Psychological burden of anaphylaxis and the fight for an EpiPen

A university student with a background of atopy presented to her general practitioner (GP) 2 weeks following an episode of throat tightening and dizziness occurring after touching cashew nut to her lip. She took antihistamine medication immediately and went to sleep, fearing for her life. On waking, she felt astounded to be alive. Her symptoms resolved gradually over the following week. She waited 2 weeks for an appointment with her GP, who referred her to allergy clinic. Eight months later, she was still waiting for her clinic appointment, and was left fearing a future fatal reaction, having been provided with no interim treatment. Not all patients who have severe allergic reactions present to the emergency department. Living with the constant fear of anaphylaxis can be overwhelming for patients and their families, and it can negatively impact mental health. Therefore, we advise early allergy counselling and early EpiPen prescription.

Acute eosinophilic pneumonia: a fatal reaction to ado-trastuzumab

Ado-trastuzumab emtansine (T-DM1) is a monoclonal antibody drug conjugate approved for the treatment of HER2-positive breast cancers. Presented here is a case report of a patient who developed fatal pulmonary toxicity in the form of acute eosinophilic pneumonia while undergoing treatment with T-DM1. Prior to beginning T-DM1 therapy, this patient had been treated with two HER2-targeted agents (trastuzumab, pertuzumab) per National Comprehensive Cancer Network (NCCN) guidelines. This case represents a novel presentation of toxicity associated with T-DM1 while perhaps demonstrating additive toxicity associated with multiple lines of HER2 targeted therapies.

Food-induced anaphylaxis in children – state of art

Food-induced anaphylaxis is the most frequent type of anaphylaxis and the most common cause of fatal acute hypersensitivity reactions in children. It typically occurs after accidental food exposure, after inhalation of food allergen, cutaneous contact and controlled oral food challenge. There is no consensus on a universal clinical definition of anaphylaxis or a uniform symptoms severity score. Recent advances in molecular allergology allow, in many cases, the detailed identification of the allergenic molecule responsible for anaphylaxis. Along with the development of precision medicine, new phenotypes and endotypes of anaphylaxis are being defined. The anaphylaxis course is entirely unpredictable, and even initially mild symptoms may herald a potentially fatal reaction. At the same time, a significant proportion of immediate food hypersensitivity episodes are mild and known as systemic allergic reactions. The occurrence and severity of clinical course of food-induced anaphylaxis are influenced by factors related directly to the child, coexisting diseases, the type and the nature of the allergen, or the presence of cofactors. The unpredictable course of anaphylaxis justifies immediate treatment based on rapid intramuscular administration of adrenaline, regardless of severity. Delayed adrenaline administration is associated with higher incidence of severe course and death. Appropriate and prompt treatment of anaphylaxis is even more critical during the COVID-19 pandemic due to difficult access to medical facilities, hence current treatment plans for food-induced anaphylaxis emphasise the need to administer adrenaline immediately after the onset of the first, even mild, but rapidly progressive symptoms and recommend that the patient have at least two adrenaline autoinjectors.

Neuroleptic Malignant Syndrome and Hyperthermia

Neuroleptic malignant syndrome (NMS) is an uncommon, potentially fatal reaction to antipsychotic medications. Most cases occur in men between the ages of 20 and 50 because they have the highest proportion of antipsychotic consumption. The prevalence of NMS has been reported as 0.07% to 2.2%, but the published diagnostic criteria for NMS varied widely until the Diagnostic and Statistical Manual of Mental Disorders addressed the issue in 2013. NMS is characterized by a constellation of clinical symptoms and laboratory abnormalities, including hyperthermia, muscle rigidity, and increased serum creatine kinase levels. Patients may also present with tremor, altered mental status, autonomic dysfunction, and leukocytosis.

Lung Endothelial Injury Induced by HNA-3a Antibodies in TRALI

Abstract 40 Transfusion related acute lung injury (TRALI) is a severe side-effect of blood transfusion characterized by the acute onset of non-cardiogenic pulmonary edema. Meanwhile, TRALI turned out to be the leading cause of transfusion related fatalities. Accumulated evidence demonstrates that antibodies against human neutrophil antigens (HNAs) play a major role in the pathomechanism of TRALI. Recent studies show that antibodies against the allelic isoform of choline transporter like protein 2 (CTL-2 Arg154 isoform; also known as HNA-3a) are associated with high TRALI mortality. The mechanism underlying this fatal reaction, however, is not clear. In this study, we aimed to identify the mechanism of fatal TRALI induced by HNA-3 antibody under in vitro as well as in vivo conditions. Analysis of mRNA by real-time PCR in different blood cells and endothelial cells (EC) revealed abundant copies of CTL-2 transcripts in ECs in comparison to neutrophils and platelets. This result was confirmed by immunochemical analysis using rabbit antibody specific for CTL-2 as well human antibodies against HNA-3a. In contrast to treatment of neutrophils, treatment of EC with HNA-3a antibodies, but not with antibodies against the antithetical allelic CTL-2 isoform (Gln154 isoform; HNA-3b), leads to significant production of reactive oxygen species (ROS). When HNA-3aa EC monolayers were treated with human anti-HNA-3a antibodies, a significant increase in albumin-FITC influx in transwell system was observed when compared to controls. In line with this observation, a strong reduction of transendothelial electrical resistance was measured. Microscopically, drastic stress fiber formation and gap formation was visible. Immunoblotting analysis of HNA-3a treated ECs showed a significant degradation of VE-cadherin. This observation indicates that anti-HNA-3a antibodies induce EC barrier disturbance via ROS-mediated destabilization of VE-cadherin in cell junctions. Accordingly, this antibody-mediated barrier leakage can be ameliorated by the vasoactive peptide adrenomedulin (ADM), which prevents cell destruction in response to oxidative stress. In an in vivo murine model of TRALI, with lipopolysaccharide primed C57BL/6 mice upon injection of HNA-3a antibodies a significant increase in lung weight and elevated concentration of albumin and number of neutrophils in the bronchoalveolar lavage was observed, indicating the formation of lung edema in these mice. Neutrophil depletion mitigated this effect in mice, but failed to prevent TRALI. Our data demonstrate the direct influence of transfused HNA-3a antibodies on endothelial barrier integrity in vitro as well as in vivo. This novel mechanism of TRALI may be helpful in defining prevention and treatment strategies in order to decrease transfusion mortality. Disclosures: No relevant conflicts of interest to declare.

Red blood cell volume as a predictor of fatal reactions in cattle infected with Theileria parva Katete

A comparison of mean corpuscular volume (MCV) and packed cell volume (PCV) was made between cattle undergoing lethal and non-lethal reactions following experimental infections with the apicomplexan protozoa, Theileria parva Katete. This work confirmed that anaemia occurs in infected animals. However, the fall in PCV was steeper in lethal reactions compared to non-lethal reactions. Our results show that animals with initially lower MCV values are more prone to fatal reaction, despite having normal PCV profiles. The study also found that small red blood cells are more likely to be infected with T. parva. These findings suggest that animals with a higher proportion of small red blood cells in circulation will be more likely to succumb to T. parva infections. The potential for using MCV as a predictor of the outcome of infection challenge is discussed.