The new frontiers of ultrasound in the complex
world of vasculitides and scleroderma
Francesco Porta1, Luna Gargani2, Olga Kaloudi3, Wolfgang A. Schmidt4,
Eugenio Picano2, Nemanja Damjanov5and Marco Matucci-Cerinic1
Modern US equipment allows rheumatologists to directly visualize vascular, musculoskeletal, dermal and
internal organ structure. In multisystemic and challenging diseases such as vasculitides and scleroderma,
where new outcome measures are required in both clinical practice and trials, US measures promise
reproducible and objective scores of disease activity and extension. US reveals early pathognonomic
abnormalities and may help start early treatment.
Key words: ultrasound, systemic sclerosis, vasculitis, heart, vascular, musculoskeletal, skin, lung.
In the past decade, US has been employed in the inves-
tigation of organ involvement in SSc and vasculitides. US
is non-invasive, largely available, low cost, does not
employ ionizing radiation , and could be employed in
diagnosis, follow-up and prognostic stratification. Along
with well-established US applications, such as echocar-
diography as a screening test for pulmonary hypertension
(PH), new US techniques have recently entered the clinical
arena. In this review, we briefly summarize some of the US
applications in SSc and vasculitides.
Cardiac involvement, which is very frequent in SSc and
vasculitis, leads to a fatal outcome in a substantial per-
centage of patients. It is usually asymptomatic, however,
and by the time it becomes clinically evident extensive
damage to the myocardium has already occurred and
treatment is rarely effective. In SSc, clinical evidence of
cardiac involvement may be found in 20?25% of patients,
while at post-mortem examination the heart is affected in
up to 80% of patients. The endocardium, myocardium
and pericardium, separately or concomitantly, can be af-
fected. Echocardiography is crucial because it makes it
possible to detect not only cardiac abnormalities respon-
sible for the symptoms, but subclinical alterations as well.
Echocardiography is routinely employed in SSc for the
assessment of PH. Although right heart catheterization is
necessary for diagnostic confirmation, US is a routine
screening tool for this condition. Primary myocardial in-
volvement, characterized by vascular alterations and fi-
brosis thatlead toischaemia,
myocardial disfunction, could be found in SSc patients
independently of PH and significant renal or pulmonary
involvement. Echocardiography is also routinely employed
in vasculitis,to assess
hypertension-related damage, sequelae of vasculitis-
related ischaemia and, of course, systolic and diastolic
function. A main limitation of echocardiography is that
ejection fraction is often the only parameter provided to
evaluate cardiac function, whereas more subtle myocar-
dial dysfunction cannot be assessed.
Several studies have recently proposed novel echocar-
diographic techniques, such as Doppler tissue imaging
(DTI) and speckle tracking-derived strain analysis, as ef-
fective tools for early detection of right and left ventricular
systolic and diastolic dysfunction . All studies employ-
ing these techniques consistently showed significant al-
terations of cardiac mechanics in SSc patients compared
with controls [2, 3]. These abnormalities are independent
of the presence of PH and are often detectable in asymp-
tomatic patients with otherwise normal hearts on echocar-
diogram . Left ventricular speckle tracking has also
been reported as decreased during the acute phase of
Kawasaki disease, probably due to myocardial swelling
1Department of Internal Medicine, Section of Rheumatology, University
of Florence, Florence,2Institute of Clinical Physiology, National
Research Council, Pisa,3Second Division of Internal Medicine,
Rheumatology Unit, Prato, Italy,4Medical Centre for Rheumatology
Berlin-Buch, Berlin, Germany and5Institute of Rheumatology, Medical
School, University of Belgrade, Belgrade, Serbia.
Correspondence to: Francesco Porta, Department of Internal
Medicine, Section of Rheumatology, University of Florence, V. le
Pieraccini 18, 50139 Florence, Italy. E-mail: email@example.com
Submitted 15 February 2012; revised version accepted
12 October 2012
! The Author 2012. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: firstname.lastname@example.org
by guest on January 11, 2016
caused by myocarditis. Although very promising, inter-
vendor variability is a significant limitation of speckle
tracking- and DTI-derived strain analysis; moreover,
normal cut-off values are still lacking. Pulsed-wave DTI,
with specific reference values, is the sole technique that
has gained clinical relevance.
Three-dimensional echocardiography is another emerg-
ing US technique that could detect very early abnormal-
ities of right and left ventricular function and assess left
atrial volume. Nevertheless, its role in SSc and vasculitis
patients is still to be determined.
