Characteristics of adverse reactions due to subcutaneous allergen immunotherapy applied between 2011-2021: Single center experience.

Introduction: The aim of this study was to elucidate the incidence of local, large local and systemic reactions after subcutaneus immunotherapy (SCIT) injections in our clinic and to determine the characteristic features of these adverse reactions. Materials and Methods: A total of 6000 SCIT injections administered to 163 patients between January 2011 and December 2021 were retrospectively evaluated. The study population consisted of patients with allergic rhinoconjunctivitis who underwent SCIT due to pollen, house dust mite or cat allergy, or patients who underwent SCIT due to venom allergy. Demographic characteristics of the patients, diagnoses, allergen sensitivities, immunotherapy protocol applied, adverse reactions, and the characteristics of these reactions were recorded. Result: Totally, 163 patients with a mean age of 36.8 ± 12.7 years were enrolled in this research. Sex distribution was as follows: 55.2% (n= 90) were females. During the study, 218 allergic reactions were detected in 83 patients. The incidence of adverse reactions per injection was 3.6%. The probability of developing an adverse reaction in a patient during the entire subcutaneous immunotherapy was 53.9%. Of the adverse reactions that developed, 94 (43.1%, n= 47) were observed locally while 56 (25.7%, n= 40) were large local reactions, and 68 (31.2%, n= 30) were systemic. Incidence of adverse reactions per injection were 1.5%, 0.9%, and 1.1% for local reaction, large local reaction, and systemic reaction, respectively. Conclusions: The results of this analysis elaborated that subcutaneous immunotherapy is a safe and tolerable treatment modality. However, before initiating treatment, the benefits and risks should be evaluated. The risk of systemic reactions is quite low, but fatal anaphylaxis can occur, so physicians need to be aware of the potential risks.

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.

Venom immunotherapy and difficulties encountered before and during immunotherapy: Double sensitization, systemic reactions, treatment with omalizumab, and high dose VIT.

BACKGROUND: Venom immunotherapy (VIT) is the most effective treatment method to prevent recurrent systemic reactions to Hymenoptera stings. In this study, the demographic characteristics of VIT patients, the success rates of VIT, the difficulties we encountered during VIT, and solutions for these difficulties in our clinic were presented. METHODS: We retrospectively analyzed patients with venom allergy who applied venom immunotherapy between 2013- 2020. Data on age, gender, Hymenoptera species with the first reaction, grade of the reaction, beekeeping history, skin prick and specific IgE and component results, double sensitization, blood groups, and reactions with VIT and/or sting during built-up and maintenance periods were recorded. RESULTS: A total of 73 patients were enrolled in the study. The median time from the first sting reaction to the application to the allergy outpatient clinic was 12 (0.5-24) months. The first sting reaction of 38 (52.1%) of the patients was with honey bees, and 24 (32.9%) were with wasps. Double positivity was present in 29 (40%) of the patients in prick results and 26 (36%) serologically. There was no correlation between the severity of first reactions and Apis Mellifera or Vespula prick diameters (p = 0.643; r = -0.056; p = 0.462; r = 0.089, respectively). High-dose VIT was administered to 4 patients. Omalizumab has been used as an alternative agent to achieve the maintenance dose in 2 patients with frequent systemic reactions during VIT. DISCUSSION: Most patients were able to tolerate VIT. Double positivity is one of the most common difficulties before VIT. In patients who develop systemic reactions in the VIT maintenance phase, a maintenance dose increase should be considered in the maintenance phase. Adding omalizumab does not seem to be a permanent solution in patients who develop a severe systemic reaction.

The adequacy of current diagnostic criteria for making a diagnosis of ABPA.

