Laboratory Test Abnormalities are Common in Polymyositis and Dermatomyositis and Differ Among Clinical and Demographic Groups.
ABSTRACT Given the difficulties regarding the interpretation of common laboratory test results in polymyositis (PM) and dermatomyositis (DM) in clinical practice, we assessed their range of abnormalities, differences among phenotypes and interrelationships in a large referral population.
We retrospectively assessed 20 commonly measured blood laboratory tests in 620 well-defined PM/DM patients at different stages of illness and treatment to determine the frequency, range of abnormalities and correlations among clinical, gender, racial and age phenotypes.
Myositis patients at various stages of their disease showed frequent elevations of the serum activities of creatine kinase (51%), alanine aminotransferase (43%), aspartate aminotransferase (51%), lactate dehydrogenase (60%), aldolase (65%) and myoglobin levels (48%) as expected. Other frequent abnormalities, however, included elevated high white blood cell counts (36%), low lymphocyte counts (37%), low hematocrit levels (29%), low albumin levels (22%), high creatine kinase MB isoenzyme fractions (52%), high erythrocyte sedimentation rates (33%) and high IgM and IgG levels (16% and 18%, respectively). Many of these tests significantly differed among the clinical, gender, racial and age groups. Significant correlations were also found among a number of these laboratory tests, particularly in the serum activity levels of creatine kinase, the transaminases, lactate dehydrogenase and aldolase.
Laboratory test abnormalities are common in PM/DM. Knowledge of the range of these expected abnormalities in different myositis phenotypes, gender and age groups and their correlations should assist clinicians in better interpretation of these test results, allow for a clearer understanding what level of abnormality warrants further evaluation for liver or other diseases, and may avoid unnecessary laboratory or other testing.
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ABSTRACT: We retrospectively analyzed electromyogram (EMG), laboratory and clinical data of 93 patients with polymyositis (PM) to help improve early diagnostic accuracy. Data were collected from hospitalized patients who were diagnosed with PM between January 1, 2006 and April 1, 2010 at Chinese People's Liberation Army General Hospital. Eighty-six (92.47%) patients exhibited an isolated myopathic EMG pattern, 3 (3.23%) showed myopathy combined with neuropathy and 1 (1.08%) had diabetes mellitus. Among the 4 without myopathic EMG, 1 had inflammatory myopathy, and 3 had prior corticosteroid treatment with clinical improvement before EMG examination. Muscle biopsy, performed in 40 cases, inclusive of the 7 cases that did not show an isolated myopathic EMG patterns, revealed that 80% exhibited typical pathological features of PM, 17.5% showed nonspecific muscle fiber necrosis and 2.5% were normal. EMG showed that tibialis anterior and biceps brachii exhibited more abnormal EMG results than abductor pollicis brevis. Patients with disease duration >3 months had significantly higher alanine aminotransferase and reduced motor unit potential (MUP) amplitudes compared to patients with shorter disease duration. Statistical analysis revealed a significant association between disease duration and MUP amplitude reduction. Patients without interstitial lung disease showed significantly longer disease duration and higher creatine kinase and lactate dehydrogenase levels than patients with interstitial lung disease. Our results show that MUP is a sensitive yardstick for diagnosis of PM and is inversely related to disease duration. Our study also highlights that selecting specific muscles for EMG may improve diagnostic accuracy in PM.The American Journal of the Medical Sciences 02/2014; · 1.52 Impact Factor
