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New treatment for patients with chronic hand eczema.

Chronic hand eczema (CHE) affects about 7% of the population and has a severe social, occupational and psychological impact on sufferers. The recent launch of alitretinoin (Toctino; Basilea Pharmaceuticals) for those with severe CHE who are unresponsive to other treatments represents a major step forwards in the treatment of this condition.

How it works

The retinoids are a group of vitamin A derivatives with a wide range of pharmacological properties and therapeutic applications in dermatology. They have been shown to affect cell proliferation and differentiation, apoptosis, angiogenesis, keratinisation and sebum secretion, and to have immunomodulatory properties. Retinoids have established applications in other dermatological diseases--for example, isotretinoin and adapalene for acne, acitretin and tazarotene for psoriasis. Alitretinoin (9-cis retinoic acid) is a naturally occurring retinoid that has anti-inflammatory and immunomodulatory effects. It directly affects cytokine production in keratinocytes and downregulates leukocyte activity. Its exact mechanism of action is not understood, although it is known that it binds to, and activates, intracellular retinoid receptors--both retinoic acid receptors and retinoic X receptors--regulating expression of genes that control cellular differentiation and proliferation. Alitretinoin is the only retinoid that is known to act on both types of retinoid receptor, and for this reason it is sometimes described as a (retinoid) panagonist.


Alitretinoin is licensed for the treatment of severe CHE in adults who are unresponsive to treatment with potent topical corticosteroids. The recommended dose is initially 30 mg per day, reducing to 10 mg if adverse effects are intolerable. High-risk patients (those with diabetes, obesity, cardiovascular risk factors or a lipid metabolism disorder) should be started with 10 mg once daily and titrated up to the maximum dose of 30 mg if necessary. A course of treatment is usually 12-24 weeks. All systemic retinoids are potent teratogens, so alitretinoin can only be prescribed to women of childbearing age if a pregnancy prevention programme is rigidly followed. It is recommended that alitretinoin should only be prescribed by dermatologists, or Reprinted with kind permission of the author and publisher from British Journal of Clinical Pharmacy, 2009, 1, 45-47 ( physicians with experience in the use of systemic retinoids who have full understanding of the risks of systemic retinoid therapy and monitoring requirements.


The evidence that supports the use of alitretinoin comes from two Phase III studies. The BACH (Benefit of Alitretinoin in Chronic Hand dermatitis) study [1] assessed the efficacy and safety of alitretinoin in 1032 adult patients with severe, refractory chronic hand eczema of at least 6 months' duration in a 24-week study. The second study examined the safety and efficacy of a second course of treatment for patients who had previously responded to treatment and relapsed within 24 weeks.

In the BACH study, patients were randomised to alitretinoin 10 mg (418), 30 mg (409), or placebo (205). All patients were given an emollient cream and told to apply it frequently. No other medication for CHE was allowed. All patients who responded were followed up for a further 24 weeks to assess relapse, and no medication active against CHE was allowed during this time. The primary endpoint was 'clear' (no residual visible dermatitis) or 'almost clear' (minimal erythema and/or scaling) skin.

Both alitretinoin dosing regimens were effective, with the 30mg dose giving a higher and faster response rate.

Adverse events were generally dose dependent and reversible. Headache was the most commonly reported adverse event affecting 20% and 11% of patients taking 30mg and 10mg alitretinoin, respectively, and 6% of those on placebo. Other common side effects included dry lips, flushing and erythema. Raised serum cholesterol and triglycerides were the most commonly reported abnormal laboratory parameters.

The second study was randomised, double-blind and placebo-controlled. Patients who had originally been treated with alitretinoin were randomised to either their previous alitretinoin dose or placebo for 12 or 24 weeks. Those patients who had responded to placebo during the BACH study were allocated placebo again. All patients received an emollient to apply several times a day. The results showed that re-treatment with alitretinoin was generally effective and well tolerated, with the highest response rates seen with a 30mg dose and adverse events similar to those seen with first exposure [2].


