NEUROLOGY 2003;61:288–290
Unicorns, dragons, polymyositis, and
other mythological beasts
Anthony A. Amato, MD; and Robert C. Griggs, MD
There are three major types of idiopathic inflamma-
tory myopathy: dermatomyositis (DM), polymyositis
(PM), and inclusion body myositis (IBM).1 In this
issue of Neurology, van der Meulen et al.2 suggest
that what has been labeled as PM is uncommon and
includes a heterogeneous group of disorders. Al-
though there are rare cases of PM, many reported
cases of so-called PM are likely to be another entity:
IBM, myositis associated with a connective tissue
disorder (CTD), dystrophies with inflammation, and
perhaps even DM (see table E-1 on the Neurology
Web site). Also in this issue, Yabe et al.3 report still
another cause for confusion, endomysial inflamma-
tion in autosomal recessive hereditary inclusion body
myopathy (h-IBM), which is caused by mutations in
the gene encoding for UDP-N-acetylglucosamine
2-epimerase/N-acetylmannosamine kinase (GNE).
The muscle biopsy in these patients may resemble
sporadic IBM, leading to misdiagnosis.
PM will be overdiagnosed with Bohan and Peter
criteria for PM and DM.4,5 These criteria do not re-
quire a muscle biopsy for the diagnosis of probable or
possible PM and DM. Furthermore, without immu-
nopathology, the biopsy abnormalities of PM and DM
are nonspecific (except for perifascicular atrophy)
and do not distinguish PM from DM or any myop-
athy with necrosis, including IBM and the muscular
dystrophies. Seventy-six of the 165 patients in the
study by van der Meulen et al.2 (all those classified
as having PM, nonspecified myositis, or possible my-
ositis) would have been classified as having probable
or definite PM by Bohan and Peter criteria. How-
ever, only 4 of 165 patients (4 of 238 if the 73 pa-
tients with IBM initially excluded were included)
were believed to have PM during the follow-up pe-
riod using more up-to-date histopathologic criteria.
Criteria for diagnosis of DM and PM need to con-
Additional material related to this article can be found on the Neurology
Web site. Go to www.neurology.org and scroll down the Table of Con-
tents for the August 12 issue to find the title link for this article.
See also pages 316 and 384
From the Department of Neurology (Dr. Amato), Brigham and Women’s Hospital, Harvard Medical School, Boston, MA; and Department of Neurology (Dr.
Griggs), University of Rochester School of Medicine, Rochester, NY.
Address correspondence and reprint requests to Anthony A. Amato, MD, Department of Neurology, Brigham and Women’s Hospital, 75 Francis Street,
Boston, MA 02115; e-mail: aamato@partners.org
288 Copyright © 2003 by AAN Enterprises, Inc.
Editorial
sider the advances in understanding of the patho-
geneses of the inflammatory myopathies: DM is not
simply PM with a rash, and IBM is not PM with
inclusions.1,6,7 DM is a humorally mediated microan-
giopathy, whereas PM is a human leukocyte antigen
(HLA)-restricted, antigen-specific, cell-mediated im-
mune response directed against muscle fibers.1,6 For
diagnosis of PM, the biopsy must show endomysial
infiltrates composed of CD8⫹ T cells and macro-
phages invading non-necrotic muscle fibers that ex-
press major histocompatibility-I (MHC-I) antigen.
Even this biopsy feature is not diagnostic for PM: it
is also seen in patients with IBM and dystrophies.8
Perivascular and perimysial inflammation is also
nonspecific and can be found in patients with DM,
PM, IBM, and dystrophies, and even occasionally in
muscle biopsies from healthy subjects. Previous ret-
rospective series have suggested that PM is the most
common type of myositis.5 However, there is increas-
ing evidence that the PM of the past includes a long
list of disorders and that “true PM” is rare and the
least common of the major types of inflammatory my-
opathy.6,9 The article by van der Meulen et al.2 ad-
dresses the matter and adds evidence to the growing
skepticism about patients with a diagnosis of PM.
Overlooked dermatomyositis. Patients with
typical DM have skin and muscle involvement. How-
ever, 10 to 25% have the rash but no weakness—
amyopathic DM or DM sine myositis.10 What about
the converse? In the study of van der Meulen et al.,2
6% of patients with DM had perifascicular atrophy
on muscle biopsy but no skin involvement—DM sine
dermatitis. These patients would have PM using Bo-
han and Peter criteria. Perifascicular atrophy is di-
agnostic for DM but is present in a minority of DM
biopsies. Biopsies from patients with DM often dem-
onstrate only perivascular and perimysial inflamma-
tion and necrotic fibers similar to the unspecified
and possible myositis subgroups described by van
der Meulen et al.2 The earliest histologic abnormality
in patients with DM is deposition of immunoglobu-
lin, complement, and membrane attack complex
(MAC) on small blood vessels with immunostaining,
and tubuloreticular inclusions in endothelial walls
on electron microscopy. Had these studies been per-
formed by van der Meulen et al.,2 DM sine dermatitis
might have been identified in some of the patients
with unspecified and possible myositis. Patients in
these two subgroups would have PM by Bohan and
Peter criteria.
