> oily skin, epidermal surface lipids. How they influence and influenced by acne

Investigation of causes of acne reveals involvement of three major pathologic factors. Androgens, hypersecretion of sebaceous glands and Propionobacterium Acnes, the bacteria implicated in acne lesions. In the following page each of these factors are further investigated. Acne is a complex, multi factorial disease whose pathogenesis proceeds according to the following scenario:

1. Hypertrophy of sebaceous glands, located deep within the dermis with nonuniform size, is due to increase in total androgens. DHT, dihydrotestosterone is the type of androgen implicated in this process and its presence suggest local presence of 5alpha reductase, the enzyme which converts testosterone to DHT. Sebaceous glands hypertrophy results in oversecretion of the sebum. What is sebum? Sebum is the substance secreted by sebaceous glands and contains mainly triglycerides, squalene and different esters. Formation of sebum is the result of destruction of fat cells in the sebaceous glands. Even though sebum is the major contributor of skin lipids, not all skin lipids are from sebaceous glands. Skin epidermis is also responsible for some of the surface lipids. Cholesterol and triglycerides have origin from sebaceous glands and epidermis while wax esters and squalene coming from sebaceous glands only.

2. Lipases derived from bacteria which are always available on the skin break down triglycerides ( sources of triglycerides are sebum and skin epidermis ) to free fatty acids and glycerols. These substances are also chemotactic and responsible for inflammation. Prolongation of inflammatory process is also involved in dearrangement of collagen bundles and resultant acne scar. A scenario which is more cumbersome to handle and treat.

Another research hypothetizes role of toll receptros in pathogenesis of acne. Finding TLR2 (Toll-like receptors) positive macrophages in acne leions suggests mediation of inflammatory response by Toll-like receptors. These receptors are activated by propionobacterium acnes by which inflammation is elicited. These receptors could be targeted for an appropriate treatment intervention. One study by university of Pensilvania indicates that a new retinoid, adapalene, mediates its effect by inhibiting inflammatory response in acne.

3. These substances (triglycerides and glycerols) induce keratinization in sebaceous follicles resulting in closure of the these ducts. Duct obstruction is due to hyperplasia in epithelial cells lining the sebaceous follicles, which conduct the sebum from sebaceous glands to the surface of the skin. In comedones , precursor of acne, change in lipid compositions and an increase in fatty acids which tend to be more solid at skin temperature have been proposed as cause of sebaceous follicle obstruction. Temporary relief of acne lesions when exposed to sunlights and also effect of UV light in treatment of acne may work through the same mechanism, that is prevention of solidification of fatty acids.

4. This irritating process (free fatty acid spillage to the dermis) to the sebaceous follicle is associated with migration of inflammatory factors. Finally the follicles rupture and inflammation pursues. This process leads to papules and in severe cases cyst formation.

As you can tell from the above scenario the major contributing factors in formation of acne are an increase in sebum production by androgens, bacterial colonization and fatty acid formation resulting in duct obstruction, and finally addition of inflammation. One can assume that most treatments may target one or several of the above mentioned factors. Indeed most therapeutic modalities work by one of these mechanisms. Isotretinoin works by inducing atrophy of sebaceous glands. Antiandrgoens such as cyproterone acetate still used for acne treatment and is shown to be effective. Anti androgens are particularly used in polycystic ovary disease as excess androgens causes acne and hirsutism. Antibiotics such as tetracycline, clindamycin reduce bacterial colonization and rendered as effective when used in combination with keratolytic agents. Linoleic acid and squalene also may be indicated in treatment of acne lesions as their quantity is less in acne subjects. Increase in sebaceous glands activity is associated with change in fatty acid composition of sebum. This increase in activity is accounted for decrease in linoleic and linolenic acid in sebum composition of acne patients.

One study suggests that free fatty acids (FFA) such as lauric acid, palmitic acid can induce human beta defensin-2 and enhance innate immunity against propionbacterium acne. According to this study FFA upregualte HBD-2 and show an antibacterial activity against gram positive. FFAs comprise 5-40% of sebum composition. Most common free fatty acid of the sebum is sapienic acid(C16). Its anti bacterial effect against MRSA methicilin resistant staph aureus renders this FFA a potential vehicle in treatment of acne. Increase in free fatty acids concurrent with hypersecretion of sebaceous glands is still viewed with skepticism. It seems that overfunctional sebaceous glands produce more cholestrol and cholestrol esters than FFA, essential fatty acids and squalene which results in a change in sebum composition in acne subjects.

Which skins are more likely to be presented with acne? Large pores are commonly associated with acne lesions. This type of skin tends to have more secretions, what is frequently called oily skin. As discussed above, sebaceous glands are under control of androgens and surge of androgens at puberty is concurrent with more skin secretions and presentation of acne lesions. Whether cause of large pores is adaptation of the skin to excess of its secretions or is determined by genetic factors calls for more research. However, combination of both mechanisms seem to be a plausible explanation for formation of large pores. Very dry skin is very much less develops acne. Dry skin pores are almost always very small to invisible.

| American Academy of Dermatology | Dermatology Online Journal | Sebaceous Glands | Dermatology Health Guide | Sebaceous follicle Carcinoma | Pathogenesis of Acne Vulgaris | Sebaceous Gland Function | Retinoids and Sebaceous Glands Activity | Pathophysiology of Acne | Macrolids for Acne |

Anatomy of sebaceous glands: Sebaceous glands are epidermal appendages located within the dermis layer and their ducts are opened into sebaceous follicles by which root of hair is surrounded. Sebaceous follicles are opened into the surface of the skin along with a hair follicle. Their secretions are to moisturize the skin and hair and their abundance is more in the face, shoulders, arms, chest and back. Sebaceous glands are under control of androgens as well as neuropeptides such as substance P. Substance P is involved in proliferation and sebaceous glands. Acne patients show more number of substance P receptors on their sebaceous glands. Some hypothesize that basal epidermal cells can differentiate into sebaceous glands under influence of androgens. Direct innervations of these glands is still under investigation and various data indicate presence of nerve endings in surrounding connective tissue.

Under influence of androgens sebaceous glands show increase in size and number of lobules. However increase in sebum production is not seen in all glands of this type. Hyper responsiveness of sebaceous glands to androgens seem to be responsible for over secretion of sebum in hyper functioning glands.