From the Guidelines
Necrotizing autoimmune myopathy (NAM) should be treated with high-dose corticosteroids (prednisone 1 mg/kg/day) combined with immunosuppressive agents, such as methotrexate (15-25 mg weekly), azathioprine (2-3 mg/kg/day), or mycophenolate mofetil (1000-1500 mg twice daily), as first-line therapy to reduce morbidity and mortality and improve quality of life 1.
Treatment Approach
The treatment approach for NAM involves a multidisciplinary approach with specialists, including rheumatologists, neurologists, dermatologists, pulmonologists, physical therapists, speech therapists, occupational therapists, and orthopedic surgeons. The major goals of treatment are to eliminate inflammation, restore muscle performance, and prevent chronic muscle disease and other organ system damage to reduce morbidity and regain quality of life 1.
First-Line Therapy
First-line immunosuppressants include methotrexate, azathioprine, or mycophenolate mofetil. Methotrexate has been used since the 1970s to treat IIM, with improvement in 17 of 22 patients with DM or PM treated with intravenous MTX, with normalization of the CK level and improvement in strength 1. Azathioprine has also been shown to improve muscle strength, but there was no significant difference compared with controls 1.
Severe or Refractory Cases
For severe or refractory cases, intravenous immunoglobulin (IVIG) at 2 g/kg divided over 2-5 days monthly may be added. Rituximab (1000 mg IV given twice, two weeks apart) is often used for anti-SRP or anti-HMGCR antibody-positive cases that don't respond to initial therapy. If statin-associated, immediate discontinuation of the statin is essential.
Monitoring and Physical Therapy
Patients require regular monitoring of muscle strength, creatine kinase levels, and medication side effects. Physical therapy is important for maintaining muscle function and preventing contractures. The disease mechanism involves autoantibodies targeting components of muscle cells, leading to complement activation and muscle fiber necrosis without significant inflammation. Early aggressive treatment is crucial as delays can lead to permanent muscle damage and disability.
Recent Guidelines
Recent guidelines suggest that myositis may be a severe condition, and immunotherapy withdrawal needs to be discussed. In the presence of life-threatening manifestations, high-dose glucocorticoids, IVIg, and/or plasma exchange should be considered; immunotherapy withdrawal is always necessary 1. Prompt recognition and early management of myositis is imperative, with discontinuation or at least interruption of CPI reported in more than 85% of patients and is mandatory in the presence of dyspnoea, bulbar symptoms, severe muscle weakness, and/or myocarditis.
From the Research
Definition and Characteristics of Necrotizing Autoimmune Myopathy
- Necrotizing autoimmune myopathy (NAM) is characterized by necrotic muscle fibers with absent or minimal inflammation 2.
- It is often accompanied by statin therapy, connective tissue diseases, cancer, and autoantibodies specific for signal recognition particle (SRP) or 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) 2, 3.
- Clinical presentation is highly variable, with severe forms often presenting with rhabdomyolysis 4.
- Elevated creatine kinase levels and myopathic changes on electromyography are common findings 2, 4.
Autoantibody Status and Clinical Phenotype
- Autoantibody status in NAM has considerable correlation with clinical phenotype, prognosis, and recommended choice of immunosuppressive agent 3.
- Patients with anti-HMGCR IMNM tend to respond well to intravenous immunoglobulin (IVIG), and IVIG monotherapy may be sufficient treatment for certain patients 3.
- In anti-SRP IMNM, early rituximab is commonly favored 3.
- Facial weakness is more common in SRP-IgG-positive patients, while myotonic discharges are more common in statin-associated NAM 2.
Treatment and Outcomes
- Prompt initiation of aggressive immunosuppression is often indicated, as both anti-SRP and anti-HMGCR IMNM can potentially cause debilitating weakness, and muscle atrophy and irreversible fatty replacement happen early in the disease course 3.
- Patients with NAM frequently require combination therapy to achieve disease control, and have a high rate of relapse when tapering immunosuppression 2, 5.
- Predictors of favorable outcome include male sex and use of 2 or more immunotherapeutic agents within 3 months of onset 2.
- Treatment is based on corticosteroid therapy, immunosuppressive drugs, or intravenous immunoglobulins, with variable response depending on the clinical form 4.