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ABSTRACT: Despite multiple reports of elevated transaminases in muscle injury, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) are not always considered indicators of muscle damage. The purpose of this study was to examine the relationship between serum AST, ALT, and creatine kinase (CK) levels at time of diagnosis of idiopathic inflammatory myopathy (IIM) and at the time of CK normalization. We conducted a retrospective chart review of all adult patients attending rheumatology clinics at a county hospital with a diagnosis of IIM. Data collected included patient demographics, serial CK measurements, and serial serum transaminase measurements. We identified 85 patients with IIM. At myositis presentation, 75 (88%) had CK above the upper limit of normal (ULN), 72 (85%) had AST above the ULN, and 68 (80%) had ALT above the ULN. The average CK was 5302 U/L (range, 23-38,461 U/L [SD, 7096]), average AST 215 U/L (range, 16-1270 [SD, 227]), and average ALT 137 U/L (range, 10-621 [SD, 137]). The average AST and ALT at first available normalized CK was 26 U/L (range, 9-139 [SD, 18]) and 26 U/L (range, 5-96 [SD, 19]). We found a strong correlation between CK and AST (r= 0.832; P < 0.001) and ALT (r = 0.775; P < 0.001) at initial presentation and also at the time of peak CK levels (r = 0.874 [P < 0.001] and r = 0.842 [P < 0.001], respectively). In our series, we found a strong correlation between CK and serum transaminases. Serum transaminases were elevated in 80% of patients at the time of presentation and normalized in 85% of the patients at the time of CK normalization. Appropriate recognition of these laboratory changes in IIM may help reduce unnecessary hepatic evaluation, delayed diagnosis, unnecessary avoidance of second line immunosuppressants, and misdiagnosis of primary liver disease.Journal of clinical rheumatology: practical reports on rheumatic & musculoskeletal diseases 04/2014; 20(3):130-2. · 1.19 Impact Factor
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ABSTRACT: Clinical registries and biorepositories have proven extremely useful in many studies of diseases, especially rare diseases. Given their rarity and diversity, the idiopathic inflammatory myopathies, or myositis syndromes, have benefited from individual researchers' collections of cohorts of patients. Major efforts are being made to establish large registries and biorepositories that will allow many additional studies to be performed that were not possible before. Here, we describe the registries developed by investigators and patient support groups that are currently available for collaborative research purposes.Current opinion in rheumatology. 09/2014;
54 The Open Rheumatology Journal, 2012, 6, 54-63
1874-3129/12 2012 Bentham Open
Laboratory Test Abnormalities are Common in Polymyositis and
Dermatomyositis and Differ Among Clinical and Demographic Groups
Rita Volochayev1, Gyorgy Csako2, Robert Wesley2, Lisa G. Rider1 and Frederick W. Miller*,1
1Environmental Autoimmunity Group, Program of Clinical Research, National Institute of Environmental Health
Sciences, National Institutes of Health, HHS, Bethesda, Maryland, USA
2The Clinical Center, National Institutes of Health, HHS, Bethesda, Maryland, USA
Abstract: Objective: Given the difficulties regarding the interpretation of common laboratory test results in polymyositis
(PM) and dermatomyositis (DM) in clinical practice, we assessed their range of abnormalities, differences among
phenotypes and interrelationships in a large referral population.
Methods: We retrospectively assessed 20 commonly measured blood laboratory tests in 620 well-defined PM/DM patients
at different stages of illness and treatment to determine the frequency, range of abnormalities and correlations among
clinical, gender, racial and age phenotypes.
Results: Myositis patients at various stages of their disease showed frequent elevations of the serum activities of creatine
kinase (51%), alanine aminotransferase (43%), aspartate aminotransferase (51%), lactate dehydrogenase (60%), aldolase
(65%) and myoglobin levels (48%) as expected. Other frequent abnormalities, however, included elevated high white
blood cell counts (36%), low lymphocyte counts (37%), low hematocrit levels (29%), low albumin levels (22%), high
creatine kinase MB isoenzyme fractions (52%), high erythrocyte sedimentation rates (33%) and high IgM and IgG levels
(16% and 18%, respectively). Many of these tests significantly differed among the clinical, gender, racial and age groups.
Significant correlations were also found among a number of these laboratory tests, particularly in the serum activity levels
of creatine kinase, the transaminases, lactate dehydrogenase and aldolase.
Conclusion: Laboratory test abnormalities are common in PM/DM. Knowledge of the range of these expected
abnormalities in different myositis phenotypes, gender and age groups and their correlations should assist clinicians in
better interpretation of these test results, allow for a clearer understanding what level of abnormality warrants further
evaluation for liver or other diseases, and may avoid unnecessary laboratory or other testing.
