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Linear Darier’s disease successfully treated with 0.1% tazarotene gel “short-contact” therapy

European Journal of Dermatology. Volume 16, Number 1, 59-61, January-February 2006, Therapy

Summary

Author(s) : Valeria Brazzelli, Francesca Prestinari, Tania Barbagallo, Camilla Vassallo, Marina Agozzino, Giovanni Borroni , Department of Human and Hereditary Pathology, Institute of Dermatology, University of Pavia, IRCCS Policlinico S.Matteo, Pavia, Italy.

Summary : We report the case of a 25 year old man affected by linear Darier’s disease. The patient presented with brownish keratotic papules involving the trunk in a linear pattern. These lesions were successfully treated within 6 weeks with 0.1% tazarotene gel “short contact”. The good response that was obtained suggests that the use of “short contact” tazarotene could be useful in the treatment of linear Darier’s disease

Keywords : Darier’s disease, 0.1% tazarotene gel

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ARTICLE

Auteur(s) : Valeria Brazzelli, Francesca Prestinari, Tania Barbagallo, Camilla Vassallo, Marina Agozzino, Giovanni Borroni

Department of Human and Hereditary Pathology, Institute of Dermatology, University of Pavia, IRCCS Policlinico S.Matteo, Pavia, Italy

accepté le 14 Septembre 2005

Darier’s disease is an uncommon inherited skin disease transmitted in autosomal dominant pattern characterized by brownish keratotic papules particularly dense in the seborrheic areas of the body, palmar pits and nail dystrophy [1].The disease is often exacerbated by sun exposure, perspiration and heat.The causative gene has been localized on chromosome 12q23-24.1 with a consequent defect in synthesis or maturation of the tonofilament-desmosome complex and abnormal adhesion between keratinocytes [2, 3].The histological features are characterized by suprabasal clefting, acantholysis and dyskeratosis (corps ronds, grains) [4].In 1906 Kreibich [5] reported a localized form of Darier’s disease in which the typical lesions occurred in a unilateral distribution, often following the lines of Blaschko. Since then more than 50 cases of localized linear Darier’s disease have been reported [3].We report a case of linear Darier’s disease successfully treated with 0.1% tazarotene gel “short contact” therapy.

Case report

A healthy 25-year-old male presented with asymptomatic skin lesions on the left side of the trunk persisting for several years. Sunlight and heat aggravated the condition.

A physical examination showed discrete keratotic brownish papules arranged in a linear pattern ( (figure 1A) ). No other lesions were detected on examination of the skin, nails and mucosa. There was no family history of similar skin disease.

Biopsy specimens were obtained. On histological examination suprabasal clefts, acantholytic and dyskeratotic cells at all levels of the epidermis, hyperkeratosis and parakeratosis were seen (( figure 2 )).

All laboratory investigations were within normal limits.

Both clinical and histopathologic findings were suggestive of Darier’s disease in a linear pattern.

The patient was treated with topical 0.1% tazarotene gel applied once a day for 15 minutes, over the course of 6 weeks.

The drug was well tolerated and the patient showed a good clinical remission with small pinpoint residual lesions ( (figure 1B) ).

Discussion

Darier’s disease is an autosomal dominant inherited skin disorder in which adhesion between keratinocytes is abnormal. This genodermatosis is clinically characterized by generalized brownish and pruritic papules particularly dense in the seborrheic areas of the body. The disease is often exacerbated by sun exposure, heat and perspiration [1, 3, 4, 6].

Mutations in the ATP2A2 gene encoding sarco/endoplasmatic reticulum calcium pumping ATPase type 2 have been identified as the molecular basis of Darier’s disease [7-9].

A localized form of Darier’s disease characterized by keratotic papules disposed in a linear pattern was first described by Kreibich in 1906 [5].

The average age of onset of the disease is during childhood or adolescence, without sex predilection. The most common site of involvement is the trunk and the condition is aggravated by sunlight, heat or sweating. The skin outside the segmental manifestation is perfectly normal. These patients have no family history of Darier’s disease or similar skin conditions [4].

To date, more than 50 cases of localized Darier’s disease have been described in the literature [3]. There is still some debate concerning the classification of this entity. The differential diagnosis includes Grover’s disease and epidermal nevus with acantholytic dyskeratosis [10-13].

A wide variety of treatments have been reported in the literature for Darier’s disease, including topical and oral retinoids, lactic acid, salicylic acid, podophyllin and vitamin A acid in concentrations of 0.05% to 0.2% [4, 10, 11]. Among these therapies, systemic retinoids have been used successfully but they have little place in the treatment of the localized disorder. The many potential side effects of systemic retinoids would be disproportionate with the limited extent of the skin involvement [10].

Tazarotene is a new acetylenic retinoid, first introduced in 1997 for psoriasis therapy [14, 15].

Tazarotene selectively transactivates the retinoic acid receptors of the skin, the predominant RAR-γ and less prevalent RAR-β subtypes [16]. The drug has a strong antiproliferative effect on keratinocytes, modulates keratinocyte differentiation, has a low percutaneous absorption and is rapidly metabolized and eliminated [17, 18]. Tazarotene can cause an irritant contact dermatitis characterized clinically by erythema, edema, xerosis/scaling, pruritus and burning sensation. The dermatitis is usually mild to moderate in severity and concentration-dependent. The dermatitis spontaneously improves following cessation of treatment [19]. In order to avoid these side effects, short-contact therapy with tazarotene has been successfully used in psoriasis and acne since 1997 [15, 19, 20]. In 1998 tazarotene was used for the first time in the therapy of Darier’s disease [20, 21]: in particular Burkhart et al. [21] utilized 0.05% tazarotene gel associated with a weak topical steroid cream to allay the dryness and irritation. Oster-Schmidt [17] also used tazarotene in Darier’s disease but, in order to reduce its dose-related potential for local irritation, the author utilized 0.01% concentration (0.05% gel diluted with purified water) with total clearance of the skin lesions within two weeks. In 1999, Micali and Nasca [22] used tazarotene 0.1% gel in childhood Darier’s disease with a regression of the skin lesions without any side effects.

In our case, in order to avoid side effects, we used tazarotene 0.1% gel on “short-contact” therapy: the gel was applied once a day, for only 15 minutes, for a mean period of 6 weeks with clinical remission and good tolerance of the therapy.

In conclusion, we suggest 0.1% tazarotene gel “short-contact” therapy as a safe, effective, well tolerated treatment for linear Darier’s disease and we propose it as one of the drugs of choice for this disease.

A clinical study based on a larger number of patients is necessary to confirm these results.

References

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