Elevated Baseline Serum Tryptase Research Articles

ELEVATED BASELINE SERUM TRYPTASE AND HEREDITARY ALPHA TRYPTASEMIA (HAT)

<h3>Introduction</h3> Hereditary alpha tryptasemia (HaT) is an autosomal dominant genetic trait characterized by elevated basal serum tryptase levels due to extra allelic copies of the tryptase alpha/beta 1 (TPSAB1) gene. HaT has been associated with multisystem complaints and as a modifier of mast cell-associated disorders and anaphylaxis. <h3>Case Description</h3> A 38-year-old male presented for evaluation of food and environmental allergies. He had severe oropharyngeal symptoms and a throat-closing sensation immediately after ingesting raw fruits and tree nuts. He also had symptoms of perennial allergic rhinoconjunctivitis with seasonal variation. Allergy skin testing showed IgE sensitivities to tree, grass and weed pollens, dust mites, mold spores, cat, dog, and cockroach. He had no IgE sensitivities to any of the fruits tested. He had IgE sensitivities to walnut, hazelnut, and almond. Given the severity of his oropharyngeal symptoms a baseline serum tryptase was checked, which was elevated at 20.3 mcg/L. Repeat determinations again showed baseline serum tryptase above 20 mcg/L. CBC with differential and CMP were within normal limits. 24-hour urinary histamine and N-methylhistamine were both within normal. Kit D16 mutation analysis was negative. TPSAB1 copy number analysis showed extra allelic alpha-tryptase copies, consistent with hereditary alpha tryptasemia (HaT). The patient received counseling and standard treatment for environmental/food allergies and tolerates allergen-specific immunotherapy. <h3>Discussion</h3> HaT is an inherited condition considered a biochemical trait and can be present in around 5% of the general population. Patients with elevated baseline serum tryptase may benefit from testing for extra allelic copies of TPSAB1.

Overexpression of FcεRI on Bone Marrow Mast Cells, but Not MRGPRX2, in Clonal Mast Cell Disorders With Wasp Venom Anaphylaxis.

BackgroundUncertainties remain about the molecular mechanisms governing clonal mast cell disorders (CMCD) and anaphylaxis.ObjectiveThis study aims at comparing the burden, phenotype and behavior of mast cells (MCs) and basophils in patients with CMCD with wasp venom anaphylaxis (CMCD/WVA+), CMCD patients without anaphylaxis (CMCD/ANA-), patients with an elevated baseline serum tryptase (EBST), patients with wasp venom anaphylaxis without CMCD (WVA+) and patients with a non-mast cell haematological pathology (NMHP).MethodsThis study included 20 patients with CMCD/WVA+, 24 with CMCD/ANA-, 19 with WVA+, 6 with EBST and 5 with NMHP. We immunophenotyped MCs and basophils and compared baseline serum tryptase (bST) and both total and venom specific IgE in the different groups. For basophil studies, 13 healthy controls were also included.ResultsHigher levels of bST were found in CMCD patients with wasp venom anaphylaxis, CMCD patients without anaphylaxis and EBST patients. Total IgE levels were highest in patients with wasp venom anaphylaxis with and without CMCD. Bone marrow MCs of patients with CMCD showed lower CD117 expression and higher expression of CD45, CD203c, CD63, CD300a and FcεRI. Within the CMCD population, patients with wasp venom anaphylaxis showed a higher expression of FcεRI as compared to patients without anaphylaxis. Expression of MRGPRX2 on MCs did not differ between the study populations. Basophils are phenotypically and functionally comparable between the different patient populations.ConclusionPatients with CMCD show an elevated burden of aberrant activated MCs with a significant overexpression of FcεRI in patients with a wasp venom anaphylaxis.

