Rapid drug desensitization to taxanes: a descriptive study from Turkey.

AIM: To present the characteristics of drug hypersensitivity reactions (DHRs) among taxane recipients with non-small cell lung carcinoma (NSCLC), and to describe the results of rapid drug desensitization (RDD). METHODS: A retrospective cross-sectional study included 45 patients who were treated with taxane for NSCLC and were found to be hypersensitive to taxane. All patients were administered the standard 3-bag, 12-step RDD protocol following the development of DHR. RDD success was evaluated separately for each cycle, and successful RDD was defined as the completion of the cycle with application of 12 steps of the desensitization protocol and the absence of early and/or late reactions afterwards. RESULTS: Among 45 patients hypersensitive to taxane 43 (95.6%) successfully received taxane cycles with desensitization. Failed RDD occurred in only 2 (4.4%) patients. The total number of desensitization cycles was 183, of which 181 (98.9%) were successful. The mean age of patients with successful desensitization was 59.42 ± 10.48 years and 37 (86.0%) of them were male. CONCLUSION: RDD is a reliable procedure that enables effective administration and completion of first-line taxane treatments in taxane-sensitive patients.

Platin desensitizations in thoracic malignancies and risk factors for breakthrough reactions.

Although platin desensitization is a safe and effective alternative for patients with hypersensitivity reactions (HSRs), sometimes breakthrough reactions (BTRs) can be encountered. However, data about the risk factors for BTRs are limited. The aim of this study is to define the outcomes of desensitization, the characteristics of BTRs, and to identify the risk factors for BTRs with platins in thoracic malignancies. This is a retrospective report of patients with thoracic malignancies who underwent platin desensitization. Patients' demographics, initial HSR characteristics, skin test results, desensitization outcomes, and BTR characteristics were recorded. Thirty-three lung cancer and 14 malignant pleural mesothelioma (MPM) patients were included in the study. The culprit drug was cisplatin in 29 and was carboplatin in 18 patients. Skin test positivity was 43.5% with cisplatin, 50% with carboplatin, and it was found to be higher if the interval between the initial HSR and skin testing (ST) was ˃20 days (p = 0.027). One hundred and five desensitization courses were performed. Twenty-two patients had 33 BTRs. Skin test positivity was higher in the BTR-positive group (p = 0.025). BTRs (18.2%; n = 6) were more severe than initial HSR. In the case of epinephrine administration during initial HSR, epinephrine administration during the first BTR was found to be more (p = 0.036). The target dose was achieved in 92.4% of desensitization courses. The number of previous platin infusions ≥10 was found to be an independent risk factor for BTR development (p = 0.036 OR:17.641, 95% CI: 1.211-256.971). Identification of risk factors for BTR will guide appropriate management and desensitization approaches for platin HSRs.

Successful desensitization under antihistamine suppression in a case with urticaria due to osimertinib.

INTRODUCTION: Osimertinib is an approved therapy for patients with a Thr790met (T790M) mutation diagnosed with non-small cell lung cancer (NSCLC) that progresses during epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) therapy. However, in 7-13% of patients, drug-related side effects lead to discontinuation of osimertinib treatment. In such cases, osimertinib desensitization is a treatment option that can be considered. CASE REPORT: A 59-year-old female patient, who was followed up with the diagnosis of stage 4 NSCLC, was consulted to the allergy clinic because of urticaria. The patient developed urticaria plaques 20 h after the third dose of osimertinib tablet. MANAGEMENT & OUTCOME: With the diagnosis of osimertinib-induced urticaria, desensitization was planned for the patient. Treatment was started with a dose of 0.1 mg/day osimertinib. The procedure was completed in approximately 50 days, and a dose of 80 mg/day was reached with antihistamine suppression. DISCUSSION: Here, a successful osimertinib desensitization in a patient with a history of osimertinib-related type 1 allergic reaction is reported. Osimertinib desensitization is a treatment option that should be considered in cases where treatment has to be ceased due to drug-related side effects.

COVID-19 in a patient with severe asthma using mepolizumab.

Background: There is a lack of information about the course of coronavirus disease 2019 (COVID-19) in patients with severe asthma who were treated with biologics. Some reports indicated that treatment with benralizumab, dupilumab, and omalizumab in patients with severe asthma was not associated with significant adverse effects during COVID-19. Methods: Asthma itself or the biologic agents used to treat asthma can have a positive effect on the course of COVID-19. There seem not to be any cases that specifically reported the use of mepolizumab in a patient who was infected with COVID. Results: We reported of a 55-year-old woman with a diagnosis of severe asthma for; 3 years and who was being treated with mepolizumab, with no evidence of loss of asthma control, at the time of contracting COVID-19 and who had been followed up in the allergy clinic. In addition, there are no data on mepolizumab therapy in patients with elevated liver enzyme levels. Conclusion: With this case, we also reported that no adverse effects were observed during mepolizumab treatment in a patient with elevated liver enzyme levels.

