Tryptase as severity marker in drug provocation tests

BACKGROUND: In the absence of objective symptoms, it is difficult to assess an adverse reaction during drug provocation testing. We evaluated the value of serum tryptase levels to distinguish between positive, negative and, even more important, so-called 'hysterical' reactions (conversion symptoms). The latter are occasionally observed in drug provocation tests when the patient experiences ambiguous subjective symptoms. METHODS: In a prospective single-center study, 303 patients underwent 785 drug provocation tests. Blood was taken for tryptase measurement on each test day before and after drug challenge, and the changes in serum tryptase levels in patients with no reactions were compared with those who experienced immediate reactions to a drug. RESULTS: Thirty-four of 785 drug provocations were clinically judged as being positive. Despite objective symptoms, median serum tryptase values in the afternoon were even lower than baseline levels. However, this decrease was not statistically significant. In the 751 patients suffering no objective reactions, the median values of post-testing tryptase values were statistically significantly decreased as compared with pretesting values. CONCLUSIONS: The measurement of serum tryptase levels does not appear to be helpful to differentiate mild allergic or nonallergic reactions from 'hysterical' ones. The milder decrease in the group with objective drug reactions might indicate slight mast cell activation in some patients. More severe clinical drug reactions led to stronger mast cell degranulation. Mild reactions did not increase the tryptase levels consistently.     

Serum tryptase levels in adverse drug reactions

We evaluated the usefulness of individual tryptase levels and variations after adverse drug reactions in 64 patients. Our aim was to find a tool for the diagnosis of drug allergy. Thirty-seven subjects were confirmed to have drug allergy, 12 had nonsteroidal anti-inflammatory drug (NSAID) reactions, five had negative controlled drug challenges (NAAR), and 10 had symptoms after placebo intake (PLA). Serum tryptase levels greatly increased after anaphylactic shocks (2242%) and anaphylaxis (710.5%). Patients with allergic urticaria and those with idiosyncratic responses to acetylsalicylic acid (ASA) exhibited a small increase in serum tryptase (49.5% and 38.2%, respectively). In the other two groups (NAAR and PLA), no variation in this serum protease was observed. The time of appearance of the serum tryptase peak differed considerably among patients with similar clinical reactions (from 30 min to 6 h) and was independent of the latent period, severity of symptoms, or the amount of tryptase released. We conclude that serum tryptase determinations are helpful in the diagnosis of anaphylactic shock and anaphylaxis, but serial measurements may be needed to confirm mast-cell participation in milder reactions.     

Heparin-induced recurrent anaphylaxis

BACKGROUND: Heparin-related immediate-type hypersensitivity reactions like urticaria, angio-oedema or bronchospasm are very rare, and only a few cases of anaphylaxis-like responses because of heparin have been described. However, the mechanisms underlying these reactions and the role of mast cells in their pathogenesis have not been elucidated. OBJECTIVES: We report a patient with end-stage renal disease who presented with recurrent anaphylaxis after receiving heparin during haemodialysis. The underlying aetiology was obscured by the initiation of haemodialysis with its known anaphylactic-like side-effects. The diagnosis of hypersensitivity to heparin was confirmed by the clinical picture, positive skin tests and elevated serum tryptase levels. MATERIALS AND METHODS: We performed prick and intradermal skin tests with heparin, enoxaparin and danaparoid heparinoid. Total and mature tryptase levels were measured in serum by ELISAs at 1, 24 and 36 h following the reaction. RESULTS: An elevated mature tryptase level was found at 1 h, which returned to normal levels at 24 and 36 h. A high total tryptase level was detected at 1 h, but remained somewhat elevated at 24 h. Prick tests were negative with the three compounds. Intradermal skin tests with heparin and enoxaparin were both positive, while with danaparoid negative. Following negative skin test results, danaparoid was used as an anticoagulant during dialysis for the next 3 years without any adverse effects. CONCLUSIONS: In conclusion, we report the first case of heparin-induced anaphylaxis confirmed by an elevated level of mature tryptase in serum. Following skin tests, the patient was treated with danaparoid during haemodialysis sessions three times a week without any adverse effects. Because of increasing use of heparin in daily medical practice, physicians should be aware of possible immediate hypersensitivity reactions to this medication and know how to diagnose and treat them.     