Maintenance venom immunotherapy administered at 12-week intervals in patients with high basal tryptase

Venom immunotherapy (VIT) is highly effective in patients with Hymenoptera venom allergy (HVA), with a capacity to protect against reactions to stings that lasts even after its cessation after a recommended duration of at least 5 years.1 However, in patients with severe initial systemic reactions and elevated baseline serum tryptase (which is currently estimated as >11.4 mcg/L) or mast cell disorders, VIT may be less protective, requiring an increase in maintenance common dosage of 100 mcg up to 200 mcg.

Idiopathic anaphylaxis: Diagnosis and management.

Introduction: Idiopathic anaphylaxis (IA) is a diagnosis of exclusion and is based on the inability to identify a causal relationship between a trigger and an anaphylactic event, despite a detailed patient history and careful diagnostic assessment. The prevalence of IA among the subset of people who experienced anaphylaxis is challenging to estimate and varies widely, from 10 to 60%; most commonly noted is ∼20% in the adult anaphylactic population. Comorbid atopic conditions, such as food allergy, allergic rhinitis, and asthma, are present in up to 48% of patients with IA. Improved diagnostic technologies and an increased understanding of conditions that manifest with symptoms associated with anaphylaxis have improved the ability to determine a more accurate diagnosis for patients who may have been initially diagnosed with IA. Methods: Literature search was conducted on PubMed, Google Scholar and Embase. Results: Galactose-α-1,3-galactose (α-gal) allergy, mast cell disorders, and hereditary a-tryptasemia are a few differential diagnoses that should be considered in patients with IA. Unlike food allergy, when anaphylaxis occurs within minutes to 2 hours after allergen consumption, α-gal allergy is a 3-6-hour delayed immunoglobulin E-mediated anaphylactic reaction to a carbohydrate epitope found in red meat (e.g., beef, lamb, pork). The more recently described hereditary α-tryptasemia is an inherited autosomal dominant genetic trait caused by increased germline copies of tryptase human gene alpha-beta 1 (TPSAB1), which encodes α tryptase and is associated with elevated baseline serum tryptase. Acute management of IA consists of carrying an epinephrine autoinjector to be administered immediately at the first signs of anaphylaxis. Long-term management for IA with antihistamines and other agents aims to potentially reduce the frequency and severity of the anaphylactic reactions, although the evidence is limited. Biologics are potentially steroid-sparing for patients with IA; however, more research on IA therapies is needed. Conclusion: The lack of diagnostic criteria, finite treatment options, and intricacies of making a differential diagnosis make IA challenging for patients and clinicians to manage.

Hereditary alpha tryptasemia is not associated with specific clinical phenotypes

Hereditary alpha tryptasemia (HαT) is found in approximately 7% of the population. Associations with a variety of clinical symptoms including gastric reflux, joint hypermobility, dysautonomia, flushing and pruritus, and hymenoptera allergy have variably been described in prior reports. However, our understanding of this genetic trait is limited by a paucity of published studies, referral bias, and conflicting findings at clinical presentation. The purpose of this study was to assess the clinical phenotype of HαT in a random biorepository population and in patients with and without mastocytosis referred to the allergy clinic. Tryptase copy number allele was assessed using digital droplet PCR. Participants with or without HαT were interviewed and examined by a clinician and surveyed regarding their medical history and symptomology. HαT was identified in 7.5% of the random biorepository samples and in 18% of patients with mastocytosis. There was no difference in the clinical symptomology or medical history of individuals with HαT compared to controls. Average baseline serum tryptase was higher in individuals with HαT compared to controls, but there was no difference in urinary mast cell activation products. Elevated baseline serum tryptase was the only consistent phenotypic marker for HαT in this study. There wasa higher frequency of HαT in patients with mastocytosis than in the general population.

