Gerd Plewig

UVA irradiation induces collagenase in human dermal fibroblasts in vitro and in vivo

SummaryWe report the effect of UVA irradiation on collagen metabolism of fibroblasts, including both synthesis of the collagen degrading enzyme collagenase and de novo synthesis of type I collagen as the major structural component of the dermis. For this purpose confluent fibroblast monolayers were irradiated under standardized conditions (5, 15, 35, 60 J/cm2 using UVASUN 3000, Mutzhas, Munich, FRG, and UV source Sellas sunlight type 2.001, Sellas, Gevelsberg, FRG). Subsequently, total RNA was isolated and subjected to dot blot and northern blot analysis using oligolabelled cDNA clones for human type I collagen, collagenase and Β-actin. Collagen type I and Β-actin mRNA levels remained unaltered following irradiation, suggesting that the synthetic pathway of collagen metabolism at the pretranslational level is not affected by short-term UVA irradiation. However, collagenase mRNA was found to be dose-dependently induced in fibroblasts after irradiation, thus probably contributing to the actinic damage to the dermis. These in vitro data were confirmed in vivo using in situ hybridization on frozen sections of biopsy material obtained from UVA irradiated patients.

Experimental reproduction of skin lesions in lupus erythematosus by UVA and UVB radiation.

Sunlight is a well-established factor in the induction and exacerbation of lupus erythematosus. Although experimental reproduction of lupus erythematosus lesions with wavelengths shorter than 320 nm was demonstrated previously, the effect of wavelengths longer than 320 nm was not investigated adequately. In this study we show that the action spectrum of lupus erythematosus reaches into the UVA region. A total of 128 patients with lupus erythematosus underwent phototesting with the use of polychromatic UVB and long-wave UVA. Subsets of the disease consisted of discoid lupus erythematosus (n = 86), subacute cutaneous lupus erythematosus (n = 22), and systemic lupus erythematosus (n = 20). Skin lesions clinically and histologically compatible with lupus erythematosus were induced in 64% of patients with subacute cutaneous lupus erythematosus, 42% of patients with discoid lupus erythematosus, and 25% of patients with systemic lupus erythematosus. The action spectrum of the induced lesions was within the UVB range in 33% of patients, in the UVA range in 14%, and in the UVB and UVA range in 53%. In positive test reactions patchy dark erythema and urticarial plaques developed within a few days. In some patients typical discoid lesions persisted for months.

Diseases Caused by Bacteria

Gonorrhea is an infectious bacterial disease, which predominantly affects the urogenital mucous membranes, caused by Neisseria gonorrhoeae (gonococcus). Gonorrhea attacks the urogenital organs in men and women. Disease of the sexual organs is considerably dangerous, because during this process, through adhesion and scarring of the epididymis or Fallopian tubes caused by inflammation, permanent sterility may occur.

Stratum corneum Lipid Function

The stratum corneum contains a complex mixture of polar and nonpolar lipids in its intercellular spaces. These lipids, present in form of multiple lamellae, have been investigated for their role in providing the epidermal barrier to transcutaneous water loss, the selective barrier from the inside to the outside of the organism and partly the process of physiological desquamation. The composition of these lipids varies from species to species, with the body region and the degree of keratinocyte differentiation. The most undifferentiated layers of the epidermis contain typical membrane lipids, phospholipids, while more differentiated layers contain ceramides, cholesterol and free fatty acids. Essential fatty acids are essential for the maintenance of the lamellar structures and epidermal barrier function. Epidermal linoleic and arachidonic acids derive from exogenous sources. Only recently attempts have been made to elucidate the timing and regulation of epidermal fatty acid metabolism. Keratinocytes do not express a low molecular weight fatty acid binding protein like other cells active in lipid metabolism, but may employ alternative ways in fatty acid uptake and metabolism.

Pathogenesis and classification of solar urticaria: A new concept

Although its exact mechanism remains unknown, evidence supports the immunologic nature of solar urticaria. On the basis of experimental findings in the literature and our own observations, a new concept of the pathogenesis and classification of solar urticaria is presented. We propose two types of solar urticaria: type I, IgE-mediated hypersensitivity to specific photoallergens, which are generated only in patients with solar urticaria, and type II, induction of IgE-mediated hypersensitivity to a nonspecific photoallergen, which is generated both in patients with solar urticaria and in normal persons.

Is the origin of atopy linked to deficient conversion of ω-6-fatty acids to prostaglandin E1?

