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loose anagen syndrome

What is loose anagen hair syndrome

Loose anagen hair syndrome is a rare benign hair disorder in which the hair is ‘loose’ and can be easily and painlessly pulled out from the scalp. Essentially, hairs are not anchored into the scalp properly with no known cause; as a result affected patients have a ‘bed head’ appearance and hair that doesn’t seem to grow. Most of the hair is in the anagen phase and lacks an external epithelial sheath. Hair grows back quickly and the condition improves spontaneously with aging. Loose anagen hair can be associated with other anomalies, such as coloboma. Most often loose anagen syndrome has been classically described in children, predominately blonde girls, though this condition has even been reported occasionally in adults. However, recent literature has suggested that a diagnosis of loose anagen syndrome should be considered in all children of all skin types who have characteristic features. There is some evidence that loose anagen syndrome is possibly an inherited condition, but this has not been confirmed. The classic patient with loose anagen syndrome is a girl aged 2-5 years with blonde hair; however, cases of loose anagen syndrome in boys, in adults, and in individuals with dark hair have also been reported. Loose anagen hair syndrome diffuse hair loss must be distinguished from other types of non-scarring alopecia and may account for up to 10% of cases of childhood alopecia 1.

Loose anagen hair syndrome should be suspected in people with sparse fine hair that is able to be painlessly removed from the scalp without effort, and often tangled hair at the back of the head. There is no inflammation or scarring present on the scalp. Diagnosis is made is made by microscopic examination of pulled hairs. This shows ruffled hair cuticles (outer layer of hair), sometimes described as a rumpled sock or hockey stick, which differ from the normal smooth and straight cuticles in unaffected patients. Rarely, even the eyebrow has been reported to be affected by loose anagen syndrome.

Loose anagen hair syndrome has an estimated incidence of 2 cases per million per year and is either spontaneous or inherited in an autosomal dominant pattern with incomplete penetrance 2. Loose anagen syndrome has been reported overwhelmingly in white persons. Most but not all are light complexioned with fine blond hair. However, it may be rarely evident in individuals of African or Asian descent 3.

Loose anagen hair syndrome has been categorized into 3 groups:

  1. Loose anagen syndrome type A presents with sparse, short hair.
  2. Loose anagen syndrome type B presents with curly, sometimes patchy hair that is difficult to control.
  3. Loose anagen syndrome type C is the adult type, where hair presents with normal thickness, but falls out excessively.

The diagnosis of loose anagen hair syndrome can often be mistakenly confused with other conditions of hair loss including alopecia areata, telogen effluvium, and trichotillomania. By using a patient’s history and looking at the hair under a microscope, a dermatologist can prevent this confusion and avoid unnecessary treatments.

Loose anagen syndrome has a known association with Noonan Syndrome, a congenital syndrome that includes heart defects, short stature, learning difficulties, and other characteristics. Other than Noonan Syndrome, no additional diseases have been shown to be strongly associated with loose anagen syndrome. Though a relationship with atopic disorders (asthma, allergies, and atopic dermatitis) has been suggested, it has not been confirmed because these conditions have been increasing in prevalence in recent years.

Loose anagen hair syndrome is typically considered a benign condition that will resolve in time. However, some cases of persistent loose anagen syndrome have been reported for up to 14 years. One treatment for this condition beyond watchful waiting is to recommend biotin supplements, though no data has shown this to be a scientifically supported treatment. Nevertheless, the only required treatment for loose anagen hair syndrome is reassurance that the condition is benign and addressing cosmetic concerns within reason.

What causes loose anagen hair syndrome

Although loose anagen hair syndrome occurrence is typically sporadic, familial cases of loose anagen syndrome have been observed. Inheritance appears to be in an autosomal dominant pattern with variable penetrance. Loose anagen syndrome has not been consistently associated with any other disorder; however, individual cases associated with the following syndromes have been reported (associations were most likely coincidental):

