What are the environmental factors that activate alopecia areata ?

The precise causes that trigger the onset of alopecia areata, a complex autoimmune condition characterized by non-scarring hair loss, remain elusive. However, contemporary research has expanded our understanding of several factors that may influence the course of alopecia areata and might potentially be triggers for the onset of alopecia areata episodes. It’s important to note that not every initiating factor will be present in every patient. Different people likely develop their alopecia areata as a result of different triggers and disease modifiers. However, there is enough research published that we can suggest a range of factors that affect alopecia areata.

Genetic predisposition: Before exploring the possible environmental triggers for alopecia areata onset, a few words may be needed on genetics. It has been shown that there is a higher incidence of alopecia areata occurring in genetically related individuals. This suggests that at least some people are genetically predisposed towards the development of alopecia areata. It is generally believed that alopecia areata susceptibility is polygenic – there are a number of genes which, if present, make that individual more likely to develop alopecia areata. Several research groups have been examining the genetic make-up of people who develop alopecia areata and so far they have found 14 genes to be much more common in people with alopecia areata compared to the general population. The more susceptibility genes that are present, the more likely a person may be to develop AA. The triggers for the actual onset of alopecia areata are most likely all environmental (as below), but susceptibility to development of alopecia areata, the resistance of the alopecia areata lesion to treatment, and its persistence and regression and its extent over the body might be influenced by the presence and interaction of several genes. As such, who develops AA is probably determined by the interactions of environmental factors with the genetics of each person. There are several possible triggers for the onset of AA including:

Long term chronic stress: A wealth of case-lore and research studies with patients suggest that stress is an important precipitating factor in alopecia areata. Various reports support the stress hypothesis, but so far it has only been shown by statistical correlation – no direct biological link has been demonstrated in humans. However, there are now a great many studies on chronic stress in alopecia areata patients, and they all say pretty much the same thing. Given these studies come from across the world, with different patients involved, different doctors involved, and so many studies have been published every year since the 1950s, we can conclude that chronic stress is linked to alopecia areata – at least in a subset of patients.

Stress is suggested as an environmental trigger in people predisposed to alopecia areata development (due to genetic susceptibility for example) rather than the primary basis for alopecia areata development. Studies in other autoimmune diseases have shown that stress hormones can stimulate the immune system and much the same problem could be occurring in AA. There is also some research using models of AA that show the development of AA also actives stress hormones at a biological level. This means that while stress can promote alopecia areata, the immune mechanisms active in AA also promote stress hormones. This is potentially a positive feedback loop that may be difficult to break out of.

Shock and sudden extreme stress: There have been a number of reports on individual cases where clearly defined sudden stress events have preceded alopecia areata development. The emotional trauma of a family death or being involved in a car accident without major injury have been suggested as triggers for alopecia areata onset. These highly stressful events can occur a few days to a few weeks before the onset of hair loss is first apparent. This time lag between stress event and start of hair loss fits with what we know from research using disease models. When a trigger to induce AA is given to a model of AA, the immune system takes some time to build up its activity to a level where hair loss starts to occur. This time lag varies anywhere from about 3 weeks up to 25 weeks in some AA model studies.

Physical trauma: There is a reasonable amount of case history evidence to show that physical trauma can trigger the onset of alopecia areata in some people. Anything that stimulates the immune system from being hit on the head to an infection can be a potential trigger. There is only very limited research evidence to explain how injury and inflammation could trigger the onset of AA. However, researchers believe AA could develop as a result of an injury – probably as a result of increased inflammatory activation through a molecule called interferon gamma.

The immune system is involved in helping to heal wounds – this is why wounds go red and feel sore as they are healing. Physical injury activates the immune cells to help in wound healing, and as part of this, there is increased production of the interferon gamma signalling molecule. For someone genetically predisposed to AA development, the wound healing activation signal might also activate some immune cells that are auto-immune in nature. These autoimmune cells then induce AA onset while most other immune cells are busy correctly helping with wound healing.

