Shigetsuna Komatsu

ATX-S10(Na)-PDT shows more potent effect on collagen metabolism of human normal and scleroderma dermal fibroblasts than ALA-PDT

Recent study revealed that photodynamic therapy (PDT) with a novel photosensitizer (ATX-S10(Na)) shows more potent effects for various skin diseases than ALA-PDT. The effect of ATX-S10(Na)-PDT on dermal fibroblasts is still unknown. Using dermal fibroblasts derived from normal and scleroderma patients, and mouse skin in vivo, we compared the effects of ATX-S10(Na)-PDT and ALA-PDT. Fibroblasts from normal, scleroderma patients or mice skin were treated with ATX-S10(Na)-PDT or ALA-PDT. After the PDT treatments, the expression of matrix metalloproteinases (MMPs) Tissue inhibitors of metalloproteinases (TIMPs) and collagen synthesis was assayed using ELISA and reverse transcription-PCR (RT-PCR). The expression of MMP-1 and MMP-3 was slightly decreased and collagen I mRNA was significantly increased in scleroderma fibroblasts compared with normal fibroblasts. Both ATX-S10(Na)-PDT and ALA-PDT increased the expression of MMP-1 and MMP-3 in protein and mRNA levels in both normal and scleroderma fibroblasts with more potent effect by ATX-S10(N)-PDT. Collagen I synthesis was markedly decreased by ATX-S10(Na)-PDT and by ALA-PDT again with more potent effect by ATX-S10(Na)-PDT in both normal and scleroderma fibroblasts. In mice skin the effect of PDT for MMPs and collagen I was also detected and the effect was more potent in ATX-S10(Na)-PDT. In contrast, MMP-2, TIMP-1, TIMP-2, and collagen III expression was not affected by the ATX-S10(Na)-PDT or ALA-PDT treatment. ATX-S10(Na)-PDT is more potent modulator for dermal matrix components than ALA-PDT and might be useful for scleroderma patients.

Correlation of disease activity and serum level of carcinoembryonic antigen in acquired idiopathic generalized anhidrosis: A case report

Hypohidrosis and anhidrosis are congenital or acquired conditions which are characterized by inadequate sweating. Acquired idiopathic generalized hypohidrosis/anhidrosis (AIGA) includes idiopathic pure sudomotor failure (IPSF), which has the following distinct features: sudden onset in youth, increased serum immunoglobulin E and responds favorably to systemic corticosteroid. No clinical markers reflecting the disease severity or activity have been established. Here, we report a case of AIGA in a Japanese patient successfully treated with repeated methylprednisolone pulse therapy. In this case, serum carcinoembryonic antigen (CEA) levels increased up to 19.8 ng/mL along with aberrant CEA immunoreactivity of eccrine sweat glands. Interestingly, the serum CEA level normalized as sweating improved with repeated methylprednisolone pulse therapy. Therefore, serum CEA level may serve as a useful clinical marker of hypohidrosis or anhidrosis.

Cutaneous necrotizing vasculitis as a manifestation of familial Mediterranean fever

Familial Mediterranean Fever (FMF) is a hereditary autoinflammatory disease, which is characterized by recurrent and paroxysmal fever, peritonitis, arthritis, myalgia, and skin rashes. Although various skin lesions such as “erysipelas‐like erythema”, urticaria, nonspecific purpura, and subcutaneous nodules have been described, cutaneous vasculitis is rare. We report a Japanese case of sporadic FMF accompanied by cutaneous arteritis at the time of febrile attacks of FMF. Gene analysis revealed M694I mutation in a single allele of the MEFV gene, and oral colchicine successfully controlled both periodic fever and subcutaneous nodules of arteritis. Cutaneous necrotizing vasculitis repeatedly emerging with febrile attacks should be included among the skin manifestations of FMF.

Transient perforating folliculitis induced by sorafenib

Figure 1. Isolated, dark-red papules with central coneshaped keratotic plugging surrounded by erythema. Dear Editor, Sorafenib is an oral multikinase inhibitor originally developed as a Raf-1 kinase inhibiting agent, but has been demonstrated to inhibit other kinases such as vascular endothelial growth factor receptor-2, vascular endothelial growth factor receptor-3, plateletderived growth factor receptor-b, and FLT3, as well. Cutaneous side-effects (including hand–foot syndrome, facial erythema, alopecia, xerosis, pruritus and subungual splinter hemorrhages) are frequently associated with sorafenib. Rarely, the drug induces perforating folliculitis (PF), keratosis pilaris-like eruption and follicular hyperplasia. Herein, we present a case of PF associated with sorafenib. To our knowledge, this is the first report of sorafenib-associated PF in Japan. A 77-year-old Japanese man was treated with sorafenib (two doses of 400 mg ⁄day) for metastatic renal cell carcinoma. Two weeks after the onset of the therapy, he noticed hair loss, which was followed by typical hand–foot syndrome with symmetrical red palms and soles and patchy hyperkeratosis on plantar pressure areas. Sorafenib was continued without lowering the dose and 7 weeks after the beginning of the therapy asymptomatic, solitary dark-red papules of up to 6 mm surrounded by erythema developed on the extensor side of the lower extremities, on buttocks and lumbar area (Fig. 1). Each papule contained a central cone-shaped keratotic plug. Histopathological examination disclosed prominent keratotic plugging, and dilated follicular infundibula filled with compact parakeratotic cornified cells, an example of which can be seen in Figure 2a. Neutrophils were infiltrating into the cornified cells. Upper follicular epithelial cells showed marked vacuolization (Fig. 2b) and dyskeratosis. Perifollicular lymphocytic infiltration and vascular proliferation were also noticed. The patient was diagnosed with PF associated with sorafenib. Although topical corticosteroid therapy

