A study of the pathogenesis of Rosacea: how angiogenesis and mast cells may participate in a complex multifactorial process

Abstract

In the present study we evaluated, in involved and clinically uninvolved skin of Rosacea, microvessels density (MVD) and total vascular area (TVA) in addition to multiple morphologic characteristics of microvessels and also mast cells (MCs) number. We examined also the relationship between angiogenesis, MCs number and disease clinicopathological data. The study included 69 patients with Rosacea. A skin biopsy with a 4-mm punch was performed from clinically involved skin in each case. In nine randomly selected patients, facial biopsy specimens were obtained from both involved and clinically uninvolved skin. Histological sections, immunostained for factor VIII, were evaluated by image analysis for the quantification of MVD, TVA and several morphometric parameters related to the vessel size or shape. MCs detection in the dermis was carried out using the chloracetate esterase method (Fast Blue RR) in parafin sections. Serum antibodies against H.pylori were detected. Statistically important differences concerning the factors of angiogenesis between lesional and clinically non-lesional skin were demonstrated. A statistical important correlation was found also between high vascular density, PPR clinical type and the presence of ocular manifestations. MVD or TVA showed no correlation with the degree of solar elastosis or inflammation and with the Demodex density as well. However, high MVD values were found to correlate with granuloma formation in the dermis. MCs number were significantly greater in lesional compared to clinically non-lesional skin. Statistical significance was shown between MCs density and disease duration. However, no correlation between MCs number and blood vessel density was found. Angiogenesis seems to play an important role in the pathogenesis especially of the more severe clinical form of Rosacea. MCs seem to participate in evolution to disease chronicity by contributing to inflammation, angiogenesis and tissue fibrosis.

Four Polymorphisms ofVEGF(+405C>G, −460T>C, −2578C>A, and −1154G>A) in Susceptibility to Psoriasis: A Meta-Analysis

“…A sustained increase in new blood vessel formation, known as cutaneous angiogenesis, can be seen in cutaneous disease, including primary and metastatic cutaneous malignant melanoma (Hubler and Wolf, 1976;Marcoval et al, 1997), rosacea (Aroni et al, 2008), and psoriasis (Creamer and Barker, 1995). Evidence from clinical trials suggests that VEGF, as a key cytokine in skin inflammation, is a main angiogenic mediator in psoriasis (Detmar et al, 1994;Kunstfeld et al, 2004).…”

Tetracycline Actions Relevant to Rosacea Treatment

“…In patients with rosacea, significantly increased dermal expression of the potent angiogenesis factor vascular endothelial growth factor in lesional versus nonlesional skin (88.9 vs. 55.6%, respectively) was observed. Furthermore, more microvessels were observed in lesional compared to clinically nonlesional skin, and a high microvessel density was found to be correlated with granuloma formation in the skin [19] . There was also a correlation between high vascular density and the presence of ocular manifestations [19] .…”

“…Furthermore, more microvessels were observed in lesional compared to clinically nonlesional skin, and a high microvessel density was found to be correlated with granuloma formation in the skin [19] . There was also a correlation between high vascular density and the presence of ocular manifestations [19] .…”

“…Angiogenesis seems to be involved in the pathogenesis of rosacea [19,86] and to be linked to MMP activity [36] . In patients with rosacea, significantly increased dermal expression of the potent angiogenesis factor vascular endothelial growth factor in lesional versus nonlesional skin (88.9 vs. 55.6%, respectively) was observed.…”

Current Drug Therapies for Rosacea: A Chronic Vascular and Inflammatory Skin Disease

“…Mast cells may participate in a complex multifactorial process to promote localized vasodilation, angiogenesis, and tissue fibrosis. 33 Flushing may involve the nervous system, since symptoms of rosacea are triggered when patients are under emotional stress. [34][35][36] One active form of cathelicidin found in rosacea is LL-37.…”