松永 佳世子

61歳男性。NSAIDsとメトトレキサートの内服治療に抵抗性の関節症性乾癬に対してinfliximabを投与した。Infliximab投与により関節症状は劇的な改善を認めたが、2クール終了後にニューモシスチス肺炎(Pneumocystis pneumonia;以下PCP)を発症した。乾癬患者では、現在のところ生物学的製剤によるPCP発症のリスク評価とST合剤の予防投薬の明確なガイドラインがない。生物学的製剤の使用に際しては低頻度ではあるもののPCP発症の可能性について慎重に経過観察していく必要があると考えられる。(著者抄録)

Reticulate acropigmentation of Kitamura (RAK) is a rare genetic disorder of cutaneous pigmentation with an autosomal dominant pattern of inheritance and a high penetration rate. The characteristic skin lesions are reticulate, slightly depressed pigmented macules mainly affecting the dorsa of the hands and feet, which first appear before puberty and subsequently expand to the proximal limb and the trunk. To identify mutations that cause RAK, we performed exome sequencing of four family members in a pedigree with RAK. Fifty-three SNV/Indels were considered as candidate mutations after some condition narrowing. We confirmed the mutation status in each candidate gene of four other members in the same pedigree to find the gene that matched the mutation status and phenotype of each member. A mutation in ADAM10 encoding a zinc metalloprotease, a disintegrin and metalloprotease domain-containing protein 10 (ADAM10), was identified in the RAK family. ADAM10 is known to be involved in the ectodomain shedding of various substrates in the skin. Sanger sequencing of four additional unrelated RAK patients revealed four additional ADAM10 mutations. We identified a total of three truncating mutations, a splice site mutation and a missense mutation in ADAM10. We searched for mutations in the KRT5 gene, a causative gene for the similar pigmentation disorder Dowling-Degos disease (DDD), in all the patients and found no KRT5 mutation. These results reveal that mutations in ADAM10 are a cause of RAK and that RAK is an independent clinical entity distinct from DDD.

Morphea is a type of localized scleroderma. It is a skin disease involving the development of fibrosis in the dermis and subcutaneous fat tissue beneath without a visceral lesion, and the cause is still unclear. An involvement of epithelial-mesenchymal transition (EMT) has been reported as a cause of tissue fibrosis, but this was mostly observed in pulmonary and hepatic fibrosis, and the involvement of EMT in a skin disease, morphea, has not been studied. Thus, we analyzed the involvement of EMT in skin fibrosis in morphea patients using pathological techniques. Skin lesions of six morphea patients were analyzed (five female and one male patient). As a control, non-light-exposed skin lesions of 11 healthy females were analyzed. Concretely, tissue samples were prepared from these subjects and subjected to immunostaining of transforming growth factor (TGF)-beta 1, alpha-smooth muscle actin (alpha-SMA) and fibronectin, which have been reported to be associated with fibrosis, and Snail1 and E-cadherin, which are considered to be involved in EMT, and expressions of these were analyzed. In morphea patients, dermal expression of TGF-beta 1, alpha-SMA and fibronectin, which are involved in fibrosis, was enhanced, and, at the same time, enhanced expression of Snail1 and reduced expression of E-cadherin, which are involved in EMT, were observed in the dermal eccrine glands. These findings suggested the progression of EMT in the dermal eccrine glands in morphea.

Background: Adapalene gel 0.1% is an efficacious treatment for acne vulgaris in Asians. It is generally well tolerated, but may still cause cutaneous side effects among patients with sensitive skin. Objective: To assess the ability of a moisturizing lotion (Cetaphil (R)) in improving the local tolerance of adapalene. Methods: In this 4-week, randomized, investigator-blinded, split-face study among 30 healthy volunteers of Chinese origin, adapalene gel was applied once daily to the whole face and the moisturizing lotion was applied once daily to only one side of the face according to the randomization scheme. Results: At each study visit, both investigators and subjects reported better tolerance on the side of moisturizing lotion + adapalene gel than the side of adapalene gel only, with significant differences reported by the subjects during the first 2 weeks (p = 0.039 and 0.013, respectively). Global worst score, defined as the average of worst scores for erythema, desquamation, dryness, stinging/burning and pruritus, was significantly lower for the side of moisturizing lotion + adapalene gel than for the side of adapalene gel alone (0.43 +/- 0.34 vs. 0.59 +/- 0.44, p = 0.032). Conclusion: The adjunctive usage of an effective moisturizer improves local tolerance of adapalene gel and may contribute to better adherence.

