Colitis in a patient with familial Mediterranean fever: Is it Crohn's disease or ulcerative colitis?

A 24-year-old woman was referred to our hospital with joint pain, fever, abdominal pain, and diarrhea. A colonoscopy revealed longitudinal ulcers with a cobblestone appearance throughout the entire colon, suggestive of Crohn's disease. However, treatment with 5-aminosalicylic acid, azathioprine, and infliximab failed to achieve clinical remission. A colonoscopy 5 months later revealed a diffusely spreading granular mucosa without visible vasculature, compatible with active ulcerative colitis. Based on these serial changes in colonic lesions, we tested the patient for MEFV gene mutations and found variants E148Q and L110P in exon 2. Administration of colchicine resulted in complete clinical remission. Our experience suggests that drastic changes in the features of colonic inflammation may be a clue to the diagnosis of enterocolitis associated with familial Mediterranean fever.

Potential interventions and interactions of bioactive polyphenols and functional polysaccharides to alleviate inflammatory bowel disease - A review.

Inflammatory bowel disease is a multifaceted condition that is influenced by nutritional, microbial, environmental, genetic, psychological, and immunological factors. Polyphenols and polysaccharides have gained recognition for their therapeutic potential. This review emphasizes the biological effects of polyphenols and polysaccharides, and explores their antioxidant, anti-inflammatory, and microbiome-modulating properties in the management of inflammatory bowel disease (IBD). However, polyphenols encounter challenges, such as low stability and low bioavailability in the colon during IBD treatment. Hence, polysaccharide-based encapsulation is a promising solution to achieve targeted delivery, improved bioavailability, reduced toxicity, and enhanced stability. This review also discusses the significance of covalent and non-covalent interactions, and simple and complex encapsulation between polyphenols and polysaccharides. The administration of these compounds in appropriate quantities has proven beneficial in preventing the development of Crohn's disease and ulcerative colitis, ultimately leading to the management of IBD. The use of polyphenols and polysaccharides has been found to reduce histological scores and colon injury associated with IBD, increase the abundance of beneficial microbes, inhibit the development of colitis-associated cancer, promote the production of microbial end-products, such as short-chain fatty acids (SCFAs), and improve anti-inflammatory properties. Despite the combined effects of polyphenols and polysaccharides observed in both in vitro and in vivo studies, further human clinical trials are needed to comprehend their effectiveness on inflammatory bowel disease.

Causal Relationship Between Autism Spectrum Disorder and Inflammatory Bowel Disease: A Bidirectional Mendelian Randomization Study.

Patients with autism spectrum disorder (ASD) are often accompanied by inflammatory bowel disease (IBD) in observational research; however, the potential causal link between the two conditions remains unknown. In this study, we used a two-sample bidirectional Mendelian randomization (MR) approach to assess the causal relationship between ASD and IBD and its main subtypes, Crohn's disease (CD), and ulcerative colitis (UC). Independent genetic instruments from a genome-wide association study (GWAS) for IBD (25,042 cases and 34,915 controls) were used to investigate the association of IBD with ASD data obtained from the PGC and the iPSYCH consortia (N = 46,351). The primary analysis employed the random effects inverse variance weighting (IVW) method. Horizontal pleiotropy was detected using the MR Egger regression and the MR-pleiotropy residual sum and outlier (MR-PRESSO) analysis while heterogeneity was detected using Cochran's Q. The IVW method indicated a positive causal relationship of IBD with ASD (odds ratio (OR) = 1.028, 95% confidence interval (CI) = 1.001-1.056, p = 0.042). In subtype analyses, CD was positively related to ASD (OR = 1.036; 95% CI = 1.004-1.069; p = 0.02); however, UC showed no relationship (OR = 1.021; 95% CI = 0.999-1.044; p = 0.065). In contrast, no evidence of a causal relationship between ASD and IBD or its subtypes (p > 0.05) was found. Our findings provided evidence in support of potential causal associations between IBD/CD and ASD.

