Insights into renal and urological complications of inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a chronic condition characterized by immune-mediated inflammation in the gastrointestinal tract, which follows a relapsing and remitting course. Apart from affecting the gastrointestinal tract, IBD also has extra-intestinal manifestations (EIMs). While the etiology of extraintestinal manifestation remains unclear, it is theorized to be based on immunological responses influenced by genetic factors. Renal involvement is one of the EIMs observed in ulcerative colitis and Crohn's disease. The renal manifestations in IBD patients encompass a range of conditions including nephrolithiasis, amyloidosis, tubulointerstitial nephritis, glomerulonephritis (GN), obstructive pathologies, and chronic kidney disease (CKD). The incidence of CKD in IBD patients varies from 5%-15%. The decline in renal function can stem from various factors such as direct inflammatory damage to the kidneys leading to glomerular or tubular injury, or from complications like recurrent stones, amyloidosis, or GN. Additionally, nephrotoxic medications used in treating IBD, such as TNF-α inhibitors, calcineurin inhibitors, and aminosalicylates, can exacerbate the decline in renal function. Currently, there is a lack of consensus regarding these patients' screening and renal function monitoring. This review aims to assess the existing literature on the different renal complications among individuals with IBD, shedding light on their pathophysiology and management.

Genital rash: A manifestation of metastatic Crohn's disease.

Metastatic Crohn's disease is the rarest cutaneous manifestation of Crohn's disease, it presents as cutaneous lesions in areas that are anatomically non-contiguous with the gastrointestinal tract. It requires a high index of suspicion for diagnosis which is confirmed on histopathology. Infliximab can be an effective treatment.

Clinical presentation of celiac disease in adult patients: current real-life experience.

BACKGROUND AND AIMS: The clinical presentation of celiac disease (CD) has changed over time with more patients presenting with non-classical symptoms, extra-intestinal manifestations (EIM) or no symptoms. We aimed to investigate the main symptoms/signs leading to the diagnosis of CD in adult patients. As secondary end-point, we evaluated the outcome of gastrointestinal (GI) symptoms following gluten-free diet (GFD). METHODS: All consecutive CD adult patients referring to our University Hospital from September 2022 to February 2024 were included. Clinical data were retrospectively evaluated. RESULTS: 134 patients, 104 females/30 males, median age at diagnosis 35 years, were included. 79 patients reported GI symptoms (i.e., diarrhea, abdominal bloating, dyspepsia) as the main symptom leading to CD diagnosis. In 40 patients, the leading symptom/sign was an EIM (i.e., iron deficiency anemia, infertility/miscarriages, dermatitis, osteoporosis, elevated transaminase levels). Fifteen patients were asymptomatic, being diagnosed because of a positive family history or concomitant autoimmune hypothyroidism. Of the 79 patients reporting GI symptoms, 20 did not experience complete resolution with the GFD. Among the 17 patients who reported a strict adherence to GFD (vs 1 patient with low-adherence, 2 non-compliant), lactose intolerance and irritable bowel syndrome overlap were diagnosed in 2 and 15 patients, respectively. CONCLUSION: GI manifestations remain the main symptoms at presentation of CD, however clinicians should be aware of the EIM of CD and the association with other autoimmune disorders. In non-responsive CD patients, an overlap with functional disorders might be considered.

Inflammatory Bowel Disease-Associated Arthritis Is Associated with Concomitant Autoimmune and Inflammatory Disorders.

BACKGROUND: Extraintestinal Manifestations (EIMs) are a common and potentially debilitating complication of Inflammatory Bowel Diseases (IBD), sometimes requiring additional treatment beyond those used to control intestinal disease. IBD-associated arthritis (IAA), a form of spondyloarthritis, is associated with several factors including disease location, sex, and IBD type. However, much remains unknown about other clinical factors predicting development of EIMs. Our goal was to identify additional factors associated with IAA. METHODS: Participants in the LOCATION-IBD cohort were included in this analysis. We performed univariate and multivariate analysis of demographics, clinical data, and patient-reported outcomes data. RESULTS: The LOCATION-IBD cohort included 182 participants with (n = 53) and without (n = 110) joint EIMs and with joint pain of unclear etiology (n = 19). In a multivariate analysis comparing those with and without joint EIMs, female sex (OR = 2.5, p = 0.014), the presence of concomitant autoimmune and inflammatory disorders (OR = 2.5, p = 0.038), and Crohn's disease (OR = 2.9, p = 0.026) were associated with the presence of joint EIMs. CONCLUSION: This analysis reveals patients with IAA are more likely to have concomitant autoimmune disorders. Further studies are needed to confirm this association, understand the mechanisms underlying the common pathogenesis of these concurrent disorders, and evaluate their impact on the treatment of IAA.

