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Epidemiology of rheumatoid arthritis in Finland
Epidemiology of Rheumatoid Arthritis in Finland Kimmo Aho, Oili Kaipiainen-Sepp~inen, Markku Heli6vaara, and ]]mo Klaukka Objectives: To review the work pertaining to rheumatoid arthritis (RA) morbidity in Finland and to compare the data with that available from other countries. Methods: Extensive investigations in Finland of the epidemiology of RA, based on nationwide registers designed primarily for administrative purposes and on extensive population studies, frequently in combination. Results: According to several surveys with somewhat different study designs, the prevalence of clinically significant RA is about 0.8% of the adult Finnish population. Five national health interviews from a 30-year period have revealed figures about 50% higher, but with no clear change in prevalence. The incidence of clinically significant RA is about 40 per 100,000 of the adult population, which is in accordance with the prevalence figures. The mean age at diagnosis increased by 7.6 years from 1975 to 1990. Between 1978 and 1980, 5.8% of the severe disability in the adult Finnish population was attributable to RA. Some evidence suggests that severe disability resulting from RA diminished during the 1980s, possibly because of joint replacement surgery. Conclusions: Monitoring sickness insurance statistics is a useful means of following the epidemiology of RA. Semin Arthritis Rheum 27:325-334. Copyright © 1998 by ltV.B. Saunders Company
INDEX WORDS: Rheumatoid arthritis; incidence; prevalence; disability. N MANY RESPECTS, Finland provides good opportunities for epidemiological research. The population is quite homogeneous and sufficiently large (about 5 million) for investigation of most relevant problems. Attitudes toward researchrelated interviews and examinations are positive and accordingly, participation rates in most surveys are high. The health care system is mainly public and is well organized. In addition, several nationwide registers designed primarily for administrative purposes also can be used for research. Extensive investigations have been undertaken in Finland on various aspects of the epidemiology of rheumatoid arthritis (RA). Recently, mortality studies in RA performed in Finland and elsewhere were reviewed (1). Here, we report the prevalence and incidence of RA in Finland, as well as the disability resulting from this disease, and compare our data with that of other countries.
I
MATERIAL AND METHODS
Finnish Population Although the majority of Europeans speak IndoEuropean languages, about 24 million Europeans speak Finno-Ugric languages, such as Hungarian, Finnish, and Estonian. Based originally on the linguistic relationship of Finnish with languages
spoken by certain ethnic groups in Russia, it has traditionally been thought that the Finns migrated to their current location from a common origin in the East, either in the Altai, the Ural, or the Volga region. Yet studies of nuclear gene frequencies have shown that the greatest proportion of the Finnish gene pool is "European," although Finns appear to differ from other European populations more than Europeans in general differ from each other (2, 3). Recent studies on mitochondrial DNA sequences found that European populations, including Finns, are part of one homogeneous mitochondrial gene pool (4).
From the National Public Health Institute, Helsinki, Department of Medicine, Kuopio University Hospital, Kuopio, and Social Insurance Institution, Helsinki, Finland. Address reprint requests to Kimmo Aho, MD, National Public Health Institute, Mannerheimintie 156, FIN-O0300 Helsinki, Finland. Kimmo Aho, MD: Professor, National Public Health Institute, Helsinki, Finland; Oili Kaipiainen-SeppSnen, MD: Consultant Rheumatologist, Department of Medicine, Kuopio University Hospital, Kuopio, Finland; Markku HeliOvaura, MD: Physician in Chief National Public Health Institute, Helsinki, Finland; Timo Klaukka, MD: Medical Research Officer, Social Insurance Institution, Helsinki, Finland. Copyright © 1998 by W.B. Saunders Company 0049-0172/98/2705-000758. 00/0
Seminars in Arthritis and Rheumatism, Vo127, No 5 (April), 1998: pp 325-334
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The present Finnish population is thought to stem largely from immigration about 2,000 years ago by a small number of settlers. The population subsequently remained isolated with little immigration. Genetic epidemiological studies show that many genetic diseases occur at substantially different frequencies (sometimes higher, sometimes lower) in Finland than in the rest of Europe, as would be expected from a founder effect caused by a population bottleneck (5). In two Finnish series of recent-onset RA patients, HLA-DR4 was present in 54% and in 68% of the cases (6, 7). In a community-based series of RA patients, the DR4 allele occurred in 54% and the shared RA susceptibility epitope in 75% of cases (8). The HLA-B27 allele occurs in the Finnish population more frequently (14%) than in most other European populations. In addition to DR4, B27 also occurs in Finnish RA patients more frequently than in control subjects (9). B27-bearing haplotypes in RA patients were found to carry DR1 and DR4 genes more often than did B27 haplotypes in controls (10). It is probable that the increased frequency of the B27 allele in RA patients is secondary to the increase in D-locus risk alleles, but the possibility cannot be excluded that the susceptibility to RA is enhanced when DR1 or DR4 occurs in haplotypic combination with B27.
Nationwide Registers Several computerized data registers cover the entire Finnish population. Thus, migration does not influence the statistics. Each Finnish citizen has a unique identification code that allows for identification in various registers and linking registers, although this is strictly regulated. Those registers most important for rheumatological research follow. The Population Register Center maintains a file on all Finnish citizens and foreigners living permanently in Finland. Thus, it is possible to determine if the person is alive unless he/she has moved permanently out of the country. One of the duties of Statistics Finland (formerly the Central Statistical Office of Finland) is to maintain the cause-of-death register. Causes of death are classified by Statistics Finland according to International Classification of Diseases (ICD) codes as outlined by the World Health Organization. The final code is not always the same as that marked by the attending physician on the death certificate.
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The Social Insurance Institution has files on disability pensions (grouped according to ICD codes) and on sickness insurance benefits. The Sickness Insurance Act provides for specially reimbursed medication for certain chronic diseases including inflammatory rheumatic diseases. Glucocorticoids, nonsteroidal antiinflammatory, and disease-modifying antirheumatic drugs are reimbursed for rheumatic diseases. This is usually a lifetime entitlement, but can also be for a fixed period. For a patient to be eligible, a comprehensive medical certificate must be written by the attending physician and approved by an expert adviser on behalf of the sickness insurance scheme. The rules for approval are uniform throughout the country. The certificates are written to provide evidence that a patient has the disease and needs treatment, but they are not keyed to any set of criteria. All inflammatory rheumatic diseases are grouped under one code. According to statistics of the Social Insurance Institution, the prevalence of patients with reimbursed drugs for these diseases varies to some degree among various parts of the country; these figures, however, are influenced by the age structure of the population. In recent years, most patients (approximately 95%) with clinically significant RA ultimately gain eligibility (11, 12), but a delay of several years can occur, particularly in patients with insidious onset of disease. The National Research and Development Center for Welfare and Health (STAKES) maintains a register, generally known as the Hospital Discharge Register, of patients treated as inpatients in general hospitals. Among others, the hospital code, hospitalization time, and ICD codes of the main diagnoses are listed. RESULTS
Prevalence The growing importance of rheumatic disorders as a public health problem led to studies on the prevalence of these diseases in the 1920s, mainly in insured populations. In Finland, Holsti and Rantasalo (13) published a population-based epidemiological survey on the occurrence of arthritis in 1936. The study covered 37 rural communities with a total population of 195,000. The practical work was performed by 47 community health nurses, all well acquainted with their own districts. The prevalence of chronic arthritis was 0.6%, corresponding
EPIDEMIOLOGY OF RA IN FINLAND
