Tetracycline Actions Relevant to Rosacea Treatment
Skin Pharmacology and Physiology
Pathophysiology of Rosacea Rosacea is a common chronic, often underdiagnosed, skin disease of uncertain etiology. The various clinical manifestations associated with this disease most frequently occur in the light-skinned Caucasian population, and in persons between 30 and 50 years of age [1, 2] . Until now the conventional wisdom has been that rosacea is more common in women than in men  , whereas a recent analysis based on a cross-sectional study of rosacea
... 00)(2001)(2002) in 50,235 outpatients indicates that overall both sexes are equally affected by the disease  . The dermatological condition of rosacea mainly affects the cheek, nose, chin and central forehead. Furthermore, the disease may be linked to ocular manifestations  . The earliest symptoms associated with rosacea are intermittent, central facial flushing and erythema. More than 90% of the patients with rosacea experience flushing with episodes lasting up to 30 min occurring daily in more than 60% of the affected individuals    . With repetitive cycles, flushing becomes more prominent and facial redness deepens, in the end repeated episodes of facial flushing may cause persistent erythema and telangiectasia  . Many patients suffer from a stinging pain associated with episodes of flushing which can appear unpredictably or in relation to environmental, chemical, food or emotional triggers, especially exposure to sun  . Abstract Until today, the pathogenesis of rosacea is not known in detail. Yet in recent years evidence has been accumulating that rosacea with its common symptoms such as inflammatory lesions, erythema, telangiectasia, phymatous changes, and ocular symptoms is of inflammatory nature. Tetracycline derivatives like doxycycline successfully used in the treatment of skin diseases like acne and rosacea seem to inhibit different inflammatory pathways involved in the pathogenesis by various modes of action. Although data for skin diseases are relatively scanty, the following modes of action of tetracyclines seem to be most relevant for an effective treatment of acne and rosacea: inhibition of matrix metalloproteinases, downmodulation of cytokines, inhibition of cell movement and proliferation, inhibition of granuloma formation, inhibition of reactive oxygen species, nitric oxide, and angiogenesis, whereas inhibition of phospholipase A2 seems to be of lower importance. The role of the saprophytic mite Demodex folliculorum remains to be clarified. Additional studies are necessary to further elucidate how tetracyclines work in rosacea treatment.