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March 1996 Volume 1 Number 4
Adapalene (Differin®, Galderma) is a new retinoid-like compound that is more stable to light and oxidation than earlier retinoids.1,2 In large multicentre studies of patients with acne vulgaris, adapalene gel applied once daily was at least as effective as tretinoin gel 0.025% and usually caused less burning, pruritus, erythema, scaling, and dryness.1,2,3 Adapalene gel 0.1% is formulated in a micro-suspension, which is not comedogenic, phototoxic, or photo-allergic and is fragrance and alcohol free. Adapalene is not mutagenic or carcinogenic.1,2
Acne vulgaris, topical treatment
Adapalene is available in France and approved for this use in seven other countries, including Canada, where it will be launched this year. It is awaiting approval in the USA and elsewhere.2
As there are no relevant reports or studies, the drug is not recommended in these situations. However, there is minimal systemic absorption from topical application to intact skin.2
Adapalene is very stable on the skin. In the gel formulation, restriction of particle size to 3-10µm has been shown to optimize delivery to the pilo-sebaceous unit. Very little drug penetrates the skin, and that which does remains mainly in the epidermis, with some progressing to the dermis. Absorbed drug has a half life of about 13 hours.2
Retinoids act through one of the known high affinity binding proteins for retinoic acid.4 The activity of adapalene in the epidermis appears to be mediated mainly by its specific binding to b and g nuclear retinoic acid receptors (RARs). This binding profile differs from tretinoin, which binds to a, b and g RARs. Furthermore, unlike tretinoin, adapalene does not bind to cellular retinoic acid binding proteins (CRABPs) or to nuclear retinoid X receptors. The relevance to therapeutic efficacy of these differences between retinoids is not yet fully understood. However, future research will probably result in other novel retinoids, each with distinct advantages for treating particular diseases based upon receptor-specific targeting.1,2
Results from clinical trials with adapalene gel demonstrate its anti-acne activity being equivalent to earlier retinoids, but less irritating to the skin and better accepted by patients. If these results are confirmed following widespread clinical usage, dermatologists will have another much needed treatment option for the management of acne.
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Atopic dermatitis (AD) is an inflammatory skin disease that follows a chronically relapsing course.1 During periods of acute exacerbation, topical and even systemic steroids are often required for symptom relief. However, because long-term therapy with corticosteroids has a variety of side effects, various forms of phototherapy with ultra-violet radiation ( PUVA, UVB, UVAB) have been tested as alternative treatments. Recent studies suggest that monotherapy with high doses of ultraviolet A1 radiation (UVA1; 340-400 nm) could be effective in the management of severe exacerbations of AD.2
Recent data from a randomized clinical trial confirm that monotherapy with high doses of UVA-1 is effective in the management of severe exacerbations of AD.6 Using an established clinical scoring system, high-dose UVA-1 (130 J/cm2 for 10 days in 20 patients) was found to be significantly superior to fluocortolone (applied topically, once daily for 10 days in 17 patients) (p=0.002). Both treatments were significantly more effective than conventional UVA-UVB therapy (once daily for 10 days, dose based on individual MEDs, in 16 patients) (p=0.0001).
Clinical changes were accompanied by concomitant changes in laboratory test parameters. Elevated serum levels of eosinophilic cationic protein and blood eosinophil counts were both significantly reduced in patients receiving high-dose UVA-1 irradiation or fluocortolone treatment, but not in UVA-UVB recipients.6
Professor Krutmann (University of Düsseldorf) concluded:
High-dose UVA-1 radiation may not only exert beneficial effects on the chronic phase of atopic eczema by downregulating in-situ expression of IFN-g, but may also affect the initiation phase of this disease, and thereby help to prevent the frequent re-exacerbation of this chronic inflammatory skin disease.
He feels that this technique's place in therapy is in the
treatment of severe, acute exacerbations of AD or as an
alternative to glucocorticoids or cyclosporine.6
No treatment is consistently effective against this condition, but symptoms are usually improved by PUVA. Four patients with severe generalized UP who responded to high-dose UVA-1 (five times a week for two weeks) were recently described.7 One patient had previously been treated with PUVA but had relapsed after six months. Therapy was well-tolerated; relief from itching was noted after three treatments; and after 23 months, none of the patients had relapsed.
This is another skin condition that has no satisfactory treatment. Two presentations at the Annual Meeting of the Photomedicine Society, Washington, DC, February 9, 1996 suggested that UVA-1 therapy may prove effective. In a pilot study in five patients, high-dose UVA-1 therapy (130 J/cm2 once daily for 30 exposures) softened and reduced the diameter of sclerotic lesions, and several plaques cleared completely. Control plaques did not improve. Therapy was well-tolerated in all patients.8 In another study in ten patients with severe LS, treatment with low-dose UVA-1 phototherapy (20 J/cm2 once daily four times a week for six weeks) completely cleared 80% of lesions, with no side effects.9 Kerscher et al commented that low-dose UVA-1 phototherapy can be highly effective for clearance of sclerotic plaques, even in patients with advanced LS.9
The metal halogen lamps employed in the above studies produce exclusively UVA-1 radiation, in contrast to the fluorescent bulbs used in standard PUVA therapy. In Europe, UVA-1 equipment is approved by regulatory bodies for general use by dermatologists and is readily available. Examples are UVASUN 30,000 BIOMED (Mutzhas, Munich), filtered with UVACRYL and UG1, and SELLAMED 24,000 System (Sellas Medizinische Geräte GmbH, Gevelsberg-Vogelsang, Germany).6 In the USA, regulatory approval for UVA-1 therapy is still pending.6 UVATECH Inc. of Sherman Oaks, California, market a Dermalight Sol 5 UVA-1 unit.
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