Serum basal tryptase may be a good marker for predicting the risk of anaphylaxis in children with food allergy

A relationship between serum basal tryptase (sBT) levels, anaphylactic reactions, and clonal mast cell diseases was shown recently in adults with venom allergy, but the relationship between sBT levels and IgE‐mediated food allergy and anaphylaxis is not known. In this study, children with food allergy (FA; n = 167) were analyzed in two groups according to the presence (FA+/A+; n = 79) or absence of anaphylaxis (FA+/A?; n = 88) and were compared with a control group (n = 113). Median sBT values in FA+/A+, FA+/A?, and control groups were 4.0 ng/ml (2.8–5.8), 3.6 (2.3–4.5), and 3.3 (2.4–4.4), respectively (P = 0.022). sBT measurements higher than the cutoff values of 5.7 and 14.5 were associated with 50% and 90% predicted probabilities, respectively, of moderate to severe anaphylaxis. Children with tree nuts/peanut allergies had significantly higher levels of sBT than children with milk and egg allergy (P = 0.022). Results suggest that sBT levels may predict moderate to severe anaphylaxis in children with food allergy, which may follow a particular pattern according to the food allergy phenotype.     

Biphasic systemic anaphylaxis: An inpatient and outpatient study

We attempted to ascertain the incidence of systemic biphasic anaphylactic reactions in both outpatients and inpatients. Madigan Army Medical Center is a large teaching facility. The Allergy Clinic staff sees approximately 20,000 patients per year, and an average of 27,000 allergy immunotherapy injections are administered each year. During the years 1988 to 1991 we collected data from a total of 35 patients who had experienced, during the 30-minute waiting period in the clinic, symptoms and signs consistent with anaphylaxis. A total of 44 anaphylactic reactions were noted, with only two (5%) involving a biphasic systemic pattern. All patients were observed and treated within the clinic until symptoms and signs had resolved. None of the patients were treated with or were presently using glucocorticosteroids during the time of their reactions. Of the reactions noted, 25 (57%) involved only cutaneous manifestations of anaphylaxis, three (7%) involved the laryngeal/upper airway area, eight (18%) involved bronchospasm alone, three (7%) involved the rhinoconjunctivae, and five (11%) involved more than one site or type. None of the patients experienced any symptoms or signs of cardiovascular compromise or collapse after allergy extract injections. During the years 1986 to 1992 a total of 59 patients were admitted to the medical ward or intensive care unit with the diagnosis of systemic anaphylaxis. Of 59 patients, four (7%) experienced a recurrent (biphasic) anaphylactic reaction without reexposure to the initial inciting agent. The remaining 55 patients (93%) did not experience any further systemic anaphylaxis after initial hospital admission and treatment. Two of the patients with biphasic anaphylaxis were first seen with hypotension and generalized urticaria. Of the remaining two patients, one had lip and tongue angioedema, and the other had urticaria only. The biphasic reaction involved antibiotics in two cases and food (shrimp) in the remaining two cases. Forty-two male patients and 17 female patients were included in the study. The age range of male patients was 6 months to 77 years and that of the female patients was 10 to 81 years. There were no deaths in this study. Of the causes for anaphylactic episodes 20 (34%) were drug- or medication-related, 12 (20%) were idiopathic, 13 (22%) were related to food, six (10%) were secondary to exercise, two (3%) were related to vaccine administration and three (3%) were secondary to Hymenoptera stings. The four remaining episodes were secondary to contrast dye administration, allergen skin test extract administration, horse serum administration, and allergen extract injection. We conclude that the incidence of biphasic anaphylactic events is lower than that reported in previously published studies. (J ALLERGY CLIN IMMUNOL 1994;93:977-85.)     

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.     

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.     

Mastocytosis and Hymenoptera venom allergy

PURPOSE OF REVIEW: Mastocytosis is a rare disease characterized by increased mast cells in skin and/or internal organs. We evaluate the impact of mastocytosis on diagnosis and treatment of Hymenoptera venom allergy. RECENT FINDINGS: Patients with Hymenoptera venom allergy who suffer from mastocytosis develop life-threatening sting reactions more often than those who do not. When patients with Hymenoptera venom allergy were systematically examined for mastocytosis, it was found to be represented to an abnormally high extent. Most patients with mastocytosis tolerate venom immunotherapy with no or only minor systemic symptoms. Venom immunotherapy was found to be marginally less effective in patients with mastocytosis than in those without evidence of mast cell disease (defined as absent cutaneous mastocytosis combined with a serum tryptase concentration of <11.4 microg/l). Several deaths from sting reactions were reported in patients with mastocytosis after venom immunotherapy was stopped. These patients should have venom immunotherapy for the rest of their lives. SUMMARY: Patients suffering from mastocytosis and Hymenoptera venom allergy are at risk from a particularly severe sting anaphylaxis. They need optimal diagnosis and treatment. In patients presenting with Hymenoptera venom allergy, screening tests by measurement of serum tryptase concentration, and a careful skin examination, are highly recommended.     

