Hair biology
Hair is a defining characteristic of mammals. Evolution has robbed humans of the fine pelage seen on our simian ancestors, but vestigial hair remains on the scalp, axillary, beard and perineal areas. The importance of hair to humans is obvious, not only to those who deal with diseases of the hair and scalp, but also to those who profit from it in the hairdressing and hair cosmetic industries.
The human skin supports approximately five million hair follicles, of which only one hundred thousand are on the scalp. Most of these follicles produce vellus hairs that are cosmetically insignificant. Many never produce hairs long enough to protrude from the follicular ostium. The majority of hairs on the scalp are terminal hairs that uncut may grow up to a metre long. Hair can be red, blond, brown or black and straight, wavy or curly. These natural variations are an important part of our identity that can be manipulated according to the dictates of fashion or society.
Each hair arises from a follicle consisting of epidermis that has invaginated the dermis to form a sleeve-like structure. The base of the follicle is intimately associated with the dermal papilla, and hair is the product of interaction and communication between dermis and epidermis. The hair shaft consists of keratinocytes that are compacted and cemented together. The final product is remarkably strong and resistant to the extremes of nature.
Types of hair
The type of hair produced by an individual follicle can change with age or under the influence of hormones. The three, main recognized types of hair are listed below.
1 Lanugo hair is formed and shed during the seventh or eighth month in utero. It consists of fine, soft, nonpigmented hair that has no central medulla.
2 Vellus hair is the fine, unmedullated hair found on glabrous skin that is usually shorter than 2 cm and nonpigmented
3 Terminal hair is the coarse pigmented, long hair found on the scalp, eyebrows and eyelashes prior to puberty and additionally in the pubic, axillary, chest and beard areas of adults.
Intermediate or indeterminate forms of hair also exist on the scalp of infants at 3 months and last until the age of 2 years. They are coarser than lanugo hair and sparsely pigmented, however, they do not have a well-defined medulla like that found in terminal hair. Similar hair also appears on adult scalps in the context of androgenetic alopecia, a process that results in miniaturization of terminal hairs and ultimate reversion into vellus hairs.
Hair anatomy
The sites of attachment of the arrector pili muscle and the sebaceous gland act as anatomical boundaries separating the hair follicle into three parts:
1 the bulb, which extends from the base of the follicle to the insertion of the arrector pili muscle;
2 the isthmus, which extends from the insertion of the arrector pili muscle to the sebaceous duct;
3 the infundibulum, which runs from the entrance of the sebaceous duct to the follicular ostium.
Each terminal hair consists of either two or three elements depending on whether it is of sufficient size and calibre to develop a central core or medulla. If present, this central medulla, which arises from hair matrix cells, may occur intermittently along the hair. It is encased by the hair cortex, which forms the major part of the hair shaft and contributes most to the colour and the mechanical properties of hair. The cortex is in turn encircled by the hair cuticle, a shield that protects the hair cortex and is responsible for the lustre and texture of hair.
The medulla exists as a framework of spongy keratin supporting thin shells of amorphous material bounding air spaces of variable size. It is best seen on light microscopy of hair where, because of refraction of light, the air spaces appear dark. In animals the central air canal of hair provides an insulating effect crucial to thermoregulation. However, in humans the medulla is a vestigial structure.
The cortex consists of closely packed spindle cells containing cytoplasmic filaments that run parallel to the long axis of hair. These filaments are hard alpha keratin fibres that appear different to the tonofibrils found in epidermal keratinocytes. Each cell is separated by a narrow gap containing proteinaceous material that cements the cells together and contributes to the incredible strength of the hair shaft. Melanocytes are found only in the hair matrix at the base of the cortex and produce melanin granules that intersperse throughout the cortex.
The cuticle consists of a single layer of cells that overlap in a similar way to roof tiles, with the free margin pointing towards the tip of the hair. These cells are the first part of the emerging hair to harden by undergoing keratinization, and determine the shape of the emerging hair. If the cuticle is damaged the cortex will quickly degenerate, resulting in broken hairs and split ends. The strength of the cuticle comes from the strong high sulphur protein present in the outer part of each cuticular cell. Absence of this protein, which occurs in trichothiodystrophy produces weakened, fragile hairs that break off close to the root.
The inner root sheath is one of the two root sheaths that surround the hair shaft. It is also produced by the hair matrix and comprises three distinct layers of cells. The single-cell layer of Henle is outermost, the double cell layer of Huxley is central and the innermost inner root sheath cuticle consists of a single layer of overlapping cells akin to roof tiles, but in contrast to the hair cuticle, the free margin of these cells points downwards allowing the two cuticles to interlock. The two cuticles are so completely integrated that the interlocking cells appear as a single cell layer on light microscopy. The inner root sheath forms trichohyaline granules (which are more eosinophilic than keratohyaline granules) and keratinizes before the hair shaft does and so is an important scaffold for the developing hair and it determines the ultimate shape of the hair shaft. The hair that ultimately emerges from the follicle is devoid of its inner root sheath. This disintegrates at the isthmus and the residue is discharged into the pilosebaceous canal.
The outer root sheath is also known as the tricholemma (Greek: coating or sac around the hair). Its upper part surrounding the follicular ostium merges imperceptibly with the adjacent epidermis. In the dermis the outer root sheath is thickest at the isthmus and narrowest at the bulb where it is only one or two cells thick. The outer layer is a germinative layer resting on a basement membrane that is continuous with basal epidermis. Differentiation occurs centrally towards the inner root sheath with the cells enlarging, flattening and becoming vacuolated. The exact fate of the cells adjacent to the inner root sheath is not known but it is presumed they keratinize without the formation of keratohyaline granules and are shed into the pilosebaceous canal along with cells of the inner root sheath. The vitreous or glassy membrane lies external to the basement membrane of the outer root sheath and is a noncellular connective tissue sheath enveloping the follicle.
The arrector pili muscle arises from of the outer root sheath at the junction between the bulb and isthmus. It inserts predominantly into a bulge on the posterior wall, but some fibres insert circumferentially. This bulge contains a group of germinative cells that can be identified histochemically. With the onset of anagen, bulge cells proliferate and repopulate the transient portion of the follicle that involutes with catagen. The cells within the bulge are the immortal stem cells of the hair follicle, and destruction of the bulge will permanently destroy the follicle.
Cells of the outer root sheath express different keratin markers to the cells of the medulla, cortex, cuticle and inner root sheath which all express similar keratins. This reflects the common origin of these latter hair components from specialized matrix, while the outer root sheath derives from adjacent epidermis.
The dermal papilla consists of an oval mass of spindle cells resting in a local environment rich in mucopolysaccharides. The papilla is surrounded by hair matrix epithelium from which it is separated by a thick basement membrane except where it sits on a dermal fibroelastic plate called the Arao-Perkins body. The papilla receives a rich neurovascular supply. It plays a vital role in stimulating embryological follicle formation and regulating the hair cycle. There is a close relationship between the mitotic activity of the dermal papilla fibroblasts and the hair matrix keratinocytes and the size of the dermal papilla correlates closely with the size of the hair follicle.
The vascular supply surrounding the hair follicle arises from the subdermal arterial plexus. It is richest at the bulb and the insertion of the sebaceous duct. It too involutes during hair dormancy (late catagen) and regenerates early in anagen.
Sensory nerves and neural end organs (predominantly Pinkus corpuscles) encase the entire length of the hair follicle like a glove, however, nerve axons do not penetrate the outer root sheath. All hairs are innervated, usually by several myelinated nerve fibres. While hairs may act as subtle organs of touch, the physiological and pathological significance of this innervation requires further investigation. Additional efferent autonomic nerve fibres supply the arrector pili muscles, and stimulation produces the sensation of goose bumps.
Hair embryology
The full quota of hair follicles is present at birth, and no new follicles develop thereafter. Secondary sexual hair is the result of an androgen triggered switch to the production of terminal hairs rather than vellus hairs in preexisting follicles.
Hair follicles develop as epidermal down growths that invaginate the dermis and subcutaneous fat and enclose at their base a small stud of highly specialized dermis known as the dermal papilla. The site of these down growths is probably determined by the location of these papillae in the dermis. Follicles exist as pilosebaceous units that also give rise to the sebaceous glands, arrector pili muscles and in certain areas the apocrine glands.
In the ninth week of embryonic development, rudiments of hair follicles appear on the eyebrows, upper lip and chin; sites in which vibrissae (whiskers) are present in other mammals. At 16 weeks hair is developing within these follicles while the development of other follicles is gradually extending cephalocaudally.
