Review

Authors: Brian Veauthier, Jaime R Hornecker

Crohn's disease is a chronic inflammatory condition that affects the gastrointestinal tract. It can cause lesions from mouth to anus and may result in extraintestinal complications. The prevalence of Crohn's disease is increasing in adults and children. Genetic predispositions to Crohn's disease have been identified, and specific environmental factors have been associated with its development. Common presenting symptoms include diarrhea, abdominal pain, rectal bleeding, fever, weight loss, and fatigue. Physical examination should identify unstable patients requiring immediate care, include an anorectal examination, and look for extraintestinal complications. Initial laboratory evaluation identifies inflammation and screens for alternative diagnoses. Measurement of fecal calprotectin has value to rule out disease in adults and children. Endoscopy and cross-sectional imaging are used to confirm the diagnosis and determine the extent of disease. Treatment decisions are guided by disease severity and risk of poor outcomes. Patients commonly receive corticosteroids to treat symptom flare-ups. Patients with higher-risk disease are given biologics, with or without immunomodulators, to induce and maintain remission. For children, enteral nutrition is an option for induction therapy. All patients with Crohn's disease should be counseled on smoking avoidance or cessation. Patients with Crohn's disease are at increased risk of cancer, osteoporosis, anemia, nutritional deficiencies, depression, infection, and thrombotic events. Maximizing prevention measures is essential in caring for these patients.

Topics: Adult; Child; Crohn Disease; Diagnosis, Differential; Female; Humans; Male; Risk Factors

PubMed: 30485038
DOI: No ID Found

Review

Authors: L Petagna, A Antonelli, C Ganini...

Chron's Disease is a chronic inflammatory intestinal disease, first described at the beginning of the last century. The disease is characterized by the alternation of periods of flares and remissions influenced by a complex pathogenesis in which inflammation plays a key role. Crohn's disease evolution is mediated by a complex alteration of the inflammatory response which is characterized by alterations of the innate immunity of the intestinal mucosa barrier together with a remodeling of the extracellular matrix through the expression of metalloproteins and increased adhesion molecules expression, such as MAcCAM-1. This reshaped microenvironment enhances leucocytes migration in the sites of inflammation, promoting a T1 response, through the production of cytokines such as IL-12 and TNF-α. IL-12 itself and IL-23 have been targeted for the medical treatment of CD. Giving the limited success of medical therapies, the treatment of the disease is invariably surgical. This review will highlight the role of inflammation in CD and describe the surgical approaches for the prevention of the almost inevitable recurrence.

Topics: Crohn Disease; Humans; Immunity, Innate; Inflammation; Recurrence

PubMed: 33160400
DOI: 10.1186/s13062-020-00280-5

Review

Authors: Daniel C Baumgart, William J Sandborn

Crohn's disease is a relapsing systemic inflammatory disease, mainly affecting the gastrointestinal tract with extraintestinal manifestations and associated immune disorders. Genome wide association studies identified susceptibility loci that--triggered by environmental factors--result in a disturbed innate (ie, disturbed intestinal barrier, Paneth cell dysfunction, endoplasmic reticulum stress, defective unfolded protein response and autophagy, impaired recognition of microbes by pattern recognition receptors, such as nucleotide binding domain and Toll like receptors on dendritic cells and macrophages) and adaptive (ie, imbalance of effector and regulatory T cells and cytokines, migration and retention of leukocytes) immune response towards a diminished diversity of commensal microbiota. We discuss the epidemiology, immunobiology, amd natural history of Crohn's disease; describe new treatment goals and risk stratification of patients; and provide an evidence based rational approach to diagnosis (ie, work-up algorithm, new imaging methods [ie, enhanced endoscopy, ultrasound, MRI and CT] and biomarkers), management, evolving therapeutic targets (ie, integrins, chemokine receptors, cell-based and stem-cell-based therapies), prevention, and surveillance.

Topics: Colonic Diseases; Crohn Disease; Drug Therapy, Combination; Genome-Wide Association Study; Humans; Intestinal Fistula; Metagenome; Postoperative Care

PubMed: 22914295
DOI: 10.1016/S0140-6736(12)60026-9

Authors: Ella Cockburn, Shahed Kamal, Andrea Chan...

