Multicentric Observational Study on Safety and Tolerability of COVID-19 Vaccines in Patients with Angioedema with C1 Inhibitor Deficiency: Data from Italian Network on Hereditary and Acquired Angioedema (ITACA).

Angioedema due to C1 inhibitor deficiency (AE-C1-INH) is a rare disease characterized by recurrent and unpredictable attacks of angioedema. Multiple trigger factors, including trauma, emotional stress, infectious diseases, and drugs, could elicit angioedema attacks. The aim of this study was to collect data on the safety and tolerability of COVID-19 vaccines in a population of patients affected by AE-C1-INH. Adult patients with AE-C1-INH, followed by Reference Centers belonging to the Italian Network for Hereditary and Acquired Angioedema (ITACA), were enrolled in this study. Patients received nucleoside-modified mRNA vaccines and vaccines with adenovirus vectors. Data on acute attacks developed in the 72 h following COVID-19 vaccinations were collected. The frequency of attacks in the 6 months after the COVID-19 vaccination was compared with the rate of attacks registered in the 6 months before the first vaccination. Between December 2020 and June 2022, 208 patients (118 females) with AE-C1-INH received COVID-19 vaccines. A total of 529 doses of the COVID-19 vaccine were administered, and the majority of patients received mRNA vaccines. Forty-eight attacks of angioedema (9%) occurred within 72 h following COVID-19 vaccinations. About half of the attacks were abdominal. Attacks were successfully treated with on-demand therapy. No hospitalizations were registered. There was no increase in the monthly attack rate following the vaccination. The most common adverse reactions were pain at the site of injection and fever. Our results show that adult patients with angioedema due to C1 inhibitor deficiency can be safely vaccinated against SARS-CoV-2 in a controlled medical setting and should always have available on-demand therapies.

Gadolinium-Based Contrast Agents Hypersensitivity: A Case Series.

Gadolinium-based contrast agents (GBCAs) are considered to be safe, although sometimes patients report a hypersensitivity reaction when undergoing magnetic resonance imaging (MRI). The mechanisms of these reactions and of the sensitization to GBCAs are still largely unknown. We describe four cases of patients who experienced immediate adverse reactions to GBCAs with a demonstrated cutaneous hypersensitivity suggesting an IgE-mediated mechanism.

SIRM-SIAAIC consensus, an Italian document on management of patients at risk of hypersensitivity reactions to contrast media.

Hypersensitivity reactions (HRs) to contrast media (CM) can be distinguished in immune-mediated (including allergic reactions) and non-immune-mediated reactions, even if clinical manifestations could be similar. Such manifestations range from mild skin eruptions to severe anaphylaxis, making it important for radiologists to know how to identify and manage them. A panel of experts from the Società Italiana di Radiologia Medica e Interventistica (SIRM) and the Società Italiana di Allergologia, Asma e Immunologia Clinica (SIAAIC) provided a consensus document on the management of patients who must undergo radiological investigations with CM. Consensus topics included: the risk stratification of patients, the identification of the culprit CM and of a safe alternative by an allergy workup, as well as the use of premedication and the correct procedure to safely perform an elective (i.e., scheduled) or urgent examination. The most important recommendations are: (1) in all patients, a thorough medical history must be taken by the prescribing physician and/or the radiologist to identify at-risk patients; (2) in patients with hypersensitivity reactions to CM, the radiologist must consider an alternative, non-contrast imaging study with a comparable diagnostic value, or prescribe a different investigation with another class of CM; (3) if such options are not feasible, the radiologist must address at-risk patients to a reference centre for an allergy evaluation; (4) if timely referral to an allergist is not viable, it is recommended to use a CM other than the responsible one, taking into account cross-reactivity patterns; in the case of patients with histories of severe reactions, the presence of an anesthesiologist is also recommended and a premedication is suggested.

Large local reaction to Hymenoptera stings: Sound studies are needed to change a shared concept.

The natural history of large local reactions to Hymenoptera stings allowed to estimate the risk to develop a systemic reaction after an initial large local reaction in about 4% of patients. A recently published study claimed that such risk concerns instead around one-fourth of patients. However, such study is flawed by serious imprecision, particularly the unreliable identification by patients of the culprit insect, as well as the dubious identification of the causative venom in multisensitized patients. Also, the authors criticized previous studied because of the limited number of patients, while they included in the study 662 patients. Indeed, when only patients clearly restung by the same insect according to their history data were considered, the number of patients fell to 35. These data are unable to change the current shared concept on the low risk of systemic reactions in patients with initial large local reaction.