Keywords: Myositis, phenotypes, laboratory testing.
group of autoimmune muscle diseases of which polymyositis
(PM) and dermatomyositis (DM) are the most frequently
recognized forms . Although the IIM are the most
commonly acquired muscle diseases in adults, they are still
rare in the general population with an estimated annual
incidence of only 10 new cases per million persons. These
diseases are difficult to diagnose and categorize into
predictive groups . Their diagnosis and treatment are
often delayed because patients initially present with vague or
nonspecific symptoms such as fatigue, myalgias, and
arthralgias, which are also common in other types of
The idiopathic inflammatory myopathies (IIM) are a
most commonly performed enzyme test for the diagnosis and
monitoring of myositis [1, 4, 5]. This is due to the relative
muscle specificity of the enzyme and the infrequent
The serum activity level of creatine kinase (CK) is the
*Address correspondence to this author at the Environmental Autoimmunity
Group, National Institute of Environmental Health Sciences, National
Institutes of Health, CRC 4-2352, MSC 1301, 10 Center Drive, Bethesda,
MD 20892-1301, USA; Tel: 301-451-6273; Fax: 301-451-5585;
involvement of other organs that can generate CK (brain,
cardiac muscle) in patients with IIM . Although elevations
of CK and other serum muscle enzyme activities are used as
one criterion for diagnosis , few studies have assessed the
other laboratory blood tests often ordered in myositis
patients, leading to misconceptions and a lack of
understanding of the meaning of the test results obtained .
Our anecdotal experience is that many unnecessary tests are
performed on myositis patients to assess for other conditions
in response to laboratory abnormalities that are actually the
result of the myositis. For example, elevations of serum
activities of the so called “liver enzymes”, the transaminases
and lactate dehydrogenase (LD) in myositis patients due to
myoblast activation, have resulted, and in our experience
continue to result, in the misdiagnosis of liver disease and
inappropriate liver biopsies . Likewise, elevations in the
serum activity of the CK-MB fraction isoenzyme (CK-MB)
can result in the misdiagnosis of myocardial infarction .
The current study was conducted to address these issues by
assessing the results of 20 routine blood laboratory tests
from a large group of myositis subjects evaluated at the
National Institutes of Health (NIH). This population would
be representative of a referral population at different stages
of disease progression and with various levels of disease
activity undergoing different treatments. Our findings of
Laboratory Evaluation of PM/DM The Open Rheumatology Journal, 2012, Volume 6 55
frequent abnormalities in these tests and differences among
phenotypes should aid clinicians in better understanding the
utility of various laboratory tests in myositis patients seen in
MATERIALS AND METHODOLOGY
620 patients (181 men and 439 women; 351 with PM and
269 with DM; 427 Caucasians, 130 blacks and 63 of other
races) of the initial 800 consecutive individuals with
myopathies who were evaluated in natural history and
therapeutic research protocols in the National Institute of
Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
between 1985 and 2005. All subjects signed informed
consent for NIAMS institutional review board approved
protocols. Most subjects were referred for recommendations
for therapy, possible inclusion in therapeutic trials or for
diagnostic purposes. Selection criteria for this study included
adult patients with the diagnosis of PM or DM on the basis
of the exclusion of other forms of myopathy and meeting
probable or definite Bohan and Peter criteria , and who
had results for at least 15 of the 20 laboratory tests
commonly assessed in myositis patients at the NIH. All
laboratory tests were performed in the NIH Department of
Laboratory Medicine of the NIH Clinical Center and data
from the first time that at least 15 concurrent laboratory test
values were available were used. Subjects with criteria for
possible myositis (n=35), muscular dystrophies (n=29),
inclusion body myositis (n=28), cancer-associated myositis
(n=9), juvenile myositis (n=5) metabolic myopathies (n=4),
PM or DM but fewer than 15 concurrent laboratory tests
available (n=27), and undefined myopathies (n=43) were
excluded from study.
Patient population. The participants in the study were
cohort study included demographics (age, gender and race),
clinical information (the presence of Gottron’s papules or
sign or Heliotrope rash to define DM), and 20 laboratory
tests commonly performed on myositis patients at the NIH.