Tryptase levels as an indicator of mast-cell activation in systemic anaphylaxis and mastocytosis

Better methods are needed to assess mast-cell activation in vivo and to distinguish the activation of mast cells from that of basophils. Tryptase, a neutral protease selectively concentrated in the secretory granules of human mast cells (but not basophils), is released by mast cells together with histamine and serves as a marker of mast-cell activation. In 17 patients with systemic mastocytosis, concentrations of tryptase in plasma were linearly related to those of histamine (P less than 0.01). Eleven of the 17 patients had tryptase levels of 4 to 88 ng per milliliter, indicating ongoing mast-cell activation. In each of six patients who experienced corresponding anaphylactic reactions after penicillin, aspirin, or melon ingestion, a wasp sting, exercise, or antilymphocyte globulin injection, tryptase levels in serum ranged from 9 to 75 ng per milliliter, indicating mast-cell activation during each of these events. In contrast, serum tryptase levels were less than 5 ng per milliliter in all patients presenting with myocardial disease (n = 8, 6 with hypotension) or sepsis (n = 6, 3 with hypotension) and in the controls (n = 20). One patient had a myocardial infarction after anaphylaxis in response to a wasp sting and an elevated tryptase level of 25 ng per milliliter. Thus, the plasma or serum tryptase level is a diagnostic correlate of mast-cell-related events.     

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.     

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.     

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.     

Identification of alpha‐gal sensitivity in patients with a diagnosis of idiopathic anaphylaxis

IgE antibodies (Ab) specific to galactose‐α‐1,3‐galactose (alpha‐gal) are responsible for a delayed form of anaphylaxis that occurs 3‐6 hours after red meat ingestion. In a unique prospective study of seventy participants referred with a diagnosis of idiopathic anaphylaxis (IA), six (9%) were found to have IgE to alpha‐gal. Upon institution of a diet free of red meat, all patients had no further episodes of anaphylaxis. Two of these individuals had indolent systemic mastocytosis (ISM). Those with ISM had more severe clinical reactions but lower specific IgE to alpha‐gal and higher serum tryptase levels, reflective of the mast cell burden. The identification of alpha‐gal syndrome in patients with IA supports the need for routine screening for this sensitivity as a cause of anaphylaxis, where reactions to alpha‐gal are delayed and thus may be overlooked.     

Influence of total IgE levels on the severity of sting reactions in Hymenoptera venom allergy

BACKGROUND: Detection of specific IgE for Hymenoptera venoms and skin tests are well established diagnostic tools for the diagnosis of insect venom hypersensitivity. The aim of our study was to analyze the effect of total IgE levels on the outcome of generalized anaphylactic reactions after a Hymenoptera sting. METHODS: Two hundred and twenty patients allergic to bee, wasp, or European hornet venom were included in the study. Their specific and total IgE levels, serum tryptase levels, skin tests, and sting history were analyzed. RESULTS: In patients with mild reactions (grade I, generalized skin symptoms) we observed higher total IgE levels (248.0 kU/l) compared to patients with moderate reactions (grade II, moderate pulmonary, cardiovascular, or gastrointestinal symptoms; 75.2 kU/l) and severe reactions (grade III, bronchoconstriction, emesis, anaphylactic shock, or loss of consciousness; 56.5 kU/l; P < 0.001). Accordingly, 25% of the patients with low levels of total IgE (<50 kU/l), but no individual with total IgE levels >250 kU/l, developed loss of consciousness (P = 0.001). Additionally, specific IgE levels were related to total IgE levels: Specific IgE levels increased from 1.6 to 7.1 kU/l in patients with low (<50 kU/l) and high (>250 kU/l) total IgE levels, respectively (P < 0.001). Specific IgE levels correlated inversely to the clinical reaction grades, however, this trend was not statistically significant (P = 0.083). CONCLUSION: Patients with Hymenoptera venom allergy and high levels (>250 kU/l) of total IgE, predominantly develop grade I and grade II reactions and appear to be protected from grade III reactions. However, this hypothesis should be confirmed by extended studies with sting challenges.     

