Characterization of Alopecia: Areata, Totalis, and Universalis
Alopecia is a broad term that is used to describe hair loss of many different kinds. In fact, the technical term for male-pattern baldness is actually Androgenic Alopecia. Unlike male pattern baldness, Alopecia Areata (AA) is an autoimmune disorder that targets the anagen (or growing) hair follicle and results in patchy hair loss. As of 2012, there were approximately 4.5 million Americans that were suffering from AA (Gilhar 2012). The prevalence of AA in the world is 0.1-0.2 %, with a calculated lifetime risk of about 1.7-2.0 % (Gilhar 2007/2012, Hordinsky 2004). The disease usually presents itself in patients when they are children, teenagers, and/or young adults, but the onset of symptoms has also been noted in adults in more rare cases.
Autoimmune Alopecia tends to manifest itself in different ways and is named depending on the location and severity of hair loss. Alopecia Areata, as mentioned before, is characterized by patchy hair loss on the scalp, while Alopecia Totalis (AT) results in total loss of scalp hair and Alopecia Universalis (AU) results in complete loss of body hair. While each of these versions of Alopecia are named differently, they all result under the same metabolic conditions. In other words, the generation of hair loss between AA, AT, and AU does not differ depending on the subtype of Alopecia. As such, most papers focus on all three types of alopecia. For the sake of clarity, AA will be used to denote any of these three types unless specifically noted. AA can be easily diagnosed because of its solely physical manifestation. AA separates itself from other skin diseases because it is both non-scarring and non-inflammatory. There are also secondary characteristics by which physicians can recognize AA such as premature graying or whitening of a patient’s remaining hair or the disruption of the nail matrix on patients’ hands. Diagnosing AA with these secondary characteristics, however, is not a perfect method because not all patients experience premature graying or disruption of the nail beds. In rare cases, a skin biopsy may be needed to confirm the diagnosis. This biopsy is generally successful because they search for certain histological features around the hair follicle, as exemplified by figure 1 (Gilhar 2007). There is also epidemiological evidence that suggests AA is associated with lupus erythematosus in 0.6% of patients, vitiligo in 4%, and autoimmune thyroid disease in 8 to 28%. The overall risk of an AA patient being afflicted with a secondary autoimmune disorder is about 16% (Gilhar 2012). This number is small, but not entirely insignificant given the number of those afflicted with AA. Using the statistic from above, this would mean that approximately 720,000 of the 4.5 million diagnosed with AA also show symptoms of other autoimmune diseases.
Biology of the Hair Follicle
In order to understand the overall impact that AA has on the growth and function of the hair follicle, the normal function of a healthy hair follicle must be examined. Unlike many other parts of the human body, hair follicles undergo cycles of growth and rest throughout their entire lifespan. The typical human hair follicle exists in three separate phases: anagen, a phase characterized by extensive growth and proliferation of the hair follicle; catagen, an apoptosis mediated shrinking of the hair follicle back to its normal size (organ involution); and telogen, a state of rest before re-entering the anagen phase. In AA patients, CD8+ and CD4+ T cells and Natural Killer (NK) cells accumulate and attack only hair follicles that are in the anagen phase. Because of this, hair growth is suppressed rather than completely eliminated because the hair follicle itself is not destroyed and remains entirely intact. While hair regrowth is sporadic and difficult to coerce, the mechanism of AA allows for the possibility as the hair follicle is essentially being held in a state of rest by its own immune system. (Gilhar 2007) A figure from Gilhar et. al.’s 2007 AA review summarizes this information quite nicely (figure 2).
The immunology of the healthy hair follicle is also extremely important to understand in the context of AA. In a healthy person, hair follicles are generally granted “immune privilege.” Immune privilege is a term given to any part of the body that can tolerate the presence of an antigen without an extensive inflammatory response from the immune system. Besides for the hair follicle, the eyes, placenta in pregrant women, and testicles are also granted immune privilege (Gilhar 2007). There are a number of mechanisms by which tissues are granted immune privilege, and all act together in order to suppress an immune response. The most common and relevant to AA mechanisms of immune privilege are the low expression of MHC class I molecules, the local production of immunosuppressive molecules (i.e. transforming growth factor-β1 or Interleukin 10), and the absence of lymphatics near the hair follicle (Paus 2005).
In healthy people, all three of these mechanisms grant their hair follicles protection from their own immune system. The normal function of MHC molecules is to recognize and present small parts of an antigen to T cells, which begins the process of specific immunity. Therefore, low expression of MHC class I molecules ensures that auto-active CD8+ T cells cannot recognize the MHC presenting an autoantigen because the MHC is absent, thus preventing an immune response. The low expression of MHC class I molecules opens up the possibility of attack by NK cells, since they generally act to destroy MHC class I negative cells. The hair follicle seems to control this by down-regulating the production of NK stimulating ligands while simultaneously up-regulating the production of molecules that inhibit NK cell function, TGF- β1 amd IL-10 (Gilhar 2012). TGF-β1 and IL-10 also both contribute to immune privilege by acting as secreted agents that maintain the current immune state. In other words, TGF- β1 and IL-10 are both secreted when a harmful autoantigen is not sequestered correctly and work to destroy this autoantigen and prevent it from being recognized by the immune system (Gilhar 2007). It is not surprising, then, to see the onset of AA be linked to the collapse of immune privilege within the hair follicles. There would be no need for immune privilege if there was no danger of developing autoimmunity against specific tissues, which is seen in most parts of the body.
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