Differential Diagnosis of HyperCKemia

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.

Pain during and after COVID-19 in Germany and worldwide: a narrative review of current knowledge

“…However, the relatively low cut-off value of >200 U/L, which was used to define the CK increase, 52 does not allow the differentiation between myogenic or neurogenic origin, because a slight increase in CK might also be related to neuropathies of a different origin, whereas in the course of myositis, significantly higher serum CK concentrations are usually expected. 43 From a pathomechanistic point of view, both direct nerve and muscle affection as well as an autoimmune reaction might potentially play a role. A SARS–CoV-induced cytokine storm could be hypothesized as one possible underlying mechanism for the symptom complex of persistent myalgia and fatigue while also explaining other symptoms such as parainfectious headache and joint pain.…”

Membrane Repair Deficit in Facioscapulohumeral Muscular Dystrophy

“…However, with rather low DUX4 expression in the absence of cre recombinase, FLExDUX4 mice show no sign of spontaneous sarcolemmal fragility (no increase in serum creatine kinase level at rest), similar to humans with FSHD. Indeed, serum creatine kinase is usually only slightly or moderately elevated in patients when measured at rest, providing further evidence that FSHD may not be characterized by an unstable or fragile sarcolemma despite previous reports of sarcolemmal structural abnormalities identified in patient biopsies [13][14][15]52]. Instead, the deficits in sarcolemmal repair we identified may compromise recovery from muscle injury, or conditions in which muscle strain results in disruption of the plasma membrane [53].…”

“…Current evidence suggests that repeated cycles of muscle damage, necrosis, and regeneration contribute to the development of fibrosis and intramuscular fat-common pathological features of FSHD that can contribute to impaired muscle performance [11,12]. However, in many patients with FSHD, plasma CK (a measure of muscle damage) levels are only slightly (<600 U/L) or moderately elevated (600-1500 U/L) [13][14][15] when measured at rest, and can be variable from day to day based on the individual's level of physical activity [16,17]. The lower levels of plasma CK at rest indicate that FSHD is not characterized by baseline muscle fragility (as is found in Duchenne Muscular Dystrophy), but instead may demonstrate impaired responses to larger stresses-especially those that damage the sarcolemma.…”

An integrated approach to the evaluation of patients with asymptomatic or minimally symptomatic hyperCKemia

“…Patients exhibiting the acute or subacute onset of muscle weakness or a rapid disease course were suspected of having inflammatory myopathy and were required to undergo a specific work‐up 28 . The medical causes of hyperCKemia, such as statins or other drug‐based treatment associated with CK elevation, abnormalities in thyroid function, and other endocrine or metabolic causes, were ruled out 29 . Furthermore, we excluded patients with primary involvement of the respiratory or cardiac system.…”