Arthropathies are a major clinical problem in patients with inflammatory bowel disease (IBD). Often it is difficult to control the articular symptoms with the anti-inflammatory strategies used for IBD. Studies evaluating specific treatments aimed at articular manifestations in patients with IBD are rare. Although there has been considerable interest in the gut–joint axis over the last decade, the pathophysiological mechanisms driving IBD-associated arthropathy are still unknown. Recently, interest in the multidisciplinary approach to patients with IBD and arthropathy has been increasing. New research and clinical projects aimed at understanding the mechanisms of disease may advance the development of effective therapies. In this review, the pathophysiology of IBD-associated arthropathy is discussed, as well as clinical manifestations, the classification and current therapeutic strategies.
- Inflammatory bowel diseases
- ulcerative colitis
- crohn's disease
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Arthropathies, an umbrella term for inflammatory joint manifestations and non-inflammatory peripheral joint pain, are the most common extra-intestinal manifestation in patients with inflammatory bowel disease (IBD) and these arthropathies are a major problem causing significant morbidity and disability. Articular manifestations affect approximately 30% of patients with Crohn's disease and those with ulcerative colitis.1–4 Since 1930, IBD-associated arthritis has been investigated and it was commonly accepted that peripheral arthritis associated with IBD was similar to rheumatoid arthritis (RA). However, studies on arthritis in IBD demonstrated arthritis to be a distinct clinical entity.5 6 Over the last few decades, IBD-associated arthritis is considered to be part of the group of spondyloarthritis (SpA),7 together with ankylosing spondylitis (AS), undifferentiated SpA, psoriatic arthritis, reactive arthritis, arthritis associated with acute anterior uveitis and idiopathic arthritis. Sixty per cent to 70% of SpA patients have gut inflammation, mainly chronic inflammation discovered by ileocolonoscopy,8–12 and 7% will develop IBD.9 11 Thus, several studies confirmed the close relationship between gut and joint inflammation suggesting a common aetiology, but the precise origin is still unknown.
In this review, the pathophysiology of the gut–joint axis in patients with IBD will be discussed. Furthermore, the clinical presentation, diagnosis, prevalence and management of joint manifestations in such patients are covered, as well as novel methods for the classification of joint manifestations.
Pathophysiology of the gut–joint axis in IBD
IBD results from the interaction of environmental factors, such as the intestinal flora, with host immune mechanisms in genetically susceptible individuals. So far, genome-wide association studies (GWAS) have linked pathogenesis of IBD to pathways such as autophagy, Th17 and nuclear factor-κB. Epidemiological studies suggest that ulcerative colitis and Crohn's disease share some, but not all, susceptibility genes, a hypothesis that has gained support from recent GWAS studies. However, further research should be carried out to identify the exact pathogenic mechanisms of IBD. Although a third of patients with IBD suffer from arthropathies, the understanding of the gut–joint axis remains elusive.
In AS, genetics seem to play a key role. There is a strong genetic association between HLA-B27 and patients with AS. Approximately 8% of Caucasian Europeans are HLA-B27 positive and more than 90% of patients with AS carry HLA-B27.13 In addition, 25–78% of patients with IBD and AS are HLA-B27 positive.14–16 Recently, interleukin 23 receptor (IL23R) variants and the major histocompatibility complex (MHC) have been shown to be associated with Crohn's disease and AS.17–19 For the MHC, it is not known (yet) whether this is a non-B27 association, due to a maximum signal centred around the HLA-B gene which extended further than the specific associated haplotype(s).18
In 2010, a cohort of 182 patients with AS was genotyped for single nucleotide polymorphism (SNP) markers corresponding to 39 Crohn's disease risk loci. Polymorphisms in the NOD2 gene, which plays an important role in the immune response by activating nuclear factor-κB, are not involved in the susceptibility of AS20–24 and therefore, were excluded in the study. Significant associations were confirmed with the MHC (p=0.00004) and IL 23R (p=0.04) loci, and a novel AS susceptibility locus, rs2872507 (p=0.03).25 Rs2872507 maps to a locus closely linked to the ORMDL3 gene in lymphoblastoid cells; this gene encodes a transmembrane protein and is likely involved in protein folding.
In summary, genetic studies have so far identified three loci which could explain IBD-associated arthropathies. It is likely that, with the recent sharp increase of GWAS studies in very large patient cohorts, the coming years will reveal novel insights into the genetics of the gut–joint axis.
