Patient Adherence to Written Instructions following Complete Allergological Evaluation for Suspected Beta-Lactam Allergy: A Tertiary Hospital Study in Greece.

BACKGROUND: Beta-lactam (BL) antibiotics are among the most prescribed groups of drugs worldwide and have been implicated in a variety of allergic reactions. There is a paucity of literature regarding patient adherence to prescribed instructions following comprehensive allergy assessments. OBJECTIVE: The objective was to follow up the clinical course of BL allergy in patients who underwent thorough allergological investigation for suspected BL allergy at a tertiary hospital and ascertain patients' compliance with the provided written instructions. MATERIALS: An observational study in patients referred for suspected BL allergy who underwent a comprehensive allergy workup (in vivo ± in vitro tests, DPT in culprit and/or alternative BL) and who subsequently received written instructions was conducted. Data on the nature of the reported drug hypersensitivity reaction, the culprit BL drug, the allergological workup, and the detailed instructions provided in a written drug allergy report were collected retrospectively. Patients' compliance with the instructions was recorded by a telephone survey using a pre-defined questionnaire. RESULTS: Among the 212 patients meeting the inclusion criteria, 87 patients (72.4% women; mean age 50.1 years; age range 6-84 years) responded to the telephone survey and were included in this study. Surprisingly, 45 out of 87 (51.7%) patients did not adhere to the written instructions. The primary factor contributing to non-compliance was the fear of re-occurrence of a drug-induced allergic reaction (personal and/or triggered by their treating physician reluctance), accounting for 77.7% of cases. The analysis demonstrated that the initial reaction's severity and type, as well as the outcomes of skin testing, did not correlate with compliance to instructions (p > 0.05). Surprisingly enough, a drug provocation test (DPT), irrespectively of the result, emerged as a negative predictor for adherence, with only 40.6% of DPT patients complying compared to 77.8% of those who did not undergo DPT (p = 0.005; odds ratio = 0.195; 95% confidence interval: 0.058-0.655). Variables such as performing DPT with alternative or incriminated drugs or the result of the DPT (positive-negative) were not associated with patient compliance. Conversely, the type of instructions provided exhibited a noteworthy correlation with compliance. Patients who were explicitly instructed to entirely avoid all BL antibiotics demonstrated markedly higher adherence rates (83.3%) compared to those who were advised to have a partial or complete release of BLs (31.8% and 58.1%, respectively; p < 0.05). Notably, among compliant patients who received either the original culprit drug or the alternative (32 out of 87, 36.7%), no allergic reactions were reported. In contrast, among the 12 patients with written avoidance of all BLs, subsequent BL intake led to immediate reactions (Grade I and IV) in 2 patients (16.6%). CONCLUSIONS: A notable disparity in patient adherence to written instructions prohibiting or releasing beta-lactams was demonstrated. Less than half of the patients ultimately complied with the provided instructions, underscoring the need for tailored patients' education and strategies to improve adherence in the management of suspected BL allergy.

Case of Polyethylene Glycol Allergy Confirmed with Basophil Activation Test and Oral Challenge Successfully Immunized with SARS-CoV-2 Vaccine.

Polyethylene glycols (PEG) or macrogols are polymers of ethylene oxide widely used in drugs either as active substances or, more commonly, as excipients. We report a Caucasian 32-year-old woman with referred anaphylaxis almost instantly after oral intake of a macrogol-containing laxative. Despite an anaphylactic reaction, the patient showed negative results for both the skin test and specific IgE to monomer, while the basophil activation test and oral challenge were positive. The patient was later successfully vaccinated with a polysorbate 80-containing SARS-CoV-2 vaccine following an additional work-up. As a result, the inactive form of PEG cannot be fully diagnosed, and it is considered a "hidden" allergen. Allergens like polysorbates need special consideration due to their possible cross-reactivity by their specific derivatives.

Adrenaline autoinjector is under-prescribed in typical cold urticaria patients living in tropical climate countries.

