Desonide (as a cream, ointment, or lotion formulation) is widely used for the treatment of steroid-responsive dermatoses. This paper provides information on its safety record, as determined from adverse event reports and published trial results. A pharmacovigilance program, initiated in 1992 for all countries where desonide is available, collected reports of adverse events associated with topical desonide over nine years. Published accounts of randomized, controlled trials of desonide in comparison with hydrocortisone were reviewed. Sixty-two reports have been collected; most were from consumers and were not medically substantiated. There were no serious reactions directly attributable to desonide treatment and the majority of events reported were classified as expected local reactions, generally mild in nature. This level of reporting is against a background of extensive prescribing of desonide; almost one million packs are dispensed per annum in the US alone. The excellent safety profile of desonide revealed by this pharmacovigilance program is supported by a review of published clinical trial results.

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Introduction

Long-term corticosteroid use has been associated with local side effects (skin atrophy, contact dermatitis, striae, telangiectasia, and depigmentation), although such complications are generally linked to the higher potency preparations. The choice of topical steroid, therefore, requires balancing efficacy with tolerability while accurately matching the potency of any chosen drug with the severity of the skin condition being treated. The anticipated length of treatment is also critical when deciding on treatment. For long-term treatment, or when large areas of skin are involved, low-potency corticosteroids are preferred.

The potential for hypothalamic-pituitary-adrenal (HPA) axis, most serious of all the risks associated with the long-term use of topical corticosteroids (1), is of particular concern when treating pediatric patients. Their relatively large body surface area to mass ratio increases exposure to the corticosteroid and thereby the likelihood of suppression increases (2). These concerns preclude or limit the choice of corticosteroids that can be used safely in children.

When considering topical steroid therapy, disease characteristics, anticipated length of treatment, region of the body involved, age of the patient, potency of the steroid, its formulation and safety profile and, finally, the likelihood of patient compliance should all influence the decision-making process. In this context, this paper reviews the safety profile of topical desonide, a mild to moderately potent corticosteroid that has been available in the US for several decades.

Desonide: Post-marketing Surveillance of Safety

A global post-marketing surveillance program to monitor adverse events associated with the use of all desonide formulations was initiated by Galderma in 1992. The program, in accordance with the International Conference on Harmonization E2 guidelines, collects safety-relevant information using a database which enables any safety concerns to be detected at the earliest possible opportunity. The two most important sources for this database have been direct reporting by consumers and healthcare professionals. Additional sources include published clinical trials where desonide products were used as comparators, and case reports in the literature.

Estimating Desonide Usage

To put the output of this database in context, it is helpful to consider the usage and, therefore, the potential exposure of patients to desonide over the same period. The preparation of desonide 0.05% known as Desowen[R]. (Galderma Laboratories) is available on many world markets including those of the US and Canada, many Central and South American countries, India, Korea, Singapore and Hong Kong, and the list is growing.

To estimate usage, sales of all three formulations of Desowen in the US between 1992 and 2000 have been calculated in terms of individual packs. Each pack, irrespective of size and formulation, has been considered as one unit. By 2000, total Desowen sales per annum approached one million units, with the newest formulation (Desowen lotion 0.05%) showing an almost ten-fold increase in the volume of sales between 1992 and 2000, from 14.6% to 87.2%. Therefore, in this one market alone, the exposure of patients to desonide has been extensive.

Adverse Events Reported

The pharmacovigilance program, since 1992, has collected reports of adverse events affecting just 62 people (Table I). Thirty-seven of these reports (~60%) of these reports have come directly from the consumer and therefore have not been medically confirmed. Furthermore, these consumer reports are often poorly documented and provide little information regarding outcome. On the other hand, physicians may under-report "minor" events, such as local allergic or skin reactions, which are known to be associated with topical corticosteroids.

The incidence of adverse events is given in Table II according to their nature (expected local skin reactions, exacerbation of the existing condition/lack of drug effect, unexpected or other reactions) and the formulation of desonide. The numbers involved in any one category are small and any apparent differences between formulations should not be over-interpreted.

Serious Reactions

In the nine-year surveillance period, only two events associated with the use of desonide have been classified as serious according to the International Conference on Harmonization guidelines. One involved a 41-year-old female from the US who developed a rash under her jaw line, and experienced itching and burning sensations on her face for several days. The time to onset was not reported. This patient had applied desonide ointment onto streaked skin with open lesions (bleeding), inflammation, and pruritus that followed use of a "chemical peel." The event was considered unlikely to be related to the desonide ointment.

The other event concerned a 6-month-old child who was hospitalized with bulging fontanels and mild fever; she had been prescribed desonide ointment 0.05% for atopic dermatitis 10 weeks previously and was also receiving the anti-histamine hydroxyzine. Desonide therapy was temporarily interrupted and the hydroxyzine was discontinued. The patient made an uneventful recovery and the adverse event was considered unlikely to be related to the use of desonide.

