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Desensitisation, Old and New


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

Most doctors over 50 will remember dutifully injecting weekly doses of Allpyral or Migen for respiratory allergic complaints. Sometimes the injections worked, sometimes not. Sometimes they seemed to make patients worse. Allergic reactions to the treatment itself were common, a curious paradox. These reactions were usually only a nuisance, but rare fatalities occurred, a potent reminder (if ever needed) that allergies can sometimes be lethal.

Several double-blind trials had showed that hyposensitisation was efficacious (1), but it was simply too capricious and too risky (not to mention too cumbersome) and in this country it was never a popular method. Since drug treatment of hay fever and asthma is reasonably effective, few doctors were grief-stricken when in 1986 the Committee on Safety of Medicines (CSM – the forerunner of today’s MHRA) published its review of therapeutic deaths (2).

Within weeks, hyposensitisation ceased to be practised in the UK except in the hands of a few dedicated enthusiasts (by contrast, it remains popular in North America and mainland Europe, where allergy is a recognised medical speciality and allergists are well organised). I myself had already stopped using hyposensitisation in 1985, when it became clear that new desensitisation methods, which had been reported in the literature, were far safer and more efficacious. Both were developed from continuing research in this country and the USA.

Enzyme-potentiated desensitisation

This is based on a discovery made at St.Mary’s Hospital, London (where injection therapy for hay fever was originally invented by Leonard Noon in 1911). The Wright-Fleming Institute at St. Mary’s has been at the forefront of allergy and clinical immunology research for a century, and one of its brightest pharmacologists in the 1970’s was L. M. McEwen. McEwen followed earlier reports that hyposensitisation could be improved by the addition of certain enzymes to the vaccine. In painstaking work over two decades. testing each stage on animals and patients, McEwen discovered that the enzyme beta-glucuronidase is the crucial ingredient, and that the precise dose of enzyme and allergen are both critical (3).

McEwen left St. Mary’s in the reorganisation of the 1980’s and started his own manufacturing laboratory at Henley-on-Thames. In clinical trials (4) involving many thousands of patients EPD is shown to be at least as effective as conventional hyposensitisation and far safer.

Neutralisation

Another development of classic hyposensitisation, this time in the USA, led in another, quite unexpected direction. C. Lee and J. Miller were attempting to make hyposensitisation safer and more accurate by first titrating the degree of sensitivity to each allergen in each patient. They did this by preparing several different dilutions of each substance then injecting each intracutaneously, to find out the threshold dose for inflammation. They observed, to their astonishment, that when certain dilutions were injected, pre-existing allergic symptoms were abolished, sometimes within minutes. They had discovered the neutralisation phenomenon, which is now used as a central therapeutic technique by several specialists in this country and the USA because of its speed, range and flexibility.

An extra benefit is intrinsic safety, since every substance is first tested in the patient, before treatment begins, and demonstrated to be non-inflammatory at that dilution. The vaccine is so safe that patients can administer it themselves in their own homes.

The CSM strictures regarding hyposensitisation do not apply either to EPD or to neutralisation (although the preliminary testing required for the latter is still potentially hazardous and should not be attempted in the GP’s surgery).

It should be noted that I do not use skin-testing to make allergy diagnoses. No skin test is accurate enough to be relied on for that (5). The skin-testing that I do is to determine the optimum dilution for use in treatment. (See other essays on this website devoted to the problems of diagnosis, which in truth warrant a monograph to themselves).

Both EPD and neutralisation are developments of the last few decades, and have not yet appeared to my knowledge in the general medical literature. Both are still controversial, EPD slightly (6) and neutralisation extremely (7). The main problem with neutralisation. probably, is that it just seems too good to be true, and its name has also been associated somewhat with “alternative” practitioners. Nevertheless, eight double-blind trials in this country and the USA demonstrate its efficacy (8-9) and only two, to my knowledge, have failed to do so (8,10). In my own practice the advent of neutralisation has virtually doubled my therapeutic success rate, and five-and ten-year follow-up studies published in the USA (11) show its long term safety, as do my own audit surveys. Quasi-allergic reactions of the intoxication type, brought about by alkaloids or lectins in foods, do not appear to respond to neutralisation (10), although experience is limited. The mechanisms of action of EPD and neutralisation are still uncertain.

Desensitisation offers a chance of eliminating root causes rather than simply suppressing symptoms and should he considered (a) when conventional treatments are ineffective or accompanied by unacceptable side effects, and (b) for patients who are averse to long term drugs (as am I). It is more cumbersome than conventional treatments, but as desensitisation is often curative, the overall cost is often considerably lower than longterm medication. The newer forms of desensitisation are not suitable, by and large, for general practice and remain the province of specialists.

References

1. Patterson, R., Lieberman, P. Irons, J. S., et at: Immunotherapy. In Middleton. E., Reed, C. E. Ellis. E. F.,(eds) Allergy. Principles and Practice. St. Louis. C. V. Mosby. 1983 pp 880-1

2. Committee on Safety of Medicines: CSM Update - desensitising vaccines. Br. Med. J. (1986) 293—348

3. McEwen, L. M.. Nicholson, M.. Kitchen, 1., White, S., Enzyme—potentiated hyposensitisation HI: control by sugars and diols of the immunological effect of beta glucuronidase in mice and patients with hay fever. Ann.Allergy (1973) 31: 543—550

4. McEwen, L. M., Enzyme-Potentiated Desensitisation. obtainable from author. McEwen Laboratories, 12 Horseshoe Park, Pangbourne, tel 0118-984-1288

5. Haahtela, T., Jaaknomaki, I.,: Relationship of allergen-speciflc IgE antibodies, skin-prick tests and allergic disorders in unselected adolescents. Allergy (1981) 36: 25 1-256

6. David,T. J., Unhelpful recent developments in the diagnosis and treatment of allergy and food intolerance in children In Dobbing, J. (ed) Food Intolerance. London, Bailliere Tindall, 1987, pp 196-197

7. Pearson, D. J., David, T. J., Freed, D. L. J., Brostoff. J. et al. ibid pp 172-184

8. Freed, D. L. J., The provocation-neutralisation technique, ibid pp 151-171

9. King, W. P., Fadal, R. G., Ward W. A. et al: Provocation-neutralisation part II. Subcutaneous neutralisation therapy: a multi-centre study. Otolaryngology -Head and Neck Surgery (1988) 99: 272-7

10. Birtwistle. S.. Hunter, J. 0. A double-blind trial of desensitisation by the intradermal provocation or neutralisation technique in irritable bowel syndrome. Personal communication, unpublished

11. Rea, W. J., Peters, D. W., Smiley, R. E., et at. Recurrent environmentally-triggered thrombophiebitis: a five year follow up. Ann. Allergy 1981 47:338-344. (10 year follow—up results reported orally by same authors at 2nd International meeting on Man and his Environment, Harrogate 1987)

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