Preparation and Being Proactive is Key

Allergies affect about 10-20% of the population. This means that up to 1/5 of us suffer from seasonal allergies. Most people without allergies do not appreciate how disabling and crippling allergies can be.

Studies have shown that the majority of allergy sufferers have moderate to severe intermittent or persistent limitations on their quality of life from allergies. It’s nothing to sneeze at!

We have had a pretty cold winter this year in 2013-2014 but for allergy sufferers it’s well known that tree pollen season is just around the corner.

In Ontario, the tree pollen typically starts sometime in March 2014. This is followed by grass allergy season starting in May, June, and July.

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So what can patients do to prepare?

Well, it’s not exactly practical to avoid going outside or having your windows closed entirely.

We need for some way to decrease the symptoms or try to “cure” the problem. Pharmacotherapy (medications) and allergen immunotherapy (allergy shots or tablets) have been around for a long time and offer patients a solution to allergies.

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Which of the two above do you think has been around longer? It’s actually allergy immunotherapy in the form of injections (shots).

Allergy shots have been around since 1900 when a fellow by the name of Curtis surmised that you can vaccinate against allergies. He took patients with weed allergies and started to inject them with weeds. His patients did improve!

Through a series of experiments and trial and error we have now worked out over the past 104 years exactly how much and how frequently to administer these shots to patients in a controlled and evidence based way. As allergists, we now have practice parameters based on studies that have taken the guess work out of allergy immunotherapy and standardized the practice so that safety and efficacy (effectiveness) are known quantifiable entities.

For tree allergies, currently what exists is a series of injections normally started in January of each year in Ontario. For grass allergies it is started normally in March of each year. One can do tree and grass combined usually starting in January as well. There are several companies in Canada that make these allergen immunotherapy injections.

Allergen immunotherapy works! We can actually measure and see the changes to the immune system including but not limited to how the cells actually talk to one another. By injecting tree pollens in controlled and discrete increasing amounts, your body eventually starts to no longer see the pollen as some parasite over time. This doesn’t work for everyone but meta analysis (large pooled data from multiple well designed trials) show that allergen immunotherapy is of benefit for ~70% of patients.

What is exciting this year is that we now have two forms of grass tablet based immunotherapy. This is essentially grass pollen in a tablet form. The tablet is melted under your tongue where it dissolves and delivers a discrete reproducible controlled amount of grass pollen. This is normally started 8 weeks prior to grass allergy season but it may depend on local climate and weather forecasts.

Neither one of these modalities are “side effect free”. There is a 1 in 2.5 million chance of death to allergy immunotherapy injections and about a 1/1000 chance of experiencing anaphylaxis to either the shots or the tablets. One must wait around 30 minutes after getting each allergy immunotherapy injection and for the tablets the first dose needs to be taken at your allergist’s office and if you are “ok” then you must take the tablets daily at home until the end of grass allergy season which has been historically at the end of July. Most people with the injections just experience local swelling where the injection is done.

The coolest thing about all this is that after about 3 years of the tablets you are able to experience persistent benefit for the grass allergies even if you stop taking the tablets. This effectively is a “cure” or as we like to call it in medicine, disease modification. The same disease modification occurs with allergy injections too, but may take 3-5 years. There is even data that is a 10 year follow up study in children showing that if children receive allergy immunotherapy injections (SCIT) that they are much less likely to develop asthma. The same studies are being now done on tablet based immunotherapy (SLIT) but I suspect the results may be even better.

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So why is SLIT potentially better than SCIT? It offers an obvious convenience of home administration however there is something to be said about the mouth being a tolerant organ. Your mouth is exposed to millions of different things everyday from the act of eating. It is trained to recognize what is harmful from you to what is food. It needs to be able to do this or otherwise you’d experience allergic reactions every time you ate something foreign. Unless you’re a cannibal eating your own identical twin, everything is technically foreign to your immune system and mouth. Given that the mouth is an “expert” or special place in your body, it may be the case that it is better at retraining the body for allergies.

Side effects are also possible with SLIT and most people do experience itchiness in the mouth as you are putting something your body is allergic to in the mouth. Keep in mind that multiple safety studies have been done in controlled settings to determine what is the best dose and way of doing this. SLIT has undergone rigorous studies, in fact one could even argue that much more so than drugs like antihistamines or nasal steroids for the treatment of allergies.

Compared to antihistamines and nasal steroids SLIT and SCIT offer superior efficacy for allergies and offers the potential for disease modification. As a physician this is certainly more satisfying that I am shaping the course of a person’s disease in the right direction.

