Understanding Drug-Induced Myositis
Myositis is a general term for inflammation of the muscles. While it can result from infections, injuries, or autoimmune conditions, a significant number of cases are triggered by medications [1.2.5]. This is known as drug-induced myositis or myopathy. The clinical presentation can range from mild muscle aches (myalgia) and weakness to severe, life-threatening conditions like rhabdomyolysis, where muscle tissue breaks down rapidly [1.3.4]. Several criteria help determine if myositis is drug-induced: the absence of muscle symptoms before starting the drug, symptom onset after treatment begins, resolution of symptoms after discontinuing the medication, and a lack of other identifiable causes [1.4.2].
Common Symptoms and Diagnosis
The hallmark symptoms of drug-induced myositis include muscle pain, tenderness, and weakness, particularly in the proximal muscles around the shoulders, hips, and thighs [1.4.4, 1.4.5]. This can make everyday activities like climbing stairs, lifting objects, or even brushing your hair difficult [1.4.5]. Other general symptoms may include fatigue, night sweats, and unintentional weight loss [1.4.1, 1.4.5].
Diagnosis involves a combination of methods:
- Blood Tests A key indicator is an elevated level of creatine kinase (CK), an enzyme that leaks from damaged muscle cells [1.3.5]. Doctors may also test for specific autoantibodies, such as anti-HMGCR, which is strongly associated with statin-induced autoimmune myositis [1.3.1].
- Physical Examination A doctor will assess muscle strength and look for tenderness or swelling [1.4.4].
- Electromyography (EMG) This test measures the electrical activity of muscles and can reveal abnormalities consistent with myopathy [1.4.3].
- Muscle Biopsy In some cases, a small sample of muscle tissue is removed and examined under a microscope. This can reveal signs of inflammation, muscle fiber damage (necrosis), or other characteristic changes that help pinpoint the cause [1.3.5, 1.4.3].
Key Medications Known to Cause Myositis
A wide array of pharmaceuticals across different classes has been linked to myositis. The mechanisms, severity, and presentation can vary significantly depending on the drug.
Statins (HMG-CoA Reductase Inhibitors)
Statins, widely prescribed to lower cholesterol, are the most notorious group of drugs associated with myopathy [1.2.2]. The incidence of myopathy in patients taking statins can be as high as 27.8% in some populations [1.3.4]. Statin-associated muscle symptoms (SAMS) can manifest as myalgia, myositis, or a rare but severe immune-mediated necrotizing myopathy (IMNM) [1.3.2].
The proposed mechanisms for statin toxicity are complex. They are thought to involve mitochondrial dysfunction, reduced production of coenzyme Q10, and an autoimmune response where the body develops antibodies against the HMG-CoA reductase enzyme itself [1.6.1, 1.6.3, 1.6.5]. Risk factors include high statin doses, being of older age, and the use of lipophilic statins like simvastatin and atorvastatin, which penetrate muscle tissue more easily than hydrophilic statins like pravastatin and rosuvastatin [1.2.2, 1.3.4].
Immune Checkpoint Inhibitors (ICIs)
Used in cancer immunotherapy, ICIs like pembrolizumab, nivolumab, and ipilimumab have revolutionized cancer treatment but can cause a range of immune-related adverse events, including myositis [1.3.3, 1.7.2]. The overall incidence is low (less than 1%), but it is a serious and potentially fatal complication [1.3.3, 1.7.1]. ICI-myositis often presents acutely within the first month of therapy and can overlap with other serious conditions like myocarditis (heart muscle inflammation) and myasthenia gravis, significantly worsening the prognosis [1.7.2]. The mechanism involves the drug removing the natural 'brakes' on the immune system, leading to T-cells attacking healthy muscle tissue [1.7.4].
