Pathophysiology of Immunologic and Nonimmunologic Systemic Reactions Including Anaphylaxis.

There is a myriad of immunologic and nonimmunologic pathways by which the clinical phenotype of anaphylaxis can be produced. An understanding of these pathways is essential for the prevention as well as the treatment of anaphylactic episodes.

Mast cell disorders and idiopathic anaphylaxis: Evaluation and management.

Background: Our understanding of mast cell activation disorders continues to grow, and our management of these syndromes is improving with this increase in knowledge. Despite these advances, there remain some areas of confusion. Conclusion: In this article, we discussed these areas and offered thoughts about establishing the diagnosis and management.

Anaphylaxis-a 2020 practice parameter update, systematic review, and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) analysis.

Anaphylaxis is an acute, potential life-threatening systemic allergic reaction that may have a wide range of clinical manifestations. Severe anaphylaxis and/or the need for repeated doses of epinephrine to treat anaphylaxis are risk factors for biphasic anaphylaxis. Antihistamines and/or glucocorticoids are not reliable interventions to prevent biphasic anaphylaxis, although evidence supports a role for antihistamine and/or glucocorticoid premedication in specific chemotherapy protocols and rush aeroallergen immunotherapy. Evidence is lacking to support the role of antihistamines and/or glucocorticoid routine premedication in patients receiving low- or iso-osmolar contrast material to prevent recurrent radiocontrast media anaphylaxis. Epinephrine is the first-line pharmacotherapy for uniphasic and/or biphasic anaphylaxis. After diagnosis and treatment of anaphylaxis, all patients should be kept under observation until symptoms have fully resolved. All patients with anaphylaxis should receive education on anaphylaxis and risk of recurrence, trigger avoidance, self-injectable epinephrine education, referral to an allergist, and be educated about thresholds for further care.

Idiopathic anaphylaxis yardstick: Practical recommendations for clinical practice.

Anaphylaxis is considered idiopathic when there is no known trigger. The signs and symptoms of idiopathic anaphylaxis (IA) are identical to those of anaphylaxis because of a known cause and can include cutaneous, circulatory, respiratory, gastrointestinal, and neurologic symptoms. Idiopathic anaphylaxis can be a frustrating disease for patients and health care providers. Episodes are unpredictable, and differential diagnosis is challenging. Current anaphylaxis guidelines have little specific guidance regarding differential diagnosis and long-term management of IA. Therefore, the objective of the Idiopathic Anaphylaxis Yardstick is to use published data and the authors' combined clinical experience to provide practical recommendations for the diagnosis and management of patients with IA.

Who needs to carry an epinephrine autoinjector?

Patients who have had anaphylaxis or who are at risk of it (eg, due to food allergy or Hymenoptera hypersensitivity) should carry an epinephrine autoinjector at all times. However, the risks and benefits must be considered on an individual basis, especially in patients with atherosclerotic heart disease, elderly patients on polypharmacy, patients receiving allergen immunotherapy, those with large local reactions to insect stings, and individuals with oral allergy syndrome.

The changing face of anaphylaxis in adults and adolescents.

BACKGROUND: Our institution has published serial studies of adults and adolescents with anaphylactic events. The first series was published in 1993 and the last was published in 2006. It was our perception that the nature of anaphylactic episodes had changed over the 2 decades since the last review. OBJECTIVE: To determine whether the etiologies and presentations of anaphylaxis have changed during the past decade in our population. METHODS: Patient charts were identified based on International Classification of Diseases, Ninth Revision codes for anaphylactic shock. Charts identified were analyzed for clinical symptoms reported, comorbidities, etiology, investigative testing, and subsequent treatment. These cases were categorized as definitive, probable, or idiopathic based on history and results from testing, similar to our prior reports. RESULTS: We identified 281 possible cases, of which 218 met criteria for anaphylaxis. Of these cases, median age was 42 years (range 9-78) and 64% were female. In the review of cases, 85 (39%) were determined to have a definitive etiology, 57 were determined to have a probable etiology (26%), and 76 (35%) were idiopathic. Interestingly, of those with a definitive cause, the most common etiology identified was galactose-α-1,3-galactose, accounting for 28 cases (33%). Foods were the second leading cause, accounting for 24 cases (28%). CONCLUSION: In this follow-up report on anaphylaxis etiology from a single center, the most common etiology was galactose-α-1,3-galactose. This differs greatly from prior reports from our center. Interestingly, the percentage of cases attributed to idiopathic anaphylaxis decreased from 59% in our previous report to 35% in the present report, which could largely be explained by the number of galactose-α-1,3-galactose cases.

Electronic Clinical Decision Support System for allergic rhinitis management: MASK e-CDSS.

BACKGROUND: Allergic rhinitis (AR) management has changed in recent years following the switch from the concept of disease severity to the concept of disease control, publication of the AR clinical decision support system (CDSS) and development of mobile health (m-health) tools for patients (eg Allergy Diary). The Allergy Diary Companion app for healthcare providers is currently being developed and will be launched in 2018. It incorporates the AR CDSS to provide evidence-based treatment recommendations, linking all key stakeholders in AR management. OBJECTIVE: To produce an electronic version of the AR CDSS (e-CDSS) for incorporation into the Allergy Diary Companion, to describe the app interfaces used to collect information necessary to inform the e-CDSS and to summarize some key features of the Allergy Diary Companion. METHODS: The steps involved in producing the e-CDSS and incorporating it into the Allergy Diary Companion were (a) generation of treatment management scenarios; (b) expert consensus on treatment recommendations; (c) generation of electronic decisional algorithms to describe all AR CDSS scenarios; (d) digitization of these algorithms to form the e-CDSS; and (e) embedding the e-CDSS into the app to permit easy user e-CDSS interfacing. RESULTS: Key experts in the AR field agreed on the AR CDSS approach to AR management and on specific treatment recommendations provided by Allergy Diary Companion. Based on this consensus, decision processes were developed and programmed into the Allergy Diary Companion using Titanium Appcelerator (JavaScript) for IOS tablets. To our knowledge, this is the first time the development of any m-health tool has been described in this transparent and detailed way, providing confidence, not only in the app, but also in the provided management recommendations. CONCLUSION: The Allergy Diary Companion for providers provides guideline and expert-endorsed AR management recommendations. [MASK paper No 32].