  • Noonan syndrome 4
  • Ocular coloboma syndrome 5
  • Trichorhinophalangeal syndrome
  • Nail-patella syndrome
  • Hypohidrotic ectodermal dysplasia and ectrodactyly-ectodermal dysplasia-clefting syndrome 6
  • Acquired immunodeficiency syndrome
  • Woolly hair 7
  • Alopecia areata
  • Loose anagen syndrome with features resembling uncombable hair syndrome 8
  • Colobomas and dysmorphic features including low-set ears, hypertelorism, left microphthalmia, frontal bossing, a thin upper lip, a simple philtrum, and slight left facial hypoplasia 9
  • Noonan-like syndrome characterized by short stature, a distinctive facial phenotype, macrocephaly, enlarged cerebral spinal fluid spaces, a short neck with redundant skin, severe growth hormone deficiency, mild psychomotor delay with attention deficit/hyperactivity disorder, and increased skin pigmentation 10

The precise pathogenesis of loose anagen syndrome is not known, but theories postulating an abnormality in the hair’s anchoring mechanism predominate 11. SHOC2 mutations may be linked with ectodermal abnormalities, including loose anagen hair syndrome 12.

The inner root sheath is thought to play an integral role in anchoring the hair shaft within the follicle. In loose anagen syndrome, mutations in genes coding for cytokeratins have been identified in some cases and are thought to result in abnormal keratinization of the inner root sheath 13. This faulty keratinization leads to impaired adherence of the deformed hair shafts to their follicles. The impaired attachment may result in premature cessation of the anagen phase and account for reduced hair length. One author has also reported reduced follicle size due to delayed maturation. This may be responsible for sparse hair growth.

Loose anagen hair syndrome pathophysiology

Each hair follicle is divided into bulb, suprabulbar, isthmus, and infundibular zones. The normal scalp hair collectively participates in the normal hair cycle that is divided into 3 phases: the active growth anagen phase, followed by a brief catagen phase, and finally the resting telogen phase. Typically, 85-95% of hairs are in the anagen phase, which lasts about 3 to 5 years with a growth rate of 1 cm per month 14. Long inner root sheaths cover anagen hairs, and the outer root sheaths are rooted deeply in the reticular dermis. Therefore, under normal circumstances, these are difficult to detach and do not come off with routine hair brushing or light traction. Anagen follicles are continuously and actively replicating and sensitive to nutritional and metabolic insults 15. An anagen hair shaft has 3 layers: the medulla, cortex, and cuticle from the center out. The cuticle interlocks with the inner root sheath cuticle and it is abnormal keratinization of this inner root sheath that is central to loose anagen hair syndrome 15.

A K6HF mutation of keratin has been described in some families with loose anagen hair syndrome 16. This mutation results in premature keratinization of the inner root sheath and impaired adhesion of the cuticle of the inner root sheath to neighboring structures 1.

Less than 1% of hairs are in catagen, the transitional phase, which lasts from a few days to weeks. The telogen phase, which accounts for 5-15% of hairs and lasts about 3 months, ends when the new anagen hair emerges from the follicle. A telogen count of 20% is considered the upper limit of normal. In healthy individuals, removing hair with light traction yields few hairs, almost all of which are in the telogen phase. These hairs are readily identified by their dry, nonpigmented, clublike roots and the absence of an inner and outer root sheath.

Loose anagen hair syndrome symptoms

Parents often report that the child’s hair is thinning and that haircuts are never needed or are needed only very infrequently. Parents may have noticed that hair traction, either accidental during playing or intentional, yields clumps of painlessly removed hair. Many parents complain that hair is unmanageable, lusterless, dry, dull, or matted. There may be a history of atopic dermatitis, but the association may be coincidental 17.

Parents or siblings occasionally have a history of similar symptoms. Children who are affected are healthy and free from underlying nutritional deficiencies or other illnesses. Growth and development are normal.

Physical examination reveals sparse growth of thin, fine hair and diffuse or patchy alopecia without inflammation or scarring. Gentle traction results in hair that is painlessly removed; however, hair is not fragile or easily breakable. Hair may be of varying lengths and may have an unkempt, lackluster appearance. In particular, hair overlying the occiput tends to be rough or sticky and does not lie flat.

No scalp inflammation or scarring is present. Eyebrows, eyelashes, and body hair are rarely involved. Other structures of ectodermal origin (eg, skin, teeth, nails) are not affected.

