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Rheumatology 2001; 40: 1256-1261
© 2001 British Society for Rheumatology
Original Papers |
The prevalence and incidence of peripheral arthritis in patients with inflammatory bowel disease, a prospective population-based study (the IBSEN study)
1 Department of Rheumatology, Østfold Central Hospital, N-1701 Sarpsborg,
2 Department of Rheumatology, Institute of Clinical Medicine, University of Tromsø, N-9038 Tromsø,
3 Department of Gastroenterology, Østfold Central Hospital, N-1603 Fredrikstad and
4 Department of Gastroenterology, Aker University Hospital, N-0514 Oslo, Norway
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Abstract |
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Objectives. To estimate the occurrence of peripheral arthritis (PA) 6 yr after diagnosis of inflammatory bowel disease (IBD).
Methods. In a population-based cohort of 654 patients with a definite diagnosis of IBD, 521 patients (80%) were clinically examined by a rheumatologist 6 yr after IBD diagnosis.
Results. PA related to IBD (PAIBD) was detected at examination in four patients (point prevalence 0.8%). If the patients’ own reports of PA were accepted, 12% of the cases had developed such manifestations. The striking difference may be explained by the nature of PAIBD exhibiting a short-lasting, self-limiting, non-destructive course and by possible differences in the validity of both methods of ascertainment.
Conclusion. Our results indicate that PAIBD occurs in a considerable number of IBD patients during the first years after diagnosis, but the point prevalence of PAIBD is low.
KEY WORDS: Arthritis, Crohn's disease, Epidemiology, Extra-intestinal manifestations, Incidence, Inflammatory bowel disease, Peripheral arthropathy, Prevalence, Ulcerative colitis.
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Introduction |
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Peripheral arthritis (PA) is observed rather frequently in inflammatory bowel disease (IBD) and it is usually classified as a part of the seronegative spondyloarthropathy complex. The arthritis involves predominantly the joints of the lower limbs, and in most cases it accompanies the activity of the intestinal disease. Usually a pauciarticular, asymmetric, migratory and non-deforming joint disease is observed [1]. In patients with IBD, PA is reported in 0.4–34.6% [2], the variation most likely reflecting differences in selection of cases for study. In some surveys, patients were selected from tertiary referral centres of medicine or surgery, whereas other studies have been based on cases seen in populations or general hospitals. Furthermore, the duration of IBD varies considerably in the studies, a factor of particular importance when estimating the cumulative occurrence of PA [3]. Finally, in some studies, PA was not defined or did not correspond to current definitions of inflammatory joint disease [4, 5]. It was therefore of interest to estimate the present and cumulative occurrence of PA 6 yr after IBD diagnosis in a population-based group of patients.
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Materials and methods |
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TopAbstractIntroductionMaterials and methodsResultsDiscussionReferences |
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Study population
All newly diagnosed cases of IBD or possible IBD between 1 January 1990 and 31 December 1993 in four well-defined areas in southeastern Norway (the counties of Oslo, Østfold, Telemark and Aust-Agder) were recorded by the local departments of gastroenterology. To ensure complete ascertainment, all 1236 general practitioners and clinicians at the 14 hospitals of the four participating counties received information about symptoms consistent with IBD, and were invited to refer all potential cases of ulcerative colitis (UC) or Crohn's disease (CD) to the local gastroenterological out-patient clinic. The information was given prior to the start of the study by three written reminders. In addition, information about the study was presented at local meetings and also practising gastroenterologists, internists, surgeons and paediatricians were informed of the study. The total study population was 966 427 on 1 January 1992.
Endoscopy was chosen as the main instrument for diagnosis and for determining the distribution of disease in the colon. At IBD diagnosis, all patients were evaluated by gastroenterologists concerning rheumatic complaints, and cases diagnosed as IBD-associated rheumatic disease were registered. A total of 618 cases diagnosed as UC and indeterminate colitis and 225 cases of CD were diagnosed, revealing an annual incidence of 13.6/100 000, which is consistent with the high incidence reported in other studies in Norway and Scandinavia in the 1970s and 1980s. The annual incidence was similar throughout the study period, indicating complete ascertainment [6, 7]. In a follow-up between 1 and 2 yr later, the diagnoses were re-evaluated. Ninety-eight per cent were available for follow-up. Four per cent were excluded, as the diagnosis of IBD could not be definitely confirmed [8].
