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Recently,
dermoscopy has begun to be used for the observation of nailfold capillaries in
connective tissue disease (CTD). However, dermoscopic features of other skin lesions
and the utility of such information remains unclear. In this review, we
summarize the typical dermoscopic findings of nailfold capillaries in CTD and
discuss their significance. We compared the findings between dermoscopy and
video capillaroscopy, and propose that dermoscopy could serve as a substitute
to some extent for video capillaroscopy. The utility of dermoscopy for othe
skin lesions of CTD remains unknown. However, dermoscopy findings may help to
differentiate discoid lupus erythematosus from other skin disorders in patients
with systemic lupus erythematosus. Interestingly, telangiectasia found in the
skin other than nailfold resembles the nailfold capillary changes in patients
with systemic sclerosis. Gottron’s sign accompanied with punctate hemorrhage
may reflect the existence of rapidly progressive interstitial pneumonia. We
propose that daily use of dermoscopy could improve the clinical care of CTD
patients, since it enables the recognition of vascular structures and other
subtle features that are less visible to the naked eye. We hope that this
review will promote increased use of dermosopy for clinical practice in
patients with CTD, and believe that further investigation will yield additional
valuable information in the near future.
INTRODUCTION
Connective tissue disease (CTD) causes various skin lesions that are
composed of vascular tissue and inflammation. Dermoscopy has been widely used
in differentiating malignant skin disorders. However, dermoscopy may be useful
for evaluating nonpigmented skin disorders, since it provides an improved view
of vascular structures and other subtle features that are usually not visible
to the naked eye (1-4).
Much work has been done to show that nailfold video capillaroscopy(NVC)
can distinguish the Raynaud’s phenomenon associated with scleroderma spectrum
disorder (SSD; systemic sclerosis (SSc) and its related diseases) from primary
Raynaud’s phenomenon (Raynaud’s disease) (5-8). Distinct NVC patterns are also
be useful in evaluating the severity and stage of SSD microvascular damage.
Furthermore, NVC changes are as prevalent and as prominent in dermatomyositis
(DM) as in SSD (9, 10). However, such findings are not found in patients with
other connective tissue diseases. Routine
use of NVC at the bedside has yet to become fully integrated into standard
clinical practice, since the equipment is relatively expensive and not easily
transported. Recently, it has been suggested that dermoscopy can replace NVC, to
some extent, for detection of representative nailfold capillary abnormalities
(11-15). However, dermoscopic finding
and its significance of nailfold capillaries have not been summarized yet.
Furthermore, there are few studies regarding the use of dermoscopy for
other skin lesions of CTD and an overview of them is missing. In this review,
we show some representative dermoscopic findings and pictures of skin lesions
in CTD.,
Usage of dermoscopy for
nailfold capillaries
NVC observation
Given a patient with Raynaud’s phenomenon and no other symptoms, it is
first important to determine whether the patient has “Raynaud’s disease” or
“Secondary Raynaud’s phenomenon associated with CTD”. Raynaud’s phenomenon is
most frequently found in patients with SSD, and is usually the first symptom of
the disease. Therefore, the existence of SSD or other CTD must be determined.
Blood examination for antinuclear antibodies, including CTD-specific
autoantibodies, enable the most accurate diagnosis. However, NVC findings are
also useful for early diagnosis of SSD, especially in patients negative for
CTD-specific autoantibodies. When we use dermoscopy for evaluating CTDs the
established findings of capillaroscopy are definitely useful. Therefore, we
would like to review capillaroscopic findings of CTD before discussing our
findings using dermoscopy.
Scleroderma NVC
pattern
We used a video capillaroscopy system (Kekkan bijin, Kenkou Kagaku
Kenkyu-kai, Co., Ltd, Kyoto, Japan). Diagnostic capillaroscopy patterns are
grouped as follows: normal pattern, scleroderma pattern, and nonspecific
pattern(12). The normal pattern in Figure 1A. shows homogeneous capillary
distribution in the nailfold plexus without capillary loss (normal linear
density: 30 capillaries per 5 mm) and no morphological alterations. The scleroderma
pattern in Figures 1B-D is defined according to Maricq et al. (16, 17), with
modifications according to Bergman et al. (13).Two or more of the following
abnormalities are observed:①enlarged capillaries (Figures 1B
and C);②hemorrhages (more than two
punctuate hemorrhages per finger or confluent hemorrhage areas)(Figure 1C);③disorganization of the normal capillary distribution (Figure 1B-D);④moderate or extensive capillary loss (avascular areas)(Figure 1 D), and
⑤tortuous, crossed, and/or ramified capillaries (Figure 1D). The
nonspecific pattern lacks the complete scleroderma pattern criteria.
