Generalized Morphea Successfully Treated With Tacrolimus 0.1% Ointment

January 2013 | Volume 12 | Issue 1 | Editorials | 14 | Copyright © 2013

Carmen Cantisani MD, Emanuele Miraglia MD, Antonio G. Richetta MD, Carlo Mattozzi MD,and Stefano Calvieri MD

Department of Dermatology, “Sapienza” University of Rome, Rome, Italy

Abstract

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Morphea, or localized scleroderma (LS), is a rare fibrosing disorder of the skin that may also involve the underlying muscle, connective tissue, and brain. It differs from systemic scleroderma because it does not involve the internal organs and patient prognosis is more favorable.1 The characteristic lesion is a circumscribed sclerotic plaque with an ivory-colored center and, if the disease is in an active inflammatory stage, a blue-pink or violaceous border (lilac ring).2 Even when spontaneous remission occurs, the residual damage created by previously active disease (eg, pigment change, atrophy, contracture, limb length discrepancy) may be severe.3

Although no causal treatment for LS exists, a variety of therapeutic options are available. In general, treatment options might be divided into topical and systemic therapies. The majority of patients can be successfully treated with topical therapy (eg, corticosteroids, vitamin D) and phototherapy, although most data about treatment efficacy of localized scleroderma are based on case series.4,5 Here, we report our treatment experience with topical tacrolimus in a patient with generalized morphea.

A 55-year-old Caucasian woman was referred to the Department of Dermatology at “Sapienza” University of Rome in Rome, Italy, complaining of multiple erythematous, thickened plaques that had appeared approximately 10 months earlier. Examination revealed a 4 × 5 cm, ill-defined, erythematous, thickened, and indurated plaque on the abdominal area and similar lesions of a different size on the legs and on her back (Figure 1). Complete blood count, urinalysis, liver function tests, serum protein level, plasma glucose level, chest radiograph, and serology were all normal, but thyroid function tests showed hypothyroidism with high antithyroid autoantibody titers, a clinical presentation compatible with Hashimoto disease. Histologic examination was consistent with a diagnosis of morphea.

We prescribed topical tacrolimus 0.1%, without occlusion, twice daily on the left side of the body. After 8 weeks of treatment, the treated lesion had softened, and the erythema had disappeared. Five months later, the site of the topical tacrolimus–treated lesion was almost normal in appearance (Figure 2).

table 1

These beneficial effects were detected in the topical tacrolimus– treated lesions, but not in the untreated control plaques. Therefore, it is unlikely that the observed changes were caused by spontaneous remission. Unlike corticosteroids, which modify the function and growth of many cell types, including fibroblasts and keratinocytes, tacrolimus acts specifically on inflammatory cells. Its mechanism of action is unknown but may be exerted through the inhibition of interleukin 2 primarily and interferon secondarily. One of the major immunomodulating effects of macrolides is their suppressive effect on the activation of different cytokine-coding genes. Tacrolimus induces anti-inflammatory and immunomodulatory effects with suppression of the inflammatory infiltrate, including reduction of chemotactic activity of fibroblasts and the inhibition of collagen synthesis.6 None of the treatment-related local or systemic side effects associated with tacrolimus therapy that have been previously mentioned in the literature, such as paresthesia, burning sensation, itching, or skin atrophy, were observed in


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