Twelve-Hour Ultrarush Immunotherapy in a Patient With Mastocytosis and Hymenoptera Sting Anaphylaxis

To the Editor: Mastocytosis (MC) denotes a heterogeneous group of clinical disorders caused by abnormal growth and accumulation of mast cells (incidence in the general population presumably 7 new cases per 1,000,000 persons each year). It ranges from primarily cutaneous manifestations of urticaria pigmentosa to systemic mastocytosis (SM), in which virtually every tissue can be involved, to rare malignant forms such as mast cell leukemia. Awell-established serum marker of SM is tryptase (>and A-tryptase forms). The current assays are thought to measure pro-tryptase, resulting from continuous release from mast cells in various organs (reference range, G1Y11.4 ng/mL in our system). In SM, tryptase levels normally exceed 20 ng/mL. But as tryptase can also be elevated because of other diseases (eg, myelodysplastic syndrome), it is only a minor criterion for SM. Patients with SM are overrepresented in the group of persons with anaphylaxis to Hymenoptera venom (prevalence between 1% and 2.6%). As type 1 sensitization to venoms detected by skin test or serology is reported to be comparatively low in some studies, additional immunoglobulin E (IgE)-independent pathways are thought to be important: direct action of histamine-liberating or complement-activating substances present in venom such as mast cellYdegranulating peptide, mellitin, or phospholipases. In contrast to this, Ruëff et al could demonstrate comparable specific venom sensitization in patients after insect anaphylaxis with and without MC. Generally, MC patients are endangered by life-threatening reactions after insect stings secondary to increased mediator release. Therefore, specific venom immunotherapy (VIT), the only available causal treatment of insect venom hypersensitization so far, is urgently recommended. On the other hand, these patients tend to express more serious side effects, in some cases, VIT even had to be stopped prematurely. In addition to this, Dubois and the group of Ruëff et al found an increased rate of sting reactions during or after VIT in MC patients, even with fatal outcomes. These data suggest that the efficacy of VIT may be reduced in patients with mastocytosis, particularly in vespid-allergic patients. As ultrarush or rapid VIT (RVIT) has been proven reliable and efficacious with a low incidence of systemic reactions, we chose this protocol for an MC patient with wasp venom anaphylaxis. The 41-year-old female patient had histologically confirmed cutaneous mast cell disease with typical urticaria pigmentosa. Tryptase level was slightly elevated to 16.3 ng/mL (average, about 5 ng/mL in controls), so that indolent SM was also discussed, but a bone marrow biopsy was not feasible for confirmation. In September 2003, she experienced an anaphylactic reaction grade III to IV, including local and remote skin reactions according to Mueller HL, lightheadedness, hypotension, and dyspnea after a wasp sting. Although being informed about the potentially higher risk, she explicitly selected RVIT in January 2004 to reduce hospitalization time. Four months later, she was checked for allergy status. Total serum IgE was less than 10 IU/mL. The patient had no history of atopy, and prick tests with perennial and seasonal aeroallergens were negative. Bee venom remained negative in prick test until 300 Kg/mL, whereas vespula venom was positive here at 0.1 Kg/mL. Intracutaneous tests were performed with serial 10-fold dilutions of vespula venom. The end point concentration still resulting in a positive reaction here was 0.00001 Kg/mL. The initial wasp-specific IgE was 2 kU/L (class 2) (CAP Test, Fa. Phadia, Sweden), and specific IgG resulted in 11.5 mg/L (= intermediately elevated). The VIT followed a modified ultrarush protocol (Table 1), with a subcutaneous injection of 0.00001 Kg wasp venom (Venomil wasp, Fa. Bencard, Munich, Germany) and increasing doses 10-fold every 30 minutes until 10 Kg, followed by 20, 30, 50, and 100 Kg in 30-minute intervals. The maximum single dose of 100 Kg was reached after 12 hours with only local side effects. The patient was pretreated with intravenous dimetindene 6 mg just before VIT. On day 2, she was discharged. Booster injections of 100 Kg were given at 7, 14, and 21 days, and then every 4 weeks on an outpatient basis. In Figure 1, both the increase of wasp-specific IgG and the continuous decrease of specific IgE from class 2 to below detection limit after 18 months of therapy are presented. In August 2004, the patient has tolerated a natural wasp sting with only local symptoms.