Publisher Correction: A database of the coseismic effects following the 30 October 2016 Norcia earthquake in Central Italy.

In the original version of the Data Descriptor the surname of author Anne Socquet was misspelled. This has now been corrected in the HTML and PDF versions of the Data Descriptor. Some authors were also not appropriately associated with their affiliations in the HTML version, due to formatting errors made by the publisher. This has now been corrected in the HTML version of the Data Descriptor, the affiliations in the PDF were correct from the time of publication.

A database of the coseismic effects following the 30 October 2016 Norcia earthquake in Central Italy.

We provide a database of the coseismic geological surface effects following the Mw 6.5 Norcia earthquake that hit central Italy on 30 October 2016. This was one of the strongest seismic events to occur in Europe in the past thirty years, causing complex surface ruptures over an area of >400 km2. The database originated from the collaboration of several European teams (Open EMERGEO Working Group; about 130 researchers) coordinated by the Istituto Nazionale di Geofisica e Vulcanologia. The observations were collected by performing detailed field surveys in the epicentral region in order to describe the geometry and kinematics of surface faulting, and subsequently of landslides and other secondary coseismic effects. The resulting database consists of homogeneous georeferenced records identifying 7323 observation points, each of which contains 18 numeric and string fields of relevant information. This database will impact future earthquake studies focused on modelling of the seismic processes in active extensional settings, updating probabilistic estimates of slip distribution, and assessing the hazard of surface faulting.

Hereditary and Acquired Angioedema: Heterogeneity of Pathogenesis and Clinical Phenotypes.

Recurrent angioedema (AE) without wheals is increasingly recognized as a clinical entity and a frequent cause of admission to the emergency room. The Hereditary Angioedema Working Group (HAWK) classification allowed the scientific community to go beyond the semantic confusion that dominated this topic for decades. This classification distinguishes hereditary and acquired forms of AE, either related or unrelated to C1 inhibitor deficiency. Recently, additional mechanisms have been involved in the AE pathogenesis, including the uncontrolled activation of factor XII, generation of vasoactive mediators that induce dysregulation of endothelial functions, and bidirectional interactions between mast cell-derived mediators and the plasma contact system. Thus, recurrent AE can be determined by multiple and concurrent mechanisms that may generate distinct clinical phenotypes of the disease. Frequency, severity, and the location of attacks are quite different from patient to patient and, even in the same patient, they may change throughout the course of life. The severity of the clinical phenotype strongly influences the burden of the disease and patients' quality of life. Despite major advances in our understanding of recurrent AE, many unsolved questions remain, leaving several unmet needs for patients and caregivers. This review is focused on a description of different AE phenotypes and the concurrent mechanisms leading to their pathogenesis. A better definition of cellular and molecular pathways responsible for the distinct AE phenotypes may help to improve diagnosis and may lead to a personalized approach to prophylaxis and treatment of the disease.

Risk of anaphylaxis in patients with large local reactions to hymenoptera stings: a retrospective and prospective study.

BACKGROUND: In the few studies available, the risk of developing systemic reactions (SR) to hymenoptera stings in patients with previous large local reactions (LLRs) to stings ranges from 0 to 7 %. We evaluated both retrospectively and prospectively the risk of SRs in patients with LLRs to stings. METHODS: An overall number of 477 patients, 396 with an SR as the first manifestation of allergy and 81 with a history of only LLRs after hymenoptera stings, were included in the study. All patients had clinical history and allergy testing (skin tests and/or specific IgE) indicative of allergy to venom of only one kind of Hymenoptera. Of the 81 patient with LLRs, 53 were followed-up for 3 years by annual control visits, while the 396 patients with SR were evaluated retrospectively. RESULTS: Among the 396 patients with an SR, only 17 (4.2 %) had had a previous LLR as debut of allergy, after an history of normal local reactions to Hymenoptera stings. All the 81 patients with a history of only LLRs had previously had at least two LLRs, with an overall number of 238 stings and no SR. Among the 53 patients who were prospectively evaluated we found that 31 of them (58.3 %) were restung by the same type of insect, with an overall number of 59 stings, presenting only LLRs and no SR. CONCLUSIONS: Our findings confirm that patients with repeated LLRs to stings had no risk of SR, while a single LLR does not exclude such risk. This has to be considered in the management of patients with LLRs.

A nationwide survey of hereditary angioedema due to C1 inhibitor deficiency in Italy.