Granulomas without foreign body giant cells in perianal fistula tissue suggest Crohn's disease.

OBJECTIVES: Histopathological characteristics of granulomas in perianal fistula of patients with Crohn's disease (CD) remain unexplored. We aimed to assess the histopathological features of granulomas in perianal fistula in CD. METHODS: A retrospective analysis was conducted by reviewing the medical and pathological records of 4430 cases who underwent perianal fistulectomy at our hospital between June 2015 and June 2023. The patients were divided into the CD group, tuberculosis (TB), and non-CD group, respectively, based on their final diangosis. The detection rate of granulomas and differential histopathological features were investigated. RESULTS: Among the 4430 patients, granulomas were identified in 41 cases, including 25 had CD, 2 had pulmonary TB, and 14 only exhibiting perianal lesions with no other comorbidities. Additionally, there were altogether 93 CD cases, resulting in a detection rate of granuloma of 26.9%, which was considerably higher than that in the non-CD group (26.9% vs 0.3%, p < 0.001). The majority (85.7%) of the perianal fistula tissues in the non-CD group contained foreign body giant cells, while this was observed in only 1 (4.0%) out of the 25 cases with CD. We proposed that granulomas in the perianal fistula in the non-CD group were mostly foreign body granulomas. Moreover, granulomas in the non-CD group were larger than that of the CD group (1135 µm vs 519 µm, p < 0.001). CONCLUSION: Most CD cases have less granulomas (≤3) and no foreign body giant cells. Ribbon-like granulomas can be seen only in CD cases.

Machine learning as a tool predicting short-term postoperative complications in Crohn's disease patients undergoing intestinal resection: What frontiers?

The recent study, "Predicting short-term major postoperative complications in intestinal resection for Crohn's disease: A machine learning-based study" investigated the predictive efficacy of a machine learning model for major postoperative complications within 30 days of surgery in Crohn's disease (CD) patients. Employing a random forest analysis and Shapley Additive Explanations, the study prioritizes factors such as preoperative nutritional status, operative time, and CD activity index. Despite the retrospective design's limitations, the model's robustness, with area under the curve values surpassing 0.8, highlights its clinical potential. The findings align with literature supporting preoperative nutritional therapy in inflammatory bowel diseases, emphasizing the importance of comprehensive assessment and optimization. While a significant advancement, further research is crucial for refining preoperative strategies in CD patients.

Crohn's disease and ulcerative colitis share two molecular subtypes with different mechanisms and drug response.

BACKGROUND AND AIMS: Several therapies have been approved to treat crohn's disease (CD) and ulcerative colitis (UC), indicating that both diseases may share the same molecular subtypes. The aim of this study is to identify shared patient subtypes with common molecular drivers of disease. METHODS: Five public datasets with 406 CD and 421 UC samples were integrated to identify molecular subtypes. Then, the patient labels from six independent datasets and eight treatment datasets were predicted for validating subtypes and identifying the relationship with response status of corticosteroids, infliximab, vedolizumab, and ustekimumab. RESULTS: Two molecular subtypes were identified from the training datasets, in which CD and UC patients were relatively evenly represented in each subtype. We found six S1-specific gene modules related to innate/adaptive immune responses and tissue remodeling and nine S1-specific cell types (cycling T, Tregs, cd8+ lamina propria, follicular B, cycling B plasma, inflammatory monocytes, inflammatory fibroblast, and post-capillary venules). Subtype S2 was associated with three modules related to metabolism functions and four cell types (immature enterocytes, transit amplifying, immature goblet and WNT5B+). The subtypes can be replicated in six independent datasets based on a 20-gene classifier. Furthermore, response rates to four treatments in subtype S2 were significantly higher than those in subtype S1. CONCLUSIONS: This study discovered and validated a robust transcriptome-based molecular classification shared by CD and UC and built a 20-gene classifier. Because two subtypes have different molecular mechanisms and drug response, our classification may aid interpretation of heterogeneous molecular and clinical information in IBD patients.

