2. Plain Films

3. Radiographs

4. PA and Lateral Views

5. CT Chest

7. Polymyositis Overlap Syndromes, Anti-Synthetase Syndrome

8. Epidemiology DM/PM Syndrome affects mostly adults with a female:male ratio of 3:1 DM/PM Syndrome affects mostly adults with a female:male ratio of 3:1 Relative prevalence exhibits regional latitude in Europe increasing from North (Iceland; RP:0.08) to South (Greece; RP:0.56) ( Hengstman, van Venrooij et al. Ann. Rheum. Dis. ; 2000 ) Relative prevalence exhibits regional latitude in Europe increasing from North (Iceland; RP:0.08) to South (Greece; RP:0.56) ( Hengstman, van Venrooij et al. Ann. Rheum. Dis. ; 2000 ) Jo-1 antibodies are correlated with HLA-DR3 in Caucasians Jo-1 antibodies are correlated with HLA-DR3 in Caucasians Prevalence of antisynthetase antibodies is 20- 40% in patients with DM/PM Prevalence of antisynthetase antibodies is 20- 40% in patients with DM/PM

9.  Thought to have precedent viral exposure leading to persistent presence of auto- antigens (molecular mimicry)  UV-B is thought to play a role given prevalence in European countries along latitude. UV-B stimulates dermal expression of TNF- alpha and other type-1 cytokines UV-B stimulates dermal expression of TNF- alpha and other type-1 cytokines  Spectrum includes both humoral mediated (DM) and cell mediated (CD8+ cytotoxic cells in PM) mechanisms  Due to these different mechanisms, both DM, PM, and the overlap syndromes have differing responses to anti-inflammatory agents Pathophysiology

10.  Features Raynaud’s Raynaud’s Proximal muscle weakness vs. combined proximal and distal weakness in inclusion body myositis Proximal muscle weakness vs. combined proximal and distal weakness in inclusion body myositis Photodermatitis Photodermatitis Mechanic’s hands Mechanic’s hands Elevated inflammatory markers, variable elevations in CK Elevated inflammatory markers, variable elevations in CK Capillary dilation with periungal inflammation Capillary dilation with periungal inflammation May have amyopathic disease May have amyopathic disease Subcutaneous calcinosis (anti-synthetase syndrome) Subcutaneous calcinosis (anti-synthetase syndrome) Interstitial Lung Disease (anti-synthetase syndrome) Interstitial Lung Disease (anti-synthetase syndrome) Symmetric, deforming (but not erosive) polyarthritis (anti-synthetase syndrome) Symmetric, deforming (but not erosive) polyarthritis (anti-synthetase syndrome) Clinical Presentation

11. Physical Exam Findings Adapted from Targoff et al

12. Physical Exam Findings Adapted from Targoff et al

13. Physical Exam Findings Adapted from Targoff et al

14. Autoantibodies  Note that 40% of these DM/PM/Overlap patients have detectable antibodies. Clinical presentation and muscle biopsy then becomes paramount.  + ANA in 80% of cases, don’t discount a negative ANA DiseaseEntity Auto- antibody Dermatomyosit is Anti-Mi2 PolymyositisAnti-SRP Polymyositis- Scleroderma Anti-PM- Scl DM/PM, Polyarthritis, ILD Jo-1/anti- synthetase DM/SLERNP

15. ANA Patterns  + ANA, Speckled pattern. DM/PM (anti-Mi2 and SRP antibodies)  + ANA, nucleolar pattern. Overlap of PM with Scleroderma (anti-PM- Scl)  Negative ANA, cytoplasmic pattern. Anti-synthetase syndromes

16.  Anti-Synthetase antibodies These autoantibodies are directed towards aminoacyl- tRNA synthetases (responsible for transfer of AA to conjugate transfer RNAs) These autoantibodies are directed towards aminoacyl- tRNA synthetases (responsible for transfer of AA to conjugate transfer RNAs) These are found in the cytoplasm, therefore ANA stains are cytoplasmic and are thus reported as negative (20% of all inflammatory myopathies) These are found in the cytoplasm, therefore ANA stains are cytoplasmic and are thus reported as negative (20% of all inflammatory myopathies) Antigen Auto- antibody Histidyl- tRNA synthetase Jo-1 Threonyl- tRNA Threonyl- tRNA PL-7 Alanyl-tRNAPL-12 Isoleucyl- tRNA OJ Glycyl-tRNAEJ Anti-Synthetase Syndrome

