Immune-Mediated Necrotizing Myopathy (IMNM)

Signs and Symptoms

The hallmark feature of people with immune-mediated necrotizing myopathy (IMNM) is the presence of proximal muscle weakness. Most affected people experience only weakness, and the presence of other (extra-muscular) symptoms, such as skin or lung manifestations, suggests that they may have another type of IIM rather than IMNM.

Myositis autoantibody tests are important blood tests that can be helpful for diagnosis and prognosis. In particular, myositis specific autoantibodies (MSAs) are classically associated with distinct clinical presentations. In IMNM, there are two MSAs, anti-HMGCR and anti-SRP that are associated with muscle biopsies that show significant necrosis (cell death) or an immune-mediated necrotizing myopathy.

Three forms of IMNM with different autoantibody associations have been described:

Myositis specific autoantibody	Clinical presentation	Therapy recommendations
anti-SRP Presence of autoantibodies to signal recognition particle (SRP) in serum	Severe muscle involvement Extra-muscular features are common	Intense and early immunosuppressant therapy recommended Intravenous immunoglobulin (IVIG) Intravenous immunoglobulin (IVIG)
anti-HMGCR myopathy Presence of autoantibodies to hydroxy-3-methylglutaryl-CoA reductase (HMGCR) in serum	Often associated with statin exposure, but is not required	Intense and early immunosuppressant therapy recommended Intravenous immunoglobulin (IVIG) treatment may be an effective treatment Rituximab
Autoantibody-negative IMNM	No known autoantibodies in serum Remains poorly described	Important to rule out muscular dystrophies or other connective tissue diseases associated with IMNM such as systemic lupus erythematosus or systemic sclerosis

Other complications

Rarely in IMNM, complications can occur. People with autoantibody-negative IMNM, in particular, may experience:

• Difficulties with swallowing (dysphagia)
• Breathing problems (lung inflammation, respiratory insufficiency)
• Inflammation of the heart (myocarditis)
• Increased risk of cancer (malignancies)

References

1. Dalakas MC. Inflammatory Muscle Diseases. Longo DL, ed. N Engl J Med. 2015;372(18):1734-1747. doi:10.1056/NEJMra1402225
2. Pinal-Fernandez I, Casal-Dominguez M, Mammen AL. Immune-Mediated Necrotizing Myopathy. Curr Rheumatol Rep. 2018;20(4):21. doi:10.1007/s11926-018-0732-6
3. Allenbach Y, Guiguet M, Rigolet A, Marie I, Hachulla E, Drouot L, et al. Efficacy of Rituximab in Refractory Inflammatory Myopathies Associated with Anti- Synthetase Auto-Antibodies: An Open-Label, Phase II Trial. PloS One 2015;10:e0133702.
4. Allenbach Y, Mammen AL, Benveniste O, Stenzel W, Immune-Mediated Necrotizing Myopathies Working Group. 224th ENMC International Workshop:: Clinico-sero-pathological classification of immune-mediated necrotizing myopathies Zandvoort, The Netherlands, 14-16 October 2016. Neuromuscul. Disord. NMD 2018;28:87–99.
5. Mammen AL, Tiniakou E. Intravenous Immune Globulin for Statin-Triggered Autoimmune Myopathy. N. Engl. J. Med. 2015;373:1680–2.

Last update: Feb 2023
Reviewed by Julie Paik, MD, MHS; Johns Hopkins University