Trichorrexhis Nodosa

Investigation: When numerous fibers are affected, small white spots are easily seen on the hair with the naked eye and can be confirmed with a hand lens. Transmitted or plane polarized light microscopy shows characteristic focal burst along the fiber or brush breaks where the node has parted. Additional observations should be made of the apparently normal parts of the fiber to rule out any predisposing conditions, such as piliannulati or pilitorti, that may previously have gone unnoticed.

While it is important to exclude any underlying pathology or metabolic changes, it is unlikely that a patient who previously had normal hair will have developed significantly weaker hair. It must be remembered that where trichorrhexis nodes appear toward the tips on longer fibers, that part of the hair was actually formed many months before the patient presented with trichorrexhis nodosa. It is, therefore, unlikely that a fundamental fiber weakness has “grown in.” It is most probable that the trichorrehexis nodes are a result of cosmetic practices. These practices may create only minimal damage to the fiber. However, the combination of insults and insuffi cient care may result in catastrophic fiber damage. In order to understand the severity of a patient’s cosmetic regimen it may be useful to measure the distance from the scalp to the fi rst onset of trichorrhexis nodosa as an indication of how long the best part of the fiber can withstand the current level of trauma. It is probable that a chemical (permanent wave) or thermal (tongs) insult is indicated in the process. The current fashion trend for perfectly straight hair has spawned a number of treatments and straightening irons that claim to be good for the hair. The author has observed an increase in trichorrhexis nodosa among young females who are seemingly “wedded” to their straightening irons.

Permanent Changes in Hair Shape

Two main practices are involved in permanently changing the shape of individual fibers, i.e., permanent waves and relaxers. While different chemistry is used by these two processes, both have a similar clinical impact on the fiber.

Permanent waves, generally used to increase curls, are based on alkaline ammonium thyoglycollate. This reduces disulphide bonds in the cuticle and cortex and allows hydrogen peroxide to reform bonds in their new position. As covalent bonds adopt new positions, the extensive network of salt bridges and hydrogen bonds do so as well. Although the process and formulations are quite different, it should be remembered that thyoglycollates are also the bases for effective depilatories. When used for hair removal the reductive step is left to progress further and is not neutralized by hydrogen peroxide. There are a number of recorded cases of severe hair breakage following permanent waves, no doubt caused by poor control of the reductive step.

Straightening or relaxing techniques are designed to remove curls. These processes use high-pH sodium or guanidine hydroxide. Those that use the latter are termed no-lye relaxers. Most relaxers are used to straighten curly hair, in which case the term relaxer is something of a misnomer. It suggests the hair is in perhaps a “less stressed” state than before! In order to straighten the hair it must also be pulled straight to form its new shape, so straight hair is not a relaxed state of a curl. Relaxers or straighteners require additional tension to pull the fiber straight on already weak hair, and may also involve the use of hot irons resulting in hair that is particularly weak but far from relaxed. One should remember that high concentrations of sodium hydroxide are a useful tool for dissolving hair for analytical tests. Relaxers left on for too long can certainly cause widespread hair breakage close to the scalp as well as extensive scalp irritation.

Both permanent waves and relaxers remove the f-layer from the fiber and damage intercellular cements. In addition, changes in the extractable proteins and amino acid profiles are always evident. These combined effects result in fibers that are hydrophilic, of reduced tensile and torsional strength, are prone to tangling, and show an increased rate of weathering.

Hair High-Lift Bleaches

The peroxide blonde hair color worn by Marilyn Monroe cannot be achieved with hydrogen peroxide alone. The addition of ammonium persulphate, which is usually supplied as a powder, is required to completely decolorize melanin and achieve the platinum blonde effect. This process causes damage of a much higher magnitude than conventional permanent colors and hence the degree of haircare must be suitably increased.

Permanent colors and high-lift bleaches are biologically aggressive treatments that are well-tolerated by the hair when utilized properly. Problems such as hair breakage and strawlike appearance can result from a lack of understanding of how the hair is changed by these processes. A patient with shoulder-length hair will require treatments once every six to eight weeks. As a result, the ends of the fibers will have experienced significantly more chemical and physical insult compared to the roots.

