Immediate-type Hypersensitivity Reactions Research Articles

Cross-hypersensitivity reactions to non-steroidal anti-inflammatory drugs, manifested as urticaria and/or angioedema, anaphylaxis

BACKGROUND: The main mechanism of drug hypersensitivity to non-steroidal anti-inflammatory drugs is associated with inhibition of cyclooxygenase type 1, which leads to cross-hypersensitivity reactions to non-steroidal anti-inflammatory drugs from various subgroups of different chemical structures. Clinically, cross-hypersensitivity usually manifests in the form of urticaria and/or angioedema. AIM: To characterize a group of patients with cross-hypersensitivity to non-steroidal anti-inflammatory drugs manifesting as urticaria / angioedema / anaphylaxis. MATERIALS AND METHODS: To achieve this aim a prospective single-center study was conducted. Patients with a presumptive diagnosis of drug hypersensitivity to non-steroidal anti-inflammatory drugs (n=307) were consulted. A group of patients (n=237) with high probability of such reactions was identified, of which cross-hypersensitivity manifested as urticaria / angioedema / anaphylaxis was observed in 127 patients. This group was divided into 2 phenotypes: a group with concomitant chronic urticaria (n=67) and without it (n=60). We assessed demographic data, drug triggers, clinical manifestations, concomitant atopy, and compared these indicators between both groups. Selected patients underwent a drug provocation test with selective or predominantly selective non-steroidal anti-inflammatory drugs and paracetamol. RESULTS: Cross-hypersensitivity reactions manifested as urticaria / angioedema / anaphylaxis is the most common phenotype of immediate-type drug cross-hypersensitivity reactions to non-steroidal anti-inflammatory drugs (75.6%). Women develop this condition 2.5 times more frequently than men, and are more likely to develop cross-drug hypersensitivity with concomitant chronic urticaria with the onset of approximately 16 years later than men. Mild manifestations of cross-hypersensitivity (urticaria/angioedema) develop more frequently than severe ones (anaphylaxis). Angioedema in children, urticaria in adults with concomitant chronic urticaria and angioedema in adults without concomitant chronic urticaria are it's main manifestations. The most frequent non-steroidal anti-inflammatory drugs triggers are metamizole, acetylsalicylic acid and propionic acid derivatives. Non-steroidal anti-inflammatory drugs with the lowest risk of developing drug hypersensitivity are coxibs, paracetamol, and to a lesser extent ― meloxicam, nimesulide. CONCLUSION: The data obtained allowed us to expand our understanding of cross-hypersensitivity reactions to non-steroidal anti-inflammatory drugs presenting as urticaria/angioedema or anaphylaxis. Selective cyclooxygenase type 2 inhibitors and paracetamol are drugs with the highest safety profile.

Hair Product Allergy: A Review of Epidemiology and Management.

Allergy to hair products is an increasingly common issue among people given the exposure to these products on a daily basis. Allergic reactions could be in the form of delayed-type contact dermatitis or the form of immediate-type hypersensitivity reactions. Hair products contain many ingredients and chemicals that patients may have allergies to, but common allergens are hair dyes, fragrances, persulfate salts, ammonium thioglycolate, coconut fatty acid derivatives, and acrylates. Allergy to hair dye is the most common followed by other allergens such as fragrances and persulfate salts. We discussed testing for hair dye allergy along with suggestions for alternative hair dyes that patients may use.Allergy to topical scalp medications is also seen in patients using those products. Allergy to topical minoxidil is seen more often due to the increased use of minoxidil sprays and foams among patients to increase hair growth. We will discuss in this review the diagnosis and alternatives for patients with minoxidil allergy. Hairdressers are at higher risk of allergy to hair products compared to the general population due to prolonged exposure to allergens and specific measures should be implemented to minimize the hazards of exposure.

