Aspirin Allergy Research Articles

E031 Retinal vasculitis with Libman-Sacks endocarditis as presenting features of a systemic lupus erythematosus with antiphospholipid antibody syndrome patient

Abstract Background/Aims Ocular manifestations of systemic lupus erythematosus (SLE) are rarely reported at the time of disease onset. Retinal vasculitis is usually associated with the active generalised disease. We report a case of a 22-year-old lady who was diagnosed with SLE with antiphospholipid antibody syndrome (APS) as the initial presentation of retinal vasculitis and Libman-Sacs endocarditis. Methods A 22-year-old lady with a background history of benign hypermobility spectrum disorder, presented to the eye casualty with a 4-week history of right-sided visual disturbances and was diagnosed with retinal vasculitis associated with uveitis, central retinal vein occlusion with multiple emboli in the retinal artery of the right eye and a single embolus in the left eye. In terms of family history, both father and brother were diagnosed with spondyloarthropathy, and the maternal uncle had Sjogren’s syndrome. She was then referred to the medical team for proper evaluation. On query, she mentioned photosensitive rash on her face getting worse in sunlight, a history of Raynaud’s phenomenon, significant hair loss, and one miscarriage before the 10 weeks of gestation. On examination, mild alopecia and a faint butterfly rash on the face were noted. Cardiac auscultation revealed pansystolic murmur. The rest of the systemic examinations were unremarkable. Results The blood test showed thrombocytopenia (130 u/L), positive antinuclear antibody (1:80, speckled pattern) with anti-double stranded DNA (26 IU/L), low complement (C3-0.74, C4- 0.12), markedly raised anticardiolipin antibody IgG (2016 u/ml), anti beta 2 glycoprotein 1 IgG ( >6100 u/ml) including presence of lupus anticoagulant. Her urinary protein creatinine ratio was 66mg/mmol. 3 sets of blood cultures came back negative. Transthoracic echo showed vegetation on the posterior mitral valve leaflet (0.95x 1.2cm) with moderate mitral regurgitation while transesophageal echo additionally found the possibility of perforation at the junction of leaflets of the mitral valve which was later confirmed by cardiac magnetic resonance imaging (MRI). The head MRI scan did not show any central nervous system abnormality. She was initially treated with 500mg intravenous methylprednisolone for 3 days followed by 20mg oral prednisolone daily with gradual tapering. Hydroxychloroquine and mycophenolate mofetil were added. Her case was discussed in the cardiology multidisciplinary team meeting and an opinion from the cardiothoracic surgery was taken to consider valve replacement in the future. Due to aspirin allergy, only warfarin was considered for APS. She had 2 sessions of pan-retinal photocoagulation as well. In subsequent follow-up, it was noted significant improvements in terms of her symptoms. Conclusion Vaso-occlusive retinopathy is a rare, potentially vision-threatening initial manifestation of SLE, which can be an indicator of active disease. Early identification of patients is necessary for timely intervention and multidisciplinary team involvement is required for comprehensive treatment plans. Disclosure M. Islam: None. S. Quddus: None. M. Hughes: None. R. Kumar: None.

TO CHALLENGE OR AVOID? POSSIBLE ASPIRIN ALLERGY IN PATIENTS WITH CHRONIC IDIOPATHIC URTICARIA AND ANGIOEDEMA

<h3>Introduction</h3> Aspirin remains an important component of dual antiplatelet therapy following percutaneous coronary intervention (PCI). Despite studies showing safety in discontinuing aspirin post PCI through use of P2Y12 inhibitor therapy plus anticoagulation, no large, randomized trials evaluate an initial aspirin-free regimen post PCI without systemic anticoagulation. Aspirin intolerances occur in 20% of patients, with only 2% being true allergies. Most aspirin intolerances are linked to asthma, rhinitis, and chronic idiopathic urticaria (CIU). Differentiating this population is important for optimizing care. <h3>Case Description</h3> C.P. is a 54-year-old male with CIU referred for evaluation of aspirin allergy prior to coronary angiography with possible PCI. In 2001, C.P. developed right periorbital edema an hour after his third dose of daily aspirin therapy. Antihistamines reduced the swelling within hours, however due to reaction, his physician recommended discontinuing aspirin. He noted taking aspirin as a child and ibuprofen as an adult without incident. An in-clinic open oral drug challenge to aspirin was conducted. The patient was given 1/10^th of the full dose, followed by the remaining dose then monitored for 1 hour. The patient was diagnosed with NSAID exacerbated CIU and discharged with aspirin and antihistamines for control. <h3>Discussion</h3> Without clear guidelines for managing NSAID induced CIU, many physicians recommend avoidance, resulting in suboptimal care. 20-40% of CIU patients have flares triggered by NSAIDs, and many are misdiagnosed with an aspirin allergy. Our case demonstrates that through careful history and oral challenge, aspirin exacerbated CIU can be effectively managed without forgoing quality care.

