Research Unit, Hospital de la Princesa, Madrid,
1 Rheumatology, Hospital La Paz, Madrid,
2 Rheumatology, Hospital Clínico San Carlos, Madrid,
3 Rheumatology, Hospital Central de Asturias, Oviedo,
4 Clinical Epidemiology, Hospital de la Princesa, Madrid and
5 Rheumatology, Hospital de la Princesa, Madrid, Spain
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Abstract |
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Methods. Two thousand nine hundred and ninety-eight adults were selected randomly from the censuses of 20 municipalities. Trained rheumatologists administered a structured interview that included a screening questionnaire for RA. Subjects with a positive screening result were examined according to a standardized protocol. Cases were defined by the 1987 American College of Rheumatology (ACR) criteria adapted to epidemiological surveys.
Results. One hundred and eighty-six persons (8.5%) had a positive screening result for RA and 11 of these fulfilled the ACR criteria for RA. The estimated prevalence was 0.5% (95% confidence interval 0.250.85). The ratios of women to men and of urban to rural were both 4:1. Function and health perception of the cases were significantly impaired, even after controlling for age and sex.
Conclusion. The prevalence of RA in Spain is comparable to that in other Mediterranean countries. RA may be less frequent in rural settings, a finding that merits further research. A significant proportion of RA cases in the community remain undiagnosed despite impaired functional status.
KEY WORDS: Rheumatoid arthritis, Prevalence, Health survey, Epidemiology.
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Introduction |
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It is important to establish the prevalence of RA, as it might help to clarify the aetiology of the disease, assuming that different rates exist in populations with different genetic and environmental backgrounds. Furthermore, in a setting of increasing treatment costs, economic constraints and managed care, data about the prevalence of different diseases might help health-care systems to develop specific plans for the care for a given disease.
The prevalence of RA in Spain is not documented fully, and only a few studies of the epidemiology of general rheumatic diseases have been carried out [2022]. One of them estimated the prevalence of RA in the area of Tudela (Spain) and observed a relatively low frequency of the disease (0.3%) [22], raising the question of whether this result could be extrapolated to other areas. This observation prompted the Spanish Society of Rheumatology (SER) to conduct a comprehensive study to estimate the prevalence of RA, as well as of other rheumatic diseases, in a representative sample of the general population of Spain: the EPISER study.
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Subjects and methods |
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In order to optimize the participation rate, a large proportion of the study resources was directed towards the implementation of recruitment strategies. These included news in the local media (newspapers, television and radio) to inform the population about the project; up to three personalized letters notifying people about the study and providing an appointment at a given place and date; telephone calls to request individual participation; and neighbourhood-oriented approaches in places where recruitment by the means mentioned above was low. Twenty-one regionally based rheumatologists were responsible for implementing the study protocol at the local level. All of them had been trained previously in recruitment techniques and received a standardization course to ensure the homogeneity of data collection.
The study was approved by the ethics committee of the Hospital de la Princesa and by the evaluators of the Research Fund of the Social Security, and the data set used for the random sampling and location of participants was registered at the Official Agency for Data Protection, in accordance with Spanish regulations.
Data collection
A 45-min visit was scheduled for all selected subjects. Personal interviews were performed at local primary care facilities with the permission of local authorities. The visits were structured as follows. Subjects were first asked about their current health status by means of questions about chronic diseases and medication, plus a validated Spanish version of the SF-12 questionnaire to assess health-related quality of life [23]. The SF-12 yields a continuous result in two scales, physical and mental, which each range from 0 to 100 (worst to best). Subsequent questions enquired about rheumatic symptoms and functional ability by means of the Spanish validated version of the Health Assessment Questionnaire (HAQ) (range 03, best to worst) [24]. Other diagnostic outcomes of the EPISER study were low back pain, fibromyalgia, knee pain fulfilling clinical criteria for osteoarthritis (OA), hand OA, and osteoporosis by peripheral densitometry. The last part of the interview sought sociodemographic information and details of the use of anti-rheumatic medication and doctor visits. A pilot study was carried out to detect possible errors in the design of the data collection forms, to assess feasibility of the recruitment, to estimate the duration of the interviews, and to estimate the percentage of non-responders and the causes of non-collaboration (non-located subject, refusal to be interviewed, others). A basic interview, collecting demographic information, was designed for the non-responder subjects in order to compare their characteristics with those of the responders.
