Extraintestinal Manifestations of Inflammatory Bowel Disease

Nathan J. Shores

Richard S. Bloomfeld

INTRODUCTION

The nature and scope of gastrointestinal (GI) symptoms related to inflammatory bowel disease (IBD) is obviously the primary focus for patients and their physicians; however, up to 36% of IBD patients experience extraintestinal manifestations (EIMs) of disease (1,2). Although nonintestinal sequelae of IBD have been reported in nearly every organ system (including cardiovascular, pulmonary, hematologic, and renal), arthropathies, dermatologic ailments, and ocular disease are the most commonly encountered.

ARTHROPATHIES

IBD-related arthropathies are traditionally divided into peripheral and axial disease (spondyloarthropathy). As opposed to arthralgias, swelling, redness, and/or radiographic damage of the involved joints are required in addition to pain to make the diagnosis of arthritis. The peripheral arthritides can be further categorized by the pattern of joint involvement. In general, the best approach to arthropathy is to first confirm effective treatment of underlying IBD.

Type 1 (Pauciarticular) Peripheral Arthritis

Type 1 peripheral arthritis typically involves only one or a few large weight-bearing joints such as the ankle or knee (Table 13.1). This so-called oligo- or pauciarticular arthritis reportedly affects 4% to 23% and 6% to 30% of ulcerative colitis (UC) and Crohn’s patients, respectively (1,3, 4 and 5). Because of the erythema, pain, swelling, and joint distribution in these cases, concomitant rheumatoid arthritis, septic arthritis, pseudogout, and gout are often included in the differential diagnosis. Up to 80% of Type 1 peripheral arthropathy patients experience acute, self-limiting symptoms (<10 weeks) (3). When the diagnosis is in doubt, laboratory testing, joint aspiration, imaging, and referral to a rheumatologist may be necessary.

Pauciarticular, enteropathic peripheral arthritis generally parallels the course of intestinal inflammatory disease. Therefore, initiating effective IBD therapy is the best approach to arthropathy management. Data exist to support the use of systemic steroids, azathioprine (AZA)/6-mercaptopurine (6-MP), sulfasalazine, and biologic therapies. Early infliximab and adilimumab trials provide anecdotal data that anti-TNF agents effectively treat arthritis in IBD patients. An open-label study of infliximab later confirmed significant improvement in joint complaints in 61% of subjects and complete resolution in 46% (4). Standard infliximab dosing was used.

Type 2 (Polyarticular) Peripheral Arthropathy

Unlike pauciarticular arthritis, Type 2 (polyarticular) peripheral arthropathy involves smaller, more numerous (≥5) joints in the hands and feet symmetrically. This affects 6% to 25% of IBD patients, and the overt signs of arthritis are not usually present (1,3, 4 and 5). Thus, pain is often disproportionate to physical examination. Unfortunately, polyarticular disease does not typically improve as intestinal symptoms are effectively managed. In 83% of patients, pain may persist for months or
years despite the treatment of intestinal disease, including cases of small bowel resection and colectomy (1,3). We first recommend supportive care with ice and rest. Failure of conservative measures poses a therapeutic challenge, since other widely accepted arthritis treatments, such as nonsteroidal anti-inflammatory drugs (NSAIDs), may exacerbate intestinal disease activity. In the case of UC, where evidence supports aminosalicylate use to achieve and maintain remission of colonic symptoms, some clinicians capitalize on sulfasalizine’s antiarthritic properties (5). Two recent placebo-controlled trials of the selective COX-2 inhibitor, celocoxib, observed no increase in luminal inflammation in a cohort of patients with quiescent IBD at the outset (6, 7 and 8). These data suggest that a brief course of celocoxib (200 mg twice a day for 14 days) may be safe for the GI tract in enteropathic arthritis.

TABLE 13.1 Clinical Characteristics of IBD-related Arthropathy

Arthropathy	Clinical Characteristics	Treatment Options	Role of Referral
Pauciarticular arthritis	<5 joints Weight-bearing joints Parallels luminal activity May be seen with EN and uveitis	Treat underlying IBD Systemic steroids Immunosuppression Infliximab NSAIDs^a Celocoxib^a	Optional
Polyarticular arthritis	≥5 joints Small, symmetrical joints Does not parallel luminal activity May be seen with uveitis	Treat underlying IBD Sulfasalazine Acetaminophen NSAIDs^a Celocoxib^a	Optional
Spondyloarthropathy	Sacroiliitis AS Does not parallel luminal disease May be seen with EN and uveitis	Physiotherapy Rest Sulfasalazine Mesalamine Infliximab NSAIDs^a Celocoxib^a	Optional (more often needed with AS)
^aUse NSAIDs and COX-2 inhibitors with caution in IBD.
IBD, inflammatory bowel disease; EN, erythema nodosum; NSAIDs, nonsteroidal anti-inflammatory drugs; AS, ankylosing spondylitis.

Spondyloarthropathy

Spondyloarthropathy is a chronic rheumatologic disease characterized by axial skeleton arthritis. Therefore, unlike the peripheral arthropathies outlined earlier, spondyloarthropathy primarily affects the vertebral column and the sacroiliac joints. Although in most cases spondyloarthropathy occurs in isolation, ankylosing spondylitis (AS) is reported in up to 10% of patients with clinically evident Crohn’s
disease and UC (9). If purely radiologic diagnostic criteria are used, the incidence swells to 23% (10).

Subclinical gut inflammation is found in up to 45% of AS cases in non-IBD patients (11). Although NSAID use could be a confounding factor, concurrent intestinal inflammation raises the question of blood-gut barrier disruption perpetuating axial arthropathy. Also, HLA-B27 prevalence appears increased in the IBD population with concomitant symptomatic sacroiliitis (SI) (12). Despite this, HLA-B27 typing does not have a role in the management of individual patients and routine testing is not recommended in clinical practice.

IBD clinicians generally subdivide spondyloarthropathy into two entities: SI and AS. Low-back pain and morning stiffness are the most common manifestations of spondyloarthropathy in IBD (Fig. 13.1

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