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DOI: 10.1055/s-0043-124361
Differential Diagnosis of HyperCKemia
Publikationsverlauf
Publikationsdatum:
07. März 2018 (online)
![](https://www.thieme-connect.de/media/10.1055-s-00033101/201801/lookinside/thumbnails/134_10-1055-s-0043-124361-1.jpg)
Abstract
Elevated serum creatine kinase (CK) activity is usually an indicator of muscle damage. HyperCKemia is often an incidental finding and should be controlled after refraining from physical activity for some days, especially in asymptomatic patients. Furthermore, data from recent studies indicate that the upper limits of normal (ULN) need to be revised upward. This review includes an algorithm for the differential diagnosis of CK elevation in patients without muscular symptoms. In the field of neurology, in particular myopathies and neuropathies with affection of the lower motor neuron can cause symptomatic hyperCKemia, with CK values >1000 U/l (16,7 µkat/l) being indicative of a primary muscle disorder. Diseases with very high CK values include subtypes of muscular dystrophies, idiopathic inflammatory myopathies and metabolic myopathies. However, a normal or only slightly elevated CK value does not exclude the presence of a myopathy. The individual diagnostic procedure (e. g., muscle imaging, special laboratory studies, muscle biopsy and genetic testing) depends on the clinical phenotype and the results of electrophysiological studies. HyperCKemia can also be an adverse effect of several drugs including statins. In asymptomatic patients, statin-associated CK elevations <5 times the ULN can be tolerated. In patients with higher CK values and/or muscle symptoms, LDL-cholesterol lowering therapy should be changed. Rhabdomyolysis is a potentially life-threatening condition and is accompanied by highly elevated CK values. Acute phase treatment includes preserving renal function and restoring metabolic derangements.
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References
- 1 Abraham A, Albulaihe H, Alabdali M. et al. Frequent laboratory abnormalities in CIDP patients. Muscle Nerve 2016; 53: 862-865
- 2 Ahmad Z. Statin intolerance. Am J Cardiol 2014; 113: 1765-1771
- 3 Argov Z. Statins and the neuromuscular system: a neurologist’s perspective. Eur J Neurology 2015; 22: 31-36
- 4 Berciano J, Garcia A, Peeters K. et al. NEFL E396K mutation is associated with a novel dominant intermediate Charcot-Marie-Tooth disease phenotype. J Neurol 2015; 262: 1289-1300
- 5 Bosch X, Poch E, Grau JM. Rhabdomyolysis and acute kidney injury. N Engl J Med 2009; 361: 62-72
- 6 Brewster LM, Mairuhu G, Sturk A. et al. Distribution of creatine kinase in the general population: implications for statin therapy. Am Heart J 2007; 154: 655-661
- 7 Cardon MW. 50 years ago in the Journal of Pediatrics: an assessment of the creatine kinase test in the detection of carriers of Duchenne muscular dystrophy. J Pediatrics 2017; 186: 63
- 8 Dabby R, Sadeh M, Herman O. et al. Asymptomatic or minimally symptomatic hyperCKemia: histopathologic correlates. Isr Med Assoc J 2006; 8: 110-113
- 9 D'Adda E, Sciacco M, Fruguglietti ME. et al. Follow-up of a large population of asymptomatic/oligosymptomatic hyperckemic subjects. J Neurol 2006; 253: 1399-1403
- 10 Deschauer M, Wieser T, Zierz S. Muscle carnitine palmitoyltransferase II deficiency: clinical and molecular genetic features and diagnostic aspects. Arch Neurol 2005; 62: 37-41
