Perioperative management of mastocytosis.

PURPOSE: Patients with mastocytosis have an increased risk of anaphylaxis during surgical procedures with general anesthesia. Therefore, we reviewed the anesthesia course of a large cohort of patients with mastocytosis. METHODS: We retrospectively reviewed adult and pediatric patients with mastocytosis who underwent surgical procedures with general anesthesia at Mayo Clinic from January 1, 2000, through June 30, 2021. We also included any procedures with general anesthesia that occurred during the 3-year period preceding mastocytosis diagnosis and designated the patients who underwent these procedures as having an unknown diagnosis at the time of their surgical procedure. We analyzed whether patients received chronic antimediator treatment for mastocytosis and/or prophylactic medications before the procedures. We also determined whether medications indicative of mastocytosis-related adverse events were intraoperatively administered. RESULTS: We identified 113 patients who underwent 219 procedures during the study period; 25 procedures were performed before mastocytosis diagnosis. Of 194 procedures in patients with known mastocytosis, patients received chronic antimediator therapy and/or perioperative prophylactic medications for 178 (91.8%) procedures. Among these procedures, 10 were potentially complicated by mast cell activation, which was inferred from administration of inhaled albuterol (n = 3) or intravenous diphenhydramine (n = 8). In addition, there was only one case of intraoperative anaphylaxis which occurred in a patient who underwent anesthesia before mastocytosis diagnosis and therefore did not receive prophylaxis. CONCLUSION: Intraoperative anaphylaxis can be the first presenting sign of mastocytosis. Patients with mastocytosis who received chronic antimediator therapy and/or preoperative prophylactic medications had an uneventful surgical course.

Perioperative Hypersensitivity Evaluation and Management: A Practical Approach.

Perioperative hypersensitivity (POH) is an uncommon, potentially life-threatening event. Identification of POH can be difficult given the lack of familiarity, physiological effects of anesthesia, draping of the patient during surgery, and potential nonimmunological factors contributing to signs and symptoms. Given the unique nature and large number of medications administered in the perioperative setting, evaluation of POH can be challenging. In this paper, we present a practical approach to management with an emphasis on understanding what happens in the operating room, the overlap of signs and symptoms between nonimmunological and immunological reactions, acute management, and subsequent evaluation. In addition, we provide a strategy for further review of an initially negative evaluation and emphasize the importance of establishing management plans for the patient as well as providing recommendations to the medical, anesthesia, and surgical teams for future surgeries. A critical factor for successful management at all points in the process is a close collaboration between the anesthesia and the allergy teams.

Perioperative Anaphylaxis: Evaluation and Management.

Perioperative anaphylaxis (PA) is a rare but life-threatening condition that poses diagnostic and management challenges in the operating room. The incidence of severe perioperative reactions is estimated to be approximately 1:7000-10,000. Management involves both immediate stabilization of the patient and identifying the culprit agent. Identification is essential to prevent recurrence of the event in subsequent surgeries and to avoid unnecessary labeling of drug allergy. Identifying all possible exposures including medications, disinfectants, latex, and dyes and choosing the appropriate tests are essential for proper evaluation. To identify the culprit, primary testing modalities include tryptase at the time of the reaction with subsequent levels and skin testing with nonirritating concentrations to the medications and substances utilized during the procedure and those potentially used as alternates. This strategy provides guidance for future surgeries and procedures. Close collaboration between the allergy, anesthesiology, and surgery teams is essential for appropriate management of these patients at the time of the reaction, during the post event evaluation and in preparation for subsequent surgeries.

Successful encorafenib desensitization in a patient with recurrent metastatic melanoma.

Type I hypersensitivity reactions (HSR) to dabrafenib are rare but have been previously described. We present a case where a 72-year-old woman with recurrent, metastatic BRAF-mutated melanoma developed a type I HSR to dabrafenib. We, therefore, developed a desensitization protocol with encorafenib, a similar class agent, to allow the patient to continue with treatment. Patients with a history of HSR to dabrafenib may be considered for encorafenib desensitization when other therapeutic options are limited.

Incidence and risk factors for near-fatal and fatal outcomes after perioperative and periprocedural anaphylaxis in the USA, 2005-2014.

