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Intramuscular triamcinolone
This month’s selected commentary
Intramuscular triamcinolone Warren R. Heymann, MD Based on a dialogue between Drs Thomas E. Carson and Gary Brauner Dialogues in Dermatology, a monthly audio program from the American Academy of Dermatology, contains discussions between dermatologists on timely topics. Commentaries from Dialogues Editor-inChief Warren R. Heymann, MD, are provided after each discussion as a topic summary and are provided here as a special service to readers of the Journal of the American Academy of Dermatology. ( J Am Acad Dermatol 2006;54:866-7.)
T
he comparative benefits and risks of intramuscular triamcinolone (IMT) versus oral corticosteroids are controversial. In this dialogue, Dr Carson offers his perspective on the dermatologic use of IMT. Because of the dearth of recent dermatologic studies on this topic, this commentary reviews relevant nondermatologic medical literature to ascertain how other specialists view the use of IMT for chronic, steroid-responsive disorders. Panickar et al1 retrospectively reviewed markers of asthma severity in those who received one or more monthly doses of IMT for 3 periods: (1) 3 months preceding their first injection (pretreatment); (2) from the first injection to 1 month after the last injection (the treatment period); and (3) 3 months after the treatment period (the follow-up period). Five children (5-13 years old) received a single dose and 8 children (12-15 years old) received multiple doses. Multiple doses (3 to 5) of IMT were associated with a decrease in the number of asthma exacerbations and hospital admissions in both the treatment and the follow-up periods. These findings were statistically significant. The authors concluded that IMT is a useful short-term treatment for patients with difficult-to-treat asthma. They speculate as to whether its efficacy is due to improved compliance or a superior anti-inflammatory profile compared with oral steroids. According to Ulinski et al,2 noncompliance is frequent in children and adolescents with nephrotic syndrome. They studied 7 children (6 boys and 1 girl) receiving conventional steroid treatment for a median of 30 months before starting monthly IMT treatment at a dose of 1 mg/kg. The treatment was
The statements and opinions expressed in this commentary are those of the Editor-in-Chief of Dialogues in Dermatology.
866
tapered by a 10% to 20% reduction of the initial dose per month over 6 to 8 months. After a mean observation period of 14 months, the results were evaluated in terms of number of relapses and treatment tolerance. Four children showed a clear decrease in the number of relapses (1.8 to 0 per year); in the other 3 the numbers remained stable. Tolerance was excellent, with no cataract formation or arterial hypertension, and the cushingoid syndrome did not exceed the level experienced under conventional steroid therapy. Growth velocity, which decreased during IMT therapy, returned to normal after the discontinuation of the injections. The authors contend that these preliminary results demonstrate that IMT may be used in patients with the nephrotic syndrome who are suspected of treatment noncompliance. Panickar et al1 state that ‘‘concern about systemic side effects led us to limit the number of doses given to children. From adult studies it is unclear whether IM triamcinolone has a different systemic side-effect profile from regular oral prednisolone at standard doses.’’ They cite two studies, in which IMT was used to treat severe chronic asthma, that reach opposite conclusions regarding the relative safety of IMT compared with oral corticosteroids. McCleod et al3 looked at 17 patients with severe chronic asthma who completed a 48-week prospective double-blind study, with crossover at 24 weeks, in which 80 mg of IMT was administered every 4 weeks, compared with daily oral prednisolone dose of 10 mg. Despite the fact that adrenal suppression, bruising, and hirsutism were worse with triamcinolone compared with oral prednisolone, on completion of the study 16 of the 17 patients opted to continue treatment with IMT. On the other hand, in a study of 22 steroiddependent asthmatic patients, Mancinelli, Navarro,
J AM ACAD DERMATOL
Dialogues in Dermatology 867
VOLUME 54, NUMBER 5
