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Keywords:

  • cow's milk allergy;
  • sublingual immunotherapy;
  • tolerance

After the age of 5, cow's milk allergy (CMA) has a low probability of spontaneous recovery (1). The aim of this study was to apply sublingual immunotherapy (SLIT), an efficient desensitization method (2), in patients with persistent immunoglobulin E (IgE)-mediated CMA.

Eight children (>6 years) with IgE-mediated CMA were recruited and underwent two milk challenges (before and after SLIT), to determine the eliciting dose (ED). In case of symptoms difficult to interpret, a double-blind placebo-controlled food challenge (DBPCFC) was undertaken. SLIT began the day after the challenge using cow milk (CM), for 6 months. Patients kept the milk in their mouth for 2 min (0.1 ml for the first 2 weeks, increasing by 0.1 ml every 15 days until 1 ml/day).

Cow milk-specific IgE (Phadia CAP System®, Saint Quentin en Yvelines, France) were measured before each challenge.

During the first challenge, the mean ED was 39 ml, range 4–106 ml. In six patients, this ED was reached following subjective symptoms elicited by lower milk doses and disappearing spontaneously. Recurrent subjective symptoms in patient 6 led to a positive DBPCFC. Patient 8 withdrew from the SLIT protocol after 5 months because of an oral syndrome attributed to the presence of milk in the mouth. Among the remaining seven patients, six completed the protocol, with a poor compliance in one, none experiencing any side-effects (Table 1).

Table 1.   Results of cow's milk challenge, before and after the sublingual immunotherapy during 6 months
Patients no. (years)First cow's milk challengeSecond cow's milk challengeEvolution/remarks
Subjective symptoms (dose of CM)ED (ml)Objective symptomsED (ml)Symptoms
  1. ED, eliciting dose; RC, rhinoconjunctivitis; DBPCFC, double-blind placebo-controlled food challenge.

  2. *Abdominal pain, vomiting and diarrhea.

1 (12)4 (pruritus) 44Angioedema, RCNoneNormal dairy diet
2 (6)106Angioedema, urticariaNoneNormal dairy milk
3 (8)0.1 (tickly throat) 37Digestive anaphylaxis*NoneNormal dairy milk
4 (6)5 (erythema) 36Digestive anaphylaxis*150Abdominal painNormal dairy milk 3 months later
5 (17)0.5 (tickly throat)  8Asthma, RC 93Asthma 
6 (9)0.1 (tickly throat), 4 (cough) 14Asthma, urticaria 44UrticariaDBPCFC at first challenge
7 (6)9 (cough) 68Asthma 70AsthmaPoor compliance
8 (9)  4Digestive anaphylaxy*, urticariaNot done Withdrawn

During the second challenge, the mean ED increased, 143 ml, 44 to >200 ml (P < 0.01, paired t-test). Three patients did not react with 200 ml of CM and normalized their diet. Patient 4 presented abdominal pain following ingestion of 150 ml and parents denied continuing the challenge, but CM was progressively reintroduced at home until a normal diet 3 months later. The ED increased in the two others who completed the SLIT protocol and remained unchanged in the patient with a poor compliance.

Casein-specific IgE decreased in five children and increased in one, albeit with no significant differences.

Cow milk oral desensitization, based on the intake of increasing doses of CM during 6 months, was successful in 70% of patients, with 50% exhibiting side-effects and 15% withdrawn because of uncontrolled side-effects (3, 4).

We tested a SLIT, already reported for hazelnut and kiwi allergy (5, 6), to desensitize IgE-mediated CMA in children older than 6, for whom the prognosis of persistent CMA has become highly predictable (1). All patients had an immediate severe reaction to CM during the first challenge, rendering any diagnosis difficulties unlikely, with a DBPCFC still required in one case. Subjective symptoms nonetheless occurred in 75% of patients, for low doses of CM, probably reflecting anxiety, in children having previously experienced severe allergic manifestations.

The ED increased in the six children who completed the SLIT and four, with the highest milk ED at the first challenge (>30 ml), normalized their diet. The ED remained unchanged in the patient with a poor compliance. Patient 8 does not allow concluding. Recently, a younger child (4.5 years) completed the same SLIT, with an oral syndrome during the week preceding the second challenge, even though the ED increased from 37 to 177 ml (data not shown). Subjective symptoms before the second challenge might be a manifestation of anxiety.

Cow milk-specific IgE did not vary following SLIT, suggesting that tolerance relies on other mechanisms, able to counterbalance the triggering effect of IgE levels.

Briefly, SLIT, using a CM dose below the ED is safe, easy, and increased the milk ED after 6 months, suggesting a potential alternative to the elimination diet in patients with persisting IgE-mediated CMA. Confirmation with larger studies should aim at determining the optimal duration of the procedure, which might prove dependent on the ED at first challenge.

This paper has been presented in part at the 2006 Annual Meeting of the American Academy of Allergy, Asthma and Immunology (Miami, USA, March 2006) and accepted for presentation in its present version at the 1st French Congress of Allergy (Paris, France, April 2006) and the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (Dresden, Germany, June 2006).

References

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    Wilson DR, Lima MT, Durham SR. Sublingual immunotherapy for allergic rhinitis: systematic review and meta-analysis. Allergy 2005;60:412.
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    Meglio P, Bartone E, Plantamura M, Arabito E, Giampietro PG. A protocol for oral desensitization in children with IgE-mediated cow's milk allergy. Allergy 2004;59:980987.
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    Patriarca G, Nucera E, Roncallo C, Pollastrini E, Bartolozzi F, De Pasquale T et al. Oral desensitizing treatment in food allergy: clinical and immunological results. Aliment Pharmacol Ther 2003;17:459465.
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    Enrique E, Pineda F, Malek T, Bartra J, Basagana M, Tella R et al. Sublingual immunotherapy for hazelnut food allergy: a randomized, double-blind, placebo-controlled study with a standardized hazelnut extract. J Allergy Clin Immunol 2005;116:10731079.
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