Hair Shaft Disorders in Children – An Update

Abstract

Disorders of hair shaft are a diverse group of congenital and acquired abnormalities of the hair that can pose a diagnostic and therapeutic challenge to the dermatologists. Hair shaft abnormalities can occur as an isolated phenomenon or can be associated with an underlying genetic syndrome. Any change in the texture, appearance, and growth of the hair should prompt evaluation of the patient for the presence of any hair shaft anomaly. The diagnosis can be suggested by a complete history and physical examination of the hair-bearing areas as well as other ectodermal structures (nails and teeth). A key feature in the evaluation of hair shaft defects is to determine the fragility of the hair shaft that can be elucidated by performing the “tug test.” Trichoscopy and light microscopy serve as valuable tools in establishing the specific type of hair shaft disorder. An update of the approach for the diagnosis and management is included in this review.

Introduction

Hair is an ectodermal structure that develops from the epidermis. Keratins and the keratin-associated proteins constitute the major biochemical components of the hair. Hair has no vital function, yet it may serve as an indicator of human health. Clinical and morphological abnormalities of hair can be clues to specific disorders.^[1] During the hair cycle, many different cell types are incorporated to form the medulla, inner root sheath, hair cuticle, and cortex. Changes in the properties of these structures from genetic disorders, diseases, or environmental factors result in alterations in the appearance, texture, growth or manageability of the hair shaft.^[2]

Hair shaft diseases in children can occur independently or in association with genetic or acquired diseases. The diagnosis usually can be confirmed through patient’s history, physical examination, and magnified examination of the hair shafts. Light microscopy and trichoscopy are often sufficient for the diagnosis of hair shaft disorders.

Disorders of the hair shaft can be broadly divided into groups with and without increased fragility [Table 1]. Graphic representations of various hair shaft disorders are illustrated in Figure 1.

Table 1: Classification of hair shaft disorders

Figure 1: Graphic representation of various hair shaft disorders

Approach to a patient with hair shaft disorder

The evaluation should include a thorough history of hair loss, the age of onset, and family history. Many hair shaft disorders begin in infancy or early childhood, and depending on the disorder, there might be a family history of similar findings. Examination includes the general appearance, color, lustre, length, curl, and the pattern of the hair abnormality – diffuse or focal. Hair fragility can be determined by looking for broken hairs and performing a tug test [Figure 2] by holding the hairs several centimeters from the hair tip and then tugging at the ends. If the hair is fragile, short 2–4-mm hair fragments will break off easily and the distal ends of hairs, against a piece of paper of contrasting color, assist the visualizing of the blunt tips characteristic of broken or cut hairs.^[2,3]

Figure 2: A tug test to assess hair shaft fragility

Because invasive procedures in the pediatric age group are cumbersome, trichoscopy serves as a simple, effective, non-invasive, rapid but expensive tool that helps in analyzing the structure and size of the hair shaft, allowing simultaneous examination of multiple scalp hairs and other hair-bearing sites without the need for plucking them. It not only improves the diagnostic accuracy but also helps in evaluating treatment response photographically at each follow up visit [Figure 3].^[4] It can be performed in nonpolarized, polarized contact, or noncontact modes. Trichoscopy helps to differentiate between monilethrix and pseudomonilethrix and to visualize the perifollicular abnormalities that can be missed by light microscopy alone. Trichoscopy gives comparable results to light microscopy while diagnosing pili torti, trichorrhexis nodosa (TN), woolly hair (WH), and pili annulati (PA). Trichothiodystrophy (TTD) is the only hair shaft disorder where simple trichoscopy is insufficient for making the diagnosis. However, polarizing transilluminating trichoscopy has been introduced as a new method for the diagnosis of TTD, precluding the need for microscopic examination.^[5]

Figure 3: Trichoscopy using videodermoscope

Light microscopy of hair serves as a valuable bedside tool for the diagnosis of various hair and scalp disorders. The hair needed for microscopy is either clipped or plucked and a wet or a dry mount is prepared for the examination. It is a simple, economically feasible tool requiring minimal training and is minimally invasive. However, it usually requires a sample of 50 hairs. Nevertheless, Netherton syndrome (NS) is an exception in which repeated samples of hairs may be needed to confirm the diagnosis as most diagnostically useful hairs are short and are often missed by forceps. In such cases, trichoscopy serves as a method of choice.

