Risk Of Anaphylactic Reactions Research Articles

Emicizumab in Type 3 von Willebrand Disease: Report of a Case with an Alloantibody and Literature Review

AbstractType 3 von Willebrand disease (VWD), the most severe form of VWD, is an inherited recessive bleeding disorder caused by the complete deficiency of von Willebrand factor (VWF). The reported prevalence is 1 per million but varies worldwide according to the frequency of consanguineous marriages. The clinical phenotype is characterized not only by mucocutaneous bleedings, but also by hemarthroses and muscle hematoma, as in patients with moderate hemophilia. Long-term prophylaxis with factor (F)VIII/VWF concentrates is recommended in patients with a history of severe and frequent bleeds. A rare complication of replacement therapy is the development of alloantibodies against VWF, with the consequences of an ineffective therapy and risk of anaphylactic reactions upon treatment. Emicizumab is the first bispecific monoclonal antibody that mimics FVIII coagulant activity and is approved for prophylaxis of bleeding in patients with inherited hemophilia A with or without inhibitors and recently also for acquired hemophilia. In this manuscript we report and discuss available data in the literature on the use of emicizumab in type 3 VWD and describe the case of a female patient with type 3 VWD with a history of alloantibodies against VWF and posttransfusion anaphylaxis, recently and successfully put on off-label prophylaxis with emicizumab.

NMBAs: risk of anaphylactic reactions with prior use of pholcodine

NMBAs: risk of anaphylactic reactions with prior use of pholcodine

P012 Cross-specialty audit of Infliximab prescribing at the Great North Children’s Hospital (GNCH)

Abstract Background/Aims Infliximab is an anti-TNF biologic licensed for use in children and young people (CYP) with juvenile idiopathic arthritis (JIA) uncontrolled by methotrexate and children with inflammatory bowel disease uncontrolled by thiopurines. Key side-effects include immunosuppression, neutropenia, liver derangement, latent TB reactivation and risk of anaphylactic reactions. Infliximab is administered intravenously on paediatric day units. Between-specialty inconsistencies complicate the administration and monitoring of infliximab. This retrospective audit aimed to explore adherence to local / national guidance governing Infliximab administration. It is part of an ongoing programme of work towards improved cross-regional quality of care provided to CYP on systemic immunomodulatory therapies. Methods All patients prescribed Infliximab at GNCH in Newcastle between January and December 2020 were identified from pharmacy records. Adherence to local and national guidelines was audited, with particular emphasis on pre-medication investigations, rate of administration, frequency of complications and duration of post-infusion monitoring. Results The rheumatology team at GNCH prescribe infliximab in accordance with local trust guidelines based on BSPAR guidance. The gastroenterology team follow updated ESPGHAN guidelines (European Society for Paediatric Gastroenterology, Hepatology and Nutrition). A total of 155 patients were identified (138 gastroenterology patients and 17 rheumatology patients - 16 JIA, 1 Behcets disease). 17 gastroenterology patients with Crohn’s disease, matched by age, were selected for this audit. Table 1 details audit results for adherence to local/national guidance for Infliximab administration in GNCH. One child with JIA who was non-compliant with second immunosuppressant had an anaphylactic reaction after 5th Infliximab dose. Conclusion Current gastroenterology and rheumatology guidance suggest different pre-screening tests, dose regimens, rates of infusion and duration of post-treatment monitoring. Specialties are not following all guidelines perfectly, in particular pre-treatment viral screening. Although different specialties will continue to require different dosing schedules for infliximab, current practice suggests that it is reasonable to develop cross-specialty guidance governing the prescribing and administration of Infliximab. A cross-specialty guideline will reduce unnecessary variation in practice, reducing the potential for prescribing and administration errors. Disclosure S. Habibollah: None. K. Hartley: None. F. Mcerlane: None.

