample of Mexican university students and to investigate the most frequent symptoms, the related foods involved, risk factors and gastrointestinal function status. A cross-sectional, descriptive study was conducted in a convenience sample of 412 university students aged from 18 to 35 years. Data were collected about their personal and family history of gastrointestinal diseases, the presence of symptoms after consumption of certain foods, and the severity of their symptoms. The prevalence of fructans food hypersensitivity was 31.1 %; it was higher in women than in men. The most frequent gastrointestinal symptoms were bloating and flatulence. The most frequent extra-intestinal symptoms were fatigue and stress. The food groups related to the occurrence of symptoms were legumes, vegetables, and fruits. Significant association was found between female sex, personal and family history of gastrointestinal diseases and the presence of fructans food hypersensitivity (p < 0.05). Most individuals with fructans food hypersensitivity had mild gastrointestinal dysfunction (67.2 %). FFH is a common condition, it was found in one third of university students and occurs mainly in women. More research and diffusion about this pathology is required.

Celiac Disease Screening in the Siblings of Pediatric Patients with a Confirmed Diagnosis: A Cross-sectional Study

Background: The close relatives of patients with celiac disease (CD), particularly their siblings, are known to be at a higher risk for CD development. Objectives: Our aim was to determine the prevalence of CD in siblings of confirmed CD patients in Lorestan province, Iran, in 2020. Methods: In this cross-sectional study, anti-tissue transglutaminase (tTG) antibody levels were measured in 140 siblings of children with CD. Duodenal biopsies were taken to confirm the diagnosis in those with positive serological tests. The subjects’ demographic and clinical data were recorded into a pre-designed questionnaire, and the collected data were analyzed by SPSS software version 22 at a significance level of 0.05. Results: Twelve out of 140 subjects (8.6%) tested positive for tTG IgA, eight of them (66.7%) were girls, and most of them (75%) were ≤ 15 years old. Half of the newly diagnosed patients were in the Marsh IIIc category. The Marsh grading had no significant relationship with the serum levels of tTG IgA antibodies (P = 0.319). The most common gastrointestinal symptom was bloating (66.7%), and the most common extraintestinal symptoms were anemia (58.3%) and dental and oral diseases (58.3%). Conclusions: We found a high prevalence (8.6%) of CD among the siblings of children with confirmed CD. Since the early diagnosis of CD can lead to better management, particularly in pediatrics, it is recommended screen patients’ family members as soon as the diagnosis of CD is confirmed.

Clinical case of atypical course of Crohn’s disease

Crohn’s disease (CD) is a chronic recurrent inflammatory bowel disease with a wide variety of clinical manifestations – from classical gastrointestinal phenotypes to predominance of extraintestinal symptoms. Atypical course of CD is observed relatively often and is manifested with a damage to almost all body systems, including hepatobiliary, immune, hematopoietic, cardiovascular, nervous, as well as eyes, skin, lungs and kidneys. Atypical manifestation often precedes intestinal, making diagnosis difficult. The presence of various clinical manifestations of CD, often an atypical course, as well as the absence of standardized diagnostic criteria can be an obstacle for physicians in the timely detection of the disease and effective treatment. Aim: to describe a clinical case of a diagnostically difficult patient of our clinic with an atypical course of CD and complications incompatible with life; highlight the problem of monitoring and possible solutions. Results. In the presented clinical case the patient with an atypical course of CD, with the prevailing displays of defeat of nervous and vascular systems is described. During hospitalization, a full range of diagnostic tests was performed, consultations with related specialists were obtained, but no direct data of inflammatory bowel disease were found. At the same time, the impossibility of performing a colonoscopy with a biopsy, due to the severity of the patient’s condition, delayed the timely diagnosis of CD and contributed to the development of complications incompatible with life. The diagnosis was made posthumously. The patient died as a result of intoxication due to the development of complications of CD – perforation of the intestine, intestinal abscess, development of peritonitis, septicemia. Conclusions. In the described clinical case CD is considered as a complex interdisciplinary problem, and emphasizes the importance of doctor’s awareness of the variants of atypical manifestations and course of inflammatory bowel disease, methods for their assessment and ways of effective management. This case also presents the latest epidemiological data on the prevalence of atypical manifestations of CD, identifies key areas of diagnostic search in case of a difficult patient.

