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Incidence and characteristics of biphasic anaphylaxis: a prospective evaluation of 103 patients.

BACKGROUND: Although it is known that anaphylaxis can follow a biphasic course, reports of its incidence are conflicting. Furthermore, little is known about predictors of biphasic reactivity. OBJECTIVE: To describe the incidence and characteristics of biphasic anaphylaxis occurring in a Canadian tertiary care center. METHODS: All patients with emergency department visits and inpatients given a diagnosis of "allergic reaction" or "anaphylaxis" during a 3-year period were evaluated. Patients were contacted within 72 hours to establish symptoms and determine the presence of biphasic reactivity. A full medical record review ensued, and uniphasic and biphasic cases were compared using the Mann-Whitney U test for continuous data and the chi2 and Fisher exact tests for ordinal data. RESULTS: A total of 134 patients with anaphylaxis were identified; complete follow-up was obtained for 103 patients. Twenty patients (19.4%) experienced confirmed biphasic reactivity. Average time to onset of the second phase was 10 hours (range, 2-38 hours); 8 patients (40.0%) had their second phase occur more than 10 hours after the initial reaction. The clinical presentations and histories of uniphasic and biphasic reactors were similar. Time to resolution of initial symptoms was significantly longer for biphasic reactors (112 vs 133 minutes; P = .03). Differences in management were noted: biphasic reactors received less epinephrine (P = .048) and tended to receive less corticosteroid (P = .06). CONCLUSIONS: Biphasic reactivity occurred with an incidence of 19.4%, consistent with first descriptions. The second-phase onset was 10 hours on average, but it occurred as late as 38 hours. Biphasic anaphylaxis may be related, in part, to undertreatment.

Adolescent↗

Nitrate anaphylaxis.

BACKGROUND: Nitrate and nitrite salts are commonly used to preserve and sustain color in a number of processed meats. To date there have been no described cases of anaphylaxis to either nitrates or nitrites in the literature. OBJECTIVE: We report a patient with anaphylaxis to nitrates and nitrites documented by double-blind, placebo-controlled capsule challenge. METHODS: A 22-year-old previously well male, presented to a tertiary referral center with a 4-year history of recurrent anaphylaxis after eating take-out food. No further episodes occurred while adhering to a strict elimination diet. We performed a double-blind, placebo-controlled capsule challenge both with food substances and starch placebo. These occurred in a hospital setting with full resuscitative procedures available. RESULTS: An acute anaphylactic reaction occurred following a challenge to nitrates and nitrites. Generalized allergic reactions were observed on separate occasions following administration of artificial colorings and metabisulfite. There was a mild urticarial reaction following salicylates. He was placed on a diet free of sulfites, nitrates, nitrites, and low in salicylates and he has had no further reactions. A computer based search of the Medline, Current Contents and EMBASE databases found no previously reported cases of urticaria, angioedema, or anaphylaxis to either nitrates or nitrites. CONCLUSION: The ingestion of processed meats containing nitrate or nitrite salts may be associated with angioedema and anaphylaxis and should be considered when investigating patients with suspected food allergy.

Adult↗

Food-induced anaphylaxis.

To date, there are no population-based epidemiologic studies providing information about the prevalence of food-induced anaphylaxis. However, statistics from the United Kingdom demonstrated an increase of anaphylaxis from 5.6 cases per 100,000 hospital discharges in 1991-92 to 10.2 cases in 1994-95. The increase for the subcategory of food-induced anaphylaxis was above the overall increase in anaphylaxis. In the UK register of fatal anaphylactic reactions, all food-induced fatalities have been accompanied by respiratory problems with respiratory arrest. Atopic individuals with bronchial asthma and prior allergic reactions to the same food are at a particularly high risk. Not only peanuts, seafood and milk can induce severe, potentially lethal, anaphylaxis, but indeed a wide spectrum of foods, according to the different patterns of food sensitivity in different countries. Foods with "hidden" allergens and meals at restaurants are particularly dangerous for patients with food allergies. Similarly, schools, public places and restaurants are the major places of risk. However, the main factor contributing to a fatal outcome is the fact that the victims did not carry their emergency kit with adrenaline (epinephrine) with them. Therefore, we suggest that the pharmaceutical industry should reintroduce an adrenaline inhaler that is more effective, especially in asthmatic reactions.