Low dose rivaroxaban therapy in aspirin allergic patients undergoing percutaneous coronary intervention

Abstract Aspirin in combination with a P2Y12 inhibitor is the mainstay of treatment post percutaneous coronary intervention (PCI) for coronary artery disease (CAD). However, patients who are allergic to or intolerant to aspirin pose a therapeutic challenge especially when encountered in the setting of acute coronary syndrome. Aspirin desensitization strategies have been used in clinical practice to build tolerance prior to coronary intervention but clearly are not practical in the setting of ACS or significant symptomatic CAD. Low dose rivaroxaban (2.5 mg twice a day) has been previously shown to be safe in combination with a P2Y12 inhibitor post ACS compared to aspirin. We therefore sought to see if low dose rivaroxaban is a safe and effective alternative to aspirin in patients post PCI who are unable to take aspirin.This study aims to compare the efficacy (Major adverse cardiovascular events (MACE)) and safety (Bleeding events as defined by Bleeding Academic Research Consortium (BARC) criteria) in patients with confirmed aspirin allergy who were treated with low dose rivaroxaban therapy in place of aspirin in combination with P2Y12 inhibitors post PCI. Methods This was a single center observational study which looked at 50 cases of patients with aspirin allergy (47 cases) or significant confirmed aspirin intolerance (3 cases) who underwent PCI between December 2017 and February 2022. Patients were advised to take low dose rivaroxaban 2.5 mg twice a day as an alternative to aspirin 75 mg once a day. A comparator group of 50 matched patients without aspirin allergy who underwent PCI during the same time period and treated with standard aspirin therapy (75mg) along with a P2Y12 inhibitor. Outcomes over follow-up were MACE (mortality, myocardial infarction, stroke, and unscheduled revascularisation) and bleeding events defined by–BARC criteria. Results The median age of the aspirin allergy cohort was 62 years old with typical comorbidities associated with CAD. The cohort included a case mix of ACS and stable angina.The P2Y12 inhibitor in the majority of cases (76%) was Clopidogrel; Ticagrelor was used in 20% of cases and Prasugrel in 4% cases. No differences existed between the rivaroxaban and matched patient groups. The median follow-up as 626 days (Interquartile range 237–549). The duration of low dose rivaroxaban therapy was for 12 months with a P2Y12 in 72%, 1–3 months for 22% and finally continued long term (with P2Y12 discontinuation at 12 months) in 6%. No difference existed in the incidence of MACE between the low dose rivaroxaban group (12%) compared to the matched cohort (10% p=0.266). No difference in bleeding outcomes (any bleeding event BARC type &amp;gt;0) were seen (14% in rivaroxaban and 16% in control, p=0.329). Conclusions This study provides more supporting evidence that low dose rivaroxaban therapy is an alternative to aspirin when used in combination with a P2Y12 inhibitor post PCI. Funding Acknowledgement Type of funding sources: None.

S1844 The Gallbladder Houdini: A Rare Presentation of Eosinophilic Cholecystitis and Gastroenteritis