Other investigations that can support the diagnosis include serum and urine analysis for amino acids and trace elements, and genetic testing. Algorithmic approach to diagnosis of various hair shaft disorders is shown in Figure 4.^[2]

Figure 4: Algorithmic approach to diagnose hair shaft disorders

Disorders with increased fragility

• 1) Monilethrix: Monilethrix, also known as “beaded hair” or “necklace hair,” is characterized by periodic thinning of hair shafts at regular intervals with a tendency to fracture at constricted sites. The defect lies in the constricted regions, whereas the nodes correspond to the normal hair caliber.^[6] It can be inherited as an autosomal dominant disorder with mutation in type 2 hair keratin genes KRT 81, KRT 83, and KRT 86, or as an autosomal recessive disorder with mutations in desmoglein 4 (DSG4) gene.^[7] The temporal and occipital areas of the scalp show the typical hair shaft abnormality. Patients present with short and fragile hair in early childhood and often do not seem to require a haircut. Various perifollicular abnormalities ranging from subtle perifollicular erythema to large hyperkeratotic follicular papules may be present.^[8] Eyebrows, eyelashes, body hair, axillary, or pubic may also be affected.^[2]
• Trichoscopy shows features of multiple beaded hair with regularly placed nodes and internodes.^[4] The big yellow dots correspond to horny follicular papules and keratotic follicular plugs with perifollicular scaling may also be observed.^[8] “Regularly bended ribbon sign” is a term that helps to differentiate monilethrix from pseudomonilethrix and other causes of hair loss. Light microscopy shows the beaded appearance of the hair.^[9] The constrictions lacking medulla may show evidence of fracture, whereas nodes have a medulla and a normal hair diameter.^[2] The conditions in which monilethrix-like hair can be seen are enumerated in Table 2.^[8]
• Monilethrix often persists into adulthood but may improve at puberty. Treatment with oral etretinate, oral acitretin, topical tretinoin, and topical minoxidil has been tried with variable results.^[10]
• 2) Trichorrhexis nodosa: In trichorrhexis nodosa (TN), hair shaft fragility occurs because of the presence of weakened points, nodes, along the hair shaft that break leaving brush-like ends. Clinically, the hair appears brittle and dry with a tendency to break at various lengths.^[8]
• TN can be classified into a primary congenital form, TN associated with syndromes, and acquired TN.^[9] It is often caused by factors that damage the hair shaft, such as heat, blow drying, and hair styling, but can also be associated with other conditions [Table 3].^[8] TN found at birth or within the first 6 months of life should prompt investigation for an underlying metabolic disorder, ectodermal dysplasia (ED), or hypothyroidism.
• Trichoscopy reveals gray white areas corresponding to the nodes, and a peculiar paintbrush bristle appearance can be seen [Figure 5a].^[4] Light microscopy shows fracture with splaying out resembling two brushes or brooms pushed together [Figure 5b].
• Treatment is limited to management of the underlying disorder. Acquired TN has a fair prognosis because limiting trauma to hair shaft prevents disease progression. TN associated with citrullinemia, argininosuccinic aciduria, and biotinidase deficiency can be treated with specialized diets introduced in infancy.^[9]
• 3) Pili torti: The term, pili torti, refers to twisted hair. There is flattening of the hair shafts at irregular intervals associated with 180° twisting around the long axis. Although mainly scalp hair is affected, other hair-bearing sites may also be involved. Hairs are dry and brittle with a tendency to break before they grow long. The classic early onset form (Ronchese type) is seen in early childhood and may be associated with ectodermal abnormalities. It typically affects females born with either normal or abnormal hair that is replaced with easily broken and spangled hair. Also, the color of the hair is lighter.^[8]
• The late onset (Beare type) is inherited as autosomal dominant and occurs after puberty; frequently associated with dark hair. Various inherited diseases and syndromes may be associated with pili torti.^[11] Acquired pili torti may be because of repetitive trauma to hair shaft, oral therapy with retinoids, and cicatricial alopecia.^[8]
• Trichoscopy shows multiple twists along the hair shaft creating a helix-like pattern and twisting of the hair shafts at irregular intervals and different angles [Figure 6a].^[12] Light microscopy demonstrates thin hair with 180° twisting of the hair shafts and flattening at irregular intervals [Figure 6b].^[13]
