Idiopathic Inflammatory Myositis J. Brian Houk, MD Assistant Professor of Clinical Medicine Division of Immunology, Allergy and Rheumatology University of Cincinnati College of Medicine

Disclosures None

Case 1 45 yo caucasian male PMH poorly controlled RA 1 year of with worsening pain in forearms with progressive weakening in grip strength

Case 2 20 yo caucasian female No PMH 5 years of persistent, diffuse myalgias, proximal > distal Occasional flares of myalgias associated with diffuse weakness and inability to get out of bed

Case 3 20 yo caucasian female No PMH 3 months of weakness in entire left upper extremity and weakness with right plantar flexion

Case 4 45 yo AA female No PMH 2-3 months increasing inability to get out of chair w/o using arms and washing her hair 1 month sensation of food getting caught in back of throat Now developing SOB with feeling that she can’t take a deep breath

Idiopathic Inflammatory Myositis What they are Adult polymyositis (PM) Adult dermatomyositis (DM) Juvenile myositis (DM >> PM) Malignancy-associated myositis Myositis in overlap with another autoimmune disease Inclusion body myositis (IBM)

Idiopathic Inflammatory Myositis What we’ll be discussing Polymyositis Dermatomyositis Antisynthetase syndrome (high yield) Subset of PM >> DM Constellation of physical findings Arthritis, Raynauds, Mechanics hands, ILD Specific autoantibodies which are all directed against enzymes which link AA to t-RNA (Jo-1 and the other 7) Roughly 30% of all cases of PM or DM

Idiopathic Inflammatory Myositis What they aren’t Endocrine myopathies Hyper/hypothyroid Drug or toxic myopathies Metabolic myopathies Mitochondrial myopathies Muscular dystrophies Infectious myositis Neuropathies/neurologic syndromes Paraneoplastic syndromes Other connective tissue disorders Miscellaneous Amyloid, Sarcoid

Idiopathic Inflammatory Myositis

Idiopathic Inflammatory Myositis Epidemiology Rare 1-10 cases / million / year Bimodal age distribution: 10-15 years of age and 45-60 years of age F:M 2:1 B:W 3-5:1

Idiopathic Inflammatory Myositis Question 1 A 36-year-old woman is evaluated for a 6-month history of fatigue and pain and stiffness of the fingers and knees. She reports weakness and heaviness in her arms and legs. She has a rash on her face, elbows, and hands. Family history is significant for a maternal aunt who has systemic lupus erythematosus. The patient takes no medications. On physical examination, temperature is 37.6 C (99.7 F), blood pressure is 102/60 mm Hg, pulse rate is 76/min, and respiration rate is 18/min. Cutaneous examination reveals mild alopecia; clumped, mildly erythematous papules over the olecranon, metacarpophalangeal joints, and proximal interphalangeal joints bilaterally; and cuticular overgrowth with periungual erythema of all digits. The appearance of the face is shown (next slide) Musculoskeletal examination reveals bilateral quadriceps and deltoid muscle weakness; synovitis of the proximal interphalangeal joints bilaterally; and small bilateral knee effusions. Distal muscle strength is normal

Idiopathic Inflammatory Myositis Question 1 A 36-year-old woman is evaluated for a 6-month history of fatigue and pain and stiffness of the fingers and knees. She reports weakness and heaviness in her arms and legs. She has a rash on her face, elbows, and hands. Family history is significant for a maternal aunt who has systemic lupus erythematosus. The patient takes no medications. On physical examination, temperature is 37.6 C (99.7 F), blood pressure is 102/60 mm Hg, pulse rate is 76/min, and respiration rate is 18/min. Cutaneous examination reveals mild alopecia; clumped, mildly erythematous papules over the olecranon, metacarpophalangeal joints, and proximal interphalangeal joints bilaterally; and cuticular overgrowth with periungual erythema of all digits. The appearance of the face is shown (next slide) Musculoskeletal examination reveals bilateral quadriceps and deltoid muscle weakness; synovitis of the proximal interphalangeal joints bilaterally; and small bilateral knee effusions. Distal muscle strength is normal

Idiopathic Inflammatory Myositis Question 1

Idiopathic Inflammatory Myositis Question 1 Laboratory CBC Normal ESR 65 (nl < 20) BUN CK 642 units/L (nl < 248) ANA 1:160 speckled SSA Positive Radiology Plain films: hands, wrists, knees Normal

