This study assessed routine laboratory test results in a comparatively large referral population of the IIM at various stages of illness to identify possible associations with disease not previously noted, to determine if laboratory test values vary among gender, racial, age and clinical groups, and to define possible correlations among these tests.
It is commonly accepted that CK, aldolase, ALT, AST, and LD are muscle-derived enzymes in myositis whose levels tend to indicate disease activity [3
]. Thus, not surprisingly, patients with PM, who typically have more severe muscle disease, were found to have higher levels of these enzymes than DM patients [1
]. Another possible explanation, however, is that patients with DM more frequently have circulating inhibitors or autoantibodies to CK or to other enzymes and these autoantibodies may result in lower serum enzyme levels [19
In terms of the sex differences, males have higher elevations in enzymes (including CK, CK-MB, CK-MM, aldolase and transaminases) compared to females reflecting their greater average muscle mass [21
]. The reasons for the lower immunoglobulin levels and lymphocyte counts in men than in women and higher WBCs in men remain unclear. In the general population, men have higher hematocrit levels and lower ESR levels compared to women [22
]. Leukocytosis has been associated with low-grade fever at the onset of myositis and in association with disease flares in certain groups [8
]. Different tests were also found to vary with respect to race. It had been known that CK levels tend to be higher in blacks than Caucasians, likely as a result of greater muscle mass in the former [13
Regarding the previously unreported abnormalities, although gender was an important determinant of hematocrit, we found that hematocrit is lower in DM than PM. Because PM tends to present with more severe disease activity than DM [1
], a lower hematocrit as a result of the anemia of chronic disease might have been expected more often in PM patients. Perhaps because DM has more vasculopathy than PM [1
], there might be less capacity to produce red blood cells or more gastrointestinal or other bleeding in DM. The more frequent vasculopathy seen in DM compared to PM [1
], with resultant capillary leak in damaged capillaries in muscle and other target organs or abnormal gastrointestinal absorption, may be the etiology of lower serum albumin, which is a negative acute-phase protein, in patients with DM than in PM. Hematocrits were also higher in Caucasians compared to blacks, in patients >50 years of age, and in PM. Higher hematocrits were reported in healthy populations of Caucasians compared to blacks in both gender groups, but the same study failed to reveal a major age effect [18
We also noted significant correlations among various laboratory findings in the IIM. Moderate to high correlations were observed among aldolase and ALT, AST, CK, LD, myoglobin, Polys, and WBC. Thus, muscle enzymes and muscle breakdown products all correlated highly, as expected. Muscle enzyme levels may be increased in patients with active disease not only due to skeletal muscle inflammation, but also due to release of these enzymes into the peripheral blood by regenerating myoblasts. CK-MB, aldolase, LD and other enzymes are known to be produced by myoblasts [24
The significant but low correlations of WBC and Polys with muscle enzyme levels and muscle metabolites such as myoglobin were unexpected. However, CK is expressed in WBC, including macrophages [28
], as well as in endothelial cells [30
], and LD is also expressed by T and B lymphocytes [31
]. Thus, while CK and LD may be increased due to active myositis and may correlate on that basis, there may also be several tissue sources outside the muscle for these enzymes, providing additional rationale for their correlation with WBC and other tests.
Although attempts were made to avoid possible confounding in all aspects of the study, there are limitations to the approaches used in this retrospective investigation. First, the data may not be reflective of a typical IIM population as subjects referred to the NIH may have more severe disease or were taking more medications that could have influenced the laboratory results. Second, missing data were inevitable in this retrospective approach, although adequate numbers existed for nearly all of the studies to allow for an appropriately powered analysis. Additionally, possible factors that could have also impacted the laboratory findings that could not be directly investigated in this retrospective study included: variations in clinical disease activity; the degree of muscle damage; disease duration; myositis autoantibodies; concomitant illnesses; lung or cardiac or other organ system involvement related to myositis; and medications or other treatment regimens. All of these important factors should be included in future prospective investigations in this area.
Nonetheless, this is the first study undertaken to describe the range of common laboratory findings from a comparatively large sample of myositis patients, in various myositis phenotypes, and involving a large number of variables. The results also serve as the foundation for future research in developing guidance to clinicians in diagnosing myositis via laboratory tests. The close correlation of some of these tests, particularly CK levels and transaminases, lactate dehydrogenase and aldolase, allow for assessment of the expected ranges of abnormalities and better guidance as to when additional evaluation for possible liver or other disease is indicated.