to about 0.9% of the adult population. Of these cases, 40% were totally disabled. Epidemiological studies of RA, aimed at uncovering etiological clues to the disease on the basis of its occurrence in representative population samples, began in England during the 1950s and were soon expanded into comparative international surveys. To obtain more precision in diagnosis, radiographs and serological tests for rheumatoid factor (RF) were included in the study protocol. As part of a collaborative study in Northern Europe, a prevalence study of rheumatic diseases with special emphasis on RA was conducted in Heinola, Finland, a "typical," small country town. The population in Heinola at the time of the study was 10,000. It is situated 130 km northeast of Helsinki in an agricultural and forestry area surrounded by many lakes. The study consisted of two samples: a 1:2 sample of the population 55 to 64 years of age (346 subjects examined) and a 1:10 sample of the population 15 years of age and over (539 subjects examined). The prevalence of RA satisfying the simplified version (later called the Rome criteria for active RA) of the American Rheumatism Association (ARA) criteria for definite RA (14) was 2% in the first sample (15) and 3% in the second sample (16). In view of the findings in the 1:2 sample and of those from later prevalence studies, the 3% prevalence in the 1:10 sample is likely to be too high. Four of the 16 subjects with definite RA in the 1:10 sample were positive for RF using the sensitized sheep cell agglutination (Waaler-Rose) test for RA (17). Thus, the prevalence of RF-positive definite RA was 0.7%. Two patients, both RF positive, were severely handicapped by the disease. Four RF-positive patients met the criteria for probable RA. A larger prevalence study of RA was undertaken as part of the Mini-Finland Health Survey (18), which was a multidiciplinary study designed to analyze the epidemiology of major public health problems, the need for and adequacy of care, and disability and handicap among the adult population. The study sample was a two-stage cluster sample selected to be representative of the Finnish population 30 years of age and over, initially composed of 8,000 people. The field survey was performed between 1978 and 1980. Serum RF was determined in 7,124 cases (89%). There were 138 cases of clinical arthritis in the series, correspond-
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ing to a prevalence of 1.9%. Fifty of these cases (0.7% of the population) showed changes characteristic of RA in hand radiographs (Table 1). The prevalence of arthritis associated with positive radiological and/or serological findings was 1%; that associated with both positive radiological and serological findings was 0.5%. Twelve of the radiograph positive cases were RF negative. Three of these were known to have been RF positive either before or after the field survey and three were rheumatoid variants typically RF negative, such as early-onset juvenile RA. Two later studies primarily designed for other purposes have provided figures on the prevalence of RA in Finland. According to Korpela (19), 1,730 subjects were entitled to specially reimbursed medication for chronic inflammatory rheumatic diseases in the city of Tampere (population 170,000)~ Of these, 1,385 were diagnosed with RA by a physician. A re-evaluation of the reimbursement certificates revealed that 1,100 subjects had definite or classical RA according to the simplified version of the ARA 1958 criteria. This corresponds to a cumulative incidence of 0.8% in the population 15 years of age and over. Hakala et al (11) performed a follow-up examination for those subjects entitled to specially reimbursed medication for chronic inflammatory rheumatic diseases in the community- of Kuusamo (population 18,000) in northern Finland. In addition to findings on examination, all earlier available data were used for classification of cases. A totN of 103 subjects satisfied the ARA 1987 classification criteria for RA (20), corresponding to a cumulative incidence of 0.8% in the population 16 years of age and over. As many as 99 of the subjects (96%) had erosive changes in the hands and/or feet, and 91
Table 1: Prevalence of Clinical Arthritis Associated With Positive Radiographic Findings and/or RF* Tests in the Mini-Finland Health Surveyt Number of Cases
Prevalence
Group X- r ay +/RF +
38
0.5
X-ray - / R F +
21
0.3
X-ray +/RF -
12
0.2
X- r ay - / R F -
67
0.9
(%)
*RF was determined using the latex slide test (>-20 IU/mL). t7,124 subjects were examined.
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subjects (88%) were or had been RF positive at some phase of the disease. At the time of follow-up examination, 75% of cases had a RF level of 20 IU/ml or higher, as measured by quantitative immunoturbidimetry (21). The Social Insurance Institution has performed five interview-based studies (in 1964, 1968, 1976, 1987, and 1995 to 1996) of samples representing the entire noninstitutionalized Finnish population. In the first three surveys, about 17,000 adults were interviewed; in the last two surveys, about one third fewer were interviewed. The work was performed by public health nurses who had received special training for this task. Figures concerning the occurrence of rheumatic complaints in the first and the third surveys were published earlier (22). As seen in Table 2, some fluctuation occurred in the prevalence of RA; yet no clear trend was discernible. In character and content, the data were not equivalent to that obtained on clinical examination. Yet one advantage of this approach to data collection is the possibility of generalizing the findings to the entire noninstitutionalized population. Because the same method was used in various stages of this survey, results obtained even at relatively long intervals are comparable.
Incidence Patients with chronic stable disease dominate the prevalence pool. On the other hand, patients whose disease remits and those who die prematurely are underrepresented. Thus, incidence is, in certain respects, a more useful measure of disease occurrence than prevalence. In the patient series collected between 1974 and 1975, the annual incidence of definite RA according to the simplified ARA 1958 criteria was 42/ 100,000 of the adult Finnish population (23). This
Table 2: Prevalence of RA in National Health Interviews by the Social Insurance Institution* Year
Number of Subjects
Subjects With RA
Prevalencet (%)
1964
16,715
185
1.24 (1.04-1.44)
1968
17,910
259
1.64 (1.42-1.86)
1976 1987
16,410 13,138
188 140
1.31 (1.09-1.53) 1.17 (0.95-1.39)
1995-1996
10,411
151
1.52 (1.27-1.77)
*Figures in parenthesis denote 95% confidence intervals. rAge adjusted to Finnish adult population in 1996.
study, however, was based on two separate series: a smaller series provided the total incidence of inflammatory rheumatic diseases and a larger series the distribution of cases according to various diagnostic categories. A more recent study covered those subjects entitled to specially reimbursed medication in 5 of the 21 central hospital districts in Finland (population basis about one million adults) over three years: 1980, 1985 and 1990 (24). The average annual incidence of RA satisfying the ARA 1987 classification criteria was 37/100,000 of the population 16 years of age and over. The combined incidence of RF-positive arthritis and RF-negative polyarthritis was 42/100,000. In 1990, a decline in incidence of about 15% compared with previous study years was observed affecting nearly exclusively RF-negative disease. In a separate report (25) based on the same basic material, it was observed that the mean age at diagnosis of new RA cases increased by 7.6 years from 1975 (50.2 years) to 1990 (57.8 years). No appreciable difference was present between men and women. Likewise, RF-positive cases and RFnegative cases behaved in the same fashion. During the study period, the life expectancy of the adult Finnish population increased by three years. This, to some extent, explains the shift in incidence toward the elderly. However, in the younger age groups, the incidence declined by 50% during the study period.
Disability From the material of the Mini-Finland Health Survey collected between 1978 and 1980, various disorders were studied for their contribution to disability (26). In two-phase clinical examination, musculoskeletal, cardiovascular, respiratory, and mental disorders were diagnosed by applying predetermined criteria in the sample of adults representative of the Finnish population over 30 years old. As part of the examination, a physician evaluated the ability of the patient to perform daily activities. Disability was labeled as "severe" if the patient was assessed as completely unable to perform daily activities. Disability was labeled as "marked" if difficulties occurred in the performance of such activities or in the patient's ability to perform more strenuous activities of daily living. The prevalence rates of at least marked disability and severe disability were 16% and 3%, respectively. As
EPIDEMIOLOGY OF RA IN FINLAND
mentioned earlier, chronic polyarthritis with changes in hand radiographs characteristic of RA or positive tests for RF was diagnosed in 1% (18). On the basis of these elements and adjusting for gender and age, the fractions of at least marked disability and severe disability attributable to RA in the Finnish population were 3% and 6%, respectively. Ten years later, in 1989, 103 subjects in the community of Kuusamo in northern Finland were diagnosed with RA satisfying the ARA 1987 classification criteria (11). The mean Health Assessment Questionnaire (HAQ) score (27) in the series was 0.85 (28). In only six cases was the index 2.5 or over, signifying total or near-total incapacity. It should be noted in this context that high-grade impairment caused by destruction of large joints was, in most instances, compensated for by total joint replacement surgery that had been performed in 20% of the cases. The total number of disability pensions because of RA in 1994 was 583, corresponding to 2% of new disability pensions in that year. The cumulative number of people on disability pension because of RA in 1994 was 6,590, corresponding to 3% of the pool of disability pensions and 0.2% of the population 16 to 64 years old. In an 8-year follow-up study of patients with recent-onset RA, 43% had retired because of arthritis and only 36% had retained adequate work capability (29).
