Curr Rheumatol Rep (2014) 16:465
DOI 10.1007/s11926-014-0465-0
INFLAMMATORY MUSCLE DISEASE (RG COOPER, SECTION EDITOR)
Amyopathic Dermatomyositis:
Definitions, Diagnosis, and Management
Elizabeth E. Bailey & David F. Fiorentino
# Springer Science+Business Media New York 2014
Abstract Amyopathic dermatomyositis can be a chal-
lenging diagnosis because patients lack traditional mus-
cle findings. “Clinically amyopathic” dermatomyositis
(CADM) accounts for the presence of subclinical mus-
cle disease in some of these patients. These patients
represent a substantial minority of dermatomyositis
cases and have similar co-morbidities to “classic” der-
matomyositis patients, including interstitial lung disease
and malignancy. Clinically amyopathic dermatomyositis
patients should not be considered as a distinct clinical
entity from “classic” dermatomyositis, as they share
antibody sub-types and associated co-morbidities, likely
representing clinical spectrum of a common disease. It
is essential for the clinician to be familiar with the
clinical presentation of clinically amyopathic dermato-
myositis, in order to facilitate early, accurate diagnosis
and appropriate clinical management.
Keywords Dermatomyositis . Clinically amyopathic .
Hypomyopathic . Premyopathic
Introduction
Amyopathic dermatomyositis provides a diagnostic chal-
lenge for both dermatologists and rheumatologists be-
cause of the lack of traditional hallmark muscle findings
in these patients. The Bohan and Peter classification
criteria for dermatomyositis include muscle findings as
This article is part of the Topical Collection on Inflammatory Muscle Disease
E. E. Bailey : D. F. Fiorentino (*)
Department of Dermatology, Stanford University School of
Medicine, 450 Broadway Drive, Redwood City 94063, CA, USA
e-mail: fiorski@stanford.edu
an essential element, which is a logical outcome when
formulating criteria for diseases that have inflammatory
myositis in common. However, it is now clear that a
substantial minority of dermatomyositis patients demon-
strate no or at least subclinical muscle disease—this is
the group of so-called clinically amyopathic patients.
Data from several dermatomyositis cohorts suggest that
up to 20 % of patients with hallmark dermatomyositis
skin findings are clinically amyopathic [1]. It is essen-
tial for clinicians managing dermatomyositis patients to
recognize this patient subset so that they may be appro-
priately screened for internal manifestations of
dermatomyositis.
Dermatomyositis was first clinically classified by Bohan
and Peter in 1975 (Table 1) [2]. Classification of a patient
having either polymyositis or dermatomyositis requires ful-
fillment of up to four criteria for definite disease, three criteria
for probable disease, and two criteria for possible disease. In
addition, classification of a patient with dermatomyositis re-
quires skin involvement (heliotrope rash, dermatitis over dor-
sal hands, knee, elbow, and medial malleoli, photo-distributed
involvement) in addition to muscle symptoms which include
symmetric limb girdle and anterior neck flexor weakness,
suggestive muscle biopsy results, elevation of muscle en-
zymes, and electromyogram (EMG) with characteristic find-
ings. Based on these clinical criteria, patients without muscle
disease would not be included under the dermatomyositis
classification.
The term “amyopathic dermatomyositis” was first coined
by Pearson in the 1960s to distinguish patients with hallmark
cutaneous findings of dermatomyositis who do not manifest
clinical evidence of myositis. This definition was later refined
to include true “amyopathic dermatomyositis” patients who
have no clinical or laboratory evidence of muscle disease, as
well as “hypomyopathic dermatomyositis” patients who had
no clinical evidence of muscle disease, but do show evidence
465, Page 2 of 7
Table 1 Bohan and peter criteria of dermatomyositis [2]
Skin criteria:
Heliotrope rash and/or scaly, erythematous dermatitis over dorsum
of hands, knees, elbows, medial malleoli, as well as face, neck,
and upper torso
Muscle criteria:
1. Symmetric weakness of limb-girdle muscles and anterior neck
flexors
2. Elevated serum muscle enzymes
3. Characteristic electromyographic abnormalities
4. Muscle biopsy findings typical of PM or DM
Definite DM requires four criteria (including rash) and definite PM
requires four criteria (without rash). Probable disease requires three
criteria (including rash) for DM and three criteria (without rash) for
PM. Possible disease require two criteria (including rash) for DM and
two criteria (without rash) for PM.