In the UK, both the 10mg and 30mg capsules cost 411.43 [pounds sterling] for a 30-capsule pack. No published economic analyses are available as yet. Ideally such analyses should be based on comparisons with other treatments for severe chronic disease--azathioprine, methotrexate, ciclosporin, retinoids and oral corticosteroids.

Common side effects

Headache is the most common side effect of alitretinoin. Patients taking retinoids are at risk of sunburn and should be warned to avoid sunbeds and excessive exposure to sunlight, and advised to use sun creams of at least SPF 15. Dryness of the lips, skin and eyes is also common. Decreased night vision sometimes occurs during treatment and could affect driving ability at night.


Alitretinoin is metabolised by cytochrome P450 3A4, so CYP3A4 inhibitors (e.g. ketoconazole) can raise plasma levels of alitretinoin.

Patients should not take vitamin A supplements or other retinoids while being treated with alitretinoin, to avoid the risk of hypervitaminosis A.

Patients who are also taking hormonal oral contraceptives should be advised not to take St John's Wort, because the interaction can cause contraceptive failure.


[1.] Ruzicka T, Lynde CW, Jemec GB et al. Efficacy and safety of oral alitretinoin (9-cis retinoic acid) in patients with severe chronic hand eczema refractory to topical corticosteroids: results of a randomized, double-blind, placebo-controlled, multicentre trial. Br J Dermatol, 2008, 158, 808-817.

[2.] Coenraads PJ, Ruzicka T, Lynde C et al. Alitretinoin re-induces response in relapsed CHE patients. 9th Biennial Congress of the European Society of Contact Dermatitis, Lisbon, Portugal, May 2008. Poster 49.

Panel 1: Key facts

Drug: Alitretinoin (Toctino).

Manufacturer: Basilea Pharmaceuticals.

Class: Systemic retinoid.

Indication: Treatment of severe chronic hand eczema in adults unresponsive to topical corticosteroids.

Dose: 30 mg per day for 12-24 weeks.

Evidence: The BACH study showed the drug to be effective with reversible adverse effects.

Side effects: Headache, dry skin.

Cautions: Teratogenic--a pregnancy prevention programme must be followed.

Cost: 411.43 [pounds sterling] for 30 capsules. Economic analyses not yet available.

Launched: September 2008.
Panel 2: Percentage of patients achieving the primary
endpoint in the BACH study

 Placebo 10 mg alitretinoin 30 mg alitretinoin

Ruzicka et al. [1] 17(34/205) 28(115/418) 48(195/409)

n = 1032

Panel 3: Chronic hand eczema

* Hand eczema is estimated to affect 10% of the general population and up to 30% of high-risk occupational groups, such as healthcare workers and workers in manufacturing industries. Approximately 7% of people with hand eczema are estimated to have a severe, chronic form.

* The condition can range in severity from a few small patches to most of the skin on the hands. In the early stages erythema, scaling and small, itchy blisters can all be features of the condition. Chronic disease is associated with thickened, scaly skin and fissuring.

* Chronic hand eczema often starts as irritant or allergic contact eczema. Common irritants include detergents, gloves and organic solvents, and common allergens include metals (e.g. nickel, chromates), preservatives and latex.

* The first-line treatment for hand eczema is avoidance of the irritant or allergen and/or protection (e.g. by wearing gloves). The next step is topical treatments--starting with emollients and adding corticosteroids, topical immunomodulators, coal tar and derivatives, or irradiation with ultraviolet (UV) light or X-rays. The final step is short courses of systemic treatments such as azathioprine, methotrexate, ciclosporin, retinoids and oral corticosteroids.

* The occupational, domestic, social and psychological impact of hand eczema should not be underestimated. Painful fissures and blisters affect all aspects of life. For manual workers, hand eczema is a major cause of lost earnings. Moreover, visible skin disease can be socially stigmatising. Severe hand eczema is associated with significantly lower quality of life, comparable to that of generalised eczema or psoriasis.

Christine Clark

Freelance journalist, chairman of the Skin Care Campaign and a member of the All

Party Parliamentary Group on Skin
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Title Annotation:Leading Article
Author:Clark, Christine
Publication:Clinical Dermatology
Date:Mar 1, 2009
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