THE RELATIONSHIP BETWEEN SELF-REPORTED SLEEP, WRIST ACTIGRAPHY, AND SYMPTOMS AMONG ADULTS WITH INFLAMMATORY BOWEL DISEASE (IBD)

Abstract BACKGROUND Recently, there has been a growing recognition of the bidirectional link between sleep and inflammation. Several studies have reported the prevalence of sleep disturbances in those with Inflammatory Bowel Disease (IBD) and found poor sleep has the potential to increase the risk of disease relapse. Additionally, sleep loss may adversely affect cognitive performance, mental health, metabolism, and pain perception. While previous research has indicated potential associations between sleep and symptoms commonly reported in IBD, few studies use objective measures of sleep. Wrist actigraphy can objectively and non-invasively measure sleep-wake cycles and has been found feasible for use in the IBD population. This study aimed to examine the relationship between self-reported sleep, wrist actigraphy, and symptoms among adults with IBD. METHODS Participants with IBD (ages 18-55) completed demographic and sleep questionnaires, a 28-day symptom diary, and wore a wrist actigraph for up to 15 days. Sleep questionnaires were the Pittsburgh Sleep Quality Index (PSQI), Patient-Reported Outcomes Measurement Information System (PROMIS) sleep disturbance, and PROMIS sleep-related impairment. Participants rated symptoms on a 4-point Likert scale, including gastrointestinal-related symptoms such as abdominal pain, diarrhea, bloating, constipation, fatigue, and extraintestinal symptoms, including anxiety, depression, and stress. Data analysis included descriptive statistics and Pearson correlations. RESULTS Twenty-five participants (Crohn’s Disease=18; Ulcerative Colitis=7) were included. The mean age was 33.5 (SD 8.3) years of age, 60% were female, 92% were White, 88% were non-Hispanic or Latino, and 36% had active endoscopic disease. Most (64%) participants had poor quality sleep (PSQI global ≥ 5). In contrast, the averages for onset latency, efficiency, wake after sleep onset (WASO), and total sleep time were all within normal values at 17.4 min (SD 26.7), 84.2% (SD 7.5), 48.7 min (SD 27.3), and 435.8 min (69.2), respectively. PROMIS sleep disturbance was significantly correlated with abdominal pain (r=0.56), bloating (r=0.43), constipation (r=0.46), fatigue (r=0.50), and stress (r=0.42). PROMIS sleep-related impairment was significantly correlated with bloating (r=0.47), constipation (r=0.50), fatigue (r=0.60), depression (r=0.42), and stress (r=0.46). Onset latency was significantly correlated with anxiety (r=0.41) and stress (r=0.42). Sleep time was significantly correlated with fatigue (r=0.42). CONCLUSION This study highlights sleep disturbances are prevalent in those with IBD and significantly correlated with both GI and extraintestinal symptoms. Future work is needed to explore these relationships further and the potential benefit of sleep interventions in this population.

THE GUT MICROBIOME REGULATES EFFICACY OF SULFASALAZINE THERAPY FOR SPONDYLOARTHRITIS IN INFLAMMATORY BOWEL DISEASE

Abstract Joint inflammation, or spondyloarthritis (SpA), is the most common extra-intestinal manifestation of inflammatory bowel disease (IBD), but the specific role for therapies targeting SpA is not well defined. One of the earliest medications used for the treatment of IBD is sulfasalazine (SAS). SAS is a prodrug composed of two chemical moieties, the anti-inflammatory 5-aminosalicilate and the antibiotic sulfapyridine. The efficacy of SAS in peripheral arthritis is thought to depend on its “antibacterial” properties, however the impact of SAS on the IBD-SpA microbiome and how it may improve extra-intestinal symptoms is unknown. Therefore, our study aims to diagnostically evaluate the role for the fecal microbiome in clinical response to SAS therapy and identify microbial and immunologic therapeutic targets associated with clinical response. We have designed an observational study to longitudinally follow IBD patients with SpA who have a medical indication for SAS therapy. Clinical data and fecal samples from 22 patients were collected before initiation of SAS and at week 12 after initiation of SAS. Eleven IBD-SpA patients were concomitantly enrolled as controls and followed by 12 weeks. Metagenomic sequencing was used to define the effect of SAS on the IBD-SpA fecal microbiome and to evaluate its relationship with improvement in joint symptoms. Mouse models and in vitro assays were used to test the sufficiency of the SAS effect observed in patients. The fecal microbiome of SAS-responders was distinct from that observed in non-responders and 6 pre-treatment microbial markers (including the short chain fatty acid (SCFA) producer Faecalibacterium prausnitzii) predicted SAS-response (AUC = 0.9). Fecal metabolome of SAS responders had lower thymine and higher deoxyuridine compared to non-responders consistent with evidence of a folate trap in response to SAS treatment. SAS therapy in SPF mouse-model of chemically-induced colitis alleviated colitis in GPR 109a-dependent fashion consistent with a synergistic role for SCFA. In vitro assays revealed SAS direct regulation of F. prausnitzii metabolic function and butyrate synthesis. CONCLUSIONS: Collectively, these findings highlight the potential role for microbial diagnostics to improve SAS efficacy, and drug modulation of microbial markers to potentiate therapy for IBD patients with SpA.