Introduction: Eosinophilic gastroenteritis (EG) is an inflammatory condition with eosinophilic infiltration of the GI tract, but biliary tract involvement is rare. We report a rare case of EG with concurrent eosinophilic cholecystitis. Case Description/Methods: A 24 y/o WF with a history of Samter’s triad (nasal polyposis, asthma, aspirin allergy) managed with dupilumab, presented to the ER with chronic LUQ abdominal pain, N/V, dysphagia, diarrhea, and weight loss. Lab revealed normal LFTs and an elevated WBC to 13.6k with 9.2% eosinophils (eos). RUQ US showed fatty liver and cholelithiasis with normal caliber CBD. She underwent laparoscopic cholecystectomy with surgical pathology revealing early acute on chronic cholecystitis and cholelithiasis with extensive eosinophilic inflammation. She noted persistent symptoms with follow up labs showing increasing WBC to 26k with 67% eos. Repeat CT scan was unremarkable. Initial EGD showed gastritis with distal esophageal biopsies showing 100 eos/hpf. She was started on PPI. Repeat EGD showed gastritis and duodenitis with biopsies remarkable for eosinophilia of the stomach and proximal small bowel. Colonoscopy with TI intubation was endoscopically normal with normal biopsies of the TI and colon. She was started on PPI for eosinophilic esophagitis and a prednisone taper for eosinophilic gastroenteritis with symptom resolution. Discussion: The prevalence of EG is highest in children but can occur in adults often with concomitant atopic disease in the 3rd-5th decades. The clinical presentation varies, depending on the depth of inflammation (mucosal, muscular, or serosa) and location of involvement and may include abdominal pain, N/V, diarrhea, and weight loss. Diagnosis is based on pathology obtained during endoscopy or surgery. It is prudent to obtain multiple biopsies given patchy disease and consider transmural biopsies to identify processes limited to the muscular layer. Imaging can show non-specific inflammation. Peripheral eosinophilia is present in ∼80% of cases. The mainstay of therapy is corticosteroids, with a 90% symptomatic response. Azathioprine can be considered as a steroid sparing agent. Eosinophilic cholecystitis has rarely been reported in the literature but often in association with other illnesses. We present a unique case of eosinophilic cholecystitis in a patient with concurrent eosinophilic gastroenteritis. Upon review of the literature only 5 other similar cases have been described.

Patients Who Do Not Receive Aspirin Because of Allergy Have an Increased Risk of Venous Thromboembolism Following Total Joint Arthroplasty.

Patient-reported allergies to aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs) may preclude certain patients from receiving aspirin as venous thromboembolism (VTE) prophylaxis after total joint arthroplasty (TJA). The purpose of the study was to (1) determine whether the use of non-aspirin agents due to a self-reported aspirin or NSAID allergy was associated with a higher incidence of VTE and (2) determine the rate of true allergic reactions in patients who reported an allergy but still received aspirin. Prospectively collected data from 45,171 patients who underwent primary TJA between 2000 and 2019 were reviewed. Patients who reported an allergy to aspirin or NSAIDs were identified (n = 823). Using a validated VTE risk calculator, each patient was assigned a risk score based on 26 comorbidities. Bleeding complications, VTEs that occurred within 90 days postoperatively, and allergic reactions were collected as end points. Multivariable logistic regression was performed to determine the factors associated with VTE. The overall incidence of aspirin or NSAID allergy was 1.8%. Only 80 of 267 patients (30%) reported an allergy to only aspirin and still received aspirin. Compared with patients who received aspirin without a history of allergy (n = 17,648), patients who received non-aspirin thromboprophylaxis due to allergy (n = 383) had a higher incidence of VTE (2.87% versus 0.24%, p < 0.001). On multivariable regression, these patients had an 8-fold increase in VTE risk (adjusted odds ratio, 7.94; 95% confidence interval, 2.86 to 22.07; p < 0.001). The incidence of true allergic reactions to aspirin among those with a reported allergy was 1.8% (number needed to harm = 55). No patients developed anaphylaxis or severe hypersensitivity reactions. Patients with a self-reported allergy to aspirin or NSAIDs were at a significantly increased risk for VTE if they received non-aspirin thromboprophylaxis agents following TJA. Future research should evaluate the usefulness of preoperative allergy testing when selecting a VTE prophylactic agent in patients with self-reported allergies. Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

