This large multicenter observational study of clinical outcomes in hospitalized children with new-onset HSP revealed that early corticosteroid exposure is associated with statistically significant decreased HRs for needing abdominal surgery, endoscopy, and abdominal imaging and a decreased HR for NSAID and opioid use during hospitalization. Furthermore, the direction of our estimates was consistent when each patient’s hospitalization charges for days 1 and 2 were included in the model as a proxy for severity of illness at the time of admission.
Two additional findings warrant discussion. First, with observational studies of medical interventions, one must consider the possibility of potential confounding-by-indication bias, which arises when the patients with more severe forms of disease are more likely to both receive the intervention and experience poorer outcomes, which results in the apparent association of the intervention with poorer outcomes. In our study, if we accept the premise that patients who are more ill consume more health care resources, we do find evidence that patients who were more ill at the time of admission were more likely to receive corticosteroids, as demonstrated in . Our analytic methods, with multivariable adjustment for patient characteristics, likely minimized but did not eliminate this confounding by indication, which raises the possibility that corticosteroids have an even greater beneficial effect on inpatient outcomes than we are able to demonstrate.
Second, in our analysis the only secondary outcome with an HR of >1 (although not to a statistically significant degree) was hospital readmission. Why this 1 possible counter-example to the otherwise apparent beneficial effects of corticosteroid? Our clinical experience suggests that children treated with corticosteroids may be (1) given too short a course of corticosteroids, (2) weaned off corticosteroids too quickly and experience rebound symptoms, or (3) more severely ill at the time of hospital admission. Unfortunately, we cannot evaluate these possibilities in the PHIS inpatient database, because it does not record whether children treated with corticosteroids as inpatients were sent home on corticosteroids, how long they were treated, or how the course of therapy was tapered and stopped.
These findings should be interpreted in the context of 4 specific limitations of our study. First, this was a study of inpatient HSP outcomes; therefore, our results are not generalizable to children with milder disease who are treated as outpatients. Second, the PHIS database does not contain outpatient data; thus, we do not know whether subjects in this study were previously diagnosed with HSP or treated with corticosteroids as an outpatient before admission. Similarly, we were not able to capture mild recurrences that did not necessitate readmission (ie, visit to a pediatrician or emergency department). Third, the results of this study reflect the impact of corticosteroid exposure in actual hospital practice and not the controlled setting of a clinical trial. Finally, the association of corticosteroids and renal disease was not examined in this study, because our outcomes of interest were limited to short-term outcomes that could be assessed during the initial hospitalization.
With these caveats kept in mind, our study findings indicate that the effect of corticosteroids on outcomes for pediatric inpatients with HSP warrants further investigation with a prospective randomized controlled clinical trial. If further studies confirm that corticosteroids are beneficial in the inpatient setting, then evidence-based practice guidelines could be established. Future studies should (1) address whether corticosteroid exposure is associated with improved clinical outcomes during hospitalization as well as subsequent long-term HSP outcomes, including kidney disease, (2) evaluate the optimal dose and duration of treatment with corticosteroids, and (3) if applicable, investigate the impact of standardized care guidelines for the management of inpatient HSP on resource utilization and outcomes of care, including kidney disease.