Primary sclerosing cholangitis (PSC) is characterized by idiopathic intra- and extrahepatic bile duct inflammation and biliary fibrotic changes. Recurrent bile duct stones due to PLKR and UGT1A1 mutation is an extremely rare complications of PSC.

A 26-year-old male patient complains a history of recurrent yellow skin and urine for over a year.

Following dynamic magnetic resonance cholangiopancreatography imaging, colonoscopic manifestation, liver biopsy and whole exome sequencing, the patient was finally diagnosed with PSC - ulcerative colitis with PLKR and UGT1A1 mutation.

Following resolution of the obstruction, a long-term regimen of 1000 mg/d ursodeoxycholic acid in combination with 10 mg/d obeticholic acid to improve cholestasis, 8 g/d colestyramine to facilitate adsorption of excess bile acids and 1.2 g/d rifaximin to prevent biliary tract infection were prescribed.

The patient's liver biochemical parameters have improved significantly. His condition is stable and has not undergone liver transplantation at this time.

Close and dynamic detection of the patient's biliary ductal lesions play an important role in the diagnosis of PSC. In the event of relatively rare biliary complications, attention should be paid to the presence of gene mutation.

In patients with inflammatory bowel disease (IBD), co-occurring spondyloarthritis (SpA) leads to poorer outcomes and impaired quality of life, highlighting the importance of early detection and effective treatment. This is the first study to assess the prevalence and distribution of axial symptoms and magnetic resonance imaging (MRI)-detected involvement of the spine and sacroiliac joints (SIJs) in early IBD.

Newly diagnosed patients with IBD from a prospective, population-based cohort were consecutively recruited. Rheumatological interview, clinical, ultrasound, and MRI assessment for SIJ and spine inflammatory and structural lesions were made using validated scoring methods and consensus definitions of axial SpA (axSpA).

Of 110 patients (ulcerative colitis: 70, Crohn's disease: 40, mean age of 42 years, and 40% male), 48 (44.9%) reported back and/or buttock pain, and 10 (9.1%) had inflammatory back pain. Seventeen (16.7%) patients had MRI findings indicative of axSpA; only 10 of these patients had axial symptoms. Inflammatory MRI lesions were present in SIJs and the spine of 27 (26.5%) and 30 (30.3%) patients, respectively. The Assessment of SpondyloArthritis International Society classification criteria for axSpA were met in 11 (10%) cases. MRI findings typical of axSpA were associated with peripheral joint and entheseal inflammation detected by ultrasound ( P = 0.04). No differences in clinical or imaging findings were found between patients with ulcerative colitis and Crohn's disease.

One-in-6 newly diagnosed patients with IBD had MRI findings indicative of axSpA. As 40% of these patients were asymptomatic, this suggests that axSpA is underdiagnosed in early IBD. Multidisciplinary collaboration is essential to ensure early detection of axial inflammation and to enable optimal therapy preventing future structural damage and disability.

Musculoskeletal [MSK] manifestations in patients with inflammatory bowel disease [IBD] are common and associated with poorer outcomes. Hence, early detection is important to optimally tailor treatment. We aimed to determine the prevalence and distribution of inflammatory lesions in peripheral joints and entheses in newly diagnosed IBD patients.

Patients with newly diagnosed IBD from a prospective population-based inception cohort were consecutively included. Data on MSK symptoms were collected by questionnaires and by structured rheumatological interview. Peripheral joints and entheses were assessed clinically and by ultrasound [US], using standardized definitions.

Of 110 included patients (mean age: 42 years, 40% male, 70 with ulcerative colitis [UC], 40 with Crohn's disease [CD]), a history of ≥1 peripheral musculoskeletal symptom was reported by 49%. Clinical examination revealed peripheral MSK manifestations in 56 [52.3%] patients; 29 [27.1%] had ≥1 tender and/or swollen joints and 49 [45.8%] ≥1 tender entheses. Small peripheral joints were predominantly affected. US found inflammation in ≥1 joint or enthesis in 52 [49.5 %] patients; 29 [27.4 %] had US synovitis in ≥1 joint, while 36 [34%] had US enthesitis. Fibromyalgia classification criteria were fulfilled in seven [7.9%] patients. There was no difference in clinical or US findings between patients with UC and CD, nor between patients with active and inactive IBD.

