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Amyopathic Dermatomyositis
A Review by the Italian Group of Immunodermatology
Marzia Caproni, MD;
Carla Cardinali, MD;
Aurora Parodi, MD;
Barbara Giomi, MD;
Manuela Papini, MD;
Mario Vaccaro, MD;
Angelo Marzano, MD;
Clara De Simone, MD;
Marcello Fazio, MD;
Alfredo Rebora, MD;
Paolo Fabbri, MD
Arch Dermatol. 2002;138:23-27.
ABSTRACT
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Objective To analyze the average age, sex distribution, duration of follow-up,
clinical course, serologic abnormalities, and incidence of possibly associated
malignancy in patients with amyopathic dermatomyositis.
Design Retrospective study.
Setting University hospitals.
Patients Thirteen patients with amyopathic dermatomyositis.
Results The 13 patients represented 8.2% of 157 patients with dermatomyositis
seen retrospectively in a 10-year period by the Italian Group of Immunodermatology
of the Italian Society of Dermatology and Venereology. Gottron papules and
sign and periungual telangiectasias were found in approximately 50% of cases
(papules in 7 patients, Gottron sign and periungual telangiectasias in 6),
while periorbital violaceous erythema was seen in 70% (9 patients). Arthralgias
occurred in 2 patients and Raynaud phenomenon in 4. An elevated erythrocyte
sedimentation rate was detected in 6 patients, hepatitis B virus antigen in
3, speckled antinuclear antibodies in 7, and anti-Ro and antimitochondrial
antibodies in 1 case each. None of our patients had evidence of internal malignancy.
Neither cardiopulmonary nor esophageal dysfunction was demonstrated. Electromyography
showed a protopathic muscle abnormality in 3 patients. Muscle biopsy disclosed
myositis and a neurogenic myopathy in another one.
Conclusions Amyopathic dermatomyositis is a rare disease. So far, only 2 series
of a few cases each have been reported. The "amyopathic" subset of dermatomyositis
is peculiar in that its cutaneous lesions are predominant for long periods
or even permanently, although they are indistinguishable from those of classic
dermatomyositis. The minimal or absent muscle disease and the rarity of serum
immunologic findings imply a favorable prognosis in white patients.
INTRODUCTION
THE TERM amyopathic dermatomyositis (ADM) (or
dermatomyositis sine myositis) refers to patients who, after 2 years of biopsy-confirmed
classic cutaneous manifestations of dermatomyositis (DM), have "minimal" muscle
disease1 (after complete evaluation with electromyography
[EMG], muscle biopsy, and magnetic resonance imaging) or no evidence of inflammatory
myopathy.2-3
Amyopathic dermatomyositis is a rare disease. Only 2 series of a few
cases each have been reported so far. Rarity, however, may be only apparent
depending in part on the lack of qualitative differences in the clinical features
and immunohistopathologic findings between the cutaneous manifestations of
ADM and those of classic DM.4 Other reasons
are the diagnostic difficulty in patients in whom concurrent treatment with
drugs, such as hydroxyurea, alfuzosin hydrochloride, and phenytoin, may induce
DM-like reactions,4 and the racial differences
in the published reports. In fact, 1 of the 2 series comprised only Chinese
patients and the other a mixed population of blacks and whites.
To determine whether the conclusions of the 2 mentioned series could
also apply to Mediterranean patients, the Italian Group of Immunodermatology
of the Italian Society of Dermatology and Venereology reviewed retrospectively
the cases of ADM observed during the last 10 years.
PATIENTS AND METHODS
Thirteen patients (12 women and 1 man; mean age, 53 years; range, 19-86
years) from the centers (Florence, Genoa, Messina, Milan, Rome, and Terni)
of the Italian Group of Immunodermatology were reviewed. They belonged to
a series of 157 consecutive patients with DM (8.2%). A questionnaire with
clinical, laboratory, and immunologic items was sent to the study centers.
The recruited records were then examined. The diagnosis of DM was accepted
when patients proved to fulfill Bohan and Peter's clinicopathologic criteria5 and satisfied the exclusion and Sontheimer's additional
criteria.4
Eleven patients had had their skin disease for at least 2 years (confirmed
ADM),4 while 2 had it for longer than 6 months
but shorter than 24 months (provisional ADM).4
In the juvenile case, the disease had begun at age 13 years; no familial cases
were included. All patients had the characteristic histopathologic changes
of DM, with basal keratinocyte liquefaction degeneration and lymphohistiocytic
inflammation of papillary dermis. Patients were observed during a mean follow-up
of 6.8 years.
