Resensitization in suspected penicillin allergy.

BACKGROUND: The diagnosis of allergic reactions to penicillins (AR-PEN) is very complex as there is a loss of sensitization over time, which leads to negative skin tests (STs) and specific IgE in serum, and even to tolerance to the drug involved. However, STs may become positive after subsequent exposure to the culprit drug (resensitization), with the risk of inducing potentially severe reactions. The exact rate of resensitization to penicillins is unknown, ranging from 0% to 27.9% in published studies. OBJECTIVES: To analyze the rate of resensitization in patients with suggestive AR-PEN by repeating STs (retest) after an initial evaluation (IE). MATERIAL AND METHODS: Patients with suspected AR-PEN were prospectively evaluated between 2017 and 2020. They underwent STs, and a randomized group also underwent a drug provocation test (DPT) with the culprit. Only patients with negative STs and/or DPT were included. All included cases were retested by STs at 2-8 weeks. RESULTS: A total of 545 patients were included: 296 reporting immediate reactions (IRs) and 249 non-immediate reactions (NIRs). Eighty (14.7%) cases had positive results in retest (RT+): 63 (21.3%) IRs and 17 (6.8%) NIRs (p < 0.0001). The rate of RT+ was higher in anaphylaxis compared with all other reactions (45.8% vs 9.1%, p < 0.0001). The risk of RT+ was higher from the fifth week after IE (OR: 4.64, CI: 2.1-11.6; p < 0.001) and increased with the patient's age (OR: 1.02; CI: 1.01-1.04; p = 0.009). CONCLUSIONS: Due to the high rate of resensitization, retest should be included in the diagnostic algorithm of IRs to penicillins after an initial negative study, especially in anaphylaxis, to avoid potentially severe reactions after subsequent prescriptions of these drugs.

What lies beyond Asthma Control Test: Suggestions for clinical practice.

BACKGROUND: Asthma Control Test (ACT ™) validity relies on Global Initiative for Asthma (GINA) definition of control. It includes neither reversibility nor inflammation assessment despite their importance as hallmark of asthma, partially unrelated to symptoms. Furthermore though rhinitis may affect the patient's perception of asthma control, its impact on ACT accuracy has not been systematically evaluated. OBJECTIVE: To explore ACT validity according to a definition of control including: forced expiratory volume in 1 s (FEV1) ≥ 80%, negative reversibility test, exhaled nitric oxide at a flow rate of 50 ml/s (FeNO) < 50 ppb. RESULTS: 177 asthmatics referring to our Unit have been studied. ACT with cut-off score ≥20 showed a good positive predictive value (83.5%) but low sensitivity (47.8%), specificity (66.7%), and negative predictive value (26.5%). ROC curves analysis indicates that ACT in patients with mild intermittent rhinitis is more reliable (AUC: 0.714; p < 0.05) than in patients with nasal polyposis/chronic rhino-sinusitis (AUC: 0.176; p > 0.05). Considering asthma classification, the probability that ACT detects patients with uncontrolled asthma is significantly higher in moderate persistent asthma subgroup than in mild persistent asthma one (OR 5.464; IC 95%: 2.5-11,9; p < 0.05). CONCLUSIONS: As ACT mainly relies on patient's reported outcomes, it may not completely reflect the airways inflammation and airways obstruction. The presence and severity of rhinitis may affect ACT outcome. The awareness of the variables that could influence ACT evaluation is much more important in the primary care setting where ACT may often represent the only tool for asthma assessment.

Dupilumab-induced hypereosinophilia: review of the literature and algorithm proposal for clinical management.

INTRODUCTION: Dupilumab is a human monoclonal antibody that targets both IL-4 and IL-13 signaling. It is currently indicated for the treatment of asthma, moderate-to-severe atopic dermatitis, and chronic rhinosinusitis with nasal polyps (CRSwNP). Eosinophilia has been reported as a potential adverse event in treated patients. AREAS COVERED: A selective search on PubMed and Medline up to January 2022 was performed, by focusing on dupilumab-induced hypereosinophilia described in clinical trials, real-life studies, and case reports. The possible mechanisms underlying dupilumab-induced hypereosinophilia and the eosinophil-related morbidity have also been explored. EXPERT OPINION: Dealing with dupilumab-induced hypereosinophilia represents a clinical challenge for clinicians managing patients on dupilumab therapy. An algorithm for the practical management of dupilumab-induced hypereosinophilia has been proposed, in order to properly investigate potential eosinophil-related morbidity and avoid unnecessary drug discontinuation.

Is mild asthma truly mild? The patients' real-life setting.

