Specific oral tolerance induction in children with very severe cow-milk allergy

The prevalence of food allergy is high in early childhood and it seems to be increasing [1]. The prognosis is good in most cases, with gradual recovery over time [2]. The tolerance is antigen dependent and develops progressively, in many cases by 6 years of age. The only current option is strict food avoidance. In recent years, a limited volume of evidence regarding the efficacy of specific oral tolerance induction (SOTI) has been reported [3–10].

We have recently published a study proving the feasibility of SOTI in patients affected by very severe cow-milk allergy, with interesting results [11].

We selected patients with very severe food allergy, over the age of 6 years, presenting severe reactions after the ingestion of only trace amounts of antigen or even after skin contact or smell inhalation. For these children, the risk of fatal reactions is real [12] and increases with the child’s age, in conjunction with reduced parental control over their diet [13]. For them, we have set up a SOTI protocol: the first step taking place in a hospital, with quick increases in dosage during a 10-day period, eventually followed by a slow rising phase at home.

The protocol was evaluated in 60 children that tested positive during a challenge to very small amounts of milk. A total of 30 children were subjected to SOTI, while 30 were kept on a milk-free diet. After 1 year, 11 out of 30 children (36%) in the treatment group tolerated large volumes of milk, 16 (54%) could take limited amounts (5–150 ml) and three (10%) were not able to complete the protocol because of reactions. In the diet group, the challenge performed after 1 year was positive in all 30 cases. The total number of reactions in the treatment group during the study was high and four patients required intramuscular adrenaline.

In this experience, SOTI was effective in a significant percentage of cases and was perceived as an important improvement in the quality of life for these patients. The number of reactions to milk was significant, and data are still needed to estimate the risk of fatal or near-fatal events in these subjects and to confirm the safety of this intervention that should, therefore, be restricted to highly defined assistance settings.

Actually, this approach was attempted after gaining significant experience taking care of allergic children younger than 6 years of age, with less-severe clinical history, using protocols similar to those already published [4,10]. Our results in this setting are comparable with ones available in the current literature [3,14], with success in approximately 70% of cases, so we never published our data on this topic. Our activity became ‘unique’, primarily for the habit – developed many years ago – of performing a food challenge in allergic children approximately 3 years of age, not only to verify the diagnosis, but mostly to assess tolerance achievement or to determine the actual sensitivity of each patient and find a threshold value. If the food challenge is positive but the child is able to ingest at least 4 ml of whole milk, he is invited immediately to continue milk intake, following an increasing dosage schedule at home and starting the day after the food challenge.

This strategy is far from the standard guidelines. According to these guidelines, in the case of positive food challege, the child should follow a strict exclusion diet and be rechallenged after 6–12 months [15]. In spite of this, our behavior has a theoretical justification and reproduces what naturally happens over time in children who finally stop suffering from food allergy. We should underline that, even if the prevalence of food allergy is increasing, this kind of disorder has always existed, long before the discovery of IgE and allergic mechanisms. As a matter of fact, the natural history of food allergies has been the same through the centuries, with a large percentage of spontaneous recoveries. Even without tools for allergy diagnosis and follow-up, all mothers at one point offered a very little amount of the offending food to her child and, in the absence of an adverse reaction, continued to administer increasing doses over time, which removed the tolerance. This is the same approach adopted by us, and it turned out to be so effective in such a high percentage of children in our series that it became our actual standard practice. To date, our experience regarding these children involves more than 200 patients with an allergy to cow milk, hen eggs and wheat, dramatically changing, in most cases, the quality of life of the child and of the entire family. The critical issues to be considered regarding this strategy are safety and the cost–benefit ratio. As far as safety is concerned, both the existing literature [3–10,15] and our experience show that SOTI for children without a history of very severe reactions can be considered reasonably safe when managed by skilled physicians dealing with families with a good degree of reliability. To the best of our knowledge, only minor reactions with no cases of fatal or near-fatal reactions have been reported. As far as the cost–benefit ratio is concerned, one should always consider that the great majority of these children will spontaneously acquire a tolerance to the allergen in the forthcoming years. The benefit of intervention is that the possibility of introducing even small amounts of the incriminated food reduces the risk of a reaction from contamination or inadverted contact, which is perceived by families as a major improvement in their quality of life. This benefit must be weighed case by case against the costs of family engagement for milk administration and the risk of reactions. Furthermore, this approach is time consuming and requires a defined level of commitment by the staff involved. Once the challenge is over, the greatest job is still to come: thorough explanation to the parents to continue milk consumption, acquisition of informed consent and availability of personnel for easy telephone consultation in order to manage any problems or reactions. We have no data to confirm the cost–benefit efficacy of this approach but this approach is what most families choose when the option of continuing milk consumption with a good follow-up is offered to them. Future research will be needed to address the SOTI cost–benefit ratios, specifically for children with both severe and nonsevere allergy.

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.