A Case of Serum Sickness-Like Reaction and Anaphylaxis - Induced Simultaneously by Rifampin

Rifampin is commonly used as a first-line anti-tuberculosis drug, but it can induce a serum sickness-like reaction or anaphylaxis. However, it is possible for 1 drug antigen to induce 2 or more simultaneous immunologic reactions. Here, we report a case of a serum-sickness-like reaction and anaphylaxis induced concurrently by rifampin. A 25-year-old male presented with high fever and a maculopapular rash with vesicles on the hands, which developed 2 weeks following regular administration of anti-tuberculosis drugs for tuberculous meningitis, including rifampin. Elevated liver enzymes, peripheral neuropathy, and decreased serum C3 and C4 levels were found. Interestingly, these symptoms were accompanied by severe hypotension. A serum-sickness-like reaction was considered after excluding other potential causes for the fever. A drug provocation test showed that the fever developed after oral administration of rifampin, suggesting that rifampin was the cause of the allergic reaction. However, hypotension, epigastric discomfort, and diarrhea also accompanied these symptoms, indicating that IgE-mediated type I hypersensitivity could be part of the serum sickness-like reaction. An intradermal skin test clearly showed an immediate positive reaction to rifampin. This case was diagnosed as concurrent serum-sickness-like reaction and anaphylaxis induced by rifampin. One drug may therefore induce combined allergic reactions via 2 or more simultaneous hypersensitivity responses.     

Late-onset anaphylaxis to fermented soybeans: the first confirmation of food-induced, late-onset anaphylaxis by provocation test.

BACKGROUND: Late-onset anaphylactic reactions without early-phase reactions are rarely reported. The hypothesized mechanism of late-onset anaphylaxis to fermented soybeans is delayed absorption or release into the bowel rather than an immunologic phenomenon. OBJECTIVES: To investigate the mechanisms of late-onset anaphylaxis to fermented soybeans in 2 patients and to characterize the allergens involved in anaphylaxis caused by fermented soybeans. METHODS: Two patients underwent skin prick-by-prick tests with fermented soybeans as is. We used an open challenge for the provocation test of anaphylaxis and measured changes in plasma histamine, plasma tryptase, serum eosinophil cationic protein, and plasma leukotriene B4 levels in 1 patient. In addition, specific IgE against fermented soybeans and the allergens of fermented soybeans were detected by enzyme-linked immunosorbent assay and immunoblotting, respectively. RESULTS: The results of the prick-by-prick tests with fermented soybeans as is were positive in both patients and negative in control subjects. The challenge with 50 g of fermented soybeans caused generalized urticaria and dyspnea 13 hours after ingestion of fermented soybeans in 1 patient. In addition, his plasma histamine and tryptase levels transiently elevated during the anaphylactic event. In enzyme-linked immunosorbent assay, the patients showed elevated IgE levels to the proteins of fermented soybeans. Serum IgE antibodies of patients 1 and 2 were bound to approximately 5- and 26-kDa proteins in immunoblotting of fermented soybeans, respectively. CONCLUSION: To our knowledge, this is the first report of late-onset anaphylaxis provoked by the challenge test half a day after ingestion of fermented soybeans.     

The Utility of Serum Tryptase in the Diagnosis of Food-Induced Anaphylaxis

Purpose

This study investigates the utility of serum tryptase for the confirmation of shrimp-induced anaphylaxis.

Methods

Patients with a history of shrimp allergy and positive skin prick tests (SPT) to commercial shrimp extract were recruited for shrimp challenges. Serum total tryptase was obtained at baseline and 60 min (peak) after the onset of symptoms.