- 11 Dobloug C, Garen T, Bitter H. et al Prevalence and clinical characteristics of adult polymyositis and dermatomyositis; data from a large and unselected Norwegian cohort. Ann Rheum Dis 2015; 74: 1551-1556
- 12 Dräger B, Young P. Pragmatische Diagnostik hereditärer Neuropathien. Akt Neurol 2016; 43: 256-266
- 13 Dubowitz V. The female carrier of Duchenne muscular dystrophy. Br Med J (Clin Res Ed) 1982; 284: 1423-1424
- 14 Echaniz-Laguna A, Dubourg O, Carlier P. et al. Phenotypic spectrum and incidence of TRPV4 mutations in patients with inherited axonal neuropathy. Neurology 2014; 82: 1919-1926
- 15 Fernandez C, de Paula AM, Figarella-Branger D. et al Diagnostic evaluation of clinically normal subjects with chronic hyperCKemia. Neurology 2006; 66: 1585-1587
- 16 Filosto M, Tonin P, Vattemi G. et al. The role of muscle biopsy in investigating isolated muscle pain. Neurology 2007; 68: 181-186
- 17 Ghosh PS, Lahoria R, Milone M. et al. Pearls & Oysters: HyperCKemia with limb-girdle weakness: Think beyond myopathies. Neurology 2014; 83: e209-e212
- 18 Gibson SB, Kasarskis EJ, Hu N. et al. Relationship of creatine kinase to body composition, disease state, and longevity in ALS. Amyotroph Lateral Scler Frontotemporal Degener 2015; 16: 473-477
- 19 Hattori N, Yamamoto M, Yoshihara T. et al. Demyelinating and axonal features of Charcot-Marie-Tooth disease with mutations of myelin-related proteins (PMP22, MPZ and Cx32): a clinicopathological study of 205 Japanese patients. Brain 2003; 126: 134-151
- 20 Hørder M, Elser RC, Gerhardt W. et al. International federation of clinical chemistry, scientific division committee on enzymes: approved recommendation on IFCC methods for the measurement of catalytic concentration of enzymes. Part 7. IFCC method for creatine kinase (ATP: creatine N-phosphotransferase, EC 2.7.3.2). Eur J Clin Chem Clin Biochem 1991; 29: 435-456
- 21 Joy JL, Oh SJ. Asymptomatic hyper-CK-emia: an electrophysiologic and histopathologic study. Muscle Nerve 1989; 12: 206-209
- 22 Karabul N, Kruijshaar ME, Schober A. et al. Pain in adult patients with Pompe disease. Mol Gen Metab Rep 2014; 1: 139-140
- 23 Kley RA, van der Ven Hellenbroich Y, Peter FM. et al. Clinical and morphological phenotype of the filamin myopathy: a study of 31 German patients. Brain 2007; 130: 3250-3264
- 24 Koeks Z, Bladen CL, Salgado D. et al. Clinical outcomes in Duchenne muscular dystrophy: a study of 5345 patients from the TREAT-NMD DMD Global Database. 2017; 4: 293-306
- 25 Kyriakides T, Angelini C, Schaefer J. et al. EFNS guidelines on the diagnostic approach to pauci- or asymptomatic hyperCKemia. Eur J Neurol 2010; 17: 767-773
- 26 Lane R, Phillips M. Rhabdomyolysis. BMJ 2003; 327: 115-116
- 27 Lee SH, Lee JH, Lee KA. et al. Clinical and genetic characterization of female dystrophinopathy. J Clin Neurol 2015; 11: 248-251
- 28 Lev EI, Tur-Kaspa I, Ashkenazy I. et al. Distribution of serum creatine kinase activity in young healthy persons. Clin Chim Acta 1999; 279: 107-115
- 29 Leverenz D, Zaha O, Crofford LJ. et al. Causes of creatine kinase levels greater than 1000 IU/L in patients referred to rheumatology. Clin Rheumatol 2016; 35: 1541-1547
- 30 Lilleng H, Abeler K, Johnsen SH. et al. Variation of serum creatine kinase (CK) levels and prevalence of persistent hyperCKemia in a Norwegian normal population. The Tromsø Study. Neuromuscul Disord 2011; 21: 494-500
