Bhupendra Tank

Cyclosporine in atopic dermatitis:Modulation in the expression of immunologic markers in lesional skin

BACKGROUND In previous studies, oral cyclosporine was highly effective in the treatment of patients with severe atopic dermatitis. In this study seven patients with severe and therapy-resistant atopic dermatitis underwent therapy with cyclosporine, 5 mg/kg/day, for 6 weeks. OBJECTIVE The effect of cyclosporine on the expression of cytokines, which probably play a role in this disease, was examined. METHODS The study was performed with a panel of antibodies as markers of inflammatory cells, adhesion molecules, and cytokines (interferon-gamma [IFN-gamma], tumor necrosis factor-alpha [TNF-alpha] and interleukins 1 alpha, 1 beta, and 8 [IL-1 alpha, IL-1 beta, and IL-8, respectively]). They were visualized by indirect immunoperoxidase techniques. RESULTS After 2 weeks of cyclosporine therapy, a reduction of 60% in the disease (severity and extent) was observed. This reduction was 89% after 4 weeks and 90% after 6 weeks of therapy. Results of indirect immunoperoxidase stains performed on lesional skin sections after 2 weeks of treatment showed statistically significant reduced numbers of CD14+, CD25 (IL-2R+) and IL-8+ inflammatory cells in the dermis and CD36(OKM5)+ cells in both the epidermis and dermis. The number of cells expressing IFN-gamma and TNF-alpha, assumed to be the products of the helper T-cell (TH)1 subset, was unaltered despite the impressive clinical benefit observed. Keratinocytes in lesional atopic skin did not express intercellular adhesion molecule type 1 (ICAM-1). The expression of the adhesion molecules ICAM-1, lymphocyte function-associated (LFA) type 1, and LFA-3 on inflammatory cells also remained unaffected by cyclosporine treatment. CONCLUSION A statistically significant reduction in the number of activated T cells and in the number of cells expressing the IL-2 receptor (CD25) paralleled a marked improvement in the disease and supports the view that atopic dermatitis is based on a T-cell-mediated immune inflammation.

Mast cell distribution in normal adult skin

Aims: To investigate mast cell distribution in normal adult skin to provide a reference range for comparison with mastocytosis. Methods: Mast cells (MCs) were counted in uninvolved skin adjacent to basal cell carcinomas and other dermatological disorders in adults. Results: There was an uneven distribution of MCs in different body sites using the anti-tryptase monoclonal antibody technique. Numbers of MCs on the trunk, upper arm, and upper leg were similar, but were significantly different from those found on the lower leg and forearm. Two distinct groups were formed—proximal and distal. There were 77.0 MCs/mm2 at proximal body sites and 108.2 MCs/mm2 at distal sites. Adjusted for the adjacent diagnosis and age, this difference was consistent. The numbers of MCs in uninvolved skin adjacent to basal cell carcinomas and other dermatological disorders were not different from those in the control group. Differences in the numbers of MCs between the distal and the proximal body sites must be considered when MCs are counted for a reliable diagnosis of mastocytosis. A pilot study in patients with mastocytosis underlined the variation in the numbers of MCs in mastocytosis and normal skin, but showed a considerable overlap. The observed numbers of MCs in adults cannot be extrapolated to children. Conclusions: MC numbers varied significantly between proximal and distal body sites and these differences must be considered when MCs are counted for a reliable diagnosis of mastocytosis. There was a considerable overlap between the numbers of MCs in mastocytosis and normal skin.

Premalignant Nature of Oral Lichen Planus

The issue as to whether oral lichen planus is a premalignant disorder is still controversial. This study aimed to examine oral malignancies associated with oral lichen planus and to investigate whether oral lichen planus has an intrinsic malignant potential or whether there are also contributing external risk factors. A retrospective cohort study in 200 Caucasian patients with oral lichen planus was conducted between 1991 and 2003. Aspects such as sex, age, clinical variant, affected anatomical sites, duration of the disease, histopathology, prior immunosuppressive treatment, exposure to potential carcinogens and other concomitant diseases were examined. Histopathological examination was repeated during the follow-up if a malignancy was suspected. Three (1.5%) of the 200 patients developed an oral squamous cell carcinoma at the same site following the initial diagnosis of oral lichen planus after a period of 3-6 years (mean 4.3 years). Contributing external risk factors were also noted in two of the three patients (smoking for 20 years and systemic immunosuppressive treatment for 2 years). The exact incidence of malignant transformation is difficult to establish, because of the low number of patients and because of the possible contribution of external risk factors, which may be relevant in oral malignancy.

Mastocytosis in childhood.

Mastocytosis is a primary, abnormal accumulation of mast cells in the absence of an apparent cause. Mast cell infiltrates may be present anywhere in the body. The skin is the most frequent site of involvement (1,2). Mastocytosis is associated with a broad range of local and systemic symptoms primarily caused by the release of mast cell mediators. Adult-onset mastocytosis and childhood onset mastocytosis vary in both clinical symptoms and course. They also differ in association with genetic mutations of growth factor receptor c-kit. In this review, attention has been focused on pediatric mastocytosis.

