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Small-vessel vasculitis surrounding an uninflamed temporal arteryA new diagnostic criterion for polymyalgia rheumatica.

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ARTHRITIS & RHEUMATISM
Vol. 58, No. 8, August 2008, pp 2565–2573
DOI 10.1002/art.23700
© 2008, American College of Rheumatology
Small-Vessel Vasculitis Surrounding an Uninflamed
Temporal Artery
A New Diagnostic Criterion for Polymyalgia Rheumatica?
Denis Chatelain,1 Pierre Duhaut,1 Robert Loire,2 Sylvie Bosshard,2 Hélène Pellet,2
Jean-Charles Piette,3 Henri Sevestre,1 and Jean-Pierre Ducroix1
Objective. To assess the prevalence and clinical
significance of small-vessel vasculitis (SVV) surrounding an uninflamed temporal artery (TA) in patients
diagnosed as having giant cell (temporal) arteritis
(GCA) and/or polymyalgia rheumatica (PMR).
Methods. Patients with GCA and/or PMR (n ⴝ
490) were included in this multicenter prospective
study. Slides of TA biopsy specimens were reviewed by 2
pathologists who were blinded with regard to clinical
information. SVV was defined as aggregates of mononuclear inflammatory cells surrounding a capillary,
distant from an uninflamed temporal artery. Clinical
and biologic data of patients in the SVV group (n ⴝ 35)
were compared with data of patients with biopsy-proven
GCA (n ⴝ 280) and with negative TA biopsy findings
(n ⴝ 175).
Results. SVV was diagnosed in 18 women and 17
men (mean ⴞ SD age 74.5 ⴞ 9.4 years). The group of
patients with SVV had a higher proportion of men than
in the entire GCA series, had systemic symptoms,
headache, jaw claudication, and an abnormal temporal
artery less frequently at clinical examination, but had
symptoms of PMR more often than patients in the
biopsy-proven GCA group (P ⴝ 2.6 ⴛ 10ⴚ7, odds ratio
9.17 [95% confidence interval 3.44–24.4]). Levels of
inflammation markers were significantly lower in the
SVV group. Patients in the SVV group had fever less
frequently than patients in the group with negative TA
biopsy findings, but otherwise shared the same clinical
(including PMR symptoms) and biologic features. Eighteen of the 94 patients with pure PMR (19%) had SVV.
Conclusion. SVV is often neglected by pathologists, and appears to be strongly associated with PMR
symptoms in patients with a clinical diagnosis of GCA
and/or PMR. However, SVV as a new diagnostic criterion for PMR must be assessed in prospective studies.
Microscopic examination of temporal artery
(TA) biopsy specimens is still the gold standard for the
diagnosis of giant cell (temporal) arteritis (GCA) (1–4).
Patients with GCA are usually ⬎50 years, and present
with headache, jaw claudication, and an increased erythrocyte sedimentation rate (ESR) (1,2). Microscopic examination of TA biopsy specimens shows infiltration of
mononuclear inflammatory cells, often with multinucleated giant cells in the arterial wall, and interruption of
the internal elastic laminae (3,4). Polymyalgia rheumatica (PMR) is observed in 40–60% of patients with
GCA (4,5). The incidence of temporal arteritis in patients with pure PMR is still controversial, ranging
between 0% and 41% in clinical series (6).
Small-vessel vasculitis (SVV) surrounding an uninflamed temporal artery is an infrequent, but perhaps
underestimated, finding during microscopic examination
of TA biopsy specimens (7–10). SVV can be defined as
aggregates of mononuclear inflammatory cells, without
polynuclear neutrophils and eosinophils and without
fibrinoid necrosis of the vessel wall, surrounding a small
capillary distant from an uninflamed temporal artery.
1
Denis Chatelain, MD, Pierre Duhaut, MD, PhD, Henri
Sevestre, MD, PhD, Jean-Pierre Ducroix, MD: Centre Hospitalier
Universitaire du Nord and RECIF, Amiens, France; 2Robert Loire,
MD, Sylvie Bosshard, MD, Hélène Pellet, MD, PhD: Lyon-GrangeBlanche and RECIF, Claude Bernard University, Lyon, France;
3
Jean-Charles Piette, MD: Hôpital de la Pitié Salpêtrière and RECIF,
Paris, France.
Address correspondence and reprint requests to Denis Chatelain, MD, Department of Pathology, Centre Hospitalier Universitaire
du Nord, Place Victor Pauchet, 80054 Amiens Cedex 01, France.
E-mail: chatelain.denis@chu-amiens.fr.
Submitted for publication October 11, 2007; accepted in
revised form April 18, 2008.
2565
2566
CHATELAIN ET AL
SVV has been reported in various inflammatory, infectious, or neoplastic diseases but its clinical significance is
still unclear (7–10).
The aims of our study were to assess the prevalence of SVV on TA biopsy specimens in patients with a
clinical diagnosis of GCA or PMR and to evaluate its
clinical significance in these patients.
PATIENTS AND METHODS
Patients. The recruitment of patients with GCA and
PMR and the inclusion and exclusion criteria used in this study
have been previously described (11,12). Members of every
internal medicine, rheumatology, geriatrics, neurology, and
ophthalmology department at university hospitals in France,
and those at internal medicine departments affiliated with the
French Society of Internal Medicine, were contacted by mail in
January 1991. (See Appendix A for members of the Groupe de
Recherche sur l’Artérite à Cellules Géantes [GRACG] and
their locations.) We only included newly diagnosed patients,
using preestablished criteria in order to best avoid misclassification and recall bias.
Each new patient completed a questionnaire to provide medical history and clinical examination data, and a blood
sample was obtained before corticosteroid treatment was
started or, at most, 48 hours after treatment began. The
questionnaire had to be completed directly by the patient, and
not using data recorded in the medical chart.