RA screening
A screening questionnaire for RA, previously validated by MacGregor et al. [25], was included in the interview. The questions of the original English questionnaire were translated and back-translated by one of the investigators (LC) and a lay native speaker of English (M Sloan) until a consensus was reached (see original and Spanish version Appendix 1). Positive screening for RA was defined by at least one of the following: (i) two swollen joints in the past or at the time of the interview; (ii) a diagnosis of arthritis in the past. The original questionnaire, tested in a British community, had a sensitivity of 100% and a positive predictive value of 1015% [25].
RA cases were defined by the 1987 American College of Rheumatology (ACR) criteria adapted to epidemiological surveys [26], which permit the estimation of active and inactive cases of the disease, yielding the lifetime cumulative prevalence of RA. By these criteria, a subject with a written report stating the presence of signs of previous RA or clear RA deformities, but not with active disease, may be ascertained as an RA case (Table 1). Subjects who could not be classified on the basis of clinical criteria alone underwent rheumatoid factor analysis by the agglutination latex method and standard X-rays of both hands.
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Statistical analysis
All prevalence estimates and 95% confidence intervals (CI) were obtained with the statistical program CSAMPLE provided with EpiInfo 6.04b (Centers for Disease Control & Prevention, Atlanta, GA, USA), which allows correction of the variance for the design effect by adding variables for the stratum and for the primary sampling unit. All participants had a weight assigned, which was the inverse of the probability of the participant's being selected during the sampling process. Odds ratios and P values for 2 tests for comparison between groups were also obtained with EpiInfo and the results are shown corrected for design. Continuous variables were tested with the Wilcoxon rank sum test or multivariate analysis of variance (ANOVA) to control for covariates, for which the Stata 5.0 program (Stata Corporation, College Station, TX, USA) was used.
Sample size was calculated to obtain a prevalence estimate between 0.5 and 1% with 95% confidence and a statistical power of 80%, and was increased by 50% to account for the design effect and recruitment failures.
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Results |
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Prevalence of RA in Spain
A total of 186 subjects (8.5%) had a positive screening result for RA. Of these, nine women and two men were classified as having RA according to the ACR criteria. The estimated prevalence of RA in the adult Spanish population was 0.5% (95% CI 0.250.85). The prevalence of RA was 0.8% (95% CI 0.41.1) in women and 0.2% (<0.5) in men. Extrapolating to the total population of the country (around 40 million), there are 150000200000 cases of RA in Spain.
Predictive value of RA screening
The rheumatologists did not identify any case of RA, by inspection or through interview questions, without positive screening. Therefore, the negative predictive value of the screening was 100%. The positive predictive value (PPV) of the screening questionnaire in the general population of Spain was 5.9%. Individual items of the screening questionnaire (see Appendix 1) had a different PPV. Having a previous diagnosis of arthritis was the best-discriminating single item for RA (PPV 16%), followed by having inflammation for more than 6 weeks (PPV 12.4%); if inflammation had occurred in two or more peripheral joints the PPV rose to 40.9%. Morning stiffness lasting longer than 30 min and pain for more than 4 weeks had a low PPV (8 and 2.4% respectively).
A hand X-ray in one case and determination of rheumatoid factor in another were needed to confirm criteria. These techniques were used mainly to verify the absence of the disease in subjects who otherwise had a positive screening result.
Regarding individual criteria for RA (historical or current) in subjects with a positive screening result, (i) all cases plus four non-cases presented or had presented morning stiffness for more than 1 h for a period of at least 6 months; (ii) all cases plus eight non-cases presented or had presented synovitis in three or more joints; (iii) all cases plus 13 non-cases presented or had presented synovitis in hand joints; (iv) all cases plus five non-cases presented or had presented symmetrical synovitis; (v) only one case presented or had presented rheumatoid nodules; (vi) five cases presented or had presented rheumatoid factor positivity; and (vii) X-ray changes were confirmed in four cases and were considered to be unnecessary in the rest. None of the subjects with fewer than four clinical criteria of RA had an X-ray compatible with RA.
