Myopathy Presentation PDF

Myopathy Nov 15, 2024 Steve S Lee, DO, FACR Rheumatologist, Kaiser Fontana Associate Clinical Professor Western University of Health Sciences Assistant Clinical Professor Loma Linda University School of Medicine. UCR School of Medicine  OUTLINE...

Myopathy Nov 15, 2024 Steve S Lee, DO, FACR Rheumatologist, Kaiser Fontana Associate Clinical Professor Western University of Health Sciences Assistant Clinical Professor Loma Linda University School of Medicine. UCR School of Medicine  OUTLINE Definition Epidemiology Pathophysiology Classification; diagnosis Clinical Features Special myopathic cases Treatment Idiopathic Inflammatory Myopathy Uncommon heterogeneous inflammatory muscle disorders featuring proximal muscle weakness – Adult Polymyositis – Adult Dermatomyositis – Special Cases: Childhood DM PM/DM associated with other CTD Immune mediated necrotizing myopathy (anti-HMGCoA)  Epidemiology Rare: incidence from 2 - 10 new cases/ million persons (underestimate?) Bimodal: 10-15 yrs, 45-55 yrs 3-4:1 African-American to White F:M 2-3:1 Overlap syndromes: – Scleroderma – lupus, MCTD  Common Pathophysiology B lymphocytes (myositis specific auto-Ab) Cytotoxic CD8+T cells for polymyositis CD4+T cells for dermatomyositis Pro-inflammatory cascade: – chemokines – complement activation – IL-1 and TNF – focal inflammation – death, repair  Polymyositis Dermatomyositis – Inflammatory infiltrate within – Perivascular infiltrate around fascicles. fascicle. – Necrotic fibers in group. – Scattered/isolated necrotic fibers. – Target= blood vessels. – Target= myofiber. Hematoxylin and Eosin cross-section of polymyositis: necrosis, regeneration and inflammation lymphocytic infiltration 6  Polymyositis: longitudinal myofiber destruction; areas of degeneration and necrosis of myofibers in association with interstitial lymphocytic infiltration  Bohan and Peter Classification (1975) 1. Symmetrical proximal muscle weakness insidious and proximal muscles 2. Muscle biopsy evidence of myositis necrosis, phagocytosis, regeneration, atrophy, perivasc infiltrate 3. Increase in serum skeletal muscle enzymes CPK, aldolase, LDH, AST, ALT 4. Characteristic electromyographic pattern short polyphasic motor units, fibrillations, irritability and repetitive dc’s 5. Typical rash of dermatomyositis heliotrope, gottrons, shawl, v neck Polymyositis: Dermatomyositis: Definite: all of 1-4 Definite: 5 plus any 3 of 1-4 Probable: any 3 of 1-4 Probable: 5 plus any 2 of 1-4 Possible: any 2 of 1-4 Possible: 5 plus any 1 of 1-4 2017 ACR/EULAR Criteria for Immune Mediated Myopathy  Case 1 A 67 year-old female presents to her internal medicine physician with complaints of a rash on her face, in particular the eyelids. She states it is aggravated when she is in the sunlight. Additionally, she reports of muscle aches and weakness. She has the most difficulty when climbing the stairs or standing up from a seated position. Physical examination is remarkable for a rash that is purple in color and located on the eyelids. She also appears to have a papular rash affecting the knuckles. Lastly, she has weakness of the hip girdle muscles, with the motor strength of bilateral hip flexors and extensors being 3/5. Which muscle enzyme is most sensitive for the detection of this condition? A. Creatine phosphokinase (CPK) B. Lactate dehydrogenase (LDH) C. Aldolase D. AST E. ALT  Case 1 A 67 year-old female presents to her internal medicine physician with complaints of a rash on her face, in particular the eyelids. She states it is aggravated when she is in the sunlight. Additionally, she reports of muscle aches and weakness. She has the most difficulty when climbing the stairs or standing up from a seated position. Physical examination is remarkable for a rash that is purple in color and located on the eyelids. She also appears to have a papular rash affecting the knuckles. Lastly, she has weakness of the hip girdle muscles, with the motor strength of bilateral hip flexors and extensors being 3/5. Which muscle enzyme is most sensitive for the detection of this condition? A. Creatine phosphokinase (CPK) B. Lactate dehydrogenase (LDH) C. Aldolase D. AST E. ALT Diagnosis: Muscle Enzymes Diagnosis; monitoring – Enzymes leak Sensitivity: CPK>aldolase>ALT/AST>LDH LDH may be most treatment specific Variations: – Muscle mass – Genetics – Kidney function  Diagnosis: Muscle Biopsy Gold standard for confirmation Pitfalls: – patchy disease and sampling error – Most myopathic muscle has highest yield – Biopsy the contralateral muscle to EMG Role of MRI mapping?  Clinical Features - Muscle Nonspecific fatigue, fevers, weight loss (constitutional, malignancy) Usually painless symmetrical muscle weakness – proximal>distal – stairs, toileting, abduction, neck flexion – gait abnormalities Dysphagia, nasal regurgitation of liquids Hoarseness or dysphonia (nasal voice) Ocular or facial weakness→ uncommon – consideration of another diagnosis – MuSK and ACH ab  Clinical Features - Skin May precede, develop simultaneously or subsequently – Heliotrope rash – Shawl sign – V neck sign – Gottron’s papules scaly, erythematous or violaceous papules/plaques over hand IP joints – Holster sign – Samitz sign  Heliotrope rash Erythematous/violaceous rash over the eyelids, face with/without perioribital edema  Clinical Features: Skin FIGURE 4.  