Diagnostic criteria. Patients had to meet the following
preestablished diagnostic criteria: 1) ⬎50 years of age; 2) ESR
(Westergren) ⬎40 mm/hour (except for a few cases with
typical symptoms, for whom TA biopsy findings were positive
on microscopic examination); 3) clinical response within 72
hours to corticosteroid therapy (disappearance of fever and
pain); 4) positive TA biopsy findings; 5) clinically abnormal
temporal artery (tenderness, swelling, redness, nodular artery); 6) visual disturbances (blindness, diplopia, blurred vision), including those occurring during the first week of
treatment; 7) jaw claudication; 8) headache, temporal headache, facial pain, or sensation of facial swelling; 9) systemic
symptoms, such as fever, loss of ⬎10% of total weight,
anorexia, malaise, asthenia; and 10) PMR symptoms with
persistent proximal muscle pain, tenderness, or morning stiffness lasting ⬎1 hour, involving the neck, shoulders, and/or
pelvic girdle (duration ⬎2 weeks). All patients had to fulfill the
first 3 criteria. In addition to meeting these 3 criteria, patients
included in the biopsy-proven GCA group had to fulfill
criterion 4. Patients included in the negative-biopsy group had
to fulfill 2 criteria among criteria 5–9. The symptoms in
criterion 10 could be present or not.
Patients diagnosed as having GCA met the American
College of Rheumatology classification criteria (13). Pure
GCA was defined as GCA with no sign or symptom of PMR.
Patients diagnosed as having PMR fulfilled the criteria described by Chuang et al (14). Pure PMR was defined as PMR
with no sign or symptom of GCA.
Exclusion criteria consisted of current malignant diseases, current infectious diseases, or other inflammatory or
vasculitis diseases, notably a history of rheumatoid arthritis
(RA), systemic lupus erythematosus, or polyarteritis nodosa.
All patients were followed up over a 5-year period, and the
mean followup in this series was 4 years.
The patients were classified into subgroups once the
inclusion criteria were reviewed by physicians at the coordinating center (PD, SB), and the TA biopsies were reviewed by the
pathologists (DC, RL).
Variables at the time of diagnosis. There were 3 types
of data: initial clinical signs and symptoms, biologic data, and
time of diagnosis and the delay between the onset of symptoms
and the diagnosis. Initial clinical signs and symptoms included
systemic symptoms, such as fever, anorexia, malaise, weight
loss, and asthenia; recent headache, either temporal, diffuse,
or facial; malaise; jaw claudication; visual problems, such as
blindness, diplopia, or blurred vision; abnormal temporal
artery on clinical examination; or symptoms of PMR. Biologic
data included ESR (Westergren), C-reactive protein (CRP),
haptoglobin, fibrinogen, hemoglobin level, mean globular volume, and platelet count.
Pathologic examination of TA biopsy specimens. TA
biopsy has been the standard technique for diagnosis of GCA.
This was a multicenter study, and the surgeons performed the
biopsies according to the usual standards. TA biopsy specimens were fixed in 10% buffered formalin and processed
routinely. In most of the cases they were cut transversely in
small, 3–4-mm artery segments. TA biopsy specimens were
embedded in paraffin, and 4-␮m–thick paraffin-embedded
tissue segments were cut and stained with hematoxylin–eosin–
saffron. The number of levels examined per arterial segment
varied from 1 (1 case) to 38 (1 case) (median 6), depending on
the participating center.
A copy of the initial pathologic report on the TA
biopsy specimens was requested, and the slides were reviewed
by 2 senior pathologists (DC, RL) without clinical information.
Histologic criteria were assessed and recorded on a preestablished form. Quality of the biopsy (excellent, good, medium,
poor), orientation of the arterial segments (transverse or
longitudinal), number of arterial segments, and number of
levels generated from the paraffin blocks were assessed. During microscopic examination, there is always some connective
tissue surrounding the adventitia, and this connective tissue
contains capillaries, arterioles, small nerves, and sometimes
small veins. SVV surrounding a spared temporal artery was
defined as aggregates of mononuclear inflammatory cells
around capillaries and not arterioles (ⱖ15 inflammatory cells)
surrounding an uninflamed temporal artery. There was neither
fibrinoid necrosis of the capillary wall nor leukocytoclasia.
Small capillaries were 0.5–1.5 mm from the arterial wall. We
did not call them vasa vasorum because the lesions we described never involved arterioles and venules, only capillaries,
located outside the arterial wall.
Control group of patients without GCA and/or PMR.
We studied a control group of patients who had TA biopsy
specimens but had not been diagnosed as having GCA and/or
PMR. We extracted all information on TA biopsies performed
in 2004 from the archives of the Department of Pathology of
Amiens University Hospital.
Statistical analysis. We compared the 3 groups of
patients: patients with SVV were compared with patients with
biopsy-proven GCA and with patients with negative-biopsy
PMR and/or GCA. Data analysis was performed with SAS
SVV AS A DIAGNOSTIC CRITERION FOR PMR
Table 1.