Permanent Hair Coloring

The aim of this section is to look at the changes induced in the hair fiber by coloring processes and not the detailed chemistry of hair coloring. However, a brief overview gives a greater understanding of how and why the fundamental structure of the fiber is affected. Permanent hair colors result in a change to the natural color of hair that, although subject to fading, will only be completely lost when the hair is cut or re-colored. This class of products also includes products designed to lighten, or bleach, the natural color of hair. Permanent colorants typically contain three components: two for coloring and one for conditioning. To change the natural color of hair the following steps must occur: (i) remove or lighten the natural hair color, i.e., with bleach melanin, and (ii) form new colors (dye couples) within the hair cortex. To achieve the color, low pH hydrogen peroxide (developer) is mixed with high pH dyes (tint). The activated or alkaline hydrogen peroxide both bleaches melanin in the cortex and develops the new colors from the tint. In particular, blonde shades are not simply achieved by bleaching melanin and they require the formation of new dye colors to offset red and brass tones left by the incomplete degradation of melanin.

As alkaline hydrogen peroxide diffuses through the fiber it encounters transition metal ions that occur naturally in hair, as well as those acquired from the environment, e.g., copper absorbed from tap water. Rapid degradation of peroxide forms the highly damaging and nonspecific hydroxyl radical.

A fundamental challenge to the colorant formulator is accessing and decolorizing melanin that occurs only in the cortex while minimizing damage to the rest of the fiber. This presents two problems. First, alkaline peroxide must travel through the cuticle and will cause damage en route. Second, the path of the peroxide is not specific to melanin. Due to the relatively low concentration of melanin in Caucasian hair there is a greater chance that the peroxide will interact with the hair structure and damage the proteins in the cortex than that it will interact with melanin. As a result, permanent hair colors cause measurable damage to the tensile and torsional properties of the hair fi ber. Of greater importance is the effect on the hair surface. All unmodified cuticle cells are covered in a covalently bound fatty acid on the outer aspect of the cell. The fatty acid 18-methyl eicosanoic acid, termed the f-layer (4), is readily cleaved by perhydrolysis, which changes the surface of the cell from hydrophobic to hydrophilic. The consequence of this change is two-fold. First, when the hair is wet the hair fibers are held tightly together by films of water. This makes the hair difficult to detangle. Second, many conventional silicone-based conditioners, which are typically hydrophobic in nature, fail to deposit on the hair and as a result provide little or no protection.

Fortunately, the level of damage is relatively low and can be managed as is evidenced by the numerous examples of individuals with long hair who have used colorants multiple times. But it is essential for patients to understand that the hair is changed by the coloring process and, while its appearance is enhanced its properties are altered. Failure of patients to increase conditioning, which will counteract these changes, will lead to rapid weathering and breakage and is often typified by trichorrhexis nodosa. The patient must be encouraged to reduce the frequency of coloring and the amount of styling, while greatly increasing the amount of conditioning.

Hair Conditioning Agents

Conditioning hair is critical to its sustained integrity as it inevitably weathers over time. Chemical and physical processing remove the outer lipid coating (the f-layer) and result in amino acid degradation in the cortex of up to 50%.

Conditioners are substances that increase the manageability, shine, and moisture content of each hair shaft. Modern products are designed to provide one or more of the following functions: increase the ease of wet and dry combing; smooth, seal and realign damaged areas of the hair shaft; minimize porosity; impart sheen and a silken feel to hair; provide some protection against thermal and mechanical damage; moisturize; add volume and body; and eliminate static electricity. Dry, woolly hair generally requires heavier deposits of conditioners than other hair types. The use of leave-in or “intensive” conditioners is growing. The use of moisture-retaining ingredients (humectants) such as panthenol, can be augmented by cationic ingredients (e.g., polyquarternium derivatives), which leave hair manageable.

Treatment with polymeric conditioning agents that bond to the hair at points of damage also aid in improving resistance to breakage.

Regular conditioning contributes significantly to the preservation of the external architecture and internal chemistry of each hair shaft. Frequent chemical processing makes conditioning even more important.

Hair Moisturizing Shampoos

The latest generation of shampoos, designed for dry hair, can include essential oils such as petrolatum as well as the surfactant systems described above. They are orientated toward those with hair of African origin or hair that is excessively dry. They leave the hair feeling moisturized and easy to comb. These products are also designed to help weathered and colored hair.

Originally there were no shampoos specifically designed for African hair. The prevailing belief was that a shampoo was a shampoo, and that anything available in the general market could be used for all hair types. However, African hair benefits from shampoos that contain mild cleansing agents (detergents) that help detangle the hair and are pH balanced in the range of 4.5–5.5. Shampoos formulated for other hair types may not help to detangle hair sufficiently, contributing to combing damage. Variants for African hair can be purchased in North America and Southern Africa.