Gut inflammation in SpA and animal models
In the gut mucosa of patients with Crohn's disease, as well as in non-inflamed gut mucosa and inflamed synovium of patients with SpA, macrophages expressing the scavenger receptor CD163 are increased.26 27 Previously, this molecule has been shown to act as a receptor for haemoglobin–haptoglobin complexes and to mediate cell–cell interactions between macrophages and developing erythroblasts in erythroblastic islands. Recently, however, it has been demonstrated that CD163 plays a role in host defence, functioning as a macrophage receptor for bacteria. Expression of CD163 in monocytic cells promoted bacteria-induced proinflammatory cytokine production.28 These findings identify CD163 as an innate immune sensor and inducer of local inflammation both in mucosal and synovial compartments.
Up to now, the animal models HLA-B27/human β2-microglobulin transgenic rats and TNFΔARE mice are applicable to investigate the gut–joint axis. The HLA-B27/human β2-microglobulin transgenic rats spontaneously develop intestinal inflammation and arthritis resembling human SpA. Inflammation did not occur in animals maintained in germ-free conditions until reintroduction of gut flora, suggesting an important role of intestinal bacteria in the pathogenesis of B27 associated gut and joint inflammation.29 Another hypothesis in the pathogenesis of B27 associated gut and joint inflammation includes defective stimulation of T cells by dendritic cells that exhibit several molecular deficiencies.30 31 Furthermore, misfolding of the HLA-B27 beta-pocket activates an unfolded protein response that results in inflammation.32
In another model, the TNFΔARE mouse model with over-expression of tumour necrosis factor α (TNFα), the development of Crohn's disease-like ileitis arises along with peripheral arthritis, enthesitis and sacroiliitis.33 This model could prove particularly helpful for further research on the pathogenesis of Crohn's disease and SpA.
Aberrant homing of mucosal lymphocytes to the joints
Although distinct immune mechanisms underlying the pathophysiology of IBD-associated arthropathy have not been clearly defined, it is interesting to discuss the potential aberrant homing of gut-primed lymphocytes to the joints. Under normal conditions, naive lymphocytes migrate continuously from the blood into the lymphoid tissues of the gut in search of their cognate antigens. The lymphocyte recirculation directs naive lymphocytes into the Peyer's patches in a multistep extravasation cascade by recognising high endothelial venules (HEVs), regulated by the expression of multiple adhesion molecules and chemokines. When the lymphocyte becomes activated, by exposure to its cognate antigen, the cell starts to differentiate and proliferate before returning to the systemic circulation via the efferent lymphatic system. The activated mucosal lymphocyte has the ability to home back to the gut, where it arrives in the lamina propria and exerts its effector functions.34 35 Lymphocyte recruitment from the circulation to the gut is a highly regulated process, depending on the expression of α4β7 integrin and its endothelial ligand mucosal addressin cell adhesion molecule-1 (MAdCAM-1). α4β7–MAdCAM-1 interaction causes rolling and the adherence of lymphocytes to mucosal venules. The interaction between chemokine receptor CCR9 and its ligand CCL25 promotes the specific homing of gut lymphocytes to the small bowel, but not to the colon.34 35 In IBD, destructive infiltration of leucocytes into the bowel occurs, due to changes in the mucosal vasculature, including vasodilatation, hyperaemia and increased permeability of the vessel wall which are induced by the release and actions of various inflammatory mediators.36–39 MAdCAM-1 expression increases during gut inflammation resulting in a sustained recruitment of α4β7+ lymphocytes.40 Furthermore, the migration pathways of lymphocytes are altered by aberrant expression patterns of adhesion molecules and chemokines.
