Rhabdomyolysis is etiologically heterogeneous, most cases being apparently the result of acquired causes, such as mechanical or vascular damage.
Recurrent rhabdomyolysis preceded by exercise or infection is more likely to have an underlying metabolic defect,and strategic diagnostic procedures are warranted.
History and physical examination are likely to identify the acquired and drug-related forms.
However, one has to bear in mind that sometimes myoglobinuria with episodes of dark urine is ignored, and pronounced muscle pain after only light exercise is not considered as a sign of disease.
Screening for metabolic disorders (carnitine profile, amino acids, tandem mass spectrometry) may point in specific directions.
Muscle biopsy for histologic and biochemical analysis should be performed.
However, in a significant proportion of individuals, no cause of rhabdomyolysis can be identified.
Acquired causes of rhabdomyolysis
Excessive use of muscle force (e.g., sports, seizures, dystonia)
Muscle damage (e.g., crush, cold, ischemia, embolism)
Inflammatory myopathies (polymyositis, vasculitis)
Drug-related cases of rhabdomyolysis
- Induction of an autoimmune reaction (e.g., cyclosporine, penicillamine)
- Hypokalemia (amphotericin, caffeine)
- Membrane disruption (cimetidin, colchicine)
- Disturbance of Na/K ATPase (antidepressants, arsen, azathioprin, bezafibrates)
- Neuroleptic syndrome (all neuroleptics, lithium)
- Serotonergic syndrome (amphetamines, MAO-inhibitor, SSRI)
Metabolic-toxic causes of rhabdomyolysis
Defects of glucose/glycogen metabolism (e.g., McArdle disease, Tarui disease).
Deficiencies of the six enzymes involved in glycogen breakdown (phosphorylase, phosphorylase kinase, phosphofructokinase, phosphoglycerate kinase, phosphyglycerate mutase, lactate dehydrogenase) result in exercise intolerance and recurrent rhabdomyolysis.
Defects of lipid metabolism (carnitine deficiency).
Mitochondrial β-oxidation of long-chain fatty acids is a major source of energy production, particularly at times of stress or fasting.
Skeletal muscle can use carbohydrates or lipids as fuel, depending on the degree of activity.
At rest or during prolonged low-intensity exercise, about 70% of the energy requirement is met by the oxidation of long-chain fatty acids.
Two defects of lipid metabolism primarily affecting the skeletal muscle are known: carnitine palmitoyltransferase II deficiency and primary carnitine deficiency characterized by progressive proximal weakness and cardiomyopathy.
Defects of oxidative phosphorylation (complex II deficiency, complex III defect, cytochrome c oxidase deficiency)
Dystrophinopathies (Duchenne muscular dystrophy,Becker muscular dystrophy)