avoided during the treatment period. Three weeks after the third injection, foods shown to provoke symptoms during the open trial were again reintroduced. The outcome was assessed by a single criterion: the ability of each child to resume a full normal diet without recurrence of migraine. The results of this experiment, which involved forty children, are shown in Table 3. Eighty per cent of children receiving active treatment, but only twenty-five per cent of those receiving placebo, were able to resume a normal diet without recurrence of headache (p=0.001).

The adjuvant role of beta-glucuronidase in enhancing hyposensitization was discovered by McEwen in 1967⁵⁵. Uncontrolled case reports of the usefulness of EPD for hyposensitization of adolescents and adults with immediate hypersensitivity responses to specific foods were first published in 1975⁵⁶. Double blind placebo-controlled trials have demonstrated the effectiveness of EPD in decreasing the symptoms of seasonal allergic rhinitis provoked by grass pollen⁵⁶ and in hyposensitization of children with food-induced hyperkinetic syndrome⁵⁴. The mechanism by which EPD reverses food intolerance is not known. Its effectiveness in the treatment of hayfever⁵⁷ implies an immunologic effect. Nonetheless, unlike conventional pollen desensitization, which elicits production of blocking antibodies⁵⁸, EPD treatment of patients with allergic rhinitis does not induce blocking antibody (MS Starr, personal communication). Antigen-induced

leukocyte migration inhibition demonstrates in vitro a cell-mediated immune response which is present in IgE-mediated hayfever⁵⁹. The leukocytes of cow's milk-sensitive patients with atopic eczema are also inhibited by cow's milk in this test. Brostoff showed that after successful EPD for milk allergy this inhibition disappeared (J. Brostoff, personal communication). This finding suggests that EPD hyposensitizes by reducing cellular responsiveness to allergens. The effectiveness of EPD in the treatment of childhood migraine gives weight to the hypothesis that the basis of migraine for most children is a non-atopic immunologic response to foods or other antigens.

A parallel to the combined immunologic/metabolic hypersensitivity of migraineurs can be found in atopic asthma. It is now widely accepted that atopic asthma has multiple mechanisms of pathogenesis. Contact with specific allergen (e.g. house dust mite) triggers immunologic hypersensitivity^60,61, but hyper-responsiveness of the airway to pharmacologic mediators (e.g. histamine⁶²) is also extremely important. Prolonged allergen avoidance not only decreases the frequency of allergen triggered asthmatic attacks but also decreases non-specific bronchial reactivity to histamine challenge⁶³. Asthma is thus an excellent model of the immunologic priming of pharmacologic responsiveness. We believe that lessons learned from asthma research are relevant to migraine and that, for migraine, altered intestinal permeability may be a link between humoral/metabolic and immunologic reactivity.

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