Mastocytosis anaphylaxis

In one study, 26% of anaphylactic reactions were reported to have developed after a combination of elicitors [4]. In other patients with mastocytosis, anaphylaxis remains idiopathic despite an extensive search for an allergic basis. 

Finally, patients suffering from mastocytosis have a higher risk of developing severe anaphylaxis after an insect sting [34]. In venom-allergic patients with mastocytosis, elevated baseline serum tryptase levels were foimd to be associated with severe anaphylactic reactions to stings [35]. 

De Swert LF, Bullens D, Raes M. Dermaux AM Anaphylaxis in referred pediatric patients demographic and chnical features, triggers, and therapeutic approach. Eur J Pediatr 2008 167 1251-1261. Brockow K, Jofer C, Behrendt H, Ring J Anaphylaxis in patients with mastocytosis a study on history chnical features and risk factors in 120 patients. AUergy 2008 63 226-232. 

Shapiro GG, Metcalfe DD Omalizumab for the treatment of unprovoked anaphylaxis in patients with systemic mastocytosis. J Allergy Clin Immunol 2007 119 1550-1551. 

Adding another layer of complexity to the regulation of mast cell activation levels in vivo is the observation that activated mast cells can respond to, and in some cases produce, a myriad of mediators that may serve to amplify FceRI-induced responses. For example, stem cell factor (SCF), the ligand for KIT, both can enhance FceRI-dependent activation of mouse or human mast cells and, under certain circumstances, can directly induce mast cell degranulation [6, 25, 62]. Thus, elevated SCF levels and/or activating KIT mutations (such as those that occur in mastocytosis) may exacerbate mast cell-driven reactions. Indeed, patients (both adult and children) with extensive skin disease associated with mastocytosis are at increased risk to develop severe anaphylaxis [63]. Moreover, it was recently reported that cases of idiopathic anaphylaxis are... 

BrockowKjJoferQ BehrendtH,RingJ Anaphylaxis 70 in patients with mastocytosis a study on history, clinical features and risk factors in 120 patients. Allergy 2008 63 226-232. 71... 

Mast cells express high-affinity IgE Fc receptors (FceRI) on their surface, contain cytoplasmic granules which are major sources of histamine and other inflammatory mediators, and are activated to release and generate these mediators by IgE-dependent and non-IgE-dependent mechanisms [1]. Disturbances either in the release of mast cell mediators or in mast cell proliferation are associated with clonal mast cell disorders including monoclonal mast cell activation syndrome (MMAS) and mastocytosis respectively, which are in turn associated with some cases of anaphylaxis [2], Molecular mechanisms have been identified which may link increased releasability of mast cell mediators and conditions leading to increased mast cell numbers [3]. Patients with mastocytosis have an increased risk to develop anaphylaxis [4, 5] and those with anaphylaxis may suffer from unrecognized mastocytosis or may display incomplete features of the disease [6-8]. 

The most frequent symptoms of anaphylaxis in patients with mastocytosis are decreased blood pressure and tachycardia. Also observed are dizziness, dyspnea, flushing, nausea and diarrhea [4]. Severe reactions are typical for patients with mastocytosis. In 55 patients with insect sting allergy and confirmed mastocytosis, 81% of patients experienced severe anaphylaxis with shock or cardiopulmonary arrest, whereas clinical reactions of this severity occurred in only 17% of 504 patients without evidence for mastocytosis and normal tryptase levels [29]. In another study in... 

Hymenoptera venom is a prominent trigger of systemic reactions. Severe and fatal reactions have been described in patients with mastocytosis [9, 30, 31]. In few cases with urticaria pigmentosa and Hymenoptera venom anaphylaxis, no sensitization could be detected by means of skin tests and determination of specific IgE antibodies [32]. However, larger series found evidence that these systemic reactions are normally IgE-mediated insect sting allergies [7,33]. 

Mastocytosis may present as anaphylaxis [9]. Sometimes the diagnosis of MPCM is made during the course of the evaluation of an anaphylactic episode. Thus in all... 