The first sign of hair follicle development is the focal crowding of basal cell nuclei in the fetal epidermis to form what is called the primitive hair germ. These appear on the skin surface in groups of three at fixed intervals of between 274 and 350 um. The hair germs enlarge asymmetrically and grow obliquely downwards into the dermis to form a solid column of cells known as the hair peg. The lower end of the enlarging hair peg becomes bulbous and encloses a group of mesodermal cells destined to become the papilla.
At the same time two or three swellings develop on the posterior wall of the hair peg. The upper bulge is the germ of the apocrine gland. It is uncertain whether apocrine glands only develop in the axilla, groin, external ear canal, eyelid and breasts or if they initially develop in all follicles, only to later involute other than in these selected sites.
The middle swelling is the germ of the sebaceous gland, while the lower swelling becomes the site of attachment of the arrector pili muscle. This lower swelling persists as the hair bulge and is a source of f ollicular stem cells crucial to the regeneration of anagen hairs during the hair cycle. The arrector pili muscle was previously assumed to attach only to the bulge on the posterior wall of the hair follicle, but recently it has been shown to attach circumferentially.
The cells immediately surrounding the dermal papilla constitute the hair matrix, comprising undifferentiated proliferating cells that produce the hair medulla, cortex and cuticle as well as the inner root sheath. The outer root sheath of the hair is derived from epidermis, while the mesodermal cells surrounding the bulb give rise to the connective tissue sheath.
The hair cycle
In man hair follicles show intermittent activity. Thus each hair grows to a maximum length, is retained for a period of time without further growth and is eventually shed and replaced. The duration of activity varies greatly from region to region and subtle variation also occurs with age and between males and females.
Anagen is the period of active growth and in a vellus follicle lasts between 6 and 12 weeks. In terminal hairs anagen lasts 4-14 weeks on the moustache, 6-12 weeks on the arms, 19-26 weeks on the leg and 2-5 years on the vertex of the scalp.
Anagen can be subdivided into six stages that to some extent recapitulate the embryological development of the hair follicle. The first five are collectively known as proanagen and are characterized by progressively higher levels of the new hair tip within the follicle. Anagen 6, also known as metanagen, is defined by the emergence of the hair above the skin surface.
Catagen is the transitional phase that follows anagen and usually lasts 2 weeks. It is not clear what triggers induce the spontaneous cessation of mitosis, rapid terminal differentiation of keratinocytes and apoptosis within the regressing hair bulb that all occur in catagen. Changes in the vasculature appear to be secondary events. With the onset of catagen, melanin production ceases and melanocytes resorb their dendrites. Keratinization of the hair and inner root sheath continues and the result is a nonpigmented expansion at the base of the hair in the shape of a club.
Telogen is the resting phase of the hair cycle. The club hair with its nonpigmented bulb is held in a sac and is retained in the follicle until the development of the next anagen hair is well established. Telogen usually lasts 3 months on the scalp before the follicle spontaneously reenters anagen, however a premature anagen can be triggered by plucking the resting club hair.
Hair stem cells in the bulge begin to proliferate at the end of telogen and daughter cells differentiate into the new anagen bulb (anagen 1). The new bulb grows downwards, encloses the dermal papilla (anagen 2) and anagen is once again under way. Finally the new anagen hair pushes the old club hair out just before it emerges from the follicular ostium.
In animals the hair cycle is synchronized such that the entire pelage grows continuously through winter. When summer comes growth abruptly ceases and a cephalocaudal malt ensues. This synchronized growth pattern also occurs in human hair in utero. Hairs first appear on the scalp at 20 weeks gestation and then grow over the rest of the body cephalocaudally. Initially all hairs are in anagen. At 26 weeks the scalp hairs enter catagen and then telogen in a progressive wave from the frontal to the parietal region over a period of seven days. These telogen hairs are mostly shed in utero. Occipital hairs, however, remain in anagen until about 38 weeks and then they too enter catagen. Meanwhile the frontal and parietal hairs have reentered anagen and formed the second pelage. When these hairs subsequently enter catagen the second wave forms.
At full term there are two consecutive waves of hair, each of which is running from the forehead to the occiput. Over the occiput the primary hairs do not enter telogen until 8-12 weeks after birth and then fall producing a well-defined area of alopecia. This has been described as occipital alopecia of the newborn and the only contribution of rubbing the head on the pillow (which is often blamed) is to facilitate release of telogen hairs.
Following the first two synchronized moults of the child and towards the end of the first year of life there is a change in the relationship of adjacent hairs such that a random mosaic pattern emerges in which each hair follows its own intrinsic rhythm. This asynchrony continues throughout life, unless modified by pregnancy or illness. At any one time there will be a uniform distribution of hairs in each stage of the cycle reflecting the relative duration of the hair cycle phases.
On the scalp approximately 86% of hairs will be in anagen, 1% in catagen and 13% in telogen. As there are about 100 000 hairs on the scalp of which 13 000 are in telogen, and telogen lasts around 3 months, approximately 100-200 hairs are shed each day in times of health.
Systemic and local influences on the hair cycle
Circulating androgens increase both the rate of hair growth and the calibre of the hair (transforming vellus to terminal hairs) in androgen dependant sites such as the beard. Paradoxically in the scalp of a person genetically predisposed to androgenetic alopecia, androgens reduce both the rate of scalp hair growth and the calibre (transforming terminal to vellus hairs) of the hair, while antiandrogens partially restore it. It is not known why or how the same chemical can induce exactly opposite effects on different hair follicles. Despite these relatively site specific changes, most hairs on the body are relatively uninfluenced by androgens. This insensitivity is most likely due to the differences in follicular metabolism of androgens, possible related to regional variation in the distribution of 5a reducíase isoenzymes.
Oestrogens reduce the rate of hair growth, but prolong the duration of anagen. This is best seen during pregnancy when there is decreased hair shedding. Post-partum, large numbers of hairs enter catagen and subsequently telogen, which is followed by sometimes massive shedding, approximately 3 months after the birth, known as telogen effluvium gravidarum.
Thyroxine hastens the onset of anagen in resting follicles and corticosteroids delay it. There is also a seasonal variation on the rate of hair growth in man such that it grows faster in summer and falls in winter. It is mediated through the pineal gland but the exact mechanism is obscure.
In regions of the body other than the scalp anagen is relatively short and telogen relatively long (Table 1.1). At any given time up to half the follicles in a particular region will be dormant. Events that cause epithelial hyperplasia such as wounds will also initiate a new anagen in a resting follicle. Interestingly the inflammation of a ringworm infection synchronizes hairs into telogen in the area surrounding the lesions, thus limiting extension of the infection.
Cutting or shaving has no influence on the rate of hair growth or on the calibre of the hair produced by the follicle. Maximum hair length is genetically determined. It depends on the duration of anagen and the rate of growth. Hair will not achieve its maximum length if it is intrinsically weak or extrinsically damaged.
Changes in hair growth have been observed in skin affected by a variety of neurological abnormalities. Terminal hairs overlying a neural tube defect (faun tail) or around ectopic neural tissue on the scalp (the hair collar sign) are well recognized. Shorter hair was noted on the right side of the scalp in a patient with syringomyelia with impaired pain and temperature sensation in the region. Causalgia has been associated with decreased hair growth in affected areas, reflex sympathetic dystrophy may produce hypertrichosis, while denervation of skin can produce either decreased hair growth or hypertrichosis. The mechanism of these changes is not understood.
Physical properties of hair
Much information of the physical properties of hair has been derived from research on the keratin fibres in wool. The strength of human hair resides in the cortex where longitudinally orientated keratin fibres embedded in a sulphur rich matrix are packaged in cell envelopes. This composite structure allows hair to be deformed by mechanical stress and the energy dissipated evenly into the fibre at the fibre matrix interface. The cuticle also plays a vital role in hair resistance to external stress, as is evidenced by the relative fragility of weathered hair that has lost its cuticle.
Hair shaft dimensions show variation between races. Mongoloid hair is circular in cross-section and large with a mean diameter of 120 pm. Caucasoid hair is elliptical in cross-section and smaller. It has a mean diameter of between 50 and 90 um with the variation being due to the larger calibre of dark hair compared to fair hair. Negroid hair is flattened, curled and oval in cross-section. Longitudinal grooving is common. The different cross-sectional shapes of hair correspond to the flat straight appearance of Mongoloid hair, the wavy fuller bodied Caucasoid hair and the tightly curled Negroid hair.
When dry hair is rubbed or combed static electricity is produced. This is associated with 'fly away' hair. Certain shampoos and conditioners decrease fly away hair and lessen the static charge by reducing the frictional force during combing and increasing hair moisture.
Hair colour, canites and poliosis
Hair without pigment is white due to reflection and refraction of incident light. This is accentuated by a broad medulla as found in the hairs of many arctic animals. The variety of colours seen in animal hair is due to the combinations of pigments produced which include porphyrins, carotenoids and melanin. In contrast the range of human hair colour is limited as it is produced entirely by melanin within the keratinocytes of the cortex with a small contribution from the medulla.
