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CHaPtEr 56 Inflammatory Muscle Diseases 759

TABLE 56.1 Idiopathic Inflammatory to the aminoacyl-tRNA (transfer RNA) synthetases, of which
Myopathy: Diagnostic Criteria Jo-1 is the best known, have a characteristic syndrome called
antisynthetase syndrome, which usually includes interstitial lung
Bohan and Peter disease, nondeforming inflammatory arthritis, fevers, mechanic’s
Criteria hands, and Raynaud phenomenon, in addition to myositis. Those
1. Symmetrical proximal with antibodies to the signal recognition particle (anti-SRP)
muscle weakness
2. Skeletal muscle have an IMNM manifested by severe disease of abrupt onset,
enzyme elevation often in the autumn. According to some studies, cardiac involve-
3. Abnormal EMG a ment is less common and survival is better in patients with
4. Muscle biopsy anti-SRP than has previously been reported. Those with antibod-
6
abnormalities ies to the nuclear antigen Mi-2 almost always have the V and
5. Typical skin rash shawl rashes and cuticular overgrowth in addition to myositis.
of DM b
A recently discovered antibody, anti-3-hydroxy-3-methylglutaryl-
coenzyme A reductase (anti-HMGCR), is tightly linked to
7,8
IMNM. Interestingly, the HMGCR is the pharmacological target
of statin drugs, such as atorvastatin, and a subset of patients
with anti-HMGCR antibodies develop this antibody in the context
a Polyphasic, short, small motor-unit potentials; fibrillation, positive sharp waves,
increased insertional irritability; bizarre, high-frequency, repetitive discharges. of previous statin exposure, although it is also seen in statin-naïve
b Gottron sign, heliotrope rash. individuals, albeit to a lesser extent. Patients with anti-HMGCR
Possible PM = any two of the first four criteria; possible DM = criterion 5 (rash) + any antibodies present with profound proximal muscle weakness
two criteria. Probable PM = any three of the first four criteria; probable DM = criterion
5 (rash) + any three criteria. Definite PM = all four of the first four criteria; definite and a marked creatine kinase (CK) elevation. Further, compared
DM = criterion 5 (rash) + all four other criteria. with statin-exposed individuals, statin-naïve anti-HMGCR
DM, dermatomyositis; EMG, electromyography; PM, polymyositis.
positive patients tend to be younger, have higher CK levels, and
have a blunted response to immunosuppressive medications
(Table 56.5). 2,8
4
and DM sine dermatitis, as separate categories (Table 56.2). IBM is different from other inflammatory myopathies. Patients
Separate classification criteria systems for IBM have been devised. with IBM rarely improve in strength with immunosuppressive
According to most of the previous IBM criteria, characteristic therapy. They tend to be older, and in contrast to patients with
muscle biopsy changes were necessary for a definite diagnosis PM and DM, who are predominantly women, patients with IBM
of IBM. However, because selective involvement of finger flexors are more commonly men. They have gradual, painless, asym-
and knee extensors is almost exclusive to IBM among other metrical, progressive weakness and focal atrophy that develop
forms of myopathy, the newly proposed ENMC IBM Research over years, and they may complain of frequent falls. Two decades
Diagnostic Criteria 2011 entails a separate category for clinically after onset, they are frequently wheelchair-bound. The forearms
defined IBM (Table 56.3). 5 of these patients exhibit a scalloped appearance, attributed to
It has been useful for some purposes to divide cases into muscle atrophy. Difficulty with swallowing can occur with any
groups: PM, DM, juvenile myositis, myositis associated with inflammatory myopathy and is frequently a major problem in
another connective tissue disease (usually systemic sclerosis, SLE, patients with IBM. The CK and other skeletal muscle–associated
or Sjögren syndrome), cancer-associated myositis (usually cases serum enzymes are normal in about one-quarter of patients
in which the diagnoses are made within 6–12 months of one with IBM and only moderately elevated in the remainder. The
another), IBM, and a miscellaneous group that includes such electromyogram in IBM frequently demonstrates both myogenic
rare entities as eosinophilic myositis (Table 56.4). This classifica- and neurogenic features secondary to the effective denervation
tion has allowed recognition of unique clinical and pathogenetic of some muscle cells by inflammation and necrosis.
features and response to therapy. In the case of cancer-associated Proposed criteria for the diagnosis of IBM rely on both
myositis, a more rational approach to workup based on recogni- pathological and clinical features. In the clinical setting of an
tion of groups at risk is now possible. inflammatory myopathy, the presence of the characteristic inclu-
sions or rimmed vacuoles is diagnostic. Among the inflammatory
KEY CONCEPtS myopathies, IBM is distinguished by substantial numbers of
Characteristic Hallmarks of rimmed cytoplasmic vacuoles with tubulofilamentous material
within myofibers. A variety of proteins have been found by
Inflammatory Myositis immunohistochemistry in the muscle cells in IBM, including
ubiquitin, β-amyloid precursor protein, and the transcription
• The clinical hallmark is proximal limb and neck weakness, rarely
associated with muscle pain. factor nuclear factor (NF)-κB. Many of the proteins accumulating
• The laboratory hallmarks are elevated serum levels of creatine kinase in the IBM muscle are also involved in other neurodegenerative
(CK), aldolase, lactic dehydrogenase, and the transaminases; a char- diseases. For example, aggregation of p62, an autophagy-related
acteristic pattern (“irritable myopathy”) is seen on electromyography protein, has been shown in IBM muscle, in Lewy bodies in
(EMG). Elevated serum levels of autoantibodies are common. Parkinson disease, and in neurofibrillary tangles in Alzheimer
• The pathological hallmarks are focal muscle necrosis, degeneration, disease, suggesting the possibility of a degenerative process in
regeneration, and inflammation.
IBM. More recently, an autoantibody to cytosolic 5′-nucleotidase
1a (c5N1A) was discovered. Although this antibody has a good
Several autoantibodies, called “myositis-specific autoantibod- specificity to distinguish IBM against other forms of autoimmune
9
ies,” are unique to myositis. These have allowed a useful alternative myopathy, it is roughly positive in 60% of IBM patients. In
classification (Table 56.5). For example, patients with antibodies addition, anti-c5N1A can be detected in other connective tissue