Mechanism for delayed food allergies

I've been reading a lot of research articles, trying to get an idea of what's going on with my delayed food allergies.
By "delayed food allergy", I mean an allergy that doesn't show up in blood tests for IgE food allergy, and is similar to the food reactions I have.
My food reactions start about 1/2 hr after eating the food and last about 4 days.  Mostly, it's a groggy sick feeling, but I've also had belly pain, back pain, frequent urination, joint pain, mild itchiness all over my body, and psychological symptoms like anxiety, tension, being more emotionally reactive.   This kind of food reaction seems to be rather common, except that I've had pain in my kidney area and I haven't heard of anyone else having this symptom.  I can have a reaction from a fraction of a milligram of food protein.
These reactions are acquired.  I have gotten many new such allergies when I ate foods often.  So they involve the immune system and are legitimately called allergies.
Here's the picture I've come up with, based on reading the research, my own experience and what I've heard from other people:
The mucous membrane lining the gut has mast cells in it.  The mast cells aren't right on the surface and normally various mechanisms suppress IgE food allergy.
When the gut barrier is somehow disrupted, or the regulatory T-cell aren't working right, or whatever - one can develop specific IgE antibodies to foods.   See "Food Allergy" by Wang and Sampson for more on how the body maintains tolerance to foods.
People who are allergic tend to have higher gut permeability, and are more likely to have IBS.  Many people with food hypersensitivities have allergy problems such as allergic rhinitis, eczema and asthma.  People with IBS and allergies tend to have higher numbers of IgE-armed mast cells in their gut, than people with IBS but no allergies.   See "Indications of ‘atopic bowel’ in patients with self-reported food hypersensitivity"  Also see "Perceived food hypersensitivity: A review of 10 years of interdisciplinary research at a reference center"

