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Intriguing Cases

Synergistic allergens and arthritis

INTRIGUING CASE 14 - part 1 of 3
(another object-lesson on the importance of timing)

a Case Report from Dr David L. J. Freed, MB, MD, MIBiol

Some 40-odd years ago I was daydreaming in a psychiatry lecture when the Professor, who must have noticed, suddenly demanded “Freed!” I snapped awake, and he continued, “What is the cause of tuberculosis?”

I hastily gathered my thoughts and replied “Mycobacterium tuberculosis Sir!”

“I see,” he continued, “and do all people who get infected by that bacterium develop clinical tuberculosis?”

I knew the answer to that one as well, because years earlier, at primary school in the 50’s (before BCG), I myself and most of my playmates had shown positive when we were Mantoux tested, and although some had Ghon foci, none of us had had the disease. The Professor developed his theme to explain that infection with M tuberculosis is a necessary, but not sufficient, cause of the clinical disease – overcrowded living conditions and malnutrition are also major factors. TB in those days was still very much associated in the common mind with dirt and poverty, and ‘respectable’ people spoke about it in hushed embarrassed voices. Infection is not enough to develop the disease, a combination of causative factors is required. I remember that Professor’s lesson to this day, though I still don’t know what it had to do with psychiatry!

But let us pray talk now about allergy. My innocent hapless friends, we are about to enter the deep (and largely uncharted) waters of allergens that are necessary but not sufficient, that is, ingested or inhaled substances which by themselves cause no health problem, but which become damaging and/or dangerous – in susceptible patients - when they are accompanied by other factors. For brevity (albeit with the loss of some precision) I shall call this the phenomenon of synergistic allergens.

I first became aware of synergistic allergens when a mother informed me that her 6-year old son got urticaria whenever he ate ice-cream with peaches. Neither ice-cream nor peaches caused the slightest trouble if consumed on their own or in combination with other foods, but that precise combination caused urticaria every time. It did not seem to matter what type or flavour of ice-cream was ingested, though I assume they all contained milk.

I put that observation to one side until, a few years later, I learned that non-food factors can also work alongside foods in this way. This was an attractive 30-year old woman (at least I thought she was attractive – I was married to her at the time) who developed asthma during her second and third pregnancies. Each time the asthma started about half-way through pregnancy and lasted for a few months after the birth, until around the time when menstruation returned. During that vulnerable time she got asthma only when she drank coffee on the same day as inhaling paint fumes. So that was a three-factor allergy (coffee, paint fumes, and the metabolic upheavals accompanying pregnancy), and I was able to spot the pattern in her seemingly random attacks (eventually) only because I lived with her and observed her day and night. A further twist to the tale was when another patient told me that she could not eat chicken and potatoes if they had been cooked together but that she could eat them freely and without problems – even in the same mouthful - if they had been cooked separately. (This is entirely plausible, I should add, because we all know that the taste of a food can be affected by whatever else it’s cooked with, and if a food’s taste changes that means its chemistry and quite likely its immunology have also changed).

Another lady developed episodic urticaria at the age of 48. I looked at the rash but to my eye it did not seem typical of allergy, so I did not feel confident enough to recommend desensitisation. We discussed possible ways of tracking down food intolerances and a few weeks later she reported that she had found the culprit – chocolate. Whenever she had chocolate she got the rash, when she avoided chocolate the rash went away. But she had never had a problem with chocolate until the age of 48, when she had silicone implants inserted into her breasts (silicone, although itself immunologically inert, has an adjuvant effect on bystander antigens, that is it enhances the immune response to other things [1]).

Later still the phenomenon of synergistic allergens became almost respectable in the guise of wheat-dependent exercise-induced anaphylaxis, that is, a genuine food allergy (usually but not always to wheat, with conventional IgE antibodies) that only causes illness when the patient has also been doing vigorous exercise. This has now been published by several academic allergists in respectable allergy journals [2-4]. Another well-published (though still rarely thought of) aggravator of food allergies is aspirin [4-6] and the enhancing effects of that drug are themselves aggravated by, and may become apparent only in - wait for it - the simultaneous presence of “commensal” staphylococcal colonisation of the patient’s nose! That is apparently because staphylococcal superantigen drives the eosinophils harder to export inflammatory cytokines [6]. The significance of that triple interaction may become apparent later, as this story unfolds in parts 2 and 3.

Given that synergistic allergens can be amplified either by other foods or by non-dietary factors, we can now return to the first case I cited, of the six-year-old with urticaria after peaches and ice-cream. It may well have been the cold of the ice-cream was the final straw, reducing the temperature of the stomach and impeding its enzymes for long enough to allow the peaches and ice-cream ingredients – clearly synergistic allergen(s) for this child – to be absorbed in undigested or part-digested form (“leaky gut”).

Spotting multiple-cause synergistic allergies is very difficult, requiring longterm observation and much serendipity. For all we know such multiple causations may be very common, but are rarely reported because we are searching for a precise combination of needles in a haystack when we don’t know what combination (or even how many needles) we are searching for. The simple paradigm of “one allergen, one illness” that most of the medical profession still thinks is the norm may actually be only the tip of the iceberg, limiting the usefulness of withdrawal-and-challenge studies to the fortunate few in which one allergen does indeed cause one illness.

Reactions to foods take many forms. Foodstuffs have a wide repertoire of methods with which to damage us, alone or in complex partnerships. Many foods contain alkaloids, lectins, enzymes and/or anti-enzymes, and numerous other toxins as well as allergens [7]. It is not good enough to describe all adverse effects of foods as “allergies”, and expect them all to behave the same way. Differences in timing are one clue that we should be on the lookout for.

In the following instalments I am going (sheepishly) to report again about my own health, but I plead in extenuation that (a) I am my own best-observed patient, (b) if you wait long enough and observe carefully enough, time and luck can sometimes help you unravel even multi-factor synergistic aetiologies, (c) some illnesses don’t appear to be food-related even when they are, because the ancillary factors are not always there and attacks therefore appear to be random, and finally (d) if I have done it, other sufferers possibly can. Be aware, please, of the possibility. But also be warned, this is a complex case and if I hadn’t had decades in which to ponder it, I doubt if I’d have spotted the patterns. You’ll need all your neurones for this one (I had to use both of mine!)

See next thrilling instalment!

References to part 1

1) Y. Shoenfeld, N. Agmon-Levin. ‘ASIA’: Autoimmune/inflammatory syndrome induced by adjuvants. (2011) Journal of Autoimmunity 36: 4-8

2) Kidd JM, Cohen SH, Sosman AJ, Fink JN. Food dependent exercise-induced anaphylaxis (1983). J Allergy clin Immunol, 50: 651-60

3) Maulitz RM, Pratt DS, Schocket AL. Exercise-induced anaphylactic reaction to shellfish (1979) J Allergy clin Immunol, 63: 433-4.

4) Matsuo H, Morimoto K, Akaki T, Kaneko S, Kusatake K, Kuroda T, Niihara H, Hide M, Morita E. Exercise and aspirin increase levels of circulating gliadin peptides in patients with wheat-dependent exercise-induced anaphylaxis (2005) Clin Exp Allergy, 35: 461-6

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