Hair shaft disorders

INTRODUCTION — Hair shaft disorders are a diverse group of congenital and acquired abnormalities of the hair shaft. Some hair shaft disorders cause fragility of the hair shaft leading to increased hair breakage; others lack fragility but alter the appearance or texture of the hair. Hair shaft disorders can occur independently or in association with genetic or acquired diseases.

The causes, features, and prognosis of various hair shaft disorders will be reviewed here. An overview of the evaluation of patients with hair loss is provided separately. (See "Evaluation and diagnosis of hair loss".)

GENERAL PRINCIPLES — The hair shaft is composed of multiple layers, including the medulla, cortex, and cuticle. The medulla, a loosely packed region near the center of the hair, may be continuous, discontinuous, or absent along the length of the hair shaft even in the same individual. Its function is not known, but it contains mitochondrial DNA. The medulla is surrounded by the cortex, which contains keratin proteins and structural lipids. The medulla and cortex are surrounded by a cuticle, a protective layer of overlapping cells that envelop the hair. Genetic disorders, diseases, or environmental factors can lead to changes in the properties of these structures, resulting in fragility or alterations in hair shaft texture, appearance, or manageability.

Most hair shaft disorders are not curable. Some may improve over time or with treatment of the underlying cause. In general, patients with hair fragility should avoid physical or chemical trauma to the hair to reduce additional hair breakage and loss.

PATIENT EVALUATION — Hair shaft disorders may present with short, sparse, and/or brittle hair that seems to grow poorly or hair texture that differs significantly from the hair texture of the patient's family members or ethnic/racial group. The diagnosis usually can be confirmed through review of the patient history, physical examination, and a magnified examination of hair shafts.

The evaluation should include a thorough history of hair loss with particular attention to the age of onset and family history. Many hair shaft disorders begin in infancy or early childhood, and, depending on the disorder, there may be a family history of similar findings. In addition, knowledge of the patient's hair care routine may be helpful. For example, trichorrhexis nodosa, a common hair shaft disorder, can result from physical, chemical, or thermal hair care practices. (See "Evaluation and diagnosis of hair loss", section on 'Patient interview'.)

The physical examination should include a careful examination of the scalp and hair to identify signs of hair fragility. Hair fragility can be assessed through grasping a small cluster of hair shafts and tugging in opposite directions [1,2]. In addition, looking at the distal ends of hairs against a piece of paper of contrasting color (eg, dark-colored hair on white paper) assists with visualizing the blunt tips characteristic of broken or cut hairs [2]. (See "Evaluation and diagnosis of hair loss", section on 'Physical examination'.)

The physical examination should also include an assessment for features suggestive of alternative causes of hair loss. Examples include signs of scalp inflammation (scale, erythema, inflamed papules, pustules) or smooth patches of complete hair loss. In addition, teeth, nails, and the remaining skin should be examined to detect abnormalities that may be seen in conditions associated with specific hair shaft disorders. (See "Evaluation and diagnosis of hair loss", section on 'Physical examination'.)

Magnified examination of the hair shaft is critical for the diagnosis of hair shaft disorders. Light microscopy or dermoscopy of the hair (also known as trichoscopy) is often sufficient for diagnosis. Electron microscopy is an additional diagnostic tool that can be helpful for visualizing hair shaft abnormalities in challenging cases. Techniques for light microscopic and dermoscopic examination are reviewed separately. (See "Evaluation and diagnosis of hair loss", section on 'Microscopic examination' and "Overview of dermoscopy of the hair and scalp".)

DISORDERS WITH FRAGILITY — Fragility of the hair is characterized by weakening or breaks along the hair shaft. Hair shaft disorders that lead to fragility include trichorrhexis nodosa, pili torti, monilethrix, trichorrhexis invaginata, and trichothiodystrophy.

Trichorrhexis nodosa — In trichorrhexis nodosa, hair shaft fragility is related to the presence of weakened points along the hair shaft called nodes. Fracture of the hair at these nodes leads to characteristic splaying of the hair shaft (figure 1).

Etiology — Trichorrhexis nodosa is often related to external factors that damage the hair shaft, such as heat, blow drying, and hair styling. The condition can also be associated with rare genetic diseases and other disorders. Examples of associated diseases include:

●Argininosuccinate lyase deficiency (argininosuccinic aciduria) [3]

●Argininosuccinate synthetase deficiency (citrullinemia)

●Biotin deficiency

●Hypothyroidism

●Hypotrichosis type 7

●Kabuki syndrome [4-6]

●Menkes disease [7,8] (see "Overview of dietary trace elements", section on 'Menkes disease')

●Trichohepatoenteric syndrome [9]

●Trichothiodystrophy types 1 and 4 (see "Autosomal recessive congenital ichthyoses", section on 'Trichothiodystrophy')

In addition, trichorrhexis nodosa may occur in conjunction with other hair shaft abnormalities that make the hair shaft weak, such as monilethrix and trichorrhexis invaginata. (See 'Monilethrix' below and 'Trichorrhexis invaginata' below.)