Although, activated human intestinal lymphocytes are capable of binding vessels in normal gut and inflamed synovial vessels in vitro, they do not bind inflamed peripheral lymph node vessels. The binding of intestinal lymphocytes to inflamed synovium does not depend on α4β7–MAdCAM-1 interaction.41 It has been shown that vascular adhesion protein-1 (VAP-1) was present in all synovium specimens and MAdCAM-1 was totally absent. VAP-1 mediates the binding of small intestinal lymphocytes (naive cells and memory cells) and in particular, large immunoblasts from normal gut to inflamed synovium. The adherence of macrophages is mainly P-selectin dependent.42 Gut-derived mucosal leucocytes from patients with IBD have the property to bind inflamed synovial vessels as well. Multiple adhesion molecules that contribute to this adherence are shown in figure 1. Small IBD lymphocytes use VAP-1, CD44, as well as interactions between α4 integrins and vascular cell adhesion molecule-1 (VCAM-1), CD18 integrins and intracellular adhesion molecule-1 (ICAM-1), and L-selectin and peripheral lymph node addressins (PNAd). Furthermore, immunoblasts mainly use VAP-1, and the binding of mucosal macrophages mostly relies on P-selectin and its ligand P-selectin glycoprotein ligand-1 (PSGL-1) interactions. E-selectin and VAP-1 also have a significant role in the binding of mucosal macrophages to synovium.43
In conclusion, lymphocyte homing to the gut depends on α4β7–MAdCAM-1 interactions. MAdCAM-1 expression is increased during intestinal inflammation. In patients with IBD, mucosal lymphocytes and macrophages can also bind to inflamed synovial vessels, but this aberrant homing to the joints does not depend on α4β7–MAdCAM-1 interactions. Several other adhesion molecules result in the binding of mucosal leucocytes to inflamed joint vessels, of which VAP-1 supports the binding of lymphocytes as well as macrophages.
Peripheral arthropathies in IBD
Clinical presentation and diagnosis
Peripheral arthritis in IBD is diagnosed clinically by the presence of pain and swelling in one or more joints (figure 2A). During physical examination, which involves inspection and palpation, stiffness, tenderness and a decreased range of motion of the affected joint may be present. Peripheral arthritis in patients with IBD may be classified as type 1 and type 2 arthritis.45 Type 1 is a pauciarticular peripheral arthritis affecting four or fewer joints in acute episodes, usually resolves within 10 weeks and often parallels IBD relapses. In contrast, type 2 is a polyarticular arthritis affecting five or more joints with persistent symptoms for months to years and occurs independently of IBD activity. The type 1 and type 2 subdivision of arthritis associated with IBD is commonly used in gastroenterological studies3 46 but not widely known in rheumatology literature. Aspiration of synovial fluid is necessary when an alternative diagnosis, such as reactive arthritis, gout, crystal-induced arthritis, Lyme's disease or septic arthritis, is suspected. Laboratory tests, like C-reactive protein (CRP) and white blood cell count, usually reflect the bowel activity and cannot be used as a diagnostic tool.
Peripheral arthritis in patients with IBD is predominantly oligoarticular and asymmetric and is mostly encountered in Crohn's disease. The onset is usually acute and arthritis mostly occurs during exacerbations of IBD activity without joint damage.2 3 46–48 The onset may precede the onset of bowel symptoms although it usually coincides with or presents after the onset of IBD.3 45 47 The prevalence in patients with IBD varies from 7 to 16%;15 45–49 in ulcerative colitis the prevalence is 5–14%;45–49 and in Crohn's disease it is 10–20%.45–49
Peripheral arthritis in patients with IBD can occur during an IBD exacerbation; however, it can also follow a course independent of bowel disease activity. When the onset of peripheral arthritis occurs in patients during active bowel disease, treatment of the IBD relapse should be the principal goal. To relieve pain, swelling and stiffness in patients with IBD and arthritis, conventional non-steroidal anti-inflammatory drugs (NSAIDs) or selective cyclooxygenase (COX)-2 inhibitors can be prescribed and/or steroids can be injected into the affected joint. In literature, the risk of onset of IBD relapse due to NSAIDs has been controversial.50 51 However, placebo-controlled trials showed that the use of COX-2 inhibitors is safe in patients with IBD. Etoricoxib therapy, with a dose ranging between 60 and 120 mg once a day for 3 months, in patients with Crohn's disease or ulcerative colitis was safe and no increased exacerbation rate of IBD versus the placebo group was observed. In addition, in a placebo-controlled trial in patients with ulcerative colitis who were in remission, celecoxib 200 mg twice daily for 14 days was not associated with a greater clinical and endoscopic relapse rate than placebo.52 53 Treatment options of more resistant peripheral arthritis in patients with IBD are based on the recommendations for the management of peripheral SpA. Sulfasalazine has been shown to be effective in the treatment of peripheral joint symptoms.54 Furthermore, in a small study of patients with Crohn's disease and active SpA, peripheral arthritis (poorly or not responsive to conventional treatments) was successfully treated with infliximab.55 The results of several other small studies are encouraging; infliximab has been shown to improve peripheral arthritis in Crohn's disease.56–59
No clinical trials are available for most of the other common drugs, such as methotrexate and azathioprine. Based on the good experience of the use of methotrexate in RA, this drug is regularly used by rheumatologists for the treatment of patients with RA. Azathioprine, often used for the treatment of IBD, does not seem to have any specific effect on peripheral arthritis.