Serum carcinoembryonic antigen (CEA) as a clinical marker in acquired idiopathic generalized anhidrosis: a close correlation between serum CEA level and disease activity

Hypohidrosis/anhidrosis are congenital or acquired sweating impairments. Among them, acquired idiopathic generalized anhidrosis/hypohidrosis (AIGA) is the most common, and characterized by favourable response to systemic corticosteroid, however, no clinical markers for disease severity or activity have been developed.

Cutaneous Langerhans cell histiocytosis in elderly with chronic myelomonocytic leukemia

Langerhans cell histiocytosis (LCH) is a rare histiocytic neoplasm characterized by clonal proliferation of Langerhans cells in multi‐organ systems including skin, bone, pituitary gland, liver and spleen. Skin‐limited involvement of LCH usually indicates an indolent clinical course; however, in rare cases, LCH is accompanied by other myeloproliferative disorders, which may determine the prognosis. An 82‐year old Japanese man presented with numerous asymptomatic facial papules clinically simulating rhinophyma. Although findings of histopathology and general examination including bone marrow biopsy led to the diagnosis of cutaneous LCH, he died from chronic myelomonocytic leukemia, which emerged 10 months after the initial diagnosis of LCH. The previously reported cases of LCH concomitant with other hematological disorders are also summarized and described compared with the present case.

Olanzapine‐induced limb edema simulating episodic angioedema with eosinophilia

fragments on and around the left orbital region (Fig. 1a). The fragments had slightly injured the left cornea. Dermoscopy revealed tiny dust and metal particles (arrows) mostly on or partly inside the skin (Fig. 1b), which we removed through careful and intensive brushing with a toothbrush. The brushing was performed after wiping off the gels. The left cornea was carefully washed and the particles were removed. On 22 July, we used dermoscopy to evaluate the treatment (Fig. 1c) and confirmed that most of the particles had been eliminated (Fig. 1d). A second dermoscopic evaluation on 3 August showed similar results, with the remaining particles forming a traumatic tattoo (Fig. 1e,f). Dermoscopy was useful for evaluating the precise appearance of particles on and within the skin. It could be used as a guide for brushing with a toothbrush before treatment, because the distribution of metal particles is the most important point of treatment. It was also a useful tool for assessment after treatment. Using dermoscopy, we were able to brush the affected lesion sufficiently and eliminate almost all of the metal particles, even though some particles remained as a tattoo. Qswitched ruby laser, Q-switched alexandrite laser and Qswitched 1064-nm neodymium:yttrium–aluminum–garnet laser would be useful for the residual fragments. Future victims may benefit from dermoscopic evaluation of their treatments.

Toxic epidermal necrolysis with prominent facial pustules: a case with reactivation of human herpesvirus 7.

A 37-year-old Japanese man presented with confluent erythemas and progressive erosive lesions on the almost entire body including the oral mucosa and genitalia. This was accompanied with prominent facial pustules. Although a lymphocyte stimulation test was positive only for acetaminophen, he took other agents including carbamazepine for his depression. He was diagnosed as having toxic epidermal necrolysis with prominent facial pustules and treated by methylprednisolone pulse therapy, which resulted in a good response. During the course, human herpesvirus 7 (HHV-7) DNA was detected in his peripheral blood. The HHV-7 reactivation might be related to facial pustulosis, which is occasionally observed in drug-induced hypersensitivity syndrome/drug rash with eosinophilia and systemic symptoms.

Mucous membrane pemphigoid accompanied by ovarian cancer: A case with autoantibodies solely against γ2-subunit of laminin-332

phigus is greater than the general population, there may be a possibility of simple coincidence of IgA pemphigus and MM in these four patients. Further studies on the pathological role of MM in patients with IgA pemphigus are needed to elucidate the pathogenesis of this association. Jae Yong SUNG, Sang Eun LEE, Soo-Chan KIM Department of Dermatology and Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul, and Department of Dermatology, CHA Bundang Medical Center, CHA University, Seongnam, Korea

Eyelash trichomegaly: report of a case following diffuse hair loss associated with transient malnutrition.

We thank the following physicians for offering clinical information: Dr U. Oyunchimeg and Dr Kh. Naranchimeg from the National Center for Maternal and Child Health, Mongolia. We are also grateful to Dr Z. Zaya for taking care of us in Tarialan, Uvs prefecture, Mongolia, where we got the samples including that of the patient, and Professor K. Hayasaka, Department of Pediatrics, Yamagata University Faculty of Medicine, Yamagata, for helpful discussion. This work was supported by a grant from the Ministry of Health, Labor, and Welfare of Japan (Health and Labor Sciences Research Grants; Research on intractable diseases; H24-039) to T. S.