COVID-19 infection in patients with mast cell disorders including mastocytosis does not impact mast cell activation symptoms

COVID-19 infection in patients with mast cell disorders including mastocytosis does not impact mast cell activation symptoms

Patients with mast cell activation symptoms and elevated baseline serum tryptase level have unique bone marrow morphology

Patients with mast cell (MC) activation symptoms and elevated baseline serum tryptase level (MCAS-T) may not necessarily have a clonal MC disorder. Many are diagnosed with hereditary α-tryptasemia (HαT), a genetic trait characterized by autosomal dominant inheritance of multiple copies of TPSAB1 encoding α-tryptase and increased risk for severe anaphylaxis. The aim of our study was to identify and characterize bone marrow MC histopathologic features specific for MCAS-T. A total of 43 patients with MCAS-T underwent evaluation, including bone marrow biopsy, for a MC disorder. The results of the work-up for clonal MC disorders such as systemic mastocytosis and monoclonal MC activation syndrome were negative. Bone marrow MC histopathology was reviewed to identify characteristic features of MCAS-T. Asubgroup of patients was available for tryptase genotyping. Patients with MCAS-T showed unique morphologic and histologic features when compared with controls. MCs were larger (P< .01), hypogranular (P< .01), frequently detected in paratrabecular (P< .05) and perivascular (P< .01) locations, and associated with bone marrow eosinophilia (P< .01). Atotal of 10 patients who were available for tryptase genotyping were all confirmed to have HαT. This subgroup was representative of the larger MCAS-T cohort. We report unique bone marrow MC phenotypic and histopathologic changes in patients with MCAS-T. These morphologic changes are associated with an elevated tryptase level that has been confirmed to be caused by HαT in all patients available for testing.

M105 COMPLETION OF ULTRARUSH VENOM IMMUNOTHERAPY IN A PATIENT WITH ELEVATED BASELINE TRYPTASE

Baseline serum tryptase should be drawn in all patients with severe insect sting anaphylaxis, especially in those with hypotension and without urticaria. Elevated levels help identify patients with mastocytosis, using REMA scores to guide the need for bone marrow biopsy. Even without mastocytosis, elevated baseline serum tryptase is a risk factor for anaphylaxis to field stings and for reactions during desensitization itself.

Predictors of severe anaphylaxis in Hymenoptera venom allergy: The importance of absence of urticaria and angioedema

BackgroundSevere anaphylaxis (SA) in Hymenoptera venom allergy has been associated with a number of risk factors. However, the effect of several of those risk factors on the severity of anaphylaxis is poorly defined. ObjectiveTo evaluate risk factors for SA in Hymenoptera venom allergy. MethodsWe evaluated data from 500 patients who were referred to our department for the diagnosis of Hymenoptera venom allergy during a period of 11 years to identify risk factors for SA. ResultsSix significant risk factors for SA were identified (P < .05): short interval from sting to reaction, absence of urticaria or angioedema (U/A) during anaphylaxis, older age, male sex, elevation of baseline serum tryptase (BST) level, and diagnosis of systemic mastocytosis. Moreover, elevation in BST level was significantly associated with the absence of U/A and older age. No association could be established between SA and comorbidities, concurrent cardiovascular medication, or the severity of the systemic reaction during the initiation of venom immunotherapy. ConclusionApart from BST and older age, male sex, short interval from sting to reaction, and absence of U/A are also risk factors for SA. The association between elevated BST level and SA was largely confined to those who had an absence of U/A after field sting, possibly because of the higher risk of concurrent systemic mastocytosis. Patients with an SA after a field sting do not have an elevated risk of systemic reactions during the initiation of venom immunotherapy compared with patients with mild anaphylaxis; therefore, additional preventive measures are not necessary.

Insect Sting Anaphylaxis—Or Mastocytosis—Or Something Else?

