Laird Harrison
January 20, 2016
Vomiting, behavior changes, and sleep disturbances each affect about one child in 20 taking a short course of oral corticosteroids, a new study shows.
Moreover, almost one in 100 gets an infection while receiving the commonly prescribed medications, researchers say.
“We should perhaps alert families of children taking short-course corticosteroids in the same way we do with children taking them on a more long-term basis,” coauthor Sharon Conroy, BPharm, PhD, assistant professor of pharmacy, Division of Medical Sciences & Graduate Entry Medicine, School of Medicine, University of Nottingham, Royal Derby Hospital Centre, United Kingdom, toldMedscape Medical News.
Fahad Aljebab, PhD, also from the Division of Medical Sciences & Graduate Entry Medicine, and colleagues published the findings online January 14 in the Archives of Diseases in Childhood.
Clinicians have used corticosteroids for more than 50 years in many clinical conditions, mostly to suppress immune responses or reduce inflammation. And most are familiar with common adverse reactions, particularly with long-term use, Dr Conroy said.
However few studies have examined the risks associated with short-term use or compared the commonly used medications in this class against each other.
“Corticosteroids are prescribed so often in children, and we know they have a number of side effects,” Dr Conroy said. “However, when you look at the literature, these are reported somewhat generically. We wanted to quantify them so that when we get questions from our patients we can say something about the likelihood.”
To find out, the researchers analyzed all the studies they could find on corticosteroids administered to patients aged from 28 days to 18 years of age, for up to 14 days of treatment.
The researchers found 38 studies including 22 randomized controlled trials. Among the conditions treated were asthma, bronchiolitis, croup, acute renal failure, allergic rhinitis, dengue fever, infantile spasms, nephrotic syndrome, acute leukemia, acute idiopathic thrombocytopenic purpura, and systemic lupus erythematosus. Prednisolone and dexamethasone were the most commonly used drugs.
These studies documented 850 adverse reactions in 3200 children. Vomiting was the most frequent adverse reaction, affecting 5.4% of children, followed by behavioral changes, which affected 4.7%, and sleep disturbances, which affected 4.3%.
Other adverse events included nausea (1.9%), increased appetite (1.7%), abdominal pain (1.3%), facial swelling and flushing (1.1%), infection (0.9%), and cough (0.2%).
The researchers also documented other gastrointestinal symptoms, drowsiness, throat irritation, diarrhea, excessive urination, and rash, but without determining incidence.
Clinicians stopped the medication in 44 patients because of adverse reactions, most often vomiting, for a rate of 1.4%.
“One of the things that did surprise me was that the most frequent adverse event was vomiting,” Dr Conroy said. This reaction can pose challenges for clinicians trying to administer the drugs, she said.
In the three studies comparing oral prednisolone with oral dexamethasone, the risk of vomiting was much greater with prednisolone (relative risk = 3.62; P = .0001). However, these results are difficult to compare because patients usually had only multiple doses of prednisolone but only one dose of dexamethasone, Dr Conroy said.
Infection was the most serious adverse reaction; one child died from exposure to herpes zoster.
“I think perhaps it’s something that doctors, pharmacies, nurses should perhaps be a little bit more aware of and alert parents to,” said Dr Conroy. “And if their child does come into contact with something like chicken pox while they are taking these corticosteroids, parents should perhaps notify their healthcare providers.”
In those studies where patients were examined for hypothalamic-pituitary-adrenal (HPA) axis suppression, 81% showed signs of this condition. The finding contrasts with research in adults that shows they can take doses as high as 50 mg per day of oral prednisolone without HPA axis suppression, the researchers report.
The children in the studies reviewed did not necessarily have symptoms of HPA axis suppression, and all returned to normal levels of endogenous cortisol secretion within 10 to 12 days after discontinuing corticosteroid use.
Still, this phenomenon could illuminate the mechanism of other adverse events and bears further research, Dr Conroy said. “If our own production of steroids is suppressed, it does mean our body is less able to fight off infections, cope with stress, that sort of thing.”
Meta-analysis across three randomized controlled trials showed a greater risk for HPA axis suppression with oral corticosteroids compared with inhaled corticosteroids.
Corticosteroids had other systemic effects as well. They increased blood pressure in a third of the children tested for hypertension, but the majority did not need antihypertensive drugs. More than a third of patients gained weight.
The results of this study can help clinicians, patients, and families weigh the risks against the benefits of short courses of corticosteroids by quantifying the risks, concluded Dr Conroy. “When a pharmacist dispenses these medications, we have to give an information leaflet. And in that, every side effect that’s ever been experienced is listed, which is quite alarming for a parent potentially.”
The authors have disclosed no relevant financial relationships.
Arch Dis Child. Published online January 14, 2016. Full text