Hanako Yamaoka

A novel small compound accelerates dermal wound healing by modifying infiltration, proliferation and migration of distinct cellular components in mice

BACKGROUND Impaired wound healing in skin ulcer is one of the major medical issues in the aged society. Wound healing is a complex process orchestrated by a number of humoral factors and cellular components. TGF-β is known to stimulate collagen production in dermal fibroblasts while inhibiting proliferation of epidermal keratinocyte. A screening of small compounds that suppress type I collagen production in fibroblasts has identified HSc025 that antagonizes the TGF-β/Smad signal. OBJECTIVE We examined the effects of HSc025 on dermal wound healing and elucidated the underlying mechanisms. METHODS Effects of HSc025 on the wound closure process were evaluated in a murine full-thickness excisional wound healing model. Cell proliferation and migration were estimated using primary cultures of human keratinocytes and fibroblasts. Comprehensive analyses of gene expression profiles were performed using untreated and HSc025-treated fibroblasts. RESULTS Oral HSc025 administration suppressed macrophage infiltration and accelerated wound closure as early as at day 2 after the dermal excision. Treatment of cultured keratinocytes with HSc025 counteracted the inhibitory effects of TGF-β on cell proliferation and migration. On the other hand, HSc025 stimulated migration, but not proliferation, of dermal fibroblasts independently of TGF-β. Experiments using an artificial dermis graft revealed that HSc025 stimulated migration of collagen-producing cells into the graft tissue. A cDNA microarray analysis of untreated and HSc025-treated fibroblasts identified pirin as a critical mediator accelerating fibroblast migration. CONCLUSION HSc025 accelerates wound healing by modifying infiltration, proliferation and migration of distinct cellular components, which provides a novel insight into the therapy for intractable skin ulcer.

Elevation of serum KL‐6 levels during treatment with tumor necrosis factor‐α inhibitor in patients with psoriasis

1 Roujeau JC, Bioulac-Sage P, Bourseau C et al. Acute generalized exanthematic pustulosis: analysis of 63 cases. Arch Dermatol 1991; 127: 1333–1338. 2 Bircher AJ, Levy F, Langauer S, Lepoittevin JP. Contact allergy to topical corticosteroids and systemic contact dermatitis from prednisolone with tolerance of triamcinolone. Acta Derm Venereol 1995; 75: 490–493. 3 Demitsu T, Kosuge A, Yamada T. Acute generalized exanthematous pustulosis induced by dexamethasone injection. Dermatology 1996; 193: 56–58. 4 Mussot-Chia C, Flechet ML, Napolitano M et al. Methylprednisoloneinduced acute generalized exanthematous pustulosis. Ann Dermatol Venereol 2001; 128: 241–243.

Case of generalized pustular psoriasis with end-stage renal disease successfully treated with granulocyte monocyte apheresis in combination with hemodialysis

Granulocyte monocyte apheresis (GMA) is an extracorporeal apheresis instrument that removes activated neutrophils and monocytes. Generalized pustular psoriasis (GPP) is characterized by neutrophil infiltration into the epidermis that causes Kogojs spongiotic pustule. Thus, GMA is one of the useful therapies for GPP, and it was approved for the treatment in 2012 in Japan. Herein, we report a case of GPP with end‐stage renal disease (ESRD) successfully treated with GMA in combination with hemodialysis (HD). A 54‐year‐old Japanese female visited our outpatient clinic because of erythema with pustules on her trunk and extremities over the past 4 months. Histopathological examination showed an intraepidermal pustule filled with numerous neutrophils and spongiosis. These findings led to the diagnosis of GPP. She had ESRD and had been treated with HD twice a week for approximately 4 years. During maintenance HD twice a week, weekly GMA was started at Tokai University Hospital. The skin symptoms disappeared after five administrations of GMA. We suggest that GMA is an effective therapy for GPP patients with ESRD who are treated with HD.

