Human skin is covered in microscopic pilosebaceous units. The whole of acne centres around these units.
All skin areas, excluding the palms and soles, contain appendages called pilosebaceous units. The pilosebaceous unit is so named because it produces ‘pilus’ (hair) and an oily substance called sebum. It is comprised of a hair follicle, an arrector pili muscle and a sebaceous gland with its related sebaceous duct. Let’s now look at these components in detail since acne cannot be understood without a detailed knowledge of the structure of the pilosebaceous unit.
A hair follicle is a circular sheath of lining cells which surround the hair root (the living part of a hair). The hair root ends in an enlargement called the hair bulb which is attached to the bottom of the hair follicle. The remainder of the hair, which is dead, is called the hair shaft. The lining cells are keratinocytes, the same cells which make up the epidermis. These keratinocytes are continually shed off and replaced in the same fashion. As they undergo terminal differentiation, they normally follow a very strict and formal path towards the centre of the follicular canal.
The space within the hair follicle that the hair sits in is called the follicular canal and it leads up to the skin pores which are tiny openings to the skin surface for the sebaceous glands and hair follicle below, allowing sebum, which is produced by the gland, to escape and for hair to extend out. The obvious roles of the often overlooked follicular canal are to provide the physical space for the hair to grow within and for the delivery of sebum to the skin pore. There is another fundamental purpose which we must discuss in order to understand acne. Remember the hair follicle is made up of primarily keratinocytes just like the epidermis? Because of their position, which is due to the basement membrane being vertical rather than horizontal, they desquamate into the follicular canal where they mix with sebum. Suitably lubricated, they slide up to the skin surface in the space between the hair follicle and the hair shaft (if present). Acne occurs when this goes wrong, as we will see.
The hair follicle can be anatomically divided into three regions. The lower segment is called the inferior segment, the middle segment is called the isthmus and the upper segment is called the infundibulum. The lumens of these segments of the hair follicle collectively comprise the follicular canal. The lumen of the infundibulum and isthmus contains the hair shaft and the lumen of the hair bulb contains the hair root.
Within the inferior segment are the hair bulb and suprabulb. The suprabulb is below the isthmus and above the hair bulb. The suprabulb is comprised of three layers. These include the outer root sheath, the inner root sheath and the hair shaft. The follicular canal widens out here, making room for the hair bulb below. The internal root sheath is the innermost layer of the hair follicle, extending from the hair bulb, protecting hair up as far as the isthmus. The external root sheath, which is formed from the basal cell layer in the same way that the epidermis is, is the inner side of the hair follicle, facing into the follicular canal. It is made up of keratinocytes.
The hair bulb, which is where the hair grows from contains rapidly dividing cells which produce the outer root sheath and inner root sheath. Along with the dermal papilla (the protrusions from the top layer of the dermis called the papillary layer) it constitutes the root of the hair. As previously mentioned, the hair bulb is connected to the very bottom of the hair follicle. The papillae are important here as they bring hormone-rich blood supply to the hair bulb, stimulating hair growth and providing nutrients. The papillary layer of the dermis is below the hair follicle.
The isthmus, which marks the end of the internal root sheath and is where lining cells begin to desquamate, is the short segment of the hair follicle which extends from the attachment of the erector pili muscle to the entrance of the sebaceous duct, which is the tube which connects the sebaceous gland to the isthmus. The wall of the isthmus consists of two or three rows of corneocytes constituting the stratum corneum. There is a bulge region present, which is part of the outer root sheath, at the level of insertion of the arrector pili muscle. It contains stem cells. These stem cells can be used for the regeneration of the hair follicle and can be used to produce epidermal keratinocytes and sebaceous gland cells.
The infundibulum, which has profound depth, is the part of the hair follicle which has the most to do with acne. It extends from the entrance to the sebaceous duct all the way to the skin pore. The lumen of the infundibulum contains the hair shaft, dead skin cells and sebum. Sometimes it also contains Malassezia yeasts, bacteria and parasitic mites called Demodex. The hair shaft lies unprotected in the infundibulum in contrast to the isthmus, where it is surrounded by the inner and outer root sheaths.
Before we look at the infundibulum in detail, we must first talk about the different types of hair follicles. There are three different types of hair follicle which can exist and all types are present on the face. These include vellus follicles, terminal follicles and sebaceous follicles . The former two rarely produce acne. In other words, acne occurs in sebaceous follicles.
Terminal follicles, which give rise to facial hair, contain long and thick hairs and vellus terminals give rise to short, fine, lightly-coloured hair. In both of these follicles, the size of the follicular canal and skin pore are proportional to the diameter of the hair. This means that the diameter of the hair is great enough to occupy almost the entire width of the follicular canal. As a result, the follicular canal is kept free of debris by the flow of sebum. The infundibulum of both of these types of follicles have a well defined stratum corneum similar to that of the adjacent epidermis which desquamates appropriately.
