Alopecia areata: a review of disease pathogenesis

Summary Alopecia areata is a disease that causes hair loss, although it does not always look the same and its course is unpredictable. It typically presents as small spots of reversible hair loss on the beard or scalp that can easily be treated. It can also result in total scalp baldness (called alopecia totalis) with devastating psychological impacts for some patients, inadequate treatment options, and frequent relapses. This article is a narrative review of the main events that cause alopecia areata, conducted by researchers based in Iran and the U.S.A. Many environmental and genetic factors are involved in the development of alopecia areata but the mainstream event is an attack on hair follicles by the immune system, which usually serves to protect the body from harmful ‘foreign’ substances or illnesses. In a normal state, hair follicles are kept in a sanctuary out of reach of the immune system. A breach in this sanctuary activates the immune cells against hair follicles. This happens because the immune system has never been exposed to the hair follicles so it recognizes them as foreign material. What causes this breach is a matter of debate. It could happen as a result of a problems in the central immune system or a disturbance in the follicular environment, i.e. close to the follicles. Psychological stress has also been linked to both the initiation and exacerbation of alopecia areata. A cell line called the mast cells is the link between the immunologic (immune system) events and psychological stress. Stress activates mast cells leading to the release of histamine and other inflammation‐causing factors. Multiple treatment strategies have emerged in recent years aiming at immunological targets, called biologic agents, but most of them have not been able to establish long‐lasting remissions. This may be due to the complex nature of the immunologic events which cannot be targeted with a single agent. Overlooking strategies that aim to kick‐start the regrowth of hair, after treatments that restore the immune sanctuary, might be another reason for treatment failures.