based on magnetic resonance imaging (MRI), EMG, or mus-
cle biopsy [3]. Collectively, these patients were all included
under the umbrella term “clinically amyopathic dermatomyo-
sitis” (CADM). “Premyopathic dermatomyositis” (PRMDM)
has subsequently been used to describe those patients who
have hallmark skin findings and no muscle weakness for less
than six months [4]. A subset of patients with CADM who
subsequently evolve into “classic” DM with clinically signif-
icant muscle disease more than 6 months after initial presen-
tation has also been described [4].
Data suggest that cutaneous and histopathologic findings in
amyopathic dermatomyositis patients are no different from
those found in “classic” dermatomyositis patients, and that
the same systemic disease associations are present in both
groups including an association with malignancy and
lung disease [4, 5, 6]. In this article, we will review
the known clinical features and current diagnostic and
management issues for patients with “clinically
amyopathic dermatomyositis” (CADM).
Disease Definitions
Several different definitions for amyopathic dermatomyositis
have been proposed, some of which have attempted to differ-
entiate between patients with absolute absence of any evi-
dence of muscle disease (clinical, laboratory, imaging and
histologic), those who have evidence of subclinical myositis,
and patients without myositis that may experience onset mus-
cle disease in the future [7]. Many of these definitions are not
clinically useful, however, in that they either require extensive
workup for myositis that may not be clinically indicated, or
can only be made retrospectively. In addition, there is overlap
between these clinical groups, lack of uniform distinction
between these groups in clinical studies, and no real evidence
that these distinctions are based in pathophysiology or
Curr Rheumatol Rep (2014) 16:465
differences in clinical outcome. Thus, as proposed by
Sontheimer, our discussion will pertain specifically to “clini-
cally amyopathic dermatomyositis” (CADM) patients—that
is, those who do not show clinical evidence of muscle disease
on physical examination or muscle enzyme analysis for at
least 6 months [7]. These patients, on further evaluation such
as MRI imaging or muscle biopsy, may indeed have evidence
of subclinical myositis but would still be included in this
group. As mentioned above, these patients all share charac-
teristic cutaneous findings. These skin findings, which have
been categorized previously by Sontheimer et al. include
Gottron’s papules (violaceous erythematous papules over in-
terphalangeal joints) and Gottron’s sign (symmetric macular
violaceous erythema over interphalangeal joints, olecranon
processes, patellas, medial malleoli), both of which have been
proposed to be “pathognomonic”. “Characteristic” skin find-
ings include heliotrope rash (periorbital violaceous erythema),
periungual telangiectasias and dystrophic cuticles, macular
violaceous erythema over dorsal hands, forearms, arms, shoul-
ders, neck, V area of neck and chest, and forehead. “Compat-
ible” findings include poikiloderma atrophicans vasculare,
subepidermal bullous lesions and superficial erosions, and
calcinosis cutis [3, 8]. Using these observations, Sontheimer
has proposed “hallmark” cutaneous manifestations of derma-
tomyositis, which include heliotrope rash, Gottron’s papules,
and Gottron’s sign as possible major criteria, and the addition-
al skin criteria listed initially, as well as pruritus and mechan-
ic’s hands, as minor criteria (Table 2) [3]. Interestingly, al-
though these criteria have not been formally validated, they
are often cited in studies as inclusion criteria for CADM
patients.
