Publications

Published: July 1998

Poorly Recognised Adverse Effects of Inhaled Corticosteroids

Prescriber Update 16: 16–19
July 1998

Dr Sonya Havill, Dermatology Registrar and Dr Marius Rademaker, Dermatologist, Health Waikato, Hamilton

Inhaled corticosteroids are increasingly being used for the first line management of asthma. Adverse effects such as adrenal suppression and osteoporosis are well documented. Less well recognised adverse effects include glaucoma, skin fragility, acne vulgaris and hirsutism. Be aware of the cumulative effect if co-prescribing various dose forms of corticosteroids such as inhaled, intranasal, oral and topical preparations. The lowest dose necessary to achieve optimal disease control should always be prescribed. Consider monitoring intraocular pressure if prescribing >1500µg/day inhaled beclomethasone (or equivalent).

Inhaled corticosteroids have been used in the management of asthma for more than 20 years. Treatment is now being advocated earlier in the course of the disease which has led to a considerable increase in the use of inhaled corticosteroids, particularly at higher dosages.1,2 Topical corticosteroids are generally preferred to systemic steroids because of enhanced control of local disease and a potential reduction in adverse effects.

Systemic effects particularly at >1500 µg beclomethasone inhaled per day

The adverse effects of topical steroids occur either locally, at the site of action of the drug, or as a result of systemic absorption. Although local adverse effects of inhaled steroids are most common (e.g. oral candidiasis and dysphonia),3 there is increasing evidence of systemic adverse effects associated with inhaled steroid use, particularly at higher dosages (>1500µg beclomethasone per day).2

Inhaled steroids are absorbed via the oropharynx, lungs and gut. Absorption which bypasses the gut, and hence does not undergo first-pass metabolism in the liver, has a greater chance of causing systemic adverse effects. Adrenal suppression, osteoporosis, decreased growth in children and behavioural changes are all well recognised dose-dependent adverse effects of inhaled steroids.2 Less well recognised systemic adverse effects of inhaled steroids include glaucoma, skin fragility, acne vulgaris and hirsutism.

Glaucoma - increased risk with high dose and ≥ 3 months therapy

Topical ophthalmic steroids can precipitate ocular hypertension and secondary open-angle glaucoma, as can systemic corticosteroids. The mechanism is thought to involve an increase in intraocular pressure by alteration of the resistance to aqueous humour outflow.4 Whilst this has long been recognised, it has only recently been observed that high dose inhaled steroids may do the same.5 A case-control study in Québec demonstrated an increased risk of ocular hypertension or open angle glaucoma in patients receiving prolonged (≥ 3 months) continuous dosages of inhaled corticosteroids in excess of 1500µg beclomethasone dipropionate (BDP) per day. In these patients it may be advisable to check intraocular pressures. There do not appear to be any reports of glaucoma associated with prolonged continuous use of lower dosages of inhaled steroids.

Skin fragility - dose related purpura, bruising and skin thinning reported

Skin atrophy is a well recognised adverse effect from both topical and systemic corticosteroids. This atrophy leads to purpura, loss of subcutaneous tissue, and increased skin mobility with consequent fragility and traumatic tearing of the skin. The degree of cutaneous atrophy is dose related.6

There are now several reports of skin thinning and purpura in association with long-term inhaled steroids.7-9 One study noted significant purpura and skin thinning in 21 patients using long term high dose (1000-2250µg BDP/day) inhaled steroids for asthma. The authors comment on the confounding factor of some patients having had short courses of systemic steroids.7 A UK questionnaire-based study found easy bruising to be the most commonly reported symptom in a group of patients using inhaled steroids for asthma.8 Patients that reported easy bruising tended to be older, on higher daily dosages and have increased duration of use. Women appear to be more likely to develop skin bruising.9 The common sites of bruising are the forearms and lower legs which suggests a possible cumulative effect with chronic ultraviolet exposure.

Patients should be encouraged to regularly use moisturisers on their arms and legs, as these may reduce bruising and tearing of the skin from minor trauma. Sun protection of these areas, either from clothing or the application of a sunscreen, should also be recommended.

Acne vulgaris - predominantly truncal and affecting older patients

There are several reports of sudden-onset moderately severe acne vulgaris in patients on inhaled steroids.10,11 Unusual features of the acne include the age of the patients (35-75 years of age) and the predominance of truncal acne. This pattern of acne is classical for patients on systemic steroids.

Steroid-induced acne does respond to conventional acne treatments but only if the steroid is discontinued. If the steroid is to be continued, isotretinoin (Roaccutane) may be indicated.

Hirsutism - risk higher in women and those with prolonged use

Over the last few years there have been several reports, to the Centre for Adverse Reactions Monitoring (CARM) and WHO, of patients who have developed hirsutism in association with long-term inhaled steroids. The hirsuties is more marked in female patients who usually note an increase in fine downy hair on the sides of the face, as well as over the upper lip and chin areas. The mechanism of action is likely to be the same as hirsutism associated with oral corticosteroids.

Treatment of this type of hirsuties is unrewarding, particularly if the steroids are to be continued. It is unclear whether the new laser treatments for hair removal will be effective for steroid-induced hirsutism.

Intranasal steroids - lower dosage, less potential for adverse effects

There do not appear to be reports of similar adverse effects from intranasal steroid use, presumably reflecting the lower daily dosages of intranasal steroids (≤ 400µg /day beclomethasone or equivalent). Care does, however, need to be taken when intranasal steroids are used concomitantly with other dose forms of corticosteroids such as potent topical creams (>50g/week), medium dosage inhaled steroids (e.g. 800 - 1000µg BDP /day) or low dose oral steroids. In these situations, it may be wise to monitor intraocular pressure and promote the use of moisturisers and suncreens.

Conclusion

The aim of this article is to bring less well recognised adverse effects of inhaled corticosteroids to the attention of prescribers. Whilst inhaled steroids have a more favourable side effect profile than systemic steroids, they are not free from adverse effects. The dose of inhaled steroids used should be carefully monitored, and kept at the lowest dose necessary to maintain adequate control of the patient’s disease process. Be particularly aware of the cumulative effect of co-prescribing various dose forms of corticosteroids (inhaled, intranasal, oral and topical preparations).

If the cumulative dose of steroids is in excess of 1500µg BDP/day (or equivalent), consider monitoring intraocular pressure, recommend the use of a moisturiser and encourage the use of a sunscreen on the face and arms.

Correspondence to Dr Marius Rademaker, Director of Dermatology, Health Waikato, Hamilton. phone 07 839 8944, fax 07 839 8787, e-mail rademakm@hwl.co.nz.

References
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