乌鸦传媒

Patients with sickle cell disease (SCD) have an increased risk of vaso-occlusive episodes (VOE) after exposure to corticosteroids, according to a French population-based study.

Those taking systemic corticosteroids were nearly four times more likely to be hospitalized for a VOE a month after exposure (adjusted odds ratio [aOR] 3.8, 95% CI 2.4-5.6), reported Ondine Walter, MD, of Toulouse University Hospital in France, and colleagues in the journal .

Hydroxyurea therapy somewhat mitigated this risk, as patients treated with the drug when exposed to steroids were less likely to be hospitalized (aOR 2.6, 95% CI 1.1-6.4) compared with those not on the therapy (aOR 4.0, 95% CI 2.5-6.3).

In explaining the rationale behind their study, Walter and team noted that while it has been suspected that exposure to systemic corticosteroids increases the incidence of VOE, this has not been measured in comparative studies, and is still a subject of debate.

"Therefore, given the lack of clear recommendations regarding the prescription of corticosteroids in patients with SCD, corticosteroids are still widely prescribed in this population," they wrote.

"Vaso-occlusive events and related hospitalization appear to follow corticosteroid prescription fairly quickly. This evidence suggests corticosteroids may be contributing to the events and should be avoided as much as possible in these patients," said Walter in a press release.

Commenting on the study, Julie Kanter, MD, director of the Adult Sickle Cell Clinic at the University of Alabama at Birmingham, told 乌鸦传媒 that many SCD patients have reported anecdotally that steroids triggered "the worst crisis" they ever had.

"Often, corticosteroids are prescribed by urgent care physicians, emergency medicine doctors, or primary care physicians during viral infections or pharyngitis to alleviate -- ostensibly -- the related inflammation," Kanter said. "While seemingly benign, steroids can cause multiple secondary complications for all individuals and should not be used haphazardly."

Walter and colleagues used data from the French national health insurance database, from which they identified 14,166 adults and children with SCD who were hospitalized at least once for a VOE, accounting for a total of 103,204 hospitalizations (0.78 VOE per patient-year) from 2010 to 2018. About 13% of hospitalizations required a stay in an intensive care unit. The median duration of hospital stay for VOE was 3 days.

After exclusions, 5,151 patients were included in the analysis, of whom 45% were exposed at least once to systemic corticosteroids during the study period. Corticosteroid exposure was defined as having been prescribed the drug within 28 days of a VOE, while hydroxyurea exposure was defined as having been prescribed the drug at least once during the 3 months preceding a VOE.

VOEs and related hospitalizations followed corticosteroid exposure fairly rapidly -- a median of 5 days.

When broken down by age and sex, the risk of VOE remained high among subgroups, with aORs of 2.8 (95% CI 1.5-5.3) in children and 4.5 (95% CI 2.4-8.4) in adults, and 6.5 (95% CI 3.5-12.3) in women and 2.1 (95% CI 1.1-4.0) in men.

Walter and team suggested that the difference in risk between men and women was unrelated to gynecologic or obstetric issues, since it was also observed in patients younger than 15 years. They also noted that women were more likely to be prescribed corticosteroids, and had more frequent hospital stays than men.

"In accordance, some studies have found a greater propensity to develop VOEs in women than in men," they wrote. "In addition, the pharmacological effects of corticosteroids differ according to sex, highlighting the need of studies to explore the pathophysiological hypothesis underlying these findings."

The authors pointed out that their study was restricted to patients in France, limiting its generalization to SCD patients worldwide. They also noted that corticosteroid use was measured according to dispensing data, which could differ from intake by patients.

"However, systemic corticosteroids are prescribed for acute conditions," they wrote. "Consequently, a significant unmeasured time from dispensing to intake is unlikely."

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