Loose anagen hair syndrome diagnosis

Clinical history is usually that of a young female child with light hair that sheds easily. The diagnosis of loose anagen syndrome is confirmed by firmly pulling locks of hair (the gentle hair pull) and by microscopically examining those extracted hairs. A gentle hair pull normally yields only 0-2 hairs per pull, but, in loose anagen syndrome, the number extracted may be much higher. Patients with loose anagen syndrome feel no discomfort as hairs are extracted. In normal individuals, only telogen hairs are extracted during a gentle hair pull. The presence of anagen hairs on a gentle pull test, as found in loose anagen syndrome, is pathologic. Easily extractable hairs may be seen in active lesions of lupus erythematosus or lichen planopilaris. They differ from the hairs of loose anagen syndrome in that they lack the characteristic “rumpled sock” cuticle. Forcible plucking with a hemostat in patients with loose anagen syndrome also results in easy and painless hair extraction. The hair is not fragile, and plucking does not cause breaks within the hair shaft.

Under light microscopy 18, the epilated hairs are predominantly in anagen phase. The proximal end demonstrates a distorted hair bulb that is often bent at an acute angle to the hair shaft. The hair bulb may also appear long and tapered or twisted in relation to the long axis of the hair shaft. The hairs lack an inner and outer root sheath, and the cuticle has a characteristic rippled or ruffled, sawtooth, baggy-stocking appearance (rumpled sock appearance).

On scanning electron microscopy, loose anagen hairs may demonstrate abnormal ridging and fluting of the hair shaft.

Trichoscopy may show rectangular black granular structures, solitary yellow dots, and major predominance of follicular units with single hairs 19.

Although a scalp biopsy is not indicated to diagnose loose anagen syndrome, a few investigators have reported histologic findings. However, the histologic features of loose anagen syndrome have not yet been critically studied.

Cleft formations between hair shafts and inner root sheaths and fragmentation of the inner root sheaths may be visualized. Regressive changes of the inner root sheath, including homogenization and crumbly degeneration, may be seen, particularly on transversely cut biopsy specimens. Loose anagen hairs may demonstrate abnormal configurations on cross-section rather than the typical round or oval shape seen in normal hair shafts.

Anagen follicles showing premature keratinization in the cells of Henle and Huxley layers have been reported in hairs from patients with loose anagen syndrome. Although keratinization occurs at more distal areas of the follicle in normal anagen hairs, it may be seen at the lower bulbar level in loose anagen hairs.

Notably, no inflammatory infiltrates are present in loose anagen syndrome.

Loose anagen hair syndrome treatment

Treatment is often unnecessary as the disease is often self-limited and improves with age. No therapy is currently available for loose anagen syndrome 20. Reassure the patient’s parents and adults who are affected that the syndrome is of cosmetic significance only and usually improves with increasing age, particularly after puberty 21. If treatment is pursued, topical minoxidil has been used as first-line therapy for those with significant disease burden 1. A 2-year-old girl on a tapering regimen of minoxidil 5% solution over 28 months had substantial clinical benefit without experiencing adverse effects 22, although a hair color change may be noted 23. The mechanism by which minoxidil is thought to be beneficial is by prolongation of the anagen phase 24. Biotin therapy has been shown to be of no benefit 25 and otherwise, only gentle hair care to avoid removal of loosely anchored hairs is recommended 15.

Loose anagen hair syndrome prognosis

The diffuse hair loss that occurs in loose anagen syndrome often raises considerable concern among patients, parents, and clinicians. In individuals who are affected, hair typically increases in length and density over time and darkens in color; however, the loose anagen characteristic persists and hair continues to be easily and painlessly pulled from the scalp. Although no treatment is currently available, the condition is of cosmetic significance only, and symptoms generally improve over time and most recovering by adulthood 1.

