• Hymenoptera;
  • immunotherapy;
  • mastocytosis;
  • Omalizumab;
  • venom

Pure venom immunotherapy (VImRx) is associated with adverse reactions, particularly in individuals with mastocytosis, occasionally leading to treatment withdrawal (1). The present report refers to a patient suffering from indolent systemic mastocytosis and multiple reactions during VImRx; his treatment progressed without further adverse events on high-dose omalizumab pretherapy, administered 1 week to 1 h earlier.

N.A., a 45-year-old man, with a near fatal anaphylactic reaction to a bee sting, was observed to suffer from indolent systemic mastocytosis [serum tryptase (42.5 μg/l, UniCAP Tryptase Pharmacia/Upjohn), a positive Tc99m-MDP bone san, as well as bone marrow biopsy]. Allergological evaluation (IDST and RAST; Unicap Pharmacia/Upjohn) confirmed IgE sensitization to bee venom (W = 12 × 25, F = 40 × 70 at 0.01 μg/ml vs histamine 10 × 18, 60 × 78 mm, respectively).

An inpatient modified rush VImRx scheme was initiated and patient was placed on H1 and H2 antagonist (Levocetirizine, cetirizine, dimethindene at 8-h intervals and ranitidine every 12 h.) for prophylaxis because of frequent adverse reactions. VImRx was progressed slowly to a cumulative dose of 150–200 μg in three to four divided doses at 28-day intervals. Mild-to-moderate reactions occurred 20- to 30-min postinjection in all but one, session; when there was a severe one at 18 months of VImRx that led to a trial of omalizumab; patient gave written informed consent.

One week prior to the subsequent monthly schedule of VImRx course, the patient received 300 mg omalizumab s.c. – twice the recommended dose based on weight (84 kg) and IgE (62 KU/ml) – without adverse events. Seven days later, he tolerated a cumulative dose of 150 μg venom (double the previous month’s reduced dose) without any reaction. The same procedure was repeated successfully a month later and H1–H2 antagonists were discontinued. Omalizumab was administered at progressively shorter intervals, until 1 h between the two treatments was reached (Fig. 1). Patient tolerated the single 100 μg maintenance dose (never achieved before) without adverse events.


Figure 1.  Time course of venom immunotherapy before and after omalizumab treatment, observed adverse reactions and serum tryptase levels in patient NA with indolent systemic mastocytosis.

Download figure to PowerPoint

Serum tryptase measurements showed a progressive reduction (Fig. 1) and IDST, repeated at 8 months, 3 × 2 mm erythema at 1 μg/ml of venom. Two and three weeks later patient tolerated single stings by unknown Hymenoptera. Heat-induced flushing – the only subjective complaint of mastocytosis – ceased to be a problem, even at temperatures exceeding 45°C.

Omalizumab, the humanized m-antibody to the Fcɛ, blocks the binding of free IgE to its corresponding FcɛRI on basophil and mast cells, thus inhibiting their activation by allergens. Furthermore, it causes rapid reduction in the FcɛRI expression by basophils (2) and a slower one by dermal mast cells (3), while it exerts additional immune-modifying effects.

Omalizumab, administered 9 weeks before rush pollen immunotherapy, significantly reduced reactions (4), while unprovoked anaphylaxis was aborted in two systemic mastocytosis patients (5). A single case-report suggests the protective effect of Omalizumab against VImRx reactions (6).

The present case represents the first report on combining omalizumab with specific immunotherapy to improve the safety of the latter in mastocytosis patients.

When omalizumab treatment was initiated in our patient, it was hypothesized that a higher than the recommended dose would be required for efficacious down-regulation of FcɛRI expression on pathologically increased numbers of mast cells. The 7-day interval between the two treatments was chosen, because of the reported reduced responses to allergens as early as one week post-Omalizumab (3). However, shorter intervals – up to 1 h – were gradually applied with success, making the combined therapy more convenient.

The continuous decline in serum tryptase over 8 months noted in our case had not been observed in the two mastocytosis cases reported by Carter et al. (5), who received the recommended for asthma dose over 24 months. The dose at double the levels administered to our patient might account for the observed difference.

Our search of the literature failed to identify previous reports on Omalizumab in mastocytotic venom immunotherapy reactors; further studies are required with emphasis on dose response.

The author wishes to thank Mr and Mrs N.A. for their patience and confidence in our treatment options. Dr Michael Makris’s (presently at Allergy Unit, Attikon Un. Hospital, Athens, Greece) help during the first year of VImRx is also recognized.

No financial or other relations with the manufacturing company of either drug used in the present case.


  1. Top of page
  2. References
  • 1
    Haeberli G, Bronnimann M, Hunziker T, Muller U. Elevated basal serum tryptase and Hymenoptera venom allergy: relation to severity of sting reactions and to safety and efficacy of venom immunotherapy. Clin Exp Allergy 2003;33:12161220.
  • 2
    Lin H, Boesel KM, Griffith DT, Prussin C, Foster B, Romero FA et al. Omalizumab rapidly decreases nasal allergic responses and FcɛRI on basophils. J Allergy Clin Immunol 2004;113:297302.
  • 3
    Beck LA, Marcotte GV, MacClashan DW, Togias A, Saini S. Omalizumab – induced reduction in mast cell FcRI expression and function. J Allergy Clin Immunol 2004;114:527530.
  • 4
    Casale TB, Busse WW, Kline JN, Ballas ZK, Moss MH, Townley RG et al. Omalizumab decreases acute reactions after rush immunotherapy for ragweed-induced allergic rhinitis. J Allergy Clin Immunol 2006;117:134140.
  • 5
    Carter MC, Robyn JA, Bressler PB, Walker JC, Shapiro GG, Metcalf DD. Omalizumab for the treatment of unprovoked anaphylaxis in patients with systemic mastocytosis. J Allergy Clin Immunol 2007;119:15501551.
  • 6
    Schulze J, Rose M, Zielen S. Beekeepers anaphylaxis: successful immunotherapy covered by omalizumab. Allergy 2007;62:963964.