Background: The diagnosis of typical cold urticaria (ColdU) relies on whealing in response to local cold stimulation testing (CST). It can also manifest with cold-induced anaphylaxis (ColdA). Till date, it is largely unclear how often patients with ColdU receive adrenaline treatment and are provided with an adrenaline autoinjector (AAI). Methods: An international, cross-sectional study, COLD-CE (i.e., comprehensive evaluation of ColdU and other cold-induced reactions), was carried out at 32 UCAREs. Detailed histories were taken and CST with an ice cube and/or TempTest® performed. ColdA was defined as an acute cold-induced (i.e., by cold water, air, or surfaces) involvement of the skin and/or visible mucosal tissue and at least one of the symptoms (cardiovascular manifestations, difficulty breathing, or gastrointestinal symptoms). Results: Of the 551 ColdU patients, 75% (n = 412) had a positive CST. Of them, concomitant chronic spontaneous urticaria was diagnosed in 10%. Of 372 patients with stand-alone ColdU, 69% were women and 91% adults. Their median age was 36 (IQR 26 - 48) years. Patients were also categorized into residents of countries with a tropical (n = 33), temperate (n = 264), or cold (n = 75) climate (Table 1: R13C1, R17C1, R21C1). AAI was more often prescribed to residents of temperate than tropical countries (30% vs. 12%, p = .038; Table 1: R31C1), although the frequency of ColdA did not significantly differ between these countries (44% vs. 42%, p = 1.000; R29C2). Residents of tropical countries had a higher frequency of ColdA induced by cold air than residents of temperate (36% vs. 12%, p = .001; R29C4) or cold (36% vs. 12%, p = .007; R25C4) countries. Cardiovascular manifestations induced by cold air were diagnosed in 33% (n = 11) of residents of tropical countries, but only 18% (n = 2) and 36% (n = 4) of them had received adrenaline and AAI, respectively (R13 - 15C7). Furthermore, hypotension and/or loss of consciousness induced by cold air occurred in 18% (n = 6) of patients, but only 17% (n = 1) received adrenaline (R13 - 14C10). ColdA was induced by complete cold water immersion in 9% (n = 3) of patients, and none of them received adrenaline treatment nor AAI (R13 - 15C3). Conclusion: Our findings suggest that ColdA is undertreated and call for changes in ColdU management.

Risk factors for systemic reactions in typical cold urticaria: Results from the COLD-CE study.

BACKGROUND: Cold urticaria (ColdU), that is, the occurrence of wheals or angioedema in response to cold exposure, is classified into typical and atypical forms. The diagnosis of typical ColdU relies on whealing in response to local cold stimulation testing (CST). It can also manifest with cold-induced anaphylaxis (ColdA). We aimed to determine risk factors for ColdA in typical ColdU. METHODS: An international, cross-sectional study COLD-CE was carried out at 32 urticaria centers of reference and excellence (UCAREs). Detailed history was taken and CST with an ice cube and/or TempTest® performed. ColdA was defined as an acute cold-induced involvement of the skin and/or visible mucosal tissue and at least one of: cardiovascular manifestations, difficulty breathing, or gastrointestinal symptoms. RESULTS: Of 551 ColdU patients, 75% (n = 412) had a positive CST and ColdA occurred in 37% (n = 151) of the latter. Cold-induced generalized wheals, angioedema, acral swelling, oropharyngeal/laryngeal symptoms, and itch of earlobes were identified as signs/symptoms of severe disease. ColdA was most commonly provoked by complete cold water immersion and ColdA caused by cold air was more common in countries with a warmer climate. Ten percent (n = 40) of typical ColdU patients had a concomitant chronic spontaneous urticaria (CSU). They had a lower frequency of ColdA than those without CSU (4% vs. 39%, p = .003). We identified the following risk factors for cardiovascular manifestations: previous systemic reaction to a Hymenoptera sting, angioedema, oropharyngeal/laryngeal symptoms, and itchy earlobes. CONCLUSION: ColdA is common in typical ColdU. High-risk patients require education about their condition and how to use an adrenaline autoinjector.