Epidemiology
The fact that CADM patients exist is now a widely accepted
phenomenon. Several case series and retrospective reviews of
dermatomyositis cohorts have described patients with cutane-
ous manifestations of dermatomyositis without clinical evi-
dence of muscle disease. The first case series of patients with
amyopathic dermatomyositis (that were not destined to even-
tually develop muscle disease) was reported in 1991 by Euwer
and Sontheimer [7]. They presented six patients with classic
cutaneous findings with no clinical or laboratory evidence of
muscle disease for at least 2 years after skin disease onset,
which comprised 11 % of the total dermatomyositis seen
during a 15-year period in Dallas, Texas [7]. Inclusion criteria
were presence of what they described as pathognomonic
cutaneous signs of dermatomyositis (with all except one pa-
tient exhibiting Gottron’s papules and one additional patient
who had violaceous erythema of the knuckles without discrete
papules and presence of a periorbital heliotrope rash), skin
biopsy consistent with dermatomyositis, and no clinical
Curr Rheumatol Rep (2014) 16:465
Table 2 Sontheimer’s proposed hallmark cutaneous manifestations of
dermatomyositis [3]
Major cutaneous criteria
Heliotrope rash
Macular violaceous erythema with or without associated scale
of the eyelids or periorbital skin. Secondary or associated
cutaneous findings, such as scale, pigmentary change,
telangiectasia, or edema also can be present.
Gottron’s papules
Violaceous papules or small plaques overlying the dorsal and
dorsal-lateral aspects of interphalangeal or metacarpophalangeal
joints. When fully formed, these papules become slightly
depressed at the center, which can assume a white, lacy
appearance. Associated scale-hyperkeratosis, pigmentary
change, or telangiectasia may be present
Gottron’s sign
Macular violaceous erythema with or without associated
scale-hyperkeratosis, pigmentary change, or telangiectasia
involving extensor aspects of the knuckles, elbows, knees,
or medial malleoli
Minor cutaneous criteria
Macular violaceous erythema (with or without associated
scale-hyperkeratosis, pigmentary change, or telangiectasia)
involving:
Scalp or anterior hairline
Malar eminences of face, or forehead, or chin
V-area of neck or upper chest (open collar area; V-sign)
Nape of the neck or posterior aspects of shoulders (shawl sign)
Extensor surfaces of the arms or forearms
Linear streaking overlying extensor tendons on the dorsal
aspects of the hands
Periungual areas
Lateral surface of the thighs or hips (holster sign)
Medial malleoli
(involvement of each above anatomic region qualifies as a
single minor criterion)
Periungual nailfold telangiectasia or cuticular hemorrhage-infarct
with or without dystrophic cuticles
Poikiloderma (concurrence of hyperpigmentation,
hypopigmentation, telangiectasia, and superficial atrophy)
Mechanic’s hand lesions
Cutaneous calcinosis
Cutaneous ulcers
Pruritus
The hallmark cutaneous manifestations of DM are presumed to be present
if the following conditions are met: presence of two major criteria or one
major criterion and two minor criteria (biopsy of at least one skin lesion
should show changes consistent with cutaneous DM)
evidence of muscle disease or elevation of muscle enzymes
(creatine kinase (CK) and aldolase) within 2 years of diagno-
sis. None of the patients in that study had an associated
underlying malignancy.
In the retrospective case review by el-Azhary and Pakzad,
746 patients with dermatomyositis seen at Mayo Clinic in
Page 3 of 7, 465
Rochester, Minnesota, were analyzed. The authors defined
amyopathic dermatomyositis patients as having skin eruptions
typical of dermatomyositis (consistent skin biopsy,
poikiloderma, lichenoid dermatitis) but lacking subjective
symptoms of motor weakness and/or objective evidence of
muscle involvement [9]. This group included 37 patients,
representing 5 % of the dermatomyositis cohort. They noted
that almost all of these patients had acral skin involvement.
Cancer developed in five (13.5 %) patients. No patients in the
group developed severe lung disease, although five patients
did have radiographic changes indicative of interstitial
pulmonary fibrosis.
In 2006, a systematic review of CADM patients (divided
into either amyopathic or hypomyopathic groups) described a
total of 291 reported cases from other 19 countries, as well as
10 patients with “premyopathic dermatomyositis” (PRMDM)
[4]. Patients were included based on diagnostic skin biopsy or
hallmark cutaneous manifestations of disease by the authors,
given lack of consensus criteria for CADM. Over half of these
patients had corresponding skin biopsies with
dermatomyositis-associated histopathologic changes includ-
ing vacuolar interface dermatitis and mucin present in the
dermis, but presence of skin biopsy was not required for study
inclusion if characteristic clinical skin findings were present.