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Table 3: Relationship of RF and RA in Three Population Samples Number of Subjects With RF* Investigator
Subjects
RA
+
RA
-
Aho et al 1961 (17)
539
8
8
Aho et al 1985 (31)
2,268
17
32
Aho et al 1989 (18)
7,124
40
129
*RF was measured with the sensitized sheep ceil agglutination test,
the length of period between taking the specimens and the onset of disease; when the period is short (less than two years), the prevalence is nearly the same as in established disease. Follow-up of the Mini-Finland Health Survey showed that 9 of 129 (7%) healthy subjects with a positive sensitized sheep cell agglutination test result and 12 of about 7,000 subjects with a negative test result developed RF-positive RA during a 10-year period. This means that healthy subjects with positive sensitized sheep cell agglutination test results have approximately a 40 times higher risk of developing RFpositive RA than subjects with negative results. False-positive RF also predicted death from cardiovascular causes in a statistically significant fashion (33). The relative risk, however, was only 1.9. DISCUSSION Prevalence
RF
RF can be detected in clinical settings in most cases with RA, but only occasionally in the sera of healthy subjects. However, only a minority, about one third or even less, of those living in the community and exhibiting positive RF reactions show clinical and/or radiological evidence of RA (30). Subjects with RA have, on the average, higher RF levels than those with false-positive RF reactions. The proportion of RA cases among RF positives is thus dependent on the sensitivity of the test techniques (31). Another determinant in this respect is the prevalence of RA in the population. The relationship of RF and RA has been studied in three Finnish population samples (Table 3) (17, 18, 31). The proportion of RA cases declined from 50% to 25%. The small number of cases in the first sample precludes firm conclusions regarding this trend. Positive RF reactions in healthy subjects can precede the onset of clinical RA (32). The prevalence of RF in preillness specimens is dependent on
About one-third of patients initially presenting with symptoms and signs compatible with RA are RF negative using conventional tests (34). Such patients have some type of inflammatory joint disease. RF-negative RA tends to run a more favorable course than its RF-positive counterpart. One would thus expect that the relative proportion of RF-negative RA cases encountered in crosssectional surveys will be less than one third; however, the reverse is true (35). In the Mini-Finland Health Survey, half of the subjects with clinical arthritis were RF negative and nonerosive (18). Follow-up study showed that RF-positive and/or erosive arthritis were associated with considerable excess mortality (standardized mortality ratio of 1.8), whereas no excess mortality was noted in subjects with RF-negative and nonerosive arthritis (33). O'Sullivan and Cathcart reported a 3 to 5 year follow-up of subjects originally classified as probable and definite RA in a 1964 survey in Sudbury,
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Massachusetts (36). Of 78 cases with probable RA, 73 were reexamined and only 11 of these (15%) still met three or more ARA criteria. Of the 40 cases with definite RA, 36 were reexamined and 19 of these (53%) met three or more ARA criteria. It appears reasonable to assume that RF-positive and erosive cases were those that pursued a chronic course, although the issue was not examined. Many cases of RF-negative and nonerosive disease encountered in population surveys probably have osteoarthritis associated with an inflammatory component. A weakness of the ARA criteria is that much importance is placed on soft-tissue swelling which, on its own, is of little specificity, and has poor interobserver reproducibility (37). As an example of conflicting findings most likely resulting from problems in interpretation, surveys in England (37) yielded higher prevalence rates when the New York criteria was used (38) than when the ARA definite category was used. O'Sullivan and Cathcart (36), on the other hand, recorded only 17 cases by the New York criteria and as many as 40 definite RA cases by the ARA criteria. In many diseases (eg, in cancer and coronary artery disease), geographic comparisons have aided researchers in defining the relationship between disease occurrence and potential risk factors such as diet. The early prevalence studies of RA aimed at finding etiological clues on the basis of its occurrence in representative population samples were disappointing, however. Differences in prevalence were recorded, but it could not be determined with certainty whether these were real or only because of observer assessment. Subsequently, it has been firmly established that the prevalence of RA among certain Native Ameri-
can tribes is appreciably higher than in populations of European origin (39, 40). On the other hand, RA may be a rare disease in certain tropical areas. It is commonly stated that the prevalence of arthritis satisfying the simplified ARA 1958 criteria for definite RA or the 1987 classification criteria for RA is about 0.5% to 1% of the adult population in most Western countries (39, 40). Because of the previously mentioned problems, considerable differences in true prevalence may be concealed behind these figures. For the purposes of comparison, clinical arthritis (or deformities of past arthritis) associated with positive serology and/or characteristic radiographic changes is, in our experience, a more reliable measure of clinically significant chronic peripheral arthritis appropriately referred to as RA than RA defined by the ARA criteria. The prevalence of this type of arthritis (1%) recorded in the Mini-Finland Health Survey (18) in the population 30 years of age and over closely corresponds to the cumulative incidence figure of 0.8% in the population 16 years of age and over noted in the context of studies by Korpela (19) and by Hakala et al (11). On this basis, about 30,000 cases of clinically significant chronic arthritis appropriately referred to as RA are present in Finland. Of these, about 60% are under 65 years of age, which is the official retirement age. Clinical arthritis associated with both positive tests for RF and characteristic radiographic changes underestimates the prevalence of clinically significant disease. Yet the prevalence may be a useful index for comparative purposes. We have found seven studies sufficiently large to give some meaningful information that provided the necessary data (Table 4). Figures from the Mini-Finland Health Survey performed between 1978 and 1980 (18), the
Table 4: Prevalence of RA Associated With Positive Radiographic Findings and RF Tests in Seven Populations Investigator
Country
Age
Number of Subjects
Prevalence (%)
Engel et al 1966 (42) Kellgren 1966 (30) Lawrence 1968 (45) Allander 1970 (41) Aho et al 1989 (18) Recht et a11990 (44) Mau et a11991 (43)
USA England Pima Indians Sweden Finland Faroe Islands Germany
18-79 ->15 35-64 31-74 ->30 40-74 25-74
6,287 2,607 632 12,136 7,124 1,624 8,907
0.2 0.6 2 0.5 0.5 0.3 0.15
EPIDEMIOLOGY OF RA IN FINLAND
331
population survey done by Allander in Stockholm, Sweden in the late 1960s (41), and the Arthritis and Rheumatism Council Survey performed in England in the late 1950s (30) were similar. Because the English study consisted of subjects 15 years of age and over and the Finnish and Swedish studies subjects 30 years of age and over, the prevalence in England may have been slightly higher than in Finland and Sweden. In contrast, the prevalence noted in the National Health Examination Survey in the United States (42) performed between 1960 and 1962, in a German study by Raspe et al in the 1980s (43), and in a study by Recht et al (44) on the Faroe Islands were lower. A high prevalence was recorded in Pima Indians (45). Figures concerning new disability pensions for RA were available from Finland, Sweden, and Germany. As seen in Table 5, these figures are in line with those from the previously mentioned prevalence studies and indicate that RA is somewhat less prevalent in Germany than in Finland and Sweden° Incidence Cross-sectional surveys have provided information on the prevalence of RA. Yet patients with chronic stable disease are overrepresented in the prevalence pool; patients who remit and those who die prematurely are underrepresented. Accordingly, incidence is, in certain respects, a more useful measure of the occurrence of RA than is prevalence. The diagnosis of RA cannot always be established on the basis of one single observation; frequently it emerges only after continuous followup. It may be appropriate to separate transient and chronic forms, erosive and nonerosive cases, as well as RF-positive and RF-negative cases, and to analyze the subsets independently rather than to incorporate all into one common disease category.
In a community-based follow-up study of recentonset arthritis from Finland, the majority of RFpositive arthritis patients developed erosive disease, whereas virtually all patients with RFnegative oligoarthritis attained remission (46). The outcome of RF-negative polyarthritis was bimodal: a majority of patients showed a favorable outcome and a minority did not fare well. Therefore, the incidence of RF-positive arthritis to some degree underestimates, and the combined incidence of RF-positive arthritis and RF-negative polyarthritis to some degree overestimates, the incidence of progressive, (ie, clinically significant) arthritis appropriately referred to as RA. On the basis of figures from a recent incidence study from Finland previously discussed (24), it can be estimated that about 1,500 cases of clinically significant RA occur in Finland per year. In the previously mentioned study, the annual incidence of RA satisfying the ARA 1987 classification criteria was 37/100,000 of the population 16 years of age and over. This figure was based on cumulative incidence of symptoms and signs to the time when diagnosis was established and the certificate for reimbursed drugs was written. In a recent population-based study from England (47), the annual incidence of RA in the adult population using the same criteria was 25/100,000; however, this figure was based on symptoms and signs recorded at the time of presentation. Thus the true incidence rates in these two surveys as defined by the ARA 1987 criteria were similar. One important difference was apparent, however: the incidence of RF-positive arthritis in the Finnish series was about 30/100,000, whereas it can be computed on the basis of figures given in the paper by Symmons et al (47) that the corresponding figure in the English series was only 13/100,000. Two recent incidence studies from the United
Table 5: New Disability Pensions for RA in Finland, Sweden, and Germany in 1994 New Pensions Population
Number
Percent of Population
Country
(millions)
All
Due to RA
All
Due to RA
Finland Sweden Germany
3.34* 5.55* 30.27t
20,793 48,531 294,437
583 1,093 2,703
0.63 0.82 0.97
0.017 0.020 0.009
*Total population 15 to 64 years of age. tlnsured population (up to 64 years of age).
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States covering the somewhat select populations in health maintenance organizations (48, 49) provided figures similar to those reported from Finland and England. On the other hand, Guillemin et al (50) noted appreciably lower figures (9/100,000) in France. As previously indicated, about 30,000 cases of clinically significant RA are present in Finland and the annual incidence of such new cases is about 1,500; thus the ratio of prevalence to incidence rates is about 20. In this context, it is of interest to note that in a recent study covering subjects with specially reimbursed medication for RA who had died over one year, the mean disease duration was 14 years in men and 17 years in women (12).