[Mycobacterium abscessus infection management: Macrolide and quinolone desensitization]. / Mycobacterium abscessus enfeksiyonu yönetimi: Makrolid ve kinolon desensitizasyonu.

Antibiotic hypersensitivity reactions can lead to marked morbidity, mortality and inadequate treatment options. Mycobacterium abscessus infection is a difficult management system for clinicians since it most commonly involves the lungs, progresses if untreated, and the organism is resistant to many antibiotics, as well as the agents used in treatment can cause undesirable side effects. Although macrolides are one of the most reliable antibiotic groups in terms of allergic reactions, early type hypersensitivity reactions against macrolides, one of the main antibiotics used in the treatment of Mycobacterium abscessus lung disease, may make the treatment management of the disease difficult. Due to the rapid increase in the use of quinolone in recent years, the frequency of developing allergic reactions with these agents also increases. In cases where antibiotic hypersensitivity is detected, the use of the responsible agent should be avoided, but desensitization may be necessary in cases without different treatment options. In this study, it was aimed to present a case of successful desensitization with clarithromycin and moxifloxacin in a patient who was diagnosed with Mycobacterium abscessus lung disease and developed anaphylaxis with clarithromycin and moxifloxacin after treatment was initiated.

COVID-19 in patients with severe asthma using biological agents.

As the COVID-19 pandemic continues, case reports have been published where patients with severe asthma using biological agents survived with a mild course of illness and encouraged the continuation of biological therapies in patients with severe asthma. However, contrary to previous information, a more severe course of COVID-19 has recently been reported in severe asthmatics using biological therapy compared to the general population. To evaluate the COVID-19 rate and disease severity in severe asthmatics using biological agents. A retrospective study was conducted in patients with severe asthma treated with biological agents. Data concerning whether the subjects had contracted COVID-19 and the severity of the disease were evaluated. Eihgty-four severe asthmatics using biological agents (omalizumab or mepolizumab) aged 48.3 ± 10.6 years (mean ± standard deviation) with female/male ratio: 53 (63.1%)/31 (36.9%) were included in the study. Among participants 13 (15.5%) had contracted COVID-19. The course of COVID-19 was mild in five (38.5%) and moderate in eight patients (61.5%), while none of the patients had a severe course of COVID-19. Mechanical ventilation or intensive care follow-up was not required in any of the six patients (46.2%) who were treated as inpatients. All participants survived COVID-19 in full recovery and no deaths occurred in the cases. A higher rate of COVID-19 was found in patients with severe asthma using biologics compared to those reported in previous reports. However, all patients with COVID-19 have a mild to moderate disease course.

A novel clinical index for the assessment of RVD in acute pulmonary embolism: Blood pressure index.

BACKGROUND: This study aims to investigate the role of the blood pressure index (BPI), which is a new index that we developed, in detection of right ventricular dysfunction (RVD) in acute pulmonary embolism (APE). METHODS: A total of 539 patients, (253 males and 286 females), diagnosed with APE using computer tomography pulmonary angiography were included in the study. The BPI was obtained by dividing systolic blood pressure (SBP) by diastolic blood pressure (DBP). RESULTS: Mean DBP (75±11mmHg vs 63±15mmHg; p<0.001, respectively) was found to be higher in RVD patients compared to those without RVD, whereas BPI (1.5±0.1 vs 1.9±0.2; p<0.001, respectively) was lower. Examining the performance of BPI in prediction of RVD using receiver operating characteristic curve analysis (area under curve±SE=0.975±0.006; p<0.001), it was found that BPI could predict RVD with very high sensitivity (92.8%) and specificity (100%) and had a positive predictive value of 100% and a negative predictive value of 42.1%. According to the analysis, the highest youden index for the optimal prediction value was found to be 0.478 and the BPI≤1.4 was found to predict mortality 68.6% sensitivity and 80.8% specificity (Area under curve±SE=0.777±0.051; p<0.001). CONCLUSIONS: We found that BPI was an index with high positive predictive value and low negative predictive value in detection of RVD.

Diagnostic validity of hematologic parameters in evaluation of massive pulmonary embolism.