Abstract No. 471 Allergy testing for verification of contrast allergy prior to radiology procedures

Allergy to contrast material can limit the diagnostic and therapeutic options for patients, especially if the reaction to contrast media is listed as anaphylaxis (IgE-mediated allergic reactions). Many patients with physiologic response to contrast are labeled as being allergic to contrast because the patient or caregiver do not understand the differences between dose-related responses and allergy. Other patients with a history suggesting only a mild reaction may be at risk for anaphylaxis. Our goal is to provide appropriate documentation for the existences or lack of contrast allergy which facilitate best therapeutic and diagnostic options for the patient. Pre-procedure patients with written documentation of contrast allergy were, at the discretion of a licensed independent practitioner, referred to the Allergy and Immunology department for contrast media testing. Patients were tested using an established protocol. Based on reaction clinical history and skin testing patients were classified into four groups: Nonallergic (Negative skin testing, and negative clinical evaluation), predominantly histamine mediated reaction (Negative skin testing, clinical evaluation consistent with histamine mediated symptoms), allergic- like reaction (Negative skin testing, convincing clinical allergic-like reaction), and IgE- mediated allergic reaction (Positive skin testing and positive clinical history) Ten patients completed contrast allergy testing. Referral to allergy and immunology changed the management as follows: avoided steroids in 8/10 (80%) and avoided premedication completely in 6/10 (60%). The testing also confirmed IgE mediated reaction to contrast (Risk of anaphylactic reaction) in 1 patient (10%). Testing in this preliminary patient population suggests significant clinical benefit from referral to allergy and immunology for contrast media testing in patients with reported contrast allergy. Standardization of patient testing may reduce procedure cancellations, excessive use of steroids and potentially the risk of contrast induced anaphylaxis.

Risk for Anaphylactic Reaction from Cardiac Catheterization in Patients Receiving β-Adrenergic Blockers or Angiotensin-Converting Enzyme-Inhibitors

β-Adrenergic blockers (BBs) have been associated with increased risk for severe anaphylactic reaction (AR) from contrast media; however, this was shown with intravenous contrast media, before widespread use of low osmolar contrast media, angiotensin-converting enzyme-inhibitors (ACE-Is), and cardioselective BBs. To assess the risk for AR during cardiac catheterization (CC) associated with BB or ACE-I exposure. Patients who experienced adverse reactions during CC from January 2004 to December 2013 were identified; 1 to 2 matched controls were assigned for each case. We analyzed AR rates in association with demographic variables, medication exposures (BBs, ACE-Is, angiotensin-receptor blockers, aspirin), and comorbidities: cardiovascular disorders, asthma, and atopy. We analyzed 71,782 CCs. Of these, severe 70 reactors were identified-46 (0.06%) fulfilled AR criteria. There were 35 cases of mild to moderate AR and 11 cases of severe AR (0.015%). There were no significant differences in age (61.3% vs 61.5%), sex (63% vs 64% males), cardiovascular disorder rate (78% vs 93%), and exposure to BBs (46% vs 51%; cardioselective: 77% vs 80%) and ACE-Is (37.0% vs 37.2%) in cases versus controls. Via multivariate logistic regression, BB exposure was not associated with greater AR frequency (P= .35) or severity (P= .40). Neither cardioselective BBs (P= 0.2) nor noncardioselective BBs (P= .5) influenced AR severity. ACE-Is had no effect on AR frequency (P= .35) or severity (P= .14). Lower AR frequency was associated with cardiovascular disorder (P= .01). In this case-control study, severe AR was rarely observed. Exposure to BBs or ACE-Is did not significantly influence AR frequency or severity; however, most BBs were cardioselective. Our findings imply that cardioselective BB or ACE-I suspension is not warranted in association with CC.

Adjuvant Allergen Fusion Proteins as Novel Tools for the Treatment of Type I Allergies.

While acute allergic symptoms can be managed by emergency medication, to date, allergen-specific immunotherapy (SIT) with allergen extracts is the only available curative treatment option. However, the risk of anaphylactic reactions, long treatment duration, varying extract quality, and underrepresentation of certain allergens currently prevent many patients from successfully undergoing SIT. Novel strategies are needed to enhance efficacy, safety, and convenience of allergy treatment. Fusion proteins combining allergen and adjuvant into a single molecule can efficiently induce immune responses by targeting the allergen to the relevant immune cells in vivo. Simultaneous co-delivery of both antigen and adjuvant to the same cell in a fixed molecular ratio triggers the uptake and presentation of the conjugated allergen in the context of the adjuvant-induced immune cell activation. This review summarizes the published strategies to improve the treatment of type I allergies using fusion proteins consisting of allergen (peptides) and either (1) immune-activating bacterial (flagellin, MPLA, S-layer, cholera-, and tetanus toxin), (2) viral (PreS, VP-1, TAT), or (3) fungal (FIP-fve) components, (4) immune-activating DNA motifs, (5) forced delivery of allergens to the MHC-II loading pathway, and (6) killing of immune cells expressing allergen-specific IgE by fusion of the allergen to diphtheria toxin.