Results

Thirty-nine patients were challenged. There were 12 patients with anaphylaxis, 20 with mild reactions and 7 without symptoms (control group). Characteristic features and baseline tryptase were not different among the 3 groups. The peak tryptase levels were higher than the baseline in anaphylaxis and mild reaction groups (P<0.05). The delta-tryptase (peak minus baseline) and the tryptase ratio (peak divided by baseline) in the anaphylaxis group were higher than the mild reaction and control groups (P<0.01). The optimum cut-off for peak tryptase to confirm anaphylaxis was 2.99 µg/L with 50% sensitivity, 85% specificity, 3.33 positive likelihood ratio (LR) and 0.59 negative LR. The manufacturer''s cut-off for peak tryptase was >11.4 µg/L with 17% sensitivity, 100% specificity, infinity positive LR and 0.83 negative LR. The best cut-off for delta-tryptase was ≥0.8 µg/L with 83% sensitivity, 93% specificity, 11.86 positive LR and 0.18 negative LR. The best cut-off for tryptase ratio was ≥1.5 with 92% sensitivity, 96% specificity, 23 positive LR and 0.08 negative LR.

Conclusions

The peak tryptase level should be compared with the baseline value to confirm anaphylaxis. The tryptase ratio provide the best sensitivity, specificity, positive and negative LR than a single peak serum tryptase for the confirmation of shrimp-induced anaphylaxis.     

Clinical and laboratory parameters of mast cell activation as basis for the formulation of diagnostic criteria

Mast cell (MC) activation occurs in a number of different pathologic conditions. Acute activation is commonly seen in patients with allergic reactions, with consecutive massive release of vasoactive and proinflammatory mediator substances from MCs, leading to the clinical signs and symptoms of anaphylaxis. In these patients, serum tryptase concentrations usually increase subtantially above baseline levels. Chronic MC activation is more difficult to diagnose, especially when symptoms are mild or atypical, and no underlying disease is found. In these patients, serum tryptase levels usually are normal. In a smaller group of patients, tryptase levels are constantly elevated and may point to an occult form of mastocytosis. These patients have to be examined for MC monoclonality, other criteria of a primary MC disease, non-MC hematopoietic neoplasms, and reactive disorders producing chronic MC activation or MC accumulation. In most patients in whom MC activation is found, histamine-induced symptoms can be documented and usually respond to treatment with histamine receptor antagonists or MC stabilizers. If this is not the case, alternative explanations for symptoms and differential diagnoses have to be considered.     

A Case of Pranlukast-Induced Anaphylactic Shock

Leukotriene receptor antagonists, which are generally considered safe with a few adverse drug reactions, are increasingly used in the treatment of various allergic diseases, including asthma and allergic rhinitis. Although a few anaphylactic reactions to montelukast have been reported worldwide, there is still a lack of reports about severe adverse drug reactions associated with pranlukast. Here, we report a case of severe hypersensitivity reaction associated with pranlukast. A 65-year-old woman developed anaphylactic shock that presented as generalized urticaria, angioedema, collapse, and loss of consciousness after receiving pranlukast. A positive response to oral challenge and skin prick testing with pranlukast was observed in the patient. In this case, it was demonstrated that pranlukast can induce anaphylaxis, possibly mediated by the IgE-dependent pathway.     

IgE-mediated immediate-type hypersensitivity to the pyrazolone drug propyphenazone

BACKGROUND: Propyphenazone (1,2-dihydro-1,5-dimethyl-4-(1-methylethyl)-2-phenyl-3H-pyrazol-3-one; PP) is a nonsteroidal anti-inflammatory drug frequently used as mild analgesic medicament. It belongs to the chemical group of pyrazolones. Severe adverse reactions to PP are frequent and have generally been regarded as pseudoallergic or intolerance reactions. Presently, there are no useful in vitro test systems available for the detection of antibodies directed against analgesic drugs. OBJECTIVE: The purpose of this study was to unequivocally demonstrate that IgE-mediated Type I allergy is the main mechanism leading to immediate-type adverse reactions to the analgesic drug PP. METHODS: We investigated 53 young adult patients with adverse reactions to PP. All patients developed symptoms suggestive of IgE-mediated anaphylaxis within 30 minutes after intake of a painkiller containing PP. Patients were subjected to skin tests (prick test and intracutaneous test). In addition, a novel ELISA system was developed to prove the existence of specific IgE antibodies in patients' sera. RESULTS: In 44 of 53 (83%) patients, skin tests showed typical wheal and flare reactions. Significant amounts of PP-specific serum IgE was detected in 31 of 53 (58%) of the serum samples. Moreover, in 7 of 9 patients with skin test negative results, PP-specific IgE could be detected. The assay was PP-specific because only PP, but no other pyrazolone derivative (antipyrine, aminophenazone, or metamizol), was able to inhibit IgE-binding in the system. CONCLUSION: Propyphenazone is a sensitizing agent in susceptible individuals and can elicit IgE-mediated anaphylaxis. By using skin tests and our ELISA system we were able to confirm Type I allergy in 51 of 53 (96%) patients in this study.     

