Pressure effects on the growth of human scar fibroblasts.

Although pressure therapy is the mainstay of treatment for hypertrophic scars, its actual mechanism remains unknown. An in vitro study was designed to investigate the effects of positive pressure on the growth of human scar-derived fibroblasts through its transforming growth factor beta1 (TGF-beta1) secretion. A pneumatic pressure system connecting to a cell culture chamber was designed. Six-well cultured plates with fibroblasts implanted were treated with different pressure settings. Cells were treated with constant pressure 20 mm Hg above atmosphere pressure (group A n = 18) or with 40 mm Hg above atmosphere pressure (group B n = 18) daily for nine successive days. Cells without pressure were treated as the control study (group C n = 6). Each experimental group was divided into daily pressure applied at 24 hours (n = 6), 18 hours (n = 6), and 12 hours (n = 6). Cell counting was performed on the 2nd, 4th, 7th, 9th, 11th, and 14th day after implantation. On day 4, the concentration of transforming growth factor beta1 was measured, and cell doubling time was calculated. Compared with the control group, there was a significant decrease in cell count and the concentration in the 18-hour and 24-hour 20 mm Hg or 40 mm Hg pressure treated group. The cell doubling time was significantly increased in the 24-hour 20 mm Hg or 40 mm Hg pressure treated groups, and the 18-hour 40 mm Hg pressure treated group. (P < .05) Pressure inhibits the growth and activity of human scar fibroblasts, and a higher pressure application can shorten the daily application period. There should be an optimal pressure level corresponding to a daily application period to achieve the most effective results on pressure therapy for scars.

Pathogenic human monoclonal antibody against desmoglein 3.

Pemphigus vulgaris (PV) is a potentially fatal autoimmune mucocutaneous disease associated with production of IgG autoantibodies to desmoglein 3 (Dsg3), a 130-kDa epidermal cadherin protein. The binding of pathogenic antibody to Dsg3 on epidermal keratinocytes leads to loss of intercellular adhesion and results in intraepithelial blister formation. Here, we describe a human monoclonal antibody, PVMAB786, a Dsg3-specific IgG4 antibody, from an untreated patient with active PV. The antibody reacts with a 130-kDa protein on keratinocyte cell surfaces and recombinant Dsg3 protein, but not desmoglein 1 protein. PVMAB786 induces acantholysis in normal human skin and mucous membranes and induces a clinical and histological profile similar to human PV when injected into neonatal mice. PVMAB786 will be a valuable tool in identifying the role of Dsg3 in epithelial cell adherence and acantholysis, mechanisms of Dsg3 processing/presentation and V gene and isotype usage in PV pathogenesis.

Treatment of pemphigus vulgaris: current and emerging options.

BACKGROUND: Pemphigus vulgaris is a rare, chronic, autoimmune mucocutaneous blistering disease. The disease can progress to involve the skin and multiple mucosae. Pemphigus vulgaris can be associated with a high morbidity and significant mortality rate. Treatment of the condition can be challenging. Conventional therapy primarily consists of systemic corticosteroids and immunosuppressant agents. In some patients with pemphigus vulgaris, these agents fail to provide an effective clinical response or have significant adverse effects. METHODS: We evaluated data on 792 patients with pemphigus vulgaris retrieved from PubMed, covering the period 1973-2004. Only patients reported in the English literature were included in this review. Recently, several new therapeutic agents and treatment modalities have been described for the treatment of patients with pemphigus vulgaris. Some therapeutic agents that were used in the past and abandoned have recently regained favor. This review focuses on the therapeutic uses of dapsone, methotrexate, mycophenolate mofetil, chlorambucil, dexamethasone-cyclophosphamide pulse therapy, immunoablative therapy with cyclophosphamide, plasmapheresis, and extracorporeal photochemotherapy. Newer agents, such as intravenous immunoglobulin (IVIg) therapy and rituximab (an anti-CD20 chimeric monoclonal antibody), are also discussed. RESULTS AND CONCLUSIONS: Among the oral agents, dapsone may be considered a first-line agent. This is primarily because the risk of potentially fatal adverse effects with this drug is lower than that associated with other available chemotherapeutic agents. In patients who are refractory to oral agents, alternative treatments have been used to prevent further disease progression. Recently, the use of IVIg therapy, with a defined protocol, has been reported to be beneficial. This therapy is promising since it may allow for discontinuation of all other therapies and is safe. The adverse effects from IVIg therapy are minimal. Furthermore, compared with other therapies, it provides a better quality of life.