Other Implicated Medications
Beyond statins and ICIs, numerous other drugs can induce myopathy:
- Rheumatologic Agents: Colchicine (used for gout), D-penicillamine, hydroxychloroquine (Plaquenil), and TNF-alpha inhibitors have all been linked to myositis [1.2.1, 1.2.2]. Colchicine myopathy risk is higher in patients with renal impairment [1.10.1]. D-penicillamine can cause an inflammatory myopathy resembling polymyositis or dermatomyositis [1.3.5, 1.8.4].
- Antiretrovirals: Zidovudine (AZT), a drug used to treat HIV, is known to cause mitochondrial myopathy after long-term use, with an incidence of around 17% in treated patients [1.3.5, 1.9.2].
- Cardiovascular Agents: Amiodarone and procainamide are other drugs that have been reported to cause myopathy or a lupus-like syndrome with muscle involvement [1.2.1, 1.11.1].
- Corticosteroids: Long-term use of corticosteroids like prednisone can lead to steroid-induced myopathy, characterized by proximal muscle weakness, though typically with normal CK levels [1.3.5, 1.5.5].
| Drug Class | Examples | Typical Onset/Features | Risk Factors |
|---|---|---|---|
| Statins | Atorvastatin, Simvastatin, Rosuvastatin | Varies from mild myalgia to severe autoimmune myopathy [1.3.2]. | High dose, lipophilic statins, older age, certain genetics [1.2.2]. |
| Immune Checkpoint Inhibitors | Pembrolizumab, Nivolumab, Ipilimumab | Acute onset, often within 1 month of starting therapy [1.7.2]. | Combination therapy (e.g., CTLA-4 + PD-1 inhibitors) [1.7.2]. |
| Rheumatologic Agents | Colchicine, D-penicillamine, Hydroxychloroquine | Subacute weakness. Colchicine myopathy often has associated neuropathy [1.3.5, 1.10.1]. | Renal impairment (for colchicine), underlying autoimmune disease [1.10.1]. |
| Antiretrovirals | Zidovudine (AZT) | Long-term therapy (over 9 months) [1.9.1, 1.9.2]. | High cumulative dose [1.3.5]. |
| Corticosteroids | Prednisone, Dexamethasone | Slow, progressive weakness after long-term use [1.4.3, 1.5.5]. | High doses (>40mg/day prednisone equivalent) [1.5.5]. |
Management and Treatment
The primary step in managing drug-induced myositis is discontinuing the offending medication, if possible [1.5.1, 1.5.5]. For many patients, especially those with milder forms, symptoms will improve or resolve completely within weeks to months after stopping the drug [1.3.5].
However, for more severe or persistent cases, such as statin-induced autoimmune myopathy or ICI-myositis, further treatment is often necessary. This typically involves immunosuppressive therapy:
- Corticosteroids: High-dose steroids like prednisone are the first-line treatment to reduce inflammation [1.5.3, 1.5.4].
- Immunosuppressants: For those who do not respond to steroids or to help reduce the steroid dose, other immunosuppressive drugs like methotrexate, azathioprine, or mycophenolate mofetil may be used [1.5.2, 1.5.4].
- Intravenous Immunoglobulin (IVIG): IVIG is often effective, particularly for severe, refractory cases of immune-mediated necrotizing myopathy [1.5.2].
- Plasma Exchange (Plasmapheresis): In life-threatening situations, this procedure, which removes harmful antibodies from the blood, may be employed [1.5.5].
Physical therapy is also a crucial component of recovery, helping to maintain muscle function and range of motion [1.5.1, 1.5.3].
Conclusion
Drug-induced myositis is a recognized and potentially serious side effect of many common medications. While statins are the most well-documented cause, clinicians and patients should be aware of the risk associated with newer drug classes like immune checkpoint inhibitors and older drugs such as colchicine and zidovudine. Prompt recognition of symptoms like muscle weakness and pain, followed by appropriate diagnostic workup, is essential. The cornerstone of management is the withdrawal of the causative agent, though many patients with immune-mediated forms require immunosuppressive therapy to control the inflammatory process and regain muscle strength. You can find more authoritative information at The Myositis Association.