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years later by Hakala et al in Kuusamo, revealed fairly good retention of health status and functional ability (28, 51). Indeed, the HAQ scores were better than the earlier results from community-based studies in England (52) and the United States (53). Most of the improvement can probably be explained by the advent of total joint replacement surgery; few operations were performed on RA patients during the 1970s. Some recent data, however, indicate that the long-term use of diseasemodifying antirheumatic drugs retards the progression of destructive joint disease (54) and retains functional ability in patients (55). Whether changes have occurred in the natural course of RA remains an interesting possibility (56).
Disability RA commonly leads to disability. The prevalence of disability in a population, however, is simultaneously determined by many diseases and disorders. The nature and severity of disability vary depending on the causes. Therefore, it is difficult to estimate how much of the burden of disability a single disease such as RA contributes in the general population. The Mini-Finland Health Survey may be the only study providing reliable elements for such an estimation. In terms of the populationattributable fraction, 3% of at least marked disability and 6% of severe disability in Finnish adults were explained by a combination of arthritis and either hand radiographs characteristic of RA or positive RF reaction. Because cases with RFnegative nonerosive cases were not included, these fractions may have slightly underestimated the impact of RA defined by the ARA criteria. A central finding of the Mini-Finland Health Survey was that comorbid diseases and other determinants of functional state did not confound the association between arthritis and disability (26). Comorbidity in arthritis was relatively low and, unlike most musculoskeletal and mental disorders, arthritis was not concentrated in population groups prone to disability such as those with limited education, low income, and physical and mental stress at work. Despite the relatively low prevalence of RA, the impact of this disease was strong. The more severe the disability was considered, the larger that part was explained by RA. Although using indices different from those used in the MiniFinland Health Survey, studies undertaken ten
CONCLUSIONS
In the absence of specific diagnostic tests for RA, diagnosis depends on recognition of patterns of clinical manifestations. The new ARA criteria are classification criteria rather than diagnostic criteria. One problem in their use is that routine patient records are seldom keyed to these criteria; in particular, information on morning stiffness is frequently lacking. According to our experience, more importance should to be given to typical radiographic changes and to RA as an immunologic disease. Development of quantitative immunoturbidimetric RF testing offers better reproducibility and comparability than the earlier test techniques. There probably still is a place for surveys on the prevalence of RA, particularly in various exotic populations. It appears unlikely, however, that further descriptive studies on the prevalence of RA in Western societies will generate clues of etiological and pathogenetic importance (39). On the other hand, large population surveys or registers that provide information on incidence rates may provide some new insight. Examples along these lines are the continuous monitoring of the Norfolk Arthritis Register in England and the register covering sickness insurance benefits in Finland. Available data from England and the United States indicate a recent decline in the occurrence of RA (40). Figures from Finland reveal no clear decline either in prevalence or in incidence; yet a marked shift was noted in the incidence of RA toward elderly patients (25). Subsequently, a simi-
EPIDEMIOLOGY OF RA IN FINLAND
333
lar shift was also reported in Japan (57). Accordingly, the epidemiology of RA is not static but dynamic, and the trends may reflect changes in the host-environment relationship. A decline has occurred in severe disability caused by RA. Functional restrictions can be studied by simple and reproducible methods. Monitoring the occurrence of RA, disability, and its
determinants at the community level likely will be useful in assessing management approaches. ACKNOWLEDGMENT
The authors thank Professor I.B. Linda.hl from Stockholm, and Professor H. Raspe and Ms. R. Deck from Ltibeck for providing work disability statistics from Sweden and Germany.
REFERENCES 1. Myllykangas-Luosujfirvi RA, Aho K, Isom~iki HA. Mortality in rheumatoid arthritis. Semin Arthritis Rheum 1995;25:193202. 2. Nei M, Roychoudhury AK. Genetic relationship and evolution of human races. In: Heckt MK, Wallace B, Prance GT, eds. Evolutionary biology. New York, NW: Plenum, i982:1-59. 3. V~maranta-Knowles K, Sistonen P, Nevanfinna HR. A population genetic study in Finland: Comparison of the Finnish- and Swedish-speaking populations. Hum Hered 1991;41:248-64. 4. Lahermo R Sajantila A, Sistonen E et al. The genetic relationship between the Finns and the Finnish saami (Lapps): Analysis of nuclear and mitochondrial DNA. Am J Hum Genet 1996;58:1309-22. 5. Norio R, Nevanlinna HR, Perheentupa J. Hereditary diseases in Finland: Rare flora in rare soil. Ann Clin Res 1973;5:109-41. 6. Mttttnen TT. Prediction of erosiveness and rate of development of new erosions in early rheumatoid arthritis, Ann Rheum Dis 1988;47:648-53. 7. Paimela L, Leirisalo-Repo M, Helve T, Koskimies S. The prognostic value of HLA DR4 and B27 antigens in early rheumatoid arthritis. Scand J Rheumatol 1993;22:220-4. 8. Hakala M, Silvennoinen-Kassinen S, Ik~eimo I, Isosomppi I, Tiilikainen A. HLA markers in a community-based rheumatoid arthritis series. Ann Med 1997;29:291-6. 9. Isom~iki H, Koota K, Martio J, NJssila M, Tiilikainen A. HLA-27 and arthritis. Ann Clin Res 1975;7:138-45. 10. Ilonen J, Hakala M, Reijonen H, Tiilikainen A. B27bearing HLA baplotypes in rheumatoid arthritis: Characterization in Finnish patients. Hum Immunol 1991;30:7-10. 11. Hakala M, P611~inen R, Nieminen R The ARA 1987 revised criteria select patients with clinical rheumatoid arthritis from a population based cohort of subjects with chronic rheumatic diseases registered for drug reimbursement. J Rheumatol 1993;20:1674-8. i2. Myllykangas-Luosujfirvi R, Aho K, Kautiainen H, Isomhki H. Shortening of life span and causes of excess mortality in a population-based series of subjects with rheumatoid arthritis. Clin Exp RheumatoI 1995; 13:149-53. 13. Holsti (3, Rantasalo V. On the occurrence of arthritis in Finland. Acta Med Scand 1936;88:180-95. 14. Ropes MS, Bennett GA, Cobb S, Jacox R, Jessar RA. 1958 revision of diagnostic criteria for rheumatoid arthritis. Bull Rheum Dis 1958;9:175-6. 15. Laine V, de Graaf R, Lawrence J. Rheumatoid arthritis in Northern Europe. Atti del X Congresso della Lega Internazionale contro il Rheumatismo. Vol I. Relazioni. Torino: Minerva Medica, 1961:31-6.