The laboratory tests included were serum levels of albumin,
creatinine, aldolase, CK (total level and isoenzymes CK-BB,
CK-MB, CK-MM), quantitative immunoglobulins (IgG, IgM
and IgA levels), erythrocyte sedimentation rate (ESR), total
white blood cell count (WBC) and differential (including
percent basophils, lymphocytes and polymorphonuclear
leukocytes), hematocrit, aspartate aminotransferase (AST),
alanine aminotransferase (ALT), LD, and myoglobin. When
the normal reference ranges changed during the study period,
laboratory results were expressed in relation to the upper
limits of the normal range and recalculated based upon the
current normal range.
Data recording. Data collected in this retrospective
Statistical Package for the Social Sciences (SPSS) version
10.0 (SPSS, Inc., Chicago IL.), following the SPSS Base
10.0 for Windows User's Guide (SPSS Inc., Chicago IL.),
and Stata version 11 (Austin, TX). Because analyses using
the Shapiro-Wilk test showed that all 20 of the laboratory
measurements were not normally distributed, the summary
measures reported are medians and interquartile ranges. The
proportions of subjects with abnormally high and low values
were calculated based on the normal ranges established for
healthy individuals at the NIH Department of Laboratory
Statistical analysis. Data analyses were performed using
Medicine (established to cover 95% of normal individuals).
Due to the non-normality of the distribution of
measurements, the primary analyses to assess possible
differences in laboratory tests in demographic groups (i.e.,
male and female gender; Caucasian, black, and other races;
age tercile groups of <37, 37-50, and >50 years) and in
clinical groups (i.e., PM and DM), were performed via the
nonparametric Wilcoxon rank sum test (for two groups), the
Kruskal-Wallis test (for the three unordered racial
categories), or Kuzick’s nonparametric trend test (“nptrend”
test in Stata) for the three ordered age categories.
non-normality of the values. For this study we defined
Rho correlations as falling
0.7-1.0 = high correlation; 0.5- <0.7 = moderate correlation;
0.3- <0.5 = low correlation; and <0.3 = little correlation .
Correlations of selected
laboratory values used
to accommodate correlation the
into four categories:
prediction intervals based on linear regression models. For
these analyses either logarithms of the raw values were used
(14 of the parameters) or the inverse hyperbolic sine
transformed-values were used (for six parameters: basophils,
lymphocytes, Polys, ESR, and the three CK isoenzyme
values; this transformation is very similar to a log
transformation, but is more flexible in allowing 0, or even
negative, values). As indicated by the Shapiro-Wilk test and
other confirmatory tests, these transformations greatly
reduced the skewness of the distributions and resulted in
more Gaussian-like distributions. The multiway ANOVA
analyses were used to confirm the primary univariate group
comparisons, by including in each analysis gender, race, and
diagnosis. In assessing the effect of age, all three factors of
gender, race, and diagnoses were taken into account.
Additional analyses used multiway ANOVA or
value of <0.05 was considered significant for these analyses,
with no correction for multiple comparisons.
Because this was an exploratory study, a two-sided p
expected, many of the IIM patients frequently had various
enzyme values above the normal limits (Table 1). The
abnormal laboratory results included skeletal muscle markers
such as aldolase, CK, CK-MB, LD, myoglobin, and
transaminases (ALT and AST), as well as acute and chronic
inflammatory markers (WBC count, polymorphonuclear
leukocytes, ESR, and immunoglobulins IgG and IgM).
Laboratory test abnormalities in IIM patients. As
below the normal range. Of these, low CK-MM levels,
lymphocyte counts, and creatinine levels have been
previously reported in patients with IIM [5, 11, 12]. Low
hematocrit and serum albumin levels, however, have not
been systematically described in myositis.
In contrast, a number of other test results were frequently
race, age, and IIM clinical groups. CK levels were
significantly higher in men compared to women, in blacks
compared to Caucasians and in PM compared to DM (Fig.
1), as previously described . CK-MB levels were also
significantly higher in men compared to women with IIM.
The median aldolase levels were also above normal in all
groups and they were significantly higher in men, blacks and
Differences in laboratory test results among gender,
56 The Open Rheumatology Journal, 2012, Volume 6 Volochayev et al.
in patients with PM. Age also seemed to impact the aldolase
levels. There was a significant trend for values to go down in
older age groups primarily due to the oldest age tercile (>50
years) being significantly lower than the other two terciles.
Similar age-related trends were seen in all three skeletal
muscle markers (CK, CK-MB and aldolase; Fig. 1).