Hen’s egg allergy: an update

Hen’s egg allergy is one of the most common problems in pediatrics. This pathology is associated with severe clinical manifestations, often with a risk of anaphylactic reactions. This review presents current data on the epidemiology and clinical presentation, as well as aspects of the natural history and management of hen’s egg allergy. The paper will provide data on allergenic proteins of hen’s egg, including data on structure, physicochemical properties, IgE-binding capacity, and cross-reactivity. Finally, practical information about egg allergy and immunization will be presented.

A case of selective immunoglobulin A deficiency associated with autoimmune gastritis

Selective immunoglobulin A (IgA) deficiency is considered to be the most common primary immune deficiency. Up to now, no specific genetic mutation causing this disorder has been found. True prevalence of selective IgA deficiency in the population is unknown, because in most cases it is asymptomatic and occurs as an incidental laboratory finding. In some patients, it can manifest by respiratory and gastrointestinal infections, as well as allergic and autoimmune disorders. According to the literature, autoimmune disorders in patients with selective IgA deficiency have a more aggressive course and a worse prognosis. This clinical case of a combination of selective IgA deficiency and autoimmune gastritis demonstrates that patients with primary immunodeficiency, especially adults, may not know about their disease for a long time. The paper may be of interest for practicing doctors of various specialties, first of all, for gastroenterologists, internists, general practitioners, and is intended to increase awareness about diagnosis of selective IgA deficiency. There is no specific treatment for this immunodeficiency, but one should bear in mind that blood transfusions and intravenous immunoglobulin preparations with high IgA content are contra-indicated in these patients due to a high risk of anaphylactic reactions.

Recurrent episodes of anaphylaxis in a patient with haemophilia B: a case report.

Haemophilia B is an X-linked disorder resulting in coagulation factor IX (FIX) deficiency that is treated with the administration of exogenous FIX obtained from plasma of healthy donors or by a DNA recombinant technique1. The development of an inhibitor antibody against exogenous FIX is a serious complication and occurs in 1–3% of patients with haemophilia B and in 25–30% of patients with haemophilia A. Interestingly, in patients with haemophilia B, inhibitor development is associated with the risk of anaphylactic reaction to FIX administration. This reaction can occur concurrently with inhibitor detection or weeks or months apart regardless of which source of FIX replacement is used, plasma or recombinant. For this reason, the guidelines recommend that the first 20 administrations of FIX concentrate should be performed in hospital1,2. Common features of patients who develop a factor IX inhibitor are occurrence of an allergic/anaphylactic reaction early in life, a high inhibitor titre (>5 Bethesda units [BU]), exposure to various types of factor IX products, and the presence of abnormalities of the factor IX gene (F9)3. Patients with complete gene deletions or rearrangements of F9 have an approximately 50% risk of inhibitor development, while those with nonsense or frame shift mutations have a risk of approximately 20%4–5. This suggests that the greater the impairment of FIX synthesis, the higher the risk of anaphylaxis, although this phenomenon may occur in patients with nonsense mutations4–6. The precise mechanism of this adverse reaction remains unclear and the various hypotheses that had been considered include extracellular distribution of the small FIX protein with potential mast cell activation7,8, complement activation by IgG1 antibody formation9, an IgE-mediated hypersensitivity response10, higher amounts of exogenous protein (the concentration of FIX is much higher than that of factor VIII)11 and the absence of tolerance to FIX in patients with mutations resulting in a complete absence of FIX production12. Moreover, in contrast to antibodies against FVIII, antibodies against FIX may form circulating immune complexes that can initiate anaphylaxis when the individual is re-exposed to FIX concentrate6. We describe a case of three anaphylactic reactions in a patient with haemophilia B after exposure to FIX of different origins.

A Case of Wernicke-Korsakoff Syndrome Treated 1 Year After the Onset of Symptoms.

A Case of Wernicke-Korsakoff Syndrome Treated 1 Year After the Onset of Symptoms.

