Monday, January 12, 2009

Ask A Scientist: Hair Loss (Alopecia Areata)

By request, I present a brief review of alopecia areata, also known as AAAAAGH!!!! My hair is falling out for no reason!!.

First, let me present you with a confusing medical fact: there is a poor distinction between a 'syndrome' and a 'disease'. Generally speaking, a syndrome is a collection of symptoms. Chronic fatigue syndrome is an example: it is a condition defined largely by how people feel, rather than a specific etiology (cause). A disease is (or should be) something with a well-known cause. Ebola virus is a disease. Wilson Disease, whose genetic cause is known, is a disease. AIDS is called 'immune deficiency syndrome,' but in fact the etiology, the HIV virus, is well known; it would, in my opinion, better be called a disease, but historical inertia prevents this.

At the same time, a lot of things with vague diagnoses are also 'diseases.' Graves' disease, for example, is caused by an autoimmune response to the thyroid. But what causes the immune problem to start with? Who knows.

Alopecia is something like this. It is defined as* hair loss with T-cell infiltration (a type of white blood cell).

Now let me give you my completely Mickey-Mouse-level understanding of autoimmunity:
T cells react to antigens- short bits of protein- but only when these bits of protein have been chewed up and 'presented' on the surface of other cells. So for T cells to be in the scalp, they have to be reacting to a secondary stimulus: another cell has to have, wrongly, recognized a hair protein as foreign. (There is a complicated process of selection which is supposed to kill off all your immune cells that would recognize and attack bits of your body. Obviously, every so often something goes wrong.)

B cells (another kind of white blood cell) start their life with an antibody stuck to their surface. (They are also selected to not attack one's own body.) When the antibody meets something it recognizes, it gloms onto it. Then it eats it along with its antibody. Then it chews it up and goes and shows it to a T cell. Lots of complicated things then happen, including that you get more T and B cells that specifically recognize that antigen. Some of the B cells become a new and exciting kind of B cell that secretes, or puts out, antibodies of various kinds.
Now back to alopecia.

According to several papers, up to 90% of alopecia patients have antibodies to hair follicles or hair proteins in their blood. This means that a B cell has to have been stimulated to produce antibody.

I don't know where the original antigen came from. When cells die in a 'pre-programmed' way (this is called apopotosis; it's natural when cells come to the end of their lifetimes or meet various kinds of trauma or... etc.) they blob off into little bits which are supposed to be eaten up by the body's internal vacuum system. Maybe some of them escape. Who knows.

The main problem in autoimmune diseases is, there shouldn't be anything there to react to bits-o'-body. But there is. As our understanding of what to do to the immune system to make it better is largely at a throwing-rocks level, the treatments for autoimmune diseases are, almost universally, immune suppression.

A relatively recent article in NEJM* suggests that injected steroids can benefit many patients. Small volumes are injected all over the affected area; in a few weeks (possibly due to hair life cycle?) hair may start to grow. Side effects, as with all steroids, include skin effects; usually the dose is too small to get many systemic effects. This treatment can be done with or without minoxidil. Side effects commonly include unwanted facial hair growth, either because it gets rubbed off onto a pillow, or because the face is, after all, near the scalp.

Several studies, which I am too lazy to link, suggest that topical steroids have little effect, but people do it anyways because it's cheap and relatively low-risk.

A meta-analysis* has also been done on all known double-blind studies. They conclude that no treatment is particularly effective and one might as well do nothing, or something equally depressing. However, meta-analyses are always tricky to interpret. They are comparing dozens of unrelated studies by criteria that may not have even been measured in the original study. In this one, they are defining clinical success as 50% hair regrowth. The authors note that patient satisfaction might have been a better, if less scientific, measure.

Interestingly, persons with other immune conditions- eczema, allergies, thyroid problems- are more likely to experience alopecia areata at some point. Some people theorize that this connection is indicative of a common genetic cause: something is slightly wonky in the MHC alleles (if you don't know what these are, trust me, you don't want to) and it manifests itself as various small problems. This makes sense, but is hard to test because who wants to fund hair loss? That's right. Nobody.

*Subscription on most articles; contact me if you want a copy.