Characteristics of the RA cases identified
Despite the low number of cases in the present study, it may be possible to obtain some preliminary descriptors of the disease in the general population. The most important characteristics of the patients identified are shown in Table 3. Female sex was confirmed as a risk factor for the presence of the disease, with an odds ratio of 3.90 (95% CI 1.1713.00). The disease was detected more frequently in cities than in villages, with an estimated prevalence of 0.6% (95% CI 0.21.3) in urban areas and 0.2% (95% CI <0.5) in rural areas, although the difference was not statistically significant (P>0.05). The mean age of the subjects with RA was 59 yr (range 2292 yr), RA occurring more frequently between the fourth and sixth decades (Table 3
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The general health status perception was regular to poor in 55% of the subjects with RA compared with 27% of subjects without RA (P>0.05). People with RA scored an average 40.75±14.01 in the physical component of the SF-12 questionnaire vs 50.23±9.23 in non-RA subjects (P<0.05). The mean score for the mental component of the SF-12 questionnaire was 45.33±10.72 in RA cases and 49.69±9.91 in non-RA participants (P>0.05). After adjustment for age and sex in an ANOVA model, the physical score of the RA cases increased to a mean of 43.65±2.55 (P=0.010). Interestingly, one case had a very low SF-12 physical component score despite a reasonably favourable HAQ score. This is because the SF-12 measures more physical resistance and self-perception of health while HAQ measures more specific daily activities. This woman was able to walk outside without difficulty (HAQ) but she believed that her health restricted her ability to walk outside for 1 h (SF-12).
Seventy-three per cent of the individuals with RA had visited an out-patient clinic in the last year as a consequence of rheumatic symptoms, compared with 33% of the general population. Persons with RA consulted several specialists: rheumatologists (63.6%), general practitioners (27.3%) and orthopaedic surgeons (9.1%). The drugs used most frequently by the RA patients in the last year were non-steroidal anti-inflammatory drugs (NSAIDs) (63.6%) and analgesics (45.5%). Only four patients (36.4%) were receiving disease-modifying drugs: three such patients were on gold salts and one had received methotrexate in the previous year.
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Discussion |
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In order to obtain a more precise picture of the disease, active and inactive cases of RA were ascertained by adaptation of the ACR classification criteria to epidemiological surveys [26]. The authors of this modification call the estimate of the prevalence obtained by this criteria the RA lifetime cumulative prevalence. Using this approach, we found that the prevalence of RA in the general population of Spain is 0.5%. This figure is somewhat lower than estimates yielded by US studies but higher than those reported in countries in the Mediterranean region. In Northern Greece, for instance, the prevalence of RA in 1991 was 0.2% in men and 0.5% in women [29] and in a nationwide study in France the estimated prevalence was 0.3% in 1998 [30]. However, when the methods used for case ascertainment in these two studies are taken into account, the prevalences in France and Greece may turn out to be higher. In the Greek study, cases were established from clinical records in Ioannina health registers and extrapolated to the population census in 1991. In the French study, cases were obtained from patient groups and out-patient clinics. It is possible that RA cases in the community remain undiagnosed, as has been demonstrated in the EPISER study, and therefore the prevalence estimates in both Greece and France result from miscalculation of the real frequency of the disease in those countries.
Previous epidemiological studies in Spain have shown discordant results. One study in the 1980s in a small village in Central Spain showed a high prevalence of RA by New York criteria [1], namely 1.6% [21]. Another study in northern Spain, in 1990, estimated the prevalence by ACR criteria as 0.7% [20]. In both studies, the sample size was too small to give a reliable estimate of the prevalence of RA, although it was adequate to estimate the prevalences of other rheumatic diseases. In 1997, Ibañez Bosch et al. [22] selected a random sample of 6027 subjects older than 16 yr from the census of Tudela, an area with a half-rural, half-urban population. In this study, RA cases were identified by initial screening with a mailed questionnaire and subsequent examination of positive cases. Ibañez Bosch et al. estimated the prevalence of RA as 0.37% (95% CI 0.220.80). The main limitation of the study was a low percentage of respondents (38.1%) despite the investigators' efforts. Analysis of the respondents' data showed no differences between those who participated and a random sample of non-respondents, to whom a further letter was sent. Interestingly, the 95% CI for the estimate in the Tudela study was identical to that obtained in the EPISER study after correction of the variance.
RA was more frequent in women than in men, as expected. Interestingly, prevalence seems to be higher in urban areas than in rural settings, a trend that needs to be confirmed. This lower prevalence in rural areas is consistent with the study by Ibañez et al. [22] and with a study conducted, at the same time as the EPISER study, in two villages in the province of Cordoba (Spain), where the prevalence was 0.34% [31]. African RA studies hint that the rate of RA may be affected by the place of residence: no cases of RA were found in a rural Nigerian population [2]. Furthermore, a Taiwanese study reported lower rates of the disease in rural than in urban and suburban settings [9]. Why the prevalence of RA varies with the type of residence is an uninvestigated question that merits in-depth research.