Etoposide hypersensitivity reactions and outcomes of desensitizations in immediate-type hypersensitivity reactions

Aims: This study aims to define characteristics of hypersensitivity reactions with etoposide, and outcomes of desensitizations in immediate-type hypersensitivity rections
 Methods: This is a retrospective observational study of patients who had hypersensitivity reactions with etoposide from January 2019 to December 2023. 
 Results: A total of 39 patients with lung cancer were included in the study. Ten (25.6%) patients had known other drug allergies and three (7.7%) patients had previous chemotherapeutic hypersensitivity two with paclitaxel and one with docetaxel. Most of the initial hypersensitivities were in the first or second cycle (n=29, 74.4%). Ten (25.4%) patients had hypersensitivity reactions at the first application of etoposide. Thirty (76.9%) patients had immediate-type hypersensitivity reactions. There was no significant difference in terms of patient and initial hypersensitivity characteristics between patients who had immediate or non-immediate type hypersensitivity reactions. Of the 30 patients with immediate-type hypersensitivity reactions, initial reaction was mild in 16 (53.3%) and moderate in 14 (46.7%) patients. Most common symptoms were erythema in 29 (96.7%), dyspnea in 13 (43.3%), chest tightness in 8 (26.7%), discomfortness in 7 (23.3%), and hypertension in 6 (20%). Skin tests were negative in five patients who underwent skin testing. A total of 98 desensitization courses were performed in 27 patients and 3 (11.1%) patients had breakthrough reactions.
 Conclusion: Most of the hypersensitivity reactions to etoposide are immediate-type and not severe. Desensitization is an effective and safe procedure to manage these reactions. Further research is needed to elucidate the mechanisms of hypersensitivity reactions.

Сучасні аспекти діагностики та лікування анафілаксії. Частина 1

Abstract. The aim of this review is to characterize the epidemiology, determine the phenotypes and endotypes of anaphylaxis, pathogenetic mechanisms of its development, systematize on their basis of clinical manifestations and degrees of severity of this condition, evaluate possible biomarkers of anaphylaxis for their wider implementation in clinical practice. Anaphylaxis is the most severe of allergic reactions, putting patients at high risk of losing their lives and requiring prompt recognition and immediate treatment. However, since its symptoms mimic the manifestations of other diseases, such as asthma and urticaria, the diagnosis of anaphylaxis is often insufficiently effective due to the very rare determination of the tryptase level, so the treatment of patients is delayed, and epinephrine (adrenaline) is used late. The main causes of anaphylaxis are poorly understood, and death due to anaphylaxis is often difficult to investigate due to misdiagnosis of the condition. Key words: anaphylaxis, phenotypes and endotypes of anaphylaxis, anaphylactic shock, immediate-type hypersensitivity reactions, IgE, monoclonal antibodies, epinephrine.

A systematic review and meta-analysis of proteomic and metabolomic alterations in anaphylaxis reactions.

Anaphylaxis manifests as a severe immediate-type hypersensitivity reaction initiated through the immunological activation of target B-cells by allergens, leading to the release of mediators. However, the well-known underlying pathological mechanisms do not fully explain the whole variety of clinical and immunological presentations. We performed a systemic review of proteomic and metabolomic studies and analyzed the extracted data to improve our understanding and identify potential new biomarkers of anaphylaxis. Proteomic and metabolomic studies in both human subjects and experimental models were extracted and selected through a systematic search conducted on databases such as PubMed, Scopus, and Web of Science, up to May 2023. Of 137 retrieved publications, we considered 12 for further analysis, including seven on proteome analysis and five on metabolome analysis. A meta-analysis of the four human studies identified 118 proteins with varying expression levels in at least two studies. Beside established pathways of mast cells and basophil activation, functional analysis of proteomic data revealed a significant enrichment of biological processes related to neutrophil activation and platelet degranulation and metabolic pathways of arachidonic acid and icosatetraenoic acid. The pathway analysis highlighted also the involvement of neutrophil degranulation, and platelet activation. Metabolome analysis across different models showed 13 common metabolites, including arachidonic acid, tryptophan and lysoPC(18:0) lysophosphatidylcholines. Our review highlights the underestimated role of neutrophils and platelets in the pathological mechanisms of anaphylactic reactions. These findings, derived from a limited number of publications, necessitate confirmation through human studies with larger sample sizes and could contribute to the development of new biomarkers for anaphylaxis. https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024506246.

Detection of Intracellular Complement Activation by Nanoparticles in Human T Lymphocytes.

