Management of anaphylaxis: a systematic review

To establish the effectiveness of interventions for the acute and long‐term management of anaphylaxis, seven databases were searched for systematic reviews, randomized controlled trials, quasi‐randomized controlled trials, controlled clinical trials, controlled before–after studies and interrupted time series and – only in relation to adrenaline – case series investigating the effectiveness of interventions in managing anaphylaxis. Fifty‐five studies satisfied the inclusion criteria. We found no robust studies investigating the effectiveness of adrenaline (epinephrine), H1‐antihistamines, systemic glucocorticosteroids or methylxanthines to manage anaphylaxis. There was evidence regarding the optimum route, site and dose of administration of adrenaline from trials studying people with a history of anaphylaxis. This suggested that administration of intramuscular adrenaline into the middle of vastus lateralis muscle is the optimum treatment. Furthermore, fatality register studies have suggested that a failure or delay in administration of adrenaline may increase the risk of death. The main long‐term management interventions studied were anaphylaxis management plans and allergen‐specific immunotherapy. Management plans may reduce the risk of further reactions, but these studies were at high risk of bias. Venom immunotherapy may reduce the incidence of systemic reactions in those with a history of venom‐triggered anaphylaxis.     

Human seminal plasma anaphylaxis (HSPA): case report and literature review

Human seminal plasma anaphylaxis (HSPA) is rare but may be life-threatening. The antigen or antigens involved in these reactions reside in a glycoprotein fraction of human seminal plasma (HSP). We report a woman who experienced HSPA. Literature on the subject is reviewed.     

Adrenaline for the treatment of anaphylaxis: cochrane systematic review

Background:  Anaphylaxis is a serious allergic reaction that is rapid in onset and may cause death. Adrenaline is recommended as the initial treatment of choice for anaphylaxis.
Objectives:  To assess the benefits and harms of adrenaline in the treatment of anaphylaxis.
Methods:  We searched the Cochrane Central Register of Controlled Trials (CENTRAL) ( The Cochrane Library 2007, Issue 1), MEDLINE (1966 to March 2007), EMBASE (1966 to March 2007), CINAHL (1982 to March 2007), BIOSIS (to March 2007), ISI Web of Knowledge (to March 2007) and LILACS (to March 2007). We also searched websites listing ongoing trials: http://www.clinicaltrials.gov/ , http://www.controlledtrials.com and http://www.actr.org.au/ and contacted pharmaceutical companies and international experts in anaphylaxis in an attempt to locate unpublished material. Randomized and quasi-randomized controlled trials comparing adrenaline with no intervention, placebo or other adrenergic agonists were eligible for inclusion. Two authors independently assessed articles for inclusion.
Results:  We found no studies that satisfied the inclusion criteria.
Conclusions:  On the basis of this review, we are unable to make any new recommendations on the use of adrenaline for the treatment of anaphylaxis. In the absence of appropriate trials, we recommend, albeit on the basis of less than optimal evidence, that adrenaline administration by intramuscular injection should still be regarded as first-line treatment for the management of anaphylaxis.     

Clinical immunology review series: an approach to the patient with anaphylaxis

Anaphylaxis is a severe, life-threatening, generalized or systemic hypersensitivity reaction. While there is agreement as to this definition of anaphylaxis, the clinical presentation is often variable and it is not uncommon for there to be debate after the event as to whether anaphylaxis had actually occurred. The management of anaphylaxis falls into two distinct phases: (1) emergency treatment and resuscitation of a patient with acute anaphylaxis and (2) the search for a cause for the event and the formulation of a plan to prevent and treat possible further episodes of anaphylaxis. Both aspects are important in preventing death from anaphylaxis and are covered in this review.     

