We in functional medicine have long been aware that children can start out with a clearly identified food allergy. As the child ages, the primary allergic symptoms fade and some other clinically relevant presentation appears in its place. For example: we’ll see a classic milk allergy in infancy — often as milk colitis. The child outgrows the milk colitis. The parents reintroduce milk as per the instruction of the pediatrician; the child then develops recurrent otitis media (ROM). More often than not, no connection is made to the reintroduction of milk, and the child continues to suffer with ROM. The ear infections will eventually wind down as the child hit his teens, but other medical issues pop up in its place: inflammatory arthritis, eczema, migraine headaches, various gastroenteropathies or sinusitis.
This is an all-too-common clinical scenario that has been largely unrecognized in medicine. However, if the individual is fortunate enough to have a functional medicine clinician identify the pattern, the food(s) will be removed and wellness is restored.
There is a dearth of research validating the observation of this age-specific food allergy phenotype.
A reasonable body of research exists that identifies the myriad clinical presentations that milk allergy can take, from colitis to sinusitis, migraine headache and eczema. Research on the evolving age-specific phenotypic expression of milk allergy, however, is far more limited.
In 2014 at the American Headache Society’s 56th annual meeting, Dr. Amy Gefland presented her research identifying infant colic as an early form of migraine. When I saw the news, I was quite excited that science was starting to connect the dots that we observe in clinical practice. I immediately scoured the report for any mention of an association with milk allergy. I was thrilled to see that she did indeed find that milk allergy-induced colic could also be associated with later migraine.
My suspicion was that we’d see a corresponding change in food specific antigen/antibody formation track with the phenotypic change (the transition from colic to migraine). So, milk/IgE antigen/antibody complexes would abound in the younger milk allergy presentation; but as the individual ages and migraines begin, milk/IgG4 complexes would be seen in the place of IgE complexes.
The IgE to IgG4 immunoglobulin class shift is well understood in the process of developing tolerance. For instance: when allergy shots are used to treat hay fever, a corresponding drop in IgE and rise in IgG4 can be observed, as symptoms of hay fever abate.
I strongly suspect, however, that while the formation of food/IgG4 complexes (as opposed to environmental antigen/IgE complexes) means an end to the acute IgE allergic response, the accumulation of these complexes over the long term can lead to problems.
In the case of milk allergy, the sheer quantity of dairy we consume (about 1.5 cups daily in the US) dwarfs the trace amounts of inhalant allergens we’re exposed to. It’s possible — as has been proposed — that these food/antibody complexes can be deposited in tissue and generate immune-reactivity.
Most recently, food/IgG4 complexes have been observed in high quantity in biopsy specimen and serum of adults with eosinophilic esophagitis (EoE). These complexes, rather than IgE, are thought to be central in the pathogenesis of EoE. In fact, when the researchers blocked IgE formation using omalizumab, there was no noted improvement in EoE symptoms, nor in eosinophil deposition in the esophagus as compared with placebo.
We are getting closer to fleshing out the complexity surrounding the age-related allergic phenotype. While I have seen eczema, migraine, colitis and sinusitis directly connected to food/IgG4 serum levels, (and clinical improvement with elimination of offending foods), piecing together the full allergy story from childhood IgE food allergy to adult IgG4 food sensitivity remains to be fully elucidated.
IgE and IgG4 results in an 8 year old with severe atopic dermatitis covering about 80% of his body. The first panel shows serum IgE foods and the second panel is serum IgG4 foods. After removal of the top offenders, his atopic dermatitis cleared completely. He was able to introduce all foods except dairy, which always caused a flare in eczema. His IgG4 to dairy remained high long after IgE levels normalized.
IgG4 food antibodies identified in the serum of a 60 year old woman with migraine headaches. Removal of these foods (especially egg) resulted in a significant reduction in migraine frequency and intensity.
IgG4 food antibodies in the serum of a 66 year old female with seronegative inflammatory arthritis and psoriasis. Removal of these foods resulted in a resolution of psoriasis and improvement in arthritis.