Akira Maeda

Overactivation of IL-4-induced activator protein-1 in atopic dermatitis

Atopic dermatitis is regarded as mediated by Th2-type immunity. In fact, it frequently coincides with the elevation of immunoglobulin (Ig)-E in patients sera. Due to the pivotal role of interleukin (IL)-4 in regulation of IgE, we hypothesized if atopic dermatitis represents a hyper-reactive condition in response to IL-4 when it coincides the higher serum level of IgE. To address this possibility, peripheral blood mononuclear cells (PBMC) isolated from patients with atopic dermatitis with the high serum IgE level, from those with psoriasis or from healthy volunteers were stimulated with recombinant IL-4 and analyzed for activation of transcription factors including activator protein (AP)-1 or signal transducers and activators of transcription (STAT)-6 by employing electrophoretic mobility shift assays. Although no significant difference between atopy patients and other groups was observed in the STAT-6 binding activity in IL-4-stimulated PBMC, it over-activated the binding of AP-1 in PBMC of the patients with atopic dermatitis. The AP-1 binding was interfered by the use of an antibody directed against JunB. This is the indication that IL-4-overactivated AP-1 is composed of JunB. Furthermore, semi-quantitative RT-PCR analyses revealed marked down-modulation of a Th1 cytokine, interferon (IFN)-gamma, in IL-4-stimulated PBMC derived from atopy patients, but not that from healthy individuals. Together, our present study indicates that AP-1 is over-activated by IL-4 in PBMC of the atopic patients with the higher IgE level, thereby implying that IL-4-induced over-activation of AP-1 might be one of pathogenic factors in atopic dermatitis.

Disseminated scleroderma of a Japanese patient successfully treated with bath PUVA photochemotherapy.

BackgroundLocalized scleroderma is known to be resistant to therapies. Recently, it has been reported that bath PUVA photochemotherapy is effective for treating this dermatosis.ObjectivesAlthough according in earlier reports mainly white populations have been treated successfully with bath PUVA therapy, there is little knowledge of whether it is effective in treating colored populations. We treated a 64-year-old Japanese woman suffering from disseminated scleroderma with bath PUVA photochemotherapy to see its effects.ConclusionAlthough rather high cumulative UVA doses were required for this patient compared with those needed in earlier reports, no adverse effects were observed. The lesions were markedly improved, suggesting that this therapeutic modality is well-tolerated and useful for colored patients such as the Japanese. Furthermore, it turns out that the thermographical assessment is useful to estimate clinical improvement of this sclerosing skin disorder.SommaireAntécédentsLa sclérodermie localisée s’est avérée résistante aux divers traitements. On a rapporté récemment que la PUVAthérapie est efficace dans le traitement de cette dermatose.ObjectifBien que, selon certains rapports antérieurs, la PUVAthérapie ait donné d’excellents résultats surtout chez les blancs, il existe peu de données indiquant si elle est efficace chez les gens de couleur. Toutefois, une Japonaise de 64 ans souffrant de sclérodermie disséminée a été traitée par PUVAthérapie.ConclusionBien que d’assez fortes doses cumulatives d’UV-A aient été nécessaires dans le cas de cette patiente comparativement aux sujets qui ont fait l’objet de rapports antérieurs, aucun effet indésirable n’a été observé. Les lésions étaient nettement atténuées, ce qui fait croire que ce mode de traitement est bien toléré et qu’il est également efficace chez les patients de couleur comme cette Japonaise. En outre, il s’est avéré que l’examen thermographique est utile pour évaluer l’amélioration clinique de cette affection sclérosante de la peau.

Tinea barbae due to Trichophyton rubrum with possible involvement of autoinoculation.

q 2000 British Association of Dermatologists, British Journal of Dermatology, 142, 1047±1070 and a partial nail-plate excision was performed almost simultaneously. The lesions reduced progressively until they disappeared. At follow-up 9 months later, the patient remained asymptomatic. The presence of paronychia and excess granulation tissue of the periungual areas has been described during treatment with different drugs such as retinoids. Recently, these same findings were reported in association with antiretroviral agents. The aetiological role of a particular drug on these lesions is difficult to determine, as HIV-positive patients are usually treated with multidrug regimens. The reverse transcriptase inhibitor lamivudine and the protease inhibitor indinavir are the drugs suspected of causing this effect. A patient with severe paronychia due to zidovudine-induced neutropenia has also been described. In our patient, the simultaneous involvement of several nails from distant sites such as the toes and fingers, the lack of similar prior episodes or known risk factors for paronychia, the lack of healing after antibiotic therapy, and the regression once indinavir was withdrawn, suggest that this process was drug-induced and that indinavir was the most likely causative agent for the skin manifestations. Previously reported features include acute paronychia in all patients, and lateral ingrowing nails or formation of granulation tissue in some. The lesions are usually limited to one or both great toes, although fingernails may also be involved. The delay in the appearance of nail complications ranges from 1 to 12 months after the commencement of therapy. Patients differ widely in their degree of immunosuppression. Histological studies are lacking except for those in one patient who showed the histological picture of granulation tissue, similar to our patient. Despite topical or surgical treatment, lesions tend to recur. The development of these lesions seems to be unpredictable, related neither to daily nor to cumulative dose. The course of the lesions after the discontinuation of the suspected drug is not defined in the literature except for six patients with complete or partial regression within 9±12 months. The mechanism by which antiretroviral drugs lead to the development of paronychia and granulation tissue remains unclear. We consider that the description of new cases will delineate the real role of antiretroviral agents on this probably not uncommon, but at present rarely described, side-effect.