Cutaneous Eruption in a Crohn's Disease Patient Under Tumor Necrosis Alpha Inhibitor Treatment: A Rare Case of Syphilis.

Reaching a diagnosis of a cutaneous eruption in a Crohn's disease (CD) patient treated with anti-tumor necrosis factor alpha (anti-TNFα) can be challenging. Differential diagnosis must include extra-intestinal manifestations of CD, adverse reactions to the therapy itself as well as infectious diseases with cutaneous manifestations. We report the case of a 28-year-old man on infliximab for Crohn's colitis, who presented with painless, non-pruritic genital and body exanthema. After a thorough evaluation, early secondary syphilis was confirmed with a fluorescent treponemal antibodies-absorbed test. Intramuscular (IM) benzathine penicillin G 2.4 million units in a single dose was administered and clinical manifestations resolved completely within a couple of weeks.

Granulomatous hepatitis with Crohn's disease: a case report.

A 45-year-old man who was regularly followed up for Crohn's disease (CD) and maintained clinical remission with vedolizumab (VDZ). At 37 years old, he was diagnosed CD from longitudinal ulcers in the distal ileum by balloon-assisted enteroscopy (BAE). During the follow-up, liver enzyme elevation, splenomegaly and thrombocytopenia were in progress. Esophagogastric varices suggested chronic liver disease and portal hypertension. Magnetic resonance elastography (MRE) showed liver stiffness of 3.4 kPa and proton density fat fraction (PDFF) of 1.86%. He was diagnosed with granulomatous hepatitis based on a liver biopsy. The hepatic venous pressure gradient (HVPG) was mildly elevated at 7 mmHg, consistent with the pre-sinusoidal portal hypertension due to granulomatous hepatitis. We report a rare case with granulomatous hepatitis diagnosed from liver injury and portal hypertension, despite the stable intestinal symptoms of CD.

Peripheral Joint and Enthesis Involvement in Patients With Newly Diagnosed Inflammatory Bowel Disease: Symptoms, and Clinical and Ultrasound Findings - A Population-Based Cohort Study.

OBJECTIVES: 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. DESIGN: 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. RESULTS: 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. CONCLUSION: 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.

Skin gluten-related disorders: new and old cutaneous manifestations to be considered.

The term gluten-related disorders (GRD) refer to a spectrum of different clinical manifestations triggered by the ingestion of gluten in genetically susceptible individuals, including coeliac disease (CD), wheat allergy and non-celiac gluten sensitivity (NCGS). GRD are characterized by a large variety of clinical presentations with both intestinal and extra-intestinal manifestations. The latter may affect almost every organ of the body, including the skin. Besides the well-known association between CD and dermatitis herpetiformis, considered as the cutaneous specific manifestation of CD, many other muco-cutaneous disorders have been associated to GRD. In this review, we analyzed the main features of dermatological diseases with a proven association with GRD and those that improve after a gluten-free diet, focusing on the newly described cutaneous manifestations associated with NCGS. Our main hypothesis is that a "cutaneous-gluten sensitivity," as specific cutaneous manifestation of NCGS, may exist and could represent a diagnostic marker of NCGS.

Acute idiopathic pancreatitis is associated with more aggressive disease course in Crohn's disease but not in ulcerative colitis.

