Etiology of Alopecia Areata
Alopecia areata is an autoimmune condition mediated by T lymphocytes that attack hair follicles, resulting in the collapse of hair follicle immune privilege. 1
Primary Autoimmune Mechanism
The fundamental pathophysiology involves cytotoxic CD8+ T cells targeting melanocyte-associated proteins (such as tyrosinase) within the hair follicle, driven by an IFN-γ-mediated immune response. 2, 3 This autoimmune attack specifically targets the proximal hair follicle without destroying it completely, which explains why the hair loss is non-scarring and potentially reversible. 2
Collapse of Hair Follicle Immune Privilege
- The anagen hair bulb normally maintains an immunosuppressive microenvironment known as "hair follicle immune privilege" that protects it from immune surveillance. 4
- IFN-γ is a key factor that triggers the collapse of this immune privilege, allowing autoreactive T cells to infiltrate and attack the hair follicle. 4, 5
- This collapse is central to disease pathogenesis and represents the critical step that permits autoimmune inflammation to proceed. 5
Genetic Susceptibility
- Approximately 20% of patients have a family history of alopecia areata, indicating significant genetic predisposition. 1
- Genome-wide association studies demonstrate involvement of both innate and acquired immunity pathways, particularly T cell and natural killer cell activation pathways. 2, 3
- The genetic background creates susceptibility to organ-specific autoimmune targeting of hair follicles. 3
Associated Autoimmune Conditions
Alopecia areata strongly associates with other autoimmune diseases, reinforcing its autoimmune etiology: 1
- Thyroid disease (most common association) 1
- Vitiligo 1
- Lupus erythematosus 1
- Atopic dermatitis 2
- Psoriasis 2
The coexistence with these conditions provides additional evidence for shared autoimmune mechanisms and genetic susceptibility. 6
Environmental Triggers
While the underlying cause is autoimmune, certain triggers may activate autoreactive T cells in genetically susceptible individuals: 5
- Viral infections (particularly influenza) that cause excess IFN production can precipitate disease onset. 4
- Physical or emotional stressors may trigger activation of autoreactive T cells. 5
- Trauma to the scalp has been implicated as a potential trigger. 5
- Hormonal changes may influence disease expression. 4
Immunological Cascade
The specific immune mechanisms involve: 6, 3
- Lymphocytic infiltrations around hair follicles (predominantly CD8+ T cells) 6
- IgG antibodies against hair follicle cells detected in affected patients 6
- IFN-γ-induced chemokines that recruit additional immune cells 3
- Upregulation of inflammatory pathways that perpetuate follicular damage 2
Contributing Nutritional Factors
While not causative, certain nutritional deficiencies may contribute to disease severity or persistence: 1
- Vitamin D deficiency (present in 70% of alopecia areata patients versus 25% of controls) shows inverse correlation with disease severity 1
- Zinc deficiency, with lower serum levels in patients with alopecia areata, particularly those with resistant disease >6 months 1
- Iron deficiency (assessed via serum ferritin) may contribute to chronic hair loss 1
Important Caveat
These nutritional factors are associations rather than primary causes—the fundamental etiology remains T-cell-mediated autoimmunity. 1 However, addressing deficiencies may support treatment response. 1