Rheumatology 2001; 40: 928-932
© 2001 British Society for Rheumatology
Paediatric Rheumatology |
Changes in the incidence of juvenile rheumatoid arthritis in Finland
Paediatric Rheumatology/Series Editor: P. Woo
Department of Medicine, Kuopio University Hospital, Kuopio and
1 Rheumatism Foundation Hospital, Heinola, Finland
Abstract
Objective. To study trends in the incidence of juvenile rheumatoid arthritis (JRA).
Methods. The study covered subjects who were entitled under the nation-wide sickness insurance scheme to receive specially reimbursed medication for juvenile rheumatic diseases in 11 of 21 central hospital districts in Finland (the base population comprised about 445 000 children <16 yr of age) in 1995. Data from the years 1980, 1985 and 1990 were compared with data from 1995 concerning the central part of the area, which had been included in a previous study by us.
Results. A total of 87 incident cases (58 girls and 29 boys) satisfied criteria for JRA in 1995 in the study area. The incidence of JRA was 19.5 per 100 000 [95% confidence interval (CI) 15.6–24.1] of the population <16 yr of age for the whole area. It was 22.7 per 100 000 (95% CI 17.3–29.2) for the area that had been covered by the earlier study (five districts) and 14.9 per 100 000 (95% CI 9.8–21.7) for the new area (six additional districts). The incidence of JRA was significantly higher than in the earlier years (1980, 1985 and 1990) in the same district (trend, P=0.024). The highest incidence, 60.3 per 100 000 (95% CI 35.8–95.4), was noted in 1995 among girls in the age group 10–15 yr in the southernmost part of the study area.
Conclusions. There was both temporal and regional variation in the incidence of JRA. Results of the present study suggest that environmental factors may influence the frequency of JRA.
KEY WORDS: Juvenile arthritis, Incidence, Epidemiology.
The prevalence of juvenile rheumatoid arthritis (JRA) or juvenile chronic arthritis (JCA) has been estimated to be about 0.1% [1–5] and its incidence has varied in population based studies from 10 to 23/100 000 in the child population [3–9]. JRA has been defined as arthritis of one or more joints persisting for at least 6 weeks [10] and JCA has been defined as arthritis of one or more joints for at least 3 months [11]. In contrast to JRA, JCA also includes juvenile ankylosing spondylitis, juvenile psoriatic arthritis and arthritis in association with inflammatory bowel disease.
A predominance of girls presenting with JRA has been noted in studies from Western countries [1–9]. A high incidence of juvenile arthritis (47/100 000) was reported among Alaskan Inupiat Eskimo boys [12]. In this series, all six patients were male, 
9 yr of age, and five had spondyloarthropathy.
Secular trends in the incidence of JRA may help to uncover causative associations. Cyclical patterns in the incidence of JCA/JRA have been noted in Sweden [4], Canada [13] and Rochester, Minnesota, USA [14]. Infectious agents have been proposed as environmental triggers of juvenile arthritis. In the Canadian study, increases in Mycoplasma pneumoniae infections were concurrent with peaks in the incidence of JRA [13]. An association between contact with an influenza virus in utero and later development of polyarticular JCA was suggested in the UK [15]. A decrease in the incidence of JRA in the 1980s was reported from Rochester, but it may have reflected a change in clinical practice [14].
In the present work we continued to analyse the trends in the incidence of JRA in Finland based on statistics from the nationwide sickness insurance scheme, which covers the entire population. Under this programme there has been special reimbursement for drugs for certain chronic diseases, including chronic inflammatory rheumatic diseases, but, since an amendment in 1994, non-steroidal anti-inflammatory drugs (NSAIDs) have not been included in the group of drugs attracting the higher rate of reimbursement.
Patients and methods
Since 1966, the Sickness Insurance Act has provided reimbursement for the prescription of drugs for certain chronic diseases, including chronic inflammatory rheumatic diseases [in 1995, 75% of the costs of disease-modifying anti-rheumatic drugs (DMARDs) and corticosteroids were reimbursed]. The entitlement is usually for life among adults, but among children it is often for a fixed period.
Eligibility requires a comprehensive medical certificate written by the attending physician and approved by an expert adviser on behalf of the sickness insurance scheme. All inflammatory joint diseases and connective tissue diseases are grouped under one code in the population register of the Social Insurance Institution. The main diagnostic subsets are rheumatoid arthritis, juvenile chronic arthritis, ankylosing spondylitis, chronic reactive arthritis, psoriatic arthritis and connective tissue diseases.
