SLIT and food challenges/initial threshold?

[booandbrimom]

I was surprised to see the post by the blogger in the "reactions" area about doing three years of SLIT to work up to half a peanut.

When my son did the challenge this summer, he started to react at the 1/2 peanut level, and had the full out reaction around 2 1/2 peanuts. The clinician running the challenges said that was pretty typical.

I guess my question/comment is: if most people take a half-peanut to react, doesn't that essentially make SLIT voodoo? What's the point of spending all that money and time to work up to a level that most peanut-allergic people are already at?

Isn't there any type of challenge testing to determine thresholds with SLIT? Or do they just treat everyone the same, regardless of what they can naturally tolerate?

[CMdeux]

I'm not sure that I have hard data to answer any of the questions associated with SLIT, but I question translating the anecdotal information you got re: threshold dosing to a valid statement regarding the entire peanut-allergic population.

I'm thinking that the people with LOWER thresholds probably are self-selecting OUT of the pool for most studies even if they qualify, and recall that there is some tantalizing reasearch suggesting that the lower the reaction threshold, the more probable very severe reactions become for an individual.  Obviously there are ethical constraints in exploring that particular portion of the patient population with any degree of certainty...

just noting that they seem to exist.  I have no idea what that tail of the bell curve looks like; but if this is a normal distribution, then it stands to reason that as many as 5-10% of people with a clinial peanut allergy might have that kind of low-and-sometimes-variable threshold.  Since, clearly, there are about that many PA people with thresholds so high that they really CAN just take a bite of something to "see" if it is contaminated.  KWIM?

DD reacts to amounts that can't be seen with the naked eye, for example.  So she's probably at some several-decimal-places out, 5-sigma location on the anecdotal bell curve that was mentioned to you, Boo.  Would we ever put her through an oral challenge to particpate in a study?  Probably not, even if the researchers running it would do it (which is doubtful in light of her particular history).

Does that mean that we're contributing to selection bias in the patient population that undergoes these things?  Yes, undoubtedly. 

One thing that our allergist has hinted at, but that I've never had the opportunity to fully explore with him is the idea that there is a patient population for which desensitization in an aggressive sense is just... well, ill advised.  I'm thinking that this isn't necessarily a tiny percentage, and that a drifting reaction threshold or unpredictable and low-threshold reactions might play into it. 

  I'm guessing that those people  might participate in SLIT where they would opt OUT of participation in other types of protocols.  They aren't "weeded" out, in other words, they just never show up in the first place, is what I'm thinking.

So who is more likely to opt "in" to a desensitization protocol or study to start with?  They are clearly "self-selected" from the general population, and it's unlikely that it represents a true population sample, but more probable that some set of factors makes families either more or less likely to opt in to begin with.  My guess?  People who see an initial challenge as quite low-risk (maybe even "NO" risk) relative to the benefits of the study/treatment.  Who are those people?  Well, most of them probably have higher thresholds and want to be "not allergic" anymore.  I'm thinking that families like yours or mine, where there is clear risk in our minds from participating, are less usual.


I simply cannot imagine a parent who has seen very rapid severe anaphylaxis to a tiny amount (as in, seconds to full collapse) being willing to sign on for a challenge even under optimal conditions.

I'm reminded of MommaB's DS, who finally gave up on even SLIT because of repeated reactions.   

I don't know what makes peanut 'different' (or perhaps even if it IS actually different) from other allergens in this respect. 

I'm just skeptical that half a peanut (which is probably, what... 150mg?  200?) is the "average" threshold dose for the general population of PA persons.  Then again, maybe it is and I just don't want to think about what it means that my kid seems to have a threshold dose several orders of magnitude lower than that.  That's possible, I guess, since it makes me feel lonely and vulnerable, and not-terribly optimistic about efforts to improve labeling.   

[twinturbo]

Having had an in office oral challenge for milk performed by an allergist from a top school we had an acute anaphylactic reaction from a "minimum" starting dose. I was not in a good space emotionally after that because I had argued with Dr. before the challenge began that his challenge "minimum" dose was too big. It didn't win me anything being right but now I know someone else's usually passes minimum will absolutely spell immense danger for us.

[booandbrimom]

http://www.johnweisnagelmd.com/peanutallergy.htm#minimumdose

More than you probably ever wanted to know on the topic...but I was curious.

