Myositis

Myositis encompasses polymyositis and dermatomyositis. They are a group of autoimmune connective tissue disorders that primarily affect the proximal muscles. They fall under a larger group of chronic autoimmune conditions known as idiopathic inflammatory myopathies (IIMs).

The conditions that fall under IIMs include:

• Polymyostis
• Dermatomyositis
• Juvenile dermatomyositis
• Necrotising myopathy
• Inclusion body myositis
• Overlap myositis

We shall focus on polymyositis and dermatomyositis but briefly shall consider the other conditions as well…

Pathophysiology

The IIMs are heterogenous and have differing, complex and incompletely understood aetiologies and pathophysiologies. They are characterised by a dysregulation immune response that causes inflammation of muscles as well as muscle weakness. Genetic, environmental and immunological factors all play a role. Triggers may include infections, medications, smoking, and UV exposure.

Each subtype of IIM is associated with distinct autoantibodies known as myositis-specific autoantibodies (MSAs) or myositis-associated autoantibodies (MAAs).

Let’s discuss the pathophysiology of each subtype in a little more detail:

• Polymyositis (PM) - is characterised by cell-mediated cytotoxicity in which CD8+ T-cells with MHC-I expressing muscle fibres. The muscle fibres are essentially antigen-presenting cells. The T-cells attack such muscle fibres leading to their inflammation.
• Dermatomyositis (DM) - is characterised by a humoral immune response that targets the endothelium within blood vessels in muscle tissue. The complement activation results in formation of a membrane attack complex (MAC), this results in destruction of the capillaries and microinfarcts which lead to inflammation and muscle atrophy. There is an increase in type 1 interferon activity. These interferons increase inflammation through expression of MHC-I and presentation of muscle autoantigens which results in the autoimmune response.
• Juvenile dermatomyositis (JDM) - it is similar to the adult DM, with vascular involvement and type 1 interferon activity. The additional change is the deposition of calcium salts in the inflamed tissues (calcinosis).
• Necrotising myopathy - this involves muscle necrosis with minimal inflammatory infiltrates. It is associated with autoantibodies against signal recognition particles (which are involved in protein synthesis and targeting proteins to their correct locations in the cell) as well as HMG-CoA reductase which links NAM to the use of statins. The inflammation is minimal as compared to DM and PM, however, the cells undergo necrosis.
• Inclusion body myositis - this combines both inflammatory and degenerative mechanisms. CD8+ T-cell cytotoxicity is present (just as seen in PM). Unique to inclusion body myositis, however, is the presence of autophagic vacuoles that contain beta-amyloid and other proteins associated with degeneration (tau, ubiquitin, presenillin). It is not confirmed as to the relation between inflammation and protein aggregation but this is distinct from the other forms of myositis.
• Overlap myositis - as the name suggests there is overlap with other autoimmune conditions such as SLE and systemic sclerosis. This is due to associated autoantibodies such as anti-synthetase antibodies (such as anti-Jo-1).

💡 Myositis may also be the result of a paraneoplastic syndrome therefore we should also assess for underlying malignancy when considering the diagnosis.

The types of cancers associated with myositis include:

1. Lung cancer - the most common.
2. Breast cancer
3. Ovarian cancer
4. Gastrointestinal cancers
5. Bladder cancer
6. Lymphoma

⚠️ Risk factors

• >40 years
• HLA-DRB1*03:01 and HLA-B*08:01
• Female sex - for polymyositis and dermatomyositis
• Black ethnicity - for polymyositis and dermatomyositis
• Male sex - for inclusion body myositis
• White ethnicity - for inclusion body myositis
• Statins - necrotising myopathy.
• Smoking
• Viral infections

😷 Presentation

Polymyositis

😷 Presentation

Polymyositis develops over weeks to months with a progressive pattern.

• It affects multiple muscles with proximal muscle weakness and atrophy. This makes tasks like getting up from a chair, climbing stairs, or raising objects overhead difficult. Distal muscles are spared early on so fine motor movements are not affected until later in the disease course. Despite the atrophy, there is no loss of tendon reflexes and no abnormalities with sensation.
• Myalgia is not always present (only 1/3rd of patients have pain). However, muscles may be tender on palpation. There also may be a grainy sensation when palpating them.
• Pharyngeal muscle weakness may lead to dysphagia and dysphonia.
• Facial muscle weakness may be affected in severe disease (without extraocular muscles affected).
• Interstitial lung disease is a common complication for many PM patients and is a major source of mortality.

🔍 Investigations

• Creatine kinase - elevated.
• Other muscle enzymes: lactate dehydrogenase (LDH), AST and ALT may also be elevated.
• Electromyography (EMG) - enhanced electrical activity (indicating muscle inflammation), spontaneous activity, low amplitude motor unit potentials (due to loss of muscle fibres).
• Myositis-specific and myositis-associated autoantibodies
• Anti-Jo1 - associated with antisynthetase syndrome. It is the most common MSA in polymyositis. Also associated with interstitial lung disease.
• Anti-SRP - associated with poorer prognosis.
• Muscle biopsy - confirms the diagnosis.

Dermatomyositis and juvenile dermatomyositis

Dermatomyositis and juvenile dermatomyositis has the same proximal muscle weakness seen in polymyositis but myalgia is seen more commonly.

The distinguishing feature for DM and JDM is of course the dermatological manifestations of the disease.

• Gottron papules - scaly erythematous to violaceous lesion on the knuckles and extensor surfaces.
• Heliotrope rash - a blue-purple rash on the face and periorbital regions accompanied with periorbital oedema.
• Photosensitive macular rash - on the back and shoulders and neck.
• Calcinosis - may also occur, especially in JDM
• Dilated capillary loops near the nail cuticle
• Rough and cracked palmar surface of the hands
• Raynaud’s phenomenon is also more common
• Dysphagia and dysphonia
• Cardiac issues - such AV conduction issues, tachyarrhythmias and cardiomyopathy.
• Interstitial lung disease
• GI ulceration - more common in JDM.

🔍 Investigations

• Creatine kinase - elevated.
• Other muscle enzymes: lactate dehydrogenase (LDH), AST and ALT may also be elevated.
• Electromyography (EMG) - enhanced electrical activity (indicating muscle inflammation), spontaneous activity, low amplitude motor unit potentials (due to loss of muscle fibres).
• Myositis-specific and myositis-associated autoantibodies:
• Anti-Jo-1 - They are also associated with a pattern of disease which included interstitial lung disease and Raynaud’s phenomenon and arthritis. However, they’re less common with dermatomyositis as compared to polymyositis.
• Antinuclear antibodies (ANA) - common finding.
• Anti-Mi-2 - specific for dermatomyositis.
• Muscle biopsy - confirms the diagnosis.

🧰 Management

🚨 Complications

• GI ulceration
• Cardiac manifestations of dermatomyositis
• Interstitial lung disease
• Dysphagia
• Malignancy