Modified Basophil Degranulation Test in Diagnosis of Bee and Wasp

A modified basophil degranulation test proved reliable and easily reproducible in the investigation of 50 patients with allergies to bee and/or wasp stings. Its diagnostic value is comparable to that of the RAST and it is, in addition, simpler, quicker and cheaper. Its disadvantage is that it has to be performed within 24-36 hours after withdrawal of blood.     

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.     

Development of a new,more sensitive immunoassay for human tryptase: Use in systemic anaphylaxis

Tryptase, a neutral protease, is selectively concentrated in the secretory granules of human mast cells, and its release into the circulation serves as a clinical marker of mast cell activation. The current study describes a new, more sensitive ELISA utilizing a newly developed, mouse monoclonal IgG1 antibody for capture called B12 and capable of detecting tryptase in normal plasma and serum. The greater sensitivity of the new immunoassay results in part from a greater portion of tryptase being detected. Mean levels of tryptase in serum from normal subjects from Richmond, Virginia (4.9 ng/ml;n=56), Munich, Germany (3.8 ng/ml;n=19), and Amersfoort, The Netherlands (1.9 ng/ml;n=8) were as indicated. In 62 subjects with ongoing allergic rhinitis, tryptase levels were no different in serum than for 19 normal controls, indicating that local mast cell activation is not necessarily reflected in the circulation. In 61 subjects sensitive to honey bee or yellow jacket venom by history, the 17 destined to have a severe, hypotensive response to a sting challenge had higher levels of tryptase at baseline than mild reactors, nonreactors, and controls, suggesting that baseline levels of tryptase may predict the severity of the clinical response to allergen in sensitive subjects.     

Anaphylactic reactions in children--a questionnaire-based survey in Germany

BACKGROUND: Severe anaphylactic reactions are medical emergencies requiring immediate recognition and treatment. Despite this, little is known on their clinical features, especially in infants and children. OBJECTIVE: To evaluate trigger factors, patterns of clinical reaction, site of occurrence and treatment modalities of reported reaction in infants and children below 12 years of age in Germany. METHODS: Paediatricians throughout Germany were asked by questionnaire to report accidental anaphylactic reactions over the previous 12 months. Severity of reported reactions was classified in grades I-IV according to reported symptoms. RESULTS: Hundred and three cases of anaphylaxis were evaluated. Median age was 5 years, 58% were boys. Site of occurrence was the child's home in the majority of cases (58%). Foods were the most common causative allergen (57%), followed by insect stings (13%) and immunotherapy (SIT) (12%); in 8% anaphylactic agent was unknown. Among foods, peanuts and tree nuts were the most frequent allergens (20% of food allergens in each case). Severe reactions with cardiovascular involvement occurred in 24% of cases. No fatal reaction was observed. Recurrent episodes of anaphylaxis were reported in 27% of cases, half of these caused by the same allergen again. For treatment, 20% of children received adrenaline, in 8% of cases intravenously. Thirty-six per cent of patients with grade-IV reactions received adrenaline, 24% intravenously. In 17% of all children an adrenaline self-injector was prescribed after the episode. CONCLUSION: Our data: (i) shows an uncertainty of physicians in diagnosing anaphylaxis, (ii) reveals remarkable under-treatment of the majority of children with anaphylaxis, (iii) reflects the need for guidelines and training for physicians in managing children with anaphylaxis and (iv) should encourage the development of self-management programmes for patients and families.     

Prevalence of allergy and anaphylactic symptoms in 210 adult and pediatric patients with mastocytosis in Spain: a study of the Spanish network on mastocytosis (REMA)

BACKGROUND: Mast cells (MCs) play a key role in allergic diseases through the release of inflammatory mediators, which are responsible of allergic symptoms. Mastocytosis is characterized by an abnormal proliferation and accumulation of mast cells, in which mediators are released intermittingly or continuously. Despite these clinical similarities, few studies have addressed the presence of allergic symptoms in mastocytosis patients, including anaphylaxis. OBJECTIVE: A prospective evaluation was carried out to study the prevalence of allergic diseases in patients with mastocytosis and their impact on the natural history of mastocytosis. METHODS: A questionnaire was given to 210 patients with mastocytosis to evaluate the history of asthma, rhinitis, conjunctivitis, atopic dermatitis, urticaria and anaphylaxis. Patients underwent total IgE, Phadiatop infant (aeroallergens and food allergens), specific IgE to latex and to Anisakis simplex determinations. Skin tests were done to 72 patients. RESULTS: The prevalence of allergy, as defined by clinical symptoms associated to specific IgE, was 23.9%. Total IgE level was significantly higher in patients with allergy as compared with patients without allergy (median 58 vs. 16.5 kU/L, P<0.0001). Anaphylactic symptoms were present in 36 patients (22%), in nine the allergen was identified. Males had more allergy and anaphylactic symptoms than females (61.5% vs. 38.5% and 72% vs. 28%, respectively). CONCLUSIONS: Allergic diseases coexist in patients with mastocytosis with similar frequency as compared with the general population. Anaphylactic symptoms are more prevalent in males with mastocytosis and in patients with elevated IgE. CAPSULE SUMMARY: The prevalence of allergy in mastocytosis is similar to the general population. Anaphylactic symptoms are more prevalent in males and in patients with elevated IgE. The coexistence of atopy does not influence mastocytosis-associated symptoms.     

