In a previous paper, we have reported the clinical features which were characteristic of drug fever induced by parenteral administration of β-lactam antibiotics and have pointed out that the drug fever was frequently associated with a transient elevation of the serum level of lactate dehydrogenase (LDH), In the present study, the sources from which the increased serum LDH was derived and the significance of LDH for the diagnosis of drug fever were investigated. In addition, the diagnostic value of immunological tests was estimated.
It was found that, between drug fever episodes with elevated LDH level and those without it, there was no significant difference in the ratio of episodes with a transient elevation of the serum level of glutamic pyruvic transaminase (GPT) which is derived almost exclusively from liver cells.
The drug fever episodes in the present study were classified into the following three groups, namely, episodes with both a transient and slight decrease of neutrophils and that of platelets (Group I), those with either of them (Group II) and those with neither of them (Group III). Of a total of 20 episodes of drug fever with elevated LDH level, 12 belonged to group I, four to group II and four to group III, respectively. Of a total of 21 episodes of drug fever without elevated LDH level, six belonged to group I, five to group II and ten to group III. Thus it was known that neutrophils and platelets decreased more frequently in drug fever episodes with elevated LDH level than in those without it (P<0.05).
In ten episodes of drug fever with elevated LDH level, individual activities of five isozymes of LDH were determined twice, namely, when the clinical symptoms were manifest and LDH level was elevated and when patients were recovering from the episodes. Then the differences in the activities between the above two periods were calculated. As the result, a significant change in activity of LDH-3 was demonstrated in six patients and that of LDH-2 in three other patients, respectively.
These data suggested that the elevated LDH level was caused by a release of LDH mainly from blood cells. Serum LDH level might be a comparatively sensitive indicator of the destruction of neutrophils and platelets, which was possibly caused by the same immune mechanism as that which was responsible for drug fever.
When hypersensitivity to antibiotics was skin-tested in 15 patients with drug fever immediately before and one week after treatment, only one of them showed a weakly positive Arthus reaction after treatment. A circulating antibody which was specific to the administered β-lactam antibiotic was found, as shown by passive hemagglutination test, in only 5 of 15 patients with drug fever.
In contrast, migration of leukocytes was inhibited by an antibiotic which was related to drug fever in 9 of 11 patients examined (82%). The mean degree of migration inhibition was higher in patients with drug fever than in those who had received β-lactam antibiotics for more than two weeks without adverse reactions (P<0.05).
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