Hydrocortisone — the revolutionary topical treatment for atopic eczema
Although topical hydrocortisone is freely available in pharmacies nowadays, prejudice against its use continues and some patients are still under-treated, explains Jenny Bryan
With all the pomp and pageant of the Diamond Jubilee festivities, you may not have noticed that the cornerstone of modern dermatology, hydrocortisone, is also celebrating a memorable anniversary this year. It is 60 years since the first published report of its topical efficacy in atopic eczema.1
Before hydrocortisone creams and ointments were developed, the treatment of eczema was unsatisfactory, with patients scratching until their skin bled or using messy tar-based products that smelt bad, stained clothing and provided inadequate symptomatic relief.
“Hydrocortisone really was a revolutionary treatment that made a huge difference to eczema patients and remains very useful, especially on facial and genital skin. But, despite all the years of experience with topical steroids, some patients are still under-treated because of fears about side effects, usually based on prejudice rather than understanding of the evidence,” explains Anthony Bewley, consultant dermatologist at Barts and The London NHS Trust.
Turning crystals into creams
Crystals of Factor F, as hydrocortisone was called in 1952, were originally supplied by Merck to leading New York dermatologist Marion Sulzberger and colleague Victor Witten for the study that was to change the treatment of eczema.1 Sulzberger and Witten prepared an ointment of hydrocortisone 25mg, with lanolin 15 per cent and liquid paraffin 10 per cent and white petrolatum qs as the base. Of 19 patients with refractory dermatoses who took part in the first study of topical hydrocortisone, six had proven or presumptive atopic dermatitis and two had possible disease. Patients were chosen for symmetrical sites of lesions, so that the effects of Factor F could be compared with those of the ointment base.
Slightly greater improvements were seen in five out of six of the confirmed cases of atopic dermatitis, and one of the possible cases was much improved. Improvements were seen after a week, and continued throughout the four weeks of treatment. In one responder, improvement was seen in lesions away from the treatment site.
This promising efficacy of topical hydrocortisone must have been a great relief to dermatologists. Sulzberger and Witten had previously shown the beneficial effects of oral cortisone acetate in atopic dermatitis, but adverse effects, including moon face, weight gain, hypertrichosis and hyperpigmentation, led the researchers to recommend that treatment should be limited to the most seriously affected patients, and appropriate monitoring carried out.2
By 1955, a series of studies had shown that about two-thirds of patients with atopic eczema responded to topical hydrocortisone without systemic effects.3 In an early British study of eczema and dermatitis, improvement or complete healing was recorded in 76 per cent of 105 patients treated with 1 per cent hydrocortisone ointment (2.5 per cent in a few resistant cases), compared with 17 per cent of 23 controls.3 The researchers reported that response appeared to depend on the ease of hydrocortisone absorption, and that eroded and exuding eczema and dermatitis healed rapidly, while lichenified eczema showed little improvement.
The hydrocortisone ointment used in this study was supplied by Upjohn (now part of Pfizer) and, in the years following Sulzberger and Witten’s pioneering work, numerous formulations of hydrocortisone in a range of strengths were developed and marketed in the US and Europe. Related topical corticosteroids, notably triamcinolone and betamethasone, were marketed in the early 1960s, and clobetasone in 1975. Before long, the expanding range of topically available steroids was classified according to potency which, as Dr Bewley explains, is based on the vasoconstrictor effects of a steroid on the skin, rather than any inherent “strength” of the molecule.
“Vasoconstriction is used as a measure of potency because it is the most immediate and reproducible effect, but we still aren’t sure of the relationship between the strength of different topical steroids and their immunomodulatory effects. Clearly, the stronger steroids are more effective, and are also more likely to cause side effects,” he says.
The National Institute for Health and Clinical Excellence lists 30 preparations for the treatment atopic eczema, including products of mild potency, such as hydrocortisone (0.5 per cent to 2.5 per cent) and fluocinolone acetonide (0.0025 per cent), moderately potent products, such as betamethasone valerate (0.025 per cent) and clobetasone butyrate (0.05 per cent), potent agents, such as betamethasone valerate (0.1 per cent), fluticasone propionate (0.05 per cent) and mometasone furoate (0.1 per cent), and very potent products, including clobetasol propionate (0.05 per cent) and halcinonide (0.1 per cent).4
The move to OTC
Topical hydrocortisone (0.5 per cent) was approved for OTC use in the US in 1979 after considerable discussion about the potential harms of such a decision,5 and a similar debate ensued in the UK. Critics argued that occasional systemic absorption of hydrocortisone could lead to Cushing’s syndrome, especially in the young, and that repeated use could lead to skin thinning, striae, telangectasia (especially on the face), perioral dermatitis, rosacea and reduced resistance to bacterial and fungal infection.6 In addition, they warned that long-term use could lead to habituation, with rebound inflammation and scaliness if treatment was stopped.
