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Intriguing Cases


Dr David L. J. Freed, MB, MD, MIBiol

Male student (of economics) age 21.

7-year history of sore red swelling of the lips. Biopsy at the Dental Department of the local University Hospital showed "oedema and heavy chronic inflammatory cell infiltration in the lamina propria with perivascular extension of inflammation into deeper tissues". Histological diagnosis: orofacial granulomatosis (OFG).

The histology of OFG is very similar to that of Crohn's disease, and Warner has noted that, like Crohn's Disease, it often responds to simple dietary manipulations [1,2]. In the memorable phrase of American allergist Joe Miller, "Crohn's disease is a piece of cake", and that reminds us of two things: (a) that it can often be resolved easily, without surgery or steroids, and (b) that the foodstuffs to be avoided in the first instance are exactly the list of comestibles that are used to make a cake - wheat, milk, fruit, chocolate, sugar, egg.

The patient had thought about the possibility of food allergy, even obtaining a high-street "electro-dermal allergy test" (touted as "one of the world's most advanced and accurate screening devices"), which instructed him to avoid milk/dairy, egg, chocolate, beer, several fruits, yeast and potato. Disappointingly though, it allowed him to continue consuming wheat, other grains and pulses. On this dietary regimen, however, he was in fact a bit better.

On presentation his lips were markedly swollen (see photo)(in spite of his daily steroids), tender, dark red and indurated with a "woody" feel, suggesting, in line with the histology, that the tissues were distended not so much with fluid but with inflammatory cells. A dietary history disclosed that apart from milk avoidance, his diet was a typical student intake of wheat/grain products, chocolate, fruit, sugar, additives etc.

I had never seen a case of orofacial granulomatosis before but I have treated several cases of Crohn's disease with good results, so I thought the chances were quite good. I did some neutralisation testing for four basic foodstuffs, using my variation of the Miller technique (simultaneous injection of several dilutions [3]) and issued neutragen injections to cover those. Wheat and milk, interestingly, both gave immediate (weal- and-flare) classic Type I reactions, whilst cod and chicken did not. Even more interestingly, the following day there were hot red Type IV reactions at the higher strengths of wheat and milk, though not enough to change the end-points.

Immediate-type inflammation, as in hay fever and urticaria, is caused by IgE and mast cell degranulation - Type I or Type A allergy. "Late" inflammation (that supervenes after 6-12 hours) is probably due to the action of complement and neutrophils. (Type III) and follows a totally different path leading to eventual healing. But "delayed" inflammation appearing only 24 hours or more later, lasting possibly weeks or months (or years) is caused by the cytoxic effects of lymphocytes (Type IV) and is often irreversible, healing only by scarring. In tuberculosis it is this kind of inflammation that leads to the cough, the sweats, the cachexia and death. Neutralisation has been shown to be helpful for Type I and Type B allergies, but not ( apart from anecdotal reports [3]) for Type IV inflammation. The histology and the delayed skin reactions strongly suggested a Type IV pathogenesis in this case, so the use of neutralisation was really a shot in the dark.

I did nothing else at that stage; after two months he claimed to be significantly better and had been able to stop all steroid therapy. He attributed this improvement to taking the daily neutragen injections and cutting down on wheat (though I had not yet told him to do that).

I now asked him to embark on a full rotating stone-age diet. After another two months he reported that he had adhered faithfully to the diet. There was now visible improvement, but he was still getting flare-ups and was not sure why.

I therefore neutralised him for every foodstuff that I wanted him to eat (meats, fishes, greens etc) plus a reasonable range of inhalants (appendix). There were numerous type I reactions but I doubted whether these were very relevant - some Crohn's patients produce Type I reactions to foods but most do not. More interesting, next day there were hot, red, type IV reactions to haddock, leek, courgette - and chicken, even though identical testing with the same extract a few months earlier had not shown a delayed reaction. That would explain why he was still getting reactions - he was Type IV-allergic (or had newly become allergic) to some of the "safe" foods. A "stone-age diet" will not help if the patient is immunologically allergic to the permitted meats, fishes or greens. He went away to take his neutragen (six bottles in all, one injection daily from each) and keep to his diet.