The potential clinical utility of serum alpha-protryptase levels.

BACKGROUND: Because biopsy criteria for diagnosing systemic mastocytosis are not precise, the value of serum alpha-protryptase levels in the work-up of suspected systemic mastocytosis should be considered. OBJECTIVE: A retrospective analysis was performed on subjects with total tryptase serum levels that were high (>/=20 ng/mL), while beta-tryptase serum levels were normal (<1 ng/mL) or modestly elevated (1 to 5 ng/mL). METHODS: Over a 3.5-year period, 52 qualifying specimens were identified from 1369 consecutive samples. The corresponding subjects were divided into those with suspected mastocytosis and those with suspected anaphylaxis. Subjects with suspected mastocytosis were subdivided into 3 subgroups on the basis of biopsy results (positive, negative, or not available). Subjects with suspected anaphylaxis were subdivided into living and deceased subgroups. RESULTS: Among the 15 subjects who underwent biopsy, alpha-protryptase serum levels (the difference between directly-measured levels of serum total tryptase and beta-tryptase), when greater than 75 ng/mL (n = 9), were always associated with a positive biopsy result for systemic mastocytosis; levels from 20 to 75 ng/mL (n = 6) were associated with a positive biopsy result in 50% of subjects. alpha-Protryptase serum levels may be a more sensitive screening test than a bone marrow biopsy for this disorder. Also, elevated alpha-protryptase serum levels in some adult patients return to normal over time, suggesting that mast cell hyperplasia resolved in these patients. Finally, a high alpha-protryptase level may reveal anaphylaxis to be a presenting manifestation of systemic mastocytosis or mast cell hyperplasia. CONCLUSION: Levels of serum alpha-protryptase, relative to those of beta-tryptase, appear to be useful in the diagnostic work-up and follow-up of subjects with suspected systemic mastocytosis.     

Diagnosis of Hymenoptera venom allergy

The purpose of diagnostic procedure is to classify a sting reaction by history, identify the underlying pathogenetic mechanism, and identify the offending insect. Diagnosis of Hymenoptera venom allergy thus forms the basis for the treatment. In the central and northern Europe vespid (mainly Vespula spp.) and honeybee stings are the most prevalent, whereas in the Mediterranean area stings from Polistes and Vespula are more frequent than honeybee stings; bumblebee stings are rare throughout Europe and more of an occupational hazard. Several major allergens, usually glycoproteins with a molecular weight of 10-50 kDa, have been identified in venoms of bees, vespids. and ants. The sequences and structures of the majority of venom allergens have been determined and several have been expressed in recombinant form. A particular problem in the field of cross-reactivity are specific immunoglobulin E (IgE) antibodies directed against carbohydrate epitopes, which may induce multiple positive test results (skin test, in vitro tests) of still unknown clinical significance. Venom hypersensitivity may be mediated by immunologic mechanisms (IgE-mediated or non-IgE-mediated venom allergy) but also by nonimmunologic mechanisms. Reactions to Hymenoptera stings are classified into normal local reactions, large local reactions, systemic toxic reactions, systemic anaphylactic reactions, and unusual reactions. For most venom-allergic patients an anaphylactic reaction after a sting is very traumatic event, resulting in an altered health-related quality of life. Risk factors influencing the outcome of an anaphylactic reaction include the time interval between stings, the number of stings, the severity of the preceding reaction, age, cardiovascular diseases and drug intake, insect type, elevated serum tryptase, and mastocytosis. Diagnostic tests should be carried out in all patients with a history of a systemic sting reaction to detect sensitization. They are not recommended in subjects with a history of large local reaction or no history of a systemic reaction. Testing comprises skin tests with Hymenoptera venoms and analysis of the serum for Hymenoptera venom-specific IgE. Stepwise skin testing with incremental venom concentrations is recommended. If diagnostic tests are negative they should be repeated several weeks later. Serum tryptase should be analyzed in patients with a history of a severe sting reaction.     