Antihistamines, eye drops, nose sprays of course also help but doesn’t offer the chance of a cure. They are certainly convenient and generally safe however.

Well the time to start grass immunotherapy is quickly slipping away. To learn more about this check out my patient educational websites at grassallergies.com or ocularallergies.com

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Cold Induced Urticaria – Allergies to the Cold!

As the winter weathers entrench themselves I thought cold induced urticarial would be a fitting topic for my winter blog entry.  Also I had a suggestion from my small but very appreciated twitter followers!  Thank you.

Urticaria is essentially the medical word for “hives”.  We define acute versus chronic somewhat arbitrarily based on whether or not the hives occur for less than 6 weeks of more than this amount of time for the later.

Now there is a subset of chronic urticaria that really presents as acute intermittent urticarial.  What I mean by this, if a person is exposed to a particular trigger, it becomes chronic based on definition alone (i.e. the hives are occurring on more days than not for more than 6 weeks).  When the triggers to the hives are physical triggers this is termed physical urticaria.

Physical urticaria encompasses many different stimuli including, but not limited to: pressure, heat, sweating (cholinergic), vibration, light, and you guessed it cold.

Now the critical concept not discussed in most medical texts and journal articles is why we even have the ability to form urticarial lesions in the first place.  For this we have to go back to the fundamental understandings of the immune system.

As humans, like most animals on this planet, need a robust way of dealing with all manner of critters that are out to either live off us, harm us, or even worse kill us.  As such we needed a way to counter this so that we don’t succumb to these attacks.  The “hive” that you are getting is actually your body “naturally” committing chemical warfare on whatever parasite, bacteria, or virus is coming in! 

There are a lot of junk science articles out there that explain hives as a being the end result of an underactive immune system.  This is simply wrong!  Incidentally, stating that it’s the end result of an over active immune system is also kind of wrong!  It’s technically best described as an incorrect regulation of the immune system. 

In most developed countries we are no longer subjected to a barrage of attacks from little critters and as such forget why we even need this type of immune response.  If a parasite is burrowing it’s way into you, your body may sense some vibration, pressure, or temperature change at that site.  Naturally your body needs a way of letting you know something is happening there and hence substances such as histamine get released to cause you to itch (i.e. alert you that something is trying to breach your borders!).

Other chemicals also get released in a hive reaction such as major basic protein (that fights micro-organisms) and heparin (helps open the blood vessels up so that other white blood cells can get in on the action later).  It also increases the propensity, first locally then systemically (throughout your body) to alert other first, second, and third line defenders of the immune system to be on “red alert” (no pun intended!) through the release of cytokines and chemokines (the chemical signals that your immune system uses to communicate) and activating factors such as “stem cell factor” which temporarily increases the longevity and aggressiveness of some lines of your immune system.

So now in terms of cold urticaria there are really 2 broad types of cold induced urticaria. 

1)   systemic (requires a fall in body temperature)

2)   local (requires only a part of your body to become cold)

Some people will also split up the categorizations by whether of not one responds to the “ice cube challenge” test done in the clinic.  There are now all sorts of fancy devices that can tell a physician exactly what temperature is required to induce an urticarial reaction but in a public health care system don’t expect this to be available any time soon!

In any event, systemic cold induced urticaria is far more rare.  This occurs when there is a fall in the core body temperature of someone.  So this would be someone who gets urticaria after going outside on a cold day.  The hives will occur not only on areas of exposed skin but throughout the body (systemic).

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Local cold induced urticaria is more common than systemic.  This occurs in skin that is exposed to cold.  Various temperature thresholds are required and it varies from patient to patient. 

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Occasionally cold induced urticaria is associated with an underlying medical problem.  Some things your physician should rule out if this has become chronic is cryoglobulins, cryofibrinogens, presence of low complement levels, some hematologic malignancies, hepatitis (whether it be autoimmune or viral), renal disease, and other auto immune conditions.

There are a known few familial forms of this including the recently described one herein http://www.ncbi.nlm.nih.gov/pubmed/22236196 or as part of CAPs syndromes.  However, routine testing is very difficult to do.  Even in cases of CAPs, not all gene mutations have been identified so the genetic testing is not always necessary or useful in whether or not we decide to test for the mutations.

Treatment includes avoidance like anything in allergy.  Two particular situations patients need to be careful about is swimming and ice cold beverages or things such as ice cream.  Swimming can induce urticaria throughout the body resulting in hypotension (low blood pressure).  In some cases the diffuse urticaria will cause in drowning due to loss of consciousness.  Occasionally some patients with this condition will experience angioedema with the ingestion of cold beverages and as such eating something cold can potentially cause throat constriction.