OBJECTIVES: Asthma exacerbations and, more rarely, fatal asthma attacks have been reported in mild asthma patients, suggesting poor disease control and awareness of its potential burden. Our study aimed to explore outside the hospital/specialist setting the perspective and disease treatment behavior of patients self-reporting a mild asthma diagnosis. METHODS: Computer-Assisted Personal Interviewing (CAPI) technique was used to investigate the identified study population. Questions about diagnosis, symptoms, comorbidities, treatment strategy, ongoing assessments, and quality of life were administered. RESULTS: Overall, 258 patients were considered for the analysis. As the most relevant results, 22% of them reported severe respiratory symptoms, 52% experienced at least one exacerbation/year, and 7% needed Emergency Room care. Sixty-six percent of the respondents assumed as needing short-acting bronchodilators only. Of note, 22% of patients were using oral steroids (OCS) intermittently and 72% of them considered their quality of life unsatisfying. CONCLUSION: Outside the hospital/specialist setting, mild asthma burden is still not negligible and the treatment approach is not correct. In particular, the reported OCS use is disproportionate. Our data suggest that mild asthma, especially when self-assessed might be other than mild, suggesting that efforts to increase disease awareness, improve the disease control limiting the OCS abuse are required.

Clonal mast cell disorders in patients with systemic reactions to Hymenoptera stings and increased serum tryptase levels.

BACKGROUND: Anaphylaxis after Hymenoptera stings has been reported in subjects with mastocytosis, but few data exist regarding disease prevalence in populations allergic to these insects. OBJECTIVE: The incidence of clonal mast cell (MC) disorders in subjects with both systemic reactions to Hymenoptera stings and increased serum baseline tryptase (sBT) levels was assessed by using bone marrow (BM) aspirates and biopsy specimens. METHODS: Subjects with a history of a systemic reaction caused by a Hymenoptera sting underwent the standard diagnostic work-up for Hymenoptera allergy, and sBT levels were measured. Subjects with an increased sBT level had BM evaluation that included histology/cytology, flow cytometry, and detection of KIT mutations. RESULTS: Forty-four (11.6%) of 379 subjects with systemic reactions had increased sBT levels (>11.4 ng/mL), and 31 (70.5%) of these had a history of anaphylaxis. Thirty-four subjects with increased sBT levels underwent a BM analysis. Histology detected diagnostic or subdiagnostic MC infiltrates in 22 (65%) of 34 patients. Abnormal MCs were identified by means of flow cytometry and cytology in 26 (78.8%) of 33 and 20 (58.8%) of 34 subjects, respectively. A KIT mutation was detected in 17 (54.8%) of 31 subjects. The diagnosis was indolent systemic mastocytosis in 21 (61.7%) of 34 subjects and monoclonal MC activation syndrome in 9 (26.5%) of 34 subjects. All subjects with anaphylaxis had one of those 2 disorders. CONCLUSION: The concomitant presence of systemic reactions (especially anaphylaxis) after Hymenoptera stings and increased sBT levels strongly suggests that a BM examination is indicated for the diagnosis of clonal MC disease.

Safety and pharmacoeconomics of a cluster administration of mite immunotherapy compared to the traditional one.

Accelerated schedules of administration of immunotherapy (rush or clustered) allow to reach the maintenance dosage in shorter times with respect to traditional schedules. Nowadays formal assessments of the safety and economic aspects of those schedule lack for inhalant allergens. We compared in a prospective randomized open study a cluster and a traditional immunotherapy with standardized mite extracts. Thirty eight adult patients with persistent allergic rhinitis due to mites were randomized to receive either a traditional (N= 19) or a cluster (N=19) up-dosing scheme, lasting 13 and 3 weeks respectively. Side effects were carefully evaluated and recorded by physician and costs were calculated as well. In the cluster and traditional updosing 148 and 241 injections were given respectively. With the cluster up-dosing there were 8 local reactions (15.9% of patients and 5.4% of injections). With the traditional schedule 6 local reactions (31.5 % of patients and 2.4% of injections) occurred. There was no difference between the two treatments in occurrence of side effects per patient and per injection (chi-square 1.31 and 2.23, p= NS). No systemic reaction was recorded. Considering the cost of the extract, the cost of injections and the time spent, the cluster regimen resulted in a global spare of 244.95 euros per patient in the build-up phase. The cluster up-dosing is as safe as the traditional one and allows a significant economical save.

Fatal asthma; is it still an epidemic?

BACKGROUND: Asthma mortality has declined since the 1980s. Nevertheless the World Health Organization (WHO) identified asthma as responsible for 225.000 deaths worldwide in 2005, and 430.000 fatal cases are expected by 2030. Some unexpected and concentrated fatal asthma events all occurred between 2013 and 2015 in Veneto, a North Eastern region of Italy, which prompted a more in-depth investigation of characteristics and risk factors. METHODS: A web search including key words related to fatal asthma in Italy between 2013 and 2015 has been performed. Concerning the cases that occurred in Veneto, subjects' clinical records have been evaluated and details about concomitant weather conditions, pollutants and pollen count have been collected. RESULTS: Twenty-three cases of asthma deaths were found in Italy; 16 of them (69%) occurred in the Veneto Region. A prevalence of male and young age was observed. Most of patients were atopic, died in the night-time hours and during the weekends. The possible risk factors identified were the sensitization to alternaria, previous near fatal asthma attacks and the incorrect treatment of the disease. Weather condition did not appear to be related to the fatal exacerbations, whereas among the pollutants only ozone was detected over the accepted limits. Smoking habits, possible drug abuse and concomitant complementary therapies might be regarded as further risk factors. DISCUSSION: Although not free from potential biases, our web search and further investigations highlight an increasing asthma mortality trend, similarly to what other observatories report. The analysis of available clinical data suggests that the lack of treatment more than a severe asthma phenotype characterizes the fatal events. CONCLUSIONS: Asthma mortality still represents a critical issue in the management of the disease, particularly in youngsters. Once more the inadequate treatment and the lack of adherence seem to be not only related to the uncontrolled asthma but also to asthma mortality.

