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respiratory MEDICINE
CME
CASE REPORT
Servei de Pneumologia, Hospital Clinic, Universitat de Barcelona, Villarroel 170, 08036 Barcelona, Spain
KEYWORDS Summary
Insulin; Some prednisone-resistant asthma patients respond to intramuscular triamcinolone
Refractory asthma; acetonide (TA). The use of TA has been questioned on the basis of its potential toxicity.
Severe asthma; TA’s ratio of clinical efficacy to systemic effects compared with oral prednisone has not
Steroid-dependent been clearly defined.
asthma; We report the case of a prednisone-insensitive severe asthma patient with insulin-
Triamcinolone dependent diabetes, hypertension and diabetic retinopathy treated with repeated sessions
acetonide of laser therapy. By daily monitoring the needs of insulin doses we compared the systemic
effects of prednisone and TA.
The analysis of the balance between systemic effects (insulin doses) and beneficial effects
(PEF values) show that TA has a better benefit/risk profile than prednisone. The patient has
been followed up for 3 years and has received injections of TA repeated at intervals
ranging from 21 to 60 days according to patient response and the evolution of PEF and
clinical symptoms. During this period the patient lost 3 kg of weight, while presenting
increased bone mineral density, normalized arterial tension, and improved proliferative
diabetic retinopathy.
The present case report shows that TA has a better benefit/risk profile than prednisone. TA
can be a valuable alternative in the control of some patients with severe prednisone-
resistant asthma.
& 2008 Elsevier Ltd. All rights reserved.
Introduction
1755-0017/$ - see front matter & 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.rmedc.2008.01.005
ARTICLE IN PRESS
112 C. Picado
The so-called steroid-resistant asthma, constitutes a infections, physical activity, cold air, and exposure to
therapeutic challenge that at present has no efficacious irritants (paints, smoke). Attacks often occurred at night
alternative therapy.1 or in early morning. He had a chronic morning cough that
There is, however, an extended literature on the use of produced scanty clear secretions. He had visited the
the intramuscular injection of triamcinolone acetonide (TA) emergency department on many occasions and had been
in asthmatic patients who do not respond to prednisone. In admitted to hospital five times, but never to the intensive
most of these studies, asthma patients insensitive to care unit. The patient has never smoked, had no history of
prednisone show a very good response when treated allergy and the prick test to common allergens was negative.
with AT.2–9 He was followed by a specialist in pulmonary medicine
Two reasons are usually suggested to explain these and treated with fluticasone (1000 mg/day), salmeterol
differences in the response: (1) the improvement after the (100 mg/day), montelukast (10 mg/day), and oral prednisone
intramuscular injection of TA reflects nothing more than (daily doses fluctuating between 10 and 70 mg). He often
improvement in adherence to the treatment, and (2) used salbutamol as rescue medication and was also provided
triamcinolone is released from the acetonide or depot form with a nebulizer to self-administer at home a combination of
of the drug by a slow enzymatic process of deacetonization. salbutamol and ipratropium bromide that he has used
This results in a long pharmacological half-life with regularly (ranging from 2 to 6 nebulizations daily).
remarkable therapeutical efficacy but also with a high rate The patient had a history of diabetes mellitus that began
of corticosteroid-related toxicities. Thus, the injection of TA at the age of 18 and treated with insulin (Unilong 375, Lilly,
represents the use of a potent corticosteroid with pros and Spain; mean daily dose 40 units, ranging from 30 to 70
cons similar to those observed with very high doses of units). He presented various common complications asso-
prednisone.10 ciated with diabetes mellitus including: diabetic retino-
Nevertheless, some observations do not appear to support pathy, and erectile and urinary blander dysfunction. He had
these arguments. In fact, prednisone-resistant asthma required laser therapy four times to treat the retinopathy.
patients who are good compliant subjects, respond to TA He also suffered from arterial hypertension treated with
without apparently suffering from an evident increase in enalapril maleate.
