Successful treatment of lichen amyloidosus associated with atopic dermatitis using a combination of narrowband ultraviolet B phototherapy, topical corticosteroids and an antihistamine.

Lichen amyloidosus (LA) is a type of primary localized cutaneous amyloidosis characterized by multiple pruritic discrete hyperkeratotic papules with amyloid deposition in the papillary dermis. Clinical regression is usually difficult to achieve, even after treatment. In this study, we report a case of an adult man with LA associated with atopic dermatitis (AD) which was successfully treated with narrowband ultraviolet B (NB-UVB) phototherapy, topical corticosteroids and an oral antihistamine. This case suggests that NB-UVB phototherapy may be a useful adjuvant for LA associated with AD.

Pigmented spots as a sign of mammary Paget's disease.

Pigmented mammary Paget's disease is a rare variant of mammary Paget's disease. The clinical appearance mimics malignant melanoma. This paper describes a case of asymptomatic, slightly pigmented spots on the right mammary nipple. The pigmented nipple was histopathologically diagnosed as mammary Paget's disease with an underlying intraductal carcinoma. This case suggests the importance of conducting skin biopsies of developing pigmented spots on the nipples in elderly people.

Autoantibodies directed against the protease inhibitor calpastatin in psoriasis.

Psoriasis is believed to be a T cell-mediated autoimmune disease, but also exhibits autoantibody production. Calpastatin is an endogenous inhibitor of calpain, a ubiquitous protease that regulates inflammatory processes. Anti-calpastatin autoantibody was first identified as an autoantibody specific to rheumatoid arthritis, but has been also detected in other autoimmune diseases. In this study, we examined the presence and levels of anti-calpastatin antibody in 77 psoriasis patients by enzyme-linked immunosorbent assay. Compared with normal controls, psoriasis patients exhibited significantly elevated IgG anti-calpastatin antibody levels that were similar to those found in rheumatoid arthritis patients. Remarkably, IgG anti-calpastatin autoantibody in sera from psoriasis patients inhibited calpastatin activity. Calpain II expression was up-regulated in psoriasis skin lesions compared with normal skin while calpastatin expression was normal. The results of this study reveal the presence of anti-calpastatin autoantibody in psoriasis.

Decreased expression levels of L-selectin on subsets of leucocytes and increased serum L-selectin in severe psoriasis.

L-selectin is a leucocyte adhesion molecule involved in leucocyte interactions with vascular endothelial cells. Following leucocyte activation L-selectin is endoproteolytically released from the cell surface. To assess whether psoriasis vulgaris results in systemic leucocyte activation, we examined expression levels of L-selectin on subsets of peripheral blood leucocytes from patients with psoriasis (n = 25) and normal control subjects. Serum levels of soluble L-selectin were quantified by ELISA in patients with psoriasis (n = 75), pustulosis palmaris et plantaris, and contact dermatitis, as well as normal control subjects. Psoriasis severity was evaluated by psoriasis area and severity index (PASI). L-selectin expression levels on CD4+ T cells, B cells, monocytes, and neutrophils from patients with severe-type psoriasis (PASI > or = 15) was significantly decreased compared with leucocytes from normal control subjects. Furthermore, L-selectin expression on CD4+ T cells showed good inverse correlation with PASI scores. Monocyte L-selectin expression was restored when the skin lesions of psoriasis were remitted. The frequencies of L-selectin+ CD4+ T cells or L-selectin+ CD8+ T cells from patients with psoriasis were almost normal. Serum L-selectin levels in patients with severe-type psoriasis were significantly higher than those in normal control subjects. These results suggest that subsets of leucocytes may be activated in psoriasis, and that L-selectin expression levels on some leucocyte subsets, especially CD4+ T cells, tend to correlate with disease severity of psoriasis.

High frequency of DNA aneuploidy detected by DNA flow cytometry in Bowen's disease.