Profile of autoantibody to basement membrane zone proteins in patients with mucous membrane pemphigoid: long-term follow up and influence of therapy.

Mucous membrane pemphigoid (MMP) is an autoimmune mucocutaneous blistering disease characterized by autoantibodies to components within the basement membrane zone. In this study, we report the titers of autoantibodies to antigens in the BMZ, in the sera of 13 patients, treated with intravenous immunoglobulin as monotherapy over a consecutive 18-month period. Using bovine gingiva lysate as substrate in an immunoblot assay, autoantibodies to human bullous pemphigoid antigens (BPAg1 and BPAg2), human beta4 integrin, and laminin 5 were measured. A statistically significant (P < 0.05) decline in the autoantibody titers to beta4-integrin was observed after 3.42 months of initiating the IVIg therapy. These titers were undetectable after 13 months of therapy. The titers of antibodies to BPAg1 and BPAg2 did not correlate with disease activity or response to therapy. Antibodies to laminins were not detected. In patients with MMP, autoantibody titers to beta4-integrin correlate with disease activity and response to therapy.

Vancomycin-induced linear IgA disease manifesting as bullous erythema multiforme.

BACKGROUND: Vancomycin-induced linear immunoglobulin A (IgA) disease, an autoimmune, blistering disease in response to vancomycin administration, is characterized by a subepidermal, vesiculobullous eruption and linear IgA deposition along the basement membrane zone on direct immunofluorescence. CASE REPORT: We report the case of an 81-year-old man treated with vancomycin who developed diffuse erythema multiforme and tense bullae involving the palmoplantar surfaces. Discontinuation of vancomycin therapy resulted in complete resolution of this patient's cutaneous eruption. RESULTS: Biopsy of a representative skin lesion demonstrated lichenoid interface dermatitis with focal subepidermal clefting, dyskeratosis, and prominent eosinophils. Direct immunofluorescence showed linear basement membrane staining with immunoreactants to IgA; indirect immunofluorescence demonstrated the presence of circulating IgG antibodies binding in an intercellular pattern. Immunoprecipitation studies using the patient's serum revealed 210, 130, and 83 kDa target antigens. CONCLUSIONS: Presenting with an initial clinical picture suggestive of bullous erythema multiforme, this patient's subsequent clinical course and direct immunofluorescence confirm the diagnosis of linear IgA bullous disease (LABD). His indirect immunofluorescence findings and immunoprecipitation results suggest that circulating non-IgA antibodies may represent a newly recognized immunopathologic feature of vancomycin-induced linear IgA disease, underscoring the variable and unpredictable manifestations of this drug-induced cutaneous disease.

Blistering diseases in the elderly: diagnosis and treatment.

This article discusses the major blistering diseases in the geriatric population. The diagnosis of both immune- and non-immune-mediated blistering disorders can be confirmed with the help of histologic and immunopathologic studies. Various serologic assays, which are more specific, also can be used to confirm the diagnosis of autoimmune blistering diseases. These techniques have facilitated the diagnosis and allowed the institution of early treatment. The treatment of blistering disorders has included both localized and systemic treatments. Localized treatment involves topical care including the following measures: the prevention of trauma; soaking of blisters in antiseptic (potassium permanganate or aluminum subacetate) solutions; topical and intralesional corticosteroids; and the prevention and early treatment of infections with local or systemic antibiotics. Conventional oral systemic therapies that have proved to be beneficial include systemic corticosteroids, anti-inflammatory agents, and immunosuppressive agents. Because the elderly are more prone to the side effects of these systemic agents, it is crucial that routine hematologic tests be done and monitored until the treatments have been discontinued. Recently, newer alternative treatment modalities have proved to be successful in patients who failed to respond or developed multiple side effects to the conventional oral systemic agents. In conclusion, as clinicians gain a greater understanding into the pathogenesis of these diseases, more specific molecular-targeted treatments will most likely become available.

Zosteriform connective tissue nevus: a case report.

Because of its distinctive clinical features and histopathological characteristics, zosteriform connective tissue nevus is considered a separate entity from other connective tissue nevi. Only two cases have previously been reported in the worldwide dermatological literature. Here we report a zosteriform connective tissue nevus in a 3-year-old boy with similar clinical presentation.