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Seronegative polyarthritis in giant cell arteritis.

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Nineteen of 520 patients with biopsy-proven giant
cell arteritis were found to have persistent seronegative,
symmetric polyarthritis with a mean joint count of 20
(swollen plus tender), In 9 patients in the onset of
polyarthritis occurred prior to the diagnosis of giant cell
arteritis, 3 had simultaneous onset, and 7 developed
polyarthritis within 3 years after the onset of giant cell
arteritis. Ten of the 19 patients demonstrated radiographic features of joint space narrowing and/or erosions. In 1 patient in a synovial biopsy was performed,
revealing marked multinucleated giant cell infiltration.
A persistent seronegative polyarthritis, although uncommon in giant cell arteritis, may be its presenting
symptom. Other symptoms of giant cell arteritis should
be sought in patients who exhibit this feature, especially
in those whose arthritis begins at age 50 or older.
Giant cell arteritis (GCA) is an idiopathic
granulomatous vasculitis predominantly affecting the
medium-sized and large branches of the arteries arising from the arch of the aorta. While headache and
visual disturbance are common symptoms of involvement of cranial arteries, a wide variety of systemic and
less specific manifestations of giant cell arteritis have
been recognized in recent years (1,2). Such manifestations include respiratory symptoms of cough and
hoarseness, fever of unknown origin, anemia, and a
From the Division of Rheumatology, Department of Internal Medicine, Mayo Foundation, Rochester, Minnesota.
William W. Ginsburg, MD; Marc D. Cohen, MD; Stephen
B. Hall, MD; Randall S . Vollertsen, MD; Gene G. Hunder, MD.
Address reprint requests to William W. Ginsburg, MD,
Division of Rheumatology, Mayo Foundation, Rochester, MN
Submitted for publication January 30, 1985; accepted in
revised form May 6, 1985.
Arthritis and Rheumatism, Vol. 28, No. 12 (December 1985)
wasting illness associated with elevation of the erythrocyte sedimentation rate and abnormal findings on
liver function tests (1-4).
Approximately half of the cases of biopsyproven giant cell arteritis occur in association with
polymyalgia rheumatica, a syndrome of proximal limb
girdle aching and stiffness. This latter condition may
be due to a mild synovitis of the axial joints, particularly affecting the synovial tissues of the shoulder
joints, hip joints, sternoclavicular joints, and other
proximal structures (5-10). While erosions of such
joints occasionally have been noted on long-term
followup, the synovitis of polymyalgia rheumatica has
not been considered a destructive arthropathy
(5,11,12). Recently, we treated several patients whose
initial symptom of GCA was a peripheral polyarthritis
clinically indistinguishable from rheumatoid arthritis.
To determine the frequency of and character of
polyarthritis in giant cell arteritis, we reviewed the
records of GCA patients seen over a 13-year period.
All patients with biopsy-proven giant cell arteritis
treated at the Mayo Clinic between January 1, 1970 and
December 31, 1982 were identified through the use of the
Central Diagnostic Index and the combined surgical register.
All patient records were reviewed and data tabulated. Relevant radiographs were reviewed and all available surgical
specimens were reexamined. Patients with polyarthritis
were identified, and only those whose arthritis was indistinguishable from definite or classic rheumatoid arthritis (RA)
were included for study. Specific exclusions were ankylosing
spondylitis, Reiter's syndrome, psoriasis, a history of documented inflammatory bowel disease, urate or calcium
Tablle 1. Symptoms in 19 patients with giant cell arteritis
No. of patients
Visual disturbance
Jaw claudication
Poly myalgia rheurnatica
Scalp tenderness
Tender temporal artery
Aodic arch syndrome
pyrophosphate crystal-induced synovitis, or any other
known cause of an inflammatory arthropathy. All patients
were followed by members of the Division of Rheumatology.
Of 520 patients with biopsy-proven giant cell
arteritis seen during the 13-year period reviewed, 22
patients with inflammatory polyarthritis clinically indistinguishable from definite or classic RA were identified. Three of these patients were seropositive for
rheumatoid factor and have been described elsewhere
(13). The remaining 19 patients who were seronegative
are described here. There were 17 females and 2
males, with a median age of 70 years (range 64-82).