Melanocytes present in the hair bulb at the apex of the dermal papilla are able to produce two types of melanin pigment; eumelanin which is responsible for black and brown hair and pheomelanin which produces auburn and blond hair. Pheomelanin is unique to hair and is not found in the epidermis. It is produced by a modification of the eumelanin synthesis pathway that involves an interaction of dopaquinone with cysteine. Usually an individual will only produce either pheomelanin or eumelanin throughout life, however, some people's hair colour changes spontaneously, and a number of blond children grow up to become brunettes.
Nonfunctional melanocytes are also present in the outer root sheath of the lower part of the follicle. They do not contribute to hair colour, but become involved in the repigmentation that occurs with resolution of vitiligo or with wound healing. Epidermal and hair melanocytes are independently involved in certain disorders. For example vitiligo can have pigmented hairs arising from depigmented skin. The reverse occurs in poliosis or canites, when hair turns grey.
Subtle variations in hair colour are due to variations in the number of melanocytes present in a follicle, the density of melanin formation within melanosomes and melanosome shape (oval melanosomes being more readily degraded), the transfer of melanosomes to hair matrix cells and the distribution and metabolism of the melanosomes within the hair cortex keratinocytes.
Melanocytes are only functionally active during anagen and lie dormant in telogen hairs. When anagen restarts, melanocytes reawaken and new melanocytes are produced by replication. Despite this proliferation of melanocytes, melanoma arising in the hair follicle does not seem to occur. Anagen hairs are usually uniformly pigmented. An exception to this is nose hair arising from the nasal mucosa,which have a nonpigmented 2-3 mm tip, that gradually darkens.
Hair colour varies according to the body site with eyelashes being darkest. Scalp hair is usually lighter than pubic hair which often has a red tinge. A red tinge is also common in axillary and beard hair even in people with essentially brown hair on their scalp. Sunlight bleaches hair, and after death hair is slowly oxidized which lightens the colour.
Hormones such as melanin stimulating hormone (MSH) can darken light hair as can oestrogens and progestogens during pregnancy. Drugs that can change hair colour include: antimalarials such as chloroquine, mephenesin, triparanol, butyrophenone and phenylthiourea that all produce lightening, while carbidopa, bromocryptine, minoxidil and diazoxide tend to produce darkening.
Inheritance of hair colour is complex and appears to be controlled by multiple loci in the genome. A putative gene locus for red hair has been identified, but awaits further confirmation.
Greying of hair, or canites
This occurs in both man and primates and is a manifestation of ageing. It is due to a progressive reduction in melanocyte function rather than number. Canites can occur prematurely in autoimmune disorders such as pernicious anaemia, vitiligo, the premature ageing syndromes progeria, pangeria and Down's syndrome; and rare metabolic disorders such as prolidase deficiency. In addition when vitiligo directly involves the scalp or hair bearing skin, depigmentation can occur within affected patches. Conversely darkening of the hair has been described in Addison's disease.
Greying commences in the third decade on the temples and spreads later to the crown and occiput. By the age of 50 years, 50% of the population have at least 50% grey hairs. Except in the earliest phases of canites and the early regrowth of alopecia areata (AA), greying is usually irreversible, however, there are anecdotal reports of repigmentation occurring following electron beam therapy and in porphyria cutánea tarda. Temporary repigmentation may also occur following large doses of paraamino benzoic acid.
Sudden overnight greying, as is reputed to have affected Marie-Antoinette on the eve of her decapitation, is due to a diffuse AA preferentially affecting the pigmented hairs.
Poliosis or piebaldism
This is a congenital, localized variant of albinism inherited as an autosomal dominant trait. The genetics have not yet been determined; however, affected individuals may be mosaic for the relevant gene. In the scalp there is a localized patch of white hair. The abnormality is due to either the absence of or a deficiency of melanin production in a group of neighbouring follicles. In addition pigment production is impaired in the surrounding interfollicular epithelium and melanocyte numbers appear to be reduced in affected skin and hair. While any part of the scalp can be involved, the most commonly affected site is the central frontal hairline of the forelock, and this may be the only manifestation. The white area often extends forwards to the base of the nose.
On the trunk and limbs there may be additional patches of depigmented skin that remain fixed. Islands of normally pigmented skin often occur within the hypomelanotic areas.
Poliosis has been associated with congenital perceptual deafness and this may be a forme fruste of Waardenburg's syndrome. Poliosis also occurs in up to 60% of cases of tuberous sclerosis and may be the earliest manifestation. A patch of poliosis overlying a scalp neurofibroma in Von Recklinghausen's disease has been described.
The opposite of poliosis, a black hair naevus, occurs as an isolated developmental anomaly.
Waardenburg's syndrome
This is the combination of a white forelock (present in 20%), lateral displacement of the medial canthi with dystopia canthorum, hypertrophy of the nasal root, confluent eyebrows, partial or total dyschromia of the iris, and perceptive deafness in about 20%. Abnormal patterns of hair growth, with a beard covering the entire cheeks and terminal hairs on the nose have been described as has premature canites.
Teitz's syndrome is a similar condition with generalized patches of white skin and hair associated with deafness and eyebrow hypoplasia. The Vogt-Koyanagi-Harada syndrome consists of bilateral uveitis, labyrinthine deafness, tinnitus, vitiligo, poliosis and AA. Alezzandrini's syndrome combines facial vitíligo, retinitis, and poliosis of the eyebrows and eyelashes.
Albinism
In both tyrosinase positive and tyrosinase negative autosomal recessive oculocutaneous albinism, the hair is yellowish-white in colour, although it can be cream, yellow, yellowishred or vibrant red on occasion.
Chediak-Higashi syndrome
This is an autosomal recessive defect of membrane-bound organelles in white cells, platelets and a variety of neuroectoderm derived cells including melanocytes. A lethal immune deficiency, oculocutaneous hypopigmentation, hepatosplenomegaly and lymphadenopathy occur as does an increased risk of lymphoma.
Phenylketonuria
Phenylketonuria, an inherited deficiency of phenylalanine hydroxylase, results in accumulation of the tyrosine precursor phenylalanine and a reduction in melanin formation. The skin is pale and the hair is fair.
Hair weathering
Hair weathering is defined as the microscopic changes in the hair shaft structure not seen at the root end and which become progressively more obvious or frequent towards the tip. It manifests as a progressive degeneration from root to tip of, initially, the cuticle, and later the cortex. Weathering occurs to some extent in all hairs allowed to grow long enough, in response to routine wear and tear.
Hairs with intrinsic structural defects are less able to withstand routine wear and tear and weather prematurely with the recognizable changes occurring close to the root. It is the proximity of these changes to the root that distinguishes these defective hairs from weathered hairs.
At the root end of normal hair, the cells of the cuticle are closely opposed to each other and to the underlying hair cortex. They are arranged with each cell partially overlapping the adjacent cell, akin to roof tiles.
In normal hair the earliest manifestations of weathering can be seen within a few centimetres of the scalp. Exposed to the vigours of a variety of cosmetic and environmental stresses, the free margin of the cuticle cells lifts up and breaks irregularly. Progressive scale loss leads to areas of the hair shaft that are totally denuded of cuticle. The exposed cortex is weak and fractures and produces nodes or frayed tips. Proximal to the terminal fraying, longitudinal fissures, otherwise known as split ends, may develop.
The tips of long hairs will have been subjected to considerable wear and tear and may show transverse fissures and nodes of the type seen in trichorrhexis nodosa. If the wear and tear has been excessive these changes will occur closer to the root, but rarely will they occur as close to the root as seen in the structural hair shaft disorders.
As weathering occurs to some extent in all hair, longer hair exhibits a greater degree of terminal weathering. Weathering is also modified by a number of factors that are listed in Table.
Hair patterns
Regional variations in hair pattern are related to age, genetic constitution and endocrine status. While eunuchs do not develop secondary body hair, and castration or hypogonadism of males results in a loss of body hair, there is not a direct relationship between the volume of body hair and the level of circulating free testosterone. In addition dark-haired people have both an increased amount and more noticeable body hair than their fair-haired counterparts.
Pubic hair
Three patterns of distribution of pubic hair based on the upper border of the pubic triangle have been described:
horizontal, acuminate and disperse. The horizontal pattern is found in 90% of women and 20% of males. The acuminate pattern is seen in 10% of women and 50% of men, while the diffuse pattern is generally only seen in middle-aged men with much terminal hair on their thighs and chest.
An acuminate pattern often reverts to a horizontal pattern in women following the menopause. A change to a horizontal from an acuminate pattern also occurs in men following oestrogen treatment for carcinoma of the prostate.
