Bernard Yu-Hor Thong

World Allergy Organization Guidelines for the Assessment and Management of Anaphylaxis

The illustrated World Allergy Organization (WAO) Anaphylaxis Guidelines were created in response to absence of global guidelines for anaphylaxis. Uniquely, before they were developed, lack of worldwide availability of essentials for the diagnosis and treatment of anaphylaxis was documented. They incorporate contributions from more than 100 allergy/immunology specialists on 6 continents. Recommendations are based on the best evidence available, supported by references published to the end of December 2010.The Guidelines review patient risk factors for severe or fatal anaphylaxis, co-factors that amplify anaphylaxis, and anaphylaxis in vulnerable patients, including pregnant women, infants, the elderly, and those with cardiovascular disease. They focus on the supreme importance of making a prompt clinical diagnosis and on the basic initial treatment that is urgently needed and should be possible even in a low resource environment. This involves having a written emergency protocol and rehearsing it regularly; then, as soon as anaphylaxis is diagnosed, promptly and simultaneously calling for help, injecting epinephrine (adrenaline) intramuscularly, and placing the patient on the back or in a position of comfort with the lower extremities elevated. When indicated, additional critically important steps include administering supplemental oxygen and maintaining the airway, establishing intravenous access and giving fluid resuscitation, and initiating cardiopulmonary resuscitation with continuous chest compressions. Vital signs and cardiorespiratory status should be monitored frequently and regularly (preferably, continuously).The Guidelines briefly review management of anaphylaxis refractory to basic initial treatment. They also emphasize preparation of the patient for self-treatment of anaphylaxis recurrences in the community, confirmation of anaphylaxis triggers, and prevention of recurrences through trigger avoidance and immunomodulation. Novel strategies for dissemination and implementation are summarized. A global agenda for anaphylaxis research is proposed.

World Allergy Organization anaphylaxis guidelines: Summary

The uniqueWorld Allergy Organization (WAO) Guidelines for the Assessment and Management of Anaphylaxis were created in response to the absence of global guidelines for anaphylaxis. They were developed after documenting that essential medications, supplies, and equipment for assessment andmanagement of anaphylaxis are not universally available worldwide. Additionally, they were developed with the awareness that any health care professional might, at some time, have to assess and manage anaphylaxis in a low-resource environment, whether this be a country, a region, or a specific location, such as an aircraft cabin or a remote area. They incorporate contributions frommore than 100 allergy/immunology specialists on 6 continents received through the WAO member societies and the WAO Board of Directors. In order to transcend language barriers, the principles of anaphylaxis assessment and management set forth in the guidelines are summarized in 5 comprehensive illustrations. The guidelines review patients’ risk factors for severe or fatal anaphylaxis, cofactors that amplify anaphylaxis, and anaphylaxis in vulnerable patients, such as pregnant women, infants, and the

International Consensus on drug allergy

When drug reactions resembling allergy occur, they are called drug hypersensitivity reactions (DHRs) before showing the evidence of either drug‐specific antibodies or T cells. DHRs may be allergic or nonallergic in nature, with drug allergies being immunologically mediated DHRs. These reactions are typically unpredictable. They can be life‐threatening, may require or prolong hospitalization, and may necessitate changes in subsequent therapy. Both underdiagnosis (due to under‐reporting) and overdiagnosis (due to an overuse of the term ‘allergy’) are common. A definitive diagnosis of such reactions is required in order to institute adequate treatment options and proper preventive measures. Misclassification based solely on the DHR history without further testing may affect treatment options, result in adverse consequences, and lead to the use of more‐expensive or less‐effective drugs, in contrast to patients who had undergone a complete drug allergy workup. Several guidelines and/or consensus documents on general or specific drug class‐induced DHRs are available to support the medical decision process. The use of standardized systematic approaches for the diagnosis and management of DHRs carries the potential to improve outcomes and should thus be disseminated and implemented. Consequently, the International Collaboration in Asthma, Allergy and Immunology (iCAALL), formed by the European Academy of Allergy and Clinical Immunology (EAACI), the American Academy of Allergy, Asthma and Immunology (AAAAI), the American College of Allergy, Asthma and Immunology (ACAAI), and the World Allergy Organization (WAO), has decided to issue an International CONsensus (ICON) on drug allergy. The purpose of this document is to highlight the key messages that are common to many of the existing guidelines, while critically reviewing and commenting on any differences and deficiencies of evidence, thus providing a comprehensive reference document for the diagnosis and management of DHRs.