Introduction: Currently, there are four different diagnostic criteria systems for allergic bronchopulmonary aspergillosis (ABPA): The Rosenberg-Patterson, Seropositive ABPA (ABPA-S), Central Bronchiectasis and ABPA (ABPA-CB), and the International Society for Human and Animal Mycology (ISHAM) ABPA study group criteria. This study aims to retrospectively compare these four diagnostic criteria in ABPA patients. Materials and Methods: Patients who were followed up with the diagnosis of ABPA were retrospectively re-evaluated using these four diagnostic criteria, and the superiority of these criteria to each other was determined. Result: A total of 10 ABPA patients were included in the study. Seven patients were diagnosed according to ISHAM ABPA study group diagnostic criteria and six patients according to the Rosenberg-Patterson diagnostic criteria. None of the patients fulfilled the criteria when evaluated individually with ABPA-S and ABPA-CB. Of patients diagnosed by ISHAM, five had a total IgE level above 1000 IU/mL and two had below 1000 IU/mL. Conclusions: We demonstrated that the diagnostic criteria developed by the ISHAM ABPA study group were superior to the others in diagnosing ABPA in cases with a total IgE level above 1000 IU/mL. However, all these criteria seem to be sufficient to diagnose ABPA in patients with a total IgE below 1000 IU/mL. We believe the necessity to demonstrate presence of Aspergillus fumigatus precipitating antibodies or specific IgG positivity should be questioned particularly in patients with radiologic findings compatible with ABPA and a total IgE level below 1000 IU/mL.

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.

Effectiveness of mepolizumab therapy on symptoms, asthma exacerbations, steroid dependence, and small airways in patients with severe eosinophilic asthma

Background/aim: The efficacy of mepolizumab has been largely demonstrated in clinical trials in patients with severe eosinophilic asthma (SEA). However, reports on experience with mepolizumab in a real-life cohort are limited. Moreover, data about the effectiveness of mepolizumab on small airways is scarce. This study evaluated the effectiveness of mepolizumab therapy on symptoms, asthma exacerbations, blood eosinophils, steroid dependence, and small airways in a real-life cohort of patients with SEA. Materials and methods: We retrospectively analyzed patients with SEA who were receiving fixed-dose mepolizumab. The effects of mepolizumab on clinical, laboratory, functional parameters were evaluated at 12th, 24th, and 52nd weeks. Small airways were assessed with the FEF 25-75. Results: A total of 41 patients were enrolled in the study. Mepolizumab significantly reduced asthma exacerbation rates, reduced mOCS dose, and improved asthma control test (ACT) scores at 12th, 24th, and 52nd weeks. However, we found no significant changes in FEV1 and FEF25-75 values at baseline, 12th, 24th, and 52nd weeks (78.9 ± 23.3%, 82.9 ± 23.4%, 81.9 ± 23.9%, and 78.9 ± 23.5% for FEV1; 45.1 ± 23.1%, 48.8 ± 23.5%, 48.7 ± 23.1%, and 41.0 ± 20.1% for FEF25-75, respectively) Conclusion: In this study, mepolizumab significantly improved all outcomes (symptom scores, asthma exacerbations, OCS sparing, and blood eosinophils) except functional parameters. Still, despite the dose reduction in mOCS dosage, no significant deterioration was observed in FEV1 and FEF25-75 values.

A case of hypersensitivity developing against trace element solution in total parenteral nutrition, proved by skin prick test.

Total parenteral nutrition (TPN) is a commonly used treatment method for patients whose oral intake is insufficient or who cannot use the gastrointestinal system. In the literature hypersensitivity reactions to contents of PN and fats are very rare. But these reactions can be seen in a wide spectrum from minor reactions such as pruritus to life-threating reactions such as anaphylaxis. In this case, a hypersensitivity reaction case will be presented against the trace element product in PN. As far as we know, there are no other cases in the literature that are definitely associated with trace element solution.

Effectiveness of as-needed antihistamines in chronic spontaneous urticaria patients under omalizumab treatment.

The question how second-generation antihistamines (sgAHs) should be used when chronic spontaneous urticaria (CSU) is under control with omalizumab is still unanswered. This study aimed to investigate the effectiveness of as-needed sgAHs in patients with well-controlled urticaria under omalizumab treatment. Patients from four different urticaria centers who were treated with omalizumab 300 mg/4 weeks for at least 3 months, had well-controlled urticaria (Urticaria Control Test: 16 > UCT≥12) and were using sgAHs only if needed, were included in this study. In order to assess effectiveness of sgAHs, change in the itch, hives, and total itch-hives scores before and after sgAHs were evaluated using modified urticaria activity score-twice daily. Fifty-three patients [38 female (71.7%)] with mean age 41.1 ± 11.4 years were included in this study. Median sgAH intake per patient throughout the 4 week-intervals was 3 (2-5) tablets. sgAH intake decreased itch, hives and total itch-hives scores 45.7% ± 52.9, 42.4% ± 39.1, and 50.2% ± 51.1, respectively (P < .001 for all). This decrease was similar in both isolated-urticaria and urticaria-and-angioedema phenotypes. Baseline IgE levels were positively correlated with the decrease of three symptom scores (r = 0.31, P = .05; r = 0.375, P = .017; r = 0.31, P = .05, respectively) that showed in patients with higher baseline total IgE levels, as needed sgAH intake decreased the symptom scores less. Our study showed that sgAHs may still be an effective option for the treatment of the intermittent symptoms in patients with well-controlled urticaria under omalizumab treatment. Baseline total IgE levels may be used as a potential biomarker for sgAH effectiveness in these patients.