In a second follow-up 5 yr after inclusion, all cases were reviewed by gastroenterologists and patients without confirmed diagnoses of UC or CD were excluded along with patients who had died [9]. The remaining patients (454 with UC and 200 with CD) were invited to a structured interview and clinical examination by a rheumatologist. A total of 521 patients responded to the invitation and underwent a clinical examination (Table 1
). Information on the remaining 133 patients (33 patients had moved out of the area, 23 patients suffered from concomitant serious illness or old age, and 77 patients did not respond to the invitation) was based on hospital records, telephone interviews, mailed questionnaires and case notes.
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Diagnostic criteria and grading classification of intestinal disease
Uniform methods and diagnostic criteria were applied. The initial classification of UC and CD required symptoms consistent with IBD for more than 4 weeks, excluding infections and other acute or chronic non-IBD.
The diagnosis of UC was based on the presence of at least three of the following criteria: (1) a history of diarrhoea and/or blood/pus in stools; (2) macroscopic appearance by endoscopy with continuous mucosal inflammation affecting the rectum in continuity with some or all of the colon; (3) microscopic features on biopsy compatible with UC; (4) no suspicion of CD at small bowel X-ray, ileoscopy or biopsy [6].
The diagnosis of CD was based on established criteria [10] as follows: (1) typical clinical features including abdominal pain, diarrhoea and weight loss; (2) macroscopic appearance at surgery or endoscopy; segmental, discontinuous and/or patchy lesions with or without rectal involvement, discrete or aphthous ulcerations, fissuring and penetrating lesions, cobblestone or strictures; (3) radiological evidence of stenosis in the small bowel, segmental colitis or findings of fistulae; (4) histological evidence of transmural inflammation or epithelial granulomas with giant cells. Two or more of these criteria were required for the diagnosis of CD.
The extent and localization of colonic disease were based on endoscopical findings with characteristic histological signs of inflammation. Proctitis was defined as mucosal changes in the rectum up to 15 cm from the anus, left side colitis up to the splenic flexure and, finally, inflammation beyond the splenic flexure was classified as extensive colitis. When the extent of disease changed during follow-up, the maximum extent of bowel involvement was recorded. The patients with CD were classified according to the Vienna classification [11].
Diagnostic criteria of arthritis and other extra-intestinal disease
Arthritis was defined as at least one anamnestic or current episode of pain, swelling and increased skin temperature in one or several joints. PA diagnosed at the clinical examination and peripheral joint disease diagnosed by disease history were recorded separately. X-rays were performed when clinical findings were suggestive of erosive arthritis. The diagnoses of rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, reactive arthritis and gout were based on both present and past clinical findings and followed standard diagnostic criteria [12]. PA was considered associated with IBD when other causes of joint disease were ruled out. Dactylitis was diagnosed when typical findings of sausage fingers or toes due to inflammation had been present. Enthesopathy was diagnosed when signs of inflammation of the insertion of the tendon to the bone had been present without preceding infection or trauma.
Erythema nodosum was diagnosed when tender, bluish-red nodules (mainly on the extensor side of the limbs) were observed and pyoderma gangrenosum when typical chronic ulcers with undermined necrotic bluish margins persisted for several weeks or longer. Uveitis was recorded when diagnosed by an ophthalmologist. The diagnosis of sclerosing cholangitis was based on typical findings at endoscopic retrograde cholangiography.
Ethics
The study was approved by the Regional Ethics Committee and the Norwegian Data Registry. Confidentiality of both patient identity and records was maintained, using guidelines suggested by the National Health Department.
Statistics
Fisher's exact test and 
2 test were used for statistical analyses and a P value of less than 0.05 was regarded as significant.
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Results |
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Findings at clinical examination and direct interview
Occurrence of PA
PA was found in 18 of the 521 patients (3.5%) clinically examined. Additionally, 66 patients had PA according to disease history, suggesting a cumulative occurrence of PA in 84 patients (UC=51, CD=33) (16%). However, PA was related to other rheumatic diseases in 22 cases (rheumatoid arthritis in five patients, ankylosing spondylitis in seven patients, reactive arthritis in three patients, psoriatic arthritis in three patients, SAPHO syndrome in one patient and gout in three patients). These patients (13 UC, nine CD) were excluded from further analyses. Consequently, 62 patients with PA related to IBD (PAIBD) were found, suggesting a cumulative occurrence of PAIBD of 12%. Four of the patients (0.8%), two with UC and two with CD, had arthritis detected at examination. At IBD diagnosis 6 yr earlier, 38 patients (4.5%) had PAIBD according to gastroenterologists, current or disease history. Age at onset of the disease and occurrence rates are listed in Table 2
.