Clinical features and diagnosis — Patients with trichorrhexis nodosa exhibit hair that is sparse, short, dull, and brittle. Examination of the hair shaft with light microscopy reveals splayed areas that resemble two brushes or brooms pushed together (picture 1). Similar changes can be viewed on dermoscopy or electron microscopy (picture 2). Trichorrhexis nodosa related to damaging hair styling practices often affects the distal portion of the hair shaft.

Trichorrhexis nodosa found at birth or within the first six months of life should prompt investigation for an underlying metabolic disorder, ectodermal dysplasia, or hypothyroidism. (See 'Etiology' above.)

Prognosis — Trichorrhexis nodosa related to external factors will improve with reduced trauma to the hair shaft (ie, gentle hair care). Treatment of medical causes may also lead to improvement.

Pili torti — Pili torti is characterized by flattening of the hair shaft at irregular intervals and twisting of the hair shaft approximately 180 degrees on the long axis (figure 2).

Etiology — Although often an isolated defect, pili torti can occur in association with various conditions. Examples include:

●Abnormal hair, joint laxity, and developmental delay (HJDD; OMIM #261990)

●Anorexia nervosa [10]

●Autosomal recessive congenital ichthyosis type 11

●Bazex syndrome

●Biotin deficiency

●Björnstad syndrome [11,12]

●Ectodermal dysplasias (including ectodermal dysplasia-syndactyly syndrome 1, Rapp-Hodgkin syndrome [13] trichodysplasia-xeroderma syndrome) (see "Ectodermal dysplasias")

●Hypotrichosis type 6 [14]

●Menkes disease [15]

●Retinoid therapy [16]

●Trichothiodystrophy

Clinical features and diagnosis — Hair is short, lusterless, hypopigmented, and feels rough (picture 3A-B). In infants with congenital pili torti, hair is often a dull blonde or dull light brown color that grows poorly. Examination with light microscopy or dermoscopy shows hair shafts bent at different angles at irregular intervals (picture 4).

Prognosis — Pili torti often improves after puberty and, for patients with Menkes disease, when they receive copper therapy. Treatment of other underlying disorders may also lead to improvement.

Monilethrix — Monilethrix, also known as "beaded hair" or "necklace hair," exhibits regular thinning of the hair shaft resulting in a beaded appearance (figure 3).

Etiology — Monilethrix is a genetic disorder caused by autosomal dominant mutations in keratin genes (KRT81, KRT83, KRT86) and autosomal recessive mutations in the desmoglein 4 gene (DSG4) [17-19]. There is also a rare association with Holt-Oram syndrome (TBX5 gene) [20,21].

Clinical features and diagnosis — Hair is normal at birth and then becomes short and brittle within first year of life. Sparse hair is noted all over, but accentuation of low-density hair is present on the occipital scalp (picture 5). Eyebrows and eyelashes may also be affected. Perifollicular hyperkeratosis is a consistent feature, and keratosis pilaris on the face, arms, and legs is common. Nails may exhibit koilonychia.

Light microscopy and dermoscopy show regular thinning of the hair shaft that is described as beaded (picture 6A-B).

Prognosis — Monilethrix is usually stable; however, there are reports of improvement with pregnancy and in adulthood. Case reports describe marginal benefit of etretinate [22] and improvement during treatment with acitretin [23]. In a case series of four patients, use of 2% minoxidil for one year appeared to increase the number of normal hair shafts [24]. Improvement during treatment with low-dose oral minoxidil is also documented in case reports [25].

Trichorrhexis invaginata — Trichorrhexis invaginata, also known as "bamboo hair" or "golf tee hair," occurs when the distal shaft intussuscepts the proximal shaft creating a "ball and socket" appearance (figure 4).

Etiology — Trichorrhexis invaginata occurs in Netherton syndrome, a rare autosomal recessive congenital ichthyosis, and is usually present from infancy. Netherton syndrome results from mutations in the serine protease inhibitor of Kazal type 5 gene (SPINK5). Examples of other features of Netherton syndrome include congenital ichthyosiform erythroderma, atopic diathesis, and ichthyosis linearis circumflexa (picture 7A-B) [26]. (See "Netherton syndrome".)

Clinical features and diagnosis — Trichorrhexis invaginata usually manifests as short, brittle scalp and eyebrow hair (picture 8A-B). Light microscopy, electron microscopy, or dermoscopy will show the characteristic "ball and socket" appearance (picture 9) [27,28]. Often, only a small percentage of hairs exhibit this finding. The lateral eyebrows are a good location to detect abnormal hairs. (See "Netherton syndrome", section on 'Hair abnormalities' and "Netherton syndrome", section on 'Hair examination'.)

