Overt Crohn's Disease Research Articles

Prevalence and Progression of Incidental Terminal Ileitis on Non-diagnostic Colonoscopy: A Systematic Review and Meta-analysis.

Incidentally diagnosed terminal ileitis [IDTI] has been reported among asymptomatic persons undergoing non-diagnostic colonoscopy. The purpose of our study was to determine the prevalence and long-term outcomes of asymptomatic terminal ileitis. We performed a systematic review using three biomedical databases [Medline, Embase, and Web of Science] and relevant scientific meeting abstracts. We identified observational studies that reported the prevalence of IDTI in adults undergoing screening or polyp surveillance colonoscopy and/or the long-term outcomes of such lesions. A random-effects meta-analysis was conducted to determine the pooled prevalence rate of IDTI. The progression of IDTI to overt Crohn's disease [CD] was also described. Of 2388 eligible studies, 1784 were screened after excluding duplicates, 84 were reviewed in full text, and 14 studies were eligible for inclusion. Seven studies reported the prevalence of IDTI in 44 398 persons undergoing non-diagnostic colonoscopy, six studies reported follow-up data, and one study reported both types of data. The pooled prevalence rate of IDTI was 1.6% (95% confidence interval [CI] 0.1-21.8%) with significant heterogeneity [I2 = 99.7]. Among patients who had undergone non-diagnostic colonoscopy and had follow-up data [range 13-84 months reported in five studies], progression to overt CD was rare. IDTI is not uncommon on non-diagnostic colonoscopies. Based on limited data, the rate of its progression to overt CD seems low, and watchful waiting is likely a reasonable strategy. Further long-term follow-up studies are needed to inform the natural history of incidental terminal ileitis, factors that predict progression to CD, and therapeutic implications.

Interleukin-17 Inhibition in Spondyloarthritis Is Associated With Subclinical Gut Microbiome Perturbations and a Distinctive Interleukin-25-Driven Intestinal Inflammation.

To characterize the ecological effects of biologic therapies on the gut bacterial and fungal microbiome in psoriatic arthritis (PsA)/spondyloarthritis (SpA) patients. Fecal samples from PsA/SpA patients pre- and posttreatment with tumor necrosis factor inhibitors (TNFi; n = 15) or an anti-interleukin-17A monoclonal antibody inhibitor (IL-17i; n = 14) underwent sequencing (16S ribosomal RNA, internal transcribed spacer and shotgun metagenomics) and computational microbiome analysis. Fecal levels of fatty acid metabolites and cytokines/proteins implicated in PsA/SpA pathogenesis or intestinal inflammation were correlated with sequence data. Additionally, ileal biopsies obtained from SpA patients who developed clinically overt Crohn's disease (CD) after treatment with IL-17i (n = 5) were analyzed for expression of IL-23/Th17-related cytokines, IL-25/IL-17E-producing cells, and type 2 innate lymphoid cells (ILC2s). There were significant shifts in abundance of specific taxa after treatment with IL-17i compared to TNFi, particularly Clostridiales (P = 0.016) and Candida albicans (P = 0.041). These subclinical alterations correlated with changes in bacterial community co-occurrence, metabolic pathways, IL-23/Th17-related cytokines, and various fatty acids. Ileal biopsies showed that clinically overt CD was associated with expansion of IL-25/IL-17E-producing tuft cells and ILC2s (P < 0.05), compared to pre-IL-17i treatment levels. In a subgroup of SpA patients, the initiation of IL-17A blockade correlated with features of subclinical gut inflammation and intestinal dysbiosis of certain bacterial and fungal taxa, most notably C albicans. Further, IL-17i-related CD was associated with overexpression of IL-25/IL-17E-producing tuft cells and ILC2s. These results may help to explain the potential link between inhibition of a specific IL-17 pathway and the (sub)clinical gut inflammation observed in SpA.

Macrophage phenotype in the subclinical gut inflammation of patients with ankylosing spondylitis

Long-term evolution of subclinical gut inflammation to overt Crohn's disease (CD) has been described in AS patients. The aim of this study was to evaluate macrophage polarization occurring in the inflamed gut of patients with AS. Twenty-seven HLA-B27(+) AS patients, 20 CD patients and 17 normal controls were consecutively enrolled. Classic M1 (iNOS(+)IL-10(-)), resolution phase (iNOS(+)IL-10(+)), M2 and CD14(+) macrophages were characterized by immunohistochemistry and flow cytometry. Quantitative gene expression analysis of IFN-γ, IL-4, IL-5, IL-33 and STAT6 was performed by real time PCR. Classic M1 macrophages were expanded in CD and AS, where resolution phase macrophages predominate. A large increase in CD163(+) (M2) macrophages was observed in AS strictly correlated with the expression of IL-33, a Th2 cytokine involved in M2 polarization. Unlike in CD, CD14(+) macrophages were virtually absent in the gut of AS patients and controls. The absence of CD14(+) macrophages together with the expansion of resolution phase and M2 macrophages is the immunological signature of subclinical ileal inflammation in AS.

