What are the causes of myositis?

Causes of Myositis

Myositis arises from four major etiologic categories: autoimmune/idiopathic inflammatory processes, infections (viral, bacterial, parasitic), drug-induced mechanisms (especially statins and immune checkpoint inhibitors), and malignancy-associated paraneoplastic syndromes. 1, 2, 3

Autoimmune/Idiopathic Inflammatory Myopathies

These represent the most clinically significant category requiring aggressive immunomodulation:

Polymyositis

• Characterized by symmetric proximal muscle weakness developing over weeks to months, mediated by CD8+ cytotoxic T-cell invasion of non-necrotic muscle fibers. 1, 2
• Persistently elevated creatine kinase (CK) levels accompany the subacute onset. 2

Dermatomyositis

• Distinguished by pathognomonic cutaneous manifestations including heliotrope rash, Gottron papules, periorbital edema, and periungual telangiectasias, coupled with proximal muscle weakness. 1, 2
• Juvenile dermatomyositis (age <18 years) frequently presents with calcinosis cutis, cutaneous vasculitis, and gastrointestinal vasculopathy. 1, 2
• The presence of any skin manifestation mandates reclassification from polymyositis to dermatomyositis, which carries different prognostic and therapeutic implications. 2

Immune-Mediated Necrotizing Myopathy (IMNM)

• Presents with severe proximal muscle weakness and CK elevations exceeding 10 times the upper limit of normal, with minimal inflammatory infiltrate on muscle biopsy. 1, 2
• Triggered by viral infections, statin exposure, and underlying malignancies. 1, 2
• Statin-induced necrotizing myopathy is associated with antibodies against 3-hydroxy-3-methylglutaryl-coenzyme A (HMGCR) protein upregulated in regenerating muscle. 1, 4

Sporadic Inclusion Body Myositis

• Shows degenerative neuromuscular features with muscle fiber vacuolization and abnormal accumulation of amyloid-β and phosphorylated tau proteins analogous to Alzheimer disease. 1, 4

Drug-Induced Myositis

Statin-Associated Myopathy

• Statins are considerably more likely than other medications to cause drug-induced muscle disorders and represent a major trigger for immune-mediated necrotizing myopathy. 2, 4
• A persistent CK elevation exceeding 10 times the upper limit of normal suggests necrotizing myopathy rather than benign reversible myopathic effects. 2

Immune Checkpoint Inhibitor (ICI)-Associated Myositis

• PD-1/PD-L1 inhibitors provoke myositis more frequently than CTLA-4 blockade (e.g., ipilimumab), with median onset approximately 4 weeks after therapy initiation. 2
• ICI-related myositis can present with fulminant necrotizing phenotype including rhabdomyolysis and myocardial involvement, and may be fatal if not promptly treated. 2
• Patients exhibit markedly elevated CK levels with proximal muscle weakness (difficulty standing, lifting arms, climbing stairs) and myalgia in severe cases. 2

Infectious Myositis

Viral Myositis

• Acute viral myositis typically resolves within 3–7 days and is characterized by normal to mildly elevated CK levels that normalize rapidly, supporting a self-limited course. 2
• Viruses implicated include influenza, HIV, and SARS-CoV-2. 3
• Distinguished from inflammatory myopathies by benign self-limited course, bilateral lower extremity involvement, preserved strength, absence of rash, and normal or mildly elevated CPK. 5

Bacterial, Fungal, Protozoal, and Parasitic

• Infectious necrotizing myositis requires immediate surgical debridement and broad-spectrum antibiotics, with mortality rate of 36.5% even with treatment. 5, 6
• Toxoplasma infection has been implicated in some cases. 6

Malignancy-Associated (Paraneoplastic) Myositis

• Myositis can arise as a paraneoplastic syndrome linked to occult malignancy, necessitating dedicated oncologic evaluation beyond standard immunomodulatory therapy. 2
• Elderly patients with inflammatory myositis have higher risk of associated malignancy. 4

Overlap Myositis

• Myositis occurring with associated connective tissue diseases (e.g., systemic lupus erythematosus, scleroderma, rheumatoid arthritis) represents a distinct entity with different underlying pathogenetic mechanisms. 6, 7

Key Diagnostic Distinctions

Laboratory Markers

• Myositis-specific autoantibodies (anti-Jo-1, anti-Mi-2, anti-MDA5, anti-TIF1-γ, anti-NXP2, anti-SRP) define distinct autoimmune phenotypes, predict extramuscular organ involvement (pulmonary, cardiac), and offer prognostic significance. 1, 2, 8
• Persistently elevated CK is a reliable indicator of true inflammatory myositis. 2
• Inflammatory markers (ESR, CRP) are typically markedly elevated in immune-mediated myositis. 2

Critical Pitfalls

• Polymyalgia rheumatica-like presentations feature severe myalgia and fatigue without objective muscle weakness; CK levels remain normal, and MRI/EMG show no myopathy. 2
• Do not overlook cardiac evaluation; silent arrhythmias and diastolic dysfunction are common and may be sources of embolic complications. 2
• Asymmetric weakness or true muscle weakness (not just pain-related limitation) indicates inflammatory myopathy requiring immunosuppression. 5