Half of the patients with newly diagnosed IBD had inflammation in their peripheral joints and/or entheses, documented by rheumatological clinical and US evaluations. This indicates a need for multidisciplinary collaboration to ensure an optimal therapeutic strategy for suppressing inflammation in all disease domains.

(1) Background: Inflammatory bowel disease (IBD) is frequently associated to other immune-mediated inflammatory diseases (IMIDs). This study aims at assessing physicians' awareness of the issue and the current status of IMID management. (2) Methods: A web-based survey was distributed to all 567 physicians affiliated to IG-IBD. (3) Results: A total of 249 (43.9%) physicians completed the survey. Over 90% of the responding physicians were gastroenterology specialists, primarily working in public hospitals. About 51.0% of the physicians had access to an integrated outpatient clinic, where gastroenterologists collaborated with rheumatologists and 28.5% with dermatologists. However, for 36.5% of physicians, integrated ambulatory care was not feasible. Designated appointment slots for rheumatologists and dermatologists were accessible to 72.2% and 58.2% of physicians, respectively, while 20.1% had no access to designated slots. About 5.2% of physicians report investigating signs or symptoms of IMIDs only during the initial patient assessment. However, 87.9% inquired about the presence of concomitant IMIDs at the initial assessment and actively investigated any signs or symptoms during subsequent clinical examination. (4) Conclusions: While Italian physicians recognize the importance of IMIDs associated with IBD, organizational challenges impede the attainment of optimal multidisciplinary collaboration. Efforts should be directed toward enhancing practical frameworks to improve the overall management of these complex conditions.

The fungal secondary metabolite deoxynivalenol (DON) that can contaminate cereal-based food products not only induces inflammation but also reduces bile acid absorption by a healthy human intestine. Bile acid malabsorption is commonly observed in individuals with an inflamed intestine. Here we studied the effects of DON on inflammation and primary bile acid transport using an in vitro model for an inflamed intestine. An inflamed intestinal in vitro model was established by co-culturing a Caco-2 cell-layer and LPS-pre-stimulated THP-1 macrophages in Transwells. We observed a decreased transport of 5 primary bile acids across inflamed co-cultures compared to healthy co-cultures but not of chenodeoxycholic acid. DON exposure further reduced the transport of the affected primary bile acids across the inflamed co-cultures. DON exposure also enhanced the secretion of pro-inflammatory cytokines in the inflamed co-cultures, while it did not increase the pro-inflammatory cytokines secretion from LPS-pre-stimulated THP-1 monocultures. Exposure of Caco-2 cell-layers to pro-inflammatory cytokines or THP-1 conditioned media partly mimicked the DON-induced effects of the co-culture model. Local activation of intestinal immune cells reinforces the direct pro-inflammatory effects of DON on intestinal epithelial cells. This affects the bile acid intestinal kinetics in an inflamed intestine.

There is a high variability of out-of-packet patient costs of inflammatory bowel diseases (IBDs), but the issue is not widely recognised. Therefore, we compared patient costs of IBDs between 12 European countries.

A questionnaire-based study was conducted among adult patients with IBD. Data on patient characteristics and out-of-pocket expenses were anonymously collected. Ordered logit regression models were used to analyse the responses provided by patients. The results were adjusted for confounders and multiplicity.