Subclassification of
scleroderma NVC pattern
The NVC scleroderma pattern is subdivided further as previously
reported (18). The subclasses are as follows: (1) Early NVC pattern (Figure
1B): few enlarged/giant capillaries, few capillary hemorrhages, relatively
well-preserved capillary distribution, and no evident loss of capillaries; (2)
Active NVC pattern (Figure 1C): frequent giant capillaries, frequent capillary
hemorrhages, moderate loss of capillaries with some avascular areas, mild
disorganization of the capillary architecture, and absence of ramified
capillaries; and (3) Late NVC pattern (Figure 1D): irregular capillary
enlargement, few or absent giant capillaries, absence of hemorrhages, severe
loss of capillaries with large avascular areas, severe disorganization of the
normal capillary array, and frequent ramified/bushy capillaries. We have
summarized the typical findings from each scleroderma pattern in Figure 1E
(19). This subclassification has been useful for evaluation of activity and
severity of vascular injury. In severe SSc cases with anti-topoisomerase I Ab
present, the NVC pattern progresses quickly to the characteristic Late pattern,
within two years of disease onset. On the other hand, mild SSc patients who
have anticentromere Ab, gradually progress to the late pattern, more than 20
years after disease onset (20). NVC findings can be improved after treatment of
SSc (21)(22).
NVC
pattern in other CTD
NVC
patterns are also found at high frequency in patients with DM and are generally
similar to the patterns found in SSD patients [9], although the frequency of
Raynaud’s phenomenon is much lower. NVC patterns are referred to as a
“scleroderma-like pattern” if thepattern is found in DM or disorders other than
SSD. Although subtle capillary abnormality such as mild disorganization can be
detected in patients with systemic lupus erythematosus (SLE), a typical
scleroderma-like pattern is rarely found.
Nailfold
capillary findings using dermoscopy
Nailfold
capillaries may also be observed using dermoscopy. Although we use several
types of dermoscopy, the picutres in this review were taken using dermoscopic
camera lens with adaptor (Heine Optotechnik, Herrsching, Germany). We usually choose the third or fourth finger
for examination. In a healthy person, we can see homogeneously-lined capillary
distribution around the nailfold without hemorrhage (Figure 2A). Most specific
NVC findings can also be detected by dermoscopy [11-15]. Our dermoscopic
observations of nailfold capillariesare as follows:
1) Disorganization of the capillary architecture
Disorganization
of capillary loops can be found in patients with CTD including SSD (Figure
2B~2D), DM (Figure 2E~G), and SLE (Figure 2H).
2) Enlarged/giant capillaries
Enlarged
capillaries can be found in patients with CTD-associated Raynaud’s phenomenon.
Extremely enlarged capillaries (giant capillaries) are specific for SSD (Figure
2C) and DM (Figure 2F). The enlarged/giant capillaries are considered to be an
abnormal angiogenic response, secondary to peripheral ischemia.
3) Capillary hemorrhages
4) Capillary loss or avascular areas
The existence of moderate to severe loss of
capillaries (avascular areas) is characteristic for SSD (Figure 2D) or DM
(Figure 2G). The severity reflects the peripheral circulatory disturbance of
SSD or DM. SSD patients with severe capillary loss frequently develop
intractable digital
5) Ramified/bushy capillaries
Usage
of Dermoscopy for Skin Lesions of CTD
Dermoscopic findings in inflammatory skin
diseases
Dermoscopic
evaluation for inflammatory skin diseases should include the following: I.
vascular morphology (dot, globule, linear, glomerulus-like); II. vascular
arrangement (regular, clustered, patchy, peripheral, in rings); III. background
color (dull-red, light red, yellowish); IV. scale colour (white, yellow); V.
scale distribution (patchy, peripheral, diffuse, central); VI. presence of
white crossing streaks (Wickham-striae) [1,23].
Systemic lupus erythematosus
Malar rash and discoid lupus erythematosus (DLE)
are specific skin lesions of SLE. However, DLE is sometimes clinically
difficult to distinguish from other skin diseases such as lichen planus,
psoriasis vulgaris, nummular eczema, and cutaneous sarcoidosis.
The dermoscopic findings of DLE are not necessarily
specific to the disease (Figure 3). The background colour is usually light red
or orange, and often accompanies partial/whitish homogeneous lesions and/or
white scales. Variously arranged dilated capillaries with varied morphology are
highly visible. It has been reported that follicular keratin plugs, which
correlate histologically with prominent hyperkeratosis in follicular openings,
are detected only in active lesions (Figure 3B), not in scars or healed skin of
DLE (Figure 3C) [24]. The finding of
keratin plugs may therefore be useful as an estimate of disease activity or
response to treatment in patients with DLE.Malar rash and discoid lupus erythematosus
(DLE) are specific skin lesions of SLE. However, DLE is sometimes clinically
difficult to distinguish from other skin diseases such as lichen planus,
psoriasis vulgaris, nummular eczema, and cutaneous sarcoidosis.