systemic side effects. On the contrary, these patients often The patient appeared to be compliant with respect to the
lose weight, their cushingoid appearance of the face medication and he used inhalers adequately. He had a
normalizes, and their blood pressure decreases, when they normal weight for his height, gender and age, and he had a
are switched from high doses of daily prednisone to shots mild cushingoid face appearance.
of TA.7,9 The patient was followed up in the out-patient clinic and
These observations support the notion that TA may be the presence of the comorbidities sometimes associated
more effective than prednisone through a mechanism other with refractory asthma (cardiac insufficiency, gastroesopha-
than improved compliance, as well as suggesting that its geal reflux, and obstruction of the upper airway), was
therapeutic efficacy is not necessarily associated with the excluded. The patient remained symptomatic with daily
induction of more severe and unacceptable steroid-related symptoms, frequent night awakening and regular use of
systemic side effects. bronchodilator therapy. The daily dose of prednisone
Systemic side effects of glucocorticoids can be assessed ranged from 10 to 60 mg. With high doses of prednisone
by measuring cortisol levels at baseline and after cortico- (60–70 mg/day), the symptoms appeared to slightly improve
tropin. However, these methods are not very useful in the but when the dose of prednisone was tapered below
daily monitoring of the systemic effects of glucocorticoids, 25–20 mg, they worsened again and the patients had to
particularly in severe asthma patients who are usually use nebulized bronchodilator therapy 5–6 times a day. Daily
treated with fluctuating doses of systemic glucocorticoids. PEF measurements showed values from 150 to 230 L/m
In patients with diabetes mellitus treated with insulin, changing in parallel to variations in the oral dose of
the use of glucocorticoids is usually associated with a prednisone.
proportional increase in the units of insulin needed to A bone mineral densitometric (BMD) study showed a spine
control serum glucose levels.11 osteopenia (BMD ¼ 0.979 g/cm2; T-score ¼ 2.0; normal
We report the case of a corticosteroid-insensitive severe values T-scoreX1.0).
asthma patient who was also an insulin-dependent diabetic. To check the adequate use of medication and the
By monitoring the needs of insulin doses on a daily basis, we response to glucocorticoids, the patient was admitted to
compared the systemic effects of prednisone and TA. We hospital and treated with 70 mg of prednisone (1 mg/kg of
also evaluated the response of asthma to prednisone and TA weight) for 4 days, and the dose was progressively tapered
through daily monitoring of PEF, as well as through the by 10 mg every 3 days. The patient was discharged on day
assessment of clinical symptoms and the use of short-acting ten and followed up in the out-patient clinic. The morning
b2-agonist agents as rescue medication. PEF slowly improved from a baseline value of 160 L/m to a
maximal of 230 with glucocorticoid therapy, but the
improvement slowed down when the dose of oral prednisone
Case report was progressively tapered (Figure 1). The forced expiratory
volume in the 1 s (FEV1), rose from a baseline value of 54% of
A 56-year-old man was referred to the Severe Asthma Clinic predicted to a maximal value of 63% predicted. Clinical
of our Institution for evaluation. Asthma has developed at symptoms followed a similar pattern to that of PEF, with an
the age of 39 with the characteristics of a severe process. initial improvement followed by a progressive deterioration
Exacerbations occurred frequently, triggered by respiratory when the dose of prednisone was reduced. When the patient
ARTICLE IN PRESS
Triamcinolone in steroid-resistant asthma 113
explanation accounting for the contrasting side effects 4. Panickar JR, Bhatnagar N, Grigg J. Exhaled nitric oxide after a
exerted by TA on weight, hypertension, and bone miner- single dose of intramuscular triamcinolone in children with
alization compared to skin atrophy. Skin atrophy has been difficult to control asthma. Pediatr Pulmonol 2007;42:573–8.
observed with fluorinated glucocorticoids administered by 5. Ogirala RG, Sturm TM, Aldrich TK, Meller FF, Pacia EB, Keane
all routes (inhaled, systemic, and topical)16,17 but the AM, et al. Single, high-dose intramuscular triamcinolone
mechanisms involved in varying intensities of the systemic acetonide versus weekly oral methrotrexate in life-threatening
asthma: a double-blind study. Am J Respir Crit Care Med 1995;
side effects of these drugs on different tissues and organs
152(5, part 1):1461–6.
are as yet unclear. 6. McLeod DT, Capewell SJ, Law J, MacLaren W, Seaton A.