The questionnaires obtained from 3687 patients were analysed. Patients with comorbidities and active disease indicated higher out-of-pocket expenses than those without comorbidities and with disease in remission, respectively. Compared with other IBD, patients with ulcerative colitis indicated higher expenses on medications prescribed or recommended by physicians [odds ratio (OR) 1.99, 95% CI 1.48-2.67]. Expenses on dietary supplements, special diet or equipment, ostomy pouches, and transportation to a medical facility differed slightly between patients at different ages and were lower among men than among women (OR 0.71, 95% CI 0.54-0.93). The expenses differed significantly between countries. An adjusted mean patient cost per month varied from €77 (patient with Crohn disease in remission from Denmark) to €376 (patient with active ulcerative colitis from Romania). Compared with active disease, patients with IBD in remission had a lower out-of-pocket cost by 29-62% (€10-€22 monthly; p < 0.001).

The study revealed a high relevance of the out-of-pocket cost of IBD in the context of economic evaluation and a high variability of the cost between countries.

It is unclear whether inflammatory bowel diseases (IBDs) affect the phenotype and severity of co-occurring immune-mediated inflammatory diseases (IMIDs). We aimed to investigate the characteristics of IMIDs in relation to co-occurring IBD.

We conducted a systematic review of Medline and EMBASE databases from inception to September 2020. We identified studies reporting the phenotype, severity, or disease course of IMIDs among patients with or without co-occurring IBD. A meta-analysis was conducted using random effects models.

The electronic search yielded 13 220 studies that we narrowed down to 73 eligible studies for full-text review, including 42 on primary sclerosing cholangitis, 12 on axial spondyloarthropathies, and 8 studies on psoriasis. In primary sclerosing cholangitis, IBD was associated with less frequent involvement of extrahepatic bile ducts (risk ratio [RR], 0.50; 95% confidence interval [CI], 0.33-0.75), longer liver transplantation-free survival (hazard ratio, 0.70; 95% CI, 0.60-0.82), and no increased risk of cholangiocarcinoma (RR, 0.88; 95% CI, 0.59-1.31). Patients with axial spondyloarthropathies and co-occurring IBD were characterized by an increased risk of dactylitis (RR, 2.06; 95% CI, 1.24-3.42), a lower Bath Ankylosing Spondylitis Radiology Index (mean difference [MD] = -2.28; 95% CI, -3.26 to -1.30), and better Schober's test results (MD = 1.07; 95% CI, 0.64-1.49). Psoriasis and co-occurring IBD was associated with reduced disease severity (RR, 1.41; 95% CI, 1.02-1.96) and less frequent presentation in nails (RR, 0.14; 95% CI, 0.05-0.42), with no apparent impact on psoriatic arthritis (RR, 0.94; 95% CI, 0.27-3.31).

This systematic review with meta-analysis found IBD is associated with a distinct disease phenotype among the IMIDs investigated. Our findings emphasize the importance of multidisciplinary approaches to patients with co-occurring IMIDs and IBD.

Personalized care in inflammatory bowel diseases (IBD) hinges on parsing the heterogeneity of IBD patients through prognostication of their disease course and therapeutic response to allow for tailor-made treatment and monitoring strategies to optimize care. Herein we review the currently available predictors of outcomes in IBD and those on the both near and far horizons. We additionally discuss the importance of worldwide collaborative efforts and tools to support clinical use of these prognostication tools.

Autoimmune pancreatitis (AIP) and inflammatory bowel disease (IBD) are categorized into immune-mediated inflammatory disorders (IMIDs). While AIP is a pancreato-biliary IMID with an increased incidence and prevalence among patients with IBD, its features are still unclear. This systematic review and meta-analysis aims to assess the prevalence and clinical characteristics of AIP-IBD patients.

Electronic databases were searched to identify observational studies assessing AIP and IBD. The primary outcome was the prevalence of IBD among AIP patients, and vice versa. Secondary outcomes included clinical findings and outcomes of each IMID in AIP-IBD patients. The pooled rate of each outcome was determined using a random effects model.