Gottron’s papules dilated capillary nailfold loops Samitz sign  Special Myopathic Syndromes Anti-Synthetase Syndrome: – Cracking or fissuring over fingers – ‘mechanic's hands’ Seen in polymyositis with anti-tRNA synthetase More fevers, arthritis and interstitial lung disease  Anti-synthetase syndrome (mechanic’s hands): hyperkeratotic changes, cracking of the skin on the lateral aspects of the fingers  Special Myopathic Syndromes: (Pediatric) Dermatomyositis: Calcinosis Subcutaneous, fascial or intramuscular Microtrauma Complications: – ulceration → secondary infection – joint contractures Delayed treatment  Special Myopathic Syndromes: Amyopathic Dermatomyositis Classical cutaneous DM No clinically apparent myopathy May herald future myopathy (50%) Special Myopathic Syndromes: Autoantibodies Case 2: cc: diffuse muscle soreness HPI: 24 yo African American man with 10 lb wt gain. He usually lifts weights regularly but is just not lifting quite as many pounds as before but there is no definite weakness on exam. CPK: What do you do next? – urgent muscle biopsy – EMG – TSH – urine for myoglobin – aldolase Case 3 24 year old college student notes significant myalgias after track and field practice and feels like he is even dragging his feet. Case 3 24 year old college student notes significant myalgias after track and field practice and feels like he is even dragging his feet. Skipped breakfast and lunch that day as he was running late for class. Case 3 24 year old college student notes significant myalgias after track and field practice and feels like he is even dragging his feet. Skipped breakfast and lunch that day as he was running late for class. Is seen in the health center and labs are unremarkable except: Case 3 24 year old college student notes significant myalgias after track and field practice and feels like he is even dragging his feet. Skipped breakfast and lunch that day as he was running late for class. Is seen in the health center and labs are unremarkable except: Case 3 24 year old college student notes significant myalgias after track and field practice and feels like he is even dragging his feet. Skipped breakfast and lunch that day as he was running late for class. Is seen in the health center and labs are unremarkable except: Case 3 24 year old college student notes significant myalgias after track and field practice and feels like he is even dragging his feet. Skipped breakfast and lunch that day as he was running late for class. Is seen in the health center and labs are unremarkable except: Treatment Case 3 24 year old college student notes significant myalgias after track and field practice and feels like he is even dragging his feet. Skipped breakfast and lunch that day as he was running late for class. Is seen in the health center and labs are unremarkable except: Treatment What is this condition? – Muscle infarction – Metabolic myopathy – Polymyositis – Muscular dystrophy What was the treatment? – glucocorticoids – hemodialysis – infliximab – plasmapheresis – cautious monitoring and diet and exercise counseling  Differential Diagnosis ‘tiredness’ vs ‘fatigue’ vs ‘low energy’ clinical weakness – motor task (muscle weakness) – repetitive performance (fatigue) ROS (constitutional, ENT, skin, pulmonary) Neurological – Guillain barre – Myasthenia gravis – Amyotrophic lateral sclerosis Rheumatic – Lupus, vasculitis Other – Neoplastic, metastatic disease – Endocrine General type Subtypes/examples Denervating conditions Spinal muscular atrophies, amyotrophic lateral sclerosis Sarcoidosis Neuromuscular disorders Eaton–Lambert syndrome, myasthenia gravis Genetic muscular dystrophies Duchenne's facioscapulohumeral, limb girdle, Becker's, Emery–Dreifuss type, distal, ocular Glycogen storage diseases Adult-onset acid maltase deficiency, McArdle's disease Lipid storage myopathies Carnitine deficiency, carnitine palmityltransferase deficiency Endocrine myopathies Hypothyroidism, hyperthyroidism, acromegaly, Cushing's disease, Addison's disease, hyperparathyroidism, hypoparathyroidism, vitamin D deficiency myopathy, hypokalemia, hypocalcemia Metabolic myopathies Uremia, hepatic failure Toxic myopathies Acute and chronic alcoholism, drugs including penicillamine, clofibrate, chloroquine, emetine, statins, niacin, colchicine, checkpoint inhibitors Nutritional myopathies Vitamin E deficiency, malabsorption Acute rhabdomyolysis Proximal neuropathies Guillain–Barré syndrome, acute intermittent porphyria, diabetic lower-limb chronic plexopathies, chronic autoimmune polyneuropathy Septic myositis Including Staphylococcus, Streptococcus, Clostridium perfringens (welchii) and leprosy  Treatment: Medications/non-drug Glucocorticoids: – high dose prednisone 1 mg/kg/day – taper gradually after 4 weeks Immunosuppressants: – Azathioprine – Methotrexate (unless ILD) – Mycophenolate mofetil – Tacrolimus IVIg – monthly x 6 B cell depletion: – Rituximab Rehabilitation: muscle reserves – passive/active assisted ROM exercises – Strengthening/hypertrophy of reserves  Prognosis Dermatomyositis and Polymyositis – 5 year survival is 95% – 10 year survival is 84% Mortality: – pulmonary or systemic complications – malignancy – medications, infections Poor markers: – older age at diagnosis – delayed treatment – cardiac and pulmonary involvement  In Summary Recognize proximal muscle weakness 2017 myopathy guidelines Skin, vascular changes Muscle enzymes Auto antibody work up; medication effects Treatments and complications 49