Action plans for the long-term management of anaphylaxis: systematic review of effectiveness

BACKGROUND: Anaphylaxis is a severe, potentially life-threatening allergic reaction. Most reactions occur in the absence of a healthcare professional and there is a considerable risk of recurrence in those with a past history of anaphylaxis. The concept of action plans has been developed to facilitate long-term self-management of chronic disorders with a view to promoting patient empowerment and improving health outcomes. Although increasingly advocated for use in anaphylaxis, the effectiveness of this approach in this context is unknown. OBJECTIVES: To assess the effectiveness of action plans as part of the long-term self-management of anaphylaxis in improving health outcomes. METHODS: Standard systematic review techniques were used. We searched CENTRAL, Cochrane, Medline and Embase databases, contacted an international panel of anaphylaxis experts and relevant pharmaceutical companies and searched key web-based databases of trials (http://www.clinicaltrials.gov, http://www.controlledtrials.com and http://www.nrr.nhs.uk) for published, unpublished and on-going randomized or quasi-randomized controlled trials of action plans in anaphylaxis management. There was no restriction used with respect to the language of publication. Searches were completed in summer 2006. RESULTS: None of the 1026 potentially relevant studies identified fulfilled the inclusion criteria for this review. CONCLUSIONS: Although there are potential major benefits of routinely issuing anaphylaxis action plans, there is currently no robust evidence to guide clinical practice. Pragmatic randomized-controlled trials of anaphylaxis action plans are urgently needed; in the meantime, national and international guidelines should make clear this major gap in the evidence base.     

H1-antihistamines for the treatment of anaphylaxis: Cochrane systematic review

BACKGROUND: Anaphylaxis is an acute systemic allergic reaction, which can be life-threatening. H(1)-antihistamines are commonly used as an adjuvant therapy in the treatment of anaphylaxis. We sought to assess the benefits and harm of H(1)-antihistamines in the treatment of anaphylaxis. METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library); MEDLINE (1966 to June 2006); EMBASE (1966 to June 2006); CINAHL (1982 to June 2006) and ISI Web of Science (1945 to July 2006). We also contacted pharmaceutical companies and international experts in anaphylaxis in an attempt to locate unpublished material. Randomized and quasi-randomized-controlled trials comparing H(1)-antihistamines with placebo or no intervention were eligible for inclusion. Two authors independently assessed articles for inclusion. RESULTS: We found no studies that satisfied the inclusion criteria. CONCLUSIONS: Based on this review, we are unable to make any recommendations for clinical practice. Randomized-controlled trials are needed, although these are likely to prove challenging to design and execute.     

Idiopathic anaphylaxis: long-term follow-up, cost, and outlook

To determine the efficacy of oral corticosteroids, antihistamines, and sympathomimetics in treating patients with idiopathic anaphylaxis, the charts of 225 patients diagnosed with idiopathic anaphylaxis from 1971 to 1990 treated at a single center were reviewed. Sixty-one patients (34 females and 27 males) were available for long-term follow-up. Ages ranged from 10 to 68 years with an average of 39 years. Patients with frequent episodes were treated with a protocol of oral corticosteroids, antihistamines, and sympathomimetics. Patients with infrequent episodes were treated for acute episodes only. The number of emergency room visits, hospitalizations, intensive care unit admissions, and length of time in remission were recorded. Sixty-five percent of patients with infrequent episodes and 91% of patients with frequent episodes of idiopathic anaphylaxis went into remission. Significant decreases in emergency room visits occurred for the idiopathic anaphylaxis-generalized-frequent group ( P< 0.016). the idiopathic-anaphylaxis-generalized-infrequent group ( P< 0.0001), and the idiopathic anaphylaxis-angioedema-infrequent group ( P <0.039). Significant decreases in the number of hospitalizations ( P < 0.022) and intensive care unit admissions ( P < 0.009) occurred for the idiopathic anaphylaxis-generalized-infrequent and frequent groups, respectively. Overall, an estimated 184740 was saved with the treatment program, for 546 patient-years. Idiopathic anaphylaxis can be controlled and remission induced in most patients. An estimated 11 million per year can be saved for patients in the USA on the basis of the estimated prevalence in this country.     