2567
Characteristics of the patients with SVV versus the patients with biopsy-proven GCA*
No. male/female (male:female ratio)
Age, mean ⫾ SD years
Clinical diagnosis
Pure GCA
GCA with PMR symptoms
Pure PMR
Duration of symptoms, median (range) days
Corticosteroid response
Systemic symptoms
Fever
Asthenia
Anorexia
Weight loss
Headache
Malaise
Jaw claudication
Visual impairment
Blindness
PMR symptoms
Abnormal TA on clinical examination
ESR, median (range) mm/hour
CRP, median (range) mg/liter
Haptoglobin, median (range) gm/liter
Fibrinogen, mean ⫾ SD gm/liter
Hemoglobin, median (range) gm/liter
Mean globular volume, median (range) ␮3
Platelet count, median (range) ⫻ 109/liter
Ferritin, median (range) ␮g/liter
Patients with
SVV
(n ⫽ 35)
Patients with biopsyproven GCA
(n ⫽ 280)
17/18 (0.94)
74.5 ⫾ 9.4
73/207 (0.35)
75.4 ⫾ 8
5 (14)
12 (34)
18 (51)
36 (1–730)
30 (86)
27 (77)
6 (17)
22 (63)
11 (31)
4 (11)
12 (34)
5 (14)
8 (23)
7 (20)
1 (3)
30 (86)
6 (17)
72 (21–130)
62 (2–156)
3.8 (1.7–6.8)
5.5 ⫾ 1.4
122 (85–143)
91 (78–111)
335 (159–700)
250 (3–786)
165 (59)
108 (39)
7 (3)
52 (0–2,113)
259 (95)
255 (91)
122 (44)
227 (81)
129 (46)
83 (30)
229 (82)
22 (8)
116 (42)
91 (32)
25 (9)
111 (40)
168 (60)
88 (11–150)
83 (3–590)
4.6 (1–12.7)
6.7 ⫾ 1.8
113 (65–158)
87 (70–104)
417 (92–954)
327 (23–4,987)
P
0.005
0.47
⬍0.001
0.282
0.144
0.018
0.003
0.013
0.1
0.023
1.16 ⫻ 10⫺8
0.203
0.033
0.175
0.333
2.6 ⫻ 10⫺7
1.3 ⫻ 10⫺6
0.004
0.075
0.008
0.0001
0.001
0.0001
0.005
0.06
* Except where indicated otherwise, values are the number (%). SVV ⫽ small-vessel vasculitis surrounding an uninflamed temporal artery (TA); GCA ⫽ giant cell arteritis; PMR ⫽ polymyalgia rheumatica;
ESR ⫽ erythrocyte sedimentation rate; CRP ⫽ C-reactive protein.
software (SAS Institute, Cary, NC). The chi-square test or
Fisher’s exact test, when appropriate, was applied to dichotomous variables. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were computed. For continuous or ordinal
variables, Wilcoxon’s rank sum test was performed. All tests
were 2-sided, and P values less than 0.05 were considered
significant.
RESULTS
Population. TA biopsy specimens from 142 men
and 348 women (n ⫽ 490) were reviewed (83% of
requested biopsies). Among them, 197 patients had pure
GCA, 192 had GCA with PMR symptoms, and 101 had
pure PMR (Tables 1 and 2). Two hundred eighty
patients were diagnosed as having biopsy-proven GCA:
patients in the group with a positive TA biopsy finding
could have clinical symptoms of GCA without PMR
symptoms (clinically pure GCA; n ⫽ 165), mixed symptoms of GCA and PMR (n ⫽ 108), or PMR symptoms
with no GCA symptoms (n ⫽ 7) (Table 1). One hundred
seventy-five patients had a negative TA biopsy finding
and presented with GCA or PMR symptoms (27 clini-
cally pure GCA, 76 clinically pure PMR, 72 mixed
clinical symptoms of GCA and PMR) (Table 2). Thirtyfive patients had a pathologic diagnosis of SVV: 5
patients with GCA symptoms, 12 with both GCA and
PMR symptoms, and 18 with PMR symptoms (Tables 1
and 2).
SVV subgroup. Isolated SVV was diagnosed in 35
of 490 patients (7%) (18 women and 17 men, mean ⫾
SD age 74.5 ⫾ 9.4 years) (Tables 1 and 2). Thirty of the
35 patients had PMR symptoms (86%). Five patients
had a clinical diagnosis of GCA, 12 had a clinical
diagnosis of GCA with PMR symptoms, and 18 had a
clinical diagnosis of PMR (Tables 1 and 2). None of
these patients had symptoms of another inflammatory,
infectious, or neoplastic disease on the followup examination.
On microscopic examination, SVV consisted of
mononuclear inflammatory cells, essentially small lymphocytes, surrounding a capillary distant from the temporal artery (Figures 1 and 2). The number of mononuclear inflammatory cells ranged from 15 to 90
2568
CHATELAIN ET AL
Table 2.
PMR*
Characteristics of the patients with SVV versus the patients with biopsy-negative GCA and/or
No. male/female (male:female ratio)
Age, mean ⫾ SD years
Clinical diagnosis
Pure GCA
GCA with PMR symptoms
Pure PMR
Duration of symptoms, median (range) weeks
Corticosteroid response
Systemic symptoms
Fever
Asthenia
Anorexia
Weight loss
Headache
Malaise
Jaw claudication
Visual impairment
Blindness
PMR symptoms
Abnormal TA on clinical examination
ESR, median (range) mm/hour
CRP, median (range) mg/liter
Haptoglobin, median (range) gm/liter
Fibrinogen, mean ⫾ SD gm/liter
Hemoglobin, median (range) gm/liter
Mean globular volume, median (range) ␮3
Platelet count, median (range) ⫻ 109/liter
Ferritin, median (range) ␮g/liter
Patients with SVV
(n ⫽ 35)
Patients with biopsy-negative
GCA and/or PMR
(n ⫽ 175)
17/18 (0.94)
74.5 ⫾ 9.4
52/123 (0.42)†
73.9 ⫾ 7.4
5 (14)
12 (34)
18 (51)
36 (1–730)
30 (86)
27 (77)
6 (17)
22 (63)
11 (31)
4 (11)
12 (34)
5 (14)
8 (23)
7 (20)
1 (3)
30 (86)
6 (17)
72 (21–130)
62 (2–156)
3.8 (1.7–6.8)
5.5 ⫾ 1.4
122 (85–143)
91 (78–111)
335 (159–700)
250 (3–786)
27 (15)
72 (41)
76 (43)
53 (0–767)
164 (94)
148 (85)
65 (37)‡
132 (75)
63 (36)
44 (25)
87 (50)
19 (11)
23 (13)
28 (16)
3 (2)
148 (85)
34 (19)
77 (40–145)
64 (3–271)
3.8 (0.8–9.8)
6 ⫾ 1.7
118 (71–165)
90 (77–104)
363 (130–617)
259 (18–1,330)
* Except where indicated otherwise, values are the number (%). See Table 1 for definitions.