PURPOSE: Patients with inflammatory bowel disease (IBD), whether Crohn's disease (CD) or ulcerative colitis (UC), have an increased risk of acute pancreatitis. The prognostic value of diagnosing acute idiopathic pancreatitis in patients with IBD is not well understood. METHODS: A retrospective review of 56 patients with IBD and acute pancreatitis was conducted in a tertiary center from 2011 to 2020. Aggressive disease course was defined as (i)biologic change, (ii)biologic dose escalation, or (iii)IBD-related surgeries occurring within 1 year of acute pancreatitis diagnosis. Logistic regression modelling identified associations between covariates and an aggressive disease course. RESULTS: Baseline characteristics between idiopathic pancreatitis and other causes of acute pancreatitis, in both CD and UC cohorts, were similar. Idiopathic pancreatitis was significantly associated with an aggressive disease course in CD (P = 0.04). No confounding factors were associated with an aggressive disease course in CD. Idiopathic pancreatitis, however, was not associated with an aggressive disease course in UC (P = 0.35). CONCLUSION: The diagnosis of acute idiopathic pancreatitis may provide a prognostic indicator of a more severe disease course in CD. No such association appears to exist with UC. To the best of our knowledge, this is the first study that identifies an association and possible prognostic value between idiopathic pancreatitis and a more severe disease course in CD. More studies with a larger sample size are needed to validate these findings, further define idiopathic pancreatitis as an extraintestinal manifestation of IBD and elucidate a clinical strategy to optimize care in patients with aggressive CD and idiopathic pancreatitis.

Prevalence of and Factors Associated with Respiratory Symptoms Among Patients with Inflammatory Bowel Disease: A Prospective Study.

BACKGROUND: No large, prospective study has investigated respiratory symptoms in patients with inflammatory bowel diseases. We aimed to describe the prevalence of and factors associated with respiratory symptoms in patients with inflammatory bowel disease. METHODS: In an observational, prospective, cross-sectional study, we evaluated the frequency of respiratory symptoms using a validated self-reporting questionnaire from February 2019 to February 2021 during routine follow-up outpatient visits of patients with inflammatory bowel disease followed in the Gastroenterology Department of the Nancy University Hospital. In case of a positive questionnaire, patients were systematically offered a consultation with a pulmonologist in order to investigate a potential underlying respiratory disease. RESULTS: There were 325 patients included, and 180 patients had a positive questionnaire (144 with Crohn's disease). Of the included patients, 165 (50.8%) presented with respiratory symptoms, with dyspnea being the most frequent symptom (102 patients). There were 102 patients (56.7%) who benefited from a consultation in the pulmonology department: 43 (42.2%) were diagnosed with a respiratory disease, mainly asthma (n = 13) or chronic obstructive pulmonary disease (n = 10). Fourteen patients (13.7%) had obstructive sleep apnea. A body mass index increase, being a smoker or ex-smoker, and having articular extra-intestinal manifestations were independently associated with a higher prevalence of respiratory symptoms. CONCLUSIONS: Half of patients with inflammatory bowel disease reported respiratory symptoms in our study. Patients with inflammatory bowel disease should be systematically screened, as pulmonary disease is frequently present in this population, with specific attention being given to smokers or ex-smokers and patients with extra-articular intestinal manifestations.

We conducted a large-scale, prospective study, finding a high prevalence of respiratory symptoms in patients with inflammatory bowel disease, which led to a variety of respiratory diseases, including asthma and obstructive pulmonary disease. Patients should therefore be systematically screened for pulmonary manifestations.

Identifying the Presence, Activity, and Status of Extraintestinal Manifestations of Inflammatory Bowel Disease Using Natural Language Processing of Clinical Notes.

BACKGROUND: Extraintestinal manifestations (EIMs) occur commonly in inflammatory bowel disease (IBD), but population-level understanding of EIM behavior is difficult. We present a natural language processing (NLP) system designed to identify both the presence and status of EIMs using clinical notes from patients with IBD. METHODS: In a single-center retrospective study, clinical outpatient electronic documents were collected in patients with IBD. An NLP EIM detection pipeline was designed to determine general and specific symptomatic EIM activity status descriptions using Python 3.6. Accuracy, sensitivity, and specificity, and agreement using Cohen's kappa coefficient were used to compare NLP-inferred EIM status to human documentation labels. RESULTS: The 1240 individuals identified as having at least 1 EIM consisted of 54.4% arthritis, 17.2% ocular, and 17.0% psoriasiform EIMs. Agreement between reviewers on EIM status was very good across all EIMs (κ = 0.74; 95% confidence interval [CI], 0.70-0.78). The automated NLP pipeline determining general EIM activity status had an accuracy, sensitivity, specificity, and agreement of 94.1%, 0.92, 0.95, and κ = 0.76 (95% CI, 0.74-0.79), respectively. Comparatively, prediction of EIM status using administrative codes had a poor sensitivity, specificity, and agreement with human reviewers of 0.32, 0.83, and κ = 0.26 (95% CI, 0.20-0.32), respectively. CONCLUSIONS: NLP methods can both detect and infer the activity status of EIMs using the medical document an information source. Though source document variation and ambiguity present challenges, NLP offers exciting possibilities for population-based research and decision support in IBD.