Expression of interferon‐gamma receptors and interferon‐gamma‐induced up‐regulation of intercellular adhesion molecule‐1 in basal cell carcinoma; decreased expression of IFN‐γR and shedding of ICAM‐1 as a means to escape immune surveillance

The peritumoural inflammatory infiltrate in basal cell carcinoma (BCC) of the skin consists mainly of T lymphocytes which hardly invade the tumour nests. The absence of intercellular adhesion molecule‐1 (ICAM‐1) on BCC cells may explain the lack of tumour‐infiltrating cells and the lack of an active cell‐mediated immune response in this tumour. In this study, the induction of ICAM‐1 was investigated in BCC biopsies using recombinant human interferon‐gamma (rHuIFN‐γ). The expression of interferon‐gamma receptors (IFN‐γR) in the biopsies was also investigated. The results showed that BCC cells expressed ICAM‐1 after incubation with rHuIFN‐γ, but to a lesser degree than normal epidermal cells. The levels of shed ICAM‐1 were significantly increased in the culture supernatants of tumour biopsies compared with those from normal skin biopsies, after culturing in the presence of rHuIFN‐γ. The expression of IFN‐γR was significantly decreased on the tumour cells compared with the overlying epidermis. The decreased expression of IFN‐γR on the tumour cells and the shedding of ICAM‐1 into the peritumoural stroma may be a plausible mechanism by which the tumour cells are protected against an active cell‐mediated immune response.

Interferon-γ-induced ICAM-1 and CD40 expression, complete lack of HLA-DR and CD80 (B7.1), and inconsistent HLA-ABC expression in basal cell carcinoma: a possible role for interleukin-10?

Basal cell carcinomas (BCCs) of the skin show varying degrees of peritumoural inflammatory infiltrate consisting mainly of T cells, but lack an effective T‐cell‐mediated immune response. This may be caused by the absence of the major histocompatibility complex (MHC) class I and II antigens, intercellular adhesion molecule‐1 (ICAM‐1), CD40 and CD80 (B7.1). Interferon‐γ(IFN‐γ) is known to induce or up‐regulate their expression on epithelial cells, whereas interleukin‐10 (IL‐10) down‐regulates their expression. The induction and up‐regulation of HLA‐ABC, HLA‐DR, ICAM‐1, CD40, and CD80 in BCC and normal skin from BCC patients were investigated in a culture system using recombinant human IFN‐γ (rHuIFN‐γ). The levels of IL‐10 were determined in the supernatants after culture. The results showed that only ICAM‐1 expression was significantly up‐regulated on BCC cells. However, in the normal epidermis of BCC patients and in the epidermis overlying the tumour nests, significant up‐regulation of ICAM‐1, CD40, and CD80 and slight up‐regulation of HLA‐DR were observed. No changes in HLA‐ABC expression were observed in either normal skin or BCC. High levels of IL‐10 were present in the supernatants of BCC biopsies after culture. It may be concluded that it is highly likely that the presence of IL‐10 in BCC is directly or indirectly responsible for the complete lack of expression of HLA‐DR, ICAM‐1, CD40 and CD80 and the inconsistent expression of HLA‐ABC on BCC cells in situ and may be a way of escaping immune surveillance. Copyright

Intralesional treatment of basal cell carcinoma with low-dose recombinant interferon gamma

In this pilot clinical trail the efficacy of intralesional low-dose human recombinant interferon-gamma was investigated in seven outpatients with nodular basal cell carcinoma. There was no antitumor response in any case. Toxic side effects were minimal. All tumors were excised surgically 8 weeks after completion of therapy.

Correlation Between the Static and Dynamic Stiffness Indices of Medical Elastic Compression Stockings

BACKGROUND Compression therapy with medical elastic compression stockings (MECS) has been used effectively for treating patients with chronic venous insufficiency for many years. OBJECTIVE To study the correlation between static stiffness and the dynamic stiffness index of 18 different brands of MECS. METHODS In all, 18 different brands of MECS were divided into 5 categories (class II round-knit, class II flat-knit, class III round-knit, class III flat-knit, and class IV flat-knit) and tested. The tension of the textile of the MECS at the B1 level was measured according to the Institut de Textile France method to calculate the static stiffness index. The dynamic pressure pulsations were measured with a newly developed dynamic pressure-determining device to calculate the dynamic stiffness index. RESULTS The results showed that there was a positive correlation between the static stiffness index and the dynamic stiffness index. The dynamic stiffness indices were higher than the static stiffness indices. CONCLUSION Although the stiffness of MECS is a further refinement to the current classification, which classifies MECS according to the pressure they exert at the B level, the dynamic stiffness index does not have any additional value over the static stiffness index as far as the classification of MECS is concerned. Either or both of these characteristics should be used to select the most suitable MECS for the patient.

Placebo-controlled study of psoriasis patients treated topically with a 10% cyclosporine gel

The efficacy of a gel formulation containing 10% cyclosporine was investigated in nine patients with chronic plaque psoriasis. 10% cyclosporine gel was ineffective in patients with chronic plaque-type psoriasis

Benign persistent papular acantholytic and dyskeratotic eruption: a case report and review of the literature

Summary We report a case of a 35‐year‐old female with a persistent pruritic acantholytic and dyskeratotic eruption on the chest and vulva. The light and electron microscopic studies showed suprabasal epidermal clefting with acantholysis and dyskeratotic cells. We suggest that the most appropriate term for this case is that of benign persistent papular acantholytic and dyskeratotic eruption.