Haircare Regimens

A hair-care regimen can vary from zero to six products a day. While previous generations may have had nothing and relied solely on grooming, in an increasingly competitive society, the prolonged wearing of unwashed, matted, and neglected hair is considered unusual at the very least.

In some developed societies, bar soaps for washing the scalp, particularly among men, are still common. These harsh anionic surfactant systems are not just poor cleansers, but also lead to extensive calcium salt buildup in the hair and reduced grooming capability.

Daily shampooing alone can be harmless to the hair shaft, and in itself can improve the ability to groom and style. Haircare products, in comparison to skin care are inexpensive and ubiquitous.

Hair Shampoos

Modern high-quality shampoos have evolved from agents that once merely and harshly removed grease (sebum), perspiration, environmental dirt, and dead corneocytess. In the twenty-first century they contain agents that enhance the natural beauty of hair and mitigate the damage inflicted by the owners.

Shampoos consist of three major components: primary surfactants for detergency and foaming power, secondary surfactants to improve and condition the hair, and additives that complete the formulation and add special aesthetic effects. The surfactants or detergents act by removing the dirt from the hair with a lipophilic component and transferring it to the rinse water with hydrophilic component.

Haircare

The “care” of hair is of greater social importance than perhaps is immediately apparent. It is a key component of the so-called “physical attractiveness phenomenon” and is the last aspect of our appearance we attend to in the mirror as we leave for work or play.

Advice on haircare is an increasingly frequent part of the dermatologist/trichologist’s role. Patients with diffuse hair loss, the recovering alopecia areata, and post-chemotherapy patients all rightly expect cosmetic advice as part of holistic management.

In recent decades, haircare products have been transformed from the functional but often unpleasant, to versatile and creative and quality-of-life enhancing. A haircare regimen includes a basic cleansing and conditioning product often with a number of variants to meet consumer needs. These products are generally used separately, and conditioning usage is much less than shampoo. Combination, or 2-in-1, products developed by Procter and Gamble in the late 1980s delivered for the first time cleansing and conditioning benefi ts from a single bottle.

Regimen ranges were classically designed for three hair types: normal, dry, or damaged hair. Subsequent generations of products were created to deliver a desired end-benefit, such as “smooth and sleek,” “perfect curls,” and “color radiant.” A range of styling products to create long-lasting styles has also emerged to complement the cleansing and conditioning products. These can enhance or alter most common aesthetic styling problems. Foremost among these is the control of “volume,” either too little or too much. Managing frizzy hair is important and products for so-called “ethnic” hair are emerging.

Hair and Ethnic Allegiance

The wearing of dreadlocks is very closely associated with ethnic allegiance, has biblical associations (Leviticus 21:5), and is in deliberate opposition to the straighter hair of Caucasian persons. Interestingly, dreadlocks are no longer exclusive to people of direct African descent. Indeed there are ascetic groups within nearly every major religion that have at times worn their hair in this fashion. The way to form natural dreadlocks is to allow hair to grow in its natural pattern, without cutting, combing, or brushing, and washing it with pure water.

During the 1960s and 1970s, Black Power and other black pride movements in the United States brought about the emergence of the Afro hairstyle. Men and women grew their hair out to significant diameters away from their head as a rejection of Eurocentric standards of beauty, an embracing of African heritage and roots, and a confirmation of the idea that “Black Is Beautiful.”

The Afro is sometimes texturized so that it is not in its true African state, but slightly relaxed with a frizzier and more wiry appearance that springs out. Eventually, this hairstyle grew away from its political and cultural connotation and was embraced by the mainstream. Afros became popular even among those with loosely curled hair.

Other hairstyles often worn by people of African descent are cornrows and braids, two styles that survived in the African diaspora. While recent years have brought about a movement among women of African descent to wear their hair naturally, most in the Western world have their hair relaxed or straightened (Fig. 21).

Celebrity Hair

Hairstyles in the West have been greatly influenced by changing fashions for generations. For the moneyed classes, wigs were worn until the advent of World War I. Elizabeth I transformed Europe for redheads, who had hitherto been reviled. Many stained-glass representations of Judas depict him with red hair. Balding royalty, most notably Louis XIV, drove a wig culture for a time. Civil wars and religion have influenced fashions with the long curling locks of the royalist Anglican Cavaliers and the cropped hair of the parliamentarian Puritan Roundheads. The portraits of Flemish artist Sir Anthony Van Dykes influenced facial hairstyles in the late seventeenth century.