Risk factors and indicators of severe systemic insect sting reactions

Hymenoptera venom allergy ranks among the top three causes of anaphylaxis worldwide, and approximately one-quarter of sting-induced reactions are classified as severe. Fatal sting reactions are exceedingly rare, but certain factors may entail a considerably higher risk. Delayed administration of epinephrine and upright posture are situational risk factors which may determine an unfavorable outcome of the acute anaphylactic episode and should be addressed during individual patient education. Systemic mastocytosis and senior age are major, unmodifiable long-term risk factors and thus reinforce the indication for venom immunotherapy. Vespid venom allergy and male sex likewise augment the risk of severe or even fatal reactions. Further studies are required to assess the impact of specific cardiovascular comorbidities. Available data regarding potential effects of beta-blockers and/or ACE inhibitors in coexisting venom allergy are inconclusive and do not justify recommendations to discontinue guideline-directed antihypertensive treatment. The absence of urticaria/angioedema during sting-induced anaphylaxis is indicative of a severe reaction, serum tryptase elevation, and mast cell clonality. Determination of basal serum tryptase levels is an established diagnostic tool for risk assessment in Hymenoptera venom-allergic patients. Measurement of platelet-activating factor acetylhydrolase activity represents a complementary approach but is not available for routine diagnostic use.     

Intraoperative anaphylaxis to bacitracin during pacemaker change and laser lead extraction.

BACKGROUND: Bacitracin is widely used in operating rooms to soak implants, irrigate compound fractures, and apply to surgical incisions. However, bacitracin is a known sensitizer and causes not only allergic contact dermatitis but also anaphylaxis. OBJECTIVE: To describe a 72-year-old woman with anaphylaxis after irrigation and packing of an infected pacemaker pocket with a bacitracin solution. METHODS: Skin prick testing to bacitracin and latex; serum tryptase, serum histamine, serum IgE to latex, and serial cardiac enzyme measurements; blood cultures, transthoracic echocardiograms, and venograms were performed to characterize the reaction. RESULTS: Six hours after the anaphylactic event, the patient had an elevated serum tryptase level of 49 ng/mL (reference range, 2-10 ng/mL), which normalized the next morning. She had immediate-type skin prick test reactions to full-strength bacitracin ointment (500 U/g) and bacitracin solution (150 U/mL). Serum IgE level to latex was undetectable, and results of skin testing to latex were negative. CONCLUSIONS: To our knowledge, this is the first case report of anaphylaxis to bacitracin during pacemaker surgery. This case illustrates that intraoperative anaphylaxis to bacitracin can be life-threatening.     

Human mast cell tryptase in biology and medicine

The most abundant prestored enzyme of human mast cell secretory granules is the serine-protease tryptase. In humans, there are four tryptase isoforms, but only two of them, namely the alpha and beta tryptases, are known as medically important. Low levels of continuous tryptase production as an immature monomer makes up the major part of the baseline serum tryptase levels, while transient release of mature tetrameric tryptase upon mast cell degranulation accounts for the anaphylactic rise of serum tryptase levels. Serum tryptase determination contributes to the diagnosis or monitoring of mast cell disorders including mast cell activation – induced anaphylaxis, mastocytosis and a number of myeloproliferative conditions with mast cell lineage involvement. Baseline serum tryptase levels are predictive of the severity risk in some allergic conditions.     

Raised tryptase without anaphylaxis or mastocytosis: heterophilic antibody interference in the serum tryptase assay

Mast cell tryptase (MCT) is a key diagnostic test for mastocytosis and anaphylaxis. High serum tryptase levels are also one of the risk factors for adverse reaction in venom immunotherapy, yet occasional patients are seen with raised levels in the absence of either diagnosis. False positive results can be due to assay interference by heterophilic antibodies such as rheumatoid factor (RF) and human anti-mouse antibodies (HAMA). We therefore investigated heterophilic antibody interference by rheumatoid factor activity and HAMA as a cause of raised MCT results in the Phadia tryptase assay. Serum samples from 83 patients were assayed for MCT and rheumatoid factor before and after the use of heterophilic antibody blocking tubes (HBT). Samples with more than 17% reduction in MCT with detectable RF were then assayed for HAMA. Fourteen (17%) of the 83 samples with positive RF showed a >17% decrease in mast cell tryptase after HBT blocking. Post-HBT, eight of 14 (57%) reverted from elevated to normal range values with falls of up to 98%. RF levels were also decreased significantly (up to 75%). Only one of the 83 tested was apparently affected by HAMA in the absence of detectable IgM RF. In conclusion, any suspicious MCT result should be checked for heterophilic antibodies to evaluate possible interference. False positive MCT levels can be caused by rheumatoid factor. We suggest a strategy for identifying assay interference, and show that it is essential to incorporate this caveat into guidance for interpretation of MCT results.     

