CH.
369: POLIOMYOSITIS (PM), DERMATOMYOSITIS
(DM) & INCLUSION BODY MYOSITIS (IBM)
The inflammatory myopathies, classified into 3 groups: a.)
DM, b.) PM, c.) IBM, represent the largest group of
acquired and potentially treatable causes of skeletal muscle
weakness.
Clinical Features
• DM: children> adults, F> M
• IBM: M> F, Caucasian> Blacks, persons >50 y/o
• These disorders present as progressive, symmetric
muscle weakness
• Increasing difficulty with tasks requiring use of proximal
muscles (i.e.climbing steps, combing hair)
• Fine-motor movements that depend on strength of
distal muscles: late in PM and DM; early in IBM
• Falling is common in IBM due to early involvement of
quadriceps muscles with buckling of knees
• Ocular muscles are spared
• Facial muscles: unaffected in PM and DM; mild
weakness in IBM
• All forms: pharyngeal and neck flexor muscles are
involved causing dysphagia or difficulty in holding head
up (head drop)
• Respiratory muscles involved in advanced and rarely
acute cases
• Severe weakness if untreated associated with muscles
wasting
• Sensation: normal
• Tendon reflexes are preserved but may be absent in
severely weakened or atrophied muscles especially in
IBM, where atrophy of distal muscles and quads are
common
• Myalgia and muscle tenderness may occur early in
disease particularly in DM associated with CT
disorders
• Weakness progression: subacutely over
weeks/months, rarely acutely in PM and DM; very
slowly (years) stimulating a late-life muscular
dystrophy or progressive motor neuron disorder in IBM
Specific Features
A. Polymyositis
• Actual onset not easily determined
• Patients delay seeking medical advice
• Mimics many other myopathies and is diagnosis of
exclusion
• Subacute inflammatory myopathy affecting adults,
rarely children, who do not have any of the ff:
o Rash
o Involvement of extrocular and facial
muscles
o Family hx of neuromuscular disease
o History of exposure to myotoxic drugs or
toxins
o Endocrinopathy
o Neurogenic disease
o Muscular dystrophy
o Biochemical muscle disorder (muscle
enzyme deficiency)
o IBM as excluded by muscle biopsy
analysis
• Occurs in association with systemic, autoimmune ,
or connective tissue disease, or with known viral
or bacterial infection
• Drugs (i.e. D-penicillamine, zidovudine (AZT)) may
produce inflammatory myopathy similar to PM
B. Dermatomyositis
• Identified by characteristic rash, accompanying or
preceding muscle weakness
• Rash, which worsens after sun exposure, may
present as:
o Heliotrope Rash: blue-purple
discoloration on upper eyelids with
edema
o Gottron Rash: erythema on knuckles with
raised violaceous scaly eruptions
o V sign: erythematous rash on neck and
anterior chest
o Shawl Sign: rash on back and shoulders
o Flat red rash on face and upper trunk,
knees, elbows, malleoli
• Rash may be pruritic, especially on scalp, chest,
and back
• Dilated capillary loops at the base of the
fingernails
• Mechanic’s hands: irregular, thickened and
distorted cuticles; lateral and palmar areas of
finger are rough and cracked, with irregular “dirt”
horizontal lines
• Muscle strength may appear normal, hence, the
term: dermatomyositis sine myositis
• Usually occurs alone but may overlap with
scleroderma and mixed CT disease
• Fasciitis and thickening of the skin similar to that
seen in chronic cases have occurred in patients
with eosinophilia-myalgia syndrome associated
with ingestion of contaminated L-tryptophan
C. Inclusion Body Myositis
• Most common of the inflammatory myopathies
among 50 years old and above
• Often misdiagnosed as PM and only suspected
later when presumed PM does not respond to
therapy
• Weakness and atrophy of distal muscles,
especially foot extensors and deep finger flexors
(clue to early diagnosis)
• Knees collapse due to early quadriceps weakness
• Weakness in small muscles of the hands leading
to inability to hold objects
• Occasionally, weakness and atrophy may be
asymmetric and selectively involve the quads,
iliopsoas, triceps, biceps and finger flexors,
resembling LMN disease
• Dysphagia may occur leading to choking
• Sensory exam: normal
• Mildly diminished vibratory sensation at the angles
presumable age-related
• Pattern of distal weakness (resemble motor
neuron or peripheral nerve disease) results from
myopathic process affecting distal muscles
• Disease progression is slow
• Most require assistive devices such as cane,
walker
• Familial Inflammatory IBM: familial aggregation of
typical IBM
• Hereditary IBM (h-IBM): heterogenous group of
recessive, less frequently dominant inherited
syndrome; non-inflammatory myopathies
• Subset of h-IBM: spares quadriceps linked to
chromosome 9p1 and results from mutations in
the GNE gene
Associated Clinical Findings
A. Extramuscular Manifestations
- may present to varying degree in PM or DM,
including:
1. Systemic symptoms: fever, malaise, Raynaud’s
phenomenon especially when associated with CT disorder