In the 1890s the Gibson Girl’s pompadour was combed over a pad, making a high wide frame for the face, and swept up behind. Heated irons, such as the waving iron invented by the French hairdresser Marcel Grateau in the 1870s, allowed women to achieve curls, crimping, and the natural-looking Marcel wave. In the twentieth century the broad reach of print and electronic media increasingly influenced the world of fashion, including hairstyles. In Asia, permanent hair dyeing is epidemic—not always to best effect (Fig. 20).

Long Hair

In the ancient world, long hair and long-haired wigs were the province of aristocracy. Sumerians and Persians powdered, curled, crimped and dyed their hair, and the horse-borne barbarians who overran Europe in the Middle Ages wore long fl owing locks and beards.

In Africa, where hair frequently denoted sex and status, the Massai males wore their hair waist-length, whereas, women and noncombatants shaved their heads.

Chinese and Japanese women traditionally wore long hair, possibly under a bandeau or worn as a knot, which might be decorated. Unmarried girls signified their status with long plaits. In Japan, the introduction of pomade in the seventeenth century led to the familiar sweep, arranged with combs, bars, ribbons, and ornamental hairpins, which revealed the nape of the neck.

In Muslim cultures, the hair was and still is frequently concealed in public. In many parts of the world a henna rinse is common. In the fifteenth century, fashionable ladies of northern Europe plucked their hairline to make their foreheads seem higher and scraped their hair back under an elaborate pointed or wired headdress.

In the twenty-first century, when hair fashions are so driven by celebrity, long hair in the West is associated with young females and males of an artistic bent. Unlike the rebellious 1960s and 1970s, long hair is now uncommon as a male phenomenon.

Short Hair

Short hair has obvious benefits. In Classical Greece and Rome, where hairdressing matured into a public service, hair was worn short and was a clear sign of civilization in comparison to the barbarian neighbors. This trend persisted in Europe until the thirteenth and fourteenth centuries when pageboy styles emerged as part of an aristocratic fashion. The clerical puddingbasin, ear-revealing style of the early fifteenth century was superseded by a longer pageboy style—rough in the north and coiffured in Italy. By contrast, in Mesoamerica Inca chiefs wore relatively short hair, and commoners wore progressively longer hair.

The French Revolution and the accompanying militarism induced short styles for both men and women. Women classically adopted short curls that framed the face or smooth plaits around the head. They also wore colored wigs.

In the industrial nineteenth century, among the emerging middle class, men wore short curled and dressed hair with a moustache, sideburns, or beard. The exigencies of the World Wars, particularly World War I, prompted a return to short hair and loss of facial adornment, which apart from the counterculture of the 1960s established a norm that has persisted into the twenty-first century.

In the West, women cut or “bobbed” their hair as a symbol of their political and social emancipation after World War I. This trend was followed by a succession of celebrity-inspired short, head-clinging hairstyles. The permanent wave, invented by the German Charles Nessler around 1905, offered styling to the masses. In the same vein, the invention of rollers for waving made possible the very short, layered Italian look. In the 1960s the availability of natural-looking hair pieces in the form of full wigs, half wigs, or long falls, at all prices, enabled almost every woman to own one or more to suit her taste and mood.

Shaved Hair

In pharaonic Egypt, hair was often shaved, especially among children, where long hairstyles would prove uncomfortable or parasites, such as head lice, were a problem. Wigs were the privilege of the ruling classes, a trend that recurred for the next 5000 years as evinced by the fashionable courts of Europe and the British judiciary.

Shaved heads may also indicate a religious sect or aspiration. Buddhist monks shave their heads as a renunciation of the world, and Muslim men may wear a single long lock of hair on their otherwise shaved heads to evince hair’s religious signifi cance. As a rite of passage, Hindu males shave their heads when they reach adolescence. The Manchu of China left only a braided queue residue as a mark of submission, which became a mark of dignity and manhood. As a tribal signal, pre-Columbian Native Americans in eastern North America were sometimes entirely shaven, save for a ridge, or comb, of hair along the crown. Plains Indians wore two long plaits.

The habit of shaving has persisted into the twenty-fi rst century. Shaving hair has similarly been imposed on residents of military and penal institutions and World War II female collaborators. This act implies diminution of status (the Samson effect).

