The First Big SLIT Trial Just Ended...

...and the results are...interesting.

For those of you who are not obsessed with the current smorgasbord of clinical trials underway, SLIT stands for sub-lingual immunotherapy. The therapy has been used successfully in Europe for many years to treat environmental allergies. It's been used more sporadically and with less certain results to treat food allergies. I know of at least one clinic in the United States that has been administering SLIT for several decades.

The question has been...does it really work? Other trials have shown mixed results. (I wrote an article on this back in July if you're really interested.) This most recent study was a more comprehensive approach involving 40 kids, sponsored by the National Institute of Health and held at several locations.

Kids who participated were given either placebo or drops containing peanut protein. About a third of the kids in the peanut drop group experienced an itchy mouth or throat, but only a few had symptoms more severe than that. (However, one subject did have an anaphylaxic event after a dose at home and ended up dropping out of the study.) At the end of the 44 weeks, the kids who suffered through dose after dose of saline for nothing got to choose whether to participate in an accelerated higher-dose SLIT experiment over the next 24 weeks. Kids in the first peanut group just continued with their slower build-up.

The kids varied a lot with regard to how much peanut they could tolerate at the outset. For some kids, the first symptom occurred at just 6 mg. Keep in mind that a peanut is about 300 mg, so this means these kids could detect 1/50th of a peanut. However, the actual dose they consumed before having a objectively-confirmable reaction was as high as 196 mg, or 2/3^rds of a peanut.

So what was interesting about it?

It worked...kind of. Of the kids in the original peanut group, 14 out of 20 were able to consume 10x the amount of peanut after SLIT as they did before. The problem was that many of these kids did not get up to a very high dose at the start, so 10x the amount of peanut was still not very much peanut. The median dose they achieved at the midpoint of the study was 496 mg (about 1 2/3 peanuts). At the end of the 68 weeks, the median was 996 mg, or just over three peanuts. This is definitely some significant wiggle room with regard to cross-contamination, but it's clearly not full desensitization, at least for most kids.

The kids who got the shorter course of peanut drops after placebo did almost as well. There were seven "responders" out of 16 in this group (some people dropped out along the way for various reasons, including fear of more challenges and even pregnancy!). The median amount they could eat after just 20 weeks of SLIT was that magical 496 mg number.

The amount of time SLIT was given did make a difference in a few cases. The study goal for desensitization was 5 whole GRAMS of peanut (5000 mg). During the 44-week challenge, no one made it to full desensitization. However, after 68 weeks, three of the kids were able to consume 5 grams (16 peanuts), and one ate 10 grams (32 peanuts).



Peanut-specific IgE levels didn't go down. The kids who got the peanut saw their IgE levels go up at the beginning of the dosing, then back down toward the end. However, in the end, the level of IgE ended up at about the same point as when they started and wasn't any different from the placebo group.

However, there was a noticeable difference in IgG4 levels: in the peanut kids, they went up much more than with the placebo group. Just as with good and bad cholesterol, it may be that a change in the "good" number (IgG4) is a more important marker of tolerance than the "bad" (IgE) number. Skin tests also changed significantly for the peanut kids. Bottom line is that IgE doesn't really seem to be telling us much with regard to development of tolerance.

Spontaneous tolerance DOES occur. Here was the weirdest part of the study for me: two kids in the placebo group  were actually able to pass the 16-peanut challenge at the end without any real therapy. Keep in mind that these were kids who had already failed a challenge just a few months before (one got just hives and itching; the other got hives, plus felt sick).

The study authors just kind of shrugged about this one and said "hey, we really don't know how this all works and maybe even older kids, or kids whose IgE isn't all that low, can spontaneously develop tolerance." One of the kids saw a decrease in IgE/increase in IgG4; the other saw an increase in IgE and a decrease in IgG4. No help there!

So what changed? Maybe the time in the year the kids were tested made a difference. They were both teen boys, so maybe testosterone kicked in and suppressed inflammation. Whatever the reason, both kids are now openly eating peanut.

So...if you're anything like me, you found the information about SLIT interesting and the information about the kids who got placebo and passed anyway INTERESTING! You can tell when you read the study that those kids really mucked up the nice, neat results. Sometimes, though, it's the thing that you're not looking for that ends up being the most important part of a research study.