TRENDS AND RELATED FACTORS OF QUALITY OF LIFE IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE

Abstract INTRODUCTION Inflammatory bowel disease(IBD) affects health-related quality of life(HRQoL). The short inflammatory bowel disease questionnaire(SIBDQ), measuring physical, social, and emotional status(score 10-70, poor to good HRQoL), is known to be well correlated to HRQoL of IBD patients. AIM/METHODS We aimed to evaluate factors that impact IBD patients' HRQoL. This prospective study included a cohort of patients with ulcerative colitis(UC) and Crohn’s disease(CD). IBD patients completed a SIBDQ questionnaire at enrollment and 20% of those patients completed a second SIBDQ questionnaire at follow-up. Data were analyzed using multiple linear regression analysis and Pearson’s correlation. RESULTS A total of 1,058 patients with IBD(UC 68%, CD 32%) were included. A SIBDQ score was median 52(IQR: 44-58). The first and follow-up SIBDQ score were not significantly different between UC and CD patients (p=0.243 and p=0.893, respectively). The distributions of SIBDQ change were as follows: decrease over 10%: 28%, -10% &amp;lt; change &amp;lt; 10%: 29%, increase over 10%: 43%. In UC patients, significant factors that negatively associated with SIBDQ score, were physician’s global assessment(r=-3.562, p&amp;lt;0.001), corticosteroids use(r=-5.478, p&amp;lt;0.001), fecal calprotectin level(r=-2.313, p=0.008), presence of joint symptoms(r=-2.925, p=0.017). In CD patients, significant factors that negatively associated with SIBDQ score, were Crohn's disease activity index score(r=-0.035, p=0.009), level of abdominal pain(r=-3.400, p=0.013) and presence of skin symptoms(r=-3.842, p=0.016). Factors that associated with SIBDQ score in both UC and CD patients were stool frequency(r=-2.913, p&amp;lt;0.001 in UC patients; r=-2.347, p=0.014 in CD patients). CONCLUSION SIBDQ questionnaire shows that IBD patients' HRQoL was mainly affected by the patient-reported outcome. However, it was also influenced by biochemical markers and extraintestinal symptoms depending on the specific type of IBD.

ARTHRITIS AND ARTHRALGIA AS EXTRAINTESTINAL MANIFESTATIONS IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE TREATED WITH VEDOLIZUMAB: A META-ANALYSIS

Abstract BACKGROUND Vedolizumab is a humanized gut selective drug that specifically targets α4β7 integrin and has been used successfully in the treatment of Inflammatory Bowel Disease (IBD). Although Vedolizumab is an effective treatment for IBD and acts specifically on the gastrointestinal system, some studies have reported extraintestinal manifestations as adverse events. One of the most frequently reported non-infectious adverse events is articular manifestations. However, it is difficult to know for sure whether the joint symptoms are due to the vedolizumab adverse event or due to extraintestinal symptoms of the disease itself. AIMS This systematic review and meta-analysis aimed to assess the incidence of extraintestinal manifestations in patients receiving Vedolizumab and to investigate whether these adverse events are indeed drug-related. METHODS Pubmed, Cochrane, and Scopus were searched for randomized clinical trials reporting the incidence of articular events in patients with Crohn’s Disease or Ulcerative Colitis who were treated with Vedolizumab. The considered outcomes were new-onset or worsening of pre-existing joint manifestations. We used Revman to calculate the pooled incidence of the reported outcomes and their corresponding 95% confidence intervals (95% CI). RESULTS The search strategy yielded 4.206 articles. After removal of duplicates and screening of results, 4 randomized studies met the inclusion criteria (Figure 1). A total of 2.466 patients with moderately to severe IBD were included. Of those, 1822 were randomized to intervention group, with Vedolizumab administration, and 644 to placebo. In the intervention group, 232 patients developed arthritis or arthralgia of any kind, versus 66 patients of placebo group (95% CI 0.7%-1.3%; Figure 2). Of those patients, 73,8% and 33% had prior treatment with anti-TNF and immunomodulators, respectively. 63% and 15% also had prior anti-TNF and immunomodulators previous failure, respectively. CONCLUSION The meta-analysis presented above shows a result without statistical significance to say that vedolizumab is responsible for the manifestations previously described. Therefore, it is necessary to hypothesize that the new onset of worsening arthritis and arthralgia may be associated with the course of the disease itself, the body's response to the drugs or the exclusion of corticosteroids or anti-TNF from concomitant treatment with Vedolizumab. More studies with larger samples are needed, especially randomized clinical trials comparing Anti-TNF, corticosteroids and immunomodulators to assess the incidence of joint manifestations and even other rheumatologic manifestations in patients with Inflammatory Bowel Disease.

