Inflammatory bowel disease-associated spo ndyloa rth ropath ies

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.     

Association of inflammatory bowel disease with ankylosing spondylitis and rheumatoid arthritis: A nationwide population-based study

Objectives: Tantalizing connections between autoimmune rheumatic diseases (ARDs) and inflammatory bowel disease (IBD) have become evident with regard to their genetic and immunologic background. However, the association between these two disease entities remains unclear. The aim of this study is to investigate the association between each ARD and IBD.

Methods: A nationwide population-based cross-sectional study was performed using the Korean National Health Insurance Claims database. The data of patients with IBD and age- and sex-matched controls between 2009 and 2013 were collected from the database. The prevalence of ARDs, including systemic lupus erythematosus (SLE), inflammatory myositis (polymyositis and dermatomyositis), systemic sclerosis (SSc), Sjögren’s syndrome (SjS), ankylosing spondylitis (AS), and rheumatoid arthritis (RA), was determined. The associations between each ARD and IBD were analyzed using multivariate logistic regression models.

Results: A total of 40,843 IBD patients (28,197 patients with ulcerative colitis and 12,646 with Crohn’s disease) and 122,529 controls were enrolled. The nonstratified analysis revealed that patients with IBD had significant risk of being concomitantly affected by AS (odds ratio [OR] 5.140, 95% confidence interval [95% CI] 4.069–6.492) and RA (OR: 3.474, 95% CI: 2.671–4.519) after adjusting for age and sex. No significant association was observed between IBD and other ARDs including SLE, inflammatory myositis, SSc, and SjS.

Conclusion: IBD is significantly associated with AS and RA in the large-scaled population-based study. This result suggests that etiopathogenesis of IBD might be shared with AS and RA.     

Prevalence of spondyloarthritis in Turkish patients with inflammatory bowel disease

Rheumatic manifestations are the most common extraintestinal findings of inflammatory bowel disease (IBD), although there are wide variations among different studies. The only previous Turkish study reported a rather high prevalence of spondyloarthritis (SpA) in patients with IBD. We aimed to determine the frequency of SpA and ankylosing spondylitis (AS) in patients with IBD attending a gastroenterology clinic from a referral centre. The study was conducted in 122 patients with established diagnosis of IBD [28 with Crohn’s disease (CD) and 94 with ulcerative colitis (UC)]. A detailed medical history was obtained and a complete physical examination was performed in all the patients. Standard pelvic X-rays for examination of the sacroiliac joints were performed only when clinically indicated. The X-rays were read blindly by an experienced rheumatologist and reported according to the established grading system. The modified New York criteria were used to classify AS, and the European Spondyloarthropathy Study Group criteria for SpA. The prevalence of AS and SpA in patients with IBD was 8.2 and 28.7%, respectively. SpA was found to be significantly more common in the patients with CD compared to patients with UC, but the frequency of AS was not different between these two groups. There was no correlation between localisation or extent of the intestinal inflammation and presence of AS and SpA. A higher frequency of women was observed in patients diagnosed as SpA. Almost half of the patients with SpA (45.7%) had not been diagnosed before the study, although they had a history of IBP and/or peripheral arthritis. This study suggests that the prevalences of SpA and AS in Turkish patients with IBD are similar to those in many other populations. There may be a significant female predominance of SpA among patients with IBD.     

Characterization and outcome of uveitis in 350 patients with spondyloarthropathies

This retrospective study analyzed 350 patients with the diagnosis of spondyloarthropathies (SPA) (207 with ankylosing spondylitis (AS), 80 with undifferentiated spondyloarthropathies (USPA) and 63 with psoriatic arthritis (PsA)) attended at a tertiary referral hospital for a minimum period of 5 years. All the patients presented complete clinical (axial and peripheral involvement, heel enthesopathies, extra-articular manifestations) and radiologic (sacroiliac, lumbar, dorsal and cervical spine) evaluation. HLA-B27 and respective alleles were searched. These data were compared with the occurrence of uveitis during the follow-up of the SPA patients. Thirty AS patients (14.5%) presented 55 episodes of acute anterior uveitis; there was statistical association between uveitis and juvenile-onset AS (P = 0.0094) and achillean (P = 0.0003) and plantar (P = 0.0067) enthesopathies; one AS patient presented a single episode of posterior uveitis, associated to tuberculosis. Seven USPA patients (8.8%) presented 13 episodes of acute anterior uveitis; it was not observed statistical association with any variable; one patient presented a single episode of posterior uveitis, associated to toxoplasmosis. Five HLA-B27 positive PsA patients (8%) presented 13 episodes of acute anterior uveitis. All the 26 positive HLA-B27 SPA patients with anterior uveitis tested for the HLA-B27 alleles were HLA-B*2705. No patient presented ophthalmologic severe sequelae of the anterior uveitis. Concluding, anterior uveitis was associated to the juvenile onset of the disease and to the enthesophatic involvement of the lower limbs in AS patients. The HLA-B*2705 allele was predominant in the anterior uveitis patients, whilst posterior uveitis was rare and associated to infectious disease.     