Management includes carrying of epinephrine in some cases as well if there has been any prior anaphylaxis.  I typically advise patients to avoid swimming.  A medic alert bracelet identifying that the patient carries epinephrine autoinjectors (EPI pen ® or Allerject ® / Auvi-Q®) with anaphylaxis labeled is highly advised as well.

There are two exciting developments though that I’d also like to share.  If a patient has been diagnosed as having a CAPs syndrome, two new drugs in the class of anti-IL-1 monoclonal antibodies are a game changer.  In particular they are called anikinra® and elaris®.  However I want to emphasize that these conditions are extremely rare and that it is best if you speak to your specialist clinical immunologist and allergist about this.  If you’ve seen me, don’t worry I’ve already thought about it and ruled it out in most cases.

The other really exciting development, as is the case in all causes of chronic urticaria is the use of another monoclonal antibody called Xolair ®.  This is currently approved to treat moderate-severe asthma where it works great!  However, most dermatologists and clinical immunologists and allergists who remembered a little bit about basic science immunology suspected it would likely work even better on chronic urticaria.  I have my own theories on the exact mechanism of action on this and I am told there are already ongoing studies globally and in Montreal exploring the postulated mechanisms.

The very first study on chronic “spontaneous” urticaria patients published in the New England Journal specifically excluded patients with cold induced urticaria strangely enough for reasons that are unclear.  However subsequent studies show that it is very effective in cold induced urticaria as well.  It is unclear if this is permanent.  

So the $1 000 000 question is what causes people to be “allergic” to the cold?  Well it depends.  Most of the time we do not know!  The theory is that there is something that agitates the cells that cause most of the hives (mast cells).  I do want to emphasize that it can be a self limited and self resolving condition in most benign cases.

Of the known causes it is important to treat the underlying condition. 

With that I wish everyone the best in 2014!

Dr. Jason K Lee, MD, FRCPC

Twitter @lee_jasonk
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Cases of Anaphylaxis and a Recap of ACAAI 2013 Meeting

Ken Lieu
Zainab Bukola Abdurrahman
Shudeshna Nag
Michelle Halbrich
Rhoda Kagan
Audrey Segal
Elana Lavine

November 19th, 2013 Cases of Anaphylaxis and a Recap of ACAAI 2013 Meeting

It was an intellectually stimulating night where eight physicians put their minds together to solve the mysteries of difficult patient cases.

Ken Lieu case #1
67 year old female. ? anaphylaxis in Mar 2012.

Began with palpitations, hives, angioedema of face, tongue, and chest tightness.

Went to ER, had HTN on presentation. Treated with EPI.
6 hours after recovered.

April 2012. Similar symptoms. Self treated with Benadryl. This time no angioedema and no respiratory symptoms.

PMHx
No ARC, ? asthma
HTN

Allergies
Demerol drug allergy. ? Lipitor allergy

Meds
Norvasc, atacand, zopiclone

tryptase, look for other food triggers, total IgE, seasonal?
5HIAA, catecholine, metanephrines, vma, serotonin

Diagnosis?
grossly elevated serotonin found. Patient sent to heme by Dr. Liew.

Dr. J Lee suggested referral to GI and ruling out of carcinoid syndrome.

Rhoda Kagan case #1
10 year old male
4 episodes of reactions

Poached pears, nut megs, lamb, brandy. Flushing

French fries, pita pit erythema, SOB.

? McDonald’s -> had a reaction

spices ->

No issues with nuts.

? oil
? sesame ? borderline ? latex ?tartrazine
fully worked up for idiopathic anaphylaxis and no abnormal results.

Diagnosis?
Dr. E Lavine suggested possibly sending to Dr. Sicherer in US, will do a test to >150 food tests. IZAC chip.

No consensus on diagnosis. Possibly sesame oil or tartrazine or carmine suggested by Dr. J Lee. Dr. Z Abdurrahman suggested possible spices. Dr. E Lavine mentioned that not many ketchups have tartrazine in ingredients.

Other possibilities include pure exercise induced anaphylaxis.

Elanna Lavine
Shared a case where dry powder bug spray has corn starch.

Zainab Abdurrahman
Severe asthma case. 8 year old male. On prednisone several times a day.

Pre and post bronchodilator > 40%. On zenhale, now improved.

? Consideration of biologic agents in this age group? Patient referred to Hamilton’s firestone clinic.

Audrey Segal
Minute maid orange juice. Shower anaphylaxis with urticarial, syncope, and angioedema.

Nausea, diarrhea. Swelling in joints. Decreased ROM in EOM by ophthalmology.

Skin prick test positive to mango.

