Discussion
In this study, about 90% of the 31,570 patients with anaphylaxis treated with adrenaline were also treated with glucocorticoids. The overall proportion of biphasic reactions was 11.2%. There were no significant differences in rates of biphasic reactions or 7-day all-cause mortality between those treated with and without glucocorticoids.
Previous studies have failed to show that glucocorticoids reduce the rate of biphasic reactions in patients with anaphylaxis of varying severity.7,8 In the present study, which included only patients with severe anaphylaxis, we also found no evidence that glucocorticoids reduce the rate of biphasic reactions.
Biphasic reactions occurred on the day of the initial anaphylactic reaction in about 90% of the patients in our study. A previous study reported a median time between initial symptom resolution and onset of biphasic reaction of 11 hours (range 0.2–72 hours.1The anti-allergic effects of glucocorticoids, which are thought to be responsible for any effect on biphasic reactions, occur within 4 to 6 hours.6 Therefore, the failure of glucocorticoids to reduce the rate of biphasic reactions may be attributable to the difference between the time required for glucocorticoids to take effect and the time of onset of biphasic reactions.
Long-term steroid administration is associated with adverse effects, including infection, osteoporosis, hypertension, mood disorder, peptic ulcer, and adrenal insufficiency. Even short-term administration may result in avascular necrosis.13,14 Short-term steroid use can also be associated with development of hyperglycemia within a few hours.15 Given that this study showed no significant association between glucocorticoid use and rate of biphasic reaction, routine use of glucocorticoids to prevent biphasic reaction may not be indicated, not even in patients with severe anaphylaxis requiring intramuscular adrenaline.
This study has several limitations. First, it was a retrospective observational study. Although we used propensity score matching to adjust for confounding factors, our results may have been affected by unmeasured confounding factors, including symptoms of anaphylaxis, time from onset of anaphylaxis to treatment, use of epinephrine autoinjectors, and the results of laboratory tests. Future research is expected to be prospective or to use registries that include detailed clinical data. Second, in this study, severe anaphylaxis was defined as anaphylaxis requiring admission to hospital and treatment with adrenaline. However, some patients without severe clinical symptoms receive adrenaline, potentially resulting in misclassification and underestimation of the effects of glucocorticoids.