Clinical presentation and diagnosis
Entheses are the attachments of tendons, ligaments, fascia or joint capsules to bone and their function is to reduce mechanical stress at the attachment site, for example, the insertion of the plantar fascia into the calcaneus. Enthesopathy is any pathological disorder of the entheses, commonly a consequence of overuse injuries due to sport and exercise whereas enthesitis is the inflammation of the entheses. Peripheral enthesitis may cause mild to severe pain and swelling, resulting in a limitation of mobility, for instance difficulty in walking on heels during Achilles enthesitis (figure 2B). Enthesopathy and enthesitis can be diagnosed clinically, but ultrasonography is a highly sensitive and non-invasive imaging method to use as a diagnostic tool for enthesitis and also MRI is a useful imaging tool to detect enthesitis.60 61
The prevalence of enthesitis in patients with IBD varies from 5 to 10%, is predominantly seen in Crohn's disease and affects particularly the Achilles tendon or plantar fascia insertion (Achilles enthesitis or plantar fasciitis).2 3 14 15
Enthesitis can be treated with analgesics, NSAIDs/COX-2 inhibitors, ortheses, physiotherapy and local steroid injection, especially when it is the predominant clinical manifestation. In very persistent, disabling cases, treatment with a TNF blocker can be considered.62
Clinical presentation and diagnosis
Different types of dactylitis are recognised, based on tissue involvement: tuberculous, syphilitic, sarcoid, sickle cell disease, SpA and blistering distal dactylitis.63 The SpA dactylitis (figure 2C), also known as a sausage-like digit, has been observed in patients with IBD and is a painful and diffuse swelling of the entire finger or toe which can be diagnosed clinically with a 100% sensitivity and specificity compared with MRI.63 64 Ultrasound and MRI studies showed that the sausage-like appearance in SpA dactylitis is due to flexor tenosynovitis and peritendinous soft tissue swelling in which joint synovitis is often present.63 64
Prevalence studies of dactylitis in patients with IBD are limited. A population-based study3 investigated the occurrence of arthropathies in a cohort of 160 patients with IBD who were interviewed and examined by a rheumatologist. In three of the 160 (2%) patients, dactylitis was present. This is in line with the findings of another study that reported a prevalence of 4%.15
SpA dactylitis can be treated with NSAIDs/COX-2 inhibitors and/or steroid injections in the flexor synovial sheaths.
Clinical presentation and diagnosis
Arthralgia, non-inflammatory joint pain, is diagnosed clinically. Physical examination, which involves palpation of the joints, reveals pain, but no swelling or effusion.
Arthralgia in patients with IBD can have several causes. Patients treated with anti-TNF therapy may develop a delayed hypersensitivity reaction/serum sickness-like reaction including arthralgia or may develop arthralgia as an adverse event.65–67 Chronic widespread pain and fibromyalgia in patients with IBD may also occur.68 69 A major problem in patients with IBD is the unexplained arthralgias, which will be discussed here.
Most studies on arthropathies in IBD exclude arthralgia or mention it without further investigation or do not make a clear distinction between arthralgia and peripheral arthritis.
A hospital-based study45 with 1459 patients with IBD and a population-based study70 with 521 patients with IBD, respectively reported a prevalence of 8% and 16% of clinically-investigated arthralgia in patients with IBD. However, in a small study with 103 patients with IBD, the prevalence of a history of painful joints was 30%.14 Arthralgia occurs more often in patients with Crohn's disease compared to patients with ulcerative colitis.45 70 In a population-based cohort70 of 521 patients with IBD, the characteristics of arthralgia and its impact on patients' health-related quality of life (HRQOL), assessed by the SF-36 and IBDQ, were described. Arthralgia was defined as joint pain without the presence of inflammatory or degenerative joint disease or chronic pain syndromes. A polyarticular (6.3%) distribution was found somewhat more frequently than a monoarticular (4.8%) or oligoarticular (4.8%) involvement. No differences in articular distribution were found between Crohn's disease and ulcerative colitis. Furthermore, in 19% of the patients with IBD, arthralgia coincided with exacerbation of IBD. The estimated HRQOL score was significantly lower in patients with IBD and arthralgia, in comparison with patients with IBD without arthralgia. Thus, arthralgia is a common problem in patients with IBD resulting in morbidity and disability.
