Epinephrine: the drug of choice for anaphylaxis. A statement of the World Allergy Organization

Anaphylaxis is an acute and potentially lethal multi-system allergic reaction. Most consensus guidelines for the past 30 years have held that epinephrine is the drug of choice and the first drug that should be administered in acute anaphylaxis. Some state that properly administered epinephrine has no absolute contraindication in this clinical setting. A committee of anaphylaxis experts assembled by the World Allergy Organization has examined the evidence from the medical literature concerning the appropriate use of epinephrine for anaphylaxis. The Committee strongly believes that epinephrine is currently underutilized and often dosed suboptimally to treat anaphylaxis, is under-prescribed for potential future self-administration, that most of the reasons proposed to withhold its clinical use are flawed, and that the therapeutic benefits of epinephrine exceed the risk when given in appropriate i.m. doses.     

Allergy practice worldwide: a report by the World Allergy Organization Specialty and Training Council

In 2004 the World Allergy Organization's Specialty and Training Council conducted a survey of World Allergy Organization (WAO) member societies to obtain information about the status of the specialty of allergy worldwide. Responses were received from 33 countries, representing a population of 1.39 billion people, of whom it was estimated that 22% may suffer from some form of allergic disease. Allergy was reported by 23 respondents to be a certified or accredited specialty in their country, and the number of certified allergists per head of population ranged from 1:25 million to 1:16,000. Allergists were ranked as the fifth most likely clinicians to see cases of allergic asthma, third most likely to see allergic rhinitis, and fourth most likely to see eczema or sinusitis. Nine countries only reported that children with allergic diseases would be seen by a pediatrician with appropriate training. The survey results highlight a pressing need for the development of allergy services worldwide.     

Second symposium on the definition and management of anaphylaxis: summary report--Second National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network symposium

There is no universal agreement on the definition of anaphylaxis or the criteria for diagnosis. In July 2005, the National Institute of Allergy and Infectious Disease and Food Allergy and Anaphylaxis Network convened a second meeting on anaphylaxis, which included representatives from 16 different organizations or government bodies, including representatives from North America, Europe, and Australia, to continue working toward a universally accepted definition of anaphylaxis, establish clinical criteria that would accurately identify cases of anaphylaxis with high precision, further review the evidence on the most appropriate management of anaphylaxis, and outline the research needs in this area.     

Allergy to bumblebee venom I. Occupational anaphylaxis to bumblebee venom: diagnosis and treatment

We describe six patients with severe occasional anaphylaxis, caused by stings of bumblebees. Sensitization to bumblebee venom was confirmed by intracutaneous tests and RAST with purified bumblebee venom. Three patients changed their occupation and will probably not be stung by bumblebees in the future. The other patients started immunotherapy with newly purified bumblebee venom extract. After 1 year of treatment, no severe side-effects had occurred and clinical benefit in two patients could be demonstrated, as both skin sensitivity or serum IgE to bumblebee venom had decreased. Moreover, both patients were unresponsive to in-hospital sting challenge.     

Anaphylaxis: guidelines from the European Academy of Allergy and Clinical Immunology

Anaphylaxis is a clinical emergency, and all healthcare professionals should be familiar with its recognition and acute and ongoing management. These guidelines have been prepared by the European Academy of Allergy and Clinical Immunology (EAACI) Taskforce on Anaphylaxis. They aim to provide evidence‐based recommendations for the recognition, risk factor assessment, and the management of patients who are at risk of, are experiencing, or have experienced anaphylaxis. While the primary audience is allergists, these guidelines are also relevant to all other healthcare professionals. The development of these guidelines has been underpinned by two systematic reviews of the literature, both on the epidemiology and on clinical management of anaphylaxis. Anaphylaxis is a potentially life‐threatening condition whose clinical diagnosis is based on recognition of a constellation of presenting features. First‐line treatment for anaphylaxis is intramuscular adrenaline. Useful second‐line interventions may include removing the trigger where possible, calling for help, correct positioning of the patient, high‐flow oxygen, intravenous fluids, inhaled short‐acting bronchodilators, and nebulized adrenaline. Discharge arrangements should involve an assessment of the risk of further reactions, a management plan with an anaphylaxis emergency action plan, and, where appropriate, prescribing an adrenaline auto‐injector. If an adrenaline auto‐injector is prescribed, education on when and how to use the device should be provided. Specialist follow‐up is essential to investigate possible triggers, to perform a comprehensive risk assessment, and to prevent future episodes by developing personalized risk reduction strategies including, where possible, commencing allergen immunotherapy. Training for the patient and all caregivers is essential. There are still many gaps in the evidence base for anaphylaxis.     

Revised nomenclature for allergy for global use: Report of the Nomenclature Review Committee of the World Allergy Organization, October 2003

The nomenclature proposed in the October 2003 report of the Nomenclature Review Committee of the World Allergy Organization is an update of the European Academy of Allergology and Clinical Immunology Revised Nomenclature for Allergy Position Statement published in 2001. The nomenclature can be used independently of target organ or patient age group and is based on the mechanisms that initiate and mediate allergic reactions. It is assumed that as knowledge about basic causes and mechanisms improves, the nomenclature will need further review.     