Inflammatory bowel disease and airway diseases

Airway diseases are the most commonly described lung manifestations of inflammatory bowel disease(IBD). However,the similarities in disease pathogenesis and the sharing of important environmental risk factors and genetic susceptibility suggest that there is a complex interplay between IBD and airway diseases. Recent evidence of IBD occurrence among patients with airway diseases and the higher than estimated prevalence of subclinical airway injuries among IBD patients support the hypothesis of a two-way association. Future research efforts should be directed toward further exploration of this association,as airway diseases are highly prevalent conditions with a substantial public health impact.     

Frequency of axial spondyloarthritis in Tunisian patients with inflammatory bowel diseases

Aim of the work

To determine the frequency, clinical and radiological features of axial spondyloarthritis in patients with inflammatory bowel diseases (IBD) and to characterize differences between patients with and without axial spondyloarthritis.

Prevalence of self-reported spondyloarthritis features in a cohort of patients with inflammatory bowel disease

BACKGROUND:

Musculoskeletal symptoms belonging to the spectrum of ‘seronegative spondyloarthritis’ (SpA) are the most common extraintestinal manifestations in patients with inflammatory bowel disease (IBD) and may lead to important disease burden. Patients with suspected SpA should be referred to a rheumatologist for further evaluation.

OBJECTIVE:

To investigate the self-reported prevalence of musculoskeletal SpA features in a cohort of patients with IBD and to compare this with actual referrals to a rheumatologist.

METHODS:

Consecutive patients with IBD visiting the outpatient clinic were interviewed by a trained research nurse about possible SpA features using a standardized questionnaire regarding the presence or history of inflammatory back pain, peripheral arthritis, enthesitis, dactylitis, psoriasis, uveitis and response to nonsteroidal anti-inflammatory drugs. All patient files were verified for previous visits to a rheumatologist and any rheumatic diagnosis.

RESULTS:

At least one musculoskeletal SpA feature was reported by 129 of 350 (36.9%) patients. No significant differences between patients with Crohn disease and ulcerative colitis were found. Review of medical records showed that 66 (51.2%) patients had ever visited a rheumatologist. Axial SpA was diagnosed in 18 (27.3%) patients, peripheral SpA in 20 (30.3%) patients and another rheumatic disorder in 14 (21.2%) patients.

CONCLUSION:

Musculoskeletal SpA features are frequently present in patients with IBD. However, a substantial group of patients is not evaluated by a rheumatologist. Gastroenterologists play a key role in early referral of this often debilitating disease.     

Seronegative spondyloarthropathies in Greece: a population-based study of prevalence, clinical pattern, and management. The ESORDIG study

The objective of this study was to determine the prevalence, clinical pattern, and management of seronegative spondyloarthropathies (SpA) in the general adult population of Greece. This population-based study was conducted on a target adult (19-year-old) population of 14,233 subjects by rheumatologists who visited households in nine dispersed areas. An interview (standardized questionnaire) was conducted, clinical evaluation and laboratory investigation were done, and established diagnostic classification criteria were used. The age-adjusted and sex-adjusted prevalence (prevalence_asa) of SpA was 0.49% [95% confidence interval (CI): 0.38–0.60], with a male to female ratio of 5.5:1; the prevalence increased with age until the 59- to 68-year-old age group and declined thereafter. The prevalence_asa of ankylosing spondylitis (AS) and psoriatic arthritis (PsA) was 0.24% (95% CI: 0.16–0.32) and 0.17% (95% CI: 0.10–0.24), respectively. The mean age (years) at onset was younger in AS (25.83±6.5) than in PsA (45.24±12.94) (p<0.01). Familial clustering was noticed in 5.3% of AS probands. Sacroiliitis was observed in 39.8% and asymmetrical oligoarthritis in 40.6% of PsA patients. Fifty-nine percent of SpA patients had previously visited rheumatologists (91.3% diagnosed correctly vs 11.6% of those who visited other specialists, p<0.0005); 56.5% of the former had taken disease-modifying antirheumatic drugs compared to none of the latter. The SpA in Greeks are as common as in other European Caucasians, with a high male preponderance. The PsA onset occurs at an older age than AS and frequently presents with a spondylitic pattern. The correct diagnosis was arrived at and appropriate treatment was given when patients consulted rheumatologists.     