Vitamin D status in hospitalized patients with chronic obstructive pulmonary disease.

INTRODUCTION: Vitamin D deficiency and chronic obstructive pulmonary disease (COPD) are both world-wide health problems. Vitamin D has known to be important in infectious pathologies. However, there are conflicting results in the role of vitamin D in COPD exacerbation. This study was design to evaluate the prevalence of vitamin D deficiency among patients with COPD exacerbation in relation with surrogate markers of exacerbation and long-term mortality in hospitalized patients with COPD. MATERIALS AND METHODS: 117 hospitalized COPD patients were included between January 2010 to June 2013. Information was obtained through the patients' records and the electronic database of the hospital. The patients who had on vitamin D and/or calcium therapy, and who were suspected of asthma were excluded from the study. RESULT: The study included 117 patients and none of them were on vitamin D replacement on entry. The mean age was 67.95 ± 9.8 years. The number of male/female patients was 104/13. The mean forced expiratory volume in one second in percent predicted (FEV1%) was 39.97 ± 18.45. One hundred fifteen patients had vitamin D deficiency whereas only two patients had vitamin D ≥ 30 ng/dL. Seventy nine (69.5%) of the patients had severe vitamin D deficiency (< 10 ng/dL). The percentage of frequent exacerbators, patients who had microorganism growth and the median duration of hospital stay, mean FEV1 and survival did not differ between the group of vitamin D < or ≥ 10 ng/dL. There was no meaningful correlation of vitamin D level and any of the surrogate markers of exacerbation. CONCLUSIONS: Severe vitamin D deficiency is heavily prevalent in Turkish COPD patients. However, it did not have an association on exacerbation and long term survival.

Efficacy of mepolizumab treatment in oral corticosteroid-dependent severe eosinophilic asthma patients with chronic rhinosinusitis with nasal polyps: single center, real life study

Background/aim: Oral corticosteroid (OCS)-dependent severe eosinophilic asthma with chronic rhinosinusitis with nasal polyps (SEA-CRSwNP) would be a suitable phenotype for mepolizumab treatment. This study evaluated the short-term efficacy of mepolizumab treatment in OCS-dependent SEA-CRSwNP. Materials and methods: Baseline and 24th week results [daily OCS doses, asthma exacerbation frequency, asthma control test (ACT) scores, blood eosinophil levels, FEV1 values, and numerical analog scale (NAS) of CRSwNP symptoms] of patients who were treated for at least 24 weeks with mepolizumab were retrospectively evaluated and compared. Results: A total of 16 patients were enrolled in the study. Mepolizumab was discontinued in one patient due to side effects. The daily OCS dosage was reduced from baseline in all patients, and at week 24 OCS was discontinued in 40% of the patients (baseline mean steroid dose: 9.2 ± 5.2 mg, 24th week: 1.3 ± 1.4 mg; P < 0.001). The number of asthma exacerbations within 24 weeks significantly decreased after beginning mepolizumab treatment (2.1 ± 2.7 vs. 0.07 ± 0.26; P = 0.012), and a significant increase in ACT scores (baseline mean ACT: 18 ± 5.7; 24th week mean ACT: 23.3 ± 3; P = 0.006) was observed despite the decrease in daily OCS dosages. There was no significant difference in FEV1 values between baseline and week 24. Evaluation of the general symptoms of CRSwNP, as per NAS, revealed that the baseline mean NAS was 5.6 ± 4.4, and the 24th week mean NAS was 3.2 ± 3.2 (P = 0.021). Conclusion: This is the first real-life study evaluating the short-term efficacy of mepolizumab treatment on OCS-dependent SEA-CRSwNP. This study demonstrates that mepolizumab is an effective and safe biologic for the treatment of this severe asthma subphenotype.