Management of primary antibody deficiency with replacement therapy: summary of guidelines

This article summarizes the guidelines for using replacement therapy in the management of patients who have primary antibody deficiency.     

Comparison of international guidelines for the emergency medical management of anaphylaxis

BACKGROUND: Guideline-based treatment approaches for managing anaphylaxis are widely believed to result in good outcomes, but the strength of evidence underpinning the recommendations made therein is unclear. OBJECTIVE: To identify and compare national guidelines for the emergency medical management of anaphylaxis and to describe the extent to which the evidence base in support of key recommendations is made clear. METHODS: We systematically searched key medical databases and contacted the World Allergy Organization and anaphylaxis charities in several countries to identify national guidelines. Full text copies of relevant papers were obtained and, where necessary, translated. Data were abstracted onto a customized data extraction sheet; this process was independently checked by a second reviewer. RESULTS: Guidelines originating from Australia, Canada, Russia, UK, Ukraine and the USA were identified. While these were in agreement on the broad principles of management, there were important variations in relation to the treatments to be used and the dose and route of administration of these preparations. Most guidelines failed to make clear the strength of evidence underpinning the recommendations being made. CONCLUSIONS: There are important international differences in the recommended emergency management of anaphylaxis. It is important that an agreed core evidence-based guideline for the management of anaphylaxis is now developed, which can then be adapted for national/local use. Clinicians need to be aware of the limitations of existing guidelines.     

BSACI guidelines for the investigation of suspected anaphylaxis during general anaesthesia

Investigation of anaphylaxis during general anaesthesia requires an accurate record of events including information on timing of drug administration provided by the anaesthetist, as well as timed acute tryptase measurements. Referrals should be made to a centre with the experience and ability to investigate reactions to a range of drug classes/substances including neuromuscular blocking agents (NMBAs) intravenous (i.v.) anaesthetics, antibiotics, opioid analgesics, non‐steroidal anti‐inflammatory drugs (NSAIDs), local anaesthetics, colloids, latex and other agents. About a third of cases are due to allergy to NMBAs. Therefore, investigation should be carried out in a dedicated drug allergy clinic to allow seamless investigation of all suspected drug classes as a single day‐case. This will often require skin prick tests, intra‐dermal testing and/or drug challenge. Investigation must cover the agents administered, but should also include most other commonly used NMBAs and i.v. anaesthetics. The outcome should be to identify the cause and a range of drugs/agents likely to be safe for future use. The allergist is responsible for a detailed report to the referring anaesthetist and to the patient's GP as well as the surgeon/obstetrician. A shorter report should be provided to the patient, adding an allergy alert to the case notes and providing an application form for an alert‐bracelet indicating the wording to be inscribed. The MHRA should be notified. Investigation of anaphylaxis during general anaesthesia should be focussed in major allergy centres with a high throughput of cases and with experience and ability as described above. We suggest this focus since there is a distinct lack of validated data for testing, thus requiring experience in interpreting tests and because of the serious consequences of diagnostic error. Cite this as: P. W. Ewan, P. Dugué, R. Mirakian, T. A. Dixon, J. N. Harper and S. M. Nasser, Clinical & Experimental Allergy, 2010 (40) 15–31.     

Diagnosis and Rationale for Action Against Cow's Milk Allergy (DRACMA): a summary report

The 2nd Milan Meeting on Adverse Reactions to Bovine Proteins was the venue for the presentation of the first consensus-based approach to the management of cow's milk allergy. It was also the first time that the Grading of Recommendations, Assessments, Development, and Evaluation approach for formulating guidelines and recommendations was applied to the field of food allergy. In this report we present the contributions in allergen science, epidemiology, natural history, evidence-based diagnosis, and therapy synthesized in the World Allergy Organization Diagnosis and Rationale for Action against Cow's Milk Allergy guidelines and presented during the meeting. A?consensus emerged between discussants that cow's milk allergy management should reflect not only basic research but also a newer and better appraisal of the literature in the light of the values and preferences shared by patients and their caregivers in partnership. In the field of diagnosis, atopy patch testing and microarray technology have not yet evolved for use outside the research setting. With foreseeable breakthroughs (eg, immunotherapy and molecular diagnosis) in the offing, the step ahead in leadership can only stem from a worldwide organization implementing consensus-based clinical practice guidelines to diffuse and share clinical knowledge.     