Three months later his mouth was virtually normal. He had had some flare-ups following unauthorised "cheats" when joining his mates at the pub, and had absorbed that lesson. Worryingly, though, when he did get flare-ups, these were now worse than before he started. In particular he had had severe reactions to mussels and beef, both of which he was neutralised for and which should have been safe. I wondered whether antibiotics in the animal feed might be responsible - in particular beef has a reputation for carrying traces of streptomycin [4]. I cautiously neutralised him for ampicillin and erythromycin and at the same time re-tested the beef and mussel. There were no changes to the endpoints of the latter, but erythromycin produced delayed reactions at the higher strengths and I issued the appropriate neutragen. I also neutralised a wider range of foods in the hope that he would be able gradually to reintroduce some of the more hazardous ones (wheat etc).

A year after I first saw him he rang to say he was fine (see photo). He gradually cut down his neutragen injections and expanded his diet, and now, 5 years after first seeing him, he reports that he's cured; he takes no treatment of any kind, he eats pizzas and drinks beer and apart from being cautious with chemical additives, consumes pretty much what he likes. I continue to worry about the dietary liberties that he takes now but I can't argue with success. I submit this case is evidence that Type IV allergy to foods may be responsible for OFG, and that it can respond to neutralisation as well as Type I allergy.

OFG before and after

Orofacial granulomatosis before (left) and after (right) treatment
with elimination diet and neutralisation.
Apart from the change in the lips, note also how the face has slimmed down following diet.

This case was remarkable for the good cooperation I received from his hospital doctors and his second GP (after the patient moved from the North to London). The dermatologist sent me the results (negative) of the standard patch-test battery, the orofacial surgeon sent me pre-treatment photos and the biopsy report; and the second GP prescribed the neutragen (though not the first GP. who sent me a huffy letter saying he thought my suggestion "a very unsatisfactory way of proceeding").

REFERENCES for Orofacial Granulomatosis

1) Warner JO. Artificial food additive intolerance: fact or fiction? In (ed) Dobbing J Food Intolerance. Bailliere Tindall, London, 1987, p 141.

2) Alun Jones V, Dickinson RJ, Workman E, Wilson AJ, Freeman AH, Hunter JO. Crohn's disease: maintenance of remission by diet. Lancet 1985, ii: 177-80.

3) Freed DLJ, Morison SR. The neutralisation technique. BSAENM Newsletter 1996, 5(1): 15-20.

4) Tinkelman DG, Bock SA. Anaphylaxis presumed to be caused by beef containing streptomycin. Annals of Allergy 1984, 53: 243-4.


Composition of specific neutragen for Case B
Bottle 1: chicken, pork, celery, parsley, fennel, lemon, pineapple, tea, pepper mix, lamb, venison, rabbit meat, spinach, cucumber, courgette, apple, pear, nettle tea, halibut, haddock, cod, salmon, trout, sardine, tuna.
Bottle 2: sunflower oil, lettuce, tomato, leek, cress, capsicum, peppermint tea, beef, cabbage, cauliflower, brussels sprouts, watercress, kiwi fruit, coffee, maize*, mussel, cow milk, nystatin**, perfume mix.
Bottle 3: Alternaria, Chlorella, Cladosporium, Penicillium, Aspergillus, Sporobolomyces, C albicans, sheep wool, birch pollen, grass pollens, D. pteronyssinus, book dust, flu vaccine, aviary mix, crushed grass, ethanol, formaldehyde, London tap water ***, Manchester tap water***, diesel fumes, petrol fumes, swimming-pool water***, cigarette smoke, sodium salicylate****.
Bottle 4: phenol.
Bottle 5: turkey, prawn, herring, plaice, broccoli.
Bottle 6: hen egg, burnt gas fumes.

*maize is included NOT so that the patient should eat it, but to protect him against toothpaste, stamp-licking and other hidden sources of corn.
**Nystatin is included in case later I want to put the patient on it.
*** Waters are freeze-dried to yield the sediment, which is then resuspended in phenol/glycero/saline and diluted out.
****Sodium salicylate is included in the hope of protecting the patient against the natural salicylate of fruits, wine etc, and also in case later I wish to inject sodium salicylate into any rheumatic patches.

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