Enteropathic Arthritis

Definition, Etiology, PathogenesisTop

Enteropathic arthritis refers to inflammatory arthritis associated with inflammatory bowel disease (IBD): ulcerative colitis (UC) (see Ulcerative Colitis) and Crohn disease (CD) (see Crohn Disease). Several mechanisms may underly concurrent inflammation in the gut and joint, but the precise pathogenic pathways are yet to be determined. A disturbance of the gut barrier is thought to be the first and primary process for most of these proposed mechanisms. Alternatively, shared genetic and environmental factors may be the main predisposing factors.

Clinical Features and Natural HistoryTop

Peripheral arthritis is acute, migratory, asymmetric and most frequently involves the knees and ankles. It is generally nonerosive.

Types of peripheral joint involvement:

1) Type 1: Acute oligoarthritis (involvement of ≤5 joints) that may precede gastrointestinal manifestations or occur early in the disease course and is often associated with IBD flares, self-limiting (2-6 months), and frequently accompanied by extraintestinal features (eg, erythema nodosum). It affects 5% to 10% of patients with IBD.

2) Type 2: Polyarthritis (>5 joints) is usually independent of IBD activity, has a chronic course (months or years), and is not associated with extraintestinal features except for uveitis. It affects 3% to 4% of patients with IBD.

Spondyloarthritis with axial involvement: Inflammatory back pain (see Table 1 in Ankylosing Spondylitis) is the typical presentation of axial disease, occurring with or without peripheral arthritis. It is usually unrelated to bowel disease activity. From 10% to 20% of patients can develop clinical and radiographic features similar to ankylosing spondylitis (AS). Imaging studies can be negative in early spondyloarthritis. Additionally, up to 20% of asymptomatic patients may have imaging evidence of axial disease. It is important to consider that arthralgia (in the absence of inflammatory arthritis) is very common in IBD, affecting ~10% to 50% of patients.

Involvement of other organs in the course of IBD: see Ulcerative Colitis; see Crohn Disease.

Natural history: Type 1 peripheral arthritis typically occurs early and is self-limiting (<6 months). Patients with type 2 peripheral arthritis may continue to have recurrent flares for many years. In most cases peripheral enteropathic arthritis does not cause permanent joint damage or deformity. Axial enteropathic arthritis can follow the course of ankylosing spondylitis, causing disability and significantly impacting the quality of life.

DiagnosisTop

Diagnostic Tests

1. Laboratory tests: Markers of inflammation (elevated erythrocyte sedimentation rate [ESR]/C-reactive protein [CRP], thrombocytosis, anemia) can be confounded by bowel disease. Rheumatoid factor (RF) is usually negative. HLA-B27 is positive in 50% to 75% of patients with IBD-associated axial arthritis.

2. Synovial fluid examination: Findings are nonspecific and characteristic of inflammatory arthritis.

3. Imaging studies:

1) Radiography: Peripheral enteropathic arthritis is usually nonerosive, with <10% of patients having erosions of the affected joints. Radiographs may show soft-tissue swelling, periarticular osteopenia, and mild periostitis. Radiographic features in axial involvement are similar to AS. Asymptomatic sacroiliitis can occur in up to 20% of patients.

2) Magnetic resonance imaging (MRI): Similarly to AS, MRI can be used to assess for axial disease where radiographs are normal or to exclude inflammatory disease in mechanical back pain (when indicated).

Diagnostic Criteria

1. Diagnosis of UC or CD.

2. Features of peripheral arthritis or axial spondyloarthritis (diagnosis of axial spondyloarthritis often requires confirmation by imaging studies).

Differential Diagnosis

1. Peripheral enteropathic arthritis: Atypical rheumatoid arthritis, infectious arthritis, reactive arthritis, psoriatic arthritis.

2. Spondyloarthritis: Other spondyloarthritides.

TreatmentTop

Treatment of the Underlying Condition

Many drugs used for IBD itself can benefit the articular manifestations. In addition, type 1 peripheral arthritis usually mirrors IBD disease activity and improves with improvement of the underlying IBD.

Treatment of Joint Involvement

1. Physiotherapy is helpful for the maintenance of functional capacity, particularly in patients with axial enteropathic arthritis.

2. Pharmacotherapy:

1) Use acetaminophen (INN paracetamol)-based products for pain control. Nonsteroidal anti-inflammatory drugs (NSAIDs) are generally avoided because of the potential risk of worsening IBD; however, NSAIDs (cyclooxygenase 1 [COX-1] and 2 [COX-2] inhibitors) can be used for arthritis if IBD is quiescent and in consultation with a gastroenterologist.

2) Sulfasalazine is the first-line disease-modifying antirheumatic drug (DMARD) in patients with peripheral enteropathic arthritis.Evidence 1Strong recommendation (benefits clearly outweigh downsides; right action for all or almost all patients). Low Quality of Evidence (low confidence that we know true effects of the intervention). Quality of Evidence lowered due to indirectness. Olivieri I, Cantini F, Castiglione F, et al. Italian Expert Panel on the management of patients with coexisting spondyloarthritis and inflammatory bowel disease. Autoimmun Rev. 2014 Aug;13(8):822-30. doi: 10.1016/j.autrev.2014.04.003. Epub 2014 Apr 13. Review. PubMed PMID: 24726868. If it is ineffective or not tolerated, consider methotrexate or azathioprine. DMARDs are ineffective in patients with axial spondyloarthritis. Agents, dosage, contraindications, and adverse effects of DMARDs: see Table 3 in Rheumatoid Arthritis.

3) Intra-articular glucocorticoids can provide effective short-term relief in monoarthritis or oligoarthritis. Short-term systemic glucocorticoids may provide rapid short-term relief in patients with peripheral enteropathic arthritis.

4) Anti–tumor necrosis factor (TNF) agents (infliximab, adalimumab, golimumab, certolizumab) have beneficial effects on both intestinal manifestations and arthritis (axial and peripheral).Evidence 2Strong recommendation (benefits clearly outweigh downsides; right action for all or almost all patients). Moderate Quality of Evidence (moderate confidence that we know true effects of the intervention). Quality of Evidence lowered due to the risk of bias and imprecision. Luchetti MM, Benfaremo D, Ciccia F, et al. Adalimumab efficacy in enteropathic spondyloarthritis: A 12-mo observational multidisciplinary study. World J Gastroenterol. 2017 Oct 21;23(39):7139-7149. doi: 10.3748/wjg.v23.i39.7139. PMID: 29093622; PMCID: PMC5656461. Olivieri I, Cantini F, Castiglione F, et al. Italian Expert Panel on the management of patients with coexisting spondyloarthritis and inflammatory bowel disease. Autoimmun Rev. 2014 Aug;13(8):822-30. doi: 10.1016/j.autrev.2014.04.003. Epub 2014 Apr 13. PMID: 24726868. Rispo A, Scarpa R, Di Girolamo E, et al. Infliximab in the treatment of extra-intestinal manifestations of Crohn's disease. Scand J Rheumatol. 2005 Sep-Oct;34(5):387-91. doi: 10.1080/03009740510026698. PMID: 16234187. Etanercept is ineffective for the treatment of IBD itself.