I have always said my kid must have a pretty high threshold. I was surprised when the clinician said he was pretty much average for the kids they were testing. Keep in mind, though - the study is only a handful of kids.

But I agree about really sensitive people self-selecting out. No one is going to do SLIT if they're having contact reactions. Those who would volunteer for a clinical trial are also somewhat self-selecting.

[Tina]

I should clarify my post. The SLIT we did probably went as far as .001 of a peanut. Because there was no higher dose, we switched to OIT. There, we spent 6 weeks getting to, now, 100 mg (less than half a peanut). My thought, although there is now way to see what is going on, is that the super low does SLIT we did may have helped prepare us for OIT. One of the kids on our first day had a significant reaction at one of the very low doses (for OIT), so she is probably on of the low threshold people. I kind of think we would have been in that category if not for the SLIT prior to the OIT. Our DD's first reaction was huge, and her 'scores' have only gone up with time. It's so hard to tell..

[booandbrimom]

High RAST numbers don't correspond to severe reactions. Increasing numbers don't indicate she's becoming more allergic, just that she's growing.

I think it's great that you guys are doing OIT...but I would be pretty angry if we had spent all the money on SLIT, only to realize we could have started out with OIT off the bat.

(Obviously I'm not betting on either, since we're doing FAHF-2...)

As an aside, I think a question that has yet to be answered is whether you can outgrow a true Ara h 2 allergy. I did ask at the UKnow conference this week and their answer was that the molecular measurements are quantitative, just like RAST, and have the potential to fall, just like RAST. However, it made me wonder if the 20% who outgrow are perhaps allergic to different proteins.

I would guess the final tolerance level a child can reach is somewhat dependent on which protein(s) as well.

[CMdeux]

I'm guessing that as well, Boo.

As you know, this has been what I've speculated w/r/t egg and milk for years as well-- that whether the allergy is independent of tertiary protein structure may play a role too (that is, cooked versus not in the case of milk/egg and hydrolyzed proteins in any allergen), as well as the specific protein subtypes involved.

I think that much has yet to be learned about this puzzle, and that individual binding interactions are the keys-- the keys to who CAN 'outgrow,' who WILL outgrow and maybe even when, who can't gain tolerance, who will have a tiny threshold, and who can actually die from a reaction.

We're a long way from having that much clinically-linked data, for sure, but it is going to be terrific when that day finally comes.  Because then docs will be able to give parents a little more than false hope and a hearty handshake.

Applied proteomics, baby.... gotta love it!

[twinturbo]

I know I'm rethinking how to interpret allergic considering the child of mine who anaphylaxed from minimum starting challenge dose of milk regularly drinks casein hydrolysate. Extensively hydrolyzed? Yes, and the casein versus whey numbers differ quite a bit on RAST post-challenge. It's forced me to realize that absolute avoidance of all forms of any allergen isn't always necessary assuming I can pinpoint which proteins in what forms can be tolerated. A dangerous game, that, and would it yield any more freedom in cooking or progress in tolerance down the road who knows.

[booandbrimom]

http://www.ncbi.nlm.nih.gov/pubmed/11678861

This one is from 2001 and says the key is allergy to linear epitopes from alpha(s1)- and beta-casein.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2841053/

This one from 2010 says it's not the pattern, but the IgG4 increase.

http://www.phadia.com/en/Allergen-information/ImmunoCAP-Allergens/Food-of-Animal-Origin/Allergen-Components/nBos-d-4--lactalbumin-Milk/

Phadia says it's several proteins - some of them in very small quantities (and not tested for via RAST).

Interestingly, I met someone on Facebook who saw one of the "research" docs. He used component testing to determine her daughter did not have persistent milk allergy. Apparently the epitopes on the casein protein are the ones that signal persistence. As a result of the test, he had her introduce baked milk...which her daughter could tolerates.

I don't know what to make of it. Our son was impressively allergic and reacted to hydrolyzed formula, boiled milk - all of it when he was young. When we went for the baked milk challenge, he had a wheal the size of Mt. Rushmore to plain milk. I told his allergic this (a new one who joined our practice fresh off the OIT trials) and she just shrugged and said it doesn't matter. It DIDN'T matter.

We're not currently doing baked milk because they've asked us not to muddy the waters for FAHF-2...but we'll go back to it as soon as we finish the trial. He certainly wasn't tolerating everything, but that he was tolerating anything was something of a miracle to us.

