1. 42 yoWF with hx of hypothyroidism, depression has a 2 week hx myalgia, weakness and a CPK of Adm to PHD CPK of and AST 225, ALT 107, LDH 1380 and CRP 2.6 mg/dl. EMG was classic for DM. She was d/c on Prednisone 80 mg qd but worsened w/ difficulty with stairs, and combing her hair, proximal weakness and muscle pain. The patient also complains of subjective fever, fatigue, myalgia, indigestion, and depression. CPK worsened at home to and was re-admitted. Rx with steroids, IVIG and MTX
21 yoBF with SLE x 2 yrs Rx with Plaquenil and Imuran. She developed progresive weakness in the arms over 2-3mos and was hospitalized with 2 pillow orthopnea and some RUQ pain and CPK of 12,112 and a Aldoase of 79. Started on prednisone 80 mg/day and Arava 100/wk and discharged with CPK She complains of difficulty with stairs, and combing her hair, and proximal weakness. She denies shortness of breath, dysphagia, and skin rash. Repeat CPK up to Steroid increased and pt put on MTX
56 yoWF wih RA since 2003, On Plaquenil, MTX, failed Enbrel. 2/04, she reports progressive worsening of weakness to arms and legs. She has difficulty with stairs, getting off the toilet, chairs, upper pharyngeal dysphagia, mainly to pills and water, not food. Also c/o Weight loss of 15 lbs, SOB cough, dry eyes/moutn. found to have mild CPK elevation 458, mild LFTs elevation, with normal aldolase. EMG mixed myopathic/neuropathic. Bx showed autophagic vacuoloar myopathy

2. Antimalarial Neuromyopathy
Not dose or duration dependant
Insidious painless LE/UE weakness
Clinical myopathy 6.7%; Chemical myopathy 18.8%
Bx: classic vacuolar myopathy and EM curvilinear bodies/complex lysosomes
Rx: improvement within 2 mos of d/c
Casado E. Ann Rheum Disease 2005

3. Polymyositis Dermatomyositis
F:M = 2.5:1
Acute onset; all ages (bimodal)
Incidence 2-7/million/year
Weakness (+ myalgia): Proximal > Distal
Skeletal muscle: dysphagia, dysphonia
Sx: Rash, Raynauds, dyspnea
65% elevated CPK, aldolase
50% ANA (+)
90% +EMG; 85% + muscle biopsy

4. Proposed Criteria for Myositis
Symmetric proximal muscle weakness
Elevated Muscle Enzymes (CPK, aldolase, AST, ALT, LDH)
Myopathic EMG abnormalities
Typical changes on muscle biopsy
Typical rash of dermatomyositis
PM Dx is Definite w/ 4/5 criteria and Probable w/3/5 criteria
DM Dx Definite w/ rash and 3/4 criteria and Probable w/ rash and 2/4 criteria

5. Polymyositis Classification Bohan & Peter
Primary idiopathic dermatomyositis
Primary idiopathic polymyositis
Adult PM/DM associated with neoplasia
Childhood Dermatomyositis (or PM)
often associated with vasculitis
Myositis associated with collagen vascular disease

6. MYOPATHY: HISTORICAL CONSIDERATIONS
Age/Sex/Race
Acute vs. Insidious Onset
Distribution: Proximal vs. Distal
Pain?
Drugs/Pre-existing Conditions
Neuropathy
Systemic Features

7. MYOPATHIES Toxic/Drugs Infectious Congenital neuromuscular disorders
Etoh, Cocaine, Steroids, Plaquenil, Penicilamine, Colchicine, AZT, Lovastatin, Clofibrate, Tryptophan
Infectious
Coxackie A9, HBV, HIV, Stept., Staph, Clostridial, Toxoplasma, Trichinella
Congenital neuromuscular disorders
Muscular dystrophies, hereditary myopathies
Neuropathic/Motor Neuron Disorders
Myasthenia gravis, amyotrophic lateral sclerosis
Endocrine/Metabolic
Glycogen storage diseases, mitochondrial