† P ⫽ 0.03 versus patients with SVV.
‡ P ⫽ 0.02 versus patients with SVV.
Figure 1. Small-vessel vasculitis surrounding an uninflamed temporal
artery (arrow) (hematoxylin–eosin–saffron stained; original magnification ⫻ 4).
Figure 2. Mononuclear inflammatory cells around a capillary distant
from the temporal artery (arrow) (hematoxylin–eosin–saffron stained;
original magnification ⫻ 25).
SVV AS A DIAGNOSTIC CRITERION FOR PMR
Table 3.
2569
Quality of TA biopsy specimens in patients with SVV versus patients with biopsy-proven GCA*
Quality of the biopsy specimen
Excellent
Good
Medium
Bad
Orientation of the arterial segment
Transverse
Longitudinal
No. of arterial segments, median (range)
No. of levels, median (range)
Patients with SVV
(n ⫽ 35)
Patients with biopsy-proven
GCA (n ⫽ 280)
1 (3)
23 (66)
4 (11)
7 (20)
8 (3)
137 (49)
63 (22)
72 (26)
31 (89)
4 (11)
3 (1–22)
6 (2–33)
227 (81)
53 (19)
3 (1–26)
6 (1–38)
* Except where indicated otherwise, values are the number (%). See Table 1 for definitions.
(median 20). Inflammatory cells extended into the connective tissue surrounding capillaries in 6 cases and
surrounded small nerves in 4 cases. There was no
necrosis of the capillary wall or leukocytoclastic vasculitis. SVV lesions were focal and were seen in only 1
arterial segment in 32 cases (91%) and in 2 arterial
segments in 3 cases (9%). SVV was seen in 1–10 levels
(median 3), and in all levels in only 9 cases (26%). The
temporal artery showed mild to moderate arteriosclerosis without inflammatory infiltrates. Calcifications were
seen in the media in 13 cases (37%). The initial pathology reports noted the presence of SVV in 3 cases (9%)
and described the TA biopsy findings as normal (6 cases)
or showing evidence of arteriosclerosis (29 cases).
Comparison of the 3 subgroups of patients. Biopsy quality. The quality of the TA biopsy specimens,
number of arterial segments (average of 3 arterial
segments in the 3 subgroups of patients), and number of
levels generated from the paraffin blocks were similar in
the SVV group, in the biopsy-proven GCA group, and in
the biopsy-negative group (Tables 3 and 4).
Clinical features. The proportion of men was
higher in the SVV group than in the biopsy-proven GCA
group (Table 1) and the negative TA biopsy group
(Table 2). The age of the patients and the time to
diagnosis were similar among the 3 groups (Tables 1 and
2). Patients in the SVV group had fewer systemic
symptoms and fewer occurrences of asthenia, fever,
weight loss, headache, jaw claudication, and abnormal
temporal artery at clinical examination than patients in
the biopsy-proven GCA group (Table 1).
Patients in the SVV group had PMR symptoms
more often than patients in the biopsy-proven GCA
group (P ⫽ 2.6 ⫻ 10⫺7, OR 9.17 [95% confidence
interval 3.44–24.4]). SVV with a spared temporal artery
was seen more frequently in patients with PMR symptoms than in patients with GCA symptoms (Table 1).
There was only 1 case of blindness in the SVV group,
compared with 25 cases in the biopsy-proven GCA
group (P ⫽ 0.33) (Table 1) and 3 cases in the biopsynegative group (P ⫽ 0.51) (Table 2).
Patients in the SVV group had fever less often
than patients in the negative TA biopsy group, but
otherwise had the same clinical signs and symptoms
Table 4. Quality of TA biopsy specimens in patients with SVV versus patients with biopsy-negative
GCA and/or PMR*
Quality of the biopsy specimen
Excellent
Good
Medium
Poor
Orientation of the arterial segment
Transverse
Longitudinal
No. of arterial segments, median (range)
No. of levels, median (range)
Patients with SVV
(n ⫽ 35)
Patients with biopsy-negative
GCA and/or PMR (n ⫽ 175)
1 (3)
23 (66)
4 (11)
7 (20)
6 (3)
116 (66)
40 (23)
13 (7)
31 (89)
4 (11)
3 (1–22)
6 (2–33)
161 (92)
14 (8)
3 (1–21)
6 (2–18)
* Except where indicated otherwise, values are the number (%). See Table 1 for definitions.
2570
CHATELAIN ET AL
(including PMR symptoms) (Table 2). Seventy-six patients (43%) in the negative TA biopsy group had a
clinical diagnosis of PMR (Table 2).
Biologic features. ESR, haptoglobin level, fibrinogen level, and platelet count were higher in the biopsyproven GCA group than in the SVV group (Table 1).
Patients in the SVV and negative TA biopsy groups
shared the same biologic features (Table 2).
In our study, 18 of the 94 patients (19%) diagnosed as having pure PMR and with an uninflamed TA
on microscopic examination showed signs of SVV on the
TA biopsy, whereas the biopsy findings were negative in
the remaining 76 patients.
