Oral calcitriol: a new therapeutic agent in cutaneous lichen sclerosis

Journal of Drugs in Dermatology, Jan, 2003 by S Ronger, AM Viallard, Meunier-Mure F, B Chouvet, B Balme, L Thomas

Abstract

Background: Lichen sclerosus remains an elusive disease with an uncertain relationship to morphea and scleroderma. The disorder has been difficult to treat, with no consistent and reproducible efficacious therapy. Recently, a beneficial effect of treatment with oral calcitriol (1-25 dihydroxyvitamin D3) in patients with scleroderma or morphea was described. This fact could be ascribed to the immunomodulatory effects of calcitriol observed in vitro and to inhibition of fibroblastic growth. Because of the success of calcitriol in localized scleroderma, we attempted this therapy in a patient with LS.

Observation: One patient with cutaneous generalized LS resistant to different therapeutics was treated with calcitriol in an oral daily dose of 0.5 mcg. After 6 months of treatment, the skin extensibility increased, and the lesions improved. The improvement persisted after discontinuation of therapy during a follow-up period of one year. The only side effect was hypercalciuria, which resolved with dose reduction.

Conclusion: Calcitriol has shown a beneficial effect in scleroderma and morphea during open studies. A case is reported of a patient with LS who had a dramatic response to calcitriol. Double blind, placebo-con trolled trials are needed to assess the therapeutic value of calcitriol in patients with LS.

Introduction

The controversy about the relationship between cutaneous lichen sclerosis (LS) and morphea began early and continues to this day. Although most recent reports classify LS as an entity of scleroderma, this remains a topic of research and debate. Despite the administration of several therapeutic regimens, no efficient therapy for LS has been described.

Recently, several cases of morphea and scleroderma have been treated with calcitriol (1-25 dihydroxyvitamin D3) with beneficial effects. Calcitriol is the biologically active form of vitamin D and acts on target cells such as fibroblasts and lympbocytes. This observation prompted an exploration of the possible use of the hormone in the treatment of LS.

Case Report

A 53 year old man developed symptomless hypopigmented and atrophic plaques on the upper part of the chest, present since May 1995 (Figure 1). In 1997, they expanded to the back, the shoulders, and the upper part of the legs and arms (Figure 2). Lesions were hypopigmented, atrophic in the center, erythematous, and crumbling on the border. The individual lesions were small and of ivory color, with shiny papules and macules. The surface displayed prominent dilated pilosebaceous or sweat duct orifices. There was also a hemorrhagic and bullous plaque on the sacrum. The oral and genital mucosa aspects were normal. Physical examination revealed induration and sclerosis which led to discomfort, especially on the arm areas (Figure 3). This clinical aspect was in conformance with the diagnosis of cutaneous lichen sclerosis.

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Histology confirmed the diagnosis, showing orthohyperkeratosis with keratotic plugging, epidermal atrophy with degeneration of basal cells, edema, and homogenization of the collagen in the upper dermis, as well as inflammatory infiltrate in the mid-dermis (Figure 4).

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Multiple therapies have been tried without success for these conditions (topical corticosteroids, Piascledine, Amoxicillin, etc.). To prevent the skin lesion spreading to the arms and legs, we proposed a treatment trial with calcitriol (Rocaltrol[TM], from Roche), and obtained the patient's informed consent prior to beginning the trial. This was particularly important in this case due to the possible side effects, as well as the innovative aspects of the treatment, which revolves around the as-yet unknown relationship between morphea and LS, and the beneficial effects of calcitriol in morphea and scleroderma.

In August 1997, we began calcitriol therapy with an oral daily dose of 0.5 mcg. After a 4 to 6 month period, the patient felt better and noticed improvement in his skin appearance. After one year of treatment, hypopigmented lesions were lessened (Figure 5) with a corresponding decrease in infiltration (Figure 6). The bullae and hemorrhagic sacrum plaque disappeared (Figure 7) and the treatment was discontinued in September of 1998. From then through now, no new lesions have appeared and to date there is no sign of recurrence.

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Overall, the patient responded very well to the calcitriol treatment except for a transient hypercalciuria in April of 1998 that responded immediately to a temporary (one month) interruption of the treatment.

An anatomicopathological examination in January of 1999 presented a cicatrical aspect with a decrease of hyperkeratosis, dermis infiltration, and hyalinized dermic superficial band (Figure 8).

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Discussion

Lichen sclerosis was described clinically by Hallopeau (1) in 1889 and histologically by Darier in 1892 (2). It is an inflammatory disease of unknown cause and insufficiently characterized pathogenesis (3). LS can affect all age groups (4) and while most patients described in the literature are Caucasian, the majority of whom are women, the female-to-male ratio provides a wide range which goes from 10:1 (5) to about 1:1 (6).