2. Joint contracture, mostly in DM and especially children
3. Dysphagia and GI symptoms due to involvement of
oropharyngeal striated muscles and upper esophagus
especially in DM and IBM
4. Cardiac disturbances: including AV conduction defects,
tachyarrythmas, dilated cardiomyopathy, and low ejection
fraction. CHF and myocarditis from diseases itself or from
HPN due to use of glucocorticoids
5. Pulmonary dysfunction: due to weakness of thoracic
muscles, interstial lung disease, or drug –induced
pneumonitis that can cause dyspnea, aspiration
pneumonia, nonprod. Cough
6. Subcutaneous calcifications: in DM, extruding on skin
and causing ulcerations and infections
B. Association with Malignancies
• Increased only in patients with DM, not in PM or
IBM
• Most common tumors associated with DM: ovarian
CA, breast CA, melanoma, colon CA and non-
Hodgkin lymphoma
• Tumors are usually uncovered by abnormal
findings in the history and P.E.
• Common annual P.E. (urinalysis, CBC, CXR,
pelvic, breast exam) would suffice
• Nasopharyngeal CA: common in Asians
C. Overlap Syndromes
• Association with CT diseases
• DM can have manifestations of systemic sclerosis
or mixed CT disease (i.e. calcium deposits,
contractures)
• Signs of R.A., SLE, or Sjoregren’s syndrome rare
in DM
• DM + systemic sclerosis: have specific ANA, the
anti-PM/Scl
Pathogenesis
-an autoimmune etiology is indirectly supported by
association with other CT diseases; presence of
autoantibodies, association with MHC; demonstration of T
cell-mediated myotoxicity or complement-mediated
microangiopathy; & response to immunotherapy.
A. Autoantibodies and Immunogenetics
• Antibodies to cytoplasmig antigens are directed
against riboucleoprotiens involved in protein
synthesis (anti-synthetase) or translational
transport (anti-signal-recogntion particles)
• Anti-Jo-1: Ab directed against histidyl-transfer
RNA synthetase with majority of patients having
interstitial lung disease; accounts for 75% of all
anti-synthetases
• May also have Raynaud’s phenomenon,
nonerosive arthritis and MHC molecules DR3 and
DRw52
B. Immunopathologic Mechanisms
• DM
o Humoral immune mechanisms, resulting in
microangiopathy and muscle ischemia
o Endomysial inflammatory infiltrates composed
of B cells located in proximity to CD4 T cells
and macrophages
o Relative absence of lymhocytic invasion of
nonnecrotic muscle fibers
o Complement C5b-9 membranolytic attack
complex activation triggers release of
cytokines and chemokines, induce expression
of VCAM 1 and ICAM1 on endothelial cells,
and facilitates migration of activated lymphoid
cells to the perimysial and endomysial spaces
o Occurrence of endothelial cell necrosis,
decreased endomysial capillaries, ischemia
and muscle-fiber destruction
o Remaining capillaries have dilated lumens
due to ischemia
o Residual perifascicular atrophy reflects
endofascicular hypoperfusion that is
prominent in periphery of muscle fascicles
• PM and IBM
o T cell mediated cytotoxicity
o CD8 t cells with macrophages invade and
destroy healthy muscle fibers that
express class I MHC
o Cytokines secreted induces MHC-I
expression
o CD8/MHC-I complex characteristic of PM
and IBM
o Cytotoxic CD8 T cells contain perforin
and granzyme granules directed towards
muscle fibers inducing myonecrosis
C. Role of Non-immune Factors in IBM
• Presence of vacuoles with B-amyloid deposits
within vacuolated muscle fibers and abnormal
mitochondria with cytochrome oxidase-negative
fibers suggest autoimmune component and
degenerative process
• Amyloid deposits are immunoreactive against
amyloid precursor protein (APP), chymotrypsin,
apolipoprotein E, and phosphorylated tau.
• Mitochodrial abnormalities secondary to aging or
bystander effect of upregulated cytokines
D. Association with Viral Infections and Role of
Retroviruses
• Coxsackieviruses: autoimmune myositis
triggered by molecular mimicry due to structural
homology between histidyl-transfer RNA
synthetase that is target of Jo-1 antibody and
genomic RNA of encephalomyocarditis virus
• Retroviruses: best evidence of viral connection in
PM and IBM; distinguished from toxic myopathy
related to long-term therapy with AZT (inhibits y-
DNA polymerase, an enzyme found in
mitochondrial matrix)
o AZT-induced myopathy: mitochondrial
disorder characterized by “ragged red”
fibers
Differential Dx
• Skin rash w/ proximal or diffuse muscle weakness has
few causes other than DM
• Proximal weakness w/ out rash has many causes other
than PM or IBM
A. Subacute or Chronic Progressive Muscle Weakness
• Denervating muscle conditions
- Spinal musclular atrophies
- Amytrophic Lateral Sclerosis
- Weakness followed by UMN signs
and denervation on EMG
• Muscular Dystrophy
- Rare over 30 y/o
- Develop over years no months
• Difficult to differentiate chronic PM vs rapidly
advancing muscular dystrophy even with
biopsy
- Ex- facioscapulohumeral muscular
dystrophy, dsyferlin myopathy, and
dystrophinopathies all with early
inflammatory cell infiltrate
- Dx- glucocorticoid trial tx and detection of
MHC/CD8 by immunohistochem
 • Metabolic myopathies dx via muscle biopsy:
- glycogen storage disease due to
myophosphorylase or acid maltase
deficiency
- lipid storage myopathy due to
carnitine deficiency
- mitochondrial diseases
• Endocrine myopathy
- hypercorticosteroidism
- hyper/ hypothyroidism
- hyper/ hypoparathyroidism
• Muscle wasting w/ neoplasm due to cachexia,
disuse, rare to paraneoplastic myopathy
• NMJ diseases
- myasthenia gravis
- Lambert Eaton Myasthenic
syndrome
- both with fatiguing weakness, eye
and cranial nerve weakness
- dx- repetitive nerve stimulation and
EMG
B. Acute Muscle Weakness
• Guillain Barre Syndrome, transverse myelitis,
a neurotoxin, or viral infection such as polio or
West nile virus
• Acute weakness + painful muscle cramps,