Chest hair
This appears in the normal male soon after puberty and continues to increase until the sixth decade. There is a wide individual and racial variation in the amount of hair developed. In about 20% of individuals with extensive chest hair, circular bare areas known as pectoral alopecia are present around the nipples. Such individuals frequently have accompanying hair on their shoulders and back.
Axillary hair
Terminal hair in the axilla usually appears 2 years after the first pubic hair, but there is much individual variation in this figure and axillary hair occasionally appears first. Mongoloids tend to have sparser hair than Caucasoids and it is not infrequently absent among older subjects of both sexes.
Most Caucasoids have a fairly extensive cover of hair over the extensor aspect of the arms. In about a quarter the hair is limited to the forearms and a small minority has no terminal hair.
The fingers tend to show hairs over the proximal phalanx, while in most people the middle phalanx is hairless. Hair over the proximal phalanx of the thumb and the middle phalanges shows individual and racial variation.
Peroneal alopecia
This refers to the bare areas over the anterolateral aspect of the lower leg It occurs in up to 35% of people and is probably unrelated to wearing socks, except that friction from socks may cause premature release of telogen hairs.
Trichoglyphics
Hair does not grow vertically but leaves the scalp at an angle that is precisely determined so that streams and patterns are formed. At certain sites the individual follicles are curved away from the axis of the emergent shaft to form whorls. Whorls and streams probably appear as early as 12 weeks gestation. They can be usually seen on the parietal region of the scalp, the inner canthus of the eye and other sites of skin depressions such as the axilla and back.
A single parietal whorl is seen in 95% of people and it is usually clockwise. The remainder have two or rarely three whorls. A frontal cowlick due to a counter stream of hair from the forehead is present in 7%. Abnormal scalp hair patterns with absent or aberrant whorls may be seen on the heads of children with abnormal brain development, such as microcephaly. Multiple scalp whorls are more common among mentally retarded children.
The ridgeback anomaly is due to the hair waves growing towards the vertex rather than the normal spiral away from the crown. It too may be associated with intellectual impairment.
Displacement of the scalp line occurs in a number of syndromes. A congenitally low anterior line occurs in Cornelia de Lange syndrome, lipoatrophic diabetes, fetal hydantoin syndrome and Rubinstein-Taybi syndrome, while a low posterior line occurs in Noonan's and Turner's syndromes. A congenitally high anterior line is seen in myotonic dystrophy.
Investigation of hair and hair follicle diseases
Accurate diagnosis of hair disorders is important for management. Even if therapy is limited for a specific condition, advice regarding the natural history of the condition, associated manifestations of the disorder and genetic counselling for hereditary disorders can be of enormous value to the patient.
Following clinical assessment of a disorder the clinician should have established whether the condition is congenital or acquired, diffuse or focal; and in the case of alopecia, scarring or nonscarring. Any associated abnormalities of skin, nails and teeth should be noted and if virilism is suspected a directed history, examination and biochemical investigations are appropriate.
The hair pull test is an easy method of confirming that abnormal hair loss is occurring and also its distribution. To do this test a clump of hairs are grasped at their base between the thumb and forefinger. Firm traction is then applied, being careful not to produce pain, as the examiner's hand slides along the hairs from the base to the tip. This can be repeated at various sites in the scalp. Normally 2-5 telogen hairs will be obtained after five or six passes done in this way, depending on when the scalp was last shampooed.
Telogen hairs can be recognized with the naked eye by their nonpigmented tip.
Except in loose anagen syndrome, protein calorie malnutrition, anagen effluvium, occult poisoning, and occasionally early diffuse AA, normally only telogen hairs should be obtained as normal anagen hairs are firmly anchored in the scalp. Occasionally patients swear their hair is falling out but a hair pull test is normal. In such cases it is valuable to ask the patient to collect all the hairs shed during the course of a day in the shower, sink, pillow, brush, etc. and to count them. The normal loss is less than 100 per day. In active telogen effluvium it can be several hundred per day.
In cases where one wishes to establish anagen/telogen ratios (a trichogram), for example, in attempting to differentiate androgenetic alopecia from telogen effluvium, a hair pluck should be performed. For accuracy the scalp should not be washed for 3-6 days before the procedure (as this removes telogen hairs) and at least 50 hairs should be plucked. The best instrument for this is a haemostat with the tips covered with rubber tubing. The hairs are grasped at the base and extracted with a sharp quick pluck, as slow traction deforms the morphology of the root and prolongs the discomfort.
The hairs can be mounted between two glass slides for microscopic examination either using double sided sticky-tape or cyanoacrylic glue that will allow the hair slide to be kept permanently for future reference. In the absence of glue, immersion oil can be used and gives a clear image as it has the same refractive index as glass. The normal scalp anagen to telogen ratio in children is over 90% while in adults it is approximately 85%. Dysplastic anagen hairs are a nonspecific finding in many alopecias and can be produced by slow extraction of the hair.
For fungal microscopy only half a dozen or so hairs need be plucked. If the suspected pathology is increased hair shaft fragility, it is important to examine both plucked and cut hairs to avoid over diagnosing artefacts from the act of plucking. Plucked hairs allow assessment of an abnormality in relation to its distance from the hair root. Any abnormality occurring within the first 2 cm is likely to be of intrinsic origin, while distal abnormalities will simply reflect extrinsic weathering.
The epiluminescence hand-held microscope (dermato-scope), more commonly used for examination of pigmented naevi, can also be of use (without the oil) in examining the scalp for hair shaft defects. In patchy disorders such as monilethrix the optimal site to obtain hair for microscopy can be determined. In addition the dermatoscope can be used with oil in the assessment of scarring alopecias.
Light microscopy of hair allows visualization of structures larger than 0.2 um and has a narrow depth of focus. Transmission electron microscopy gives very high resolution down to 2 nm and has a depth of focus of 100 nm. A diamond knife is required for cutting ultra-thin sections of hair without distortion, and the hair is then stained with a heavy metal such as gold to give anatomical detail. Scanning electron microscopy gives a wealth of information about surface architecture. However, for many conditions, sufficient diagnostic information is gained from light microscopy.
Polarized light microscopy gives additional information regarding the structural composition of the hair and makes fine structural abnormalities more obvious, but is not essential. Striking alternating dark and light bands (reminiscent of a tiger's tail) are seen on polarized microscopy in the sulphur deficient hairs of trichothiodystrophy.
Scalp biopsy relies on good technique to provide useful histological information. The site of biopsy is important, and the active edge of a scarring alopecia is likely to yield more information than the 'burnt-out' centre. Often multiple 3 or 4 mm punch biopsies are more useful than a single incisional biopsy. The biopsy should be angled in the direction of hair growth to avoid transecting hairs, and must include subcutaneous fat in order to include anagen hair bulbs. Because follicles in a biopsy specimen tend to bend before hardening, cross cutting is common. This can be avoided by placing the biopsy face down on a piece of cardboard, before putting it in the formalin. The scalp is very vascular and biopsies will usually need to be sutured. Horizontal processing often gives complementary information to the traditional longitudinal biopsy particularly regarding follicle type and density and anagen to telogen ratios, but requires an experienced pathologist for interpretation.
Scalp histology is necessary to establish the diagnosis in scarring alopecia and is also useful in trichotillomania and unexplained diffuse hair loss. It has also been used to determine the potential for regrowth in long-standing apparent nonscarring alopecias. Elastin stains are useful to assess scarring. Immunofluorescence of fresh or frozen tissue should be performed if lupus erythematosus or a bullous disorder is suspected.
The psychological importance of hair
An appreciation of the special psychological significance of the hair is important for those involved in the assessment and management of diseases of the hair and scalp. Hair is central to our perceptions of beauty and attractiveness. Either too little hair on the scalp or too much hair on the face of a woman can make her feel unattractive, self-conscious and miserable. It is not uncommon for such people to be and feel stared at in public and as a consequence shy away from personal contact. Perhaps the greatest testimony to the importance of hair is the time and money spent in hairdressing salons around the world and the multibillion dollar annual turnover of the hair cosmetic and trichology industries. Disorders of hair frequently produce profound anxieties out of keeping with their objective severity or physiological importance.
The association of hair with attractiveness can be confirmed by even the most superficial surveys of the visual arts, literature and advertising in magazines. Unfortunately fashion magazines portray an inaccurate stereotype for women, and this contributes to the common misconception that women do not go bald.
Many societies associate shaving of the head with celibacy or chastity, as seen in monks and nuns of Buddist and Christian faith as well as Hindu priests and women. Covering the hair among Catholic nuns and in Muslim and orthodox Jewish society has a similar connotation. Today shaving the head may be simply a fashion statement.
Some societies cut women's hair as punishment for adultery. Similar punishment was handed out in Europe after the Second World War for women who had consorted with soldiers of occupying armies.