Value of a Second Dose of Epinephrine During Anaphylaxis: A Patient/Caregiver Survey.

BACKGROUND: Anaphylaxis guidelines recommend prescription of more than 1 epinephrine autoinjector (EAI) for patients at risk. A second epinephrine dose is required in 16% to 36% of patients. OBJECTIVE: To evaluate real-world use of EAIs and understand the patients'/caregivers' adherence to guidelines. METHODS: We collected survey responses from US patients and caregivers with an EAI prescription in November 2015. The survey covered several domains relevant to anaphylaxis and EAI use. RESULTS: The survey was completed by 953 respondents (505 patients and 448 caregivers). Most respondents were women (71%). Most of the respondents had previously administered an EAI (75%). The mean age of the respondents was 28 ± 14.0 years. A total of 786 (82%) respondents did not carry 2 EAIs all the time, and the main reason given was to have 1 EAI in another location. Most respondents kept at least 1 EAI at home (84%). The percentages of respondents with more than 1 EAI available at locations surveyed were low (patients: 22% at home, 2% at work; caregivers: 27% at home, 10% at school). During training, most respondents (64%) were instructed to always carry 1 EAI and keep the other in another location. Half of the respondents reported the use of a second epinephrine dose in a previous event. Forty-five percent of the 73 respondents who sought emergency care did so because of the unavailability of a second dose. CONCLUSIONS: Our study suggests poor adherence in patients and caregivers to anaphylaxis guidelines recommending more than 1 EAI available at all times and implies that this can result in adverse outcomes.

Epinephrine auto-injector needle length: what is the ideal length?

PURPOSE OF REVIEW: The purpose of this manuscript is to review the literature on the clinical effects of the needle length of epinephrine (adrenaline) auto-injectors. RECENT FINDINGS: Epinephrine has maximal pharmacodynamic effect within 10 min of intramuscular administration into the thigh. Prefilled epinephrine auto-injectors are designed for simplicity of use and safety. Auto-injectors are primarily used by patients in an unsupervised setting in cases of anaphylaxis. There are weight-appropriate doses of epinephrine available with auto-injectors that are prefilled, to prevent dosing errors, with 0.15, 0.30, and 0.50 mg amounts. In addition, needle lengths vary from 1.17 to 2.50 cm. The recommended needle lengths differ between adults and pediatric patients. In addition, the needle lengths differ between devices as well. There are concerns that the needle length may be too short in select obese patients. Yet, there are also concerns that the needle length may be too long in some patients. Factors that affect the depth of the injection, and therefore the pharmacokinetics of the drug, include not only the needle length but also the BMI, obesity, compression of soft tissue, and propulsion. SUMMARY: Epinephrine auto-injectors have different needle lengths. Using the right device with appropriate needle length based on BMI, obesity, and employing the proper technique can improve the outcome in an anaphylactic event.

Mast Cells and Anaphylaxis.

For half a century, it has been known that the mast cell is the cell responsible for the majority of anaphylactic events. Its mediators, taken as a whole, are capable of producing all of the clinical manifestations of these events. With the discovery of immunoglobulin E (IgE), it was originally felt that the vast majority of anaphylactic episodes were due to antigen coupling with two cell-bound IgE molecules. More recently it has been learned that many episodes are produced by direct activation of mast cells, not involving antigen binding to IgE, and that monomeric IgE under certain conditions can also cause degranulation. Of note--in regard to antigen independent degranulation--are recent reports that the human G-protein-coupled receptor, MRGPRX2, may be the receptor for many drugs and cationic proteins capable of producing direct mast cell degranulation and anaphylactic events.

Risk multipliers for severe food anaphylaxis.

Anaphylaxis is a severe, life threatening allergic reaction. In most fatal cases of food anaphylaxis, the fatality is not due merely to a simple, linear relationship between the allergen and exposure in a sensitized individual. Compounding factors such as the allergic disease burden-particularly the presence of asthma; comprehension of the potential severity of an event, training in the appropriate use of epinephrine, and emerging metabolic factors should be considered when assessing risk and establishing management strategies. This paper reviews the factors that contribute to the risk of severe anaphylactic events and provides a framework for the ongoing management of patients at risk of severe food allergy.

Current controversies and challenges in allergic rhinitis management.

There are many obstacles in the path of effective allergy management, in general, and allergic rhinitis (AR) control, in particular. Chief among them are: insufficient symptom relief in some patients provided by some currently considered first-line AR treatments in real life; an over-reliance on randomized controlled trials to direct AR guideline recommendations; the need for a broader interpretation of the AR evidence base (to include randomized controlled trials and real-life studies); poorly designed and interpreted studies; and lack of an AR control concept and common language of control. These controversies are fully reviewed here and challenging solutions have been presented.