Thirty-six CADM cases (13 %) were found to have interstitial
lung disease, as well as all ten patients in the PRMDM group.
Forty-two (14 %) of 301 patients with CADM or PRMDM
had an associated malignancy, most commonly nasopharyn-
geal carcinoma and breast carcinoma.
Cao et al. reported on a series of 16 patients who had
presented to a local hospital in Shanghai, China, between
1998 and 2004 [10]. Patients were included in this study if
they had classic dermatomyositis skin findings, consistent
skin biopsy findings, and had no subjective muscle weakness
and no elevation in muscle enzymes for more than 6 months to
2 years after diagnosis. All these patients had Gottron’s pap-
ules, periungual telangiectasias, and/or erythema. Fifteen of
16 patients had periorbital heliotrope rash, and one patient had
poikiloderma. None of the patients had subjective muscle
symptoms or abnormalities in CK and Lactate dehydrogenase
(LDH) for at least 2 years. Two patients developed muscle
symptoms, at 2 and 3 years after diagnosis. Of the 16 patients,
12 had radiographic changes consistent with interstitial fibro-
sis, and one had rapidly progressive dyspnea and severe
hypoxemia resistant to treatment and died 3 weeks after onset
of respiratory symptoms. Four patients were found to have an
internal malignancy (pancreatic carcinoma, metastatic adeno-
carcinoma with unknown primary, and two with nasopharyn-
geal carcinoma). Two malignancies were diagnosed at the
time of presentation with dermatomyositis, and another two
were discovered after the 2-year follow-up period.
In the only population-based study to look at the preva-
lence of CADM among dermatomyositis patients, a small
465, Page 4 of 7
study out of Olmsted County, Minnesota, found that CADM
patients (without clinical evidence of muscle disease within
6 months of skin disease) represented 20 % of all dermato-
myositis cases (6 cases) among a total of 29 cases [1]. One
CADM patient had developed a malignancy 1.5 years before
developing dermatomyositis, and no patients with CADM
developed lung disease.
These studies provide strong evidence for the existence of a
subset of CADM patients. Importantly, several studies from
different geographic regions suggest that this subset of pa-
tients are at risk for typical dermatomyositis systemic associ-
ations, including malignancy and interstitial lung disease.
These data help reinforce the importance of performing sim-
ilar work-up and screening for clinically amyopathic patients
as for patients with “classic” DM based on the presence of
characteristic skin findings alone.
Myositis in CADM
Certainly, there is no question that many CADM patients do
indeed have subclinical evidence for myositis based on histo-
pathologic or imaging studies. In a study of histopathologic
changes observed in muscle biopsies of patients with derma-
tomyositis, three patients were included with CADM [11].
Although inflammation, perifascicular atrophy, and
microinfarcts were not seen, patchy capillary loss of discrete
microvascular units was observed and C5b9 membranolytic
attack complex deposits were seen in muscle biopsies of all
three CADM patients, which are thought to be signs of early
muscle disease. In a clinical study of five patients with skin
manifestations of dermatomyositis with normal muscle en-
zyme levels and EMG studies, MRI and ultrasound studies
were performed to evaluate for evidence of muscle disease
[12]. Some of these patients showed evidence of muscle
inflammation on MRI or ultrasound, which provides further
evidence that some of these patients may have subclinical
disease within the category of CADM. Another study by
Lam et al. found that among ten patients with CADM, three
showed abnormal muscle hyperintensity on MRI consistent
with muscle inflammation [13]. A functional MRI study
showed that patients with amyopathic dermatomyositis
showed inefficient metabolism in muscles at exercise com-
pared to controls, while classic DM patients showed abnor-
malities in metabolism at rest [14].