Prognosis — Trichorrhexis invaginata and the associated hair fragility generally do not improve over time.

Trichothiodystrophy — Trichothiodystrophy (TTD) is a disorder that results in sulfur deficiency in the hair. There are eight types that are autosomal recessive and one type that is X-linked dominant (TTD type 5) [29]. Affected hair exhibits trichoschisis (transverse fractures of the hair shaft and a light and dark alternating pattern when viewed under polarizing light) (figure 5) [30,31]. (See "Autosomal recessive congenital ichthyoses", section on 'Trichothiodystrophy'.)

Etiology — There are both photosensitive and nonphotosensitive forms of TTD. Most photosensitive forms of TTD result from mutations in DNA repair, such as ERCC2, ERCC3, and GTF2H5 [32,33]. In nonphotosensitive TTD, pathogenic variants in the AARS1, GTF2E2, MARS1, MPLKIP, RNF113A, and TARS1 genes have been identified [33-37].

Clinical features and diagnosis — Hair is short and brittle, including eyebrows, and nails are short and spoon shaped (picture 10). Patients often display ichthyosis and intellectual and developmental delay. They can also display decreased fertility, ocular abnormalities, short stature, and infections.

Trichoschisis can be visualized with light microscopy (picture 11). Alternating bands of light and dark can be seen on polarized light microscopy or polarized light dermoscopy (picture 12) [38]. The term "tiger-tail banding" is used to refer to this pattern. Electron microscopy shows a defective cuticle.

Prognosis — In general, hair abnormalities do not improve over time.

HAIR SHAFT DISORDERS WITHOUT FRAGILITY — Hair shaft disorders not typically associated with fragility include pili annulati, pili bifurcati, pili multigemini, woolly hair, and uncombable hair.

Pili annulati — Patients with pili annulati exhibit light and dark banding of the hair shaft (figure 6). This finding is related to clusters of air pockets in the hair shaft that appear brighter than regularly pigmented hair. There are a few reports of pili annulati with fragile hair [39-42].

Etiology — Pili annulati is usually an autosomal dominant disorder with no other associations. The genetic defect has been mapped to chromosome 12q24.32-24.33 [43]. In addition, pili annulati has occurred in patients with alopecia areata, primary immunoglobulin A deficiency, and other autoimmune disorders [44]. Pili annulati in association with Rothmund-Thompson syndrome is described in a case report [45].

Clinical features and diagnosis — Hair appears as multiple colors and shimmers due to banding of the light and dark areas.

Light microscopy or dermoscopy can detect the characteristic banding (picture 13). Electron microscopy is rarely necessary to see this finding.

Management — Pili annulati is a chronic condition with no effective treatment. Hair growth is normal, and many individuals consider the appearance of hair favorable.

Pili bifurcati — Pili bifurcati is characterized by bifurcation of the hair fiber at irregular intervals (figure 7) [46]. Each branch has its own cuticle.

Etiology — Pili bifurcati is rare and has been reported in the setting of telogen effluvium, pili canaliculi, monilethrix, pseudomonilethrix, mosaic trisomy 8, or protein deficiency [47,48].

Clinical features and diagnosis — Hair is thin and short on the scalp, eyebrows, and eyelashes.

Light microscopy, dermoscopy, and electron microscopy reveal bifurcation of the hair shaft [47].

Prognosis — Pili bifurcati is typically a transitory defect of the hair shaft that resolves.

Pili multigemini — Pili multigemini is characterized by the presence of multiple hairs with their own cuticle emerging from the same follicle opening (figure 8).

Etiology — Pili multigemini is often an incidental finding [49]. Occurrence in association with cleidocranial dysostosis has also been reported [50].

Clinical features and diagnosis — Pili multigemini is most often diagnosed on the beards of men or scalp of children. Affected individuals have patchy, short, irregular hair. Folliculitis can be present around the hair tufts, particularly in the beards of men.

Dermoscopy or trichoscopy is helpful for visualizing multiple hairs emerging from the same follicular opening. Electron microscopy shows multiple distorted hair shafts (each with its own normal cuticle) within a common root sheath [51].

Prognosis — Pili multigemini is a chronic condition with no clear effective treatment.

Woolly hair — Woolly hair describes a group of congenital hair shaft disorders characterized by fine but tightly coiled/curled hair (figure 9).

