Arthritis Associated with Ulcerative Colitis and Crohn’s Disease

Kyriakos A. Kirou

Allan Gibofsky

KEY POINTS

Intestinal inflammation is closely linked to the spondyloarthropathies (SpA).
Among extraintestinal manifestations of inflammatory bowel disease (IBD), the musculoskeletal ones are most common and include peripheral arthritis (PeA) type I and II, asymptomatic sacroiliitis, ankylosing spondylitis (AS), and enthesitis.
Type I PeA resembles reactive arthritis (ReA), may precede enteritis, usually parallels bowel disease activity, and is mostly benign with regard to joint damage.
Type II PeA may resemble rheumatoid arthritis and causes more persistent symptoms independent of bowel disease activity.
IBD-associated AS has the same course and prognosis as idiopathic AS.
Therapy that is targeted at the intestinal inflammation, such as with sulfasalazine, 6-mercaptopurine, and/or azathioprine, is also effective against type I PeA.
Nonsteroidal anti-inflammatory drugs (NSAIDs) should be used with caution because they may sometimes exacerbate intestinal disease.
Anti-tumor necrosis factor (anti-TNF) agents appear to be very effective for all musculoskeletal symptoms of IBD, but only the anti-TNF monoclonal antibodies may ameliorate intestinal inflammation. These agents should be reserved for more severe cases and those refractory to other treatments.

Ulcerative colitis (UC) and Crohn’s disease (CD), the two major forms of inflammatory bowel disease (IBD), share several extraintestinal manifestations among which
musculoskeletal involvement is the most common and arguably the most important. Enteritis has been pathogenetically linked to arthritis in IBD and therefore such arthritis is also called enteropathic.

IBD-associated arthritis is one of the spondyloarthropathies (SpA) that are characterized by axial and/or peripheral joint involvement, enthesitis, anterior uveitis, mucocutaneous inflammation, occasional aortitis and heart block, seronegativity for rheumatoid factor, and familial aggregation with a strong association with human leukocyte antigen (HLA)-B27 (see Chapter 5).

Notably, subclinical gut inflammation has been documented in all SpA forms, including ankylosing spondylitis (AS), their prototypic disorder.

ETIOPATHOGENESIS

I. INFECTIOUS TRIGGERS

Bacteria have been thought to play a significant role in these diseases, either because of increased exposure to normal intestinal flora (as occurs with increased intestinal permeability in IBD), or because of enteric infection with certain arthritogenic bacteria [in reactive arthritis (ReA)].
Synovial fluid cultures, however, are characteristically negative, and septic arthritides are excluded from the group.

II. Genetic factors

determine whether patients with IBD will develop arthritis.

Although patients with IBD have normal incidence of HLA-B27, patients with IBD-related type I peripheral arthritis (PeA) and IBD-associated AS (IBD-AS) demonstrate increased incidence of this allele.
Loss-of-function mutations of CARD 15 (NOD2; chromosome 16) are associated with an increased risk for CD. Gut inflammation may occur through defective mucosal defenses against luminal bacteria.
Among patients with CD, those with sacroiliitis have an increased prevalence of CARD 15 mutations.

PREVALENCE

The prevalence of IBD is between 50 and 100/100,000.
PeA occurs in 5% to 20% of patients with IBD and is slightly more common in patients with CD. It is seen mainly in the setting of IBD colonic involvement.
Axial involvement in the form of inflammatory spinal pain occurs in 6% to 18% depending on the study. However, AS occurs in 1% to 9% of patients with IBD (IBD-AS). IBD-AS is more common in patients with CD, and not associated with any particular intestinal localization.

CLINICAL MANIFESTATIONS

The European Spondyloarthropathy Study Group (ESSG) classification criterion has greater than 85% sensitivity and specificity for the SpA (Table 40-1).

PeA
- Men and women are equally affected, and peak age of onset is between 25 and 44 years.
- Recently PeA has been classified as type I PeA, which resembles ReA both clinically (asymmetric, large joint, lower extremity, and pauciarticular) and genetically (26% prevalence of HLA-B27), and type II PeA that clinically appears to resemble seronegative rheumatoid arthritis (RA) (Table 40-2).
- Resection of affected colon in UC usually induces remission of type I PeA.

AXIAL ARTHRITIS

Unlike primary AS, in IBD-associated AS there is no male predominance, it can occur after 40 years of age, and only 50% to 70% of patients are HLA-B27–positive. In fact, AS in HLA-B27–negative patients should predict IBD or psoriatic arthritis.

Table 40-1 The European Spondyloarthropathy Study Group (ESSG) Classification Criteria

Criterion	Definition
Inflammatory spinal pain with at least four of the following components: Three-months duration Age of onset <45 y Insidious (gradual) onset Improved by exercise Associated with morning stiffness	History of past symptoms or current symptoms of spinal pain (low, middle, and upper back or neck region)
Synovitis	Past or present asymmetric arthritis, or arthritis predominantly in the lower limbs
One or more of the following:	Family history: first- or second-degree relatives with AS, psoriasis, acute uveitis, reactive arthritis, or inflammatory bowel disease Psoriasis (past or present) diagnosed by a physician Inflammatory bowel disease (past or present) diagnosed by a physician and confirmed by radiography or endoscopy Nongonococcal urethritis, or cervicitis occurring within 1 month before onset of arthritis Episode of diarrhea occurring within 1 month before the onset of arthritis Enthesopathy: past or present spontaneous pain or tenderness at examination of the insertion site (enthesis) of Achilles tendon or plantar fascia Buttock pain (past or present) alternating between right and left gluteal regions Sacroiliitis: either bilateral grade 2–4, or unilateral grade 3–4^a
Spondyloarthropothy is diagnosed when criterion 1 or 2 is present together with one or more of the eight conditions in criterion 3 ^a Grades are—0, normal; 1, possible; 2, minimal; 3, moderate; 4, ankylosed (completely fused). AS, ankylosing spondylitis. Adapted from Dougados et al. The ESSG preliminary criteria for the classification of spondylarthropathy. Arthritis Rheum 1991;34:1218–27.