The symptoms of giant cell arteritis were similar to those described in previous reports and did not
d i f i r between patients whose arthritis developed prior
to the recognition of GCA and those whose arthritis
followed the onset of GCA. Symptoms in the group as
a whole are shown in Table 1.
Nine patients had onset of polyarthritis prior to
the diagnosis of arteritis, 3 had onset of polyarthritis
simultaneously with symptoms of giant cell arteritis,
and 7 developed polyarthritis after, but within 3 years
of, the diagnosis of arteritis. The interval between the
onset of polyarthritis and that of temporal arteritis in
the group whose arthritis occured first was < 1 year in
3 patients, between 1 and 2 years in 3 patients,
between 2 and 3 years in 2 patients, and 9 years in 1
patient. For the 7 patients whose polyarthritis followed the onset of giant cell arteritis, the delay was < 1
year in 1 patient, 1-2 years in 2 patients, and 2-3 years
in 4. patients. Five patients in the latter group were
receiving corticosteroids at the time of onset of
The distribution of involved joints is shown in
Table 2. There were no discernible differences regarding the joints of those whose arthritis preceded giant
cell arteritis and those whose arthritis developed sub-
sequently. In all cases the arthritis was polyarticular,
symmetric, and clinically indistinguishable from
seropositive definite or classic rheumatoid arthritis.
However, no patient developed subcutaneous rheumatoid nodules or any other extraarticular manifestations
of RA.
Synovial fluid analysis in 7 patients showed a
median white blood cell count of 12,600 X 103/pl
(range 4,700-27,000). The differential leukocyte count
showed a median neutrophil count of 75% (range
63-90). Fluids were sterile in all cultures. Total
hemolytic complement in synovial fluid was normal in
all 7 patients tested.
In 10 of the 19 patients, radiographic examination demonstrated joint space narrowing or erosions
(Figure 1). Such radiographic changes were evident in
the knees (7 patients), hands and wrists (8 patients),
and metatarsophalangeal joints (2 patients). One patient underwent total knee arthroplasty for severe
destructive arthritis 1 I years after the onset of arthritis
and 14 years after the diagnosis of arteritis. Pathologic
examination of the synovial tissue revealed a slightly
thickened synovial intima and infiltration of the subsynovium with mononuclear cells, but multinucleated
giant cells were the predominant cell type (Figure 2).
As would be expected, all patients whose arthritis
preceded the recognition of giant cell arteritis experienced dramatic symptomatic improvement in the arthritis following the institution of high-dose corticosteroid therapy for the vasculitis.
Blood tests at the time of diagnosis of, and prior
to treatment for, giant cell arteritis showed an elevated
erythrocyte sedimentation rate in all patients, with a
mean value of 85 mm/hour (range 45-131) (Westergren). The mean hemoglobin level was 11.2 gm/dl
(range 9.5-12.6) and the mean platelet count was
501,OOO/pl (range 410,000-625,OOO). All patients were
antinuclear antibody-negative.
Table 2. Distribution of involved joints in 19 patients with giant
cell arteritis
Joints involved*
No. of patients
Proximal interphalangeal
* All patients had symmetric involvement.
Nineteen of the 520 patients with biopsy-proven
giant cell arteritis were found to have developed a
symmetric polyarthritis indistinguishable from definite
or classic rheumatoid arthritis. However, none had
nodules or other extraarticular features. Ten patients
developed radiographic evidence of erosions or joint
space narrowing. In some instances, the arthritis preceded symptoms of giant cell arteritis, and in others, it
developed simultaneously or after the diagnosis of RA
was established. In 7 patients, the arthritis developed
within a year of symptoms of giant cell arteritis. All
patients had elevations of erythrocyte sedimentation
rate, normochromic normocytic anemia, and elevated
platelet counts.
Polyarthritis previously has been associated
with giant cell arteritis in a few instances (2,1416). A
Figure 1. Radiograph of the hand of a patient with giant cell arteritis
of 10 years duration. Joint space narrowing is seen at the
metacarpophalangeal joints. The surface of the second proximal
phalanx is eroded. There is also narrowing in the intercarpal joints,
with an erosion of the navicular bone.