16. Laine V. Rheumatic complaints in an urban population in Finland. Acta Rheum Scand 1962;8:81-8. 17. Aho K, Julkunen H, Laine V, Ripatti N, Wager O. Clinical evaluation of the serological tests in rheumatoid arthritis. I. Normal series collected by random sampling. Acta Rheum Scand 1961;7:201-8. 18. Aho K, Helitvaara M, Sievers K, Maatela J, Isomaki H. Clinical arthritis associated with positive mdiological and serological findings in Finnish adults. Rheumatol hat 1989;9:7-11. 19. Korpela M. Rheumatoid arthritis and the kidneys (in Finnish with English summary). Publications of the Social Insurance Institution ML 1993; 122:1-194. 20. Amett FC, Edworrhy SM, Bloch DA, et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 1988;31:315-24. 21. Hakala M, Sajanti E, Aho K. High prevalence of rheumatoid factor in a community-based series of patients with rheumatoid arthritis meeting the new ARA criteria. Scand J Rheumatol 1997;26:234. 22. Klaukka 3", Sievers K, Takala J. Epidemiology of rheumatic diseases in Finland in 1964-76. Scand J Rheumatol 1982; 11 (Supp147):5- !3. 23. IsomLki H, Raunio J, von Essen R, H&meenkorpi R. Incidence of inflammatory rheumatic diseases in Finland. Scand J Rheumatol 1978;7:188-92. 24. Kaipialnen-Sepp~nen O, Aho K, Isomhki H, Laakso M. Incidence of rheumatoid arthritis in Finland during 1980-1990. Ann Rheum Dis 1996;55:608-11. 25. Kaipiainen-Sepp~inen O, Aho K, Isomfiki H, Laakso M. Shift in the incidence of rheumatoid arthritis toward elderly patients in Finland during 1975-1990. Clin Exp Rheumatol i996; 14:537-42. 26. M~ikei~iM, Helitvaara M, Sievers K, Knekt P, Aromaa A. Musculoskeletal disorders as determinants of disability in Finns aged 30 years or more. J Clin Epidemiol 1993;46:549-59. 27. Fries JF, Spitz R Kraines RG, Holamn HR. Measurement of patients' outcome in arthritis. Arthritis Rheum 1980;23:137-45. 28. Hakala M, Nieminen R Koivisto O. More evidence from community based series of better outcome in rheumatoid arthritis. Data on the effect of multidisciplinary care on the retention of functional ability. J Rheumatol 1994;21:1432-7. 29. Kaarela K, Lehtinen K, Luukkainen R. Work capacity of patients with inflammatory joint disease. An eight-year follow-up study. Scand J Rheumatol 1987;16:403-6. 30. Kellgren JH. Epidemiotogy of rheumatoid arthritis. Arthritis Rheum 1966;9:658-74. 31. Aho K, Palosuo T, Niemelg N, Takala J. Rheumatoid
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factor seroconversions in relation to clinical rheumatoid arthritis. Ann Ctin Res 1985;17:15-8. 32. Aho K, Palosuo T, Kurki E Marker antibodies of rheumatoid arthritis: Diagnostic and pathogenetic implications. Semin Arthritis Rheum 1994;23:379-87. 33. Heli6vaara M, Aho K, Knekt R Aromaa A, Maatela J, Reunanen A. Rheumatoid factor, chronic arthritis and mortality. Ann Rheum Dis 1995;54:811-4. 34. Masi AT, Feigenbaum SL. Seronegative rheumatoid arthritis. Fact or fiction? Arch Intern Med 1983; 143:2167-72. 35. Lichtenstein MJ, Pincus T. Rheumatoid arthritis identified in population based cross sectional studies: Low prevalence of rheumatoid factor. J Rheumatol 1991; 18:989-93. 36. O'Sullivan JB, Cathcart ES. The prevalence of rheumatoid arthritis: Follow-up evaluation of the effect of criteria on rates in Sudbury, Massachusetts. Ann Intern Med 1972;76: 573-7. 37. Lawrence JS. Rheumatism in populations. London: Heinemann, 1977. 38. Bennett PH, Burch TA. New York symposium on population studies in the rheumatic diseases, new diagnostic criteria. Bull Rheum Dis 1967;17:453-8. 39. Gran JT. The epidemiology of rheumatoid arthritis. In: Schlumberger HD, ed. Epidemiology of allergic diseases (Monographs in Allergy, vo121). Basel: Karger, 1987:162-196. 40. Silman A J, Hochberg MC. Epidemiotogy of the rheumatic diseases. New York, NY: Oxford, 1993. 41. AUander E. A population survey of rheumatoid arthritis. Acta Rheum Scand 1970;16(Suppl 15):1-146. 42. Engel A, Roberts J, Butch TA. Rheumatoid arthritis in adults, United States 1960-1962. Public Health Service Publ 1000, ser 11, No 17, 1966. 43. Man W, Wasmus A, Raspe H-H. Epidemiologie und Versorgung der rheumatoiden Arthritis (rA) im Stadtgebiet von Hannover. Forschusberichte des Projekttr~gers 2/91. GSFForschungszentrum fOr Umwelt und Gesundheit, 1991. 44. Recht L, Helin P, Rasmunssen JO, Jakobsen J, Lithman T, Schersten B. Hand, handicap and rheumatoid arthritis in a fish-eating society. J Intern Med 1990;227:49-55. 45. Lawrence JS. Geographical studies of rheumatoid arthritis. In: Bennett PH, Wood PHN, eds. Population studies of the rheumatic diseases (International Congress Series No 148). Amsterdam: Excerpta Medica Foundation, 1968:45-54.
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46. Kaarela K, Sarna S. Seronegative oligoarthritis. Scand J Rheumatol 1984; 13 (supp152):9-12. 47. Symmons DPM, Barrett EM, Barddlead CR, Scott DGJ, Silman AJ. The incidence of rheumatoid arthritis in the United Kingdom: Results from the Norfolk arthritis register. Br J Rheumatol 1994;33:735-9. 48. Dugowson CE, Koepsell TD, Voigt LF, Bley L, Nelson JL, Daling JR. Rheumatoid arthritis in women. Incidence rates in group health cooperative, Seattle, Washington, 1987-1989. Arthritis Rheum 1991 ;34:1502-7. 49. Chan K-WA, Felson DT, Yood RA, Walker AM. Incidence of rheumatoid arthritis in central Massachusetts. Arthritis Rheum 1993;36:1691-6. 50. Guillemin F, Briancon S, Klein J-M, Sauleau E, Puurel J. Low incidence of rheumatoid arthritis in France. Scand J Rheumatol 1994;23:264-8. 51. Hakala M, Nieminen R Functional status assessment of physical impairment in a community-based population with rheumatoid arthritis: Severely incapacitated patients are rare. J Rheumatol 1996;23:617-23. 52. Owen SG, Friesen WT, Roberts MS, Francis H, Flux W. Functional capacity and treatment data from a community based study of patients with rheumatoid arthritis. Ann Rheum Dis 1986;45:293-303. 53. Sherrer YS, Bloch DA, Mitchell DM, Roth SH, Wolfe E Disability in rheumatoid arthritis: Comparison of prognostic factors across three populations. J Rheumatol 1987;14:705-9. 54. MOtt6nen T, Paimela L, Ahonen J, Helve T, Hannonen R Leirisalo-Repo M. Outcome in patients with early rheumatoid arthritis treated according to the "saw tooth" strategy. Arthritis Rheum 1996;39:996-1005. 55. Fries JF, Williams CA, Morfeld D, Singh G, Sibley J. Reduction in long-term disability in patients with rheumatoid arthritis by disease-modifying antirheumatic drug-based treatment strategies. Arthritis Rheum 1996;39:616-22. 56. Silman AJ. Are there secular trends in the occurrence of rheumatoid arthritis? Scand J Rheumatol 1989;18(Supp179):25-30. 57. Imanaka T, Shichikawa K, Inoue K, Shimaoka Y, Takenaka Y, Wakitani S. Increase in age at onset of rheumatoid arthritis in Japan over a 30 year period. Ann Rheum Dis 1997;56:313-6.
INDEX WORDS: Rheumatoid arthritis; incidence; prevalence; disability. N MANY RESPECTS, Finland provides good opportunities for epidemiological research. The population is quite homogeneous and sufficiently large (about 5 million) for investigation of most relevant problems. Attitudes toward researchrelated interviews and examinations are positive and accordingly, participation rates in most surveys are high. The health care system is mainly public and is well organized. In addition, several nationwide registers designed primarily for administrative purposes also can be used for research. Extensive investigations have been undertaken in Finland on various aspects of the epidemiology of rheumatoid arthritis (RA). Recently, mortality studies in RA performed in Finland and elsewhere were reviewed (1). Here, we report the prevalence and incidence of RA in Finland, as well as the disability resulting from this disease, and compare our data with that of other countries.
I
MATERIAL AND METHODS
Finnish Population Although the majority of Europeans speak IndoEuropean languages, about 24 million Europeans speak Finno-Ugric languages, such as Hungarian, Finnish, and Estonian. Based originally on the linguistic relationship of Finnish with languages
spoken by certain ethnic groups in Russia, it has traditionally been thought that the Finns migrated to their current location from a common origin in the East, either in the Altai, the Ural, or the Volga region. Yet studies of nuclear gene frequencies have shown that the greatest proportion of the Finnish gene pool is "European," although Finns appear to differ from other European populations more than Europeans in general differ from each other (2, 3). Recent studies on mitochondrial DNA sequences found that European populations, including Finns, are part of one homogeneous mitochondrial gene pool (4).