Sebaceous follicles, which are only present in humans and thus animals do not suffer from acne, possess a tiny hair bulb which produces a wispy hair whose width is less than one-tenth that of the diameter of the follicular canal leaving ample room for the accumulation of debris. Instead of having a small sebaceous gland like you’d expect, it is in fact exceptionally large and multi-lobulated and the skin pores are large, meaning that there is a generous opening to the skin surface. Even more peculiar are the distinct infundibulum properties compared to the other two hair follicles types. As you go down the infundibulum, deeper into the hair follicle, the properties change, giving rise to two distinct portions.
The most terminal portion of the infundibulum, called the acroinfundibulum, is similar to that of the other hair follicle types, having a similar epithelium to the adjacent epidermis. It comprises the upper fifth of the infundibulum.
The portion below, which makes up the other four fifths of the infundibulum including the lining of sebaceous ducts, is called the infrainfundibulum, unlocks the key to understanding acne. It keratinizes just like the epidermis but produces a very thin stratum corneum with corneocytes that desquamate very soon (28 – dif ref to the below) since there are decreased desmosomes and tonofilaments . The corneocytes have been described as fragile (28). This leads to a mass of loose disorganized dead skin cells occupying the follicular canal which normally are carried out by a stream of sebum (7) but acne occurs when a plug forms in the follicular canal. The follicular canal of the hair follicle is frequently colonized by bacteria which rely on dead skin cells and sebum as a source of nutrients. The stratum granulosum is only one cell thick with tiny keratohyalin granules.
The highest density of sebaceous follicles, which are limited to the face and upper trunk, is found on the face and upper back, especially on the forehead, where there may be as many as 900 glands per square centimetre in some areas (20). Elsewhere on the body, there may be fewer than 100 pilosebaceous units per centimetre squared (23). This is why these areas are prone to acne. The rest of this book will use the term ‘hair follicle’ to mean ‘sebaceous follicle’.
Above the arrow is the acroinfundibulum. Below the arrow is the infrainfundibulum. Notice the well-defined stratum corneum of the acroinfundibulum, as shown in orange. Notice how the infrainfundibulum does not have a defined stratum corneum.
As seen in the figure, the basement membrane is vertical, wrapping around the entire pilosebaceous unit. This means that the stratum basale is also vertical, and thus the basal keratinocytes undergo their terminal differentiation cycle until they are sloughed off into the follicular canal rather than directly onto the skin surface (see image below). This vertical basement membrane is called the vitreous layer. The basement membrane of the epidermis and the vitreous layer wrapping around the pilosebaceous unit is continuous because both are produced under the influence of the keratinocyte basal cells which are above them.
Remember that the basement membrane separates the ‘non-self’ epidermis from the ‘self’ dermis? The vitreous layer does exactly the same. All of the cells enclosed within the vitreous layer are considered ‘non-self’ whilst the cells on the other side of the vitreous layer are considered ‘self’. This is why an inflammatory reaction pursues when the sebaceous duct bursts, releasing the ‘non-self’ material under the skin into the ‘self’ dermis, leading to an ‘inflammatory’ acne lesion. This horizontal basement membrane, called the glassy membrane, turns and extends downwards, allowing it to wrap around the pilosebaceous unit until it emerges itself into the fibrous root sheath. This root sheath wraps around the infundibulum tightly and extends down to wrap around the pilar and the sebaceous parts as well. This tightness of the wrap provides support to the otherwise weak tubular cellular structures. This wrap limits their expansion and under normal conditions prevents them from over-expanding or simply bursting. The thickness of the wrap is particularly obvious in the eccrine sweat glands and their ducts—they are only one cell thick and would easily burst without this support.
A word on hair
The surrounding of the papilla, the deepest part of a hair follicle, is called the hair matrix. It is a collection of cells. It’s purpose is to produce hair on a cyclic schedule, under the collective influence of both estrogens and androgens. The first sign of the hair starts in the papilla, the deepest part of the pilar unit. Within the pilar unit, the hair starts out wrapped in the inner and outer root sheathes. The hair and the inner root sheath are produced by cell division of the hair matrix cells. They are one of the fastest growing cell populations in the human body. As the new hair is forced upwards, it separates from the inner and outer root sheathes in the suprabulb area of the hair follicle. The now-independent hair shaft acquires a protective and lubricating sebum coat. This thin and ever-renewing coat as the hair is pushed through the follicular canal is due to sebocytes dissolving around it. Eventually the head of the hair reaches the outside world.