Myocardial fibrosis, the final pathological hallmark of
cardiac involvement in these patients, is reported in
50?80% of cases at necropsy. It can be imaged on a
transthoracic echocardiograph by proprietary integrated
increased myocardial echodensity. However, in spite of
the promising experimental and initial clinical results ,
this technique, being technically demanding, subject to
artefacts and dependent on good image quality, is not
widely employed. Myocardial late enhancement detected
by cardiac MRI is the current non-invasive gold standard
for myocardial fibrosis assessment. Its presence has been
reported in a relatively high percentage of both SSc and
vasculitis patients. Future studies are needed to define the
clinical additive value of cardiac MRI when combined with
A very promising US tool in vasculitis (especially in
Kawasaki disease) is coronary artery US imaging, which
showed comparable accuracy to CT in the evaluation of
proximal coronary artery. On the other hand, CT provides
more information for distal segments, although with a
non-negligible radiation burden .
In large-vessel vasculitides, inflamed artery walls are usu-
ally homogeneously thickened: the wall swelling is circum-
ferential and differs from atherosclerotic lesions, which are
asymmetric and inhomogeneous with calcifications. US
reveals homogeneous vascular wall swelling, determines
the grade of stenosis and the presence of retrograde flow
Linear probes with a frequency of at least 10 MHz are
used to examine the common superficial temporal artery.
Typical features are the hypoechoic wall swelling, turbu-
lent flow and acute arterial occlusions (Fig. 1) . Other
arteries, such as the occipital and facial arteries, may be
examined depending on symptoms. Two meta-analyses
found sensitivities of temporal artery US for the presence
of wall swelling, stenosis and/or occlusion in relation to
the clinical diagnosis of temporal arteritis of 75% and
86%, and specificities of 83% and 96%, respectively [7,
8]. A third meta-analysis described a sensitivity of 68%
and a specificity of 91% for the presence of wall swelling
alone . Diagnostic accuracy varies greatly between stu-
dies and centres and depends on the experience of the
sonographer, the quality of equipment and the use of
Axillary arteritis is common in GCA. An intima?media
complex of >1.0mm is suspicious for large-vessel GCA.
The diagnosis is definite if the homogeneous wall swelling
is >1.5mm . The subclavian and common carotid
arteries may also be involved. Temporal artery histology
or US is positive in only ?60% of cases. Nearly 50% of
patients with newly diagnosed GCA have large-vessel
GCA in terms of proximal arm vasculitis. Experienced
centres have replaced temporal artery biopsies in patients
with typical US findings. Furthermore, axillary artery US
results in a greater number of patients diagnosed with
large-vessel vasculitis and helps in starting effective treat-
ment early in the course of the disease. The arteries most
commonly involved in Takayasu’s arteritis are the sub-
clavian, common carotid and vertebral arteries .
Kawasaki’s disease is an acute self-limiting medium-
sized vessel vasculitis of childhood. It is characterized
by fever, polymorphous exanthema, membranous des-
quamation of fingertips, conjunctivitis, mucositis and cer-
vical lymphadenopathy. Aneurysms occur in coronary
arteries in ?25% of untreated cases. Transthoracic echo-
cardiography reveals these aneurysms with a sensitivity of
95% and a specificity of 99% .
Application of colour Doppler US for the evaluation of
medium- and large-size vessels and the detection of in-
tima?media thickness as a marker of accelerated athero-
sclerosis is well known. Microvascular assessment of
digital arteries in SSc patients has been elegantly
described by Schmidt et al.  as delineating a smaller
artery lumen, reduced pulsation and thickened, slightly
hyperechoic artery walls in SSc digital arteries. It seems
that US can even help differentiate between primary and
secondary RP , thus enabling us to distinguish severe
from mild disease, and acute from chronic vascular occlu-
sion. US depicts the same anatomical structures as finger
US may also detect early renal vascular damage in SSc
patients without clinical evidence of nephropathy. Doppler
indices of renal vascular resistance are closely related to
the duration of the disease, age and plasma renin activity
and they make possible early detection of high risk of
scleroderma renal crisis .
ischeaper, faster and
Assessment of the lung has long been considered
off-limits for US, since US energy is rapidly dissipated
by air. However, this is true in a normal, aerated lung,
where there is no acoustic mismatch that can reflect the
US beam. The presence of structures other than air, such
as exudate, transudate, blood, cells or fibrotic tissue, cre-
ates an acoustic mismatch in the lung and opens the pre-
viously locked pulmonary acoustic window.
In recent years, lung US (LUS) has emerged as a new,
promising technique for the evaluation of many pulmonary
abnormalities. Interstitial lung disease (ILD) can be imaged
by the presence of B-lines (also called US lung comets).
B-lines are a sonographic sign of interstitial syndrome,
originating from thickened interlobular septa. They can
US in vasculitides and scleroderma
by guest on January 11, 2016
be easily assessed by either a sector/cardiac, convex/ab-
dominal or a linear/vascular probe. B-lines have been re-
ported in different forms of diffuse parenchymal lung
disease, including pulmonary fibrosis. More recently, the
validity of LUS has been demonstrated by comparing this
new technique with CT signs of pulmonary fibrosis in SSc
patients (Fig. 2) . There is good correlation between
B-line number and the semi-quantitative Warrick score
(r=0.72, P<0.001) . Moreover, it seems very promis-
ing as a screening tool in patients at high risk of de-
veloping ILD . The utility of LUS in patients with
connective tissue disorders has been further confirmed
by employing a simplified method, in order to maximize
efficiency and underline its potential role in routine
high-volume clinical practice .
