Liborija Lugović

Atopic dermatitis: immunophenotyping of inflammatory cells in skin lesions

Abstract

Prominent Involvement of Activated Th1-Subset of T-Cells and Increased Expression of Receptor for IFN-Gamma on Keratinocytes in Atopic Dermatitis Acute Skin Lesions

Background: Atopic dermatitis (AD) is an allergic skin disease mediated by antigen-specific IgE and an important role has been ascribed to CD4+ cells (Th cells). The objective of the study was to evaluate humoral and cellular immunological factors in the blood and the skin lesions of AD patients, and to analyze the presence of inflammatory cell-surface markers in blood and skin biopsies. Methods: The parameters for monitoring of 40 AD patients included results of prick test to inhalant allergens and epicutaneous (patch) test to contact allergens; values of total IgE, serum immunoglobulins (IgG, IgA, IgM) and different cell markers in the sera (CD3, CD4, CD8, CD20, CD21, CD23, HLA-DR). We also analyzed the presence of inflammatory cell-surface markers (CD3, CD4, CD8, CD20, CD20, CD1a, CD23, CD29, CD45Ro, IFNγ+ markers) in the biopsies of skin lesions from 10 AD patients and 5 healthy controls (HCs) by immunohistochemical analysis (method of avidin-biotin immunoperoxidase). Results: Beside increased total serum IgE and positive skin tests, a significantly higher percentage of CD23+ cells with lower percentage of CD21+ cells was revealed in peripheral blood of AD patients in comparison to HCs. A positive epidermal expression of the majority of markers of T cells (CD3+, CD4+, CD8+, CD29+, CD45Ro+, IFNγ+) and those of Langerhans’ cells (LCs) (CD1a, CD23+), without those of B cells (CD20+) were noted in AD patients, but no in the skin of HCs. Furthermore, significant difference was also found between the two groups for increased expression of CD3, CD4, CD8, CD29, CD45Ro, IFNγ+ markers (markers for IFNγ receptor) and higher intraepidermal CD23+ LCs and intradermal CD1a+ LCs in AD skin lesions. Conclusions:The obtained results suggest involvement of various humoral factors with increased production of IgE and cooperation between Th subsets and LCs, with higher production of related cytokines, and disturbed cellular immunity, including epidermal LCs with IgE receptors of high and low affinity in AD. The annotation of activated Th1 cells with increased producing of IFNγ in acute AD skin lesions is notable, and might lead to IFNγ binding to keratinocytes and consequently inflammatory skin changes in the disease.

Histamine intolerance - Dermatologic sequels

Autoimmune bullous diseases are a group of intraand subepidermal disorders with different course and prognosis. Most of them are serious diseases which have to be treated for longer period and controlled by experienced dermatologist. Pemphigus group of diseases is characterized by acantholysis in the epithelium of mucous membranes or / and the skin. These diseases can have significant morbidity and morality as a result of complications of the disease or side-effects of the therapy. Mainstay of the therapy of pemphigus are corticosteroids. Usually together with corticosteroids, steroid-sparing agents i.e. azathioprine or mycophenate mofetil are introduced to reduce side-effects of corticosteroids and to make remision periods longer. Patients who do not respond to these therapies should be treated with intravenous immunoglobulins, cyclophosphamide or rituximab.Histamine intolerance (HIT) develops as a result of an impaired diamine oxidase (DA0) activity due to gastrointestinal disease or through DA0 inhibition, as well as through a genetic predis-position which was proven in a number of patients. The intake of histamine- rich foods as well as alcohol or drugs which cause either the release of histamine or the blocking of DA0 can lead to various disorders in many organs (gastrointestinal system, skin, lungs, cardiovascular system and the brain), depending on the expression of histamine receptors. Dermatologic sequels can be rashes, itch, urticaria, angioedema, dermatitis, eczema and even acne, rosacea, psoriasis and other. The recognizing of symptoms due to HIT is especially important in treating such patients. Because of the possibility of symptoms affecting numerous organs, a detailed history of symptoms following the intake of histamine rich foods or drugs that interfere with histamine metabolism is essential for making a diagnosis of HIT. Considering that such symptoms ran be a result of multiple factors, the existence of HIT is usually underestimated, 5 expectations are being made from the future studies.