The transition of acute to chronic bowel inflammation in spondyloarthritis

That gut and joint inflammation are linked in spondyloarthritis (SpA) has been recognized for almost three decades. Intriguingly, microscopic gut inflammation, which occurs frequently in patients with SpA, is an important risk factor for clinically overt Crohn's disease and ankylosing spondylitis. This Review describes current insights into the underlying mechanisms that lead to chronic gut inflammation in patients with SpA. We propose that the development of chronic bowel inflammation in these individuals occurs through a transition phase, in which inflammation evolves from an acute into a chronic state. Our transition model implies that different cell types are involved at different stages during disease progression, with stromal cells having an important role in chronicity. In addition, deficient regulatory feedback mechanisms or genetically determined alterations in antigen presentation, endoplasmic reticulum stress, autophagy or cytokine signaling might also favor a transition from self-limiting acute inflammation to chronic inflammation. We anticipate that this transition phase might be an important window for therapeutic intervention.

Linking Crohn's Disease and Ankylosing Spondylitis: It's All about Genes!

Linking Crohn's Disease and Ankylosing Spondylitis: It's All about Genes!

Looking in the mouth for Crohnʼs disease

It is widely acknowledged among gastroenterologists that the oral cavity may be involved in Crohn's disease (CD). However, the specific manifestations are poorly appreciated. Although oral aphthous ulceration is probably not diagnostically useful in patients with suspected CD, disease-specific manifestations do occur and are particularly common in children presenting with CD. These manifestations can be subtle, often are subclinical, yet commonly harbor diagnostically useful material (granulomas). Orofacial granulomatosis (OFG) is conventionally used to describe patients with overt oral disease without obvious involvement of the gastrointestinal tract. However, many patients with OFG have subclinical intestinal CD or will progress to develop overt intestinal CD with time. The management of severe oral disease is challenging and lacks a clear evidence base.

The changing face of spondyloarthropathies under TNF α blockade.

ObjectivesTumor necrosis factor alpha (TNF-α ) therapy has been implicated in the development of autoimmune diseases. Our aim was to describe three patients with spondyloarthropathies who responded to infliximab, a chimeric monoclonal antibody specific for TNF-α but developed new symptoms of spondyloarthropathies. In parallel, a review of the literature on psoriasis induced by TNF-α blockers was undertaken.ResultsThe first patient had been suffering from ankylosing spondylitis (AS) for more than 12 years. Infliximab induced a remission of AS, but he developed overt Crohn's disease two years after starting treatment. The second patient had AS for more than 20 years. Infliximab had an excellent effect on his AS, but he developed palmo-plantar psoriasis a few months after initiating therapy with the drug. The third patient, whose long-term and severe psoriasis had responded to infliximab developed peripheral arthritis. A review of the literature revealed 63 cases of psoriasis induced by TNF-α blockers (33 on Infliximab, 16 on Etanercept and 14 on Adalimumab). The underlying diseases were variable, including all the spectrum of conditions for which TNF-α blockers are indicated. Patients developed psoriasis after a mean duration of treatment of 11 months. Interstingly, a substantial proportion of patients continued treatment with TNF α blockers, the psoriasis improving in a majorityof cases under topical treatment only.ConclusionWhile Infliximab may change the course of spondyloarthropathy, depressing the original symptoms it may uncover other occult aspects of these diseases.

Gut inflammation and spondyloarthropathies.

Spondyloarthropathies (SpA) are a group of related disorders with common clinical and genetic characteristics. The prototype disease in this group is ankylosing spondylitis; other entities include reactive arthritis, psoriatic arthritis, and arthritis in patients with inflammatory bowel disease. Over recent years, there has been a special interest in the relation between spondylitis/synovitis and gut inflammation in patients with SpA. Two thirds of patients with undifferentiated SpA show histologic signs of gut inflammation, and a fraction of these patients go on to develop clinically overt Crohn's disease. In this review, the authors will focus on 1) the growing evidence that has been provided that gut inflammation in SpA is immunologically related to Crohn's disease, based on the molecular characterization of the inflammation (lymphocyte homing markers and ligands, T cell cytokines, macrophage markers, and serology); and 2) on the therapeutic implications resulting from this concept. The recent introduction and positioning of anti-tumor necrosis factor-alpha therapy in patients with ankylosing spondylitis and other types of SpA is, in large part, based on this concept.

Treatment of active spondyloarthropathy with infliximab, the chimeric monoclonal antibody to tumour necrosis factor α

The spondyloarthropathies (SpA) are a group of chronic autoimmune disorders of the joint.1 Entities belonging to this group are ankylosing spondylitis (AS), psoriatic arthritis (PsA), reactive arthritis, arthritis related to...

Colorectal Cancer in Regional Ileitis

Six patients, with overt Crohn's disease of the small bowel developed colorectal cancer. Three distinct clinical patterns were observed. Three patients had advanced rectal adenocarcinoma and a relatively long duration of Crohn's disease, two patients had an early adenocarcinoma and a short antecedent history, and a sixth patient had advanced cloacogenic cancer of the anorectum. The prognosis for a patient with carcinoma in association with regional enteritis was poor when there was advanced disease at the time of diagnosis. The late diagnosis of the cancer may have been the result of three erroneous assumptions. First, scepticism as to the association of Crohn's disease and cancer despite the evidence to the contrary; second, misinterpretation of the intestinal symptoms of the carcinoma as those of the underlying inflammatory bowel disease; and third, confusing the clinical picture of colorectal cancer with that of benign perianal disease with stricture formation. Increased awareness of the association of cancer and Crohn's disease, particularly the development of cancer in apparently normal bowel, and careful evaluation of all new symptoms should improve the prognosis of this potentially lethal complication of inflammatory bowel disease.