Transcript Inflammatory disease of muscle

Inflammatory disease of muscle
三軍總醫院風濕免疫過敏科
陳相成 醫師
Hsiang-Cheng Chen, MD, PhD, FACR
臨床病人 hints（為什麼想到這
個病）

對稱性近端肌肉無力：廁所無法站起 爬
樓梯困難 拿吹風機吹頭髮無法長久
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皮膚疹
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抽血肌肉指數偏高 (GOT, GPT, CK,
LDH)
V sign rash
Introduction (PM and DM):
Dermatomyositis (DM) and polymyositis (PM) are
conditions of presumed autoimmune etiology in which
the skeletal muscle is damaged by a nonsuppurative
inflammatory process dominated by lymphocytic
infiltration.
PM and DM are the most common forms of ‘idiopathic
inflammatory myopathy’, the latter distinguished by the
presence of a characteristic rash.
 Overlap syndromes with other autoimmune rheumatic
diseases occur in 15-20% of cases.
 One-tenth with a malignancy.
Etiology
The precise cause of these diseases is unknown, but
interplay between host genetic factors, viral infection of
muscle, and autoimmune mechanisms is probably
contributory.
Familial occurrence of these diseases, and the increased
frequency of HLA-DR3 and -DRw52 antigens in patients,
suggest an underlying genetic and immunologic predisposition.
The presence of serum antibodies to several cytoplasmic
ribonucleoproteins involved in translation [especially histidyl
tRNA synthetase or Jo-1 and signal recognition particle
(SRP)] may result from an immune response to an altered
virus that serves as an immunogen in polymyositis. These
antibodies probably represent a cross-reactive phenomenon.
Epidemiology
 PM has an estimated incidence of 2-8 per million
 Incidence increases with age and is highest between the
ages of 40-65 years
 Peak age of onset is bimodal in distribution: one peak at
10-15 years of age, and the other at 45-55 years
 The female to male ratio is 2:1, but is lower in myositits
associated with malignancy, and higher during the childbearing
year (5:1)
In the US, African-Americans are affected more commonly
than whites at a ratio of 3-4:1
MAC in vessel
Double immunofluorescent
staining: anti-CD8 (green)
Polymyositis:intermyofibril infiltration
Classification
------------------------------------------------------------------------------------------Group I: Primary idiopathic polymyositis
Group II: Primary idiopathic Dermatomyositis
Group III:DM(or PM) associated with neoplasia
Group IV:Child DM(or PM) associated with vasculitis
Group V:PM(or DM) associated with collagen vascular disease
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Modification of Bohan and Peter’s Classification 1975
1.Primary idiopathic polymyositis
2.Primary idiopathic dermatomyositis
3.1 or 2 above, with maliganancy
4.Juvenile poly (dermato)myositis
5.Overlap syndromes with other autoimmune rheumatic diseases
6.Inclusion-body myositis
7.Rare myositis:
granulomatous
eosinophilic
focal
orbital
8. Drug-induced
Focal Inflammation
Clinical manifestation
(1)Group I: Primary Idiopathic Polymyositis
 This group comprises about one-third of all cases of
inflammatory myopathy. It is usually insidiously progressive over
weeks, months, or even years. Affected females outnumber
males 2:1.
 Patients first become aware of weakness of the proximal limb
muscles, especially the hips and thighs, and find difficulty in
arising from the squatting or kneeling position and in climbing or
descending stairs. When shoulder girdle muscles are involved,
placing an object on a high shelf or combing the hair becomes
difficult.
 Aching pain in the buttocks, thighs, and calves is experienced
in about 10 percent of the cases, and tenderness on palpation in
another 20 percent. In the majority of patients the disorder is
painless. Early symptoms of dysphagia and weakness of
flexor muscles of the neck in a patient with a chronic myopathy
suggest the diagnosis of polymyositis.
Ocular muscles are almost never affected except in a rare
association with myasthenia gravis. The distal muscles are
spared in about 75 percent of cases.
Muscle atrophy, contractures, and diminished tendon reflexes
are rare in early myositis and never as pronounced as in
muscular dystrophies and denervating conditions.
