Consensus clinical scoring for suspected perioperative immediate hypersensitivity reactions.

BACKGROUND: Grading schemes for severity of suspected allergic reactions have been applied to the perioperative setting, but there is no scoring system that estimates the likelihood that the reaction is an immediate hypersensitivity reaction. Such a score would be useful in evaluating current and proposed tests for the diagnosis of suspected perioperative immediate hypersensitivity reactions and culprit agents. METHODS: We conducted a Delphi consensus process involving a panel of 25 international multidisciplinary experts in suspected perioperative allergy. Items were ranked according to appropriateness (on a scale of 1-9) and consensus, which informed development of a clinical scoring system. The scoring system was assessed by comparing scores generated for a series of clinical scenarios against ratings of panel members. Supplementary scores for mast cell tryptase were generated. RESULTS: Two rounds of the Delphi process achieved stopping criteria for all statements. From an initial 60 statements, 43 were rated appropriate (median score 7 or more) and met agreement criteria (disagreement index <0.5); these were used in the clinical scoring system. The rating of clinical scenarios supported the validity of the scoring system. Although there was variability in the interpretation of changes in mast cell tryptase by the panel, we were able to include supplementary scores for mast cell tryptase. CONCLUSION: We used a robust consensus development process to devise a clinical scoring system for suspected perioperative immediate hypersensitivity reactions. This will enable objectivity and uniformity in the assessment of the sensitivity of diagnostic tests.

Management of a surgical patient with a label of penicillin allergy: narrative review and consensus recommendations.

Unsubstantiated penicillin-allergy labels are common in surgical patients, and can lead to significant harm through avoidance of best first-line prophylaxis of surgical site infections and increased infection with resistant bacterial strains. Up to 98% of penicillin-allergy labels are incorrect when tested. Because of the scarcity of trained allergists in all healthcare systems, only a minority of surgical patients have the opportunity to undergo testing and de-labelling before surgery. Testing pathways can be modified and shortened in selected patients. A variety of healthcare professionals can, with appropriate training and in collaboration with allergists, provide testing for selected patients. We review how patients might be assessed, the appropriate testing strategies that can be used, and the minimum standards of safe testing.

The risk of asthma exacerbation after reducing inhaled corticosteroids: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Asthma guidelines suggest reducing controller medications when asthma is stable. METHODS: The purpose of the study is to estimate the risk of asthma exacerbation in stable asthmatics who reduce inhaled corticosteroids (ICS) compared to those who maintain a stable ICS dose. We identified articles from a systematic review of English and non-English articles using MEDLINE, EMBASE, Web of Science, and CENTRAL (inception to May 25, 2013). We included randomized controlled trials (RCTs) with a stable asthma run-in period of 4 weeks or more, an intervention to reduce ICS, and a follow-up period of at least 3 months. RESULTS: The search strategy identified 2253 potential articles, of which 206 were reviewed at the full-text level and 6 met criteria for inclusion. The relative risk of an asthma exacerbation in individuals who reduced ICS compared to those who maintained the same ICS dose was 1.25 (95% CI 0.96, 1.62; P = 0.10; I(2)  = 0%) in studies with a mean follow-up of 22 weeks. Individuals who reduced ICS had a decreased% predicted FEV1 of 0.87% (95% CI -1.58%,3.33%; P = 0.49, I(2)  = 58%) and a decreased mean morning peak expiratory flow of 9.57 l/min (95% CI 1.25, 17.90; P = 0.02; I(2)  = 74%) compared to those individuals who maintained a stable ICS dose. CONCLUSIONS: Asthma exacerbations were statistically no more likely among individuals who reduced ICS compared to those who maintained their ICS dose, supporting current guidelines which recommend decreasing ICS by 50% after a period of asthma stability.

Anaphylactoid reaction to intravenous contrast in patient with systemic mastocytosis.