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.     

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.     

Introducing chemists to food allergy

Adverse reactions to food may be toxic or non toxic, depending on the susceptibility to a certain food; non toxic reactions that involve immune mechanisms are termed allergy if they are IgE-mediated. If no immunological mechanism is responsible, it is termed intolerance . The following disorders are considered a consequence of food allergy: gastrointestinal reactions (oral allergy syndrome, vomiting, diarrhea, protein-induced enterocolitic syndrome, eosinophilic gastroenteritis); respiratory reactions (rhinitis, asthma, laryngeal edema); cutaneous reactions (urticaria-angioedema, atopic dermatitis); anaphylaxis. There is much recent evidence to consider celiac disease an immunological disorder. Food allergy diagnosis is based on history, SPT, specific IgE, food challenges. DBPCFC is fundamental for diagnosing true food allergy; patients who have had anaphylaxis to food must not undergo DBPCFC. Rapidly progressive respiratory reactions and anaphylactic shock are life-threatening reactions that can be caused by food allergy. The doses of food inducing anaphylaxis can be very low, therefore commercial cross-contamination with an unsuspected food during food processing can be risky for the food allergic patient. The prevention of severe anaphylactic food reactions may lie in interdisciplinary collaboration among allergologists, chemists, food technologists, and experts in food industry research.     

Late-onset allergic reactions, including serum sickness, after insect stings

Allergic reactions after insect stings may have a delayed onset, differing from the usual immediate anaphylactic pattern. Ten patients, aged 6 to 78 years, had allergic reactions 1 to 2 weeks after an insect sting. Six patients had had multiple stings preceding the reaction. In two instances, immediate anaphylaxis also occurred. Four of the 10 patients had serum sickness-type reactions; two other patients had more severe anaphylactic symptoms, including throat edema. All patients in this group had venom-specific IgE; four of the 10 patients had serum venom-specific IgG. Eight patients subsequently received venom immunotherapy (VIT). There have been no reactions from seven re-stings. Five patients had generalized hives starting 6 to 24 hours after an insect sting. All patients in this group had venom-specific IgE; three patients have received VIT. Two other patients developed hives, one with throat edema 3 days after an insect sting. Both patients had high titers of serum venom-specific IgE; neither patient has received VIT, one patient because of extreme sensitivity. These observations suggest that after an insect sting, patients may develop delayed-onset allergic symptoms that range from typical anaphylaxis to serum sickness and are mediated by venom-specific IgE. VIT is recommended for patients with these reactions.     

Usefulness of UniCAP‐Tryptase fluoroimmunoassay in the diagnosis of anaphylaxis

BACKGROUND: Serum tryptase level measured by RIA is the main in vitro tool to confirm the diagnosis of anaphylaxis. METHODS: Serum tryptase levels were determined by UniCAP-Tryptase fluoroimmunoassay (Pharmacia & Upjohn, Uppsala, Sweden), in 30 consecutive patients who presented at the emergency room with a clinical allergic reaction of less than 6-h duration to assess the value of this method in the diagnosis of anaphylaxis. Anaphylaxis was established by clinical criteria and by immunoallergic study. Baseline tryptase levels were determined 1 month later in 21 patients. The receiver operating curve (ROC) was used to establish the best cutoff point of tryptase levels to confirm the diagnosis of anaphylaxis. RESULTS: Seventeen patients were diagnosed with anaphylaxis. In this group, tryptase levels were higher than in the nonanaphylaxis group, composed mostly of patients with urticaria or angioedema (P<0.001). ROC established the best cutoff of tryptase levels at 8.23 ng/ml with a 94.12% sensitivity and 92.31% specificity, whereas the 13.5 ng/ml cutoff recommended by the manufacturers showed 35.29% sensitivity and 92.31% specificity. The reaction-tryptase/baseline-tryptase ratio was 2.85 in the anaphylaxis group and 1.29 in the nonanaphylaxis group. CONCLUSIONS: Serum tryptase levels of >8.23 ng/ml by UniCAP-Tryptase fluoroimmunoassay identify anaphylaxis in patients with symptoms of less than 6-h duration. The usefulness of this determination is higher if baseline tryptase levels are available.     