Extraintestinal manifestation of Celiac disease: A case series

Celiac disease (CD) is a multisystem chronic inflammatory disorder with an autoimmune component in genetically susceptible individuals elicited by gluten and related prolamines. CD is becoming a common disorder arising at any age with a broad spectrum of symptoms ranging from intestinal to extraintestinal manifestations. Extraintestinal symptoms being more common after 2 years of life, can affect various systems and organs of the body. Knowledge of the extraintestinal manifestations of celiac disease is of utmost importance for the diagnosis of CD. Owing to the high risk of complications among the undiagnosed cases of CD, patients with extraintestinal manifestations should undergo appropriate diagnosis and treatment for CD.

Co-occurrence of Whipple's disease and hyperparathyroidism - coincidence or causal relationship?

Whipple's disease is a rare infectious disease with multiple clinical manifestations. The diseaseis named after GeorgeHoyt Whipple, who first recorded the illness in 1907 after conducting the autopsy of a 36-year-old man with weight loss, diarrhea, and arthritis. Under the microscope, Whipple discovered a rod-shaped bacterium in the patient's intestinal wall, which was not confirmed as a new bacterial species until 1992, when it was named Tropheryma whipplei.Recurrence of Whipple's disease can occur years after an initial diagnosis and often manifests with extraintestinal symptoms such as arthritides or skin efflorescences, years before a gastrointestinal complaint. However, the simultaneous occurrence of primary hyperparathyroidism in the present case is a hitherto unknown clinical picture and opens up new questions and perspectives in the context of diagnostics and therapy.

Magnetic Resonance Neuroimaging of Inflammatory Bowel Disease

Inflammatory bowel disease (IBD) is a lifelong, relapsing, chronic inflammatory disease of the digestive tract that can be brought on by a number of different etiologies. Studies have shown that patients with IBD also have nervous system involvement in addition to well-known extra-intestinal symptoms like arthritis and iritis, and researchers believe that neurological lesions in patients with IBD may be an important extra-intestinal manifestation. Currently, tentative findings from studies employing magnetic resonance imaging to study the brain structure and function of patients with IBD have been made.