I guess my point is that I was pretty bitter when I realized we had been scrupulously avoiding all these years...and it may have been the worst thing we could have done. Where was the magic turning point? Who knows...

[twinturbo]

I've been working on our allergist lately to turn the conventional wisdom of oral challenging on most potent forms first on all children to case-by-case challenging on the lesser allergenic (no one quote me on that term) forms of suspected allergens. Take soy for example. DS2 tests highly positive on RAST but SPT is 2mm which is on the border clinically speaking. Given his history and frequency of severe reactions, not even including systemic non-anaphylactic reactions, I vetoed the straight soy challenge. I said hey, we know he's tolerating refined soy oil, let's try soy lecithin in the next year and see how that goes.

Here's my dilemma with challenges: it forces the most potent forms first on kids and if there's a fail then the prescriptive mode of operation is strict avoidance. Well, what if that's too restrictive and not in the patient's best interest in nutrition, life quality and chance to outgrow? I regret not sticking to my guns about trying a high heat treated baked milk oral challenge because that was a chance to marginally increase the incorporation of that allergen into an intensively restricted diet.

DH and I wonder how much of this really comes down to how busy the allergist is, because there's so much to work through that isn't part of the core of services they offer to the lowest common denominator in allergic patients that we actually get less attention than more attention despite top shelf health insurance and our working knowledge of this autoimmune issue well beyond 99.8% of his patients.

So, if the office isn't going to pony up and figure things out at a granular level when needed why not seek privatized services? KWIM?

[CMdeux]

I don't know, twinturbo, but I do know that we've been incredibly fortunate to have an allergist that follows the evolution of best practices in the field, and is willing to individualize based on individual patient history like that.

I don't know if it has to do with his training, if it's just his personality and philosophy, or if he's just brighter than most docs and therefor able to use greater bandwidth on patient care and applied research.  He's pretty conservative about high risk patients like DD-- but not without reason.  (He was, for example, eager to try the Duke egg desens. protocol with DD, then a year later, advised AGAINST rapid oral desensitization w/egg for her, then two years after THAT, encouraged us to do a high-heat baked egg challenge.) 

I don't know exactly why he's so responsive and nuanced in his care of DD.  I just know that we are really, REALLY lucky.  He figured out early on that we keep up with the research and, just as importantly, that we are not irrationally afraid of change, plus we understand the technical aspects of things when he explains them to us, and we trust his judgment.

We'd be in a really, really different place if not for our allergist.  I'd nominate him for some award professionally, truly.  He hasn't suggested anything about component testing to us, and I suspect that the reason is that with MFA and potent and abundant anaphylaxis hx, it would change absolutely nothing.

[twinturbo]

http://www.ncbi.nlm.nih.gov/pubmed/11678861

This one is from 2001 and says the key is allergy to linear epitopes from alpha(s1)- and beta-casein.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2841053/

This one from 2010 says it's not the pattern, but the IgG4 increase.

http://www.phadia.com/en/Allergen-information/ImmunoCAP-Allergens/Food-of-Animal-Origin/Allergen-Components/nBos-d-4--lactalbumin-Milk/

Phadia says it's several proteins - some of them in very small quantities (and not tested for via RAST).

Interestingly, I met someone on Facebook who saw one of the "research" docs. He used component testing to determine her daughter did not have persistent milk allergy. Apparently the epitopes on the casein protein are the ones that signal persistence. As a result of the test, he had her introduce baked milk...which her daughter could tolerates.

I don't know what to make of it. Our son was impressively allergic and reacted to hydrolyzed formula, boiled milk - all of it when he was young. When we went for the baked milk challenge, he had a wheal the size of Mt. Rushmore to plain milk. I told his allergic this (a new one who joined our practice fresh off the OIT trials) and she just shrugged and said it doesn't matter. It DIDN'T matter.

We're not currently doing baked milk because they've asked us not to muddy the waters for FAHF-2...but we'll go back to it as soon as we finish the trial. He certainly wasn't tolerating everything, but that he was tolerating anything was something of a miracle to us.

I guess my point is that I was pretty bitter when I realized we had been scrupulously avoiding all these years...and it may have been the worst thing we could have done. Where was the magic turning point? Who knows...

bumping for myself