Backgroud: : More effective treatment strategies are needed for the chronic skin ulcers. Recently, it has been reported that clinical application of stem cells improve wound healing. Objective: We aimed to determine the dynamic time-course movement of epidermal stem cell markers especially p75 neurotrophin receptor (p75NTR) and Integrin beta-1 in wound healing process. Furthermore, we also investigated the presence of these markers in human. Methods: Epidermal Integrin beta-1(+) and p75NTR(+) cells were counted in wound healing process in mice. Both cells were also counted in human skin specimen obtained from chronic skin ulcers and healthy controls. Growth factor gene expression levels by purified mouse epidermal p75NTR. cells were also analyzed using real-time RT-PCR. Results: Integrin beta-1(+) and p75NTR(+) cells were proliferated from 3 days after wounding. Reepithelization was completed 7 days after wounding, and the numbers of cells were returned to the baseline levels by 14 days after wounding. Integrin beta-1(+) cells were proliferated in the basal layer, and p75NTR(+) cells were proliferated in the upper layer of epidermis. In human skin, Integrin beta-1(+) and p75NTR(+) cells were 81% +/- 12% and 36% +/- 15% of the basal cells, respectively. In patients with chronic skin ulcers, the percentage of Integrin beta-1(+) cells in the epidermis was identical to healthy controls. Surprisingly, p75NTR(+) cells were significantly decreased in chronic skin ulcer patients (1.2% +/- 2.6%; p < 0.0005) compared to healthy controls. Purified mouse epidermal p75NTR(+) cells expressed higher transforming growth factor-beta2 and vascular endothelial growth factor-alpha transcripts and lower epidermal growth factor transcripts than p75NTR(-) cells. Conclusion: These results suggest that Integrin beta-1(+) and p75NTR(+) cells play an important role in wound healing process, and that p75NTR may be a key molecule and a candidate for new therapeutic target besides preexisting molecules for chronic skin ulcer patients. (C) 2013 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

Background: Adapalene gel 0.1% is an efficacious treatment for acne vulgaris in Asians. It is generally well tolerated, but may still cause cutaneous side effects among patients with sensitive skin. Objective: To assess the ability of a moisturizing lotion (Cetaphil (R)) in improving the local tolerance of adapalene. Methods: In this 4-week, randomized, investigator-blinded, split-face study among 30 healthy volunteers of Chinese origin, adapalene gel was applied once daily to the whole face and the moisturizing lotion was applied once daily to only one side of the face according to the randomization scheme. Results: At each study visit, both investigators and subjects reported better tolerance on the side of moisturizing lotion + adapalene gel than the side of adapalene gel only, with significant differences reported by the subjects during the first 2 weeks (p = 0.039 and 0.013, respectively). Global worst score, defined as the average of worst scores for erythema, desquamation, dryness, stinging/burning and pruritus, was significantly lower for the side of moisturizing lotion + adapalene gel than for the side of adapalene gel alone (0.43 +/- 0.34 vs. 0.59 +/- 0.44, p = 0.032). Conclusion: The adjunctive usage of an effective moisturizer improves local tolerance of adapalene gel and may contribute to better adherence.

48歳、女性。1989年発症の全身性エリテマトーデス(SLE)に対し、当院内科でステロイド内服薬他多種類の免疫抑制薬を使用し治療を受けていた。2001年より陰部に皮膚結節が多発したため当科を受診した。皮膚生検の結果、伝染性軟属腫と診断し、摂子による摘除、手術療法、液体窒素療法など種々の治療を行ったが、全身に自家感染を起こし治療に難渋していた。患者から従来法以外の治療の希望があったため、可変型ロングパルスダイレーザー(Candela社製Vbeam、USA)治療を同意のもと行った。その結果、照射部位の結節を縮小もしくは消失させることができ、本人の満足度も高く、現在も継続的にレーザー治療を行っている。従来の治療に反応しない伝染性軟属腫に対し、ダイレーザー治療を試みることは有用であると考えた。(著者抄録)