Question 1: Which of the following is the most likely diagnosis? Dermatomyositis Inclusion body myositis Mixed connective tissue disease Sjogren’s Syndrome Systemic lupus erythematosus

Idiopathic Inflammatory Myositis Symptoms Symmetric proximal weakness Need to use arms to get out of chair out of chair Need to rock back and forth to get out of chair Can’t get up from seated position on the floor Can’t comb or wash hair Can’t carry groceries

Idiopathic Inflammatory Myositis Symptoms Weakness progressive over weeks to months Never distal Dysphagia and SOB from striated muscle involvement Myalgia is usually mild or absent 50-70% of the time

Idiopathic Inflammatory Myositis Symptoms Dysphagia Proximal 1/3 esophagus is striated muscle and can be affected, distal 2/3 is smooth muscle and not involved Difficulty initiating swallow Food getting caught in back of throat

Idiopathic Inflammatory Myositis Symptoms Shortness of breath Muscle involvement Intercostals Diaphragm ILD Classically with Antisynthetase Syndrome but can be seen in PM or DM More often associated with certain autoantibodies } Low FVC:DlCO or low NIF on PFTs suggests muscle involvement as opposed to ILD

Idiopathic Inflammatory Myositis Signs Rashes of DM Gottron’s papules Heliotrope V-neck Shawl sign Holster Periungual telangiectasia and hemorrhages

Gottron’s papules

Gottron’s papules

Gottron’s papules

Heliotrope

V-Neck

Shawl sign

Holster sign

Periungual telangiectasia and hemorrhages

Idiopathic Inflammatory Myositis Signs Mechanics hands in Antisynthetase Syndrome Cracking and fissuring on the radial side of the digits and the palms

Idiopathic Inflammatory Myositis Studies Muscle enzymes EMG MRI Biopsy Autoantibodies

Idiopathic Inflammatory Myositis Studies Muscle enzymes CK, Aldolase, AST, ALT, LDH Normal GGT One or all can be normal in early disease and in up to 5% of symptomatic patients

Idiopathic Inflammatory Myositis Studies Muscle enzymes CK can be elevated in the absence of muscle disease BM > BF > WM > WF Healthy asymptomatic AA have higher serum CK levels than Caucasians or Hispanics Exercise and manual labor Idiopathic hyperCKemia

Idiopathic Inflammatory Myositis Studies EMG/NCS Insertional activity Indicates membrane instability Complex repetitive discharges “Myopathic potentials” Short, low amplitude, polyphasic potentials Small damaged muscle fibers not firing in unison due to damage 10% can be normal due to sampling error

Idiopathic Inflammatory Myositis Studies MRI Edema seen on T2 imaging read as hyperintense signal throughout the affected muscles; perimuscular edema may also be seen Up to 99% sensitive Much less specific than EMG/NCS Rhabdomyolysis Muscular dystrophy Metabolic myopathy Toxic myopathy

Idiopathic Inflammatory Myositis Studies MRI Quads affected Hamstrings spared

Idiopathic Inflammatory Myositis Studies Muscle biopsy

Idiopathic Inflammatory Myositis Studies Muscle biopsy Guided by MRI or EMG - NEVER blind biopsy Contralateral muscle with EMG Skin biopsy is sufficient for diagnosis of DM in appropriate clinical scenario

Idiopathic Inflammatory Myositis Studies Muscle biopsy - PM Increased Class I MCH antigens on muscle fibers and inflammatory infiltrate with within the fascicle

Idiopathic Inflammatory Myositis Studies Muscle biopsy - DM Injury to capillaries and perifascicular myofibers Perfasicular atrophy C5b-9 attack complex deposition on capillary walls Fasicle Perfasicular atrophy Damage to capillary Fasicle

Idiopathic Inflammatory Myositis Question 2 A 42-year-old woman presents with few weeks h/o fever, Raynaud’s, fatigue and reports that her limbs feel heavy. She has also noted worsening shortness of breath and nonproductive cough. Her serum CK level was 8000 units/L, and ANA and anti–Jo-1 antibody test results are positive. Muscle biopsy show lymphocytic invasion of non-necrotic muscle fibers. She has normal mammogram and pap’s smear a month ago. On physical examination, temperature is 36.6 °C (97.9 °F), blood pressure is 132/68 mm Hg, pulse rate is 86/min, and respiration rate is 20/min. Cardiac examination is normal. Pulmonary examination reveals bibasilar crackles. Hyperkeratotic fissuring of the palms and lateral aspects of the fingers are noted. There is bilateral quadriceps and deltoid muscle weakness. The MCP and PIPs are mildly tender without synovitis. Laboratory studies reveal a normal complete blood count, an ESR of 50 mm/h. Chest radiograph is normal.

