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Arthritis & Rheumatism (Arthritis Care & Research)
Vol. 61, No. 3, March 15, 2009, pp 405– 410
© 2009, American College of Rheumatology
A Growing Need for Capillaroscopy
ROSSELLA DE ANGELIS,1 WALTER GRASSI,1
Use of Capillaroscopy in Rheumatology
In 1973, Maricq and LeRoy published the ﬁrst article
describing the speciﬁc capillaroscopic pattern in systemic
sclerosis (SSc; scleroderma) (1). This was the ﬁrst in a
series of studies that contributed to the initial spread of the
technique and highlighted the remarkable diagnostic potential of in vivo capillary microscopy in detecting scleroderma microangiopathy (1– 6).
However, several years later, despite its undisputed diagnostic value, the growth in capillaroscopy had only partially fulﬁlled its initial potential and had failed to make
a signiﬁcant impact in rheumatology. This may be related
to the fact that capillaroscopic ﬁndings of the so-called
scleroderma pattern have only been more recently included in the classiﬁcation criteria of SSc (7–9), in the last
few years. A Medline search performed with the words
“capillaroscopy” and “nailfold capillary microscopy” revealed that there were 717 articles published between
1980 and 2008, with an average of 25 articles per year.
Fewer than 200 papers that focused on rheumatic diseases
were found, and only 123 of those published were in
rheumatology journals. Therefore, one reason for the limited use of capillaroscopy in rheumatology may be the
scarce dissemination of its value in rheumatology venues.
Although capillaroscopy performed using photographic
equipment is generally economical, it is a complex and
time-consuming process. The recent availability of images
obtained using digital systems has led to a renewed interest toward videocapillaroscopy, and makes this technique
more reliable and user-friendly. We consider videocapillaroscopy to be one of the best diagnostic tools for the early
recognition of SSc and related conditions. In this article,
we will describe the use and value of capillaroscopy in
First-line examination of patients with Raynaud’s phenomenon. According to epidemiologic surveys, Raynaud’s
phenomenon (RP) has a prevalence ranging from 2% to
22% (6,10 –12). There is substantial agreement regarding
the fact that every patient with RP should undergo a
capillaroscopic examination (6,7,11), which may signiﬁcantly assist in characterizing the clinical and evolving
proﬁle (11). Capillaroscopic ﬁndings associated with RP
may vary, ranging from a normal pattern to abnormalities
that show microvascular involvement, including microhemorrhages, irregularly enlarged loops, megacapillaries
or giant loops, neoangiogenesis, architectural derangement, and loss of capillaries (1–3,6).
In a patient with clinically isolated RP, even a single
morphologic abnormality such as a megacapillary or an
irregularly enlarged loop (especially with an aneurysmlike appearance) should alert the physician to the possibility of an underlying scleroderma spectrum disorder
(secondary RP) (11,12). In secondary RP, the presence of
abnormalities that characterize the scleroderma pattern
(Figure 1) supports a high speciﬁcity and a positive predictive value for the diagnosis of SSc and related disorders, more than a positive antinuclear antibodies test. Similarly, a normal capillaroscopic pattern is likely to indicate
primary RP (11,13,14). Other adjunctive tests that may
have prognostic and diagnostic value in clinical use for
detecting secondary RP include laser Doppler ﬂowmetry,
thermography, and ﬁnger systolic blood pressure (5,11).
Rossella De Angelis, MD, PhD, Walter Grassi, MD: Polytechnic University of the Marche, Ancona, Italy; 2Maurizio
Cutolo, MD: University of Genoa, Genoa, Italy.
Address correspondence to Rossella De Angelis, MD, PhD,
Clinica Reumatologica, Universita Politecnica delle Marche,
via dei Colli, 52 Jesi (Ancona), Italy 60035. E-mail: rossella.
Submitted for publication August 5, 2008; accepted in
revised form October 24, 2008.
Transition from primary to secondary RP. Patients
with primary RP should undergo a careful capillaroscopic
analysis every 6 months in order to detect, at the earliest
time and in the most reliable manner, the transition to
the secondary form of RP (15). The combination of capillaroscopy with laser Doppler imaging of the nailfold microcirculation seems to be signiﬁcant in distinguishing
whether a reduced blood ﬂow is due to primary or secondary RP (16,17).