The complement system is complex and includes two main components: the systemic or plasma complement and the so-called intracellular complement or complosome. The complement proteins expressed by the liver and secreted into blood plasma compose the plasma complement system, whereas complement proteins expressed by and functioning inside the cell represent the intracellular complement. The complement system plays an essential role in host defense; however, complement activation may lead to pathologies when uncontrolled. When such undesirable activation of the plasma complement occurs in response to a drug product, it leads to immediate-type hypersensitivity reactions independent of immunoglobulin E. These reactions are often called complement activation-related pseudoallergy (CARPA). In addition to the blood plasma, the complement protein C3 is found in many cells, including lymphocytes, monocytes, endothelial, and even cancer cells. The activation of the intracellular complement generates split products, which are exported from the cell onto the membrane. Since the activation of the intracellular complement in T lymphocytes was found to correlate with autoimmune disorders, and growing evidence is available for the involvement of T lymphocytes in the development of drug-induced hypersensitivity reactions, understanding the ability of nanomaterials to activate intracellular complement may aid in establishing a long-term safety profile for these materials. This chapter describes a flow cytometry-based protocol for detecting intracellular complement activation by engineered nanomaterials.

Heparin-induced Anaphylaxis shock.

Introduction: Anaphylaxis is a fatal condition that can be easily managed if discovered early. Only a few examples of anaphylaxis-like reactions caused by heparin have been documented, and immediate-type hypersensitivity reactions to heparin are extremely uncommon. Case Presentation: We report a case of a 53-yearold gentleman known to have an End Stage Renal Disease (ESRD) on Hemodialysis for two years, who went to the dialysis facility in his usual state of health. After two hours of dialysis, a new lock of taurolidine/heparin was installed; one minute later, the patient started to vomit and became restless, blood pressure dropped to 60/47 mmHg, and urticarial hives and a reddish rash developed on his skin, covering his trunk and limbs. He was immediately given three doses of epinephrine intramuscularly, which he did not respond to. Therefore, an epinephrine infusion was started. IV hydrocortisone and diphenhydramine were given for symptomatic relief. The patient was shifted to the emergency department, where he became vitally stable and returned to baseline. Heparininduced anaphylaxis was assumed based on the quick response to the above medications. Conclusion: This case can be added to the growing literature regarding this rare reaction, and more studies should be done to understand the nature of the reaction better. We recommend that the healthcare team becomes vigilant of heparin as a possible cause of anaphylaxis.

Anaphylatoxin Complement 5a in Pfizer BNT162b2-Induced Immediate-Type Vaccine Hypersensitivity Reactions.

The underlying immunological mechanisms of immediate-type hypersensitivity reactions (HSR) to COVID-19 vaccines are poorly understood. We investigate the mechanisms of immediate-type hypersensitivity reactions to the Pfizer BNT162b2 vaccine and the response of antibodies to the polyethylene glycol (PEG)ylated lipid nanoparticle after two doses of vaccination. Sixty-seven participants, median age 35 and 77.3% females who tolerated two doses of the BNT162b2 vaccine (non-reactors), were subjected to various blood-sampling time points. A separate group of vaccine reactors (10 anaphylaxis and 37 anonymised tryptase samples) were recruited for blood sampling. Immunoglobulin (Ig)G, IgM and IgE antibodies to the BNT162b2 vaccine, biomarkers associated with allergic reaction, including tryptase for anaphylaxis, complement 5a(C5a), intercellular adhesion molecule 1 (ICAM-1) for endothelial activation and Interleukin (IL)-4, IL-10, IL-33, tumour necrosis factor (TNF) and monocyte chemoattractant protein (MCP-1), were measured. Basophil activation test (BAT) was performed in BNT162b2-induced anaphylaxis patients by flow cytometry. The majority of patients with immediate-type BNT162b2 vaccine HSR demonstrated raised C5a and Th2-related cytokines but normal tryptase levels during the acute reaction, together with significantly higher levels of IgM antibodies to the BNT162b2 vaccine (IgM 67.2 (median) vs. 23.9 AU/mL, p < 0.001) and ICAM-1 when compared to non-reactor controls. No detectable IgE antibodies to the BNT162b2 vaccine were found in these patients. The basophil activation tests by flow cytometry to the Pfizer vaccine, 1,2-dimyristoyl-rac-glycero-3-methoxypolyethylene glycol (DMG-PEG) and PEG-2000 were negative in four anaphylaxis patients. Acute hypersensitivity reactions post BNT162b2 vaccination suggest pseudo-allergic reactions via the activation of anaphylatoxins C5a and are independent of IgE-mechanisms. Vaccine reactors have significantly higher levels of anti-BNT162b2 IgM although its precise role remains unclear.