Opportunistic infections changed before and after SARS-CoV-2 infection in inflammatory bowel disease patients: a retrospective single-center study in China.

Objective: SARS-CoV-2 transmission has become a serious worldwide public health concern. However, there is currently insufficient data to determine whether SARS-CoV-2 infection would affect opportunistic infections in inflammatory bowel disease (IBD) patients. Methods: A retrospective study included 451 IBD patients (294 UC and 157 CD). The IBD patients were divided into two groups: before SARS-CoV-2 infection and after SARS-CoV-2 infection, and outcomes were measured for these groups. The primary outcome was the presence and distribution of opportunistic infections. The secondary outcomes included factors associated with opportunistic infections, based on which a nomogram prediction model was developed and validated. Results: After SARS-CoV-2 infection, the proportion of IBD patients with opportunistic infections by Clostridium difficile (21.31% vs. 14.01%, p = 0.044) and Epstein-Barr virus (13.93% vs. 4.35%, p = 0.001) was significantly higher compared to that before. Conversely, the proportion of patients with hepatitis B virus (3.69% vs. 10.14%, p = 0.006) and herpes simplex virus type I (1.23% vs. 4.35%, p = 0.04) infections was significantly lower after the infection. Additionally, pre-SARS-CoV-2 infection factors associated with opportunistic infections in IBD include duration of illness, red blood cell count, the presence of comorbid chronic illnesses, and alcohol consumption, while post-SARS-CoV-2 infection, the primary risk factors involve corticosteroid use, red blood cell count, protein level, and high-sensitivity C-reactive protein. Conclusion: After the SARS-CoV-2 infection, there has been a shift in the occurrence of opportunistic infections among IBD patients. It might be attributed to the use of corticosteroids and also the strengthening of containment measures, heightened public health awareness, and widespread vaccination.

The Potential Benefits of Exercise in Managing Inflammatory Bowel Disease: A Systematic Review.

Adults with inflammatory bowel disease (IBD) experience a significant decline in quality of life due to various symptoms. Exercise has emerged as a potential therapeutic approach to improve IBD management, but its effectiveness requires further investigation. This systematic review, adhering to PRISMA 2020 guidelines, explored the effects of exercise on IBD progression and its potential as a treatment in adults. A comprehensive search strategy was conducted across three databases and two registries from May 12, 2024, to May 22, 2024. Methodological rigor and potential bias were minimized through quality assessment using the Cochrane risk-of-bias tool 2 (RoB 2) for randomized controlled trials (RCTs), the Newcastle-Ottawa Scale (NOS) for cohort studies, and the Joanna Briggs Institute (JBI) critical appraisal checklist for studies evaluating the effectiveness of non-randomized interventions. This process yielded 12 high-quality studies for analysis. The review identified positive evidence from both RCTs and observational studies. Exercise interventions demonstrated improvements in cardiorespiratory fitness, disease activity, quality of life, and mental health in adults with IBD. Studies explored various modalities, including aerobic exercise, resistance training, and mind-body interventions. However, further research is needed to optimize exercise prescription and elucidate the underlying mechanisms of action. This review strengthens the evidence for exercise as a beneficial intervention for IBD patients. Personalized exercise programs based on individual needs hold promise for improved IBD management and patient outcomes. However, limitations exist due to study design variations and the need for long-term follow-up studies.

Treatment trajectories and outcomes in inflammatory bowel disease: a tertiary single-centre experience.

Background: There is an increasing diversification in the treatment landscape for inflammatory bowel diseases (IBD) leading to therapeutic challenges that can only incompletely be covered by prospective randomized double-blind trials. Real-world observations are therefore an important tool to provide insights into therapeutic strategies. Objectives: To describe the real-world treatment algorithms in an IBD referral centre. Design: Single-centre retrospective cohort study. Methods: We retrospectively analysed prospectively collected data on treatment sequences and outcomes from 502 patients with Crohn's disease (CD) and ulcerative colitis (UC) treated with infliximab, adalimumab, vedolizumab or ustekinumab at a large German tertiary referral centre. Results: Treatment decisions correlated to baseline patient characteristics. Over time, infliximab continued to be the preferred first-line option in CD and UC, although ustekinumab and vedolizumab, respectively, became increasingly important choices. Remission rates decreased with the advancement of therapy lines. Conclusion: We provide insights into the evolution of tertiary centre real-world treatment sequences that might - together with other observations - help to guide the selection of therapies in IBD. Our data also strongly underscore the unmet need for biomarkers supporting treatment decisions. Trial registration: None.