Incidence of anaphylaxis with circulatory symptoms: a study over a 3-year period comprising 940 000 inhabitants of the Swiss Canton Bern

BACKGROUND: Diagnosis of anaphylaxis is clinically based and usually straightforward. However, data on the epidemiology of anaphylaxis, particularly the most profound and life-threatening form such as anaphylactic shock are limited and thought to be under-reported. OBJECTIVE: The primary aim of this study was to investigate the incidence and the causes of severe anaphylaxis with circulatory signs in the Canton Bern, which comprises about 940 000 inhabitants or approximately one-seventh of the population of Switzerland. METHODS: During a 3-year period, 1 January 1996 to 31 December 1998, all medical records (7739 documents) from the two allergy clinics of the Canton Bern have been reviewed. In addition, all seven board-certified specialists of the Foederatio Medicorum Helveticorum (FMH) in Allergology and Clinical Immunology of this Canton as well as all 17 hospitals with emergency units of this area have been contacted for cases with an anaphylactic event not referred to the allergy clinics. RESULTS: Overall, 226 individuals, 106 females (47%) with a mean age of 41 years (range, 5-74 years) and 120 males (53%) with a mean age of 38 years (8 months-83 years) were diagnosed as having presented generalized, life-threatening anaphylaxis with circulatory symptoms. Altogether, these patients experienced 246 episodes of severe systemic reactions. In addition, death due to anaphylaxis occurred in three subjects. The annual incidence of anaphylaxis per 100 000 inhabitants per year ranged between 7.9 and 9.6 cases. Hymenoptera stings (58.8%), drugs (18.1%), and foods (10.1%) were the most commonly identified culprits for anaphylaxis. In 5.3% of all anaphylactic events, the cause could not be identified. CONCLUSION: The incidence rate of severe life-threatening anaphylaxis with circulatory signs in the Canton Bern, Switzerland, with 7.9-9.6 per 100 000 inhabitants per year is comparable to the findings of other epidemiological investigations. In most events, a causal agent or allergen could be identified by a careful allergological examination.     

Food anaphylaxis

Anaphylaxis is a life-threatening allergic reaction, and food is one of the most common responsible allergens in the outpatient setting. The prevalence of food-induced anaphylaxis has been steadily rising. Education regarding food allergen avoidance is crucial as most of the fatal reactions occurred in those with known food allergies. The lack of a consensus definition for anaphylaxis has made its diagnosis difficult. Symptoms affect multiple organ systems and include pruritus, urticaria, angioedema, vomiting, diarrhoea, abdominal cramps, respiratory difficulty, wheezing, hypotension, and shock. Prompt recognition of anaphylaxis is essential as delayed treatment has been associated with fatalities. Although epinephrine is accepted as the treatment of choice, timely administration does not always occur, partly due to a lack of awareness of the diagnostic criteria. Several novel tools are currently being investigated, which will potentially aid in the diagnosis and treatment of food-induced anaphylaxis.     

Lessons for management of anaphylaxis from a study of fatal reactions

BACKGROUND: The unpredictability of anaphylactic reactions and the need for immediate, often improvised treatment will make controlled trials impracticable; other means must therefore be used to determine optimal management. OBJECTIVES: This study aimed to investigate the circumstances leading to fatal anaphylaxis. METHODS: A register was established including all fatal anaphylactic reactions in the UK since 1992 that could be traced from the certified cause of death. Data obtained from other sources suggested that deaths certified as due to anaphylaxis underestimate the true incidence. Details of the previous medical history, the reaction and necropsy were sought for all cases. RESULTS: Approximately half the 20 fatal reactions recorded each year in the UK were iatrogenic, and a quarter each due to food or insect venom. All fatal reactions thought to have been due to food caused difficulty breathing that in 86% led to respiratory arrest; shock was more common in iatrogenic and venom reactions. The median time to respiratory or cardiac arrest was 30 min for foods, 15 min for venom and 5 min for iatrogenic reactions. Twenty-eight per cent of fatal cases were resuscitated but died 3 h-30 days later, mostly from hypoxic brain damage. Adrenaline (epinephrine) was used in treatment of 62% of fatal reactions but before arrest in only 14%. CONCLUSIONS: Immediate recognition of anaphylaxis, early use of adrenaline, inhaled beta agonists and other measures are crucial for successful treatment. Nevertheless, a few reactions will be fatal whatever treatment is given; optimal management of anaphylaxis is therefore avoidance of the cause whenever this is possible. Predictable cross-reactivity between the cause of the fatal reaction and that of previous reactions had been overlooked. Adrenaline overdose caused at least three deaths and must be avoided. Kit for self-treatment had proved unhelpful for a variety of reasons; its success depends on selection of appropriate medication, ease of use and good training.