Insect sting anaphylaxis and mast cell disorders are intertwined in a specific and unusual way. There may be specific subsets of clonal mast cell disorders that are predisposed to sting anaphylaxis. The clinical characteristics of the sting reactions should raise suspicion of underlying mastocytosis (eg, hypotension without hives especially in a male). A baseline serum tryptase level is helpful in the evaluation of patients with insect sting anaphylaxis because it correlates with important risks for these patients, and they have a high frequency of abnormally elevated baseline levels. Elevated baseline serum tryptase level has been reported to correlate with clonal mast cell disease in patients with insect sting anaphylaxis but may also indicate one of several possible underlying syndromes, including mast cell activation syndrome (MCAS), familial hypertryptasemia, and idiopathic anaphylaxis. There is some overlap in these conditions, so it is important to evaluate the clinical pattern at presentation as well as laboratory markers, and to consider bone marrow biopsy to make a final and specific diagnosis of clonal mast cell disease. The presence of venom-IgE does not prove that the patient's previous sting reactions were IgE-mediated, but even low levels of venom-IgE in patients with mastocytosis predispose to severe sting anaphylaxis. Evaluation of all these possible factors will affect the recommendation for venom immunotherapy.

Humoral and cellular responses to casein in patients with food protein–induced enterocolitis to cow's milk

Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated food allergy manifesting within 1 to 4hours of food ingestion with repetitive emesis and lethargy. We sought to characterize immune responses to casein in children with FPIES caused by cow's milk (CM). Total IgE and IgM, CM-specific IgG, and casein-specific IgE, IgG, IgG4, and IgM levels, as well as immunoglobulin free light chains, were measured in both patients with active and those with resolved CM-FPIES. Proliferating casein/T-effector cell counts were measured in children with CM-FPIES, children with IgE-mediated CM allergy, and those tolerating CM. Cytokine concentrations in the supernatants were quantified. Serum cytokine and tryptase levels were measured before and after a positive oral food challenge (OFC) result and compared with levels in those with a negative OFC result. We found low levels of CM and casein-specific IgG and casein-specific IgG4 in patients with CM-FPIES versus those tolerating CM (P<.05). Although we found both a high CD4+ Tcell-proliferative response and TH2 cytokines production after casein stimulation in children with CM-FPIES, results were similar to those in control subjects. Significantly lower secretion of IL-10 and higher secretion of IL-9 by casein-stimulated Tcells were found in patients with CM-FPIES versus those with IgE-mediated CM allergy. Lower baseline serum levels of IL-10 and higher tryptase levels were found in active CM-FPIES versus resolved CM-FPIES. We found a significant increase in serum IL-10 and IL-8 levels after a positive OFC result. We confirm the paucity of humoral response in patients with CM-FPIES. IL-10 might play a key role in acquisition of tolerance in patients with CM-FPIES. Increased serum IL-8 levels in patients with active FPIES suggest neutrophil involvement. Elevated baseline serum tryptase levels in patients with active FPIES suggest low-grade intestinal mast cell activation or increased mast cell load.

Mastocytosis: the puzzling clinical spectrum and challenging diagnostic aspects of an enigmatic disease.

Mastocytosis is a complex disorder characterized by the accumulation of abnormal mast cells (MC) in the skin, bone marrow and/or other visceral organs. The clinical manifestations result from MC-derived mediators and, less frequently, from destructive infiltration of MCs. Patients suffer from a variety of symptoms including pruritus, flushing and life-threatening anaphylaxis. Whilst mastocytosis is likely to be suspected in a patient with typical skin lesions [i.e. urticaria pigmentosa (UP)], the absence of cutaneous signs does not rule out the diagnosis of this disease. Mastocytosis should be suspected in cases of recurrent, unexplained or severe insect-induced anaphylaxis or symptoms of MC degranulation without true allergy. In rare cases, unexplained osteoporosis or unexplained haematological abnormalities can be underlying feature of mastocytosis, particularly when these conditions are associated with elevated baseline serum tryptase levels. The diagnosis is based on the World Health Organization criteria, in which the tryptase level, histopathological and immunophenotypic evaluation of MCs and molecular analysis are crucial. A somatic KIT mutation, the most common of which is D816V, is usually detectable in MCs and their progenitors. Once a diagnosis of systemic mastocytosis (SM) is made, it is mandatory to assess the burden of the disease, its activity, subtype and prognosis, and the appropriate therapy. Mastocytosis comprises seven different categories that range from indolent forms, such as cutaneous and indolent SM, to progressive forms, such as aggressive SM and MC leukaemia. Although prognosis is good in patients with indolent forms of the disease, patients with advanced categories have a poor prognosis.

