Myositis

Myositis is a group of inflammatory, immune-mediated disorders that cause muscle weakness, intense fatigue, and difficulty with daily activities, such as climbing stairs and lifting objects.^1,2 Myositis also can affect other organs, including the lungs and heart, and the gastrointestinal tract, and can cause potentially life-threatening complications such as interstitial lung disease.^1-3 There are several subtypes of myositis. Each subtype presents with similar but unique symptoms in different populations.¹ The diagnosis of myositis frequently involves extensive testing and muscle or skin biopsies. Treatment can be challenging.^1-3 This article covers the types, causes, risk factors, symptoms, diagnosis, and treatment of myositis.

Types of Myositis

Myositis is a heterogeneous group of disorders.⁴ It commonly is classified into the following subtypes^1,2,4:

• Inclusion body myositis (IBM);
• Dermatomyositis (DM);
• Polymyositis (PM);
• Necrotizing autoimmune myopathy (NAM);
• Juvenile myositis (JM); and
• Antisynthetase syndrome overlap myositis (anti-SS-OM).

Inclusion body myositis is the most common type of myositis in people age 50 years and older.^1,2,4 Its symptoms develop slowly and progressively over years, and the condition generally does not respond to treatment.

Dermatomyositis presents with skin changes, such as a rash that turns into scaling discoloration, as well as muscle weakness.^1,2,4 It affects children and adults.

Polymyositis is characterized by chronic muscle inflammation and weakness that starts in the trunk.^1,2,4 It typically affects people age 20 years and older, more often women than men.

Necrotizing autoimmune myopathy, which also is sometimes called immune-mediated necrotizing myopathy (IMNM), causes severe muscle weakness and is characterized by evidence of muscle cell death and high creatine kinase levels.^1,2,4

Juvenile myositis occurs in people younger than age 18 years.¹ Its muscle weakness may or may not be accompanied by a rash.

Antisynthetase syndrome overlap myositis is characterized by the presence of antisynthetase antibodies.⁴ It causes mild-to-moderate proximal muscle weakness, systemic sclerosis-like lesions, arthritis, and interstitial lung disease.

Read more about Rheumatoid Arthritis.

Epidemiologic Characteristics

Myositis is rare, with an estimated prevalence of approximately 14 to 21 cases per 100,000 people in the United States.⁵ Inclusion body myositis is most common in older adults, occurring in approximately 18 per 100,000 people age 50 years and older (compared with 5 per 100,000 in the population overall).^1,6

While IBM is more prevalent in older men than women, DM occurs more frequently in women and can affect individuals of any age.¹ Dermatomyositis has an estimated prevalence of 13 cases per 100,000 people.⁵ Children and adolescents younger than age 18 years with myositis most commonly have JM, which presents similarly to adult DM (with rash).

Polymyositis often is found in people age 21 years and older and more often in women than in men.¹ Although historically NAM was grouped with PM, it is now recognized as a unique form of myositis.

Myositis Causes and Risk Factors

Myositis is an autoimmune disorder. Diverse immunological pathways have been implicated in its pathogenesis.³ Recent advances in understanding changes to the immune system that mediate inflammatory infiltration in muscle and skin cells have revealed B cells, T cells, and specific cytokines as potential targets for treatment.⁴ There is also some evidence that suggests a noninflammatory pathway, but this is not well understood.

Researchers have found an association between cancer and inflammatory myopathies, especially in DM and NAM.⁴ The body may create antibodies in response to cancerous cells. Immune checkpoint inhibitors can also trigger myositis by causing uncontrolled T-cell activation.

Viral infections can trigger myositis by initiating immune responses that activate T cells and autoantibodies, leading to inflammation and muscle tissue damage. Specifically, HIV and human T-lymphotropic virus type 1 are associated with IBM or PM.^4,6 Hepatitis C may be connected to IBM, but the relationship has not been well established. Some evidence suggests that infection with SARS-CoV-2 may also be associated with NAM, but further research is needed.⁴ While some researchers have observed a connection between statin use and NAM, this has not been validated.

