Perioperative Allergic Reactions: Allergy Assessment and Subsequent Anesthesia.

BACKGROUND: Evidence-based guidelines are needed in the United States to improve evaluation of perioperative allergic reactions including recommendations for subsequent anesthesia. OBJECTIVE: To identify causative agent(s) and evaluate patients' tolerability of subsequent anesthesia in patients evaluated by Allergy/Immunology (A/I) at Massachusetts General Hospital. METHODS: We performed a retrospective review of patients referred to the outpatient A/I clinic for perioperative allergic reactions between October 2003 and May 2017. Patient demographics, atopic history, and prior adverse drug reactions were reviewed. Patients underwent a comprehensive evaluation with testing including skin testing (ST), drug challenges (when appropriate), tryptase level measurement, and specific IgE to latex measurement. Tolerance of subsequent procedures requiring anesthesia was assessed. RESULTS: Of 123 patients referred, 74 (60%) were female and the mean age was 46 (±18) years. At least 1 causative agent was identified in 28 patients (24%, n = 28 of 118). Seventeen of 28 (61%) patients were ST positive to an antibiotic, including 13 (46%) positive to cefazolin; 3 patients (11%) had a positive latex specific IgE. Of 85 patients who had subsequent anesthesia with a known outcome, 78 (91%) did not have another perioperative allergic reaction. Two of 5 patients with an elevated baseline tryptase level did not tolerate subsequent anesthesia. CONCLUSION: The majority of patients safely received subsequent anesthesia after comprehensive A/I evaluation for their perioperative allergic reactions; however, improved algorithmic care is needed in the United States. Among ST-positive patients (24%), antibiotics (especially cefazolin) were the most common culprits. An elevated baseline tryptase level was associated with an increased risk of recurrent perioperative allergic reactions.

The Impact of a Reported Penicillin Allergy on Surgical Site Infection Risk.

Background: A reported penicillin allergy may compromise receipt of recommended antibiotic prophylaxis intended to prevent surgical site infections (SSIs). Most patients with a reported penicillin allergy are not allergic. We determined the impact of a reported penicillin allergy on the development of SSIs. Methods: In this retrospective cohort study of Massachusetts General Hospital hip arthroplasty, knee arthroplasty, hysterectomy, colon surgery, and coronary artery bypass grafting patients from 2010 to 2014, we compared patients with and without a reported penicillin allergy. The primary outcome was an SSI, as defined by the Centers for Disease Control and Prevention's National Healthcare Safety Network. The secondary outcome was perioperative antibiotic use. Results: Of 8385 patients who underwent 9004 procedures, 922 (11%) reported a penicillin allergy, and 241 (2.7%) had an SSI. In multivariable logistic regression, patients reporting a penicillin allergy had increased odds (adjusted odds ratio, 1.51; 95% confidence interval, 1.02-2.22) of SSI. Penicillin allergy reporters were administered less cefazolin (12% vs 92%; P < .001) and more clindamycin (49% vs 3%; P < .001), vancomycin (35% vs 3%; P < .001), and gentamicin (24% vs 3%; P < .001) compared with those without a reported penicillin allergy. The increased SSI risk was entirely mediated by the patients' receipt of an alternative perioperative antibiotic; between 112 and 124 patients with reported penicillin allergy would need allergy evaluation to prevent 1 SSI. Conclusions: Patients with a reported penicillin allergy had a 50% increased odds of SSI, attributable to the receipt of second-line perioperative antibiotics. Clarification of penicillin allergies as part of routine preoperative care may decrease SSI risk.

The Impact of Reporting a Prior Penicillin Allergy on the Treatment of Methicillin-Sensitive Staphylococcus aureus Bacteremia.

