MYOSITIS (Infammatory Myopathies) VAMSI KRISHNA MURTHY GINJUPALLI & DINESH VELAGAPUDI

“Myositis means muscle inflammation, and can be caused by infection, injury, certain medicines, exercise, chronic disease, or autoimmune disease” Infammatory Myopathies…………? NIH organization for research on Myositis-13 May 2014

The inflammatory myopathies are a group of diseases that involve chronic muscle inflammation which accompanied by :

Infammatory Myopathies Polymyositis Dermatomyositis Inclusion body myositis Overlap myositis Immunopathology Diagnosis Treatment

Polymyositis Dermatomyositis Inclusion body myositis Overlap myositis Immunopathology Diagnosis Treatment

Polymyositis Symmetric proximal muscle weakness. Affects skeletal muscles. Elevated serum muscle enzymes* CK, CK-MB, AST, ALT, LD, Aldolase Myopathic changes on Electromyography ( EMG ) Muscle biopsy cellular infiltrate is predominantly within the fascicle with inflammatory cells invading individual muscle fibers cell–mediated, increased numbers of cytotoxic CD8+ T cells, which appear to recognize an antigen on the muscle fiber surface

Researchers are finding that each case of PM is quite different from others. Sometimes, cases originally diagnosed as PM and not responding to treatment are later found to be inclusion-body myositis (IBM). Patients with certain types of PM may have one or more other autoimmune diseases.

Polymyositis

Symptoms of Polymyositis: Weakness of muscles. Patients can also feel fatigue. eyes can be surrounded by a violet. Heart and lung involvement Skin rash fatigue, a general feeling of discomfort, and have weight loss and/or low-grade fever.

Dermatomyositis Polymyositis Inclusion body myositis Overlap myositis Immunopathology Diagnosis Treatment

Dermatomyositis Symmetric proximal muscle weakness Dermatomyositis is an idiopathic inflammatory myopathy with characteristic cutaneous findings that occur in children and adults. Systemic disorder most frequently affects the skin and muscles but may also affect the joints; the esophagus; the lungs; and, less commonly, the heart. Symmetric proximal muscle weakness Elevated serum muscle enzymes Myopathic changes on EMG Muscle biopsy humorally–mediated disorder (CD4 cells), cellular infiltrate, located principally in perifascicular regions, focused around blood vessels  Rash

Dermatomyositis - histology

Symptoms of Dermatomyositis: muscle weakness Trouble with swallowing muscles ache hardened bumps of calcium deposits under the skin

Dermatomyositis – skin findings Gottron’s sign Heliotrope rash Shaw sign & V sign Mechanic’s hands Psoriasiform changes in scalp

Both polymyositis and dermatomyositis can sometimes be associated with cancers, including lymphoma, breast, lung, ovarian, and colon cancer. The cancer risk is reported to be much greater with dermatomyositis than polymyositis. (See polymyositis).

Inclusion body myositis Polymyositis Dermatomyositis Inclusion body myositis Overlap myositis Immunopathology Diagnosis Treatment

Inclusion body myositis An amyloid-beta-related degenerative process and an immune dysregulation insidious onset more prominent distal muscle weakness & atrophy (wrists, fingers, anterior tibial) Asymmetric muscle involvement On average, serum muscle enzyme levels are lower in IBM than in PM presence of typical inclusion bodies on muscle biopsy

The first muscles affected in inclusion-body myositis are usually those of the wrists and fingers, and the muscles at the front of the thigh. The muscles that lift the front of the foot also may be affected.

Symptoms of Inclusion body myositis Muscle weakness. Painless Heart and lungs are not affected in IBM.

Overlap myositis Polymyositis Dermatomyositis Inclusion body myositis Immunopathology Diagnosis Treatment

Overlap Myositis Myopathy associated with the other connective tissue diseases Scleroderma, systemic lupus erythematosus, mixed connective tissue disease Varies from clinically insignificant to typically severe PM or DM in which myopathy dominates the clinical picture

Immunopathology Diagnosis Treatment Polymyositis Dermatomyositis Inclusion body myositis Overlap myositis Immunopathology Diagnosis Treatment

DERMATOMYOSITIS target Endothelium of the endomysial capillaries Attack mAc Activation of cytokines And chemokines Migration of TGFb into endomysial Or Spaces lymphoid cells

IMMUNOPATHOLOGY OF POLYMYOSITIS AND INCLUSION BODY MYOSITIS : In polymyositis and inclusion body myositis the primary effector cells mediating muscle fiber injury are CD8 cells that are surround and invade MHC-1 antigen expressing, non-necrotic, muscle fibers. T- cell mediated cytotoxicity. These cells have perforin and necrosis granules – myoncerosis. Antigen driven T- cell response. Co- stimulatory molecules are up regulated.