It has been stated that adults with mastocytosis as well as children with bullous lesions and with more severe involvement, and especially those with previous reactions, are at increased risk for anaphylaxis [4]. Thus, we recommend that patients at risk carry an emergency kit for self-medication which includes epinephrine and, as warranted, an antihistamine and a corticosteroid [38]. 

Diet should be modified only in cases where foods have been proven to elicit symptoms. Patients with mastocytosis and Hymenoptera venom exposure are at risk for severe anaphylaxis. Thus, specific immunotherapy should be considered in patients with Hymenoptera venom allergy and then administered under close supervision [31]. The majority of patients with mastocytosis reportedly tolerate immunotherapy without significant side effects and appear protected following this approach [33,40]. However, there does appear to be some increased risk for adverse reactions during initiation of immunotherapy, as well as for therapy failures [31, 33]. An increased maintenance dose of insect venom has been reported to carry better success rates by sting provocation [41]. Also, in the light of 2 fatal cases of anaphylaxis after discontinuation of SIT in patients with mastocytosis [30], lifelong immunotherapy should be considered [26]. 

In rare cases, initiation of specific immunotherapy with insect venom leads to recurrent anaphylaxis, even with antihistamine premedication. In those cases, comedication with omalizumab (anti-IgE) has been reported to induce tolerance. In a case of recurrent anaphylaxis to induction of specific immunotherapy, the injection of 300 mg of omalizumab between 4 days and 1 h reportedly led to tolerance [42]. This approach also appears worthy of consideration in patients with both idiopathic recurrent anaphylaxis and mastocytosis who do not respond to standard antimediator therapy, as has been described in 2 atopic patients with ISM [43]. Most patients with mastocytosis and idiopathic anaphylaxis, however, are sufficiently controlled by standard antimediator therapy with antihistamines with or without low-dose corticosteroids. 

Fatal anaphylaxis after ayellow jacket sting, despite 41 venom immunotherapy, in two patients with mastocytosis. J Allergy Clin Immunol 1997 99 153-154. 

Gonzalez de Olano D, Alvarez-Xwose I, Esteban-Lopez MI, et al Safety and effectiveness of immunotherapy in patients with indolent systemic mastocytosis present- 44 ing with Hymenoptera venom anaphylaxis. J Allergy Clin Immunol 2008 121 519-526. 

Tryptase is at the present moment the main clinical marker for anaphylaxis and mastocytosis. There are two major human mast cells tryptases, a- and (3-tryptase, encoded by two genes located at chromosome 16. The haploid genotype for tryptase is (3a or (3(3.25% of individuals are a-tryptase-deficient a-tryptase shows a 90% amino acid sequence identity with (3-tryptase. 

Two immunoassays have been developed to measure tryptase in human fluids, one that measures mature a/(3-tryptases, i.e. total tryptase, available commercially, and one developed by Schwartz et al. [7] that measures both mature (3-tryptase and immature a/(3-tryptases. This distinction is of clinical relevance since immature tryptases reflect mast cell burden whereas mature tryptases indicate mast cell activation. Thus, for the diagnosis of anaphylaxis it would be extremely important to be able to differentiate between acute anaphylaxis and increases in tryptase due to increase in numbers of mast cells as happens in mastocytosis. Total tryptase would be high in both conditions, whereas mature tryptase will be only high in anaphylaxis but negligible in mastocytosis. 

Schwartz LB Diagnostic value of tryptase in anaphylaxis and mastocytosis 2. Immunol Allergy Clin North Am 2006 26 451-463. 

Mechanism of Action An antiasthmatic and antiallergic agent that prevents mast cell release of histamine, leukotrienes, and slow-reacting substances of anaphylaxis by inhibiting degranulation after contact with antigens. Therapeutic Effect Helps prevent symptoms of asthma, allergic rhinitis, mastocytosis, and exercise-induced bron-chospasm. 

Table 4.4 Total and mature tryptase levels in semm of normal subjects and patients with anaphylaxis or systemic mastocytosis...

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