In inflammatory bowel disease and extraintestinal manifestations:What role does microbiome play?

Inflammatory bowel disease(IBD)is a systemic disorder affecting intestinal tract and other organs outside the gut,known as extraintestinal manifestations(EIMs).These EIMs are complex and diverse,and early treatment may reduce teratogenic rates and improve quality of life.However,our understanding of EIMs in IBD is currently limited by a lack of mechanistic insight.Fortunately,advances in our understanding of intestinal microecology are allowing us to uncover the underlying mechanisms of EIMs.The gut microbiota can drive aberrant immune activation and intestinal inflammation.Intriguingly,chronic inflammation can also shape the microbiome in reverse and aggravate dysbiosis.Recent research has revealed that microbiome-derived signal molecules play a crucial role in catalyzing enterocolitis and altering mucosal barrier function.Furthermore,gut microbiota-associated antigens can translocate from the intestine to extraintestinal sites,leading to systemic inflammatory responses.The microbiome is showing its potential in treating IBD and EIMs,and microbial engineering approaches,such as probiotic engineering and engineered fecal microbiota transplantation,are exhibiting great promise for IBD therapeutics.

Growth differentiation factor-15 serum concentrations reflect disease severity and anemia in patients with inflammatory bowel disease

BACKGROUND Population of patients with inflammatory bowel disease(IBD)is burdened by various extraintestinal manifestations which substantially contribute to greater morbidity and mortality.Growth-differentiation factor-15(GDF-15)is often overexpressed under stress conditions,such as inflammation,malignancies,heart failure,myocardial ischemia,and many others.AIM To explore the association between GDF-15 and IBD as serum concentrations of GDF-15 were shown to be an independent predictor of poor outcomes in multiple diseases.An additional aim was to determine possible associations between GDF-15 and multiple clinical,anthropometric and laboratory parameters in patients with IBD.METHODS This cross-sectional study included 90 adult patients diagnosed with IBD,encompassing both Crohn’s disease(CD)and ulcerative colitis(UC),and 67 healthy age-and sex-matched controls.All patients underwent an extensive workup,including colonoscopy with subsequent histopathological analysis.Disease activity was assessed by two independent gastroenterology consultants specialized in IBD,employing well-established clinical and endoscopic scoring systems.GDF-15 serum concentrations were determined following an overnight fasting,using electrochemiluminescence immunoassay.RESULTS In patients with IBD,serum GDF-15 concentrations were significantly higher in comparison to the healthy controls[800(512-1154)pg/mL vs 412(407-424)pg/mL,P<0.001],whereas no difference in GDF-15 was found between patients with CD and UC[807(554-1451)pg/mL vs 790(509-956)pg/mL,P=0.324].Moreover,multiple linear regression analysis showed that GDF-15 levels predict CD and UC severity independent of age,sex,and C-reactive protein levels(P=0.016 and P=0.049,respectively).Finally,an association between GDF-15 and indices of anemia was established.Specifically,negative correlations were found between GDF-15 and serum iron levels(r=-0.248,P=0.021),as well as GDF-15 and hemoglobin(r=-0.351,P=0.021).Accordingly,in comparison to IBD patients with normal hemoglobin levels,GDF-15 serum levels were higher in patients with anemia(1256(502-2100)pg/mL vs 444(412-795)pg/mL,P<0.001).CONCLUSION For the first time,we demonstrated that serum concentrations of GDF-15 are elevated in patients with IBD in comparison to healthy controls,and the results imply that GDF-15 might be involved in IBD pathophysiology.Yet,it remains elusive whether GDF-15 could serve as a prognostic indicator in these patients.