The effect of inhaled corticosteroids in the outcomes of community-acquired pneumonia: ICCAP study (TURKCAP Database).

OBJECTIVE: We aimed to investigate the effect of inhaled corticosteroids (ICS) in the outcomes of community-acquired pneumonia (CAP), as well as to determine if ICS usage is exist among the risk factors for mortality in those patients. MATERIALS AND METHODS: In this retrospective cross-sectional multicentre study, 1069 hospitalised CAP patients were investigated using CAP Database of Turkish Thoracic Society (TURKCAP Database). The patients were divided into two groups, depending on their ICS use. The data were analysed by appropriate statistical methods. RESULTS: 172 (75.8%) of the 227 patients who were on ICS had COPD and 37 (16.3%) had asthma. There were fewer patients with fever among ICS-users compared to non-ICS users (P = 0.013), and less muscle pain (P = 0.015) and fewer GIS symptoms (P = 0.022). No statistically significant difference was found between ICS use/ type of ICS and the duration of hospitalisation (P = 0.286). The multivariate regression analysis showed that patients using ICS had lower body temperature and, less crackles/bronchial sound. In the multivariate logistic regression model lung cancer (OR: 6.75), glucose (OR: 1.01) and CURB-65 (OR: 1.72) were significantly associated with mortality in the CAP patients. ICS usage were not found to be associated with mortality. CONCLUSION: The use of ICS by the patients with CAP admitted to the hospital is not independently related with any radiological pattern, hospitalisation duration and mortality. ICS usage may diminish fever response and may suppress the findings of crackles and/or bronchial sounds. This needs further confirmation.

Last station in the eosinophilic asthma with chronic rhinosinusitis and/or nasal polyposis march: Eosinophilic asthma with radiological findings associated with blood eosinophilia.

OBJECTIVE: Eosinophilic asthma with chronic rhinosinusitis and/or nasal polyposis (EA-CRS/NP) is a subphenotype of adult-onset eosinophilic asthma. Blood eosinophil levels are shown to be highly elevated in patients with EA-CRS/NP and have potential for tissue infiltration. We aimed to demonstrate the clinical features of the patients who have a blood eosinophil level above 10% and have thorax computed tomography findings due to blood eosinophilia. METHODS: Patients who were followed up in our clinic between 2012 and 2017 were retrospectively evaluated. Inclusion criteria were as follows: 1) Eosinophilic severe asthma, 2) eosinophilia >10%, 3) chronic sinusitis and/or nasal polyps, 4) patients with pathologic findings on thorax computed tomography, 5) regular follow-up for at least 1 year. RESULTS: We identified 36 patients who met the above criteria. We defined this group as "Eosinophilic Asthma with chronic Rhinosinusitis and/or nasal polyposis with Radiological findings related to blood eosinophilia" (EARR). The mean age was 44.9 ± 11 years and 64% were females. Nasal polyps, aspirin exacerbated respiratory disease, and atopy, were present in 81%, 47%, and 25% of the patients, respectively. The mean blood eosinophil count was 1828.6 cells/mm3 (19%). The majority of EARR patients had upper lobe dominant ground-glass opacities. The mean follow-up period was 3.2 ± 2.5 years. EARR patients did not evolve into eosinophilic granulomatous polyangiitis in the follow-up. CONCLUSIONS: This phenotype is the first eosinophilic asthma sub-phenotype reported in the literature. EARR is the final stage of the allergic march of EA-CRS/NP.

Omalizumab Treatment for Atopic Severe Persistant Asthma: A Single-Center, Long-Term, Real-Life Experience with 38 Patients.