Anaphylaxis↗

Rocuronium and anaphylaxis--a statistical challenge.

Drug induced anaphylaxis is frequently attributed to the use of muscle relaxants during anaesthesia. Recently The Norwegian Medicines Agency recommended that rocuronium bromide (Esmeron) be withdrawn from routine practice due to frequent reports of anaphylaxis. Over a period of two and a half years approximately 150,000 patients received rocuronium as part of their anaesthesia. In this period the Norwegian drug authorities received 29 reports of anaphylaxis or anaphylactoid reactions in patients treated with rocuronium. This is in stark contrast to the situation in other Nordic countries where a total of only seven cases of anaphylaxis in approximately 800,000 patients treated with rocuronium had been recorded by December 2000. This situation highlights the many potential problems of the surveillance of adverse drug reactions: reporting bias may lead to an over-estimate of the risk of one drug compared to another, and the possibility of under-reporting of adverse events (due to a weak reporting culture) further limit the validity of such comparisons. The surveillance of adverse drug reactions also represents a statistical challenge. While adverse event reports may help us to estimate the anaphylaxis rate we need to appreciate the uncertainty of such estimates. Adverse reactions are rare, random, and mostly independent events, resulting from the successive exposure of patients to a low risk intervention. The frequency distribution of adverse events will therefore conform to that of a Poisson process. The resulting Poisson distribution may inform us about the variability of adverse event data. An understanding of these methodological problems and statistical challenges will allow anaesthesiologists to make informed decisions concerning the use of muscle relaxants and other drugs associated with severe adverse reactions.

Adverse Drug Reaction Reporting Systems↗

Rye gamma-70 and gamma-35 secalins and barley gamma-3 hordein cross-react with omega-5 gliadin, a major allergen in wheat-dependent, exercise-induced anaphylaxis.

Patients with wheat-dependent, exercise-induced anaphylaxis experience severe allergic reactions when exercising after ingestion of wheat. The major wheat allergen associated with these reactions is a omega-5 gliadin, and patients following a gluten-free diet have remained free of symptoms. The aim of this study was to examine whether allergens cross-reacting with wheat omega-5 gliadin are present in rye, barley and oats. Sera from 23 adult patients with wheat-dependent, exercise-induced anaphylaxis were examined. Cereal allergens cross-reacting with wheat omega-5 gliadin were identified by immunoblot inhibition. The cross-reactive allergens were purified by gel filtration and reversed-phase chromatography and submitted to amino acid sequencing. Cross-reactivity was further studied by IgE ELISA and ELISA inhibition, and in vivo reactivity by skin prick testing. In immunoblotting rabbit anti-omega-5 gliadin antibodies bound to 70 kDa and 32 kDa proteins in rye and a 34-kDa protein in barley, but not to proteins in oats. N-terminal sequencing identified these proteins as rye gamma-70 secalin, rye gamma- 35 secalin and barley gamma-3 hordein, correspondingly. In ELISA 21/23 (91%) patients with wheat-dependent, exercise-induced anaphylaxis showed IgE antibodies to purified gamma-70 secalin, 19/23 (83%) to gamma-35 secalin and 21/23 (91%) to gamma-3 hordein. In ELISA inhibition omega-5 gliadin inhibited over 90% of the IgE binding of pooled patient sera to solid-phase gamma-secalins and gamma-3 hordein. Skin prick testing gave positive reactions to gamma-70 secalin in 10/15 (67%) patients, to gamma-35 secalin in 3/15 (20%) patients and to gamma-3 hordein in 7/15 (47%) patients. The results of this study show that gamma-70 and gamma-35 secalins in rye and gamma-3 hordein in barley cross-react with omega-5 gliadin, a major allergen in wheat-dependent, exercise-induced anaphylaxis. These findings suggest that also rye and barley may elicit symptoms in patients with wheat-dependent, exercise-induced anaphylaxis.