Hair is a defining characteristic of mammals. Evolution has robbed humans of the fine pelage seen on our simian ancestors, but vestigial hair remains on the scalp, axillary, beard and perineal areas. The importance of hair to humans is obvious, not only to those who deal with diseases of the hair and scalp, but also to those who profit from it in the hairdressing and hair cosmetic industries.
The human skin supports approximately five million hair follicles, of which only one hundred thousand are on the scalp. Most of these follicles produce vellus hairs that are cosmetically insignificant. Many never produce hairs long enough to protrude from the follicular ostium. The majority of hairs on the scalp are terminal hairs that uncut may grow up to a metre long. Hair can be red, blond, brown or black and straight, wavy or curly. These natural variations are an important part of our identity that can be manipulated according to the dictates of fashion or society.
Each hair arises from a follicle consisting of epidermis that has invaginated the dermis to form a sleeve-like structure. The base of the follicle is intimately associated with the dermal papilla, and hair is the product of interaction and communication between dermis and epidermis. The hair shaft consists of keratinocytes that are compacted and cemented together. The final product is remarkably strong and resistant to the extremes of nature.
Types of hair
The type of hair produced by an individual follicle can change with age or under the influence of hormones. The three, main recognized types of hair are listed below.
1 Lanugo hair is formed and shed during the seventh or eighth month in utero. It consists of fine, soft, nonpigmented hair that has no central medulla.
2 Vellus hair is the fine, unmedullated hair found on glabrous skin that is usually shorter than 2 cm and nonpigmented
3 Terminal hair is the coarse pigmented, long hair found on the scalp, eyebrows and eyelashes prior to puberty and additionally in the pubic, axillary, chest and beard areas of adults.
Intermediate or indeterminate forms of hair also exist on the scalp of infants at 3 months and last until the age of 2 years. They are coarser than lanugo hair and sparsely pigmented, however, they do not have a well-defined medulla like that found in terminal hair. Similar hair also appears on adult scalps in the context of androgenetic alopecia, a process that results in miniaturization of terminal hairs and ultimate reversion into vellus hairs.
Hair anatomy
The sites of attachment of the arrector pili muscle and the sebaceous gland act as anatomical boundaries separating the hair follicle into three parts:
1 the bulb, which extends from the base of the follicle to the insertion of the arrector pili muscle;
2 the isthmus, which extends from the insertion of the arrector pili muscle to the sebaceous duct;
3 the infundibulum, which runs from the entrance of the sebaceous duct to the follicular ostium.
Each terminal hair consists of either two or three elements depending on whether it is of sufficient size and calibre to develop a central core or medulla. If present, this central medulla, which arises from hair matrix cells, may occur intermittently along the hair. It is encased by the hair cortex, which forms the major part of the hair shaft and contributes most to the colour and the mechanical properties of hair. The cortex is in turn encircled by the hair cuticle, a shield that protects the hair cortex and is responsible for the lustre and texture of hair.
The medulla exists as a framework of spongy keratin supporting thin shells of amorphous material bounding air spaces of variable size. It is best seen on light microscopy of hair where, because of refraction of light, the air spaces appear dark. In animals the central air canal of hair provides an insulating effect crucial to thermoregulation. However, in humans the medulla is a vestigial structure.
The cortex consists of closely packed spindle cells containing cytoplasmic filaments that run parallel to the long axis of hair. These filaments are hard alpha keratin fibres that appear different to the tonofibrils found in epidermal keratinocytes. Each cell is separated by a narrow gap containing proteinaceous material that cements the cells together and contributes to the incredible strength of the hair shaft. Melanocytes are found only in the hair matrix at the base of the cortex and produce melanin granules that intersperse throughout the cortex.
The cuticle consists of a single layer of cells that overlap in a similar way to roof tiles, with the free margin pointing towards the tip of the hair. These cells are the first part of the emerging hair to harden by undergoing keratinization, and determine the shape of the emerging hair. If the cuticle is damaged the cortex will quickly degenerate, resulting in broken hairs and split ends. The strength of the cuticle comes from the strong high sulphur protein present in the outer part of each cuticular cell. Absence of this protein, which occurs in trichothiodystrophy produces weakened, fragile hairs that break off close to the root.
The inner root sheath is one of the two root sheaths that surround the hair shaft. It is also produced by the hair matrix and comprises three distinct layers of cells. The single-cell layer of Henle is outermost, the double cell layer of Huxley is central and the innermost inner root sheath cuticle consists of a single layer of overlapping cells akin to roof tiles, but in contrast to the hair cuticle, the free margin of these cells points downwards allowing the two cuticles to interlock. The two cuticles are so completely integrated that the interlocking cells appear as a single cell layer on light microscopy. The inner root sheath forms trichohyaline granules (which are more eosinophilic than keratohyaline granules) and keratinizes before the hair shaft does and so is an important scaffold for the developing hair and it determines the ultimate shape of the hair shaft. The hair that ultimately emerges from the follicle is devoid of its inner root sheath. This disintegrates at the isthmus and the residue is discharged into the pilosebaceous canal.
The outer root sheath is also known as the tricholemma (Greek: coating or sac around the hair). Its upper part surrounding the follicular ostium merges imperceptibly with the adjacent epidermis. In the dermis the outer root sheath is thickest at the isthmus and narrowest at the bulb where it is only one or two cells thick. The outer layer is a germinative layer resting on a basement membrane that is continuous with basal epidermis. Differentiation occurs centrally towards the inner root sheath with the cells enlarging, flattening and becoming vacuolated. The exact fate of the cells adjacent to the inner root sheath is not known but it is presumed they keratinize without the formation of keratohyaline granules and are shed into the pilosebaceous canal along with cells of the inner root sheath. The vitreous or glassy membrane lies external to the basement membrane of the outer root sheath and is a noncellular connective tissue sheath enveloping the follicle.
The arrector pili muscle arises from of the outer root sheath at the junction between the bulb and isthmus. It inserts predominantly into a bulge on the posterior wall, but some fibres insert circumferentially. This bulge contains a group of germinative cells that can be identified histochemically. With the onset of anagen, bulge cells proliferate and repopulate the transient portion of the follicle that involutes with catagen. The cells within the bulge are the immortal stem cells of the hair follicle, and destruction of the bulge will permanently destroy the follicle.
Cells of the outer root sheath express different keratin markers to the cells of the medulla, cortex, cuticle and inner root sheath which all express similar keratins. This reflects the common origin of these latter hair components from specialized matrix, while the outer root sheath derives from adjacent epidermis.
The dermal papilla consists of an oval mass of spindle cells resting in a local environment rich in mucopolysaccharides. The papilla is surrounded by hair matrix epithelium from which it is separated by a thick basement membrane except where it sits on a dermal fibroelastic plate called the Arao-Perkins body. The papilla receives a rich neurovascular supply. It plays a vital role in stimulating embryological follicle formation and regulating the hair cycle. There is a close relationship between the mitotic activity of the dermal papilla fibroblasts and the hair matrix keratinocytes and the size of the dermal papilla correlates closely with the size of the hair follicle.
The vascular supply surrounding the hair follicle arises from the subdermal arterial plexus. It is richest at the bulb and the insertion of the sebaceous duct. It too involutes during hair dormancy (late catagen) and regenerates early in anagen.
Sensory nerves and neural end organs (predominantly Pinkus corpuscles) encase the entire length of the hair follicle like a glove, however, nerve axons do not penetrate the outer root sheath. All hairs are innervated, usually by several myelinated nerve fibres. While hairs may act as subtle organs of touch, the physiological and pathological significance of this innervation requires further investigation. Additional efferent autonomic nerve fibres supply the arrector pili muscles, and stimulation produces the sensation of goose bumps.
Hair embryology
The full quota of hair follicles is present at birth, and no new follicles develop thereafter. Secondary sexual hair is the result of an androgen triggered switch to the production of terminal hairs rather than vellus hairs in preexisting follicles.
Hair follicles develop as epidermal down growths that invaginate the dermis and subcutaneous fat and enclose at their base a small stud of highly specialized dermis known as the dermal papilla. The site of these down growths is probably determined by the location of these papillae in the dermis. Follicles exist as pilosebaceous units that also give rise to the sebaceous glands, arrector pili muscles and in certain areas the apocrine glands.
In the ninth week of embryonic development, rudiments of hair follicles appear on the eyebrows, upper lip and chin; sites in which vibrissae (whiskers) are present in other mammals. At 16 weeks hair is developing within these follicles while the development of other follicles is gradually extending cephalocaudally.
The first sign of hair follicle development is the focal crowding of basal cell nuclei in the fetal epidermis to form what is called the primitive hair germ. These appear on the skin surface in groups of three at fixed intervals of between 274 and 350 um. The hair germs enlarge asymmetrically and grow obliquely downwards into the dermis to form a solid column of cells known as the hair peg. The lower end of the enlarging hair peg becomes bulbous and encloses a group of mesodermal cells destined to become the papilla.