Midazolam as an induction agent in comparison with propofol as a safe and effective alternative

Introduction: Propofol produce rapid and smooth induction of anesthesia, with rapid metabolism, which would allow it to be used for the maintenance of anesthesia and free from the risk of anaphylactic reactions. Midazolam a new short acting water soluble Benzodiazepine with cardio vascular effects similar to that of diazepam may be an effective alternative for induction of anesthesia. Methods: In this randomized study, all together 48 patients undergoing various surgical procedures belonging to Orthopedic, General Surgery and Gynecological Surgeries constituted the study group. Group-I (Midazolam Group) received intra-venous Midazolam 0.15mg/Kg for induction of anesthesia and Group-II (Propofol Group) received 2mg/kg intravenous Propofol for Induction of Anesthesia. Induction time, Heart Rate, Non invasive blood Pressure is recorded at 1minute interval for 5 minutes and after that at an interval for 5 minutes for another 30 minutes. Demographic data was analyzed by Student’s t-test. Results: The study showed no statistical significance in hemodynamic responses with either Midazolam or Propofol as an induction agent for General Anesthesia but there was statistically difference with respect to heart rate (P=0.001). Conclusion: Midazolam was proven effective compared to Propofol as an induction Agent. DOI: http://dx.doi.org/10.3126/joim.v34i1.9119 Journal of Institute of Medicine, April, 2012; 34:1 25-32

Anaphylaxis in the Young Adult Population

It is critical that clinicians treating young adults understand the presentation and management of anaphylaxis. The most common trigger for anaphylaxis in this population is food. The prevalence of food allergy is growing, with 8% of US children and adolescents affected. All patients at risk for anaphylaxis should be prescribed epinephrine autoinjectors, as epinephrine is the only life-saving medication for a severe anaphylactic reaction. The presentation of anaphylaxis can involve multiple organ systems (eg, mucocutaneous, respiratory, cardiovascular, gastrointestinal) and, as such, patient education is needed to assist in prompt recognition. Appropriate training of patients and caregivers about how to identify anaphylaxis and what to do in an emergency is critical. Training of school and college staff also is essential, as 1 in 4 first-time reactions occurs outside the home. Additional counseling for adolescents at risk for anaphylactic reactions should address increased risk-taking behavior, decreased adult supervision, dating, and the transition of disease management from an adult to the patient.

Provocation test in patients with different phenotypes of aspirin hypersensitivity

Background Aspirin (ASA) hypersensitivity has a complex clinical presentation with three major phenotypes: aspirinexacerbated respiratory disease (AERD; asthma and/or nasal polyps), chronic urticaria and aspirin-induced anaphylaxis. In patients with AERD asthma is often severe and difficult to control. Moreover, NSAID ingestion may provoke life-threatening attack. Thus, diagnosing of ASA hypersensitivity is an important issue. In everyday practice ASA hypersensitivity is confirmed by oral (OPT), nasal (NPT) or bronchial provocation tests. However their protocols vary in terms of maximum cumulative dose. Besides, phenotype of hypersensitivity is not taken into consideration when choosing the protocol. Aim of the study The aim of this study was to compare responsiveness to ASA in patients with different phenotypes of ASA hypersensitivity (AERD, chronic urticaria, anaphylaxis). Patients and methods 238 patients (179 women, 59 men) aged 19-71 with the history suggesting hypersensitivity to NSAIDS were provoked with aspirin. The group comprised 92 patients with AERD, 83 with chronic urticaria and 63 with suspicion of anaphylaxis caused by ASA. Single-blind oral provocation test was performed according to two-day protocol (day 1placebo, day 2- increasing doses of ASA: 50, 100, 150, 300, 400 mg). Anterior rhinomanometry, spirometry and clinical monitoring were used to assess the reaction. The test was considered positive in case of clinical symptoms of hypersensitivity, significant decline of FEV1 or positive nasal response in anterior rhinomanometry. Results Provocation test was positive in 81 (34%) patients, including 26 with chronic urticaria, 45 with asthma and/or nasal polyps and 10 with history of anaphylaxis. Proportions of positive results in the subgroups were 31%, 49% and 16%, respectively. The mean dose provoking reaction was significantly lower in AERD group compared to patients with chronic urticaria (212 mg vs. 604 mg, p<0.05). 36% of positive responders with asthma reacted to doses iU200 mg. 19 subjects (8%) responded to placebo making the provocation impossible to evaluate. Conclusions Patients with AERD usually respond to smaller doses of ASA compared to patients with chronic urticaria. As an oral provocation test is associated with the risk of anaphylactic reaction and its severity is dose-dependent it may be suggested to introduce new protocol for patients with severe asthma, based on lower first doses of ASA.

