Prevalence and management of rheumatoid arthritis in thegeneral population of Greece—the ESORDIG study
A. Andrianakos1,2, P. Trontzas3, F. Christoyannis1, E. Kaskani4, Z. Nikolia5,E. Tavaniotou1, A. Georgountzos3 and P. Krachtis1 for the ESORDIG study groupy
Objective. To assess the prevalence and management of rheumatoid arthritis (RA) in the general adult population of Greece. Methods. This cross-sectional study was conducted on the total adult population (!19 yrs old) of seven communities(8547 subjects), and on 2100 out of 5686 randomly selected subjects in two additional communities. The study, based ona standardized questionnaire and clinical evaluation and laboratory investigation when necessary, was carried out byrheumatologists who visited the target population at their homes. Diagnosis of RA was based on the American College ofRheumatology (ACR) 1987 criteria. Results. A total of 8740 subjects participated (response rate 82.1%). RA was diagnosed in 59 individuals. The prevalence of RAwas 0.68% (95% CI 0.51–0.85); it was significantly higher in females than males (P < 0.0005), and increased significantlywith age up to and including the 50–59-yr-old group (P < 0.002), and then decreased slightly. On their first medical visit, 19%(95% CI 9.7–30.9) of the RA patients had consulted a rheumatologist, while during the first year after disease onset, 61%(95% CI 48.6–73.4) had done so. Early consultation with a rheumatologist and disease-modifying anti-rheumatic drug(DMARD) combination therapy were negatively associated with ACR functional classes II–IV [adjusted odds ratios 0.18(95% CI 0.04–0.85) and 0.17 (95% CI 0.04–0.72), respectively]. Conclusions. The prevalence of RA in the general adult population of Greece is similar to that in many other Europeancountries; early consultation with a rheumatologist and DMARD combination therapy are associated with a better RAoutcome.
KEY WORDS: Rheumatoid arthritis, Prevalence, Epidemiology, Management, Greece.
Rheumatoid arthritis (RA) is a chronic and deforming inflam-
disability. Epidemiological studies have shown that the prevalence
Details on the ESORDIG study population, subject recruitment
of RA varies broadly from 0.2 to 1.0% in various European,
and evaluation, as well as on quality control have been reported
North American, Asian and Australian populations . Most
previously . The ESORDIG study was conducted from March
studies in European countries have suggested a prevalence in adult
1966 to April 1999 on the total adult population (aged !19 yrs
populations ranging from 0.5 to 1.0% [1–7]. However, some
old) of two urban, one suburban and four rural areas located in
studies, especially those from southern European countries,
northern, central and southern mainland Greece (8547 subjects),
including Greece, have shown a lower prevalence (0.18–0.34%),
as well as on 2100 out of 5686 randomly selected adult subjects in
which raises important questions about the possible involvement
one additional rural and one suburban community. In the latter
of different environmental and/or genetic factors in the aetiology
areas, every second and third household from a randomly chosen
of RA among various European populations [8–10]. Few
starting point, respectively, was selected (systematic sampling)
population-based studies have assessed the care of RA patients
(Fig. 1); this was for practical reasons since there were only two
[11–13] and data on the association between care and the outcome
investigators available for the suburban and one for the rural area.
of RA in the general population are limited.
Sixteen rheumatologists conducted the study by visiting the target
This part of the ESORDIG (epidemiological study of the
population at their homes. Each visit involved an interview with
rheumatic diseases in Greece) study aimed at assessing the
each participant that was based on a standardized questionnaire
prevalence and management of RA in the general adult
aimed at obtaining a variety of information on socio-demographic
characteristics, medical history, and on a specific standardized
1Rheumatic Disease Epidemiology Section, Hellenic Foundation for Rheumatological Research, 2Third Department of Internal Medicine, AthensUniversity Medical School, Sotiria Hospital, 3Rheumatology Department, 3rd IKA Hospital, 4IKA Health Center, Halandri and 5DEH Health Center,Athens, Greece.
Received 18 November 2005; accepted 16 December 2005. yIn addition to the authors, the following physicians are members of the ESORDIG study group: P. Dantis, D. Karamitsos, G. Kaziolas, L. Kontelis,
Correspondence to: A. Andrianakos, Hellenic Foundation for Rheumatological Research, 8 Rodon Street, Kantza Pallini Attikis, 153 51 Athens,
ß The Author 2006. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: [email protected]Eligible adult population (19 years) n = 14233 Total adult populationin 7 areas Selected samplein 2 areas [Suburban: 1486 out of4458 (ratio 1:3)n = 8547 Rural: 614out of 1228 (ratio 1:2)]n = 2100 Final target adult population n = 10647 Participants (Interviewed and evaluated by rheumatologists attheir homes)n = 8740 Participation rate: 82.1%)
FIG. 1. Flow chart showing the ESORDIG study design.
questionnaire aimed at revealing all subjects suffering from RA.