Finland is divided into five university hospital regions, which cover 21 central hospital districts. Each university hospital works both as a central hospital and also as a university hospital for its neighbouring district. The study embraced subjects entitled to specially reimbursed medication in 1995 in 11 central hospital districts (Hämeenlinna, Joensuu, Jyväskylä, Kotka, Kuopio, Lahti, Mikkeli, Savonlinna, Seinäjoki, Tampere and Vaasa). The central part of this area (the central hospital districts of Jyväskylä, Kotka, Kuopio, Lahti and Tampere) had also been included in our previous study [8]. The study area consists of the university hospital regions of Kuopio (the central hospital districts of Joensuu, Jyväskylä, Kuopio, Mikkeli and Savonlinna) and Tampere (the central hospital districts of Hämeenlinna, Lahti, Seinäjoki, Tampere and Vaasa) and the central hospital district of Kotka, which is a part of the university hospital region of Helsinki. The whole country was not included in the study because this study was an extension of our earlier study concerning all age groups.
Children with chronic arthritis are primarily referred to central hospitals and, when needed, to university hospitals, which serve as secondary care centres, or to the Rheumatism Foundation Hospital, Heinola, which acts as the tertiary care centre for the whole country. The study area covered 1 797 286 inhabitants (445 856 of whom were <16 yr of age; 264 916 lived in the five districts included in the previous study).
Information on the patients was obtained from the drug reimbursement certificates. Copies of the certificates were collected from separate local offices of the Social Insurance Institution. Certificates were written mostly by paediatricians. If they proved insufficient for classification purposes, additional information was obtained from hospital records. Juvenile arthritis was the reason for entitlement in 95 cases in the group <16 yr of age in 1995.
The patient was defined as an incident case of JRA if his or her age at diagnosis was <16 yr and if he or she met the American College of Rheumatology classification criteria for JRA [10] and had no prior entitlement to anti-rheumatic medication for a fixed period. Although the term ‘juvenile idiopathic arthritis’ has recently been proposed and criteria for it have been published [16], we used criteria for JRA because this study was an extension of our previous study [8]. As in the previous study, classification into subtypes was done at the time of diagnosis as follow-up information was not available because of the nature of the data collection method.
The patient was defined as an incident case of juvenile spondyloarthropathy if he or she had back pain and signs of sacroiliitis or enthesopathy-related arthritis or if he or she had inflammatory arthritis associated with psoriasis. For the present purposes the date on the drug reimbursement certificate was taken as the date of diagnosis. All patients with JRA had had symptoms for more than 6 weeks but less than 3 yr (mean 6 months, median 5 months).
Information on the age distribution of the population in the central hospital districts included in the study was obtained from the Finn Region database maintained by Statistics Finland at VTKK Group Ltd (formerly the State Computer Centre) with the help of Raimo Tuomainen.
Statistical analysis
Statistical analysis was done using the SPSS/PC+ program (SPSS, Chicago, IL, USA). Confidence intervals (CI) were calculated using the Poisson distribution. The significance of the relationship between the incident cases and the time period was tested by the use of the Mantel–Haenszel (log-rank) test for linear association. The difference in the mean age at diagnosis between the study years was tested by analysis of variance (ANOVA).
Results
A total of 87 incident cases satisfied the criteria for JRA in 1995. The annual incidence of JRA was 19.5/100 000 (95% CI 15.6–24.1) of the population <16 yr of age; in the previous study area it was 22.7/100 000 (95% CI 17.3–29.2) and in the new area it was 14.9/100 000 (95% CI 9.8–21.7). Five children had spondyloarthropathy and the incidence of juvenile spondyloarthropathy was 1.1/100 000 (95% CI 0.4–2.6) for the whole area. Of these five patients, four were girls. Two of them had psoriasis of the skin and three had sacroiliitis and/or enthesopathy-related arthritis. Three additional children had prolonged reactive arthritis: a 3-yr-old HLA B27-negative girl with increased antibodies against Yersinia, a 13-yr-old boy with arthritis after Salmonella infection and a 15-yr-old HLA B27-positive girl with conjunctivitis, arthritis and enthesitis of the Achilles tendon. The incidence rates of JRA in different central hospital districts are shown in Table 1
and Fig. 1. The incidence rates and the mean and median ages at diagnosis in the five central hospital districts included in our previous study are given in Table 2.