Crohn's disease (CD) is a chronic, relapsing and remitting inflammatory bowel disease (IBD) that is increasing in incidence and prevalence globally. Management aims to achieve endoscopic healing, symptom resolution and improvement in quality of life. Therapeutic approaches in CD vary depending on disease phenotype. Thiopurines are important in steroid-sparing maintenance therapy, while anti-tumour necrosis factor agents play a fundamental role, especially in fistulising CD. Suboptimal response to these medications may require escalation to other immunosuppressive and biologic therapies, and surgical intervention is still required in a proportion of patients. Tailoring treatment to target specific patient phenotypes, disease severity and patient wishes is becoming more feasible with the growing array of therapeutic options in CD.

Topics: Humans; Crohn Disease; Quality of Life; Immunosuppressive Agents; Remission Induction

PubMed: 38065612
DOI: 10.7861/clinmed.2023-0493

Review

Authors: Esther Caparrós, Reiner Wiest, Michael Scharl...

Crohn's disease (CD) is a major form of inflammatory bowel disease characterized by transmural inflammation along the alimentary tract. Changes in the microbial composition and reduction in species diversity are recognized as pivotal hallmarks in disease dynamics, challenging the gut barrier function and shaping a pathological immune response in genetically influenced subjects. The purpose of this review is to delve into the modification of the gut microbiota cluster network during CD progression and to discuss how this shift compromises the gut barrier integrity, granting the translocation of microbes and their products. We then complete the scope of the review by retracing gut microbiota dysbiosis interactions with the main pathophysiologic factors of CD, starting from the host's genetic background to the immune inflammatory and fibrotic processes, providing a standpoint on the lifestyle/exogenous factors and the potential benefits of targeting a specific gut microbiota.

Topics: Bacterial Translocation; Crohn Disease; Dysbiosis; Fibrosis; Gastrointestinal Microbiome; Humans; Inflammation

PubMed: 34313550
DOI: 10.1080/19490976.2021.1949096

Authors: Fernando Gomollón, Axel Dignass, Vito Annese...

This paper is the first in a series of two publications relating to the European Crohn's and Colitis Organisation [ECCO] evidence-based consensus on the diagnosis and management of Crohn's disease and concerns the methodology of the consensus process, and the classification, diagnosis and medical management of active and quiescent Crohn's disease. Surgical management as well as special situations including management of perianal Crohn's disease of this ECCO Consensus are covered in a subsequent second paper [Gionchetti et al JCC 2016].

Topics: Crohn Disease; Endoscopy, Gastrointestinal; Evidence-Based Medicine; Humans; Intestines; Magnetic Resonance Imaging; Recurrence; Remission Induction; Tomography, X-Ray Computed

PubMed: 27660341
DOI: 10.1093/ecco-jcc/jjw168

Review

Authors: Sarah C Mills, Alexander C von Roon, Paris P Tekkis...

INTRODUCTION

Crohn's disease is a chronic condition of the gastrointestinal tract. It is characterised by transmural, granulomatous inflammation that occurs in a discontinuous pattern, with a tendency to form fistulae. The cause is unknown but may depend on interactions between genetic predisposition, environmental triggers, and mucosal immunity.

METHODS AND OUTCOMES

We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of medical treatments to induce remission in adults with Crohn's disease? What are the effects of surgical interventions to induce and maintain remission in adults with small-bowel Crohn's disease? What are the effects of surgical interventions to induce remission in adults with colonic Crohn's disease? What are the effects of medical interventions to maintain remission in adults with Crohn's disease; and to maintain remission following surgery? What are the effects of lifestyle interventions to maintain remission in adults with Crohn's disease? We searched: Medline, Embase, The Cochrane Library, and other important databases up to December 2009 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).

RESULTS

We found 93 systematic reviews, RCTs, or observational studies that met our inclusion criteria.

CONCLUSIONS

In this systematic review we present information relating to the effectiveness and safety of the following interventions: aminosalicylates, antibiotics, azathioprine/mercaptopurine, ciclosporin, corticosteroids (oral), enteral nutrition, fish oil, infliximab, methotrexate, probiotics, resection, segmental colectomy, smoking cessation, and strictureplasty.

Topics: Crohn Disease; Humans; Life Style; Remission Induction

PubMed: 21524318
DOI: No ID Found

Review

Authors: Nicole M Garcia, Nathaniel A Cohen, David T Rubin...