INTRODUCTION: Hereditary angioedema due to C1-inhibitor deficiency (C1-INH-HAE type I) or dysfunction (C1-INH-HAE type II) is a rare disease characterized by recurrent episodes of edema with an estimated frequency of 1:50,000 in the global population without racial or gender differences. In this study we present the results of a nationwide survey of C1-INH-HAE patients referring to 17 Italian centers, the Italian network for C1-INH-HAE, ITACA. METHODS: Italian patients diagnosed with C1-INH-HAE from 1973 to 2013 were included in the study. Diagnosis of C1-INH-HAE was based on family and/or personal history of recurrent angioedema without urticaria and on antigenic and/or functional C1-INH deficiency. RESULTS: 983 patients (53% female) from 376 unrelated families were included in this survey. Since 1973, 63 (6%) patients diagnosed with C1-INH-HAE died and data from 3 patients were missing when analysis was performed. Accordingly, the minimum prevalence of HAE in Italy in 2013 is 920:59,394,000 inhabitants, equivalent to 1:64,935. Compared to the general population, patients are less represented in the early and late decades of life: men start reducing after the 5(th) decade and women after the 6(th). Median age of patients is 45 (IQ 28-57), median age at diagnosis is 26 years (IQ 13-41). C1-INH-HAE type 1 are 87%, with median age at diagnosis of 25 (13-40); type 2 are 13% with median age at diagnosis of 31 (IQ 16-49). Functional C1INH is ≤50% in 99% of patients. Antigen C1INH is ≤50% in 99% of type 1. C4 is ≤50% in 96% of patients. The chance of having C1-INH-HAE with C4 plasma levels >50% is < 0.05. CONCLUSION: This nationwide survey of C1-INH-HAE provides for Italy a prevalence of 1:64,935. C1-INH-HAE patients listed in our database have a shorter life expectancy than the general population. An increased awareness of the disease is needed to reduce this discrepancy. Measurement of C4 antigen can exclude diagnosis of C1-INH-HAE with an accuracy > 95%. This parameter should be therefore considered for initial screening in differential diagnosis of angioedema.

Chloramine-induced anaphylaxis while showering: a case report.

INTRODUCTION: Sodium-N-chlorine-p-toluene sulfonamide, commonly known as chloramine-T, is a derivative of chlorine which is widely used as a disinfectant. For many years, chloramine-T has been described as a cause of immediate-type hypersensitivity, especially with regard to asthma and rhinitis, and as a cause of occupational dermatoses in cleaning personnel in hospitals, although no anaphylactic reaction has yet been reported. Hence, to the best of our knowledge we present the first case of anaphylaxis to chloramine-T with evidence of specific immunoglobulin E antibodies. CASE PRESENTATION: We describe the case of a 25-year-old Caucasian woman who was in good health and with a negative history for atopy, including no respiratory symptoms of rhinitis or asthma, and with no professional exposure to chloramine-T. She, while showering, applied a chloramine-T solution to a skin area with folliculitis on her leg, and within a few minutes developed generalized urticaria and angioedema, followed by vomiting and collapse with loss of consciousness. A skin prick test with a chloramine-T solution at 10mg/mL concentration was positive, and specific immunoglobulin E to chloramine-T was quantified at a value of 2.9 optical density as measured by the enzyme allergosorbent test technique. CONCLUSION: The strict cause-effect relationship and the results of the skin test and the in vitro test make certain the causative role of chloramine-T in this case of anaphylaxis. This suggests that chloramine-T, based on its wide use as a disinfectant, should be considered a possible cause in anaphylaxis of unknown origin.

Hypersensitivity to Hymenoptera venom: advances in diagnosis and implications for treatment.

Diagnosis and treatment of hypersensitivity to Hymenoptera venom took a landmark step forward in the late 1970s with the introduction of venom as an adequate material instead of whole body extracts. Since then, venom immunotherapy (VIT) has provided allergic subjects with a complete protection from fatal anaphylaxis and prevented about 90% of all reactions to stings. The cross-reactivity among some venom components, particularly important in the case of cross-reacting carbohydrate determinants, has often made it difficult to recognize the true causative venom to be used in VIT. Recently, the introduction of purified and recombinant allergens, such as Api m 1 from honeybee venom, Ves v 5 from yellow jacket venom, and Pol d 5 from wasp venom, have allowed a more precise diagnosis with identification of the causative venom component. This paves the way for a patient-tailored VIT in the near future. Another issue which needs to be addressed is the improvement in the safety of VIT with honeybee venom, which is significantly less favourable in comparison to vespid venom. A number of molecular approaches are under investigation in order to achieve this objective. Alternative routes of administration, such as the sublingual and the intralymphatic, have also been proposed, but there are not yet sufficient data available to demonstrate their feasibility. This review also presents patents on new trends in therapies for the management of hypersensitivity to hymenoptera venom.