B-PO05-209 PERICARDIAL EFFUSION AFTER LEFT ATRIAL APPENDAGE OCCLUSION RESULTING FROM AN AORTIC DISSECTION

Atrial fibrillation (AF) affects 2.3 million Americans. In those unfit for long-term anticoagulation, left atrial appendage occlusion (LAAO) is an alternative for stroke prophylaxis. N/A N/A A 68-year-old female with a history of AF, 4.3 cm ascending aortic aneurysm, hemoptysis on anticoagulation, and an aspirin allergy successfully underwent a LAAO with a 27 mm Watchman device. Postoperatively, she developed a moderate pericardial effusion without tamponade physiology. The effusion and her 3.5 cm aortic root (Fig. 1A) remained stable after anticoagulation reversal and over 48-hour observation. Warfarin and clopidogrel were restarted at discharge. The patient was readmitted 48 hours later with back pain. She was diagnosed with a Stanford type A dissection from the aortic root to the renal arteries, with extension into the pericardial space without evidence of tamponade (Fig. 1B, C). Unlike previously reported post-LAAO effusions, this effusion was not caused by the LAAO device. It is most likely that the new initiation of anticoagulation and possible injury during catheter manipulation potentiated the propagation of a pre-existing aortic dissection. Cardiothoracic surgery was emergently consulted, but she suffered a cardiac arrest and expired prior to intervention. When evaluating a pericardial effusion after LAAO, the differential should extend past a procedural complication to include other life-threatening conditions, like an aortic dissection which was uniquely presented in this case. Peri-procedural echocardiograms should include an appraisal of the aortic root and ascending aorta to rule out acute pathology.

2020 American Heart Association and American Red Cross Focused Update for First Aid.

2020 American Heart Association and American Red Cross Focused Update for First Aid.

Aspirin allergy labeling after desensitization: education, communication, and patient safety

Hypersensitivity reactions to aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most common causes of drug-induced hypersensitivity and constitute a spectrum of diverse immunologic and inflammatory processes.1 For many patients with NSAID hypersensitivity, aspirin desensitization can allow for administration of aspirin for therapeutic purposes, such as in aspirin-exacerbated respiratory disease (AERD)2 or coronary artery disease (CAD).3 However, desensitization only induces a transient tolerance, contingent on daily and regular ingestion of a fixed aspirin dose; desensitization does not resolve the underlying hypersensitivity process.

Higher-starting-dose protocols in patients with coronary artery disease and aspirin hypersensitivity

Aspirin is first-line treatment in patients with coronary artery disease (CAD), but in patients with acute coronary syndrome (ACS) or those who require dual antiplatelet therapy after myocardial revascularization, aspirin therapy becomes critical and time sensitive.1 Approximately 1.5% of patients with CAD report aspirin allergy.2 Most reactions are considered nonimmunologic, related to aspirin's inhibition of cyclooxygenase that causes allergic-like symptoms.3 A subset of patients have aspirin-exacerbated respiratory disease (AERD) or chronic idiopathic urticaria (CIU) exacerbated by aspirin.

Validation of a claims-based algorithm identifying eligible study subjects in the ADAPTABLE pragmatic clinical trial.

ObjectiveValidate an algorithm that uses administrative claims data to identify eligible study subjects for the ADAPTABLE (Aspirin Dosing: A Patient-centric Trial Assessing Benefits and Long-Term Effectiveness) pragmatic clinical trial (PCT).Materials and methodsThis study used medical records from a random sample of patients identified as eligible for the ADAPTABLE trial. The inclusion criteria for ADAPTABLE were a history of acute myocardial infarction (AMI) or percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG), or other coronary artery disease (CAD), plus at least one of several risk-enrichment factors. Exclusion criteria included a history of bleeding disorders or aspirin allergy. Using a claims-based algorithm, based on International Classification of Diseases, 9th Edition, Clinical Modification (ICD-9-CM) and 10th Edition (ICD-10) codes and Current Procedural Terminology (CPT) codes, we identified patients eligible for the PCT. The primary outcome was the positive predictive value (PPV) of the identification algorithm: the proportion of sampled patients whose medical records confirmed their ADAPTABLE study eligibility. Exact 95% confidence limits for binomial random variables were calculated for the PPV estimates.ResultsOf the 185 patients whose medical records were reviewed, 168 (90.8%; 95% Confidence Interval: 85.7%, 94.6%) were confirmed study eligible. This proportion did not differ between patients identified with codes for AMI and patients identified with codes for PCI or CABG.ConclusionThe estimated PPV was similar to those in claims-based identification of drug safety surveillance events, indicating that administrative claims data can accurately identify study-eligible subjects for pragmatic clinical trials.