and Sharma4 reported that cushingoid facies, weight gain, and hypertension were less frequent during IMT treatment than during the pretreatment period. In the report by Panickar et al, two children developed a transient, mild cushingoid appearance, suggesting that IMT therapy is associated with clinically detectable side effects. They observed subcutaneous atrophy in two children in whom the drug had been given in the lateral aspect of the thigh. Cleary5 presented a case of lipoatrophy of the thigh in a 1-year-old girl given 20 mg of IMT for a ‘‘croupy cough.’’ He states that glucocorticoids have been shown to affect subcutaneous tissue by decreasing the synthesis of collagen, acid mucopolysaccharides, and elastin by inhibiting fibroblasts. This complication can be reduced by giving the injection deep in the gluteal area, thus avoiding leakage into the dermis. One of the most devastating concerns of utilizing systemic corticosteroids, regardless of the route of administration, is the potential for osteonecrosis of the femoral head. Miyanishi et al6 examined 39 rabbits (3 groups of 13) that were injected intramuscularly with either 25 mg/kg prednisolone sodium succinate, 20 mg/kg methylprednisolone acetate, or 20 mg/kg triamcinolone acetonide. Four weeks after the corticosteroid injection, the bilateral femora and humeri were examined histologically for the presence of osteonecrosis. Seventeen of 26 proximal femora of the methylprednisolone group (65%) demonstrated osteonecrosis compared with 4 of 26 (15%) in those given IMT and 3 of 26 (12%) that received prednisolone, allowing the authors to conclude that injection of methylprednisolone in rabbits is associated with a significant increase in the risk of osteonecrosis compared with the risk of those receiving IMT or prednisolone. In their discussion, the authors note that ‘‘to date, there have been no reports comparing the incidence of human osteonecrosis according to the different corticosteroid compounds used.’’ To their knowledge, ‘‘there seem to be no or few adult osteonecrosis cases which have proved to be caused by systemic administration of triamcinolone alone.’’ Nasser and Ewan7 reported the case of a 42-year-old of Sri Lankan origin who developed bilateral avascular necrosis of the femoral head after 16 intramuscular injections, 9 with IMT and 7 utilizing methylprednisolone. The authors stated that avascular necrosis has been reported to
develop after as little as 2 weeks of corticosteroid treatment, but susceptibility factors remain elusive. Other than corticosteroids, alcohol and substance abuse have been implicated. In conclusion, in some circumstances, IMT may be valuable for use in patients with recalcitrant, steroid-responsive diseases. It remains, however, that corticosteroids, regardless of their route of administration, require careful monitoring for their myriad adverse effects. REFERENCES 1. Panickar JR, Kenia P, Silverman M, Grigg J. Intramuscular triamcinolone for difficult asthma. Pediatr Pulmonol 2005;39: 421-5. 2. Ulinski T, Carlier-Legris A, Schlect D, Ranchin B, Cochat P. Triamcinolone acetonide: a new management of noncompliance in nephritic children. Pediatr Nephrol 2005;20:759-62. 3. McCleod DT, Capewell SJ, Law J, MacLaren W, Seaton A. Intramuscular triamcinolone acetonide in chronic severe asthma. Thorax 1985;40:840-5. 4. Mancinelli L, Navarro L, Sharma OP. Intramuscular high-dose triamcinolone in the treatment of severe chronic asthma. West J Med 1997;157:322-9. 5. Cleary JD. Local atrophy following steroid injection. Ann Pharmacother 2002;36:726. 6. Miyanishi K, Yamamoto T, Irisa T, Motomura G, et al. Effects of different corticosteroids on the development of osteonecrosis in rabbits. Rheumatology (Oxford) 2005;44:332-6. 7. Nasser SM, Ewan PW. Depot corticosteroid treatment for hay fever causing avascular necrosis of both hips. BMJ 2001;322: 1589-91.
Additional topics from the April 2006 issue of the Dialogues in Dermatology: 1. Skin cancer in Australia With Robin Marks, MBBS, interviewed by Maurice Thew, MD 2. Hand dermatitis I With Frances J. Storrs, MD, interviewed by Gary Brauner, MD Dialogues in Dermatology is published monthly by the American Academy of Dermatology in both audio cassette and CD formats. Corporate and editorial offices: 930 E Woodfield Dr, Schaumburg, IL 60173-4729. 2006 subscription rates: $150 for individuals in the United States, Canada, and Mexico; $200 International. ª 2006 by the American Academy of Dermatology, Inc. Subscriptions are available by calling toll-free: 866-503-7546 or faxing 847-240-1859. Additional information is available in the Marketplace section of www.aad.org.