Pharmacologic Methods to Reduce Postoperative Bleeding in Adult Cardiac Surgery. A Mini-review

Because blood for transfusion is a scarce resource and since allogeneic transfusion may even be harmful, there is a growing awareness among surgeons and anesthesiologists regarding the use of multimodal blood conservation programs in cardiac surgery in order to reduce bleeding, transfusion and re-exploration. Pharmacologic methods should be part of a multimodal blood conservation programs. Three drugs for anti-fibrinolytic prophylaxis have been available for more than two decades: Aprotinin, tranexamic acid and epsilon aminocaproic acid. These drugs can be administered intravenously and topically in the pericardium during cardiac surgery. However, aprotinin marketing was temporarily suspended in 2007/2008 based on results from a randomized study indicating a risk for increased mortality associated with the use of aprotinin. This mini-review on the use of anti-fibrinolytic drugs and other pharmacologic methods to reduce perioperative bleeding in cardiac surgery is provided as aprotinin probably will become increasingly available again in several western countries. A number of randomised and observational studies suggest a minor advantage of aprotinin over the synthetic lysine analogues, which in contrast are cheaper and without the risk of anaphylactic reactions. Other drugs that have been used in order to reduce bleeding in cardiac surgery are recombinant activated factor VIIa, desmopressin and prothrombin complex concentrate, but the value and risks of these drugs in cardiac surgery needs further clarification. Every patient should be evaluated individually according to the risk/benefit ratio of any drug used. Safety issues as well as cost-effective analyses should be in focus in future clinical studies.

Contrast-enhanced ultrasound performed under urgent conditions. Indications, review of the technique, clinical examples and limitations

Contrast-enhanced ultrasound (CEUS) is an imaging technique with various indications, most of which refer to scheduled examinations. However, CEUS can also be performed under urgent conditions for the investigation of many different clinical questions. This article reviews basic physics of ultrasound contrast agents and examines the commonest urgent clinical applications of CEUS. These include, among others, abdominal solid organ trauma and infarcts, scrotal and penile pathology and blood vessel imaging. Patients can be examined with a very short time delay at their bedside, without exposure to ionising radiation or risk of anaphylactic reaction and renal failure, while contraindications are minimal. CEUS technique is described for various urgent indications and imaging examples from our department’s experience are presented. Safety matters and limitations of CEUS are also mentioned. Teaching Points Contrast-enhanced ultrasound (CEUS) can be performed urgently for various clinical applications. Abdominal indications include solid organ trauma and infarcts. CEUS in abdominal organ trauma correlates well with CT and can replace it for patient follow-up. CEUS images testicular torsion, infection and infarction, as well as testicular and penile trauma. Blood vessels can be assessed with CEUS for obstruction, aneurysm, thrombosis and dissection.

Plasma Substitutes Therapy in Pediatrics

Hypovolemia is the most common cause of circulatory failure in children and may lead to critical tissue perfusion and eventually multiple-organ failure. Administration of fluids to maintain or restore intravascular volume represents a common intervention after hemorrhagic shock occurring during surgical procedures or in patients with trauma. Notwithstanding, there is uncertainty whether the type of fluid may significantly influence the outcome, especially in pediatrics. Both human albumin and crystalloids are usually administered: the advantages of crystalloids include low cost, lack of effect on coagulation, no risk of anaphylactic reaction or transmission of infectious agents. However, large amount of crystalloid infusion has been correlated with pulmonary oedema, bilateral pleural effusions, intestinal intussusception, excessive bowel edema, impairing closure of surgical wounds and peripheral edema. Moreover, intravascular volume expansion obtained by crystalloids is known to be significantly shorter and less efficacious than colloids. Among synthetic colloids, gelatins have been used for many years in children, also in early infancy, to treat intravascular fluid deficits. Hydroxyethylstarch (HES) preparations have been introduced recently, becoming very popular for vascular loading both in adults and children. However, the number of pediatric studies aimed at evaluating HES efficacy and tolerance is limited. Given the ongoing controversies on the use of colloids in childhood, this review will focus on the pharmacodynamics of synthetic and non synthetic colloids for the treatment of critical blood loss in pediatrics.