Abstract 16817: Single Anti Platelet Agent vs. Dual Anti Platelet Agents in Patients Undergoing Percutaneous Coronary Intervention: A Tertiary Care Center Experience

Introduction: Data on P2Y12 inhibitor (single agent) use in percutaneous coronary intervention (PCI) is sparse. Hypothesis: Long term outcomes in patients undergoing PCI with only P2Y12 inhibitors vs. dual antiplatelet therapy (DAPT). Methods: We used PCI registry of Guthrie clinic system from the year 2001 to 2012. We identified patients discharged only on P2Y12 inhibitors (Plavix, Ticagrelor, Prasugrel) due to aspirin allergy. We created propensity score using patient demographics (age, gender), risk factors (hypertension, diabetes, hyperlipidemia etc.), medications detail (statin, B blocker etc.) and catheterization detail (vessel involved, type of stent and culprit vessel etc.) for patients discharged only on P2Y12 inhibitors vs DAPT. Propensity score match (1:100) analysis was conducted using greedy’s method for adjusting confounders. The primary outcome was MACE(myocardial infarction(MI), stroke, death, coronary artery occlusion) up to 8 years and secondary outcomes were death and recurrent myocardial infarction(MI) up to 8 years. Sensitivity analysis was done using Cox-proportional hazard regression. Results: 7742 patients with successful intervention were identified during the study period. Out of which, 43(0.65%) had aspirin allergy and received only P2Y12 inhibitor. Hyperlipidemia (78.8%), hypertension (72.8%), obesity (48.7%) and diabetes (31.6%) were most common risk factors. &gt;90% patients were on optimum medical treatment. 59% of patients received drug-eluting stent/s and 17.5% patients underwent multivessel PCI. Right coronary artery(37.6%) and left anterior descending artery(35.8%) were commonest culprit vessels. Median follow up period was 1828 days (~ 5 years). After adjusting with propensity score match, primary outcome (HR:1.73, 95% CI: 1.17-2.67, p-0.005) and secondary outcomes (MI: HR: 2.46, 95% CI:1.28-4.51, p-0.005), (death: HR:1.85, 95% CI:1.09-2.23, p-0.023) were higher in patients discharged only on P2Y12 inhibitors. Sensitivity analysis showed similar results. Conclusions: Only P2Y12 inhibitor was inferior to DAPT in patients undergoing PCI. Future clinical trials will be needed to reinforce our findings.

HIGHER STARTING DOSE PROTOCOLS IN CORONARY ARTERY DISEASE PATIENTS WITH ASPIRIN HYPERSENSITIVITY

Introduction Aspirin is a cornerstone of atherosclerosis therapy, but 1.5% of coronary artery disease (CAD) patients report aspirin allergy. Past protocols of challenge and/or desensitization for aspirin allergy excluded acute coronary syndrome (ACS) patients and/or started at low doses. Recent studies propose higher starting doses with fewer steps. The safety and efficacy of these newer protocols are not established, especially in the acute setting where the ability to tolerate aspirin is time-sensitive. Methods A retrospective chart review was conducted for all inpatient allergy consults for patients with suspected CAD and aspirin allergy. Three categories of aspirin protocols were evaluated for patient characteristics, safety, and efficacy: challenge (graded or direct without premedication), challenge-desensitization (starting dose 20.25-40.5 mg with premedication), and slow desensitization (starting dose 0.1 mg with premedication). Results From 2007 to 2017, 144 aspirin challenges or challenge-desensitizations in patients without a history of anaphylaxis to aspirin were done with 98.9% success. A total of 126 procedures were done prior to cardiac intervention, and though 107 presented with ACS, none had direct cardiovascular complications from the aspirin protocol. There were 18 reactions (12.5%): 14 mild and 4 moderate, with 1 requiring epinephrine. Three were AERD patients with expected reactions, 4 were challenges who then underwent successful challenge-desensitization. There was no difference in the number of reactions between the challenge-desensitization versus the slow desensitization group (p=0.10). Conclusions Higher dose starting protocols for CAD patients with self-reported aspirin allergy are safe and effective, with similar success rate to protocols starting at lower doses.

Prognosis of Chronic Rhinosinusitis With Nasal Polyps Using Preoperative Eosinophil/Basophil Levels and Treatment Compliance.

