Autoantibodies in PM and DM Autoantibodies:>90% Autoantibodies:>90% Positive ANA:60-80% Positive ANA:60-80%  More in overlap  Low in IBM Defined antibodies:50% Defined antibodies:50% Myositis-specific antibodies: 35-40% Myositis-specific antibodies: 35-40% Most common Ab (Jo-1):20% Most common Ab (Jo-1):20%

Myositis-Specific Antibodies High disease specificity High disease specificity Appear prior to disease onset Appear prior to disease onset Absence does not exclude Absence does not exclude Assist in diagnosis and classification Assist in diagnosis and classification

Established Myositis- Specific Autoantibodies Anti-synthetases25% Anti-synthetases25%  Anti-Jo-120%  Non-Jo % Anti-Mi % Anti-Mi % Anti-SRP5% Anti-SRP5%  “signal recognition particle” (Anti-PM-Scl)5 - 10% (Anti-PM-Scl)5 - 10%

Anti-Synthetases: Indirect Immunofluorescence Anti-Jo-1Anti-OJAnti-PL-12

Anti-Synthetase Syndrome Myositis95% Interstitial Lung Disease70-90% Arthritis50-90% Raynaud’s Phenomenon60% Fevers85% Recurrences60% Mechanic’s Hands70%

Anti-Mi-2: Indirect Immunofluorescence

Anti-Mi-2: Clinical Picture High specificity for myositis High specificity for myositis  low sensitivity Relative specificity for dermatomyositis Relative specificity for dermatomyositis Adults and children Adults and children Rash often prominent Rash often prominent

Anti-SRP: Indirect Immunofluorescence

Signal Recognition Particle Autoantibodies Acute onset Acute onset Severe weakness Severe weakness No skin involvement No skin involvement Biopsy may lack inflammation Biopsy may lack inflammation  Immune-mediated necrotizing myopathy

DIAGNOSIS and the Myositis Autoantibodies High specificity, Low sensitivity High specificity, Low sensitivity Define patient subgroups Define patient subgroups May help when extra-muscular features predominate May help when extra-muscular features predominate

Inclusion Body Myositis Older age of onset Older age of onset Slow Progression Slow Progression  Longer duration to diagnosis Distal involvement: IBM>PM/DM Distal involvement: IBM>PM/DM  Forearm flexors  Quadriceps Lesser degree of Creatine Kinase elevation Lesser degree of Creatine Kinase elevation

HISTOLOGIC FEATURES INCLUSION BODY MYOSITIS Light Microscopy Light Microscopy  Rimmed vacuoles with basophilic granules  Eosinophilic inclusions Electron Microscopy Electron Microscopy  Inclusion bodies with microtubular filaments

Histopathology of IBM Dalakas: Rheum Dis Clin NA 28:779,2002 Endomysial Inflammation Sourrounding Non-necrotic fibers

Inclusion Body Myositis: Rimmed Vacuoles

IBM Pathology Dalakas Rheum Dis Clin NA 28:779,2002 Rimmed vacuoles; Basophilic Granules EM: Tubulofilaments

Extra-Muscular Manifestations Systemic Systemic Pulmonary Pulmonary  Interstitial Lung Disease  Respiratory Muscle Weakness  Aspiration  Infection  Toxicity Cardiac Cardiac GI GI

Malignancy and Myositis 32% DM, 15% PM 32% DM, 15% PM  Risk greatest in 1 st year  Increased risk in those age >45 May have paraneoplastic course May have paraneoplastic course Ovarian cancer overrepresented Ovarian cancer overrepresented Colon, lung, pancreatic, breast, lymphoma Colon, lung, pancreatic, breast, lymphoma Risk is higher with anti-p155/140 Risk is higher with anti-p155/140  lower with other myositis antibodies

Differential Diagnosis of Idiopathic Inflammatory Myopathy Other myopathies (dystrophy, metabolic) Other myopathies (dystrophy, metabolic) Neuropathies (ALS, Myasthenia gravis) Neuropathies (ALS, Myasthenia gravis) Drug-induced myopathies Drug-induced myopathies Infectious myopathies Infectious myopathies Endocrine myopathies (hypothyroidism, Cushing’s syndrome) Endocrine myopathies (hypothyroidism, Cushing’s syndrome)

DRUG-INDUCED MYOPATHY D-Penicillamine D-Penicillamine Zidovudine Zidovudine Lipid Lowering Agents Lipid Lowering Agents Colchicine Colchicine L-Tryptophan L-Tryptophan Drugs of Abuse Drugs of Abuse Endocrine Endocrine Chloroquine Chloroquine

Suggested Reading Primer on the rheumatic diseases Primer on the rheumatic diseases For greater depth: For greater depth:  Miller FW: Inflammatory Myopathies: Polymyositis, Dermatomyositis, and Related Conditions (Chapter 75). In: Koopman et al, Arthritis and Allied Conditions Miller FW: Inflammatory Myopathies: Polymyositis, Dermatomyositis, and Related Conditions (Chapter 75). In: Koopman et al, Arthritis and Allied Conditions Miller FW: Inflammatory Myopathies: Polymyositis, Dermatomyositis, and Related Conditions (Chapter 75). In: Koopman et al, Arthritis and Allied Conditions