Oral antibiotic adverse reactions after penicillin skin testing: multi-year follow-up

BACKGROUND: Long-term follow-up data on adverse drug reactions after oral antibiotic use in penicillin allergy history positive individuals with penicillin skin test done in advance of need are rare. METHODS: Oral antibiotic associated adverse drug reactions in 83 penicillin skin test positive individuals were compared to a sex, age, and length of follow-up matched sample of 166 penicillin skin test negative individuals, all of whom had at least one post penicillin skin test oral antibiotic. The mean post penicillin skin test follow-up interval was 34.5 +/- 16.6 months. There were 1655 total oral antibiotic exposures. RESULTS: In penicillin skin test positive individuals, the adverse drug reaction rate was not significantly different with cephalosporin or non-beta-lactam use (P = 0.12). In penicillin skin test negative individuals the adverse drug reaction rate was significantly lower with cephalosporin vs. non-beta-lactam use (P = 0.005). Penicillin was safely used in penicillin skin test negative individuals. Overall cephalosporins caused fewer adverse drug reactions independent of penicillin skin test status (P = 0.005). CONCLUSIONS: Penicillin skin testing was only able to predict penicillin associated adverse drug reactions in penicillin skin test positive individuals. Excluding accidental penicillin exposure in penicillin skin test positive individuals, non-beta-lactams were associated with adverse drug reactions more often than penicillins or cephalosporins, independent of the penicillin skin test result. Cephalosporins were used as or more safely than non-beta-lactams in both penicillin skin test positive and negative individuals.     

Cutaneous manifestations in Hymenoptera and Diptera anaphylaxis: relationship with basal serum tryptase

Objectives To compare the clinical presentation of systemic anaphylaxis to Hymenoptera and Diptera with regard to basal serum tryptase (BT) and to evaluate mastocytosis in patients with elevated tryptase.
Patients and Methods The medical records of 140 patients with a history of a systemic reaction to venom were retrospectively reviewed. Symptoms and severity of anaphylaxis and BT were recorded. Most patients with elevated tryptase were screened for mastocytosis: a dermatological examination with a skin biopsy was performed in 19 cases and a bone marrow biopsy in 14 cases.
Results Tryptase was elevated in 23 patients. These patients reported fewer usual skin reactions (urticaria in 26.1% of cases with raised tryptase vs. 76.1% of cases with normal tryptase), more flushing (52.2% vs. 4.3%) and frequently did not present skin reaction (26.1% vs. 9.4%). They presented a more severe reaction (mean grade of severity: 3.48 vs. 2.69). Mastocytosis was diagnosed in seven patients with elevated tryptase: indolent systemic mastocytosis in six cases and cutaneous mastocytosis without systemic involvement in one case. In five cases, mastocytosis was previously undiagnosed. Lesions of cutaneous mastocytosis, diagnosed in five patients, consisted of urticaria pigmentosa in all cases and were often inconspicuous.
Conclusion These results demonstrate particular clinical features of the allergic reaction in patients with elevated BT and the higher frequency of mastocytosis in this population. In patients with a severe anaphylactic reaction without urticaria, but with flushing, tryptase should be assayed and an underlying mastocytosis should be considered.     

Is unrecognized anaphylaxis a cause of sudden unexpected death?