Background Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) have a high risk of disease recurrence and revision surgery. The ability to predict a polyp recurrence in this patient population is critical in order to provide adequately tailored postoperative management. Objective We aim to explore the role of appropriate postoperative care in the prognosis of CRSwNP patients in relation to preoperative eosinophil and basophils levels. Methods This was a retrospective case series; data were collected for 102 CRSwNP patients over a period of 15 months after surgery. Baseline eosinophil and basophil levels were compared between patients with and without polyp recurrences. The analysis was then stratified based on clinical diagnosis, comorbidities (atopy, asthma, and aspirin allergy), a single versus multiple episodes of sinonasal polyp recurrences, and medication adherence. Results Of the 102 included patients, 65 (63.7%) of the patients experienced no recurrences, 26 (25.5%) experienced a single episode of recurrence, and 11 (10.8%) experienced multiple recurrences. Mean baseline eosinophil count and percentage of total white blood cells were significantly higher in the multiple recurrences group (0.70 × 109/L and 10%) compared with the no recurrences group (0.36 × 109/L and 5%). Adherence to prescribed medical therapy prior to the first episode of recurrence was significantly lower for the single exacerbations group (42.3%) than the multiple recurrences group (88.9%). Conclusions Patients with multiple recurrences of nasal polyps had significantly higher baseline eosinophil counts and significantly higher medication adherence compared to single exacerbations of nasal polyps. Single exacerbations may not reflect true failures of surgery but rather a failure of postoperative medical care. Basophil levels were inadequate to predict polyp recurrence rates.

Lambl’s excrescences and a review of therapeutic strategies

Background: Lambl’s excrescences (LEx) are thin, filiform structures that arise on the lines of closure of heart valves. Although rare, we have come across various case reports in the literature describing thromboembolic events associated with LEx. We report the case of a 63-year-old female who presented with TIA-like symptoms and was found to have a LEx on the aortic side of native aortic valve. We conducted a comprehensive literature review with emphasis on different therapeutic strategies utilized to provide insight for future encounters.Case presentation: A 63-year-old female with a past medical history significant for hypertension and hyperlipidemia presented to the emergency room with symptoms of dysarthria and unsteady gait. While in the hospital, the patient returned to her baseline gait and speech without intervention. Work-up for including computed tomography of the head, magnetic resonance imaging, and carotid doppler, as well as prolonged telemetry monitoring was negative. A transthoracic echocardiogram showed a 0.81 cm linear echodensity attached to the aortic side of the aortic valve, highly suggestive of LEx that was later confirmed on transesophageal echocardiogram. Patient was placed on clopidogrel alone for antiplatelet therapy due to an aspirin allergy and she was subsequently discharged home.Discussion: No standard management for LEx currently exists. We aim to add to the evidence of effective management and explore the literature of patients who have experienced TIA/CVA symptoms secondary to LEx.

Wishing It True Doesn't Make It So: Commentary on an article by Gregory M. Mendez, MD, et al.: "Aspirin for Prophylaxis Against Venous Thromboembolism After Orthopaedic Oncologic Surgery".