Adolescent↗

An inhibitor of poly(adenosine 5'-diphosphoribose) synthetase, 3-aminobenzamide, does not improve cardiovascular depression, bronchospasm, or survival associated with systemic anaphylaxis in rabbits in vivo.

We investigated whether an inhibitor of poly(adenosine 5'-diphosphoribose) synthetase (PARS) is beneficial in anaphylaxis. Twenty-eight rabbits were randomly allocated to three groups: Group I (control) received .9% NaCl solution 10 min before antigen challenge followed by the infusion of the same solution. Group II (3-aminobenzamide 20 mg.kg-1) received 20 mg.kg-1 of 3-aminobenzamide (a PARS inhibitor) 10 min before antigen challenge followed by the continuous infusion of 20 mg.kg-1 of 3-aminobenzamide. Group III received 40 mg.kg-1 10 min before antigen challenge followed by the continuous infusion of 20 mg.kg-1 of 3-aminobenzamide. Survival were similar between three groups. Heart rate, mean arterial pressure (MAP), central various pressure, and pulmonary resistance did not differ between three groups. Dynamic pulmonary compliance did not differ in the early phase after the antigen challenge; however, it was significantly lower in Group III than in Groups I and II 15 min after the initiation of anaphylaxis. 3-aminobenzamide per se did not affect heart rate, MAP, central venous pressure, pulmonary resistance, or dynamic pulmonary compliance in animals without systemic anaphylaxis. In conclusion, this PARS inhibitor did not improve cardiovascular depression or bronchospasm in the early phase of systemic aggregated anaphylaxis in rabbits in vivo, implying that the pathophysiological changes associated with systemic anaphylaxis may not be related to activation of an energy-consuming DNA repair cycle triggered by PARS.

Anaphylaxis↗

Update on the clinical features of food-induced anaphylaxis.

Food-induced anaphylaxis has become the leading cause of anaphylactic reactions that occur outside hospital. We introduce the present review with a definition of food-induced anaphylaxis, including its prevalence and proposed etiology. Second, we discuss an entity that is increasingly being recognized: exercise-induced food anaphylaxis, which may be triggered by specific foods or at times where no specific food has been identified. Third, we review current attempts to identify specific food antigens that are responsible for anaphylaxis to well-known triggers (i.e. peanut, as well as more unusual antigens). Fourth, we discuss current treatment options available (i.e. patient education, food avoidance, acute symptom recognition, and early use of self-administered epinephrine). Additionally, we discuss outcome data regarding the morbidity and mortality related to food allergy and anaphylaxis. Finally, information regarding experimental immunomodulatory therapy is presented.

Anaphylaxis↗

Emergency treatment and prevention of insect-sting anaphylaxis.

PURPOSE OF REVIEW: Hymenoptera stings are thought to cause systemic allergic reactions in 0.4-5% of individuals, and to account for 40-100 deaths annually in the USA. This review examines current research on insect-sting anaphylaxis in the emergency department (ED), and provides suggestions on how to improve ED treatment and prevention. RECENT FINDINGS: Few published studies since January 2005 examine the emergency management of insect-sting allergic reactions. Earlier studies found that few ED patients with this problem received health education, a prescription for self-injectable epinephrine or referral to an allergy specialist at ED discharge. A recent multicenter study by our group demonstrated that ED patients with insect-sting allergic reactions continue to receive care discordant with national guidelines for the emergency management of anaphylaxis. SUMMARY: Concordance with national guidelines for the treatment of anaphylaxis remains poor among insect-sting allergy patients. The development of a simple, clinical definition of anaphylaxis is urgently needed to facilitate identification of cases. Such a definition would help tremendously with dissemination of emergency management guidelines and the creation of systems for their implementation. All of these steps are essential for the improved treatment and prevention of insect-sting anaphylaxis in the ED.

Anaphylaxis↗

Vasopressin may be useful in the treatment of systemic anaphylaxis in rabbits.