How much specific is the association between hymenoptera venom allergy and mastocytosis?

Background:  The preferential association of mastocytosis with hymenoptera sting reactions is well known, but there is no data on the prevalence of clonal mast cell disorders in subjects with severe systemic reactions due to foods or drugs.
Methods:  Patients with food- or drug-induced severe systemic reactions, including anaphylaxis, and increased serum tryptase were studied for the presence of mastocytosis, and compared with a population of patients with hymenoptera allergy. The aetiological role of foods or drugs was assessed according to current recommendations. Systemic reactions were graded in severity according to the procedure described by Mueller. Serum tryptase was considered increased if the level was >11.4 ng/ml. Subjects with increased tryptase had dermatological evaluation and Bone marrow(BM) aspirate-biopsy, which included histology/cytology, flow cytometry and detection of KIT mutations.
Results:  A total of 137 subjects (57 male, mean age 42 years) were studied. Of them, 86 proved positive for drugs and 51 for foods. Overall, out of 137 patients, only nine (6.6%) had a basal tryptase >11.4 ng/ml, and only two (1.5%) were diagnosed with mastocytosis. This was clearly different from patients with hymenoptera allergy, where 13.9% had elevated tryptase and 11.1% had a clonal mast cell disorder.
Conclusion:  The association of clonal mast cell disorders with hymenoptera allergy seems to be more specific than that with food- or drug-induced systemic reactions.     

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.     

Anaphylaxis: can we tell who is at risk of a fatal reaction?

PURPOSE OF REVIEW: Anaphylaxis is frightening and patients commonly fear their next reaction will be fatal. This review looks at the characteristics of fatal reactions to find if a fatal recurrence is predictable. RECENT FINDINGS: Most publications on fatal anaphylaxis are case reports that do not help predict risks. Most epidemiological studies focus on non-fatal reactions. The UK fatal anaphylaxis register demonstrates that over two-thirds of those dying from sting reactions and over four-fifths dying from drug anaphylaxis had no previous indication of their allergy, whereas those dying from food allergy had usually had previous reactions but these were typically not severe. Recent reports of anaphylaxis epidemiology based on diagnostic coding or attendance for treatment may be biased by differences in health service resource utilization according to the cause and course of the reaction. SUMMARY: Most fatal anaphylactic reactions are unpredictable. The appropriate management after recovery from a severe reaction may be protective against a fatal recurrence. An accurate identification of the cause and effective avoidance is a crucial part of this management, together with effective treatment of asthma for those with food allergy, immunotherapy for sting allergy, the avoidance of drugs that potentiate anaphylaxis, and effective training in self-treatment.     

Insect-sting challenge in 138 patients: relation between clinical severity of anaphylaxis and mast cell activation.

One hundred thirty-eight patients with a previous anaphylactic reaction to a yellow jacket or a honeybee sting, as well as eight volunteers, were subjected to an in-hospital sting challenge. Plasma levels of histamine, tryptase, and prostaglandin D2 (PGD2) during sting challenge were studied in relation to clinical symptoms. Prechallenge levels (mean +/- SD) of histamine, tryptase, and PGD2 were 2 +/- 1 nmol/L, 0.3 +/- 0.3 U/L, and 320 +/- 223 ng/L, respectively. In the volunteers and in none except for one of the nonreacting patients, these levels did not change significantly after challenge. In contrast, mean increases in the group of 18 patients with a mild reaction were significant for histamine and tryptase at one or more time points after the challenge. (Five patients demonstrated no increase in histamine; nine demonstrated no increase in tryptase.) Except for histamine levels in one patient, these increases were considerably more in all 17 patients with a severe reaction, starting from the first anaphylactic symptoms. Fifteen minutes later, peak values were reached of 1275 +/- 2994 nmol of histamine per liter (range, 3 to 12800 nmol/L; median, 11 nmol/L) and 406 +/- 1062 U of tryptase per liter (range, 1.8 to 4400 U/L; median, 17 U/L). This rise in levels inversely correlated with the mean arterial pressure. Plasma levels of PGD2 in severely reacting patients did not differ significantly from those in patients with a mild or no reaction. In conclusion, only 28% of patients with a history of Hymenoptera anaphylaxis developed an anaphylactic reaction after an in-hospital challenge.(ABSTRACT TRUNCATED AT 250 WORDS)