Extraintestinal manifestations of inflammatory bowel disease impact on patient experience, but are poorly captured by electronic health records. Natural language processing systems are capable of not only detecting extraintestinal manifestations, but also inferring activity information by automated analysis of clinical notes.

Analysis of immunologic comorbidities in ulcerative colitis patients: a tool to prevent exacerbations in ulcerative colitis cases.

There have been previous studies, especially in Western countries and even in some areas in Asia, about extra-intestinal manifestations (EIMs) and its link with the outcome of inflammatory bowel disease (IBD), which includes Crohn's disease (CD), and ulcerative colitis (UC). This link is crucial when discussing a patient's prognosis and important when dealing with UC management. The aim of this study was to clarify the most common comorbidities associated with UC, emphasizing immunologic comorbidities in Japan. This study was a retrospective analysis performed at Nagoya University Hospital. The data collection started in March, 2019, and continued for two years. We retrieved the medical records of 105 patients with UC diagnosis, from which the data of 176 EIMs were extracted and analyzed. Results showed that EIMs with UC in the active phase accounted for 43.7% of total EIMs. Twenty-six patients with immune-mediated inflammatory disease frequently had an active phase (odds ratio [OR] 3.84, 99% CI, 1.44-10.27). Comorbidities showing an active manifestation of symptoms and UC in the active phase were significantly correlated in patients with immunological comorbidities, such as peripheral arthritis (r = 0.97, p < 0.01) and rheumatoid arthritis (RA) (r = 0.99, p < 0.01), as well as in patients with primary sclerosis cholangitis (PSC) (r = 0.98, p < 0.01). In conclusion, this analysis suggests the importance of having full comprehension of how immunological comorbidities affect the natural development of UC, which is of vital importance to prevent further UC complications and properly adjust the management of the disease.

Extraintestinal Manifestations of Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is primarily a disease of the digestive tract system, though it may affect other organ systems outside of the intestines. Extraintestinal manifestations (EIMs) can occur in up to one third of patients with Crohn's disease or ulcerative colitis. The most common EIMs involve dermatologic and musculoskeletal manifestations. EIMs may either parallel intestinal inflammation or be completely independent of disease activity. Physicians should be aware of EIMs and think systematically when evaluating patients with IBD, as nearly every organ can be involved, and a multidisciplinary treatment approach should be undertaken to improve outcomes and quality of life.

An unusual presentation of celiac disease in adult patient.

Pyoderma gangrenosum is among the exceptional extra-intestinal manifestations of celiac disease. We report a case of a 52-year-old patient who presented with pyoderma gangrenosum that turned out to be the initial presentation of celiac disease.

[Aseptic nasal septal abscess in patients with ulcerative colitis: two case reports. Case report].

Ulcerative colitis (UC) may be associated with different extra-intestinal manifestations (EIM), which are often difficult to diagnose and treat, and may complicate the course of the disease. EIM are a multidisciplinary problem encountered by doctors of various specializations. However, many incidences of EIM in patients with UC remain unknown. The coexistence of UC and aseptic nasal abscess (ANA) is uncommon. Here, we describe two cases of ANA in young female patients with UC. ANA run in parallel with intestinal disease activity and led to necrosis of the septal cartilage. Moreover, pyoderma gangrenosum was described in one of them. Aseptic abscess syndrome should be kept in mind when a microbial factor is not identified, the diagnosis is not clear or a patient is not improving on appropriate antibacterial therapy. ANA can present as a rare complication of UC.

The impact of biologic therapies on extra-intestinal manifestations in inflammatory bowel disease: A multicenter study.