To detect DNA aneuploidy in Bowen's disease, we investigated DNA flow cytometric analysis. Single cell suspensions were prepared from 18 fresh samples histopathologically diagnosed as solitary Bowen's disease and analyzed by DNA flow cytometry. In 16 (89%) of 18 lesions, DNA aneuploidy was demonstrated with a single aneuploid peak. DNA indices ranged from 1.29 to 1.74. The incidence of DNA aneuploidy in Bowen's disease is higher than those of cutaneous squamous cell carcinoma, which was 25-80% in the previous reports. Therefore, in Bowen's disease. DNA aneuploidy may not imply a good marker for characteristics of non-melanoma skin cancer. A single aneuploid peak commonly observed in Bowen's disease suggests that this disease consists of the monoclonal proliferation of keratinocytes containing abnormal DNA content.

Role and interaction of connective tissue growth factor with transforming growth factor-beta in persistent fibrosis: A mouse fibrosis model.

Skin fibrotic disorders are understood to develop under the influence of some growth factors, such as transforming growth factor-beta (TGF-beta), basic fibroblast growth factor (bFGF), or connective tissue growth factor (CTGF). To establish an appropriate animal model of skin fibrosis by exogenous application of growth factors, we investigated the in vivo effects of growth factors by injecting TGF-beta, CTGF, and bFGF into the subcutaneous tissue of newborn mice. A single application of TGF-beta or bFGF resulted in the formation of transient granulated tissue that disappeared despite 7 days of consecutive injections. A single CTGF injection also caused slight granulation. However, injecting TGF-beta plus CTGF produced long-term fibrotic tissue, which persisted for at least 14 days. Also, fibrotic tissue was observed when CTGF was injected from 4 to 7 days after TGF-beta injections for the first 1-3 days. In situ hybridization analysis revealed the expression of CTGF mRNA in the fibroblasts at least in a few fibrotic conditions. These findings suggest that either CTGF mRNA or an application of exogenous CTGF protein is required for the development of persistent fibrosis. From our study, it appears that interaction of several growth factors is required for persistent fibrotic tissue formation, with TGF-beta causing the induction and CTGF needed for maintenance of skin fibrosis. The animal model on skin fibrosis by exogenous application of growth factors developed in this study may prove useful for future studies on fibrotic disorders.

Antiepiligrin (laminin 5) cicatricial pemphigoid associated with an underlying gastric carcinoma producing laminin 5.

Although bullous pemphigoid and cicatricial pemphigoid are sometimes associated with malignancy, it remains uncertain whether such an association is pathogenetically related or just a coincidence attributable to the advanced age of the patients. We report a 61-year-old patient with antiepiligrin (laminin 5) cicatricial pemphigoid (AeCP) associated with an advanced gastric carcinoma. The gastric carcinoma cells in this patient were shown to produce laminin 5 by immunofluorescence microscopy, and the patient's serum contained autoantibodies directed against laminin 5 on immunoprecipitation. Furthermore, the blistering symptoms and the titre of antibasement membrane zone antibodies coordinately changed with the resection and subsequent relapse of the gastric cancer. These observations suggest that the gastric carcinoma producing laminin 5 may have induced the production of autoantibodies to this laminin, which were pathogenic to the skin and mucous membranes in this patient. This report demonstrates a link between this autoimmune subepithelial blistering disease and malignancy. It is of interest and potential great importance to examine other cases of AeCP for such a potential association.

Pigmented dermatofibrosarcoma protuberans (Bednár tumor) occurring in a Japanese infant.

A case of pigmented dermatofibrosarcoma protuberans (Bednár tumor) occurring in a Japanese infant is reported. A 6-month-old girl developed a 16 x 10 mm erythematous tumor with a slight elevation on the lower back at 1 month of age. Histological examination revealed proliferation of spindle-shaped, fibroblast-like cells in the myxoid interstitium. Subsequently the tumor grew gradually to a red-purplish tumor measuring 45 x 36 mm. The second biopsy specimen presented hypercellular proliferation composed of spindle-shaped cells showing slight nuclear atypia and a characteristic storiform pattern, with scattered slender dendritic cells containing a large amount of brown pigment. Immunohistochemical studies of the second biopsy specimen showed that the spindle-shaped tumor cells were positive for vimentin and CD34 and negative for factor XIIIa. The number of CD34-reactive spindle-shaped tumor cells increased in the second biopsy specimen compared with the first biopsy.

