Rheumatol Int (2003) 23: 70–74
DOI 10.1007/s00296-002-0251-6
O R I GI N A L A R T IC L E
Ioannis A. Papadopoulos Æ Pelagia Katsimbri
Yannis Alamanos Æ Paraskevi V. Voulgari
Alexandros A. Drosos
Early rheumatoid arthritis patients: relationship of age
Received: 5 March 2002 / Accepted: 18 August 2002 / Published online: 15 October 2002

Springer-Verlag 2002
Abstract The aim of this study was to investigate if age
at disease onset comprises a separate parameter for
disease expression, prognosis, and outcome in early
rheumatoid arthritis (RA) patients. Four hundred thir-
ty-eight patients with early RA (disease duration less
than 1 year) were studied. All of them fulfilled the
American College of Rheumatology criteria for RA. The
demographic, clinical, laboratory, radiologic, and ther-
apeutic characteristics of the disease at diagnosis and
during and at the end of follow-up (time period 1981–
2000) were analyzed according to age at disease onset
(young patients aged less than 60 years at disease onset
vs elderly patients aged more than 60 years at disease
onset). We found 317 young and 121 elderly patients
with early RA. The male:female ratio, which was 1:3.2 in
the young patients, was nearly equal in the elderly
(1:1.4). In addition, at disease onset elderly patients
showed more severe joint involvement (decreased grip
strength) associated with high titers of acute phase
response (erythrocyte sedimentation rate and C-reactive
protein) than the younger patients. However, there were
no differences between the two groups in the numbers of
tender and swollen joints or acute phase response at the
end of the study period. Furthermore, no differences
were seen between the two groups concerning the pres-
ence of rheumatoid factor. Finally, the two patient
groups showed the same degree of radiological changes
and functional ability and were treated similarly, except
for more frequent corticosteroid use in the elderly.
I.A. Papadopoulos Æ P. Katsimbri
P.V. Voulgari Æ A.A. Drosos (&)
Division of Rheumatology,
Department of Internal Medicine, Medical School,
University of Ioannina, 45 110 Ioannina, Greece
E-mail: adrosos@cc.uoi.gr
Tel.: +30-6510-99755/97503
Fax: +30-6510-97054
Y. Alamanos
Department of Hygiene and Epidemiology,
Medical School, University of Ioannina,
45 110 Ioannina, Greece
We conclude that elderly patients present with more
severe joint involvement at disease onset. However, at
the end of the study, no differences were seen concerning
radiological changes and functional ability. It seems that
age at disease onset does not influence the clinical course
and outcome of early RA patients.
Keywords Age Æ Early rheumatoid arthritis Æ
Early treatment Æ Elderly Æ Young
Introduction
The severity and outcome of rheumatoid arthritis (RA)
have been shown by many previous studies to be influ-
enced by a variety of factors such as gender, race [1, 2]
age at disease onset, duration of disease [3, 4, 5], joint
scores for pain and swelling, systemic manifestations,
and radiological changes [6, 7, 8, 9, 10]. Furthermore,
other factors which may influence disease expression and
outcome are the values of the acute phase reactants
(erythrocyte sedimentation rate and C-reactive protein)
[11, 12, 13, 14], the presence of rheumatoid factor (RF)
[14, 15, 16, 17, 18, 19], and human leukocyte antigen
(HLA) phenotype [20, 21, 22].
Studies show conflicting results regarding the age at
disease onset, with some showing a milder picture in
elderly onset RA (EORA) [3, 4, 23] and others showing
elderly patients as having worse outcome, especially
regarding functional ability, the degree of destructive
arthropathy, and mortality rate [8, 13, 14].
Thus, the present study investigates the course and
outcome of Greek patients with early onset RA with
regard to age at disease onset (old >60 years vs young
<60 years).
Material and methods
We studied the course and outcome of 454 patients with early-onset
RA (disease duration prior to diagnosis less than 1 year and age
greater than 16 years) from a total of 1,271 patients with RA
