Rheumatology 1999;38:826830

Microvascular abnormalities in Sjogrens

syndrome: nailfold capillaroscopy
M. Tektonidou, E. Kaskani, F. N. Skopouli1 and
H. M. Moutsopoulos
Department of Pathophysiology, Medical School, National University, Athens
and 1Harokopio University, Athens, Greece
Abstract
Objective. To describe microvascular abnormalities by nailfold capillaroscopy in patients
with primary Sjogrens syndrome (SS) with or without Raynauds phenomenon (RP) and
those with anticentromere antibodies (ACA).
Methods. Forty patients with SS (14 without RP, 16 with RP, 10 with ACA), 20 patients
with scleroderma (SSc) (10 with limited and 10 with diffuse disease) (disease control group)
and 40 healthy controls (control group) were evaluated by nailfold capillaroscopy.
Results. Capillaroscopic abnormalities in SS ranged from non-specific findings (crossed
capillaries) to more specific findings (confluent haemorrhages and pericapillary haemorrhages)
or scleroderma-type findings. SS patients with RP presented capillary abnormalities in higher
frequency than patients without RP. The majority of SS patients with ACA (80%) presented
scleroderma-type findings.
Conclusion. Nailfold capillaroscopy can be used as a simple non-invasive method to
evaluate the microvascular abnormalities in SS patients, especially in those with RP and those
with ACA.
K : Sjogrens syndrome, Nailfold capillaroscopy, Anticentromere antibodies, Raynauds
phenomenon, Scleroderma.

The microvasculature may be affected in several connective tissue diseases. One manifestation connoting vascular
dysregulation is Raynauds phenomenon (RP) [1].
Nailfold capillaroscopy is a non-invasive method of
assessing skin microvasculature, contributing to the
differential diagnosis and prognosis of several autoimmune disorders. The most characteristic capillaroscopic pattern, with prognostic value, is the scleroderma
pattern [2]. In systemic lupus erythematosus (SLE ),
typical capillary findings have been detected [3]. Less
specific capillary changes have been observed in other
autoimmune disorders [4, 5]. In Sjogrens syndrome
(SS ), nailfold capillaroscopy was carried out in the
context of studying different connective tissue diseases
[6 ]. One-third of SS patients present RP [7]. Recently,
we described a group of SS patients with anticentromere
antibodies (ACA) characterized by a low incidence of
parotid gland enlargement, anti-La (SSB) antibodies
and no clinical manifestations of scleroderma (SSc)
besides RP [8].
The aims of the present study were (1) to investigate

the microvascular abnormalities by nailfold capillaroscopy in patients with SS with and without RP, and to
define possible differences between them (SS patients
with ACA were also evaluated in order to investigate a
possible distinct SS group) and (2) to compare the
above abnormalities with the scleroderma pattern.

Patients and methods

Patients
Nailfold capillaroscopy was performed in 40 selective
SS patients: 14 patients without RP, 16 age- and sexmatched patients with RP with a similar disease duration, and 10 patients with ACA. The diagnosis of SS
was made according to the European classification criteria [9]. Nailfold capillaroscopy was also carried out
in 20 age-matched patients with SSc: 10 with limited
disease ( lSSc) and 10 with diffuse disease (dSSc) (disease
control group) [10], and in 40 age-matched healthy
volunteers from the nursing and administrative personnel (control group).
The following data were taken from the patients files:
presence of parotid gland enlargement, RP (diagnosed
by careful history or observation of colour change on
exposure of the extremities to cold), puffy hands, sclerodactyly, digital ulcers, telangiectasias, calcinosis
(diagnosed by hand X-rays), oesophageal dysmotility

Submitted 15 December 1998; revised version accepted 24 March

1999.
Correspondence to: H. M. Moutsopoulos, Department of
Pathophysiology, Medical School, National University of Athens, 75
M. Asias Str., 115 27 Athens, Greece.