Systemic mastocytosis is a rare disorder characterised by tissue infiltration of morphologically abnormal mast cells and has been associated with severe anaphylactoid reactions during general anaesthesia. We report the case of a 43-year-old woman who developed a severe anaphylactoid reaction to iodinated contrast media. Persistently elevated serum tryptase levels led to further evaluation and the eventual diagnosis of systemic mastocytosis. This case highlights the importance of repeated measurements of serum tryptase levels following severe anaphylactoid reactions. The anaesthetist should also be aware of the propensity of these patients to develop severe anaphylactoid reactions during general anaesthesia and use treatment strategies to minimise this risk.

Effects of (R)- and (S)-isomers of beta-adrenergic agonists on eosinophil response to interleukin-5.

BACKGROUND: Racemic beta2-adrenergic receptor agonists (beta2-agonists) are used frequently to treat patients with asthma. Potential differences in the biological activities and clinical efficacies among racemic beta2-agonists and their isomers are controversial, and research into these possible differences is limited. OBJECTIVE: We hypothesized that the (S)- and the (R)-isomers of beta2-agonists have opposing effects on the activation of inflammatory cells. METHODS: Isolated human eosinophils were pretreated with 1:1 racemic (R,S)-, (R)- or (S)-albuterol, isobutyl methylxanthine (IBMX), and stimulated with IL-5. The kinetics of superoxide production were examined by reduction of cytochrome c, and the effects of pharmacological agents on superoxide production were monitored for 180 min. RESULTS: (R,S)-albuterol inhibited IL-5-induced superoxide production. This inhibition was enhanced by a cyclic adenosine monophosphate (cAMP) phosphodiesterase inhibitor, IBMX, and was reversed by the selective beta2-adrenergic receptor antagonist, ICI 118, 551, verifying the involvement of both cAMP and the beta2-adrenergic receptor. In addition, (R)-albuterol alone, similarly to (R,S)-albuterol, significantly inhibited IL-5-induced superoxide production up to 60 min (P<0.05, n=4), but the inhibition was lost with longer incubation. In contrast, (S)-albuterol with IBMX did not inhibit IL-5-induced superoxide production before 60 min, but it significantly enhanced IL-5-mediated superoxide production after 60 min (P<0.05, n=4). When both were present as racemic (R,S)-albuterol, the inhibitory effect of (R)-albuterol was not affected by (S)-albuterol. CONCLUSION: When incubated with IL-5-activated eosinophils, (R)-albuterol shows anti-inflammatory effects and (S)-albuterol shows pro-inflammatory effects in the presence of IBMX. The kinetics of these effects are different, and when used simultaneously, (R)-albuterol predominates. When marked usage of the (S)-isomer is anticipated, racemic (R,S)-albuterol should be used clinically with caution.

Preventing and managing drug-induced anaphylaxis.

Drug-induced anaphylaxis and anaphylactoid reactions have increased in frequency with more widespread use of pharmaceutical agents. Anaphylaxis is a systemic, severe immediate hypersensitivity reaction caused by immunoglobulin (Ig) E-mediated immunological release of mediators of mast cells and basophils. An anaphylactoid reaction is an event similar to anaphylaxis but is not mediated by IgE. The incidence of anaphylactic or anaphylactoid reactions differs amongst classes of medications. Antibacterials are the most usual offenders, and penicillins are the most studied. Other compounds commonly causing reactions include non-steroidal anti-inflammatory drugs, anaesthetics, muscle relaxants, latex and radiocontrast media. Prevention, if possible, is the purpose of detailed patient history taking and physical examination. Simple strategies can be employed to decrease the risk of anaphylaxis. These include consideration of the route of drug administration, identification of patients with known causes of anaphylaxis, and the knowledge that certain medications cross react and are contraindicated in those with known history of anaphylaxis. Tests are available, and include IgE-specific skin tests and radioallergosorbent tests. Penicillins are the only compounds whose antigenic determinants are well documented, it is therefore difficult to determine the negative predictive value of other compounds tested. Oral challenge remains an alternative, though entails risk. Desensitisation procedures, as well as gradual dose escalation protocols, are available and can be implemented based on patient history and diagnostic testing. The management of anaphylaxis is based on control of the airway, breathing and circulation. Treatment consists of epinephrine (adrenaline) and supportive measures. Rapid diagnosis and intervention are important in these life-threatening reactions. After stabilisation, all individuals with a documented history of anaphylaxis require a Medic-Alert bracelet or necklace, and an identification card for their wallet or purse.