Recent studies demonstrate that vasopressin is useful when treating hemorrhagic and septic shock. The effect of vasopressin on systemic anaphylaxis has not been investigated except in clinical case reports. Vasopressin increases blood pressure because of vasoconstriction through the V1 receptor. Thus, we evaluated the effect of vasopressin on circulatory depression and bronchoconstriction provoked by systemic anaphylaxis and survival rates in rabbits. In the first set of experiments, 15 nonsensitized rabbits received normal saline (control) and vasopressin at 0.8 or 0.08 U/kg. In the second set, 40 sensitized rabbits received horse serum to induce anaphylaxis, and then received the same drugs as in the first set. In the first set, mean arterial pressure (MAP) in vasopressin groups increased by 18% to 24% compared with the control. Vasopressin at 0.8 U/kg decreased MAP insignificantly before the increases of MAP occurred. In the second set, vasopressin at 0.08 U/kg improved the survival rate. At 45 min after antigen challenge, 69% of the rabbits that received vasopressin at 0.08 U/kg were alive, whereas 29% of the control rabbits and 23% of the rabbits that received vasopressin at 0.8 U/kg were alive. Vasopressin increased MAP by 36% to 109% compared with the control within 5 min, however, at 2 min, vasopressin at 0.8 U/kg had no effect on MAP. Pulmonary dynamics were similar. In conclusion, vasopressin at 0.08 U/kg improved survival rates and severe hypotension provoked by systemic anaphylaxis, suggesting that this agent may be useful in the treatment of systemic anaphylaxis.

Anaphylaxis↗

Update on epinephrine for the treatment of anaphylaxis.

PURPOSE OF REVIEW: Epinephrine is the treatment of choice for anaphylaxis--a life-threatening and potentially fatal event. The purpose of this review is to highlight recent publications relevant to the management of anaphylaxis and identify potential barriers which prevent or delay appropriate administration of epinephrine. RECENT FINDINGS: Experts have moved towards a consensus on how to define anaphylaxis, which has a variable clinical presentation. A clear definition, across specialties, is necessary for more accurate determinations of prevalence, diagnosis and management. Epinephrine injected intramuscularly is the treatment of choice, but there remain gaps in physician knowledge despite increases in hospitalization rates for anaphylaxis. Epinephrine is also underused by parents, day-care centers and schools. Barriers to access for treatment exist in lower socioeconomic groups. Women appear to be at risk for suboptimal treatment when autoinjectors are used. Given these issues, other routes of administration of epinephrine have been explored. Epinephrine delivered via a sublingual route has been successful in animal studies. SUMMARY: Epinephrine is the primary therapy for anaphylaxis, yet studies show that it is underutilized. By addressing the contributory factors that have been identified, acute and long-term care of individuals with this potentially life-threatening disorder can be optimized.

Administration, Sublingual↗

Evaluation of left ventricular diastolic function in IgE-mediated anaphylaxis in dogs.

Depressed left ventricular (LV) systolic function remains controversial in patients with anaphylaxis and anaphylactic animal models. However, LV diastolic function has not yet been investigated in either patients or animal models. Therefore, we assessed LV diastolic and systolic function in IgE-mediated anaphylaxis in dogs. Seven dogs sensitized to Ascaris suum antigen were studied. An aqueous extract of Ascaris suum antigen was administered over 30 s into the systemic circulation to induce anaphylaxis. To assess LV function, the time constant of the fall of isovolumic LV pressure (T), as an index of LV diastolic function, and the maximum rate of rise of LV pressure (dP/dtmax), as an index of LV systolic function, were measured for a period of 120 min after antigen challenge. T was prolonged during the period of 5 to 15 min; however, changes in T were not significantly different from prechallenge values. LV d}/dtmax significantly decreased to 0.49 +/- 0.12 times the prechallenge value 5 min after antigen challenge, and significantly increased during the period from 30 to 120 min. However, these changes in dP/dtmax almost paralleled the changes in LV end-diastolic pressure, indicating that left ventricular systolic function was relatively well preserved. In conclusion, LV diastolic function, i.e., isovolumic relaxation, is little impaired in anaphylaxis, and LV systolic function is relatively well preserved during the early stage following the onset of anaphylaxis.