Commentary In this article, Mendez et al. offer their experience with use of aspirin for venous thromboembolism (VTE) prophylaxis specifically in orthopaedic oncology patients. They conclude that aspirin is a “suitable” chemoprophylactic agent. I wish this were so because aspirin is such a simple agent to prescribe and use. However, few topics in orthopaedics are as controversial as the selection of appropriate prophylaxis postoperatively. Prophylaxis for VTE in general has been the focus of numerous randomized prospective clinical trials with Level-I evidence, but even those have not always agreed. Hence, study panels of the American College of Chest Physicians (ACCP), American Academy of Orthopaedic Surgeons (AAOS), and American Society of Clinical Oncology (ASCO) continue to publish guidelines based on their interpretation of the latest literature. Despite these guidelines, there is considerable flexibility in a physician’s or surgeon’s choices for VTE prophylaxis. The controversy about VTE prophylaxis has been particularly contentious with respect to aspirin. As noted by Mendez et al., the ACCP guidelines recommended against its use in 2008 but then added aspirin as an acceptable agent in 2012. ASCO guidelines recommend against aspirin use and suggest only unfractionated heparin or low-molecular-weight heparin (LMWH) be used for patients with cancer who are undergoing major surgery. However, they do allow for aspirin use in patients on chemotherapy for myeloma. Citing ambiguity in the evidence, the AAOS guidelines allow use of aspirin as well as a pneumatic compressive device or any other chemotherapeutic agent for postoperative VTE prophylaxis following hip and knee arthroplasty. Mendez et al. are correct in asserting that universal surgical guidelines do little to direct the orthopaedic oncologist in the selection of VTE prophylaxis. However, does their article provide us the missing but desired direction? I believe that it is difficult to know how to use their findings. First, the number of patients in their study was relatively small (130 patients with a total of 142 procedures). In a recent systematic review and meta-analysis of computerized clinical decision support systems for VTE prophylaxis, 11 publications (including 9 prospective cohort trials) involving 156,366 subjects (an average 14,408 subjects per trial) were reviewed1. Even among 7 prior studies of VTE in orthopaedic oncology, the average number of patients was 348 (range, 94 to 986). Moreover, 5 of those studies were focused on incidence and risk factors for VTE. The only 2 treatment studies in orthopaedic oncology involved 348 subjects (treated with aspirin and a pneumatic compression device or with LMWH and a pneumatic compression device) and 986 subjects (treated with LMWH)2,3. Second, although this was a retrospective study, and hence intention-to-treat (ITT) analysis was not applicable, the authors clearly intended for all of their patients to receive aspirin; however, only 73% did so. Reasons for protocol deviation included an outpatient operative procedure not requiring chemoprophylaxis, patient refusal, aspirin allergy, VTE history, and a desire for a readily reversible option in case an early return to the operating room was necessary. Third, the orthopaedic oncology patient population studied by Mendez et al. was broad in its scope of inclusion criteria, which included metastatic carcinoma, myeloma, lymphoma, and sarcoma, further diluting the numbers for subgroup analysis. It also differs somewhat from prior reports in that more than one-half of the patients had metastatic carcinoma whereas some larger studies in orthopaedic oncology included predominantly or exclusively patients with sarcoma4,5. Thus, we must greatly temper our enthusiasm for the conclusion that aspirin is a suitable agent with the realization that the data are based on a small number of patients relative to the large body of literature on this topic. Also, the study was not a pure evaluation of patients treated only with aspirin, but rather a real-practice evaluation in which there were protocol deviations for various reasons; hence, its conclusions should not be extended to patients who had outpatient surgical procedures or a VTE history, for instance. Finally, although a broad range of orthopaedic oncology diagnoses were included, this actually makes it difficult to know how readily the results could be applied to patients with any one of those diagnoses. In conclusion, as much as I want aspirin to be a safe and efficacious VTE chemoprophylactic agent for all of my orthopaedic oncology patients, these results should not be interpreted as definitive support until additional studies are done.

A Novel Two Day Desensitization Protocol to Oral Mesalamine

Ulcerative proctosigmoiditis is a chronic inflammatory condition that is initially treated with mesalamine, a preferred treatment to steroids and immunomodulators. Hypersensitivity reactions to mesalamine have been reported and a limited number of desensitization protocols have been published taking between 3 days to weeks. We present a case of a patient with ulcerative proctosigmoiditis and aspirin allergy with adverse reactions to mesalamine who failed an oral mesalamine challenge. She subsequently underwent successful mesalamine desensitization with a rapid 2 day protocol. The desensitization took place in the intensive care unit. The starting dose of mesalamine was 1mg. On day 1, incremental doses were given every 30 minutes up to 500mg. On day 2, the patient received a total of 2.5 grams of mesalamine, which was her targeted daily dose. The patient was successfully desensitized after 2 days with one hypersensitivity reaction. She developed mild shortness of breath with a drop in FEV1 from 450 to 350 on day 1 of the desensitization, which resolved with nebulized albuterol and fexofenadine. Since discharge from the hospital, she continued mesalamine 2.4 grams daily without adverse reactions. This case demonstrates a patient with mesalamine hypersensitivity can be safely offered a rapid 2 day oral desensitization protocol, and maintained on the medication for long term management of ulcerative proctosigmoiditis.

PREVALENCE AND MANAGEMENT OF ASPIRIN ALLERGY IN AN AMBULATORY CARDIOLOGY PRACTICE AND IN PATIENTS UNDERGOING PERCUTANEOUS CORONARY INTERVENTION

The prevalence and management of aspirin (ASA) allergy are not well established. We conducted an electronic medical record review of 11375 individuals, 5052 (44%) in the ambulatory setting, and 6323 (56%) admitted for percutaneous coronary intervention (PCI) from January 2012 to December 2013. The

Acute severe asthma (status asthmaticus).