17.  Clinical Manifestation Patients with antisynthetase syndrome typically present with two or more components of myositis, ILD, and joint involvement Patients with antisynthetase syndrome typically present with two or more components of myositis, ILD, and joint involvement ILD may occur in absence of myositis, particularly associated with PL-12 autoantibodies ( Friedman, Targoff, Arnett. Semin Arthritis Rheum; 1996 ) ILD may occur in absence of myositis, particularly associated with PL-12 autoantibodies ( Friedman, Targoff, Arnett. Semin Arthritis Rheum; 1996 ) Clinical manifestation Prevalence Myositis 90% Interstitial lung disease (ILD) 60% Arthritis 50-90% Raynaud's40% Fever 20% Anti-Synthetase Syndrome

18. Physical therapy and an active exercise regimen Physical therapy and an active exercise regimen Corticosteroids 1mg/kg/day with good success (remission rates of 25-68% achieved) Corticosteroids 1mg/kg/day with good success (remission rates of 25-68% achieved) Non-steroidals (methotrexate.3mg/kg/week, azathioprine 2.5mg/kg/day, cyclophosphamide 3mg/kg/day) used with mild-moderate success Non-steroidals (methotrexate.3mg/kg/week, azathioprine 2.5mg/kg/day, cyclophosphamide 3mg/kg/day) used with mild-moderate success Use IVIG in refractory cases Use IVIG in refractory cases Case reports describe use of Rituximab in refractory cases Case reports describe use of Rituximab in refractory cases Treatment

19. In older patients, consider occult malignancy workup In older patients, consider occult malignancy workup Non-Hodgkin’s Lymphoma associated with DM/PM Non-Hodgkin’s Lymphoma associated with DM/PM May order DEXA scan given prolonged course of corticosteroids May order DEXA scan given prolonged course of corticosteroids Complications can include steroid induced myopathy (progressive weakness with improved CK) Complications can include steroid induced myopathy (progressive weakness with improved CK) Most common cause of mortality = complications from ILD leading to pulmonary HTN and hypoxia Most common cause of mortality = complications from ILD leading to pulmonary HTN and hypoxia Considerations

20. Gratuitous photos

21. References  Hengstman GJD, van Venrooij WJ, Vencovsky J, Moutsopoulos HM, van Engelen BGM. The relative prevalence of dermatomyositis and polymyositis in Europe exhibits a latitudinal gradient. Ann. Rheum. Dis. 59:141-142; 2000.  Plotz PH, Targoff I. Myositis associated antigens. Aminoacyl-tRNA synthetases. In : Manual of Biological Markers of Disease. Eds,WJ Van venrooij and R Maini. Kluwer Academic Publications. The Netherlands. pp B6.1: 1-18; 1994.  Love LA, Leff RL, Fraser DD, Targoff IN, Dalakas M, Plotz PH, Miller FW. A new approach to the classification of idiopathic inflammatory myopathy: myositis-specific autoantibodies define useful homogeneous patient groups. Medicine (Baltimore) 70:360-74; 1991.  Friedman AW, Targoff IN, Arnett FC. Interstitial lung disease with autoantibodies against aminoacyl-tRNA synthetases in the absence of clinically apparent myositis. Semin Arthritis Rheum 26:459-67; 1996.  Grathwohl KW, Thompson JW, Riordan KK, Roth BJ, Dillard TA. Digital clubbing associated with polymyositis and interstitial lung disease. Chest 108:1751-2; 1995.  Kalenian M, Zweiman B Inflammatory myopathy, bronchiolitis obliterans/organizing pneumonia, and anti-Jo-1 antibodies: an interesting association. Clin Diagn Lab Immunol 4:236-40;1997.  Targoff IN, Arnett FC Clinical manifestations in patients with antibody to PL-12 antigen (alanyl-tRNA synthetase). Am J Med 88:241-51; 1990.  Lee W, Zimmermann B 3rd, Lally EV.Relapse of polymyositis after prolonged remission. J.Rheumatol 24:1641-4; 1997.  Dalakas MC. Current treatment of the inflammatory myopathies. Curr Opin Rheumatol 6:595-601; 1994.