Our hypothesis on the origin of atopy links alterations in ω-6-fatty acid metabolism in atopic persons (i.e., reduced formation of δ-6-desaturase products) to deficient T cell differentiation and function. We suggest that a relative deficiency in dihomo-γ-hnolenic acid-derived prostaglandin E 1 is the major etiologic factor for diminished T cell maturation postpartum. Its precursors, γ-linolenic acid and dihomo-γ-linolenic acid, are physiologically provided in colostrum and mature breast milk of healthy mothers. Depressed cell-mediated immunity and uncontrolled B-cell response with increased IgE synthesis are explained as prostaglandin E 1 -dependent defects of T cell differentiation caused by insufficient supply of prostaglandin E 1 precursors during early infancy. Thus, in our opinion atopy is a metabolic disorder and the associated immunologic disturbances are epiphenomena.

Lipid composition of outer stratum corneum and nails in atopic and control subjects

The presence of generalized dry skin is a characteristic feature of atopic dermatitis, and correlates with a disturbed water permeability barrier, a diminished stratum corneum hydration, and an increased incidence of irritant contact dermatitis [7, 2 5 27]. At an ultrastructural level the water permeability barrier is represented by the intercellular multilamellar lipid sheets of the stratum corneum [4, 12] which are derived from exocytosis of lamellar bodies [3]. One of the major lipid constituents of the intercorneocyte lipid membranes are the ceramides, a unique heterogeneous group of complex sphingolipids. The ceramides consist of at least six subfractions [13]. They are functionally important for the stability of the intercellular multilamellar lipid sheets. Of particular interest is an acylceramide (ceramide 1), which is predominantly linked to linoleic acid and appears to act as a molecular rivet in locking together the multilamellar lipid sheets of the stratum corneum [28]. The ceramides play an important role in the water permeability and water retention properties of the stratum corneum [10, 11]. Previously, we have suggested that decreased stratum corneum ceramides might be related to the appearance of atopic dry skin and impaired barrier function [16, 18]. In the present study, we examine the composition of stratum corneum and nail lipids ofnon-atopic and atopic subjects, and confirm a deficiency of ceramides in atopic individuals. Twenty patients with atopic dermatitis and 19 nonatopic control subjects were diagnosed according to the criteria of Hanifin and Rajka [9]. Immunological abnormalities of atopy were demonstrated by the presence of

Benign Epithelial Tumors

A wide variety of cutaneous tumors have epithelial elements. In this chapter we discuss neoplasms which appear to show epidermal differentiation. The tumors of apparent adnexal differentiation are covered in Chapter 57. Epidermal tumors can be identified with antibodies against specific cyto-keratins or against a cocktail of such molecules, but this is seldom needed. Many of the neoplasms discussed here have histologic patterns which can also be seen in keratinization disorders (Chap. 17) and epidermal nevi (Chap. 52).

Solar urticaria: studies on mechanisms of tolerance

The mechanisms by which tolerance is induced in solar urticaria were investigated in two patients whose eruptions were induced by wavelengths in the range 320–455 nm in one patient and 400–495 nm in another. Tolerance to radiation was induced by repeated exposures of the skin to the eliciting wavelengths of light. Weal and flare responses to intradermal injections of histamine and the histamine‐releasing agent (codeine) were unaltered in the tolerant skin when compared with adjacent normal skin. Intradermal injection of in vitro irradiated serum or plasma from the patients induced an urticarial reaction in the unexposed skin but not in tolerant skin and repeated injections induced tolerance to the eliciting radiation. The results suggest that tolerance is not due to exhaustion of the photoallergen in the skin, or to an increase of the mast‐cell degranulation threshold caused by exposure to ultraviolet radiation, or mast‐cell mediator depletion, or histamine tachyphylaxis. It is likely that binding sites of IgE on mast cells remain occupied by the photoallergen during the state of tolerance, and that histamine release from mast cells is blocked.

Plasmapheresis in solar urticaria

Three patients with solar urticaria were treated with plasmapheresis. By intradermal injection of in vitro irradiated serum the existence of a circulating photoallergen was demonstrated in cases 1 and 2 but not in case 3. Plasmapheresis induced complete remission of solar urticaria in case 1 and transient improvement in case 2. In case 3, however, no beneficial effect was observed. It is suggested that some patients with solar urticaria, probably those with a circulating photoallergen, may benefit from plasmapheresis.