Correspondence
Myopathy in Children Receiving High-Dose Inhaled Fluticasone
N Engl J Med 2004; 350:1157-1159March 11, 2004
- Article
To the Editor:
Inhaled corticosteroids are primary controllers of asthma, and they are safe if used in moderate doses.1 Myopathy is a known side effect of oral corticosteroid therapy,2 but it has so far not been linked to the use of inhaled corticosteroids in children. Fluticasone propionate is a potent inhaled corticosteroid that has been associated with adrenocortical insufficiency if given in high doses (>400 μg per day).3
A girl, 7.9 years old, was referred for evaluation because of fatigue leading to her withdrawal from competitive ice-skating, then to half-time absence from school, and ultimately to her requiring a wheelchair for mobility. When she was 7.0 years old, fluticasone and salmeterol were started in response to her worsening asthma; the condition had previously been treated with beclomethasone dipropionate and oxitropium bromide. Concurrent nasal obstruction was treated with budesonide or fluticasone nasal spray (Figure 1Figure 1
Results of Laboratory and Technical Investigations in Relation to Daily Drug Doses at Various Ages in a Girl (Upper Panel) and a Boy (Lower Panel)., upper panel). After six weeks of high-dose fluticasone, at 7.1 years of age, the girl had increasing fatigue, which was attributed to adrenocortical insufficiency: the dose of fluticasone was reduced, and montelukast was added, together with hydrocortisone — without substantial improvement, however.On admission, the patient's muscle weakness was found to be extreme4 — in particular, proximally in the limbs. No hematologic, metabolic, or virologic screening tests were positive. Serum creatine kinase levels were normal; the urinary creatine level was elevated. Electromyography showed diffuse myogenic abnormalities.5 The girl was depressive, with suicidal episodes, despite the absence of a predisposition for depression. On the basis of a presumptive diagnosis of steroid myopathy, fluticasone was replaced by budesonide and disodium cromoglycate, and salmeterol and montelukast were continued. Furthermore, psychotherapy and treatment with citalopram hydrobromide were initiated. This approach was followed by a slow recovery, including regular attendance at school within 6 months and resumption of competitive ice-skating after 12 months.
A boy 15.5 years of age was referred to us because of fatigue and dyspnea, which had been present for at least one year. Between early childhood and the age of 12.0 years, this boy had been treated continuously with disodium cromoglycate and intermittently with beclomethasone dipropionate or budesonide for asthma. When he was 14.0 years old, fluticasone therapy was begun because of exacerbations of asthma (Figure 1, lower panel). The original pattern of symptoms was gradually replaced by persistent breathlessness, which was interpreted as indicative of undertreatment of asthma; salmeterol and montelukast were added when the boy was 15.0 years of age.
On admission, the boy's muscle strength was found to be reduced4 — in particular, proximally in the limbs. Screening tests for other causes were negative. Serum creatine kinase levels were normal; the urinary creatine level was elevated. Electromyography showed diffuse myogenic abnormalities.5 A diagnosis of steroid myopathy was considered; fluticasone was replaced by beclomethasone dipropionate and disodium cromoglycate, and salmeterol and montelukast were continued. Recovery occurred within two months and included a 50 percent increase in the peak expiratory flow.
Within months, not only adrenocortical insufficiency but also myopathy may develop in children receiving high-dose fluticasone. These disorders can masquerade as incapacitating fatigue or difficult breathing.
5 ReferencesLiliane F. De Swert, M.D.
Carine Wouters, M.D., Ph.D.
Francis de Zegher, M.D., Ph.D.
University of Leuven, 3000 Leuven, Belgium
liliane.deswert@uz. kuleuven. ac. be 1
NHLBI/WHO workshop report: global strategy for asthma management and prevention. Rev. ed. Bethesda, Md.: National Heart, Lung, and Blood Institute, 2002. (NIH publication no. 02-3659.)
2
Decramer M ,de Bock V ,Dom R . Functional and histologic picture of steroid-induced myopathy in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1996;153:1958-1964
Web of Science | Medline3
Todd GR ,Acerini CL ,Ross-Russell R ,Zahra S ,Warner JT ,McCance D . Survey of adrenal crisis associated with inhaled corticosteroids in the United Kingdom. Arch Dis Child 2002;87:457-461
CrossRef | Web of Science | Medline4
Escolar DM ,Henricson EK ,Mayhew J , et al. Clinical evaluator reliability for quantitative and manual muscle testing measures of strength in children. Muscle Nerve 2001;24:787-793
CrossRef | Web of Science | Medline5
Lacomis D . Electrodiagnostic approach to the patient with suspected myopathy. Neurol Clin 2002;20:587-603
CrossRef | Web of Science | Medline
- Citing Articles (6)
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Camilla Christensson, Anders Thorén, Bengt Lindberg. (2008) Safety of Inhaled Budesonide. Drug Safety 31:11, 965-988
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Michael A. Kaliner. (2006) Pharmacologic characteristics and adrenal suppression with newer inhaled corticosteroids: A comparison of ciclesonide and fluticasone propionate. Clinical Therapeutics 28:3, 319-331
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Giorgio Scano, Loredana Stendardi. (2006) Dyspnea and asthma. Current Opinion in Pulmonary Medicine 12:1, 18-22
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Shabnam Foroughi, Ananth Thyagarajan, Kelly D Stone. (2005) Advances in pediatric asthma and atopic dermatitis. Current Opinion in Pediatrics 17:5, 658-663
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Allen W Root. (2004) Endocrinology and metabolism, 2004. Current Opinion in Pediatrics 16:4, 415-418
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