Creatine Kinase – How High is Too High?

Cardiologists and rheumatologists have one common bond – we pay attention to elevations in creatine kinase (CK). But how high does this value have to be for us, as rheumatologists, to become really excited?

Typically, rheumatologists get referrals for patients with CK values > 1000 IU/L. Sometimes, it is debatable why a CK was measured in the first place. Patients may be asymptomatic, have complained of non-specific symptoms such as fatigue, or have had vague complaints of "weakness." Other patients may have clear symptoms of an inflammatory myopathy such as symmetrical muscle weakness, or a rash typical of dermatomyositis. However, this is not always the case, and often it is up to the rheumatologist to extract these clinical symptoms and signs when assessing a patient. But how many of these patients referred with an elevated CK who don't have a prior diagnosis of an inflammatory myopathy go on to develop an autoimmune inflammatory myopathy?

David Leverenz and his group from Vanderbilt University (poster abstract #300) identified patients from their database who had a CK > 1000 IU/L, were 18 years of age or older, and whose charts contained the word "rheumatology." Patients were excluded if the rheumatology involvement was not related to the elevation in CK. Overall, 192 patients were identified and determined to have an inflammatory myopathy if they fulfilled the Bohan and Peter criteria for dermatomyositis and polymyositis, the Grigg's criteria for inclusion body myositis, or by clinical diagnosis for patients with an overlap syndrome, necrotizing myopathy, or DM/PM not meeting classification criteria.

Fifty-five percent of patients were diagnosed with an inflammatory myopathy, the majority being diagnosed with dermatomyositis, polymyositis or an overlap syndrome. Less than 1% were diagnosed as having inclusion body myositis. Non-inflammatory myopathy causes of an elevation in CK included drug or toxin exposures (8%), infection (6%), trauma (5%), myocardial injury (3%), hypothyroidism (2%), and muscular dystrophy (2%), among others; and 6% of cases were idiopathic. Patients with inflammatory myopathies were significantly younger, female, had symptoms for > 6 months, had an ANA > 1:40, and 11% had a positive Jo-1 antibody. Patients without an inflammatory myopathy had more cardiac and renal dysfunction. Interestingly, there was no significant difference in CK levels between patients with inflammatory and non-inflammatory causes of elevated CK.

So what is the take home message? In this cohort, more than half of the patients referred with an elevated CK went on to have an underlying rheumatological diagnosis of an inflammatory myopathy. I think we can all agree that CK values > 1000 IU/L are significant. However, the clinical context is always important when evaluating these patients, and aspects such as the presence of weakness, ingested drugs or toxins, as well as the time course of CK elevation (i.e., persistently elevated) are also important. The take home message is that rheumatologists should have a low threshold to evaluate patients with a significant elevation in their CK levels. A grey area would be situations involving patients with a CK < 1000 IU/L (e.g., 500-600 IU/L), which may be more in keeping with a metabolic myopathy or inclusion body myositis. But once again, a good history and physical exam can help distinguish between these diagnoses.

More reports from ACR 2015