Magical Thinking and Food Allergies

So we got our FAHF-2 clinical trial email notification this week.

No, it's not the trial results. It was just a brief little note:

We are pleased to let you know that study participants have completed all study visits and we are now able to inform you of which treatment arm you or your child were part of (active or placebo).

[FAB's kid] was on active treatment medication.

At this time we can only provide you with your treatment assignment.  We are unable to share any information pertaining to other study participants.  Once the data is fully analyzed and peer reviewed, we will be able to share the overall study results. 

So...good. We weren't crazy.

The problem is that history is always written after the fact. While you're living your way through something, cause and effect are never clear. When people ask us whether the medication has made all the difference in my son's life, I have to just shrug and say "I don't know." There HAVE been some major changes since last winter:

• He's now eating all soy (including soy cheese) without restriction. 
• He's eating baked milk in everything without issue. (The only thing preventing us from introducing baked cheese is our own fear and busy schedules.) 
• While I know some of you really do not like the concept, he is eating "may contain" for peanut without any issues at all, which has significantly increased the number of processed foods available to him, especially chocolate. 
• He's started to expand his list of restaurants. While we're still not at the point (and probably will never be) where he can just eat something without asking about it, we no longer worry about cross-contamination.

What we don't know is whether we can attribute all that change to the medication. Is it possible that he had already outgrown soy, that he would have tolerated baked milk at this level without the medication, that "may contain" was always o.k. for him, and that we overreacted when it came to restaurants and cross-contamination?

Of course it's possible. Perhaps even likely. 

On the other had, we did see a measurable, really significant change in his tolerance to peanut. It is just as possible that the process that created that new tolerance also affected his response to these other allergens. But we'll really never know for sure, because the other allergens were not measured as part of the trial. 

It's so easy to see how food-allergy families can have such a diverse approach. The actual evidence we have for severity and tolerance may consist of a single reaction when our child was very young. In the years that follow, some people choose to believe their child's allergy has magically disappeared. Others may re-write it as a completely out-of-control, always life-threatening monster.  Our doctors know nothing. We know next-to-nothing. But, being human, we make up stories to fill the gap. 

Thanksgiving is just around the corner again. The spread of food always prompts the inevitable questions: 

How are his allergies? Did the study cure him? Can he eat what I brought now? Will he be able to take the medication again? Do you want him to do it if he can? Was it worth it? Do you think it worked? Will it work for others? 

Our family will be challenged to write the story that goes with this clinical trial. People really hate the very short story we've told up until now: we just don't know.

Everyone wants a definitive ending...even if we have to make it up. It's human nature. 

Follow me on Facebook or Twitter  

The Very Hungry Food-Allergic Caterpillar

My gangly teen caterpillar hatched out of his egg a l-o-n-g time ago. But he's still hungry!

On Monday, he ate through one muffin baked using real milk and butter.

On Tuesday, he ate through yeast coffee cake (butter, milk, yum!).

On Wednesday, he ate some of a Stouffer's spinach souffle.

On Thursday, he actually ate a store-bought Sara Lee pound cake. (Went back for seconds on that one!)

On FRIDAY, he ate...7 1/2 edamame.





OK, everything was not as straightforward as a children's book, but my son has been really pushing the limits of his baked-milk tolerance over the last couple of weeks (especially over spring break) to see just where he's at. The great news is that he's doing AMAZINGLY well tolerating everything we've been giving him.

Today (Friday) was his soybean food challenge, which he passed with flying colors! The grand total after two hours was 7 1/2 soybeans, with nary an itch, cough or stomach hiccup. (He's actually even back in school for his last class of the day.)

Best of all, his doctor agrees with our assessment that he's ready for a lot freer eating, including restaurant food. Since clearance for soy + baked milk = most bakery breads, that means he can have a hamburger or hot dog and French fries at just about any restaurant in town.

We have instructions to do no more soy today, to let him eat as much of the package tomorrow as he likes and then to gradually introduce soy into his diet without restriction. Our doctor also has no concern about doubling up on baked milk and soy, so that opens up a whole WORLD of processed frozen foods.