BACKGROUND: The incidence of fatal and near-fatal outcomes after perioperative anaphylaxis is unknown in the USA. Previously identified risk factors of neuromuscular-blocker-induced fatal perioperative anaphylaxis include male sex, obesity, and use of beta blockers. We examined the incidence of fatal and near-fatal outcomes after perioperative anaphylaxis in the USA and the underlying risk factors using a large national database. METHODS: Using the Nationwide Inpatient Sample from 2005 to 2014, we identified cases of fatal and near-fatal perioperative anaphylaxis, defined as perioperative anaphylaxis cases complicated by respiratory or cardiac arrest, using the International Classification of Diseases, Ninth Revision, Clinical Modification codes. RESULTS: Amongst 5223 perioperative anaphylaxis cases, the proportion of near-fatal or fatal cases attributable to perioperative anaphylaxis was 7.0% (95% confidence interval [CI]: 6.2-7.7), with near-fatal perioperative anaphylaxis cases accounting for 5.0% (95% CI: 4.4-5.6%) and fatal cases accounting for 2.0% (95% CI: 1.5-2.5%) of cases overall. Thus, the incidence of fatal or near-fatal perioperative anaphylaxis is 1.26 in 100 000 procedures. Risk factors for fatal or near-fatal perioperative anaphylaxis include age (≥65 yr); undergoing a cardiac procedure; and comorbid conditions of weight loss, non-metastatic solid tumours, metastatic cancer, paralysis, coagulopathy, renal failure, congestive heart failure, fluid and electrolyte disorder, and neurological disorders. Individuals with near-fatal or fatal perioperative anaphylaxis reactions had increased lengths of stay and hospital costs compared with controls. CONCLUSIONS: The incidence of fatal or near-fatal perioperative anaphylaxis in the USA was 1.26 in 100 000 procedures. Risk factors for fatal or near-fatal outcomes include older age, cardiac procedures, and specific comorbidities.

Incidence of and risk factors for perioperative or periprocedural anaphylaxis in the United States from 2005 to 2014.

BACKGROUND: The estimated worldwide incidence of perioperative or periprocedural anaphylaxis (PA) is between 1 in 1250 and 1 in 20,000 procedures. OBJECTIVE: To evaluate the incidence of PA in the United States and compare patient characteristics and underlying risk factors using a large national database. METHODS: Using deidentified data from the nationwide inpatient sample from 2005 to 2014, we identified cases of PA through the International Classification of Diseases, Ninth Revision, Clinical Modification codes and conducted a retrospective analysis. RESULTS: Among 35,647,347 surgeries and procedures, there were 5458 (0.015%) PA cases identified. The incidence of PA was 15.3 cases per 100,000 procedures. When compared with controls, PA cases had an increased mortality (3.4% vs 1.4%; P < .001), median length of stay (5 vs 3 days; P < .001), and median hospital cost ($45,155 vs $24,734; P < .001). The age group between 18 and 34 years (odds ratio [OR], 1.34; 95% confidence interval [CI], 1.13-1.58; P < .001) and female sex (OR, 1.40; 95% CI, 1.31-1.49; P < .001) were associated with increased odds of PA. Transplant (OR, 3.35; 95% CI, 2.59-4.34; P < .001), hematologic (OR, 1.63; 95% CI, 1.30-2.05; P < .001), vascular (OR, 1.49; 95% CI, 1.30-1.67; P < .001), and cardiac (OR, 1.47; 95% CI, 1.30-1.67; P < .001) procedures were at increased risk for PA. Several comorbidities were associated with PA including chronic pulmonary disease (OR, 1.41; 95% CI, 1.31-1.51; P < .001). CONCLUSION: The incidence of PA is 1 in 6531 procedures, with a mortality of 1 in 191,652 procedures. PA has worsening outcomes compared with controls. The risk factors of PA include age, sex, procedure type, and comorbidities.

Asthma control in eosinophilic granulomatosis with polyangiitis treated with rituximab.