Anaphylaxis↗

Cardiopulmonary distress during obstetrical anaesthesia: attempts to diagnose amniotic fluid embolism in a case series of suspected allergic anaphylaxis.

BACKGROUND: Cardiopulmonary distress during obstetrical anaesthesia may result from a drug-induced allergic reaction, but, in the obstetrical setting, allergic anaphylaxis may be inseparable from amniotic fluid embolism in terms of the clinical presentation. Further investigations, using allergy tests and other laboratory analyses, are then needed to pursue a diagnostic clarification. METHODS: Twelve women suspected of having developed anaphylaxis during obstetrical anaesthesia underwent allergy follow-up investigations and further serological tests with the amniotic fluid embolism marker sialyl Tn and complement factors (C3 and C4) in an attempt to differentiate amniotic fluid embolism from drug-induced allergic anaphylaxis. RESULTS: The diagnostic programme revealed one case of probable amniotic fluid embolism and four cases of probable drug-induced allergic anaphylaxis. Of the remaining seven cases, there were two cases that, by diagnostic exclusion, could be classified as possible cases of amniotic fluid embolism. The cause of the reactions remained unresolved in five cases. CONCLUSIONS: It can be difficult to differentiate between anaphylaxis and amniotic fluid embolism, especially amongst survivors. Diagnostic markers that can be applied on peripheral blood samples are promising, but larger studies are needed to validate their use in the diagnosis of causes of cardiopulmonary distress during obstetrical anaesthesia.

Adult↗

Immunologic and clinical responses to parenteral immunotherapy in peanut anaphylaxis--a study using IgE and IgG4 immunoblot monitoring.

BACKGROUND: Specific desensitisation to food allergens, which produce anaphylaxis after ingestion, has not been considered as a treatment for food allergy until recently. The purpose of this study was to assess if a parenteral immunotherapy program, using a partially characterised crude peanut extract, could induce a state of immunological tolerance in a patient who exhibited anaphylaxis, asthma and urticaria on exposure to peanut and other legumes. A further aim was to measure the serum antibody responses to the immunotherapy. METHODS AND RESULTS: We report the successful desensitisation towards all of the legumes tested of a male patient on parenteral immunotherapy using a partially characterised peanut extract. The immunologic parameters measured during treatment included specific IgE and IgG4 for peanut, soybean, pea and lentil extracts. Immunoblots of specific IgE and IgG4 were made before and after therapy. The antibody response followed the same pattern seen in successful desensitisation of patients with bee venom anaphylaxis. The IgG4 levels increased strongly from a low pre-treatment level in proportion to the antigen dose received. The antigen-specific IgE levels gradually fell from a high pretreatment level, but remained significantly elevated. Immunoblotting for specific IgE and IgG4 demonstrated that acquisition of clinical tolerance after therapy was associated with declines in the number and intensity of bands in IgE blots and the development of more bands of increasing density in the IgG4 blots. CONCLUSIONS: Parenteral immunotherapy may offer an alternative treatment to lifelong dietary restriction and epinephrine injections in patients who exhibit life-threatening IgE-mediated anaphylaxis to peanut. Cross desensitisation to other legumes appears to have occurred in this study. The quality and potency of the extract used is an important factor in achieving the desired acquisition of clinical tolerance. In our patient this tolerance correlated with his ability to maintain high levels of specific IgG4, which acted as a marker of protection against anaphylaxis. The use of IgG4 immunoblotting may provide an improved level of discrimination in the assessment of correlation of clinical efficacy with the immunologic response.

Adolescent↗

Cardiac anaphylaxis. Complement activation as an amplification system.