Combined therapeutic approach： Inflammatory bowel diseases and peripheral or axial arthritis

Inflammatory bowel diseases （IBDs）, particularly Crohn＇s disease （CD） and ulcerative colitis （UC）, are associated with a variety of extra-intestinal manifestations （EIMs）. About 36% of IBD patients have at least one EIM, which most frequently affect the joints, skin, eyes and the biliary tract. The EIMs associated with IBD have a negative impact on patients with UC and CD, and the resolution of most of them parallels that of the active IBD in terms of timing and required therapy; however, the clinical course of EIMs such as axial arthritis, pyoderma gangrenosum, uveitis, and primary sclerosing cholangitis is independent of IBD activity. The peripheral and axial arthritis associated with IBD have traditionally been treated with simple analgesics, non-steroidal anti-inflammatory drugs, steroids, sulfasalazine, methotrexate, local steroid injections and physiotherapy, but the introduction of biological response modifiers such as tumor necrosis factor-α blockers, has led to further improvements.     

The role of the gut and microbes in the pathogenesis of spondyloarthritis

The intestinal microbiota is firmly implicated not only in the pathogenesis of inflammatory bowel disease (IBD) but increasingly also in the development of inflammation at extraintestinal tissue sites. Significant clinical, genetic, immunological, and microbiological overlap exists between IBD and spondyloarthritis (SpA), which indicates that pathophysiological mechanisms are shared between these diseases and may center on the intestinal microbiota. Recently, culture-independent techniques have enabled the microbiota in health and disease to be described in increasing detail. Moreover, functional studies have identified myriad host effector and regulatory pathways that shape or are shaped by this microbial community. We consider the complex relationship between SpA pathogenesis and gut microbes, with a discussion of how manipulation of the gut microbiota itself may be a promising future target for SpA therapy.     

P选择素与炎症性肠病

炎症性肠病(IBD)包括溃疡性结肠炎(UC)和克罗恩病(CD),目前认为血小板功能异常在其发病机制及发展过程中起着重要作用.P选择素是细胞黏附分子中选择素家族成员,介导血小板活化及炎症反应等.研究表明P选择素在炎症性肠病的病理过程中起重要作用.     

From bench to bedside: Fecal calprotectin in inflammatory bowel diseases clinical setting

Fecal calprotectin(FC) has emerged as one of the most useful tools for clinical management of inflammatory bowel diseases(IBD). Many different methods of assessment have been developed and different cutoffs have been suggested for different clinical settings. We carried out a comprehensive literature review of the most relevant FC-related topics: the role of FC in discriminating between IBD and irritable bowel syndrome(IBS) and its use in managing IBD patients In patients with intestinal symptoms, due to the high negative predictive value a normal FC level reliably rules out active IBD. In IBD patients a correlation with both mucosal healing and histology was found, and there is increasing evidence that FC assessment can be helpful in monitoring disease activity and response to therapy as well as in predicting relapse, post-operative recurrence or pouchitis. Recently, its use in the context of a treat-to-target approach led to a better outcome than clinically-based therapy adjustment in patients with early Crohn's disease. In conclusion, FC measurement represents a cheap, safe and reliable test, easy to perform and with a good reproducibility. The main concerns are still related to the choice of the optimal cut-off, both for differentiating IBD from IBS, and for the management of IBD patients.     

Inflammatory bowel diseases and human reproduction: A comprehensive evidence-based review