8. Drug-induced myopathy
Amiodarone
Amphetamines
Chloroquine
Cimetadine
Cocaine
Colchicine
Corticosteroids
Cyclosporin
Danazol
Emetine
Ethanol
Fibric-acid Rx
Heroin
Hydralzaine
Hydroxychloroquine
Hydroxyurea
Levodopa
Nicotinic acid
Pancuronium
Penicillamine
Pentazocine
Phenylbutazone
Phenytoin
Procainamide
Rifampin
Statins
Sulfonamides
Tiopronin
Vecruonium
Vincristine
Zidovudine

9. NONMYOPATHIC CONSIDERATIONS
Fibromyalgia
Polymyalgia Rheumatica
Caucasians, > 55 yrs, M=F, ESR > 100, normal strength, no synovitis RA
SLE
Adult Still's Disease
Vasculitis

10. INCLUSION BODY MYOSITIS
Bimodal age distribution, maybe hereditary
Slow onset, progressive weakness
Painless, distal and proximal weakness
Normal or mildly elevated CPK
Poor response to corticosteroids
Dx: light microscopy may be normal or show CD8+ lymphs. Tubulofilamentous inclusion bodies on electron microscopy
Role for amyloid?

11. INFLAMMATORY MYOSITIS Immunopathogenesis
Infiltrates - T cells (HLA-DR+) & monocytes
Muscle fibers express class I & II MHC Ags
T cells are cytotoxic to muscle fibers
t-RNA antibodies: role? FOUND IN <50% OF PTS
Infectious etiology? Viral implicated
HLA-B8/DR3 in childhood DM
DR3 and DRW52 with t-RNA synthetase Ab

12. Presentation of PM/DM Presentation Frequency (%)
Painless proximal weakness (over 3-6 mos)
55%
Acute/subacute proximal pain and weakness (wks-2 mos)
30%
Insidious proximal/distal weakness (< 10 yrs)
10%
Proximal myalgia alone 5%
Dermatomyositis sine myositis
<1%

13. Skeletal Muscle Weakness
Painless; proximal > distal
Upper Extremity: combing hair, dressing
Lower: Stairs, toilet, car, falling, gait
Dysphagia, hoarseness, regurgitation
Inability to raise head from the pillow

14. DERMATOMYOSITIS 5 Skin Features
Heliotrope Rash: over eyelids
Seldom seen in adults
Gottrons Papules (60-80%): MCPs, PIPs, MTPs, knees, elbows
V-Neck Rash (Shawl sign): violaceous erythema ant. chest w/ telangiectasias
Periungual erythema, digital ulcerations
Calcinosis
Mechanics Hands

22. Calcinosis

25. DIAGNOSTIC TESTING
Physical Examiniation: Motor Strength (Gowers sign), Neurologic Exam
Acute phase reactants unreliable
Muscle Enzymes
CPK: elevated >65%; >10% MB fraction is possible
Muscle specific- Aldolase, Troponin, Carb. anhydraseIII
AST > LDH > ALT
Beware of incr. creatinine (ATN) and myoglobinuria
Electromyogram: increased insertional activity, low amplitude, polyphasics, positive sharp waves
Beware of neuropathic changes, incremental/decremental MU changes

26. DIAGNOSTIC TESTING Muscle Biopsy (an URGENT not elective procedure)
Call the neuropathologist! 85% Sensitive.
Biopsy involved muscle (MRI guided)
Avoid EMG/injection sites or sites of trauma
Magnetic Resonance Imaging - detects incr. water signal, fibrous tissue, infiltration, calcification
Investigational: Tc-99m Scans, PET Scans
Serologic Tests: ANA (+) 60%, Abs against t-RNA synthetases