Recent developments in the treatment of acute abdominal and facial attacks of hereditary angioedema: focus on human C1 esterase inhibitor.

Hereditary angioedema (HAE) is a potentially fatal genetic disorder typified by a deficiency (type I) or dysfunction (type II) of the C1-inhibitor (C1-INH) and characterized by swelling of the extremities, face, trunk, abdominal viscera, and upper airway. Type III is normal estrogen-sensitive C1-INH HAE. Bradykinin, the main mediator of HAE, binds to endothelial B2 receptors, increasing vascular permeability and resulting in edema. HAE management includes short- and long-term prophylaxis. For treating acute episodes, C1-INH concentrate is recommended with regression of symptoms achieved in 30–90 min. Infusions of 500–1000 U have been used in Europe for years. Two plasma-derived C1-INH concentrates have been licensed recently in the United States: Berinert® for treating acute attacks and Cinryze® for prophylaxis in adolescent/adult patients. A recombinant C1-INH that is being considered for approval (conestat alfa) exhibited significant superiority versus placebo. Ecallantide (Kalbitor®) is a selective kallikrein inhibitor recently licensed in the United States for treating acute attacks in patients aged >16 years. It is administered in three 10-mg subcutaneous injections with the risk of anaphylactic reactions. Icatibant (Firazyr®) is a bradykinin B2 receptor competitor. It is administered subcutaneously as a 30-mg injection and approved in Europe but not in the United States.

Aprotinin reexposure: Risk of anaphylactic reaction starts immediately after first exposure

Aprotinin reexposure: Risk of anaphylactic reaction starts immediately after first exposure

Recombinant Proteins and Peptides as Diagnostic and Therapeutic Reagents for Arthropod Allergies

Domestic arthropods are chief sources of potent allergens that trigger sensitization and stimulate IgE-mediated allergies. Diagnosis and immunotherapy of arthropod allergies rely on the use of natural allergen extracts which are associated with low specificity and efficacy, the risk of anaphylactic reactions, and the extended period of treatment. Most of the problems associated with natural allergen extracts for allergy diagnosis and immunotherapy can be circumvented with the use of recombinant allergens and peptides. Recombinant allergens are recently developed for microarray-based multi-allergen tests which provide component-resolved diagnosis (CRD) of the patient's sensitization profile. Moreover, recombinant protein technology and peptide chemistry have been used to construct isoallergens, allergen mutants, allergoids, T and B cell peptides, hypoallergens, and mimotopes with reduced allergenicity but enhanced immunogenicity for allergen-specific immunotherapy (SIT) and vaccination. The basics of recombinant arthropod allergen technology are in place providing a lucid future for the advancement of diagnosis and immunotherapy of arthropod allergies.

Effets indésirables des médicaments chez la femme enceinte

A Prospective pharmacovigilance survey of adverse drug reactions (ADRs) in pregnant women was performed in collaboration with gynaecologists and obstetricians of Midi-Pyrenees area (south west of france). The aim of the study was to evaluate the incidence of adverse drug reactions in pregnant women. The incidence of ADRs in pregnant women was low: 0.3%. Moreover, a retrospective pharmacoepidemiological study was conducted to characterize ADRs in pregnant women. Reports of ADRs collected in the Midi-Pyrenees pharmacovigilance centre from 1982 to 2002 were used: type of ADRs, drugs involved and potential risk factors were compared for pregnant women and for age-matched non pregnant women. Forty seven and 94 reports of ADRs were collected in pregnant and non-pregnant women respectively. Anaphylactic reactions were only observed in pregnant women (3 cases, p = 0.04). We observed 1 ADR related stillbirth (due to anaphylactic reaction) in pregnant women. Drugs for gynaecological and cardiovascular systems were more frequently involved in ADRs in pregnant women than in controls. ADRs mainly occurred during the third trimester of pregnancy. The incidence of ADRs is very low in pregnant women. However, one must pay attention on the risk of anaphylactic reactions in pregnant women.