Clinical characteristics and risk profile of patients with elevated baseline serum tryptase

BackgroundThe clinical relevance of elevated basal serum tryptase (eBST≥11.4ng/ml) often remains unclear. MethodsBST was assessed in 15,298 patients attending our outpatient clinic. Frequency and severity of anaphylaxis was compared in 900 patients with eBST and 900 patients with normal BST. The prevalence of eBST was evaluated in patients with drug reactions, urticaria, gastrointestinal symptoms or venom allergy. Mast cell-associated symptoms were recorded prospectively in 100 patients with eBST and 100 controls using a standardised questionnaire. Results5.9% (n=900) of 15,298 patients had eBST ≥11.4ng/ml (mean 20±21ng/ml, 11.4–390ng/ml). In 47% of them BST was <15.0 and in 78% <20.0ng/ml. In patients with normal BST (4.5±2.1ng/ml), mean levels increased continuously with age (0.28ng/ml per decade; p<0.001). Fatigue, meteorism, muscle/bone ache, vertigo, tachycardia, flush, palpitations, diarrhoea and oedema were associated with eBST (p<0.05 to <0.0001) without significant differences between slightly (11.4–20ng/ml) or strongly (>20ng/ml) eBST. eBST was significantly associated with adverse reactions to drugs (34%), radio contrast media (15%) and insect stings (24%) (p<0.05). Anaphylaxis was more common in patients with eBST (21% vs. 14%, p<0.001). The relative role of insect stings, drugs and food as the most important triggers was similar in patients with elevated and normal BST. Severe reactions (grade 3/4) occurred most often in subjects with BST >20ng/ml (BST <11.4mg/ml: 2.8%; 11.5–20ng/ml: 5.9%; >20ng/ml: 12.4%). ConclusionsIn clinical practice it appears reasonable to assess BST, besides after anaphylactic reactions also in patients suffering repeatedly from vertigo, flush, tachycardia, palpitations, oedema and nausea. Even patients with slightly eBST have a higher risk of anaphylaxis and experience more severe reactions.

Treatment of Hymenoptera venom allergy: an update.

To review and summarize the studies published between 2012 and 2014 about the use of venom immunotherapy (VIT) to treat Hymenoptera hypersensitivity. Several studies reconfirm the effectiveness of VIT in both children and adults, and provide a better understanding of its immune-modulating effects. There are concerns about its cost-effectiveness; however, VIT versus self-injectable epinephrine alone when stung is the preferred treatment of choice for affected individuals when quality-of-life issues are considered. Ultrarush VIT may be as effective in children as in adults but is associated with a high risk of systemic allergic reactions (SARs). Controversy continues about the use of angiotensin-converting enzyme inhibitors and their potential for increased SARs while on VIT. Individuals with mast cell disorders, female sex, honeybee allergy, and those receiving rush or ultrarush VITs are at higher risk for SARs. Elevated baseline serum tryptase levels greater than 20 μg/l, SARs during VIT, and honeybee sensitivity are risk factors for VIT failure. VIT remains the gold standard to treat Hymenoptera-allergic individuals to prevent future sting-induced SARs in both children and adults.

Baseline Serum Tryptase Levels and Adverse Reactions to Injection Specific Immunotherapy with Airborne Allergens: Is There a Relationship?