Consensus Statements on Assessments and Vaccinations Prior to Commencement of Advanced Therapies for the Treatment of Inflammatory Bowel Diseases.

BACKGROUND: Given the introduction of new advanced therapies for inflammatory bowel diseases (IBDs), expanded risk mitigation strategies are essential. AIMS: To create a comprehensive set of statements on assessment procedures and vaccinations before starting monoclonal antibodies, Janus kinase (JAK) inhibitors or sphingosine-1-phosphate (S1P) modulators for IBD. METHODS: We examined literature, guidelines and drug product information regarding vaccination and assessment recommendations for initiating advanced IBD therapies. Using a modified Delphi approach, delegates voted anonymously on the acceptability of these statements prior to and following consensus discussion. RESULTS: We developed eight statements on the domains of infectious diseases screening, vaccinations and assessments prior to commencing JAK inhibitors and S1P modulators. Six statements received agreement. Pre-advanced therapy screening for infectious diseases was established, and the vaccination protocol was revised. Malignancy, cardiovascular and thromboembolic risk assessments are necessary before initiating JAK inhibitors. Those starting S1P modulators need cardiac and ophthalmic assessments. CONCLUSIONS: These consensus statements combine vaccination and assessments on the currently available advanced therapies for IBD as a single comprehensive document that may reduce IBD complications associated with use of advanced therapies. Knowledge gaps identified during the consensus process will provide further research opportunities.

Pancreatic Heterotopia Presenting as a Mimic of Fistulizing Crohn's Disease: Expanding the Differential Diagnosis of Inflammatory Bowel Disease.

Pancreatic heterotopia (PH) involves pancreatic tissue located outside its typical anatomical position, lacking vascular or ductal communication with the pancreas. Despite frequently having acini with the capacity to produce digestive enzymes, PH is usually asymptomatic. When symptoms do occur, they typically present in middle to late adulthood and include abdominal pain, nausea, and diarrhea. This clinical presentation is similar to that of Crohn's disease, an autoimmune inflammatory bowel disease (IBD). The presentation of symptomatic PH varies depending on the location of the ectopic pancreatic tissue and its microanatomical constituents, including exocrine and endocrine tissue as well as a duct system. We present a case of a patient who came to medical attention with abdominal pain and was found on colonoscopy to have a non-obstructing stricture of the transverse colon without an associated mass. Biopsies of the area revealed chronic active colitis, leading to a diagnosis of Crohn's disease. Her gastroenterological symptoms remained stable for several years while receiving infliximab infusions until she presented to the emergency department with severe abdominal pain, diarrhea, and sepsis, meeting the criteria for systemic inflammatory response syndrome. Imaging studies revealed a fistula between the previous colonic stricture and the jejunum, again attributed to Crohn's disease. She underwent surgery to remove the fistula between the small and large bowels. Unexpectedly, the resection specimen showed a mass insinuated between the loops of the large intestine, which histological review revealed to be ectopic pancreatic tissue. Following the resection of the ectopic pancreatic tissue, her symptoms resolved without the need for further treatment. In retrospect, the ectopic pancreatic tissue, which contained acini with digestive enzymes, ducts, and islets, may have also caused seemingly unrelated pathology in the patient. Symptomatic PH should be recognized as a pathology that can mimic IBD, prompting reconsideration of the diagnosis in cases of refractory disease while on biologics.

Isolated Gastric Crohn's Disease: A Growing Tendency.

