Myositis

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

• Polymyositis

• Dermatomyositis• Inclusion body myositis

• Overlap myositis

• Immunopathology

• Diagnosis

• Treatment

Dermatomyositis

• 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 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.

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).

• Polymyositis

• Dermatomyositis

• Inclusion body myositis• Overlap myositis

• Immunopathology

• Diagnosis

• Treatment

Inclusion body myositis

• 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

An amyloid-beta-related degenerative process and an immune

dysregulation

The first muscles affected ininclusion-body myositis areusually those of the wristsand fingers, and the musclesat the front of the thigh.The muscles that lift thefront of the foot also maybe affected.

• Muscle weakness.

• Painless

• Heart and lungs are not affected in IBM.

Symptoms of Inclusion body myositis

• Polymyositis

• Dermatomyositis

• Inclusion body myositis

•Overlap 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

• Polymyositis

• Dermatomyositis

• Inclusion body myositis

• Overlap myositis

• Immunopathology • Diagnosis

• Treatment

Endothelium of the endomysial capillaries

DERMATOMYOSITIS

target

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 thepathogenesis of polymysitis and dermatomyositis remainsunclear.

No specific target antigens have not been identified and theagents 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.

• 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. 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.

• Polymyositis

• Dermatomyositis

• Inclusion body myositis

• Overlap myositis

• Immunopathology

• Diagnosis

• Treatment

TREATMENT The goals of the therapy are to improve the ability to carry out activitesof daily living by increasing muscle strengh.

They are very few controlled clinical trails most on dermatomyositisand 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 :-

1. some patients are steroid resistance .

2. Increase dosage of steroids result in the worsening of muscle

strength.

3. Dose of prednisone for at least 2-3 month period become ineffective.

4. 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).

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

Treatment for Overlap myositis

Thank you for your attention

Vamsi and Dinesh