OBJECTIVES: Rituximab (RTX) treatment is used for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, but its benefits in eosinophilic granulomatosis with polyangiitis (EGPA) are unclear. Our aim was to characterize asthma control and glucocorticoid (GC) sparing after RTX treatment. METHODS: A retrospective, computer-assisted search was performed to identify patients with EGPA and GC-dependent asthma diagnosed between 2000 and 2017 who received RTX for remission induction. Demographic and clinical features were analyzed. RESULTS: Of the 17 patients included, the majority were myeloperoxidase-ANCA positive (n = 13, 76.5%). Uncontrolled asthma symptoms and atopy were present in 13 patients (76.5%). RTX was used for initial remission induction in patients with new onset of severe disease (n = 5, 29.4%) and after failed remission induction with other immunosuppression (n = 12, 70.6%). It was used for remission maintenance in nine patients (52.9%). GCs were used for maintenance at a median dose of 25 mg/day (interquartile range, 16.25-37.5). At the end of follow-up, 13 patients (76.5%) had non-severe or controlled asthma, and remission was achieved in 12 (70.6%). Median serum eosinophil and C-reactive protein values decreased (1.06 vs 0.10 × 109/L [P = .012] and 27.0 vs 5.0 mg/dL [P = .001], respectively), whereas pulmonary function test results remained unchanged. Median GC dose was significantly reduced at 6, 12, 18, and 24 months (P < .0001). Patients receiving RTX for maintenance required less than 10 mg of GCs for asthma control. CONCLUSION: RTX seems to be safe and have GC-sparing efficacy for asthma control in EGPA. Randomized controlled trials are needed for detailed study of RTX for treating EGPA.Key Points• In this retrospective study we have concluded that rituximab (RTX) might be considered for the control of severe corticosteroid-dependent asthma in eosinophilic granulomatosis polyangiitis (EGPA) patients especially when myeloperoxidase antibodies are positive.• Rituximab has not been studied particularly for asthma control in EGPA patients.• The most noticeable effect of RTX was the decrease in the use of corticosteroids for the control of asthma.

Anaesthetic management of patients with pre-existing allergic conditions: a narrative review.

This narrative review seeks to distinguish the clinical patterns of pre-existing allergic conditions from other confounding non-allergic clinical entities, and to identify the potential related risks and facilitate their perioperative management. Follow-up investigation should be performed after a perioperative immediate hypersensitivity to establish a diagnosis and provide advice for subsequent anaesthetics, the main risk factor for perioperative immunoglobulin E (IgE)-mediated anaphylaxis being a previous uninvestigated perioperative immediate hypersensitivity reaction. The concept of cross-reactivity between drugs used in the perioperative setting and food is often quoted, but usually not supported by evidence. There is no reason to avoid propofol in egg, soy, or peanut allergy. The allergenic determinants have been characterised for fish, shellfish, and povidone iodine, but remain unknown for iodinated contrast agents. Iodinated drugs may be used in seafood allergy. Evidence supporting the risk for protamine allergy in fish allergy and in neutral protamine Hagedorn insulin use is lacking. Conversely, cross-reactivity to gelatin-based colloid may occur in α-gal syndrome. Atopy and allergic asthma along with other non-allergic conditions, such as NSAID-exacerbated respiratory disease, chronic urticaria, mastocytosis, and hereditary or acquired angioedema, are not risk factors for IgE-mediated drug allergy, but there is a perioperative risk associated with the potential for exacerbation of the various conditions.

Severe/uncontrolled asthma and overall survival in atopic patients with eosinophilic granulomatosis with polyangiitis.

BACKGROUND: Although asthma, rhinitis/rhinosinusitis and peripheral eosinophilia are present in virtually all patients with eosinophilic granulomatosis with polyangiitis (EGPA), the role of atopy in these patients is not well defined. OBJECTIVE: To clarify the role of atopy in patients affected with EGPA. METHODS: Clinical, laboratory and standard spirometry data have been abstracted from medical records. Only patients who underwent skin and/or specific IgE testing for common aeroallergens before the vasculitic phase were included. RESULTS: Overall, 33.5% (63) of our patients underwent skin and/or specific IgE testing to aeroallergens. Atopy related to aeroallergens was confirmed in 22.3% (two-third of those tested), and was associated with more severe/uncontrolled asthma (p < 0.001), including a greater use of oral glucocorticoids for respiratory manifestations the year before the diagnosis of EGPA (p = 0.013). Atopic patients with EGPA had higher total serum IgE levels and less renal disease at EGPA diagnosis compared to non-atopic patients (p < 0.05). Among atopic patients, the majority had multiple sensitizations (76%); dust mite and grass pollen were the most common respiratory allergens identified. The number of allergens did not correlate with peripheral eosinophilia, total serum IgE, ESR, or measures of airway obstruction (p > 0.05 in all cases). The presence of atopy increased the risk of severe/uncontrolled asthma, but not the risk of severe vasculitis (Five Factor Score≥1). Atopic patients had a better overall survival (p = 0.027). CONCLUSION: In EGPA, atopy is associated with better prognosis and more severe/uncontrolled asthma manifestations in the year before the development of vasculitis, but not with more severe vasculitis at presentation.

Urinary Leukotriene E4 to Determine Aspirin Intolerance in Asthma: A Systematic Review and Meta-Analysis.