Isolated gastric Crohn's disease (IGCD) is a rare manifestation of Crohn's disease confined to the stomach, unlike its more common forms that primarily affect the ileum and colon. We report the case of a 25-year-old female presenting with a one-month history of epigastric discomfort and nausea, with no other significant gastrointestinal or systemic symptoms. Upper endoscopy revealed an aphthous ulceration on the greater curvature of the stomach, with biopsies showing non-caseating granulomas consistent with Crohn's disease. The diagnosis of IGCD was confirmed through a positive ASCA test and negative p-ANCA test, alongside the absence of ileal and colonic involvement. The patient was treated with prednisone for acute symptom management, followed by infliximab for long-term maintenance. Follow-up evaluations showed no significant relapse episodes. This case highlights the diagnostic challenges and management strategies for IGCD, emphasising the need for further research to optimise treatment protocols and improve long-term outcomes. LEARNING POINTS: This case highlights the challenges and complexities of diagnosing and managing isolated gastric Crohn's disease (IGCD), a rare manifestation of Crohn's disease confined to the stomach.Serological tests such as the anti-Saccharomyces cerevisiae antibody (ASCA) test and the perinuclear anti-neutrophil cytoplasmic antibodies (p-ANCA) test help in distinguishing Crohn's disease from other conditions.This case emphasises the importance of considering IGCD in patients with unexplained gastric symptoms, and the need for individualised treatment plans due to the lack of specific guidelines for IGCD.

The Intestinal Microbiome but not Clinical Aspects of Inflammatory Bowel Disease is Impacted by Lactose Malabsorption Compared to Lactose Digestion in Children.

BACKGROUND: Dietary exclusion of lactose from patients with inflammatory bowel disease persist with speculation that deleterious effects are mediated through intestinal microbes. OBJECTIVE: To compare inflammatory bowel disease characteristics and changes in the intestinal microbiome at diagnosis in children with and without lactose malabsorption. METHODS: A cross-sectional cohort of children (8-17 years of age) diagnosed with Crohn's disease (n=149 [63%]) or ulcerative colitis (n=86) that had undergone lactose breath hydrogen testing was evaluated. The intestinal microbiome of mucosal luminal aspirates was profiled at the time of diagnosis using 16S rRNA gene amplicon sequencing of the V6 hypervariable region. RESULTS: Of the 235 children, 61 (26%) had lactose malabsorption. Microbial characterization yielded differences in bacterial differential abundance between children that could and could not absorb lactose that varied by intestinal site and between sub-types of inflammatory bowel disease. There were no differences in the ages (13.2±3.0 years [mean±SD] versus 12.7±3.4 years; p=0.25), sex (p=0.88), extent of disease involvement or severity of disease at presentation (p=0.74) when comparing those that could or could not absorb lactose nor was there a difference in the need for initiation of biological agents (p=0.43) during two years of follow-up. CONCLUSIONS: Lactose malabsorption does not affect the clinical presentation or outcomes of children with inflammatory bowel disease. However, this study establishes that a single non-absorbed fermentable food product can alter the intestinal microbiome in both a regional and disease specific manner. As we continue to learn more about the pathophysiology of inflammatory bowel disease and the role of the intestinal microbiome in disease onset and progression, it would be of benefit to examine the impact of other potential fermentable nutrients and their products on inflammatory bowel disease outcomes.

Healthcare Access for Patients With Inflammatory Bowel Disease in the United States: A Survey by the Crohn's & Colitis Foundation.