Risk factors for myositis include sex and age, but these vary by subtype. Women are more commonly diagnosed with PM and DM, and older age increases the risk for IBM.^1,2,4

Prognosis

Myositis, particularly anti-SS-OM, is associated with interstitial lung disease, which can be life-threatening.^2,3 A 2023 study found that the 1-year survival rate for patients with myositis-associated interstitial lung disease was 86.7%. However, patients with the amyopathic subtype involving dermatologic manifestations but not substantial muscle weakness had higher all-cause mortality compared with those with myopathy.⁷ The presence of specific autoantibodies can be used as a prognostic biomarker and predict interstitial lung disease and cancer.^2,8,9

Symptoms and Diagnosis of Myositis

Patients with myositis often present with muscle fatigue and pain, difficulty climbing stairs and walking, frequent tripping, and difficulty reaching overhead. In some patients, the first sign may be a rash. Extramuscular manifestations, including interstitial lung disease, are common and may indicate anti-SS-OM.⁴ Arthritis and sclerosis-like lesions typically appear in anti-SS-OM. Severe rash is often the first or only sign of DM. Inclusion body myositis is characterized by progressive muscular dystrophy, unresponsiveness to treatment, and, in more than one-half of patients, dysphagia (difficulty swallowing).

The diagnosis is generally made based on clinical history and the progression of symptoms.⁴ The diagnosis can be confirmed with the findings of serum muscle enzyme tests, electromyography (EMG), autoantibody tests, and muscle biopsies.

Because IBM is not responsive to therapy, ruling out IBM before initiating treatment is important to prevent unnecessary exposure to immunosuppressive drugs.² The European Neuromuscular Center published its original diagnostic criteria for IBM in 2013; in April 2024, these diagnostic criteria were updated to account for the many advances in IBM research and diagnostic tools.¹⁰ According to these guidelines, the common clinical presentation of IBM is as follows:

• Progressive weakness for 1 year or more;
• Symptoms begin at age 45 years or older;
• Serum creatine kinase level less than 15 times the upper limit of normal; and
• Knee extension and/or deep finger flexion weakness at presentation (often asymmetrical and accompanied by dysphagia).

Some patients with IBM may have less common presentations (such as symptoms occurring at a younger age, for a shorter duration, or in nontypical muscle groups, with higher serum creatine kinase levels).¹⁰ However, a muscle biopsy showing inflammation consisting of endomysial lymphocytes surrounding nonnecrotic muscle fibers (with or without invasion) is mandatory for an IBM diagnosis. The following findings may or may not be present in patients with IBM:

• Rimmed vacuoles and/or cytoplasmic protein aggregates on muscle biopsy;
• Mitochondrial abnormalities with cytochrome c oxidase-negative and succinate dehydrogenase-positive fibers on muscle biopsy;
• Positive test result for anti-cN1a autoantibodies; and
• Typical muscle appearance/pattern on magnetic resonance imaging (MRI) or ultrasonography.

Physical Examination Findings

The initial physical examination should focus on assessing muscle weakness through clinical assessment and EMG.² Electromyography generally shows proximal muscle weakness and sparing of the sensory nerves. Inclusion body myositis often presents with weakness, specifically in finger and wrist flexors and knee extensors.

The skin, lungs, heart, and gastrointestinal system should also be assessed for the presence of extramuscular manifestations.² Dermatomyositis results in characteristic skin manifestations, including the following^2,4:

• Periorbital heliotrope rash;
• Erythema on the chest and back (V sign or shawl sign), neck, face, and joints;
• Gottron rash; and
• Periungual telangiectasia, irregular cuticles, and cracked fingertips.