OBJECTIVES: Omalizumab is a monoclonal antibody that is used as add-on therapy for treating moderate-to-severe persistant atopic asthma in patients with persistant symptoms and frequent exacerbations, despite step 4 treatment according to GINA guidelines. Real-life studies on omalizumab treatment are limited in Turkey. Thus, the present study aims to assess the clinical efficacy and treatment outcomes of omalizumab in patients with atopic severe persistant asthma. MATERIALS AND METHODS: Patients with atopic severe persistant asthma who were treated with omalizumab between 2009 and 2017 were retrospectively evaluated. Baseline and last results of the following variables were compared: symptom scores (GINA categorical), controller medications, blood eosinophil counts, forced expiratory volume in 1 second (FEV1) values, and the number of exacerbations that were treated with systemic corticosteroids for at least 3 days within the last 1 year. The effect of coexisting aspirin-exacerbated respiratory disease (AERD) on these parameters was also analyzed. Step-down of other asthma medications was attempted in patients with symptom control and in those without an exacerbation history within the last 6 months. RESULTS: Thirty-eight patients (mean age, 50 years; females, 30) were included in this study, of whom four showed AERD. After treating with a mean time of 30±22.1 (min: 6, max: 92) months, 26 (68%) patients showed complete controlled disease and 12 (32%) showed partly controlled disease, of whom all had uncontrolled disease before. Mean exacerbation rates within the last 1 year decreased by approximately 76% (9.4±8.4 vs. 1.8±1.5; p<0.001) and FEV1 values increased by approximately 14% (2075±729 vs. 2321±800 cc; p=0.001) compared with baseline levels. Although the reduction in eosinophil count was not significant in all patients (503.8±524.8 vs. 370.8±314.5; p=0.134), repeated measures analysis of variance revealed a more prominent reduction in eosinophil count in the AERD group than in the non-AERD group, independent from the treatment period (F: 4.23, p=0.049). The mean inhaled corticosteroid dose (budesonide eq., 1063±397 vs. 958±439 mcg; p=0.084), the number of other controller medications, and the number of patients with long-term systemic steroid use decreased after omalizumab treatment. No serious adverse events were recorded during the follow-up period. CONCLUSION: Our results confirm that omalizumab significantly improves disease control and is a safe add-on therapy. In addition, in suitable patients with controlled disease over time, the step-down of other asthma medications will be appropriate.

Combination of omalizumab and bee venom immunotherapy: does it work?

Bee venom immunotherapy (b-VIT) can be combined with omalizumab therapy in order to suppress systemic reactions developing due to b-VIT itself. Omalizumab acts as a premedication and gains time for the immunotherapy to develop its immunomodulatory effects. However, the combination of omalizumab and b-VIT is not always effective enough. Herein we present a patient in whom successful immunotherapy cannot be achieved with combination of omalizumab to b-VIT.

Treatment and retreatment with omalizumab in chronic spontaneous urticaria: Real life experience with twenty-five patients.

BACKGROUND: Previous data have shown the high efficacy of omalizumab in chronic spontaneous urticaria (CSU). However, factors that may be effective on the response to therapy, relapse rates after drug discontinuation, and efficacy of retreatment remain unclear. This study aimed to determine the efficacy of omalizumab in CSU refractory to conventional therapy, to identify possible factors affecting treatment response and relapse, and also to evaluate the efficacy of retreatment on relapsed disease. METHODS: The data of CSU patients treated with 300 mg/month omalizumab for at least 3 months were retrospectively analyzed. In order to evaluate the efficacy of treatment and retreatment, baseline and follow-up concomitant medication score (CMS) and urticaria activity score (UAS) were calculated. Possible factors affecting treatment response and relapse were identified. RESULTS: Twenty-five patients were included. The median duration of omalizumab therapy was 6 (6-12) months. Of the patients with baseline UAS 6 (5.5-6) and CMS 13 (10-15), 8 (32%) had complete response (UAS = 0) and 2 (8%) were non-responders after 3 months of therapy. None of the complete responders were positive for IgG-anti-TPO. After discontinuation of omalizumab therapy, 11 (61%) patients experienced relapse and 10 of them received retreatment with omalizumab. Half of the patients had complete response, and half had partial response (UAS = 1-4) after retreatment. No treatment related adverse events were documented. CONCLUSIONS: Omalizumab has high efficacy in both the treatment and retreatment of CSU; however, relapse rates after discontinuation are high. Autoimmune markers may be helpful in predicting treatment response and relapse.

Is nonhomogeneous expression of tissue mast cells or allergen specific IgEs bound to tissue mast cells possible?

Skin prick tests (SPTs) are widely used to demonstrate an IgE-mediated hypersensitivity reaction to a specific allergen. However, local allergic conditions cannot be diagnosed with SPTs. Local specific IgE production was only presented before in mucosal tissues. We present a patient with house dust mite sensitization that had variable SPTs results in different body regions.