- Email: [email protected]
Sublingual immunotherapy with venom is not recommended for patients with Hymenoptera venom allergy
272 CORRESPONDENCE
J ALLERGY CLIN IMMUNOL JANUARY 2009
5. Singer BD, Ziska LH, Frenz DA, Gebhard DE, Straka JG. Increasing Amb a 1 content in common ragweed (Ambrosia artemisiifolia) pollen as a function of rising atmospheric CO2 concentration. Funct Plant Biol 2005;32:667-70. 6. Beggs PJ, Walczyk NE. Impacts of climate change on plant food allergens: a previously unrecognized threat to human health. Air Qual Atmos Health 2008;1:119-23. doi:10.1016/j.jaci.2008.10.025
Reply To the Editor: We are grateful to Dr Beggs1 for encouraging more research and dialog on the interaction between climate change and allergic disease, and we agree completely that the topic has not received sufficient consideration to date. Indeed, it was our hope in producing the recent clinical review2 to stimulate interest and more targeted attention to this important area. We did not attempt a comprehensive literature review; rather, our goal for the article was to function as a conversation starter. We thank Dr Beggs for highlighting additional studies that inform and support ongoing discussion and research questions. We hope many will join us in exploring further not only the pathophysiology of climate change and allergic disease but also the primary and secondary prevention of related morbidity and mortality through mitigation and adaptation. Katherine M. Shea, MD, MPHa Robert T. Truckner, MD, MPHb Richard W. Weber, MDc David B. Peden, MDd From aMaternal and Child Health and dMedicine and Toxicology, University of North Carolina School of Public Health, Chapel Hill, NC; bthe US Environmental Protection Agency National Health and Environmental Effects Laboratory, Research Triangle Park, NC; and cthe Department of Medicine, National Jewish Health, University of Colorado Health Sciences Center, Denver, Colo. E-mail: [email protected]. Disclosure of potential conflict of interest: R. W. Weber is on the speakers’ bureau for AstraZeneca, Schering-Plough, and Genentech; received grant support from GlaxoSmithKline, Pfizer, and Novartis; is the committee chair for the American College of Allergy, Asthma & Immunology; and is an associate editor for the Annals of Allergy, Asthma, and Immunology. D. B. Peden received grant support from the National Institutes of Health, Greer Laboratories, and the US Environmental Protection Agency and has testified regarding the adverse effects of air pollution on human health. The rest of the authors have declared that they have no conflict of interest. The opinions expressed here do not necessarily reflect US Environmental Protection Agency policy.
REFERENCES 1. Beggs PJ. Climate change and plant food allergens. J Allergy Clin Immunol 2009; 123:271-2. 2. Shea KM, Truckner RT, Weber RW, Peden DB. Climate change and allergic disease. J Allergy Clin Immunol 2008;122:443-53. doi:10.1016/j.jaci.2008.10.024
Sublingual immunotherapy with venom is not recommended for patients with Hymenoptera venom allergy To the Editor: The study of Severino et al1 reported the results of sublingual immunotherapy (SLIT) with honeybee venom, which was used to treat large local reactions to honeybee stings. By using sting challenges, it was found that SLIT compared with placebo reduced the extent of large local reactions. The authors concluded that the efficacy of SLIT might also be assessed in patients with systemic anaphylactic reactions to Hymenoptera stings.