To evaluate the effects of inflammatory bowel diseases (IBDs) on human reproduction, we reviewed the current literature using a systematic search for published studies (articles and/or abstracts) without limits for English language. We searched on Medline (through PubMed), the Institute for Scientific Information, the Web of Science and the websites for the registration of controlled trials (http://controlled-trials.com/). Bibliographies of retrieved articles, books, expert opinion review articles and reviewed bibliographies from subject experts were manually searched. Titles and abstracts were screened initially, and potential relevant articles were identified and reviewed. Whenever possible, data were analyzed by comparing IBD patients vs healthy controls, and patients with active IBDs vs those with disease in remission. The effects of IBDs on female fertility, fertility in infertile couples, pregnancy and male infertility were examined separately. Patients with IBDs in remission have normal fertility. At the moment, there is no established guideline for the preservation of fertility in women with IBD undergoing surgery. Further data are needed regarding guidelines for the management of these patients. Data regarding IBDs and infertility are currently completely lacking. Considering the prevalence of intestinal pathology in young adults of childbearing age, this field is of great scientific and clinical interest, opening up important future perspectives. Another important and as yet unexplored point is the response to treatments for infertility in patients with IBDs. In particular, the question is whether the reproductive outcomes (clinical and biological) can be influenced by the IBD of one of the partners. The goals for successful reproductive outcomes in IBD population are correct counseling and disease remission. IBDs significantly affect several reproductive aspects of human (female, male, couple) reproduction. Further data are needed to develop guidelines for the clinical management of subjects of reproductive age with IBDs.     

Inflammatory bowel disease:A proposal to facilitate the achievement of an unequivocal diagnosis

Following the international guidelines criteria an adequate"diagnostic conclusion"of inflammatory bowel disease(IBD)can be achieved only if clinical,endoscopic and laboratory findings,together with sample technical adequacy and unequivocal histomorphological signs of the disease are available.Thus,a conclusive diagnosis requires a complex combination of clinical, endoscopic and histological data.A considerable number of endoscopic biopsies obtained from IBD patients do not meet the above-mentioned requirements.The aim of the present proposal is to introduce a binary system of evaluation in the"diagnostic conclusion"of the histopathological report that will help to simplify the clinical decisions and consequent patient management.In patients with no history of disease,the pathologist should classify the biopsies in"Diagnostic",when the criteria established by the international guidelines are satisfied and"not diagnostic"when one or more of the above-mentioned criteria are not met. The term"not diagnostic"should replace"highly suggestive"and"probable".This new terminology could avoid ambiguous expressions that encourage the clinician to classify the patient as affected by IBD without fulfilling all of the requirements for an accurate diagnostic approach.     

益生菌在炎症性肠病中的治疗进展

炎症性肠病(inflammatory bowel disease,IBD)是一种病因不明的慢性非特异性肠道炎症性疾病,包括溃疡性结肠炎(ulcerative colitis,UC)和克罗恩病(Crohn’s disease,CD)。许多研究显示肠道菌群的生态失调在IBD的发病中起着重要作用,而临床上相当一部分患者对常规治疗应答不佳或发生严重的不良反应,因此尝试益生菌调节肠道菌群来治疗IBD越来越受到重视。     

Antibody responses to gut bacteria in ankylosing spondylitis, rheumatoid arthritis, Crohn's disease and ulcerative colitis

Specific immunoreactive anti-Klebsiella antibodies are found in patients with ankylosing spondylitis (AS), a significant proportion of whom have occult inflammatory bowel disease. Molecular mimicry between Klebsiella or other bacterial antigens and HLA-B27 has been suggested in the pathogenesis of AS. The specificity of increased immunoreactivity against Klebsiella remains to be assessed against the abundant anaerobic bacterial flora, present either in healthy controls or in patients with ulcerative colitis (UC) and Crohn's disease (CD). Total immunoglobulin (Ig; IgG, IgA, IgM) immunoreactivity was measured by ELISA against Klebsiella pneumoniae, Proteus mirabilis, Escherichia coli and ten anaerobic isolates of the predominant normal bowel flora in 35 patients with active AS, 60 patients with inflammatory bowel disease (30 CD, 30 UC), 60 patients with active rheumatoid arthritis (RA) and 60 healthy controls. Ig immunoreactivity to K. pneumoniae was significantly elevated in AS (P < 0.001), CD (P < 0.001) and UC (P < 0.001) patients compared with RA patients and healthy controls. Furthermore, Ig immunoreactivity to P. mirabilis was significantly elevated only in RA patients, compared with the other inflammatory groups (P < 0.001) and controls (P < 0.001). There was no significant antibody response against E. coli or the ten obligate anaerobes in any of the test groups. The data suggested an increased immune response to Klebsiella in patients with AS, UC, CD and to Proteus in patients with RA. The specificity of these responses in some patients supported a possible role for enteric Klebsiella in the pathogenesis of AS and Proteus in RA. The role of Klebsiella in inflammatory bowel disease requires further study. Received: 25 September 1996 / Accepted: 18 December 1996