Establishing the prevalence rate of a given disease, such as RA, is not only a matter of scientific curiosity, but also has important implications for society as a whole: studies of RA have shown firstly that this disease has a substantial impact on the functioning and quality of life of unselected individuals of the general population, and secondly that not all patients actually benefit from the growing understanding of the disease. In the EPISER study, half of the cases identified had serious difficulty performing normal daily activities and needed help from others in these tasks. Three patients classified as having RA in the EPISER study had not been diagnosed with the disease previously, despite the fact that RA had affected their lives significantly. Furthermore, only four (36%) subjects were receiving any disease-modifying anti-rheumatic drug therapy, and some of the subjects with low functional capacity were not receiving any treatment at all or were taking only NSAIDs. This lack of adequate treatment reflects the poor management of the disease in the general population and shows the need for administrators to anticipate RA in compensation plans. In the EPISER study, only one patient (9%) was receiving disability compensation for RA.
Finally, universal health-care systems face the care of a growing number of patients with chronic, disabling diseases such as RA in a setting of increasing treatment costs and economic constraints. Because equal access to treatment for all patients should be provided by these systems, data about the prevalence and health impact of RA in the general population might help decision-makers to develop long-term, disease-specific plans for care.
Taking into account the observation that a significant proportion of RA cases (including even those with poor functional status) remain undiagnosed in the community, we conclude that the prevalence of RA in the Spanish population might be in the range of other Mediterranean countries. The prevalence of RA may be lower in rural settings, a finding that is consistent with previous studies and that merits further research. Strategies for outreach and management of undiagnosed cases in the general population are still necessary even in the developed world. Reliable prevalence rates should help to improve the planning of health-care and disability compensation in national systems with universal coverage.
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Appendix 1 |
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Original version
Report
Spanish version
The last question was asked in many different ways throughout the interview.
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Acknowledgments |
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The full study group, given in alphabetical order, is as follows: I. Aretxabala, Hospital de Cruces, Bilbao; J. Beltrán, Hospital General, Castellón; P. Benito, Hospital del Mar, Barcelona; S. Benito, Complejo Hospitalario San Millán-San Pedro, Logroño; M. Calabozo, Hospital de Cruces, Barakaldo; J. C. Cobeta, Hospital Obispo Polanco, Teruel; M. Ciria, Hospital del Mar, Barcelona; C. Fernández-Carballido, Hospital Dr Peset, Valencia; J. A. Fernández, Hospital Central de Asturias, Oviedo; J. L. Fernández-Sueiro, Hospital Juan Canalejo, La Coruña; G. Garrido, Hospital Gregorio Marañón, Madrid; Y. Grandal, Hospital General, Jerez de la Frontera; J. Graña, Hospital Juan Canalejo, La Coruña; A. Hernández, Hospital Juan Canalejo, La Coruña; A. Humbría, Hospital Universitario de la Princesa, Madrid; A. Juan Mas, Hospital Son Dureta, Mallorca; A. Laiz, Hospital Sant Pau, Barcelona; J. López-Martínez, Department of Social Psychology, Universidad Autónoma, Madrid; E. Martín-Mola, Hospital La Paz, Madrid (current President of the Spanish Society of Rheumatology); O. Martínez, Hospital de la Santísima Trinidad, Salamanca; J. Medina, Hospital General, Soria; M. Menchón, Hospital Virgen de la Arrixaca, Murcia; M. Moreno, Hospital Santa María del Rosell, Murcia; T. Navío, Madrid; F. Navarro, Hospital Virgen Macarena, Sevilla; A. M. Ortiz, HU de la Princesa, Madrid; B. Ribas, Hospital Sant Joan de Déu, Mallorca; P. Rojas, Toledo; C. Rodríguez-Lozano, Hospital Doctor Negrin, Gran Canaria; F. Romero, currently Medical Assessor for Aventis; B. Romero, Teruel; E. Ruiz, Hospital de Cruces, Barakaldo; J. M. Salazar, Hospital Infanta Cristina, Badajoz; J. Sampedro, Hospital Virgen de la Salud, Toledo; E. Trujillo, Hospital General Universitario, Tenerife; N. del Val, Hospital General, Soria; J. P. Valdazo, Hospital Virgen de la Concha, Zamora; M. Valverde, Preventive Medicine and Public Health Area, Universidad de Almería, Almería; J. Vidal, Hospital General y Universitario, Guadalajara; V. Villaverde, Hospital La Paz, Madrid; E. Yelin, Arthritis Research Group, University of California, San Francisco, USA.
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Notes |
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Correspondence to: L. Carmona, Unidad de Investigación, Hospital de la Princesa, Diego de León, 62, 28006 Madrid, Spain
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References |
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