• There is no definitive treatment other than managing the underlying disorder. The late-onset type often improves at puberty. Administration of subcutaneous copper histidinate in an infant with Menke’s disease for 2 months was found to darken the hair color. In biotin-deficient individuals, life-long supplementation with 30–100 mcg/day of biotin is adequate.^[10]
• 4) Trichorrhexis invaginata: Trichorrhexis invaginata (TI), also called bamboo hair, occurs by invagination of the distal hair shaft into the proximal hair shaft creating a ball in a cup appearance.^[14] It manifests as brittle, sparse, and short scalp and eyebrow hair. It occurs in NS that is characterized clinically by the triad of ichthyosis linearis circumflexa [Figure 7a], atopic diathesis, and trichorrhexis invaginata.
• Trichoscopy shows multiple irregularly placed small nodules along the shaft, and at high magnification, a ball-in-cup appearance can be seen [Figure 7b]. The proximal cupped end can be seen after the fracture of distal end (golf tee sign). Recently, matchstick hairs seen as short hair shafts with a bulging tip have been described in a patient with NS.^[15] Trichoscopy of the eyebrows can easily demonstrate trichorrhexis invaginata and golf tee hairs. Diagnosis of NS can be made by identifying at least one hair shaft with trichorrhexis invaginata.^[8]
• Treatment includes oral acitretin, low dose oral steroids, etretinate, psoralen ultraviolet A therapy, topical tacrolimus, and lactate lotion 12%.^[9]
• Ongoing clinical trials of immunotherapies for NS include anti-TNF-α monoclonal antibody (Adalimumab), anti-IL-17A antibody (Secukinumab), and anti-IL-4Rα antibody (Dupulimumab). Specific KLK5 and/or KLK7 inhibitors are novel disease-modifying treatments. Gene therapies such as gene addition approaches aiming at restoration of LEKTI expression using viral vector and siRNA-mediated silencing of genes encoding pro-inflammatory mediators are being developed. A non-integrative gene therapy consisting of HSV-1-mediated delivery of SPINK5 cDNA by topical application on affected skin is currently in preclinical development.^[16]
• 5) Trichothiodystrophy (TTD): TTD refers to cysteine-deficient brittle hair. The clinical presentation may vary from isolated defect of hair shaft to a more severe form with intellectual disability, developmental delay, recurrent infections, and even death in early childhood.^[10] A new clinicogenetic classification of TTD includes three types of disease^[17]:
• • (1) Photosensitive TTD, with mutations in genes encoding transcription factor IIH subunits,
  • (2) Non-photosensitive TTD, with TTDN1 mutation, and
  • (3) Non-photosensitive TTD, with no mutation in the gene encoding TTDN1 with no identified genetic basis.
• In TTD, scalp hair, eyelashes, and eyebrows are unruly, brittle, and of variable lengths. On light microscopy, the hair shafts appear wavy and undulated. Trichoschisis (with or without TN) and ribboning can be occasionally seen. The basis for diagnosis is examination by polarized light microscopy showing the characteristic “tiger tail banding” that refers to the alternating bright and dark bands. Pertinently, the diagnosis should be made if all hair shafts exhibit the tiger tail pattern. A recently described trichoscopic finding in TTD is broken hair and the “Glomerular sign” that refers to glomeruli-like curls and twists of broken hair that possibly occur because of the presence of overlying scales blocking the way of fragile soft hair of TTD.^[18] In contrast to simple trichoscopy, polarizing transilluminating trichoscopy reveals the characteristic light and dark bands of TTD and may replace polarized microscopy in the diagnosis of TTD.^[5] The diagnosis can further be confirmed by the amino acid analysis of the hair showing reduced cysteine content.
• Prognosis is poor and does not improve with age.^[10] There is no definitive treatment. Underlying genetic abnormalities in individuals with TTD and photosensitivity reduce the cell’s intrinsic repair mechanisms and thereby increase the susceptibility to damage. Thus, they should avoid UV radiation.^[19]
• 6) Bubble hair: Bubble hair is an acquired disorder caused by thermal injury to the hair shaft. Hair dryers functioning at 175°C or more and hair curling tongs operating at 125°C and applied to the hair, and chemical treatments are known to induce bubbles in hair fiber.^[20] Application of too much heat converts water in the hair fiber into steam, causing expansion of the spaces within the hair shaft thereby turning the hair into a spongy structure. These bubbles destroy the integrity of the hair shaft thus leading to weak and brittle hair.