At the same time two or three swellings develop on the posterior wall of the hair peg. The upper bulge is the germ of the apocrine gland. It is uncertain whether apocrine glands only develop in the axilla, groin, external ear canal, eyelid and breasts or if they initially develop in all follicles, only to later involute other than in these selected sites.
The middle swelling is the germ of the sebaceous gland, while the lower swelling becomes the site of attachment of the arrector pili muscle. This lower swelling persists as the hair bulge and is a source of f ollicular stem cells crucial to the regeneration of anagen hairs during the hair cycle. The arrector pili muscle was previously assumed to attach only to the bulge on the posterior wall of the hair follicle, but recently it has been shown to attach circumferentially.
The cells immediately surrounding the dermal papilla constitute the hair matrix, comprising undifferentiated proliferating cells that produce the hair medulla, cortex and cuticle as well as the inner root sheath. The outer root sheath of the hair is derived from epidermis, while the mesodermal cells surrounding the bulb give rise to the connective tissue sheath.
The hair cycle
In man hair follicles show intermittent activity. Thus each hair grows to a maximum length, is retained for a period of time without further growth and is eventually shed and replaced. The duration of activity varies greatly from region to region and subtle variation also occurs with age and between males and females.
Anagen is the period of active growth and in a vellus follicle lasts between 6 and 12 weeks. In terminal hairs anagen lasts 4-14 weeks on the moustache, 6-12 weeks on the arms, 19-26 weeks on the leg and 2-5 years on the vertex of the scalp.
Anagen can be subdivided into six stages that to some extent recapitulate the embryological development of the hair follicle. The first five are collectively known as proanagen and are characterized by progressively higher levels of the new hair tip within the follicle. Anagen 6, also known as metanagen, is defined by the emergence of the hair above the skin surface.
Catagen is the transitional phase that follows anagen and usually lasts 2 weeks. It is not clear what triggers induce the spontaneous cessation of mitosis, rapid terminal differentiation of keratinocytes and apoptosis within the regressing hair bulb that all occur in catagen. Changes in the vasculature appear to be secondary events. With the onset of catagen, melanin production ceases and melanocytes resorb their dendrites. Keratinization of the hair and inner root sheath continues and the result is a nonpigmented expansion at the base of the hair in the shape of a club.
Telogen is the resting phase of the hair cycle. The club hair with its nonpigmented bulb is held in a sac and is retained in the follicle until the development of the next anagen hair is well established. Telogen usually lasts 3 months on the scalp before the follicle spontaneously reenters anagen, however a premature anagen can be triggered by plucking the resting club hair.
Hair stem cells in the bulge begin to proliferate at the end of telogen and daughter cells differentiate into the new anagen bulb (anagen 1). The new bulb grows downwards, encloses the dermal papilla (anagen 2) and anagen is once again under way. Finally the new anagen hair pushes the old club hair out just before it emerges from the follicular ostium.
In animals the hair cycle is synchronized such that the entire pelage grows continuously through winter. When summer comes growth abruptly ceases and a cephalocaudal malt ensues. This synchronized growth pattern also occurs in human hair in utero. Hairs first appear on the scalp at 20 weeks gestation and then grow over the rest of the body cephalocaudally. Initially all hairs are in anagen. At 26 weeks the scalp hairs enter catagen and then telogen in a progressive wave from the frontal to the parietal region over a period of seven days. These telogen hairs are mostly shed in utero. Occipital hairs, however, remain in anagen until about 38 weeks and then they too enter catagen. Meanwhile the frontal and parietal hairs have reentered anagen and formed the second pelage. When these hairs subsequently enter catagen the second wave forms.
At full term there are two consecutive waves of hair, each of which is running from the forehead to the occiput. Over the occiput the primary hairs do not enter telogen until 8-12 weeks after birth and then fall producing a well-defined area of alopecia. This has been described as occipital alopecia of the newborn and the only contribution of rubbing the head on the pillow (which is often blamed) is to facilitate release of telogen hairs.
Following the first two synchronized moults of the child and towards the end of the first year of life there is a change in the relationship of adjacent hairs such that a random mosaic pattern emerges in which each hair follows its own intrinsic rhythm. This asynchrony continues throughout life, unless modified by pregnancy or illness. At any one time there will be a uniform distribution of hairs in each stage of the cycle reflecting the relative duration of the hair cycle phases.
On the scalp approximately 86% of hairs will be in anagen, 1% in catagen and 13% in telogen. As there are about 100 000 hairs on the scalp of which 13 000 are in telogen, and telogen lasts around 3 months, approximately 100-200 hairs are shed each day in times of health.
Systemic and local influences on the hair cycle
Circulating androgens increase both the rate of hair growth and the calibre of the hair (transforming vellus to terminal hairs) in androgen dependant sites such as the beard. Paradoxically in the scalp of a person genetically predisposed to androgenetic alopecia, androgens reduce both the rate of scalp hair growth and the calibre (transforming terminal to vellus hairs) of the hair, while antiandrogens partially restore it. It is not known why or how the same chemical can induce exactly opposite effects on different hair follicles. Despite these relatively site specific changes, most hairs on the body are relatively uninfluenced by androgens. This insensitivity is most likely due to the differences in follicular metabolism of androgens, possible related to regional variation in the distribution of 5a reducíase isoenzymes.
Oestrogens reduce the rate of hair growth, but prolong the duration of anagen. This is best seen during pregnancy when there is decreased hair shedding. Post-partum, large numbers of hairs enter catagen and subsequently telogen, which is followed by sometimes massive shedding, approximately 3 months after the birth, known as telogen effluvium gravidarum.
Thyroxine hastens the onset of anagen in resting follicles and corticosteroids delay it. There is also a seasonal variation on the rate of hair growth in man such that it grows faster in summer and falls in winter. It is mediated through the pineal gland but the exact mechanism is obscure.
In regions of the body other than the scalp anagen is relatively short and telogen relatively long (Table 1.1). At any given time up to half the follicles in a particular region will be dormant. Events that cause epithelial hyperplasia such as wounds will also initiate a new anagen in a resting follicle. Interestingly the inflammation of a ringworm infection synchronizes hairs into telogen in the area surrounding the lesions, thus limiting extension of the infection.
Cutting or shaving has no influence on the rate of hair growth or on the calibre of the hair produced by the follicle. Maximum hair length is genetically determined. It depends on the duration of anagen and the rate of growth. Hair will not achieve its maximum length if it is intrinsically weak or extrinsically damaged.
Changes in hair growth have been observed in skin affected by a variety of neurological abnormalities. Terminal hairs overlying a neural tube defect (faun tail) or around ectopic neural tissue on the scalp (the hair collar sign) are well recognized. Shorter hair was noted on the right side of the scalp in a patient with syringomyelia with impaired pain and temperature sensation in the region. Causalgia has been associated with decreased hair growth in affected areas, reflex sympathetic dystrophy may produce hypertrichosis, while denervation of skin can produce either decreased hair growth or hypertrichosis. The mechanism of these changes is not understood.
Physical properties of hair
Much information of the physical properties of hair has been derived from research on the keratin fibres in wool. The strength of human hair resides in the cortex where longitudinally orientated keratin fibres embedded in a sulphur rich matrix are packaged in cell envelopes. This composite structure allows hair to be deformed by mechanical stress and the energy dissipated evenly into the fibre at the fibre matrix interface. The cuticle also plays a vital role in hair resistance to external stress, as is evidenced by the relative fragility of weathered hair that has lost its cuticle.
Hair shaft dimensions show variation between races. Mongoloid hair is circular in cross-section and large with a mean diameter of 120 pm. Caucasoid hair is elliptical in cross-section and smaller. It has a mean diameter of between 50 and 90 um with the variation being due to the larger calibre of dark hair compared to fair hair. Negroid hair is flattened, curled and oval in cross-section. Longitudinal grooving is common. The different cross-sectional shapes of hair correspond to the flat straight appearance of Mongoloid hair, the wavy fuller bodied Caucasoid hair and the tightly curled Negroid hair.
When dry hair is rubbed or combed static electricity is produced. This is associated with 'fly away' hair. Certain shampoos and conditioners decrease fly away hair and lessen the static charge by reducing the frictional force during combing and increasing hair moisture.
Hair colour, canites and poliosis
Hair without pigment is white due to reflection and refraction of incident light. This is accentuated by a broad medulla as found in the hairs of many arctic animals. The variety of colours seen in animal hair is due to the combinations of pigments produced which include porphyrins, carotenoids and melanin. In contrast the range of human hair colour is limited as it is produced entirely by melanin within the keratinocytes of the cortex with a small contribution from the medulla.