If you'd like to read the whole complicated study for yourself, you'll find it here.


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On the Threshold of...

AllergyMoms reposted this week about the SLIT interview Gina Clowes did with Dr. Demetrios Theodoropoulos from Associated Allergists of LaCrosse. It's an interesting interview. You should read it. 

SLIT is something that has a lot of history in Europe, particularly for environmental allergens, and there has been some compelling research about the sublingual area being a better way to introduce proteins for tolerance induction.

The main criticism (or strength, depending on your viewpoint) of SLIT is that it generally uses very small amounts of protein for desensitization. The thought process behind it seems to be almost homeopathic — that somehow a greatly diluted poison will cure an ill. In this case, the theory seems to be that the immune system has to "get used" to the protein, and can do so through very small exposures.

Two SLIT studies, both published this year, show an interesting contrast. The first found that, after therapy, only one of the kids in the SLIT group passed a challenge.

A different study shows much more promising results — after 12 months of SLIT therapy with just 2mg of protein, kids were able to eat an average of 1710mg of peanut. That's about 5-6 peanuts — the same result as the oral immunotherapy approach, but with far fewer side effects. (The abstract for this study, however, does not indicate how many of the 18 reached this level or whether a food challenge was required to get into the study, and both of these studies involves only a handful of children.)

I've read about SLIT for years. Our allergist does not support it; my husband and I are on the fence. When FAHF-2 came along, it seemed a better bet. 

SLIT is not really what the column is about, though. As usual, what I'm interested in is the psychology of the response to this therapy. Even the headline for the AllergyMoms article — "Why Doesn't Everyone Know About This" — underlines my point: many of the same mothers who make a religion out of scrupulously avoiding every. last. particle of protein are the ones who are now embracing the miracle cure. Isn't SLIT essentially the same as eating "may contain" food? Yes, I know, varying vs. consistent dose, medical supervision vs. DIY — but still!

Which brings us to threshold.

Each kid has a threshold level at which they will react to peanut. We know thresholds change with age, other stressers on the immune system, illness, hormones, even the amount of fat in the food that contains the peanut protein. However, if these things are all constant, a child's reaction to peanut will also stay relatively constant. 

Consider clinical trial challenges. The whole point of the FAHF-2 trial we're in right now is to feed my son peanut at the beginning and end and see if his response changes. If food allergy reactions were really dramatically unpredictable, this methodology would not work. Based on the FAHF-2 study, my son's current threshold seems to be somewhere between half a peanut and three peanuts. The researchers indicated this was a pretty typical threshold. 

More or less. Depends on
the peanut you weigh.

However, a sub-population of peanut allergic have a very low threshold. According to this study, about 1% of the allergic population reacts to micro doses of less than 2mg. Another 16-18% will react to less than 65mg.

So my kid (and probably your kid) are in the other 80% of kids — the ones that typically don't react without eating overt peanut. Here's what one doctor had to say about this:

The benefits of a strict avoidance diet seem limited: reactions to the low doses and to the peanut oil refined are rare and most often slight. It is not proven that a strict avoidance facilitates the cure of allergy. On the other hand, strict avoidance could induce a worsening of allergy, with deterioration of quality of life, creation of food neophobia. In case of cure of allergy, it is difficult to normalize the diet after a strict avoidance. Outside of the rare sensitive patients to a very low dose of peanut, for which a strict avoidance is counseled, the report benefits risk is in favor of the prescription of adapted avoidance to the eliciting dose. For the majority of the peanut allergic children, it seems to us that the avoidance can and must be limited to the non hidden peanut.  

Arch Pediatr. 2006 Jul 5, Feuillet-Dassonval C, Agne PS, Rance F, Bidat E. 

Which avoidance for peanut allergic children?

I'm not as cavalier as these guys, and I'm certainly not counseling you to run right out and start feeding your kid "may contain" foods! It's important to remember that thresholds can change over time, especially at adolescence. 

On the other hand, if you have a micro-reactor, you probably already know it. These are the kids who react to the trace amounts on toys, or get the full-out reactions from kisses on the cheek, or who have had a known reaction to trace ingredients. Let's face it — since cross-contamination labeling is voluntary, we don't know what's in our food. That means people with these levels of allergy are going to have reactions. A history of serious, mystery reactions is a good indicator you're dealing with a low-threshold child.

