42 yoWF with hx of hypothyroidism, depression has a 2 week hx myalgia, weakness and a CPK of 3000. Adm to PHD CPK of 13379 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 11000 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 2000. 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 5000. 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

Antimalarial NeuromyopathyAntimalarial NeuromyopathyAntimalarial NeuromyopathyAntimalarial 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

PolymyositisPolymyositisDermatomyositisDermatomyositis

PolymyositisPolymyositisDermatomyositisDermatomyositis

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

Proposed Criteria for MyositisProposed Criteria for MyositisProposed Criteria for MyositisProposed Criteria for Myositis1. Symmetric proximal muscle weakness2. Elevated Muscle Enzymes (CPK, aldolase,

AST, ALT, LDH)3. Myopathic EMG abnormalities4. Typical changes on muscle biopsy5. 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

Polymyositis ClassificationPolymyositis ClassificationBohan & PeterBohan & Peter

Polymyositis ClassificationPolymyositis ClassificationBohan & PeterBohan & Peter

1. Primary idiopathic dermatomyositis2. Primary idiopathic polymyositis3. Adult PM/DM associated with

neoplasia4. Childhood Dermatomyositis (or PM)

often associated with vasculitis

5. Myositis associated with collagen vascular disease

MYOPATHY: HISTORICAL MYOPATHY: HISTORICAL CONSIDERATIONSCONSIDERATIONS

MYOPATHY: HISTORICAL MYOPATHY: HISTORICAL CONSIDERATIONSCONSIDERATIONS

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

MYOPATHIESMYOPATHIESMYOPATHIESMYOPATHIES Toxic/Drugs

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

Drug-induced myopathyDrug-induced myopathyDrug-induced myopathyDrug-induced myopathyAmiodarone

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

NONMYOPATHIC NONMYOPATHIC CONSIDERATIONSCONSIDERATIONSNONMYOPATHIC NONMYOPATHIC

CONSIDERATIONSCONSIDERATIONS

Fibromyalgia Polymyalgia Rheumatica

Caucasians, > 55 yrs, M=F, ESR > 100, normal strength, no synovitis

RA SLE Adult Still's Disease Vasculitis

INCLUSION BODY MYOSITISINCLUSION BODY MYOSITISINCLUSION BODY MYOSITISINCLUSION 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?

Presentation of PM/DMPresentation of PM/DMPresentation of PM/DMPresentation 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%

Skeletal Muscle WeaknessSkeletal Muscle WeaknessSkeletal Muscle WeaknessSkeletal 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

DERMATOMYOSITISDERMATOMYOSITIS5 Skin Features5 Skin Features

DERMATOMYOSITISDERMATOMYOSITIS5 Skin Features5 Skin Features

1. Heliotrope Rash: over eyelids Seldom seen in adults

2. Gottrons Papules (60-80%): MCPs, PIPs, MTPs, knees, elbows

3. V-Neck Rash (Shawl sign): violaceous erythema ant. chest w/ telangiectasias

4. Periungual erythema, digital ulcerations5. Calcinosis Mechanics Hands

CalcinosisCalcinosisCalcinosisCalcinosis

DIAGNOSTIC TESTINGDIAGNOSTIC TESTINGDIAGNOSTIC TESTINGDIAGNOSTIC 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

DIAGNOSTIC TESTINGDIAGNOSTIC TESTINGDIAGNOSTIC TESTINGDIAGNOSTIC 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

INFLAMMATORY MYOSITISINFLAMMATORY MYOSITISBiopsy FindingsBiopsy Findings

INFLAMMATORY MYOSITISINFLAMMATORY MYOSITISBiopsy FindingsBiopsy Findings

Inflammatory cells Edema and/or fibrosis Atrophy/ necrosis/ degeneration Centralization of nuclei Variation in muscle fiber size Rarely, calcification

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

PM/DM ComplicationsPM/DM ComplicationsPM/DM ComplicationsPM/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

MALIGNANCY & MYOSITISMALIGNANCY & MYOSITISMALIGNANCY & MYOSITISMALIGNANCY & 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

RHABDOMYOLYSISRHABDOMYOLYSISRHABDOMYOLYSISRHABDOMYOLYSIS 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

PM/DM DiagnosisPM/DM DiagnosisPM/DM DiagnosisPM/DM Diagnosis

Symmetric progressive proximal weakness

Elevated muscle enzymes (CPK, LFTs) Muscle biopsy evidence of myositis EMG: inflammatory myositis Characteristic dermatologic findings

INFLAMMATORY MYOSITISINFLAMMATORY MYOSITISTreatmentTreatment

INFLAMMATORY MYOSITISINFLAMMATORY MYOSITISTreatmentTreatment

Early Dx, physical therapy, respiratory Rx Corticosteroids : 60-80 mg/day

80% respond within 12 weeks

Steroid resistant Methotrexate Azathioprine

IVIG, Cyclosporin, Chlorambucil: unproven No response to apheresis

PROGNOSISPROGNOSISPROGNOSISPROGNOSIS

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. 28-47% @ 7 yrs. Relapses & functional disability are common Death: due to malignancy, sepsis, pulm. or

cardiac failure, and complications of therapy

Inflammatory MyositisInflammatory 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