Alopecia areata (AA) is a common condition causing hair loss on the scalp and other areas of the body, affecting about 2% of the global population over a lifetime. It is recognized as an autoimmune disease where the body’s immune system mistakenly attacks the hair follicles. The cause of AA is complex, involving a significant genetic contribution, but it is not purely hereditary. AA is understood as a multifactorial disorder requiring inherited susceptibility combined with external factors to trigger its onset.
The Role of Genes in Alopecia Areata Susceptibility
Alopecia areata is considered a polygenic disease, meaning that multiple genes, rather than a single gene, contribute to the overall risk of developing the condition. This complex genetic architecture explains why the disease does not follow a simple inheritance pattern. Genetic studies have identified several regions in the human genome associated with AA, primarily focusing on genes that regulate the immune system.
The strongest genetic association is found within the Human Leukocyte Antigen (HLA) complex, which plays a central role in immune recognition. Variations within these HLA genes influence how the immune system distinguishes between the body’s own cells and foreign invaders. Certain HLA types are linked to AA and other autoimmune diseases, suggesting a shared mechanism of immune dysregulation.
Beyond the HLA region, researchers have identified non-HLA genes that also increase susceptibility. These include genes involved in T-cell function and immune signaling pathways, such as CTLA4, IL2, and IL2RA. Genes involved in hair follicle integrity and development are also implicated, indicating that the genetic risk involves both the immune response and the hair follicle itself.
Understanding the Autoimmune Mechanism
The genetic predisposition manifests as a breakdown of the hair follicle’s “immune privilege.” Immune privilege is a natural mechanism where the hair follicle is protected from immune surveillance, preventing accidental self-attack. In AA, this protection collapses, allowing immune cells to target the hair bulb.
The primary mechanism involves cytotoxic T lymphocytes (T-cells), which infiltrate the area around the hair follicle. These T-cells release inflammatory chemicals, like interferon-gamma, which mediate the destruction of the hair follicle cells.
The resulting inflammation halts the hair growth cycle, causing the hair shaft to fall out. Because the stem cells of the hair follicle remain intact, the condition is categorized as non-scarring alopecia, allowing for the possibility of hair regrowth once the immune attack subsides.
Non-Genetic Factors and Environmental Triggers
While a genetic background is necessary for AA to develop, genes alone are typically not sufficient to cause the condition. Environmental factors are believed to act as the “switch” that initiates the autoimmune process in genetically susceptible individuals. These non-genetic triggers are diverse and may vary from person to person.
One commonly cited trigger is significant emotional or physical stress, with some reports indicating that at least 23% of patients experience a major stressful event before onset. Viral infections, such as those caused by the Epstein-Barr virus, have also been implicated in activating the immune response that leads to hair loss.
Other potential environmental factors include localized trauma or injury to the skin, known as the Koebner phenomenon. These external influences are thought to disrupt the delicate balance of the immune system, leading to the collapse of immune privilege and the subsequent onset of the disease.
Assessing Inheritance and Family Risk
For the average person concerned about passing the condition to their children, the overall risk remains relatively low due to the disease’s multifactorial nature. Most cases of alopecia areata are sporadic, meaning they occur without any known family history of the condition. However, a positive family history is reported in approximately 20% of AA cases.
The risk of a child developing AA if one parent has it is estimated to be around 5% to 20%, which is higher than the general population’s lifetime risk of about 2%. Studies involving identical twins, who share 100% of their DNA, further illustrate the role of non-genetic factors; if one twin is affected, the other has only about a 55% chance of developing AA.
The risk for AA is thought to increase if multiple family members are affected or if the affected relative experienced an early or severe form of the disease.