Significant methodological flaws detract from the value of the presented data. First, demographic data differed significantly between the SLIT (n 5 14) and placebo (n 5 12) groups with respect to various parameters, such as concentration of total IgE and serum tryptase concentration. Results were presented as means and SDs, but P values were not given. Second, a venom dose of 525 mg per month was used in the SLIT group, which considerably exceeds the standard dose of 100 mg for subcutaneous venom immunotherapy (VIT). In both groups there was no increase of the venom-specific IgE concentration after 6 months of treatment. However, a significant increase of the venom-specific IgG concentration was only found in patients receiving SLIT. From several studies on VIT, we know that an increase of both venom-specific IgE and IgG concentrations can be expected very early after the initiation of therapy.2-4 In the long run, venom-specific IgE concentrations will decrease and IgG concentrations will remain high. The change of these immunologic parameters over time is ambiguously associated with treatment efficacy.5,6 However, these secondary immunologic reactions allow the treating physician to be sure that the venom used for treatment has reached immune-competent cells. Third, it is possible that changes in the venom-specific IgG concentration were not a consequence of SLIT but might have been caused by field stings. No information is provided on the frequency of field stings. A different immunologic status (see above) could also have modified the response to stings, including the diagnostic sting challenge. To account for those potentially confounding effects, a control group would be required that is treated with SLIT but that has not been exposed to sting challenges or field stings. Therefore we do not know whether changes of venom-specific IgG concentrations can be attributed to SLIT or to repeated honeybee stings. Fourth, in the SLIT group the peak diameter of the large local reaction was reduced by more than 50% in 57% of the patients. These results could be interpreted quite differently, indicating a complete treatment failure in 43% of the patients and at least a partial treatment failure in 57%. If we would extrapolate these results to patients with a systemic anaphylactic sting reaction, we might conclude as well that there was not sufficient proof of treatment efficacy. On the basis of these criticisms, we caution against an overly optimistic interpretation of the results, and we strongly disagree with regarding SLIT as a therapeutic option for patients with potentially life-threatening reactions on the basis of the presented data. Subcutaneous VIT is safe and highly effective, and it is also less expensive than SLIT because the latter requires much higher doses for treatment. Franziska Ru€ eff, MDa M. Beatrice Bilo`, MDb Marek Jutel, MDc Holger Mosbech, MD, DMScd Ulrich M€ uller, MDe Bernhard Przybilla, MDa For the interest group on Hymenoptera venom allergy of the European Academy of Allergology and Clinical Immunology From aAllergieZentrum, Klinik und Poliklinik f€ur Dermatologie und Allergologie, Ludwig-Maximilians-Universita¨t, Munich, Germany; bthe Allergy Unit, Department of Internal Medicine, Allergy, Immunology and Respiratory Diseases, Ospedali Riuniti di Ancona, Azienda Ospedaliero-Universitaria, Ancona, Italy; cthe Department of Clinical Immunology, Silesian Piasts University of Medicine in Wroc1aw, Wroc1aw, Poland; dthe Allergy Unit, National University Hospital,
CORRESPONDENCE 273
J ALLERGY CLIN IMMUNOL VOLUME 123, NUMBER 1
Rigshospitalet, Copenhagen, Denmark; and eAllergiestation Medizinische Klinik, Bern, Switzerland. E-mail: [email protected]. Disclosure of potential conflict of interest: M. Jutel has served as a clinical trial investigator for Allergopharma Joachim Ganzer KG and Schering-Plough. H. Mosbech has received research support from ALK-Abello´ and has served as an expert witness on the topic of anaphylaxis. The rest of the authors have declared that they have no conflict of interest.
REFERENCES 1. Severino MG, Cortellini G, Bonadonna P, Francescato E, Panzini I, Macchia D, et al. Sublingual immunotherapy for large local reactions caused by honeybee sting: a double-blind, placebo-controlled trial. J Allergy Clin Immunol 2008;122:44-8. 2. Golden DB, Valentine MD, Kagey-Sobotka A, Lichtenstein LM. Regimens of Hymenoptera venom immunotherapy. Ann Intern Med 1980;92:620-4. 3. Graft DF, Schuberth KC, Kagey-Sobotka A, Kwiterovich KA, Niv Y, Lichtenstein LM, et al. Assessment of prolonged venom immunotherapy in children. J Allergy Clin Immunol 1987;80:162-9. 4. Ru€eff F, Wolf H, Schnitker J, Ring J, Przybilla B. Specific immunotherapy in honeybee venom allergy: a comparative study using aqueous and aluminium hydroxide adsorbed preparations. Allergy 2004;59:589-95. 5. M€uller U, Helbling A, Bischof M. Predictive value of venom-specific IgE, IgG and IgG subclass antibodies in patients on immunotherapy with honey bee venom. Allergy 1989;44:412-8. 6. Golden DB, Lawrence ID, Hamilton RH, Kagey-Sobotka A, Valentine MD, Lichtenstein LM. Clinical correlation of the venom-specific IgG antibody level during maintenance venom immunotherapy. J Allergy Clin Immunol 1992;90:386-93. doi:10.1016/j.jaci.2008.10.028
