Systematic Review of the Toxicity of Long-Course Oral Corticosteroids in Children

Abstract

BackgroundLong courses of oral corticosteroids are commonly used in children in the management of chronic conditions. Various adverse drug reactions (ADRs) are known to occur with their use. This systematic review aimed to identify the most common and serious ADRs and to determine their relative risk levels.MethodsA literature search of Embase, Medline, International Pharmaceutical Abstracts, CINAHL, Cochrane Library and PubMed was performed with no language restrictions in order to identify studies where oral corticosteroids were administered to patients aged 28 days to 18 years of age for at least 15 days of treatment. Each database was searched from their earliest dates to January 2016. All studies providing clear information on ADRs were included.ResultsOne hundred and one studies including 33 prospective cohort studies; 21 randomised controlled trials; 21 case series and 26 case reports met the inclusion criteria. These involved 6817 children and reported 4321 ADRs. The three ADRs experienced by the highest number of patients were weight gain, growth retardation and Cushingoid features with respective incidence rates of 21.1%, 18.1% and 19.4% of patients assessed for these ADRs. 21.5% of patients measured showed decreased bone density and 0.8% of patients showed osteoporosis. Biochemical HPA axis suppression was detected in 269 of 487 patients where it was measured. Infection was the most serious ADR, with twenty one deaths. Varicella zoster was the most frequent infection (9 deaths).ConclusionsWeight gain, growth retardation and Cushingoid features were the most frequent ADRs seen when long-course oral corticosteroids were given to children. Increased susceptibility to infection was the most serious ADR.

Use of systemic corticosteroids for atopic dermatitis: International Eczema Council consensus statement

“…Most children will have fewer comorbidities complicating the use of immunomodulatory agents such as ciclosporin. As such, while systemic CS should be used rarely for severe AD in general, their use should be even more limited in children, particularly given concerns regarding infection, growth delay and increased rates of obesity …”

“…Based on their use in other conditions, the long‐term intermittent use of systemic CS is well known to cause a multitude of side‐effects, and even use for 30 days or less has been associated with increased rates of sepsis, venous thromboembolism and fracture . A recent systematic review of studies in children taking systemic CS for > 2 weeks found significant increases in infections, growth delay and obesity …”

Oral corticosteroids for asthma exacerbations might be associated with adrenal suppression: Are physicians aware of that?

“…18 Evidences of HPA dysfunction due to ICS have been reported in the literature in up to 40% 10,19-23 of cases and due to OCS in up to 80%. 24 Symptomatic AS can be seen in children treated with inhaled beclomethasone even at initial doses as low as 200 mcg/day, depending on individual sensitivity and genetic predisposition. 23 The Canadian Society of Allergy and Clinical Immunology recommends screening for AS in children receiving high-dose ICS based on morning serum cortisol level.…”

Advances in treatment of glucocorticoid-induced osteoporosis

“…In children, weight gain, growth retardation, and Cushingoid features are the most frequent adverse reaction to chronic oral glucocorticoid use, but a recent meta-analysis that included a total of 6817 children noted a 21% incidence of decreased bone mineral density [40]. Growth retardation, whether directly or through suppression of the hypothalamic-pituitary axis or of sex steroid hormone production, puts children at considerable risk of osteoporosis in adulthood, as peak bone mass is achieved in late adolescence and early adulthood.…”