Can clarithromycin be used without testing in patients with penicillin allergy?

BackgroundPenicillin hypersensitivity is a common cause of suspected and proven drug allergy and drug-induced anaphylaxis in medical records and causes social and economic burdens. ObjectiveSince the rate of clarithromycin hypersensitivity is low in the general population, we aimed to investigate whether clarithromycin can be prescribed to patients with penicillin allergy without a provocation test. MethodsThe medical records of 186 patients referred to our clinic between 2015 and 2021 with a history of penicillin allergy were evaluated retrospectively. Patients having a history of at least two immediate-type hypersensitivity reactions with penicillin antibiotics or having a history of immediate-type hypersensitivity with penicillin and diagnosed by positive penicillin V/G specific IgE and/or penicillin skin tests were included in the study. Penicillin skin tests were performed according to the manufacturer's instructions. Concentrations of serum specific IgE against phenoxymethylpenicillin (penV) and benzylpenicillin (pen G) were determined using The Phadia CAP System FEIA method. An oral drug provocation test with clarithromycin was performed in all patients. ResultsThe data of 64 patients diagnosed with penicillin allergy and who underwent clarithromycin oral provocation test were analyzed. Oral provocation test with clarithromycin was positive in only two of these patients (3%). These two patients had a history of multidrug hypersensitivity, and one of them also had food and venom allergies. ConclusionWe suggest that clarithromycin can be given without an oral provocation test when an alternative antibiotic is required in patients with penicillin allergy and without multidrug hypersensitivity.

Patient Characteristics Associated With Reactions to Mrgprx2-Activating Drugs in an Electronic Health Record–Linked Biobank

Mas-related G protein-couple receptor x2 (Mrgprx2) activation underlies many common non-IgE-mediated adverse drug reactions (ADRs), yet the features of patients with reactions to Mrgprx2-activating drugs are unknown. To characterize the patient-specific comorbidities and laboratory characteristics associated with listed reactions to Mrgprx2-activating drugs, including fluoroquinolones, morphine, neuromuscular blockade agents, vancomycin, and leuprolide. We used a retrospective, observational cohort study design using electronic health record data from adults with an Mrgprx2-activating drug exposure recorded within a hospital system clinical Biobank. Odds ratios (ORs) and incidence rate ratios for clinical characteristics associated with ADRs, including immediate hypersensitivity reactions, were calculated using multivariable logistic regression. Among 59,763 patients exposed to Mrgprx2-activating drugs, 4846 had a listed ADR. Female sex, White race, asthma (OR: 1.81, 95% confidence interval [CI]: 1.68-1.94), chronic urticaria (OR: 1.73, 95% CI: 1.46-2.05), and mastocytosis (OR: 12.79, 95% CI: 5.98-27.02) were associated with increased odds of a reaction. Overall, patients with allergic disease had 1.21 times the rate of an ADR compared with patients without allergic disease. Elevated absolute eosinophil count was inversely associated with reactions, and there was no association with elevated total IgE. Observed associations were similar in a patient subgroup with immediate-type hypersensitivity reactions. Specific allergic diseases and common allergic biomarkers are differentially associated with ADRs to Mrgprx2-activating drugs. These findings from a large, "real world" drug-exposed population highlight clinical factors that may contribute to non-IgE-mediated drug allergy.

