Taku Fujimura

Profiles of Foxp3+ regulatory T cells in eczematous dermatitis, psoriasis vulgaris and mycosis fungoides

Background  It is well known that regulatory T cells (Tregs), identified by their expression of CD4, CD25 and Foxp3, play a crucial role in maintaining peripheral tolerance. Recently, it has been demonstrated that a Treg population resides in normal human skin. However, only a few studies have demonstrated the presence of Foxp3+ Tregs in inflammatory skin disorders.

Inhibitory effect of the polyinosinic-polycytidylic acid/cationic liposome on the progression of murine B16F10 melanoma

Cellular proteins, retinoic acid inducible gene‐I and Toll‐like receptor 3, sense dsRNA including polyinosinic‐polycytidylic acid (PIC) to stimulate innate immune response. The local administration of PIC has been demonstrated to be effective in anti‐tumor immunotherapy. However, the effects of PIC delivered cross the cell membrane have not yet been examined. To address this issue, we used a complex of PIC and cationic liposome (PIC liposome) and examined its anti‐tumor effects in vitro and in vivo. PIC liposome could directly suppress the growth of B16F10 melanoma in vitro and repeated peritumoral injections of PIC liposome inhibited melanoma growth in a dose‐dependent manner. This treatment induced tyrosinase‐related protein‐2 (TRP‐2)‐tetramer+ CD8+ cells in the lymph nodes. As the mechanism for its anti‐tumor immune response, we showed that the intradermal injection of PIC liposome induced the maturation of dendritic cells (DC). Moreover, the intratumoral injection of immature DC after treatment with PIC liposome significantly increased the number of TRP‐2‐specific IFN‐γ‐producing cells in the lymph nodes as well as spleen, which resulted in an augmentation of the anti‐tumor immune response. These studies demonstrate the potential of peritumoral injection of PIC liposome as immunotherapy for malignant melanoma.

Myxofibrosarcoma (myxoid malignant fibrous histiocytoma) showing cutaneous presentation: report of two cases

Myxofibrosarcoma or myxoid malignant fibrous histiocytoma is one of the most common fibroblastic sarcomas in older patients. It is characterized by a tendency for predominantly subcutaneous, multinodular, diffusely infiltrative growth, which may extend to the overlying dermis and present as a cutaneous lesion. Histologically, it comprises a spectrum ranging from hypocellular low‐grade myxoid to high‐grade pleomorphic sarcoma. Because the dermal presentation usually appears relatively banal, accurate diagnosis is sometimes challenging. In this report, we present two cases of myxofibrosarcoma with dermal involvement.

CCR4 Expression by Atypical T Cells in Systemic Pilotropic Lymphoma: Its Behavior under Treatment with Interferon Gamma, Topical PUVA and Systemic Retinoid

We describe an 88-year-old Japanese patient with pilotropic T cell lymphoma involving the peripheral blood as well as lymph nodes. This patient presented with multiple red follicular papules, confluent, infiltrated erythematous plaques and nodules. Moreover, he was conspicuous for the presence of total alopecia of the scalp and eyebrows. Histopathologically, the lesional skin showed dense follicular and perifollicular infiltrates of atypical lymphocytes. The flow cytometry disclosed the presence of weakly CD4+ CCR4+ cell populations that would not be detected in the peripheral blood from healthy controls. The patient responded well to topical PUVA and systemic etretinate (retinoid-PUVA) and intravenous IFN-γ. Parallel with the decrease in atypical cells in the peripheral blood, the percentage of weakly CD4+ CCR4+ T cells declined. However, about 1 week after we discontinued this treatment because of the side effects, the lymph node swelling became prominent, and, 4 weeks later, the patient died before restarting any specific chemotherapy.