Reply To the Editor: We thank Ru€eff et al1 for their comments on our work on sublingual immunotherapy (SLIT) in large local reactions caused by Hymenoptera venom2 and for giving us the opportunity to clarify some aspects of our study. Moreover, these comments testify to the interest raised by our article and, hopefully, will stimulate further scientific debates. Going to the specific points, our rebuttals are as follows. It is true that some differences between the 2 groups seem to exist at baseline, but those differences were not statistically significant, and this is the reason why a P value was not explicitly reported. It is difficult to hypothesize, for instance, that a mean difference in tryptase of 1.3 mg/L (with the normal threshold value being 20 mg/L) would have represented an imbalance factor in favor of one of the 2 groups. The dosage used was empirically chosen based on previous experiences with SLIT for aeroallergens, in which it has been shown that a dose-response relationship exists3,4 and that higher amounts of allergen are needed than in subcutaneous immunotherapy. Indeed, as we mentioned in the discussion, dose-finding studies are needed to identify the optimal dose. Concerning the immunologic aspect, it is well known that the changes in circulating immunoglobulins are less pronounced with SLIT than with injections,5 but this does not affect the efficacy of the treatment, as shown in numerous trials. In other words, we should be cautious in stating that SLIT does not work because it does not modify specific IgE levels. As acknowledged by Dr Ru€eff herself, the immunoglobulin changes over time are weakly correlated with the clinical effect, and a judgment on the efficacy of an immunotherapy course is essentially clinical. We acknowledge that in our article no mention was made of field stings, and this is an important point. We take this opportunity to clarify that none of the patients received field stings
during the 6-month period of the study. Thus the mentioned confounding factor can be reasonably excluded. Concerning the efficacy, we could also state that there was a full success in 57% and a partial success in 43% of the patients, but we think that such sophisms are not helpful in interpreting the data and for research in general. There are thus far no standard criteria to define the ‘‘failure’’ or ‘‘success’’ of venom immunotherapy according to the reduction of large local reactions at the sting challenge. Finally, Ru€eff et al1 express a ‘‘strong disagreement’’ about the use of SLIT in anaphylaxis after Hymenoptera sting. We do not understand their disagreement because such a scenario was not mentioned in our article. We simply envisaged the possibility of testing the efficacy of SLIT in systemic reactions, which might be, for instance, generalized urticaria. To conclude, we would underline once more that our study was a proof-of-concept trial and did not imply recommendations or suggestions for the clinical use of SLIT in patients with Hymenoptera allergy but only the possibility of exploring a new clinical approach. Giovanni Passalacqua, MDa Maurizio G. Severino, MDb Gabriele Cortellini, MDc Patrizia Bonadonna, MDd Donatella Macchia, MDb Walter G. Canonica, MDa From aAllergy and Respiratory Diseases, Department of Internal Medicine, University of Genoa, Genoa, Italy; bthe Allergy Clinic, Nuovo Ospedale San Giovanni di Dio, Florence, Italy; cInternal Medicine and Rheumatology, Rimini Hospital, Rimini, Italy; and dthe Allergy Unit, Verona General Hospital, Verona, Italy. E-mail: passalacqua@ unige.it. Disclosure of potential conflict of interest: The authors have declared that they have no conflict of interest.
REFERENCES 1. Ru€eff F, Bilo` MB, Jutel M, Mosbech H, Mu¨ller U, Przybilla R. Sublingual immunotherapy with venom is not recommended for patients with Hymenoptera venom allergy. J Allergy Clin Immunol 2009;123:272-3. 2. Severino MG, Cortellini G, Bonadonna P, Francescato E, Panzini I, Macchia D, et al. Sublingual immunotherapy for large local reactions caused by honeybee sting: a double-blind, placebo-controlled trial. J Allergy Clin Immunol 2008; 122:44-8. 3. Durham SR, Yang WH, Pedersen MR, Johansen N, Rak S. Sublingual immunotherapy with once-daily grass allergen tablets: a randomized controlled trial in seasonal allergic rhinoconjunctivitis. J Allergy Clin Immunol 2006;117:802-9. 4. Didier A, Malling HJ, Worm M, Horak F, Ja¨ger S, Montagut A, et al. Optimal dose, efficacy, and safety of once-daily sublingual immunotherapy with a 5-grass pollen tablet for seasonal allergic rhinitis. J Allergy Clin Immunol 2007;120: 1338-45. 5. Akdis CA, Barlan IB, Bahceciler N, Akdis M. Immunological mechanisms of sublingual immunotherapy. Allergy 2006;61(suppl 81):11-4. doi:10.1016/j.jaci.2008.10.029
Advances in allergic skin disease: Omalizumab is a promising therapy for urticaria and angioedema To the Editor: The review by Drs Sicherer and Leung1 entitled ‘‘Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insects in 2007’’ is a valuable update on the current literature for allergic skin disease.
