Alopecia Areata: A tissue specific autoimmune disease of the hair follicle
Section snippets
Clinical features of alopecia areata
AA is characterized by the sudden appearance of round or oval patches of non-scarring hair loss with spontaneous remissions and exacerbations. The patches are well circumscribed, may have a mild peachy hue, occasionally with “exclamation point” hairs around their margin. “Exclamation point” hairs are broken short hairs with a broader distal segment as compared to the proximal end. The involved skin is usually smooth and almost always totally devoid of hair.
The most common clinical presentation
Genetic factors
The family history of AA in patients ranges from 10% up to 42% of cases and there are reports of identical twins developing AA simultaneously. AA has HLA association with DQB1*03 [2], HLA B-18, and possibly HLA-A2 [3]. These associations with HLA-DR and HLA-DQ suggest a role for CD4+ T-cells in AA. However, association with HLA-A, B and C were not examined in the most recent studies. An association with DQB1*0301 was found in patients with persistent and chronic alopecia totalis but not in
Evidence for an autoimmune pathogenesis
There is increasing evidence that AA is a tissue-specific autoimmune disease. The most characteristic histological feature of AA is lymphatic infiltration around and within the hair follicles. Loss of hair during active disease is coincidental with an infiltrate of activated CD4+ cells around the hair follicles, along with a CD8+ intrafollicular infiltrate [8]. Immunosuppressive agents such as systemic corticosteroids and cyclosporine as well as immunotherapy with contact sensitizers exhibit a
Hair follicle is an immune privileged site
Hair follicles in both mice, and humans have properties of an immune privileged site. The proximal (lower) hair follicular epithelium of normal hair follicles does not express major histocompatibility complex (MHC) class I or class II molecules [16]. There is also a decrease of Langerhans dendritic cells density [17]. Other mechanisms of immune privilege in the anagen hair follicle include production of immunosuppressive cytokines alpha-MSH, TGF-beta, and IGF-1 [18], [16].
Both humans and
Transfer of alopecia areata in human scalp graft/SCID mouse models
We demonstrated that AA can be transferred from patients to human scalp transplants grafted on SCID mice by injection of autologous lesional T-cells [22]. Lesional scalp skin grafts on SCID mice spontaneously regrew hair. Hair loss was observed only in the group of mice injected with T-cells which had been cultured with follicular homogenate. Injection of scalp T-cells which had been cultured with non-follicular scalp homogenate failed to induce hair loss [23]. The necessity of the follicular
Melanocyte autoantigens and alopecia areata
AA patients show an increased incidence of autoimmune diseases including pigmentary defects. Remarkably, white or greying hair follicles are relatively spared in AA, while regrowing hair shafts are usually white before they become repigmented. The sudden appearance of fulminant AA affects mostly pigmented hair follicles. Thus, only pre-existing grey or white hair is observed. This phenomenon is known as “overnight greying”. Collectively, such evidence points to follicular melanocytes as a
Emotional stress and neuropeptides
Many medical conditions can be exacerbated by stress. It is also likely that in a subset of patients, stressful life events lead to both the onset and the progression of AA [30]. A definitive relationship has yet to be statistically proven. However, alopecia areata is also associated with an increased incidence of depression and anxiety disorders, which may be secondary to hair loss [31].
Neuropeptides produced by cutaneous nerves have been found to modulate inflammation in the skin, providing a
Animal models
The aging C3H/HeJ mice is a model for human AA [37]. Female mice, 6 months of age and older spontaneously develop AA at a frequency of approximately 20%. Lesions first appear on the ventral surface of the mice and are characterized histologically by a perifollicular inflammatory infiltrate of lymphocytes, as well as abnormal expression of HLA-DR, HLA-A,B,C and ICAM-1 by follicular epithelium. Response to intralesional steroid injection and to topical immunotherapy is similar to the human
Loss of immune privilege induces alopecia areata in C3H/HeJ mice
It was possible to accelerate the development of autoimmune hair loss (alopecia areata) in C3H/HeJ mice by injection of intravenous injection INF-γ at doses shown to induce follicular expression of MHC class I and II [40]. The histologic, and immunochemical features of the hair loss were typical for alopecia areata of C3H/HeJ mice, and not consistent with telogen effluvium, which is hair loss induced non-specifically by illness or medication. Furthermore, the hair loss could only be induced in
Final comments
Alopecia is a clinically and scientifically important model of tissue specific autoimmune disease. There is evidence for loss of immune privilege coupled with T-cell mediated attack of hair follicle autoantigens. The accessibility of hair follicles as well as the availability of animal models makes this condition a useful system to study induction of autoimmunity.
Take-home messages
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Alopecia areata is a tissue restricted autoimmune disease of the hair follicle resulting in hair loss. It is among
References (40)
- et al.
Incidence of alopecia areata in Olmsted County, Minnesota, 1975 through 1989
Mayo Clin Proc
(1995) - et al.
The genetic basis of alopecia areata: HLA associations with patchy alopecia areata versus alopecia totalis and alopecia universalis
J Investig Dermatol Symp Proc
(1999) - et al.
Heritable factors distinguish two types of alopecia areata
Dermatol Clin
(1996) - et al.
T cell subpopulations in alopecia areata
J Am Acad Dermatol
(1984) - et al.
Alopecia areata, endocrine function, and autoantibodies in patients 16 years of age or younger
J Am Acad Dermatol
(1987) - et al.
Autoantibodies to hair follicles in C3H/HeJ mice with alopecia areata-like hair loss
J Invest Dermatol
(1997) - et al.
Immunology of the hair follicle: a short journey into terra incognita
J Investig Dermatol Symp Proc
(1999) - et al.
Response of grafts from patients with alopecia areata transplanted onto nude mice, to administration of interferon-gamma
Clin Immunol Immunopathol
(1993) - et al.
Alopecia areata is a T-lymphocyte mediated autoimmune disease: lesional human T-lymphocytes transfer alopecia areata to human skin grafts on SCID mice
J Investig Dermatol Symp Proc
(1999) - et al.
Role of cytotoxic T cells in chronic alopecia areata
J Invest Dermatol
(2000)
Transfer of alopecia areata in the human scalp graft/Prkdcscid (SCID) mouse system is characterized by a TH1 response
Clin Immunol
Ultrastructural observations on the hair bulb melanocytes and melanosomes in acute alopecia areata
J Invest Dermatol
Melanocyte associated T-cell epitopes can function as autoantigens for transfer of alopecia areata to human scalp explants on Prkdcscid mice
J Invest Dermatol
Children with alopecia areata: psychiatric symptomatology and life events
J Am Acad Child Adolesc Psychiatry
Neuropeptides: role in inflammatory skin diseases
J Eur Acad Dermatol Venereol
Calcitonin gene-related peptide upregulates melanogenesis and enhances melanocyte dendricity via induction of keratinocyte-derived melanotrophic factors
J Investig Dermatol Symp Proc
Experimental induction of alopecia areata-like hair loss in C3H/HeJ mice using full-thickness skin grafts
J Invest Dermatol
Successful treatment of alopecia areata-like hair loss with the contact sensitizer squaric acid dibutylester (SADBE) in C3H/HeJ mice
J Invest Dermatol
Resistance to alopecia areata in C3H/HeJ mice is associated with increased expression of regulatory cytokines and a failure to recruit CD4+ and CD8+ cells
J Invest Dermatol
Alopecia areata induced in C3H/HeJ mice by interferon-gamma: evidence for loss of immune privilege
J Invest Dermatol
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