From the Guidelines
Alopecia areata is an autoimmune disorder characterized by non-scarring hair loss, where the immune system mistakenly attacks hair follicles, involving CD8+ T lymphocytes and NK cells infiltrating the hair bulb, targeting melanocyte-associated antigens in the follicle, as suggested by the British Association of Dermatologists' guidelines 1. The pathophysiology of alopecia areata is complex and multifactorial, with genetic factors playing a significant role, including associations with major histocompatibility complex (MHC) and cytokine genes, as identified in a genome-wide association study 1. Key points about the pathophysiology of alopecia areata include:
- Genetic predisposition, with about 20% of people with alopecia areata having a family history of the disease 1
- Autoimmune nature, with the hair follicle being an immunologically 'privileged tissue' that is sheltered from immune surveillance by autoreactive T cells, and failure of such immune privilege playing a key role in the pathogenesis of alopecia areata 1
- Involvement of T lymphocytes in the hair follicle lesion, with the association between alopecia areata and other autoimmune diseases suggesting that alopecia areata is itself an autoimmune disease, although this is unproven 1 The exact mechanisms of alopecia areata are still not fully understood, but it is clear that the condition involves a complex interplay between genetic, environmental, and immune system factors, with the JAK-STAT signaling pathway and cytokines like interferon-gamma playing a critical role in promoting inflammation, as seen in other autoimmune diseases 1. The characteristic "exclamation mark" hairs seen clinically result from structural weakening at the follicle, causing hair shafts to break, and autoantibodies against hair follicle components are often present, although their exact pathogenic role remains unclear 1.
From the Research
Pathophysiology of Alopecia Areata
The pathophysiology of Alopecia Areata (AA) is a complex process involving the collapse of the immune privilege of the hair follicle, caused by a combination of genetic and environmental factors 2, 3, 4.
- The exact cause of AA is still not fully understood, but it is known to be an autoimmune disease resulting in hair loss, affecting up to 2% of the general population 2.
- The disease is characterized by lymphocytic infiltrations around the hair follicles and the presence of IgG antibodies against the hair follicle cells, as well as the involvement of IFN-γ 5.
- The loss of immune privilege in the hair follicle is a key factor in the development of AA, allowing the immune system to attack the hair follicle and disrupt the hair growth cycle 6, 3.
- The immune response in AA is mediated by cytotoxic CD8+ T-cells and involves the upregulation of inflammatory pathways, leading to T-cell-mediated inflammation in the hair follicle area 3.
- Genetic factors, including multiple immune-related genes, also play a crucial role in the pathogenesis of AA, with associations found between AA and genes involved in cytokines, chemokines, regulatory T-cell functions, and other pathways 4.
Key Factors Involved in the Pathophysiology of AA
- Genetic factors: multiple genetic studies have identified associations between AA and immune-related genes 4.
- Environmental factors: environmental triggers can contribute to the development of AA, although the exact mechanisms are not fully understood 2, 3.
- Immune privilege: the collapse of the immune privilege of the hair follicle is a key factor in the development of AA 2, 6, 3.
- Inflammatory pathways: the upregulation of inflammatory pathways plays a crucial role in the immune response in AA 3.
- Cytotoxic CD8+ T-cells: these cells mediate the immune response in AA, leading to T-cell-mediated inflammation in the hair follicle area 3.