Although acknowledging evidence of skin atrophy after use for several months or years, and possibly rosacea, those in favour of reclassification of topical hydrocortisone, argued that there was a lack of data to support increased risk of systemic effects.7 They pointed to the fact that barely more than a handful of adverse events — none serious — was reported in the first few years after hydrocortisone was made available as an OTC product in the US. Topical hydrocortisone finally became a pharmacy medicine for atopic dermatitis in the UK in 1987.
Concerns over the safety of topical steroids — especially the more potent agents prescribed in dermatology clinics — spilled from medical journals to consumer publications, and the term “steroid phobia” came into common use.
Three quarters of dermatology outpatients with atopic eczema who took part in a survey published in 2000 said they were worried about using topical steroids on their own or their child’s skin, and almost a quarter admitted to non-compliance with treatment because of these worries.8 A third of concerns related to skin thinning, and nearly one in 10 patients were worried about systemic absorption leading to effects on growth and development. The survey showed that misconceptions about steroid potency were common, and a third of patients who used hydrocortisone thought it was classified as either strong or very strong or did not know the potency.
“It is understandable that people are concerned about the potential for side effects with topical steroids because, if you use too much for too long, you can get acne or striae or suppress the hypothalamic pituitary adrenal axis. But when topical steroids are used correctly, we really don’t see these effects. In my experience, problems only arise when patients have repeat prescriptions without supervision or borrow creams without realising that they are more potent than those they were prescribed,” explains Dr Bewley.
Warning patients to apply topical steroids “sparingly” or “thinly” may contribute to steroid phobia and under-treatment of eczema, and it has been proposed that advising patients to “apply enough to cover affected areas” carries a more positive message.9 Better patient understanding of “finger tip units” and how these relate to areas of skin to be treated is also recommended.9
“It’s right to protect patients against risks, but it’s important that topical steroids are used appropriately. We’re not saying ‘slap it on’, and we want to avoid patients using it on unaffected skin. But advising patients to cover affected areas encourages them to use enough to achieve a clinical effect,” says Dr Bewley.
He concludes that topical hydrocortisone will continue to maintain its place as a valuable treatment for inflammatory skin disorders, though patients can become allergic to it and require a switch to a different steroid:
“Some people don’t like using topical steroids because they don’t think they’re natural. But, in reality, they are more natural than many alternative remedies because steroids occur naturally in the body. It’s right that people can choose what to use on their skin, as long as decisions are based on good knowledge of the risks and benefits of all the options.”
1 Sulzberger MB, Witten VH. The effect of topically applied compound F in selected dermatoses. Journal of Investigative Dermatology 1952;19:101–2.
2 Sulzberger MB, Witten VH, Yaffe SN. Cortisone acetate administered orally in dermatologic therapy. AMA Archives of Dermatology and Syphilology 1951;64:573–9.
3 Church R. Hydrocortisone treatment in the eczemas. BMJ 1955;1:517–9.
4 National Institute for Health and Clinical Excellence. Atopic dermatitis. TA 81, August 2004.
5 Ravis SM, Eaglstein WH. Topical hydrocortisone from prescription to over-the-counter sale. Archives of Dermatology 2007;143:413–5.
6 Shuster S. Over the counter sale of topical corticosteroids: the need for debate. BMJ 1985;291:38–9.
7 Greaves M. Over the counter sale of topical corticosteroids: evidence versus anecdote. BMJ (Clinical Research edition) 1985;291:276–7.
8 Charman CR, Morris AD, Williams HC. Topical corticosteroid phobia in patients with atopic eczema. British Journal of Dermatology 2000;142:931–6.
9 Bewley A; Dermatology Working Group. Expert consensus: time for a change in the way we advise our patients to use topical corticosteroids. British Journal of Dermatology 2008;158:917–20.
Citation: The Pharmaceutical Journal URI: 11103129
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