When the reflexes are disproportionately reduced, carcinoma
with polymyositis and polyneuropathy should be considered.
At presentation about 25 percent of patients have dysphagia,
about 5 percent have significant respiratory impairment, and 5
percent are unable to walk. Dysphagia is due to involvement of
striated muscles of the pharynx and upper esophagus.
At some time in the course of the disease, cardiac
abnormalities are observed in about 30 percent of cases; these
include electrocardiogram (ECG) changes, arrhythmias, and
heart failure secondary to myocarditis. About half of the fatal
cases have pathologic evidence of cardiac disease with necrosis
of myocardial fibers, usually with only modest inflammatory
reaction.
In a few cases there is dyspnea due to lymphocytic pneumonitis,
obliterating bronchiolitis, pulmonary edema, or pulmonary fibrosis.
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Group II: Primary Idiopathic Dermatomyositis
This group comprises just over one-third of all cases of myositis.
The skin changes may precede or follow the muscle syndrome
and include a localized or diffuse erythema, maculopapular
eruption, scaling eczematoid dermatitis, or, rarely, an exfoliative
dermatitis.
The classic lilac-colored (heliotrope) rash is on the eyelids,
bridge of the nose, cheeks (butterfly distribution), forehead, chest,
elbows, knees and knuckles, and around the nail beds. The skin
lesions may occasionally ulcerate. Subcutaneous calcification
may occur, especially in children.
 Nailfold abnormalities: periungual erythema, dilated capillary
loops.
Heliotrope rash
Gottron’s sign
Subcutaneous calcification: seen nearly exclusively
in the juvenile form of DM
Mechanic’s hand: characterized by cracking and
fissuring of the skin of the finger pads
Group III: Polymyositis or Dermatomyositis With
Neoplasia
Malignancy, is uncommon in myositis seen in children and in
association with a connective tissue disorder. The malignancy
may antedate or postdate the onset of the myositis by up to 2
years.
The incidence of neoplasia is higher in patients over the age of
40 and is particularly high in patients over age 60. The most
common malignancies are lung, ovary, breast,
gastrointestinal tract, and lymphoproliferative disorders.
The myositis is a paraneoplastic syndrome, the cause of which
may lie in an altered immune status, cross-reactive antigens
between tumor and muscle, or an occult viral infection of the
muscle.
Group IV: Childhood Polymyositis And Dermatomyositis
Associated With Vasculitis
This group comprises about 8 to 20 percent of all cases of
myositis in various series. Inflammatory myopathy in childhood is
frequently associated with skin involvement and clinical or
histologic evidence of vasculitis in skin, muscles, gastrointestinal
tract, and other organs.
Degeneration and loss of capillaries in a perifascicular
distribution occur in the skeletal muscles; often necrotizing lesions
of the skin, and ischemic infarction of kidneys, gastrointestinal tract,
and rarely brain may be seen.
Subcutaneous calcification is frequently present in childhood
dermatomyositis.
Group V: Polymyositis Or Dermatomyositis
With An Associated Connective Tissue
Disorder
This "overlap group" of myositis comprises
about one-fifth of all cases that occur in
association with several connective tissue
diseases. Progressive systemic sclerosis,
rheumatoid arthritis, mixed connective tissue
disease (the rheumatologic overlap disorder),
and lupus erythematosus are the most
common associated conditions; polyarteritis
nodosa and rheumatic fever are more rarely
associated.
Demonstration of increased serum
creatine kinase (CK), electromyography
(EMG), and muscle biopsy are often
required to make this diagnosis. Though
patients in this overlap group usually respond
to glucocorticoid therapy, the prognosis for
recovery of function is poorer than in pure
dermatomyositis-polymyositis.
Dysphagia in group V patients with
progressive systemic sclerosis is often due to
involvement of the smooth muscle of the
distal third of the esophagus.
LABORATORY FINDINGS
(1) Elevated serum levels of the enzymes present in skeletal
muscle, such as CK, aldolase, serum glutamic
oxaloacetic transaminase, lactic acid dehydrogenase,
and serum glutamic pyruvate transaminase.
