Abstract and Introduction
BackgroundPatients with papulopustular rosacea (PPR) frequently complain of dry, sensitive skin. We have previously demonstrated that patients with PPR have reduced skin surface hydration levels in the presence of normal sebum casual levels, suggesting that it may be the quality and not the quantity of sebum that plays a role in PPR.
Objectives To compare the sebaceous fatty acid composition of patients with PPR to that of controls with normal facial skin.
Methods The sebaceous fatty acid composition of 25 patients with PPR and 24 age- and sex-matched controls was analysed by gas chromatography - mass spectrometry.
Results Myristic acid (C14:0) was present in greater concentrations in PPR sebum, while the long chain saturated fatty acids arachidic acid (C20:0), behenic acid (C22:0), tricosanoic acid (C23:0) and lignoceric acid (C24:0) as well as the monounsaturated fatty acid cis-11-eicosanoic acid (C20:1) were present in the sebum of patients with PPR in lesser concentrations as compared with controls.
Conclusions There is increasing evidence that sebaceous fatty acids play a role in the maintenance of skin barrier integrity. We have shown for the first time that patients with PPR have an abnormal sebaceous fatty acid composition, with reduced levels of long chain saturated fatty acids. These new findings may have therapeutic implications for the development of sebum-modifying nonantibiotic treatments for patients with PPR.
The role of sebum in the pathogenesis of rosacea is unknown. The composition of sebaceous lipids in rosacea was studied in 1976 and no difference was found between the sebum of patients with rosacea as compared with controls. The authors concluded that rosacea was not primarily a disorder of the pilosebaceous apparatus.
Since then rosacea has been classified into different subtypes. The possible role of sebum in the pathogenesis of subtype 2 or papulopustular rosacea (PPR) has been suggested by certain observations.
Firstly, the erythema, papules and pustules of PPR have a centrofacial distribution, paralleling the density of the sebaceous follicles of facial skin. PPR tends to spare the periocular skin but there is involvement of the lid margins, which contain modified sebaceous glands – meibomian glands. Two-thirds of patients with primary meibomianitis have associated rosacea. Minocycline (a treatment used for cutaneous and ocular rosacea) has been shown to alter the meibomian lipid composition in rosacea meibomianitis.
Secondly, perifollicular inflammation (consisting mainly of T lymphocytes) is a significant histological feature of PPR.[6–9]
Thirdly, oral retinoids – which are sebaceous gland-modifying agents – have been shown to reduce erythema and papulopustules in patients with rosacea. The diminution of sebaceous gland size and decreased sebum production in patients with rosacea treated with 13-cis retinoic acid led the authors of another study to conclude that sebaceous gland dysfunction may play a role in the pathogenesis of rosacea.
Fourthly, the composition of sebum is influenced by commensal microorganisms inhabiting the pilosebaceous apparatus such as Malassezia yeast and Propionibacterium acnes, which release free fatty acids from sebaceous triglycerides. It is possible that the sebaceous profile may in turn affect the proliferation of specific microorganisms. The Demodex mite, which lives in the pilosebaceous follicle of the face, has been shown to be present in increased numbers in patients with rosacea. The sebaceous microenvironment may play a role in facilitating this association.
Finally, patients with rosacea often report symptoms such as dryness, stinging and burning of the facial skin. Epidermal barrier dysfunction, characterized by increased transepidermal water loss, has been shown to be present in PPR. Another measure of skin barrier function, a skin irritation test, was reactive in 68% of patients with PPR compared with 19% of controls. Sebum is recognized as an important contributor to skin barrier integrity, and an abnormality of sebum may result in the signs and symptoms outlined above.
Sebaceous lipids have both pro- and anti-inflammatory properties. Sebum plays an important role in the innate defence system of the skin, which has been shown to be altered in patients with rosacea. Sebocytes express antimicrobial peptides (AMPs) such as cathelicidin and human β-defensin-2, as well as proinflammatory cytokines/chemokines which are upregulated in the presence of bacteria. The free fatty acid components of sebum, along with AMPs, form part of the innate immune defence of the skin surface against microbial colonization and infection. Sapienic acid, lauric acid, palmitoleic acid and oleic acid have all been demonstrated to have direct bactericidal activity. In addition, lauric acid, palmitoleic acid and oleic acid have been shown to enhance the skin's innate antibacterial defence by inducing the expression of human β-defensin-2 in sebocytes.
In light of these factors, and because the sebum of patients with rosacea has not been studied for over 30 years, we examined the sebaceous lipid fatty acid composition and enzyme activity of the sebum of patients with PPR. In addition, we examined the effects of minocycline – a common treatment for this type of rosacea – on the fatty acid profile of sebum from patients with PPR.
The British Journal of Dermatology. 2012;166(2):279-287. © 2012 Blackwell Publishing