Background: Serum tryptase levels reflect mast cell activation and correlate with anaphylactic reactions. Elevated post-mortem serum tryptase levels have been found in witnessed fatal anaphylaxis. Objective: This study was designed to examine whether or not unwitnessed anaphylaxis may be a hitherto unrecognized cause of sudden unexplained death. Methods: Mast cell tryptase was measured by immunoassay in 68 post-mortem sera remaining from a previous study which reported elevated venom-specific IgE antibodies in 22 (23%) of 94 victims of sudden unexpected death. Autopsies were performed in all cases. The cause of death was independently reported by pathologists unfamiliar with the nature of this study. Results: Serum tryptase levels were elevated (> 10ng/mL) in nine of 68 cases. The levels could not be predicted from the clinical circumstances surrounding death. Sera from four individuals contained both elevated tryptase and previously reported elevated venom-specific IgE. Conlusions: We conclude that mast cell activation may accompany up to 13% of sudden unexpected deaths in adults. Measurement of both tryptase and specific IgE antibody levels in post-mortem sera from persons experiencing sudden, unexpected death may identify a small subset of cases due to clinically unrecognized fatal anaphylaxis, including those due to insect stings.     

Anaphylaxis to Patent Blue V. I. Clinical aspects

Background:  The dye Patent Blue V (PBV) is increasingly used for staging procedures in operable breast cancer, but is reported to cause adverse reactions. The aim of this study was to present the clinical features and the results of follow-up examinations in patients with such reactions.
Methods:  We studied nine patients with hypersensitivity reactions to PBV between 1999 and 2006 who were identified through the Norwegian network for reporting and investigating allergic reactions during anesthesia.
Results:  We observed incidences of 0.5% (7/1418) for all kinds of PBV reactions and 0.4% (5/1418) for anaphylaxis. Typical clinical features included: (i) cardiovascular and/or cutaneous symptoms, (ii) a delay in symptoms, compared to the time of dye injection, (iii) poor response to ephedrine and intravenous fluid, and (iv) need for adrenaline administration, sometimes prolonged, for circulatory stabilization. Cutaneous manifestations were noted in five of the seven patients with anaphylaxis and two additional patients without circulatory instability. During anaphylactic reactions, serum tryptase was increased in six patients and normal in one. Serum tryptase was normal in one patient with skin symptoms only. Skin prick tests to PBV were positive in all eight patients tested, including the two with skin manifestations only.
Conclusion:  The clinical features and the results of follow-up studies strongly suggest that these reactions are IgE mediated.     

Elevated basal serum tryptase and hymenoptera venom allergy: relation to severity of sting reactions and to safety and efficacy of venom immunotherapy

BACKGROUND: Mastocytosis and/or elevated basal serum tryptase may be associated with severe anaphylaxis. OBJECTIVE: To analyse Hymenoptera venom-allergic patients with regard to basal tryptase in relation to the severity of sting reactions and the safety and efficacy of venom immunotherapy. METHODS: Basal serum tryptase was measured in 259 Hymenoptera venom-allergic patients (158 honey bee, 101 Vespula). In 161 of these (104 honey bee, 57 Vespula), a sting challenge was performed during venom immunotherapy. RESULTS: Nineteen of the 259 patients had an elevated basal serum tryptase. Evidence of cutaneous mastocytosis as documented by skin biopsy was present in 3 of 16 patients (18.8%). There was a clear correlation of basal serum tryptase to the grade of the initial allergic reaction (P<0.0005). Forty-one of the 161 sting challenged patients reacted to the challenge, 34 to a bee sting and 7 to a Vespula sting. Thereof, 10 had an elevated basal serum tryptase, i.e. 1 (2.9%) of the reacting and 2 (2.9%) of the non-reacting bee venom (BV) allergic individuals, as compared to 3 (42.9%) of the reacting and 4 (8%) of the non-reacting Vespula venom-allergic patients. Thus, there was a significant association between a reaction to the sting challenge and an elevated basal serum tryptase in Vespula (chi2=6.926, P<0.01), but not in BV-allergic patients. Systemic allergic side-effects to venom immunotherapy were observed in 13.9% of patients with normal and in 10% of those with elevated basal serum tryptase. CONCLUSIONS: An elevated basal serum tryptase as well as mastocytosis are risk factors for severe or even fatal shock reactions to Hymenoptera stings. Although the efficacy of venom immunotherapy in these patients is slightly reduced, most of them can be treated successfully. Based on currently available data, lifelong treatment has to be discussed in this situation.