AST and ALT in most groups, while above normal for LD in
all groups (Fig. 2). There were statistically significant
differences in gender, race and clinical diagnosis groups for
AST and ALT. Men had higher levels of these enzymes than
women, as has been described in healthy populations .
On the other hand, LD was significantly higher only in
blacks and in patients with PM. Higher serum LD in blacks
compared to Caucasians is consistent with the observation
that enzymes catalyzing reactions in phosphagenic (CK) and
glycolytic (e.g., LD) metabolic pathways have significantly
higher activities (by 30-40%) in skeletal muscle biopsy
tissue of Africans compared to Caucasians .
The median values tended to be borderline high for both
normal reference intervals, there were several statistically
significant differences for WBC count, percent lymphocytes,
and ESR (Fig. 3). WBCs were higher in males than females
and in Caucasians than blacks, while lymphocytes were
lower in males than females and tended to decrease with age.
This conflicts with data in other populations describing
higher WBC counts in women . ESR levels were higher
in females compared to males and in blacks compared to
Caucasians, as previously reported for healthy populations
Although all subgroup medians fell within the respective
intervals for serum albumin and hematocrit, but they were at
the low end of the reference interval for serum creatinine,
consistent with the expected loss of muscle mass in myositis
patients. On the other hand, serum albumin levels were
significantly higher in Caucasians than blacks and
significantly lower in PM compared to DM patients. Similar
to a healthy population, serum creatinine levels were
The median values were within the respective reference
Laboratory Test Results for Myositis Patients in the Study*
% Below Lower
Limit of Normal
% Above Upper
Limit of Normal
Aldolase 1-6 U/L 507 0.0 39.6 60.4 5.0 9.0 21.0
ALT 6-41U/L 618 0.3 56.6 43.0 22.0 35.0 68.0
AST 9-34 U/L 617 0.5 49.0 50.6 23.0 35.0 65.0
F 38-252 U/L
M 52-386 U/L
613 7.2 42.4 50.4 82.0 297.0 1136.0
CK-MM 97-100 % 350 63.7 36.0 0.3 89.0 95.0 100.0
CK-MB 0-3 % 355 0.6 47.0 52.4 0.0 3.0 6.0
CK-BB 0 % 355 0.0 96.6 3.4 0.0 0.0 0.0
LD 113-226 U/L 577 0.5 35.0 64.5 200.0 264.0 392.0
Myoglobin 0 ng/ml 269 0.0 52.0 48.0 30.0 64.0 246.0
Albumin 3.7-4.7 g/dL 602 21.9 73.8 4.3 3.7 4.1 4.4
F 0.56-1.16 mg/dL;
M 0.77-1.19 mg/dL
618 34.1 62.9 2.9 0.6 0.8 1.0
F 3.98-10.04 k/?L
M 4.29-9.07 k/?L
619 2.8 61.7 35.5 5.8 8.2 11.5
609 0.0 99.8 0.2 0.0 0.2 1.0
607 37.4 61.9 0.7 9.9 18.0 28.0
F 1.56- 6.13%
606 1.2 62.5 36.3 59.5 71.0 83.0
619 28.8 65.6 5.7 36.5 39.5 42.4
F 0-42 mm/hour
M 0.25 mm/hour
604 1.7 65.4 33.0 12.0 24.5 47.0
IgG 642-1730 mg/dL 536 4.9 77.4 17.7 891.5 1120.0 1400.0
IgM 34-342 mg/dL 536 0.8 83.8 15.5 95.0 142.0 213.0
IgA 91-499 mg/dL 536 1.5 90.5 8.0 149.0 204.0 280.0
*Abbreviations: creatine kinase total level (CK) and isoenzyme fractions (CK-MM, CK-MB, CK-BB), quantitative immunoglobulins (IgG, IgM and IgA), erythrocyte sedimentation
rate (ESR), total white blood cell count (WBC) and differential (including percent polymorphonuclear leukocytes (Polys)), alanine aminotransferase (ALT), aspartate
aminotransferase (AST), and lactate dehydrogenase (LD), female (F), male (M).