Laboratory tests included erythrocyte sedimentation rate, serum muscle
enzyme levels (creatine kinase, lactate dehydrogenase, aspartate aminotransferase,
and aldolase), antinuclear antibodies, anti–double-strand DNA, anti-extractable
nuclear antigens, and antimitochondria, anti–smooth muscle, and antithyroid
antibodies. Serologic tests for hepatitis B and C virus were also performed.
Electromyography was performed on deltoids and quadriceps in 8 of 13
patients. Muscle biopsy specimens were obtained from 2 cases. Complaints of
Raynaud phenomenon and arthralgias were also recorded. Pulmonary investigations
(x-ray films, carbon monoxide diffusion capacity) and esophageal motility
studies were performed in all patients.
Search for neoplasia included clinical examination, standard biological
tests, and chest x-ray films. Specific investigations were also performed
only if indicated by direct abnormal symptoms.
RESULTS
Gottron papules (Figure 1)
and sign (Figure 2) were found in
7 (54%) and 6 (46%) of our patients, respectively. Among the characteristic
skin lesions, periorbital violaceous erythema (Figure 3 and Figure 4) was seen in 9 patients (69%) and periungual telangiectasias (Figure 1) in 6 patients (46%). Poikiloderma was observed in only
1 case. Two patients complained of photosensitivity, while in 3 the cutaneous
lesions were accompanied by severe pruritus. Arthralgias occurred in 2 patients
(15%) and Raynaud phenomenon in 4 (31%).
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Figure 1. Gottron papules prominent over
joints on the dorsal aspects of the fingers and periungual nailfold telangiectasia.
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Figure 2. Gottron sign: symmetric violaceous
erythema overlying the dorsal aspect of the hands.
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Figure 3. Facial erythema with periorbital
edema. Periorbital changes represent heliotrope eruption.
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Figure 4. Facial erythema with periorbital
edema. Periorbital changes represent heliotrope eruption.
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An elevated erythrocyte sedimentation rate was detected in 6 patients
(46%). Hepatitis B virus antigen was present in 3 patients (23%). Speckled
antinuclear antibodies were found in 7 patients (54%) with a titer ranging
between 1:80 and 1:640. Anti-Ro and antimitochondrial antibodies were found
in 1 case each. Antithyroid and anti–smooth muscle antibodies were detected
in another one.
None of our patients had evidence of internal malignancy. Neither cardiopulmonary
nor esophageal dysfunction was demonstrated.
The EMG showed no signs of muscle involvement in 5 of the 8 cases in
which it was performed, while a protopathic muscle abnormality was demonstrated
in 3 patients. Muscle biopsy showed myositis in 1 patient who was not in the
positive EMG group, while in another case a neurogenic myopathy was demonstrated.
Thus, 4 patients of 10 investigated with EMG and muscle biopsy showed minimal,
subclinical muscle involvement without subjective and laboratory (normal serum
levels of muscle enzymes) evidence of muscle weakness.
COMMENT
Only 8% of our 157 patients with DM had ADM. This prevalence is lower
than reported elsewhere (10%-20%).6 Recently,
an even higher incidence of ADM (25%) has been reported in a Chinese study.7 Apparently, ADM is less common in the Mediterranean
area.
Most cases have been reported in middle-aged adults. Until now, juvenile
patients have been described only in case reports8
and small case series,1, 9 but,
in a recent study,10 27 juvenile-onset cases
of ADM have been analyzed. Elderly patients have also been described, including
an 84-year-old man presenting with blisters on the neck and oral ulcers in
association with the typical skin manifestations of DM.11
We observed an 86-year-old woman.
Most patients with ADM are said to be women9, 12-14;
only the Chinese series showed a prevalence of men.7
In our series, the female predominance was almost absolute (92%) (Table 1). The characteristic heliotrope
erythema was slightly more frequent than the pathognomonic Gottron papules
(69% vs 54%). Although the difference was not statistically significant, we
support Callen's opinion12 that heliotrope
erythema is a pathognomonic lesion.
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Epidemiologic Characteristics, Clinical Features, and Laboratory Results
in ADM Series*
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Periungual alterations affected only 46% of our patients. In a previous
study,9 periungual nailfold telangiectasias
were present in the 3 cases studied. In contrast, all 6 patients described
by Euwer and Sontheimer1 presented with Gottron
papules, periungual erythema telangiectasias, and violaceous discoloration
of the face, neck, and upper part of the chest, or had had them at some time
during the course of the disease. Also, in the study by Rockerbie et al,15 Gottron papules and heliotrope erythema were the
most frequent lesions (80%). On the contrary, in the patients with associated
malignancies in the Chinese series,16 the most
common cutaneous lesions (83%) were erythematous, violaceous macules or papules
on the face, limbs, and trunk (Table 1).
