Results

Tables 1 and 2 show the general characteristics of the IBD population. Only three patients with ulcerative colitis and one with Crohn’s disease were diagnosed as having psoriasis. Coincident joint disease was present in 83 patients with ulcerative colitis and 21 with Crohn’s disease, and included osteoarthritis, seropositive rheumatoid arthritis, gout, lumbar disc problems, and trauma. Rheumatoid factor was checked in 82% of patients with type 2 arthropathy and was negative in all cases. In both groups of peripheral arthropathy no patients had destructive bony lesions and the clinical course was not compatible with either rheumatoid or crystal arthropathies, and none of the patients required joint replacement. Table 3 shows the prevalence of joint disease related to the IBD. Figures for inflammatory back pain and ankylosing spondylitis are included for the sake of completeness but were not analysed in the context of peripheral arthropathies. Women were significantly more likely to develop both type 1 (p=0.009) and type 2 arthropathy (p=2.3×10⁻⁵). Ankylosing spondylitis occurred in 0.9% of patients with ulcerative colitis and 1.2% of those with Crohn’s disease, 50% of whom had peripheral joint involvement. The median length of follow up of patients with peripheral arthropathy (10.1 years in ulcerative colitis and 10.3 years in Crohn’s disease) was similar to that of the population as a whole (10.7 years in ulcerative colitis and 10.2 years in Crohn’s disease).

In a small number of cases the arthropathy either predated the diagnosis of IBD or was present at the time of diagnosis. In type 1 arthropathy five (14%) of 35 patients with ulcerative colitis and three (10%) of 29 with Crohn’s disease had an acute self-limiting arthropathy 10–36 months before diagnosis. In a further six (17%) of 35 with ulcerative colitis and four (14%) of 29 with Crohn’s disease it was present at the time of diagnosis. Type 2 arthropathy was rarely apparent before diagnosis in ulcerative colitis (n=1) or at the time of diagnosis (n=1). Two (10%) of 20 patients with Crohn’s disease developed the arthropathy before diagnosis and in a further five (25%) it was present at the time of diagnosis. Most patients, therefore, developed the joint complications after the diagnosis of IBD had been made, and overall the likelihood of developing the joint complications did not increase with the length of follow up.

Figure 1 shows the distribution of the peripheral arthropathies. Type 1 arthropathy was asymmetrical in 80% of patients with ulcerative colitis and in 76% of those with Crohn’s disease. By contrast, type 2 arthropathy was symmetrical in 83% of patients with ulcerative colitis and 79% of those with Crohn’s disease—a significant difference for both diseases with at p=5.9×10⁻⁶ in ulcerative colitis and p=0.0006 in Crohn’s disease. The most commonly affected joint in type 1 arthropathy was the knee for both ulcerative colitis and Crohn’s disease; the small joints of the hands were very rarely involved. In type 2 arthropathy the metacarpophalangeal joints (MCP) were most commonly involved, but a wide variety of other joints were also affected.

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Figure 1

Articular distribution of peripheral arthropathies in inflammatory bowel disease. UC, ulcerative colitis; CD, Crohn’s disease; MCP, metacarpophalangealjoint; PIP, proximal interphalangeal joint; DIP, distal interphalangeal joint; MTP, metatarsophalangeal joint.

Table 4 shows the natural history of the peripheral arthropathies. Type 1 is significantly more likely to be associated with relapsing IBD than type 2 for both ulcerative colitis and Crohn’s disease. Similarly type 1 occurs significantly more often as acute, self-limiting episodes than type 2 in ulcerative colitis (83% v 13%, p=2.6×10⁻⁸) and Crohn’s disease (79% v11%, p=1.2×10⁻⁷). These episodes always lasted for less than 10 weeks and resulted in resolution of the joint symptoms. However, the number of episodes was higher in Crohn’s disease: four patients with Crohn’s disease had more than three episodes, whereas none of the patients with ulcerative colitis had more than three. Type 2 arthropathy generally had more persistent symptoms, lasting for a median of three years in both ulcerative colitis and Crohn’s disease.

The distribution of gut involvement in ulcerative colitis was the same in patients with and without arthropathy. In Crohn’s disease there was a trend towards more colonic involvement with type 1 arthropathy but this was not statistically significant.