Ceftriaxone to PRevent pneumOnia and inflammaTion aftEr Cardiac arresT (PROTECT): study protocol for a randomized, placebo-controlled trial

BackgroundPneumonia is the most common infection after out-of-hospital cardiac arrest (OHCA) occurring in up to 65% of patients who remain comatose after return of spontaneous circulation. Preventing infection after OHCA may (1) reduce exposure to broad-spectrum antibiotics, (2) prevent hemodynamic derangements due to local and systemic inflammation, and (3) prevent infection-associated morbidity and mortality.MethodsThe ceftriaxone to PRevent pneumOnia and inflammaTion aftEr Cardiac arrest (PROTECT) trial is a randomized, placebo-controlled, single-center, quadruple-blind (patient, treatment team, research team, outcome assessors), non-commercial, superiority trial to be conducted at Maine Medical Center in Portland, Maine, USA. Ceftriaxone 2 g intravenously every 12 h for 3 days will be compared with matching placebo. The primary efficacy outcome is incidence of early-onset pneumonia occurring < 4 days after mechanical ventilation initiation. Concurrently, T cell-mediated inflammation bacterial resistomes will be examined. Safety outcomes include incidence of type-one immediate-type hypersensitivity reactions, gallbladder injury, and Clostridioides difficile-associated diarrhea. The trial will enroll 120 subjects over approximately 3 to 4 years.DiscussionThe PROTECT trial is novel in its (1) inclusion of OHCA survivors regardless of initial heart rhythm, (2) use of a low-risk antibiotic available in the USA that has not previously been tested after OHCA, (3) inclusion of anti-inflammatory effects of ceftriaxone as a novel mechanism for improved clinical outcomes, and (4) complete metagenomic assessment of bacterial resistomes pre- and post-ceftriaxone prophylaxis. The long-term goal is to develop a definitive phase III trial powered for mortality or functional outcome.Trial registrationClinicalTrials.gov NCT04999592. Registered on August 10, 2021.

Successful Desensitization to mRNA COVID-19 Vaccine in a Case Series of Patients With a History of Anaphylaxis to the First Vaccine Dose.

BackgroundCoronavirus disease 2109 (COVID-19) vaccines have recently been approved to curb the global pandemic. The risk of allergic reactions to the vaccine polyethylene glycol (PEG) component has raised significant public concern. Desensitization is suggested in cases of vaccine related hypersensitivity reactions. After comprehensive literature review on the topic, our aim was to establish a safe and effective desensitization protocol for patients with suspected or confirmed immediate type hypersensitivity reactions to the COVID-19 vaccine.MethodsParticipants were referred to the McGill University Health Center (MUHC) Allergy-Immunology department for clinical evaluation following a reported reaction to their first dose of Moderna® mRNA-1273 or Pfizer-BioNTech® BNT162b2 vaccines. They underwent skin prick testing (SPT) with higher and lower molecular weight (MW) PEG and polysorbate 80, as per published protocols. Their second dose was administered following a desensitization protocol consisting of multiple dose-administration steps followed by a 60-min observation period.ResultsAmong a cohort of 142 patients with an increased risk for allergic reactions to the COVID-19 vaccines, six individuals were selected to undergo desensitization. All were female with allergic background including chronic spontaneous urticaria, anaphylaxis to medications, and/or vaccines. The main symptom after their first dose was difficulty swallowing with lightheadedness or immediate urticaria, angioedema, and/or dizziness. Two patients had positive skin testing. One patient was on chronic antihistamines which resulted in an inconclusive PEG skin test and the skin testing was negative for the three other patients. During the desensitization, two patients reported cutaneous symptoms of an immediate reaction and were managed with antihistamines. One of these patients also complained of ear pressure and had a drop in her systolic blood pressure, treated with intravenous fluids.ConclusionThis study suggests that some individuals with an immediate-type hypersensitivity reaction to their first dose of mRNA COVID-19 vaccine may safely receive their second dose using a desensitization protocol. The success of this desensitization protocol is a step forward in the fight against COVID-19, allowing more individuals to be immunized.