- 31 Lilleng H, Johnsen SH, Wilsgaard T. et al. Are the currently used reference intervals for creatine kinase (CK) reflecting the general population? The Tromsø Study. Clin Chemistry Laboratory Med 2012; 50: 879-884
- 32 Limaye V, Bundell C, Hollingsworth P. et al. Clinical and genetic associations of autoantibodies to 3-hydroxy-3-methyl-glutaryl-coenzyme a reductase in patients with immune-mediated myositis and necrotizing myopathy. Muscle Nerve 2015; 52: 196-203
- 33 Lopate G, Streif E, Harms M. et al. Cramps and small-fiber neuropathy. Muscle Nerve 2013; 48: 252-255
- 34 Malandrini A, Orrico A, Gaudiano C. et al. Muscle biopsy and in vitro contracture test in subjects with idiopathic HyperCKemia. Anesthesiology 2008; 109: 625-628
- 35 McGrowder DA, Fraser YP, Gordon L. et al. Serum creatine kinase and lactate dehydrogenase activities in patients with thyroid disorders. Niger J Clin Pract 2011; 14: 454-459
- 36 McKenney JM, Davidson MH, Jacobson TA. et al. Final conclusions and recommendations of the National Lipid Association Statin Safety Assessment Task Force. Am J Cardiol 2006; 97: 89C-94C
- 37 Melli G, Chaudhry V, Cornblath DR. Rhabdomyolysis: an evaluation of 475 hospitalized patients. Medicine 2005; 84: 377-385
- 38 Moghadam-Kia S, Oddis CV, Aggarwal R. Approach to asymptomatic creatine kinase elevation. Cleve Clin J Med 2016; 83: 37-42
- 39 Molster CM, Lister K, Metternick-Jones S. et al. Outcomes of an international workshop on preconception expanded carrier screening: some considerations for governments. Frontiers Public Health 2017; 5: 25
- 40 Mosshammer D, Schaeffeler E, Schwab M. et al. Mechanisms and assessment of statin-related muscular adverse effects. Br J Clin Pharmacology 2014; 78: 454-466
- 41 Nardin RA, Zarrin AR, Horowitz GL. et al. Effect of newly proposed CK reference limits on neuromuscular diagnosis. Muscle Nerve 2009; 39: 494-497
- 42 Nicholson GA, McLeod JG, Morgan G. et al. Variable distributions of serum creatine kinase reference values. Relationship to exercise activity. J Neurol Sci 1985; 71: 233-245
- 43 Norwood FLM, Harling C, Chinnery PF. et al. Prevalence of genetic muscle disease in Northern England: in-depth analysis of a muscle clinic population. Brain 2009; 132: 3175-3186
- 44 Parker BA, Capizzi JA, Grimaldi AS. et al. Effect of statins on skeletal muscle function. Circulation 2013; 127: 96-103
- 45 Prelle A, Tancredi L, Sciacco M. et al. Retrospective study of a large population of patients with asymptomatic or minimally symptomatic raised serum creatine kinase levels. J Neurol 2002; 249: 305-311
- 46 Reijneveld JC, Notermans NC, Linssen WH. et al. Benign prognosis in idiopathic hyper-CK-emia. Muscle Nerve 2000; 3: 575-579
- 47 Reiner Z, Catapano AL, de Backer G. et al ESC/EAS Guidelines for the management of dyslipidaemias: the task force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS). Eur Heart J 2011; 32: 1769-1818
- 48 Rhodes LE, Freeman BK, Auh S. et al. Clinical features of spinal and bulbar muscular atrophy. Brain 2009; 132: 3242-3251
- 49 Riphagen IJ, van der Veer E, Muskiet FAJ. et al. Myopathy during statin therapy in the daily practice of an outpatient cardiology clinic: prevalence, predictors and relation with vitamin D. Curr Med Res Opin 2012; 28: 1247-1252