We talked through (again) the hazelnut issue. The RAST he just had done was a 2.0; the one from the clinical trial was around a 12. She wants to see one more negative SPT before believing it to be a pollen allergy and doing an outright challenge in the office. In the meantime, we're going to try green pea again and repeat scratch testing for milk, hazelnut and the rest of the beans. We're all of one mind at this point: knock off every allergen we can before college!

So...was it the FAHF-2? Hard to say. We know he was well along to outgrowing his soy allergy because his last soy reaction occurred after almost a full bowlful of soy ice cream about three years ago (I bought a look-alike product in soy instead of coconut by accident). He had a pretty serious reaction at that time that did involve trouble breathing, but it took a LOT of soy to generate it. We will be cautious, however, because it's still possible that there's a threshold above which he cannot tolerate soy and we just didn't get there today.

His doctor also indicated that it usually takes about a year of baked milk before they like to do an open challenge. That's not very long at all! I wish we had instituted baked milk about a decade ago, but hey - better late than never, right?

I'll report back as we get rolling on some of these new foods. (Chinese!)

Follow me on Facebook or Twitter  

Component Testing (Pt.2) - Why Should We Care?

So, in Part 1 of this labor of love, I talked about EIA vs. component testing for allergies. If you followed the science, you can start to see some situations where component testing might be helpful to figure out what's going on with our kids:

1. To identify cross-reactivity between food and pollen.

There are six peanut allergens that are currently the focus of component testing: Ara h 1, 2, 3, 5, 8 and 9. It's important to note that there are at least 24 identified, potentially allergenic epitopes just for Ara h 1!

The first three are what are known as seed storage proteins. They're important to the plant to ensure the next generation of little plants is grown. As a result, they're extremely durable and usually make it intact through break-down process in the stomach. Ara h 9 is a lipid transfer protein, responsible for moving fats across membranes within the cell. Again, it's a pretty hardy little beast.

In contrast, Ara h 5 and 8 are wimps. They also have homologues across many other plants, especially pollen from those plants, so the chances of cross-reactivity on a traditional allergen panel are high.

The traditional method of testing that uses a natural extract cannot tell these two types of results apart. One recent study showed that 11.8% of kids tested using a traditional RAST test showed up positive for peanut. However, when challenge tests were conducted, only a quarter of the kids actually reacted when they ate peanut. This roughly correlates with the estimated 1-2% rate of peanut allergy in the population.

The uKnow test is currently being marketed to parents whose kids had a positive peanut test but who have  never experienced an actual reaction to peanut. If you are in that category, this test could change your life.

Remember those look-alike proteins, or homologues? In the case of kids who test positive, but who really don't have a peanut allergy, there's a distinctive pattern that shows up:

Remember that Ara h 8 is a wimp. It mostly breaks down in the stomach to the point that the body doesn't react to it. That's why it often causes an itchy mouth but limited other symptoms.

This may be the explanation for the fabled "mild" peanut allergy. These kids will all have itchy mouths. Some of them may even have a few systemic symptoms. But, the thought is that they are not likely to tip over into serious anaphylaxis. (Of course, whether you're ready to turn in your epinephrine injector under those circumstances is between you and your doctor.)

Another great example of where the test is useful is my son's situation. His January RAST for hazelnut was ~3, yet the RAST just taken for the FAHF-2 study in April was a 12. That's a huge increase for a RAST in just four months!

It turns out that hazelnut (Cor a 1) and Birch (evil birch Bet v 1!) are strong homologues.¹ The large increase in his number during tree pollen season is a good indicator that we're probably looking at a less serious form of hazelnut allergy. We're hopeful that a component test can take this worry off his plate.

2. Possibly: to provide more information on the timeline to outgrow milk/egg allergy.

Milk and egg allergies are really tough on parents! For 17 years now, we've asked the question of our allergist that I'm sure all of you MA/EA parents ask each time: "when will my kid OUTGROW this allergy?!"

There are some things scientists have found out about these allergies. As with peanut, if kids are allergic to multiple allergenic proteins, it generally makes the allergy more persistent. Additionally, if a child's body can recognize epitopes when they're not folded up in a protein, that also means they're likely to have the allergy longer, maybe lifelong, and potentially have more serious reactions.

