Alopecia long post

[Guest guest]

Alopecia means hair loss, so not all alopecia is autoimmunie. There

are many, many reasons for hair loss. A good website to learn about

hair loss is, WWW.Keratin.com. Alopecia areata, universalis and

totalis, are believed to be autoimmune. They really have no clue what

causes it. I just wanted to clear this up as not all hair loss is

autoimmune.

Alopecia areata is a common, unpredictable, non-scarring form of

hair loss. This disorder affects all age groups, with a higher

prevalence in children and adolescents. Limited scalp involvement is

the most common presentation but more severe forms of the disorder,

involving the entire scalp or body, also exist. Research has linked

alopecia areata with certain HLA-Class II alleles, implicating an

autoimmune etiology. Various therapeutic modalities have been

employed to gain clinically acceptable hair regrowth.

Alopecia areata is a common disorder, hypothesized to be autoimmune

in etiology, and estimated to affect almost 2% of the US population

(1). This non-scarring alopecia affects both sexes equally and is

seen in all age groups. A higher incidence is found in children and

young adults, with common presentation before the age of five years

(2-4). The unpredictable severity and course of the disorder exacts a

high emotional cost from the affected patient and may result in

psychiatric comorbidity (5).

Etiology

The etiology of alopecia areata is as of yet unclear, but is presumed

to be due to an autoimmune reaction. Consistent evidence of

autoantibodies directed against anagen stage hair follicle structures

are found in both affected humans and in mouse models (6,7). Though

autoantibodies are postulated to play an integral role in the disease

process, current research implicates a cell-mediated autoimmune

mechanism as the underlying pathogenic etiology (8). Supporting this

theory is that activated CD4 and CD8 T lymphocytes have been found in

a characteristic peri- and intrafollicular inflammatory infiltrate of

anagen hair follicles of affected individuals (9-11). The transfer of

alopecia areata by T lymphocytes cultivated from affected scalp and

transferred to human scalp explants on a severe combined

immunodeficiency mouse model has been demonstrated (12). Recent

investigations on mouse models reported that transplanted alopecia

areata tissue to normal mice would not induce alopecia areata if a

specific monoclonal antibody, anti-CD44v10, was injected into the

mice shortly after transplant surgery (8). CD44v10 is believed to be

involved in the activation mechanism of CD4 and CD8 lymphocyte

migration into tissue and the initiation of the subsequent defense

response against antigenic stimuli (8). Similar research has

demonstrated that invivo depletion of CD4+ cells using CD4+ cell-

depleting OX-35/OX-38 monoclonal antibody (MoAb) partially restores

hair growth in rats affected with alopecia areata (11). Current

investigative efforts strongly implicate CD4 and CD8 T-cell

lymphocytes in the pathogenic autoimmune etiology of this disorder.

Alopecia areata, similar to many other autoimmune diseases, is linked

with certain HLA-Class II alleles. The HLA antigen DQ3 (DQB1*03) has

been identified as a general susceptibility marker for alopecia

areata (13-15). Patients with the more severe forms of the disorder,

alopecia totalis and alopecia universalis, were found to express the

HLA alleles DQB1*0301, DRB1*0401 and DRB1*1104 in a significantly

higher frequency (8). Milder, patchy forms of alopecia areata were

also found to be associated with a significantly higher frequency of

DRB1*1104, but no association was reported with the other two

aforementioned alleles (8).

Clinical description

Alopecia areata usually appears abruptly as a patch of clearing on

the scalp with no evidence of scarring. Scalp involvement is the most

clinically distinguishing characteristic, but axillae, eyebrows and

eyelashes may also be involved (16). Mild, limited involvement of the

scalp is the most common presentation; multiple patches may become

confluent over time. Regression may occur, with new hair growth

taking place; recurrences in different locations occur unpredictably.

Severe involvement may produce a loss of all scalp hair (alopecia

totalis) or all hair on the body (alopecia universalis). Patients

with alopecia areata that have a history of atopy may have a less

favorable prognosis (17).