From the National Public Health Institute, Helsinki, Department of Medicine, Kuopio University Hospital, Kuopio, and Social Insurance Institution, Helsinki, Finland. Address reprint requests to Kimmo Aho, MD, National Public Health Institute, Mannerheimintie 156, FIN-O0300 Helsinki, Finland. Kimmo Aho, MD: Professor, National Public Health Institute, Helsinki, Finland; Oili Kaipiainen-SeppSnen, MD: Consultant Rheumatologist, Department of Medicine, Kuopio University Hospital, Kuopio, Finland; Markku HeliOvaura, MD: Physician in Chief National Public Health Institute, Helsinki, Finland; Timo Klaukka, MD: Medical Research Officer, Social Insurance Institution, Helsinki, Finland. Copyright © 1998 by W.B. Saunders Company 0049-0172/98/2705-000758. 00/0
Seminars in Arthritis and Rheumatism, Vo127, No 5 (April), 1998: pp 325-334
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The present Finnish population is thought to stem largely from immigration about 2,000 years ago by a small number of settlers. The population subsequently remained isolated with little immigration. Genetic epidemiological studies show that many genetic diseases occur at substantially different frequencies (sometimes higher, sometimes lower) in Finland than in the rest of Europe, as would be expected from a founder effect caused by a population bottleneck (5). In two Finnish series of recent-onset RA patients, HLA-DR4 was present in 54% and in 68% of the cases (6, 7). In a community-based series of RA patients, the DR4 allele occurred in 54% and the shared RA susceptibility epitope in 75% of cases (8). The HLA-B27 allele occurs in the Finnish population more frequently (14%) than in most other European populations. In addition to DR4, B27 also occurs in Finnish RA patients more frequently than in control subjects (9). B27-bearing haplotypes in RA patients were found to carry DR1 and DR4 genes more often than did B27 haplotypes in controls (10). It is probable that the increased frequency of the B27 allele in RA patients is secondary to the increase in D-locus risk alleles, but the possibility cannot be excluded that the susceptibility to RA is enhanced when DR1 or DR4 occurs in haplotypic combination with B27.
Nationwide Registers Several computerized data registers cover the entire Finnish population. Thus, migration does not influence the statistics. Each Finnish citizen has a unique identification code that allows for identification in various registers and linking registers, although this is strictly regulated. Those registers most important for rheumatological research follow. The Population Register Center maintains a file on all Finnish citizens and foreigners living permanently in Finland. Thus, it is possible to determine if the person is alive unless he/she has moved permanently out of the country. One of the duties of Statistics Finland (formerly the Central Statistical Office of Finland) is to maintain the cause-of-death register. Causes of death are classified by Statistics Finland according to International Classification of Diseases (ICD) codes as outlined by the World Health Organization. The final code is not always the same as that marked by the attending physician on the death certificate.
AHO ET AL
The Social Insurance Institution has files on disability pensions (grouped according to ICD codes) and on sickness insurance benefits. The Sickness Insurance Act provides for specially reimbursed medication for certain chronic diseases including inflammatory rheumatic diseases. Glucocorticoids, nonsteroidal antiinflammatory, and disease-modifying antirheumatic drugs are reimbursed for rheumatic diseases. This is usually a lifetime entitlement, but can also be for a fixed period. For a patient to be eligible, a comprehensive medical certificate must be written by the attending physician and approved by an expert adviser on behalf of the sickness insurance scheme. The rules for approval are uniform throughout the country. The certificates are written to provide evidence that a patient has the disease and needs treatment, but they are not keyed to any set of criteria. All inflammatory rheumatic diseases are grouped under one code. According to statistics of the Social Insurance Institution, the prevalence of patients with reimbursed drugs for these diseases varies to some degree among various parts of the country; these figures, however, are influenced by the age structure of the population. In recent years, most patients (approximately 95%) with clinically significant RA ultimately gain eligibility (11, 12), but a delay of several years can occur, particularly in patients with insidious onset of disease. The National Research and Development Center for Welfare and Health (STAKES) maintains a register, generally known as the Hospital Discharge Register, of patients treated as inpatients in general hospitals. Among others, the hospital code, hospitalization time, and ICD codes of the main diagnoses are listed. RESULTS
Prevalence The growing importance of rheumatic disorders as a public health problem led to studies on the prevalence of these diseases in the 1920s, mainly in insured populations. In Finland, Holsti and Rantasalo (13) published a population-based epidemiological survey on the occurrence of arthritis in 1936. The study covered 37 rural communities with a total population of 195,000. The practical work was performed by 47 community health nurses, all well acquainted with their own districts. The prevalence of chronic arthritis was 0.6%, corresponding
EPIDEMIOLOGY OF RA IN FINLAND
to about 0.9% of the adult population. Of these cases, 40% were totally disabled. Epidemiological studies of RA, aimed at uncovering etiological clues to the disease on the basis of its occurrence in representative population samples, began in England during the 1950s and were soon expanded into comparative international surveys. To obtain more precision in diagnosis, radiographs and serological tests for rheumatoid factor (RF) were included in the study protocol. As part of a collaborative study in Northern Europe, a prevalence study of rheumatic diseases with special emphasis on RA was conducted in Heinola, Finland, a "typical," small country town. The population in Heinola at the time of the study was 10,000. It is situated 130 km northeast of Helsinki in an agricultural and forestry area surrounded by many lakes. The study consisted of two samples: a 1:2 sample of the population 55 to 64 years of age (346 subjects examined) and a 1:10 sample of the population 15 years of age and over (539 subjects examined). The prevalence of RA satisfying the simplified version (later called the Rome criteria for active RA) of the American Rheumatism Association (ARA) criteria for definite RA (14) was 2% in the first sample (15) and 3% in the second sample (16). In view of the findings in the 1:2 sample and of those from later prevalence studies, the 3% prevalence in the 1:10 sample is likely to be too high. Four of the 16 subjects with definite RA in the 1:10 sample were positive for RF using the sensitized sheep cell agglutination (Waaler-Rose) test for RA (17). Thus, the prevalence of RF-positive definite RA was 0.7%. Two patients, both RF positive, were severely handicapped by the disease. Four RF-positive patients met the criteria for probable RA. A larger prevalence study of RA was undertaken as part of the Mini-Finland Health Survey (18), which was a multidiciplinary study designed to analyze the epidemiology of major public health problems, the need for and adequacy of care, and disability and handicap among the adult population. The study sample was a two-stage cluster sample selected to be representative of the Finnish population 30 years of age and over, initially composed of 8,000 people. The field survey was performed between 1978 and 1980. Serum RF was determined in 7,124 cases (89%). There were 138 cases of clinical arthritis in the series, correspond-
327
ing to a prevalence of 1.9%. Fifty of these cases (0.7% of the population) showed changes characteristic of RA in hand radiographs (Table 1). The prevalence of arthritis associated with positive radiological and/or serological findings was 1%; that associated with both positive radiological and serological findings was 0.5%. Twelve of the radiograph positive cases were RF negative. Three of these were known to have been RF positive either before or after the field survey and three were rheumatoid variants typically RF negative, such as early-onset juvenile RA. Two later studies primarily designed for other purposes have provided figures on the prevalence of RA in Finland. According to Korpela (19), 1,730 subjects were entitled to specially reimbursed medication for chronic inflammatory rheumatic diseases in the city of Tampere (population 170,000)~ Of these, 1,385 were diagnosed with RA by a physician. A re-evaluation of the reimbursement certificates revealed that 1,100 subjects had definite or classical RA according to the simplified version of the ARA 1958 criteria. This corresponds to a cumulative incidence of 0.8% in the population 15 years of age and over. Hakala et al (11) performed a follow-up examination for those subjects entitled to specially reimbursed medication for chronic inflammatory rheumatic diseases in the community- of Kuusamo (population 18,000) in northern Finland. In addition to findings on examination, all earlier available data were used for classification of cases. A totN of 103 subjects satisfied the ARA 1987 classification criteria for RA (20), corresponding to a cumulative incidence of 0.8% in the population 16 years of age and over. As many as 99 of the subjects (96%) had erosive changes in the hands and/or feet, and 91
Table 1: Prevalence of Clinical Arthritis Associated With Positive Radiographic Findings and/or RF* Tests in the Mini-Finland Health Surveyt Number of Cases
Prevalence
Group X- r ay +/RF +
38
0.5
X-ray - / R F +
21
0.3
X-ray +/RF -
12
0.2
X- r ay - / R F -
67
0.9
(%)
*RF was determined using the latex slide test (>-20 IU/mL). t7,124 subjects were examined.
328
AHO ET AL
subjects (88%) were or had been RF positive at some phase of the disease. At the time of follow-up examination, 75% of cases had a RF level of 20 IU/ml or higher, as measured by quantitative immunoturbidimetry (21). The Social Insurance Institution has performed five interview-based studies (in 1964, 1968, 1976, 1987, and 1995 to 1996) of samples representing the entire noninstitutionalized Finnish population. In the first three surveys, about 17,000 adults were interviewed; in the last two surveys, about one third fewer were interviewed. The work was performed by public health nurses who had received special training for this task. Figures concerning the occurrence of rheumatic complaints in the first and the third surveys were published earlier (22). As seen in Table 2, some fluctuation occurred in the prevalence of RA; yet no clear trend was discernible. In character and content, the data were not equivalent to that obtained on clinical examination. Yet one advantage of this approach to data collection is the possibility of generalizing the findings to the entire noninstitutionalized population. Because the same method was used in various stages of this survey, results obtained even at relatively long intervals are comparable.