There's been a lot of research recently on "non-celiac gluten sensitivity".  There's a subgroup of people with NCGS who have multiple food hypersensitivities.  This subgroup tends to be allergic in other ways as well, so it seems likely that it's an allergic mechanism.  See
Celiac disease also causes higher gut permeability, I think much more so than being an allergic person.
So, people who are allergic, especially if they have a tendency to autoimmunity and develop celiac disease, are liable to develop IgE-mediated allergic reactions in their gut.
It's possible to have allergic reactions that are localized in a specific organ, so that skin and blood tests are negative - but one still has an allergy.  See "‘Entopy’: local allergy paradigm"  "Local allergic rhinitis" is IgE-mediated nasal allergy that doesn't show up on skin or blood tests.  See  Local allergies are best understood for the nose, but there's also evidence that one can have local allergies in the gut.  See for example "Local allergic reaction in food hypersensitive adults despite a lack of systemic food-specific IgE"
I don't know why some people would have local food allergies in their gut, and others systemic food allergies.  The symptoms of systemic food allergies can be immediately life-threatening, so the body has evolved to try and prevent this.  The immediate part of local food allergies may be less intense than in systemic food allergies.  See "Response to intestinal provocation monitored by transabdominal ultrasound in patients with food hypersensitivity"
The symptoms of delayed food allergies are different from systemic food allergies.  I've experienced this myself.  I had an "equivocal" result for corn allergy in a blood test for IgE antibodies, and when I ate some corn after doing an elimination diet, I got nasal congestion.  Other foods didn't do this to me.  Also, I was eating date sugar at one time (ground up dates).  Dates have a lot of yeast, and I have a yeast allergy in skin tests.  The date sugar caused awful hives on my legs, I was sick in bed for days, rubbing calamine lotion on the hives.  The hives went away when I stopped eating date sugar.  Other foods didn't cause hives, except that for awhile I had some minor itchy patches on my legs that came and went, likely caused by foods since I don't have skin allergies.
When someone has a systemic food allergy, there's some kind of control mechanism that has failed.  In the case of delayed food allergies, it hasn't failed.
One of the ways that the body suppresses IgE-mediated allergic reactions is to generate IgG antibodies.  The IgG antibodies bind to food antigens before they can reach mast cells.  See An antibody bound to an antigen is called an "immune complex".
When lots of immune complexes get into the bloodstream, they can cause symptoms elsewhere in the body, such as swollen, painful joints, a raised skin rash, nephritis (kidney damage, causing blood proteins and even red blood cells to leak into the urine), diminished blood flow to the brain, or gut spasms.  See  Does some of the mental fog that people have from delayed food allergies, result from diminished blood flow to the brain?
Many people with celiac disease say they have inflammatory reactions to other foods besides gluten.  It looks like what is going on is that celiac disease involves an autoimmune attack which damages the gut lining, causing increased intestinal permeability and other changes in the gut lining.  This results in IgE-mediated reactions to food - but since most celiacs don't have the particular defect that results in systemic food allergies, they develop delayed food allergies instead.  The body tries to prevent these symptoms, resulting in large numbers of IgG immune complexes, which get into the bloodstream and cause problems like joint pain and perhaps mental fog.
Celiac disease, like being an allergic person, may result in  increased mast cells in the gut.  Dr. Scot Lewey, a gastroenterologist who's a celiac disease specialist in Colorado (see tests for "mastocytic enterocolitis" in some of his patients with celiac disease.  The testing involves a biopsy of the small intestine with a special stain for mast cells, and the pathologist looks for excessive mast cells.  See "Mastocytic enterocolitis: increased mucosal mast cells in chronic intractable diarrhea" and "Allergic Mastocytic Gastroenteritis and Colitis: An Unexplained Etiology in Chronic Abdominal Pain and Gastrointestinal Dysmotility"  I don't think mastocytic enterocolitis has been definitely associated with the "other food intolerances" in celiac disease.  Dr. Lewey treats it with oral cromolyn, H1 and H2 antihistamines, Singulair and probiotics.
I've found that taking oral cromolyn, Singulair and loratadine at least an hour before tiny amounts of foods I'm allergic to, reduces my food reactions greatly.  I'm taking 20 mg loratadine (Claritin), which seems to be more effective than the usual 10 mg dose.  From what I've seen online, one can take 20 mg loratadine if the side effects aren't too unpleasant.  The brand name for oral cromolyn is Gastrocrom, but Gastrocrom is horribly expensive.  I get it much more cheaply in powder form from a compounding pharmacy, and I dissolve the powder in hot water and drink.
That cromolyn and antihistamines help, suggests that my food reactions do start with mast cells.  In the first couple years after I went gluten-free, my food reactions were much worse, and they might have also involved immune complexes.
A non-IgE mechanism for antigen-specific triggering of mast cells has been found - immunoglobulin free light chains (FLC's).  An immunoglobulin molecule (such as IgE) is composed of two light chains and two heavy chains, but immunoglobulin light chains also wander around by themselves.  See  FLC's are produced in some autoimmune diseases, and they may cause as much sensitivity to antigen as in IgE-mediated allergic reactions.
So perhaps delayed food allergies are mediated by FLC's rather than by IgE.  FLC's may also be involved in inhalant allergies, see "Evidence for the involvement of free light chain immunoglobulins in allergic and nonallergic rhinitis"
Both "non-IgE" (unknown mechanism actually) and IgE-mediated food allergies involve Th2 skewing of the immune system.  See "Food Allergy" by Wang and Sampson and "Antigen-specific T-cell responses in patients with non–IgE-mediated gastrointestinal food allergy are predominantly skewed to TH2"  Th2 is antibody-mediated immunity.  So it seems like these allergies aren't cell-mediated.  Also, cell-mediated allergic reactions are known to require a time period longer than 24 hours - see "Usefulness of Lymphocyte Stimulation Test for the Diagnosis of Intestinal Cow’s Milk Allergy in Infants", and delayed food allergies often start making people feel sick within a few hours of eating the food.
It's common for people with delayed food allergies, including celiacs with "other food intolerances", to become hypersensitive once they start avoiding the food.  The felt reaction that celiacs have when they accidentally get "glutened" is similar to the symptoms from "other food intolerances" - so it seems likely that celiacs develop a delayed food allergy to gluten grains, which is separate from the autoimmune process triggered by the gliadin protein in gluten.  Wheat is a major allergen, after all.
For me, delayed food allergies, both to gluten and non-gluten foods, had HUGE psychological effects.  With any of the foods I have these delayed allergies to, I tend to get irritable and more emotionally reactive.  Little things loom large.  Taking allergy medications beforehand helps prevent this.
Histamine is a neurotransmitter, see  Perhaps histamine acting as a neurotransmitter in the gut, explains the psychological aspects of delayed food allergies.