In addition to presence of subclinical muscle disease, pa-
tients with CADM can also develop clinical muscle symptoms
later in their disease course, and it is important to continue to
evaluate patients for presence of clinical muscle disease. In the
retrospective study by el-Azhary et al., there was a subset of
patients with no subjective or objective evidence of myopathy
who developed clinical weakness within 5 years of follow-up
(2 of 25 patients) [9]. A study by Cao et al. followed the
Curr Rheumatol Rep (2014) 16:465
natural history of 16 CADM patients with no clinical muscle
symptoms for more than 6 months and up to 2 years after
onset of skin symptoms [10]. Among thetotal of 16 patients
included, the 12 who underwent muscle biopsies did not show
evidence of muscle involvement. MRI was performed in 9 of
the patients, which showed evidence of subclinical muscle
involvement in two-thirds (6 patients). Over clinical follow-
up, 2 patients (12.5 %) subsequently developed clinical mus-
cle weakness with elevated CK levels more than 2 years after
initial presentation. These patients had been treated with sys-
temic immunosuppressive agents throughout their disease
course. Other studies have similarly reported that a small
proportion of patients subsequently develop muscle symp-
toms more than 2 years after presentation [4] While it is
possible that early systemic treatment may limit the subse-
quent development of clinical muscle disease (and patients
with prolonged systemic treatments within 6 months of diag-
nosis are excluded from CADM subsets in some studies for
this reason), patients can develop muscle disease later in their
disease course even while on systemic therapy and require
continued clinical monitoring.
Auto-Antibodies in CADM
With the description of this clinical population, there has been
an effort to determine if there are unique auto-antibodies that
can identify patients with CADM. A study by Sato et al.
described a 140-kd polypeptide which was associated with
clinically amyopathic dermatomyositis in a set of Japanese
patients [15]. CADM in this study was based on patients with
dermatomyositis with no clinical muscle symptoms for more
than 2 years after onset of skin manifestations. Serologic
testing of 298 patients with connective tissue diseases and
16 normal human sera found that 8 of the patients with
dermatomyositis (all with CADM) precipitated a polypeptide
of 140 kd. Thus, this antibody was termed anti-CADM-140,
the target which was eventually identified as Melanoma Dif-
ferentiation Associated-protein 5 (MDA5) [16]. A subsequent
study demonstrated that 65 % (20 of 31 participants) with
CADM tested positive for anti-MDA5 antibody [17]. Koga
et al. investigated the utility of anti-CADM-140/ anti-MDA5
antibody, and found that, among 79 patients with dermatomy-
ositis, including 21 patients with CADM, 17 patients were
positive for anti-MDA5 antibody [18]. Of these 17 patients,
14 patients had clinically amyopathic disease. Thus, anti-
MDA5 antibodies were not 100 % sensitive for identifying
CADM patients, nor were they specific, as many patients with
anti-MDA5 antibodies have clinical myositis [18].
Other studies have shown that CADM patients can also be
found in other autoantibody subgroups. One study described
10 % (3 of 31) CADM patients had antibodies against Tran-
scriptional Intermediary Factor 1-gamma (TIF1-gamma) [17].
Curr Rheumatol Rep (2014) 16:465
Another study by Hamaguchi et al. found that several anti-
aminoacyl-tRNA synthetase antibodies were detected in pa-
tients with CADM [19]. These included anti-Jo-1 (CADM
patients represented 8 % of cases), anti-EJ (18 %), anti-PL-7
(7 %), anti-PL-12 (28 %), and anti-KS (8 %). These data
provide further evidence that CADM may not represent a
unique and homogeneous disease entity, but is more likely
part of the range of clinical presentation across the spectrum of
dermatomyositis subgroups.
Lung Disease in CADM
Ample evidence suggests that patients with clinically
amyopathic dermatomyositis are susceptible, in some cases
more than classic DM patients, to the development of interstitial
lung disease (ILD). Cottin et al. performed a retrospective
review of patients with dermatomyositis, amyopathic dermato-
myositis (without “clinical evidence of muscle disease” but with
elevated muscle enzymes), and polymyositis who developed
interstitial lung disease (as defined by computed tomography
scan) [20]. Three of the 17 cases included were categorized as
amyopathic dermatomyositis. One of these patients presented
with pulmonary symptoms at the time of presentation for skin
disease, the other two were found to have pulmonary symptoms
within 3–5 months of presentation.
