Etanercept is safely used for treating psoriatic arthritis in a patient complicated with type 1 hereditary angioedema.

Hereditary angioedema (HAE) is a life-threatening disorder caused by deficiency or dysfunction of the C1 inhibitor protein. Patients with HAE are restricted in various medical treatments, which can induce an HAE attack. We herein report the first case of psoriatic arthritis (PSA) with type 1 HAE successfully treated with 25 mg of etanercept without HAE attack. Etanercept may represent a useful choice for treating patients with HAE accompanied by intractable PSA and rheumatoid arthritis (RA).

Signal transducer and activator of transcription 3 is a key regulator of keratinocyte survival and proliferation following UV irradiation.

UVB irradiation of signal transducer and activator of transcription 3 (Stat3)-deficient keratinocytes resulted in a high incidence of apoptosis compared with controls. Conversely, forced expression of Stat3 desensitized keratinocytes to UVB-induced apoptosis. Upon UVB exposure, keratinocyte Stat3 was rapidly dephosphorylated, followed by decreases of both Stat3 mRNA and protein levels in a p53-independent manner. Vanadate treatment reversed the UVB-induced down-regulation of Stat3 and generation of apoptotic keratinocytes, suggesting the involvement of a tyrosine phosphatase. Furthermore, Stat3 was required for UVB-induced proliferation of follicular keratinocytes, leading to epidermal thickening. Finally, constitutive activation of Stat3 was observed in UVB-induced squamous cell carcinomas of either mice or human origin. These data suggest that Stat3 is required for survival and proliferation of keratinocytes following UVB exposure and that Stat3 is tightly regulated as part of a novel protective mechanism against UVB-induced skin cancer.

Vitamin D and the skin.

Vitamin D was originally discovered as a factor that regulates calcium and bone metabolism. Recent advances in investigation have shown that vitamin D also functions as a regulator of cellular growth and differentiation in various tissues. The skin is not an exception from such effects of vitamin D; it is regarded as a site of its activation and action. Evidence has accumulated showing that the active form of vitamin D and its analogs suppress growth and stimulate the terminal differentiation of keratinocytes. In psoriatic lesions, epidermal keratinocytes exhibit hyper-proliferation and impaired differentiation triggered by inflammation. Therefore, it is quite reasonable that vitamin D is effective on psoriasis. Indeed, within the past decade, analogs of vitamin D3 have been used as topical therapy for psoriasis. In this review, we summarize the fundamental features of vitamin D and the development of vitamin D therapy for psoriasis. Clinical application to other skin diseases and the future of vitamin D therapy in dermatology are also discussed.

Langerhans cell histiocytosis involving the skin of an elderly woman: a satisfactory remission with oral prednisolone alone.

Langerhans cell histiocytosis (LCH) is a disorder characterized by neoplastic proliferation of Langerhans cells that rarely involves the skin in adults. A 74-year-old woman presented with a fourteen year history of eosinophilic granuloma and bone involvement caused by LCH. She had received three combination therapy courses of curettage and radiation since 1987 and had remained free of LCH signs for seven years, after which she started to notice brown nodules on her left leg. Biopsy specimens taken from the lesions showed massive proliferations of large histiocytic cells. Immunoperoxidase stainings for CD1a and S-100 protein were positive. Electron microscopy identified Birbeck granules in the cytoplasm of the atypical Langerhans cells. Treatment with oral prednisolone alone has resulted in the patient remaining in complete remission for 12 months.

STAT3 deficiency in keratinocytes leads to compromised cell migration through hyperphosphorylation of p130(cas).

We previously reported that STAT3 plays a crucial role in transducing a signal for migration of keratinocytes (Sano, S., Itami, S., Takeda, K., Tarutani, M., Yamaguchi, Y., Miura, H., Yoshikawa, K., Akira, S., and Takeda, J. (1999) EMBO J. 18, 4657-4668). To clarify the role of STAT3 in signaling the migration, we studied the intracellular signaling pathway through an integrin receptor in STAT3-deficient keratinocytes. STAT3-deficient keratinocytes demonstrated increased adhesiveness and fast spreading on a collagen matrix. Staining with anti-phosphotyrosine antibody revealed that STAT3-deficient keratinocytes had an increased number of tyrosyl-hyperphosphorylated focal adhesions. Analyses with immunoprecipitation revealed that p130(cas) was constitutively hyperphosphorylated on tyrosine residues, while other focal adhesion molecules such as focal adhesion kinase and paxillin were not. Transfection of STAT3-deficient keratinocytes with an adenoviral vector encoding the wild-type Stat3 gene reversed not only impaired migration but also the increased tyrosine phosphorylation of p130(cas). These results strongly suggest that STAT3 in keratinocytes plays a critical role in turnover of tyrosine phosphorylation of p130(cas), modulating cell adhesiveness to the substratum leading to growth factor-dependent cell migration.

Vesiculobullous dermatomyositis with panniculitis without muscle disease.

Vesicles and bullae formation is rare in dermatomyositis. We describe a 60-year-old woman who presented with vesiculobullous dermatomyositis with panniculitis and no muscle disease.