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Life-threatening anaphylaxis to kiwi fruit: Protective sublingual allergen immunotherapy effect persists even after discontinuation

2006; Elsevier BV; Volume: 119; Issue: 2 Linguagem: Inglês

10.1016/j.jaci.2006.09.041

1097-6825

R Kerzl, Anna Simonowa, Johannes Ring, Markus Ollert, Martin Mempel,

Asthma and respiratory diseases

To the Editor:We previously reported the case of a 29-year-old woman with several episodes of severe anaphylaxis after consumption of kiwi fruit, including 3 episodes of allergic shock with loss of consciousness and hospitalization, who was subsequently treated with a modified sublingual immunotherapy (SLIT) protocol enabling her to ingest substantial amounts of kiwi without symptoms.1Mempel M. Rakoski J. Ring J. Ollert M. Severe anaphylaxis to kiwi fruit: immunologic changes related to successful sublingual allergen immunotherapy.J Allergy Clin Immunol. 2003; 111: 1406-1409Abstract Full Text Full Text PDF PubMed Scopus (107) Google ScholarSublingual immunotherapy has been shown to reduce clinical symptoms in a variety of IgE-mediated respiratory allergic diseases (see review2Bousquet J. Sublingual immunotherapy: validated!.Allergy. 2006; 61: 5-6Crossref Scopus (25) Google Scholar),3Vourdas D. Syrigou E. Potamianou P. Carat F. Batard T. Andre C. et al.Double-blind, placebo-controlled evaluation of sublingual immunotherapy with standardized olive pollen extract in pediatric patients with allergic rhinoconjunctivitis and mild asthma due to olive pollen sensitization.Allergy. 1998; 53: 662-672Crossref PubMed Scopus (193) Google Scholar, 4Di Rienzo V. Marcucci F. Puccinelli P. Parmiani S. Frati F. Sensi L. Long-lasting effect of sublingual immunotherapy in children with asthma due to house dust mite: a 10-year prospective study.Clin Exp Allergy. 2003; 33: 206-210Crossref PubMed Scopus (346) Google Scholar but its therapeutic value in anaphylactic food allergy is repeatedly questioned because of the lack of standardized protocols and the great variability in allergen uptake by custom-made protocols. While information is already scarce concerning possible indication for this treatment, almost no information exists on the possible duration of the protective/beneficial effect in patients undergoing SLIT in food-associated anaphylaxis.5Rolinck-Werninghaus C. Staden U. Mehl A. Hamelmann E. Beyer K. Niggemann B. Specific oral tolerance induction with food in children: transient or persistent effect on food allergy?.Allergy. 2005; 60: 1320-1322Crossref PubMed Scopus (165) Google ScholarWe had initiated the successful SLIT in our patient in 2001 by starting with a dose of 100 μL 10−4 diluted stock solution of fresh kiwi pulps (concentration of the stock solution, 1 mg/mL) and a gradual increase (100-500-1000 μL) until the next concentration was reached. The patient was advised to keep the kiwi extract under her tongue for 1 minute before swallowing. This regimen was kept until 1 mL undiluted kiwi extract was tolerated. Thereafter, a 1 cm3 cube of fresh or frozen kiwi was given without symptoms.The patient was then followed at regular intervals and was advised to consume this dose (1 cm3 kiwi) using an identical technique (sublingual application for 1 minute before swallowing) every day. No further immunotherapies against concomitantly diagnosed sensitizations to grass pollen, birch pollen, latex, or crab meat1Mempel M. Rakoski J. Ring J. Ollert M. Severe anaphylaxis to kiwi fruit: immunologic changes related to successful sublingual allergen immunotherapy.J Allergy Clin Immunol. 2003; 111: 1406-1409Abstract Full Text Full Text PDF PubMed Scopus (107) Google Scholar were performed.Because allergic reactions to food in adults (best documented for peanut allergy), unlike reactions to milk and egg in children, do not tend to undergo spontaneous resolution,6Sicherer S.H. Leung D.Y. Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insects.J Allergy Clin Immunol. 