Thursday, 16 June 2011

Allergy and intolerance and autism

Summer is upon us yet again. The sun is shining, birds are singing and oh yes, people sneezing thanks to that most exquisite allergy to pollen, hay fever. With this in mind, so begins my mega-post on allergy and intolerance.

When I was about 10 years old, I discovered I had an allergy. Although my memory of events is a little vague, the story went something like this. My parents and I were visiting friends who had a long-haired cat. I don't remember the mugshot of the moggie in question, but I remember it had long hair. After a while stroking and playing with said moggie a la Blofeld, I remember my eyes beginning to water and becoming very itchy. As a youngish child, I couldn't resist the urge to try and rub and scratch them to try and relieve the itch. After a while of doing this, my parents noticed that I was looking a little bit worse for wear - my face was turning very red and I started to take on that boxer-look around the eyes. So much so that a quick trip down to the Accident & Emergency department of the local hospital was in order. At the hospital I remember watching all the doctors and nurses running around and all the walking wounded waiting patiently for their turn. When it was my turn my memory is faded aside from a nice medical type drawing little circles on my arm and pricking it with quite a few needles. One needle prick in particular started to become red and itchy - cat hair. And so began my long running cat allergy. Needless to say this was quite a shock to me and my parents. I had been in contact with lots of cats during my childhood, although we had never owned one. I am still cautious to this day about my contact with cats, particularly the long-haired variety, lest my Henry Cooper look makes another appearance.

Years later I found out about the science behind my allergy experience. The needles on my forearm formed part of the skin prick test and I had/have a type-1 IgE sensitivity to cat hair. The day of my cat experience, I joined quite a large number of people who have an allergy, but what exactly does that mean?

Allergy is probably one of the most nebulous terms in medicine. Nebulous because it covers such a wide range of things and is a term used interchangably (rightly or wrongly) with things like intolerance and hypersensitivity. There is quite a good lay-persons overview of allergy here. The clinical defintion of allergy is that it is a hypersensitivity reaction to some allergen initiated by an immunological reaction. Probably the most famous classification of allergy is that by Gell and Coombs who originally divided hypersensitivity into 4 types: type 1 (immediate), type 2 (cytotoxic), type 3 (immune complex) and type 4 (delayed hypersensitivity).

Type 1 immediate hypersensitivity mediated by the IgE isotype is perhaps the gold standard allergy (also called atopy) reflecting the production of allergen specific IgE, followed by the release of histamine. This is also the mechanism through which anaphylaxis is thought to operate of which peanut allergy is perhaps the most famous. Type 2 cytotoxic antibody hypersensitivity is mediated by IgG and IgM isotypes.

Intolerance, by contrast, is defined as a non-allergic hypersensitivity where IgE isotypes are specifically not involved. I have already blogged about intolerance in previous posts, most notably when talking about lactose intolerance and autism. Indeed, lactose intolerance really sums up food intolerance - the body's inability to handle a food because of problems in producing sufficient quantities of the enzyme(s) needed to digest that food. The IgG isotype has in recent years found a home in the term intolerance; indeed gluten intolerance has been noted in relation to IgG in various conditions. The suggestion being that protein fragments / peptides not properly broken down because of enzyme deficiencies enter the circulation and begin accumulating IgG antibodies. Mmm, I've heard something similar before with the opioid-excess theory and that pesky leaky gut theory.

Having spent quite a portion of this post in describing mode, I should perhaps also talk about where autism may fit (or not) in this chain of events. I have quite an interest in allergy and autism if only for the reason as to why the various dietary changes discussed in autism might potentially work. For those of you who want the full peer-reviewed scientific piece, have a look at a paper here that my colleagues and I published around this topic a few months back. For those, like me, who prefer the 'Mr Men' version, it goes something like this.

Overall, the currently available evidence seems to suggest that people with autism are perhaps more likely to suffer from various allergies as are their parents. The evidence for co-morbidity of specific IgE-mediated allergy in autism spectrum conditions suggests however no overall greater frequency to be present than in the general population (although with some evidence to the contrary specifically with Asperger syndrome in mind). It seems therefore that where allergy exists alongside autism, it does so in the most part outside of the classic type-1 hypersensitivity as witnessed by the various papers suggestive of such an association. There are caveats to these very sweeping conclusions I have made not least the n=1 principle. Determining exactly what are the main allergens causative of such as reaction is, understandably, a more individual thing.

The final question is really a question of what can we do about allergy in autism. Assuming that the underlying biochemistry of allergy is the same in autism as not-autism, the obvious answer is to avoid the allergens. Going back to the work from Harvard on lactose intolerance and autism, and the suggestions of excluding casein where milk allergy might be indicated, there is perhaps some good sense in this approach. The fact that such dietary changes might also have some knock-on effects to core and peripheral autistic symptoms is an area that requires much more description about the possible mechanisms as to why.

Although based on IgE-mediated allergy, there may also be some ground to cover with various other interventions for allergy. Before proceeding, I would add that my caveat about not giving medical advice comes into full force at this point; talk to your Medical Doctor or Pharmacist before starting any kind of medication or treatment regime. The use of anti-histamines such as cetirizine is often the first-line for treating mild allergies such as hayfever. The anti-histamine part is the important bit in that such medications are designed to block the receptors to which histamine attaches. It is interesting to note that some of the medications designed to block H2 receptors have also been looked at more directly in relation to autism. An interesting point indeed.

Another potentially relevant avenue of treatment is that of allergen-injection immunotherapy which involves graded dosages of a particular allergen building up over a period of time until tolerance is acheived. I always equate this with people like Dr Len McEwen and his similar work on enzyme potentiated desensitisation which is all but the same thing - introducing small doses of an allergen - although alongside the addition of beta glucuronidase. The evidence base is unfortunately pretty much non-existent for both these options in relation to treating allergies alongside autism at the moment, but that is not to say that they are not viable options for treating allergy more generally. The obvious problem is also that such allergy therapy involves needles and quite a few people with autism (like the rest of us supposedly strong men) don't like needles.

Allergy and intolerance are still pretty vague concepts, in terms of their description and biological mechanisms, which might have some varying applicability to some cases of autism. These are big areas of health which I have only been able to give a brief overview about without even touching on things like mast cell activation and how humoral immunity might tie into cell-mediated immunity, which have both been linked into autism in some way, shape or form.

For those unfortunate enough to suffer with allergies like hay fever, I end with some scenes which are reminiscent of symptom-free times from my part of the world.