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recorded at the Rheumatology Department of the University the original joint involvement. However, the EORA
Hospital of Ioannina, Greece, during the period of 1981–2000. group shows a higher frequency of polyarthritis at the
The patients fulfilled the American College of Rheumatology
(ACR) disease criteria for diagnosis [24]. They were divided into onset of disease (P<0.05).
two groups based on the age at disease onset: young onset RA Concerning the type of joint involvement (small/large
(YORA) (less than 60 years) and elderly onset RA (EORA) joints, upper/lower limbs) at disease onset (Fig. 2), there
(greater than 60 years). This definition was chosen because 60 is the were no significant differences between the two groups,
cutoff age most often used by previous investigators.
Records of the patients were reviewed and the following pa-
although there was a preponderance of small and
rameters were recorded in a database: demographic, clinical, labo- medium joint involvement of the upper limbs for both
ratory, radiological, and therapeutic characteristics at the time of groups (70–80%). The YORA showed more arthritis in
disease diagnosis, at the end of the follow-up period, and at regular the toes (25.9% vs 14.8%) and the EORA showed
intervals in between. Patients were excluded if they had symptoms, greater involvement of wrist (77.7% vs 69.4%) and
signs, or family history of psoriasis, inflammatory bowel disease,
ankylosing spondylitis, Reiter’s syndrome, polymyalgia rheumatica, elbow and shoulders (37.2% vs 30.9%), without a sta-
or juvenile RA. tistically significant difference. Elderly onset RA seemed
The patients selected had not used disease-modifying anti- to be more severe at disease onset, with lower values for
rheumatic drugs (DMARDs) or corticosteroids prior to diagnosis. grip strength (P=0.05) associated with higher CRP
The following parameters were recorded for each patient: gender,
age at diagnosis, duration of follow-up, distribution of joints in- (P=0.05) and ESR (P=0.05) values (Table 3). Howev-
volved (mono-, oligo-, or polyarthritis, symmetrical or asymmet- er, at the end of the study, there were no significant
rical, small or large joint involvement), morning stiffness (in differences between the two groups for any of the
minutes), grip strength (mmHg using a sphygmomanometer), parameters investigated, independently of follow-up
numbers of joints with pain and swelling, as well as the numbers of
patients with joint deformities and ankyloses at the end of the
duration (Table 4).
follow-up period.
At disease onset, during follow-up, and at the end of the study,
all patients had X-rays done of hands, wrists, and feet which were Table 1 Demographic characteristics of early rheumatoid arthritis
reviewed by the same examiner and graded using Steinbrocker’s patients. Values are given as mean±SD. NS not significant
staging system [25].
Laboratory parameters which were recorded included erythro- Young Elderly P
cyte sedimentation rate (ESR) (mm/1st h), C-reactive protein (n=317) (n=121)
(CRP) (mg/L), and RF (latex test ‡80). Functional ability of the
patients was measured at the end of the study according to the Male 76 50
ACR functional grading system (grades I–IV) [26], and global Female 241 71
evaluation of the disease by both patient and physician was graded Male:female 1:3.2 1:1.4 0.04
on a scale of bad, medium, good, or very good. Finally, the type Age at diagnosis 43.9±11.7 69.1±5.7
and length of administration of DMARDs used for the duration of (range) in years (17–60) (61–84)
follow-up were noted and studied. Disease duration 0.5 0.4 NS
Student’s t-test, the x2 test with Yates correction, analysis of before diagnosis (years)
variance (ANOVA), and least significant differences (LSD) were Follow-up (years) 5±4.1 3.7±3.2 0.001
applied when indicated during statistical analysis. In addition,
multiple logistic regression analysis was done using age group as a
dependent factor.