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Comment by Luara on January 25, 2014 at 5:09am

With your injury, it sounds like you keep on pulling on something during daily activities, so it never quite heals.  I wonder if deep heating pads would help.  I got some once, I think they put out radiant heat - IR radiation, which penetrates deeper. 

Are your muscles generally tense, perhaps from emotional tension?  I can see how being depressed might be associated with tense muscles. 

Comment by Luara on January 25, 2014 at 5:09am

The part that's bad about the allergies is that it makes my mind fuzzy.  It dampens creativity and thinking.  My thoughts have sometimes felt like foot soldiers slogging through a marsh.  I would like to go to grad school but my mind isn't working well enough.  Someone described it as like having wool in her head to me once. 

Immunotherapy such as allergy shots, directs the immune system away from the antibody-mediated immunity that's involved in most allergies, and towards cell-mediated immunity.  I would seem to need that very badly

I tried allergy drops at one time.  They use the same allergen serum that's in allergy shots, and one puts it under one's tongue.  The drops are supposed to be taken several times a day.  The drops I got, had only inhalant allergens in them. 

But even though I did as much as I could to not swallow any of the allergy drops, I still had one of my food reactions!  I tried them a second time and I had another worse food reaction.  I didn't know at the time that allergy meds could make the reaction less.  So eventually I threw them away.  I wish I hadn't, because I would be taking them now, once every 4 days, same as the the foods I'm allergic to.

I used to think my delayed food allergies were the result of celiac disease, because many celiacs say they have such allergies to foods besides gluten.  Which suggested that I should just avoid the foods until those delayed food allergies went away.  That's what the people on the celiac mailing list that I used to subscribe to, usually did. 

But now it's looking more like the delayed food allergies are another aspect of being an allergic person, which is aggravated by celiac disease. 

I started to have weird food reactions - jitteriness, fatigue, tension after eating certain foods - when I was 20, the same time as my inhalant allergies started.  That makes me think the food  reactions are part of generally being allergic. 

The part about immune complexes is quite speculative by the way. 

Comment by Ted Gresham on January 24, 2014 at 7:56pm

Hi.  I know allergies must be tough.  That's one thing (knock on wood) I haven't had trouble with.  I don't eat like I should but these days it's the least of my worries.

The origin of this nerve damage is a car wreck I was in back in '87 or '88.  I forget.  Not a lot of trouble after I got over the worst of it back then until seven years ago when I was trying to loose weight.  I started doing sit ups and apparently pulled something.  Been downhill ever since.

Comment by Luara on January 24, 2014 at 6:37pm

 I know the feeling, having to do your own research to figure out what's wrong.

Yes - I almost think that what I'm suggesting - that eating allergenic foods is actually a good thing long run, to push one's body to tolerate allergens - ought to be obvious - a kind of self-help immunotherapy - and that allergists ought to have thought of that.

At least, I HOPE it's obvious!  I don't know if it's true :) but I hope it's obvious.  I HOPE my body is basically ok, in other words, and can adjust itself back to reacting more like other bodies. 

Little is known about these kinds of food reactions, but I used to subscribe to a celiac mailing list and many people described similar reactions.  As for "common" - it's more accurate to say, common among people with celiac disease.  And apparently only vaguely understood by science, and weirdly unknown. 

So the allergists I've been to, almost all ignore that aspect of my allergies.  Doctors are uncomfortable with subjective symptoms.  They focus on my inhalant allergies, which they can test for.   But the gut apparently plays a central role in regulating the immune system - so it actually may be the root cause!

I got allergy shots for 5 years - but I would get sick for days after each shot, for some reason, so I eventually gave up.  I'm trying them again soon, though.  That would be in addition to the at-home food desensitization. 

nerve damage under my left scapula.  There's the usual stuff, motion, activity, etc, that causes pain.  I'm unable to do anything anymore without pain.  Even typing and using the mouse sometimes hurts.

That really sucks.  Can you get the nerve cut that causes the pain?  Do you have any idea about what started it? 

 I only have the VA and they're a bunch of idiots.

I have that impression too.  Perhaps being a doctor at the VA is like being an electrician that works in a hardware store.