Prevalence and characteristics of ophthalmological extra-intestinal manifestations in Chinese patients with inflammatory bowel disease

AIM：To investigate the prevalence of ophthalmological extra-intestinal manifestations（O-EIMs） in Chinese patients with inflammatory bowel disease（IBD） and to identify risk factors for the development of O-EIMs.METHODS：The study population consisted of Chinese patients with a definite diagnosis of Crohn＇s disease（CD） or ulcerative colitis（UC） in a large teaching hospital between January 1995 and December 2014.Demographic and clinical characteristics of patients were extracted retrospectively.RESULTS： In this twenty-year cohort,645 IBD patients（517 with UC,128 with CD） were registered.Among them122（18.9%） exhibited at least one EIM.Of 13 patients（2.0%） developed O-EIMs,7 of CD（5.5%） and 6 of UC（1.2%）.Clinical ophthalmological manifestations included redness（76.9%）,burning（61.5%）,pain（38.5%）,itching（15.4%） of eyes and vision change（7.7%）.O-EIMs included episcleritis（7）,uveitis（5） and dry eye（1）.OEIMs were more prevalent in female（odds ratio for male0.61,95% confidence interval 0.52-0.73,P 〈0.0001）,and patients who had IBD diagnosis at young age（odds ratio for patients aged 〉30 years 0.76,95% confidence interval0.65-0.88,P 〈0.0001）.CONCLUSION： The frequency of O-EIMs in Chinese patients with IBD is lower than the rates reported in the studies of European and American countries.Episcleritisand uveitis are the most common O-EIMs.O-EIMs are more frequent in patients with CD and more prevalent in female and patients who have IBD diagnosis at young age.

Hepatobiliar manifestations in inflammatory bowel disease: A practical approach

Inflammatory bowel diseases(IBD)are associated with various hepatobiliary disorders.They can occur at any moment in the course of the disease or associated with the treatment.The prevalence of liver dysfunction can reach up to 50%in different studies.Nonalcoholic fatty liver disease is considered the most common hepatobiliary complication in IBD,while primary sclerosing cholangitis is the most specific.Management of hepatic manifestations in IBD involves a multidisciplinary approach that includes a high index of suspicion and joint management with hepatologists.The medical confrontation with abnormal liver tests must include an exhaustive study to determine if these patterns can be related to IBD,associated diseases or to the therapies used.

Myocarditis as an extraintestinal manifestation of ulcerative colitis:A case report and review of the literature

BACKGROUND Although extraintestinal manifestations of inflammatory bowel disease(IBD) are well documented,myocarditis has only rarely been reported as an extraintestinal manifestation,and it can be fatal.The various clinical presentations and causes of myocarditis in IBD patients complicate making a correct and timely diagnosis.CASE SUMMARY Here we report a 15-year-old boy who presented with myocarditis as the initial presentation of a relapse of ulcerative colitis.In reviewing the literature for cases of myocarditis complicating IBD,we found 21 other cases,allowing us to expand our understanding of the clinical presentation,diagnosis,management,and outcomes of this rare condition.The most frequent diagnostic clues for myocarditis in IBD patients are dyspnea,chest pain,tachycardia,raised cardiac biomarkers,and abnormalities on trans-thoracic echocardiography.Additionally,we discuss the etiology of myocarditis in IBD patients,which include an extraintestinal manifestation,the adverse effects of mesalamine and infliximab,selenium deficiency,and infection,to help provide a framework for diagnosis and management.CONCLUSION Myocarditis as an extraintestinal manifestation of IBD can be life-threatening.Trans-thoracic echocardiogram and cardiac magnetic resonance may assist its diagnosis.

Patients with inflammatory bowel disease have increased risk of autoimmune and inflammatory diseases