Analgesics, such as paracetamol, NSAIDs/COX-2 inhibitors and opioids, might be considered for pain control.
Axial arthropathies in IBD
Inflammatory back pain
Clinical presentation and classification criteria
Back pain is a common symptom in both IBD and the general population. Inflammatory back pain (IBP) caused by inflammation of the sacroiliac (SI) joints and which may spread to the spine is associated with IBD. To differentiate between IBP and mechanical back pain, several clinical classification criteria exist.71–73 The most widely used IBP criteria set is the Calin criteria,71 which is fulfilled if at least four out of the five characteristics are present: (1) age of onset <40 years, (2) duration >3 months, (3) insidious in onset, (4) association with morning stiffness, and (5) improvement after exercise.
In 2009, new criteria for IBP in patients with chronic back pain for more than 3 months were developed and validated by experts from the Assessment of SpondyloArthritis International Society (ASAS) (box 1).74 In a validation cohort, a sensitivity of 80% and specificity of 72% of the new ASAS criteria was found, which performed better than the Calin criteria (sensitivity 90% and specificity 53%).74
IBP according to ASAS experts to be applied in patients with chronic back pain (>3 months)74
Age at onset <40 years
Improvement with exercise
No improvement with rest
Pain at night (with improvement upon getting up)
The criteria are fulfilled if at least four out of the five parameters are present.
In studies that use the Calin criteria the prevalence of IBP in patients with IBD ranges from 9 to 30%.2–4 15 In a population-based study,15 18% of patients with IBD, 22% with Crohn's disease and 17% with ulcerative colitis, had a history of IBP without a diagnosis of AS.
See the section below relating to the treatment of ankylosing spondylitis.
Clinical presentation and classification criteria
Isolated sacroiliitis, a uni- or bilaterally inflammation of the SI joints, is mostly asymptomatic, although this can also be the presenting symptom of AS (see below).75 Inflammation of the SI joints, results in sclerosis and cartilage destruction, and eventually leads to syndesmophytes and ankylosis. Diagnosis is based on imaging methods, in which anteroposterior (AP) pelvis radiographs remains the most widely used and available initial screening method. A scoring system for grading sacroiliitis consists of five grades from 0 (normal) to four (total ankylosis).76 Radiography has a high specificity and is the most cost-effective technique for imaging the SI joints, but has only a limited diagnostic capacity. The anatomic complexity of the S-shaped SI joints causes over-projection of the ilium with the sacrum on standard AP views and hides the SI joint space. In addition, it is difficult to differentiate between the early stages of the disease, stages 1 (suspicious changes) and 2 (minimal, abnormal changes with erosions or sclerosis, without alteration in the joint width),77 78 resulting in a prolonged interval between the onset of sacroiliitis and/or clinical signs and the appearance of objective radiographic structural findings, which are a consequence of inflammation of the SI joints. On CT, chronic bone changes can be detected better than on plain radiographs, due to improved visualisation of the complex anatomy of the SI joints.79 However, both conventional radiographs and CT can only demonstrate bone changes such as erosions, which are the consequence of inflammation, and cannot reveal present activity of sacroiliitis. Scintigraphy, on the other hand, can detect acute inflammation, but a positive scintigraphy of the SI joints is of limited diagnostic value for the early diagnosis of sacroiliitis due to a low sensitivity for patients with suspected sacroiliitis.80 Furthermore, scintigraphy is associated with non-specific factors such as age and technical problems that may increase the accumulation of radiopharmaceuticals at normal bony sites.80 MRI is of great value in the diagnosis of sacroiliitis and for monitoring the disease course, because MRI imaging has the capability to accurately visualise both acute and chronic inflammation of the SI joints with a reported sensitivity and specificity of approximately 90%.79 81–87 Furthermore, a major advantage of MRI scanning is the lack of exposure to ionising radiation. Such exposure is especially a concern with the use of CT in young (female) patients.
