Download myositis1 - Technion moodle

IIM - Epidemiology
• Rare, estimated annual incidence 5-10/million,
estimated prevalence ~ 60/million.
• PM and DM peak in prevalence in childhood (515yrs) and mid-life (30-50yrs); IBM peaks after
age 50.
• Females are preferentially affected (~2-3:1) in all
forms except in IBM (female:male~1:3).
IIM - Epidemiology
• African-Americans may be at increased risk for
IIM and poorer outcomes compared to
Caucasians.
• All races on all continents are affected.
• Anecdotal clustering of IIM onset in time and
space suggest strong environmental influences.
IIM – Systemic manifestations
• General manifestations:fatigue, fever, weight
loss.
• Musculoskeletal: myalgia, muscle tenderness and
weakness. Arthralgia, arthritis, contractures.
• Dermatologic:Photosensitive rashes and edema.
Vasculitis with infarcts and ulceration.
Subcutaneous inflammation (panniculitis) and
calcification.
IIM – Systemic manifestations
• Gastrointestinal: oropharyngeal involvement
with tongue weakness and voice changes;
dysphagia and reflux.
• Pulmonary:Atelectasis, cough. Interstitial lung
disease. Aspiration.
• Cardiovascular:Tachyrhythmias and other
conduction abnormalities. Congestive heart failure
from myocarditis or cor pulmonale. Raynaud.
IIM - Evaluation
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Careful history and physical examination to
define:
The time\tempo of symptom onset and
progression.
The exact nature of the problems and associated
factors.
Medical and family history.
Muscle bulk/strength, rashes, cardiac,
pulmonary, GI findings.
Environmental exposures temporally associated.
IIM - Evaluation
• Laboratory evaluation directed by the above:
1. Muscle enzymes, serologies, tests to R/O other
diseases.
2. Radiographic studies, muscle MRI.
3. EMG, biopsies of skin, muscle, possibly other
tissues.
4. Special serologic or genetic studies depending
upon results from the above.
IIM – Laboratory abnormalities
• Sarcoplasmic enzymes (CPK, LDH, ALT, AST,
aldolase) – useful in assessing myositis activity.
• CPK MB fraction – correlates with diseases
activity and is not usually indicative of cardiac
involvement unless the ratio of CK-MB/total CK
rapidly increases.
• ESR/CRP – elevated in <30% of pts.
• ANA – positive in 60-90% of pts; best single lab
discriminator of IIM from other myopathies.
Causes of elevated serum CPK enzyme
activity
• Physical trauma or muscle stress.
1. Any muscle trauma – falls, EMG studies,
surgery, muscle bipsy, IM injection.
2. Strenuous, prolonged exercise-marathon
running, forced marching.
• Drug effects
1. On muscle itself – clofibrate, ethanol,
amphetamines, heroin.
2. On CK metabolism/clearance-phenobarbital,
morphine, diazepam.
Causes of elevated serum CPK enzyme
activity
• Diseases
1. Directly affecting muscle-non inflammatory
myopathies of all kinds, MI, malignant
hyperthermia, infectious myopathies, IIM.
2. Affecting blood supply to muscle-emboli to
muscle, vasculitis,prolonged immobilization.
3. Affecting the CNS-cerebral ischemia,
trauma,infections.
• Possible familial cases in African-Americans.
Myositis –specific autoantibodies (MSA)
1. Anti-synthetases – Jo 1(anti histidyl tRNA
synthetase).
2. Anti-signal recognition particle (SRP).
3. Anti-Mi-2.
• They are directed at conserved conformational
epitopes on phosphorylated, cytoplasmic
ribonucleoprotein particles involved in
translation and present in all cells.
MSA
• They inhibit the function of the protein they target.
• They appear to arise months prior to myositis
onset, are antigen driven, vary in titer with
myositis disease activity and occasionally become
negative after prolonged remission.
Associations of the MSA
• Anti-synthetases (Jo1):
• Arthritis, interstitial lung disease, fevers,
mechanic’s hand, Raynaud’s.
• Acute onset, severe disease.
• Moderate response to therapy.
• Prognosis poor; 70% 5-yrs survival.
• Frequency in IIM 25-30%.
Associations of the MSA
• Anti-SRP:
• Cardiac involvement, myalgias, mostly in black
females.
• Very acute onset, very severe disease.
• Poor response to therapy.
• Poor prognosis – 25% 5 yrs survival.
• Frequency in IIM – 5%.
Associations of the MSA
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Anti-Mi-2:
Classic dermatomyositis.
Acute onset. Mild disease.
Good response to therapy
Good prognosis. Nearly 100% 5 yrs survival/
Frequency in IIM 5-10%.
IIM - pathogenesis
• Polymyositis and inclusion body myositis may be
more cellularly mediated (CD8+ T cells).
• Dermatomyositis may be more humorally
mediated (B cells).
IIM – Activity evaluation
1. Muscle strength – grading:
• 5 – normal power resistance.
• 4 – power decreased but muscle contraction
possible against resistance.
• 3 – muscle contraction against gravity only.
• 2 – muscle contraction possible only when
gravity is eliminated.
• 1 – contraction without motion.
• 0 – no contraction.
IIM – Activity evaluation
2. CPK levels.
3. EMG: fibrillations, positive sharp waves, short
small polyphasic motor units, high frequency
repetitive discharges, normal nerve conduction
velocities.
4. Muscle biopsy: myofiber
degeneration/regenaration, MNC infiltrates,
perifascicular atrophy.
IIM – Activity evaluation
4. MRI: T1-weighted images – chronic changes in
muscles, atrophy.
T2 – weighted and STIR images – active
inflammation.
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Biopsy is taken from a weak muscle, without
atrophy, not damaged by EMG, injection, etc.
Poor prognostic factors in Myositis
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Based on demographic features:
Age : older.
Gender: female.
Race: black.
Based on signs-symptoms:
Fever, dysphagia, severe myositis.
Cardiac, pulmonary or GI involvement.
Delay to diagnosis and treatment.
Failure to induce remissin.
Poor prognostic factors in Myositis
• Based on clinical or serologic group:
1. Clinical groups: polymyositis, cancer-associated
or inclusion body myositis.
2. Serologic groups: anti-synthetases or anti-SRP
autoantibodies.
Therapy
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Steroids 1-2mg/kg/d.
Cytotoxic: MTX, AZT, cytoxan
IVIG
Plaquenil (rash).
Rehabilitation and physical therapy.