BACKGROUND: Methicillin-sensitive Staphylococcus aureus (MSSA) bacteremia is a morbid infection with mortality benefit from receipt of parenteral ß-lactam therapy. A substantial portion of MSSA bacteremia patients report penicillin allergy, but infrequently have true allergy. OBJECTIVE: To determine the frequency and predictors of optimal and adequate therapy in patients with MSSA bacteremia. DESIGN: Retrospective cohort. PARTICIPANTS: Adult inpatients with MSSA bacteremia, January 2009 through October 2013. MAIN MEASURES: The primary measure was a trial of optimal therapy (OT), defined as ≥3 inpatient days or discharge on any first-line agents (nafcillin, oxacillin, cefazolin, or penicillin G, if susceptible). The secondary measure was completion of adequate therapy (AT), defined as ≥10 inpatient days or discharge on an agent appropriate for MSSA bacteremia. Data were electronically gathered with key variables manually validated through chart review. Log-binomial regression models were used to determine the frequency and predictors of outcomes. KEY RESULTS: Of 456 patients, 346 (76%) received a trial of OT. Patients reporting penicillin allergy (13%) were less likely to receive OT trial than those without penicillin allergy (47% vs. 80%, p <0.001). Adjusting for other factors, penicillin allergy was the largest negative predictor of OT trial (RR 0.64 [0.49, 0.83]). Infectious Disease (ID) consultation was the largest positive predictor of OT trial across all patients (RR 1.34 [1.14, 1.57]). Allergy/Immunology consultation was the single most important predictor of OT trial among patients reporting penicillin allergy (RR 2.33 [1.44, 3.77]). Of 440 patients, 391 (89%) completed AT, with ID consultation the largest positive predictor of the outcome (RR 1.28 [1.15, 1.43]). CONCLUSIONS: Nearly 25% of patients with MSSA bacteremia did not receive OT trial and about 10% did not receive AT completion. Reported penicillin allergy reduced, and ID consult increased, the likelihood of OT. Allergy evaluation, coupled with ID consultation, may improve outcomes in MSSA bacteremic patients.

Adverse Drug Reactions Associated with Ceftaroline Use: A 2-Center Retrospective Cohort.

BACKGROUND: Ceftaroline fosamil is a cephalosporin approved for treating skin and soft tissue infections (SSTIs), including those caused by methicillin-resistant Staphylococcus aureus and community-acquired pneumonia (CAP). OBJECTIVES: We aimed to study ceftaroline use and associated adverse drug reactions (ADRs), including hypersensitivity reactions (HSRs), among inpatients. METHODS: We performed a retrospective electronic health record review of inpatients from Massachusetts General Hospital and Brigham and Women's Hospital who received ceftaroline between May 2012 and February 2015. ADRs diagnosed by clinical providers during the course of clinical care were subsequently verified and classified. Risk factors for ADRs were identified. RESULTS: Among 96 patients (median age, 57 years; 54% females) who received a median of 28 (interquartile range, 6-63) ceftaroline doses, 54% were being treated for methicillin-resistant Staphylococcus aureus and treatment indications other than SSTI and CAP comprised 59% of care. There were 31 ADRs observed in 20 (21%) patients; hematologic (n = 15) and cutaneous (n = 9) findings were most common. Observed HSRs included rash with mucosal lesions (n = 1), rash with skin desquamation (n = 1), and possible organ-specific HSRs (n = 2). Patients who suffered an ADR received more doses of ceftaroline (median, 46 vs 21; P = .013). There was no increased risk of ceftaroline ADR among patients with reported beta-lactam allergy history (P > .5). CONCLUSIONS: Ceftaroline is used to treat a range of infections beyond SSTI and CAP. We observed a high rate of ADRs from ceftaroline, including signs of severe HSRs. More data are needed to understand the frequency and predictors of ceftaroline ADRs and HSRs.

Antibiotics Are the Most Commonly Identified Cause of Perioperative Hypersensitivity Reactions.