The joint disease required treatment in the vast majority of cases (97% of type 1 and 95% of type 2). Twenty per cent of patients with both types of arthropathy required only simple analgesia. However, 40% of patients with type 1 and 55% with type 2 arthropathy required treatment with non-steroidal anti-inflammatory drugs (NSAIDs), and in three cases of type 1 arthropathy this preceded the onset of gut symptoms. A large proportion of patients also received glucocorticoid treatment (27% with type 1 and 25% with type 2). Sulphasalazine has been used widely in spondyloarthropathies, but as most patients were already taking it for IBD, its symptom modifying effects were impossible to analyse in IBD arthropathy.

There was a significant association between type 1 arthropathy and erythema nodosum and uveitis in either ulcerative colitis or Crohn’s disease, and an association between type 2 and uveitis only (table 5). There was a trend towards increased surgery in patients with arthropathy and ulcerative colitis which was significant for type 1 if patients who developed the arthropathy after ileal pouch surgery were included (p=0.013). In contrast, patients with Crohn’s disease and type 1 arthropathy were significantly less likely to require surgery (p=0.0004). We felt that this could represent a difference in disease distribution in the gut between patients with and without joint disease. However, there was no significant difference in disease extent in either ulcerative colitis or Crohn’s disease between those with and without arthropathy.

Discussion

This study shows that peripheral arthropathy is a relatively common complication of IBD that frequently requires modification of treatment and often the use of anti-inflammatory drugs which may themselves influence the bowel disease. It also suggests that it is reasonable, on clinical grounds, to subdivide the enteropathic peripheral arthropathy associated with IBD according to the criteria in the box.

Clinically type 1 arthropathy is similar to post-dysenteric reactive arthritis, with most patients having self-limiting disease but about 20% going on to develop persistent problems.17 The arthropathy is commonly associated with an acute relapse of the IBD and responds to treatment with steroids and NSAIDs. In a few cases treatment with NSAIDs started before the acute relapse, raising the possibility that in a minority of cases ingestion of NSAIDs might have been responsible for the subsequent relapse. Type 1 arthropathy is also strongly associated with other extraintestinal manifestations, such as erythema nodosum and uveitis.

The natural history and clinical associations of type 2 arthropathy are different, particularly if those patients with acute, self-limiting joint disease are ignored (these account for two of the four cases of uveitis and one of the cases of erythema nodosum in ulcerative colitis, and they all involved a large joint). Similarly in Crohn’s disease this group accounted for one of the cases of uveitis. This suggests that either they were incorrectly categorised owing to inclusion of painful joints that were not swollen, and therefore were not part of the arthropathy (that is, coexisting type 1 arthritis and arthralgia) or that there may be a degree of overlap between the two syndromes. In support of this second possibility one patient who initially had a typical type 1 arthropathy subsequently developed a significant polyarthropathy with joint swelling.

Although both types of arthropathy normally presented after the diagnosis of IBD had been made, 31% of the type 1 arthropathies in ulcerative colitis and 24% in Crohn’s disease presented at or up to three years before the time of diagnosis. Recent studies have suggested that 6% of patients with a seronegative spondyloarthropathy will develop IBD, but that patients with normal gut histology at the time of the arthropathy do not go on to develop IBD.18 ,19 It would therefore seem good clinical practice to obtain a rectal biopsy sample from all patients presenting with an acute “reactive” arthritis, particularly if associated with diarrhoea, and further gut investigation should be pursued if the bowel disturbance is persistent. Type 2 arthropathy predated the diagnosis of Crohn’s disease in two patients but the diagnosis was made within six months as part of a general clinical work up.

Previous studies of peripheral arthropathy in IBD have failed to show any link with possession of HLA-B27,6 ,7 ,13 ,14 but the numbers were small and all the cases of peripheral joint disease were regarded as a single entity, whereas our study suggests the two arthropathies should be considered separately. In the context of other seronegative arthritides the similarity between type 1 arthropathy in this study and reactive arthritis would suggest that a link to HLA-B27 is likely. In contrast type 2 arthropathy seems to be a distinct entity.

We feel that the cause of IBD is likely to be an interaction between genetic susceptibility and environmental factors.20 It is also probable that there is genetic heterogeneity within the disease that defines its phenotypic characteristics,20 ,21although defining the precise phenotypic links has been difficult. This study demonstrates the existence of two distinct forms of peripheral arthropathy in IBD that can be distinguished by a simple classification. Use of this system may help to predict the clinical course of the joint disease and may be used as the basis of further studies of its aetiology.