rhabdomylosis, myoglobinuria
- Metabolic disorders including glycogen
storage disease such as
myophosphorylase deficiency or carnitine
palmityltransferase deficiency
• Acute viral infection
• Parasites, Parasitic polymyositis
- protozoa (toxoplasma, trypanosome)
- cestodes (cysticerci)
- nematodes (trichinae)
- with focal or diffuse inflammatory
myopathy
• Anaerobic suppuroative myositis aka Tropical
polymyositis
- Staph Aureus, Yersinia, and Strep
• Begins in childhood= periodic paralysis
developing into recurrent painless acute
muscle weakness
• Chronic Alcoholics present as:
1. Painlful myopathy with myoglobinuria
2. Painless, acute hypokalemic, reversible
myopathy
3. Asymptomatic Inc serum CK and
myoglobin
- Diff Dx of acute muscle weakness w/
myoglobinuria is severe hypokalemia or
hypophosphatemia (+) hypomagnesia
- Also common in px w/ parenteral
hyperalimentation
C. Macrophagic Myofasciitis
• Inflammation w/ diffuse myalgia, fatigue, mild
muscle weakness
• Biopsy shows connective tissue infiltration with
CD8 and PAS positive macrophages
• Limited to France and to previous sites of vaccine
w/ aluminum containing substrate
D. Drug Induced Myopathies
• Resembles true PM from D-Penicillamine and
procainamide
• DM-like with L-tryptophan
• AZT causes mitochondrial myopathy
• Toxic noninflammatory myopathy is histologically
different from PM, DM, or IBM:
- Cholesterol lowering clofibrate,
lovastatin, simvastatin, provastatin esp
when combined w/ cyclosporine or
gemfibrozil may elicit this reaction
• Rhabdomylosis and myoglobinuria
- associated with Amphotericin B,
aminocaproic acid, fenfluramine, heroin
• Myopathic muscle weakness
- use of amiodarone, chloroquine,
colchicines, carbimazole, emetine,
etretinate, ipecac syrup, chronic laxative
or licorice use causing hypokalemia, and
glucocorticoid or growth hormone
administration
• Pancuronium w/ glucocorticoid cause acute critical
illness myopathy
• Careful drug Hx is necessary
• Immunosuppressive Tx is NOT necessary
E. Pain on Movement and Muscle Tenderness
• Polymyalgia rheumatica and arthritic disorders of
adjacent joints cause inflammatory myopathy
without myositis
• Normal Biopsy or Type II muscle fiber atrophy
• FIbrositis and Fibromyalgia present as:
1. Focal/ diffuse muscle tenderness, fatigue,
aching
2. Signs of collagen vascular disorder like
increased ESR, antinuclear antibody, or
rheumatoid factor
3. Slight but transient increase in serum CK
- Muscle biopsy Normal and prognosis
good
- Respond to NSAIDS but with continued
indolent pain
• Chronic Fatigue Syndrome
- Follow viral infection
- Debilitating fatigue, fever, sore throat,
painful lymphadenopathy, myalgia,
arthralgia, sleep disorder, headache
- No muscle weakness
- Normal biopsy
Diagnosis
• Dx PM, DM, or IBM by examining muscle
enzymes, EMG, and muscle biopsy
• Most sensitive enzyme is CK.
- Increases 50x in active disease
- Levels parallel disease activity
- Can be normal in IBM or DM especially
with Connective tissue disease
- Always elevated in PM
• EMG findings
- Short duration, low amp polyphasic units
on voluntary activation
- Fibrillations, complex repetitive
discharges, positive sharp waves on
increased spontaneous activity
- Mixed (polyphasic with short and long
duration) indicate chronic process or fiber
regeneration often seen in IBM
- Not diagnostic
- Differentiate chronic vs active
- Exclude neurogenic disorders
• MRI not routine but used to guide during biopsy
• Muscle biopsy definitive test for Dx of
inflammatory myopathy
1. PM: Primary inflammation with T cell
infiltrates, within muscle fascicles
(endomysial) surrounding individual healthy
fibers causing necrosis and phagocytosis.
CD8/MHC-I lesion fundamental for dx.
Chronic PM has inc connective tissue and
positive reaction with alkaline phosphatase
2. DM: Endomysial inflammation is perivascular
or interfascicular septae. Intramuscular blood
vessels show endothelial hyperplasia w/
tuboreticular profiles, fibrin thrombi,
obliteration of capillaries. Dx for DM, are
microinfarcts w/ in muscle resulting to
perfascicular atrophy (2 to 10 layers of
 atrophy at the periphery) even without - IVIg with minimal benefit. May be used to
inflammation. halt progression of choking episodes due
3. IBM: Endomysial inflammation with T cell to dysphagia
invading MHC-I nonvacuolated fibers. Or
basophilic granules around slit like vacuole Prognosis
(rimmed) with filamentous inclusion seen on • 5 year survival rate for PM and DM is 95%
EM. Normal fibers replaced with connective • 10 year survival rate is 84%
tissue, hypertrophic fibers, and angulated or • Death from cardiac, pulmo, or other systemic
round fiber. May have eosinophilic grandules, causes
or abnormal mitochondria with ragged red • Worse prognosis in patients with delayed tx,
fibers. severe dysphagia or respi conditions, older px,
and those with associated cancer
Treatment • DM responds better and thus better prognosis
• Goal= improve muscle strength, improve than PM
functioning via ADL, and ameliorate extramuscular • 30% with residual weakness even after tx
manifestations. • Relapse may occur at any time
• CK levels decrease with improved strength.
• IBM worst prognosis
However do not just decrease levels without
- Most require cane, walker, wheelchair
improving muscle strength.
within 5 to 10 years of onset
• Agents for PM and DM: - Older age of onset of IBM, more rapidly
1. Glucocorticoids progressive course
- Oral is initial tx
- Use determined by efficacy and side
effects
- High does 1mg/kg/day initially KAT
- After 3 to 4 weeks taper for 10 RICHARDED
weeks to lowest possible
- ADL better usually by 3rd month
- If no response after 3 months,
discontinue
- DM respond better than PM
- Steroid therapy is long term use
causing increased weakness and
normal or unchanged CK levels