What I do hope is that this blog post can reduce some of the anxiety around peanut allergy. There are too many people who think of reactions as completely, wildly unpredictable and even the smallest amount of peanut as life-threatening. That's not an easy (or healthy) way to live! Understanding where your child is on the threshold continuum will hopefully help you put the risk in perspective.


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A Peanut Allergy Cure Has Been Discovered!

And now it's the day after.

What do you do? How will your life change?

I was struck today by the comments on various message boards surrounding Hugh Sampson's statement that food allergy oral tolerance therapies are not ready for prime time. This isn't really surprising — it's something doctors have been saying for some time if you read beyond the sensationalist headlines. Many of the kids in these studies do not achieve true tolerance. They are only able to eat MORE of the allergen. When stressors on the immune system occur (illness, environmental allergies, menses), their desensitization level can change, causing reactions to an amount of the food that was fine just the day before.

However, there's another side to the controversy. If you read the synopsis of the AAAAI discussion about oral tolerance studies, you'll see an important point:

Quality of life in patients on peanut OIT vs. avoidance was remarkably improved - 90% improvement in QOL scores.

90% of kids (and presumably their parents) felt that the therapy had helped them to be happier. To fit in better. To live like a "normal" kid.

As my son has gone through the introduction of baked milk, and now the FAHF-2 clinical trial, I've had to confront head-on my fears. As I've indicated in other blog posts, baked milk tolerance is not easy. There are very definitely symptoms. The FAHF-2 dosing has also not been easy so far. My son has low-grade congestion much of the time. A mystery stomach-ache. Are they side effects? If so, how can I do this to him?

Which brings me to that peanut cure. Maybe it will turn out to be FAHF-2. Maybe they'll discover the trick to making oral tolerance more effective. Maybe it will be the peanut patch.

Whatever the cure turns out to be...how much risk are you willing to take? How much discomfort will you tolerate?

We are a VERY risk-adverse community. I am concerned that many parents will simply turn down the opportunity for a cure if it involves even the smallest risk or discomfort. And the odds are, based on what we've experienced so far, that it will involve one or both.

Envision yourself the day after treatment ends. Where would you go? What would you eat? What would it feel like to never have to explain allergies again? To add spontaneity back into your life? To not worry constantly when your child is eating out? Sleeping over? Growing up?

It can be hard to even hope again. It can be even harder to discard the precautions and even phobias we've put in place. But it may be the cost of a cure.

Every young mother faces this dilemma the first time she takes her new baby in for the 2-month check-up. There are risks to vaccines. They are minor, but real. How can I do it to my beloved baby? And yet the benefits are very clear.

It's possible to avoid the shot, and therefore the risk. It's possible to find others on the Internet who will tell you that you did the right thing, that all risk is unthinkable and vaccines are a conspiracy. Most of us choose to take the risk in the name of the greater good.

The day is coming. There are more clinical trials than ever going on. Are you ready to choose when the cure finally arrives?

Maybe it's already here.


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"Total Avoidance": The Best Chance to Outgrow a Food Allergy?

I think there's a myth that's done a lot of damage to our community: Total Avoidance.

If you've been in this rodeo for any amount of time, you probably know what I'm talking about. You see statements all over the web that say "total avoidance of an allergen gives the best chance for a child to outgrow." The theory seems to be that the body somehow needs a rest from the allergen to "forget and reset."

I haven't been able to find the direct source of this myth, other than the statement that has been AAAAI policy for years: "there is no current treatment for food allergy: the disease can only be managed by allergen avoidance." (If anyone has a source, I'd love to see it.)

When my son was young, we didn't practice Total Avoidance. We read the ingredients and gave him food based on those ingredients, end of story. We even used to cut the (milk-containing) breading off chicken nuggets in restaurants, and take him out for sorbet at places where we just asked them to rinse the scooper. He seemed to have a fairly-high threshold to most of his allergies. Yes, he got stomach-aches or a tingling mouth or "that feeling" in his throat on occasion...but it wasn't anything major, so we did it.