J ALLERGY CLIN IMMUNOL JANUARY 2009
5. Singer BD, Ziska LH, Frenz DA, Gebhard DE, Straka JG. Increasing Amb a 1 content in common ragweed (Ambrosia artemisiifolia) pollen as a function of rising atmospheric CO2 concentration. Funct Plant Biol 2005;32:667-70. 6. Beggs PJ, Walczyk NE. Impacts of climate change on plant food allergens: a previously unrecognized threat to human health. Air Qual Atmos Health 2008;1:119-23. doi:10.1016/j.jaci.2008.10.025
Reply To the Editor: We are grateful to Dr Beggs1 for encouraging more research and dialog on the interaction between climate change and allergic disease, and we agree completely that the topic has not received sufficient consideration to date. Indeed, it was our hope in producing the recent clinical review2 to stimulate interest and more targeted attention to this important area. We did not attempt a comprehensive literature review; rather, our goal for the article was to function as a conversation starter. We thank Dr Beggs for highlighting additional studies that inform and support ongoing discussion and research questions. We hope many will join us in exploring further not only the pathophysiology of climate change and allergic disease but also the primary and secondary prevention of related morbidity and mortality through mitigation and adaptation. Katherine M. Shea, MD, MPHa Robert T. Truckner, MD, MPHb Richard W. Weber, MDc David B. Peden, MDd From aMaternal and Child Health and dMedicine and Toxicology, University of North Carolina School of Public Health, Chapel Hill, NC; bthe US Environmental Protection Agency National Health and Environmental Effects Laboratory, Research Triangle Park, NC; and cthe Department of Medicine, National Jewish Health, University of Colorado Health Sciences Center, Denver, Colo. E-mail: [email protected]. Disclosure of potential conflict of interest: R. W. Weber is on the speakers’ bureau for AstraZeneca, Schering-Plough, and Genentech; received grant support from GlaxoSmithKline, Pfizer, and Novartis; is the committee chair for the American College of Allergy, Asthma & Immunology; and is an associate editor for the Annals of Allergy, Asthma, and Immunology. D. B. Peden received grant support from the National Institutes of Health, Greer Laboratories, and the US Environmental Protection Agency and has testified regarding the adverse effects of air pollution on human health. The rest of the authors have declared that they have no conflict of interest. The opinions expressed here do not necessarily reflect US Environmental Protection Agency policy.
REFERENCES 1. Beggs PJ. Climate change and plant food allergens. J Allergy Clin Immunol 2009; 123:271-2. 2. Shea KM, Truckner RT, Weber RW, Peden DB. Climate change and allergic disease. J Allergy Clin Immunol 2008;122:443-53. doi:10.1016/j.jaci.2008.10.024
Sublingual immunotherapy with venom is not recommended for patients with Hymenoptera venom allergy To the Editor: The study of Severino et al1 reported the results of sublingual immunotherapy (SLIT) with honeybee venom, which was used to treat large local reactions to honeybee stings. By using sting challenges, it was found that SLIT compared with placebo reduced the extent of large local reactions. The authors concluded that the efficacy of SLIT might also be assessed in patients with systemic anaphylactic reactions to Hymenoptera stings.