2. Other Immunosuppressive drugs

- 75% require additional tx
- Occurs w/ prednisone associated
complications such as resistance,
adverse side effects, relapse, or
rapidly progressive disease with
respi failure
- Azathioprine is well tolerated with
few side effects. 3mg/kd/day
- Methotrexate has faster onset.
Associated with Jo- 1 anitbody MTX
pneumonitis.
- Cyclophosphamide with significant
toxicity
- Cyclosporine is inconsistent with
mild benefit
- Mycophenolate Mofetil
-
3. Immunomodulation
- Good with refractory DM
- IVIg improve strength and rash
- Short lived benefit (<8 weeks)

• Recommended Empirical Approach

1. Step1- high does prednisone
2. Step2- AZT or MTX
3. IVIg
4. Trial with guarded optimism based on
patient’s age, degree of disability, tolerance,
experience with drug, and general health.
Possible are cyclosporine, chlorambucil,
cyclophosphamide (px w/ insterstitial lung
disease), or mycophenolate.

• Patient with PM who doesn’t respond to any

immunotherapy most likely has IBM.
• Associated with DM, Calcinosis, is difficult to treat.
• IBM generally resisitant to immunosuppressive tx.
- Prednisone with AZT or MTX for a few
months in newly diagnosed pax
- Maintain on low dose, every other day
prednisone or weekly MTX