What is Dermatomyositis?

Dermatomyositis is an immune-mediated myopathy characterised by chronic inflammation of the skin and muscles, leading to cutaneous rashes and progressive, mainly proximal, muscle weakness.1,2 It is associated with increased morbidity and mortality.3

Dermatomyositis belongs to a rare, heterogenous group of systemic immune-mediated disorders known as idiopathic inflammatory myopathies.2

Dermatomyositis accounts for over one third of cases of idiopathic inflammatory myopathy.4

Idiopathic inflammatory myopathies

The precise pathogenesis of idiopathic inflammatory myopathies is not well understood and involves many immunological pathways.2,5

Idiopathic inflammatory myopathies are classified according to their patterns of presentation, age of onset, immunohistopathologic features, and treatment response.2

Identification of myositis-specific autoantibodies has improved the characterisation of myositis subtypes and associated clinical phenotypes – which vary in the severity of muscle involvement, extramuscular manifestations, and risk of malignancy.1

Overlap myositis, which includes anti-synthetase syndrome, is the most common idiopathic inflammatory myopathy and accounts for up to half of cases4. It is defined as

  • Myositis associated with another defined collagen vascular disease2, e.g. systemic lupus erythematous, Sjögren syndrome, rheumatoid arthritis, or systemic sclerosis1
  • Presence of “overlap autoantibodies” including myositis-specific antibodies (MSA) or myositis-associated autoantibodies (MAA)2

Anti-synthetase syndrome may have similar clinical/pathological features to a number of idiopathic inflammatory myopathies (dermatomyositis, polymyositis or necrotising autoimmune myopathy), but clinically evident myositis may be absent.2

Dermatomyositis accounts for over one third of cases of idiopathic inflammatory myopathy.4

Overview Idiopathic inflammatory myopathies:

  • Dermatomyositis (DM)
  • Polymyositis (PM)
  • Necrotising autoimmune myopathy (NAM)
  • Sporadic-inclusion body myositis (sIBM)

Features of dermatomyositis in comparison with other idiopathic inflammatory myopathies

Dermatomyositis (DM)Polymyositis (PM)Necrotising autoimmune myopathy (NAM)Sporadic-inclusion body myositis (sIBM)
Onset and disease course
  • Acute or insidiously progressive, symmetrical, proximal muscle weakness and/or a characteristic skin rash2
  • Usually painless2
  • Progressive onset of symmetrical, proximal muscle weakness2
  • Commonly painful2
  • Subacute onset, progressive symmetrical, proximal muscle weakness1,2
  • Weakness develops more rapidly than DM and PM, and is more severe2,4
  • Progresses over several years2
  • Unique versus other IIMs as it affects both the proximal and distal musculature in a symmetrical/asymmetrical pattern2
Age at onset
  • Children (Juvenile dermatomyositis)4
  • Adults4
  • Adults (usually)2
  • Adults2
  • Adults > 40 years old2
Symptoms, specific features
  • +/- dysphagia, specific skin and organ manifestation2,4
  • Rash may precede onset of muscular weakness1,2
  • Involvement of pulmonary system e.g. interstitial lung disease1,2,4
  • Malignancy in adults2,4
  • No rash2
  • Muscular and extramuscular organ involvement similar to DM2
  • No rash1,2
  • Myalgias, dysphagia may occur2
  • Creatinine kinase usually higher than in other IIMs1,2
  • Extramuscular manifestations include congestive heart failure2,4
  • No skin changes4
  • Weakness in flexor forearm muscles. Quadriceps weakness leads to falls/tripping2
  • Dysphagia very common2
  • Mild facial weakness common2
Muscle pathology
  • B cells and CD4+ T cells in perimysial and perivascular areas2
  • Perifascicular muscle fibre atrophy2
  • Membranolytic attack complex (MAC) deposition in microvasculature2
  • Invasion of endomysial cytotoxic CD8+ T cells in muscle fibres2
  • Macrophages invade non-necrotic muscle fibres2
  • Macrophage-mediated immune response2
  • Necrotic myofibres surrounded by sparse inflammatory infiltrate (predominantly lymphocytes)2
  • MAC deposition in microvasculature2
  • Similar to PM, invasion of muscle fibres by cytotoxic CD8+ T cells and macrophages2
  • Rimmed vacuoles characteristic of degenerative changes2
  • Amyloid deposits2
Treatment response
  • Usually responsive to immunotherapies2,4
  • Usually responsive to immunotherapies2,4
  • Usually responsive to immunotherapies2,4
  • Usually refractory to immunotherapies2
Histological section
(images courtesy of Prof. Patrick Cherin)