After the incidences I'd described in other posts (food allergy reaction, idiopathic anaphylaxis) we hunkered down and got educated. We read books. We found on-line communities and off-line support groups. We learned the Gospel: total avoidance was necessary, not just to avoid reactions but in the hopes of outgrowing.

It's easy for me to look back now and see that there was little evidence for this, but 12 years ago things were not so clear. Plus, this belief fed right into what I WANTED to believe. I was scared - terrified after his new allergies developed - and I wanted some control over things. Total Avoidance was a "truth" that felt emotionally right to me. It gave me control over something that felt completely out of control.

We quickly learned that Kosher symbols could be used to determine whether foods were produced on a milk line. It didn't matter if the foods contained milk, or if the line no longer even ran milk (as is the case with Oreos)...we avoided anything with a UD. And really - if we were going to control for milk, why not other allergens? We started making the calls. Calls to hundreds of manufacturers over the years, resulted in crazy direction about foods that were produced in the Ohio factory on Tuesdays when the moon was full, but in Indiana on Fridays when it wasn't.

There is no end to the slippery slope of avoidance. There was always a public surface that might be contaminated, or a child who had just eaten peanuts 10 feet away, or a swimming pool. Were we going to limit social opportunities to avoid even further? How could we not if it meant he could finally outgrow these allergies?

Around this time, I started immersing myself in the research. Before I was going to go whole-hog with this thing, I wanted to know what the scientific basis for all this avoiding actually was. Instead, what I found was Outgrowing Milk Allergy May Take Some Babies Longer Than Expected.

Hmm...provocative. It could be that the allergens themselves have changed, making these traditionally toddler-only allergies more persistent. It could be that the process of becoming allergic was different, resulting in a more persistent allergy. It could be that the length of milk/egg allergy had never been well measured, so the perception that they were outgrown in toddler-hood was simply wrong.

Or...it could be that parents were doing something different, changing the environmental factors, keeping their children away from those small exposures that led to outgrowing allergies.

This last one haunted me. I had worked hard at avoidance and felt smug in my judgement of those "lax" parents who just took the cheese off the pizza, or cut the breading off the chicken fingers, or gave their kids the foods they could tolerate and dealt with reactions if they happened.

A few years later, tolerance studies began. People who, for years, had bad-mouthed the SLIT studies were suddenly questioning their assumptions. As a result of the tolerance studies, researchers broadened their attention to milk and egg allergies. Lo and behold, 80% of kids with persistent milk allergies (ages 2-17) could tolerate baked milk.

80%. There were no predictive criteria for who would fail. It didn't matter how old the kid was. It didn't matter how big their wheal was to raw milk (my son's entire arm swelled - he still passed). It didn't matter how severe past reactions were, or what type of symptoms were experienced, or how high RAST scores were. Wow.

As I've commented before, my immersion in the group-think badly prepared me for the fun of introducing baked milk. There ARE symptoms. Just as there were when my child was a toddler and we used to cut the breading off his chicken nuggets. Only now, we're far more anxious about those symptoms because of our Total Avoidance conditioning. And, I know there's a whole generation of food-allergy-dogma-immersed parents and children behind me who are going to find working through these allergies with baked foods very painful.

Would I do it differently, knowing what I know now? It's tough to even consider that. But yes - I was a lot more carefree in my child's early years and it makes me angry that my investment in Total Avoidance was probably a waste, and possibly even detrimental.

Don't misunderstand me. I would still not give my child food with a "may contain peanut" label since we know a good percentage of those foods DO contain peanut. But...I wonder if I had to go as far as I did down that slippery slope. And I wonder a great deal if his milk allergy needed to be handled with the same extreme degree of avoidance as his peanut allergy.

After the debacle of food-allergy advice from doctors (avoid nuts during pregnancy, avoid introducing potential allergens to siblings, etc.), I know doctors are hesitant to take a position on this since they cannot be certain. Plus, they don't want the liability should a child have a serious reaction as a result of the "laxness" of parents. BUT...I do not think doctors should exempt themselves from the MENTAL health of the families they counsel. Not taking a stand IS taking a stand.

I hesitated to write this column because I do not want a parent new to food allergies thinking this is medical advice. IT'S NOT. You need to ask your doctor where he/she stands on this issue and decide for yourself.

I'm just here to bitch about it.