Kang et al. performed a retrospective review of 72 patients
with polymyositis and dermatomyositis who developed inter-
stitial lung disease, including 6 with amyopathic dermatomy-
ositis [21]. These patients with amyopathic dermatomyositis
had a typical DM rash (with either Gottron’s papules or
Gottron’s sign), without muscle weakness or elevation in
CK level. Patients were defined as having ILD if they had
compatible high-resolution computed tomography findings
(nodular, reticulonodular, linear, or ground-glass opacities;
consolidations; irregular interface; honeycombing; or traction
bronchiectasis). ILD developed in 29 patients, including 5
with amyopathic dermatomyositis. Eleven patients died dur-
ing follow-up (mean follow-up 5.9 years). Eight died from
progression of ILD, one from respiratory muscle failure, and
two from non-pulmonary malignancy. Three of these patients
had CADM features, and features of ADM were significantly
associated with shortened mean survival time of ILD.
A Japanese study investigating clinical differences between
patients with ILD related to CADM and classic DM found that
CADM was associated with a higher mortality rate from ILD
than classic DM [22]. Among 11 patients with CADM-related
ILD and 16 patients with classic DM-related ILD, patients with
CADM had a shorter mean duration of symptoms prior to
hospital admission (mean of 4.6 vs. 34.1 months) were more
likely to have acute-type disease defined as the development of
skin and pulmonary symptoms within 2 months of hospital
admission (64 % with CADM vs. 19 % with classic DM), and
Page 5 of 7, 465
had a higher mortality rate. Five of 11 patients (45 %) with
CADM ILD died; all of whom presented with acute-type ILD
with rapid progression and death within 1–2 months of presen-
tation. Only one patient died among the patients with classic
DM-related ILD, with respiratory failure 4 years after presenta-
tion. Another Japanese study examining disease-specific death
from dermatomyositis found that, among patients with CADM,
5 of 21 died from CADM-associated ILD and two died from
malignancies [23]. A study in China by Ye et al. also showed
that patients with CADM were more likely to have rapidly
progressive ILD, with an associated poorer prognosis [24]. They
performed a retrospective review of all patients with dermato-
myositis, polymyositis, or clinically amyopathic dermatomyosi-
tis seen at Shanghai Hospital from 1998 to 2005. Among
CADM patients with ILD, 12 of 21 patients with CADM-ILD
(57 %) died secondary to progressive respiratory failure. Patients
with DM-ILD or PM-ILD had a more chronic course, with
median survival time of 90 and 128 months respectively. Similar
to classic DM, there is clearly a subset of CADM patients with
early and rapid ILD which can lead to early mortality from the
disease, providing strong evidence of the importance of early
lung screening in these patients.
Malignancy in CADM
In addition to the association with ILD, amyopathic DM
patients appear to be at higher risk for internal malignancy,
although exactly how this cancer risk compares to that for
classic DM patients is currently unclear. Chen et al. performed
a case–control study investigating predictors of malignancy in
patients with dermatomyositis and polymyositis among a
patient cohort in Taiwan [25]. This study included patients
with CADM defined as typical cutaneous manifestations of
DM without clinical and/or laboratory findings of muscle
involvement for at least 6 months after onset of rash. The
study excluded patients with pre-existing malignancy. Of 143
patients, 20 (14 %) were found to have amyopathic dermato-
myositis. Of these, none were found to have an associated
malignancy. A study by Azuma et al. reported a subset of
patients with CADM in a Japanese cohort who were subse-
quently found to have an associated malignancy [26]. In a
cohort of 15 patients with CADM, three patients (20 %) had
an associated malignancy (two lung cancers, one thymic
cancer). A study by Fung et al. reported that five of the six
patients seen at their center in Hong Kong over an 8-year
period with CADM developed or presented with an associated
malignancy [27]. Malignancies included nasopharyngeal car-
cinoma (3), unknown primary (1), and non-small cell lung
carcinoma (1). Based on this evidence, it appears prudent to
perform similar malignancy screening in CADM patients as is
performed with classic DM patients, given there is evidence of
associated malignancy in some CADM patients.