Crohn's disease (CD) is a chronic immune-mediated inflammatory condition which can negatively impact a patient's quality of life. The traditional management strategy for CD has focused on symptomatic control, however, this approach fails to prevent organ damage and to change the progressive course of this disease. Thus, the field has moved towards a treat-to-target strategy that includes identifying individualized objective targets, choosing a therapy based on individual factors that include disease severity and risk, closely monitoring disease activity at predefined time points, and optimizing therapies as needed. Due to the increasing number of therapies approved for CD, this review explores the various factors which should be considered in the sequencing of treatment options together with using the treat-to-target framework to control disease activity early in its course and provide holistic patient care.

Topics: Humans; Crohn Disease; Quality of Life

PubMed: 36507876
DOI: 10.1002/ueg2.12336

Meta-Analysis Review

Authors: Charlotte M Verburgt, Mohammed Ghiboub, Marc A Benninga...

The increase in incidences of pediatric Crohn's Disease (CD) worldwide has been strongly linked with dietary shifts towards a Westernized diet, ultimately leading to altered gut microbiota and disturbance in intestinal immunity and the metabolome. Multiple clinical studies in children with CD have demonstrated the high efficacy of nutritional therapy with exclusive enteral nutrition (EEN) to induce remission with an excellent safety profile. However, EEN is poorly tolerated, limiting its compliance and clinical application. This has spiked an interest in the development of alternative and better-tolerated nutritional therapy strategies. Several nutritional therapies have now been designed not only to treat the nutritional deficiencies seen in children with active CD but also to correct dysbiosis and reduce intestinal inflammation. In this review, we report the most recent insights regarding nutritional strategies in children with active CD: EEN, partial enteral nutrition (PEN), Crohn's disease exclusive diet (CDED), and CD treatment-with-eating diet (CD-TREAT). We describe their setup, efficacy, safety, and (dis)advantages as well as some of their potential mechanisms of action and perspectives. A better understanding of different nutritional therapeutic options and their mechanisms will yield better and safer management strategies for children with CD and may address the barriers and limitations of current strategies in children.

Topics: Child; Crohn Disease; Diet; Disease Management; Disease Susceptibility; Enteral Nutrition; Humans; Nutrition Therapy; Risk Factors; Treatment Outcome

PubMed: 33450982
DOI: 10.3390/nu13010212

Review

Authors: Ashish R Srinivasan

A treat-to-target (T2T) approach applies the principles of early intervention and tight disease control to optimise long-term outcomes in Crohn's disease. The Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE)-II guidelines specify short, intermediate, and long-term treatment goals, documenting specific treatment targets to be achieved at each of these timepoints. Scheduled appraisal of Crohn's disease activity against pre-defined treatment targets at these timepoints remains central to determining whether current therapy should be continued or modified. Consensus treatment targets in Crohn's disease comprise combination clinical and patient-reported outcome remission, in conjunction with biomarker normalisation and endoscopic healing. Although the STRIDE-II guidelines endorse the pursuit of endoscopic healing, clinicians must consider that this may not always be appropriate, acceptable, or achievable in all patients. This underscores the need to engage patients at the outset in an effort to personalise care and individualise treatment targets. The use of non-invasive biomarkers such as faecal calprotectin in conjunction with cross-sectional imaging techniques, particularly intestinal ultrasound, holds great promise; as do emerging treatment targets such as transmural healing. Two randomised clinical trials, namely, CALM and STARDUST, have evaluated the efficacy of a T2T approach in achieving endoscopic endpoints in patients with Crohn's disease. Findings from these studies reflect that patient subgroups and Crohn's disease characteristics likely to benefit most from a T2T approach, remain to be clarified. Moreover, outside of clinical trials, data pertaining to the real-world effectiveness of a T2T approach remains scare, highlighting the need for pragmatic real-world studies. Despite the obvious promise of a T2T approach, a lack of guidance to support its integration into real-world clinical practice has the potential to limit its uptake. This highlights the need to describe strategies, processes, and models of care capable of supporting the integration and execution of a T2T approach in real-world clinical practice. Hence, this review seeks to examine the current and emerging literature to provide clinicians with practical guidance on how to incorporate the principles of T2T into routine clinical practice for the management of Crohn's disease.

Topics: Humans; Crohn Disease; Remission Induction; Inflammatory Bowel Diseases; Ultrasonography

PubMed: 38293329
DOI: 10.3748/wjg.v30.i1.50