Are physicians aware of the side effects of angiotensin-converting enzyme inhibitors?: a questionnaire survey in different medical categories.

STUDY OBJECTIVE: Angiotensin-converting enzyme inhibitors (ACE-I) are considered safe, but they are associated with characteristic side effects, namely cough and angioedema, usually requiring discontinuation. We perceived that referrals for these side effects have become more and more frequent; therefore, we evaluated the degree of knowledge on the safety of ACE-I in different medical categories. DESIGN: A questionnaire (13 questions) on side effects of ACE-I was posted to physicians. SETTING: Everyday clinical practice. PARTICIPANTS: Cardiologists, allergists, and general practitioners (GPs) from the National Healthcare System. MEASUREMENT AND RESULTS: Three hundred twelve physicians were contacted, and 154 returned questionnaires that could be analyzed. Of the 154 physicians (mean age, 45 years) 48 were cardiologists, 52 were GPs, and 54 were allergists. The percentage of correct answers was low: 31.9% for cardiologists, 40% for GPs, and 33% for allergists. Thus, GPs provided a significantly higher percentage of correct answers with respect to the remaining categories (p = 0.05). The lower rate of correct answers (0 to 15.9%) concerned the time of onset of cough and the action to take. Cardiologists seemed to be less aware of the fact that angiotensin receptor blockers (sartans) can cross-react with ACE-I. CONCLUSION: Overall, there was a poor knowledge of the side effects of ACE-I. This may account for the increased referrals for chronic cough and angioedema.

Anaphylaxis due to patent blue dye during lymphography, with negative skin prick test.

We report here a case of anaphylaxis due to patent blue dye, which was administered to an adult female during a lymphographic intraoperative procedure. The patient was not atopic, and other possible causes of anaphylaxis (anesthetics, latex) had been carefully excluded through routine tests. The skin-prick test and patch test carried out with patent blue (PB) dye were negative, but the intradermal test with 100 microliters of the dye showed a remarkable positivity. There was no available commercial, specific IgE assay for PB dye, but the negativity of prick tests would exclude the involvement of an IgE-mediated mechanism. We want to highlight the possible danger derived from a dye that is considered inert, and that is now increasingly being used in surgical procedures.

Nimesulide and meloxicam are a safe alternative drugs for patients intolerant to nonsteroidal anti-inflammatory drugs.

BACKGROUND: Pseudoallergic reactions to ASA and NSAIDs in general are frequent and difficult to manage. The challenge with the suspected drug is considered unethical, therefore the only possible approach is a challenge with alternative drugs. Selective COX2 inhibitors are considered the most suitable alternative drugs. We describe the comparative results and follow-up of an oral challenge with nimesulide and meloxicam, in NSAIDs intolerant patients. METHODS: 381 patients (118 male, 263 female, mean age 53.2 years) with a well documented pseudoallergic reaction to NSAIDs underwent an oral challenge with these alternative drugs. All 381 patients were given nimesulide 88 of them were also given meloxicam. All patients were re-interviewed at six-month intervals up to two years after challenge. RESULTS: 98.4% of the patients tolerated nimesulide and 95.4% tolerated meloxicam. The reactions occurred during challenges were mild and easily manageable. Three out of the six nimesulide-intolerant patients could tolerate meloxicam, whereas only one of the four meloxicam-intolerant patients could tolerate nimesulide. At the follow-up, 96% of patients with previous negative challenge could tolerate nimesulide and within the patients which took meloxicam after challenge no pseudoallergic reaction occurred. CONCLUSIONS: The herein described challenge with alternative drugs, meloxicam and nimesulide, is a safe tool for the management of NSAIDs-intolerant patients. The two tested drug are safe and reliable alternatives for these patients.

Balancing efficacy against safety in sublingual immunotherapy with inhalant allergens: what is the best approach?

Over the last 20 years, studies and clinical trials have demonstrated efficacy, safety and cost-effectiveness of sublingual immunotherapy (SLIT) for respiratory allergic diseases. Nevertheless, it seems to be mostly used as a second-line therapeutic option, and adherence to treatment is not always optimal. Selective literature research was done in Medline and PubMed, including guidelines, position papers and Cochrane meta-analyses concerning SLIT in adult patients. The most recent reviews confirm SLIT as viable and efficacious treatment especially for allergic rhinitis, even if the optimal dosage, duration, schedule are not clearly established for most of the products. Despite an optimal safety profile, tolerability and patient-reported outcomes concerning SLIT have received poor attention until now. Recently, new tools have been specifically developed in order to investigate these aspects. Regular assessment of tolerability profile and SLIT-related patient-reported outcomes will allow balancing efficacy with tolerability and all the other patient-related variables that may affect treatment effectiveness beyond its efficacy.