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The mean age at diagnosis in 1995 was 9.0 yr for cases in all 11 districts and 9.2 yr for the patients in the five central districts. There was an increase in the mean age at diagnosis in 1995 compared with the mean ages in the previous study years, but the increase was not statistically significant (P=0.064). The median age of patients in the area of our previous study was exceptionally high (10.4 yr). At diagnosis, 65 children (75%) had pauciarticular, 18 (20%) had polyarticular and four (5%) had systemic disease. The incidences of pauciarticular, polyarticular and systemic disease were 14.6 (95% CI 11.3–18.6), 4.0 (95% CI 2.4–6.4) and 0.9 (95% CI 0.2–2.3)/100 000 respectively. There were no cases with rheumatoid factor-positive polyarthritis. In the JRA group, four patients (5%) had uveitis at diagnosis and 29 patients (33%) had positive tests for antinuclear antibodies. Typing for HLA B27 was performed in 51 instances, i.e. about half of the patients with both pauciarticular and polyarticular disease. Seventeen cases (33%), 11 with pauciarticular and six with polyarticular disease, were positive for this allele. In the age group 10–15 yr, the HLA B27 allele was detected in half of the examined cases (15/29), and it was equally common among both sexes.
The incidence of JRA varied from 7.7/100 000 (95% CI 0.9–27.8) to 47.3/100 000 (95% CI 20.4–93.2) among girls and from 3.8/100 000 (95% CI 0.1–20.9) to 22.1/100 000 (95% CI 8.1–48.1) among boys in the different central hospital districts. The highest incidence was noted in the three southernmost central hospital districts. The incidence in these districts was especially high among girls in the age group 10–15 yr [60.3/100 000 (95% CI 35.8–95.4)].
Discussion
The incidence of JRA was 22.7/100 000 of the child population, which is higher than in our previous study from the same area [8] but of the same order of magnitude as the incidence figures presented in an earlier Finnish study [6] and in a study from Norway [4]. An increase in the incidence was noted in three southern central hospital districts in the area of our previous study. Entitlement to drug reimbursement has been granted to virtually all children with chronic inflammatory rheumatic diseases [17]. No changes had occurred in reimbursement practice during the study period. The mean and median period of time from symptom onset to diagnosis were similar to figures recorded in our previous study. The change in reimbursement practice since 1994 concerning NSAIDs may have had some influence on the present figures. However, prolonged treatment with only NSAIDs for JRA of pauciarticular onset is uncommon in Finland and children with polyarthritis are always treated with DMARDs. A few children with very mild pauciarticular disease may have received NSAIDs as their only treatment, and in such cases no certificates were written. Thus, the notable increase in incidence cannot be explained by changes in clinical practice. Had children receiving a regimen of only NSAIDs been included, the figures would have been even higher.
The increase in the incidence occurred in both the pauciarticular and the polyarticular group but not in the systemic JRA group. In the Rochester study, the incidence in the polyarticular group was stable whereas it decreased in pauciarticular and systemic disease [14]. Although the disease subtype could be classified only tentatively at diagnosis, the distribution of the cases was comparable with those in other community-based incidence studies [3–9, 14]. In the Lahti area, where the Rheumatism Foundation Hospital is located and where many consultant services are available, the incidence in the previous study years did not differ from that in the other central hospital districts. There is a university hospital in both Kuopio and Tampere, which lie 300 km apart. The incidence in their surrounding central hospital districts did not differ notably before 1995. Thus, the increase in the incidence in the defined geographical area is not explained by referral bias.
A cyclical pattern of the incidence of JCA has been noted in some studies [4, 13–14]. It has been suggested that presensitization to an influenza virus may lead to the development of JCA following exposure to a different but related subtype of the same virus [15]. We had incidence figures from given areas only at 5-yr intervals; therefore, details of the reported peak remain elusive. Such a peak might have occurred only in 1995. In Finland there are periodic reports on infectious agents from certain laboratories collected by the National Public Health Institute, but this system is not sensitive enough to reveal infections causing small local epidemics. However, there was no seasonal peak in the occurrence of new cases of JRA.
The highest incidence occurred among girls in the age group 10–15 yr in the three southernmost central hospital districts. It has been reported that genetic factors can contribute to the risk of JRA, and may do so in opposite ways at different ages [18]. The frequency of HLA B27-positive cases was increased in older children with pauciarticular JRA. In our series, 50% of the tested patients in the age group 10–15 yr were positive for this allele. In community-based studies, HLA B27 has been detected in 27–36% of cases with JRA in Finland [6, 19] and in 42% of cases in northern Norway, where it was equally common among the sexes [4]. Its occurrence is of the same order of magnitude as among patients with rheumatoid arthritis in Finland [20, 21]. However, no regional differences in the occurrence of HLA B27 have been reported in Finland. In Joensuu district the incidence of JRA was also high, but there was no such age predominance as was found in the three southernmost districts. Age-associated temporal and regional changes in the incidence might reflect environmental triggers of juvenile arthritis. However, some of the variation in the incidence rates can be explained by the small number of cases. Continued surveillance of new cases at the local and national level may provide clues concerning triggering agents.
Notes
Correspondence to: O. Kaipiainen-Seppänen, Department of Medicine, Kuopio University Hospital, PO Box 1777, 70211 Kuopio, Finland. 
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