Idiopathic Inflammatory Myositis Question 2 A 42-year-old woman presents with few weeks h/o fever, Raynaud’s, fatigue and reports that her limbs feel heavy. She has also noted worsening shortness of breath and nonproductive cough. Her serum CK level was 8000 units/L, and ANA and anti–Jo-1 antibody test results are positive. Muscle biopsy show lymphocytic invasion of non-necrotic muscle fibers. She has normal mammogram and pap’s smear a month ago. On physical examination, temperature is 36.6 °C (97.9 °F), blood pressure is 132/68 mm Hg, pulse rate is 86/min, and respiration rate is 20/min. Cardiac examination is normal. Pulmonary examination reveals bibasilar crackles. Hyperkeratotic fissuring of the palms and lateral aspects of the fingers are noted. There is bilateral quadriceps and deltoid muscle weakness. The MCP and PIPs are mildly tender without synovitis. Laboratory studies reveal a normal complete blood count, an ESR of 50 mm/h. Chest radiograph is normal.

Question 2: Which of the following is most appropriate next step? Right Heart Catheterization HRCT scan of chest and PFTs Echocardiogram Chest Xray

Idiopathic Inflammatory Myositis Question 2 Which of the following is most appropriate next step Right Heart Catheterization HRCT scan of chest and PFTs Echocardiogram Chest Xray Patient has Antisynthetase syndrome ILD is most frequently seen in the this setting and is major cause of morbidity and mortality

Idiopathic Inflammatory Myositis Studies Myositis specific auto antibodies Likely to be asked about: just remember high risk for raynauds, arthritis, ILD and mechanics hands DM Overlap SRP U1RNP PM-Scl Ku Mi-2 MJ PL-12 Jo-1 PL-7 PM/NM EJ TIF-1γ HMGCR MDA-5 SAE Antisynthetase

Idiopathic Inflammatory Myositis Associated diseases ILD Malignancy

Idiopathic Inflammatory Myositis Associated diseases ILD PFTs Restrictive lung disease FEV1:FVC > 80% Decreased DlCO Recall that DlCO usually normal if SOB from muscle involvement giving low FVC:DlCO

Idiopathic Inflammatory Myositis Associated diseases ILD HRCT Typically in NSIP pattern Symmetric, lower lung zone predominant in periphery

Idiopathic Inflammatory Myositis Associated diseases Malignancy Greatest risk in patients with DM Standard Incidence ratio 3 – 12.6 In one series 59% developed malignancy after dx of DM Older patients at greater risk but can occur in patient under 45 y.o.

Idiopathic Inflammatory Myositis Associated diseases Malignancy Ovarian, lung, pancreatic, stomach, colorectal, and non Hodgkin's lymphoma most common Greatest risk first three years but can occur at any time

Idiopathic Inflammatory Myositis Quick word on statin myopathies Typically statins cause myalgias, but can progress to myositis Generally happen within weeks to months of starting statin but can happen at any time Characterized as Immune-mediated necrotizing myopathy Pathology distinct from PM and DM Necrotising, non-inflammatory HMG-CoA Reductase Antibody positive ~40%

Idiopathic Inflammatory Myositis Quick word on Inclusion Body Myositis Older males Insidious onset over years DISTAL involvement Can be asymmetric Distinct biopsy findings Fatty degeneration and vacuoles on microscopic evaluation Inclusion bodies seen w/in sarcoplasm and within myonuclei on electron microscopy No effective treatment

Idiopathic Inflammatory Myositis High Yield Points Proximal weakness, never distal Myalgias are not very common, if present usually mild Muscle enzymes can be low or even normal EMG very specific Muscle biopsy is needed for definite diagnosis (unless skin biopsy c/w DM) Antisynthetase syndrome Subset of PM which in addition to muscle weakness presents with Raynauds Arthritis ILD Jo-1 is most common autoantibody Malignancy risk increased in DM Usually within 2 years of diagnosis Can also cause DM as a paraneoplastic syndrome Always screen for underlying malignancy after diagnosis of DM is made

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