Multiple eruptive dermatofibromas associated with Hashimoto's thyroiditis and myasthenia gravis

ARTICLE

Auteur(s) : Yuko Kimura, Takahide Kaneko, Eijiro Akasaka, Koji Nakajima, Takayuki Aizu, Hajime Nakano, Daisuke Sawamura

Department of Dermatology, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, 036-8562, Aomori, Japan

A 32-year-old woman was referred to our department, having multiple painful pigmented lesions on her buttocks and lower legs, which she had noticed 2 years earlier. She had been suffering from Hashimoto's thyroiditis and myasthenia gravis for 6 years and 2 years, respectively. Myasthenia gravis was well controlled by 45 mg prednisolone and 75 mg cyclosporine and no treatment was required for Hashimoto's thyroiditis at that time. Physical examination revealed multiple well-circumscribed, painful, pigmented, firm nodules measuring 2-10 mm in diameter on both sides of the buttocks and legs. Our careful examination detected twelve similar tumors (figure 1). Laboratory examination showed the presence of anti-thyroid peroxidase, and anti-thyroglobulin antibodies were positive, but the levels of triiodothyronine, thyroxin and thyroid-stimulating hormone were within normal limits. Anti-acetylcholine receptor antibodies indicative of myasthenia gravis were also present. As part of the pathologic examination, we performed an excision biopsy of one nodule on the left leg. Histopathological examination showed that the tumor cells had spread to the entire dermis (figure 1). The cells were fibrohistiocytic and arranged in a compact storiform pattern, and no mitotic figures were found. An increase in the basal pigmentation and elongated rete ridges were found in the overlying epidermis. The histological findings were consistent with dermatofibroma.

Dermatofibroma is a common benign fibrohistiocytic tumor. Most often, it occurs as a solitary lesion in a healthy individual. Multiple dermatofibromas are rare, usually painful as compared to the single lesion, and have been reported to be associated with autoimmune diseases, including systemic lupus erythematosus (SLE), Sjögren's syndrome, pemphigus vulgaris, ulcerative colitis, dermatomyositis and myasthenia gravis [1]. Recently, Basedow's disease, an autoimmune thyroid disease, was associated with multiple eruptive dermatofibromas [2]. Our patient had Hashimoto's thyroiditis and myasthenia gravis. She already noticed the skin lesions around the time that she developed myasthenia gravis, indicating that Hashimoto's thyroiditis was a possible inducing factor of dermatofibromas. Myasthenia gravis could also be responsible for the expansion of the skin lesions. To our knowledge, we present the first report indicating that Hashimoto's thyroiditis is related to dermatofibromas. Besides autoimmune diseases, immunosuppressants, such as corticosteroids, cyclosporine cyclophosphamide, azathioprine, and methotrexate are involved in occurrence of multiple eruptive dermatofibromas. Our patient was given prednisolone and cyclosporine, which might have played some role in the pathogenesis of the dermatofibroma. A recent report described a psoriasis patient treated with efalizumab, who developed multiple eruptive dermatofibromas [3]. An increasing use of biological products and drugs in clinical practice might lead to an increase in similar cases.

The pathomechanisms of multiple dermatofibromas remain unknown. Basic fibroblast growth factor (bFGF) can induce proliferation and chemotaxis of fibroblasts. Yamamoto et al. showed enhanced growth stimulatory activity in the serum of an SLE patient with multiple dermatofibromas and that this activity was inhibited by anti-bFGF antibodies [4]. However, bFGF levels in active SLE patients were higher than those in inactive patients, in spite of the presence of dermatofibromas.

Also, an interesting finding is that most reported cases are women. Transforming growth factor (TGF) β is involved in the activation of fibroblasts and estrogen has been shown to inhibit TGF-β signaling [5]. Tamoxifen, a synthetic, non-steroidal anti-estrogen has been shown to inhibit keloid fibroblast proliferation and decrease collagen production, probably through downregulation of TGF-β [6]. Thus, estrogen may have an important role in the formation of multiple dermatofibromas.

Acknowledgements

References

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