Blood tests that assess muscle enzymes may indicate elevated creatine kinase levels in all subtypes of myositis, especially in NAM.² However, normal levels do not rule out myositis because DM and anti-SS-OM often present with normal enzyme levels.^2,4

Diagnostics Workup

If myositis is suspected based on EMG, the physical examination, and serum muscle enzyme levels, additional testing is needed.² A detailed clinical history that asks specifically about immune checkpoint inhibitor use, viral infections, and cancer may help confirm myositis and reveal the trigger.

Skeletal muscle MRI can help assess the activity and distribution of myopathy.² However, the findings are often nonspecific for myositis and should not be the basis of diagnosis.⁴

Muscle biopsy can reliably diagnose myositis and differentiate between the subtypes.⁴ Immunohistochemistry that reveals CD8-positive T cells in nonnecrotic fibers expressing major histocompatibility complex-I antigens indicates PM or IBM.⁴ Some (but not all) IBM biopsies show bluish-red vacuoles and amyloid deposits.

Myositis autoantibodies and myositis-associated autoantibodies can be assessed for the early detection of myositis.² Commercially available assays can screen for more than 20 myositis autoantibodies. Autoantibodies are detected in most patients with myositis and are highly specific for each subtype.^2,4

Differential Diagnosis of Myositis

Several neuromuscular diseases can mimic myositis, with similar findings of proximal muscle weakness and elevated creatine kinase levels.² Myositis should be differentially diagnosed from the following conditions:

• Muscular dystrophy;
• Dysferlinopathy;
• Pompe disease;
• McCardle disease;
• Thyroid or mitochondrial myopathies;
• Toxic myopathies; and 
• Kennedy disease.

Hereditary diseases can be ruled out with family history and genetic testing.² Abnormal acid phosphatase stain findings during muscle biopsy may indicate toxic myopathies. Autoantibody testing is often relied on to rule out noninflammatory myopathies.

When considering a diagnosis of IBM, the following findings are likely associated with an alternative diagnosis¹⁰:

• Positive family history of neuromuscular disease;
• EMG not consistent with IBM (such as signs of severe axonal loss or fasciculations); and
• Positive test result for myositis-specific autoantibody (such as Jo-1).

Treatment of Myositis

In 2022, the British Society for Rheumatology (BSR) published guidelines for treating myositis.⁹ Because IBM does not respond to treatment, it was not included in these guidelines.

Medications for Myositis

The first-line treatment for myositis is high-dose glucocorticoids.⁹ For adults, the recommended treatment is 0.5 to 1.0 mg/kg/d of oral prednisolone. For children, 1.0 to 2.0 mg/kg/d oral prednisolone or 30.0 mg/kg/d intravenous (IV) methylprednisolone pulses (up to 1 g/d) is recommended. Intravenous methylprednisolone should be considered when gastrointestinal absorption is a concern. Individuals’ clinical responses should dictate the tapering of glucocorticoids starting approximately 6 weeks after initiation.

Disease-modifying antirheumatic drugs (DMARDs), including methotrexate, azathioprine, tacrolimus, ciclosporin, and mycophenolate mofetil, are used to reduce active muscle inflammation and steroid burden, as well as to achieve clinical remission.⁹

If the disease is severe or refractory to glucocorticoids and DMARDs, the following second-line treatment options should be considered, in this order⁹:

• Intravenous immunoglobulin;
• Rituximab (particularly effective in JM, positive autoantibody, and lower burden disease);
• Cyclophosphamide; and
• Abatacept (adults only).

Observational research on Janus kinase inhibitors and anti-tumor necrosis factor-ɑ therapy has been promising, but more clinical studies, including randomized clinical trials, are necessary before these drugs can be recommended for treating myositis.⁹

In clinical trials, no immunosuppressants or immunomodulating agents have been effective for patients with IBM.⁴ The lack of response to treatment may be because IBM is progressive and usually has greatly advanced before the patient is diagnosed. Because IV immunoglobulin may have transient effects, it should be considered for patients with life-threatening dysphagia.