Quantitative analysis of bikunin-laden mast cells in follicular eruptions and chronic skin lesions of atopic dermatitis.

Abstract. Bikunin, an inhibitor of serine proteases, is widely distributed in human tissues, including the skin, and may inhibit tryptase and modulate allergic inflammation. The purpose of the present study was to compare follicular eruptions (FE), so-called atopic skin or perifollicular accentuation, with atopic dermatitis (AD) lesions (ADL) by immunohistochemical analysis using antibodies to bikunin and tryptase. Immunohistochemically, bikunin was colocalized with tryptase in dermal mast cells, and a small quantity of bikunin was also deposited in the intercellular spaces in FE and ADL. The number of bikunin-laden mast cells per 0.78xa0mm2 of skin was 78.1±7.1 (mean±SEM, n=14) in FE, 25.4±2.3 (n=10) in normal skin from children and infants, 91.3±11.8 (n=10) in ADL, 25.6±4.8 (n=5) in nonlesional skin of AD, and 27.8±2.0 (n=13) in normal adult skin. The difference between FE and normal control skin from children and infants, between FE and nonlesional skin of AD, and between lesional and nonlesional skin of AD were significant. Based on the above findings and the occasional presence of spongiosis and lymphocyte infiltration, in FE moderate inflammation is apparent histopathologically even though little inflammation is apparent clinically.

Drug eruption induced by cefcapene pivoxil hydrochloride

Keywords: n ncutaneous adverse drug reaction; ncefcapene pivoxil hydrochloride; nantibiotics; nmedicaments; npositive patch test

A case of acral lentginous melanoma: the correlation between CD95L expression on melanoma cells and apoptosis of tumor infiltrating lymphocytes.

There is an increasing amount of evidence that melanoma cells express the ligand for CD95 (CD95L), a potent inducer of apoptosis, which contributes to creating the immune privileged circumstances of tumor sites. However, it still remains to be demonstrated whether the capacity of melanoma cells to express CD95L is acquired during the progression. We addressed this question with a case of acral lentiginous melanoma by employing immunostaining using an antibody directed against CD95L as well as by in situ TUNEL staining. H&E‐staining of tumor specimens revealed that there were two different growth patterns. The central part of the tumor showed a deeper invasion into the dermis (Breslow thickness>4‐mm). The horizontally growing edge of the tumor proliferated more superficially (Breslow thickness<3‐mm). Relatively fewer lymphocytes were observed around the melanoma nests in central areas, which expressed detectable amounts of CD95L. In contrast, more lymphocytes were observed among the melanoma cells in the peripheral lesion, where CD95L was not detected. To evaluate the relevance of the CD95L expression, in situ TUNEL staining was performed. This indicated a significant correlation of lymphocyte apoptosis with CD95L expression on melanoma cells. Together, the data suggest that expression of CD95L is turned on depending on the level of melanoma, and that it may contribute to creating immune privileged circumstances by initiating apoptosis of tumor infiltrating lymphocytes.

Chronic actinic dermatitis: a case report and immunohistological analysis in its early phase

To the Editor, Chronic actinic dermatitis (CAD) was first described by Hawk and Magnus as a disease entity with typical clinical features of chronic, long-lasting, asymptomatic lesions on sun-exposed areas (1). Lim et al. later proposed CAD to be a unifying disease concept of previously known various photosensitivity conditions (2). Although mediation of delayed type hypersensitivity (DTH) has been proposed in CAD (3) (4), there is only limited knowledge about the action of immunocompetent cells. Here, we report a case of CAD and immunohistochemical analysis of infiltrating lymphocytes in the UV-induced early lesions. A 61-year-old Japanese man had presented pruritic reddish plaque on skin of sun-exposed areas, like the face, neck and dorsa of the hand in 1995. When he visited our outpatient clinic, February 1999, pruritic, indurated, reddish plaques spread on the sun-exposed areas, including the face, dorsa of the hand and forearms, in addition to the localisation on covered areas, like the trunk and extremities. To monitor the involvement of underlying photosenstivity, photo-testing was performed. Briefly, a bank of 14 black lamps (FL32S: Toshiba Medical Supply, Gifu, Japan) with an emission peak at 352nm and a bank of seven sunlamps (FL20SE.30: Toshiba Medical-Supply) with an emission peak at 305nm were used as a light source of UVA and UVB, respectively. The irradiance of UVA or UVB was measured with a radiometer (UVR3036/S: Toshiba Medical-Supply). The patient’s minimal erythemal dose of UVA (MED-A) was 5.36J/m2 and MED of UVB (MED-B) 33mJ/cm2, both of which are far below the average for healthy Japanese individuals. Furthermore, photo-patchtesting with the application of a series of known photosensitizers (1% tetrachlorosalicylanilide, 1% 3, 3ƒ, 5-tribromosalicylanilide, 1% bithionol, 1% 4ƒ-bromosalicylanilide, 1% methylcoumarine, 1% 3, 4, 4ƒtrichlorocarbanilide in white petrolatum) followed by ex-

Case of multiple myeloma initiating from skin tumor.

We reported a 69-year-old male case of multiple myeloma. His chief complain was a skin tumor, and it was localized on his forearm. After general examination of whole the body, atypical myeloma cells were found in the bone marrow. We selected radiation therapy, because of his age, past disease history, and so on. The tumor expressed good response, and reduced clinically. But, in a short time, it formed metastatic lesions in both thoracis vetebra and forearm arround the first lesion.Multiple myeloma is a disease, which is usually found and mainly complained chronic anemia, morbid bone fracture, and lumbago. This case that we reported was found as extramedullary plasmacytoma on the skin, and in that point, it was comparatively rare clinically.