Background: Elevated baseline serum tryptase levels are associated with severe systemic reactions following hymenoptera stings or venom immunotherapy. Little is known about baseline tryptase levels in patients with respiratory allergy and whether a relationship exists with systemic reactions induced by injection specific immunotherapy (SIT) with airborne allergens. The objective of this study was to measure tryptase levels in subjects with respiratory allergy and analyze the results in the light of tolerance/intolerance to injection SIT. Methods: Baseline serum tryptase levels were measured in 106 adults allergic to different airborne allergens and in 40 normal controls. Thirty-one patients underwent injection SIT, and 15 of these 31 experienced at least one SIT-induced systemic reaction. Results: Patients and normal controls showed similar median tryptase levels (2.98 vs. 3.13 ng/ml, respectively), although these were elevated in 6 patients (6%) versus 0 of 40 controls (0%). Tryptase levels did not differ between those patients with or without a history of systemic reactions (median 3.7 vs. 5.91 ng/ml, not significant). Three of 4 patients showing elevated tryptase levels belonged to the SIT-tolerant group. Elevated tryptase levels were not associated with specific allergens nor with distance from the specific pollen season. A bone marrow aspirate performed in the only patient with a history of systemic reactions following injection SIT and tryptase >11.4 ng/ml showed a normal morphology and phenotype. Conclusions: Unlike patients with hymenoptera venom allergy, in patients with respiratory allergy, elevated serum tryptase levels do not represent a risk factor for adverse reactions to SIT.

An increase in serum tryptase even below 11.4 ng/mL may indicate a mast cell‐mediated hypersensitivity reaction: a prospective study in Hymenoptera venom allergic patients

During a systemic hypersensitivity reaction (SR), an increase in serum tryptase compared to the baseline value is an indicator of mast cell activation, most often due to an IgE-mediated mechanism. To study the relevance of an increase in serum tryptase below the upper normal value of 11.4ng/mL. Serum tryptase levels were measured in 35 patients with Hymenoptera venom hypersensitivity before and during venom exposure. Of these, 20 developed SR to stings or following venom injections during immunotherapy (reactors), while 15 tolerated reexposure to stings or venom injections during immunotherapy without SR (non-reactors). Serum tryptase was estimated at 2, 5 and 24h after exposure and was compared to a baseline value obtained before or at least 72h after exposure. Considering circadian variation of serum tryptase, a relative increase to ≥135% of the baseline value (relative delta bound) was defined to indicate mast cell activation. Such an increase was observed in 17 of 20 reactors (85%), but none of 15 non-reactors. A serum tryptase of ≥11.4ng/mL following venom exposure was observed in eight of the 20 reactors (40%) and 2 (13.3%) of the 15 non-reactors. Both these non-reactors also had an elevated baseline serum tryptase. Serum tryptase values obtained during a suspected hypersensitivity reaction must always be compared to a baseline value. A relative tryptase increase to ≥135% of the baseline value during a suspected hypersensitivity reaction indicates mast cell activation even below 11.4ng/mL.

Influence of total and specific IgE, serum tryptase, and age on severity of allergic reactions to Hymenoptera stings

The aim of this study was to analyze the influence of total serum IgE and other potential risk factors on severity of systemic allergic Hymenoptera sting reactions. In a retrospective analysis of one thousand and two patients referred for insect allergy over 5 years, 865 reported systemic allergic sting reactions, most often by honey bees and wasps. In 758, total IgE, venom-specific IgE, and baseline tryptase levels were available and analyzed together with atopy state, age, and sex in relation to severity of sting reactions according to H. L. Mueller. In a binary logistic regression model considering, besides IgE, also other risk factors for severity, an influence of total and specific IgE on severity of systemic allergic sting reactions could not be shown, while high severity of systemic allergic sting reactions was significantly more often reported in patients with a baseline tryptase of ≥11.4 μg/l (P < 0.0001) and higher age (P = 0.026). In a bivariate analysis, however, in patients with grade IV reactions total IgE (P = 0.003) and honey bee venom-specific IgE (P = 0.001) were significantly lower than in lower severity grades. Bee venom-specific mean IgE rank was significantly higher in bee than in Vespula venom allergic patients (P = 0.0001). Connection of high severity sting reactions with lower IgE is mainly because of older age, which is associated with lower total IgE, and moreover with cardiovascular disease and elevated baseline serum tryptase, which are both risk factors for severe reactions.