BACKGROUND: The aim of this study was to determine the hematologic parameter with the highest diagnostic differentiation in the identification of massive acute pulmonary embolism (APE). METHODS: A retrospective study was performed on patients diagnosing with APE between June 2014 and June 2016. All radiological and laboratory parameters of patients were scanned through the electronic information management system of the hospital. PLR was obtained from the ratio of platelet count to lymphocyte count, NLR was obtained from the ratio of neutrophil count to lymphocyte count, WMR was obtained from white blood cell in mean platelet volume ratio, MPR was obtained from the ratio of mean platelet volume to platelet count, and RPR was obtained from the ratio of red distribution width to platelet count. RESULTS: Six hundred and thirty-nine patients consisting of 292 males (45.7%) and 347 females (54.3%) were included in the research. Independent predictors of massive risk as compared to sub-massive group were; pulmonary arterial systolic pressure (PASP) (OR=1.40; P=.001), PLR (OR=1.59; P<.001), NLR (OR=2.22; P<.001), WMR (OR=1.22; P<.001), MPR (OR=0.33; P<.001), and RPR (OR=0.68; P<.001). Upon evaluation of the diagnostic differentiation of these risk factors for massive APE by employing receiver operating characteristic curve analysis, it was determined that PLR (AUC±SE=0.877±0.015; P<.001), and NLR (AUC±SE=0.893±0.013; P<.001) have similar diagnostic differentiation in diagnosing massive APE and these two parameters are superior over PASP, MPR, WMR, and RPR. CONCLUSION: We determined that the levels of NLR and PLR are superior to other parameters in the determination of clinical severity in APE cases.

What is the Best Way to Diagnose Possible Asthma Patients with Negative Bronchodilator Reversibility Tests?

Objective: The best method and strategy for the diagnosis of asthma remains unclear, especially in patients with negative bronchodilator reversibility test (BDRT). In our study, we aimed to investigate the diagnostic yield of peak expiratory flow (PEF) variability for this patient group. Methods: A total of 50 patients with suspected asthma, all with negative BDR test, were included in the study. Demographic information and symptoms were recorded and PEF variability was monitored for 2 weeks. Metacolinbronchial provocation test (mBPT) was performed. Asthma was diagnosed when PEF variability ≥20% and/or positive mBPT was observed. Results: 30 of 50 patients were diagnosed with asthma. After 1 month, 17 patients were evaluated for treatment outcomes. The sensitivity and specificity of PEF variability for different cut-off values (≥20%, >15% and >10%) were 61.5-83.3, 88.5-62.5 and 100-16.7, respectively. One of the most important findings of our study was the absence of variable airflow limitation or airway hyper reactivity in 39% patients with a previous diagnosis of asthma. Multiple logistic regression analysis revealed that a low baseline FEF25-75 value was an independent predictive factor for the diagnosis of asthma (p= 0.05). Conclusion: The most efficient diagnostic test for asthma is still unclear due to many factors. Our study is one of the few studies on this subject. Although current diagnostic recommendations generally recommend a PEF variability of 10% for the diagnosis of asthma, this threshold may not be appropriate for the BDR-negative patient group. Our results suggest using a threshold value of <15% for PEF variability when excluding asthma and ≥20% when confirming the diagnosis of asthma in patients with clinically suspected but unproven reversibility. Furthermore, FEF25-75 is considered to be an important diagnostic parameter that should be included in diagnostic recommendations for asthma.

Successful case of deferasirox slow desensitization in adults.

INTRODUCTION: When deferasirox is used in iron chelation therapy, maculopapular rash occurs in 10% of patients, but there is no accepted and implemented protocol for the management of these drug reactions in adults. CASE REPORT: A 23-year-old woman diagnosed with thalassemia major is presented. She had taken 1,500 mg oral deferasirox for 1 week. Five hours after the last dose, a pruritic maculopapular rash developed on the body, face, and hands. The rash spread to the whole body within 3 days. The absolute necessity for the patient to take the drug was clarified by the hematology department. The patient's history was evaluated. A delayed-type hypersensitivity reaction due to deferasirox was considered. MANAGEMENT: The slow desensitization protocol described in the literature and applied on a case-by-case basis in pediatric patients was modified to shorten the duration by determining appropriate doses for the current preparation. The desensitization process was started with 1/100,000 of the total dose and the therapeutic dose was reached with a 2- to 2.5-fold increase in dose. No pre-medication was applied. During the procedure, at a low dose of 0.1 mg, local flushing and erythema was observed around the auricle on the face. The reaction did not progress. CONCLUSION: Slow desensitization protocol for oral deferasirox was successfully applied in an adult patient.