Control group. Seventy-one patients had a TA
biopsy performed in 2004. Twenty-two patients had a
final diagnosis of GCA and/or PMR, and were excluded
from the control group. The ESR in all but 6 of the
remaining 49 patients was ⬎50 mm/hour at the time of
the TA biopsy. The 49 patients included 31 women
(mean ⫾ SD age 76 ⫾ 9.8 years) and 18 men (mean ⫾
SD age 69.5 ⫾ 10 years). Various final diagnoses were
made, including cancers (12 patients), headache (4
patients), fibromyalgia (1 patient), stroke (1 patient),
thrombosis of the central retinal artery (3 patients),
degenerative joint disease (4 patients), myeloproliferative disease (2 patients), non-Hodgkin’s lymphoma (3
patients), myelodysplasia (1 patient), infectious diseases
(12 patients), hemochromatosis (1 patient), polymyositis
(1 patient), and RA (4 patients). TA biopsy specimens
consisted, on average, of 3 arterial segments, and 6 levels
were cut. All patients had a negative TA biopsy finding
during microscopic examination, except 1 patient (2%),
whose specimen showed SVV. SVV lesions were seen
on 1 arterial section on the first 2 levels. This patient
was a 76-year-old woman with a severe inflammatory
syndrome who had a final clinical diagnosis of pyelonephritis.
DISCUSSION
Isolated SVV surrounding an uninflamed temporal artery is a rare finding in TA biopsy specimens. In
this study, it was found in 7% of patients with a clinical
diagnosis of GCA and/or PMR. In comparison,
Chakrabarty and Franks (15) found SVV in 22 of 172
TA biopsies (13%) performed for symptoms suggestive
of GCA, regardless of the final diagnosis, and Schmidt
and Löffler (16) found an isolated perivascular location
of inflammatory cells in 6 of 85 consecutive patients with
GCA (7%).
In our study, SVV lesions were focal, usually seen
in only 1 arterial segment during microscopic examination and only on a few levels. Chakrabarty and Franks
(15) have already shown the importance of examining
multiple levels, because in their series, SVV was found in
64% of the 22 cases (14 cases) on the first level and in
36% of the 22 cases (8 cases) on 2 additional levels. Our
study shows that SVV is a microscopic finding often
neglected by pathologists, and is described in only 9% of
the cases on the initial pathologic report. Immunohistochemical study was performed only by Disdier et al, who
showed that the inflammatory cells surrounding capillaries in SVV were mainly T lymphocytes associated with
B lymphocytes and macrophages (7). Paraffin blocks of
the TA biopsy specimens were not available in our study,
and we could not perform immunohistochemistry or
examine new levels.
The clinical significance of SVV is still unclear.
SVV has been described in patients presenting with
vascular diseases (GCA, polyarteritis nodosa, cholesterol emboli, cryoglobulinemia, and Wegener’s granulomatosis), inflammatory diseases (PMR, RA, relapsing
polychondritis, crescentic glomerulonephritis, uveitis,
and erythema nodosum), infectious diseases (hepatitis C
with mixed cryoglobulinemia, bacterial endocarditis, and
acute cytomegalovirus infection), and neoplasia (retroperitoneal schwannoma, acute necrosis of hypophyseal
tumor, and Waldenström’s macroglobulinemia) (7,8,10).
Our study is the first to show a strong association
between SVV and PMR symptoms within a large series
of patients with GCA and/or PMR diagnosed using
conventional pathologic and clinical criteria. There are
only 3 studies of SVV published in the literature, but
none showed a correlation with PMR. Disdier et al
studied a series of 28 patients with isolated vasculitis of
vasa vasorum on the TA biopsy specimen (7). Patients
had various clinical diagnoses, but only 4 patients (14%)
had a clinical diagnosis of PMR. The authors concluded
that the finding of isolated vasculitis of vasa vasorum on
the TA biopsy specimen frequently indicates a systemic
vasculitis disorder (7).
Esteban et al studied a series of 28 patients with
a finding of SVV surrounding a spared temporal artery
on TA biopsy specimens (8). Twelve patients had a
clinical diagnosis of GCA, 3 patients had a diagnosis of
systemic necrotizing vasculitis, and 13 patients had no
precise diagnosis. Interestingly, 14 patients (50%) had
PMR symptoms, but this association was not assessed in
the study. The authors concluded that, among patients
presenting with SVV surrounding a spared temporal
artery on TA biopsy specimens, a diagnosis of GCA could
SVV AS A DIAGNOSTIC CRITERION FOR PMR
be reasonably established in most, when there was no
apparent evidence of additional organ involvement (8).
Corcoran et al compared 81 TA biopsy specimens
that showed isolated SVV surrounding a spared temporal artery (among which 27 had GCA and 13 had PMR)
with 76 normal or arteriosclerotic TA biopsy specimens
with no inflammation (9). Patients had various clinical
diagnoses in both groups. Thirteen patients (16%) in the
SVV group and 11 patients (14%) in the group with no
inflammation on TA biopsy specimens had a clinical
diagnosis of PMR. The authors found no difference
between the groups and considered that SVV was probably related to aging (9).
In our study we did not review TA biopsy specimens from patients with other diseases, only from
patients who fulfilled the clinical diagnostic criteria for
GCA and/or PMR (in the GRACG study, TA biopsies
were performed even in patients with pure PMR with no
clinical symptoms of GCA). In this specific population,
in which all clinical and biologic data have been prospectively collected using preestablished questionnaires, the
association between SVV and PMR is statistically significant (OR 9.17 [95% CI 3.44–24.4]).
Patients with SVV have distinctive biologic and
clinical features. They are more often men, have fewer
systemic and cranial symptoms, and more frequently
have a normal temporal artery on clinical examination
than patients with biopsy-proven GCA. They also have
lower ESR, fibrinogen levels, haptoglobin levels, and
platelet counts.
