Retrospective Analysis of Patient-Reported Adverse Drug Reactions in an Italian Allergy Unit: ALLERG-RAF Study.

INTRODUCTION: The Italian Medicines Agency indicates that about 5% of hospital admissions are due to adverse drug reactions (ADRs). Several factors are recognized to be associated with an increased risk for ADRs, such as the female gender and polytherapy. The aim of this study was to retrospectively analyze the suspected ADRs reported by patients during the anamnestic interview at the Allergy Unit. PATIENTS AND METHODS: ALLERG-RAF study is a retrospective analysis of the medical records of patients evaluated in the Allergy Unit of ASST Spedali Civili and the University of Brescia from 2000 to 2016. The inclusion criteria were age ≥18 years and medical consultation requested for suspected ADRs. Data relating to the patient's intrinsic characteristics, the drug supposed to be the cause, and the prescribed pharmacological therapy were collected. Pseudonymized data from each patient were collected in an informatics database. RESULTS: From 2000 to 2016, 35,817 accesses to the Allergy Unit were made, and 2,171 unique events related to a suspected ADR were collected in 1,840 patients. More than two-thirds of the reports concerned females (70.4%). Antibiotics were involved in the majority of the self-reported suspected ADRs (48.7%), particularly beta-lactams (61.1%). Anti-inflammatory drugs, mainly NSAIDs, were second in incidence and suspected in 25.2% of reports. As a site of ADR manifestation, most of the reported reactions involve the skin. No clinical sequelae were reported. CONCLUSIONS: Our results underline the importance of patient reporting in pharmacovigilance. Furthermore, gender gap data emphasizes the importance of the gender-specific medicine approach.

Effectiveness and safety of dupilumab in patients with chronic rhinosinusitis with nasal polyps and associated comorbidities: a multicentric prospective study in real life.

BACKGROUND: Biologics are currently one of the main treatment options for a number of diseases. The IgG4 monoclonal antibody dupilumab targets the Interleukin-4 receptor alpha chain, thus preventing the biological effects of the cytokines IL-4 and IL-13, that are essential for the Th2 response. Several controlled trials showed that dupilumab is effective and safe in patients with atopic dermatitis (AD), severe asthma and chronic rhinosinusitis with nasal polyps (CRSwNP), thus resulting in approval by regulatory agencies. Aim of the study was to evaluate the efficacy and safety of dupilumab in adult patients with CRSwNP stratified by common overlapping comorbid conditions. METHODS: We performed a multicenter, observational, prospective study enrolling adult patients with severe CRSwNP who had started dupilumab treatment in the context of standard care from January 2021 to October 2021. Data were collected from twentynine Italian secondary care centers for allergy and clinical immunology, all of which were part of the Italian Society of Allergy, Asthma and Clinical Immunology (SIAAIC). A number of efficacy parameters were used. Patient data were compared using the Wilcoxon test for paired data. All statistical analyses were performed with SPSS version 20 (IBM, Armonk, NY, USA). RESULTS: In total, 82 patients with nasal polyposis were identified. A significant improvement was detected for all the applied efficacy parameters, i.e. 22-item Sino-Nasal Outcome Test (SNOT-22) and bilateral endoscopic nasal polyp score (NPS) scores for CRSwNP, Rhinitis Control Scoring System (RCSS) and Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) scores for allergic perennial rhinitis, Forced Expiratory Volume in the 1st second (FEV1) and Asthma Quality of Life Questionnaire (AQLQ) scores for asthma, Eczema Area and Severity Index (EASI) and Dermatology Life Quality Index (DLQI) scores for AD. A non-significant improvement was also obtained in the Urticaria Activity Score over 7 days (UAS7) for chronic spontaneous urticaria. Treatment with dupilumab was well tolerated. CONCLUSIONS: These data suggest that dupilumab treatment in patients suffering from CRSwNP and associated comorbidities may be suitable. Such outcome, although confirmation by trials is warranted, suggests the possibility to treat different disorders with a single therapy, with favorable effects especially under the cost-effectiveness aspect.

Systemic allergic reactions induced by labile plant-food allergens: Seeking potential cofactors. A multicenter study.