This specific questionnaire was analogous to that used byMacGregor et al.  and consisted of the following three
All analyses were conducted using SPSS v.12.0 for Windows. The
questions: have you ever had (i) any joint pain, not due to
chi-square test was used to compare prevalence and percentages,
trauma, lasting at least six continuous weeks? (ii) any joint
while the comparison of mean values was by Student’s t-test. Values of P < 0.05 were considered significant; 95% confidence
swelling lasting at least six continuous weeks? (iii) morning
intervals (CIs) were given where relevant. A logistic regression
stiffness in any joint, lasting at least 1 hour before maximal
model was used for assessing the association of RA with certain
improvement? The sensitivity of this questionnaire to detect cases
factors such as sex, age, marital status, body mass index (BMI),
of RA was shown to be 100% in a pilot study of 45 patients with
cigarette smoking (pack-yrs), alcohol consumption, level of
known RA, performed prior to the start of the ESORDIG study.
education, occupation, socioeconomic status and residence in
All subjects who responded positively to any of the three questions
urban, suburban or rural areas. Concerning BMI, cut-off points of
of this specific questionnaire were subsequently evaluated by
!30 kg/m2 for obesity and <30 kg/m2 for non-obesity were used
the rheumatologists conducting the study (medical history,
. The level of education was defined as low or high on the basis
clinical examination, assessment of available laboratory and
of school attendance up to 9 and >9 yrs, respectively. Multiple
imaging findings), during the same home visit. When necessary,
logistic regression analysis was also applied for assessing the
appropriate X-ray investigation and/or other requisite laboratory
association of ACR functional classes II–IV with certain factors
tests were performed on the following days, and the findings
such as sex, age, residence, BMI, disease duration, disease
were assessed by the rheumatologists during a second home visit,
remission or not, presence of rheumatoid factor or not, early or
in order to reach a definite diagnosis. The diagnosis of RA was
late consultation with a rheumatologist and disease-modifying
made on the basis of the American College of Rheumatology
anti-rheumatic drug (DMARD) combination therapy.
consequences of RA were assessed using the respective ACRcriteria [16, 17].
The effect of non-selection and random selection of suburban
and rural populations on the study results was tested in a logisticregression model in which the dependent variable was the
Of the final target adult population of 10 647 subjects, 8740
diagnosis of RA and the independent variables were the
participated in the study (participation rate 82.1%). Among the
selected/non-selected populations. As previously described ,
participants, 4269 (49%) were men and 4471 (51%) were women,
data were obtained from a random sample of non-responders on
while 31% were residents in urban, 34% in suburban and 35%
socio-demographic characteristics, past medical history, previous
in rural areas; the age range was 19–99 yrs, mean 47 yrs (S.D. 17.7).
rheumatic disease diagnosis including RA, and the reasons for
As reported previously , using Pearson correlation coefficients,
we found significant similarities in terms of age and sexdistribution between the study participants, the total targetadult population and the total adult population of Greece, even
when the data were analysed separately for urban, suburban and
The study was conducted according to the declarations of
rural populations. Logistic regression showed no effect of non-
Helsinki and written informed consent was obtained from
selection and random selection of suburban and rural populations
all the study participants. The protocol was approved by the
on the study results. Moreover, no significant difference was
appropriate committees of the Ministry of Health and the Central
found between non-responders and responders in terms of age,
Union of Municipalities and Communities of Greece.
sex and prevalence of rheumatic symptoms or disease. The reasons
Prevalence and management of RA in Greece
TABLE 1. Demographic and clinical variables of the RA patients
Values are percentages (95% CIs) unless otherwise stated; NS ¼ not significant.
for non-participation were unrelated to the presence or not ofrheumatic disease.
Of the 8740 participants, 59 were diagnosed as having had RA(Table 1). Thus, the age- and sex-adjusted prevalence of RA in thetotal target adult population was 0.67% (95% CI 0.54–0.80),while the prevalence of RA among the study participants was0.68% (95% CI 0.51–0.85). The prevalence of RA was signifi-cantly higher among females (1.0%, 95% CI 0.71–1.29) comparedwith males (0.3%, 95% CI 0.14–0.46) in the study participants(P < 0.0005), with a ratio of 3.3:1. The prevalence of RA increasedsignificantly with age up to and including the 50–59-yr-old group(P < 0.002), and then decreased slightly but non-significantly inthe last two age groups (P ¼ 0.44) (Fig. 2). There was nosignificant difference in the prevalence of RA among the urban,suburban and rural populations, nor between the selected and
FIG. 2. Prevalence of RA by age group.
non-selected populations, nor even between the studied northern,central and southern areas of the country.