Intramuscular triamcinolone Warren R. Heymann, MD Based on a dialogue between Drs Thomas E. Carson and Gary Brauner Dialogues in Dermatology, a monthly audio program from the American Academy of Dermatology, contains discussions between dermatologists on timely topics. Commentaries from Dialogues Editor-inChief Warren R. Heymann, MD, are provided after each discussion as a topic summary and are provided here as a special service to readers of the Journal of the American Academy of Dermatology. ( J Am Acad Dermatol 2006;54:866-7.)
T
he comparative benefits and risks of intramuscular triamcinolone (IMT) versus oral corticosteroids are controversial. In this dialogue, Dr Carson offers his perspective on the dermatologic use of IMT. Because of the dearth of recent dermatologic studies on this topic, this commentary reviews relevant nondermatologic medical literature to ascertain how other specialists view the use of IMT for chronic, steroid-responsive disorders. Panickar et al1 retrospectively reviewed markers of asthma severity in those who received one or more monthly doses of IMT for 3 periods: (1) 3 months preceding their first injection (pretreatment); (2) from the first injection to 1 month after the last injection (the treatment period); and (3) 3 months after the treatment period (the follow-up period). Five children (5-13 years old) received a single dose and 8 children (12-15 years old) received multiple doses. Multiple doses (3 to 5) of IMT were associated with a decrease in the number of asthma exacerbations and hospital admissions in both the treatment and the follow-up periods. These findings were statistically significant. The authors concluded that IMT is a useful short-term treatment for patients with difficult-to-treat asthma. They speculate as to whether its efficacy is due to improved compliance or a superior anti-inflammatory profile compared with oral steroids. According to Ulinski et al,2 noncompliance is frequent in children and adolescents with nephrotic syndrome. They studied 7 children (6 boys and 1 girl) receiving conventional steroid treatment for a median of 30 months before starting monthly IMT treatment at a dose of 1 mg/kg. The treatment was
The statements and opinions expressed in this commentary are those of the Editor-in-Chief of Dialogues in Dermatology.
866
tapered by a 10% to 20% reduction of the initial dose per month over 6 to 8 months. After a mean observation period of 14 months, the results were evaluated in terms of number of relapses and treatment tolerance. Four children showed a clear decrease in the number of relapses (1.8 to 0 per year); in the other 3 the numbers remained stable. Tolerance was excellent, with no cataract formation or arterial hypertension, and the cushingoid syndrome did not exceed the level experienced under conventional steroid therapy. Growth velocity, which decreased during IMT therapy, returned to normal after the discontinuation of the injections. The authors contend that these preliminary results demonstrate that IMT may be used in patients with the nephrotic syndrome who are suspected of treatment noncompliance. Panickar et al1 state that ‘‘concern about systemic side effects led us to limit the number of doses given to children. From adult studies it is unclear whether IM triamcinolone has a different systemic side-effect profile from regular oral prednisolone at standard doses.’’ They cite two studies, in which IMT was used to treat severe chronic asthma, that reach opposite conclusions regarding the relative safety of IMT compared with oral corticosteroids. McCleod et al3 looked at 17 patients with severe chronic asthma who completed a 48-week prospective double-blind study, with crossover at 24 weeks, in which 80 mg of IMT was administered every 4 weeks, compared with daily oral prednisolone dose of 10 mg. Despite the fact that adrenal suppression, bruising, and hirsutism were worse with triamcinolone compared with oral prednisolone, on completion of the study 16 of the 17 patients opted to continue treatment with IMT. On the other hand, in a study of 22 steroiddependent asthmatic patients, Mancinelli, Navarro,
J AM ACAD DERMATOL
Dialogues in Dermatology 867
VOLUME 54, NUMBER 5