Pediatric case of anaplastic lymphoma kinase-positive anaplastic large cell lymphoma forming a solitary skin tumor on the forearm

A 5‐year‐old girl noticed a rapidly growing reddish nodule on her right forearm. Although oral antibiotics had been administrated for 2 weeks, the tumor enlarged. Skin biopsy revealed excessive infiltration of atypical neoplastic cells expressing CD4, CD30 and anaplastic lymphoma kinase (ALK). These histological and immunohistochemical findings were consistent with anaplastic large cell lymphoma (ALCL). Computed tomography showed multiple lymphadenopathy, but lymph node biopsy and bone marrow examination did not show any evidence of systemic dissemination. However, due to the positive results for ALK and multiple lymphadenopathy, we diagnosed ALK‐positive ALCL forming a solitary skin tumor on the forearm. The patient received chemotherapy and presented marked improvement. This paper discusses the difficulty of diagnosing pediatric ALK‐positive ALCL limited to the skin and reviews the medical published work.

Long-term efficacy of psoriasis vulgaris treatments: Analysis of treatment with topical corticosteroid and/or vitamin D3 analog, oral cyclosporin, etretinate and phototherapy over a 35-year period, 1975–2010

Various therapies have been tried for psoriasis. In Japan, biologics began to be used for psoriasis treatment in January 2010. Their clinical efficacy is well known, but biologics cannot be used in all psoriasis patients for reasons such as side‐effects and cost. It is necessary to evaluate the effect of long‐term psoriasis treatment, but there have been no reports evaluating long‐term treatment. Therefore, the outcomes of patients who had been treated at the Tokai University Hospital for more than 5 years, before biological agents were released, were examined. Three categories, classified by initial severity, changes in severity by method of treatment and background characteristics, were investigated. In conclusion, cases of long‐term treatment with a combination of topical corticosteroid and topical vitamin D3 analog or oral cyclosporin were found to be effective therapies. Patients with a history of diabetes mellitus or cardiovascular disease of psoriasis were likely to be treatment resistant.

Diagnostic usefulness of findings in Doppler sonography for amelanotic melanoma

To evaluate the diagnostic usefulness of Doppler sonography for amelanotic melanoma (AM), the correspondence between the findings of dermoscopy and Doppler sonography was investigated in AM in comparison with other hypopigmented tumors. Seven cases with AM and 11 cases with squamous cell carcinoma (SCC), 10 cases with non‐ or hypopigmented basal cell carcinoma (NP‐BCC) and six cases with eccrine poroma (EP) as hypopigmented tumors were investigated. EP is readily recognized by differences from AM and SCC based on a single vertical and non‐torvtuous vessels. NP‐BCC is distinguished from AM based on tortuosity running in a vertical direction. Though findings of tortuosity in vessels and heterogeneity of vessel size are recognized both in AM and SCC: (i) abundant blood flow was recognized more clearly in AM; (ii) total blood flow was more than 40% in most cases of AM (average, 60.9%); and (iii) more vessels which flow into a tumor are found in AM (85.7%). There is no relationship between dermoscopic findings of vessel types and Doppler sonography findings of vessels. In this study, the diagnostic usefulness of the above‐mentioned specific findings in examination may suggest using Doppler sonography for AM as one non‐invasive method.

Development of psoriasis 10 years after allogeneic hematopoietic cell transplantation from non‐psoriatic donor: Further evidences for genetics and immunopathogenesis of psoriasis

Japan and only five instances from other countries. This scarcity of papers on adalimumab for GPP highlights the significance of our report. The case we experienced was rare in that GPP developed in a PsA patient, who refused infusion. Adalimumab elicited a favorable response to the concomitant GPP. No similar reports have been published except for a case reported by Zangrilli et al. More case records should be collected to establish evidence that adalimumab is a safe and effective treatment, even for GPP patients judged as having primary or secondary failure to infliximab therapy.