- 50 Rommel O, Kley RA, Dekomien G. et al. Muscle pain in myophosphorylase deficiency (McArdle's disease): the role of gender, genotype, and pain-related coping. Pain 2006; 124: 295-304
- 51 Ropper AH, Shahani BT. Pain in Guillain-Barre syndrome. Arch Neurol 1984; 41: 511-514
- 52 Rudnik-Schoneborn S, Lutzenrath S, Borkowska J. et al. Analysis of creatine kinase activity in 504 patients with proximal spinal muscular atrophy types I-III from the point of view of progression and severity. Eur Neurol 1998; 39: 154-162
- 53 Schneider C, Reiners K, Toyka KV. Myotone Dystrophie (DM/Curschmann-Steinert-Erkrankung) und proximale myotone Myopathie (PROMM/Ricker-Syndrom). Myotone Muskelerkrankungen mit multisystemischen Manifestationen (Myotonic dystrophy (DM/Curschmann-Steinert disease) and proximal myotonic myopathy (PROMM/Ricker syndrome). Myotonic muscle diseases with multisystemic manifestations). Nervenarzt 2001; 72: 618-624
- 54 Schumann G, Bonora R, Ceriotti F. et al. IFCC primary reference procedures for the measurement of catalytic activity concentrations of enzymes at 37 degrees C. Part 2. Reference procedure for the measurement of catalytic concentration of creatine kinase. Clin Chem Lab Med 2002; 40: 635-642
- 55 Simmons Z, Peterlin BL, Boyer PJ. et al. Muscle biopsy in the evaluation of patients with modestly elevated creatine kinase levels. Muscle Nerve 2003; 27: 242-244
- 56 Soraru G, D’Ascenzo C, Polo A. et al. Spinal and bulbar muscular atrophy: skeletal muscle pathology in male patients and heterozygous females. J Neurol Sci 2008; 264: 100-105
- 57 Stroes ES, Thompson PD, Corsini A. et al. Statin-associated muscle symptoms: impact on statin therapy-European Atherosclerosis Society Consensus Panel Statement on Assessment, Aetiology and Management. Eur Heart J 2015; 36: 1012-1022
- 58 Talameh JA, Kitzmiller JP. Pharmacogenetics of statin-induced myopathy: a focused review of the clinical translation of pharmacokinetic genetic variants. J Pharmacogenomics Pharmacoproteomics 2014; DOI: 10.4172/2153-0645.1000128.
- 59 Thompson MW, Murphy EG, McAlpine PJ. An assessment of the creatine kinase test in the detection of carriers of Duchenne muscular dystrophy. J Pediatrics 1967; 71: 82-93
- 60 Unger A, Dekomien G, Guttsches A. et al. Expanding the phenotype of BICD2 mutations toward skeletal muscle involvement. Neurology 2016; 87: 2235-2243
- 61 Urdal P, Urdal K, Strømme JH. Cytoplasmic creatine kinase isoenzymes quantitated in tissue specimens obtained at surgery. Clin Chemistry 1983; 29: 310-313
- 62 Villamar López M, Azpeitia González J, Ayuso García C. et al. Modificación del cálculo de riesgo en posibles mujeres portadoras de distrofia muscular de Duchenne (DMD) basado en niveles de CPK (Modification of the calculation of risk factors in women, possible carriers of Duchenne muscular dystrophy, based on CPK levels). An Esp Pediatr 1992; 37: 191-194
- 63 Weglinski MR, Wedel DJ, Engel AG. Malignant hyperthermia testing in patients with persistently increased serum creatine kinase levels. Anesth Analg 1997; 84: 1038-1041
- 64 Zhang Y, Huang J, Wang Z. et al. Value of muscle enzyme measurement in evaluating different neuromuscular diseases. Clin Chim Acta 2012; 413: 520-524
- 65 Zutt R, van der Kooi AJ, Linthorst GE. et al. Rhabdomyolysis: review of the literature. Neuromuscul Disord 2014; 24: 651-659