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Characteristics of PAIBD
In patients with PAIBD, the arthritis occurred before the onset of IBD in 11 patients (18%) and after the onset of bowel disease in 48 patients (77%) (Table 2
). In 5% of the cases, reliable information was not available to establish correctly the onset of arthritis. In three patients with PAIBD (5%), arthritis had occurred in five joints or more. The knees were affected in 34 cases (55%), ankles in 22 cases (35%) and the joints of fingers and toes in 11 cases (18%). Symmetrical arthritis had been present in 22 patients (35%) of whom fingers or toes were affected in only three cases.
The duration of arthritis was less than 4 weeks in 34 patients (55%). In 13 patients (21%), arthritis had lasted for 6 months or more and in three cases information regarding the duration of arthritis was not available. No difference in duration of PAIBD between UC and CD was seen (data not shown). In the subgroup of patients with ongoing PAIBD at examination, all had relapsing arthritis of knees or ankles with a duration of less than 4 weeks.
Radiological examinations of peripheral joints were performed in six patients. With the exception of two cases having coexisting osteoarthritis (in knee joints), no signs of destruction or erosions were found.
Tests for serum rheumatoid factors were performed in 61 patients (98%) and were negative in all.
Association with intestinal and extra-intestinal manifestations
The distribution of gastrointestinal inflammation was similar in patients with and without arthritis in both UC and CD. PAIBD was associated with extra-intestinal manifestations as shown in Table 3. Dactylitis and erythema nodosum occurred significantly more often in patients with PAIBD compared with patients without inflammatory joint disease (Table 3).
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Present systemic medication
The use of 5-aminosalicylic acid, sulphasalazine and corticosteroids was similar in patients with and without PAIBD (Table 3).
Findings based exclusively on hospital charts, telephone interviews and mailed questionnaires
In the 133 cases (32 patients with CD and 101 with UC) who were not clinically examined for possible joint disease, hospital charts were reviewed. PA was recorded in 10 patients (8%) of whom one patient (UC) suffered from rheumatoid arthritis, one (UC) had ankylosing spondylitis and two patients (UC and CD) had gout. Thus, in six cases (5%) PA was related to IBD. All patients had developed arthritis after the onset of IBD. The knees were affected in five patients, and one had arthritis of the elbow. Extra-intestinal manifestations other than arthritis were not registered.
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Discussion |
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TopAbstractIntroductionMaterials and methodsResultsDiscussionReferences |
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In the present study, the cumulative occurrence of PAIBD was 12%. Of the 62 patients with PAIBD, present inflammatory joint disease was detected at examination in only four patients (point prevalence 0.8%), whereas in 58 cases the occurrence of PAIBD was based on patients’ reports exclusively. IBD-associated joint disease is typically transient, usually lasting for only a few weeks and responding to treatment of the underlying intestinal disease [2, 13]. The striking difference between the point prevalence and the cumulative occurrence observed may thus be explained by the nature of PAIBD, particularly the short duration of such manifestations. Additionally, differences in validity between a patient's disease history and clinical examination by a rheumatologist may have influenced the results.
The cumulative occurrence of 12% found in the present study indicates that PAIBD affects a significant proportion of IBD patients. This occurrence, however, is clearly lower than that found in two previous studies (16.2 and 23%) [3, 4]. The diverging results may be explained by methodological differences, as the latter studies were based on patients attending referral centres and university clinics as opposed to the present population-based study. According to Berkson's bias [14], hospitalized patients tend to reveal a higher degree of association between the two disorders than that found in the general population. Furthermore, patients attending university clinics or other referral centres may represent more severe and complicated cases, which may increase the estimated occurrence of PAIBD. Such a relationship is supported by our findings of an increased incidence of erythema nodosum in patients with PAIBD compared with those without PAIBD (Table 3). Thus, the differences between the various studies estimating the occurrence of PAIBD are most likely due to different study designs.
In agreement with previous studies [3, 15], a trend towards a higher rate of PAIBD in patients with CD (14%) compared with those with UC (11%) was found. However, in our study the difference did not reach statistical significance, which may be explained by a rather low number of patients included.
Due to the frequent lack of information regarding arthritis, calculations of PAIBD based on a review of hospital records may result in under-estimations. It is noteworthy that in the present study, a lower cumulative occurrence of PAIBD of 5% was found when the results were based on hospital records of patients lost to follow-up. In the large survey by Orchard et al. [15] based on case notes, a comparable incidence of PAIBD of 6% was found. Thus, the true prevalence and incidence of PAIBD should preferably be based on longitudinal surveys of the total population of patients with IBD, and ideally with multiple and consecutive clinical joint examinations.