Significant methodological flaws detract from the value of the presented data. First, demographic data differed significantly between the SLIT (n 5 14) and placebo (n 5 12) groups with respect to various parameters, such as concentration of total IgE and serum tryptase concentration. Results were presented as means and SDs, but P values were not given. Second, a venom dose of 525 mg per month was used in the SLIT group, which considerably exceeds the standard dose of 100 mg for subcutaneous venom immunotherapy (VIT). In both groups there was no increase of the venom-specific IgE concentration after 6 months of treatment. However, a significant increase of the venom-specific IgG concentration was only found in patients receiving SLIT. From several studies on VIT, we know that an increase of both venom-specific IgE and IgG concentrations can be expected very early after the initiation of therapy.2-4 In the long run, venom-specific IgE concentrations will decrease and IgG concentrations will remain high. The change of these immunologic parameters over time is ambiguously associated with treatment efficacy.5,6 However, these secondary immunologic reactions allow the treating physician to be sure that the venom used for treatment has reached immune-competent cells. Third, it is possible that changes in the venom-specific IgG concentration were not a consequence of SLIT but might have been caused by field stings. No information is provided on the frequency of field stings. A different immunologic status (see above) could also have modified the response to stings, including the diagnostic sting challenge. To account for those potentially confounding effects, a control group would be required that is treated with SLIT but that has not been exposed to sting challenges or field stings. Therefore we do not know whether changes of venom-specific IgG concentrations can be attributed to SLIT or to repeated honeybee stings. Fourth, in the SLIT group the peak diameter of the large local reaction was reduced by more than 50% in 57% of the patients. These results could be interpreted quite differently, indicating a complete treatment failure in 43% of the patients and at least a partial treatment failure in 57%. If we would extrapolate these results to patients with a systemic anaphylactic sting reaction, we might conclude as well that there was not sufficient proof of treatment efficacy. On the basis of these criticisms, we caution against an overly optimistic interpretation of the results, and we strongly disagree with regarding SLIT as a therapeutic option for patients with potentially life-threatening reactions on the basis of the presented data. Subcutaneous VIT is safe and highly effective, and it is also less expensive than SLIT because the latter requires much higher doses for treatment. Franziska Ru€ eff, MDa M. Beatrice Bilo`, MDb Marek Jutel, MDc Holger Mosbech, MD, DMScd Ulrich M€ uller, MDe Bernhard Przybilla, MDa For the interest group on Hymenoptera venom allergy of the European Academy of Allergology and Clinical Immunology From aAllergieZentrum, Klinik und Poliklinik f€ur Dermatologie und Allergologie, Ludwig-Maximilians-Universita¨t, Munich, Germany; bthe Allergy Unit, Department of Internal Medicine, Allergy, Immunology and Respiratory Diseases, Ospedali Riuniti di Ancona, Azienda Ospedaliero-Universitaria, Ancona, Italy; cthe Department of Clinical Immunology, Silesian Piasts University of Medicine in Wroc1aw, Wroc1aw, Poland; dthe Allergy Unit, National University Hospital,
CORRESPONDENCE 273
J ALLERGY CLIN IMMUNOL VOLUME 123, NUMBER 1
Rigshospitalet, Copenhagen, Denmark; and eAllergiestation Medizinische Klinik, Bern, Switzerland. E-mail: [email protected]. Disclosure of potential conflict of interest: M. Jutel has served as a clinical trial investigator for Allergopharma Joachim Ganzer KG and Schering-Plough. H. Mosbech has received research support from ALK-Abello´ and has served as an expert witness on the topic of anaphylaxis. The rest of the authors have declared that they have no conflict of interest.
REFERENCES 1. Severino MG, Cortellini G, Bonadonna P, Francescato E, Panzini I, Macchia D, et al. Sublingual immunotherapy for large local reactions caused by honeybee sting: a double-blind, placebo-controlled trial. J Allergy Clin Immunol 2008;122:44-8. 2. Golden DB, Valentine MD, Kagey-Sobotka A, Lichtenstein LM. Regimens of Hymenoptera venom immunotherapy. Ann Intern Med 1980;92:620-4. 3. Graft DF, Schuberth KC, Kagey-Sobotka A, Kwiterovich KA, Niv Y, Lichtenstein LM, et al. Assessment of prolonged venom immunotherapy in children. J Allergy Clin Immunol 1987;80:162-9. 4. Ru€eff F, Wolf H, Schnitker J, Ring J, Przybilla B. Specific immunotherapy in honeybee venom allergy: a comparative study using aqueous and aluminium hydroxide adsorbed preparations. Allergy 2004;59:589-95. 5. M€uller U, Helbling A, Bischof M. Predictive value of venom-specific IgE, IgG and IgG subclass antibodies in patients on immunotherapy with honey bee venom. Allergy 1989;44:412-8. 6. Golden DB, Lawrence ID, Hamilton RH, Kagey-Sobotka A, Valentine MD, Lichtenstein LM. Clinical correlation of the venom-specific IgG antibody level during maintenance venom immunotherapy. J Allergy Clin Immunol 1992;90:386-93. doi:10.1016/j.jaci.2008.10.028