The clinical impact of LUS in the management of ILD
could be significant, since LUS is inexpensive, largely
available, has a very short learning curve and can be per-
formed at the bedside. In the future, LUS in SSc-related
ILD might help distinguish established pulmonary fibrosis
from alveolitis. So far it is not possible, since both condi-
tions may generate B-lines.
Musculoskeletal involvement is a major cause of disability
in SSc. Most common signs and symptoms of joint and
tendon involvement in SSc are arthralgias, reduced range
of motion and flexion contractures of joints. Clinical find-
ings typical of inflammatory arthritis are rare in SSc pa-
tients with arthralgias. Usually, no structural damage can
be found on X-rays. Only a few published studies have
assessed the sensitivity of musculoskeletal US in detect-
ing synovitis and erosions in SSc. Cuomo et al.  re-
ported that US examination detected a significantly higher
prevalence of joint pathology compared with clinical find-
ings in 45 patients with SSc. Effusion and/or synovial pro-
liferation were found in 26 of 45 patients, while joint
tenderness and/or swelling only in 15 of 45 (P<0.03).
The same study showed that US indicated a significantly
higher number of joints with osteophytes than X-rays
(59% vs 27%; P<0.005). A pilot study using a 17MHz
US transducer to evaluate hand disability in scleroderma
concluded that A1 pulley thickness, measured by US, cor-
relates with hand mobility and disease duration .
Another study found strict association of tendon friction
rubs with increased thickness of the retinacula, suggest-
ing that this was the morphological basis for this clinical
Three cutaneous phases of the disease are recognized in
SSc: oedematous, fibrotic and atrophic. The capacity to
differentiate between these phases is crucial to tailor the
correct therapeutic strategy for the patient. Usually, skin
involvement is assessed by the modified Rodnan Skin
Score (mRSS). However, an objective and reproducible
technique that can differentiate oedema from fibrosis is
still lacking in clinical practice. Despite excellent spatial
resolution of high-frequency US and good interclass and
FIG. 1 Temporal arteries in longitudinal (A, C) and transverse (B, D) views.
Temporal arteries are normal (A, B) or abnormal, showing a hypoechoic wall swelling (C, D).
Francesco Porta et al.
by guest on January 11, 2016
intraclass agreement in skin evaluation , few reports
are available about its employment in SSc.
In the early phase of the disease, US can depict a
dermal thickening due to oedema, and in the late phase
a reduction in thickness with the evolution of fibrosis and
atrophy. Dermal thickness of the dorsal aspect of the fin-
gers measured by US did not correlate with the local
mRSS, possibly meaning that mRSS is not actually mea-
suring dermal thickness. However, a correlation with the
total mRSS was found, suggesting that skin US can pro-
vide information about disease severity . A significantly
higher dermal thickness was found in SSc patients in
comparison with the controls, in both clinically involved
and uninvolved areas. US showed thicker dermis in
dcSSc patients, compared with lcSSc patients, except
for the proximal phalanx, confirming the high sensitivity
of skin US with respect to clinical evaluation [20, 21].
Another important parameter is dermal echogenicity.
Longitudinal studies reported thickened and hypoechoic
dermis in the early oedematous phase. Evolution towards
the fibrotic and atrophic phases was associated with a
progressive reduction in thickness and increased echo-
genicity. Nevertheless, not all the authors were able to
recognize an association between different echogenicity
and oedema or fibrosis .
Recently, US elastography has been used to evaluate
the skin of the forearm of SSc patients. Less elastic
dermis was found in SSc patients compared with controls,
in both involved and uninvolved areas. This confirmed the
very high sensitivity of US elastography, which made it a
very promising tool for the future use .
US is a non-invasive, low cost, rapid and repeatable
method. It provides a very precise assessment of organ
involvement in SSc and vasculitides. Despite significant
improvement of US machines, some needs are still
unmet, such as the differentiation between oedema and
fibrosis in skin and lung, the evaluation of coronary
arteries and the evaluation of myocardial oedema.
Further data are needed to evaluate the prognostic
power of US findings.
Rheumatology key messages
. US plays a crucial role in assessment of organ in-
volvement in SSc and vasculitides.
. Further studies are needed to define the role of US
in decisions about therapy and prognosis of SSc
Supplement: This paper forms part of the supplement
‘Ultrasound in rheumatology: the future is now’. This sup-
plement was supported by an unrestricted educational
grant by the Fundacio ´n Espan ˜ola de Reumatologı ´a.
Disclosure: The authors have declared no conflicts of
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