A traditional RAST test can crudely test for the different components of milk: whey, casein, α-lactalbumin, β-lactalbumin, but it can't identify specific epitopes and it can't demonstrate whether the allergy is to "folded" proteins (not as bad) or the "unfolded" strand of protein (bad). The component test, though, gets down to just the very small (sometimes just 10 amino acids) unfolded "hot spot" on the protein that's causing the problem.

For milk and egg, there are "hot spots" that have been associated with severe, persistent allergies. For egg, these hot spots are all on a protein called ovomucoid.²  For the persistent milk allergy kids, the epitopes were associated with the casein protein.³

So is this test really able to tell which kids will outgrow their milk and egg allergies? The answer is maybe. Some doctors are already using it to look at patterns in milk/egg and determine whether introducing baked milk will be helpful in speeding up the tolerance process. It's definitely something to ask your allergist about.

NOTE: Right now, ISAC (Immuno Solid Phase Allergen) testing is being done by one experimental laboratory (Phadia), with only 103 components from 47 allergens available.⁴  Your allergist may not have a relationship with this lab or be ready to roll this out to patients.

3. Future hope: to separate "potent" epitopes from less harmful ones and find the pattern for life-threatening allergies.

This is where we start to get into weighing the cost of the test against the information it provides. If you have a child who has already experienced a reaction to peanut, why might you want to have the test done?

So far, 95% of people who react to peanut in real life and who have had component testing show a sensitivity to Ara h 2. However, there also seems to be a correlation between how many epitopes of peanut you're allergic to and how allergic you are.⁵  The current theory for why is related to T cells, the first type of immune cell that responds to the allergen. (The Allergist Mom just did an awesome post on all the science behind this if you are interested.)

T cells are specific to the epitopes to which they bond, but the T cells all compete for the same pool of resources (the "antigen presenting cells" Allergist Mom mentions). Like fighting kids, they're fine if they think all the toys in the room are available to them, but when they see other kids who might want the same toys, they get upset and all hell breaks loose. So...the more epitopes a peanut-allergic person is sensitized to, the more likely it is that their reaction will be severe.⁶ 

However, so far there is no "smoking gun" epitope, or pattern of epitopes on any of the allergenic proteins, that signals potentially fatal reactions. Like fingerprints, the patterns from person to person can be very different. Scientists are still busily identifying and characterizing all the epitopes for peanut. Plus, different populations show different patterns of epitope sensitization, and even allergen sensitization (for example, Ara h 9 is more prevalent in Mediterranean populations). In order to answer these questions, they'll need a lot more data from people willing to take the test. However, those people taking the test will probably not benefit right away.

Are you willing to spend the money to get a picture of your kid's epitope "fingerprint", even though the data to understand what it means is not yet available? We're still thinking about this one.

4. Future hope: to help determine potential pitfalls for MFA kids.

When my son was around age 4, we went through a horrible period where we thought he had idiopathic anaphylaxis. Instead, it turned out that he had developed allergies to a wide range of legumes. The probable culprit? Ara h 1, which shares a seed pod protein with many other legumes.

The problem is that not all kids who are positive for Ara h 1 have allergies to other legumes! There's likely some other mechanism involved in sensitizing children to these look-alike proteins. (Remember the faces from the homologue example? Some people are just better at telling faces - and proteins - apart than others.)

This test has great potential to eventually tease out these linked proteins, far better than the crude botanical family relationships many of us use today. It's definitely not ready for prime time. But maybe someday soon, your doctor will be able to look at your child's peanut epitope pattern and make a good guess as to which tree nuts may or may not be a problem.

So...all in all, component testing is promising...but probably not 100% there yet for anything except for identifying those peanut allergies that are most likely cross-reactions to pollen. But what a gift this will be to those parents who are terrified their child is peanut allergic on the basis of testing only! And apparently, that's a good percentage of the kids out there.

PLEASE NOTE: these are MY thoughts on the value of this testing only. You should definitely discuss this with your physician. Additionally, I would love to hear from others interested in the science as to how they see this playing out in future.


Follow me on Facebook or Twitter  for updates!