Patients with SVV share the same clinical and
biologic features, including PMR symptoms, as patients
with negative TA biopsy findings (43% in this latter
subgroup were diagnosed as having PMR). In our study,
19% of patients with a clinical diagnosis of PMR had
signs of SVV during microscopic examination of TA
biopsy specimens.
The pathogenesis of PMR is still unclear, but our
findings emphasize the possible vasculitic nature of the
disease. Meliconi and colleagues’ study showed that
microscopic examination of synovial biopsy specimens
from patients with PMR indicated inflammatory infiltration in the synovial tissue in 12 of 19 patients (63%), and
6 of these 12 patients had synovial vasculitis (17).
Synovial vasculitis, described in their studies (2,17),
shared the same microscopic features as the SVV found
in the TA biopsy specimens in our studies. Weyand et al
suggested that a subclinical vasculitis may be present in
the temporal arteries of patients with PMR (18). Those
authors found in situ production of messenger RNA for
cytokines indicative of macrophage activation
2571
(interleukin-1␤ [IL-1␤], IL-6, and transforming growth
factor ␤1) and T cell activation (IL-2) in temporal artery
specimens in patients with a clinical diagnosis of PMR,
despite the lack of microscopic evidence of arteritis (18).
They suggested that patients with PMR had subclinical
vascular involvement that could correspond to the SVV
found in our study on microscopic examination of TA
biopsy specimens.
In conclusion, our results indicate that SVV is an
underestimated microscopic finding strongly associated
with PMR symptoms in patients with a clinical diagnosis
of GCA and/or PMR. SVV should not be considered as
a positive biopsy finding because it is not associated with
temporal arteritis. On the other hand, it is difficult to
consider it as an entirely negative biopsy finding because
of the presence of inflammatory infiltrates surrounding
small capillaries.
No pathognomonic test is currently available for
the diagnosis of PMR. Our findings raise the question of
whether SVV could be a pathologic marker for PMR. At
this stage, our study does not provide the answer to that
question, just a hypothesis to be tested. One patient in
the control group without GCA and/or PMR had SVV
on the TA biopsy specimen. The specificity and positive
predictive value of SVV for PMR must be assessed in
prospective studies.
ACKNOWLEDGMENT
We thank Valerie Petigny for expert technical assistance.
AUTHOR CONTRIBUTIONS
Dr. Chatelain had full access to all of the data in the study and
takes responsibility for the integrity of the data and the accuracy of the
data analysis.
Study design. Chatelain, Duhaut, Bosshard, Pellet.
Acquisition of data. Chatelain, Duhaut, Loire, Bosshard, Sevestre.
Analysis and interpretation of data. Chatelain, Duhaut, Piette, Ducroix.
Manuscript preparation. Chatelain, Duhaut, Pellet, Ducroix.
Statistical analysis. Chatelain, Duhaut.
REFERENCES
1. Weyand CM, Goronzy JJ. Giant-cell arteritis and polymyalgia
rheumatica. Ann Intern Med 2003;139:505–16.
2. Salvarani C, Cantini F, Boiardi L, Hunder GG. Polymyalgia
rheumatica and giant-cell arteritis. N Engl J Med 2002;347:261–71.
3. McDonnel PJ, Moore GW, Miller NR, Hutchins GM, Grenn WR.
Temporal arteritis: a clinico-pathologic study. Ophthalmology
1986;93:518–30.
4. Lie JT. When is arteritis of the temporal arteries not temporal
arteritis? J Rheumatol 1994;21:186–9.
5. Salvarini C, Gabriel SE, O’Fallon WM, Hunder GG. The inci-
2572
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
dence of giant cell arteritis in Olmsted County, Minnesota:
apparent fluctuation in a cyclic pattern. Ann Intern Med 1995;123:
192–4.
Schmidt WA, Gromnica-Ihle E. Incidence of temporal arteritis in
patients with polymyalgia rheumatica: a prospective study using
colour Doppler ultrasonography of the temporal arteries. Rheumatology (Oxford) 2002;41:46–52.
Disdier P, Pelissier JF, Harle JR, Figarella-Branger D, Bolla G,
Weiller PJ. Significance of isolated vasculitis of the vasa vasorum
on temporal artery biopsy. J Rheumatol 1994;21:258–60.
Esteban MJ, Font C, Hernandez-Rodriguez J, Valls-Sole J,
Sanmarti R, Cardellach F, et al. Small-vessel vasculitis surrounding a spared temporal artery: clinical and pathologic findings in a
series of twenty-eight patients. Arthritis Rheum 2001;44:1387–95.
Corcoran GM, Prayson RA, Herzog KM. The significance of
perivascular inflammation in the absence of arteritis in temporal
artery biopsy specimens. Am J Clin Pathol 2001;115:342–7.
Genereau T, Lortholary O, Pottier MA, Michon-Pasturel U,
Ponge T, de Wazieres B, et al, for the French Vasculitis Study
Group. Temporal artery biopsy: a diagnostic tool for systemic
necrotizing vasculitis. Arthritis Rheum 1999;42:2674–81.
Duhaut P, Berruyer M, Pinede L, Demolombe-Rague S, Loire R,
Seydoux D, et al, for the Groupe de Recherche sur l’Artérite à
Cellules Géantes. Anticardiolipin antibodies and giant cell arteritis: a prospective, multicenter case–control study. Arthritis Rheum
1998;41:4:701–9.
Duhaut P, Pinede L, Demolombe-Rague S, Loire R, Seydoux D,
Ninet J, et al, on behalf of the Groupe de Recherche sur l’Artérite
à Cellules Géantes. Giant cell arteritis and cardiovascular risk
factors: a multicenter, prospective case–control study. Arthritis
Rheum 1998;41:1960–5.
