There are four major causative factors involved in development of acne:
(1) Seborrhea (excess production of sebum)
(2) Comedogenesis (comedo formation due to hyper-cornification of pilosebaseous glands).
(3) Colonization of pilosebaceous duct with P. acnes (Propionibacterium acnes).
(4) The production of inflammation.
We will discus the first cause i.e. Seborrhea.
Patients with excess sebum production complain of greasy skin (seborrhea). For development of acne active functional sebaceous glands are required. Acne patients male or female on an average secrete more sebum than normal person and there is strong correlation between acne severity and sebum secretion. Normal person secrete about 0.7µg of sebum per square centimeter per minute. Patient with mild acne secrete about 1.2µg, moderate patients secrete about 1.5µg and severe acne patient secrete more than 1.8µg/cm2/minute. Sebaceous activity is dependent on androgenic sex hormone of gonadal or adrenal origin. So, high levels of sebum may be due to high androgen production, increase availability of free androgen due to less sex hormone binding globulin (SHBG) and increased capacity of the intracellular receptor to bind androgen.
Plasma testosterone (male sex hormone) levels are not high in males with acne. But in females there may be high or low testosterone level. But most studies have shown that SHBG are below normal, consequently free testosterone level is above normal. In many studies it is found that patients with acne some have high testosterone level. Some of them have low SHBG, some of the patients have high free testosterone level. Androgenic hormonal balance is disturbed to some degree in 50% to 75% of the patients with acne. But at least a quarter of the cases there is no hormonal imbalance. If acne is only related to systemic hormone levels, than acne should be present in back, face and chest. But it is seen only on face.
Sebum secretion varies from follicle to follicle. In acne patients the sebum is heterogeneous but in normal persons sebum is homogenous. From the above fact it is clear that some of the follicles are prone to acne. There is increased 5?-reduction of testosterone to its active metabolite 5? DTH, & this is supported by high 5?-reductase activity in acne prone regions and abnormally high amount of 5?-androstenidiols in the urine of female acne patients.
Androgen action on sebaceous gland may be independent of serum hormone levels. There are two forms of 5?-reductase, type I and type II. 5?-reduetase Type I is responsible for acne for two reasons. Firstly fenesteride which is an inhibitor of 5?-reductase Type II, do not reduce sebum production. Secondly, patients with deficiency of 5?-reductase II have normal sebum production. The above points prove that 5?-reduetase Type I is responsible for acne.
In clinical practice it not required to check for endocrinopathy (pathology of hormone producing glands) except for females with sudden severe acne which is not responding to conventional treatment.
Finally acne may be due to change in skin lipid composition irrespective of sebum secretion . Sebum consists of mixture of wax, cholesterol, squalene, sterol esters, triglycerides and polar lipids. As the sebum passes through pilosebaseous duct, bacteria mainly P. acne hydrolyze (break) triglycerides into Free Fatty Acids (FFA). The lipids may be responsible for ductal hyper-cornification or may be used by bacteria for growth. Samplings from acne patients have shown that they have higher levels of squalene and wax, lower levels of fatty acids and more common occurrence of particular free fatty acids. In acne patients linoleic acid (a free fatty acid) is reduced significantly in comedonal lipids and this may be related to hyper cornification of pilosebaseous duct.