Complement is activated, and C3a and C5a anaphylatoxins are generated during hypersensitivity reactions clinically associated with cardiopulmonary collapse. The administration of C3a or C5a to nonsensitized isolated guinea pig hearts mimics the events caused by antigen challenge of sensitized hearts (i.e., cardiac anaphylaxis) in the absence of complement. Thus, complement-derived anaphylatoxins may participate in immediate hypersensitivity reactions in which the heart is a target organ. To assess the contribution of complement activation and anaphylatoxin generation to cardiac dysfunction, we have elicited anaphylaxis in isolated guinea pig hearts in the presence of complement and found that the ensuing dysfunction is markedly enhanced. This amplification is most likely attributable to anaphylatoxin formation because 1) inactivation of C3 or selective C3 depletion, i.e., the loss of the component responsible for the formation of the anaphylatoxins C3a and C5a, prevents complement-induced exacerbation of cardiac anaphylaxis, whereas reconstitution with C3 and C5, or even only C3, restores it; in fact, the greater the C3 content at the time of antigen challenge, the more intense the anaphylactic crisis; and 2) the severity of cardiac anaphylaxis is markedly reduced by preexposure to C3a, and this reduction is directly related to the dose of C3a injected and to the amount of endogenous cardiac histamine depleted by C3a before antigen challenge. Complement-derived anaphylatoxins appear to promote the same mediator release that has been initiated by the antigen-antibody reaction; thus, complement activation functions as an amplification system in cardiac anaphylaxis.

Anaphylatoxins↗

Zinc and intestinal anaphylaxis to cow's milk proteins in malnourished guinea pigs.

Zinc supplementation could favor recovery from diarrhea in malnourished children. As the recent experimental evidence suggests that oxidative stress and intestinal anaphylaxis may contribute to the intestinal dysfunction associated with malnutrition, we postulated that zinc could act through antioxidant or antianaphylactic properties. Control (C), malnourished (M), and malnourished zinc-treated (MZ) guinea pigs were, respectively, fed a normal 30% protein diet, a low 4% protein diet, and a low 4% protein diet plus 1800 ppm of zinc. Milk proteins were included in the diets to trigger intestinal anaphylaxis. Milk sensitization was assessed by passive cutaneous anaphylaxis (PCA) against beta-lactoglobulin and by intestinal anaphylaxis measured in Ussing chambers by the increase in short circuit-current after addition of beta-lactoglobulin (deltaIsc(betaLg)). Oxidative stress was assessed by intestinal lipid peroxidation. The intestinal secretion was assessed by deltaIsc induced by inflammatory mediators. Malnutrition increased the level of anti-betaLg reaginic antibodies [PCA = 1.19 +/- 0.79 and 0.69 +/- 0.67 log(l/titer) in M versus C guinea pigs, p = 0.07] and enhanced intestinal anaphylaxis (deltaIsc(betaLg)) = 16.4 +/- 9.9 and 9.1 +/- 5.8 microA/cm2 in M versus C guinea pigs, p = 0.07), without inducing intestinal lipid peroxidation. Moreover, malnutrition enhanced significantly the intestinal secretory response to histamine and 5-hydroxytryptamine. Administration of pharmacologic doses of zinc during malnutrition inhibited the increase in milk sensitization induced by malnutrition, both at the systemic [PCA = 0.35 +/- 0.55 log(l/titer) in MZ guinea pigs, p = 0.03 versus M] and intestinal (deltaIsc(betaLg)) = 2.8 +/- 2.5 microA/cm2 in MZ guinea pigs; p = 0.001 versus M) level, and prevented the hypersecretion in response to histamine and 5-hydroxytryptamine. These data suggest that zinc has antianaphylactic and antisecretory properties that may contribute to its capacity to prevent intestinal dysfunction during malnutrition.

Anaphylaxis↗

Methylxanthine use in anaphylaxis: what does the evidence tell us?

OBJECTIVE: To review the literature examining the use of methylxanthines in the treatment of anaphylaxis. DATA SOURCES: A MEDLINE search (January 1966-December 1998) was performed using the terms aminophylline, theophylline, and anaphylaxis. STUDY SELECTION AND DATA EXTRACTION: Articles discussing methylxanthine use in anaphylaxis were independently examined by each author. Additional information was obtained through the references of these articles. Articles not written in English were excluded. DATA SYNTHESIS: No human studies were identified. Limited published data were found in animal models of anaphylaxis. CONCLUSIONS: Safer agents with proven efficacy exist for the treatment of bronchoconstriction in anaphylaxis. Until data are available in humans, methylxanthines should not be recommended in the treatment of anaphylactic reactions.