(2) The ESR is elevated in about two-thirds of cases. Tests for
circulating rheumatoid factor are positive in less than onehalf and for antinuclear antibodies in about three-quarters
of the cases.
(3) Anti-Jo-1 antibodies are more common in polymyositis,
especially in patients with interstitial lung disease, and
anti-nRNP antibodies are often associated with
polymyositis seen in lupus erythematosus.
(4) Myoglobin can be found in the urine when muscle
destruction is acute and extensive; rarely, acute
polymyositis causes the full syndrome of rhabdomyolysis
and myoglobinuria.
(5) In about 40 percent of cases EMG reveals a markedly
increased insertional activity (muscle irritability), together with
the typical myopathic triad of motor unit action potentials, which
are of low amplitude, are polyphasic, and have an abnormally
early recruitment. (spontaneous, high frequency discharge)
(6) Muscles recently used for EMG or intramuscular injection
must be avoided as these procedures can produce inflammatory
changes and muscle fiber damage, leading to false-positive
results.
Skeletal Muscle Pathology The principal changes in muscle
consist of infiltrates of inflammatory cells (lymphocytes,
macrophages, plasma cells, and rare eosinophils and neutrophils)
and destruction of muscle fibers with a phagocytic reaction.
* Blood vessel changes and perifascicular atrophy are more
prominent in childhood dermatomyositis than in adult
dermatomyositis and polymyositis.
DIAGNOSIS
(1) characteristic skin rash
(2) muscle weakness
(3) EMG changes
(4) elevation of serum CK
* It may be particularly difficult to obtain a diagnostic
muscle biopsy because of the patchy nature of the
disease. Thus, a therapeutic trial of
glucocorticoids should be given when full
investigation of a patient with significant disability
leaves a diagnosis of "possible polymyositis,"
usually because of a nondiagnostic muscle biopsy.
Criteria for the diagnosis of PM/DM
 Compatible weakness. Symmetrical proximal muscle
weakness developing over weeks or months
 Elevated serum muscle enzymes, CK, and aldolase
 Typical electromyographic findings (EMG changes)
: myopathic potentials (low amplitude, short duration,
polyphasic) fibrillation, positive sharp waves, increased
insertional activity, complex repetitive discharges
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Typical muscle biopsy findings
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Dermatological features of DM: Gottron’s papules,
involving fingers, elbows, knees, and medical malleoli;
Heliotrope sign around eyes; Erythematous and/or
poliodermatous rash
DIFFERENTIAL DIAGNOSIS (Optional)
*Subacute Or Chronic Progressive Muscle Weakness
-spinal muscular atrophies, amyotrophic lateral sclerosis, upper
motor neuron disease, myotonic dystrophy, metabolic
myopathy, glycogen storage disease, endocrine myopathy,etc.
*Muscle Weakness With Marked Exercise-Induced Fatigue
-Fatigue without much muscle wasting may be due to
neuromuscular junction disorders including myasthenia gravis
or the Lambert-Eaton syndrome. Repetitive nerve stimulation
and single-fiber EMG studies aid in the diagnosis of these
conditions.
*Acute Muscle Weakness
-Guillain-Barre syndrome, glycogen storage diseases, Acute
viral infections, prolonged severe hypokalemia .
*Pain On Movement And Muscle Tenderness
- polymyalgia rheumatica, Fibrositis and fibromyalgia ,etc.
Eosinophilic Fasciitis This disorder is characterized by
painful swelling and thickening of the skin in the extremities,
limitation of movement due to contractures, and mild muscle
weakness. Raised sedimentation rate, peripheral eosinophilia,
hypergammaglobulinemia, and mildly elevated CK are seen.
The EMG may show myopathic features. Histologically there is
marked thickening and infiltration of the deep fascia with
mononuclear cells and eosinophils, some involvement of the
epimysium and perimysium, and variable muscle degeneration.
Most patients respond to treatment with glucocorticoids.
Relapsing Eosinophilic Perimyositis This disease is
characterized by recurrent painful and tender areas in the neck
or lower extremities, but without muscle weakness. An
elevated sedimentation rate and peripheral eosinophilia are
frequent, and histologically there is eosinophilic infiltration of
the perimysium. Response to glucocorticoids is usually good.