World Allergy Organization Anaphylaxis Guidelines: 2013 Update of the Evidence Base

The World Allergy Organization (WAO) Guidelines for the assessment and management of anaphylaxis are a widely disseminated and used resource for information about anaphylaxis. They focus on patients at risk, triggers, clinical diagnosis, treatment in health care settings, self-treatment in the community, and prevention of recurrences. Their unique strengths include a global perspective informed by prior research on the global availability of essentials for anaphylaxis assessment and management and a global agenda for anaphylaxis research. Additionally, detailed colored illustrations are linked to key concepts in the text [Simons et al.: J Allergy Clin Immunol 2011;127:593.e1-e22]. The recommendations in the original WAO Anaphylaxis Guidelines for management of anaphylaxis in health care settings and community settings were based on evidence published in peer-reviewed, indexed medical journals to the end of 2010. These recommendations remain unchanged and clinically relevant. An update of the evidence base was published in 2012 [Simons et al.: Curr Opin Allergy Clin Immunol 2012;12:389-399]. In 2012 and early 2013, major advances were reported in the following areas: further characterization of patient phenotypes; development of in vitro tests (for some allergens) that help distinguish clinical risk of anaphylaxis from asymptomatic sensitization; epinephrine (adrenaline) research, including studies of a new epinephrine auto-injector for use in community settings, and randomized controlled trials of immunotherapy to prevent food-induced anaphylaxis. Despite these advances, the need for additional prospective studies, including randomized controlled trials of interventions in anaphylaxis is increasingly apparent. This 2013 Update highlights publications from 2012 and 2013 that further contribute to the evidence base for the recommendations made in the original WAO Anaphylaxis Guidelines. Ideally, it should be used in conjunction with these Guidelines and with the 2012 Guidelines Update.

2012 Update: World Allergy Organization Guidelines for the assessment and management of anaphylaxis.

Purpose of reviewThe World Allergy Organization (WAO) Guidelines for the assessment and management of anaphylaxis published in early 2011 provide a global perspective on patient risk factors, triggers, clinical diagnosis, treatment, and prevention of anaphylaxis. In this 2012 Update, subsequently published, clinically relevant research in these areas is reviewed. Recent findingsPatient risk factors and co-factors that amplify anaphylaxis have been documented in prospective studies. The global perspective on the triggers of anaphylaxis has expanded. The clinical criteria for the diagnosis of anaphylaxis that are promulgated in the Guidelines have been validated. Some aspects of anaphylaxis treatment have been prospectively studied. Novel investigations of self-injectable epinephrine for treatment of anaphylaxis recurrences in the community have been performed. Progress has been made with regard to measurement of specific IgE to allergen components (component-resolved testing) that might help to distinguish clinical risk of future anaphylactic episodes to an allergen from asymptomatic sensitization to the allergen. New strategies for immune modulation to prevent food-induced anaphylaxis and new insights into subcutaneous immunotherapy to prevent venom-induced anaphylaxis have been described. SummaryResearch highlighted in this Update strengthens the evidence-based recommendations for assessment, management, and prevention of anaphylaxis made in the WAO Anaphylaxis Guidelines.

2015 update of the evidence base: World Allergy Organization anaphylaxis guidelines

The World Allergy Organization (WAO) Guidelines for the assessment and management of anaphylaxis provide a unique global perspective on this increasingly common, potentially life-threatening disease. Recommendations made in the original WAO Anaphylaxis Guidelines remain clinically valid and relevant, and are a widely accessed and frequently cited resource. In this 2015 update of the evidence supporting recommendations in the Guidelines, new information based on anaphylaxis publications from January 2014 through mid- 2015 is summarized. Advances in epidemiology, diagnosis, and management in healthcare and community settings are highlighted. Additionally, new information about patient factors that increase the risk of severe and/or fatal anaphylaxis and patient co-factors that amplify anaphylactic episodes is presented and new information about anaphylaxis triggers and confirmation of triggers to facilitate specific trigger avoidance and immunomodulation is reviewed. The update includes tables summarizing important advances in anaphylaxis research.

Ocular manifestations and complications of Stevens–Johnson syndrome and toxic epidermal necrolysis: an Asian series*

Background:  To describe the acute and late ocular manifestations and complications in toxic epidermal necrosis (TEN) and Stevens–Johnson syndrome (SJS), and identify predictors for development of late complications.