Download full table as PDF

Normal muscle (courtesy of Prof. Patrick Cherin)

The precise immunopathogenesis of idiopathic inflammatory myopathies is not fully understood.2,5

Epidemiology

Epidemiological data for idiopathic inflammatory myopathies are scarce, partly due to the rarity of this group of diseases.1,6

The incidence of dermatomyositis has been estimated to be < 1 case per 100,000 persons.7

One study in the US showed that the incidence and prevalence of dermatomyositis is 1.4 and 5.8 cases per 100,000 persons, respectively.1

Dermatomyositis occurs more commonly in females than in males7-9, with a ratio of approximately 3:19,10

Immunopathogenesis

Each idiopathic inflammatory myopathy phenotype likely results from different pathogenic mechanisms due to interactions between genetic risk factors and environmental risk factors.11

Dermatomyositis is a complement-mediated microangiopathy affecting skin and muscle. Activation and deposition of complement results in lysis of endomysial capillaries and muscle ischaemia.6,8,12

  1. Antibodies against endothelial cells may trigger complement component 3 (C3) activation
  2. Activation of B cells, CD4+ T cells, macrophages & MAC complex deposition
  3. Perivascular inflammation, capillary loss, remaining capillary dilatation, and muscle ischaemia
  4. Phagocytosis, necrosis and perifascicular atrophy of muscle fibres

High levels of type I interferon (IFN-I) are found in muscles of dermatomyositis patients with overexpression of IFN-I induced genes in muscles, skin and blood, the latter demonstrated in some cases to be correlated with disease activity.11,13

Interstitial lung disease is the leading cause of death in patients with dermatomyositis.1

Prognosis

Dermatomyositis is associated with increased morbidity and mortality due to muscle weakness and visceral involvement.3

  • Patients with dermatomyositis have a nearly 8-fold increase in their risk of death during a 10-year follow-up compared with the matched general population.14
  • In a nationwide retrospective study in Finland, 58% of patients died during a 20-year follow-up.10

Malignancies and diseases of the circulatory and respiratory system are common causes of death in patients with idiopathic inflammatory myopathies14, with interstitial lung disease the leading cause of death in dermatomyositis.1

Risk factors for death include older age, cancer, respiratory and cardiac involvement, dysphagia and certain myositis-specific autoantibodies.3

Cancer screening is advisable for patients with autoantibody subtypes that are associated with increased risk of malignancy.1

References

  1. Goyal NA. Continuum (MinneapMinn) 2019; 25:1564-85.
  2. Malik A et al. Front Neurol 2016; 7:64.
  3. Marie I. Curr Rheumatol Rep 2012; 14:275-8.
  4. Schmidt J. J Neuromuscul Dis 2018; 5:109-29.
  5. Oddis CV & Aggarwal R. Nat Rev Rheumatol 2018; 14:279-89.
  6. Briani C et al. Autoimmunity 2006; 39:161-70.
  7. Okogbaa J & Batiste L. Clin Med Insights Case Rep 2019; 12:1179547619855370.
  8. Dalakas MC & Hohlfeld R. Lancet 2003; 362:971-82.
  9. Danko K et al. Medicine 2004; 83:35-42.
  10. Airio A et al. Clin Rheumatol 2006; 25:234-9.
  11. Miller FW et al. Nat Rev Rheumatol 2018; 14:255-68.
  12. Dalakas MC. Lancet 2015; 372:1734-47.
  13. Pinal-Fernandez I et al. Neurology 2019; 93:e1193-204.
  14. Dobloug GC et al. Ann Rheum Dis 2018; 77:40-7.

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