Reply To the Editor: We thank Ru€eff et al1 for their comments on our work on sublingual immunotherapy (SLIT) in large local reactions caused by Hymenoptera venom2 and for giving us the opportunity to clarify some aspects of our study. Moreover, these comments testify to the interest raised by our article and, hopefully, will stimulate further scientific debates. Going to the specific points, our rebuttals are as follows. It is true that some differences between the 2 groups seem to exist at baseline, but those differences were not statistically significant, and this is the reason why a P value was not explicitly reported. It is difficult to hypothesize, for instance, that a mean difference in tryptase of 1.3 mg/L (with the normal threshold value being 20 mg/L) would have represented an imbalance factor in favor of one of the 2 groups. The dosage used was empirically chosen based on previous experiences with SLIT for aeroallergens, in which it has been shown that a dose-response relationship exists3,4 and that higher amounts of allergen are needed than in subcutaneous immunotherapy. Indeed, as we mentioned in the discussion, dose-finding studies are needed to identify the optimal dose. Concerning the immunologic aspect, it is well known that the changes in circulating immunoglobulins are less pronounced with SLIT than with injections,5 but this does not affect the efficacy of the treatment, as shown in numerous trials. In other words, we should be cautious in stating that SLIT does not work because it does not modify specific IgE levels. As acknowledged by Dr Ru€eff herself, the immunoglobulin changes over time are weakly correlated with the clinical effect, and a judgment on the efficacy of an immunotherapy course is essentially clinical. We acknowledge that in our article no mention was made of field stings, and this is an important point. We take this opportunity to clarify that none of the patients received field stings
during the 6-month period of the study. Thus the mentioned confounding factor can be reasonably excluded. Concerning the efficacy, we could also state that there was a full success in 57% and a partial success in 43% of the patients, but we think that such sophisms are not helpful in interpreting the data and for research in general. There are thus far no standard criteria to define the ‘‘failure’’ or ‘‘success’’ of venom immunotherapy according to the reduction of large local reactions at the sting challenge. Finally, Ru€eff et al1 express a ‘‘strong disagreement’’ about the use of SLIT in anaphylaxis after Hymenoptera sting. We do not understand their disagreement because such a scenario was not mentioned in our article. We simply envisaged the possibility of testing the efficacy of SLIT in systemic reactions, which might be, for instance, generalized urticaria. To conclude, we would underline once more that our study was a proof-of-concept trial and did not imply recommendations or suggestions for the clinical use of SLIT in patients with Hymenoptera allergy but only the possibility of exploring a new clinical approach. Giovanni Passalacqua, MDa Maurizio G. Severino, MDb Gabriele Cortellini, MDc Patrizia Bonadonna, MDd Donatella Macchia, MDb Walter G. Canonica, MDa From aAllergy and Respiratory Diseases, Department of Internal Medicine, University of Genoa, Genoa, Italy; bthe Allergy Clinic, Nuovo Ospedale San Giovanni di Dio, Florence, Italy; cInternal Medicine and Rheumatology, Rimini Hospital, Rimini, Italy; and dthe Allergy Unit, Verona General Hospital, Verona, Italy. E-mail: passalacqua@ unige.it. Disclosure of potential conflict of interest: The authors have declared that they have no conflict of interest.
REFERENCES 1. Ru€eff F, Bilo` MB, Jutel M, Mosbech H, Mu¨ller U, Przybilla R. Sublingual immunotherapy with venom is not recommended for patients with Hymenoptera venom allergy. J Allergy Clin Immunol 2009;123:272-3. 2. Severino MG, Cortellini G, Bonadonna P, Francescato E, Panzini I, Macchia D, et al. Sublingual immunotherapy for large local reactions caused by honeybee sting: a double-blind, placebo-controlled trial. J Allergy Clin Immunol 2008; 122:44-8. 3. Durham SR, Yang WH, Pedersen MR, Johansen N, Rak S. Sublingual immunotherapy with once-daily grass allergen tablets: a randomized controlled trial in seasonal allergic rhinoconjunctivitis. J Allergy Clin Immunol 2006;117:802-9. 4. Didier A, Malling HJ, Worm M, Horak F, Ja¨ger S, Montagut A, et al. Optimal dose, efficacy, and safety of once-daily sublingual immunotherapy with a 5-grass pollen tablet for seasonal allergic rhinitis. J Allergy Clin Immunol 2007;120: 1338-45. 5. Akdis CA, Barlan IB, Bahceciler N, Akdis M. Immunological mechanisms of sublingual immunotherapy. Allergy 2006;61(suppl 81):11-4. doi:10.1016/j.jaci.2008.10.029
Advances in allergic skin disease: Omalizumab is a promising therapy for urticaria and angioedema To the Editor: The review by Drs Sicherer and Leung1 entitled ‘‘Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insects in 2007’’ is a valuable update on the current literature for allergic skin disease.