27. INFLAMMATORY MYOSITIS Biopsy Findings
Inflammatory cells
Edema and/or fibrosis
Atrophy/ necrosis/ degeneration
Centralization of nuclei
Variation in muscle fiber size
Rarely, calcification

30. Anti-synthetase syndrome: ILD, fever, arthritis, Raynauds,
Mechanics hands

31. Autoantibodies in PM/DMAb
Freq (%)
Clinical Syndrome
ANA 50
Myositis
U1-RNP 15
SLE + myositis Ku
<5
PSS + myositis
Mi2 30
Dermatomyositis
PM1
PSS – PM overlap
Jo-1 25
Arthritis+ ILD+ arthritis
SS-B (La)
SLE,Sjogrens, ILD, PM
PL-12,7
ILD + PM

35. INFLAMMATORY MYOSITIS
NORMAL/NOT INVOLVED:
Face Uncommon
Renal
RES: LN, spleen, liver (enzymes from muscle)
NOT UNCOMMON
RA-like arthritis
Fever/chills/night sweats
Myalgias

36. PM/DM Complications PULMONARY Intercostal, diagphragm involvement
Aspiration pneumonitis
Infectious pneumonitis
Drug induced pneumonitis
Fibrosing alveolitis
RARE:
Pulmonary vasculitis
Pulmonary neoplasia
Pulmonary hypertension
CARDIAC
Elev. CPK-MB
Mitral Valve prolapse
AV conduction disturbances
Cardiomyopathy
Myocarditis

37. MALIGNANCY & MYOSITIS Controversial Reports range from 10-25%
If real, men over age 50 yrs at greatest risk
Common tumors: Breast, lung, ovary, stomach, uterus, colon
60% the myositis appears 1st, 30% neoplasm 1st, and 10% contemporaneously
Avoid invasive, expensive searches for occult neoplasia

38. RHABDOMYOLYSIS
Injury to the sarcolemma of skeletal muscle with systemic release of muscle macromolecules such as CPK, aldolase, actin, myoglobin, etc
Maybe LIFE-THREATENING: from hyperkalemia, met. acidosis, ATN from myoglobinuria
Common causes: EtOH, Cocaine, K+ deficiency, infection, PM/DM, infection (clostridial, staph, strept), exertion/exercise, cytokines

39. PM/DM Diagnosis Symmetric progressive proximal weakness
Elevated muscle enzymes (CPK, LFTs)
Muscle biopsy evidence of myositis
EMG: inflammatory myositis
Characteristic dermatologic findings

40. INFLAMMATORY MYOSITIS Treatment
Early Dx, physical therapy, respiratory Rx
Corticosteroids : mg/day
80% respond within 12 weeks
Steroid resistant
Methotrexate
Azathioprine
IVIG, Cyclosporin, Chlorambucil: unproven
No response to apheresis

41. PROGNOSIS
Poor in pts. with delayed Dx, low CPK, early lung or cardiac findings, malignancy
Neoplasia in 10% of adults
PT for muscle atrophy, contractures, disability
Kids:50% remission, 35% chr active disease
Adult < 20 yrs. do better than >55 yrs.
Adults: Mortality rates betw. 7 yrs.
Relapses & functional disability are common
Death: due to malignancy, sepsis, pulm. or cardiac failure, and complications of therapy

42. Inflammatory Myositis
Polymyositis (PM) and dermatomyositis (DM) are types of idiopathic inflammatory myopathy (IIM). IIM are characterized clinically by proximal muscle weakness
Etiology: There is now known etiology.
Demographics: PM is more common than DM in adults. Peak incidence occurs between 40 and 60 yrs. F:M 2:1
Muscles: Proximal muscle weakness, dysphagia, aspiration. respiratory failure or death.
Skin: Gottron's papules, heliotrope rash, "V" neck rash, periungual erythema, "Mechanic's hands", calcinosis
Dx: Muscle enzymes (CPK, aldolase), EMG, Biopsy
Rx: Steroids, MTX, Azathioprine, IVIG