826

1999 British Society for Rheumatology

Capillaroscopy in Sjogrens syndrome

(diagnosed by barium swallow study or manometry),

carbon monoxide diffusing capacity (DLCO) <75%
predicted, ACA [according to their pattern in interphase
and metaphase nuclei, using indirect immunofluorescence with commercially prepared Hep-2 cells (Hep-2
ANA kit/Nova lite, Inova Diagnostics, Inc., CA 92131,
USA) as substrate], anti-Ro (SSA), anti-La (SSB) (by
counterimmunoelectrophoresis), rheumatoid factor (by
latex fixation).
Nailfold capillaroscopy technique
Nailfold capillaroscopy and photomicrography were
performed by the panoramic technique [11]. In this
study, qualitative and quantitative methods were
applied. A millimetre ruler was photographed with the
same technique as used for nailfold photomicrographs.
The capillary density was estimated as the mean number
of capillary loops/mm in the distal capillary row of the
fourth and fifth finger on both hands [12]. All the other
parameters were measured on the nailfold of all 10
fingers. Besides the nailfold, the skin of the fingers and
hands was also examined for the presence of capillary
or venular telangiectasias. The study was performed
blinded to disease group by the same investigator.
Classification of capillaroscopic findings
The classification was made according to Maricq [11]
with some modifications. According to their size, the
nailfold capillaries were classified as normal, borderline,
definitely enlarged and extremely enlarged. Capillary
loss was classified as slight, moderate and extensive [11],
and the plexus visualization score (PVS ) as low, moderate and high [12]. Haemorrhages were classified in the
following categories: (a) haemorrhages 1: less than two
punctate haemorrhages per finger; (b) haemorrhages 2:
more than two punctuate haemorrhages per finger or
confluent areas of haemorrhages; (c) pericapillary haemorrhages. The morphological types of capillaries were
the tortuous, crossed, bushy and bizarre capillaries [11,
12]. Other observed capillaroscopic abnormalities were
the thrombotic capillaries. Capillary and venular telangiectasias were also examined.
Capillaroscopic patterns
The above capillaroscopic findings were identified with
the following patterns according to their clinical significance, as previously described [2] with modifications.
We distinguished non-specific findings from other
findings which are more specific.
1.
2.
3.
4.

Normal.
Non-specific findings: tortuous, crossed, bizzare
capillaries, PVS (moderate and high), haemorrhages 1.
Other findings: haemorrhages 2, pericapillary
haemorrhages, thrombotic capillaries.
Scleroderma-type findings:
(a) Active pattern:
Definitely enlarged capillaries.
Moderate or extensive capillary loss.
Bushy capillaries.

827

(b) Slow pattern:

Definitely or extremely enlarged capillaries.
None to slight loss.
Capillary telangiectasias.
(c) Overlap pattern: findings of both active and
slow pattern.
Statistical analysis
The data were expressed as the mean .. The mean
quantitative values were compared with Students t-test.
Differences between the patient groups and control
group or between groups, in regard to the frequency of
capillaroscopic abnormalities, were analysed using x2 or
Fishers exact test. P values of 0.05 were considered
statistically significant.

Results
The demographic, clinical and laboratory findings of
the SS and disease control patients are given in Table 1.
The control group consisted of 37 women and three
men with a mean age of 54.3 9.6 yr. The mean age,
disease duration (from first symptom), duration of sicca
symptoms, and clinical and serological findings were
similar among patients with and without RP. All patients
with SS and ACA had RP.
More than half of SS patients without RP had normal
capillaroscopy. Non-specific findings were observed in
42.8%, consisting mainly of tortuous, crossed capillaries
and moderate PVS. These findings were also present in
32% of healthy individuals ( Table 2); no significant
differences between them were found. Only one patient
displayed haemorrhages (one and two simultaneously).
None had avascular areas or enlarged capillaries. The
mean capillary density was not significantly reduced
(9.8 1.5) compared to the control group (10.5 1.1;
P = 0.09).
In SS patients with RP, only two of the 16 patients
had a normal pattern (12.5%). Non-specific findings
predominated ( Table 2). A significantly higher percentage of crossed capillaries compared to the control group
(P = 0.005) was noted. A higher percentage of moderate
PVS and haemorrhages 1 compared to normals was
found, but this did not reach statistical significance
(P = 0.26, P = 0.64, respectively). Other findings were
significantly more frequent in this group compared to
the control group: haemorrhages 2 were found in 31.2%
(P = 0.001) and pericapillary haemorrhages in 18.7%
(P = 0.02). The above abnormalities were not detected
in the control group. Haemorrhages 2 were found in
similar frequencies in lSSc and dSSc. Two patients
displayed scleroderma-type findings. Both presented an
active pattern. The mean capillary density (8.4 2.0)
was significantly reduced compared to the control
group (P < 0.00001), but significantly higher than
that observed in lSSc (6.5 2.3) and dSSc (5.4 1.5)
(P = 0.03, P = 0.0004, respectively).
Comparing the capillaroscopic abnormalities between
SS patients with and without RP, non-specific findings
and other findings were found in higher frequency in