Figure 2. Synovium from the knee of a patient with giant cell
arteritis, showing infiltration with mononuclear cells and multinucleated giant cells (hematoxylin and eosin stained, original magnification x 250).
recent review cited reports of 4 cases of seropositive
RA among a group of patients with GCA (17). Two
other patients with seronegative RA were also described, and in 6 additional patients with polyarthritis,
the results of the rheumatoid factor tests were not
reported (17). Many of these patients had erosive
articular disease. All of the cases, both seropositive
and seronegative, were thought to represent the coexistence of 2 separate diseases.
We have previously described 3 other patients
with erosive, seropositive rheumatoid arthritis who
later developed giant cell arteritis after a mean of 19
years (range 10-25 years) (13). In all 3 cases, there was
considerable delay in the diagnosis of GCA because
the patients' new symptoms were initially attributed to
RA or to complications of that disease.
However, some findings in the 19 patients reported here suggest that the polyarthritis and the
arteritis may be related. These include the relatively
close temporal onset of the arthritis and vasculitis.
Moreover, only 3 of the 22 patients were positive for
rheumatoid factor, while rheumatoid factor positivity
is conventionally thought to occur in 80-90% of patients with definite rheumatoid arthritis (18).
Berkson has emphasized that the numbers of
patients with two diseases seen at referral centers are
not representative, since patients with more than one
problem are more likely to attend such institutions
than are those with a single problem (19). Nevertheless, 22 cases of rheumatoid arthritis within a group of
520 giant cell arteritis patients represents a prevalence
of 4:!.3/1,000. This figure is considerably greater than
the general prevalence of definite and classic rheumatoid arthritis reported in epidemiologic studies (20).
However, the finding of 3 cases of seropositive RA is
within the number expected by chance.
Transient joint involvement in giant cell arteriti s has been noted previously, and the polyarticular
involvement in the patients described here may represent the other end of the spectrum. The finding of
extensive multinucleated giant cells on synovial biopsy in 1 patient who underwent total knee arthroplasly is not typical of rheumatoid arthritis and lends
histopathologic support to the concept that giant cell
arteritis is associated with a specific arthropathy .
By usual definitions, these patients did not have
polymyalgia rheumatica. Several developed polyarthritis despite their receiving doses of corticosteroids
usually sufficient to control all manifestations of uncomplicated polymyalgia rheurnatica syndrome. While
joint scans, synovial biopsy, and joint fluid findings
support the contention of an active inflammatory
syncivitis underlying the clinical features of polymyalgia rheumatica, such joint involvement does not tend
to lead to chronic joint changes (5-12). Moreover,
in only 2 of the 9 patients whose polyarthritis preceded symptoms of giant cell arteritis were symptoms
of polymyalgia rheurnatica recognized, because the
affected joints were predominantly peripheral. All
patients were evaluated by a rheumatologist and
were followed at least until the time of diagnosis of
The term “seronegative rheumatoid arthritis”
is increasingly accepted as representing a heterogeneous group of disorders, rather than any single condition. These disorders are distinct from seropositive
RA in their clinical, epidemiologic, genetic, and
radiologic features (21). Although some patients with
‘‘seronegative rheumatoid arthritis” can never be categorized more precisely, in many, the condition will
eventually evolve into more recognizable syndromes
such as spondylarthropathies, psoriatic arthritis, or
inflaimmatorybowel disease. We believe that, although
it is unusual, a seronegative polyarthritis is yet another
manifestation of the systemic nature of giant cell
The presence of polyarthritis and the lack of
proximal symptoms may at times draw attention away
from underlying giant cell arteritis and lead to delay in
diagnosis and, consequently, in the institution of effective therapy. In patients over the age of 50 who
have onset of seronegative polyarthritis and a high
erythrocyte sedimentation rate, GCA should be considered as a possible cause of the clinical symptoms.
Only through direct questioning regarding specific
features of giant cell arteritis can the possible presence
of the disease be suspected; the diagnosis can then be
confirmed by temporal artery biopsy.
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giants, seronegative, arteritis, polyarthritis, cells
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