Question was, what was the cause of the decreased ROM and abnormal EOM? Presyncope? Decreased perfusion? Unclear.

Elana Lavine
Asked the question: When do tree nut allergies develop?

Interesting theoretical discussion about this.

Immunocap to oval mucoid vs immunocap to egg white was also discussed.

Immunocap not predictive of oral challenge.

Component testing for prognostication emphasized for food allergies.

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Can early exposure to nature be useful for allergies?

With an open mind I have been following David Suzuki’s latest campaign to encourage people to be spend more time outdoors with some evidence showing benefits to health in general. In his work, Suzuki highlights some studies showing an increased sense of wellbeing, decreased blood pressure, and other health benefits with increased out door activities.

I have no doubt that there are health benefits from spending more time with nature. Just the act of getting out of the house to engage in mild to moderate exercise outdoors may be helpful for the mind and body.

I then began to ponder if there are any theoretical benefits to being regularly exposed to the great outdoors in terms of allergies. There isn’t a whole lot of evidence based research on this, so I am speaking in this blog about some theoretical benefits made from what is currently known, extrapolating from other studies.

When someone develops an allergy to something, it is possible that they can eventually (if they’re lucky) develop immunologic tolerance to whatever it is that they are allergic to with repeated exposure. This concept is called anergy in immunology. Anergy is the basis of allergy immunotherapy wherein controlled escalating dose exposures can try to desensitize, aka re-train the immune system of a person to no longer react as if the harmless pollen is a parasite.

While the technique for aeroallergen desensitization through allergy immunotherapy works very well for inhalant allergies such as tree, grass, ragweed, dust mite, etc., the risks associated with food allergy desensitization are still, in my view, too high risk as many patients will experience anaphylaxis during the desensitization process. They are working on making this safer as we speak. The Cochrane Review, which is an independent body that evaluates scientific evidence behind medical interventions, gives allergen immunotherapy a class IA recommendation for asthma and a class IB recommendation for rhinitis which are the highest and second highest possible recommendations a medical intervention can receive. Immunotherapy has a 100 + year track record of safety and efficacy. Essentially, this is a method of retraining the immune system to stop reacting to the allergen as a harmful parasite.

While many clinical trials have shown that desensitization therapy is possible with just about any type of allergic sensitization including food, medications, and airborne allergens (provided it was a true allergy to begin with), I am reminded of the many patients who have tried this on their own using products such as unfiltered unpasteurized honey who have had anaphylaxis (life threatening allergic reactions). Do not attempt to desensitize yourself at home! There is a reason why I have over 13 years of training in my field!

Getting back on track, how does all this relate to early exposure to nature? When I examine the natural peaks and troughs of pollen counts outdoors, I cannot help but notice that the pollen levels naturally rise and fall. A form of allergen immunotherapy that is commonly done by an allergist is called “pre-seasonal allergen immunotherapy”. This is when a licensed medical specialist in allergies will inject you weekly with the pollens you are allergic to, with each subsequent dose being a higher dose than the previous. This has been proven to “retrain” the immune system in most patients with allergies. For example, if you have a birch tree pollen allergy, I would be injecting you with controlled doses of birch allergen before the tree season and try to “retrain” your immune system to no longer see the pollen as a foreign harmful invader by your body.

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Given that pollen counts gradually rise and peak, it is possible that if you spent every day in nature from the beginning to end of pollen season you may be able to get a similar gradual retraining of the immune system.

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This is where the evidence gets a little gray and I have to extrapolate from other studies and the collective clinical experience of “medical expert opinion”, which is actually a lower form of evidence.

In children, it generally takes 2-3 repeated seasons of exposure to develop seasonal allergies. New immigrants who come from a different part of the world where they did not have a chance to grow up with the same types of trees, grasses, and weeds will often exhibit this same 2-3 year cycle (i.e. their allergies begin to manifest after 3 years of being in their newly adopted country).

Now here is the other tricky part. Immune system “retraining” tends to work better the younger you are. There are many reasons, known and unknown, for why this is the case. One of the reasons is that the main training center organ where some parts of the immune system go to get their education, called the thymus, gets smaller as we age. The smaller the “university” for our immune system the less “retraining” that can occur. As such, there is solid randomized placebo controlled evidence demonstrating that receiving allergen immunotherapy in youth is truly disease modifying. For example, a robust trial of aeroallergen immunotherapy in children showed that using allergy immunotherapy in childhood can actually prevent the development of asthma.