Results

From the 1,271 patients, 454 were diagnosed with early

RA. Nine patients from this total were excluded from
the study because they had used various DMARDs and
steroids prior to follow-up, and seven were withdrawn
during follow-up. More specifically, three refused to
continue the treatment with any DMARD, two were lost Fig. 1 Distribution of age at disease onset
to follow-up, one moved to another city, and one died
due to acute myocardial infarction. Thus, 438 patients
(317 YORA and 121 EORA) were included. Table 2 Disease characteristics of patients with early rheumatoid
Table 1 shows that the male:female ratio in YORA arthritis. NS not significant
was 1:3.2, practically equal in EORA (1:1.4, P=0.04), Characteristics Young Elderly P
whilst the mean ages at disease onset were 43.9 years (17– (n=317) (%) (n=121) (%)
60) for YORA and 69.1 years (61–84) for EORA. The
Fever 20.8 22.3 NS
distribution of age at disease onset is shown in Fig. 1. Weight loss 16 18 NS
The YORA group was also followed up for a signifi- Site at onset
cantly longer period of time than EORA (P=0.001). Monoarthritis 1.6 1 NS
Table 2 shows no differences between the two groups Oligoarthritis 12.2 7.2 NS
Polyarthritis 86.1 91.8 0.05
in general symptoms (fever, weight loss) at the com- Symmetrical onset 94.5 93.8 NS
mencement of disease and in the degree of symmetricity of
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Table 4 Logistic regression analysis for clinical, laboratory, and

radiologic characteristics at the end of the study. Dependent factor:
age group (elderly/young). Adjusted for sex and duration of follow-
up. NS not significant
Independent parameters Odds 95% P
ratio CI

Morning stiffness (>10 min) 1.68 0.83–3.42 NS

Grip strength (<100 mmHg) 1.29 0.62–1.74 NS
N tender joints (>6) 1.50 0.60–3.74 NS
N swollen joints (>6) 0.58 0.33–1.04 NS
C-reactive protein (>10 mg/l) 0.87 0.54–1.38 NS
Erythrocyte sedimentation 1.42 0.87–2.93 NS
rate (>30 mm/h)
Fig. 2 Joint involvement in rheumatoid arthritis. MTP metatarso- Radiographic score 1.06 0.59–1.47 NS
phalangeal, PIP proximal interphalangeal, MCP metacarpopha- (Steinbrocker’s III, IV)
langeal

Table 5 Outcome of young and elderly patients with early rheu-

Table 3 Logistic regression analysis for clinical, laboratory, and matoid arthritis. ACR American College of Rheumatology, NS not
radiologic characteristics at first assessment. Dependent factor: age significant
group (elderly/young). Adjusted for sex. NS not significant
Young Elderly P
Independent parameters Odds 95% P (n=317) (%) (n=121) (%)
ratio CI
ACR stage I 63.7 68.4 NS
Morning stiffness (>10 min) 1.58 0.70–2.69 NS1 ACR stage II 27.7 21.8 NS
Grip strength (<100 mmHg) 1.96 1.21–3.37 <0.05 ACR stage III 7.4 8.8 NS
N tender joints (>6) 1.08 0.48–2.44 NS ACR stage IV 1.3 1 NS
N swollen joints (>6) 1.27 0.63–2.58 NS Physician assessmenta 73 75 NS
C-reactive protein (>10 mg/l) 1.93 1.19–3.12 <0.05 Patient assessmenta 67 69 NS
Erythrocyte sedimentation 1.91 1.10–3.31 <0.05
rate (>30 mm/h) a
Percent rated as good or very good
Rheumatoid factor positivity 0.83 0.61–1.16 NS
Radiographic score 1.04 0.69–1.41 NS
(Steinbrocker’s III, IV) rheumatoid epitope, which has been linked with more
severe forms of the disease. Greece has also been shown
to have a lower prevalence (2.05 and 4.78 patients per
Regarding the levels of functional ability between 1,000 population for men and women, respectively) and
the groups according to the ACR criteria, no differ- lower incidence of the disease (0.15–0.36 per 1,000 pop-
ences were found, and the total of patients with func- ulation) than other countries [32]. A recent study from
tional abilities in categories III and IV was less than our group also showed that RF-positive early RA
10% of the total numbers of patients for each of the patients had worse outcomes than seronegative patients
two groups. More than two thirds of the patients were [33]. In the present study, we investigated if the age at
found to have good or very good levels in the global disease onset comprises a separate parameter for disease
evaluation by patient and doctor (Table 5), whilst drug expression, prognosis, and outcome in early RA patients.
treatment for the two groups was similar, with only a The disease diagnosis was made by rheumatology
slightly increased usage of oral steroids in the EORA specialists, thus maintaining strict diagnostic criteria,
group (Table 6). and detailed recordings of clinical and laboratory man-
ifestations. Also, treatment was commenced at very
early stages of the disease using various DMARDs. Our
Discussion study showed a threefold female preponderance in the
YORA group, whilst in the EORA group, the men and
It has been reported from previous studies that RA in women were practically of equal number, in accordance
Mediterranean countries is milder than in northern with the results of other investigators [13, 14]. The
European countries [27, 28]. This may be due to factors YORA group had significantly longer lengths of follow-
such as diet (greater use of olive oil and fish), environ- up, which was also seen in Terkelbaum’s study [6]. This
mental factors such as sunlight, which has been shown to may be due to the fact that this patient group, being
possess immunomodulatory properties, and also genetic more active and more mobile, seeks medical assistance
factors [29, 30, 31]. This milder form of the disease is with greater ease than more elderly patients.
expressed both clinically with less joint and systemic We found the onset of disease in the EORA group to
involvement (except Sjögren’s syndrome) and radio- be more severe, with lower grip strength and higher CRP
graphically with less severe joint damage. In addition, and ESR [3, 13, 23] values. However, unlike other
Greeks presented with a lower frequency of the HLA studies that showed a preponderance of large joint in-
DRb1 motif [31]. This motif contains the shared or volvement, in the EORA patients we found no signifi-
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Table 6 The numbers of