Function of Human Hair

The function of human hair is, curiously, unresolved. Hypotheses vary: Is it a relic of the hypothetical aquatic phase of human development where a pelage would be an impairment? Is hair an integral adaptation for thermoregulation and ultraviolet protection, a mere adornment, or the result of Fisherian runaway sexual selection? All these theories can be disproved not least by the tendency for humans of both sexes to bald.

Hair may and often is interpreted as a marker of age, healthy nutrition, and fecundity. In its styled form it is employed in all societies to express social status or cultural affi liation. Hair in most cultures is at its zenith on the wedding day as a mark of health, wealth, and sexual attraction. By contrast, sociological studies have revealed the full impact of so-called bad hair days, where subjective and objective negative assessment of hair may reduce self-esteem.

Adaptive Changes in Hair Morphology

Since Africa is the home of humankind, it is appropriate to commence here with a discussion of hair morphology. “African” phenotypes show as much diversity as do their genotypes. The classical hair of equatorial Africa is also seen in equatorial regions of Indonesia and Australia. This type of hair is tightly coiled, with a thick appearance and feel. Curiously, some Indo-Europeans also express this phenotype (Fig. 7).

Many of the populations of northeastern Africa have looser, less tightly coiled hair than most other Africans. Andamanese peoples, the Negrito, are phenotypically African but are in fact a recent Asian branch. Their small stature, heavily pigmented skin, and tightly coiled hair represent a recent adaptation to equatorial existence. Melanesian peoples express the same traits. Late African phenotypes are thinly spread throughout the world. Indigenous Australian peoples exhibit the same phenotype and some Aboriginal infants are born with blonde hair.

Wooly hair syndrome is a condition affecting a small percentage of persons of IE and Asian heritage. It is characterized by extremely frizzy and wiry hair that looks almost wooly in appearance. Wooly hair is a rare defect in the structure of scalp hair. This hair is either present at birth or appears during the fi rst months of life. The curls, with an average diameter of 0.5 centimeter, lie closely together and usually make the hair diffi cult to comb. In addition, the hair may be more fragile than usual. The syndrome usually lessens in adulthood, when wavy hair often takes the place of wooly hair.

The difference between wooly hair in Africans and the hair found in non-Africans with the syndrome is that African hair lies typically separate and is tightly coiled or spiraled, while the curls of the latter tend to merge. This type of hair often only covers portions of the scalp.

Hair Color

Hair color is determined by the melanocytes found only in the matrix area of the follicle at the base of the cortex directly above the follicular papilla. Melanocytes transfer packages of melanin (melanosomes) to the cortical cells during anagen. Eumelanin is the dominant global pigment and confers black/brown hair. Pheomelanin, a mutation of eumelanis, is the predominant pigment found in blonde or red hair. Graying of hair is a normal manifestation of aging and illustrates progressive reduction in melanocyte function. The proportions of eumelanin and pheomelanin and the total amount of melanin determine the fi nal natural color of the hair.

Black and dark brown hair are the prevalent natural hair colors of peoples of all regions, accounting for more than 90% of all human hair. Dark hair is characterized by very high levels of the dark pigment eumelanin.

Blonde hair frequency is reported as 1.8% worldwide. Blonde hair is characterized by low levels of the dark pigment eumelanin and higher levels of the pale pigment pheomelanin. Shades range from light brown to pale blonde. In certain European populations, the occurrence of blonde hair is more frequent, and often remains throughout adulthood, leading to misinterpretation that blondeness is a uniquely European trait. Based on recent genetic information, it is probable that humans with blonde hair became more numerous in Europe about 10,000 to 11,000 years ago during the last ice age, as a result of Fisherian runaway mechanisms. Prior to this, early Europeans had dark brown hair and dark eyes, as is predominant in the rest of the world. In humans of many ethnicities, lighter hair colors occur naturally as rare mutations, but at such low rates that it is hardly noticeable in most adult populations. Light hair color is commonly seen in children, and is curiously common in children of the Australian Aboriginal population.

Lithuania has the highest percentage of people with blonde hair. Bleaching of hair is common,
especially among women. Bleached blonde hair can be distinguished from natural blonde
hair by exposing it to ultraviolet light, as heavily bleached hair will glow, while natural blonde
hair will not.

There are no comparable data for red hair, but in the areas of obvious frequency (the fringes of Western and Eastern Europe) it is at a maximum of 10%. In Scotland, 35% of the population carries the recessive gene for red hair. Eighty percent of redheads have the melanocortin-1 receptor gene anomaly. Controversial estimations of the original occurrence of the red-haired gene at 40,000 years ago are probable.