2005; 116: 153-163Abstract Full Text Full Text PDF PubMed Scopus (54) Google Scholar we decided to recommend a lifelong continuation of this treatment in an identical manner.However, because of a severe tonsillitis with pharyngeal abscess and subsequent tonsillectomy in February 2006, the patient stopped the SLIT for a period of 4 months on her ear, nose, and throat doctor's advice. After that, the patient wished to resume the immunotherapy, because she had experienced a high degree of safety under SLIT when consuming food of unknown source. At this point, skin prick test, a labial application test with diluted fresh kiwi extract, and an oral provocation with fresh kiwi were performed. The skin prick test still showed positive results, which were, however, decreased compared with pretreatment values (5/14 instead of 10/30 mm wheal/mm flare by using a 1:10 dilution of the kiwi extract stock solution). The labial application test elicited negative results, and the oral provocation was tolerated well without any adverse reactions at a dose of a 1 cm3 cube of fresh kiwi. Thus, our findings at this point were still in accordance with a persisting state of tolerance, most probably because of the ongoing effect of a successful SLIT.The clinical results were also mirrored in specific IgE testing by the Immulite system (DPC Biermann, Bad Nauheim, Germany) and by Western blotting with kiwi extract. The amount of kiwi specific IgE had dropped from70.4 kU/L after treatment to 34.6 kU/L. In Western blots with kiwi extracts, we found a clearly diminished IgE-reactivity to the dominant kiwi allergen Act c 1 (30 kd), which was strongly positive before and immediately after SLIT, together with a substantial increase in IgG4 reactivity to the same protein (Fig 1). Thus, the patient's serum showed all criteria for a persisting state of tolerance even after the cessation of kiwi intake.In consequence of our findings and the patient's personal intention for a high degree of safety, we advised her to resume the SLIT protocol without modifications (1 cm3 kiwi cube sublingually for 1 minute before swallowing).In summary, this case should encourage the consideration of SLIT protocols in patients with severe food allergies, especially in cases in which the foods are difficult to avoid. Even after accidental interruptions, the beneficial effects seem to endure. Experiences in larger collectives such as reported for hazelnut allergens7Enrique 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: 1073-1079Abstract Full Text Full Text PDF PubMed Scopus (369) Google Scholar should help to evaluate the findings in our patients and to design protocols for immunotherapy strategies in patients with food allergy. To the Editor: We previously reported the case of a 29-year-old woman with several episodes of severe anaphylaxis after consumption of kiwi fruit, including 3 episodes of allergic shock with loss of consciousness and hospitalization, who was subsequently treated with a modified sublingual immunotherapy (SLIT) protocol enabling her to ingest substantial amounts of kiwi without symptoms.1Mempel M. Rakoski J. Ring J. Ollert M. Severe anaphylaxis to kiwi fruit: immunologic changes related to successful sublingual allergen immunotherapy.J Allergy Clin Immunol. 2003; 111: 1406-1409Abstract Full Text Full Text PDF PubMed Scopus (107) Google Scholar Sublingual immunotherapy has been shown to reduce clinical symptoms in a variety of IgE-mediated respiratory allergic diseases (see review2Bousquet J. Sublingual immunotherapy: validated!.Allergy. 2006; 61: 5-6Crossref Scopus (25) Google Scholar),3Vourdas D. Syrigou E. Potamianou P. Carat F. Batard T. Andre C. et al.Double-blind, placebo-controlled evaluation of sublingual immunotherapy with standardized olive pollen extract in pediatric patients with allergic rhinoconjunctivitis and mild asthma due to olive pollen sensitization.Allergy. 1998; 53: 662-672Crossref PubMed Scopus (193) Google Scholar, 4Di Rienzo V. Marcucci F. Puccinelli P. Parmiani S. Frati F. Sensi L. Long-lasting effect of sublingual immunotherapy in children with asthma due to house dust mite: a 10-year prospective study.Clin Exp Allergy. 2003; 33: 206-210Crossref PubMed Scopus (346) Google Scholar but its therapeutic value in anaphylactic food allergy is repeatedly questioned because of the lack of standardized protocols and the great variability in allergen uptake by custom-made protocols. While information is already scarce concerning possible indication for this treatment, almost no information exists on the possible duration of the protective/beneficial effect in patients undergoing SLIT in food-associated anaphylaxis.5Rolinck-Werninghaus C. Staden U. Mehl A. Hamelmann E. Beyer K. Niggemann B. Specific oral tolerance induction with food in children: transient or persistent effect on food allergy?.Allergy. 