Table 2: Hair disorders with monilethrix like hair on trichoscopy

Table 3: Diseases associated with trichorrhexis nodosa

Figure 5: (a) Trichorrhexis nodosa. Trichoscopy showing nodular thickenings (blue arrow), and longitudinal splitting of the hair shafts leaving brush-like ends (yellow arrow; Dino-lite AF115ZT, non-polarized ×70) (b) Microscopic examination (×40) showing fracture with splaying out of hair fibers resembling two brushes or brooms pushed together

Figure 6: (a) Pili torti. Trichoscopy showing 180° rotated and flattened hair shafts at irregular intervals (yellow arrows; Dino-lite AF115ZT, non-polarized × 70) (b) Light microscopy (×40) shows twists at irregular intervals along the hair shaft

Figure 7: (a) Trichorrhexis invaginata. Icthyosis linearis circumflexa in a case of Netherton syndrome (b) Trichoscopy showing bamboo hairs with characteristic invaginations (blue arrows). The hair shafts fracture easily leaving cupped (invaginated) ends (yellow arrow; Dino-lite Edge, non-polarized ×60.5)

Clinically, hair appears broken off, kinky, and may develop localized alopecia over time. The hair appears to “come out in clumps,” with textural changes varying from soft, curly to straight and stiff.^[20]

Electron microscopy reveals loss of medulla and cortical cells. Cross-section may reveal either a single large cavity or a reticulated “Swiss cheese-like” loss of cells.^[20] Trichoscopy may show dysmorphia of the distal hair shaft in bubble hair.

