Takashi Yoshiike

Skin barrier defect in atopic dermatitis: increased permeability of the stratum corneum using dimethyl sulfoxide and theophylline

The existence of a defect in the skin barrier of patients with atopic dermatitis (AD) was demonstrated and its importance in the pathogenesis of AD was emphasized. In order to evaluate the penetration properties of the stratum corneum of AD patients, the in vivo skin response to the penetration of dimethyl sulfoxide (DMSO) and in vitro response to the penetration of theophylline utilizing a diffusion chamber were studied. Both methods demonstrated an increasing level of penetration through the epidermal stratum corneum, with greatest penetration being evident with lesional skin, followed by AD non-lesional and then the normal control. However, statistical significances existed only between non-lesional and lesional skins in the case of the DMSO test, and between the normal control and non-lesional skin in the case of the diffusion chamber analysis using theophylline. Increased penetration of a non-specific nature is important in the pathogenesis of AD.

A case of ichthyosis linearis circumflexa successfully treated with topical tacrolimus

We report a case of ichthyosis linearis circumflexa (ILC) without the typical atopic manifestations and deformities of the hair shaft. The patient responded positively to treatment with topical tacrolimus, suggesting that abnormalities in the immunoregulatory mechanism may be involved in the pathogenesis of ILC.

Sweet's syndrome associated with encephalitis.

The involvement of the central nervous system (CNS) in Sweets syndrome (acute febrile neutrophilic dermatosis) is rare. We report a 47-year-old woman who presented with acute encephalitis and was subsequently diagnosed as having Sweets syndrome. She developed altered consciousness following fever and erythematous skin plaques in the extremities. Cerebrospinal fluid (CSF) examination disclosed neutrophilic pleocytosis without decreased glucose level. Brain magnetic resonance imaging (MRI) showed abnormal signal intensity lesions in the basal ganglia and the hippocampus. Skin biopsy revealed a dense dermal infiltration of neutrophils, which is compatible with Sweets syndrome. Treatment with acyclovir and antibiotics failed, but the subsequent corticosteroid therapy was effective. Awareness of neurological complication in Sweets syndrome may avoid unnecessary empiric therapy for meningoencephalitis and will lead to a successful treatment with corticosteroids.

Atopic Dermatitis: Studies of Skin Permeability and Effectiveness of Topical PUVA Treatment

Abstract: Uttraviolet light is effective treatment for patients with atoptc dermatitis that is resistant to conservative therapy, or complicated by adverse effects of extended steroid use. We designed a protocol using topical paoraton chemotherapy with ultraviolet A (PUVA) to treat atopic dermatitis In 114 patients. Clinical results were excellent, with complete clearing in 50% of patients receiving dally treatment. Histologic and immunologic values correlated with the clinical response, including reduced epidermal thickness, and decreased numbers of epidermal Lang‐erhans cells and dermal mast and mononuclear cell Infiltrates. The pattern of keratin 14‐positive keratinocytes returned toward normal. In addition, the water‐holding capacity of the stratum corneum increased to near normal levels. We also studied stratum comeum permeability in lesional and nonlesional skin using the dimethyl sulfoxide wheallng test and theophy line absorption studies. Compared wtth controls, permeabuIity was markedly increased in lesional skin and mildly Increased In nonlesional skin in patients with atopte dennatatis. These results suggest that Immune abnormalities and barrier dysfunction participate in the patho genesis of atopic dermatitis.

Detergent-induced epidermal barrier dysfunction and its prevention

Various detergents are used as skin cleansing products. In some cases, skin cleanser removes not only dirt but also valuable skin lipids. Therefore, detergents may disrupt epidermal barrier function despite that using of detergents are required for good skin hygiene. Lipid supplements can reverse detergent-induced dysfunction of the skin barrier. Elevated transepidermal water loss (TEWL) and riboflavin penetration in 5% SLS-treated rat and human skin were reversed by supplementation of monoglyceride (MG), squalene (SQ), cholesterol ester (CE) and pseudo-ceramide (Cer2). MG and Cer2 achieved the best results. MG appears to inhibit elution of intercellular ceramides, since more ceramides remained when the detergent was supplemented with MG. Topical application of Cer2 is not effective for recovery from artificially induced barrier disruption, but supplemented Cer2 into skin cleanser has a beneficial effect for prevention of detergent-induced barrier disruption. In conclusion, the prevention of barrier disruption is most important matter for maintaining skin health and barrier function. Therefore, we think that Cer2-supplemented skin cleanser is useful for conservation of skin barrier function.