Melanocytes present in the hair bulb at the apex of the dermal papilla are able to produce two types of melanin pigment; eumelanin which is responsible for black and brown hair and pheomelanin which produces auburn and blond hair. Pheomelanin is unique to hair and is not found in the epidermis. It is produced by a modification of the eumelanin synthesis pathway that involves an interaction of dopaquinone with cysteine. Usually an individual will only produce either pheomelanin or eumelanin throughout life, however, some people's hair colour changes spontaneously, and a number of blond children grow up to become brunettes.
Nonfunctional melanocytes are also present in the outer root sheath of the lower part of the follicle. They do not contribute to hair colour, but become involved in the repigmentation that occurs with resolution of vitiligo or with wound healing. Epidermal and hair melanocytes are independently involved in certain disorders. For example vitiligo can have pigmented hairs arising from depigmented skin. The reverse occurs in poliosis or canites, when hair turns grey.
Subtle variations in hair colour are due to variations in the number of melanocytes present in a follicle, the density of melanin formation within melanosomes and melanosome shape (oval melanosomes being more readily degraded), the transfer of melanosomes to hair matrix cells and the distribution and metabolism of the melanosomes within the hair cortex keratinocytes.
Melanocytes are only functionally active during anagen and lie dormant in telogen hairs. When anagen restarts, melanocytes reawaken and new melanocytes are produced by replication. Despite this proliferation of melanocytes, melanoma arising in the hair follicle does not seem to occur. Anagen hairs are usually uniformly pigmented. An exception to this is nose hair arising from the nasal mucosa,which have a nonpigmented 2-3 mm tip, that gradually darkens.
Hair colour varies according to the body site with eyelashes being darkest. Scalp hair is usually lighter than pubic hair which often has a red tinge. A red tinge is also common in axillary and beard hair even in people with essentially brown hair on their scalp. Sunlight bleaches hair, and after death hair is slowly oxidized which lightens the colour.
Hormones such as melanin stimulating hormone (MSH) can darken light hair as can oestrogens and progestogens during pregnancy. Drugs that can change hair colour include: antimalarials such as chloroquine, mephenesin, triparanol, butyrophenone and phenylthiourea that all produce lightening, while carbidopa, bromocryptine, minoxidil and diazoxide tend to produce darkening.
Inheritance of hair colour is complex and appears to be controlled by multiple loci in the genome. A putative gene locus for red hair has been identified, but awaits further confirmation.
Greying of hair, or canites
This occurs in both man and primates and is a manifestation of ageing. It is due to a progressive reduction in melanocyte function rather than number. Canites can occur prematurely in autoimmune disorders such as pernicious anaemia, vitiligo, the premature ageing syndromes progeria, pangeria and Down's syndrome; and rare metabolic disorders such as prolidase deficiency. In addition when vitiligo directly involves the scalp or hair bearing skin, depigmentation can occur within affected patches. Conversely darkening of the hair has been described in Addison's disease.
Greying commences in the third decade on the temples and spreads later to the crown and occiput. By the age of 50 years, 50% of the population have at least 50% grey hairs. Except in the earliest phases of canites and the early regrowth of alopecia areata (AA), greying is usually irreversible, however, there are anecdotal reports of repigmentation occurring following electron beam therapy and in porphyria cutánea tarda. Temporary repigmentation may also occur following large doses of paraamino benzoic acid.
Sudden overnight greying, as is reputed to have affected Marie-Antoinette on the eve of her decapitation, is due to a diffuse AA preferentially affecting the pigmented hairs.
Poliosis or piebaldism
This is a congenital, localized variant of albinism inherited as an autosomal dominant trait. The genetics have not yet been determined; however, affected individuals may be mosaic for the relevant gene. In the scalp there is a localized patch of white hair. The abnormality is due to either the absence of or a deficiency of melanin production in a group of neighbouring follicles. In addition pigment production is impaired in the surrounding interfollicular epithelium and melanocyte numbers appear to be reduced in affected skin and hair. While any part of the scalp can be involved, the most commonly affected site is the central frontal hairline of the forelock, and this may be the only manifestation. The white area often extends forwards to the base of the nose.
On the trunk and limbs there may be additional patches of depigmented skin that remain fixed. Islands of normally pigmented skin often occur within the hypomelanotic areas.
Poliosis has been associated with congenital perceptual deafness and this may be a forme fruste of Waardenburg's syndrome. Poliosis also occurs in up to 60% of cases of tuberous sclerosis and may be the earliest manifestation. A patch of poliosis overlying a scalp neurofibroma in Von Recklinghausen's disease has been described.
The opposite of poliosis, a black hair naevus, occurs as an isolated developmental anomaly.
Waardenburg's syndrome
This is the combination of a white forelock (present in 20%), lateral displacement of the medial canthi with dystopia canthorum, hypertrophy of the nasal root, confluent eyebrows, partial or total dyschromia of the iris, and perceptive deafness in about 20%. Abnormal patterns of hair growth, with a beard covering the entire cheeks and terminal hairs on the nose have been described as has premature canites.
Teitz's syndrome is a similar condition with generalized patches of white skin and hair associated with deafness and eyebrow hypoplasia. The Vogt-Koyanagi-Harada syndrome consists of bilateral uveitis, labyrinthine deafness, tinnitus, vitiligo, poliosis and AA. Alezzandrini's syndrome combines facial vitíligo, retinitis, and poliosis of the eyebrows and eyelashes.
Albinism
In both tyrosinase positive and tyrosinase negative autosomal recessive oculocutaneous albinism, the hair is yellowish-white in colour, although it can be cream, yellow, yellowishred or vibrant red on occasion.
Chediak-Higashi syndrome
This is an autosomal recessive defect of membrane-bound organelles in white cells, platelets and a variety of neuroectoderm derived cells including melanocytes. A lethal immune deficiency, oculocutaneous hypopigmentation, hepatosplenomegaly and lymphadenopathy occur as does an increased risk of lymphoma.
Phenylketonuria
Phenylketonuria, an inherited deficiency of phenylalanine hydroxylase, results in accumulation of the tyrosine precursor phenylalanine and a reduction in melanin formation. The skin is pale and the hair is fair.
Hair weathering
Hair weathering is defined as the microscopic changes in the hair shaft structure not seen at the root end and which become progressively more obvious or frequent towards the tip. It manifests as a progressive degeneration from root to tip of, initially, the cuticle, and later the cortex. Weathering occurs to some extent in all hairs allowed to grow long enough, in response to routine wear and tear.
Hairs with intrinsic structural defects are less able to withstand routine wear and tear and weather prematurely with the recognizable changes occurring close to the root. It is the proximity of these changes to the root that distinguishes these defective hairs from weathered hairs.
At the root end of normal hair, the cells of the cuticle are closely opposed to each other and to the underlying hair cortex. They are arranged with each cell partially overlapping the adjacent cell, akin to roof tiles.
In normal hair the earliest manifestations of weathering can be seen within a few centimetres of the scalp. Exposed to the vigours of a variety of cosmetic and environmental stresses, the free margin of the cuticle cells lifts up and breaks irregularly. Progressive scale loss leads to areas of the hair shaft that are totally denuded of cuticle. The exposed cortex is weak and fractures and produces nodes or frayed tips. Proximal to the terminal fraying, longitudinal fissures, otherwise known as split ends, may develop.
The tips of long hairs will have been subjected to considerable wear and tear and may show transverse fissures and nodes of the type seen in trichorrhexis nodosa. If the wear and tear has been excessive these changes will occur closer to the root, but rarely will they occur as close to the root as seen in the structural hair shaft disorders.
As weathering occurs to some extent in all hair, longer hair exhibits a greater degree of terminal weathering. Weathering is also modified by a number of factors that are listed in Table.
Hair patterns
Regional variations in hair pattern are related to age, genetic constitution and endocrine status. While eunuchs do not develop secondary body hair, and castration or hypogonadism of males results in a loss of body hair, there is not a direct relationship between the volume of body hair and the level of circulating free testosterone. In addition dark-haired people have both an increased amount and more noticeable body hair than their fair-haired counterparts.
Pubic hair
Three patterns of distribution of pubic hair based on the upper border of the pubic triangle have been described:
horizontal, acuminate and disperse. The horizontal pattern is found in 90% of women and 20% of males. The acuminate pattern is seen in 10% of women and 50% of men, while the diffuse pattern is generally only seen in middle-aged men with much terminal hair on their thighs and chest.
An acuminate pattern often reverts to a horizontal pattern in women following the menopause. A change to a horizontal from an acuminate pattern also occurs in men following oestrogen treatment for carcinoma of the prostate.