Clinical variants of alopecia areata exist (16). Ophiasis alopecia

areata describes band-like hair loss affecting the temporal and

occipital regions of the scalp. Reticular alopecia areata describes a

type that clinically shows patches of hair loss in various stages of

disease activity. Diffuse alopecia areata has been attributed to a

short anagen phase and subsequent inability of hair to grow. Alopecia

areata has also been linked with a number of autoimmune diseases

(18).

Alopecia areata produces nail changes in 3-30% of affected patients

(3,18-20). In one study of 201 affected children under 16 years nail

changes were clinically evident in 60 (3). Of these 60 children, nail

changes were more common in severely affected children (18 out of 34)

than in children with localized disease (42 out of 167). In another

study, 21 patients had clinical evidence of nail changes out of a

total of 136 patients (103 adults, 33 children) affected with

alopecia areata. Nail changes were found to be more common in

children, especially in children with severe, long-standing disease

(19). The nail changes associated with alopecia areata usually

accompany hair loss, but may occasionally precede or follow the onset

of hair loss by months or years (16). The main patterns of nail

changes are: diffuse fine pitting (most common), thin and brittle

fingernails and toenails, longitudinal ridging and rough surface

trachyonychia (3,20-22).

Systemic associations

Atopy, vitiligo and autoimmune thyroid disease, namely Hashimoto's

thyroiditis and Graves' disease, are more prevalent in patients with

alopecia areata ????. Serum thyrotropin measurement has been

recommended for all children with this disorder. (23) Although

children are frequently screened for thyroid disease, the presence of

disease in these patients is only 10% (3). A recent study on the

evaluation of thyroid function in northern Indian patients with

alopecia areata revealed that thyroid disease was clinically evident

in only 16 (0.85%) of the 1700 affected patients evaluated over the

interval of 1983-1997 (24). The incidence of thyroid structural and

functional abnormalities is much higher in affected patients (78

percent) than in controls (33 percent) (21). One study of 45 affected

children, 16 years of age and younger, reported thyroid function

abnormalities in 24 percent of these children (25). Thyroid function

abnormalities include abnormal thyroid hormone (T3,T4) and thyroid

stimulating hormone (TSH) values and the presence of antithyroid and

antimicrosomal antibodies (25). Celiac disease, systemic lupus

erythematosus and diabetes mellitus may also possibly be increased in

incidence in patients with alopecia areata (2,3,26-29).

Differential diagnosis

Mild forms of alopecia areata are seen as solitary areas of non-

scarring hair loss on the scalp and should be distinguished from

trichotillomania and tinea capitis. Other forms of non-scarring

alopecia, including traumatic alopecia and congenital hair loss

syndromes such as congenital triangular alopecia, must also be

considered in the differential diagnosis (30-33). Alopecia

neoplastica, a rare form of alopecia, is associated most commonly

with breast cancer; it may resemble localized alopecia areata

(34,35). Systemic lupus erythematosus, syphilis and post-febrile

alopecia may also at times resemble alopecia areata (16).

Alopecia areata may be first evident in young patients as the sudden

onset of diffuse alopecia (16,17). Telogen effluvium, believed to be

associated with high fever, severe emotional stress, sudden

starvation and certain medications, must also be considered in the

differential diagnosis of diffuse alopecia. Other conditions

associated with diffuse alopecia include acrodermatitis

enteropathica, arsenicism and thallium poisoning, though these

conditions usually have systemic symptoms (16). Recent research has

identified the human hairless gene, equivalent to a gene studied in

mouse models (hairless IRS/3 mouse), and has confirmed its

association with a disease called atrichia or atrichia with papules

(8,36). This condition was previously named alopecia universalis

congenita. These patients are born with hair, but the hair matrix

cells progressively undergo apoptosis by the third month, culminating

in permanent hair loss (8,36).

A skin biopsy specimen is diagnostic of alopecia areata, and is

sometimes necessary to make a diagnosis (37,38). On histological

examination a peribulbar lymphocytic infiltrate resembles a " swarm of

bees. " (39). Scarring is characteristically absent.

Treatment

Treatment of alopecia areata may be divided into four different

categories of widely accepted therapeutic modalities (9,18,23,40-55):

immune inhibitors such as steroids or psoralen and UV-A light (PUVA);

topical sensitizers such as squaric acid dibutylester (SADBE) and

diphenylcyclopropenone (DPCP); non-specific irritants (anthralin) and

the vasodilator minoxidil. Treatment goals are hair regrowth that is

cosmetically acceptable to the patient; hair loss is not prevented

with these treatments (23,53,56).