References
  1. Cantatore-Francis JL, Orlow SJ. Practical guidelines for evaluation of loose anagen hair syndrome. Arch Dermatol. 2009 Oct;145(10):1123-8.
  2. Maxfield L, Cook C. Loose Anagen Syndrome. [Updated 2019 Jun 5]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2019 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK526030
  3. Agi C, Cohen B. A case of loose anagen syndrome in an African American girl. Pediatr Dermatol. 2015 May-Jun. 32 (3):e128-9.
  4. Tosti A, Misciali C, Borrello P, Fanti PA, Bardazzi F, Patrizi A. Loose anagen hair in a child with Noonan’s syndrome. Dermatologica. 1991. 182(4):247-9.
  5. Murphy MF, McGinnity FG, Allen GE. New familial association between ocular coloboma and loose anagen syndrome. Clin Genet. 1995 Apr. 47(4):214-6.
  6. Azon-Masoliver A, Ferrando J. Loose anagen hair in hypohidrotic ectodermal dysplasia. Pediatr Dermatol. 1996 Jan-Feb. 13(1):29-32.
  7. García-Hernández MJ, Price VH, Camacho FM. Woolly hair associated with loose anagen hair. Acta Derm Venereol. 2000 Sep-Oct. 80(5):388-9.
  8. Lee AJ, Maino KL, Cohen B, Sperling L. A girl with loose anagen hair syndrome and uncombable, spun-glass hair. Pediatr Dermatol. 2005 May-Jun. 22(3):230-3.
  9. Hansen LK, Brandrup F, Clemmensen O. Loose anagen hair syndrome associated with colobomas and dysmorphic features. Clin Dysmorphol. 2004 Jan. 13(1):31-2.
  10. Mazzanti L, Cacciari E, Cicognani A, Bergamaschi R, Scarano E, Forabosco A. Noonan-like syndrome with loose anagen hair: a new syndrome?. Am J Med Genet A. 2003 Apr 30. 118A(3):279-86.
  11. Dhurat RP, Deshpande DJ. Loose anagen hair syndrome. Int J Trichology. 2010 Jul. 2(2):96-100.
  12. Okazaki T, Saito Y, Sugita K, Nosaka K, Ohno K, Hiraoka Y, et al. Recurrent Erythema Nodosum in a Child with a SHOC2 Gene Mutation. Yonago Acta Med. 2019 Mar. 62 (1):159-162.
  13. Mirmirani P, Uno H, Price VH. Abnormal inner root sheath of the hair follicle in the loose anagen hair syndrome: an ultrastructural study. J Am Acad Dermatol. 2011 Jan. 64(1):129-34.
  14. Baden HP, Kvedar JC, Magro CM. Loose anagen hair as a cause of hereditary hair loss in children. Arch Dermatol. 1992 Oct;128(10):1349-53.
  15. Cheng AS, Bayliss SJ. The genetics of hair shaft disorders. J. Am. Acad. Dermatol. 2008 Jul;59(1):1-22; quiz 23-6.
  16. Chapalain V, Winter H, Langbein L, Le Roy JM, Labrèze C, Nikolic M, Schweizer J, Taïeb A. Is the loose anagen hair syndrome a keratin disorder? A clinical and molecular study. Arch Dermatol. 2002 Apr;138(4):501-6.
  17. Dey VK, Thawani M. Loose anagen hair syndrome: Is there any association with atopic dermatitis?. Indian Dermatol Online J. 2016 Jan-Feb. 7 (1):56-7.
  18. Smith VV, Anderson G, Malone M, Sebire NJ. Light microscopic examination of scalp hair samples as an aid in the diagnosis of paediatric disorders: retrospective review of more than 300 cases from a single centre. J Clin Pathol. 2005 Dec. 58(12):1294-8.
  19. Rakowska A, Zadurska M, Czuwara J, Warszawik-Hendzel O, Kurzeja M, Maj M, et al. Trichoscopy findings in loose anagen hair syndrome: rectangular granular structures and solitary yellow dots. J Dermatol Case Rep. 2015 Mar 31. 9 (1):1-5.
  20. Loose Anagen Syndrome Treatment & Management. https://emedicine.medscape.com/article/1072899-treatment
  21. Herskovitz I, de Sousa IC, Simon J, Tosti A. Short anagen hair syndrome. Int J Trichology. 2013 Jan. 5(1):45-6.
  22. Chandran NS, Oranje AP. Minoxidil 5% solution for topical treatment of loose anagen hair syndrome. Pediatr Dermatol. 2014 May-Jun. 31(3):389-90.
  23. Cranwell WC, Sinclair R. Loose anagen hair syndrome: Treatment with systemic minoxidil characterised by marked hair colour change. Australas J Dermatol. 2018 Mar 22.
  24. Mirmirani P, Uno H, Price VH. Abnormal inner root sheath of the hair follicle in the loose anagen hair syndrome: an ultrastructural study. J. Am. Acad. Dermatol. 2011 Jan;64(1):129-34.
  25. Zarbo A, Shwayder T. Loose Anagen Hair Syndrome. J. Pediatr. 2018 Aug;199:282-282.e1
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