BACKGROUND: Heat-and-pepsin-sensitive plant food allergens (PR-10 and profilin) sometimes cause systemic reaction. OBJECTIVE: To detect the risk factors for systemic reactions induced by labile food allergens. METHODS: A retrospective multicenter study was performed on patients with a documented history of systemic allergic reaction to labile plant food allergens and on age-matched controls with a history of oral allergy syndrome (OAS) induced by the same foods. Offending foods, their amount, and state (solid or liquid), and potential cofactors (nonsteroidal anti-inflammatory drugs, protonic pump inhibitors, exercise, alcohol, and fasting) were considered. RESULTS: We studied 89 patients and 81 controls. Sensitization to PR-10 or profilin, IgE to Bet v 1 and/or Bet v 2, and foods causing OAS were similar in the two groups. Twenty patients experienced >1 systemic allergic reaction. Tree nuts, Rosaceae, Apiaceae, and soymilk were the main offending foods. Seventeen (19%) patients were taking a PPI when the systemic reaction occurred (vs 5% in controls; P < .025). The ingestion of the offending food in liquid form (soymilk) was frequent among patients (15%) but unusual among controls (2%; P < .025). Soy milk-induced systemic reactions were independent of PPI treatment. Fasting and excess of allergen, but not NSAID and exercise, were other relevant cofactors for systemic reactions. Systemic reactions occurred without any identifiable cofactor in 39 (44%) cases. CONCLUSION: PR-10- and profilin-induced systemic reactions are facilitated by PPI, ingestion of large amounts of unprocessed foods, and fasting. Soybean beverages represent a risk for PR-10 hypersensitive patients and should be avoided.

Omalizumab in chronic spontaneous urticaria: Efficacy, safety, predictors of treatment outcome, and time to response.

BACKGROUND: Omalizumab is a recombinant anti-immunoglobulin E (IgE) antibody used in the treatment of patients with chronic spontaneous urticaria (CSU). OBJECTIVE: This multicentric study assessed the safety and efficacy of omalizumab in patients (n=322) with CSU refractory to second-generation antihistamines, also investigating predictors of poor treatment outcome and time lag to response to anti-IgE therapy by serum auto-reactivity. METHODS: This retrospective observational study comprised a 4-week pretreatment period, a 24-week treatment period with omalizumab (300 mg/month), and a 16-week follow-up period. Primary efficacy endpoints were mean and median change in 7-day urticaria activity score (UAS7), weekly itch severity score (ISS), and hive score from baseline to 4-, 12-, and 24-week values. Secondary endpoints included the proportion of patients (defined "responders") with well-controlled urticaria (UAS7 ≤ 6) and complete treatment response (UAS7=0). Safety in terms of side effects was also assessed. RESULTS: Omalizumab significantly and consistently reduced the mean UAS7, ISS, and hive score from baseline to weeks 4, 12, and 24, with a clear decreasing trend over time. At the end of the treatment period (week 24), 84.2% of patients had a UAS7 score of 6 or less and 66.7% had a UAS7 of 0. Higher pretreatment IgE levels were less likely to be associated with poor treatment response (ie, UAS7 > 6). Patients with a positive autologus serum skin test (ASST) were significantly more likely to be "slow responders" to omalizumab treatment (ie, response beyond 8 days since omalizumab administration) than ASST-negative patients (P < .001). No treatment-related adverse events were recorded. CONCLUSION: Monitoring baseline characteristics of patients before introduction of omalizumab therapy may help to predict treatment outcome in CSU patients.

Effects of Cardiac Rehabilitation on Sleep Quality in Heart Disease Patients with and without Heart Failure.