Nonpharmacological Treatments for Myositis

According to the BSR guidelines, all patients with myositis should engage in exercise programs developed by a specialized physiotherapist or occupational therapist to improve quality of life and muscle function.⁹ Several studies have found that 12-week training programs involving resistance training or endurance training in coordination with pharmacotherapy have anti-inflammatory results.³ Speech and language therapy should be considered for patients with dysphagia.⁹

Adverse Effects of Myositis Treatments

Glucocorticoids are associated with substantial adverse effects, including cardiovascular disease, osteoporosis, immunosuppression, and hyperglycemia.¹¹ Monitoring these adverse effects and adjusting the dose is an important component of myositis treatment.⁹ In 2022, the American College of Rheumatology published guidelines on preventing and managing glucocorticoid-induced osteoporosis.¹²

The adverse effects of IV immunoglobulin are generally minor, such as headache and vasomotor symptoms.¹³ Rarely, kidney failure, arrhythmia, or thrombosis can occur.

Methotrexate can have serious toxic effects and lead to liver damage.¹⁴ Methotrexate interacts with sulfonamides and salicylates (including aspirin).¹⁵ Managing the dose and excluding patients with concomitant conditions such as leukopenia or impaired kidney function is crucial.¹⁴

Cyclophosphamide has substantial adverse effects such as bladder scarring, hair loss, infertility, and an increased risk for infection and cancer.¹⁶ Live vaccines should be avoided. Intravenous cyclophosphamide has fewer adverse effects than oral cyclophosphamide.⁹ Rituximab is generally well tolerated.³

Complications of Myositis

The most serious myositis complication is interstitial lung disease, which occurs in 20% to 80% of patients with myositis and is a frequent cause of death.⁷ The anti-SS-OM subtype is associated with a higher risk for interstitial lung disease, and patients with this subtype or other high-risk features should undergo frequent lung screening.^4,9 According to the BSR guidelines, high-dose steroids; cyclosporin or tacrolimus; and cyclophosphamide or rituximab are recommended for patients with rapidly progressing interstitial lung disease.⁹

Dysphagia can be life-threatening and should be treated with IV immunoglobulin.^4,9 Clinical studies have shown that glucocorticoid, rituximab, DMARD, and cyclophosphamide therapy can improve dysphagia.⁹

Mild rashes can be managed by avoiding the sun, wearing sunscreen, and avoiding medications that increase photosensitivity.³ Topical glucocorticoids or calcineurin inhibitors might help, although according to the BSR guidelines, the evidence is insufficient.⁹ For patients with a rash that doesn’t respond to glucocorticoids or DMARDs, rituximab and IV immunoglobulin therapy are recommended. Calcinosis is a common skin manifestation that can be difficult to treat with medications; surgery to remove the calcinotic regions may be necessary.³

Patients diagnosed with myositis have an increased risk for cancer.^4,9 One study found that 21% of patients with myositis developed cancer, usually within 1 year of their myositis diagnosis.⁴ The presence of the following risk factors may indicate a greater likelihood of cancer⁹:

• Anti-TIF1-γ autoantibodies; 
• Anti-NXP2 autoantibodies; 
• Male sex; 
• Dysphagia; 
• Cutaneous necrosis; 
• Resistance to immunosuppressive therapy; 
• Older age;
• Rapid onset; and 
• Negative test results for known myositis-specific autoantibodies.

Computed tomography scanning should be considered in all adults with myositis to detect cancers. Routine cancer screening in JM is not recommended unless cancer is suspected.

Myositis Guidelines

The following resources may be useful for diagnosing and treating patients who have myositis^9,10,12:

• 2022 BSR guideline on idiopathic inflammatory myopathy;
• 2024 European Neuromuscular Centre diagnostic criteria for IBM; and
• 2023 ACR guideline on preventing and treating glucocorticoid-induced osteoporosis.