Introduction: Patients with inflammatory bowel disease (IBD) have a high risk of developing extra-intestinal manifestations (EIMs). We aimed to assess the cumulative incidence and clinical course of EIMs in patients treated with Vedolizumab (VDZ) and non-gut selective biologic drugs. Materials and methods: In this multicenter observational study, we enrolled 1,182 patients with IBD under biologic treatment in tertiary care centers, collecting the rate of new-onset EIMs and the clinical course of new and pre-existing EIMs since the introduction of the ongoing biologic drug (259 VDZ vs. 923 non-gut selective agents, median time 3 vs. 4 years). Results: Among 1,182 patients with IBD (median age of 46 years; 55% men) on biologics, the overall cumulative incidence of new onset EIMs was 4.1% (49/1,182), in particular 6.6% (17/259) on VDZ vs. 3.5% (32/923) on non-gut selective biologics (p = 0.02). Among 224 patients reporting new or pre-existing EIMs, those on VDZ showed a higher rate of clinical worsening compared with non-gut selective therapies (15.5 vs. 7.3%, p = 0.08). However, both showed a similar rate of modification of the therapeutic regimen. Female gender [hazard ratio (HR) 2.18], a longer course of ongoing biologic therapy (HR 1.18), ulcerative colitis (UC) (HR 1.83), and VDZ therapy (HR 1.85) were significant risk factors for developing new EIMs. Discussion: Our study suggests that the type of biologic treatment might affect the risk of developing EIMs, with a slightly higher risk in patients on gut-selective therapies. However, a similar clinical course is observed in the two groups.

Acute Myopericarditis in the Setting of Crohn's Colitis: Challenging Management Decisions.

Myopericarditis is a rare extraintestinal manifestation of Crohn's disease (CD). Myopericarditis has also been attributed to treatment with mesalamine and heart failure to tumor necrosis factor inhibitor (TNFi) use. When a patient with CD, controlled on these medications, presents with myopericarditis and/or heart failure, it can confound both the differential diagnosis and management of such patients. Our case is acute myopericarditis in a 34-year-old male, with a history of CD controlled with mesalamine and infliximab, who had been off TNFi therapy for over six months due to loss of insurance coverage and had been intermittently using leftover mesalamine. He presented to the ED complaining of a one-day history of abdominal pain with bloody diarrheal stools, chest discomfort, and fever. A colonoscopy performed two days back had demonstrated active colonic CD. Findings included ECG evidence of pericarditis, elevated cardiac biomarkers, and reduced left ventricular function on ventriculography consistent with myopericarditis. We present the differential, diagnostic and management challenges encountered in this situation, review the pertinent literature, and discuss decision making in what appears to be myopericarditis attributed to an extraintestinal manifestation of active GI Crohn's.

Presence of spondyloarthritis associated to higher disease activity and HLA-B27 positivity in patients with early Crohn's disease: Clinical and MRI results from a prospective inception cohort.

OBJECTIVE: To determine the SpA prevalence and identify its associated factors in Crohn's disease (CD) patients receiving a systematically rheumatological and imaging assessment, including magnetic resonance imaging (MRI) of the sacroiliac joints and spine. METHODS: CD patients either naive to biologics or without them for three months prior enrollment were recruited in a subgroup of the German Spondyloarthritis Inception Cohort (GESPIC-Crohn). A structured assessment of SpA manifestations was performed by a rheumatologist, including MRI of sacroiliac joints and spine. Demographic and clinical parameters including disease activity in CD (Harvey Bradshaw Index-HBI) and SpA (C-reactive protein - CRP, Bath Ankylosing Spondylitis Disease Activity Index, and Ankylosing Spondylitis Disease Activity Score) were collected. Univariable and multivariable logistic regression analyses were performed to identify factors associated with the presence of SpA. RESULTS: A total of 103 patients with CD were included in the cohort. The mean CD disease duration was 1.3±2.4years and 95.1% were naïve to biologics. The most frequent musculoskeletal manifestation was back pain (65.0%), followed by chronic back pain (50.5%), and arthralgia (43.7%). Prevalence of SpA was 19.4% with slightly higher proportion of axial SpA than peripheral SpA, and higher proportion of radiographic axial SpA (7.4%) than non-radiographic axial SpA (2.8%). Changes in MRI compatible with axial SpA were found in 15 (14.7%) patients, of which 9 (81.1%) patients had the clinical diagnosis of axial SpA. HLA-B27 positivity (OR 9.02, CI 95% 2.29-35.55) and higher disease activity of CD as reflected by the HBI (OR 1.14, 95%CI 1.01-1.30) were significant and independently associated with the presence of SpA. CONCLUSION: SpA was present in nearly one out of five patients with CD and it was associated with the expression of HLA-B27 and a higher clinical activity of CD. Our findings raise awareness to rheumatologists and gastroenterologists on the high concomitance between both diseases and may help to reduce the delay in SpA diagnosis.