People can also lose the tolerance they have already developed for their immune system without exposure. In children with peanut allergy for example, a child who outgrows their peanut allergy can actually re-acquire their allergy if they avoid that food for a long time. In fact, this is the very danger of going to a non board certified clinical immunologist and allergist who may not be aware of this nuance and suggest that you in fact avoid things based simply on skin prick testing results being positive. A person can actually lose their established tolerance and have symptoms from losing their anergic state by unnecessary avoidance! ALWAYS seek guidance about allergies from a board certified clinical immunologist and allergist.

Another common scenario that I see often in clinical practice is someone moving out of their parents’ house where they grew up with a cat and/or dog and returning to that house after a prolonged absence (say in University). When they return, they start to notice allergic symptoms around the cat and dog where previously they didn’t have symptoms. This is a real life demonstration of losing anergy.

It is possible that the immune system can reacquire tolerance on its own as no one fully understands how this occurs. However very few people are able to do this. It is also possible to reacquire the tolerance using allergen immunotherapy in a controlled, methodical, and safe way.

I digress, going back to the topic at hand. With exposure daily to nature I wondered if it is possible to have the same retraining effects on the immune system naturally as the pollen exposures “naturally” gradually increase to a peak. This would necessitate near daily exposure however to the outdoors which is difficult in modern society with our busy work schedules and commitments. Studies done with a placebo controlled arm for allergen immunotherapy do in fact show that some patients get some of the possible “retraining” changes in the placebo arms during pollen seasons suggesting that this idea is at least plausible.

New methods such as sublingual tablet immunotherapy (getting the pollens in a controlled tablet form) are now available that try to mitigate the risk of oral desensitization. While all forms of allergen immunotherapy have some risk, it does appear that tablet immunotherapy offers a safe and effective option for patients.

So I’ll throw the question out there – is it possible that not enough early and frequent childhood exposure to nature or the outdoors is increasing the prevalence of allergies that affect the nose, eyes, and lungs? Are we keeping our children indoors too much?

In conclusion, I cannot make any specific recommendations to your particular case for obvious medical legal reasons over this blog, but I do wonder if there are benefits in the field of allergies by being more in touch with nature.

Dr. Jason K Lee

Twitter @lee_jasonk
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Allergies – Why are they increasing in prevalence ?

One of the most frequent questions that I get asked by people is “why are allergies increasing?”.  By this they mean why is the prevalence (the presence of allergies in the general population) increasing?

I read an interesting column by a news reporter in LA a few years ago who thought that there was a mass hysteria induced self diagnosis of helicopter parents of food allergies.

Well this is wrong for several reasons.

It is known that the real prevalence rate of food allergies is in fact increasing at a substantial rate where now 3-5% of patients have physician diagnosed food allergies.

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So why the increase?

We used to attribute most of food allergy and allergy prevalence increases to the hygiene hypothesis.  The theory distilled down proposes that it is the lack of exposure to pathogens or “germs” that predisposes our bodies’ immune systems to over react to harmless things like peanut proteins, pollens, etc…

It turns out there is substantial evidence to support this theory.  We know for example that children who grow up with many older siblings and thereby exposed to more infections are less likely to develop allergies.  Similarly, children who grow up with a dog are less likely to develop allergies.

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When children do get infections such as hepatitis A, they seem to markedly decrease their risk of developing allergies in general. Have we become too clean and hygienic?  Well I am by no means advocating for purposely getting our children sick. But perhaps playing in the dirt every now and then can contribute to our children not developing the tendency to develop allergies.

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Behind the complex interactions of our immune system and the environment, there appear to be other factors we are now discovering.

An interesting discovery in the field of epi-genetics has also shed light into this phenomena of increasing food allergies lately.  It now appears that if your maternal grandmother smoked, the grandchildren are more likely to develop allergies. Why is this so?  It has now been demonstrated that although the DNA and genes do not themselves mutate at a fast enough rate to increase allergies, as complex living beings we have also developed an ability to have a dimmer switch on our genes (i.e. how many of them get turned on and to what level).  This gives many species to rapidly adapt to a changing environment without having to rely on the painfully slow process of actually introducing base pair changes in our DNA.  Put in another way, our genes are formed from DNA with a four letter alphabet A, G, C, and T.  The letters in the alphabet typically do not mutate or “change” in their order.  However just like how we have accents in our alphabet there appear to be various accents that can change how we say the words that are spelt out with the addition and removal of various punctuations and accents–this is known as epi-genetic markers.

As such if your maternal grandmother smoked, somehow the gene dimmer switches changes so that future offspring can now better handle a polluted environment.  This unfortunately results in some aspects of the immune system becoming hyper active.  The dimmer switches are made up of these accents / epigenetic changes.

Twitter @lee_jasonk

 

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