Development of a novel Ag‐specific immunotherapy using CpG oligodeoxynucleotides in a new, unique mouse cutaneous eosinophilic inflammation model

The number of patients with severe atopic dermatitis (AD) has been on the rise recently. We are therefore urgently in need of a treatment that can suppress Th2 cell‐mediated responses in an Ag‐specific fashion. Oligodeoxynucleotides (ODN)containing CpG motifs (CpG ODN) have been highlighted as immunomodulators that reduce Th2‐mediated responses. To determine the effect of CpG ODN on Th2‐mediated skin inflammation, we first developed a reproducible murine model of protein Ag‐induced eosinophilic inflammation that is accompanied by epidermal acanthosis and increased serum IgE levels as seen in AD. In this model we found that treatment with CpG ODN during epicutaneous sensitization in previously i.p.‐primed mice prevented the development of Th2‐mediated responses. Furthermore, to evaluate the therapeutic effect of CpG ODN on established eosinophilic inflammation, mice were treated with a course of the immunotherapy at a skin site remote from the area of Ag application prior to the second 1‐wk epicutaneous exposure to Ag. Therapeutic treatment with CpG ODN plus Ag, but not that with CpG ODN alone, could reverse the established eosinophilic inflammation. The presented results provide strong evidence for the feasibility of a novel Ag‐specific immunomodulator to treat cutaneous eosinophilic inflammation such as that characteristically found in patients with severe AD.

Neurofibromatosis 1 associated with an intracranial artery abnormality, moyamoya disease and bilateral congenital large hairy pigmented macules.

following intermediate filament assembly shown in in vitro assembly studies for K5 and K14. The K5 amino-terminal end also has a role in desmoplakin I binding, an interaction that binds keratin intermediate filaments to desmosomes. These findings suggest that the P25L mutation has an effect on filament structure and integrity. Another interesting aspect of EBS-MP is the aetiology of pigmentation. However, the exact molecular mechanism remains unclear. Further studies with molecular models of the V1 domain of K5 will be necessary to define fully the role of this domain in keratin interactions with other structural molecules and intracellular organelles.

Therapy-resistant skin ulcers on hypoplastic leg associated with neurofibromatosis type 1.

We describe a case of therapy‐resistant skin ulcers in sporadic neurofibromatosis type 1. A 40‐year‐old woman had suffered from neurofibromata on her trunk and extremities since 30 years prior. She suffered from hypoplasia of her right leg from a young age and had a 1‐year history of therapy‐resistant skin ulcers on the leg and inguinal region. Magnetic resonance angiography disclosed a narrowed femoral artery at the level of the upper thigh with poor root in the inner side corresponding to the ulcerated lesions. The vascular changes were thought to be the cause of the skin ulcers.

Angioleiomyoma with the features of the dermatofibroma

Dear Editor, Angioleiomyoma is a common, deep dermal or subcutaneous, benign tumor that originates from vascular smooth muscle and usually presents as a discolored macule or erythematous nodule. Here we present a case of angioleiomyoma associated with hypermelanosis in the basal layer, which resulted in a brownish tint. The histopathological feature was similar to that in dermatofibroma, and the clinical view was unique as angioleiomyoma. A 30-year-old Japanese woman visited our hospital with a 10-year history of an asymptomatic subcutaneous tumor on her left lower leg. Physical examination revealed a brownish, elastic-hard tumor 20 mm × 20 mm in size on the lateral side of the left lower leg. The tumor was poorly demarcated and clinically mimicked dermatofibroma (Fig. 1). Laboratory examination showed no abnormal changes. The biopsied specimen showed a tumor mass composed of interlacing bundles of uniform smooth muscle cells together with numerous small vessels in the dermis (Fig. 2a,b). Hypermelanosis was prominent in the basal layer of epidermis

Generalized Mucinosis in a Patient with Erythroderma

We describe an 81-year-old Japanese patient with erythroderma overlapping with widespread and symmetrical deposits of mucin in the upper dermis. Clinically, the mucinous lesions on the nape and upper trunk were localized papular mucinosis. Histologically, there was a perivascular infiltrate of lymphohistiocytic cells mingled with plasma cells in the upper dermis but no sclerosis. Immunohistochemical staining revealed that more than 90% of these infiltrating plasma cells produced immunoglobulin λ-chain. Both the erythroderma and generalized mucinosis responded to topical steroid and PUVA therapy. To the best of our knowledge, this is the first case of erythroderma accompanied by generalized mucinosis.