Disorders without increased fragility

• 1) Pili annulati (PA): PA, or “ring hair,” is an autosomal dominant disorder characterized by the presence of alternating white and dark bands (rings) within the hair shafts. The gene locus for PA has been mapped to chromosome 12q24.32-24.33. The bands are because of the presence of air-filled gaps in the cortex.^[8,21] It manifests at birth or during infancy and clinically presents as shiny spangled or speckled appearing scalp hair.^[9] Hair in the scalp area is most commonly affected, although axillary, pubic, and beard hair may also be affected. Although most cases are not associated with fragility, there are reports of few cases with fragility.^[22,23] There are some reports of association between primary immunoglobin A deficiency and autoimmune thyroid disease in patients with PA.^[24]
• On trichoscopy, alternating white and dark bands in hair shafts can be seen in both blond and dark hairs. These light-colored bands cover 50–100% of the hair shaft thickness.^[8] Light microscopy of hair shafts also shows alternating light and dark bands. As light does not pass through the air-filled gaps in the cortex, the abnormal spaces appear dark under a light microscope. Conversely, the bands appear white macroscopically and in trichoscopy as the abnormal areas reflect more light.^[8]
• PA has an excellent prognosis, and treatment is usually unnecessary.^[25]
• 2) Pili bifurcati (PB): In PB, bifurcation of the hair fiber occurs at irregular intervals. Each branch has its own cuticle. PB is rare and has been reported in the setting of telogen effluvium, pili canaliculi, monilethrix, pseudomonilethrix, mosaic trisomy 8, or protein deficiency. Hair is short and thin on the scalp, eyebrows, and eyelashes.
• Light microscopy, trichoscopy, and electron microscopy reveal bifurcation of the hair shaft.
• PB is usually a temporary defect that resolves with basic hair care. Topical 2% minoxidil application for 3 months has shown significant improvement in case of PB and pseudomonilethrix.^[26]
• 3) Pili multigemini: In pili multigemini, multiple hairs of similar thickness arise from the same follicular opening.^[27] Clinically, patches of short and irregular hairs can be seen.^[28] Trichoscopic examination shows two hair shafts of different sizes with separate cuticles emerging through a single hair canal. The condition occurs because of kinetic papilla splitting at the upper end from single tipped to double tipped during anagen.^[28,29] Perifollicular erythema and peripilar cast around each tuft are also noted.^[27] In adults, the beard is commonly affected, whereas the scalp is involved in children.^[28] Cleidocranial dysostosis is associated with this disorder.^[26] The cause of PM is unknown, but there are some reports that hypothesize a genetic link.^[28]
• Staged excision or laser treatments lead to excellent prognosis.^[26] A long-pulsed fixed Q alexandrite lambda ruby laser (694.2 nm) at a fluence of 17.8 J/cm² has been found to reduce the number of multigeminate hairs and associated folliculitis.
• 4) Woolly hair (WH): WH is a group of hair shaft disorders characterized by tightly curled, short, and kinked hair [Figure 8a].^[30] Hutchinson and colleagues classified the condition into three variants [Table 4]^[8]:
• • (1) Woolly hair nevus,
  • (2) Autosomal dominant woolly hair (hereditary woolly hair), and
  • (3) Autosomal recessive woolly hair (familial woolly hair).
• WH can be associated with fatal cardiomyopathies such as Carvajal syndrome or Naxos syndrome when accompanied by palmoplantar keratoderma.^[31]
• WH may be an isolated finding or may be associated with additional signs and symptoms. Congenital ichthyosis, keratosis pilaris, Noonan syndrome, cardiofaciocutaneous syndrome, nail dystrophy, osteoma cutis, and severe neurologic disorders are reported with WH.^[9] Trichoscopy shows variable thickness of hair shafts, kinking, irregular shaft diameter, and “crawling snake” appearance of the hair shaft [Figure 8b].^[32] Light microscopy reveals TN, 180° longitudinal twisting, ovoid cross-sections, and PA. WH mostly manifests during childhood and the appearances can improve with age.^[33] Treatment with non-ablative fractional lasers was found to stimulate normal hair growth in autosomal recessive WH.^[34]
• 5) Uncombable hair syndrome – UHS (Pili trianguli et canaliculi): Most reported cases of UHS are sporadic, but autosomal dominant and autosomal recessive inheritance have also been reported.^[9] Mutations occur in genes involving PADI3 (peptidyl arginine deiminase 3), TGM3 (transglutaminase 3), and TCHH (trichohyalin).^[35] Hair shaft analysis has found no consistent physical or chemical abnormalities in UHS, although some studies have demonstrated high sulfur protein content in exocuticle and decreased solubility of abnormal fibrous proteins in the hair shaft. The disorder is thought to arise from a triangular-shaped inner root sheath that undergoes premature keratinization. Others postulate that the longitudinal grooves arise from an asymmetric defect in the matrix. It most often presents in infancy or early childhood in the form of dry curly blond hair. The hairs have a spun-glass appearance and usually resist all efforts of styling [Figure 9a]. Hair grows normally and is not fragile.^[9] Several conditions reported in association with UHS are ectodermal dysplasia, juvenile cataract retinal dysplasia/pigmentary dystrophy, tooth enamel anomalies, oligodontia, phalango-epiphyseal dysplasia, and digital abnormalities.
• The definitive diagnosis of UHS requires scanning electron microscopy. Light microscopy reveals light pigmented hairs and flattened surface or very shallow grooves lacking periodicity [Figure 9b].^[36] The prognosis is good, expected to improve with age, and there is no definitive treatment.^[26] Oral biotin supplementation (5 mg/day) has been hypothesized to strengthen hairs by altering hair matrix and has been used to manage uncombable hairs.^[37]
• 6) Trichonodosis: Trichonodosis is a common yet rarely reported hair shaft disorder and is characterized by knotted hair on the hair shaft.^[38] It can occur spontaneously as well as secondary to mechanical factors such as vigorous scratching or combing the hair. There may be abnormal scalp and body hair growth. On combing or brushing the hair, the knots usually get caught in fine-toothed combs and less commonly in hair brushes. Light microscopy of the hair shaft shows knotted portions of hair and trichoschisis also has been observed in some cases.^[38]
• 7) Ectodermal dysplasia (ED): ED is a large group of disorders described by dysplasia of two or more ectodermal structures (hair, teeth, or nails) [Figure 10a]. The main dermatological features in patients having ED are hair shaft abnormalities.^[8,39] Scalp hair in these patients is often thin, sparse, dry, lightly pigmented, curly, and brittle. The various hair shaft anomalies observed include TN, pili torti, trichoschisis, pili canaliculi, TTD, or monilethrix-like hair [Figure 10b].^[39]
• 8) Trichoptilosis: Trichoptilosis refers to splitting or fraying of the distal end of the hair shaft in response to trauma. The use of curling irons, excessive hair-coloring agents, pulling a comb forcefully through tangled hair, and repeated combing may lead to longitudinal fracture of the distal end of the hair shaft into two or several divisions [Figure 11]. TN may also coexist. The split commences from the distal tip thus differentiating it from PB or multigemini.^[40]