I had a boyfriend who was a vet.  That was in 2003 when I was just finding out about my delayed food allergies and celiac disease ... I would make gluten-free meals, and he would always slip out and get something to eat with gluten in it.  He said he loooved hard Canadian wheat, it's hard because there's a lot of gluten in it (gluten intolerant people seem to tend to be addicted).  And he said he had weird stomach pains, that were undiagnosed by the doctors at the VA.  I kept on telling him he should get tested for celiac disease, he did ask for the celiac blood test at the VA, and it was positive!  Not that missing the diagnosis was their fault really - I had info they didn't.

Comment by Ted Gresham on January 24, 2014 at 5:13pm

Lots of research and work you've done.  I know the feeling, having to do your own research to figure out what's wrong.  I have a really strange illness, or maybe I should say I have an unusual set of symptoms for my illness, which is nerve damage under my left scapula.  There's the usual stuff, motion, activity, etc, that causes pain.  I'm unable to do anything anymore without pain.  Even typing and using the mouse sometimes hurts.  But then the pain can be brought on by eating, especially spicy food.  That's the weird part.

 I only have the VA and they're a bunch of idiots.  Seven years of switching drs and going for tests that have nothing to do with the pain and I'm still not diagnosed.  Bunch of fuckin' idiots.  I live on Gabapentin which barely helps at all.  Nothing else will.  Narc's either do nothing or just make the pain worse.  I've applied for disability and my Psych says I should get it.  I'm going the route of depression/etc., which for some reason is more acceptable to the SS admin than the fact that I can't do a damn thing.  When I get it I'm going to a real dr, maybe get a diagnosis.  

There's no hope for a cure or fix for this problem.  Nerve damage is just there.  So, I go on.

Anyway, that's TMI but yeah, great research.  Been there, done that.

Comment by Michael Penn on January 23, 2014 at 8:04am

HA! It was supposed to read "any ideas."

Comment by Michael Penn on January 23, 2014 at 8:03am

You have good knowledge in tracing this stuff all down. I try to trace my condition and get more lost doing so.

I want to say my stomach got twice as big overnight. It must have been longer by 3 years or so, but I have a 40 inch waist now even if I am as strong as a horse. I cannot drink beer like before, and I cannot eat so much now. I'm really bloated if I eat or drink. Gas, belching, and very uncomfortable. I love milk and have thought I might be lactose intolerant. I take Bragg real vinegar, and it helps. Maybe I need some probiotic thing to take daily. I have breathing problems and have even thought of heart failure. (Some of it fits.)

Even though I have Medicare and VA insurance coverage, I hate going to the doctor. They always want to "run one more test." If you want to kill me quickly, then start piling a bunch of bills on me. I'm still very active and won't go the doctor route until I have to.

Ant ideas?

Comment by Luara on January 23, 2014 at 7:39am

The symptoms you have sounds like other diseases

One thing that might possibly cause my symptoms is IgA deficiency. But I think I did get tested for that and it was negative. 
IgA deficiency causes allergies, autoimmune diseases and vulnerability to infections. I do have repeated bladder infections and autoimmune diseases as well as allergies.

If anyone knows of a possible cause for one's immune system to become so sensitized to so many things, I'd be eager to hear about it.

My impression so far is that it's more of a long-term buildup from many different causes.  I inherited tendencies to allergies and autoimmune diseases.  Then emotional stress from abuse when I was a child, likely gut dysbiosis from eating a lot of fructose, celiac disease attacking my gut and making things worse, etc. etc.

The article in Reader's Digest was all new to me

You mean the article about "multiple chemical sensitivity" that you mentioned? 

Thanks for the info.

It's only my best guess :)

Comment by Donald R Barbera on January 21, 2014 at 4:40pm

Laura--I am sorry that you suffer as they say an "allergy to life," but you have done an excellent job of explaining it. The symptoms you have sounds like other diseases, but they in other sicknesses the symptoms are singular to that specific disease. There may be other symptoms associated with them, but there is only one of the type you describe while you suffer from a variety. How do manage to stay healthy with the foods out there today? I went to a couple the resources you listed and found some interesting information. I cannot begin to imagine what it must be like. The article in Reader's Digest was all new to me. Now, you have given me something else to think about. I have only one allergy and that is to penicillin. Thanks for the info. Don



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