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/

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• 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

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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
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PolymyositisDermatomyositis

• FM 2.51
• Acute onset all ages (bimodal)
• Incidence 2-7/million/year
• Weakness ( myalgia) Proximal gt Distal
• Skeletal muscle dysphagia, dysphonia
• Sx Rash, Raynauds, dyspnea
• 65 elevated CPK, aldolase
• 50 ANA ()
• 90 EMG 85 muscle biopsy

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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

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Polymyositis ClassificationBohan 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

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MYOPATHY HISTORICAL CONSIDERATIONS

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

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MYOPATHIES

• 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

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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
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NONMYOPATHIC CONSIDERATIONS

• Fibromyalgia
• Polymyalgia Rheumatica
• Caucasians, gt 55 yrs, MF, ESR gt 100, normal
  strength, no synovitis
• RA
• SLE
• Adult Still's Disease
• Vasculitis

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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?

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INFLAMMATORY MYOSITISImmunopathogenesis

• 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 lt50 OF PTS
• Infectious etiology? Viral implicated
• HLA-B8/DR3 in childhood DM
• DR3 and DRW52 with t-RNA synthetase Ab

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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 (lt 10 yrs) 10
Proximal myalgia alone 5
Dermatomyositis sine myositis lt1
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Skeletal Muscle Weakness

• Painless proximal gt distal
• Upper Extremity combing hair, dressing
• Lower Stairs, toilet, car, falling, gait
• Dysphagia, hoarseness, regurgitation
• Inability to raise head from the pillow

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DERMATOMYOSITIS5 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

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Calcinosis
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DIAGNOSTIC TESTING

• Physical Examiniation Motor Strength (Gowers
  sign), Neurologic Exam
• Acute phase reactants unreliable
• Muscle Enzymes
• CPK elevated gt65 gt10 MB fraction is possible
• Muscle specific- Aldolase, Troponin, Carb.
  anhydraseIII
• AST gt LDH gt ALT
• Beware of incr. creatinine (ATN) and
  myoglobinuria
• Electromyogram increased insertional activity,
  low amplitude, polyphasics, positive sharp waves
• Beware of neuropathic changes, incremental/decreme
  ntal MU changes

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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

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INFLAMMATORY MYOSITISBiopsy Findings

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

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Anti-synthetase syndrome ILD, fever, arthritis,
Raynauds, Mechanics hands
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Autoantibodies in PM/DM
Ab Freq () Clinical Syndrome
ANA 50 Myositis
U1-RNP 15 SLE myositis
Ku lt5 PSS myositis
Mi2 30 Dermatomyositis
PM1 15 PSS PM overlap
Jo-1 25 Arthritis ILD arthritis
SS-B (La) lt5 SLE,Sjogrens, ILD, PM
PL-12,7 lt5 ILD PM
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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

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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

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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

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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

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PM/DM Diagnosis

• Symmetric progressive proximal weakness
• Elevated muscle enzymes (CPK, LFTs)
• Muscle biopsy evidence of myositis
• EMG inflammatory myositis
• Characteristic dermatologic findings

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INFLAMMATORY MYOSITISTreatment

• 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

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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
• Kids50 remission, 35 chr active disease
• Adult lt 20 yrs. do better than gt55 yrs.
• Adults Mortality rates betw. 28-47 _at_ 7 yrs.
• Relapses functional disability are common
• Death due to malignancy, sepsis, pulm. or
  cardiac failure, and complications of therapy

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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. FM 21
• 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