Autoantibodies in PM and DM

Autoantibodies: >90% Positive ANA: 60-80%

More in overlap Low in IBM

Defined antibodies: 50% Myositis-specific antibodies:

35-40% Most common Ab (Jo-1): 20%

Myositis-Specific Antibodies

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

Established Myositis-Specific Autoantibodies

Anti-synthetases 25%Anti-Jo-1 20%Non-Jo-1 4 - 8%

Anti-Mi-2 5 - 10% Anti-SRP 5%

“signal recognition particle” (Anti-PM-Scl) 5 - 10%

Anti-Synthetases: Indirect Immunofluorescence

Anti-Jo-1 Anti-OJ Anti-PL-12

Anti-Synthetase Syndrome

Myositis 95%

Interstitial Lung Disease 70-90%

Arthritis 50-90%

Raynaud’s Phenomenon 60%

Fevers 85%

Recurrences 60%

Mechanic’s Hands 70%

Anti-Mi-2: Indirect Immunofluorescence

Anti-Mi-2: Clinical Picture High specificity for myositis

low sensitivity Relative specificity for dermatomyositis Adults and children Rash often prominent

Anti-SRP: Indirect Immunofluorescence

Signal Recognition Particle Autoantibodies

Acute onset Severe weakness No skin involvement Biopsy may lack inflammation

Immune-mediated necrotizing myopathy

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

predominate

Inclusion Body Myositis

Older age of onset Slow Progression

Longer duration to diagnosis Distal involvement: IBM>PM/DM

Forearm flexorsQuadriceps

Lesser degree of Creatine Kinase elevation

HISTOLOGIC FEATURES INCLUSION BODY MYOSITIS Light Microscopy

Rimmed vacuoles with basophilic granules

Eosinophilic inclusions Electron Microscopy

Inclusion bodies with microtubular filaments

Histopathology of IBMDalakas: 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 Pulmonary

Interstitial Lung Disease Respiratory Muscle Weakness Aspiration Infection Toxicity

Cardiac GI

Malignancy and Myositis

32% DM, 15% PM Risk greatest in 1st year Increased risk in those age >45

May have paraneoplastic course Ovarian cancer overrepresented Colon, lung, pancreatic, breast, lymphoma Risk is higher with anti-p155/140

lower with other myositis antibodies

Differential Diagnosis of Idiopathic Inflammatory Myopathy

Other myopathies (dystrophy, metabolic) Neuropathies (ALS, Myasthenia gravis) Drug-induced myopathies Infectious myopathies Endocrine myopathies (hypothyroidism,

Cushing’s syndrome)

DRUG-INDUCED MYOPATHY

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

Suggested Reading

Primer on the rheumatic diseases For greater depth:

Miller FW: Inflammatory Myopathies: Polymyositis, Dermatomyositis, and Related Conditions (Chapter 75). In: Koopman et al, Arthritis and Allied Conditions