Clinical features and epidemiology of spondyloarthritides associated with inflammatory bowel disease

Inflammation of axial and/or peripheral joints is one of the most frequent extra-intestinal manifestations complicating the clinical course and therapeutic approach in inflammatory bowel diseases(IBD).The frequency of these complications seems to be similar for both diseases, Crohn's disease and ulcerative colitis.Arthritis associated with IBD belongs to the category of spondyloarthropathies.Axial involvement ranges from isolated inflammatory back pain to ankylosing spondylitis, whereas peripheral arthritis is noted in pauciarticular and in polyarticular disease.Asymptomatic radiological involvement of the sacroiliac joints is reported to occur in up to 50% of patients.Other musculoskeletal manifestations such as buttock pain, dactylitis, calcaneal enthesitis, and thoracic pain are frequently underdiagnosed and, consequently, are not treated appropriately.Several diagnostic approaches and criteria have been proposed over the past 40 years in an attempt to correctly classify and diagnose such manifestations.The correct recognition of spondylarthropathies needs an integrated multidisciplinary approach in order to identify common therapeutic strategies, especially in the era of the new biologic therapies.

Clinical significance of NOD2/CARD15 and Toll-like receptor 4 gene single nucleotide polymorphisms in inflammatory bowel disease

AIM： To evaluate the role of genetic factors in the pathogenesis of Crohn＇s disease （CD） and ulcerative colitis （UC）, we investigated the single nucleotide polymorphisms （SNPs） of NOD2/CARD15 （R702W, Gg08R and L1007finsC）, and Toll-like receptor 4 （TLR4） genes （D299G and T399I） in a selected inflammatory bowel disease （IBD） population coming from Southern Italy. METHODS： Allele and genotype frequencies of NOD2/ CARD15 （R702W, Gg08R and L1007finsC） and TLR4 （D299G and T399I） SNPs were examined in 133 CD patients, in 45 UC patients, and in 103 healthy controls. A genotype-phenotype correlation was performed. RESULTS： NOD2/CARD15 R702W mutation was significantly more frequent in CD （9.8%） than in controls （2.4%, P = 0.001） and in UC （2.3%, P = 0.03）. No significant difference was found between UC patients and control group （P 〉 0.05）. In CD and UC patients, no significant association with G908R variant was found. L1007finsC SNP showed an association with CD （9.8%） compared with controls （2.9%, P = 0.002） and UC patients （2.3%, P = 0.01）. Moreover, in CD patients, G908R and L1007finsC mutations were significantly associated with different phenotypes compared to CD wild-type patients. No association of IBD with the TLR4 SNPs was found in either cohort （allele frequencies： D299G-controls 3.9%, CD 3.7%, UC 3.4%, P 〉 0.05; T399I-controls 2.9%, CD 3.0%, UC 3.4%, P 〉 0.05）. CONCLUSION： These findings confirm that, in our IBD patients selected from Southern Italy, the NOD2/ CARD15, but not TLR4 SNPs, are associated with increased risk of CD.

Mucosal healing in inflammatory bowel disease： Maintain orde-escalate therapy

In the past decade, thanks to the introduction of biologic therapies, a new therapeutic goal, mucosal healing(MH), has been introduced. MH is the expression of an arrest of disease progression, resulting in minor hospitalizations, surgeries, and prolonged clinical remission. MH may be achieved with several therapeutic strategies reaching success rates up to 80% for both, ulcerative colitis(UC) and Crohn's disease(CD). Various scoring systems for UC and for the transmural CD, have been proposed to standardize the definition of MH. Several attempts have been undertaken to de-escalate therapy once MH is achieved, thus, reducing the risk of adverse events. In this review, we analysed the available studies regarding the achievement of MH and the subsequent treatment de-escalation according to disease type and administered therapy, together with non-invasive markers proposed as predictors for relapse. The available data are not encouraging since de-escalation after the achievement of MH is followed by a high number of clinical relapses reaching up to 50% within one year. Unclear is also another question, in case of combination therapies, which drug is more appropriate to stop, in order to guarantee a durable remission. Predictors of unfavourable outcome such as disease extension, perianal disease, or early onset disease appear to be inadequate to foresee behaviour of disease. Further studies are warranted to investigate the role of histologic healing for the further course of disease.

Inflammatory bowel disease-associated spondyloarthropathies

This issue presents a symposium held in Messina talking about inflammatory bowel disease(IBD) and associated spondyloarthropathies.The topic covers epidemiology and clinical manifestations of IBD-related arthropathies, common genetic and immunologic features, combined therapies for gut and joint inflammation, and future biologic therapies etc.I believe this series of articles will deeply facilitate understanding of and the approach to IBD and associated arthropathies.