Serum Enzyme Alterations in Polymyositis
Possible Pitfalls in Diagnosis
B. DOUGLAS MORTON, III, M.D., AND BERNARD E. STATLAND, M.D., PH.D.
Morton, B. Douglas, III, and Statland, Bernard E.: Serum
enzyme alterations in polymyositis. Possible pitfalls in diagnosis. Am J Clin Pathol 73: 556-557, 1980. We report serum
enzyme patterns in three patients with polymyositis or dermatomyositis whose cases posed potential problems in distinguishing malignancy, hepatocellular damage, and myocardial
infarction from myositis. The alanine aminotransferase
showed five- to 16-fold elevations. The creatine kinase MB
isoenzyme and a predominance of lactate dehydrogenase
isoenzymes 2 and 3 were present in each of the three
patients. However, none of the patients showed any evidence
of hepatocellular damage, myocardial infarction, or malignancy. We suggest that, although the individual occurrences
are indicative of other processes, the concurrence of elevated
alanine aminotransferase, creatine kinase MB, and elevated
lactate dehydrogenase isoenzymes 2 and 3 is consistent with
the diagnosis of polymyositis. (Key words: Polymyositis;
Dermatomyositis; Alanine aminotransferase; Creatine kinase;
Lactate dehydrogenase.)
IT IS WELL KNOWN that the damaged muscle cell
in polymyositis and dermatomyositis releases certain
enzymes, including aldolase, creatine kinase, lactate
dehydrogenase, aspartate aminotransferase (syn. SGOT),
and alanine aminotransferase (syn. SGPT). However,
little information is available on the degree of elevation
of alanine aminotransferase in serum.2-6-7 Although the
creatine kinase and lactate dehydrogenase isoenzyme
patterns in neuromuscular diseases have been studied,8-9
there are few previous reports on these isoenzyme
patterns in polymyositis. 3 ' 4 ' 5 Our report describes the
cases of three patients with polymyositis who had fiveto 16-fold elevations of serum alanine aminotransferase
and characteristic isoenzyme patterns for creatine
kinase and lactate dehydrogenase.
Case Reports
The patients were two men and one woman ranging
in age from 45 to 53 years who presented with proximal
muscle weakness. One of the men had a rash consistent
with that seen in dermatomyositis. Serum enzyme
Received April 18, 1979; received revised manuscript and accepted
for publication May 21, 1979.
Address reprint requests to Dr. Morton: Department of Pathology,
University of North Carolina, Chapel Hill, North Carolina 27514.
Department of Pathology, University of North Carolina,
Chapel Hill, North Carolina
findings are shown in Table 1. In each case a thorough
search did not reveal malignancy. EKGs did not show
evidence of myocardial infarction. Muscle biopsy
specimens from all three patients were consistent
with polymyositis, showing necrosis, regeneration, and
perivascular chronic inflammation. Electromyograms
showed myopathic changes. All three patients were
treated with steroids, and the two men showed marked
improvement. The woman (Patient 1, Table 1),
however, died after repeated episodes of aspiration
pneumonia. An autopsy showed tan, edematous, inflamed muscles, but did not show evidence of malignancy,
hepatocellular disease, or myocardial infarction.
Discussion
These patients met the established criteria for the
diagnoses of polymyositis and dermatomyositis. 1 All
showed strikingly similar enzyme patterns: the
aspartate aminotransferase was 20-32 times the upper
reference limit; alanine aminotransferase, 5-16 times;
creatine kinase, 30-130 times; lactate dehydrogenase, 10-14 times; and aldolase, 30-38 times the
upper reference limit. All three patients demonstrated
the presence of the creatine kinase-MB (CK-MB) isoenzyme, and all had predominately the lactate dehydrogenase isoenzymes 2 and 3.
Most reports on polymyositis emphasize the increases seen in serum of lactate dehydrogenase,
aldolase, aspartate aminotransferase, and creatine
kinase. Although alanine aminotransferase is found in
muscle and is released when muscle is damaged, few
studies document the degree of rise in alanine aminotransferase. Rose and Walton reported an elevated
alanine aminotransferase in seven of 14 patients who
had polymyositis. 7 Bohan and associates reported
elevation of alanine aminotransferase in 130 of 153
patients who had polymyositis and dermatomyositis. 2
Munsat and associates reported a mean increase in
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556
vol. 73 . No. 4
BRIEF SCIENTIFIC REPORTS
557
Table 1. Values of Selected Serum Enzyme Activities for Each of Three Patients*
Aspartate
Aminotransferase
(5-25)
Alanine
Aminotransferase
(7-35)
Aldolase
(1.2-7.6)
Alkaline
Phosphatase
(30-90)
Creatine
Kinase
(10-130)
Patient 1
Before therapy
After steroid therapy
572
551
173
170
157
Not done
76
70
Patient 2
Before therapy
After steroid therapy
810
172
526
280
Not done
Not done
Patient 3
Before therapy
After steroid therapy
497
121
373
195
285
Not done
Creatine
Kinase
Isoenzymest
MM
MB
3,880
4,120
+
+
-
+
+
-
Not done
Not done
17,330
9,190
+
+
42
Not done
10,090
2,490
+
+
• In U/l measured at 30 C (aspartate aminotransferase analysis with addition of 0.1 mmol/l
pyridoxal phosphate). Expected reference intervals are presented within the parentheses.