For primary outcomes, 40 observational studies with 4031 AIP patients were included and the pooled prevalence of IBD was 10.5% (95% CI 7.2-15.0%). Meanwhile, five studies with 10,551 IBD patients were included and the pooled prevalence of AIP was 0.6% (95% CI 0.2-1.9%). For secondary outcomes, 53 observational studies with 469 AIP-IBD patients were assessed. The rates of type 2 AIP and ulcerative colitis were 79.2% (95% CI 69.1-86.6%) and 74.8% (95% CI 68.2-80.4%), respectively. We also demonstrated AIP-IBD patients were at a significant increased risk of AIP recurrence and colectomy compared with patients with either AIP or IBD (RR = 1.9, 95% CI 1.1-3.1 and P = 0.014 and RR = 3.7, 95% CI 1.9-6.9, P < 0.001, respectively).

Our meta-analysis reported the prevalence of AIP-IBD patients and demonstrated patients with both IMIDs had a high risk of poor outcomes.

Inflammatory bowel diseases (IBD), encompassing Crohn's disease and ulcerative colitis, are chronic, inflammatory diseases of the gastrointestinal tract. We have initiated a Danish population-based inception cohort study aiming to investigate the underlying mechanisms for the heterogeneous course of IBD, including need for, and response to, treatment.

IBD Prognosis Study is a prospective, population-based inception cohort study of unselected, newly diagnosed adult, adolescent and paediatric patients with IBD within the uptake area of Hvidovre University Hospital and Herlev University Hospital, Denmark, which covers approximately 1 050 000 inhabitants (~20% of the Danish population). The diagnosis of IBD will be according to the Porto diagnostic criteria in paediatric and adolescent patients or the Copenhagen diagnostic criteria in adult patients. All patients will be followed prospectively with regular clinical examinations including ileocolonoscopies, MRI of the small intestine, validated patient-reported measures and objective examinations with intestinal ultrasound. In addition, intestinal biopsies from ileocolonoscopies, stool, rectal swabs, saliva samples, swabs of the oral cavity and blood samples will be collected systematically for the analysis of biomarkers, microbiome and genetic profiles. Environmental factors and quality of life will be assessed using questionnaires and, when available, automatic registration of purchase data. The occurrence and course of extraintestinal manifestations will be evaluated by rheumatologists, dermatologists and dentists, and assessed by MR cholangiopancreatography, MR of the spine and sacroiliac joints, ultrasonography of peripheral joints and entheses, clinical oral examination, as well as panoramic radiograph of the jaws. Fibroscans and dual-energy X-ray absorptiometry scans will be performed to monitor occurrence and course of chronic liver diseases, osteopenia and osteoporosis.

This study has been approved by Ethics Committee of the Capital Region of Denmark (approval number: H-20065831). Study results will be disseminated through publication in international scientific journals and presentation at (inter)national conferences.

Inflammatory bowel diseases (IBDs), including Crohn's disease and ulcerative colitis, are chronic, progressive, immune-mediated diseases of adults and children that have no cure. IBD can cause significant morbidity and lead to complications such as strictures, fistulas, infections, and cancer. In children, IBD can also result in growth impairment and pubertal delays. IBD is highly heterogenous, with severity ranging from mild to severe and symptoms ranging from mild to debilitating. Delay in IBD diagnosis, especially in Crohn's disease, is common and associated with adverse outcomes. Early diagnosis and prompt institution of treatment are the cornerstones for improving outcomes and maximizing health. Early diagnosis requires a low threshold of suspicion and red flags to guide early specialist referral at the primary provider level. Although the armamentarium of IBD medications is growing, many patients will not respond to treatment, and the selection of first-line therapy is critical. Risk stratification of disease severity, based on clinical, demographic, and serologic markers, can help guide selection of first-line therapy. Clinical decision support tools, genomics, and other biomarkers of response to therapy and risk of adverse events are the future of personalized medicine. After starting appropriate therapy, it is important to confirm remission using objective end points (treat to target) with continued control of inflammation with adjustment of therapy using surrogate biomarkers (tight control). Lastly, IBD therapy extends far beyond medications, and other aspects of the overall health and wellbeing of the patient are critical. These include preventive health, nutrition, and psychobehavioral support addressing patients' concerns around complementary therapy and medication adherence, prevention of disability, and ensuring open communication.

