The Journal of Allergy and Clinical Immunology
Volume 121, Issue 3 , Pages 784-785, March 2008

Reply

  • Mark F. Sands, MD

      Affiliations

    • Division of Allergy, Immunology, and Rheumatology, University at Buffalo, State University of New York, Buffalo, NY
    • VA Western New York Healthcare System, Buffalo, NY
    • ,
  • Jessica W. Blume, MD

      Affiliations

    • Good Samaritan Hospital, Suffern, NY
    • ,
  • Stanley A. Schwartz, MD, PhD

      Affiliations

    • Division of Allergy, Immunology, and Rheumatology, University at Buffalo, State University of New York, Buffalo, NY

Article Outline

 

To the Editor:

We appreciate the correspondence from Spector and Tan1 regarding our article on treatment of recurrent idiopathic angioedema with omalizumab.2 We note their report on omalizumab use in chronic refractory urticaria.3

There are several common threads in both articles. The mechanisms driving neither idiopathic urticaria nor idiopathic angioedema are fully elucidated. Omalizumab, having apparent efficacy in both short series, demonstrates potential as a new therapeutic agent pending results of controlled trials. One might infer, therefore, that these partially overlapping syndromes, responding to similar treatment, might share underlying mechanisms. However, neither case series is designed to address mechanisms, so comments about mechanism in either group of patients remain highly speculative. Stated differently, some or none of the 6 patients described in either study might have responded to omalizumab because of IgE-mediated mechanisms.

We take issue with the implication by Spector and Tan1 that the presence of elevated serum IgE levels in 2 of 3 patients with angioedema carries much predictive weight mechanistically. Total serum IgE levels have limited diagnostic utility because of considerable overlap in normal and atopic populations.4 Even in the urticaria series by Spector and Tan,3 1 of 3 patients had a normal IgE level. We agree that for prospective studies, a panel of tests for antibodies directed against FCɛR1, in vitro basophil histamine release, and possibly the autologous serum skin test would be appropriate, fully recognizing that the sensitivity and specificity of these tests are less than ideal in urticaria, let alone angioedema.5, 6 We used a commercially available functional FcɛRI antibody assay.

We concede that some asthma and rhinitis studies of omalizumab demonstrated efficacy as early as 4 weeks after initial dosing.7, 8 We reiterate that IgE and downregulation of its cellular receptors have in no way been excluded as mechanisms for improvement in our series. However, the fact that this mechanism was linked to improvement in nonangioedema populations does not prove that it is operative in our series. It is intriguing that the patients of Spector and Tan,1 like ours, had rapid improvement within weeks of initiating omalizumab. This might improve the chances of identifying the mechanisms involved.

Regarding their query that lisinopril (in 1 case) may have been a confounder, it was discontinued more than 1 year before instituting omalizumab.

Angioedema and urticaria may occur independently or in combination. Nevertheless, idiopathic angioedema and urticaria, although unique entities, are not specific diseases, and thus reflect heterogeneous underlying conditions, likely with distinct mechanisms. Therefore, it is possible that some cases of idiopathic angioedema may be truly allergic and mediated by IgE mechanisms, despite the fact that our current clinical and laboratory diagnostic tools cannot detect this. Conversely, some idiopathic urticaria patients may have non–IgE-mediated mechanisms. Omalizumab responsiveness suggests a mechanistic overlap between these 2 conditions. We hope that our case series will stimulate both discussion of and investigation into mechanisms of angioedema and the apparent therapeutic efficacy of omalizumab.

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References 

  1. Spector SL, Tan RA. Omalizumab also successful in chronic urticaria. J Allergy Clin Immunol. 2008;121:784
  2. Sands MF, Blume JW, Schwartz SA. Successful treatment of 3 patients with recurrent idiopathic angioedema with omalizumab. J Allergy Clin Immunol. 2007;120:979–981
  3. Spector SL, Tan RA. Effect of omalizumab on patients with chronic urticaria. Ann Allergy Asthma Immunol. 2007;99:190–193
  4. Hamilton RG. Laboratory tests for allergic and immunodeficiency diseases. In: Middleton's Allergy Principles and Practice. 6th ed.. Philadelphia (PA): Mosby; 2003;p. 611–630
  5. Sabroe RA, Seed PT, Stat C, Frances DM, Barr RM, Black AK, et al. Chronic idiopathic urticaria: comparison of the clinical features of patients with and without anti-FcɛRI or anti-IgE autoantibody. J Am Acad Dermatol. 1999;40:443–450
  6. Asero R, Lorini M, Chong SU, Zuberbier T, Tedeschi A. Assessment of histamine-releasing activity of sera from patients with chronic urticaria showing positive autologous skin test on human basophils and mast cells. Clin Exp Allergy. 2004;34:1111–1114
  7. Bousquet J, Wenzel S, Holgate S, Lumry W, Freeman P, Pox H. Predicting response to omalizumab, an Anti-IgE antibody in patients with allergic asthma. Chest. 2004;125:1378–1386
  8. Casale TB, Condemi J, LaForce C, Nayak A, Rowe M, Watrous M, et al. Effect of omalizumab on symptoms of seasonal allergic rhinitis: a randomized controlled trial. JAMA. 2001;286:2956–2967

 Disclosure of potential conflict of interest: M. F. Sands has received research support from the Veterans Administration. S. A. Schwartz owns stock in Pfizer and Schering, has served as an expert witness about minocycline hypersensitivity, and is on the speakers' bureau for Genentech and Aventis. J. W. Blume has declared that she has no conflict of interest.

PII: S0091-6749(07)03622-6

doi:10.1016/j.jaci.2007.12.1173

The Journal of Allergy and Clinical Immunology
Volume 121, Issue 3 , Pages 784-785, March 2008

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