Mild forms of alopecia areata are mostly treated by intralesional

injection of a glucocorticoid, usually triamcinolone, every four to

six weeks (16,23). Steroid injection may produce minimal transient

atrophy or, less commonly, severe atrophy of the targeted skin; the

most common side effect of steroid injection is pain, which is a

complicating factor in treatment of children (53). Topical steroid

application to areas of hair loss, usually applied twice daily, has

also been found to be efficacious clinically, although combination

treatment with minoxidil, anthralin or injected steroids is probably

more therapeutic (23,53,57). Systemic steroids are reserved for use

in rapidly progressive or extensive alopecia areata (53).

Anthralin, the only non-specific irritant widely used for hair growth

in alopecia areata, is applied topically as a 0.5 or 1% cream to

affected areas once per day for 20-45 minutes; overnight application

can also be used in certain patients who can tolerate the side

effects (23,53). Application of topical anthralin may cause pruritus,

erythema, scaling and folliculitis, necessitating the short

application time (53). The combination therapy of anthralin and

minoxidil has also shown favorable results in a group of treatment-

resistant patients (58,59).

Minoxidil (5% topical solution) is applied twice daily to areas of

hair loss. Side effects are limited to mild local irritation and,

less frequently, allergic contact dermatitis (60-62). Topical

sensitizers induce an allergic contact dermatitis in applied areas of

hair loss; weekly re-stimulation with the potent allergen is needed.

Topical sensitizers have proven efficacy in patients with long-

standing alopecia areata involving more than 50 percent of the scalp

(23,57,63). Squaric acid dibutylester (SADBE) has shown good

tolerability and mild side effects. In one study of 144 patients with

varying degrees of alopecia areata, an 80% rate of regrowth was

demonstrated in patients with mild alopecia areata and a 49% rate of

regrowth was demonstrated in more severely affected patients (52). A

study of squaric acid dibutylester in a pediatric population of

twenty-eight children under the age of 13 with severe, long-standing,

refractory alopecia areata reported nine patients achieving

cosmetically acceptable or complete regrowth, and six patients

achieving significant regrowth (64). Diphenylcyclopropenone (DPCP) is

also an accepted modality for treatment of severe alopecia areata.

One study demonstrated a 70% response rate in DPCP-treated patients

with severe alopecia areata affecting more than 40% of the scalp

(65). Of these patients, 30.9% demonstrated complete remission, while

39.7% underwent partial remission (65). Pruritus, dermatitis,

urticaria, face and scalp edema and the development of vitiligo are

known side effects of DPCP use (66).

Cyclosporine is a potent immunomudulatory agent whose mechanism

involves inhibition of T4 lymphocyte activation (67). A known side

effect of cyclosporine is hypertrichosis, which has been attributed

to prolongation of the anagen phase of hair growth (68). In one study

of 15 alopecia areata patients treated with systemic cyclosporine,

seven patients obtained cosmetically acceptable hair regrowth (67).

Teshima et al describe a 24 week regimen containing cyclosporine (2.5

mg/kg daily) and prednisolone (5mg/day) which produced a 100%

response rate in six patients with persistence of hair regrowth six

months after cyclosporine was discontinued (69,70). A similar study

combining cyclosporine with prednisone reported two out of eight

patients developing cosmetically acceptable hair regrowth (71). Gupta

et al report cosmetically acceptable hair regrowth in three of six

patients treated with 6 mg/kg cyclosporine daily for 12 weeks; hair

loss occurred in all patients within 3 months of discontinuation of

cyclosporine (72). Larger studies need to be performed to determine

the efficacy of systemcic cyclosporine in the treatment of alopecia

areata. The significant side-effect profile of cyclosporine deters

long-term treatment (73).

Cryotherapy has also been employed to stimulate hair growth in

alopecia areata (49,50). One study, utilizing both children and

adults, revealed hair regrowth in greater than 60% of affected areas

in 70 of 72 patients (49).