465, Page 6 of 7
Conclusions
Mounting evidence shows that CADM patients are clearly
part of the spectrum of dermatomyositis. It is unlikely that
CADM is a distinct pathophysiologic subset within dermato-
myositis, as these patients present with similar clinical skin
findings as classic DM. In addition, these patients do not
appear to be characterized by a specific autoantibody, but
instead can possess many of the classic DM-specific autoan-
tibodies. Finally, these patients are at increased risk of ILD and
internal malignancy, similar to the dermatomyositis patients
with overt muscle disease. Similar to the latter group of
patients, the presentation and prognosis of CADM patients
is likely more associated with the particular autoantibody they
possess, rather than the fact that they are clinically
amyopathic. For example, it is likely that the high rate of
ILD-related mortality of CADM patients in Asia is due to
the fact that a high proportion CADM patients there have
antibodies to MDA5, which is likely the feature that has true
association with rapidly progressive ILD [28].
The inclusion of patients without clinical evidence of mus-
cle disease within the dermatomyositis classification is critical
for improved clinical care and disease understanding. The
validation of cutaneous diagnostic criteria for dermatomyosi-
tis will be critical in helping to aid in diagnosis and uniform
classification of this subgroup. Without these, accuracy of
classification will continue to be elusive based on skin exam-
ination alone, and it is clear that currently amyopathic derma-
tomyositis is often misdiagnosed as systemic lupus erythema-
tosus or undifferentiated connective tissue disease [5]. Accu-
rate diagnosis is of utmost importance to the clinician if we are
to appropriately screen our patients for the development of
eventual muscle disease, ILD, or internal malignancy. In
addition, recognition of this subset is critical if they are to be
included in both molecular studies and clinical trials.
Compliance with Ethics Guidelines
Conflict of Interest Elizabeth E. Bailey and David F. Fiorentino
declare that they have no conflicts of interest.
Human and Animal Rights and Informed Consent This article does
not contain any studies with human or animal subjects performed by any
of the authors.
References
1. Bendewald MJ, Wetter DA, Li X, Davis MD. Incidence of dermato-
myositis and clinically amyopathic dermatomyositis: a population-
based study in Olmsted County, Minnesota. Arch Dermatol.
2010;146:26–30.
2. Bohan A, Peter JB. Polymyositis and dermatomyositis. N Engl J
Med. 1975;292(344–347):403–7.
Curr Rheumatol Rep (2014) 16:465
3. Sontheimer RD. Dermatomyositis: an overview of recent progress
with emphasis on dermatologic aspects. Dermatol Clin. 2002;20:
387–408.
4. Gerami P, Schope JM, McDonald L, Walling HW, Sontheimer RD. A
systematic review of adult-onset clinically amyopathic dermatomyo-
sitis (dermatomyositis sine myositis): a missing link within the spec-
trum of the idiopathic inflammatory myopathies. J Am Acad
Dermatol. 2006;54:597–613.
5. Ghazi E, Sontheimer RD, Werth VP. The importance of including
amyopathic dermatomyositis in the idiopathic inflammatory myositis
spectrum. Clin Exp Rheumatol. 2013;31:128–34.
6. Sontheimer RD. Would a new name hasten the acceptance of
amyopathic dermatomyositis (dermatomyositis sine myositis) as a dis-
tinctive subset within the idiopathic inflammatory dermatomyopathies
spectrum of clinical illness? J Am Acad Dermatol. 2002;46:626–36.
7. Euwer RL, Sontheimer RD. Amyopathic dermatomyositis (dermato-
myositis sine myositis): presentation of six new cases and review of
the literature. J Am Acad Dermatol. 1991;24:959–66.
8. Euwer RL, Sontheimer RD. Dermatologic aspects of myositis. Curr
Opin Rheumatol. 1994;6:583–9.
9. El-Azhary RA, Pakzad SY. Amyopathic dermatomyositis: retrospec-
tive review of 37 cases. J Am Acad Dermatol. 2002;46:560–5.
10. Cao H, Parikh TN, Zheng J. Amyopathic dermatomyositis or
dermatomyositis-like skin disease: retrospective review of 16 cases
with amyopathic dermatomyositis. Clin Rheumatol. 2009;28:979–
84.
11. Gitiaux C, Kostallari E, Lafuste P, et al. Whole microvascular unit
deletions in dermatomyositis. Ann Rheum Dis. 2013;72:445–52.
12. Stonecipher MR, Jorizzo JL, Monu J, Walker F, Sutej PG.
Dermatomyositis with normal muscle enzyme concentrations: a
single-blind study of the diagnostic value of magnetic resonance
imaging and ultrasound. Arch Dermatol. 1994;130:1294–9.