Chest hair
This appears in the normal male soon after puberty and continues to increase until the sixth decade. There is a wide individual and racial variation in the amount of hair developed. In about 20% of individuals with extensive chest hair, circular bare areas known as pectoral alopecia are present around the nipples. Such individuals frequently have accompanying hair on their shoulders and back.
Axillary hair
Terminal hair in the axilla usually appears 2 years after the first pubic hair, but there is much individual variation in this figure and axillary hair occasionally appears first. Mongoloids tend to have sparser hair than Caucasoids and it is not infrequently absent among older subjects of both sexes.
Most Caucasoids have a fairly extensive cover of hair over the extensor aspect of the arms. In about a quarter the hair is limited to the forearms and a small minority has no terminal hair.
The fingers tend to show hairs over the proximal phalanx, while in most people the middle phalanx is hairless. Hair over the proximal phalanx of the thumb and the middle phalanges shows individual and racial variation.
Peroneal alopecia
This refers to the bare areas over the anterolateral aspect of the lower leg It occurs in up to 35% of people and is probably unrelated to wearing socks, except that friction from socks may cause premature release of telogen hairs.
Trichoglyphics
Hair does not grow vertically but leaves the scalp at an angle that is precisely determined so that streams and patterns are formed. At certain sites the individual follicles are curved away from the axis of the emergent shaft to form whorls. Whorls and streams probably appear as early as 12 weeks gestation. They can be usually seen on the parietal region of the scalp, the inner canthus of the eye and other sites of skin depressions such as the axilla and back.
A single parietal whorl is seen in 95% of people and it is usually clockwise. The remainder have two or rarely three whorls. A frontal cowlick due to a counter stream of hair from the forehead is present in 7%. Abnormal scalp hair patterns with absent or aberrant whorls may be seen on the heads of children with abnormal brain development, such as microcephaly. Multiple scalp whorls are more common among mentally retarded children.
The ridgeback anomaly is due to the hair waves growing towards the vertex rather than the normal spiral away from the crown. It too may be associated with intellectual impairment.
Displacement of the scalp line occurs in a number of syndromes. A congenitally low anterior line occurs in Cornelia de Lange syndrome, lipoatrophic diabetes, fetal hydantoin syndrome and Rubinstein-Taybi syndrome, while a low posterior line occurs in Noonan's and Turner's syndromes. A congenitally high anterior line is seen in myotonic dystrophy.
Investigation of hair and hair follicle diseases
Accurate diagnosis of hair disorders is important for management. Even if therapy is limited for a specific condition, advice regarding the natural history of the condition, associated manifestations of the disorder and genetic counselling for hereditary disorders can be of enormous value to the patient.
Following clinical assessment of a disorder the clinician should have established whether the condition is congenital or acquired, diffuse or focal; and in the case of alopecia, scarring or nonscarring. Any associated abnormalities of skin, nails and teeth should be noted and if virilism is suspected a directed history, examination and biochemical investigations are appropriate.
The hair pull test is an easy method of confirming that abnormal hair loss is occurring and also its distribution. To do this test a clump of hairs are grasped at their base between the thumb and forefinger. Firm traction is then applied, being careful not to produce pain, as the examiner's hand slides along the hairs from the base to the tip. This can be repeated at various sites in the scalp. Normally 2-5 telogen hairs will be obtained after five or six passes done in this way, depending on when the scalp was last shampooed.
Telogen hairs can be recognized with the naked eye by their nonpigmented tip.
Except in loose anagen syndrome, protein calorie malnutrition, anagen effluvium, occult poisoning, and occasionally early diffuse AA, normally only telogen hairs should be obtained as normal anagen hairs are firmly anchored in the scalp. Occasionally patients swear their hair is falling out but a hair pull test is normal. In such cases it is valuable to ask the patient to collect all the hairs shed during the course of a day in the shower, sink, pillow, brush, etc. and to count them. The normal loss is less than 100 per day. In active telogen effluvium it can be several hundred per day.
In cases where one wishes to establish anagen/telogen ratios (a trichogram), for example, in attempting to differentiate androgenetic alopecia from telogen effluvium, a hair pluck should be performed. For accuracy the scalp should not be washed for 3-6 days before the procedure (as this removes telogen hairs) and at least 50 hairs should be plucked. The best instrument for this is a haemostat with the tips covered with rubber tubing. The hairs are grasped at the base and extracted with a sharp quick pluck, as slow traction deforms the morphology of the root and prolongs the discomfort.
The hairs can be mounted between two glass slides for microscopic examination either using double sided sticky-tape or cyanoacrylic glue that will allow the hair slide to be kept permanently for future reference. In the absence of glue, immersion oil can be used and gives a clear image as it has the same refractive index as glass. The normal scalp anagen to telogen ratio in children is over 90% while in adults it is approximately 85%. Dysplastic anagen hairs are a nonspecific finding in many alopecias and can be produced by slow extraction of the hair.
For fungal microscopy only half a dozen or so hairs need be plucked. If the suspected pathology is increased hair shaft fragility, it is important to examine both plucked and cut hairs to avoid over diagnosing artefacts from the act of plucking. Plucked hairs allow assessment of an abnormality in relation to its distance from the hair root. Any abnormality occurring within the first 2 cm is likely to be of intrinsic origin, while distal abnormalities will simply reflect extrinsic weathering.
The epiluminescence hand-held microscope (dermato-scope), more commonly used for examination of pigmented naevi, can also be of use (without the oil) in examining the scalp for hair shaft defects. In patchy disorders such as monilethrix the optimal site to obtain hair for microscopy can be determined. In addition the dermatoscope can be used with oil in the assessment of scarring alopecias.
Light microscopy of hair allows visualization of structures larger than 0.2 um and has a narrow depth of focus. Transmission electron microscopy gives very high resolution down to 2 nm and has a depth of focus of 100 nm. A diamond knife is required for cutting ultra-thin sections of hair without distortion, and the hair is then stained with a heavy metal such as gold to give anatomical detail. Scanning electron microscopy gives a wealth of information about surface architecture. However, for many conditions, sufficient diagnostic information is gained from light microscopy.
Polarized light microscopy gives additional information regarding the structural composition of the hair and makes fine structural abnormalities more obvious, but is not essential. Striking alternating dark and light bands (reminiscent of a tiger's tail) are seen on polarized microscopy in the sulphur deficient hairs of trichothiodystrophy.
Scalp biopsy relies on good technique to provide useful histological information. The site of biopsy is important, and the active edge of a scarring alopecia is likely to yield more information than the 'burnt-out' centre. Often multiple 3 or 4 mm punch biopsies are more useful than a single incisional biopsy. The biopsy should be angled in the direction of hair growth to avoid transecting hairs, and must include subcutaneous fat in order to include anagen hair bulbs. Because follicles in a biopsy specimen tend to bend before hardening, cross cutting is common. This can be avoided by placing the biopsy face down on a piece of cardboard, before putting it in the formalin. The scalp is very vascular and biopsies will usually need to be sutured. Horizontal processing often gives complementary information to the traditional longitudinal biopsy particularly regarding follicle type and density and anagen to telogen ratios, but requires an experienced pathologist for interpretation.
Scalp histology is necessary to establish the diagnosis in scarring alopecia and is also useful in trichotillomania and unexplained diffuse hair loss. It has also been used to determine the potential for regrowth in long-standing apparent nonscarring alopecias. Elastin stains are useful to assess scarring. Immunofluorescence of fresh or frozen tissue should be performed if lupus erythematosus or a bullous disorder is suspected.
The psychological importance of hair
An appreciation of the special psychological significance of the hair is important for those involved in the assessment and management of diseases of the hair and scalp. Hair is central to our perceptions of beauty and attractiveness. Either too little hair on the scalp or too much hair on the face of a woman can make her feel unattractive, self-conscious and miserable. It is not uncommon for such people to be and feel stared at in public and as a consequence shy away from personal contact. Perhaps the greatest testimony to the importance of hair is the time and money spent in hairdressing salons around the world and the multibillion dollar annual turnover of the hair cosmetic and trichology industries. Disorders of hair frequently produce profound anxieties out of keeping with their objective severity or physiological importance.
The association of hair with attractiveness can be confirmed by even the most superficial surveys of the visual arts, literature and advertising in magazines. Unfortunately fashion magazines portray an inaccurate stereotype for women, and this contributes to the common misconception that women do not go bald.
Many societies associate shaving of the head with celibacy or chastity, as seen in monks and nuns of Buddist and Christian faith as well as Hindu priests and women. Covering the hair among Catholic nuns and in Muslim and orthodox Jewish society has a similar connotation. Today shaving the head may be simply a fashion statement.
Some societies cut women's hair as punishment for adultery. Similar punishment was handed out in Europe after the Second World War for women who had consorted with soldiers of occupying armies.