In a recent investigation, 20% of patients initially diagnosed as having primary RP were found to have transitioned to either suspected secondary RP or deﬁnitive secondary RP during an average followup period of 10 years
(18). The annual incidence of transition to suspected sec405
De Angelis et al
Figure 1. Nailfold capillaroscopy in secondary Raynaud’s phenomenon. Note the irregularly enlarged
loops, megacapillaries, and angiogenesis (arrows). (Original magniﬁcation ⫻ 200.)
ondary RP or deﬁnitive secondary RP was 2% and 1%,
respectively. Although capillary microscopy was considered in this study, its use was not fully analyzed, and its
relevance for the diagnosis was partly underestimated.
The importance of capillaroscopy for identifying RP patients at high risk for the development of a scleroderma
spectrum disorder has recently been addressed (6) using a
prognostic model based on a weighted combination of
different capillaroscopy parameters. In an additional
study, 129 subjects were referred to an outpatient unit for
analysis of primary RP (16). Based on the appearance of
the patterns on nailfold videocapillaroscopy, 19 (14.6%) of
the patients were classiﬁed as having secondary RP over a
mean ⫾ SD followup period of 29 ⫾ 10 months. Interestingly, 4.6% of these patients had exhibited a normal capillaroscopic pattern at baseline (transition from normal to
altered pattern observed in a mean ⫾ SD of 42 ⫾ 30
months) and 10% had minimal and nonsigniﬁcant microvascular alterations between the time of primary and secondary RP.
Early diagnosis of SSc. Capillaroscopy can be regarded
as the most valuable technique for detecting the early
characteristics of microangiopathy in SSc, such as the
morphologic changes in the nailfold that have been extensively studied including enlarged loops, megacapillaries,
neovascularization, loss of capillaries, architectural dis-
Figure 2. Nailfold capillaroscopy in systemic sclerosis. A–D, Features of deﬁnitely enlarged loops. E, Disorganization of the nailfold capillary, along with prominent features of neovascularization (arrows). F, Loss of capillaries. (Original magniﬁcation ⫻ 200
in A–D; ⫻ 100 in E and F.)
Capillaroscopy in Rheumatology
Figure 3. Normal capillary patterns (top left), and patterns seen in scleroderma. Early (top right): few
giant capillaries (G), and microhemorrhages (H). Active (bottom left): increased number of giant capillaries and microhemorrhages, together with loss of capillaries (L). Late (bottom right): dramatic loss of
capillaries, neoangiogenesis (N), and ﬁbrosis (F).
ruption of the nailfold microvascular network, and avascular areas (1– 6,12,19,20) (Figure 2). Such capillary abnormalities can be recognized, even in the early stages of SSc,
when clinical features of the disease are only limited to
RP. Microvascular alterations have been reclassiﬁed into 3
deﬁned and different patterns (20), which include an early
pattern (few enlarged/giant capillaries, few capillary hemorrhages, no evident loss of capillaries), an active pattern
(frequent giant capillaries, frequent capillary hemorrhages,
mild disorganization of the capillary network), and a late
pattern (irregular enlargement of the capillaries, few or
absent giant capillaries, hemorrhages, and extensive avascular areas).
A marked increase in capillary size is the most characteristic feature of the nailfold capillary bed in SSc (Figures
2A–D). The shape of the widened capillaries is largely
heterogeneous, and there is no general agreement about the
deﬁnition of loop enlargement (20 –25). A practical system to
score these microvascular alterations in scleroderma patients has recently been proposed by Sulli et al (26).
Differential diagnosis of the scleroderma-related conditions. Capillaroscopy should be performed on all patients
with RP in order to support or exclude an association with
a scleroderma spectrum disorder (SSc, dermatomyositis
[DM], and mixed connective tissue disease [MCTD]) (27).
The presence of an indicative expression of a scleroderma
microangiopathy should alert the physician to the presence of a systemic disorder (28).
In patients with DM, capillaroscopic abnormalities
may be similar to those seen in patients with SSc, such as
architectural derangement of the nailfold capillary network
and prevalent features of marked angiogenesis (12,29).
Nailfold capillary abnormalities included within the
scleroderma-like pattern can also be detectable in primary
Sjo¨gren’s syndrome, especially when associated with RP
(30), and in undifferentiated connective tissue disease
A capillaroscopic examination should be performed in
patients with morphea and eosinophilic fasciitis, which is
usually characterized by a normal pattern (32).