Laboratory Evaluation of PM/DM The Open Rheumatology Journal, 2012, Volume 6 57
significantly higher in men than women with IIM, likely due
to the larger muscle mass in men. Creatinine levels were
higher in those older than 50 years, possibly due to declining
renal function. The hematocrit was significantly higher in
males compared to females with IIM, as described in healthy
age, gender and race to the differences in certain laboratory
measures, we compared P-values based on the log values of
laboratory measures. These analyses showed that CK and
aldolase were most different among the diagnostic groups (P
= 1.2 X 10-17 and P = 5.3 X 10-9, respectively). Nonetheless,
In order to assess the relative contribution of diagnosis,
CK and aldolase also differed among races (P = 4.1 X 10-9
and P = 0.0086, respectively), and by gender (P = 0.002 and
P = 0.005, respectively), but both of these were less
significant than the differences among diagnostic groups.
Hematocrit differed most between males and females (P =
8.4 X 10-13), but less so among races (P = 0.00008), age
groups (P = 0.001) and diagnostic groups (P = 0.035).
taking into account the factors of gender, race, age and
diagnosis, confirmed all of the statistically significant
univariable results, with confirmatory P-values <0.05, except
in the following 3 cases where the multivariable P-value did
The parametric multiway ANOVA analyses, always
Fig. (1). Box plots showing the median, 25th and 75th percentiles and highest and lowest values for CK, CK-MB and aldolase in all myositis
patients and differences among groups. The shaded area depicts the normal range.*
*Abbreviations: Dx, diagnosis; DM, dermatomyositis; PM, polymyositis; B, black; W, white, Caucasian; O, other; rest per Table 1.
58 The Open Rheumatology Journal, 2012, Volume 6 Volochayev et al.
not reach significance: (1) the effect of age on lymphocytes
(P = 0.082); (2) the effect of gender on WBCs (P = 0.088);
and (3) the effect of gender on lymphocytes (P = 0.061) were
not significant. The number and magnitude of these changes
in P-values are quite minor, and serve to strongly confirm
the primary univariable results.
of significant correlations among the laboratory tests studied
were identified in the IIM (see Table 2 where only
correlations greater than 0.5 in absolute value are shown).
Moderate to high correlations were observed among
aldolase, ALT, AST, CK, LD, myoglobin, Polys, and WBC.
Muscle enzymes and muscle breakdown products all
Correlations among laboratory test results. A number
Fig. (2). Box plots showing the median, 25th and 75th percentiles and highest and lowest values for AST, ALT and LD in all myositis patients
and differences among groups. The shaded area depicts the normal range*.
*Abbreviations: per Table 1 and Fig. (1).
Laboratory Evaluation of PM/DM The Open Rheumatology Journal, 2012, Volume 6 59
correlated highly, as expected. Aldolase correlated
significantly with 14 of the other laboratory tests and
particularly strongly with ALT, AST, CK, LD, and
myoglobin. A moderate correlation was found between Polys
and WBCs. Lower correlations were found among the other
ALT, AST and LD values for all patients. The plots show the
95% and 99% prediction intervals of CK with each of these
Fig. (4) displays scatter plots for CK levels with aldolase,
four tests, thus providing guidance to clinicians of when a
test result may be considered to be outside the expected
range for patients with myositis and when further evaluation
for liver disease may be warranted. Although only limited
data were available in this retrospective study, the medical
records of the 17 individuals who had ALT, AST or LD
levels higher than the 99% prediction interval were
examined to assess the possibility of liver disease. Of these
17 individuals, four had documented liver disease (one each
Fig. (3). Box plots showing the median, 25th and 75th percentiles and highest and lowest values for WBC count, lymphocytes and ESR in all
myositis patients and differences among groups. The shaded area depicts the normal range*.
*Abbreviations: per Table 1 and Fig. (1).