Local skin injury: Cuts, scrapes, and other abrasions of normal haired skin are often the focus for the onset of a new patch of hair loss in alopecia areata susceptible people. It is a feature called the “Koebner” phenomenon. The local skin injury probably encourages immune cells to infiltrate into the local area. If some of the infiltrating cells are autoimmune in nature and able to target self-antigens in active anagen hair follicles, the result may be onset of alopecia areata. Some dermatologists have suggested that this localized induction of AA might explain why some people can have just a single small patch of alopecia areata, but don’t develop any further hair loss. Ironically, similar abrasions in areas of skin already affected by alopecia areata can be the focus of temporary hair regrowth. Injury is known to promote anagen hair follicle growth in skin immediately surrounding the injured site and it may be that this injury induced stimulation of hair growth is enough to overcome the autoimmune response – at least temporarily.

Viral/bacterial infection: In the 1990s, cytomegalovirus infection of hair follicles was implicated by at least one research group in development of alopecia areata. However, subsequent research by other groups has failed to confirm the potential link. HIV infection has also been suggested as a potential trigger for alopecia areata onset based on a few case reports. This may not be surprising as HIV infects immune cells and it can switch off part of the immunoregulatory system. There are also some case reports suggesting a link between hepatitis C, its treatment, and the development of AA. One research article on hepatitis B vaccinations suggested a link to AA development, but subsequent research failed to confirm the claim.

Dermatologists suggest general viral/bacterial infections in general may promote the immune system into an inappropriate response against hair follicles in susceptible people. In research into other chronic inflammatory diseases there is a theory cumulative viral/bacterial load over time might lead to higher levels of immune activity in general. This activity becomes less focused on removing the viruses/bacteria and gradually becomes a more widespread inflammation as a result of repeated infections. For someone susceptible to AA, this generalized inflammation might lead to activation of the hair loss mechanism.

Pregnancy/hormones: The apparent link between hormonal fluctuations and alopecia areata has been recognized since at least 1896. Most notable are the cases of alopecia onset during late stage pregnancy. Intriguingly, women who already have alopecia areata can find that they have complete, but temporary, hair regrowth around the time of childbirth. Puberty and menopause have also been suggested as a time of potential alopecia areata onset or remission. Research has shown that hormones, including estrogens and progesterones, can influence immune cell activity. Changes in the levels of these hormones probably alter the sensitivity of the immune system, including the potential for AA onset or hair regrowth.

Allergies: Statistical analysis shows that people with alopecia areata and some form of atopy (asthma, eczema, rhinitis) are inclined to have hair loss that is more extensive and/or of prolonged duration. Interestingly, at least one statistical analysis of Indians with alopecia areata showed no such link. This may suggest that the genetic composition of different ethnic groups must be taken into account when explaining susceptibility to alopecia areata development in response to allergies. However, at least some people seem to develop AA that gets better and worse in tune with the cycles of their allergy. A few reports from China and the USA have found AA seems to get worse in response to increased amounts of allergens including house dust mites (China), and pollen (USA).

Chemicals: One “outbreak” of alopecia areata in workers at a water treatment plant in a paper factory was linked to long term exposure to the chemical acrylamide. Formaldehyde and pesticides have also been suggested, although not proven, as a potential influence in the development of alopecia areata. Isolated case reports have suggested a link between alopecia areata development and Zidovudine treatment of HIV, and Fluvoxamine anti-depressive treatment. There isn’t much research in this area, mostly just case reports, but for a few people it seems exposure to inflammation stimulating chemicals can promote alopecia areata.

Initiation factors: Whatever the initiation factor for alopecia areata, it need not be permanent; rather a short sharp shock may be just enough to tip the balance of the immune system into autoimmunity. Once an autoimmune disease is initiated it can be self-perpetuating. Tissue destroyed in the early stages of the disease can be broken down and the antigens presented to immune system cells in the lymph nodes. This recruits more self-reactive cells which destroy more tissue producing more antigens and so the cycle continues. Because autoimmune conditions can feed on themselves once started, this means the initial trigger for onset of the disease does not have to be continuously present. There may be just a brief exposure to trigger onset of AA, after which the autoimmune machinery keeps running without any further input from alopecia areata triggers.

Conclusion: While the initiation factors for alopecia areata are multifactorial and complex, ongoing research continues to unravel the intricate interplay between genetics, environment, and immune responses. Understanding these factors is crucial for developing targeted therapies and management strategies for individuals affected by this challenging condition.

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