Hunder GG, Bloch DA, Michel BA, Stevens MB, Arend WP,
Calabrase LH, et al. The American College of Rheumatology 1990
criteria for the classification of giant cell arteritis. Arthritis Rheum
1990;33:1122–8.
Chuang TY, Hunder GG, Ilstrup DM, Kurland LT. Polymyalgia
rheumatica: a 10-year epidemiologic and clinical study. Ann Intern
Med 1982;97:672–80.
Chakrabarty A, Franks AJ. Temporal artery biopsy: is there any
value in examining biopsies at multiple levels? J Clin Pathol
2000;53:131–6.
Schmidt G, Loffler KU. Temporal arteritis: comparison of histological and clinical findings. Acta Ophthalmol (Copenh) 1994;72:
319–25.
Meliconi R, Pulsatelli L, Uguccioni M, Salvarani C, Macchioni P,
Melchiorri C, et al. Leukocyte infiltration in synovial tissue from
the shoulder of patients with polymyalgia rheumatica: quantification analysis and influence of corticosteroid treatment. Arthritis
Rheum 1996;39:1199–207.
Weyand CM, Hicok KC, Hunder GG, Goronzy JJ. Tissue cytokine
patterns in patients with polymyalgia rheumatica and giant cell
arteritis. Ann Intern Med 1994;121:484–91.
APPENDIX A: MEMBERS OF THE GROUPE DE
RECHERCHE SUR L’ARTÉRITE À CELLULES GÉANTES
The GRACG study was conducted at the following institutions (all in France):
Departments of pathology. CHU Nord, Amiens: M. Bensaid,
MD, A. Bruniau, MD, D. Chatelain, MD, PhD, C. Cordonnier, MD,
M. F. Gontier, MD, F. Leclercq, MD, F. Nagorniewcz, MD, A. M.
Marie, MD, H. Sevestre, MD, PhD; Centre Hospitalier, Beauvais: S.
Bendjaballah, MD; Centre Hospitalier, Belfort: C. Lassabe, MD, C.
Monnin, MD; CHU, Besançon: B. Kantelip, MD, G. Marquet, MD;
CHU, Bordeaux: J. M. Meunier, MD, C. Segretin, MD; CHU Am-
CHATELAIN ET AL
broise Paré, Boulogne-Billancourt: A. M. Bergemer, MD; CHG,
Bourg-en-Bresse: R. Angonin, MD, C. Cavailles, MD, J. H. Gasse,
MD; CHG, Bourgoin-Jallieu: B. Bringeon, MD; CHU, Brest: J. P.
Leroy, MD, P. Rivière, MD, R. Roué, MD, A. Volant, MD; CHU,
Caen: J. C. Mandart, MD, P. Rousselot, MD; CHU ClermontFerrand: A. Clemenson, MD, P. Dechelotte, MD, J. L. Kemeny, MD;
Hôpital Louis Mourier, Colombes: J. Barge, MD; CHU, Dijon: M.
Bordes, MD, L. Arnould, MD, P. Chalabreysse, MD, E. Justrabo, MD,
R. Michiels, MD, F. Piard, MD; CHG, Firminy: M. Pialat, MD; CHU,
Grenoble: H. Dufour, MD, F. Le Marc Hadour, MD, M. H. Panh,
MD, B. Pasquier, MD, N. Pinel, MD; CHG, Lagny: G. Wajcner, MD;
CHG, Libourne: M. Julien, MD, M. Augrand, MD; CHU, Lyon: C.
Agard, MD, F. Allias, MD, J. Beurlet, MD, F. Berger, MD, PhD, N.
Berger, MD, C. Crozes, MD, C. David, MD, M. Devouassoux, MD, B.
Frappart, MD, A. Jouvet, MD, M. Guillaud, MD, S. Isaac, MD, R.
Loire, MD, A. Milox, MD, M. Patricot, MD, J. Y. Scoazec, MD, PhD,
A. Tabib, MD, F. Thivolet, MD, P. Tuaillon, MD, A. Vauzelle, MD, D.
Vitrey, MD; Institut Pasteur, Lyon: M. Chevallier, MD, F. Gérard,
MD, M. Maisonneuve, MD, M. Neyra, MD; HIA Desgenettes, Lyon:
M. C. Mouden, MD, M. C. Saccharin, MD; CHG, Montanban: M. H.
Hounieu-Ritoux, MD; CHU, Montpellier, Hôpital Lapeyronie: P.
Baldet, MD, I. Serre, MD; CHU, Nancy: F. Baylac, MD, A. Duprez,
MD, J. C. Lemaire, MD, F. Plenat, MD; Hôpital Saint-Joseph, Paris:
E. Baviera, MD, P. Vaury, MD; Hôpital Tenon, Paris: P. Callard, MD;
Hôpital Cochin, Paris: A. Carlioz, MD, M. Forest, MD, B. Terris, MD,
PhD; Hôpital de la Pitié-Salpêtrière, Paris: F. Charlotte, MD; Hôpital
du Val de Grâce, Paris: H. Schill, MD, P. Camparo, MD; Hôtel-Dieu,
Paris: P. Texier, MD; Laboratoire d’Anatomie Pathologique, Perpignan: M. Guiou, MD; CHG, Roanne: S. Vancina, MD; CHG, Roanne:
P. Terdjman, MD; CHU, Saint-Etienne: S. Boucheron, MD, G.
Poulard, MD; CHG, Saint-Quentin: S. Carton, MD; Laboratoire
Anatomie Pathologique, Saint-Savine: F. Nollez, MD; CHU, Strasbourg: G. Averous, MD, J. P. Bellocq, MD, M. P. Chenard, MD, A.