Insomnia is a modifiable cardiovascular risk factor. Previous studies suggested that attending a cardiac rehabilitation program may improve sleep quality in cardiac patients and pointed out the association between heart failure and poor sleep quality. The primary aim of this study was to evaluate sleep quality in patients attending a Multidisciplinary Cardiac Rehabilitation Program (MRCP), and to compare sleep quality between patients with and without heart failure. A prospective observational study was carried out on a consecutive sample of 240 patients attending an 8-week MRCP; 50 patients (20.8%) were included due to heart failure (NYHA stages I-III) and the rest of them after having undergone any revascularization procedure or valvular surgery. Before and after the completion of the MRCP, the quality of sleep was assessed by the Pittsburgh Sleep Quality Index (PSQI) score. Post-intervention global PSQI scores were statistically significantly lower than those of pre-intervention (p = 0.008), but only 60 patients (25%) registered a clinically significant improvement. When comparing patients with heart failure with those without, no differences in sleep quality were found. This suggests that only a small percentage of patients can achieve clinically significant improvements in sleep quality attending conventional MCRP. Suggestions for future research are given.

Mollusk allergy in shrimp-allergic patients: Still a complex diagnosis. An Italian real-life cross-sectional multicenter study.

Introduction: Shellfish allergy is an important cause of food allergies worldwide. Both in vivo and in vitro diagnostics failure nowadays is caused by the poor quality of the extracts associated with the scarce availability of allergenic molecules in the market. It is known that not all patients with shellfish allergies experience adverse reactions to mollusks. It is still unclear how to detect and diagnose these patients correctly. Aim: To investigate the features of shrimp-allergic patients either reactive or tolerant to mollusks, with the currently available diagnostic methods. Methods: Nineteen centers, scattered throughout Italy, participated in the real-life study, enrolling patients allergic to shrimp with or without associated reactions to mollusks. Patients underwent skin tests using commercial extracts or fresh raw and cooked shrimp and mollusks, and IgE reactivity to currently available allergenic extracts and molecules was measured in vitro. Results: Two hundred and forty-seven individuals with a self reported adverse reactions to shrimp participated in the study; of these 47.8% reported an adverse reaction to mollusks ingestion (cephalopod and/or bivalve). Neither of the tests used, in vivo nor in vitro, was able to detect all selected patients. Accordingly, a great heterogeneity of results was observed: in vivo and in vitro tests agreed in 52% and 62% of cases. Skin tests were able to identify the mollusk reactors (p < 0.001), also using fresh cooked or raw food (p < 0.001). The reactivity profile of mollusk reactors was dominated by Pen m 1, over Pen m 2 and Pen m 4 compared to tolerant subjects, but 33% of patients were not detected by any of the available molecules. Overall, a higher frequency of IgE rectivity to shrimp was recorded in northern Italy, while mollusk reactivity was more frequent in the center-south. Conclusion: The current diagnostic methods are inadequate to predict the cross-reactivity between crustaceans and mollusks. The detection of mollusks hypersensitivity should still rely on skin tests with fresh material. The exclusion of mollusks from shrimp allergic patients' diets should occur when clinical history, available diagnostic instruments, and/or tolerance tests support such a decision.

Cinnarizine is a useful and well-tolerated drug in the treatment of acquired cold urticaria (ACU).

Old generation H1-type antihistamines are the standard therapeutic option for acquired cold urticaria (ACU), but adverse effects are common. New antihistamines are well tolerated but efficacy is often poor. The present study aims to evaluate efficacy and safety of cinnarizine in the treatment of ACU patients intolerant to old antihistamines and resistant to new drugs. We studied 14 patients (4 males and 10 females). Mean duration of the disease was 48.9 (range 7-102) months. Cold cube test was positive in 78.6 % of patients. Cold urticaria was idiopathic in 10 (71.4 %) patients. Cryoglobulins were detected in the serum of 4 cases (28.6 %). Cinnarizine (25 mg t.i.d.) was administered for 3 months, and then it was gently tapered off and stopped within 2 months. A complete or good response was obtained in 8 (57.1 %) and 2 (14.3 %) patients, respectively. Only two patients were unresponsive (21.4 %). Tapering off or stopping cinnarizine was followed by the relapse of cold urticaria in 7 cases (50.0 %). These patients were amenable to a second treatment cycle. Six patients (42.9 %) had a persistent remission. A patient interrupted the therapy because of severe vertigo. Three patients reported mild and transitory adverse effects including epigastralgia, weight gain and drowsiness. In conclusion, cinnarizine at high doses may be considered as an effective and well-tolerated treatment for ACU.