The Role of Proteases in the Pathogenesis of Bullous Dermatoses

T various kinds of protein metabolisms are very precisely controlled in normal physiology. Among them, protein catabolism, the degradation of intracellular and extracellular proteins, is an important biochemical process and is well regulated by proteases. Recently, it has become clear that specific, limited proteolysis is a generalized mechanism in many important physiologic functions, such as those mediated by the enzyme cascades of blood coagulation, fibrinolysis, complement activation, kinin generation, intracellular zymogen activation, biosynthesis, activation, degradation of polypeptide hormones, and malignant transformation of cells. This article briefly reviews proteases and their inhibitors in skin and discusses the role of proteases and their inhibitors on pathogenic mechanisms of blistering diseases.

Antibody raised against extracellular proteinases ofSporothrix schenckii inS. schenkii inoculated hairless mice

Sporothrix schenckii produces two extracellular proteinases, namely proteinase I and II. Proteinase I is a serine proteinase, inhibited by chymostatin, while proteinase II is an aspartic proteinase, inhibited by pepstatin. Studies on substrate specificity and the effect of proteinase inhibitors on cell growth suggest an important role for these proteinases in terms of fungal invasion and growth. There has, however, been no evidence presented demonstrating thatS. schenckii produces 2 extracellular proteinases in vivo. In order to substantiate the in vivo production of proteinases and to attempt a preliminary serodiagnosis of sporotrichosis, serum antibodies against 2 proteinases were assayed usingS. schenckii inoculated hairless mice. Subsequent to an intracutaneous injection ofS. schenckii to the mouse skin, nodules spontaneously formed and disappeared for a period of 4 weeks. Histopathological examination results were in accordance with the microscopic observations. Micro-organisms disappeared during the fourth week. Serum antibody titers against purified proteinases I and II were measured weekly, using enzyme-linked immunosorbent assay (EIA). As a result, the time course of the antibody titers to both proteinases I and II were parallel to that of macroscopic and microscopic observations in an experimental mouse sporotrichosis model. These results suggest thatS. schenckii produces both proteinases I and II in vivo. Moreover, the detection of antibodies against these proteinases can contribute to a serodiagnosis of sporotrichosis.

Successful treatment of relapsing neuro-Sweet's disease with corticosteroid and dapsone combination therapy.

Sweets disease with central nervous system involvement, tentatively named neuro-Sweets disease, has rarely been reported. Although systemic corticosteroid therapy is highly effective for neurologic symptoms in neuro-Sweets disease, relapse is common. Here, we describe the case of a 38-year-old Japanese man who presented with relapsing neuro-Sweets disease that was successfully treated with a combination of corticosteroid and dapsone. Dapsone should be considered as a therapeutic option for neuro-Sweets disease patients showing relapse.

A proposed guideline for psoralen photochemotherapy (PUVA) with atopic dermatitis: successful therapeutic effect on severe and intractable cases.

Psoralen photochemotherapy with UVA (PUVA) has been reported to be successfully substitutional for, or an adjunct to, conventional treatments in patients with atopic dermatitis (AD). Against the considerable advantages of utilizing PUVA for AD patients, however, it must also be balanced against the possible hazards for individual patients. We attempted herein to formulate a guideline for the selection of AD patients assigned to PUVA. According to this guideline, 114 patients were selected for PUVA treatment. Forty-five percent of the patients did not respond adequately to other conventional forms of treatment. Side effects from former treatments, particularly steroids, appeared in 39% of the patients. Subsequent to the treatments, the skin lesions significantly decreased in 81% of the inpatients and 67% of the outpatients, while some patients lesions disappeared, despite that other forms of treatment had been unsuccessful in many cases.

A Case of Antiepiligrin Cicatricial Pemphigoid Successfully Treated by Plasmapheresis

We report the case of a 73-year-old Japanese woman suffering from antiepiligrin (laminin 5) cicatricial pemphigoid (CP) with typical clinical and immunopathological features. Histologically, the lesional mucous membrane showed a subepidermal blister formation. When indirect immunofluorescence techniques with skin split by 1 M NaCl as the substrate were used, the patient’s serum reacted only to the dermal side. Immunoprecipitation studies demonstrated that the patient’s serum contained IgG autoantibodies directed against a set of polypeptides that corresponded to epiligrin (laminin 5). After corticosteroids and immunosuppressive agents had been administered systemically, the patient’s autoantibody titer decreased and the cutaneous and mucosal blister formations were suppressed. However, the ocular lesions persisted in spite of these therapeutic regimens. After combining these treatments with double-filtration plasmapheresis, the ocular lesions improved and showed almost no progression. Plasmapheresis may thus present a new option for the treatment of CP.