INVITED REVIEW ABSTRACT:Rhabdomyolysis,a syndrome of skeletal muscle breakdown
with leakage of muscle contents,is frequently accompanied by myoglobin-
uria,and if sufficiently severe,acute renal failure with potentially life-
threatening metabolic derangements may ensue.A diverse spectrum of
inherited and acquired disorders affecting muscle membranes,membrane
ion channels,and muscle energy supply causes rhabdomyolysis.Common
final pathophysiological mechanisms among these causes of rhabdomyoly-
calcium-dependent proteases,which lead to destruction of myofibrils and
lysosomal digestion of muscle fiber contents.Recent advances in molecular
genetics and muscle enzyme histochemistry may enable a specific meta-
bolic diagnosis in many patients with idiopathic recurrent rhabdomyolysis.
?2002Wiley Periodicals,Inc.Muscle Nerve25:332–347,2002 RHABDOMYOLYSIS:A REVIEW
JASON D.WARREN,BMedSc,MB,BS,FRACP,1
PETER C.BLUMBERGS,MB,BS,FRACP,2and
PHILIP D.THOMPSON,MB,BS,PhD,FRACP1,3
1Department of Neurology,University of Adelaide,Royal Adelaide Hospital,
Adelaide,South Australia,Australia
2Department of Neuropathology,Institute of Medical and Veterinary Science,
Adelaide,South Australia,Australia
3Department of Medicine,University of Adelaide,Royal Adelaide Hospital,North
Terrace,Adelaide,South Australia5000,Australia
Accepted17October2001
R habdomyolysis,literally“dissolution of striped [skeletal]muscle,”146is caused by a variety of mecha-nisms affecting myocytes and muscle membranes. These range from direct muscle injury to genetic and biochemical influences that alter the integrity of muscle membranes.Rhabdomyolysis leads to leak-age of muscle cell contents,including the oxygen-binding muscle protein myoglobin.Myoglobinuria (increased urinary excretion of myoglobin)is used interchangeably with rhabdomyolysis and is the most important consequence of significant muscle break-down.
Rhabdomyolysis is a syndrome of great antiquity. The first recorded reference appears in the Book of Numbers,where it is related that the Israelites became ill and died after eating quail,which had probably fed on hemlock seeds.12,152Epidemics of myoglobin-uria in the Baltic area in the1930s(Haff disease) may have been due to eating contaminated fish.7 Interest in rhabdomyolysis was stimulated by crush injuries with acute myoglobinuric renal failure sus-tained by civilians during the London Blitz22and, more recently,the recognition of exercise-related hyperthermic syndromes such as“white collar rhab-domyolysis,”71,80raver’s hematuria,149and the “pseudo-crush”syndrome in torture victims.13Of the many disease processes that cause rhabdomyolysis (Tables1and2),metabolic myopathies are increas-ingly recognized.139,148,153In a significant propor-tion of cases of recurrent rhabdomyolysis,no cause can be identified.51
CLINICAL FEATURES
The clinical syndrome of rhabdomyolysis comprises acute muscle necrosis with swollen,tender muscles and limb weakness.Myalgia may be accompanied by dark“tea-colored”urine indicating myoglobinuria. The extent of weakness varies considerably and rhab-domyolysis must be distinguished from other causes of severe,widespread muscular weakness,including nonnecrotizing acute myopathies,critical illness my-opathy,periodic paralysis,and Guillain–Barre′syn-drome.35In crush injuries and prolonged immobil-
Abbreviations:ATP,adenosine triphosphate;CK,creatine kinase;CPT, carnitine palmitoyl transferase;HIV,human immunodeficiency;MAOI, monoamine oxidase inhibitor;MCAD,medium-chain acyl-coenzyme A dehydrogenase;MH,malignant hyperthermia
Key words:fatty acid oxidation disorders;hyperthermic syndromes; metabolic myopathy;rhabdomyolysis
Correspondence to:P.D.Thompson;e-mail:philip.thompson@adelaide. edu.au
?2002Wiley Periodicals,Inc.
Published online1February2002;DOI10.1002/mus.10053
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