1327. Nontyphoidal salmonella infection in children and adolescent; A retrospective, multicenter study in Korea

Abstract Background Non-typhoidal salmonella (NTS) infections usually have a self-limiting course, but can cause invasive NTS (iNTS) diseases, including bacteremia, meningitis, osteomyelitis or other focal infection. However, information on NTS infections in children is scarce in Asian countries. We investigated the differences in clinical features and antimicrobial susceptibility patterns of NTS infections in Korean children. Methods From November 2006 to May 2021, we collected NTS cases isolated from patients under the age of 20 at three Severance Hospitals (Sinchon, Gangnam, and Yongin) in Korea. All NTS cases were extracted through the Severance Clinical Research Analysis Portal. NTS cases isolated from the genitourinary tract were excluded. Clinical data were collected through chart review. Results A total of 837 isolates were identified from 637 patients. 22 patients were excluded, and a 615 patients were included in the study. The median age at NTS infection was 4.6 years (IQR, 2.4-7.9 years), and those under 5 years of age accounted for 54.1% of all cases. The male to female ratio was 1.6:1 and approximately 15.8% (n=97) had at least one comorbidity. By clinical diagnosis, enterocolitis was the most common with 543 cases (88.3%), followed by bacteremia without local sign in 11 cases (1.8%), osteomyelitis in 7 cases (1.1%). The iNTS group (n=68) did not have any significant differences in age of onset, presence of fever, white blood cells, absolute neutrophils, and C-reactive protein levels, but the frequency of diarrhea (67.6% vs. 89.9%, p&amp;lt;0.001) was less than the non-invasive NTS group (n=547). Extra-intestinal symptoms were more common in the iNTS group than in the non-invasive group (30.9% vs. 14.3%, p=0.003), and the length of hospital stay (8.65±6.4 days vs. 5.13±3.3 days, p=0.001) were significantly longer in the iNTS group. Notably, 2 out of 7 patients with NTS osteomyelitis showed a poor clinical response even with cefotaxime-sensitive antimicrobial susceptibility results. Antimicrobial susceptibility pattern between the group was shown in Figure 1. Antimicrobial susceptibility pattern between the group Conclusion Children with iNTS infection showed a relatively severe clinical course compared to children with non-iNTS infection. Further studies on the epidemiology and characteristics of invasive NTS infection are needed. Disclosures Joon-sik Choi, MD, MS, Ministry of Trade, industry and Energy, Republic of Korea: Grant/Research Support.

Association of serotonin transporter promoter polymorphism (5-HTTLPR) with orocecal transit time in irritable bowel syndrome.

Irritable bowel syndrome (IBS) is a multifactorial disorder with altered intestinal motility, secretion, and sensation. Serotonin (5-HT) stimulates gut motility and alters serotonin signaling that may lead to both intestinal and extraintestinal symptoms in IBS. The aim of this study was to examine the association of serotonin transporter gene promoter polymorphism (5-HTTLPR) in IBS with orocecal transit time (OCTT) measured by lactulose hydrogen breath test. This prospective case-control study included 151 IBS patients (mean±SD 37.4±11.6 years, median 36, range 19-68). Ninety-two patients were diarrhea-predominant IBS (D-IBS), 44 constipation-predominant IBS (C-IBS), 15 alternating diarrhea and constipation IBS (M-IBS), and 100 healthy controls (mean±SD 37.2±11.4 years, median 36, range 20-64 years). 5-HTTLPR gene polymorphism was studied by polymerase chain reaction-based method. 5-HT levels were measured by enzyme-linked immunosorbent assay (ELISA). Orocecal transit time (OCTT) was measured by a non-invasive lactulose hydrogen breath test. OCTT was also compared with respect to 5-HTTLPR genotypes in differentIBS phenotypes. Serum serotonin levels were significantly higher in overall IBS patients (152±77 ng/mL, p<0.001), D-IBS (184±76 ng/mL, p<0.001), compared to healthy controls (129±56 ng/mL). There was no difference in 5-HT levels between C-IBS (124±53 ng/mL) and controls. In the case of M-IBS, 5-HT levels were (88±49 ng/mL p<0.05) significantly lower than that of controls. OCTT was significantly shorter in D-IBS patients (95±36 min) as compared to controls (112±41 min). In contrast, C-IBS showed significantly prolonged OCTT (136±54 min). There was a significant difference in OCTT between D-IBS and C-IBS patients (p<0.001). There was no significant association found between OCTT and 5-HTTLPR. Serum serotonin concentrations were increased in D-IBS compared to controls and C-IBS. OCTT was shorter in D-IBS and delayed in C-IBS patients. There was no association of 5-HTLPR polymorphism with OCTT.

A Comprehensive Review of the Neurological Manifestations of Celiac Disease and Its Treatment.

Celiac disease (CD) is a common chronic inflammatory disorder occurring in genetically predisposed individuals secondary to gluten ingestion. CD usually presents with gastrointestinal symptoms such as pain, bloating, flatulence, and constipation or diarrhea. However, individuals can present in a nonclassical manner with only extraintestinal symptoms. The neurological manifestations of CD include ataxia, cognitive impairment, epilepsy, headache, and neuropathy. A lifelong gluten-free diet is the current recommended treatment for CD. This review discusses the relevant neurological manifestations associated with CD and the novel therapeutics. Further research is required to get a better understanding of the underlying pathophysiology of the neurological manifestations associated with CD. Clinicians should keep CD in the differential diagnosis in individuals presenting with neurological dysfunction of unknown cause.