and Sharma4 reported that cushingoid facies, weight gain, and hypertension were less frequent during IMT treatment than during the pretreatment period. In the report by Panickar et al, two children developed a transient, mild cushingoid appearance, suggesting that IMT therapy is associated with clinically detectable side effects. They observed subcutaneous atrophy in two children in whom the drug had been given in the lateral aspect of the thigh. Cleary5 presented a case of lipoatrophy of the thigh in a 1-year-old girl given 20 mg of IMT for a ‘‘croupy cough.’’ He states that glucocorticoids have been shown to affect subcutaneous tissue by decreasing the synthesis of collagen, acid mucopolysaccharides, and elastin by inhibiting fibroblasts. This complication can be reduced by giving the injection deep in the gluteal area, thus avoiding leakage into the dermis. One of the most devastating concerns of utilizing systemic corticosteroids, regardless of the route of administration, is the potential for osteonecrosis of the femoral head. Miyanishi et al6 examined 39 rabbits (3 groups of 13) that were injected intramuscularly with either 25 mg/kg prednisolone sodium succinate, 20 mg/kg methylprednisolone acetate, or 20 mg/kg triamcinolone acetonide. Four weeks after the corticosteroid injection, the bilateral femora and humeri were examined histologically for the presence of osteonecrosis. Seventeen of 26 proximal femora of the methylprednisolone group (65%) demonstrated osteonecrosis compared with 4 of 26 (15%) in those given IMT and 3 of 26 (12%) that received prednisolone, allowing the authors to conclude that injection of methylprednisolone in rabbits is associated with a significant increase in the risk of osteonecrosis compared with the risk of those receiving IMT or prednisolone. In their discussion, the authors note that ‘‘to date, there have been no reports comparing the incidence of human osteonecrosis according to the different corticosteroid compounds used.’’ To their knowledge, ‘‘there seem to be no or few adult osteonecrosis cases which have proved to be caused by systemic administration of triamcinolone alone.’’ Nasser and Ewan7 reported the case of a 42-year-old of Sri Lankan origin who developed bilateral avascular necrosis of the femoral head after 16 intramuscular injections, 9 with IMT and 7 utilizing methylprednisolone. The authors stated that avascular necrosis has been reported to
develop after as little as 2 weeks of corticosteroid treatment, but susceptibility factors remain elusive. Other than corticosteroids, alcohol and substance abuse have been implicated. In conclusion, in some circumstances, IMT may be valuable for use in patients with recalcitrant, steroid-responsive diseases. It remains, however, that corticosteroids, regardless of their route of administration, require careful monitoring for their myriad adverse effects. REFERENCES 1. Panickar JR, Kenia P, Silverman M, Grigg J. Intramuscular triamcinolone for difficult asthma. Pediatr Pulmonol 2005;39: 421-5. 2. Ulinski T, Carlier-Legris A, Schlect D, Ranchin B, Cochat P. Triamcinolone acetonide: a new management of noncompliance in nephritic children. Pediatr Nephrol 2005;20:759-62. 3. McCleod DT, Capewell SJ, Law J, MacLaren W, Seaton A. Intramuscular triamcinolone acetonide in chronic severe asthma. Thorax 1985;40:840-5. 4. Mancinelli L, Navarro L, Sharma OP. Intramuscular high-dose triamcinolone in the treatment of severe chronic asthma. West J Med 1997;157:322-9. 5. Cleary JD. Local atrophy following steroid injection. Ann Pharmacother 2002;36:726. 6. Miyanishi K, Yamamoto T, Irisa T, Motomura G, et al. Effects of different corticosteroids on the development of osteonecrosis in rabbits. Rheumatology (Oxford) 2005;44:332-6. 7. Nasser SM, Ewan PW. Depot corticosteroid treatment for hay fever causing avascular necrosis of both hips. BMJ 2001;322: 1589-91.
Additional topics from the April 2006 issue of the Dialogues in Dermatology: 1. Skin cancer in Australia With Robin Marks, MBBS, interviewed by Maurice Thew, MD 2. Hand dermatitis I With Frances J. Storrs, MD, interviewed by Gary Brauner, MD Dialogues in Dermatology is published monthly by the American Academy of Dermatology in both audio cassette and CD formats. Corporate and editorial offices: 930 E Woodfield Dr, Schaumburg, IL 60173-4729. 2006 subscription rates: $150 for individuals in the United States, Canada, and Mexico; $200 International. ª 2006 by the American Academy of Dermatology, Inc. Subscriptions are available by calling toll-free: 866-503-7546 or faxing 847-240-1859. Additional information is available in the Marketplace section of www.aad.org.