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Published: March 2004
ADR update

Inhaled Corticosteroids - Watch for Skin Atrophy

Prescriber Update 25(1): 6–7
March 2004

Marius Rademaker, Hon. Associate Professor, Dermatology Department, Waikato Hospital, Hamilton

Inhaled corticosteroids can cause skin atrophy.  This adverse effect may be exacerbated by sun exposure, possibly via a cumulative mechanism.  The risk of skin atrophy can be minimised by using the lowest possible maintenance dose of inhaled steroid, as well as protecting the skin from sun exposure.  Be aware that concurrent use of other forms of steroids can collectively increase the risk of skin atrophy and other steroid-induced unwanted effects.

Inhaled corticosteroids known to have some systemic effects

Inhaled corticosteroids have an essential role in the management of asthma. Inhalation allows high concentrations of corticosteroids to reach target sites within the lung while keeping systemic exposure to a minimum.1  Although the safety profile of inhaled corticosteroids is generally superior to that of oral corticosteroids, systemic adverse effects do still occur.

A number of studies2,3 confirm that inhaled corticosteroids, even at low doses,4 can cause skin atrophy (i.e. paper-thin skin5) and purpura.  The mechanism appears to involve a reduction in collagen synthesis.4  In one study,4 there was a significant reduction in the concentrations of the two main collagen precursors in the skin after six weeks of either 400 mcg/day (n=9) or 1600 mcg/day (n=10) of inhaled budesonide.  Similar collagen changes were found in pre-pubertal children receiving inhaled budesonide in doses ranging from 200-800 mcg/day.6

Potential for adrenal suppression may correlate with risk of adverse skin effects

A meta-analysis3 of 27 studies found that marked adrenal suppression mostly occurred with doses of inhaled corticosteroid above 1500 mcg/day (750 mcg/day for fluticasone propionate).  The meta-analysis showed fluticasone had a significantly greater effect on adrenal suppression compared to inhaled beclomethasone or budesonide.  The potential for corticosteroid-induced adrenal suppression was found to correlate with the likelihood of skin bruising.3

Sun exposure can accelerate skin atrophy

The Centre for Adverse Reactions Monitoring (CARM) has received a report suggestive of sun exposure aggravating the skin atrophic effects of inhaled corticosteroids.  There is one published case report7 of the association between topical corticosteroids, sun exposure and skin atrophy.  The pathogenesis of skin atrophy from photoaging (i.e. skin changes as a result of sun exposure) is similar to that of corticosteroids, namely through changes in collagen synthesis.8-10  It is likely that the effects of sun and inhaled corticosteroids are at least cumulative, if not synergistic.

The potential for skin atrophy can be minimised

The risk of systemic side effects, including skin atrophy, with inhaled corticosteroids can be minimised by using the lowest possible maintenance dose that provides best asthma control.  Reviewing the patient's inhalation technique may also be useful.  Be aware of other dose formulations of corticosteroids (i.e. intra-nasal, topical and systemic steroids), which should also be kept to a minimum due to the potential for cumulative effects.11

There is some evidence that sun exposure can accelerate steroid-induced skin atrophy, the development of which can be limited by protecting the skin, particularly the face and arms, from the sun.  Daily use of a broad-spectrum sunscreen (UVB and UVA block) and appropriate protective clothing is recommended.10,12-14  Patients on corticosteroids should also be encouraged to regularly use moisturisers on their arms and legs, as these may reduce bruising and tearing of the skin from minor trauma.11  Evidence suggests that topical tretinoin can increase the epidermal thickness of sun-damaged atrophic skin, but long-term use may be necessary.14  In dermatological practice, topical retinoids are used to help reverse skin atrophy caused by sun exposure or corticosteroid use.

Competing interests (author): none declared.

Correspondence to Dr Marius Rademaker, Dermatology Department, Waikato, Private Bag 3200, Hamilton. E-mail: Rademakm@waikatodhb.govt.nz

References:
  1. Allen DB, Bielory L, Derendorf H, et al. Inhaled corticosteroids: past lessons and future issues. J Allergy Clin Immunol 2003;112(3 Suppl):S1-40.
  2. Capewell S, Reynolds S, Shuttleworth D, et al. Purpura and dermal thinning associated with high dose inhaled corticosteroids. BMJ 1990;300(6739):1548-1551.
  3. Lipworth BJ. Systemic adverse effects of inhaled corticosteroid therapy: A systematic review and meta-analysis. Arch Intern Med 1999;159(9):941-955.
  4. Autio P, Karjalainen J, Risteli L, et al. Effects of an inhaled steroid (budesonide) on skin collagen synthesis of asthma patients in vivo. Am J Respir Crit Care Med 1996;153(3):1172-1175.
  5. Diagnostic approach to skin diseases: Secondary skin lesions. In Beers MH, Berkow R (Eds) The Merck Manual of Diagnosis and Therapy 17th edn. 1999: Merck Research Laboratories, New Jersey, USA, p.782.
  6. Wolthers OD, Juul A, Hansen M, et al. The insulin-like growth factor axis and collagen turnover in asthmatic children treated with inhaled budesonide. Acta Paediatr 1995;84(4):393-397.
  7. Pena JM, Ford MJ. Cutaneous lymphangiectases associated with severe photoaging and topical corticosteroid application. J Cutan Pathol 1996;23(2):175-181.
  8. Kondo S. The roles of cytokines in photoaging. J Dermatol Sci 2000;23(Suppl 1):S30-36.
  9. Contet-Audonneau JL, Jeanmaire C, Pauly G. A histological study of human wrinkle structures: comparison between sun-exposed areas of the face, with or without wrinkles, and sun-protected areas. Br J Dermatol 1999;140(6):1038-1047.
  10. Whitmore SE, Levine MA. Risk factors for reduced skin thickness and bone density: possible clues regarding pathophysiology, prevention, and treatment. J Am Acad Dermatol 1998;38(2 Pt 1):248-255.
  11. Havill S, Rademaker M. Poorly recognised adverse effects of inhaled corticosteroids. Prescriber Update April 1998;(16):16-19. www.medsafe.govt.nz/profs/PUarticles/2.htm
  12. Fisher GJ, Kang S, Varani J, et al. Mechanisms of photoaging and chronological skin aging. Arch Dermatol 2002;138(11):1462-1470.
  13. Wlaschek M, Tantcheva-Poor I, Naderi L, et al. Solar UV irradiation and dermal photoaging. J Photochem Photobiol B 2001;63(1-3):41-51.
  14. Kossard S, Anderson P, Davies A, Cooper A. Histological evaluation of the effect of 0.05% tretinoin in the treatment of photo damaged skin. Geographic differences in elastosis in baseline biopsies. Australas J Dermatol 1993;34(3):89-95.

 

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