Logistic regression analysis showed that among the many
TABLE 2. Medical specialties first visited by the 59 RA patients
factors included in the model, only female sex and age !40 yrswere significantly associated with RA [adjusted odds ratios 3.7
(95% CI 2.0–6.9), P < 0.0005, and 6.1 (95% CI 2.8–13.4),
Two of the 59 RA patients (3%, 95% CI 0.4–11.7) had not beenseen by a physician prior to the study and were diagnosed by theinvestigators. Although the other 57 RA patients had soughtmedical assistance for their symptoms, on their first medical visit
administered in 21 patients and the most commonly used combi-
only 11 patients (19%, 95% CI 9.7–30.9) had consulted a
nations were hydroxychloroquine þ sulfasalazine þ methotrexate
rheumatologist and the remaining 46 (78%, 95% CI 67.4–88.6)
in six patients (29%), hydroxychloroquine þ methotrexate in five
had seen physicians of other specialties (Table 2). However, most
patients (24%), and methotrexate þ ciclosporin in four patients
of the RA patients were seen by rheumatologists at subsequent
(19%). Leflunomide and biological therapy were not available in
medical visits, and remained under their care: 36 of the RA
Greece at the time the study was conducted.
patients (61%, 95% CI 48.6–73.4) had consulted a rheumatologistduring the first year of the course of the disease (group I) and18 (30%, 95% CI 18.3–41.7) after the first year of the course of the
disease (group II), while five patients (9%, 95% CI 2.8–18.7) hadnever seen a rheumatologist. Table 3 shows the demographic and
In this part of the ESORDIG study, the prevalence and
clinical variables for the RA patients in groups I and II. Multiple
management of RA were assessed in urban, suburban and
logistic regression analysis showed a significant negative associa-
rural general adult populations of Greece. Among the study
tion of an early consultation with a rheumatologist and of
participants the RA prevalence was 0.68%; this was significantly
DMARD combination therapy with ACR functional classes II–IV
higher among women than men, and increased significantly
[adjusted odds ratios 0.18 (95% CI 0.04–0.85), P < 0.031, and 0.17
with age up to and including the 50–59-yr-old group, and then
(95% CI 0.04–0.72), P < 0.016, respectively].
decreased slightly. An early consultation with a rheumatologist
Prior to being seen by a rheumatologist, 25 RA patients had
and a DMARD combination therapy were negatively associated
been treated at different times by at least two non-rheumatologist
with ACR functional classes II–IV.
physicians. Comparative data on the diagnosis and treatment of
Our estimate of RA prevalence is comparable with that found
the RA patients by rheumatologists, orthopaedists and internists
in other population-based studies in European Caucasians, which
are shown in Table 4. The five most commonly prescribed
used the same classification criteria : 0.8% in Finland  and
DMARDs in 52 patients were: methotrexate (81%), hydroxy-
Manchester and Norfolk, UK [2, 19], 0.62% in Brittany, France
chloroquine (46%), gold salts (37%), sulfasalazine (23%) and
, and $0.5% in Sweden , Oslo, Norway , and Spain .
In a few studies from southern Europe [8–10], including Greece,
TABLE 3. Demographic and clinical variables of the RA patients by early or late consultation with a rheumatologist*
Values are percentages (95% CIs) unless otherwise stated; NS ¼ not significant. *Group I: patients consulted a rheumatologist during the first year of the disease course; Group II: patients consulted a rheumatologist after the first
TABLE 4. Diagnosis and treatment of the RA patients by rheumatologists and non-rheumatologists*
NSAIDs: non-steroidal anti-inflammatory drugs; DMARD: disease-modifying antirheumatic drug. *Prior to their visit to a rheumatologist, 32 patients had been treated by orthopaedists and 30 by internists. In addition, two patients had been
continuously followed up by orthopaedists.
**Analgesics, local or intra-articular injections of corticosteroids.
and in a recent report from France , a lower prevalence of RA
in European, North American, Asian and Australian epidemio-
(0.18–0.34%) has been reported. Although this low prevalence
logical population studies, with a female to male ratio varying
could be related to a variation in genetic and/or environmental
in the range of 2–5.6:1 [1, 4, 6–10, 20, 22, 23]. In accordance with
risk factors in these areas, it seems more possible, however, that
previous studies [1, 4, 7, 8, 22], RA prevalence increased with age
reaching a peak in the 50–59-yr age-group. The slight decline of
instance, the study in the Ioannina district of northwest Greece
RA prevalence at older ages, we found, has also been reported in
was based on RA cases diagnosed in two hospitals and private
previous studies [4, 7, 8]; this could be attributed to an increased
rheumatologists’ offices . Thus, an underestimation of the RA
mortality rate in RA patients at these ages [26, 27]. The residential
prevalence seems quite possible, since patients with severe RA
area did not affect the prevalence of RA in our study. However,
could have moved and sought healthcare in other cities outside
some studies have suggested that rural residence may be
northwest Greece, while mild cases in the community could have
associated with a lower prevalence [7, 28]. Whether a variation
remained undiagnosed or they could have been under the care of
in environmental or socioeconomic factors could be responsible
other medical specialties . Indeed, it was shown in the present
for these differences is unknown, although no association between
study that 9% of the RA patients had never been seen by a
socioeconomic status and RA was found in our study.
