From the Guidelines
Rhabdomyolysis is most commonly associated with myositis, a rare but severe complication of immune checkpoint inhibitor (ICPi) therapy.
Rheumatological Etiology of Rhabdomyolysis
- Myositis is a rare complication of ICPi therapy, but can be severe and fatal, and is more common with anti–PD-1/PD-L1 than with anti–CTLA-4 agents 1.
- The main symptom of inflammatory myositis is weakness, primarily in the proximal extremities, with difficulties in standing up, lifting arms, and moving around, and can have a fulminant necrotizing course with rhabdomyolysis 1.
- Myositis can involve the myocardium, in which case it requires urgent treatment to avoid fatal complications 1.
- Other rheumatological conditions, such as polymyalgia-like syndromes and arthritis, can also occur in patients receiving ICPi therapy, but are less likely to cause rhabdomyolysis 1.
- Statin-induced myopathy is another potential cause of rhabdomyolysis, and patients with unexplained severe muscle symptoms or fatigue while on statin therapy should be promptly evaluated for rhabdomyolysis 1.
- The management of rhabdomyolysis involves prompt discontinuation of the offending agent, aggressive fluid resuscitation, and monitoring for complications such as acute kidney injury 1.
From the Research
Rheumatological Etiology of Rhabdomyolysis
The rheumatological etiology of rhabdomyolysis is associated with various diseases, injuries, medications, and toxins that cause the breakdown of skeletal muscle tissue.
- The development of rhabdomyolysis is linked to direct injury or metabolic inequalities between energy consumption and energy production 2.
- Rhabdomyolysis can be caused by hereditary muscle enzyme defects, muscle hypoxia, metabolic and endocrine disorders, infections, temperature alterations, and miscellaneous causes 3.
- Inherited causes of rhabdomyolysis include metabolic disorders, such as mitochondrial fatty acid ß-oxidation defects, LPIN1 mutations, and inborn errors of glycogenolysis and glycolysis, as well as structural causes like muscle dystrophies and myopathies 4.
Pathophysiology of Rhabdomyolysis
The pathophysiology of rhabdomyolysis involves the breakdown of skeletal muscle fibers, leading to the leakage of potentially toxic cellular content into the systemic circulation.
- The pathology of rhabdomyolysis follows a common pathway, either by direct injury to the sarcolemma or by the failure of energy production, which leads to fiber necrosis 4.
- Rhabdomyolysis can be precipitated by febrile illness or exercise, which are associated with elevated temperature and high circulating levels of pro-inflammatory mediators such as cytokines and chemokines 4.
Diagnosis and Treatment of Rhabdomyolysis
The diagnosis of rhabdomyolysis is confirmed by elevations in serum creatine phosphokinase (CPK) and myoglobin levels, as well as the presence of myoglobinuria.
- The treatment of rhabdomyolysis involves hospitalization with aggressive intravenous fluid resuscitation and the correction/prevention of electrolyte abnormalities 2.
- Early and aggressive fluid replacement using crystalloid solution is the cornerstone for preventing and treating acute kidney injury (AKI) due to rhabdomyolysis 5.