Vincent St Aubyn Crump – Article written: June 2002

The prevalence of food allergy is estimated to be as high as 6% in young children and approximately 2 % in adults. The highest prevalence occurs between 1.5 and 3 years of age.

Almost everyone knows that about 80% of children with milk and egg allergy will outgrow their allergy by the age of five but only about 20% of peanut-allergic kids will outgrow their allergy. But the prognosis of food allergy is not that black and white. In reality there are several shades of grey, like:

• Children with milk and egg allergy, who also have peanut allergy, are less likely to outgrow their milk and egg allergy than those without peanut allergy.

• Adults can develop severe food allergies, which usually persists.

• Food allergies can be temporarily outgrown in children. There has been a recent reports from Hugh Sampson et al at Mt Sinai School of Medicine of 3 children who ‘outgrew’ their peanut allergy based on reduced CAP-RAST and negative oral challenges, who re-sensitized and developed clinical symptoms after re-introducing peanuts back into their diets. There are also 2 case reports from Spain of re-sensitization to fish after a short time of tolerance.

Food allergy tends to be a problem of early childhood and is often replaced by respiratory allergy, which appears in middle to later childhood as food allergy wanes, i.e., the atopic march.

The cause of food allergy is based on the genetic predisposition and the early exposure to the highly allergenic food. There is some evidence to suggest that sensitization can take place in utero and during breast-feeding. It is well established that neonates are more prone to sensitization than older infants.

In New Zealand, cow's milk, eggs, and peanut cause most of the immediate food allergy in children. The prevalence of reactions to different foods depends partly on the eating habits; for example allergy to soy is more frequent in Japan, while allergy to mustard seems to be more prevalent in France and fish allergy is more common in Spain and Scandinavian countries.

Multiple Food Allergies

Based on David Hill's study above, between 50% and 75% of children with cow's milk allergy (CMA) have hypersensitivity to other foods.

What factors determine whether a food allergy will be outgrown?

Poor prognostic signs for persistent food Allergy include:

• The type of allergen – Peanuts, nuts, fish and shellfish are more likely to cause life-long allergy. Why is penicillin more allergenic than paracetamol? What makes a substance an allergen, and why some allergens are more allergenic than others is the subject for another whole paper.

• An early age of onset.

• The severity of the allergy- the more severe the allergy, the less likely it will be outgrown. Patients with peanut allergy with specific peanut-IgE (RAST) level greater than 10kUA/L are unlikely to outgrow their allergy

• Multiple food allergies

• The continued exposure to the allergen

• Cross-reactions with other allergens

• Expression of more than one atopic manifestation

• Being Asthmatic

• The immunobiology of the antigen: Linear amino acid sequence or epitopes (vs. conformational epitopes) are more stable and less likely to be outgrown

Favorable prognosis of food allergy is associated with:

• Type of allergen – milk, egg, wheat, soy

• A short duration of symptoms

• Absence of respiratory symptoms - The patients who outgrow peanut allergy are more likely to have initial reactions involving the skin only

• A decreasing skin prick test wheal size or RAST level to the food allergen. Patients with peanut allergy who are older than 4 years and who have a Peanut-IgE (RAST) level less than 5 kUA/L, should be considered for a formal peanut challenge.

• Absence of anaphylaxis

• Single food allergy

• Conformational epitopes- amino acid sequence with a specific 3D shape may be altered by digestion or denatured by heat. These allergens are unstable and the allergies they cause are more likely to be outgrown.

Why do some atopics have mild transient allergies and some have life-threatening, permanent allergies?

• The reaction of the immune system to an allergen is more dependent on the hypersensitivity of the individual's immune system, rather than the strength of the allergen. This is borne out in the fact that, the more allergic (atopic) an individual, the earlier their allergies present, the more allergies they have, and the more severe the presentation of their allergies, the more severe will be their allergic reactions and the more allergens they will become allergic to.

• The more allergic the individual, the more likely that their allergy will be life-long.

• The immune system needs re-exposure to the allergen (booster doses) to remain sensitized. If a venom anaphylactic patient is not re-stung, he/she will lose their sensitization (allergy) with time.