M. Tektonidou et al.

828

T 1. Demographic, clinical and laboratory features of Sjogrens syndrome patients and disease control patients
Sjogrens syndrome

No. of patients
Female:male
Age, mean .. (yr)
Duration of disease, mean .. (yr)
Duration of RP, mean .. (yr)
Duration of sicca, mean .. (yr)

Without RPa

With RPa

With ACA

Limited

Diffuse

14
13:1
55.3 7.4
8.2 5.4

16
15:1
54.6 8.2
8.0 6.3
7.2 6.3
6.3 5.0

10
9:1
54.8 7.8
10.2 5.0
10.2 5.0
9.7 5.5

10
9:1
52.2 8.1
0.5 10.8
10.5 10.8

10
9:1
53.2 6.9
8.4 6.2
8.4 6.2

31.2
12.5
0
6.2
43.7
18.7
56.2

10
60
20
10
10
0
20

0
50
60
30
0
0
10

0
30
50
60
0
0
10

7.2 6.0
Per cent positive
35.7
7.1
0
0
42.8
21.4
50

Parotid gland enlargement

Puffy hands
Telangiectasias
DLCO <75%
Anti-Ro (SSA)
Anti-La (SSB)
Rheumatoid factor

Scleroderma

RP, Raynauds phenomenon; ACA, anticentromere antibodies; DLCO, carbon monoxide diffusing capacity.
aACA-negative patients.
T 2. Frequency of capillaroscopic findings (per cent positive) in Sjogrens syndrome patients, disease control and control group, according
to their classification in capillaroscopic patterns
Sjogrens syndrome
Without RP
(n = 14)
Normal
Non-specific findingsa
Crossed
Tortuous
Bizarre
Moderate PVS
High PVS
Haem 1
Other findingsa
Haem 2
Per haem
Thromb. Cap
Scleroderma-type findings
Slow pattern
Active pattern
Overlap

57.1
42.8
21.4
35.7
0
21.4
7.1
7.1
7.1
7.1
0
0
0
0
0
0

With RP
(n = 16)
12.5
65.2
43.7*
37.5
6.2
31.2
12.5
25
31.2
31.2*
18.7*
6.2
12.5
12.5
0
0

Scleroderma
With ACA
(n = 10)
0
40
10
10
10
30
20
10
50
50*
40*
20*
80
50
20
10

Limited
(n = 10)
0
30
0
10
20
30
10
10
40
40
40
50
100
60
30
10

Diffuse
(n = 10)
0
40
0
10
40
20
20
10
40
40
10
0
100
0
90
10

Control
(n = 4)
67.5
32.5
12.5
32.5
0
15
7.5
10
0
0
0
0
0
0
0
0

RP, Raynauds phenomenon; ACA, anticentromere antibodies; PVS, plexus visualization score; Haem, haemorrhages; Per haem, pericapillary
haemorrhages; Thromb. cap, thrombotic capillaries.
*P < 0.05 compared to the control group.
aSeveral patients had more than one type of capillaroscopic finding.

RP-positive patients, although the difference did not

reach statistical significance, perhaps because of the
small number of patients: crossed capillaries (P = 0.26),
haemorrhages 1 (P = 0.33), haemorrhages 2 (P = 0.17)
and pericapillary haemorrhages (P = 0.21). The mean
capillary density was significantly lower in patients with
RP (P = 0.04).
All SS patients with ACA had pathologic nailfold
capillaroscopy. Four out of 10 patients displayed nonspecific findings, but not in a significantly higher frequency than the control group. Other findings were
found in a significantly higher frequency than normals:
haemorrhages 2 were found in 50% (P < 0.0001), thrombotic capillaries in 20% (P = 0.03) and pericapillary
haemorrhages in 40% (P < 0.0009). Non-specific findings and other findings were found in similar frequen-

cies with those of lSSc. Eight out of 10 patients (80%)

presented scleroderma-type findings; five out of eight
had slow pattern. The mean capillary density (mean
density 7.2 1.6) in this group was significantly lower
compared to the control group (P < 0.00001), but
it was not significantly different from that found in
lSSc (P = 0.44). The mean capillary density in dSSc
was significantly lower than in SS patients with ACA
(P = 0.01).