Anaphylaxis↗

Prevalence of anti-gelatin IgE antibodies in people with anaphylaxis after measles-mumps rubella vaccine in the United States.

OBJECTIVE: Anaphylaxis after immunization, although rare, is serious and potentially life-threatening. Understanding risk factors for this reaction is therefore important. Gelatin is added to many vaccines as a heat stabilizer. Japanese researchers have demonstrated a strong association between immediate hypersensitivity reactions to measles, mumps, rubella, varicella, and Japanese encephalitis immunizations and subsequent detection of anti-gelatin immunoglobulin E (IgE) antibodies. They suggested that previous receipt by these patients of diphtheria-tetanus-acellular pertussis vaccines with trace amounts of gelatin was responsible for the sensitization. We aimed to assess whether a similar association exists for vaccinees in the United States who reported anaphylaxis after receipt of measles-mumps-rubella (MMR) or measles vaccines and to review recent trends in reporting of hypersensitivity reactions. METHODS: We conducted a retrospective case-control study. Cases of anaphylaxis that met a predefined case definition were identified from the US Vaccine Adverse Event Reporting System (VAERS). Mayo Clinic patients who received MMR vaccine uneventfully served as controls. The study subjects were interviewed to obtain the history of allergies. Sera from study subjects and their matched controls were tested for IgE antibodies to gelatin, whole egg, and vaccine viral antigens using solid-phase radioimmunoassay. Data from the Biologics Surveillance System on annual numbers of doses of MMR and varicella vaccines distributed in the United States were used to evaluate possible changes in reporting of selected allergic adverse events. RESULTS: Fifty-seven study subjects were recruited into the study and interviewed. Of these, 22 provided serum samples for IgE testing. Twenty-seven subjects served as a comparison group and provided a sample for IgE testing; 21 of these completed an allergy history questionnaire. Self-reported history of food allergies was present more frequently in the interviewed study subjects than in the controls, whereas the proportions of people with other characteristics were similar in both groups. None of the interviewed people had a history of food allergy to gelatin. The level of anti-gelatin IgE antibodies was significantly higher among study subjects than among controls, whereas the levels of IgE antibodies against egg and all 3 viral antigens did not differ significantly. Of 22 study subjects, 6 (27%) tested positive for anti-gelatin IgE, whereas none of the 27 controls did. The rate of anaphylactic reactions reported to VAERS after measles virus-containing immunization in the United States between 1991 and 1997 is 1.8 per 1 million doses distributed. No substantial increase in the number of reported allergic events after frequently used gelatin containing MMR and varicella vaccines could be observed during the first 4 years (1997-2000) since the introduction of diphtheria-tetanus-acellular pertussis vaccines for use in infancy. CONCLUSION: Anaphylactic reactions to MMR in the United States are rare. The reporting rate has the same order of magnitude as estimates from other countries. Almost one fourth of patients with reported anaphylaxis after MMR seem to have hypersensitivity to gelatin in the vaccine. They may be at higher risk of developing anaphylaxis to subsequent doses of other gelatin-containing vaccines. These people should seek an allergy evaluation before such immunization.

Anaphylaxis↗

Exercise-induced anaphylaxis.

Anaphylaxis, the most emergent manifestation of allergy, is best described by its clinical pathologic alterations. Sites of involvement include skin (urticaria), upper respiratory tract (laryngeal edema), lower respiratory tract (bronchospasm), and the cardiovascular system (severe hypotension). Ultrastructural analysis of skin biopsies obtained from individuals experiencing exercise-induced anaphylaxis prior to and immediately after exercise revealed changes indistinguishable from those observed following immunologic challenge of pulmonary mast cells. These alterations included enlargement of the mast cell granules, solubilization (discharge) of mast cell granule contents, merger of the granule membranes with adjacent granule membranes, as well as the mast cell membrane. The successful reversal of anaphylaxis requires the prompt recognition of symptoms and early institution of therapy for anaphylaxis. Patients suffering from exercise-induced anaphylaxis should avoid any foods, drinks, or pharmaceutical agents, particularly acetyl salicylic acid for four and preferably six hours prior to exercise.

Anaphylaxis↗