Regarding differential diagnosis of DLE, representative
dermoscopic findings of psoriasis vulgaris are regularly distributed, dotted,
globular, glomerular, or twisted loop-like vessels over a light red background
and white scales (Figure 4A) [3,23,25]. The tortuous and dilated blood vessels
within the elongated dermal papillae in psoriasis are present as regularty
distributed red dots, red globules, glomerule-like vessels, and twisted red
loops [2]. Dermoscopy of lichen planus shows diagnostic white crossing lines
(Wickham striae) and red dotted or globular vessels at the periphery (Figure
4B) [25,26]. In eczematous lesions including nummular eczema, serum exudates
can be seen dermoscopically as shiny yellow clods (Figure 4C) [27]. Cutaneous
sarcoidosis as well as other cutaneous granuloma show dermoscopically
translucent yellow to orange, globular-like or structureless areas associated
with linear vessels (Figure 4D) [28].
Thus, although the dermoscopic findings of DLE are not
entirely specific, dermoscopy can add important clues that help distinguish DLE
from other skin disorders.
Systemic sclerosis
Telangiecatases are frequently detected on face, hand,
mucous membranes, and other sites in patients with SSc. They are vascular
lesions composed of vasodilated post-capillary venules without evidence of
neovascularization or inflammation [29,30]. The mechanism by which
telangiectases develop in SSc patients remains unknown. However, it may be the
result of an aberrant attempt to increase blood perfusion to hypoxic tissues as
a consequence of impaired circulation [31]. A recent study reported that
increased numbers of telangiectases strongly associated with the presence of
pulmonary arterial hypertension in patients with SSc [31]. However, there are
almost no studies that have investigated the findings in detail using
dermoscopy. Morphologically, there are at least two kinds of telangiectases in
SSc.
The first are well-circumscribed dense telangiectases
referred to “matted” lesions [31]. This type is frequently detected in patients
with anticentromere Ab and the telangiectases are composed of enlarged
capillaries (Figure 5A). The second are poorly-marginated light telangiectases
referred to as “stellate” lesions [31]. This type is often found in patients
with anti-topoisomerase I Ab. Here the telangiectases are composed of fine
linear, tortuous, and/or ramified capillaries that are typically arranged in
stellatepatterns (Figure 5B). Interestingly, the dermoscopic findings of
enlarged capillaries are similar to giant capillaries/enlarged capillaries
detected as the scleroderma active-pattern in the nailfold. On the other hand,
the dermoscopic findings of fine capillaries are similar to that of tortuous,
crossed, and/or ramified capillaries found as scleroderma late-pattern in the
nailfold. However, the pathological and clinical significance of telangiectases
remains unestablished, in contrast to nailfold capillary findings.
Dermatomyositis
Dermoscopic findings of Gottron’s sign are not
specific. Irregular arrangement of venules and scales are found on a light red
background (Figure 6A and 6B). However and interestingly, the Gottron’s sign
observed by dermoscopy was impressive in one of our cases where anti- melanoma
differentiation-associated protein 5 (MDA-5) Ab was present [32]. Anti-MDA-5 Ab
is highly associated with the development of rapidly progressive interstitial pneumonia
[32]. Gottron’s sign of her elbows were usual as determined by the naked eye
(Figure 6C). However, dermoscope findings showed punctuate hemorrhage in
addition to the usual Gottron’s sign findings. In fact, she developed rapidly
progressive interstitial pneumonia. The punctuate hemorrhage thoroughly
disappeared after intensive immunosuppressive treatment and stabilization of
interstitial pneumonia. Since it is known that DM patients with anti-MDA-5 Ab exhibit
skin ulcer more frequently than patients without the Ab [33], we suspect the
hemorrhage detected on Gottron’s sign may be reflecting vascular injury
associated with rapidly progressive interstitial pneumonia.
Another
interesting finding was made by dermoscopy of poikilodermaskin lesions in
patients with DM. Enlarged
linear irregular vessels are visible and pigmentation and depigmentation are
mixed (Figure 6D). Although poikiloderma is often detected in pateints with DM,
but it is not specific for DM and usually detected by naked eyes. However, the
confirmation using dermoscopy may be useful to distinguish poikiloderma from
other skin lesions.
CONCLUSION
Our
findings are preliminary and are not based on systematic studies of large
numbers of patients. Nonetheless, we propose that dermoscopic observations are
helpful for diagnosing and evaluating disease activity in some clinical
situations. Improved visualization of vessels and color variations, that are
difficult to recognize with the naked eye, can be observed using dermoscopy. A
more detailed determination of specific dermoscopic features of skin lesions of
CTD may be a valuable resource for clinical assessment. Furthermore, these
findings may provide clues that improve our understanding of the pathogenesis
of skin lesions and of CTD itself. We hope that dermoscopy becomes widely used
for the evaluation of CTD and believe that further investigation will soon
yield information valuable to the clinical practitioner.
ACKNOWLEDGEMENTS
We thank Mr. N Mugii, for preparing pictures of
capillaroscopy.
This work was supported by funds for Research on Intractable
Diseases from the Ministry of Health, Labor and Welfare of
Japan.
CONFLICT
OF INTEREST
The authors have no conflict of interest to declare.
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