Treatment
Pathophysiology
Other Disorders Associated With Myositis
Sarcoidosis And Polymyositis The skeletal muscle contains
noncaseating granulomas with Langhans-type multinuclear giant
cells in at least one-quarter of patients with sarcoidosis.
Symptomatic polymyositis is, however, uncommon.
Giant cell or granulomatous polymyositis and myocarditis,
sometimes associated with myasthenia gravis, have been
recorded in patients with thymomas.
Focal Nodular Myositis A syndrome of acutely developing
and painful focal inflammatory nodules, sometimes occurring
sequentially in different muscles, has been termed focal nodular
myositis.
Infectious Polymyositis Rare cases of polymyositis have
been found to result from infection with known pathogens such
as toxoplasma , viruses, and spirochetes (Lyme disease).
Antibody screening will suggest the diagnosis in such cases.
Trichinosis may be confused with idiopathic polymyositis,
particularly if the history of raw or undercooked pork ingestion is
not obtained. The symptoms of trichinosis are variable and
depend upon the parasitic load. Low-grade fever, muscle pain
of variable degree, conjunctival and periorbital edema, and
fatigue are frequent. The diagnosis is made by the history of
ingestion of undercooked pork, marked eosinophilia, a positive
skin test to Trichina antigen, and the appearance of serum
antibodies to Trichina during the course of the disease.
Pyomyositis, a suppurative inflammation of muscle due to
staphylococci or streptococci, is mainly seen in the tropics but
has recently been reported in patients with AIDS.
Myopathy In Infection Caused By Human Immunodeficiency
Virus (HIV) Polymyositis occurs in AIDS . It may be the
presenting manifestation of the disorder or be due to therapy
with zidovudine (AZT), which inhibits DNA polymerase gamma
and presumably mitochondrial DNA replication.
Raised serum CK, EMG evidence of myopathy, and muscle
fiber necrosis with or without inflammatory infiltrates occur in
AIDS myopathy. Rhabdomyolysis can occur in HIV-infected
patients, possibly related to the use of drugs,or, in late cases, as
part of opportunistic infection in muscle (such as
Staphylococcus aureus), toxemia, or severe electrolyte
disturbances.
AZT myopathy is dose related and usually improves after
discontinuation of the drug or reduction of the dose. Structural
and functional mitochondrial abnormalities are usually
associated with AZT myopathy.
Inclusion Body Myositis The clinical features of this
typically sporadic, but rarely familial, disorder are similar to
those of chronic idiopathic polymyositis, except that onset is at
an older age, focal and distal muscle involvement are more
frequent, and disease duration is longer.
Muscle biopsy shows interstitial and occasional perivascular
inflammatory infiltrates, necrosis, and regeneration of muscle
fibers, but in addition there are "rimmed vacuoles" in the fibers
that stain positively with Congo-red, like amyloid.
This disorder usually responds poorly to glucocorticoids and
immunosuppressive therapy; however, some patients may
improve following treatment with intravenous immunoglobulin.
Prognosis is for a chronically progressive disorder with loss of
ambulation about 5 to 10 years after presentation.
Eosinophilic Myositis This rare disease probably represents
one manifestation of the spectrum of hypereosinophilic
syndrome. There are a number of subtypes. Subacute onset of
muscle pain and proximal weakness, elevated serum CK,
myopathic features on EMG, and histologic appearance of a
myositis with an eosinophilic inflammatory infiltrate are
characteristic.
Eosinophilia-Myalgia Syndrome A syndrome that is more
common in women has been associated with ingestion of the
essential amino acid L-tryptophan. Fever, rash, arthralgia,
cough, dyspnea, and edema are commonly accompanied by
eosinophilia (more than 1000 cells per microliter), peripheral
neuropathy, and myositis with endomysial, perimysial, and
fascial infiltration of lymphocytes and eosinophils.
.
Polymyositis
Chronic dermatomyositis:perifascicular atrophy
Polymyositis with heart involvement
Dermatomyositis
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