Myopathy 류마티스 내과 R3 윤현아

Differential diagnosis myalgia History - onset, location of pain, trauma, drug, exercise Muscle symptoms  acute onset : infection, trauma subacute onset : drug induced myopathy insidious onset : HCV carrier, hypothyroidism, vit.D deficiency… proximal muscle weakness : inflammatory myopathy… distal muscle weakness : Inclusion body myositis, motor neuron disease particular muscle pain : Myofascial pain syndrome, pyomyositis… diffuse muscle pain : Polymyalgia rheumatica, fibromyalgia, inflammatory myopathy, drug- induced myopathy, endocrine myopathy…

Neuromuscular causes of elevated muscle enzymes Rhabdomyolysis Trauma ,Exercise ,Seizure ,Electrolyte imbalance Infectious myopathy Virus ,Bacteria ,Spirochet ,Mycobacteria Drug statin, colchine, zidovudine, hydroxychloroquine, alcohol, cocaine , steroid Inflammatory myopathy Polymyositis, Dermatomyositis, Inclusion body myositis Metabolic myopathy β-oxidase defect, Carnitine deficiency, FA transport defect, MPFK deficiency Dystrophinopathy Duchenne's disease, Becker's disease, The limb-girdle dystrophy Endocrine myopathy Hypothydoidism, Acromegaly, Cushing's syndrome, Hyperparathyroidism muscle 6-phosphofructokinase - MPFK

Inflammatory myopathy Rhabdomyolysis Infectious myopathy Inflammatory myopathy Cause Trauma, Exercise, Electrolyte imbalance Viral ,Bacterial ,Spirochetal, Mycobacterial infection Polymyositis, Dermatomyositis, Inclusion body myositis Sx. Red ~ brown urine Acute onset, fever Diffuse myalgia without weakness Symmetric prox. m. weakness Typical rash of Dermatomyositis Facial m. invol.(ocular m. 제외) & distal m. invol. - IBM Lab. Muscle enzyme↑ Myoglobinuria M. Acidosis Ca - ↓/ K,P -↑ (>1000 times ) (>50 times but IBM mild evelation) ANA Anti-Jo-1, Anti-SRP, Anti-Mi-2 Ab. EMG Classic triad ① insertional activity & spontaneous fibrillation 증가 ② abnormal low amplitude. short–polyphasic potential ③ complex repetitive discharge Muscle Bx. Necrotic muscle fiber PM - direct T- cell mediated single fiber necrosis DM - mixed B &T-cell mediated perivascular inflammation perifascicular atrophy IBM - vacuolated muscle fibers muscle fiber β-amyloid deposits paired helical fibers

Metabolic myopathy Dystrophinopathy Endocrine myopathy Cause Defects of β-oxidase Carnitine deficiency Fatty acid transport defect MPFK deficiency Duchenne's ,Becker's muscular dystrophy, Limb-girdle dystrophy Hypothydoidism Acromegaly Cushing's syndrome Hyperparathyroidism Sx. Exercise intolerance Acute proximal weakness Reversible & recurrent Proximal muscle weakness  distal limb weakness Muscle weakness Myalgia & hypertrophy of thigh or calf by M.infaction in DM Lab. Muscle enzyme↑ Myoglobinuria Ca - ↓/ P, uric acid-↑ Urine dicarboxylic acids Forearm ischemic exercise test Muscle enzyme↑ Muscle enzyme : normal ~ elevation ESR ↑ in DM EMG Myotonic discharge Small polyphasic potential Muscle Bx. degeneration, regeneration, isolated opaque hypertrophic fiber, Repalcement muscle by fat & connective tissue

Forearm ischemic exercise test The standard screening test for defects in muscle glycolysis Placement of a needle in a superficial antecubital vein Resting blood samples - serum lactate, pyruvate, CK, and ammonia. The blood pressure cuff is inflated to a pressure level above the diastolic pressure Perform one per second hand grips Sequential samples of lactate, pyruvate, and ammonia are obtained at intervals of 1, 2, 3, 5, and 10 minutes after exercise. In normal individuals Three~ to fivefold rise in lactate is noted within the first one to three minutes. Serum ammonia is similar, reaches a peak at three to four minutes. Metabolic myopathy The rise in lactate is less than normal elevation.

Drug Symptom Lab finding Alcohol Acute : general myalgia Chronic : gradual onset proximal m. weakness diffuse m. atrophy Muscle enzyme↑ Muscle enzyme : normal or mild ↑ Statin Fibric acid Niacin Proximal symmetric m. weakness Muscle Bx. * early - myonecrosis without vasculitis or inflammation * later - mononuclear cell infiltration Hydroxychloroquine Prox. m. weakness without myalgia pph. sensory abnormality : vibratory sense ↓ : no deep tendon reflex Muscle enzymes : normal or mild ↑ EMG : myopathic & neuropathic . Colchicine Prox. m. weakness Subacute myalgia of lower ext. EMG- myopathic.

Hypothyroid myopathy Incidence Pathogenesis Muscle involvement in adults with hypothyroidism- 79% Hypothyroid myopathy – uncommon Pathogenesis TSH ↑ → mucopolysaccharide↑ → myxoedema TSH-responsive adenylate cyclase↑→hyaluronic acid↑→joint effusion T4 deficiency → abnormal glycogenolysis → muscle mitochondrial oxidative metabolism function ↓ triglyceride turnover → Selective atrophy of Type II fibers, hyperthrophy of Type I fiber

Hypothyroid myopathy Clinical manifestations Puffy face, macroglossia, protruding lips, dry & paleness skin Hoarseness, low voice CK↑: 57~90 % Not correlate with severity Several years before clinical manifestations of hypothyroidism Symmetric proximal myopathy  Slow progression, M/C of shoulder & hip girdle muscles Rhabdomyolysis Myalgia : 40% Stiffness, exacerbated after exercise

Hypothyroid myopathy Diagnosis TSH : most sensitive screening test. Low thyroxine Muscle biopsy is not usually required : normal or variety Type II fiber atrophy Type I fiber hypertrophy Increased numbers of internal nuclei Core-like structures in type I fibers Mitochondrial inclusions Glycogen accumulation Myofibrillar disorganization This can be sufficient to diagnose hypothyroid muscle disease.

EMG : helpful D/Dx from inflammatory myopathy. Normal or myopathic changes with increased low-amplitude, short- action potentials Inflammatory myopathy. ① insertional activity & spontaneous fibrillation 증가 ② abnormal low amplitude. short–polyphasic potential ③ complex repetitive discharge

Conventional electromyography of the right biceps brachii shows predominantly short, low voltage motor unit action potentials with a reduced mean motor unit action potential duration (12.0 ms) before (left panel) and a normal mean motor unit action potential duration (16.1 ms) 3 months after initiation of L-thyroxine substitution (right panel).

Hypothyroid myopathy Treatment & prognosis Thyroid hormone replacement. CK levels↓over several weeks, before TSH normalize Slowly recover of muscle weakness (79%, median 5.5 months)