BACKGROUND: Hypersensitivity reactions (HSRs) during the perioperative period are unpredictable and can be life threatening. Prospective studies for the evaluation of perioperative HSRs are lacking, and data on causative agents vary between different studies. OBJECTIVE: The objective of this study was to prospectively determine the success of a comprehensive allergy evaluation plan for patients with HSRs during anesthesia, including identification of a causative agent and outcomes during subsequent anesthesia exposure. METHODS: All patients referred for a perioperative HSR between November 2013 and March 2015, from a Boston teaching hospital, were evaluated using a standardized protocol with skin testing (ST) within 6 months of HSR. Comprehensive allergy evaluation included collection of patient information, including characteristics of HSR during anesthesia. We reviewed the results of ST and/or test doses for all potential causative medications Event-related tryptase levels were reviewed when available. RESULTS: Over 17 months, 25 patients completed the comprehensive allergy evaluation. Fifty-two percent (13 of 25) were female with a median age of 52 (interquartile range 43-66) years. The most frequently observed HSR systems were cutaneous (68%), cardiovascular (64%), and pulmonary (24%). A culprit drug, defined as a positive ST, was identified in 36% (9 of 25) of patients. The most common agent identified was cefazolin (6 of 9). After our comprehensive evaluation and management plan, 7 (7 of 8, 88%) patients tolerated subsequent anesthesia. CONCLUSIONS: Cefazolin was the most commonly identified cause of a perioperative HSR in our study population. Skin testing patients within 6 months of a perioperative HSR may improve the odds of finding a positive result. Tolerance of subsequent anesthesia is generally achieved in patients undergoing our comprehensive evaluation.

Hereditary angioedema: special consideration in children, women of childbearing age, and the elderly.

This review on hereditary angioedema (HAE) focused on special topics regarding HAE in children, women of childbearing age, and the elderly. HAE is a rare autosomal dominant bradykinin-mediated disorder characterized by recurrent attacks of subcutaneous or submucosal swelling that usually affects the face, upper airway, extremities, gastrointestinal tract, or genitalia. These recurrent attacks cause significant morbidity and can be life threatening, especially when the swelling affects the airway. Our objective was to summarize the published data available on the disease epidemiology, pathophysiology, clinical presentation, on demand and prophylactic therapy, and focus on management considerations for these special patient populations. Unique aspects of HAE in women with regard to contraception, hormone replacement therapy, pregnancy, lactation, and menopause were also reviewed.

Ceftaroline desensitization procedure in a pregnant patient with multiple drug allergies.

Validated skin testing is lacking for many drugs, including ceftaroline. The cross-reactivity between ceftaroline and other ß-lactam antibiotics is unknown. We report a case of a pregnant patient with cystic fibrosis and multiple drug allergies who required ceftaroline for methicillin-resistant Staphylococcus aureus pneumonia and underwent an uncomplicated empiric desensitization procedure.

Pathogenesis, newly recognized etiologies, and management of idiopathic anaphylaxis.

Idiopathic anaphylaxis (IA) is a life-threatening allergic disease and the most common diagnosis given to patients following an anaphylactic event. The inability of the healthcare provider and the patient to identify the trigger for anaphylaxis makes standard allergen avoidance measures ineffectual. IA is diagnosed after other causes of anaphylaxis have been excluded. Mast cell activation syndromes (MCAS), mastocytosis, IgE to galactose-alpha-1,3-galactose (α-gal), and certain medications have recently been recognized as causes of anaphylaxis that were previously labeled idiopathic. This review will describe the epidemiology and proposed theories of pathogenesis for IA, its diagnostic approach, its clinical management, and examine newly recognized disorders that were previously labeled as idiopathic anaphylaxis.

Identification of asthma phenotypes in a tertiary care medical center.