patients treated with different DMARD Young (n=317) Elderly (n=121) P
disease-modifying antirheumat-
N % N %
ic drugs (DMARDs) in early
rheumatoid arthritis. NS not
Hydroxychloroquine 127 40.1 41 33.9 NS
significant Gold injections 47 14.8 11 9.1 NS
Penicillamine 129 40.7 35 28.9 NS
Methotrexate 170 53.6 63 52.1 NS
Cyclosporine A 57 18 14 11.6 NS
Azathioprine 10 3.2 2 1.7 NS
Oral steroids 109 34.4 60 49.6 0.04
DMARD discontinuation
Due to inefficacy 49 15.6 11 9.3 NS
Due to adverse events 40 12.5 21 17.7 NS
Number of different DMARDs/patient
Per year of follow-up 0.4 0.5 NS

cant differences in type or size of joints involved. These
differences may be because of the stricter entry criteria in
our study, whereby elderly patients who began with an
RA-like picture but later developed other autoimmune
diseases common to this population such as polymyalgia
rheumatica were excluded due to the retrospective
nature of this study.
There were no differences in the frequency of RF
positivity between the two groups, which was also seen
in previous studies [13, 14, 23], even though our patients
showed in general a low frequency for RF positivity.
Others have shown EORA to have less frequent RF
positivity than YORA [34], which may be due to the
method used.
At the end of follow-up, there were no differences in all
the major parameters used for measurement of disease
outcome (joint involvement and deformities, laboratory,
radiological, and functional values, as well as therapeutic
strategies), thus showing a similar outcome for both
groups. Especially, no serious radiologic changes were
seen in the two groups, which is probably due to the milder
clinical picture of Greek RA patients, as seen by the dif-
fering genetic background and the early yet similar
treatment strategy for all the patients in our study. Use of
the same treatment independently of age is a common
phenomenon in most studies [35, 36], and the more fre-
quent use of steroids in EORA is also a common finding,
as these patients often cannot use NSAIDs due to the
increased side effect profile [37].
However, some limitations in the present study are
(1) its retrospective nature and (2) evaluation of the
radiographs with the Steinbrocker’s score, which gives
qualitative information, instead of using Larsen’s or
Sharp’s scores, which give a more quantitative score
damage. On the other hand, our study included (1) a
large number of patients, (2) use of very strict entry
criteria excluding patients with psoriatic arthritis or
polymyalgia rheumatica, (3) identification of early RA
patients without prior use of DMARDs or steroids, and
(4) early immunointervention before the development of
deformities of bone and joint ankyloses.
In conclusion, this study details the clinical charac-
teristics and outcome of patients with early onset RA
and shows that, apart from a more severe picture in
EORA at disease commencement, there are no signifi-
cant differences in the clinical picture, course, and out-
come of the disease when comparing the age at disease
onset [37]. Early diagnosis and a similarly early treat-
ment strategy for all patients, independently of age, seem
to produce a more favorable outcome.
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