Skin Irritation

Of the 62 adverse events recorded within the pharmacovigilance program, skin irritation was the most common complaint in 29 (47%) cases (Table II); one of these has been mentioned as a serious event. About two-thirds of the reports were made by consumers. The incidence was evenly spread between all three product formulations and typically involved the appearance of one or more of the following symptoms: burning and stinging sensations; pruritus and irritation; erythema and general redness; vesicular erythema; swelling; sensitive skin; dry skin; and blisters, welts, and "bumps." The first two categories were more prevalent.

Time to onset of skin irritation was recorded by only nine patients, and ranged from 15 seconds (intense burning, redness, and swelling) to four months (development of hypersensitive skin).

Allergic Reactions

There were nine reports of allergic reactions (14.5% of patients; Table II) of which seven were made by physicians, one by a consumer, and one was reported in the literature (3). Contact dermatitis was the presumed diagnosis for seven of these cases; this was confirmed in five patients by a positive dechallenge/rechallenge or by epicutaneous testing against constituents of the formulation.

Non-specific allergic reactions were the subject of two reports. One case involved a 75-year-old female who experienced inflammatory bowel syndrome, allergies, retention of fluids, and memory loss following the use of desonide cream over a two-year period, with the symptoms starting at nine months. The outcome was unknown. The second was an unspecified allergic-type response from which the consumer recovered without sequelae.

Eye Irritation

The incidence of eye irritation was very low. One physician reported a case of the swelling of the eyes associated with facial edema, in an 81-year-old female, following the application of desonide cream to the chest. The remaining two were consumer reports: development of iritis after using desonide cream to treat psoriasis under the eyes, and burning, irritated eyes after one application of desonide lotion to an unspecified site. Desonide cream, ointment, and lotion are not approved for ophthalmic use.

Exacerbation of Disease/Lack of Effect

Reports of exacerbation of the disease, frequently described as worsening of redness, were made on five occasions, four by physicians. Where given, the time to onset was generally within the first two weeks of desonide use. In addition, there were eight (12.9%) reports by consumers of lack of efficacy but very little detail is available. None of these were verified by a healthcare professional.

Other Adverse Effects

Eight adverse events identified by the pharmacovigilance program could not be categorized (Table II) of which one (in a six-month-old) has been described under serious reactions. Five of these reports came from consumers, and included such diverse complaints as scars on face, bleaching around the treatment area, cataract, tingling feet, and sleeping difficulty. In addition, there was a published report of topical corticosteroid-induced acne following treatment of a two-year-old girl with clotrimazole 1%, betamethasone cream 0.05%, and desonide cream 0.05% (4). Finally, hypochromia was reported by a physician in another two-year-old child but no further details are available.

Comparison of Desonide with Hydrocortisone--A Review of Published Trials

Further support for the safety profile of desonide comes from the literature on randomized, controlled clinical trials in which the mild corticosteroid hydrocortisone has been used as comparator.

Studies in Children

The safety and efficacy of desonide ointment 0.05% with 1.0% hydrocortisone was compared in 113 children (mean age: 4.8 years) with mild to moderate atopic dermatitis (3). In this multi-center, parallel group study, treatments were applied twice daily for five weeks (extended to six months in 36 patients); response to treatment was assessed at weeks 1, 3 and 5, and at months 2 to 6.

Fifty-seven patients were randomized to receive desonide and 56 to receive hydrocortisone; the majority of patients (90, or 79.6%) completed five weeks of treatment and 111 were assessable for efficacy. The response to treatment is reflected in the primary efficacy variable, the physician's overall global assessment of improvement, which is shown in Figure 1. By week one, there was a significant difference in the percentage of patients with cleared or marked improvement (P=0.05, chi-square test). Patients in both treatment groups continued to improve during the study; at the last observation made, the difference between the two groups was highly significant (69% desonide vs. 41% hydrocortisone; P=0.003).

[FIGURE 1 OMITTED]

No differences in safety were observed between desonide and hydrocortisone; neither treatment produced signs of atrophy even at the six-month evaluation, and any stinging or burning sensation reported was slight. The authors concluded that desonide 0.05% ointment showed greater efficacy but an equivalent safety profile when compared with hydrocortisone 1% for up to six months.

Lucky, et al (6) studied systemic safety, by comparing the effects of desonide ointment 0.05% with hydrocortisone 2.5% on the HPA axis of children (aged 11 months to 11 years) with a minimum of 20% of their body surface affected by atopic dermatitis. In this open-label, parallel group study, ointment was applied twice daily over a four-week period (approximately 3-g of ointment per day). Early morning serum cortisol levels were determined at baseline and on days 14 and 28, with adrenocorticotropic hormone (ACTH) stimulation of cortisol production being measured on days 0 and 28.

Even though the mean body surface area treated was quite high in both groups (desonide 38.1% and hydrocortisone 37.1%), there was no drug-induced suppression of early morning cortisol levels after four weeks of either treatment. Likewise, adrenocorticotropic hormone-stimulated mean cortisol values were not significantly different from baseline in either group (Figure 2). The authors concluded that the use of 0.05% desonide or 2.5% hydrocortisone ointment for four weeks has no adverse effect on the HPA axis of children. They emphasize that an assumption of safety may also be made for other less occlusive formulations such as lotions or creams.

