cholecalciferol and Rosacea

The production of cathelicidin, an antimicrobial peptide is strongly increased in rosacea. Cathelicidin activates innate immunity, inflammation and angiogenesis. Cutaneous proteases produce inflammatory fragments of cathelicidin. UV-B irradiation and microbial components increase vitamin D3 and TLR2 expression in keratinocytes leading to an increase of cathelicidin production. Retinoids and doxycycline inhibit inflammation, proteases, angiogenesis and TLR2 expression. A multicenter study 2010 proved that isotretinoin with a dose of 0,3 mg/kg/d for 12 weeks and doxycycline with the dose of 100 mg/d for 14 days followed with 50 mg/d were equally effective. Doxycycline 40 mg/d is also effective in milder cases.

Topics: Anti-Bacterial Agents; Antimicrobial Cationic Peptides; Cathelicidins; Cholecalciferol; Dermatologic Agents; Doxycycline; Humans; Isotretinoin; Keratinocytes; Multicenter Studies as Topic; Rosacea; Toll-Like Receptor 2; Ultraviolet Rays

Our skin is constantly challenged by microbes but is rarely infected. Cutaneous production of antimicrobial peptides (AMPs) is a primary system for protection, and expression of some AMPs further increases in response to microbial invasion. Cathelicidins are unique AMPs that protect the skin through 2 distinct pathways: (1) direct antimicrobial activity and (2) initiation of a host response resulting in cytokine release, inflammation, angiogenesis, and reepithelialization. Cathelicidin dysfunction emerges as a central factor in the pathogenesis of several cutaneous diseases, including atopic dermatitis, in which cathelicidin is suppressed; rosacea, in which cathelicidin peptides are abnormally processed to forms that induce inflammation; and psoriasis, in which cathelicidin peptide converts self-DNA to a potent stimulus in an autoinflammatory cascade. Recent work identified vitamin D3 as a major factor involved in the regulation of cathelicidin. Therapies targeting control of cathelicidin and other AMPs might provide new approaches in the management of infectious and inflammatory skin diseases.

Topics: Animals; Bacteria; Cathelicidins; Cholecalciferol; Dermatitis, Atopic; Humans; Psoriasis; Rosacea; Skin; Skin Diseases

The pathogenesis of rosacea - a common, chronic inflammatory skin disease mainly affecting the central portions of the face - is only partly understood. In affected skin the expression of cathelicidin - an antimicrobial peptide and effector of innate immunity - is strongly increased. In addition, the activity of cutaneous proteases is greatly increased leading to the generation of cathelicidin peptide fragments with pro-inflammatory activity. UV irradiation and microbial factors contribute to this inflammatory cascade by increasing vitamin D(3) metabolism and the activation of toll-like receptors (TLR). Retinoids, azelaic acid and doxycycline inhibit both skin proteases and TLR expression and could mediate their anti-inflammatory effects in rosacea through these mechanisms. These data increase our understanding of the pathogenesis and therapy of rosacea. Also, these insights might uncover novel targets for innovative therapies of this common, stigmatizing skin disease.

Topics: Antimicrobial Cationic Peptides; Cholecalciferol; Cytokines; Humans; Models, Biological; Peptide Hydrolases; Rosacea; Skin

Rosacea is a common, chronic, cutaneous disorder presenting with recurrent episodes of facial flushing, erythema, papules, pustules and telangiectasias. It is a multifactorial disease and its various clinical presentations probably represent the consequence of combined different triggers upon a specific background. Its management is largely based on long-established treatments empirically tailored to the specific presenting symptoms and no real breakthrough has occurred to date. However, recent insights into the still rather obscure pathophysiology of rosacea seem to open the way for etiologically oriented treatments. These may include, on the one side, the more effective application of traditional drugs, such as tetracyclines and metronidazole, to specifically selected patients or, on the other side, new therapeutic options, such as vitamin D receptor antagonists. It is to be remarked that the quality of most studies evaluating rosacea treatment is rather poor, mainly due to a lack of proper standardization. For a major breakthrough to occur in the management of rosacea, we need both a better understanding of its pathogenesis and the adherence of future clinical trials to clearly defined grading and inclusion criteria, which are crucial for investigators to correctly compare and interpret the results of their work.

Topics: Adrenergic alpha-Agonists; Anti-Bacterial Agents; Anti-Inflammatory Agents; Antimicrobial Cationic Peptides; Bacillus; Blind Loop Syndrome; Cathelicidins; Cholecalciferol; Gastrointestinal Tract; Helicobacter Infections; Helicobacter pylori; Humans; Mite Infestations; Permethrin; Phototherapy; Rosacea; Skin