The economic costs of severe anaphylaxis in France: an inquiry carried out by the Allergy Vigilance Network

Background:  The prevalence of severe anaphylaxis, between 1 and 3 per 10 000, has increased sharply over recent years, with a rate of lethality of 1%. The economic burden is unknown.
Objective:  The aim of this study was to estimate the economic costs of anaphylaxis, including direct costs of treatment, hospitalization, preventive and long-care measures, and the indirect cost: absenteeism.
Methods:  Analysis of 402 patients of anaphylaxis declared by 384 allergists was reported to the Allergy Vigilance Network. The global cost was estimated from the national data of hospital admissions: ICD-10 coding available for 2003, 2004 and 2005.
Results:  Three work/classroom days were lost per patient. Diagnosis required oral challenge with hospitalization in 18% of cases. The estimated mean total cost was 1895€ for food- and drug-related anaphylaxis (5610€ for the most severe), and 4053€ for Hymenoptera anaphylaxis. National statistics recorded 2575 patients in 2005; 22% more than in 2003. The estimated annual cost was 4 789 500 €. The possible reasons for this being an under-estimate include: data coming only from hospitalized patients, poor identification by medical teams unfamiliar with ICD-10 codes, peri-operative anaphylaxis being insufficiently declared, rush-immunotherapy and maintenance treatments for Hymenoptera anaphylaxis. Similarly, the extra cost of cow milk substitutes, as well as insurance costs where deaths are followed by litigation were not taken into account.
Conclusions:  The mean cost of anaphylaxis was 1895–5610€ in nonfatal patients. The prevalence was under-estimated because of many biases, leading to under-estimation of the national cost. Further studies would be necessary to evaluate the value of preventive strategies.     

American Academy of Allergy, Asthma & Immunology/American College of Allergy, Asthma and Immunology Joint Task Force Report on omalizumab-associated anaphylaxis

The American Academy of Allergy, Asthma & Immunology and the American College of Allergy, Asthma and Immunology Executive Committees formed the Omalizumab Joint Task Force with the purpose of reviewing the Genentech Xolair (omalizumab) clinical trials and postmarketing surveillance data on anaphylaxis and anaphylactoid reactions. Using the definition of anaphylaxis proposed at a 2005 multidisciplinary symposia, the Omalizumab Joint Task Force concluded that 35 patients had 41 episodes of anaphylaxis associated with Xolair (omalizumab) administration between June 1, 2003, and December 31, 2005. With 39,510 patients receiving Xolair (omalizumab) during the same period of time, this would correspond to an anaphylaxis-reporting rate of 0.09% of patients. Of those 36 events for which the time of reaction was known, 22 (61%) reactions occurred in the first 2 hours after one of the first 3 doses. Five (14%) of the events after the fourth or later doses occurred within 30 minutes. Considering the timing of these 36 events, an observation period of 2 hours for the first 3 injections and 30 minutes for subsequent injections would have captured 75% of the anaphylactic reactions. The OJTF report provides recommendations for physicians who prescribe Xolair (omalizumab) on (1) the suggested wait periods after administration and (2) patient education regarding anaphylaxis.     

Food Allergy Herbal Formula-1 (FAHF-1) blocks peanut-induced anaphylaxis in a murine model

BACKGROUND: Peanut allergy is a major cause of fatal and near-fatal anaphylactic reactions to foods. There is no curative therapy for this condition. Traditional Chinese medicines have been reported to have antiallergic properties, which might be useful for treating peanut allergy. OBJECTIVE: The purpose of this study was to investigate the effects of a Chinese herbal formula, FAHF-1, on peanut anaphylactic reactions in a mouse model of peanut allergy. METHODS: Mice were sensitized with freshly ground whole peanut in the presence of cholera toxin and boosted 1 and 3 weeks later. FAHF-1 treatment was initiated 1 week later and continued for 7 weeks. After treatment, mice were challenged with peanut, and anaphylactic symptoms, body temperatures, and plasma histamine and IgE levels were measured. T-cell proliferative responses and cytokine production were also determined. RESULTS: FAHF-1 completely blocked peanut-induced anaphylactic symptoms and markedly reduced mast cell degranulation and histamine release. Peanut-specific serum IgE levels were significantly reduced by 2 weeks of treatment at the time of challenge, and they remained lower 4 weeks after discontinuation of treatment. FAHF-1 significantly reduced peanut-induced lymphocyte proliferation as well as IL-4, IL-5, and IL-13 synthesis but not IFN-gamma synthesis. No toxic effects on liver or kidney functions were observed, nor was there any overall immune suppression. CONCLUSION: FAHF-1 protected peanut-sensitized mice from anaphylactic reactions and significantly reversed established IgE-mediated peanut allergy. This suggests that FAHF-1 might prove valuable for the treatment of peanut allergy.     

The World Health Organization classification of lymphomas

The Revised European-American Classification of Lymphoid Neoplasms (REAL) classification has been validated by a multi-institutional study, and project data showed that it is both reproducible and clinically relevant. The new World Health Organization (WHO) Classification of Neoplastic Diseases of Hematopoietic and Lymphoid Tissues, as a joint project of the Society of Hematopathology and European Association of Hematopathologists, is an update of the REAL classification, with minor changes based on newly available information. We analyzed the incidence of different histological types of non-Hodgkin s lymphomas diagnosed in Zagreb University Hospital Center, which were reclassified according to the WHO classification. Furthermore, we present a conceptual grouping of lymphomas into four categories (indolent, aggressive, highly aggressive, and localized indolent).