Idiopathic inflammatory myopathies (incl polymyositis and dermatomyositis)

Question 1

Define idiopathic inflammatory myopathies.

Answer 1

Idioathic primary inflammatory myopathies characterised by chronic inflammation of striated muscle (polymyositis and inclusion body myositis, IBM) and skin (dermatomyositis).

BMJ - They are a heterogenous group of sub-acute, chronic and rarely acute diseases of the skeletal muscle that have in common the presence of moderate to severe proximal muscle weakness and inflammation on muscle biopsy.

Question 2

What is the aetiology of inflammatory myopathies?

Answer 2

Unknown but suggested:

Infection - viruses like coxsackievirus, influenza, retrovirus, CMV, EBV are associated. also protozoa, cestodes, nematode, Borella species.

Genetic - HLA subtypes confer risk

Environmental - UV radiation contributes to dermatomyositis. Hydroxyurea has also been associated with dermatomyositis.

Immunological - autoantibodies in ~20% e.g. antisynthases anti-Jo-1 Ab associated with high incidence of interstitial lung disease.

Question 3

How common are IIMs?

Answer 3

Rare

Annual incidence of 0.2-1 in 100,000

Peaks at childhood (5-15yrs) and adult 40-60yrs

Question 4

What is the pathophysiology of dermatomyositis?

Answer 4

• Primary antigen has components of vascular endothelium of larger endomysial blood vessels.
• Activation of complement –> deposition of membranolytic attack complex on microvasculature –> capillary necrosis/infarction/inflammation –> hypoperfusion of fascicles –>perifascicular atrophy mostly at peripheries esp.
• Lymphocytes infiltrate perimysial and perivascular regions of muscles –> dermatomyositis

Summary - Probably humorally-mediated disorder with perivascular and perifascicular infiltrate in skeletal muscle.

Question 5

What is the pathophysiology of polymyositis?

Answer 5

• Antigen directed and MHC-1-restricted cytotoxicity mediated by CD8 T cells
• CD8 cells bind to MHC-1 expressed on muscle fibres
• Clonal expansion of T cells occurs and memory T cells form - death ligand mediates inhibition or T cells activation
• Adhesion to muscle fibres by activated T cells is facilitated by cytokines, chemokines, and adhesion molecule

Summary: Polymyositis - cytotoxic CD8+ T-cell infiltrate which appears to recognize an antigen on muscle fibre surface.

Question 6

Summarise the differences between dermatomyositis, polymyositis and inclusion body myositis.

Answer 6

Question 7

What are the risk factors for IIMs?

Question 8

What is the pathogenesis of inclusion body myositis?

Answer 8

Inclusion body myositis: T-cell inflammatory infiltrate into the skeletal muscle suggests an immune basis. Non-inflammed skeletal muscle fibres may contain rimmed vacuoles and amyloid deposits suggesting a degenerative process.

Question 9

What is the onset and presentation of polymyositis/dermatomyositis?

Answer 9

Gradual onset (3-6 months) of progressive painless proximal muscle weakness e.g.

• difficulty raising objects above head
• rising from chair
• climbing stairs

Question 10

What is the onset and presentation of inclusion body myositis?

Answer 10

Insidious onset (over months to years). Affects rising from chair, climbing stairs and dexterity of hands. There may be dysphagia and neck droop.

Question 11

What other symptoms are present in inflammatory myopathies?

Answer 11

• Fatigue, malaise, dyspnoea
• Myalgia and arthralgia
• Skin rash and Raynaud’s phenomenon

Question 12

What are the signs of polymyositis and dermatomyositis on examination? What about inclusion body myositis?

Answer 12

Polymyositis and dermatomyositis - Proximal muscle weakness and atrophy affecting bothe upper and lower limbs

Inclusion body myositis - proximal and distal muscle weakness and atrophy (particularly wrist and deep finger flexors, quadriceps). Weakness of erector spinae and dysphagia is common.

Question 13

Describe the skin lesions in dermatomyositis.

Answer 13

• Macular “lilac” heliotrope rash on the upper eyelids with periorbital oedema,
• rash on chest wall, neck, elbows and knees.
• Gottren’s papules (scaly erythematous raised plaques on finger joints, periungal telangiectasia, ragged cuticles)
• “mechanics” hands (fissuring dermatitis of finger pads)

Question 14

What investigations would you do for inflammatory myopathies?

Answer 14

Bloods:

• FBC - low Hb of chronic disease
• ESR - raised in one third
• CK - raised (~x50) in 95% of cases - most sensitive and specific muscle-derived serum enzyme of disease activity.
• Autoantibody titres e.g. ANA is positive in derma/polymyositis

Imaging:

EMG - raised insertional activity, increased spontaneous fibrillations, abnormal low-amplitude short-duration polyphasic motor potentials and bizarre high-frequency discharges indicative of myopathy

CT/MRI - look for malignancy

Invasive:

Muscle biopsy - required for definitive diagnosis( inclusion body myositis has typical features of inflammation as well as vacuolated uninflammed muscle fibres and amyloid deposits )

Question 15

What are the ethnic and gender differences in people affected with inflammatory myositis?

Answer 15

• Female and/or black ethnicities are affected by polymyositis and dermatomyositis
• Male and/or white ethnicity are affected more by inclusion body myositis

Question 16

What are the two major groups of antibodies present in inflammatory myositis?

Answer 16

Two major groups exist:

Severe muscle disease = anticytoplasmic antibodies against translational components (e.g., antisynthetase antibodies and anti-SRP antibodies)

Mild muscle disease = antibodies against Mi-2 and Mas antigens

Dermatomyositis = 79% have Mi-2 antibodies.