Early detection of severe microangiopathy in SSc. Progressive capillary loss characterizes the microvascular involvement in SSc (Figure 2F); it also may be relevant in
determining critical tissue hypoxia, and can serve as a
warning for the potential development of avascular areas
(12). Capillary loss has been associated with more extensive skin and/or visceral involvement and a poor prognosis (12,33,34). As mentioned above, the different SSc patterns are now well recognized, with the late pattern
indicating the late stages of SSc (Figure 3).
The deﬁnition and classiﬁcation of avascular areas and
capillary loss are not clear. However, a deletion area (or a
discrete avascular area) is deﬁned as the loss of ⬎2 consecutive capillaries in the distal row (35) or as the absence
of 3 consecutive capillary loops (6). Furthermore, avascular areas have in recent years been classiﬁed as moderate
(33– 66%) or severe (⬎66%) (36). Even if the progression of
capillary loss is thought to be related to the duration of RP
(20), avascular areas can represent the ﬁrst dramatic capillaroscopic ﬁnding in recent-onset SSc, especially in men
with very aggressive disease (12). A scoring system for the
scleroderma abnormalities (which comprises loss of capillaries) is now available, and it may also help in the
followup of scleroderma patients (26).
Therapy monitoring. There is growing interest in the
use of capillaroscopy for therapy monitoring. Capillary
changes ﬁrst described post-therapy are related to dynamic
studies, in which the parameters used are the variations of
blood ﬂow and capillary permeability. A single oral administration of nifedipine (10 mg) has demonstrated a
prompt antagonist effect on the cold-induced reduction of
capillary permeability in patients with SSc (37).
Conversely, other studies reported morphologic modiﬁcations and nailfold loop changes following vasoactive
therapy. A decreased capillary loss was observed after
administering cyclosporin A and intravenous iloprost during an open, double-arm trial of 20 patients with SSc
chosen randomly to receive either treatment with iloprost
alone or iloprost in association with low-dose long-term
cyclosporin A (38). The development of nailfold microvascularization, characterized by an increase in the loop number and a reduction in avascular areas, was described in 4
patients with SSc after a 3-year treatment sequence with
iloprost (39). Furthermore, a signiﬁcant decrease in severe
avascular areas was observed in 16% of patients with
MCTD treated with iloprost during a sequential evaluation
of ⬃3 years (24).
The development of new computer-based systems, speciﬁcally nailfold videocapillaroscopy, allows the visualization of a single loop image. When applied to longitudinal studies and clinical trials, this capability may improve
reproducibility by providing the ability to guarantee examination of the same capillaries at different points in
Most recently, nailfold videocapillaroscopy analysis
has been used to evaluate the effects of autologous hemopoietic stem cell transplantation (HSCT) in patients with
severe diffuse SSc. Three months after HSCT, the nailfold
videocapillaroscopy pattern changed from late to active,
showing frequent giant capillaries and hemorrhages, absence of avascular areas, and angiogenetic phenomena
(41). One year later, microvascular abnormalities still
showed the active pattern, therefore indicating that HSCT
with high-dose cyclophosphamide (1 gm/month for 6
months) may promote vascular remodeling. This effect
must be conﬁrmed by additional studies, but the initial
De Angelis et al
results suggest the prognostic ability of nailfold videocapillaroscopy in monitoring patients after HSCT.
Assessment of microvascular involvement in other autoimmune rheumatic disorders. The main capillaroscopic
abnormalities described in patients with systemic lupus
erythematosus (SLE) include increased tortuosity, loop
elongation, enlarged and/or branching loops, and increased
visibility of the subpapillary venous plexus, although in
⬃50% of patients the capillaroscopic pattern is similar to
that of healthy subjects (24,42). Nailfold abnormalities,
especially enlarged loops and capillary loss, have been
correlated with the presence of lung involvement (42). In a
subgroup of SLE patients, scleroderma-type ﬁndings were
found with the simultaneous presence of RP and anti–U1
RNP antibodies (43).