IMMUNOPATHOGENESIS AND AUT0ANTIBODIES : Polymyositis and dermatomyositis is an autoimmune disorder. The impotance of these antibodies and their specificity in the pathogenesis of polymysitis and dermatomyositis remains unclear. No specific target antigens have not been identified and the agents initiating of disease/tissue remains unknown. They occurs in less than 25% of patients. They also occurs in patients with interstinal lung disease. Without myositis.

Anti-Jo1,anti-PL7,anti-PL12,anti-EJ,anti-OJ,anti-KS are mostly found antibodies in polymyositis and dermatomyositis and occasionally in inclusion body myositis.

Diagnosis Immunopathology Treatment Polymyositis Dermatomyositis Inclusion body myositis Overlap myositis Immunopathology Diagnosis Treatment

Differential Diagnosis Drug induced: statins, colchicine, hydroxychloroquine, steroids, etoh, cocaine HIV ALS Myasthenia gravis  Muscular dystrophies Inherited metabolic myopathies Amyloid & Sarcoid myopathies

DIAGNOSIS : we can suspect myositis based on person’s symptoms of muscle weakness by tests : 1.Blood test : High levels of muscle enzymes such as creatine kinase may means there is muscle inflammation. Blood tests check for abnormal antibodies that may identify an autoimmune conditions. 2.MRI scan : A scanner using a high powerd magnet and a computer creats images of the muscles.it help to identify areas of myositis and changes in the muscle over time.

3. Muscle biopsy : Most accurate test for diagnosing myositis 3.Muscle biopsy : Most accurate test for diagnosing myositis. A doctor identifies weak muscle make a small incision and removes a small sample of muscle tissue for testing it is final diagnosis in most of the people. 4.EMG : By inserting needle electrodes into muscle a doctor can test the response of muscle to electrical nerves signals. EMG can identify muscles that are week or damaged by myositis.

Treatment Immunopathology Diagnosis Polymyositis Dermatomyositis Inclusion body myositis Overlap myositis Immunopathology Diagnosis Treatment

TREATMENT The goals of the therapy are to improve the ability to carry out activites of daily living by increasing muscle strengh. They are very few controlled clinical trails most on dermatomyositis and inculsion body mysoitis. And inclusion body myositis is difficult to treat. As there is no effective therapy. The hypothesis that beta amyloid protein is key to IBM has been supported in a mouse model using an Aβ vaccine that was found to be effective against inclusion body myositis in mouse models. The following agents are used in the treatment of polymyositis and dermatomyositis :- 1. Corticosteroids :- Prednisone is first line drug in treatment. Dose 80-100 mg per day for 3-4 weeks single in morning dose (after breakfast). if a patients with sever PM or DM are given IV route methylprednisolone 1mg/day for 3-5 days. With oral prednisone as above.

Initation of therapy is due to :- some patients are steroid resistance . Increase dosage of steroids result in the worsening of muscle strength. Dose of prednisone for at least 2-3 month period become ineffective. Disease is rapidly progressive with severe weakness and respiratory failure. So for this reasons we use immunosuppressive drugs. Azathioprine :- orally dose 2.5-3 mg/kg for 4-6 months. Methotrexate :- orally dose 25 mg weekly. This methotrexate act more quickly than Azathioprine.

Cyclosporin :- orally dose 100-150 mg twice daily may benefit for childhood dermatomyositis. Acts faster than other drugs but its efficancy has not been established with controlled studies. Mycophenolate mofetil :- 2mg per day for 3 months is emerging as a promising and well tolerated drug. Cyclophosphamide :- 0.5-1.0 g/m2 intravenously has shown mixed resutls. It may help for patients with interstitial lung disease. Newer agents :- Rituximab, Tancrolimus, Sirolimus (Rapamycin),TNFa blockers(Infliximab).

Treatment for Overlap myositis The treatment of Overlap myositis is mainly based on the use of corticosteroids and immunosuppressants. Biologic drugs, i.e. anti-TNFα or anti-CD20 monoclonal antibodies, have been recently introduced as alternative treatments in refractory cases. There are some concerns with the use of anti-TNF agents in patients with systemic autoimmune diseases due to the risk of triggering disease exacerbations

Thank you for your attention Vamsi and Dinesh