Figure 8: (a) Woolly hair. Short, sparse, and lightly pigmented hair over the scalp.(b) Trichoscopy showing “crawling snake” appearance (yellow circle; Dino-lite Edge, non-polarized ×70)

Table 4: Classification of woolly hair disorders

Figure 9: (a) Uncombable hair syndrome. Dry frizzy blond hair that stand from the scalp surface (b) Light microscopy (×10) showing lightly pigmented hair shaft with a longitudinal groove

Figure 10: (a) Ectodermal dysplasia. A case of 5-year-old with ectodermal dysplasia (b) Trichoscopy showing pilitorti (180°) twisting of hair shaft (blue arrow; Dino-lite Edge, non - polarized ×74.3)

Figure 11: Trichoptilosis: Light microscopy (×10) showing distal end of the hair shaft having longitudinal splitting

Conclusion

Hair shaft disorders can be evaluated and diagnosed by following a systematic approach. Proper history and examination help in classifying the disorders into two main categories: hair shaft disorders “with increased fragility” and “without increased fragility.”

There is no definite cure for hair shaft disorders. Some may improve over time or after treating the underlying cause. Patients with hair fragility can prevent hair breakage and hair loss by avoiding physical or chemical trauma to the hair. Recently, trichoscopy has emerged as an important bed-side non-invasive tool, aiding in the diagnosis of inherited and acquired hair shaft disorders. The ability to accurately identify the type of hair shaft disorder enables clinicians to initiate proper therapy and could provide clues for the presence of an underlying genetic disorder.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.