The specific gravity of sebum given by Butcher and Coonin (19) from the forehead sebum of normal individuals was 0.911 + 0.01 g/cm3 for all samples. Burton (16) confirmed this for three normal subjects when scalp sebum was used.
The surface tension (Table 4) at temperatures varying from 26.58C to 318C was found to be an average of 24.89 dynes/cm for forehead sebum of normal subjects. A very close value (22.9 + 0.9 – 24.2 + 1.1) was also obtained for scalp sebum of normal and acne patients.
The viscosity increased from 0.55 to 0.98 poise, as temperature decreased from 388C to 28.58C. The sebum separated into various components when the temperature was lowered from 298C to 308C and ceased to flow at 158C to 178C (19). Burton (16) reported a viscosity of 0.32 + 0.03 poise at 358C, 0.82 + 0.22 poise at 258C, and 1.71 + 0.70 poise at 208C. In addition, it was found that the viscosity of scalp sebum and forehead sebum was similar in normal individuals. Burton also reported that the mean viscosity of the sebum from 10 acne patients taking tetra- cycline was higher than with seven patients not taking tetracycline at 358C.
IMPORTANCE OF SEBUM TO THE PATHOGENESIS OF ACNE
The role of sebum in acnegenesis is poorly understood. Acne vulgaris, a multifac- torial disease of the skin, is found in areas rich in sebaceous follicles. It is character- ized by seborrhea, disturbed keratinization in the follicles with comedones, and subsequent inflammatory papules, pustules and nodular abscesses, and scars (15). The pathology of acne is described in various other chapters in this book but a brief review here sets the stage for relevance of the studies of sebum described later in this chapter. There are three essential factors as a group that may cause acne.
1. There is an increase in androgen production in puberty, which induces enlarge- ment of sebaceous follicles and increased sebum production (21).
2. Follicular hyperkeratinization leads to retention hyperkeratosis, that is, obstruc- tion of the pilosebaceous duct by accumulation of an excessive amount of keratin as an important factor in the pathogenesis of acne (22).
3. P. acnes proliferate in the follicle, producing a variety of extracellular inflamma- tory products, which excite an inflammatory response (23).
The primary event in acne is faulty keratinization and the production of come- dones. In the secondary stage, inflammation can occur in the comedones. Two pathways define the subsequent development of the lesions of acne. In the nonin- flammatory pathway, the microcomedo proceeds to mature into closed and open comedones through distention of the follicle wall and lumen. In the inflammatory pathway, the extracellular products of P. acnes incite inflammation. P. acnes
colonization occurs relatively early in acne, and the production of extracellular pro- ducts by this organism provides multiple potential mechanisms for the develop- ment of inflammation. Among the earliest findings, drugs that reduce fatty acids (FFA), such as tetracycline, are beneficial in inflammatory acne (24). It must be noted that skin surface-derived lipids produce an inflammatory papule or nodule when they are injected into the human skin (25). Furthermore, certain fractions of the sebaceous secretion, especially fatty acids and squalene, when applied to rabbits’ ears promoted follicular hyperkeratosis and comedone formation (26 – 28).
In the absence of comedones, the large infundibulum channels are filled with the white pasty sebaceous material. It is the normal content of a sebaceous follicle, not of an acne lesion. Sometimes, the follicles are filled with a cocoon-type skeleton of corneocytes, having 20 to 40 cells surrounding the central fine hair, with a channel left free in the sebum of which P. acnes and staphylococci may be found (15). This is called a follicular filament or follicular cast. A comedo can arise from a follicular filament. It is believed that the lipid composition of the follicular casts may play a role in acne genesis. It was demonstrated by Nordstrom et al. (7) that about 29% of the net weight of follicular casts was lipid. In addition, the hydrolysis of the triglycerides in the follicular casts was much higher than on the skin surface.