A group of rheumatologists and radiologists (The Assessment of SpondyloArthritis international Society, ASAS) described MRI findings of sacroiliitis, and also proposed by consensus a definition for active sacroiliitis.88 Active inflammatory lesions, can be seen on T1 (preferably fat suppression (FS)) after administration of intravenous gadolinium or with a short tau inversion recovery (STIR) sequence. This includes bone marrow oedema/osteitis, synovitis of the SI joints, capsulitis and enthesitis. Structural lesions are visualised best by T1-weighted turbo spin-echo sequence and include sclerosis, erosions, fat deposition and bony bridges/ankylosis. In principle, a STIR sequence is sufficient to visualise inflammation in SI joints. Furthermore, active sacroiliitis on MRI, also called ‘a positive MRI’, is defined as the presence of bone marrow oedema of at least two lesions on one slice or one lesion on at least two consecutive slices (figure 2D). Other active lesions such as synovitis as single lesions are insufficient to define a MRI positive.
The prevalence of radiological sacroiliitis in patients with IBD varies widely from 2% in a population-based study15 to 10–32% in hospital-based studies.14 48 49 89 90 In a study with 44 patients with Crohn's disease who underwent MRI of the SI joints, 27% had isolated sacroiliitis and 50% had IBP.91
See the section below relating to the treatment of ankylosing spondylitis.
Clinical presentation and classification criteria
AS is primarily a chronic inflammatory disease of the axial skeleton (sacroiliitis, spondylitis, spondylodiscitis and/or enthesitis), but it can also affect other locations for example peripheral joints. Chronic inflammation of the spine causes sclerosis, erosions, syndesmophytes and bony bridging of one or more intervertebral discs, producing the classical ‘bamboo spine’, resulting in loss of the lumbar lordosis and decreased spinal mobility. AS almost always starts in the SI joints resulting in its main symptom; inflammatory low back pain. The modified New York criteria (box 2),92 consisting of clinical IBP criteria and radiological sacroiliitis (at least grade 2 bilaterally or grade 3 unilaterally), are the most widely used criteria. As radiological sacroiliitis is a relatively late finding, there is gap of about 8 years between symptom onset and establishing the diagnosis.77 78 93 94 Ninety per cent of patients with AS are HLA-B27 positive and testing of HLA-B27 can be helpful in diagnosing early disease.13
Modified New York criteria for ankylosing spondylitis92
Low back pain and stiffness for more than 3 months, which improve with exercise, not relieved by rest.
Limitation of motion of the lumbar spine in both the sagittal and frontal planes.
Restriction of chest expansion relative to normal values corrected for age and sex.
Bilateral sacroiliitis grade ≥2 or unilateral sacroiliitis grade 3–4.
Definite ankylosing spondylitis if the radiological criterion is associated with at least one clinical criterion.
ASAS has developed criteria for the management of AS consisting of non-pharmacological and pharmacological options.54 Education is very important and physical exercise and therapy can help maintain function and relief symptoms. The first-line drug treatment for symptomatic patients with AS are NSAIDs/COX-2 inhibitors. In patients with IBD and AS and with peripheral arthritis, treatment with sulfasalazine may be considered; in patients with only axial disease, on the other hand, there is no evidence for the efficacy of sulfasalazine and other disease-modifying antirheumatic drugs (DMARDs), such as methotrexate or azathioprine. When the treatment is inadequate with the previous mentioned medications, TNFα inhibitors can be given. The monoclonal antibodies infliximab and adalimumab are both effective for the treatment of joint symptoms in AS,95–100 as well as bowel symptoms in Crohn's disease.66 101 102 Furthermore, infliximab improves the severity of pain and duration of morning stiffness of joint symptoms in Crohn's disease.55 57 59 Although the fusion protein etanercept is effective in AS, it is not effective — and may be even contraindicated103 – in the treatment of Crohn's disease.104 In daily practice, anti-TNF therapy in SpA is more effective compared to RA patients.105–108 In a retrospective study, a longer retention rate for anti-TNF for SpA versus RA (HR 1.60) was found.106 In an observational multicentre study with a large number of patients with AS or RA, the adjusted HR for treatment termination was 0.66 for patients with AS compared to those with RA.108