Which diagnostic tests for common allergies? Where to start when you face an allergy puzzle.

The picture is all too common. In fact, you probably see it in about 1 of every 10 patients who come through your door. The runny nose, scratchy throat, itchy eyes, recurrent sneezing, and annoying cough all point to an allergy. But where do you start and how far do you go in your search for the cause? In this article, Dr Volcheck describes the most commonly used tests for detecting sensitivity to specific IgE allergens and discusses the clinical usefulness and practicality of the various diagnostic procedures.

Epidemiology of anaphylaxis in Olmsted County: A population-based study.

BACKGROUND: Awareness of the clinical features of anaphylaxis and its causative triggers is important if recurrent episodes are to be avoided. The incidence of anaphylaxis in the general population is often underreported, and epidemiologic studies are few. Because an accurate profile of anaphylaxis could heighten awareness of this problem, we investigated the epidemiology of anaphylaxis in the general population of Olmsted County, Minn. OBJECTIVE: The purpose of this study was to describe the epidemiology of anaphylaxis in Olmsted County residents from 1983 through 1987. METHODS: This was a retrospective population-based cohort study. The medical records of 1255 Olmsted County residents identified by computer-linked, medical diagnostic indices (the Rochester Epidemiology Study) were reviewed retrospectively to identify residents whose clinical episodes met the criteria for anaphylaxis. We determined the incidence and rate of occurrence of anaphylaxis, rate of recurrence, prevalence of atopy, cause of anaphylaxis, frequency of referral to an allergy specialist, hospital admission rate, and case-fatality rate. RESULTS: There were 133 residents who experienced 154 anaphylactic episodes during the 5-year period: 116 residents had 1 episode of anaphylaxis, 13 residents had 2 episodes, and 4 residents had 3 episodes. The anaphylaxis occurrence rate was 30 per 100,000 person-years (95% confidence interval, 25-35). There were 110 residents who had a first lifetime episode of anaphylaxis (that was medically evaluated) during the years 1983 to 1987. The average annual incidence rate of anaphylaxis was 21 per 100,000 person-years (95% confidence interval, 17-25). Atopy was present in 53% of the cohort, and allergy consultation was obtained in 52%. A suspect allergen was identified in 68% of the cohort, most frequently a food, medication, or insect sting. The hospitalization rate was 7%, and 1 patient died. CONCLUSION: The incidence of anaphylaxis is less than 1%, and death rarely occurs. People with atopy experience anaphylaxis more frequently than people without atopy. Anaphylaxis frequently is not recognized by patients and physicians.

Dyspnea with 'wheezing' in a 75-year-old female.

This case demonstrates the importance of including upper airway obstruction in the differential diagnosis of 'asthma'. Clues to the diagnosis can be obtained from the physical examination, inspiratory and expiratory flow volume curve studies and radiologic studies. The definitive treatment is determined by the underlying etiology and the extent of the upper airway obstruction.

Anti-inflammatory drugs for controlling asthma.

Anti-inflammatory agents are the first-line treatment for controlling mild persistent, moderate persistent, and severe persistent asthma. The choice of drug and dosage must be individualized to the patient. In general, the glucocorticoids are widely accepted as the most potent and preferred asthma treatment in most adults and some children. Cromolyn, because of its safety and availability in a nebulized form, is the first-line treatment in most young children. The leukotriene inhibitors appear to be effective in mild asthma, but further clinical studies are needed to determine their role more precisely. As the mechanisms of inflammation in asthma are further defined, new pharmaceutical products will be developed to aid in arresting this process.

