Bayliff, C.D.

Paterson, N.A.M.

Sagert, G.

The Canadian Journal of Hospital Pharmacy (CJHP) / Le Journal canadien de la pharmacie hospitalière (JCPH)

32 The Canadian Journal of Hospital Pharmacy - Volume 46, No. 1, February 1993 CASE REPORT ~ Aerosol Corticosteroid Induced Purpura G. Sagert, C.D. Bayliff and N.A.M. Paterson INTRODUCTION Aerosol corticosteroids are increas-ingly being advocated for manage-ment of responsive cases of obstruc-tive pulmonary disease. With trends in both increased utilization and in-creased dose of aerosol corticoste-roids there are increasing reports of toxicity, including purpura.1-5 Purpu-ra is a manifestation of several dis-eases including systemic vasculitis, infections such as meningococcemia and measles, drug use, and senility. Inflammation of purpuric lesions does not occur in senile purpura, nor in corticosteroid-induced purpura. The existence of purpura suggests weakening of skin tissue secondary to the breakdown of collagen.6 We report a case of aerosol corticoste-roid-induced purpura and review the literature on this recently recognized complication of aerosol corticos-teroids. CASE A 7 4 year-old male was admitted to hospital with a chief complaint of shortness of breath, accompanied by fever, chills, rigors, sweats and pleu-ritic right-sided chest pain. The his-tory of his present illness included longstanding bronchitis/ emphyse-ma, for which he had received home oxygen since 1986. He was a greater than 100 pack-year smoker but "quit" in 1987, and now smokes only occasionally. He also had a history of alcohol abuse. His past medical history was extensive and included kyphosis, Duke's C carcinoma with surgical resection, cataracts and pep-tic ulcer disease. Review of systems was remarkable only for his dyspnea. On examination, the patient was thin and was dyspneic at rest. His blood pressure was 130/80 mmHg, tem-perature 3 8.3 °C, heart rate 130 beats per minute, and respiratory rate 30/minute. Chest examination re-vealed crackles over the right lower lobe, and he had modest pedal ede-ma. Non palpable purpuric lesions were evident on forearms. The re-mainder of the physical exam was unremarkable. According to the pa-tient, his medications at home in-cluded salbutamol metered dose inhaler (MDI), budesonide MDI, theophylline, and furosemide. He in-dicated that he used his MDis seven times daily (q3h while awake) ad-ministering two puffs of each MDI for each dose. Blood gases on admis-sion were PO2 59 mmHg, pH 7.49, PCO2 37 mmHg and HCO3 28 mmol/L. Serum chemistries were re-markable for an elevated glucose of 8.3 mmol/L, serum albumin 30 g/L, total bilirubin 20 µmol/L and theo-phylline serum concentration of 28 µmol/L (N 55-110). Prothrombin time and partial thromboplastin time were 9.6 and 29 seconds respective-ly. Platelet count was normal. White blood cell count was elevated at 13.6 x 109 /L. The patient was diagnosed as having an exacerbation of COPD and was prescribed amoxicillin, fur-osemide, heparin, ipratropium and salbutamol MDis and beclometha-sone MDI 250 mcg qid. When spe-cifically asked, regarding the purpur-ic lesions on his forearms, he in-dicated that these had developed one month prior to admission, and ap-proximately three months after in-creasing his budesonide from the prescribed daily dose of 800 mcg to 2800 mcg per day, (2 puffs q3h). He also reported that the higher dose made him "feel better" than the lower dose. The possibility of corti-costeroid-induced purpura was sus-pected, and the patient was strongly encouraged to comply with the pres-cribed regimen. Aside from some minor psychic changes, the patient encountered no difficulties with the lower dose. Follow up one month after discharge revealed that the pur-puric rash was still present, although it had faded somewhat. DISCUSSION Aerosol corticosteroid induced pur-pura is infrequently cited as a com-plication of aerosol corticosteroid G. Sagert, B.Sc.Phm. was a Pharmacy Resident at Victoria Hospital in London, Ontario at the time this paper was written and is now a staff pharmacist at Mt. Sinai Hospital, Toronto, Ontario. C.D. Bayliff, Pharm.D. is the Clinical Coordinator of Pharmacy Services, Victoria Hospital, London, Ontario. N.A.M. Paterson, M.B. FRCP(C) is a member of the Department of Medicine, Victoria Hospital. Acknowledgements: The authors would like to acknowledge the secretarial assistance of Ms. G. Campbell. 