Microvascular alterations were found in patients with
antiphospholipid syndrome and anticardiolipin antibody–
positive SLE patients, suggesting direct damage of the
vascular endothelium is triggered by anticardiolipin antibodies (44). Symmetric microhemorrhages at the nailfold
were present mainly in patients with both serum IgG and
IgM anticardiolipin antibodies, with marked microvascular damage related to the occurrence of thrombotic manifestation (45). Patients with rheumatoid arthritis (RA)
showed evidence of capillaroscopic abnormalities of uncertain signiﬁcance, such as elongated loops (46). When
clearly evident features of microangiopathy are present, a
careful followup examination is advisable in order to identify any possible relationship between capillaroscopic abnormalities and disease subsets and/or overlap with other
A reduction in loop length would distinguish patients
with psoriatic arthritis from those with RA (46). This has
not been subsequently conﬁrmed, despite the possible occurence of dwarf loops in patients with psoriatic arthritis
(47). The fact that it is unusual to ﬁnd elongated loops
even in patients with psoriatic arthritis is further conﬁrmation that capillary length is not speciﬁc proof of microangiopathy (47). Conversely, capillaroscopy performed
on the psoriatic plaques reveals considerable features of
angiogenesis (tortuous, coiled ball, branching loops) and
an increase in capillary diameter that appears to be related
to the intense metabolic activity of the skin (48). Patients
with mixed cryoglobulinemia demonstrate various nailfold microcirculatory changes, often clustered in a pattern
of abnormally oriented short capillaries and neoangiogenetic phenomena, more evident in nephritic patients
(49). Therefore, capillaroscopy might help to detect the
microvascular involvement in several CTDs.
The Future of Capillaroscopy in Rheumatology
Capillaroscopy represents the most reliable tool for the
early differential diagnosis between primary and secondary RP, even in the absence of other clinical symptoms of
an associated CTD.
Capillaroscopy in Rheumatology
Quantifying nailfold microvascular alterations is complex. However, as mentioned previously, a novel scoring
system is now available and the lack of reproducibility of
the capillary measurement might be of less concern to
rheumatologists (26). Nevertheless, the development of a
shared scoring method involves a multistep process in
which feasibility, reliability, validity, and responsiveness
should be evaluated in ongoing multicenter trials using
appropriate statistical analysis. This new system should
improve the application of the capillaroscopic technique
in longitudinal studies and should have the potential of
being a valuable outcome measure for microvascular disease/involvement in clinical assessment (40).
The traditional approach to capillaroscopy is frequently
based on the use of optical instruments (macrophotography, stereomicroscopy) that guarantee only an overall
evaluation of the entire nailfold area (wideﬁeld capillaroscopy). In addition to being time consuming, this procedure
limits the quality of analysis and the realization of highquality material. However, the availability of new computer-driven videomicroscopy systems has greatly simpliﬁed
the acquisition, measurement, and recording of images of
excellent quality (32,40). Digitally stored images, with the
consequent option of immediate printing for reports and/
or saving onto media support, can be sent via the Internet
for telediagnosis and teleconsultation, therefore contributing to the spread of the technique.
The teaching and training of capillaroscopy to rheumatologists was a difﬁcult issue and was neglected for years.
Previously, education and practice in capillaroscopy did
not follow standardized models and were a result of unplanned initiatives (self-study). However, capillaroscopy
courses have more recently been provided by international
faculties, such as the European League Against Rheumatism (EULAR) full-immersion courses that were held in
Genoa, Italy in 2004, 2006, and 2008. In 2008, SSc was
indicated as an “orphan disease” of prominent interest for
EULAR. The requirement of a standardized training curriculum and a recognized training program for capillaroscopy is now being considered by the Educational and
Training Committee of EULAR, in association with the
European Consortium for the Study of Scleroderma.
Previously, capillaroscopic ﬁndings of the scleroderma
pattern were not included in the classiﬁcation criteria of
SSc, and only after 2000 have they been included in published classiﬁcation criteria (7–9,50). In 2001 the sensitivity of the American College of Rheumatology (ACR) criteria to identify patients with limited disease was found to
be improved with the addition of nailfold capillary abnormalities and visible telangiectasias (from 34% to 89%)
(51). More recently, 101 SSc patients were analyzed for the
same purpose. Of these, 68 (67%) met the ACR classiﬁcation criteria. The sensitivity increased from 67% to 99%
with the addition of the nailfold capillary abnormalities
identiﬁed using a simple dermatoscope and visible telangiectasias (52). The ACR classiﬁcation criteria for SSc lack
sensitivity for the diagnosis of early disease. However, this
may be signiﬁcantly improved with the inclusion of variables such as the detection of a well-recognized scleroderma pattern. This represents the real target of the capillaroscopic analysis in RP patients (53,54).
Dr. De Angelis 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. De Angelis, Grassi, Cutolo.
Acquisition of data. De Angelis, Cutolo.
Analysis and interpretation of data. De Angelis.
Manuscript preparation. De Angelis.
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