In the present patient cohort, a previous evaluation by gastroenterologists revealed that PAIBD at the time of IBD diagnosis had occurred in 4.5% of the patients. Although these data were not confirmed by rheumatologists, they may indicate an increasing cumulative occurrence of PAIBD from 4.5% at IBD diagnosis to 12% 6 yr later. Veloso et al. [3] found that the cumulative probability of having at least one extra-intestinal manifestation of IBD increased from 12 to 30% during a 20-yr follow-up period. Thus, the duration of IBD seems to be of great importance when estimating the cumulative incidence of PAIBD, and should be considered when results from different investigations are compared.
The distribution of the gastrointestinal inflammation was similar in patients with and without PAIBD in both UC and CD. Previous studies have shown conflicting results, as early studies indicated an association between the incidence of PA and the extent of bowel inflammation in UC [16]. These findings have, however, not been confirmed by subsequent investigations [3, 15]. In patients with CD, colonic involvement seems to indicate an increased risk of PAIBD [3, 4, 17]. The same tendency was seen in the present study, possibly indicating that involvement of the distal part of the large bowel plays a critical role in the development of PAIBD.
The distribution and characteristics of peripheral joint involvement in our study were similar to those found in previous surveys [13]. It has recently been suggested that PAIBD can be classified into two types, type 1 (pauciarticular) and type 2 (polyarticular), distinguished by the number of joints affected, joint distribution, natural history and disease associations [15, 18]. In our patients with PAIBD, however, few had polyarticular involvement and only a small number of these had a duration of arthritis exceeding 1–2 months. Thus, no patient fulfilled the proposed definition of type 2 arthropathy. The majority of the patients with PAIBD could be classified into type 1 arthropathy and their articular involvement was similar to that described in previous studies [2]. However, the interesting findings made by Orchard et al. [15] were not confirmed in our study. As their study was based on patients attending a referral centre, different study designs may explain the different results, but further studies are required to estimate the prevalence of type 1 and type 2 arthritis in different populations of IBD patients.
Some methodological issues of our study should be discussed. First, the vast majority of cases with PAIBD were identified by disease history. In spite of direct patient interviews by a rheumatologist, we cannot exclude the possibility that information regarding past episodes of arthritis could, in some cases, have been incorrectly interpreted. Although patients who reported PAIBD usually provided a detailed description of the joint manifestations, we cannot completely rule out some over-ascertainment of PAIBD incidence. Second, the cumulative occurrence PAIBD found in the present study should not be compared with patients with longstanding IBD, due to the short disease duration. To calculate life time risks of PAIBD, further studies are required, preferably those designed as prospective population-based surveys.
In conclusion, in this population-based cohort of IBD patients with a disease duration of 6 yr, PAIBD occurred in a considerable number of IBD patients. The point prevalence of PAIBD was, however, very low, probably due to the nature of the arthritis, showing a short-lasting, self-limiting, non-destructive course. In a few cases, PAIBD was the initial symptom of IBD, while there was no correlation between the distribution of the gastrointestinal disease and PAIBD. Further follow-up of the present patient population will provide information regarding the incidence and characteristics of inflammatory joint disease developing in longstanding IBD as well as the impact of PAIBD on the final outcome.
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Acknowledgments |
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The authors wish to thank the following members of the IBSEN study group of gastroenterologists in Norway for gastroenterological investigations and advice: Jostein Sauar (TSS Skien), Idar Lygren (Ullevål University Hospital, Oslo), Erling Aadland (Aker University Hospital, Oslo), Tom Schulz (ASA Arendal), Njål Stray (Diakonhjemmets Hospital, Oslo), Erik Aubert, Per Sandvei, Magne Henriksen, Per Tolås (Hospital of Østfold, Moss, Fredrikstad and Halden), Kjell Hebnes (Volvat Medical Centre, Oslo), Ø. Kjellevold (Notodden and Rjukan Hospital), Per Dyrkorn (Kragerø Hospital), Morten Vatn and Olav Fausa (The National Hospital, Oslo), Tomm Bernklev (Sandefjord). The study was supported by The Research Council of Norway, The Norwegian Women Public Health Association, The Norwegian Rheumatism Association, Lions Clubs International Norway, Astra Norway AS, Nycomed Pharma AS, Østfold Hospital Research Foundation.
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Notes |
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Correspondence to: Ø. Palm.
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