Rosacea as a Disease of Cathelicidins and Skin Innate Immunity

Department of Dermatology, Graduate School of Medicine, Tohoku University, Sendai, Miyagi, Japan.
Journal of Investigative Dermatology Symposium Proceedings (Impact Factor: 3.73). 12/2011; 15(1):12-5. DOI: 10.1038/jidsymp.2011.4
Source: PubMed

ABSTRACT Rosacea is a common and chronic inflammatory skin disease most frequently seen in groups of genetically related individuals. Although the symptoms of rosacea are heterogeneous, they are all related by the presence of characteristic facial or ocular inflammation involving both the vascular and tissue stroma. Until recently, the pathophysiology of this disease was limited to descriptions of a wide variety of factors that exacerbate or improve disease. Recent molecular studies show a common link between the triggers of rosacea and the cellular response, and these observations suggest that an altered innate immune response is involved in disease pathogenesis. Understanding rosacea as a disorder of innate immunity explains the benefits of current treatments and suggests new therapeutic strategies for alleviating this disease.

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    • "Recent findings strongly indicate an important role of antimicrobial peptides and proteases as ''alarmins'' (mediators activated in the skin at an early stage of tissue injury) and are thereby part of the innate immune system. Upon activation by trigger factors, they can respond to ''danger'' molecules that may impair epidermal homeostasis (reviewed by Meyer-Hoffert and Schröder, 2011; Yamasaki and Gallo, 2011). As peripheral nerves are also part of the defense system in the epidermal skin barrier, the relationship among nerves, antimicrobial peptides, and proteases needs to be further deciphered (Figure 5 and 6; Schwab et al., 2011). "
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    ABSTRACT: Rosacea is a chronic inflammatory skin disease of unknown etiology. Although described centuries ago, the pathophysiology of this disease is still poorly understood. Epidemiological studies indicate a genetic component, but a rosacea gene has not been identified yet. Four subtypes and several variants of rosacea have been described. It is still unclear whether these subtypes represent a "developmental march" of different stages or are merely part of a syndrome that develops independently but overlaps clinically. Clinical and histopathological characteristics of rosacea make it a fascinating "human disease model" for learning about the connection between the cutaneous vascular, nervous, and immune systems. Innate immune mechanisms and dysregulation of the neurovascular system are involved in rosacea initiation and perpetuation, although the complex network of primary induction and secondary reaction of neuroimmune communication is still unclear. Later, rosacea may result in fibrotic facial changes, suggesting a strong connection between chronic inflammatory processes and skin fibrosis development. This review highlights recent molecular (gene array) and cellular findings and aims to integrate the different body defense mechanisms into a modern concept of rosacea pathophysiology.
    Journal of Investigative Dermatology Symposium Proceedings 12/2011; 15(1):2-11. DOI:10.1038/jidsymp.2011.7 · 3.73 Impact Factor
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    ABSTRACT: Rosacea is a common inflammatory facial dermatoses affecting primarily adults with fair skin, although all skin types may be affected. The diagnostic term "rosacea" reflects a spectrum of clinical features with the more common presentations characterized by increased blood flow and vasodilation during disease flares, which accentuate central facial erythema. Inflammatory lesions, usually papules and/or pustules are present in some cases. Variations in magnitude of the associated features of rosacea are noted clinically. Over time, other clinical features emerge or may be further accentuated, such as diffuse facial erythema and telangiectasias, as fixed changes in cutaneous vasculature occur. These later findings account for persistent diffuse facial erythema usually accentuated centrally on the inner cheeks, chin, nose, and/or medial forehead. Some patients may also develop phymatous changes and/or have concurrent ocular rosacea. Augmented innate immune response to certain triggers (often exogenous) and neurovascular/neuroimmune dysregulation appear to be involved early in the pathophysiological sequence of cutaneous rosacea and appear to signal other downstream inflammatory or physiochemical cascades that contribute to the pathogenesis of the disorder. In this article, Part 1 of a two-part series, emphasis is placed upon the correlation of clinical features and underlying pathophysiological changes in the more common presentations of rosacea encountered by the clinician. The importance of this information is that some of these pathogenic mechanisms are modulated by available therapies, and others remain as targets for the development of new therapeutic agents or modalities.
    Journal of Clinical and Aesthetic Dermatology 03/2012; 5(3):16-25.
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    ABSTRACT: In this article, the second part of a two-part series on rosacea, emphasis will be placed on persistent facial erythema. Despite variations in the intensity of visible redness, persistent facial erythema is a very common and consistent finding among patients with rosacea, including those with presentations classically defined as papulopustular rosacea, erythematotelangiectatic rosacea, and in many patients with phymatous rosacea. The underlying mechanisms of rosacea and their correlation with specific clinical features have been discussed in Part 1 and are referred to here where applicable. An overview of cutaneous vasculature, role of alpha-adrenoreceptors, and a discussion of available medical therapies and treatment selection are also presented, including emerging topical options for diffuse and persistent facial erythema of rosacea.
    Journal of Clinical and Aesthetic Dermatology 03/2012; 5(3):26-36.
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