Chronic sun exposure causes photoaging of human skin, a process that is characterized by clinical, histological and biochemical changes which differ from alterations in chronologically aged but sun-protected skin. Within recent years, substantial progress has been made in unraveling the underlying mechanisms of photoaging. Induction of matrix metalloproteinases as a consequence of activator protein (AP)-1 and nuclear factor (NF)-kB activation as well as mutations of mitochondrial DNA have been identified recently.T he term photoaging describes distinct clinical, histological and functional features of chronically sunexposed skin. It has evolved from a variety of terms such as heliodermatosis, actinic dermatosis, and accelerated skin aging. Photoaged, chronically sun-exposed skin has characteristics in common with sun-protected, chronologically aged skin. However, there are features which are found exclusively in photoaged skin, making it an independent entity with its own pathophysiology.Extended life-span, more spare time and excessive exposure to ultraviolet (UV) radiation from natural sunlight or tanning devices, especially in the western population, has resulted in an ever increasing demand to protect human skin against the detrimental effects of UV-exposure of the skin to ultraviolet light. Therefore, photoaging will be of increasing concern in the future.The clinical and histological characteristics of photoaged skin have been known for some time (1); however, not until recently have the underlying molecular mechanisms responsible for the specific macro-and microAbbreviations: EGF, epidermal growth factor; ERK, extracellular signal-regulated kinase; GAG, glycosaminoglycans; JNK, c-Jun amino terminal kinase; mt, mitochondrial; MAP, mitogen-activated protein; MMP, matrix metalloproteinase; MED, minimal erythema dose; NF-kB, Nuclear factor kB; nm, nanometer; OXPHOS, oxidative phosphorylation; RA, retinoic acid; ROS, reactive oxygen species; TIMP, tissue specific inhibitor of matrix metalloproteinases. 239This has increased our understanding of photoaging significantly and has led to new prophylactic and therapeutic strategies aimed at the prevention and repair of the detrimental effects of chronic sun-exposure on the skin.Key words: antioxidants; mitochondrial DNA; photoaging; reactive oxygen species; repetitive sun exposure; retinoic acid; sunscreens; ultraviolet light.scopic alterations been discovered. The role of selected transcription factors (AP-1, NF-kB) in photoaging has been demonstrated and it has been found that mutations of mitochondrial DNA may also be involved. The elucidation of these pathophysiological mechanisms provides the basis for evaluating the efficacy of photo(aging)protective substances and might help in the development of new strategies which will provide protection and repair of photoaged human skin. Previous reviews on this topic have described the different aspects of photoaging (2 -4). Hence, this review will only briefly summarize the clinical and histological features of photoa...

Mutations of mitochondrial (mt) DNA such as the 4977 base-pair large-scale deletion, also called common deletion, are increased in photoaged skin. Direct evidence for their induction by chronic exposure to ultraviolet (UV) radiation in vivo in human skin has remained elusive however. Furthermore, their fate after induction is unclear. Previously unirradiated skin of 52 normal human individuals was repetitively exposed to physiological doses of UVA light. Skin and blood specimens were investigated for the presence of mtDNA mutations employing semiquantitative nested PCR, as well as real-time PCR, after 2 weeks of UV exposure and the content of the common deletion was followed up for up to 16 mo after cessation of irradiation. As assessed by both methods, repetitive UV exposure led to an approximately 40% increase in the levels of the common deletion in normal human skin. The majority of deletions were detectable in the dermis also showing the biggest increase, whereas in the epidermis only residual levels and no increase were found. Nine individuals were examined up to 16 mo after cessation of UV exposure and some showed accumulation up to 32-fold. Thus, mtDNA mutations are induced in the human skin by repetitive UV exposure. In addition, these mutations seem to represent long-term in-vivo biomarkers for actinic damage in the human skin.

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We report on two female patients who presented with painful recurrent palpable purpura, ulcers and necroses on the extremities. The results of all examinations and laboratory tests considered together suggested a diagnosis of necrotizing leukocytoclastic vasculitis. Leukocytoclastic vasculitis is an inflammatory necrotizing condition of the superficial dermal vessels, presenting with variable clinical symptoms. In most cases it becomes manifest as palpable purpura, but hemorrhagic-necrotizing, bullous, nodular and urticarial presentations also occur. Common etiological factors include bacterial, viral or drug antigens, chronic infections (hepatitis B and C), non-Hodgkin lymphomas (monoclonal gammopathy, multiple myeloma), leukemia (hairy cell leukemia), and tumors (bronchial, breast, and gastric cancer) and also connective tissue disorders. In the course of the work-up, a plasmocytoma was discovered as the cause of the leukocytoclastic vasculitis, presenting in a similar way to livedo reticularis in one case and to pyoderma gangraenosum in the other.