BACKGROUND: Urinary leukotriene E4 (ULTE4) may be a biomarker that distinguishes aspirin-intolerant asthma from other asthma subtypes. OBJECTIVE: To estimate the diagnostic testing accuracy of ULTE4 as a marker of aspirin intolerance in patients with asthma using previously published studies. METHODS: We identified relevant clinical studies from a systematic review of English and non-English articles using MEDLINE, EMBASE, and CENTRAL (inception to February 10, 2015). Articles were screened at the abstract and full-text level by 2 independent reviewers. We included previously published studies that analyzed ULTE4 in human subjects with asthma characterized as having or not having aspirin intolerance on the basis of a specified definition: convincing history of aspirin intolerance, positive aspirin challenge, or both as the criterion standard. Individual-level data points from all included studies were obtained and analyzed. RESULTS: The search strategy identified 867 potential articles, of which 86 were reviewed at the full-text level and 10 met criteria for inclusion. The sensitivity, specificity, positive predictive value, and negative predictive values of ULTE4 to determine aspirin intolerance in subjects with asthma were 0.55, 0.82, 0.75, and 0.66 (Amersham-enzyme immunoassay); 0.76, 0.77, 0.70, and 0.78 (Cayman-enzyme immunoassay); 0.70, 0.81, 0.86, and 0.79 (mass spectrometry); and 0.81,0.79, 0.65, and 0.88 (radioimmunoassay) at optimal thresholds of 192, 510, 167 to 173, and 66 to 69 pg/mg Cr, respectively. The diagnostic odds ratio for each methodology was 6.0, 11.9, 10.5, and 19.1, respectively. CONCLUSIONS: ULTE4 is a marker for aspirin-intolerant asthma and could potentially be used as a clinical test to identify the risk of aspirin intolerance in subjects with asthma.

Asthma and Risk of Appendicitis in Children: A Population-Based Case-Control Study.

OBJECTIVE: To assess whether asthma is associated with risk of appendicitis in children. METHODS: We used a population-based case-control study design using a comprehensive medical record review and predetermined criteria for appendicitis and asthma. All children (age younger than 18 years of age) who resided in Olmsted County, Minnesota, and developed appendicitis between 2006 and 2012 were matched to controls (1:1) with regard to birthday, gender, registration date, and index date. Asthma status was ascertained using predetermined criteria. Active (current) asthma was defined as the presence of asthma symptoms or asthma-related events (eg, medication use, clinic visits, emergency department, or hospitalization) within 1 year before the index date. Inactive asthma was defined as subjects without these events. A conditional logistic regression model was used. RESULTS: Among the 309 appendicitis cases identified, when stratified according to asthma status, active asthma was associated with significantly increased risk of appendicitis compared with inactive asthma (odds ratio [OR] = 2.48; 95% confidence interval [CI], 1.22-5.03) and to no asthma (OR = 1.88; 95% CI, 1.07-3.27; overall P = .035). When controlling for potential confounders such as gender, age, and smoking status, active asthma was associated with a higher odds of developing appendicitis compared with nonasthmatic patients (adjusted OR = 1.75; 95% CI, 0.99-3.11) whereas inactive asthma was not (overall P = .049). Tobacco smoke exposure within 3 months was associated with an increased risk of appendicitis (adjusted OR = 1.66; 95% CI, 1.02-2.69). Among asthma medications, leukotriene receptor antagonists reduced the risk of appendicitis (OR = 0.18; 95% CI, 0.04-0.74). CONCLUSIONS: Active asthma might be an unrecognized risk factor for appendicitis in children whereas a history of inactive asthma does not pose such risk. Further investigation exploring the underlying mechanisms is warranted.

Perioperative course in patients with hereditary or acquired angioedema.

PURPOSE: Two types of bradykinin-mediated angioedema, hereditary angioedema (HAE) and acquired angioedema (AAE), result from deficiency or dysfunction of C1 esterase inhibitor, leading to an overproduction of bradykinin, which can lead to vascular permeability and life-threatening angioedema of the airway. The objective of this study was to review perioperative outcomes in a series of patients with HAE and AAE and to review current knowledge about anesthetic complications in patients with HAE or AAE. METHODS: Medical records were retrospectively reviewed for perioperative complications in patients with HAE or AAE who underwent general anesthesia from January 1, 2000, to December 31, 2014, at our institution. RESULTS: Twenty-four patients (13 with HAE, 10 with AAE, and 1 with unspecified angioedema) underwent 38 instances of general anesthesia with airway manipulation. All except 4 received prophylactic therapy. One patient, a 67-year-old woman who was pretreated with stanozolol and fresh frozen plasma required reintubation after postoperative airway edema developed. CONCLUSION: Life-threatening episodes of angioedema of the airway occur infrequently, but they can occur in patients who received pretreatment and in patients who have previously undergone anesthesia uneventfully. Anesthesiologists must be ready to emergently manage a difficult airway and must be familiar with recommendations provided in consensus guidelines for the treatment of HAE and AAE patients.