BACKGROUND: A prior survey disseminated in 2017 identified that healthcare access barriers exist and significantly affect patients with inflammatory bowel disease (IBD). We sought to identify, through an updated survey, the healthcare access barriers that patients continue to face, with a focus on socioeconomic factors and patient awareness of resources to navigate existing barriers. METHODS: A 52-question online survey evaluating (1) access to healthcare professionals, medications, and procedures; (2) associated financial challenges; and (3) patient awareness of education and advocacy tools to navigate IBD care barriers, was disseminated through multiple channels to IBD patients and their caregivers. RESULTS: Of the 2281 completed responses, patients on advanced specialty medications, younger than 65 years of age, or on employer insurance experienced significantly greater issues with insurance barriers to accessing medications and coverage of medically necessary tests/treatments. Patients who live in areas of concentrated poverty were more likely to experience poor health outcomes when subjected to step therapy compared to patients who did not. Additionally, patients were more likely to experience one or more financial barriers or trade-offs if the patient used an advanced specialty medicine or lived in an area with concentrated poverty. CONCLUSIONS: While there have been significant and numerous advancements in IBD treatments, patients with IBD continue to experience barriers to healthcare access and treatment and financial struggles. Ongoing awareness and advocacy efforts focused on healthcare system reform and related policies to further minimize care disparities and barriers remain vital.

Patients with inflammatory bowel disease in the United States experience financial struggles and barriers to healthcare access and treatment. Ongoing awareness and advocacy efforts focused on healthcare system reform and related policies to minimize care disparities and barriers remain vital.

Assessment of outcomes in Crohn's disease: A systematic review of randomized clinical trials to inform a multiple outcome framework.

Longstanding disease control in Crohn's disease (CD) is challenging and requires understanding treatment efficacy and outcomes assessment. With multiple novel therapeutic options, rigorous evaluation of outcomes in randomized controlled trials (RCTs) is crucial to inform clinical practice. This study systematically reviewed RCTs focusing on CD outcomes to elucidate the breadth and depth of reported outcomes and measurement instruments. A systematic search was conducted on MEDLINE and Scopus for RCTs published from 1 January 2000 to 31 January 2023. Eligible studies included full-text articles with at least 50 adult CD patients. Primary and secondary outcomes, along with their measurement instruments, were categorized according to the Outcome Measures in Rheumatology Filter 2.1 framework. From 88 included studies, 393 outcomes were analyzed. Clinical outcomes, such as clinical remission and response, were the most prevalent (50.6%); biomarkers (11.5%) and patient-reported outcomes (10.2%) were also assessed. Other outcomes included disease behavior and complications (2%), endoscopy (10.4%), histology (0.5%), radiology (1.3%), healthcare utilization (3.8%), and therapy-related safety (6.9%). Composite outcomes showed an increasing trend, reflecting a shift toward comprehensive evaluations. Coprimary endpoints, including clinical symptoms and mucosal inflammation, were reported in 21 of 88 studies. This review highlights the evolving landscape of outcome assessment in CD RCTs, emphasizing the increasing complexity of outcomes. The prominence of composite outcomes underscores efforts to capture the multidimensional nature of CD. These findings will inform the second stage of a two-round e-Delphi aimed at prioritizing key domains and outcomes for developing a multiple-component outcome for RCTs in CD research.

Defining mucosal healing in randomized controlled trials of inflammatory bowel disease: A systematic review and future perspective.

BACKGROUND: Mucosal healing (MH) is an established treatment goal in inflammatory bowel disease (IBD). However, various definitions of MH exist. We aimed to identify how MH is defined in randomized controlled trials (RCTs) in ulcerative colitis (UC) and Crohn's disease (CD). METHODS: We searched MEDLINE, EMBASE, and the Cochrane library from inception to December 2023 for phase 2 and 3 RCTs of advanced therapies in IBD. RESULTS: One hundred forty-four studies were included, 72 in UC and 72 in CD, published between 1997 and 2023. In UC, 64% (46/72) RCTs reported MH as an endpoint. 12 definitions of MH were found, from endoscopic assessment alone (35/46; 76%) to the more recent combination of histology and endoscopy (10/46; 22%). 96% (44/46) of studies used the Mayo Endoscopic Subscore. In CD, reporting of MH lagged behind UC, with only 12% (9/72) of trials specifically defining MH as an endpoint, 7 as "absence of ulceration," 2 as Simplified Endoscopic Score for CD score ≤2 or 0. Histological assessment was performed in 3 RCTs of CD. Centralized reading of endoscopy was used in 48% (35/72) of RCTs of UC and 22% (16/72) of CD. Only 1 RCT included transmural healing as an endpoint. CONCLUSIONS: A standard definition of MH in IBD is lacking. Definitions have evolved particularly in UC, which now includes the addition of histological evaluation. Transmural healing holds promise as a future target in CD. We support a greater standardization of definitions as we expect endpoints to become increasingly stringent and multimodal with computers automating the assessment.