Anaphylaxis to intravenous cyclosporine and tolerance to oral cyclosporine: case report and review.

BACKGROUND: Hypersensitivity reactions to cyclosporine are rare. The mechanism of the reaction and guidelines for subsequent use of cyclosporine are not well defined. OBJECTIVE: To investigate the mechanisms involved in hypersensitivity reactions to cyclosporine and determine the feasibility of future cyclosporine use. METHODS: We report a patient who had an anaphylactic reaction during the intravenous infusion of cyclosporine. Skin-prick tests were performed for the antibiotics he received earlier in the day and the cyclosporine. A MEDLINE search identified all the reported cases of hypersensitivity reactions to cyclosporine. Each was analyzed to determine a mechanism of the hypersensitivity reaction and subsequent management outcomes. RESULTS: Intradermal tests to intravenous cyclosporine formulation (1 mg/mL) were positive in the patient and negative in two controls. There was no reaction to the antibiotics. The literature search revealed 22 cases of hypersensitivity reaction to cyclosporine. The clinical setting and diagnostic evaluation suggest multiple mechanisms for the hypersensitivity response. All seven patients who were given an oral formulation of cyclosporine tolerated it well after a reaction to the intravenous infusion. Two patients who initially reacted to an oral solution formulation subsequently tolerated the corn oil-based soft gelatin capsule. CONCLUSIONS: Hypersensitivity reactions to cyclosporine are due to Cremophor EL. There is direct and indirect evidence for various immunologic and nonimmunologic pathways precipitating the reaction. This case suggests a role for IgE in the hypersensitivity reaction. Fortunately, a hypersensitivity reaction to one formulation of cyclosporine does not preclude use of a different formulation. The corn oil-based soft gelatin capsule appears to be the safest formulation.

Exercise-induced urticaria and anaphylaxis.

Exercise-induced urticaria and anaphylaxis have become increasingly recognized during the past 2 decades as more people participate in physical activities. These syndromes can be categorized as cholinergic urticaria or exercise-induced anaphylaxis based on the clinical manifestation. Newer subsets such as food-dependent and familial exercise-induced anaphylaxis have also been recognized. Further studies are needed to characterize the variables involved in mast cell activation and mast cell mediator release in these syndromes. The management strategy for patients who have exercise-induced syndromes with skin manifestations only differs from the management for those with systemic symptoms. Currently, antihistamines, as a single agent or in combination with other agents, may be helpful prophylactically in both groups. Avoidance of precipitating factors, modification of exercise, and use of a self-injectable epinephrine kit are recommended for patients with anaphylaxis.

Elevated serum tryptase level in a case of intraoperative anaphylaxis caused by latex allergy.

We measured serial serum tryptase levels in a case of intraoperative anaphylaxis caused by allergy to latex. The serum tryptase level was elevated 7 hours after the hypotensive episode and returned to normal after recovery 4 months later. Both skin tests to latex and serum IgE to latex confirmed latex allergy in this patient. To our knowledge, this is the first report of an elevated serum tryptase level in intraoperative anaphylaxis caused by latex allergy. This observation confirms the role of mast cell degranulation in anaphylaxis caused by allergy to latex.

Military nordic skiing injury profiles with two different types of NATO ski bindings.

Two different types of NATO ski bindings were compared during military-nordic ski training of a Marine Corps infantry battalion of 534 men, who sustained 26 injuries (3.75 injuries per 1,000 skier days). Twelve injuries occurred with the 224 subjects using the NATO 100 bindings. Fourteen injuries occurred with the 310 subjects using the NATO 120 bindings. A total of 133 days were lost from training in the NATO 100 cohort and 121 days from training in the NATO 120 cohort, a statistically significant difference. It is concluded that the NATO 120 binding is safer.