All patients described by Euwer and Sontheimer1
had moderate to severe pruritus and complained of photosensitivity. These
symptoms have been reported more rarely elsewhere and were uncommon in our
series, with 2 patients complaining of photosensitivity and 3 of severe pruritus.
Arthralgias and Raynaud phenomenon (15% and 31% of our cases, respectively)
have not been previously reported, except by Euwer and Sontheimer1 (1 patient with arthralgias).
As for the laboratory findings, positive antinuclear antibodies were
found in half of our patients, in agreement with previous data.1
In other series,14, 17 however,
they were positive in almost all patients. The speckled pattern was prevalent
in all of the studies, with lower titers only in Stonecipher and coworkers'
series.17 We confirmed the speckled pattern
of other reports and elevated titers as well.14, 16
No correlation was demonstrated between the presence of Raynaud phenomenon
and positive antinuclear antibodies, but only a fortuitous association was
made in 2 cases.
Anti–double-strand DNA autoantibodies were absent (as in other
ADM reports1, 7, 9, 17),
and anti-extractable nuclear antigen autoantibodies were found in only 1 case.
In addition, another patient had positive antithyroid and anti–smooth
muscle autoantibodies. In fact, we had also found antithyroid antibodies in
2 of the 3 patients with ADM studied previously.9
Although other authors have encountered several diagnostic autoantibodies
(anti–Jo-1, anti–Mi-2, anti-PML, and anti-Ku) in classic DM,18 we failed to do so.
First Braverman19 and Bohan et al20 suggested the possible association with malignancy
in patients with ADM, and later Stonecipher et al17
recommended examining patients with ADM, like those with classic DM. In fact,
in the Chinese series,7 60% of patients had
malignancy. None of our patients had such evidence, in agreement with other
Western series.1, 21 In the Chinese
series, nasopharyngeal carcinoma was the most common malignant disease. Chinese
findings may be coincidental given the small number of their ADM cases and
the fact that nasopharyngeal carcinoma is frequent in Southeast Asia.8 Other cases of ADM have been reported in association
with breast cancer,13, 22 transformed
malignant lymphoma,23 and papillary serous
ovarian cancer.14 We agree with other authors4 that the risk of malignancy should be considered low
in white patients.
Some patients with ADM have subclinical evidence of muscle inflammation
if investigated thoroughly with EMG, muscle biopsy, or noninvasive procedures
that can assess muscle anatomy and physiology, such as ultrasound and magnetic
resonance imaging.7 Four of 10 of our patients
who fulfilled the diagnostic criteria for ADM underwent some of those investigations,
demonstrating minimal, subclinical muscle involvement without subjective and
laboratory (normal serum levels of muscle enzymes) evidence of muscle weakness.
These findings reveal the necessity of proper classification of these
patients, and, in this regard, the use of noninvasive tests might be helpful
because a complete and reliable evaluation of muscle involvement is not possible
on the basis of only EMG and muscle biopsy. In fact, EMG is a sensitive but
not specific procedure,24 while muscle biopsy
may give confusing results because of sampling error.7
In the absence of these important noninvasive procedures, as in our study,
we treated the patients conservatively without using immunosuppressive drugs.
In conclusion, the amyopathic subset of DM is unusual in that its cutaneous
lesions are predominant for long periods or even permanently, although they
are indistinguishable from those of classic DM. The minimal or absent muscle
disease and the rarity of serum immunologic findings all imply a favorable
prognosis in the white population.
AUTHOR INFORMATION
Accepted for publication May 24, 2001.
Corresponding author and reprints: Marzia Caproni, MD, Clinica Dermosifilopatica,
Università degli Studi di Firenze, Via degli Alfani 37, 50121-Firenze,
Italy.
From the Dipartimento di Scienze Dermatologiche, Clinica Dermatologica
II, Università degli Studi di Firenze, Florence (Drs Caproni, Cardinali,
Giomi, and Fabbri); Sezione di Dermatologia, Università di Genova,
Dipartimento di Scienze Endocrinologiche e Metaboliche (DISEM), Genoa (Drs
Parodi and Rebora); Dipartimento delle Specialità Medico-Chirurgiche,
Sezione di Dermatologia di Terni, Università di Perugia, Perugia (Dr
Papini); Istituto di Dermatologia, Università degli Studi di Messina,
Messina (Dr Vaccaro); Istituto di Scienze Dermatologiche, Istituto di Ricovero
e Cura a carattere Scientifico (IRCCS) Ospedale Maggiore, Università
degli Studi di Milano, Milan (Dr Marzano); Istituto di Dermatologia, Università
Cattolica del Sacro Cuore, Rome (Dr De Simone); and Istituto Dermopatico dell'Immacolata—IRCCS,
Rome (Dr Fazio), Italy.
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