Discussion
In this study, using qualitative and quantitative methods
of nailfold capillaroscopy, the microvascular abnormalities in SS patients with or without RP, as well as
patients with ACA, were evaluated. Non-specific find-

Capillaroscopy in Sjogrens syndrome

ings were distinguished from the other findings which

are more specific. Non-specific findings have been
found in patients with several connective tissue diseases,
as well as in healthy individuals. Other findings have
predominantly been described in scleroderma and SLE
patients, and were not present in the normal population [13].
In SS patients without RP, normal and non-specific
findings were predominant. The mean capillary density
was not significantly reduced compared to normals. On
the other hand, SS patients with RP presented nonspecific findings (crossed capillaries) and other findings
(confluent haemorrhages and pericapillary haemorrhages) in significantly higher frequency than the control
group. The mean capillary density in patients with RP
was also significantly lower than that in RP-negative
patients. Two patients with RP also displayed scleroderma-type findings. The first patient had active disease
with extensive parotid gland enlargement, peripheral
neuropathy and periungual erythema. The second
patient presented mild periungual erythema. Scleroderma-type abnormalities have also been found in SLE
patients with periungual discoid lesions [14].
Most studies, investigating the capillaroscopic findings
of several autoimmune diseases, did not state whether
patients with RP differ from those without RP. Some
authors noted no significant differences in nailfold capillaroscopy among RP-positive and RP-negative patients
[15]. Others demonstrated an increase in mean capillary
diameter and a decrease in the capillary number of the
first capillary row, associated with the frequency and
severity of RP attacks [16 ]. Besides the classic mechanisms of vasospasm, the digital artery and microvascular
lesions may play a role in the pathogenesis of secondary
RP, and may explain the different capillaroscopic findings in RP-positive SS patients.
SS patients with ACA were also investigated. In a
previous study, SS patients with ACA and RP, without
telengiectasias, calcinosis, sclerodactyly and a low incidence of parotid gland enlargement and anti-La (SSB)
autoantibodies, were described [8]. The question of
whether this group of patients constitutes an overlap
between lSSc and SS was raised. In this study, all the
patients had a definite diagnosis of SS. Their predominant features were sicca manifestations and RP ( Table 1).
Some of them had clinical features similar to CREST,
but none fulfilled the three out of five ACR criteria for
the syndrome [10]. Two out of 10 patients had telengiectasias. More than half the patients had puffy hands
(60%). None presented sclerodactyly, facial scleroderma,
digital ulcers, oesophageal dysmotility or calcinosis. A
low incidence of parotid gland enlargement, anti-Ro
(SSA) and anti-La (SSB) antibodies in comparison to
other SS patients was observed ( Table 1). Nailfold capillaroscopy showed scleroderma-type findings in eight out
of 10 patients. A slow pattern predominated in these
patients, such as in lSSc ( Table 2). Non-specific findings and other findings were described in similar
frequencies with those of lSSc patients. The mean capillary density was also similar to that found in lSSc.

829

In several previous studies of idiopathic RP, the

presence of ACA was highly indicative of future development of CREST syndrome or lSSc [17]. Le Roy et al.
[18] have proposed that patients with RP, ACA and
scleroderma pattern in capillaroscopy should be included
in the spectrum of lSSc, although no cutaneous scleroderma was observed. In our patients, RP was predominant, but sicca symptoms and generally clinical and
serological features of SS were present simultaneously.
Our findings are highly suggestive that the SS-ACA
group can be included under the umbrella of lSSc, even
though it does not have clinical manifestations of this
disease in a 10 yr follow-up. The time of lSSc diagnosis
varies among individuals and it is possible that some
patients may present an atypical form of the disease for
years. The slow pattern in this group of patients may
be related to slow evolution to the limited form of SSc.
Since the presence of ACA in SS may serve as an early
predictor of lSSc, further evaluation by nailfold capillaroscopy and close follow-up should be performed.
In conclusion, SS patients, and especially those with
RP, present capillaroscopic abnormalities ranging from
non-specific to more specific findings or, on some occasions, scleroderma-type findings. The majority of
patients with SS and ACA present scleroderma-type
findings and probably constitute an overlap with a
subclinical form of lSSc.

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