13. Lam WWM, Chan H, Chan YL, et al. MR imaging in amyopathic
dermatomyositis. Acta Radiol. 1999;40:69.
14. Park JH, Olsen NJ, King L, et al. Use of magnetic resonance imaging
and P-31 magnetic resonance spectroscopy to detect and quantify
muscle dysfunction in the amyopathic and myopathic variants of
dermatomyositis. Arthritis Rheum. 1995;38:68–77.
15. Sato S, Hirakata M, Kuwana M, et al. Autoantibodies to a 140-kd
polypeptide, CADM-140, in Japanese patients with clinically
amyopathic dermatomyositis. Arthritis Rheum. 2005;52:1571–6.
16. Nakashima R, Imura Y, Kobayashi S, et al. The RIG-I-like
receptor IFIH1/MDA5 is a dermatomyositis-specific autoantigen
identified by the anti-CADM-140 antibody. Rheumatology.
2010;49:433–40.
17. Hoshino K, Muro Y, Sugiura K, et al. Anti-MDA5 and anti-TIF1-
gamma antibodies have clinical significance for patients with derma-
tomyositis. Rheumatology. 2010;49:1726–33.
18. Koga T, Fujikawa K, Horai Y, et al. The diagnostic utility of anti-
melanoma differentiation-associated gene 5 antibody testing for
predicting the prognosis of Japanese patients with DM.
Rheumatology. 2012;51:1278–84.
19. Hamaguchi Y, Fujimoto M, Matsushita T, et al. Common and distinct
clinical features in adult patients with anti-aminoacyl-tRNA synthe-
tase antibodies: heterogeneity within the syndrome. PLoS ONE.
2013;8:e60442.
20. Cottin V, Thivolet-Bejui F, Reynaud-Gaubert M, et al. Interstitial
lung disease in amyopathic dermatomyositis, dermatomyositis, and
polymyositis. Eur Respir J. 2003;22:245–50.
21. Kang EH, Lee EB, Shin KC, Im CH, Chung DH, Han SK, et al.
Interstitial lung disease in patients with polymyositis, dermatomyo-
sitis, and amyopathic dermatomyositis. Rheumatology. 2005;44:
1282–6.
22. Mukae H, Ishimoto H, Sakamoto N, et al. Clinical differences between
interstitial lung disease associated with clinically amyopathic dermato-
myositis and classic dermatomyositis. Chest. 2009;136:1341–7.
Curr Rheumatol Rep (2014) 16:465
23. Yamasaki Y, Yamada H, Ohkubo M, et al. Longterm survival
and associated risk factors in patients with adult-onset idio-
pathic inflammatory myopathies and amyopathic dermatomyo-
sitis: experience in a single institute in Japan. J Rheumatol.
2011;38:1636–43.
24. Ye S, Chen X, Lu X, et al. Adult clinically amyopathic
dermatomyositis with rapid progressive interstitial lung dis-
ease: a retrospective cohort study. Clin Rheumatol. 2007;26:
1647–54.
25. Chen YJ, Wu CY, Shen JL. Predicting factors of malignancy in
dermatomyositis and polymyositis: a case-control study. Br J
Dermatol. 2001;144:825–31.
Page 7 of 7, 465
26. Azuma K, Hidehiro Y, Ohkubo M, et al. Incidence and predictive
factors for malignancies in 136 Japanese patients with dermatomyo-
sitis, polymyositis, and clinically amyopathic dermatomyositis. Mod
Rheumatol. 2011;21:178–83.
27. Fung WKJ, Chan HLH, Lam WMW. Amyopathic dermatomyositis
in Hong Kong – association with nasopharyngeal carcinoma. Int J
Dermatol. 1998;37:659–63.
28. Chen Z, Cao M, Plana MN, et al. Utility of anti-melanoma differen-
tiation-associated gene 5 antibody measurement in identifying pa-
tients with dermatomyositis and a high risk for developing rapidly
progressive interstitial lung disease: a review of the literature and a
meta-analysis. Arthritis Care Res. 2013;65:1316–24.