by Kevin Rands | May 15, 2016 9:22 pm
HairlossTalk’s Science writer, Deborah O’Neil helps us understand Alopecia Areata a little better with this informative article.
A non-classical form of hair loss
In contrast to the gradual thinning seen in male and female pattern hair loss, the onset of alopecia areata (AA) is sudden and often extreme. This form of hair loss is the most spontaneous. A patchy, often random baldness can appear over the scalp within a staggeringly short space of time. Patients with AA commonly report finding handfuls of hair on their pillow or disappearing down the shower drain, without any prior clues or warning as to the onset of this relatively common hair loss condition, one that equally affects men and women.
The immune system is at fault
Scientific and medical research over the past few years has brought us much closer to understanding the cause of AA and it is now widely accepted that this form of hair loss is actually an autoimmune disease. This is a term given to any condition that results from the immune system targeting the body’s tissues, cells or organs, destroying them much in the same way as it would a bug (viruses and bacteria) or non-self, ‘foreign’ tissue. To date, we still do not fully understand why the immune system, which normally protects our body from infection and the onset of cancer, can turn against us in this way. Examples of common autoimmune diseases include rheumatoid arthritis, in which the soft tissue between the bone joints are destroyed and diabetes, where the insulin producing cells of the pancreas are destroyed. In AA, one or more component parts of the hair follicle appear to be the target for this inappropriate and self-destructive immune response, the result of which is the onset of one of the most insidious and upsetting forms of hair loss.
There are numerous triggers for AA, all of which combine with an already present ‘hard-wired’ genetic predisposition for the disease, to drive autoimmune mediated hair loss. These include hormonal changes induced during pregnancy or by contraceptive pills, various medications, stress, thyroid dysfunction, anemia, bacterial infections and other autoimmune diseases such as arthritis. These triggers will vary from individual to individual, but all act in an as yet undetermined way to cause an immune malfunction that results in the destruction of hair follicles over an area or areas of scalp. As upsetting as this sudden and extreme form of hair loss can be, the good news is that as with all relapsing-remitting autoimmune conditions, the hair will grow back once the trigger for the attack has been removed or the immune response that has caused is blocked.
A role for autoreactive lymphocytes
One wouldn’t normally expect to find many immune cells (the white cell component of blood in other words) within healthy scalp skin, as this area of tissue is relatively inert in terms of the need for a patrol of infection-fighting cells. In contrast, a number of investigators have reported finding numerous immune cells within skin samples obtained from the scalps of patients affected by AA. One cell type in particular, the T lymphocyte, is particularly abundant in these cases.Moreover, these cells are undoubtedly in an activated, immunogenic state. A 2002 study by Yano et al demonstrated that levels of cutaneous lymphocyte-associated antigen (CLA), a specific homing factor that recruits activated T-lymphocyte cells into the skin, correlate with AA disease activity. That is to say, blood taken from patients with severe or progressive AA have contains significantly higher levels of CLA (bound to T-lymphocytes) compared to blood samples derived from normal individuals or even AA patients recovering from the disease. CLA levels in AA patients who do not respond to oral corticosteroid therapy remain higher than in those who respond well to the treatment. In addition to this study’s findings from the patients blood, they also examined the distribution and levels of CLA within scalp skin and found high numbers of CLA bound to T-lymphocytes present around the hair follicles. These data suggest that CLA-positive T-lymphocytes may play an important role in AA and that a simple blood test may be used to monitor AA disease activity by assessing CLA levels.
Further evidence for the central role of T-lymphocyte cells in the pathology of AA comes from animal studies in which bald, lesional scalp sections, removed at biopsy from AA patients, will re-grow hair when grafted onto nude mice, a specialized laboratory species that does not produce T-cells. The reverse is also true in that hair loss can be induced from normal human scalp explants that are grafted onto a similar strain, the severe-combined lymphocyte immunodeficient (SCID) mouse, if T-lymphocytes obtained from AA scalp lesions are then injected into the host animals. In laboratory experiments, T-lymphocytes from AA patients can be activated in vitro if they are exposed to follicle and even melanocyte (pigment producing skin cells) cell preparations. Analysis of scalp biopsies reveals the presence of markers of inflammation within the epithelial cells that line the follicles of AA patients, such as the antigen presentation histocompatability molecules HLA-DR; HLA-A,B,C; and the adhesion molecule ICAM-1. These markers of inflammation are induced by interferon-gamma, an inflammatory chemical (a cytokine) released by activated T-lymphocytes.
Hair follicles are the target
A big clue as to what these T-cells might be reacting to comes from the fact that AA primarily affects the hair follicle as it enters the prolonged growth phase called anagen. During this stage in the hair cycle, proteins such as hair-specific keratin and trichohyalin are produced in the inner root sheath of the growing hair follicle. These are amongst the candidate targets for the immune system in AA currently being studied. Evidence that antibody-generating B-lymphocyte cell autoimmune responses to hair follicles appear to act in concert with the T-cells during the course of an AA attack responses comes from data generated from numerous studies demonstrating the presence of numerous anti-hair follicle antibodies in the sera of AA patients.
Treatment of AA and the potential benefit of recent scientific developments
Current treatment strategies are aimed at limiting the inflammation that the autoimmune reaction causes. As such, the most common first-line therapies are local injection of corticosteroids (cortisone) if the disease is patchy, or oral corticosteroids (cortizone tablets) if the disease is more widespread. 5% Minoxidil ointment is also employed as a therapeutic intervention. Diphencyprone (DPCP) or Squaric Acid Dibutyl Ester (SADBE) treatments are other options. These are designed to counteract the underlying immunogenic autoimmune reaction with a localized allergic reaction, inducing hair growth as a result. On the whole, current therapies are not very sophisticated or specific and are associated with significant side effects. A better understanding of the autoimmune response that drives AA is the first step in the development of novel, more targeted therapies. These include and mechlorethamine, anti-interferon-gamma and other anti-immune modulating protein antibodies that block the follicle-targeted inflammatory response. These have already been proven as efficacious in reversing hair loss in mouse models of AA and in limited human trials studies. This is very good news for the many individuals currently afflicted with this most aggressive form of hair loss and guarantees that more sophisticated, effective and safer treatments are not too far around the corner, hopefully becoming available to patients within next few years.
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