[FIGURE 2 OMITTED]

Desonide for Seborrheic Dermatitis

A double-blind, bilateral within-patient study to compare the dermal/epidermal safety of desonide cream 0.05% with hydrocortisone cream 1% in 29 adult patients with seborrheic dermatitis of the scalp was conducted by Cornell and Baker (7). Treatment was applied twice daily for eight weeks to the postauricular region (an area of naturally thin skin).

Assessment for signs of skin atrophy, made at baseline and at weeks 1, 2, 4, 6 and 8, included telangiectasia (count of the blood vessels in the application area), epidermal thinning, striae and shiny surface appearance, the presence or absence of hair loss, muscle waste, fat waste, loss of elasticity or skin markings, and purpura or bruising.

After eight weeks, the total number of telangiectasia, while few in number, was greater on the hydrocortisone treated sites than on the desonide sites. There were no signs of skin atrophy and all other safety variables were negative. The study therefore demonstrated that 0.05% desonide cream has a dermal safety profile comparable to that of 1.0% hydrocortisone cream.

Discussion and Conclusions

Desonide 0.05%, formulated as a cream or ointment, has been available since the early 1970s for the treatment of mild to moderate steroid-responsive dermatoses. Recently the range has extended to include a 0.05% lotion. With launches into additional markets imminent, the three products making up the desonide range will soon have a truly global exposure.

This overview presents the results of a comprehensive pharmacovigilance program that has been rigorously collecting post-marketing surveillance data on desonide for almost a decade. It demonstrates that the incidence of adverse events associated with the use of topical desonide 0.05% is low indeed. The majority (66%) of the 62 adverse events reported were local reactions of a type to be expected with topical corticosteroid preparations, and medical confirmation was available for only 40% of all reports. Bearing in mind the considerable volume of sales of desonide products (almost a million packs sold each year in the US alone), the reports of generally mild adverse events in only 62 people in nine years between 1992 and 2000, suggests that the safety of this product, regardless of formulation, is excellent.

Two of the reported adverse events deserve additional mention. Hypochromia and "bleaching" are known effects of topical corticosteroids. While the causal link with desonide is unknown here, these effects are readily reversible when responsible corticosteroids are discontinued. Cataracts have also been reported with topical corticosteroid use, but they are also increased in atopic dermatitis. Moreover, the solitary report of cataracts here is less than would be expected given the large number of units of desonide sold.

The safety of desonide 0.05% is further confirmed by the published results of several clinical trials. These reveal efficacy superior to that of hydrocortisone 1%, but with the safety profile for desonide being comparable to that of hydrocortisone, even in children. The risk of cutaneous atrophy during desonide usage is very low and topical tolerance is good. In addition, the comparatively new lotion formulation has been shown to have a safety profile of an equally high caliber to the more established cream and ointment formulations.

In conclusion, all three formulations of desonide are well-tolerated and effective in managing steroid-responsive skin conditions. With its proven track record for over 30 years, it is therefore reassuring to know that desonide can be selected, with confidence, whenever a mild topical corticosteroid is required.

References

1. Munro DD. Topical corticosteroid therapy and its effect on the hypothalamic-pituitary-adrenal axis. Dermatologica 1976; 152:173-180.

2. Munro DD. The effect of percutaneously absorbed steroids on hypothalamic-pituitary-adrenal function after intensive use in inpatients. Br J Dermatol 1976; 12:67-76.

3. Garner LA, Cruz PD Jr. Contact puzzle: Worsening of a recurrent facial eruption despite treatment. Diagnosis: allergic contact dermatitis caused by desonide. Am J Contact Dermat 1999; 10:81-82.

4. Brodell RT, O'Brien MJ Jr. Topical corticosteroid-induced acne. Three treatment strategies to break the 'addiction' cycle. Postgrad Med 1999; 106:225-226.

5. Jorizzo J, et al. Multicenter trial for long-term safety and efficacy comparison of 0.05% desonide and 1% hydrocortisone ointments in the treatment of atopic dermatitis in pediatric patients. J Am Acad Dermatol 1995; 33:74-77.

6. Lucky AW, et al. Effect of desonide ointment, 0.05%, on the hypothalamic-pituitary-adrenal axis of children with atopic dermatitis. Cutis 1997; 59:151-153.

7. Cornell R, Baker M. Dermal safety and comparison of 0.05% desonide cream and 1.0% hydrocortisone cream. Curr Ther Res 1993; 53:356-359.

VICKY KWAN WONG BA, BRIAN FUCHS MD, MARK LEBWOHL MD

DEPARTMENT OF DERMATOLOGY, MOUNT SINAI MEDICAL CENTER

NEW YORK, US

ADDRESS FOR CORRESPONDENCE:

Mark Lebwohl MD

Department of Dermatology

The Mount Sinai Medical Center

1 Gustave L. Levy Place

Box 1048

New York, NY 10029-6574

Phone: (212) 241-9728

Fax: (212) 876-5661

Email: sinaiderm@aol.com

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