References

1. Types of myositis. The Myositis Association. Accessed March 19, 2025. https://www.myositis.org/about-myositis/types-of-myositis/

2. Sabouri AH, Christopher-Stine L, Kafaie J. Inflammatory myopathies. Practical Neurology. July/August 2021. Accessed March 19, 2025. https://practicalneurology.com/articles/2021-july-aug/inflammatory-myopathies

3. Oddis CV, Aggarwal R. Treatment in myositis. Nat Rev Rheumatol. 2018;14(5):279-289. doi:10.1038/nrrheum.2018.42

4. Dalakas MC. Inflammatory myopathies: Update on diagnosis, pathogenesis and therapies, and COVID-19-related implications. Acta Myol. 2020;39(4):289-301. doi:10.36185/2532-1900-032

5. Hossain MM, Wilkerson J, McGrath JA, et al. The geospatial distribution of myositis and its phenotypes in the United States and associations with roadways: Findings from a national myositis patient registry. Front Med (Lausanne). 2022;9:842586. doi:10.3389/fmed.2022.842586

6. Shelly S, Mielke MM, Mandrekar J, et al. Epidemiology and natural history of inclusion body myositis: A 40-year population-based study. Neurology. 2021;96(21):e2653-e2661. doi:10.1212/WNL.0000000000012004

7. Karampitsakos T, Tzilas V, Papaioannou O, et al. Clinical features and outcomes of patients with myositis-associated interstitial lung disease. Front Med (Lausanne). 2023;9:1096203. doi:10.3389/fmed.2022.1096203

8. Tansley SL, Simou S, Shaddick G, et al. Autoantibodies in juvenile-onset myositis: Their diagnostic value and associated clinical phenotype in a large UK cohort. J Autoimmun. 2017;84:55-64. doi:10.1016/j.jaut.2017.06.007

9. Oldroyd AGS, Lilleker JB, Amin T, et al; British Society for Rheumatology Standards, Audit and Guidelines Working Group. British Society for Rheumatology guideline on management of paediatric, adolescent and adult patients with idiopathic inflammatory myopathy. Rheumatology (Oxford). 2022;61(5):1760-1768. doi:10.1093/rheumatology/keac115

10. Lilleker JB, Naddaf E, Saris CGJ, et al. 272nd ENMC international workshop: 10 years of progress—revision of the ENMC 2013 diagnostic criteria for inclusion body myositis and clinical trial readiness. Neuromuscul Disord. 2024;37:36-51. doi:10.1016/j.nmd.2024.03.001

11. Alan IS, Alan B. Side effects of glucocorticoids. In: Malangu N, ed. Pharmacokinetics and Adverse Effects of Drugs–Mechanisms and Risks Factors. IntechOpen; 2018. doi:10.5772/intechopen.72019

12. Humphrey MB, Russell L, Danila MI, et al. 2022 American College of Rheumatology guideline for the prevention and treatment of glucocorticoid-induced osteoporosis. Arthritis Rheumatol. 2023;75(12):2088-2102. doi:10.1002/art.42646

13. Guo Y, Tian X, Wang X, Xiao Z. Adverse effects of immunoglobulin therapy. Front Immunol. 2018;9:1299. doi:10.3389/fimmu.2018.01299

14. Hamed KM, Dighriri IM, Baomar AF, et al. Overview of methotrexate toxicity: A comprehensive literature review. Cureus. 2022;14(9):e29518. doi:10.7759/cureus.29518

15. Methotrexate tablets. Prescribing information. Sun Pharmaceutical Industries, Inc; 2021. Accessed March 19, 2025. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=8f1260de-b60c-4f0e-8af6-0e957b0a281b&type=display 

16. Ursani M. Cyclophosphamide (Cytoxan). American College of Rheumatology. Updated February 2024. Accessed March 19, 2025. https://rheumatology.org/patients/cyclophosphamide-cytoxan