Induction of subcutaneous tissue fibrosis in newborn mice by transforming growth factor beta--simultaneous application with basic fibroblast growth factor causes persistent fibrosis.

To establish an appropriate animal model of skin fibrosis by exogenous application of growth factors, we investigated the in vivo effects of transforming growth factor-beta by injection into subcutaneous tissue of newborn mice. Histological examination revealed that TGF-beta1, beta2, and beta3 induced granulation tissue formation after 3 days of injection, while these changes had disappeared after 7 days. The changes after 3 days of injection were more pronounced in the tissue injected with TGF-beta2 or beta3 than that with TGF-beta1. In situ hybridization analysis indicated that connective tissue growth factor mRNA was strongly expressed in the fibroblasts at the site of TGF-beta injection, which suggested that fibroblasts were activated by TGF-beta. Next, we investigated the cooperative effects of TGF-beta and other growth factors including basic fibroblast growth factor (bFGF). The simultaneous application of TGF-beta and bFGF caused apparent tissue fibrosis which persisted for at least 2 weeks, while bFGF alone caused slight fibrotic changes after 7 days of injection. Thus, we succeeded in establishing an animal model of skin fibrotic disorders by the exogenous addition of growth factors, and this animal will be useful for future studies in this area.

Induction of subcutaneous tissue fibrosis in newborn mice by transforming growth factor beta-simultaneous application with basic fibroblast growth factor causes persistent fibrosis.

To establish an appropriate animal model of skin fibrosis by exogenous application of growth factors, we investigated the in vivo effects of transforming growth factor-beta by injection into subcutaneous tissue of newborn mice. Histological examination revealed that TGF-beta1, beta2, and beta3 induced granulation tissue formation after 3 days of injection, while these changes had disappeared after 7 days. The changes after 3 days of injection were more pronounced in the tissue injected with TGF-beta2 or beta3 than that with TGF-beta1. In situ hybridization analysis indicated that connective tissue growth factor mRNA was strongly expressed in the fibroblasts at the site of TGF-beta injection, which suggested that fibroblasts were activated by TGF-beta. Next, we investigated the cooperative effects of TGF-beta and other growth factors including basic fibroblast growth factor (bFGF). The simultaneous application of TGF-beta and bFGF caused apparent tissue fibrosis which persisted for at least 2 weeks, while bFGF alone caused slight fibrotic changes after 7 days of injection. Thus, we succeeded in establishing an animal model of skin fibrotic disorders by the exogenous addition of growth factors, and this animal model will be useful for future studies in this area.

Tape stripping induces marked epidermal proliferation and altered TGF-alpha expression in non-lesional psoriatic skin.

Psoriasis is a chronic inflammatory disorder characterized by epidermal hyperproliferation. Although recent evidence suggests that T cell activation is a primary trigger for psoriasis lesions, there may be alterations in the keratinocyte growth regulatory pathways which induce epidermal hyperproliferation in psoriatic patients. To test this hypothesis, we investigated the proliferative activity of epidermal keratinocytes 48 h after tape stripping, one of the standard mechanical ways to stimulate the epidermis, in 20 psoriasis patients and in 18 controls. Epidermal cell kinetics were assessed with DNA flow cytometry, the mitotic index, bromodeoxyuridine incorporation, Ki-67 antigen expression and DNA polymerase alpha expression. The expression of TGF-alpha and EGF receptors, critical mediators of keratinocyte proliferation, were also investigated immunohistochemically. The results of multiparameter assays showed that the baseline proliferative activity in uninvolved skin was the same in psoriasis patients and normal controls. After tape stripping, although both psoriasis patients and the normal controls showed significant increases in epidermal cell proliferation, the values of all the parameters investigated were significantly greater in the psoriasis patients than in the normal controls. EGF receptors were overexpressed in basal and suprabasal keratinocytes after tape stripping in both the psoriasis patients and the normal controls. In contrast, overexpression of TGF-alpha was only observed in the patients with psoriasis, which may explain their increased proliferative response to trauma.