Dermatomyositis, Polymyositis, and Inclusion Body Myositis



Dermatomyositis, Polymyositis, and Inclusion Body Myositis


Petros Efthimiou

Lawrence J. Kagen





KEY POINTS



  • Chronic, idiopathic skeletal muscle inflammation can be considered under three general types: dermatomyositis (DM), polymyositis (PM), and inclusion body myositis (IBM).


  • All three entities present with progressive muscle weakness and loss of function, caused by persistent muscle inflammation that eventually leads to skeletal muscle loss and atrophy.


  • DM is distinguished clinically from PM by the presence of a characteristic rash.


  • IBM presents insidiously, mainly in elderly male patients, thereby delaying diagnosis and treatment.


  • An often occult, underlying malignancy can be present, especially in DM.


  • Cardiopulmonary complications, dysphagia, and calcinosis are serious complications.



  • Serum muscle enzyme level elevations; presence of autoantibodies; and magnetic resonance imaging (MRI), ultrasonographic, and electromyography (EMG) studies can provide valuable clues to diagnosis.


  • Treatment options include systemic and topical corticosteroids, often in conjunction with immunomodulators, and intravenous immunoglobulin (IVIG).

Polymyositis (PM), dermatomyositis (DM), and inclusion body myositis (IBM) represent nosologic forms of the rare “idiopathic inflammatory myopathy” (IIM) disease group, which is characterized by chronic, acquired skeletal muscle inflammation. These disorders are all marked by progressive weakness, loss of function, and pathogenic processes, which likely involve immunocompetent cells and cytokine production. A number of infectious agents, drugs, and toxins must be excluded before the diagnosis of any of these idiopathic disorders can be established. Recognition of this group of disorders by the clinician is important because these disorders represent the largest group of acquired, and potentially treatable, myopathies in both children and adults.


ETIOPATHOGENESIS



  • The causes and pathogenesis of human inflammatory myopathies remain unclear. There is evidence of an autoimmune process, in which both cellular and humoral components are involved in capillary and muscle fiber injury. Altered expression of matrix metalloproteinases and cytokines/chemokines also play an important role in the pathogenesis.


  • Genetic factors predispose to autoimmunity, and relatives of patients with myositis have increased susceptibility to myositis and other autoimmune diseases. Associations of PM with major histocompatibility complex (MHC) genes human leucocyte antigen (HLA)-DR3, DRB1*0301, and DQA1*0501 have been reported.


  • Environmental factors have long been suspected to act as disease triggers in a genetically predisposed host. A variety of infections, drugs, and toxins can induce a syndrome resembling PM.


  • Lymphocytic muscle infiltrates have a prominent role in the pathogenesis of human inflammatory myopathies. Characterization of the infiltration pattern and of cell surface markers in muscle biopsies can provide valuable clues about which form of inflammatory myopathy is present. In DM, B cells and CD4+ cells predominate in the perivascular regions, whereas in PM and IBM, cytotoxic CD8+ T lymphocytes invade the endomysium and appear to have the primary pathogenic role.


  • PM is considered an antigen-driven T-cell–mediated disease, in which CD8+ cells invade skeletal muscles, proliferate in a clonal fashion, and release toxic enzymes such as perforin and granzyme-B. Target myofibrils may be capable of engaging CD8+ cells by demonstrating MHC class I molecules on their surface. Macrophages are present in areas of necrosis and can also contribute to cytokine and enzyme release.


  • Humoral immune mechanisms are implicated in the pathogenesis of DM, in which the primary antigenic target seems to be the vascular endothelium. Vasculopathy mediated by complement through the membrane attack complex (MAC and C5-9) deposition leads to ischemic injury and perifascicular atrophy. Vasculopathy occurs not only in muscles but also in other areas of the body including the skin and the gastrointestinal tract.


  • Cytokines and chemokines have attracted increased attention as contributors in the complex inflammatory cascade that leads to capillary and muscle fiber damage.



    • Proinflammatory cytokines such as tumor necrosis factor-α (TNF-α), TNF-β, IL-1α, IL-1β IL-2, and interferon-γ (IFN-γ) have been shown to be present in elevated levels in myositis biopsy tissue. TNF-α and TNF-β may contribute to the pathophysiology by being directly toxic to the existing muscle fibers and by preventing myofiber regeneration.


    • Chemokines, monocyte chemotactic protein 1 (MCP-1), macrophage inflammatory protein-1α (MIP-1α), MIP-1β, and regulated on activation of normal T cell expressed and secreted (RANTES) present in infiltrating inflammatory cells and
      extracellular matrix can perpetuate the autoimmune attack against muscle antigens by amplifying lymphocyte activation and migration.


  • Amyloid-containing inclusions are present in IBM muscle biopsies. They are derived from β amyloid precursor protein and phosphorylated tau protein. Various hypotheses exist about the pathogenic process. Proteosomal abnormalities marked by the increased deposition of mutated ubiquitin, defects in oxidative processes, and mitochondrial abnormalities have all been implicated. The role of the aging process is also of undoubted importance.


PREVALENCE



  • DM and PM are rare disorders (incidence of 5 to 7.6 in 1 million) and affect all age groups, with a peak frequency in childhood before the age of 18 years and again another adult peak between ages 55 and 69 years. Prevalence for DM and PM varies from 5 in 10,000 to 11 in 10,000. The relative frequency of DM may increase in latitudes near the equator. More women are affected than men (female-to-male ratio is 2:1) and African American women are more frequently affected than white women (African American women-to-white women ratio is 2.8:1).


  • IBM has an incidence of 2.2 in 1 million and a prevalence of 4.9 in 1 million. When adjusted for age, the prevalence rises to 16 in 1 million inhabitants older than 50 years. Men are affected twice as commonly as women.


CLINICAL MANIFESTATIONS


I. DM



  • DM usually begins with a characteristic rash. Often sun-sensitive and pruritic, the rash tends to be erythematous and macular over flat body surfaces and heaped up or papular at bony prominences.



    • There is swelling and a purplish discoloration around the eyes, with telangiectasia of the upper lids—the “heliotrope sign” or “lilac” suffusion.


    • Over the dorsal surface of the hand and finger joints, the rash is papular (Gottron’s papules). Similar manifestations can also be seen at the elbows, knees, and ankles (Fig. 32-1).


    • Large macular areas of rash are also seen on the upper outer anus and thighs, as well as on the anterior neck and chest (V-sign), and over the shoulders and upper thorax (shawl sign).


  • The rash usually precedes the recognition of myopathy. In some cases, this interval may be quite long, rarely lasting months or even years. Patients with rash alone are designated as having amyopathic DM, although careful observation will often disclose subtle clinical or laboratory signs of myopathy in most patients.


  • The myopathy of DM manifests as pain and weakness of the proximal musculature. Muscles innervated by cranial nerves are not affected, and distal musculature is generally less affected.

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Jul 29, 2016 | Posted by in RHEUMATOLOGY | Comments Off on Dermatomyositis, Polymyositis, and Inclusion Body Myositis

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