Etiology — Woolly hair can present with or without associated cardiomyopathy. The autosomal dominant non-cardiomyopathy-associated form is associated with a missense mutation in keratin 71 or keratin 74. Autosomal recessive hypotrichosis type 7 and 8 may also present with woolly hair without cardiomyopathy [52]. Mutations in keratin 25, lipase H, and lysophosphatidic acid receptor 6 have been identified [53-56]. There is one report of woolly hair in association with epidermolysis bullosa with mottled pigmentation [57].

Disorders with cardiomyopathy and woolly hair include arrhythmogenic right ventricular dysplasia, Carvajal syndrome, and Naxos disease, which are associated with desmocollin 2, desmoplakin, and plakoglobin pathogenic variants, respectively [58-60]. These disorders may also present with palmoplantar keratoderma. (See "Arrhythmogenic right ventricular cardiomyopathy: Pathogenesis and genetics", section on 'Autosomal recessive disease and Naxos disease' and "Palmoplantar keratoderma".)

Cardiofaciocutaneous syndrome has also been associated with woolly hair.

Clinical features and diagnosis — Woolly hair may present as diffuse, tightly coiled/curled hair on the scalp. Alternatively, patients may have woolly hair nevi, which are localized, well-demarcated patches of tight, curly hair surrounded by normal-caliber hair (picture 14). Localized involvement is typically an isolated finding without associated disorder [61].

On examination with light microscopy, dermoscopy, or electron microscopy, there are waves or curves in the hair shaft that give an appearance of a moving snake (figure 9).

Prognosis — Tightly curled hair is most prominent during childhood. For many, it improves over time.

Data on treatment are limited. In one series, three men with autosomal recessive woolly hair had partial improvement after treatment with a nonablative fractional laser [62]. In an open-label study, all eight individuals with autosomal recessive wooly hair/hypotrichosis associated with LIPH pathogenic variants who were treated with 2% topical minoxidil for one year had improvement in hypotrichosis [63].

Uncombable hair — Uncombable hair, also known as "spun glass hair," exhibits pili trianguli et canaliculi, triangular-shaped hair shafts with a longitudinal groove (figure 10) [64,65]. The shape and the varied direction is related to abnormal keratinization of the internal root sheath.

Etiology — Most occurrences of uncombable hair are sporadic. However, there are autosomal dominant and autosomal recessive variants. Genes implicated in the autosomal recessive variants include PADI3 (peptidylarginine deiminase 3), TGM3 (transglutaminase 3), and TCHH (trichohyalin) [66,67]. The genetic basis for autosomal dominant inheritance is unknown.

Associated disorders have included uncombable hair in the setting of ectodermal dysplasia [68]. Case reports describe occurrences in a child with a yolk sack tumor and a child with neurofibromatosis type 1 [69,70].

Clinical features and diagnosis — Uncombable hair presents in infancy or early childhood with hair that is dry, curly, and lighter in color than other family members' hair (picture 15). Hair grows in many different directions and cannot be tamed with combing or brushing. Growth is not inhibited.

Electron microscopy can be used to confirm the diagnosis and shows irregularly shaped, triangular shafts (picture 16). Dermoscopy and light microscopy will reveal canal-like longitudinal grooves in the hair shaft.

Prognosis — Patients tend to experience some improvement with age. One report describes the use of biotin with improvement [71].

PATIENT SUPPORT — Hair disorders and hair loss can be distressing. Affected patients may benefit from access to resources for information and support. Examples of resources that may be helpful include the American Hair Research Society and the National Organization for Rare Disorders.

SUMMARY AND RECOMMENDATIONS

●General principles – Hair shaft disorders include a variety of congenital or acquired abnormalities of the hair shaft. Some hair shaft disorders result in fragility of the hair; others result in altered appearance or texture of the hair. Hair shaft disorders may occur independently or in association with genetic or acquired diseases. (See 'Introduction' above and 'General principles' above.)

●Disorders with or without hair fragility – Examples of hair shaft disorders resulting in fragility include monilethrix, pili torti, trichorrhexis invaginata, trichorrhexis nodosa, and trichothiodystrophy. Hair shaft disorders that generally do not have associated fragility include pili annulati, pili bifurcati, pili multigemini, woolly hair, and uncombable hair syndrome. (See 'Disorders with fragility' above and 'Hair shaft disorders without fragility' above.)

●Diagnosis – The diagnosis of a hair shaft disorder is made through review of the history of hair loss, physical examination, and magnified examination of hair shafts. Light microscopy, dermoscopy, and electron microscopy are utilized for magnified examination of hair shafts. (See 'Patient evaluation' above.)

●Prognosis and management – Most hair shaft disorders are chronic; some disorders exhibit some improvement over time or with treatment of the underlying cause. Individuals with disorders associated with hair fragility should avoid physical or chemical trauma to the hair shaft to reduce hair breakage and hair loss. (See 'General principles' above.)