2005; 60: 1320-1322Crossref PubMed Scopus (165) Google Scholar We had initiated the successful SLIT in our patient in 2001 by starting with a dose of 100 μL 10−4 diluted stock solution of fresh kiwi pulps (concentration of the stock solution, 1 mg/mL) and a gradual increase (100-500-1000 μL) until the next concentration was reached. The patient was advised to keep the kiwi extract under her tongue for 1 minute before swallowing. This regimen was kept until 1 mL undiluted kiwi extract was tolerated. Thereafter, a 1 cm3 cube of fresh or frozen kiwi was given without symptoms. The patient was then followed at regular intervals and was advised to consume this dose (1 cm3 kiwi) using an identical technique (sublingual application for 1 minute before swallowing) every day. No further immunotherapies against concomitantly diagnosed sensitizations to grass pollen, birch pollen, latex, or crab meat1Mempel M. Rakoski J. Ring J. Ollert M. Severe anaphylaxis to kiwi fruit: immunologic changes related to successful sublingual allergen immunotherapy.J Allergy Clin Immunol. 2003; 111: 1406-1409Abstract Full Text Full Text PDF PubMed Scopus (107) Google Scholar were performed. Because allergic reactions to food in adults (best documented for peanut allergy), unlike reactions to milk and egg in children, do not tend to undergo spontaneous resolution,6Sicherer S.H. Leung D.Y. Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insects.J Allergy Clin Immunol. 2005; 116: 153-163Abstract Full Text Full Text PDF PubMed Scopus (54) Google Scholar we decided to recommend a lifelong continuation of this treatment in an identical manner. However, because of a severe tonsillitis with pharyngeal abscess and subsequent tonsillectomy in February 2006, the patient stopped the SLIT for a period of 4 months on her ear, nose, and throat doctor's advice. After that, the patient wished to resume the immunotherapy, because she had experienced a high degree of safety under SLIT when consuming food of unknown source. At this point, skin prick test, a labial application test with diluted fresh kiwi extract, and an oral provocation with fresh kiwi were performed. The skin prick test still showed positive results, which were, however, decreased compared with pretreatment values (5/14 instead of 10/30 mm wheal/mm flare by using a 1:10 dilution of the kiwi extract stock solution). The labial application test elicited negative results, and the oral provocation was tolerated well without any adverse reactions at a dose of a 1 cm3 cube of fresh kiwi. Thus, our findings at this point were still in accordance with a persisting state of tolerance, most probably because of the ongoing effect of a successful SLIT. The clinical results were also mirrored in specific IgE testing by the Immulite system (DPC Biermann, Bad Nauheim, Germany) and by Western blotting with kiwi extract. The amount of kiwi specific IgE had dropped from70.4 kU/L after treatment to 34.6 kU/L. In Western blots with kiwi extracts, we found a clearly diminished IgE-reactivity to the dominant kiwi allergen Act c 1 (30 kd), which was strongly positive before and immediately after SLIT, together with a substantial increase in IgG4 reactivity to the same protein (Fig 1). Thus, the patient's serum showed all criteria for a persisting state of tolerance even after the cessation of kiwi intake. In consequence of our findings and the patient's personal intention for a high degree of safety, we advised her to resume the SLIT protocol without modifications (1 cm3 kiwi cube sublingually for 1 minute before swallowing). In summary, this case should encourage the consideration of SLIT protocols in patients with severe food allergies, especially in cases in which the foods are difficult to avoid. Even after accidental interruptions, the beneficial effects seem to endure. Experiences in larger collectives such as reported for hazelnut allergens7Enrique 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: 1073-1079Abstract Full Text Full Text PDF PubMed Scopus (369) Google Scholar should help to evaluate the findings in our patients and to design protocols for immunotherapy strategies in patients with food allergy.