Red hair is associated with the melanocortin-1 receptor, which is found on chromosome 16. Red hair may be an example of incomplete dominance. When only one copy of the red-hair allele is present, red hair may blend with the other hair color, resulting in different types of red hair including strawberry blonde (red-blonde) and auburn (red-brown).

Hair Follicle Morphogenesis

Hair follicle appendage formation involves a complex sequence of signals between the dermal mesenchyme and the overlying epithelium. The precise initiating stimulus is still to be defined. Morphologically, induction, organogenesis and cytodifferentiation phases can be determined, and a division of hair follicle formation events into eight distinct developmental stages in rodents and humans can be made. The development of human hair follicles first starts between the 8th and 12th weeks of gestation. Probably in response to dermal signaling elements, which are expressed in gradients over the developing fetus, thickening of the primitive epithelium forms placodes that induce the aggregation of underlying dermal cells to mesenchymal condensates – the first visible stage in hair follicle development (Fig. 1.1). The very first hair follicle placodes are seen in the eyebrow, upper lip, and chin regions. Placode formation subsequently expands in a wave caudally and ventrally over the skin of the fetus. The dermal condensates issue instructions to the cells of their associated overlying ectodermal placodes to proliferate and initiate penetration of the dermis; stage 2 of development. As the epithelial cells grow downwards into the dermis, the dermal condensate cells lead the way. The hair follicles grow into the dermis at an angle to the skin surface, with the degree of angle determined by the location of the hair follicle. The initial placode formation stage gives way to an early peg stage (stage 3) hair follicle. By 12–14 weeks’ gestation, the epithelial base of the hair pegs on the scalp invaginates to envelop the dermal cell condensates and form dermal papillae. This stage of development is described as the bulbous hair peg stage, or stage 4 in development.


In stage 5 at 13–16 weeks’ gestation, the superficial portions of the hair follicles subsequently develop two distinct, asymmetrical bulges of cells on the “posterior” side of the follicle, which is at an obtuse angle to the skin surface. The upper bulge closest to the skin surface eventually forms the sebaceous gland, while the lower bulge forms the location of the presumptive follicular stem cells and will later anchor the developing arrector pili muscle to the hair follicle. The arrector pili muscle itself develops independently of the hair follicle and is usually first seen in the dermis near the developing sebaceous gland. The arrector pili muscle grows downwards to connect with the bulge region as the follicle pushes deeper into the dermis. Notably, the arrector pili muscle does not develop in hair follicles growing perpendicular to the skin, such as eyelash hair follicles, follicles of the external auditory canal, and those of the nasal orifice. The outer cells of the bulge, destined to become the sebaceous gland, proliferate and some differentiate into lipogenic cells that progressively accumulate lipid. Maternal hormones cause sebaceous gland hypertrophy and temporarily increase the synthesis and secretion of sebum during the second and third trimesters. With release under the influence of maternal hormones at birth, the sebaceous glands become relatively quiescent until endogenous hormone production increases in puberty. In humans, some hair follicles will develop a third superficial bulge of cells above the cells destined to become the sebaceous gland. The development of this third bulge of cells indicates the formation of an apocrine gland. In humans the face and scalp are the most common locations for hair-follicle-associated apocrine gland development. While hair-follicle-associated formation of apocrine glands can be common in other mammalian species, in humans the association is relatively infrequent.

In the second trimester, the hair follicles differentiate to eventually form the seven layers of cells in concentric cylinders seen in mature hair follicles. Beginning near the bulb at the end of stage 4 or at the beginning of stage 5, a core of epithelial cells separates from the peripheral epithelial cells which later become the outer root sheath, continuous with the non-follicular epithelium. The epithelial cell core, resting on the top of the dermal papilla, further differentiates into the inner root sheath Henle, Huxley, and cuticle layers, and the central core of matrix cells that proliferate and give rise to the hair fiber cuticle, cortex and, later in terminal hairs, the medulla. Stage 6 is defined by the visible development and growth of the hair fiber. As the hair fiber and its inner root sheath elongate, the peripheral epithelial cells move aside to allow the cone of the central core of cells to move upwards away from the bulb. By 19–21 weeks’ gestation, the developing hair follicles reach stage 7, in which the hair canals form. In stage 8 the hair follicles are fully formed and the first hair fibers erupt from the skin. The initial lanugo hair of the first anagen hair growth phase grows until 24–28 weeks of gestation.