Overlooked overlap syndrome with a CTD. In
the study by van der Meulen et al.,2 43 patients had
or subsequently developed an underlying CTD. All
but the four patients with DM would have been diag-
nosed with PM using Bohan and Peter criteria. How-
ever, none of these patients had PM using current
histopathologic criteria.1 Most of the CTDs were as-
sociated with unspecified myositis.
Myositis associated with “myositis-specific
antibodies.” Jo-1 antibodies are said to be seen in
patients with either DM or PM but are more com-
mon in those with PM.11 van der Meulen et al.2 found
20% of their patients had Jo-1 antibodies. None of
these patients had PM. Nine of 42 patients with DM
and 9 of 36 patients with unspecified myositis had
Jo-1 antibodies, suggesting that DM and unspecified
myositis may share a similar pathogenesis. Again,
the nine patients with unspecified myositis and Jo-1
antibodies would have been diagnosed with PM us-
ing Bohan and Peter criteria. Moreover, these anti-
bodies are not myositis-specific; they occur in
patients with interstitial lung disease without
myositis.12
Overlooked IBM. In the study of van der Meulen
et al.,2 five of nine patients originally diagnosed with
PM were reclassified as having IBM. The Bohan and
Peter criteria do not consider the existence of IBM.
The characteristic histopathologic features in pa-
tients with IBM are endomysial inflammatory cells
invading non-necrotic muscle fibers (similar to PM)
and muscle fibers contain rimmed vacuoles and in-
clusions. However, biopsies from patients with IBM
often lack definitive histologic criteria for IBM.7
Thus, many patients with IBM are erroneously diag-
nosed with PM if the clinical pattern of weakness
(e.g., early involvement of the wrist and deep finger
flexors and quadriceps muscles) that is relative spe-
cific for IBM is not appreciated.
Overlooked muscular dystrophy (or other my-
opathy). Occasionally, prominent endomysial in-
flammatory cell infiltrate is evident on biopsies from
patients with muscular dystrophy (e.g., congenital,
facioscapulohumeral, limb-girdle), leading to the
misdiagnosis of PM.8,13-15 On muscle biopsy, deposition
of MAC may be seen on the sarcolemma of scattered
non-necrotic fibers in patients with facioscapulo-
humeral muscular dystrophy (FSHD), limb-girdle mus-
cular dystrophy (LGMD), and dysferlinopathies but not
in those with PM, DM, or IBM.14 We have also seen a
number of patients with proximal myotonic myopathy
misdiagnosed as PM and treated with immunosuppres-
sive agents. Yabe et al.3 demonstrated that inflamma-
tion can be seen in patients with h-IBM caused by
mutations in the GNE gene, which encodes a cytosolic
enzyme important to the synthesis of sialic acid. How-
ever, upregulation of MHC-I antigen, as seen in pa-
tients with PM and IBM, was not examined.
Necrotizing myopathy. Necrotizing myopathy
without major endomysial or perimysial inflamma-
tion was seen in 32 patients (19%) in the study by
van der Meulen et al.,2 and they were diagnosed with
“possible myositis.” Again, these patients would have
been diagnosed with PM using Bohan and Peter crite-
ria. Nevertheless, the pathogenic basis appears distinct
from PM, and in other reported cases, it more closely
resembles humorally mediated microangiopathy.16-19 As
in patients with DM, deposition of MAC on small blood
vessels and depletion of capillaries can be seen. How-
ever, these patients do not have a characteristic rash;
there is no perifascicular atrophy on biopsy; perivascu-
lar inflammation is sparse; and tubuloreticular inclu-
sions in endothelium are not commonly seen with
electron microscopy. So-called pipestem capillaries may
be evident on routine histochemistry and electron mi-
croscopy.16 Necrotizing myopathy should lead to a
search for an underlying CTD (usually scleroderma or
mixed CTD) and cancer.16-19 Muscular dystrophies and
toxic myopathies (e.g., statin myopathies) also need to
be excluded. However, many cases of necrotizing myop-
athy are idiopathic.2,19
Myalgia syndromes. Not infrequently patients
complain of muscle weakness, fatigue, and myalgias
but lack objective weakness and are diagnosed as
having myositis. Such patients often have fibromyal-
gia, chronic fatigue syndrome, or polymyalgia rheu-
matica. Even muscular dystrophies can manifest
with myalgias without weakness. Remarkably, in the
study of van der Meulen et al.,2 1 of 9 patients origi-
nally diagnosed with PM, 11 of 59 with DM, 13 of 65
with unspecified myositis, and 3 of 32 with possible
myositis had no objective weakness on examination.
A diagnosis of myositis is untenable in such patients
who lack weakness and immunopathology and for
those who have not been evaluated for exclusion of
muscle dystrophy with immune staining, Western
blot analysis, and genetic studies.
Reaching a new consensus in diagnosis. We
need prospective studies using up-to-date clinical
and histopathologic criteria for diagnosis of DM, PM,
and IBM to address the true incidence of these myopa-
thies, associated laboratory abnormalities (e.g.,
myositis-specific antibodies), associated medical condi-
tions (e.g., CTD, interstitial lung disease, myocarditis,
August (1 of 2) 2003 NEUROLOGY 61 289
cancer), immunopathology, molecular profiles,20 the re-
sponse to various forms of treatment, and the overall
prognosis.
Acknowledgment
The authors thank Lewis P. Rowland and Marinos Dalakas for
helpful comments on the editorial.
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