Steroids Raise Risk of Hospitalization for Pain Crises, Study Finds

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by Marta Figueiredo PhD |

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Exposure to systemic steroids — frequently used to treat asthma or ease inflammation — is significantly associated with a higher risk of painful vaso-occlusive crises (VOCs) leading to hospitalization in children and adults with sickle cell disease (SCD), a French study shows.

“Individuals living with SCD often suffer crippling episodes of pain, which can greatly impair their quality of life,” Ondine Walter, MD, the study’s first author from Toulouse University Hospital, in France, said in a press release.

VOCs and related hospitalizations “appear to follow corticosteroid prescription fairly quickly,” suggesting that “corticosteroids may be contributing to the events and should be avoided as much as possible in these patients,” Walter added.

The study, “Risk of vaso-occlusive episode after exposure to corticosteroids in patients with sickle cell disease,” was published in the journal Blood.

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While “hydroxyurea use, male gender, and younger age were associated with a lower risk of hospitalization for [VOCs] after corticosteroid exposure in our study,” Walter said, “we still need to think twice about using corticosteroids when treating patients with SCD.”

This is in line with current SCD treatment guidelines, which advise against the use of systemic steroids for pain management, and emphasize that their use for other medical conditions should be made under the guidance of an SCD expert.

Since many physicians without experience treating people with SCD may be unaware of these guidelines, it is important that patients themselves know the dangers of taking these medications.

People with SCD often experience bouts of extreme pain due to sickle-shaped red blood cells clumping together and clogging small blood vessels, preventing a healthy supply of oxygen to tissues. Called pain crises or VOCs, these episodes can last many days and are the main cause of hospital admissions in these patients.

Several clinical trials showed that steroids are effective at treating VOCs, but at the same time are associated with increased rates of relapse and hospital readmission. In addition, case reports have supported a link between the use of systemic steroids and the occurrence of VOCs.

However, no appropriately-controlled study has evaluated this potential link.

With this in mind, Walter and his colleagues in France analyzed data from the French national health insurance database between 2010 and 2018 to assess whether systemic steroid use was associated with an increased risk of VOC-associated hospitalization in SCD patients.

A total of 5,151 people with SCD with at least one hospitalization due to a VOC were included in the analysis. Systemic steroid exposure was identified using outpatient prescribing records, meaning exposure was calculated based on prescription filling, but researchers could not be sure whether patients took the medicine.

The main goal was to assess time to first hospitalization for VOC following systemic steroid use.

Analyses were adjusted for time-dependent influencing factors, such as infections and red blood cell transfusions, and stratified by exposure to hydroxyurea — an approved, standard SCD therapy used to reduce VOCs and the need for blood transfusions.

Results showed the median time between filling a prescription for a systemic steroid and VOC-associated hospitalization was five days. Also, patients using systemic steroids were nearly four times more likely to be hospitalized for VOC in the following month than those not using these medications.

In turn, patients also on hydroxyurea when exposed to systemic steroids were nearly 1.5-times less likely to be hospitalized due to these painful crises relative to those not on the standard therapy, further supporting its protective effect against VOCs.

These associations were detected in both children and adults with the disease.

In addition, the risk of VOC-associated hospitalization upon steroid exposure was lower in men than women and in children compared with adults.

While these findings cannot prove a cause-and-effect relationship, they show that “systemic corticosteroids were associated to an increased risk of hospitalization for [VOC] and should be limited in patients with SCD,” the researchers wrote.

This study adds to the growing body of evidence supporting an association between systemic steroid use and subsequent VOCs and that these medications should be used only when needed, and under the guidance of an SCD expert.

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Still, the data also highlighted that systemic steroids are commonly prescribed for conditions unrelated to underlying SCD, Walter said, with nearly half (46%) of the patients having been prescribed at least one systemic steroid during the study period.

This emphasizes the need for widespread education of both clinicians and patients about the potential risks of systemic steroids, especially when there isn’t a clear indication to use them, Walter noted.

“Corticosteroids are mostly easy to avoid, and in circumstances when they are necessary, it’s important to start them in collaboration with an SCD expert and to take all appropriate precautionary measures to administer them safely,” Walter said.

Given that previous studies also highlighted an association between systemic steroid discontinuation and pain crisis relapse, medication cessation should be gradual and closely monitored.

More studies are needed to better understand how systemic steroids may trigger VOCs, the researchers said.