The differences in the rate of sebum production in acne patients and normal controls have so far been the only consistent finding that links sebum secretion to acnegenesis (4,7). It has long been thought that acne is a result of an abnormality of sebum or sebaceous gland function. Yet, the current concept of follicular kerati- nization in the pathogenesis of the disease makes this relationship difficult to justify. However, four major reasons based on circumstantial but compelling evidence that link sebum to acne include:
1. Acne develops at puberty, when sebaceous glands become very active (29).
2. The rate of sebum secretion is generally higher in acne subjects than in normal individuals, though not all persons having high sebum secretion suffer from acne (30).
3. Some components of sebum are irritants and can be comedogenic in inflamma- tory acne.
4. Acne is improved by any modality that reduces sebaceous gland activity (31).
This indicates that sebum is probably an essential factor in the pathogenesis of acne, but not necessarily the only one.
It is possible that the changes in the horny layer could be the result of an alteration of the nature of the sebum, so that it causes keratinization of the duct and leads to comedone formation. The macromolecular structure of the sebum could change to a more crystalline state that forms a blockage and impedes its own flow through the sebaceous duct and infundibulum or alternatively cause irri- tation to the follicular epidermal lining. Gonzalez-Serva (32) and Abramovits and Gonzalez-Serva (33) have speculated that acne involves the build up of an intra- ductal calculus termed sebolith, which results from crystallization of sebum. They proposed that the sebolith punctures and erodes the follicular lining, leading to rupture and inflammation. The proliferation of bacteria could be the result of a change in sebum composition or structure, so that either it provides a richer, more bioavailable medium for bacterial growth or it no longer contains inhibitory factors. In such a manner, sebum can be involved. The authors believe that the characterization of the lipids of the sebaceous follicles and their physical
behavior may provide more detailed information on the possible role of sebum in acne vulgaris.
Electron microscopy studies on comedones showed the presence of yeasts, bacteria, keratinized cells, sebum, and hairs. In these comedones, sebum was a ubi- quitous component and appeared as an osmiophilic granular material, which varied in amount from scanty to abundant between the keratinized cells (34). Depressions between the microridges of the keratinized cells had the greatest pro- pensity for sebum. Many yeast and bacteria occupied these sebum-rich areas and their surfaces were covered with fatty material.
The composition of the lipid components of comedones was also examined by Nicolaides et al. (13) and compared with the skin surface lipids. Chapter 3 by Dr. Wertz covers this in more detail, but findings relative to the purposes of this chapter are summarized here. The lipids in comedones contain all the same lipid classes as sebum, but some are in different proportions. Triglycerides represent only a small portion of the comedonal lipids (7%) and fatty acids represent 55% of the lipids. Wax esters are only 14% of the lipids compared with 24% in surface sebum. Free cholesterol is also much higher in comedonal lipids. Another notable difference is a larger amount of saturated fatty acids in comedonal lipids—about
70% of the comedonal FFA are saturated compared with only 65% of the surface sebum. The differences between comedonal and surface lipid reflect the contri- bution of epidermal lipids to the mix. Epidermal lipids do not contain any wax esters, and cholesterol is derived from epidermal lipid. Epidermal lipids also provide saturated fatty acids to the mix. The reduced amounts of triglycerides are due to nearly complete bacterial hydrolysis of this class to FFA.
Since sebum is a mixture of the different lipid components discussed earlier, it is important to understand how each component affects the macromolecular struc- ture and the physical – chemical behavior of sebum, and how this is altered in dis- eases of the pilosebaceous unit, for example, acne. It is, therefore, useful to know how variations in the components, for example, concentration and ratio of different components, their carbon chain length, and the ratios of unsaturation to saturation, affect the macromolecular structure of sebum and how this relates to the compo- sition of sebum in acne lesions in particular comedones. The ultimate goal is to determine how this composition can be altered in the skin of acne patients to correct the defects in the infundibulum and the sebaceous duct, and to facilitate penetration of anti-acne drugs into the pilosebaceous unit.