Loose Anagen Syndrome

Loose anagen syndrome was first described in 1984. It is a hair disorder characterized by anagen hairs of abnormal morphology that are easily and painlessly pulled or plucked from the scalp. Hair is thinned in appearance and typically does not grow beyond the nape of the neck.

The precise pathogenesis of loose anagen syndrome is not known, but theories postulating an abnormality in the hair's anchoring mechanism predominate.[1] SHOC2 mutations may be linked with ectodermal abnormalities, including loose anagen hair.[2]

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.[3] 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.

Although its 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, 5]

• Ocular coloboma syndrome[6]

• Trichorhinophalangeal syndrome

• Nail-patella syndrome

• Hypohidrotic ectodermal dysplasia and ectrodactyly-ectodermal dysplasia-clefting syndrome[7]

• Acquired immunodeficiency syndrome

• Woolly hair[8]

• Alopecia areata

• Loose anagen syndrome with features resembling uncombable hair syndrome[9, 10, 11]

• 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[12]

• 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[13, 14]

Frequency

United States

The prevalence of loose anagen syndrome is unknown. Although recently described, loose anagen syndrome may actually be rather common. It is undoubtedly often misdiagnosed as alopecia areata or trichotillomania.[15] It has likely been both underdiagnosed and underreported to date.

International

The incidence and prevalence of loose anagen syndrome are unknown. It may be underreported, particularly in boys.[16]

Race

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.[17, 18]

Sex

The syndrome is more common in females than in males.

Age

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.

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.

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.[19]

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 (see following image).

Thinning, dull, lackluster blonde hair with matting over the occipital region.

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.

Trichoscopy may show rectangular black granular structures, solitary yellow dots, and major predominance of follicular units with single hairs.[20]

The normal scalp cycle 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 years. 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.

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,[24] 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) (see following image).

Microscopic view of easily plucked hair demonstrating a distorted anagen bulb lacking inner and outer root sheaths, and a ruffled, sawtooth, baggy-stocking appearance of the cuticle (original magnification X100).

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

Trichograms (forcible hair plucks) reveal an abnormally large percentage of anagen hairs lacking inner and outer sheaths. Few or no telogen hairs are present.

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.

No therapy is currently available for loose anagen syndrome. 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.[17] A 2-year-old girl on a tapering regimen of minoxidil 5% solution over 28 months had substantial clinical benefit without experiencing adverse effects,[25] although a hair color change may be noted.[26]  Oral minoxidil may be an effective and well-tolerated treatment alternative to topical formulations in selected patients.[27]

Careful and gentle grooming may help to minimize hair loss.