Crohn’s disease and ulcerative colitis (UC) are both associated with a number of extra-intestinal chronic inflammatory diseases. Arthritis is the most common extracolonic manifestation of chronic UC. Patients with Crohn’s disease also have an increased prevalence of inflammatory joint disease although arthritis is more common in patients with colitic disease than small bowel inflammation alone.

The type of arthritis associated with IBD may be either axial or peripheral (Table 1 below). Peripheral joint disease occurs in 10% to 20% of patients with IBD and is not usually associated with HLA-B27. The onset of arthritis either accompanies or follows the onset of the colitis and the activity of the joint disease generally parallels the activity of the IBD. Patients can present with an oligoarthritis (single joint arthritis) but no bowel symptoms and yet have IBD as the cause of their arthritis. The course is usually asymmetric oligoarthritis lasting 2 to 6 weeks and radiographic changes in the joints are rare.

In the case of UC, colectomy results in complete remission of the peripheral arthritis, whereas surgical therapy for Crohn’s disease results in remission of arthritis in only 50% of cases. In contrast, spondylitis and sacroiliitis occur in 2% to 7% of patients with IBD and are generally associated with HLA-B27. Isolated subclinical sacroiliitis has been reported in 24% of patients with IBD, suggesting that axial involvement may be more common than reported previously. The axial disease frequently precedes the onset of GI symptoms, and follows a chronic course which is independent of the activity of the IBD. Surgery has no effect on this axial arthropathy.

In a study of 976 patients with UC and 483 with Crohn’s disease two types of enteropathic peripheral arthropathy were found. Type 1 is a self limited disease with presentation similar to post-dysenteric reactive arthritis, different from the polyarticular (multiple joint) disease with a course independent of the IBD, type 2 (Table 2 below).

The same investigators have studied the association of peripheral arthropathies with certain genetic markers called HLA. Fifty-seven patients with type 1 arthritis and 45 with type 2, who were identified by case note review and questionnaire, underwent genotyping by sequence-specific primer polymerase chain reaction. HLA-B27 was prevalent in 27% of type 1 patients, however, DR1 antigen was present in 33% of type 1 compared with none of type 2 and 3% of 603 controls (P<0.0001). In contrast, type 2 was associated with HLA-B44 in 62% (P=0.01). These data suggest that the clinical classification into type 1 and type 2 arthropathies is consistent with immunogenetically distinct entities and establishes that in polygenic disorders, genes may determine clinical phenotype without conferring overall disease susceptibility.

Management of arthritis in IBD patients relies on good control of the underlying gastrointestinal pathology. Sulfasalazine, azathioprine, glucocorticoids, and methotrexate are widely used; experience with cyclosporine is limited. The Food and Drug Administration has approved tumor necrosis factor-alpha antibody (infliximab - Remicade) for the treatment of Crohn’s disease, which has resulted in a significant improvement of axial and peripheral arthritis related to this disease in early studies.

Low bone mineral density is a recognized complication of IBD. In a study of 34 patients with Crohn’s disease and 50 with UC (49 women and 35 men) underwent a metabolic bone assessment, bone mineral densities were measured by dual energy X-ray absorptiometry of the lumbar spine and femoral neck. Osteopenia was present in 36 patients (43%), 27 of whom were on glucocorticoid therapy. Although no patient complained of muscular or bone pain, 6 patients (7%) had vertebral crush fractures. Risk factors for the development of osteopenia were identified as age, cumulative glucocorticoid doses, increased erythrocyte sedimentation rate, and low osteocalcin level.

Another study conducted on 119 patients with Crohn’s disease (ages 5 to 25 years) showed similar results with hypoalbuminemia, total glucocorticoid exposure, requirement for total parenteral nutrition, and prior use of 6-mercaptopurine being the most powerful risk factors for low bone mineral density (BMD). Patients with IBD should be advised to consume adequate vitamin D and calcium and to participate in a regular weight-bearing exercise program. Therapy with disphosphonates may be necessary as well.

Bone densitometry should be performed, where possible, to identify those in need of treatment, to avoid unnecessary treatment, and to monitor the effect of treatment designed to prevent bone loss. The dose of glucocorticoids should be kept to a minimum, and vitamin D deficiency should be corrected.

Adopted from:

Volume 51, Number 2

Rheumatic Manifestations of Gastrointestinal Diseases

Written by: Ibrahim S. Alghafeer, MD and Leonard H. Sigal, MD