Systemic mastocytosis complicating pregnancy.

BACKGROUND: Systemic mastocytosis is a rare medical disorder in which an increased number of mast cells can precipitate immediate hypersensitivity reactions, leading to hypotension, shock, and death. It is characterized by persistent elevated serum tryptase levels. The few published reports on pregnancy complicated by systemic mastocytosis indicate favorable maternal and fetal outcomes in gravidas known to have systemic mastocytosis. CASE: A pregnant woman treated with terbutaline at 31 weeks of gestation developed severe hypotension which resulted in fetal demise; this was initially diagnosed to be an anaphylactic reaction. The finding of persistently high maternal tryptase levels led to the diagnosis of systemic mastocytosis. In her subsequent pregnancy she was treated with an H1 blocker. Hypotension during her cesarean delivery was managed with steroid and epinephrine therapy. CONCLUSION: Exacerbations of systemic mastocytosis during pregnancy can lead to significant maternal and fetal complications. Treatment with H1 blockers, and when indicated, steroids and epinephrine, can reduce these complications.

Preoperative evaluation of patients with history of allergy to penicillin: comparison of 2 models of practice.

OBJECTIVE: To study whether allergy consultation and penicillin allergy skin testing affects the selection of antibacterial prophylaxis perioperatively in surgical patients with history of allergy to penicillin (HOAP). PATIENTS AND METHODS: From January 1 through June 30, 2004, we compared 2 different models of practice at our institution. At the Preoperative Evaluation Clinic (POEC), all patients with HOAP are evaluated by an allergist and undergo skin testing for allergy to penicillin. At other (non-POEC) preoperative evaluation settings (OPES), patients with HOAP do not undergo allergy consultation and penicillin skin testing before surgery. Of the 4889 patients screened at the POEC during the study period, 412 consecutive patients with HOAP were included in the study. Of the 416 patients screened at OPES, 69 consecutive patients with HOAP were studied. Logistic regression was used to assess whether allergy consultation was associated with the choice of antibiotic for antibacterial prophylaxis perioperatively, after adjusting for age, sex, and type of surgery. RESULTS: Perioperative cephalosporin use was greater among patients screened at POEC vs those screened at OPES (70% vs 39%, P<.001 unadjusted; P=.04 adjusted for age, sex, and type of surgery). Vancomycin use was lower for patients screened at POEC vs those screened at OPES (10% vs 28%, P<.001 unadjusted; P=.03 adjusted). CONCLUSION: For patients with HOAP, evaluation at the POEC was associated with increased use of cephalosporin and decreased use of vancomycin.

Monoclonal gammopathies and malignancies in patients with chronic urticaria.

BACKGROUND: Monoclonal gammopathy of undetermined significance (MGUS) has been described in association with chronic urticaria (CU) in patients with Schnitzler syndrome. Chronic urticaria may be a manifestation of hematologic malignancies. METHODS: This study was conducted to evaluate the frequency and characteristics of MGUS or malignancy in patients with CU. The Mayo Clinic electronic database was reviewed to identify patients with the diagnosis of CU. RESULTS: Of the 1639 patients presenting with CU between 1994 and 2001, 797 (49%) underwent laboratory evaluation for the presence of a coexisting monoclonal protein. Forty-seven CU patients had MGUS, 142 had a malignancy, and 24 had both. Fifteen percent of CU patients with MGUS had a hematologic malignancy compared with 0.9% of CU patients without MGUS (P < 0.001). Patients presenting with a new diagnosis of CU at an older age (> 56 years) were more likely to have associated underlying MGUS. The occurrence of MGUS in this group was higher than the reported incidence of MGUS in the general population. CONCLUSIONS: Patients with CU younger than 43 years were unlikely to have associated MGUS or malignancy. A higher percentage of patients with CU and MGUS had an associated diagnosis of hematologic malignancy.

Successful progressive challenge after a cutaneous reaction to imatinib mesylate (Gleevec): a case report and review of the literature.

The use of imatinib mesylate (Gleevec), a selective tyrosine kinase inhibitor, has become the new gold standard for the treatment of chronic myeloid leukemia. Unfortunately, the medication has been commonly associated with mild to severe cutaneous reactions, which has limited its use for some patients. We describe a case of a successful progressive challenge of a patient with a drug-induced exanthem from imatinib mesylate and a review of the literature.