[UV exposure, skin cancer and decrease in the ozone layer]. / UV-Belastung, Hautkrebs und Ozonabnahme.

All over the world a remarkable increase in malignant tumors of the skin is reported. More than 90% of them are localized in areas of the skin exposed to sunlight. The incidence of malignant melanomas of the skin is tenfold higher today than 40 years ago. Experimental data and results of epidemiological studies indicate two different risk patterns of UV exposure for the development of skin cancer. The cumulative UV-light exposure during lifetime induces--especially in light-sensitive individuals older than 60 years--actinic elastosis, precanceroses and squamous cell carcinomas as well as lentigo maligna melanomas. Intense UV exposure in childhood and youth may lead to development of superficial spreading melanomas and nodular melanomas between the age of 20 and 40. The reduction of ozone in the stratosphere could still contribute to a higher incidence of tumors of the skin in the next decades. The evident role of UVB light in the induction of tumors of the skin offers the possibility for preventive strategies.

Complement deposits in epidermal cells after ultraviolet B exposure.

Ultraviolet B (UVB) radiation is known to induce formation of sunburn cells (SBC) in the epidermis. Since it was unknown whether this process might be accompanied by complement (C) activation, we analyzed C-deposition in skin biopsies taken before and 24 h and 48 h after UVB exposure (fourfold minimal erythema dose or fourfold minimal phototoxic dose) from 14 patients (5 receiving potentially photosensitizing drugs and 9 without such medication) by immunohistology. Local C-activation was visualized by direct or indirect immunofluorescence staining with polyclonal antibodies against C3b, C3d, C5, C9 and monoclonal antibodies to C3b, C3d, C9 and neoantigens on the terminal complement complex (TCC). Neutrophils were identified immunohistologically by antibodies to polymorphonuclear elastase. All but one specimen taken before UVB irradiation were completely negative; biopsies obtained 24 h after UVB revealed complement C3b- and/or C3d-deposits within scattered cells of the epidermis, with wide individual variations in the number of C3-positive cells. C3b and TCC were found predominantly in the cytoplasma; C3d deposits were more often accentuated at the cell surface of C-positive cells. A significantly higher number of keratinocytes was C3d-positive 48 h after UVB exposure than in specimens taken 24 h after UVB. Such a reactivity pattern might indicate a rapid decay of intracellular C3b to C3d. Patients medicated with potentially photosensitizing drugs developed significantly higher numbers of strongly C3-positive cells than those without such medication. Infiltration with elastase-positive cells, presumably representing neutrophils, was observed in the upper third of the dermis and the epidermis in all but one biopsy (n = 9) after UVB.(ABSTRACT TRUNCATED AT 250 WORDS)

Phototoxic erythema following PUVA treatment: independence of complement.

The effect of PUVA treatment on normal human serum (NHS), on isolated PMN, or on C3-deficient guinea pigs and congenic (C3-competent) control animals was tested. At a concentration of 0.1 or 1 mM/l 8-MOP and UVA doses of 5-30 J/cm2, PUVA failed to induce any detectable C3-cleavage in NHS. Furthermore, when the complement (C) activation in NHS had been induced before or after PUVA treatment by various methods. PUVA did not modulate the extent of C3-cleavage. PUVA did not affect the viability of isolated PMN, nor did it induce a release of LDH or elastase. No differences between C3-deficient and C-competent guinea pig skin exposed to PUVA were observed in erythema or histologic responses. Immunohistologic examination of specimens from normal guinea pigs revealed C3b and C3d deposits on necrotic keratinocytes, findings restricted to the PUVA-treated areas. Necrosis of keratinocytes was present in skin specimens of C3-deficient animals from PUVA-treated sites to a similar extent. However, deposits of C3-related antigens were completely absent there. From these observations, we suggest that the induction of phototoxic erythema following PUVA treatment is independent of complement.

[Complement-independent bulla formation in pemphigus vulgaris by IgG4]. / Komplement-unabhängige Blasenbildung bei Pemphigus vulgaris durch IgG4.

In cryostat sections from lesional skin of a patient with pemphigus, a typical pattern of IgG deposits was detected at the epidermal intercellular space. However, there were no deposits of complement (C) components. By the highly sensitive APAAP technique using monoclonal antibodies, it was demonstrated that the IgG deposits consisted exclusively of IgG4. IgG subclass analysis of serum autoantibodies against epidermal intercellular substance antigen revealed an identical subclass restriction to IgG4. The IgG4 portion of the serum IgG fraction was significantly increased. Since IgG4 is known to be a an almost ineffective activator of complement, the lack of deposits of C components is not surprising. Our ex vivo observations suggest that complement is not essential for the induction of pemphigus acantholysis.