1 1 d st The Canadian Journal of Hospital Pharmacy - Volume 46, No. 1, February 1993 use.5,6 The occurrence of oral and topical corticosteroid induced pur-pura is a comparatively well known phenomenon, believed to be caused by the atrophy of collagen leading to rupture of capillaries in the skin. Though these lesions resemble senile purpura, corticosteroid induced pur-pura occurs usually only on the legs below the knees and the fronts of the forearms.7 A single case report of purpura associated with aerosolized corticos-teroids has been reported to date. This involved a 54 year-old female asthmatic who, after 18 months on high dose inhaled beclomethasone (750 mcg twice daily), developed persistent and extensive bruising on her arms and legs. She received se-vere full thickness lacerations to the purpuric and atrophic areas of skin which subsequently required graft-ing. She underwent adrenal function tests and was found to have border-line adrenal impairment. The report-ing physician felt that the purpura was secondary to the use of high dose aerosol corticosteroids.6 Recently, studies have identified that a rela-tionship does exist between the development of purpura and de-pressed morning serum cortisol mea-surements. (Personal communica-tion Dr. J.H. Toogood). A recent study assessed the effect of high dose aerosol corticosteroids on the thickness of skin. 5 The inves-tigators found that those patients receiving oral prednisolone or high dose aerosol corticosteroids had sig-nificantly thinner skin (28-33% and 15-19% respectively) than those re-ceiving low dose aerosol corticoste-roids and controls. Furthermore, the occurrence of purpura was signifi-cantly greater in patients taking oral prednisolone ( 12/ 15) and in those receiving high dose aerosol corticos-teroids (10/21) than in the control group (2/ 1 7). It was concluded that skin thinning and purpura represent evidence of systemic effects of high dose aerosol corticosteroids. 5 The risk factors associated with systemic effects of aerosol corti-costeroids include increased dose (2:1500 mcg beclomethasone) and duration of treatment.5 Whether the use of spacer affects risk is un-known.8 It appears that both bude-sonide in this case and beclometha-sone5,6 in other cases may produce purpura. Pharmacists should be aware that high dose aerosol corticosteroids may cause purpura, as well as other systemic adverse effects including skin thinning, adrenocorticoid sup-pression, decreased insulin sensitiv-ity, behaviourial changes and pos-sibly posterior subcapsular cata-racts.2,3,9 Purpura is a visible sign of corticosteroid toxicity, suggesting 33 other less easily detected effects may also be occurring. Assessment of compliance is essential to identify excessive use of inhaled corticoste-roids, since higher doses increase the risk for systemic adverse effects. ~ REFERENCES 1. Stead RJ, Cooke NJ. Adverse effects of inhaled corticosteroids. BMJ 1989; 298:403-4. 2. Toogood JH. Complications of topical steroid therapy for asthma. Amer Rev Resp Dis. 1990; 141 :S89-S96. 3. Fraunfelder FT, Meyer SM. Posterior subcapsular cataracts associated with nasal or inhalation corticosteroids. Amer J Ophthal 1990; 109:489-90. 4. Fitzpatrick TB, Haynes HA. Skin lesions of general medical significance. In Petersdorf RG, Adams RD, Braunwald E, et al, eds. Harrison's principles of internal medicine. New York 1983; 263. 5. Capewell S, Reynolds S, Shuttleworth D, et al. Purpura and dermal thinning associated with high dose inhaled corticosteroids. BMJ 1990; 300: 1548-51. 6. Maxwell DL, Webb J. Adverse effects of inhaled corticosteroids (Letter). BMJ 1989; 298:827-8. 7. Scarborough H, Shuster S. Cortico-steroid purpura. Lancet 1960; i:93-4. 8. Brown PH, Bklundell G, Greening AP, et al. Do large volume spacer devices reduce the systemic effects of high dose inhaled corticosteroids? Thorax 1991; 45:736-9. 9. Connett G, Lenney W. Inhaled budesonide and behaviourial disturbances. Lancet 1991; 338:634-5. 

Aerosol Corticosteroid-Induced Purpura

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