alanine aminotransferase of 400% in 50 patients.6 Our
patients' alanine aminotransferase values ranged from
173 to 256 I U/l. Before the diagnosis of polymyositis
is made, the elevated alanine aminotransferase can
cause great concern in distinguishing muscle cell
damage from liver cell damage, since clinicians often
equate the increase in serum alanine aminotransferase
with hepatocellular destruction.
It is also recognized that muscle contains the MM
and MB isoenzymes of creatine kinase; however,
skeletal muscle has predominately the MM isoenzyme
and cardiac muscle has significantly more MB isoenzyme. A positive MB band is generally considered
diagnostic of a myocardial infarction. Our three patients all had a positive CK-MB isoenzyme, but did not
have evidence of myocardial infarction. Brownlow
and Elevitch also reported six cases of polymyositis
with positive CK-MB.3 In addition, Goto reported that
three of eight patients who had dermatomyositis had a
positive CK-MB.4
Lactate dehydrogenase isoenzyme analysis revealed
an elevation of lactate dehydrogenase isoenzyme 5,
with necrosis of type II muscle fibers, and lactate
dehydrogenase isoenzyme 1, with necrosis of type 1
fibers. Our patients all showed relative increases in
lactate dehydrogenase isoenzymes 2 and 3. Brownlow
and Elevitch's six patients had a predominant lactate
dehydrogenase isoenzyme 2, 3,4 pattern.3 Hooshmand
and co-workers reported 27 patients with acute polymyositis who had a lactate dehydrogenase isoenzyme
2, 3, 4, 5 pattern.5 The lactate dehydrogenase
isoenzyme 2, 3, 4 pattern that is seen in malignancy
may lead clinicians to suspect an occult malignancy.
The cases of all three patients posed potential
BB
Lactate
Dehydroge nase
Isoenzymest
2
3
4
5
1940
1985
13 46
14 41
27
28
8
9
6
8
-
2750
2292
9 36 31
10 54 28
11
5
13
3
-
1860
854
12 44
12 57
9
5
8
6
Not done
+
+
Lactate
Dehydrogenase
(90-315)
1
28
21
t Qualitative measurement, i.e.. presence ( + > or absence ( -> recorded.
$ Percentage of total lactate dehydrogenase.
problems in distinguishing hepatocellular destruction,
myocardial infarction, and malignancy from myositis.
All three patients had polymyositis, but did not have
evidence of malignancy, myocardial damage, or liver
cell damage. We would suggest that the combination
of an elevation of alanine aminotransferase, the
CK-MB isoenzyme, and the lactate dehydrogenase
isoenzymes 2 and 3 are a recognized part of the syndromes/diseases of polymyositis and dermatomyositis.
Acknowledgments. Drs. K. M. Brinkhous and W. W. McLendon
reviewed this manuscript.
References
1. Bohan A, Peter JB: Polymyositis and dermatomyositis.
N Engl J Med 292:344-347, 403-407, 1975
2. Bohan A, Peter JB, Bowman RL, et al: A computer-assisted
analysis of 153 patients with polymyositis and dermatomyositis. Medicine 56:255-285, 1977
3. Brownlow K, Elevitch FR: Serum creatine phosphokinase
isoenzyme (CPK 2 ) in myositis. JAMA 230:1141-1144, 1974
4. Goto I: Creatine phosphokinase isozymes in neuromuscular
disorders. Arch Neurol 31:116-119, 1974
5. Hooshmand H, Dove J, Suter C: The use of serum lactate
dehydrogenase isoenzymes in the diagnosis of muscle disease.
Neurology 19:26-31, 1969
6. Munsat TL, Baloh R, Pearson CM, et al: Serum enzyme alterations in neuromuscular disorders. JAMA 226:1536-1543,
1973
7. Rose AL, Walton JN: Polymyositis: a survey of 89 cases with
particular reference to treatment and prognosis. Brain 89:
747-767, 1966
8. Sommer H, Donner M, Murros J, et al: A serum isoenzyme
study in muscular dystrophy. Arch Neurol 29:343-345.
1973
9. Yasmineh WG, Ibrahim GA, Abbasnezhad M, et al: Isoenzyme
distribution of creatine kinase and lactate dehydrogenase
in serum and skeletal muscle in Duchene and muscular
dystrophy, collagen disease, and other muscular disorders.
Clin Chem 24:1985-1989, 1978