Incidence Patients with chronic stable disease dominate the prevalence pool. On the other hand, patients whose disease remits and those who die prematurely are underrepresented. Thus, incidence is, in certain respects, a more useful measure of disease occurrence than prevalence. In the patient series collected between 1974 and 1975, the annual incidence of definite RA according to the simplified ARA 1958 criteria was 42/ 100,000 of the adult Finnish population (23). This
Table 2: Prevalence of RA in National Health Interviews by the Social Insurance Institution* Year
Number of Subjects
Subjects With RA
Prevalencet (%)
1964
16,715
185
1.24 (1.04-1.44)
1968
17,910
259
1.64 (1.42-1.86)
1976 1987
16,410 13,138
188 140
1.31 (1.09-1.53) 1.17 (0.95-1.39)
1995-1996
10,411
151
1.52 (1.27-1.77)
*Figures in parenthesis denote 95% confidence intervals. rAge adjusted to Finnish adult population in 1996.
study, however, was based on two separate series: a smaller series provided the total incidence of inflammatory rheumatic diseases and a larger series the distribution of cases according to various diagnostic categories. A more recent study covered those subjects entitled to specially reimbursed medication in 5 of the 21 central hospital districts in Finland (population basis about one million adults) over three years: 1980, 1985 and 1990 (24). The average annual incidence of RA satisfying the ARA 1987 classification criteria was 37/100,000 of the population 16 years of age and over. The combined incidence of RF-positive arthritis and RF-negative polyarthritis was 42/100,000. In 1990, a decline in incidence of about 15% compared with previous study years was observed affecting nearly exclusively RF-negative disease. In a separate report (25) based on the same basic material, it was observed that the mean age at diagnosis of new RA cases increased by 7.6 years from 1975 (50.2 years) to 1990 (57.8 years). No appreciable difference was present between men and women. Likewise, RF-positive cases and RFnegative cases behaved in the same fashion. During the study period, the life expectancy of the adult Finnish population increased by three years. This, to some extent, explains the shift in incidence toward the elderly. However, in the younger age groups, the incidence declined by 50% during the study period.
Disability From the material of the Mini-Finland Health Survey collected between 1978 and 1980, various disorders were studied for their contribution to disability (26). In two-phase clinical examination, musculoskeletal, cardiovascular, respiratory, and mental disorders were diagnosed by applying predetermined criteria in the sample of adults representative of the Finnish population over 30 years old. As part of the examination, a physician evaluated the ability of the patient to perform daily activities. Disability was labeled as "severe" if the patient was assessed as completely unable to perform daily activities. Disability was labeled as "marked" if difficulties occurred in the performance of such activities or in the patient's ability to perform more strenuous activities of daily living. The prevalence rates of at least marked disability and severe disability were 16% and 3%, respectively. As
EPIDEMIOLOGY OF RA IN FINLAND
mentioned earlier, chronic polyarthritis with changes in hand radiographs characteristic of RA or positive tests for RF was diagnosed in 1% (18). On the basis of these elements and adjusting for gender and age, the fractions of at least marked disability and severe disability attributable to RA in the Finnish population were 3% and 6%, respectively. Ten years later, in 1989, 103 subjects in the community of Kuusamo in northern Finland were diagnosed with RA satisfying the ARA 1987 classification criteria (11). The mean Health Assessment Questionnaire (HAQ) score (27) in the series was 0.85 (28). In only six cases was the index 2.5 or over, signifying total or near-total incapacity. It should be noted in this context that high-grade impairment caused by destruction of large joints was, in most instances, compensated for by total joint replacement surgery that had been performed in 20% of the cases. The total number of disability pensions because of RA in 1994 was 583, corresponding to 2% of new disability pensions in that year. The cumulative number of people on disability pension because of RA in 1994 was 6,590, corresponding to 3% of the pool of disability pensions and 0.2% of the population 16 to 64 years old. In an 8-year follow-up study of patients with recent-onset RA, 43% had retired because of arthritis and only 36% had retained adequate work capability (29).
329
Table 3: Relationship of RF and RA in Three Population Samples Number of Subjects With RF* Investigator
Subjects
RA
+
RA
-
Aho et al 1961 (17)
539
8
8
Aho et al 1985 (31)
2,268
17
32
Aho et al 1989 (18)
7,124
40
129
*RF was measured with the sensitized sheep ceil agglutination test,
the length of period between taking the specimens and the onset of disease; when the period is short (less than two years), the prevalence is nearly the same as in established disease. Follow-up of the Mini-Finland Health Survey showed that 9 of 129 (7%) healthy subjects with a positive sensitized sheep cell agglutination test result and 12 of about 7,000 subjects with a negative test result developed RF-positive RA during a 10-year period. This means that healthy subjects with positive sensitized sheep cell agglutination test results have approximately a 40 times higher risk of developing RFpositive RA than subjects with negative results. False-positive RF also predicted death from cardiovascular causes in a statistically significant fashion (33). The relative risk, however, was only 1.9. DISCUSSION Prevalence
RF
RF can be detected in clinical settings in most cases with RA, but only occasionally in the sera of healthy subjects. However, only a minority, about one third or even less, of those living in the community and exhibiting positive RF reactions show clinical and/or radiological evidence of RA (30). Subjects with RA have, on the average, higher RF levels than those with false-positive RF reactions. The proportion of RA cases among RF positives is thus dependent on the sensitivity of the test techniques (31). Another determinant in this respect is the prevalence of RA in the population. The relationship of RF and RA has been studied in three Finnish population samples (Table 3) (17, 18, 31). The proportion of RA cases declined from 50% to 25%. The small number of cases in the first sample precludes firm conclusions regarding this trend. Positive RF reactions in healthy subjects can precede the onset of clinical RA (32). The prevalence of RF in preillness specimens is dependent on
About one-third of patients initially presenting with symptoms and signs compatible with RA are RF negative using conventional tests (34). Such patients have some type of inflammatory joint disease. RF-negative RA tends to run a more favorable course than its RF-positive counterpart. One would thus expect that the relative proportion of RF-negative RA cases encountered in crosssectional surveys will be less than one third; however, the reverse is true (35). In the Mini-Finland Health Survey, half of the subjects with clinical arthritis were RF negative and nonerosive (18). Follow-up study showed that RF-positive and/or erosive arthritis were associated with considerable excess mortality (standardized mortality ratio of 1.8), whereas no excess mortality was noted in subjects with RF-negative and nonerosive arthritis (33). O'Sullivan and Cathcart reported a 3 to 5 year follow-up of subjects originally classified as probable and definite RA in a 1964 survey in Sudbury,
330
AHO ET AL
Massachusetts (36). Of 78 cases with probable RA, 73 were reexamined and only 11 of these (15%) still met three or more ARA criteria. Of the 40 cases with definite RA, 36 were reexamined and 19 of these (53%) met three or more ARA criteria. It appears reasonable to assume that RF-positive and erosive cases were those that pursued a chronic course, although the issue was not examined. Many cases of RF-negative and nonerosive disease encountered in population surveys probably have osteoarthritis associated with an inflammatory component. A weakness of the ARA criteria is that much importance is placed on soft-tissue swelling which, on its own, is of little specificity, and has poor interobserver reproducibility (37). As an example of conflicting findings most likely resulting from problems in interpretation, surveys in England (37) yielded higher prevalence rates when the New York criteria was used (38) than when the ARA definite category was used. O'Sullivan and Cathcart (36), on the other hand, recorded only 17 cases by the New York criteria and as many as 40 definite RA cases by the ARA criteria. In many diseases (eg, in cancer and coronary artery disease), geographic comparisons have aided researchers in defining the relationship between disease occurrence and potential risk factors such as diet. The early prevalence studies of RA aimed at finding etiological clues on the basis of its occurrence in representative population samples were disappointing, however. Differences in prevalence were recorded, but it could not be determined with certainty whether these were real or only because of observer assessment. Subsequently, it has been firmly established that the prevalence of RA among certain Native Ameri-
can tribes is appreciably higher than in populations of European origin (39, 40). On the other hand, RA may be a rare disease in certain tropical areas. It is commonly stated that the prevalence of arthritis satisfying the simplified ARA 1958 criteria for definite RA or the 1987 classification criteria for RA is about 0.5% to 1% of the adult population in most Western countries (39, 40). Because of the previously mentioned problems, considerable differences in true prevalence may be concealed behind these figures. For the purposes of comparison, clinical arthritis (or deformities of past arthritis) associated with positive serology and/or characteristic radiographic changes is, in our experience, a more reliable measure of clinically significant chronic peripheral arthritis appropriately referred to as RA than RA defined by the ARA criteria. The prevalence of this type of arthritis (1%) recorded in the Mini-Finland Health Survey (18) in the population 30 years of age and over closely corresponds to the cumulative incidence figure of 0.8% in the population 16 years of age and over noted in the context of studies by Korpela (19) and by Hakala et al (11). On this basis, about 30,000 cases of clinically significant chronic arthritis appropriately referred to as RA are present in Finland. Of these, about 60% are under 65 years of age, which is the official retirement age. Clinical arthritis associated with both positive tests for RF and characteristic radiographic changes underestimates the prevalence of clinically significant disease. Yet the prevalence may be a useful index for comparative purposes. We have found seven studies sufficiently large to give some meaningful information that provided the necessary data (Table 4). Figures from the Mini-Finland Health Survey performed between 1978 and 1980 (18), the