rheumatologist, while during the first year of their disease course
Prior to the present study, most of the RA patients had been
only 61% of the patients had consulted rheumatologists. An
treated by a rheumatologist. However, on their first medical visit,
underestimation is also possible in the Belgrade study ; 18% of
only a small percentage of RA patients (19%) had consulted
the subjects with rheumatic complaints refused to undergo clinical
rheumatologists, while within the first year after disease onset,
evaluation, while patients with RA in remission were apparently
61% had visited rheumatologists; the latter finding is comparable
not included in the prevalence estimation, since the questionnaire
with that of a recent study from Germany . This delay in
used focused on symptoms during the 3 months prior. The low
consulting a rheumatologist may be related to the low percentage
response rate in the Italian study may be related to an
(18%) of correct RA diagnosis made by non-rheumatologist
underestimation of the RA prevalence , since patients with
physicians in our study and possibly to a low level of public
RA could have been unwilling to participate in a mail survey.
awareness of RA. Delayed rheumatological care may have
On the other hand, genetic and/or environmental factors could
tremendous consequences on the outcome of the disease.
account for the higher prevalence ($1.0%) in the USA [22, 23],
Indeed, logistic regression showed a significant negative associa-
the high prevalence of RA in Native American populations
tion between early rheumatological care and ACR functional
(up to 6.8%) , the low prevalence in Asian countries ($0.3%)
classes II–IV. DMARD combination therapy was exclusively
[1, 24], the rarity of RA in Africans , and the lack of RA in
prescribed by rheumatologists and it is of interest that a significant
negative association was also found between this therapy and
Female sex and age !40 yrs were strong independent predictors
ACR functional classes II–IV. Therefore, the early and aggressive
for the disease, in our study. With the exception of a Swedish
treatment prescribed by rheumatologists may account for
study , the preponderance of RA in females is well documented
the above findings. The advantages of rheumatological vs
Prevalence and management of RA in Greece
non-rheumatological care with regard to the outcome of the
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We are grateful to the inhabitants, the mayors and the local
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A 40-yr-old man presented with fever, flank pain, epistaxis,haemoglobin 12.8 g/dl, WCC 12.9 Â 103/mm3, C-reactive protein(CRP) 142 mg/l and erythrocyte sedimentation rate (ESR)101 mm. Computed tomography (CT) of abdomen showed aleft renal mass, suggesting renal cell carcinoma (RCC) (Fig. 1A)and possible metastases (Fig. 1B) on CT thorax. Followingdiscussions, it was agreed that the radiological featureswere atypical for RCC, and renal abscess was more likely. Patient remained unwell after 6 weeks of antibiotics. CRP was
FIG. 1. Initial CT showing the renal mass and pulmonary nodule
320 mg/l and ESR 124 mm. No organisms grew on blood/urine
culture. cytoplasmic-Anti-neutrophil cytoplasmic antibody was1:320 with strongly positive anti-PR3, suggesting Wegener’s
granulomatosis (WG). Biopsy of the renal mass was planned.
Pre-biopsy CT abdomen confirmed considerable reduction in
the size of the mass and new lesions in both the kidneys (Fig. 2A)compatible with vasculitis. Repeat CT thorax showed newperibronchial shadowing (Fig. 2B). Renal function deterioratedacutely and decision was made to treat for WG. Dramaticimprovement was noted. He remains well. Full blood count,renal function and CRP are normal.
Maguire et al.  reported atypical radiological findings
in 31 WG patients; only one had a renal mass. Spontaneousresolution of the mass makes our case unique. We believe thatthe mass represented oedema surrounding the underlying
FIG. 2. Repeat CT with marked reduction in the renal mass and
vasculitis. Renal biopsy, while important, should not delay
new renal and pulmonary lesions (marked with arrows).
treatment if the overall picture is suggestive of WG.
Correspondence to: Dr A. Negi, Specialist Registrar,
The authors have declared no conflicts of interest.
Department of Rheumatology, University Hospital of Wales,Heath Park, Cardiff CF14 4XW, UK.
EGI , J. P. CAMILLERI , P. N. MATTHEWS , M. D. CRANE
1Department of Rheumatology, 2Department of Urology and3Department of Radiology, University Hospital of Wales,
1. Maguire R, Fauci AS, Doppman JL, Wolff SM. Unusual radio-
graphic features of Wegener’s granulomatosis. Am J Roentgenol
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