All the features and various diagnoses that have been described so far belong to the group of SpA. This is a cluster of rheumatic inflammatory diseases with overlapping features, including arthritis associated with IBD, arthritis associated with acute anterior uveitis, AS, psoriatic arthritis, reactive arthritis, idiopathic arthritis and undifferentiated SpA. The European Spondyloarthropathy Study Group (ESSG) criteria are the most well-known classification criteria for SpA and according to these criteria patients with IBD are classified as SpA when peripheral arthritis (asymmetrical or predominantly in the lower extremities) and/or inflammatory spinal pain is present. The ESSG criteria were developed before MRI was available and therefore, are of limited value for the diagnosis of early axial SpA. The disadvantage of these criteria is that there is no differentiation between patients with (predominantly) peripheral or axial symptoms, while this has consequences for treatment. Therefore, ASAS decided to divide SpA into two main forms: peripheral SpA with predominantly peripheral joint symptoms and axial SpA with predominantly axial involvement. Axial SpA represents different stages of AS. The pre-radiographic stage, back pain without definite radiographic sacroiliitis, is identical to the early stage of AS and the radiographic stage with detectable sacroiliitis and possibly syndesmophytes in patients with back pain is the same as AS.78 The ASAS group developed two sets of new classification criteria for both axial SpA and peripheral SpA. The axial SpA criteria have two arms and can be applied to patients who have at least 3 months of back pain with an onset before 45 years. There is one imaging arm with sacroiliitis on plain radiographs (that will be classified as AS) and/or MRI (early stage of AS) plus one SpA feature (table 1).109 110 The second arm is a clinical arm classifying, HLA-B27 positive patients with two or more (other than HLA-B27) SpA features. IBD is one of the possible clinical features. The ASAS criteria for peripheral SpA classify patients with peripheral arthritis, enthesitis or dactylitis as the main symptom with one or two additional SpA features (table 2).111
The prevalence of arthropathies in patients with IBD is high. Several rheumatological classification criteria exist to classify the articular manifestations in patients with IBD, and arthritis associated with IBD is part of the SpA group. Recently, new ASAS classification criteria for SpA were developed, which focus on axial or peripheral symptoms. This division is very important, because treatment options differ in patients with predominantly axial or peripheral SpA. Furthermore, the new ASAS criteria for axial SpA provide tools for an earlier diagnosis of axial SpA, with the implementation of MRI. The precise aetiology of the gut–joint axis in IBD is still unknown. A multidisciplinary approach will lead to new research and clinical projects in order to understand the mechanisms of disease and to advance the development of effective therapies.
Peripheral arthropathies in patients with IBD: practice points
Peripheral arthropathies in inflammatory bowel disease (IBD) include arthritis, enthesitis, dactylitis and arthralgia.
Peripheral arthropathies are diagnosed clinically.
There is no laboratory test for diagnosis.
Management of active intestinal disease should be the principal focus in patients with IBD and arthropathies, which occur during a relapse.
Paracetamol, non-steroidal anti-inflammatory drugs (NSAIDs) and/or cyclooxygenase-2 (COX-2) inhibitors can be given to relieve pain and swelling.
Steroids can be injected into the affected joint.
More resistant peripheral arthritis in patients with IBD can be treated with sulfasalazine and tumour necrosis factor α (TNFα) inhibitors.
Axial arthropathies in patients with IBD: practice points
Axial arthropathies include inflammatory back pain, isolated sacroillitis, non-radiographic spondyloarthritis and ankylosing spondylitis (AS).
Inflammatory back pain is defined clinically using the ASAS criteria.
Isolated sacroillitis is diagnosed by anteroposterior (AP) pelvis radiographs or MRI (T1 (preferably fat suppression) with a STIR sequence).
Axial SpA is defined clinically and/or by imaging methods using the ASAS criteria.
Patient education is very important.
Physical exercise/therapy can help maintain function and relief symptoms.
NSAIDs/COX-2 inhibitors are the first-line drug treatment for symptomatic AS.
Start TNFα inhibitors (adalimumab or infliximab) when there is inadequate management with other medications.
We would like to thank Auke Verhaar for his help in creating the figures.
Competing interests None.
Provenance and peer review Commissioned; externally peer reviewed.
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