Drug allergy in a general hospital: results of a novel prospective inpatient reporting system

BACKGROUND Drug allergies are unpredictable immunologic adverse effects, usually immunoglobulin E-mediated immediate hypersensitivity or T-cell-mediated delayed hypersensitivity. There is a paucity of accurate prospective data on drug allergy in hospitalized patients. OBJECTIVE To describe the incidence, manifestations, and outcome of drug allergy in hospitalized patients. METHODS All newly developed cases, confirmed or suspected, of drug allergy in inpatients using a network-based electronic notification system. Each notification was evaluated by an allergist-immunologist during the same admission. RESULTS From December 1, 1997 to December 31, 1999, 366 cases were reported from a total of 90,910 admissions. After review, only 210 cases were verified to have drug allergy. Antimicrobials and anti-epileptic drugs comprised 75% of the drug allergies reported. Cutaneous eruptions were the most common clinical presentation (95.7%), with maculopapular rash being the most common morphology. Systemic manifestations occurred in 30%, of which hepatitis was the most common. Serious adverse reactions such as Stevens-Johnson syndrome, toxic epidermal necrolysis, and generalized exfoliative dermatitis occurred in 11 (5.2%) patients. There was no case of anaphylaxis attributable to drug allergy. After adjusting for underreporting, the incidence of drug allergy in our hospitalized patients was 4.20 per 1,000 (95% confidence interval [CI] 2.93 to 5.46), drug allergy developing during the course of inpatient treatment 2.07 per 1,000 (95% CI 1.45 to 2.69), and mortality attributable to drug allergy 0.09 per 1,000 (95% CI 0.06 to 0.12) hospitalizations. CONCLUSIONS A network-based, allergist-immunologist-verified, surveillance system enables more accurate labeling of drug allergy. The incidence of drug allergy and mortality in hospitalized patients is low.

Association of a common complement receptor 2 haplotype with increased risk of systemic lupus erythematosus

A genomic region on distal mouse chromosome 1 and its syntenic human counterpart 1q23–42 show strong evidence of harboring lupus susceptibility genes. We found evidence of linkage at 1q32.2 in a targeted genome scan of 1q21–43 in 126 lupus multiplex families containing 151 affected sibpairs (nonparametric linkage score 2.52, P = 0.006). A positional candidate gene at 1q32.2, complement receptor 2 (CR2), is also a candidate in the murine Sle1c lupus susceptibility locus. To explore its role in human disease, we analyzed 1,416 individuals from 258 Caucasian and 142 Chinese lupus simplex families and demonstrated that a common three-single-nucleotide polymorphism CR2 haplotype (rs3813946, rs1048971, rs17615) was associated with lupus susceptibility (P = 0.00001) with a 1.54-fold increased risk for the development of disease. Single-nucleotide polymorphism 1 (rs3813946), located in the 5′ untranslated region of the CR2 gene, altered transcriptional activity, suggesting a potential mechanism by which CR2 could contribute to the development of lupus. Our findings reveal that CR2 is a likely susceptibility gene for human lupus at 1q32.2, extending previous studies suggesting that CR2 participates in the pathogenesis of systemic lupus erythematosus.

High-dose intravenous immunoglobulins in the treatment of toxic epidermal necrolysis: an Asian series.

Toxic epidermal necrolysis (TEN) is a severe, immune‐mediated, mucocutaneous reaction resulting in extensive keratinocyte apoptosis. High‐dose human intravenous immunoglobulins (IVIG) have been proposed as an effective treatment for TEN. Retrospective data from 8 patients with TEN and 4 patients with Stevens‐Johnson syndrome‐toxic epidermal necrolysis (SJS‐TEN) overlap treated with high‐dose IVIG were analysed. The total dose of IVIG administered was 2 g/kg body weight, with the exception of 2 patients who received a total dose of 1.5 g/kg body weight. Their mean age was 49.9 ± 18.8 years (range, 19 to 70 years). The mean time from the first sign of skin lesion or mucosal or epidermal detachment to commencement of IVIG was 8.7 ± 5.5 days (range, 3 to 22 days). Of the 11 patients who survived, the mean time to objective response was 3.6 ± 1.9 days (range, 2 to 8 days). The length of stay (LOS) in hospital was 20.4 ± 8.0 days (range, 10 to 37 days). The survival rate was 91.6%. One patient developed permanent mucocutaneous sequelae following TEN. There were no adverse reactions to IVIG. We conclude that high‐dose IVIG may be a safe and effective therapy for Asian patients with TEN.