60 The Open Rheumatology Journal, 2012, Volume 6 Volochayev et al.
Table 2. Summary of Moderately to Highly Correlated
First Test Correlated Test n Rho
Aldolase ALT 506 0.77
AST 506 0.80
CK 505 0.82
LD 472 0.78
Myoglobin 177 0.82
ALT Aldolase 506 0.77
AST 617 0.86
CK 612 0.70
LD 576 0.67
Myoglobin 268 0.73
CK 611 0.76
LD 575 0.73
Myoglobin 267 0.75
CK-MB CK-MM 350 -0.77
CK Aldolase 505 0.82
ALT 612 0.70
AST 611 0.76
LD 575 0.70
Myoglobin 267 0.89
Hematocrit ESR 604 -0.58
LD Aldolase 472 0.78
ALT 576 0.67
AST 575 0.73
CK 575 0.70
Myoglobin 264 0.70
Lymphocytes Polys 606 -0.92
WBC 607 -0.50
Myoglobin Aldolase 177 0.82
ALT 268 0.73
CK 267 0.89
Polys Lymphocytes 606 -0.92
WBC 606 0.55
WBC Lymphocytes 607 -0.50
Polys 606 0.55
* All Spearman Rho rank correlation coefficient p-values were <0.00005. Moderately
to highly correlated Spearman r values were ? 0.50. Abbreviations: n, number of values
available for analysis; others as in Table 1.
with fibrotic liver disease of unknown origin, non-alcoholic
steatohepatitis, hepatomegaly of unknown cause and
hepatitis secondary to blood transfusion).
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.
This study assessed routine laboratory test results in a
and LD are muscle-derived enzymes in myositis whose
levels tend to indicate disease activity [3, 19]. 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 . 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, 20].
It is commonly accepted that CK, aldolase, ALT, AST,
elevations in enzymes (including CK, CK-MB, CK-MM,
aldolase and transaminases) compared to females reflecting
their greater average muscle mass . 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 .
Leukocytosis has been associated with low-grade fever at the
onset of myositis and in association with disease flares in
certain groups . 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, 23].
In terms of the sex differences, males have higher
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 , 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 , 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
, 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 .
Regarding the previously unreported abnormalities,
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
We also noted significant correlations among various
Laboratory Evaluation of PM/DM The Open Rheumatology Journal, 2012, Volume 6 61
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 [24-27].
with muscle enzyme levels and muscle metabolites such as
myoglobin were unexpected. However, CK is expressed in
WBC, including macrophages [28, 29], as well as in
endothelial cells , and LD is also expressed by T and B
lymphocytes . 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.
The significant but low correlations of WBC and Polys
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
Although attempts were made to avoid possible
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.
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
Nonetheless, this is the first study undertaken to describe
Fig. (4). Scatterplots and the 99% and 95% prediction intervals for the relationships among CK and aldolase (A), ALT (B), AST (C) and LD
*Abbreviations as in Table 1 and Figs. (1-3).
62 The Open Rheumatology Journal, 2012, Volume 6 Volochayev et al.
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.
range of expected routine laboratory test abnormalities in
myositis patients and the differences among subgroups in
order to effectively evaluate possible other causes of these
abnormalities. Knowledge of the expected range of
abnormalities of common laboratory tests may aid in
avoiding unnecessary expensive and invasive diagnostic
techniques in myositis patients.
This study highlights the importance of understanding the
in collecting and organizing data, the clinical assistance of
Drs. Paul Plotz and Mark Gourley and the useful critical
comments of Drs. Elizabeth Adams, Frank Pucino and
Kathleen Coyle on the manuscript.
The authors wish to acknowledge Bhanu Koneru for help
programs of the National Institute of Arthritis and
Musculoskeletal and Skin Disease and the National Institute
of Environmental Health Sciences, and the Clinical Center,
NIH, Bethesda, MD.
Funding for this project was provided by the intramural
CONFLICT OF INTEREST
ALT = Alanine aminotransferase
AST = Aspartate aminotransferase
CK = Creatine kinase
CK-BB = Creatine Kinase Isoenzyme Fractions: CK-BB is
found mostly in the brain and lungs, CK-MB- is
found mostly in the heart, CK-MM is found
mostly in skeletal muscle
DM = Dermatomyositis
ESR = Erythrocyte sedimentation rate
IIM = Idiopathic inflammatory myopathies
LD = Lactate dehydrogenase
Polys = Polymorphonuclear leukocytes
PM = Polymyositis
WBC = White blood cell
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Received: March 25, 2012
© Volochayev et al.; Licensee Bentham Open.
This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/
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Revised: May 8, 2012 Accepted: May 10, 2012