Long-term outcome after venom immunotherapy

There have been a limited number of studies examining the outcome after discontinuing venom immunotherapy (VIT), all of which showed continued protection in the great majority of patients. Several different criteria have been proposed to select patients to stop treatment based on immunologic and clinical factors. Specific high-risk factors have been reported from these published reports. There have been very few reports of the outcome more than 5 years after stopping VIT and virtually none on patients who had discontinued treatment for more than 10 years. This review will summarize the published evidence for current guidelines and recommendations, with emphasis on long-term outcomes. There has been a paucity of studies of VIT in recent years, particularly regarding long-term outcomes. These studies have raised questions about whether the long-term outcome is different with less than 3 years than with more than 3 years of treatment. Recent studies have confirmed the roughly 15% chance of systemic reaction to a sting after stopping VIT and the low risk (<3%) of a severe reaction. New and meaningful observations have been made in several reports regarding the increased risk of relapse, and even death, in patients with mastocytosis or elevated baseline serum tryptase, who had discontinued VIT. This review incorporates old and new observations that provide the basis for the guidelines and practice parameters on discontinuing VIT.

Mastocytosis and insect venom allergy

To analyse the association of systemic allergic hymenoptera sting reactions with mastocytosis and elevated baseline serum tryptase and to discuss diagnosis and treatment in patients with both diseases. In recent large studies on patients with mastocytosis a much higher incidence of severe anaphylaxis following hymenoptera stings than in the normal population was documented. In patients with hymenoptera venom allergy, elevated baseline tryptase is strongly associated with severe anaphylaxis. Fatal sting reactions were reported in patients with mastocytosis, notably after stopping venom immunotherapy. During venom immunotherapy most patients with mastocytosis are protected from further sting reactions. Based on these observations immunotherapy for life is recommended for patients with mastocytosis and venom allergy. The incidence of allergic side-effects is increased in patients with mastocytosis and elevated baseline tryptase, especially in those allergic to Vespula venom. Premedication with antihistamines, or omalizumab in cases with recurrent severe side-effects, can be helpful. In all patients with anaphylaxis following hymenoptera stings, baseline serum tryptase should be determined. A value above 11.4 microg/l is often due to mastocytosis and indicates a high risk of very severe anaphylaxis following re-stings. Venom immunotherapy is safe and effective in this situation.

Hymenoptera venom allergy

Allergic reactions to Hymenoptera stings usually present as large local reactions or systemic reactions with symptoms of immediate type allergy (anaphylaxis). In Central Europe they are predominantly elicited by stings of the honeybee or Vespula spp. Acute reactions are managed by symptomatic treatment. Long-term care includes patient education (allergen avoidance, course of action at re-sting) and prescription of an emergency kit for self-treatment. Venom immunotherapy is established as specific treatment for Hymenoptera venom allergic patients. Diagnosis of Hymenoptera venom anaphylaxis is based on history, skin tests and measurement of venom-specific serum IgE antibodies. "False negative" or "false positive" results are possible with all test methods. If standard tests are negative, additional tests using the patient's peripheral blood leucocytes can be useful. Venom immunotherapy is usually well tolerated. After reaching the maintenance dose, therapeutic efficacy should be assessed by a sting challenge test. If the patient again develops a systemic reaction, an increase of the maintenance dose (usually 200 microg are sufficient) nearly always induces protection. In most patients venom immunotherapy can be stopped after (3 to) 5 years. However, if there is an increased risk of sting anaphylaxis due to intense allergen exposure (e.g. in beekeepers) or if there are individual risk factors for particularly severe reactions (especially mastocytosis and/or elevated baseline serum tryptase concentration, severe cardiovascular disease), modifications of the standard venom immunotherapy are necessary.