In summary, intramuscular TA proved to be effective in a Intramuscular triamcinolone acetonide in chronic severe asth-
prednisone-resistant asthma patient. By assessing changes in ma. Thorax 1985;40:840–5.
insulin doses it was possible to closely monitor and compare 7. Willey RF, Fergusson RJ, Godden DJ, Crompton GK, Grant IW.
the systemic side effects of TA and prednisone, two drugs Comparison of oral prednisolone and intramuscular depot
with very different pharmacokinetic profiles. The analysis of triamcinolone in patients with severe chronic asthma. Thorax
the balance between systemic effects (insulin doses) and 1984;39:340–4.
therapeutic effects (PEF values) shows that TA has a better 8. ten Brinke A, Zwinderman AH, Sterk PJ, Rabe KF, Bel EH.
‘‘Refractory’’ eosinophilic airway inflammation in severe asth-
benefit/risk profile than prednisone. In addition, some
ma. Am J Respir Crit Care Med 2004;170:601–5.
prednisone-associated side effects decreased during the
9. Mancinelli L, Navarrro L, Sharma OP. Intramuscular high-dose
3-year follow-up treatment with TA. All in all, these findings triamcinolone acetonide in the treatment of severe chronic
suggest that TA can be a potentially valuable alternative in asthma. West J Med 1997;157:322–9.
the control of some severe, prednisone-resistant asthma. 10. Boushey HA. Treatment of chronic severe asthma. West J Med
Elucidation of the mechanisms by which TA is more 1997;157:359–60.
effective than prednisone in some severe asthmatics might 11. Braithwaite SS, Barr WG, Thomas JD. Diabetes management
help to better understand the origin of glucocorticoid during glucocorticoid therapy for nonendocrine diseases.
resistance and could also contribute to the design of Endocr Pract 1996;2:320–5.
powerful new drugs to treat these patients, who are usually 12. Kusama M, Sakauchi N, Kumaoka S. Studies of plasma levels and
urinary excretion after intramuscular injection of triamcinolone
difficult to manage.
acetonide. Metabolism 1971;20:590–6.
13. Prednisone Metabolism. In: Herdman JG, Limbird LE, editors.
Conflict of interest statement Goodman and Gilman’s. The pharmacological basis of ther-
apeutics. McGraw-Hill: New York; 2001. p. 1987.
The author has no conflict of interest to declare in relation 14. Zein WM, Noureddin BN, Jurdi FA, Schakal A, Bashsur ZF.
to this work. Panrentinal photocoagulation and intravitreal triamcinolone
acetonide for the management of proliferative diabetic retino-
pathy with macular edema. Retina 2006;26:137–42.
References 15. Laan RF, van Riel PL, van de Putte LB, van Erning LJ, van’t Hof
MA, Lemmens JA. Low dose prednisone induces rapid reversible
1. ERS Task Force Report. Difficult therapy-resistant asthma. Eur axial bone loss in patients with rheumatoid arthritis. Ann Intern
Respir J 1999;13:1198–208. Med 1993;119:963–8.
2. Peake MD, Cayton RM, Howard P. Triamcinolone in corticoster- 16. Schoepe S, Schäcke H, May E, Asadullah K. Glucocorticoid
oid-resistant asthma. Br J Dis Chest 1979;73:39–44. therapy-induced skin atrophy. Exp Dermatol 2006;15:406–20.
3. Panickar JR, Kenia P, Silverman M, Grigg J. Intramuscular 17. Heuck C, Wothers OD, Hansen M, Kollerup G. Short-term growth
triamcinolone for difficult asthma. Pediatr Pulmonol 2005;39: and collagen turnover in asthmatic adolescents treated with the
421–5. inhaled glucocorticoid budesonide. Steroids 1997;62:659–64.