AIM To investigate whether immune mediated diseases(IMD) are more frequent in patients with inflammatory bowel disease(IBD).METHODS In this population based registry study,a total of 47325 patients with IBD were alive and registered in the Danish National Patient Registry on December 16,2013. Controls were randomly selected from the Danish Civil Registration System(CRS) and matched for sex,age,and municipality. We used ICD 10 codes to identify the diagnoses of the included patients. The IBD population was divided into three subgroups: Ulcerative colitis(UC),Crohn's disease(CD) and Both the latter referring to those registered with both diagnoses. Subsequently,odds-ratios(OR) and 95%CI were obtained separately for each group and their respective controls. The use of Bonferoni post-test correction adjusted the significance level to P < 0.00125. P-values were estimated using Fisher's exact test.RESULTS There were significantly more women than men in the registry,and a greater percentage of comorbidity in the IBD groups(P < 0.05). Twenty different IMDs were all significantly more frequent in the IBD group. Sixteen were associated with UC versus twelve with CD. In both UC and CD ORs were significantly increased(P < 0.00125) for primary sclerosing cholangitis(PSC),celiac disease,type 1 diabetes(T1D),sarcoidosis,asthma,iridocyclitis,psoriasis,pyoderma gangrenosum,rheumatoid arthritis,and ankylosing spondylitis. Restricted to UC(P < 0.00125) were autoimmune hepatitis,primary biliary cholangitis,Grave's disease,polymyalgia rheumatica,temporal arteritis,and atrophic gastritis. Restricted to CD(P < 0.00125) were psoriatic arthritis and episcleritis. Restricted to women with UC(P < 0.00125) were atrophic gastritis,rheumatoid arthritis,temporal arteritis,and polymyalgia rheumatica. Restricted to women with CD were episcleritis,rheumatoid arthritis,and psoriatic arthritis. The only disease restricted to men(P < 0.00125) was sarcoidosis. CONCLUSION Immune mediated diseases were significantly more frequent in patients with IBD. Our results strengthen the hypothesis that some IMDs and IBD may have overlapping pathogenic pathways.

Infliximab is effective in the treatment of ulcerative colitis with dermatomyositis:A case report

BACKGROUND Joint,skin,oral cavity,and eye lesions are the most common extraintestinal manifestations of ulcerative colitis that can occur before or after its onset.The cases of ulcerative colitis with dermatomyositis(DM)are rare.In this study,we report a rare case of ulcerative colitis with DM that was effectively treated with infliximab.CASE SUMMARY The patient was a 57-year-old female with a 2-year history of DM.The patient was admitted to hospital with abdominal pain,diarrhea,and blood in stool lasting for more than 2 mo.Colonoscopy revealed multiple erosions and ulcers in the entire colon and rectum.Pathological sections showed chronic inflammatory cell infiltration,especially neutrophil infiltration,in the colonic mucosa;therefore,the patient was diagnosed with ulcerative colitis.Preparations of 5-aminosalicylic acid was added to her treatment based on the original treatment for DM,but its effect was unsatisfactory.The patient’s discomfort was relieved after infliximab treatment.CONCLUSION Infliximab can improve DM in the treatment of ulcerative colitis.Specialists need to raise awareness about patients with inflammatory bowel disease who have rare extraintestinal manifestations.

Pancreatic involvement in pediatric inflammatory bowel diseases

Background:Inflammatory bowel diseases(IBDs)are a group of chronic diseases affecting the gastrointestinal tract,with a disabling course.The incidence of IBDs is increasing in different geographical areas,indicating its emergence as a global disease,especially in children.Many patients with IBDs develop extraintestinal manifestations(EIMs)during follow-up,as IBDs have a potential risk of systemic involvement..Data sources:A systematic review of the literature was made to analyze latest studies on pancreatic involvement in children with IBD including our experience in assessing possible implications and its future application.Results:The involvement of the hepatobiliary system is considered a rare EIM of children with IBD,with an incidence much higher than that in the general population.Isolated pancreatic hyperenzymemia,which occurs in the absence of typical symptoms and/or characteristic imaging findings,may be found in many patients with IBD.The frequent causes of pancreatitis are drugs,bilio-pancreatic disorders,immunologic disturbances and pancreatic auto-antibodies,although in some cases idiopathic forms have been described.Conclusions:It is important to establish a correct diagnostic approach based on etiology and to assess the most appropriate therapeutic strategy,thus avoiding complications and improving the quality of life of children with IBD.