• An individual with severe food anaphylaxis might have a temporary loss of clinical sensitivity, if no re-exposure is experienced for a long time, but resensitization will be possible if regular re-exposure is resumed.

• Perhaps, the reason why some common, severe food allergies are not outgrown is because it is impossible to avoid trace exposure, by skin contact even by inhalation.

Venom anaphylaxis & the parallels with food anaphylaxis

• Venom Anaphylactic reactions tend to be more severe in atopics (compared to non-atopics)

• The more severe the initial venom anaphylactic reaction, the more likely that it will be life-long.

• Frequent stings (as in beekeeper's neighbours) are associated with higher risk of sensitization and systemic (anaphylactic) reactions

• Higher frequency of severe reactions in patients with previous severe reaction

• Higher risk that the subsequent reaction will be more severe than in patients with a history of milder systemic reactions

• The majority of patients exhibit a characteristic and individual pattern of anaphylaxis which varies only slightly in severity from one sting to another (more dependent on the number of stings, i.e., the dose of the allergen)

• Contrary to popular belief, it is quite uncommon for patients to have more severe reactions with each subsequent sting

• A substantial proportion of patients (about 60% in most studies) with a history of venom (bee and wasp) anaphylaxis have no such reaction to a subsequent sting- that is, spontaneous improvement is common

• The longer the interval from the last sting, the lower the risk of another generalised reaction

• The dose of venom injected affects the outcome – the more stings the more severe the reaction

• Patients with a history of systemic sting reaction, even when treated with venom immunotherapy (which is usually 98% effective), show a decline of venom skin tests sensitivity that is not as rapid as the decline observed in patients with positive venom skin tests but no history of allergic reaction. This is consistent with the observation that overt clinical allergy is associated with an allergen-specific IgE antibody response that persists in the absence of allergen exposure.

• Interim stings cause a transient increase in venom IgE. Recent long-term studies indicate a continuing risk of 10% per sting even 10-15 years after discontinuing immunotherapy treatment, even in patients whose last known skin test was negative.

• Based on the success rate of immunotherapy to venoms, there is no reason why immunotherapy to foods will not be possible in the near future.

The prognosis of food allergy seems to be more dependent on the genetic programming of the individual than any of the other plausible risk factors. If you are genetically programmed to have severe allergies you will have severe allergies to several highly allergenic foods at an early age and you will also be asthmatic. At present we label these patients as being ‘high risk for dying from food allergy’. Perhaps being very strongly atopic is a risk factor for dying from any of the common allergies: allergic asthma, food anaphylaxis, venom anaphylaxis or drug anaphylaxis. It also probably means that you will always be at risk of developing new severe allergies even as an adult, if you expose yourself to highly allergenic substances. It also means that your allergies are probably going to be life-long, if you get any (booster) exposure to the allergens to keep your immune system sensitized. This exposure need only be very small and infrequent, and in some cases, if the individual is that severely atopic (allergic), the sensitization could be permanent even without re-exposure. It is probably wrong to believe that if someone is that severely atopic and becomes sensitized to an allergen, that they could "outgrow the allergy" without having assistance of immunotherapy (immune vaccine therapy), and even this might have to be indefinite for some people. At present we advocate indefinite immunotherapy for venom anaphylaxis, if their initial reaction was life threatening and especially if they are asthmatic. Why should we believe that a severely peanut anaphylactic child should outgrow their peanut allergy without immunotherapy, and if they appear to do so, it is very likely that they will resensitize if they start eating peanuts again.

The benefits of environmental control in the prevention and treatment of allergies is limited vs. the genetic programming.

As we learn more about the immune system, the genetics of Atopy, and how Immunotherapy works we might be better able to permanently re-programme the immune system from atopy. Until then, if you are severely atopic (by your genetic make-up), you are likely to develop several of the severe allergies (for life) and you are at risk of dying from one of them. At present, as doctors, all we can do is to identify, and label the individuals as "severely atopic’ at an early age (vs. "severe peanut allergy" or "severe allergic asthma") and educate all these individuals and their care-givers that they are at high risk of dying from an allergic emergency, and have a very low threshold for giving adrenaline auto-injectors to all of them. We don’t see many severely allergic patients "outgrowing their allergies". Their immune system is always on high alert.

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