BACKGROUND: Asthma affects 5% to 10% of the population and its severity is assessed using 4 parameters: lung function, symptom frequency, rescue inhaler use, and number of asthma exacerbations. Asthma is increasingly recognized as a clinical syndrome rather than a single disease. However, the current classification system fails to reflect the heterogeneous characteristics of the disease. METHODS: A retrospective chart review of 139 patients with mild, moderate, and severe persistent asthma was performed. Variables including baseline and maximal forced expiratory volume over first second (percent predicted), and age of asthma onset were used to classify patients. RESULTS: This yielded 5 clusters similar to Severe Asthma Research Program (SARP). Subjects in cluster 1 (n = 32) and cluster 2 (n = 47) had early-onset atopic asthma and reduced lung function but differed in medication requirement and health care utilization. Cluster 3 (n = 32) consisted of older obese women with late-onset asthma, less atopy, and mildly reduced forced expiratory volume over first second. Members of cluster 4 (n = 20) and cluster 5 (n = 8) had atopic asthma with severe obstruction but differed in bronchodilator response, age of onset, and oral corticosteroid use. Compared with SARP, our subjects were older, had a higher percentage of African Americans and obesity, and less severe asthma (P < 0.05). The observed clusters differed from SARP clusters in the following: (1) more frequent asthma exacerbations and medication use among cluster 1 and cluster 2; (2) lower medication use in cluster 3 and cluster 4; (3) although total health care utilization was similar, there were fewer emergency department visits in cluster 3 (P < 0.05). CONCLUSIONS: The SARP algorithm may be used to classify diverse asthmatic populations into a clinically reproducible phenotypic cluster.

Angiotensin-converting enzyme inhibitor-induced unilateral tongue angioedema.

Angioedema is a frequently reported side effect of angiotensin-converting enzyme inhibitors. The literature suggests that immunosuppressed transplant patients are at an increased risk for this adverse condition. A 62-year-old African American man presented with acute unilateral angioedema attributed to angiotensin-converting enzyme inhibitor initiation. A PubMed literature search regarding unilateral angioedema produced only 3 reported cases confirming an uncommon presentation of an otherwise common adverse drug event. The cases raised questions regarding evidence-based management of drug-induced angioedema, effectiveness of current medical management regimens and the potential of other treatment options. Our objective was to review the presentation, diagnosis and acute management of a common adverse drug effect based on an uncommon patient presentation.

Increased presence of dendritic cells and dendritic cell chemokines in the sinus mucosa of chronic rhinosinusitis with nasal polyps and allergic fungal rhinosinusitis.

BACKGROUND: The aim of this study was to determine if there is a link between local dendritic cells (DCs) and various subtypes of chronic rhinosinusitis (CRS): CRS with nasal polyposis (CRSwNP), CRS without nasal polyposis (CRSsNP), and allergic fungal rhinosinusitis (AFRS). Once DC presence was established we considered possible mechanisms for DC recruitment to the sinuses. METHODS: Biopsy specimens were taken from the osteomeatal complex during endoscopic sinus surgery in patients with AFRS (n ≥ 5), CRSsNP (n ≥ 6), and CRSwNP (n ≥ 6). Control patients (n ≥ 5) were undergoing either tumor resection or repair of cerebrospinal fluid leak and had no radiographic or endoscopic evidence of inflammatory sinus disease. Tissue samples were immunohistochemically stained for DC marker, CD209, costimulatory molecules, CD80 and CD86, and chemokine receptors, CCR2 and CCR6. Sinus tissue lysates were examined for levels of the DC chemoattractants, chemokine ligand 2 (CCL2) and CCL20. RESULTS: Analysis of sinus tissue from AFRS and CRSwNP revealed elevated numbers of cells staining positive for CD209, CD80, CD86, CCR2, and CCR6 compared to controls. CCL2 and CCL20 levels were elevated in AFRS and CRSwNP compared to controls, similar to increases in their receptors, CCR2 and CCR6, respectively. While there were trends toward increases in all markers in CRSsNP, none was statistically significant compared to control. CONCLUSION: AFRS and CRSwNP have increased numbers of DCs displaying costimulatory molecules, DC chemoattractants, and their corresponding receptors in the sinus mucosa compared to controls. These differences represent a possible mechanism for increased numbers of DCs with a T helper 2 (Th2)-skewed profile seen in CRSwNP and AFRS.