Oxidative stress-related biomarkers as promising indicators of inflammatory bowel disease activity: A systematic review and meta-analysis.

Oxidative stress is believed to play an important role in the pathogenesis of inflammatory bowel disease (IBD), specifically Crohn's disease (CD) and ulcerative colitis (UC). This meta-analysis aimed to identify and quantify the oxidative stress-related biomarkers in IBD and their associations with disease activity. We systematically searched Ovid MEDLINE, Ovid Embase, and Web of Science databases, identifying 54 studies for inclusion. Comparisons included: (i) active IBD versus healthy controls; (ii) inactive IBD versus healthy controls; (iii) active CD versus inactive CD; and (iv) active UC versus inactive UC. Our analysis revealed a significant accumulation of biomarkers of oxidative damage to biomacromolecules, coupled with reductions in various antioxidants, in both patients with active and inactive IBD compared to healthy controls. Additionally, we identified biomarkers that differentiate between active and inactive CD, including malondialdehyde, Paraoxonase 1, catalase, albumin, transferrin, and total antioxidant capacity. Similarly, levels of Paraoxonase 1, erythrocyte glutathione peroxidase, catalase, albumin, transferrin, and free thiols differed between active and inactive UC. Vitamins and carotenoids also emerged as potential disease activity biomarkers for CD and UC, but their intake should be monitored to obtain meaningful results. These findings emphasize the involvement of oxidative stress in the pathogenesis of IBD and highlight the potential of oxidative stress-related biomarkers as a minimally invasive and additional tool for monitoring the activity of IBD.

A complex case of PASH syndrome: pyoderma gangrenosum, acne, suppurative hidradenitis, and Crohn's disease in a 36-year-old smoker.

Introduction and importance: PASH syndrome, is autoinflammatory condition driven by immune system dysfunction, resulting in elevated interleukin 1 levels and subsequent production of proinflammatory cytokines and chemokines. The clinical progression of PASH typically starts with acne conglobate in adolescence, followed by hidradenitis suppurativa, and pyoderma gangrenosum. Diagnosis relies on recognizing these hallmark features, but treatment remains a challenge despite current understanding. Conventional immunosuppressive therapies have shown limited efficacy in managing PASH syndrome. Case presentation: The authors present a 36-year-old man with a complex combination of pyoderma gangrenosum, acne, suppurative hidradenitis, obesity, and Crohn's disease. The patient's symptoms began in adolescence with acne and recurrent furuncles, evolving into painful skin ulcers and fistulas over time. Histological examination confirmed the diagnosis of pyoderma gangrenosum. Despite various treatment modalities, including isotretinoin, cyclosporine, azathioprine, and adalimumab, the patient experienced only partial improvement until receiving Infliximab, which led to remarkable improvement. Discussion: PASH syndrome, a rare neutrophilic dermatosis linked to autoinflammatory conditions like Braun Flaco, is characterized by Pyoderma gangrenosum, acne, and suppurative hidradenitis. This clinical entity presents diagnostic challenges due to its unique features and association with obesity and bowel diseases, such as Crohn's disease. Treatment options, including TNF-α blockers like Infliximab, have shown promising results in controlling cutaneous manifestations. Our case study underscores the complexity of treating PASH syndrome and highlights the importance of personalized therapeutic approaches for optimal outcomes. Conclusion: PASH syndrome presents significant diagnostic and treatment challenges due to its complex symptomatology and associations with conditions like Crohn's disease. The case of a 36-year-old man demonstrates the partial efficacy of conventional therapies and highlights the promising results of infliximab. This underscores the need for personalized treatment strategies and ongoing research to improve outcomes for patients with this rare and intricate syndrome.