Engelmann, MD, L. Marcellin, MD, C. Marin, MD, A. Neuville, MD,
A. Onea, MD, N. Rouyer, MD, E. Vaneenoge, MD, A. Warter, MD;
Hôpital Bretonneau, Tours: F. Fetissof, MD, R. Khallouf, MD, L.
Renjard, MD; CHG, Troyes: C. Hopfner, MD, S. Mehaut, MD; CHG,
Valence: N. Bottero, MD, V. André, Y. Suignard; Laboratoire
d’Anatomie Pathologique, Villeurbanne: C. Donne, MD.
Clinical departments. CHU Nord, Amiens: S. Canaple, MD,
R. Cevallos, MD, J. P. Ducroix, MD, P. Duhaut, MD, F. Grados, MD,
PhD, L. Le Page, MD, MPH, Z. Oukachbi, MD, A. Smail, MD, V.
Salle, MD, J. Schmidt, MD; CHG, Belfort: V. Brezovski, MD, F.
Duchêne, MD, O. Labrune-Bobey, MD, G. Simon, MD; CHU,
Besançon: M. Becker-Schneider, MD, B. De Wazières, MD, T. Fest,
MD, PhD, A. Maskani, MD, H. Gil, MD, J. L Dupont, MD; CHU,
Bordeaux: C. Mestre, MD; Hôpital Ambroise Paré, Boulogne: T.
Hanslik, MD, PhD, J. C. Boulard, MD; CHG, Bourg-en-Bresse: B.
Bocquet, MD, P. Debat, MD, P. Granier, MD, R. Philipot, MD, M.
Rousille, MD, N. Sprunck, MD; CHG, Bourgoin-Jallieu: M. Roux,
MD; CHU, Brest: A. Cenac, MD, P. Le Goff, MD, A. Saraux, MD;
CHU, Caen: L. Agron, MD; CHG, Chambéry: C. Cugnet, MD; CHG,
Chartres: R. Damade, MD; CHU, Clermont-Ferrand: M. André, MD,
O. Aumaı̂tre, MD, D. Meloux, MD, B. Sauvezie, MD, J. Schmidt, MD;
Hôpital Louis Mourier, Colombes: J. Pouchot, MD, PhD, J. Vinceneux, MD; CHG, Coulommiers: M. Gatfosse, MD; CHU, Dijon: P.
Pfitenmeyer, MD, S. Baudry-Brunet, MD; CHG, Firminy: P. Sagnol,
MD; CHU, Grenoble: T. Auday, MD, B. Imbert, MD, C. Massot, MD,
F. Sarrot-Reynauld, MD; Cabinet de Rhumatologie, La Tour du Pin:
I. Gozzo, MD, E. Sornay-Rendu, MD; Hôtel-Dieu, Le Creusot: C.
Boussuge, MD; CH Robert Boulin, Libourne: V. Meunier, MD; CHG,
Lons-le-Saunier: B. Saugier, MD; Clinique Protestante, Lyon: S.
Demolombe-Ragué, MD, C. Dolmazon, MD, L. Pinède, MD, PhD;
CHU, Lyon: P. Bourrat, MD, J. F. Brantus, MD, R. Chapurlat, MD, L.
Delattre, MD, B. Demiaux, MD, PhD, F. Duvert, MD, M. Filbet, MD,
E. Fontanges, M. H. Girard-Madoux, MD, P. Haond, MD, D. Liens,
MD, S. Martinon, MD, P. Miossec, MD, PhD, E. Noël, MD, C. Savy,
SVV AS A DIAGNOSTIC CRITERION FOR PMR
MD; Hôpital Saint-Joseph, Lyon: P. Bachet, MD, D. ManièreConstantin, MD; HIA Desgenettes, Lyon: B. Brunot, MD, P. Debouordeau, MD, A. Fléchaire, MD; CHG Montauban: C. Seigneuric,
MD; CHU Saint-Eloi: E. Braun, MD, E. Quere, MD, PhD; CHU,
Nancy: B. Mouget, MD, G. Vaillant, MD, D. Wahl, MD, PhD; Hôpital
Saint-Joseph, Paris: N. Postel-Vinay, MD; Hôpital Cochin, Paris: P.
Hilliquin, MD, C. Job-Deslandre, MD, A. Marin, MD, S. Perrot, MD,
M. Renoux, MD; Hôpital de la Pitié-Salpêtrière, Paris: Z. Amoura,
MD, PhD, D. Boutin, MD, PhD, C. Chapelon-Abric, MD, N.
Costedoat-Chalumeau, MD, PhD, J. Haroche, MD, J. C. Piette, MD;
2573
Hôpital du Val-de-Grâce, Paris: J. P. Algaxres, MD; CHG, Roanne: P.
Amaranto, MD, J. Roche, MD; CHG, Romans: H. Colomb, MD;
Cabinet de Rhumatologie, Saint-Priest: A. Lespine; CHU, SaintEtienne: K. Bouchou, MD, P. Cathebras, MD, PhD, H. Rousset, MD;
CHU, Strasbourg: S. Friess, MD, B. Goichot, MD, PhD, F. Grunenberger, MD, M. Imler, MD, R. M. Javier, MD, G. Kaltenbach, MD,
PhD, A. Pradignac, MD, J. L. Schlienger, MD, S. Vinzio, MD, C.
Wicky-Strich, MD; CHU, Tours: P. Ménage, MD; CHG, Troyes: A.
Fur, MD; CHG, Valence: B. Drouin, MD; CHG, Viriat: A. Pirolet,
MD.
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vessels, artery, rheumatic, small, vasculitis, surrounding, uninflamed, polymyalgia, temporal, criterion, new, diagnostika
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