Anaphylaxis to chlorhexidine. Case report. Implication of immunoglobulin E antibodies and identification of an allergenic determinant

BACKGROUND: There are many reports of allergic reactions, including anaphylaxis, following exposure to chlorhexidine. Reactions may occur via contact with the skin and mucous membranes or from catheters treated with the antibacterial agent. Apart from implicating chlorguanide in immunoglobulin (Ig) E antibody-binding studies on serum from an anaphylactic patient, little work has been done on the molecular basis of recognition of the agent in sensitive subjects. OBJECTIVES: The molecular basis of IgE-binding to chlorhexidine was closely examined with the view of defining its fine structural recognition features by antibodies from a subject who experienced anaphylaxis following contact with the antiseptic. METHODS: Tryptase determinations, different drug-solid phases, immunoassays and quantitative hapten inhibition studies with chlorhexidine and selected structural analogues were employed together with serum from the anaphylactic patient. Results were analysed to define the complete drug allergenic determinant and to identify the important structural features complementary to the IgE antibody combining sites. RESULTS: The subject's serum tryptase levels sampled after the reaction were elevated and employment of a chlorhexidine-EA Sepharose solid phase showed the presence of serum IgE antibodies to the drug. Lack of inhibition by 4-chlorophenol and other selected substituted phenyl compounds showed that the terminal groups at each end of the chlorhexidine molecule, alone, did not account for antibody recognition of the antibacterial agent. Although chlorguanide and alexidine, the structures of which each comprise part of the chlorhexidine molecule, showed significant inhibition of the binding of IgE antibodies to chlorhexidine, neither compound was as potent an inhibitor as chlorhexidine itself. Two molecules of chlorguanide make up the symmetrical molecule of chlorhexidine while the interior structure of alexidine (that is excluding the terminal 2-ethylhexyl groups) is identical to part of the chlorhexidine molecule. CONCLUSIONS: Taken together, for this patient, these results lead to the conclusion that the whole chlorhexidine molecule is complementary to the IgE antibody combining sites and that the 4-chlorophenol, biguanide and hexamethylene structures together comprise the allergenic determinant. Hence, like one of the trimethoprim determinants identified, but unlike most drug allergenic determinants identified so far, the chlorhexidine allergenic determinant identified here encompasses the entire molecule.     

Constant infusion of epinephrine, but not bolus treatment, improves haemodynamic recovery in anaphylactic shock in dogs

OBJECTIVE: Epinephrine (Epi) is the treatment of choice for reversing cardiovascular collapse in anaphylactic shock (AS). In this condition, most treatment guidelines have been anecdotally derived and no randomized clinical trials have been conducted. In the present study, we examined the time course of haemodynamic recovery in a canine model of AS when Epi was administered at the initiation of allergen challenge before fully developed shock had occurred. METHODS: Randomized, controlled, crossover studies were performed approximately 3-5 weeks apart in ragweed-sensitized dogs while the animals were ventilated and anaesthetized. Epi was administered by bolus intravenous (i.v.), subcutaneous (s.c.), intramuscular (i.m.) routes and by continuous i.v. infusion (CI). The findings obtained in the Epi treatment (T) studies were compared with those found in a no treatment (NT) study. In the bolus studies, Epi was administered at 0.01 mg/kg, while in the CI study, the dose of Epi was titrated to maintain mean arterial pressure (MAP) at 70% of preshock levels. MAP, cardiac output (CO), stroke volume (SV), and pulmonary wedge pressure (Pwp) were determined over a 3 h period. RESULTS: In the CI study, haemodynamics (CO, MAP, and SV) were significantly higher than those measured in the NT study and the bolus studies over approximately the first hour of the study. In the CI study, the amount of Epi infused was significantly less than in the bolus studies. CONCLUSION: When administered at the initiation of allergen challenge, bolus treatment of Epi by i.m., i.v., or s.c. routes caused limited haemodynamic improvement in AS. In contrast, constant infusion of Epi at a lower total dose produced significant haemodynamic improvement. Within the limits of this anaesthetized canine model, the results suggest that CI should be the preferred route in the treatment of AS when this treatment option is available.     

First report of anaphylactic reaction after fig (Ficus carica) ingestion

We report an anaphylactic reaction which occurred very shortly after ingestion of a fresh fig. The IgE-dependent mechanism was demonstrated on the basis of positivity of the prick test performed with fresh fig (Ficus carica) extract. In addition, we were able to detect specific IgE to the same extract in the serum. The patient did not demonstrate sensitization to other common allergens involved in respiratory and food allergies. However, detection of specific IgE to F. benjamina indicated a sensitization to weeping fig. The CAP F. benjamina was partially inhibited by preincubation of the serum with fig extract, suggesting that these two species of Ficus share some common allergens. In this context, the assumption can be made that weeping fig was responsible for the initial sensitization in this patient.     

Anaphylaxis: a history with emphasis on food allergy

In the century since Paul Portier and Charles Richet described their landmark findings of severe fatal reactions in dogs re-exposed to venom after vaccination with sea anemone venom, treatment for anaphylaxis continues to evolve. The incidence of anaphylaxis continues to be difficult to measure. Underreporting due to patients not seeking medical care as well as failure to identify anaphylaxis affects our understanding of the magnitude of the disease. Treatment with intramuscular epinephrine continues to be the recommended first-line therapy, although studies indicate that education of both the patients and the medical community is needed. Adverse food reactions continue to be the leading cause of anaphylaxis presenting for emergency care. Current therapy for food-induced anaphylaxis is built on the foundation of strict dietary avoidance, rapid access to injectable epinephrine, and education to recognize signs and symptoms of anaphylaxis. Investigation into therapy with oral and sublingual immunotherapy as well as other modalities holds hope for improved treatment of food-induced anaphylaxis.