Patients with Crohn's disease (CD) are at increased risk of co-occurring immune-mediated inflammatory diseases (IMIDs). As discrepancy exists regarding the phenotypic presentation of CD among patients with such co-occurring IMIDs, we aimed to conduct a systematic review with meta-analysis characterizing the phenotype of CD among this subgroup of patients.

PubMed, Embase, and Scopus were searched from their earliest records to October 2019 for studies reporting the behavior and localization of CD according to the Vienna or Montreal Classifications and CD-related surgery in patients with co-occurring IMIDs. These studies were the subject of a random effect meta-analysis.

After reviewing 24,413 studies, we identified a total of 23 studies comprising 1572 and 35,043 CD patients with and without co-occurring IMIDs, respectively, that fulfilled our inclusion criteria. Overall, patients with co-occurring IMIDs were more likely to have upper gastrointestinal inflammation than were patients without co-occurring IMIDs [relative risk (RR) = 1.49 (95% confidence interval (CI) 1.09-2.04), p = 0.01, I 2 = 7%]. In addition, presence of primary sclerosing cholangitis (PSC) was associated with a lower occurrence of ileal affection [RR = 0.44 (95% CI 0.24-0.81), p < 0.01, I 2 = 32%], increased occurrence of colonic affection [RR = 1.78 (95% CI 1.33-2.38), p < 0.01, I 2 = 32%] and an increased likelihood of non-stricturing and non-penetrating behavior [RR = 1.43 (95% CI 0.97-2.11), p = 0.07, I 2 = 86%]. The latter reached significance when cumulating different IMIDs [RR = 1.30 (95% CI 1.09-1.55), p < 0.01, I 2 = 88%]. CD patients with PSC also underwent fewer CD-related surgeries [RR = 0.55 (95% CI 0.34-0.88), p = 0.01, I 2 = 0%], irrespective of CD location or behavior.

This study emphasizes that CD patients with co-existing PSC are likely to have a unique inflammatory distribution primarily confined to the colon, while patients with IMIDs in general have higher likelihood of affection of upper gastrointestinal tract and a non-stricturing and non-penetrating behavior. As such a phenotype of CD is typically associated with a milder disease course; future studies are needed to confirm these results.

Although the number of biological therapies for the treatment of Crohn's disease (CD) is rapidly increasing, their efficacy in inducing healing of fistulas in perianal Crohn's disease (pCD) is practically unknown, although they occur in up to 50% of patients with CD.

We aimed to investigate the clinical effectiveness of ustekinumab for pCD in a systemic review and meta-analysis.

Studies describing the efficacy of ustekinumab on fistulas in pCD in PubMed and EMBASE database from inception until 22 September 2020, were assessed in a systemic review and meta-analysis. The random-effect model was applied for the meta-analysis.

The systematic review of the current literature yielded 2,243 studies of which nine studies with a total of 396 patients were found eligible for inclusion. The pooled proportions of patients experiencing fistula response were 41.0% (95% CI 23.9-60.6%9), I ² = 85%, 39.7% (95% CI 24.3-57.4%), I ² = 69% and 55.9% (95% CI 40.8-69.9%, I ² = 67% at weeks 8, 24, and 52, respectively. Regarding fistula remission, the pooled proportions were 17.1% (95% CI 8.1-32.7%), I ² = 45%, 17.7% (95% CI 1.8-71.9%), I ² = 68%, and 16.7% (95% CI 3.0-56.5%, I ² = 51% at week 8, 24, and 52, respectively.

In this systematic review with meta-analysis, we found a signal of efficacy of ustekinumab on fistulizing pCD, emphasizing that these patients might benefit from this therapy.