Table 4: Prevalence of RA Associated With Positive Radiographic Findings and RF Tests in Seven Populations Investigator
Country
Age
Number of Subjects
Prevalence (%)
Engel et al 1966 (42) Kellgren 1966 (30) Lawrence 1968 (45) Allander 1970 (41) Aho et al 1989 (18) Recht et a11990 (44) Mau et a11991 (43)
USA England Pima Indians Sweden Finland Faroe Islands Germany
18-79 ->15 35-64 31-74 ->30 40-74 25-74
6,287 2,607 632 12,136 7,124 1,624 8,907
0.2 0.6 2 0.5 0.5 0.3 0.15
EPIDEMIOLOGY OF RA IN FINLAND
331
population survey done by Allander in Stockholm, Sweden in the late 1960s (41), and the Arthritis and Rheumatism Council Survey performed in England in the late 1950s (30) were similar. Because the English study consisted of subjects 15 years of age and over and the Finnish and Swedish studies subjects 30 years of age and over, the prevalence in England may have been slightly higher than in Finland and Sweden. In contrast, the prevalence noted in the National Health Examination Survey in the United States (42) performed between 1960 and 1962, in a German study by Raspe et al in the 1980s (43), and in a study by Recht et al (44) on the Faroe Islands were lower. A high prevalence was recorded in Pima Indians (45). Figures concerning new disability pensions for RA were available from Finland, Sweden, and Germany. As seen in Table 5, these figures are in line with those from the previously mentioned prevalence studies and indicate that RA is somewhat less prevalent in Germany than in Finland and Sweden° Incidence Cross-sectional surveys have provided information on the prevalence of RA. Yet patients with chronic stable disease are overrepresented in the prevalence pool; patients who remit and those who die prematurely are underrepresented. Accordingly, incidence is, in certain respects, a more useful measure of the occurrence of RA than is prevalence. The diagnosis of RA cannot always be established on the basis of one single observation; frequently it emerges only after continuous followup. It may be appropriate to separate transient and chronic forms, erosive and nonerosive cases, as well as RF-positive and RF-negative cases, and to analyze the subsets independently rather than to incorporate all into one common disease category.
In a community-based follow-up study of recentonset arthritis from Finland, the majority of RFpositive arthritis patients developed erosive disease, whereas virtually all patients with RFnegative oligoarthritis attained remission (46). The outcome of RF-negative polyarthritis was bimodal: a majority of patients showed a favorable outcome and a minority did not fare well. Therefore, the incidence of RF-positive arthritis to some degree underestimates, and the combined incidence of RF-positive arthritis and RF-negative polyarthritis to some degree overestimates, the incidence of progressive, (ie, clinically significant) arthritis appropriately referred to as RA. On the basis of figures from a recent incidence study from Finland previously discussed (24), it can be estimated that about 1,500 cases of clinically significant RA occur in Finland per year. In the previously mentioned study, the annual incidence of RA satisfying the ARA 1987 classification criteria was 37/100,000 of the population 16 years of age and over. This figure was based on cumulative incidence of symptoms and signs to the time when diagnosis was established and the certificate for reimbursed drugs was written. In a recent population-based study from England (47), the annual incidence of RA in the adult population using the same criteria was 25/100,000; however, this figure was based on symptoms and signs recorded at the time of presentation. Thus the true incidence rates in these two surveys as defined by the ARA 1987 criteria were similar. One important difference was apparent, however: the incidence of RF-positive arthritis in the Finnish series was about 30/100,000, whereas it can be computed on the basis of figures given in the paper by Symmons et al (47) that the corresponding figure in the English series was only 13/100,000. Two recent incidence studies from the United
Table 5: New Disability Pensions for RA in Finland, Sweden, and Germany in 1994 New Pensions Population
Number
Percent of Population
Country
(millions)
All
Due to RA
All
Due to RA
Finland Sweden Germany
3.34* 5.55* 30.27t
20,793 48,531 294,437
583 1,093 2,703
0.63 0.82 0.97
0.017 0.020 0.009
*Total population 15 to 64 years of age. tlnsured population (up to 64 years of age).
332
States covering the somewhat select populations in health maintenance organizations (48, 49) provided figures similar to those reported from Finland and England. On the other hand, Guillemin et al (50) noted appreciably lower figures (9/100,000) in France. As previously indicated, about 30,000 cases of clinically significant RA are present in Finland and the annual incidence of such new cases is about 1,500; thus the ratio of prevalence to incidence rates is about 20. In this context, it is of interest to note that in a recent study covering subjects with specially reimbursed medication for RA who had died over one year, the mean disease duration was 14 years in men and 17 years in women (12).
AHO ET AL
years later by Hakala et al in Kuusamo, revealed fairly good retention of health status and functional ability (28, 51). Indeed, the HAQ scores were better than the earlier results from community-based studies in England (52) and the United States (53). Most of the improvement can probably be explained by the advent of total joint replacement surgery; few operations were performed on RA patients during the 1970s. Some recent data, however, indicate that the long-term use of diseasemodifying antirheumatic drugs retards the progression of destructive joint disease (54) and retains functional ability in patients (55). Whether changes have occurred in the natural course of RA remains an interesting possibility (56).
Disability RA commonly leads to disability. The prevalence of disability in a population, however, is simultaneously determined by many diseases and disorders. The nature and severity of disability vary depending on the causes. Therefore, it is difficult to estimate how much of the burden of disability a single disease such as RA contributes in the general population. The Mini-Finland Health Survey may be the only study providing reliable elements for such an estimation. In terms of the populationattributable fraction, 3% of at least marked disability and 6% of severe disability in Finnish adults were explained by a combination of arthritis and either hand radiographs characteristic of RA or positive RF reaction. Because cases with RFnegative nonerosive cases were not included, these fractions may have slightly underestimated the impact of RA defined by the ARA criteria. A central finding of the Mini-Finland Health Survey was that comorbid diseases and other determinants of functional state did not confound the association between arthritis and disability (26). Comorbidity in arthritis was relatively low and, unlike most musculoskeletal and mental disorders, arthritis was not concentrated in population groups prone to disability such as those with limited education, low income, and physical and mental stress at work. Despite the relatively low prevalence of RA, the impact of this disease was strong. The more severe the disability was considered, the larger that part was explained by RA. Although using indices different from those used in the MiniFinland Health Survey, studies undertaken ten
CONCLUSIONS
In the absence of specific diagnostic tests for RA, diagnosis depends on recognition of patterns of clinical manifestations. The new ARA criteria are classification criteria rather than diagnostic criteria. One problem in their use is that routine patient records are seldom keyed to these criteria; in particular, information on morning stiffness is frequently lacking. According to our experience, more importance should to be given to typical radiographic changes and to RA as an immunologic disease. Development of quantitative immunoturbidimetric RF testing offers better reproducibility and comparability than the earlier test techniques. There probably still is a place for surveys on the prevalence of RA, particularly in various exotic populations. It appears unlikely, however, that further descriptive studies on the prevalence of RA in Western societies will generate clues of etiological and pathogenetic importance (39). On the other hand, large population surveys or registers that provide information on incidence rates may provide some new insight. Examples along these lines are the continuous monitoring of the Norfolk Arthritis Register in England and the register covering sickness insurance benefits in Finland. Available data from England and the United States indicate a recent decline in the occurrence of RA (40). Figures from Finland reveal no clear decline either in prevalence or in incidence; yet a marked shift was noted in the incidence of RA toward elderly patients (25). Subsequently, a simi-
EPIDEMIOLOGY OF RA IN FINLAND
333
lar shift was also reported in Japan (57). Accordingly, the epidemiology of RA is not static but dynamic, and the trends may reflect changes in the host-environment relationship. A decline has occurred in severe disability caused by RA. Functional restrictions can be studied by simple and reproducible methods. Monitoring the occurrence of RA, disability, and its
determinants at the community level likely will be useful in assessing management approaches. ACKNOWLEDGMENT
The authors thank Professor I.B. Linda.hl from Stockholm, and Professor H. Raspe and Ms. R. Deck from Ltibeck for providing work disability statistics from Sweden and Germany.
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