Acute severe asthma, formerly known as status asthmaticus, is defined as severe asthma unresponsive to repeated courses of beta-agonist therapy. It is a medical emergency that requires immediate recognition and treatment. Albuterol in combination with ipratropium bromide in the emergency department (ED) has been shown to decrease the time spent in the ED and the hospitalization rates. The benefits of ipratropium are not sustained after admission to the hospital. Oral or parenteral corticosteroids should be administered to all patients with acute severe asthma as early as possible because clinical benefits may not occur for a minimum of 6 to 12 hours. Viral respiratory infections are a common trigger for acute asthma; other causes include medical nonadherence, allergen exposure (especially pets and mold [e.g., Alternaria species]) in individuals who are severely atopic, nonsteroidal anti-inflammatory exposure in patients with aspirin allergy, irritant inhalation (e.g., smoke, paint), exercise, and insufficient use of inhaled or oral corticosteroids. The patient's history should focus on the acute assessment of asthma control and morbidity, including current use of oral or inhaled corticosteroids; the number of hospitalizations, ED visits, intensive care unit admissions, and intubations; the frequency of albuterol use; the presence of nighttime symptoms; activity intolerance; current medications; exposure to allergens; and other significant medical conditions. Severe airflow obstruction may be predicted by accessory muscle use, difficulty speaking, refusal to recline < 30°, a pulse of >120 beats/min, and decreased breath sounds. More objective measures of airway obstruction via peak flow or forced expiratory volume in 1 second and pulse oximetry before oxygen administration usually are helpful. Pulse oximetry values of >90% are reassuring, although CO₂ retention and a low partial pressure of oxygen may be missed.

Utility of low-dose oral aspirin challenges for diagnosis of aspirin-exacerbated respiratory disease

BackgroundAspirin-exacerbated respiratory disease (AERD) is diagnosed through graded aspirin challenges that induce hypersensitivity reactions and eicosanoid level changes. It is not known whether diagnostically useful changes also occur after low-dose aspirin challenges that do not induce hypersensitivity reactions. ObjectiveTo investigate the utility of low-dose oral aspirin challenges for diagnosing AERD by measuring different clinical parameters and eicosanoid changes. MethodsSixteen patients with AERD and 13 patients with aspirin-tolerant asthma underwent oral challenges with low-dose (20 or 40 mg) aspirin and diagnostic oral graded aspirin challenges (up to 325 mg of aspirin). Forced expiratory volume in 1 second, nasal peak flow, the fraction of exhaled nitric oxide (FeNO), and eicosanoid levels in plasma and urine were analyzed. ResultsIn patients with AERD but not in those with aspirin-tolerant asthma, 40-mg aspirin challenges induced a significant mean (SEM) decrease from baseline in FeNO (19% [5.1%]; P = .001) without causing any hypersensitivity reaction. The FeNO decrease also occurred after higher-dose aspirin challenges (27.8% [4.9%]; P < .001). The sensitivity and specificity of 40-mg aspirin-induced FeNO changes for identifying AERD were 90% and 100% with an area under the curve of 0.98 (95% CI, 0.92–1.00). The low-dose challenge also induced a significant leukotriene E4 urine increase in patients with AERD (from 6.32 [0.08] to 6.91 [0.15] log-pg/mg creatinine; P < .001), but the sensitivity and specificity of these changes were less than for the FeNO changes. ConclusionThe low-dose aspirin-induced decrease in FeNO in patients with AERD may be useful for the diagnosis of aspirin allergy without inducing a hypersensitivity reaction. Trial Registrationclinicaltrials.gov Identifier: NCT01320072.

Rapid Aspirin Challenge in Patients with Aspirin Allergy and Acute Coronary Syndromes.

Aspirin allergy in a patient with acute coronary syndrome represents one of the more urgent challenges an allergist may face. Adverse reactions to aspirin are reported in 1.5% of patients with coronary artery disease. A history of adverse reaction to aspirin often leads to unnecessary withholding of this medication or use of alternative antiplatelet therapy which may be inferior or more costly. Aspirin therapy has been shown to reduce morbidity and mortality in patients with coronary artery disease. Rapid aspirin challenge/desensitization in the aspirin allergic patient has been consistently shown to be both safe and successful in patients with acute coronary syndromes.