Darvadstrocel for complex perianal fistulas in Crohn's disease: A systematic review and meta-analysis.

BACKGROUND: Local injection of darvadstrocel, a suspension of expanded adipose-derived allogenic mesenchymal stem cells, has been used for treatment-refractory perianal fistulas in Crohn's disease (CD). OBJECTIVE: This study aimed to investigate efficacy and safety of darvadstrocel for complex perianal fistulas in CD. METHODS: A systematic search was conducted through April 2024 in relevant databases for observational studies evaluating darvadstrocel. A random-effects meta-analysis model was used to calculate the pooled effect sizes (proportions or incidence rates [IRs]) with 95% confidence intervals (CIs) of effectiveness and safety outcomes. The risk of bias was evaluated using the Joanna Briggs Institute Critical Appraisal Tool. The I2 value assessed heterogeneity. Sensitivity and subgroup analyses were also conducted. RESULTS: Twelve studies were included with 595 patients. The pooled rate of patients achieving clinical remission, defined as fistula healing, was 68.1% at month 6 (95% CI 63.4-72.7) and 77.2% (95% CI 70.1-83.8) at month 12. Combined remission, defined as clinical remission and absence of collections >2 cm confirmed by magnetic resonance imaging, was reported in 60.6% and in 69.7% of patients at months 6 and 12, respectively. The rate of patients with treatment failure, defined as no clinical remission at the last follow-up (mean 18.7 months; SD 9.9), was 34.5%. Failure rate was independent of follow-up time (p = 0.85). For effectiveness outcomes, between-study heterogeneity was negligible. Subgroup analysis indicated that none of the covariates modified the treatment effect. Pooled IRs per 100 patient-years of adverse events (AE), serious AEs, perianal abscesses, and reoperations were 19.6, 3.2, 16.9 and 7.1, respectively. CONCLUSION: Evidence from observational studies supports the efficacy and safety of darvadstrocel for complex perianal fistulas in CD. Studies have reported high fistula healing rates that can be sustained long-term in most patients, with negligible between-study heterogeneity, as well as a favorable safety profile.

Epithelial neutrophil localization and tight junction Claudin-2 expression are innovative outcome predictors in inflammatory bowel disease.

BACKGROUND: Patients with inflammatory bowel disease (IBD) in clinical and endoscopic remission may still experience disease relapse. Therefore, there is a need to identify outcome predictors. Recently, the role of neutrophils in predicting outcomes in ulcerative colitis (UC) has been highlighted. Furthermore, the impairment of intestinal barrier plays a key role in forecasting disease outcomes in IBD. OBJECTIVE: This observational study aimed to assess the predictive role of neutrophils according to tissue localization and intestinal barrier protein expression in IBD. METHODS: IBD patients in clinical remission who underwent colonoscopy between January 2020 and June 2022 at two tertiary referral centres were enrolled. Patients with Mayo Endoscopic Score ≤1 (UC) and Simple Endoscopic Score ≤6 (Crohn's disease) were included. Histological activity was assessed using validated scores. Experienced pathologists evaluated neutrophil localization in the epithelium and lamina propria and immunohistochemical expression of Claudin-2 and junctional adhesion molecule A (JAM-A). RESULTS: Of 60 UC and 76 CD patients, 59.7% had histological activity. 25.8% of patients developed an adverse outcome within 12 months. Neutrophils in the epithelium predicted adverse outcomes for UC (hazard ratio [HR] 5.198, p = 0.01) and CD (HR 4.377, p = 0.03) patients in endoscopic remission. Claudin-2 expression correlated with endoscopic and histological activity and predicted outcomes in UC. Similar results were found for JAM-A in CD despite this protein showing less specificity as a barrier predictor of outcome. CONCLUSION: This study highlights the potential role of epithelial neutrophil localization and Claudin-2 'leaky gut' expression as tools for predicting IBD outcomes and guiding further patient-tailored therapy.