Mast cells in severe respiratory virus infections: insights for treatment and vaccine administration

&lt;abstract&gt; &lt;p&gt;Mast cells (MCs) are a part of the innate immune system and express receptors for microbial and viral pathogens characteristic of this system. The pathological role of MCs has been demonstrated for a number of highly virulent viral infections. The role of MCs and their Fc receptors for IgE in the immediate-type hypersensitivity reactions and in immunocomplex reactions is well-known, although the role of MCs and their Fc receptors for IgG (FcγR) in immunocomplex processes is much less studied. Antibody-dependent enhancement syndrome (ADE) has been observed in a number of viral infections and is associated with greater secondary infection. ADE is enhanced by virus-specific antibodies, which are not involved in the virus penetration into the cell but are capable of forming immune complexes. The role of MCs in ADE is well-established for dengue infection, RSV infection and coronavirus (CoV) infection. The involvement of IgG-mediated mast cell responses in other human viral infections including Coronavirus disease 2019 (COVID-19) is poorly understood. Recently discovered mast cell activation disease is considered one of the causes of severe post-infectious complications in COVID-19. If the role of MCs in the pathogenesis of severe viral infections, including ADE in recurrent viral infection is clarified, these cells and the products they release may serve as promising targets for such therapeutic agents as histamine receptor blockers or membrane stabilizers to prevent possible complications.&lt;/p&gt; &lt;/abstract&gt;

Immediate-Type Systemic Hypersensitivity Reactions After the Inactivated SARS-CoV-2 Vaccine in Healthcare Workers

The vaccines developed for Coronavirus disease 2019 (COVID-19) not only brought hope to the struggle against the pandemic but also raised questions about hypersensitivity reactions that might occur. Although some studies regarding these concerns with mRNA COVID-19 vaccines have been published, these data on inactivated Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) vaccine are not available. The objective of this study was to determine the safety of the inactivated SARS-CoV-2 vaccine manufactured by Sinovac by evaluating the reported systemic immediate hypersensitivity reactions (IHRs) after the administration of the vaccine to healthcare workers (HCWs). This was a retrospective analysis of inactivated SARS-CoV-2 vaccine recipients in all HCWs vaccinated at our center. Relevant data of all patients who received the vaccine were collected from the electronic medical records available at our center’s database. A statistical analysis of subjects who reported acute adverse reactions was conducted. Of the 3354 HCWs vaccinated with the first dose (female 59.9%, pre-existing allergic disorder 2.4%), four acute adverse reactions (0.12%) met the definition of a systemic IHRs were reported, and only one was confirmed to be anaphylaxis. One out of these four cases received her second dose through graded administration. For the second dose, no systemic reaction was reported in our study population. Inactivated SARS-CoV-2 vaccine appears to be well tolerated in HCWs without any pre-existing allergic disorders.

First Confirmed Case of IgE-Mediated Hypersensitivity to Evolucumab with Cross-Reactivity to Alirocumab

Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have become popular for aggressive lowering low-density lipoprotein cholesterol levels. Two Food and Drug Administration–approved PCSK9 inhibitors include evolucumab (Repatha) and alirocumab (Praluent), and adverse effects have reported to be rare.1 We report a case of immediate-type hypersensitivity reaction to evolucumab with cross-reactivity to alirocumab.

Clinical characteristics of eperisone-induced immediate-type hypersensitivity.

Eperisone is a commonly prescribed oral muscle relaxant, but few studies have been conducted of eperisone-induced hypersensitivity reactions. The purpose of this study was to investigate the clinical manifestations of eperisone-induced immediate-type hypersensitivity, and to evaluate the role of an intradermal test (IDT) in eperisone-induced anaphylaxis. This study was based on a retrospective review of medical records from 23 patients diagnosed as eperisone-induced immediate-type hypersensitivity with certain or probable causality. Intradermal tests were performed with a sterile 10 mg/mL eperisone solution. Immediate-type hypersensitivity reactions to eperisone occurred within 15 minutes in 8.7%, within 30 minutes in 52.2%, and within 60 minutes in 82.6% of the patients, cumulatively. All patients showed cutaneous symptoms. Gastrointestinal symptoms were the second-most frequent (65.2%), respiratory symptoms (56.5%) followed, and cardiovascular symptoms were the least (39.1%). Nine (39.1%) patients were categorized as severe anaphylaxis. The mean onset time of severe anaphylaxis was 28.89 minutes, which was significantly shorter than non-severe anaphylaxis (p = 0.011). Five patients among the severe anaphylaxis group were evaluated with IDT, and all showed positive results. In contrast, all of the four patients who have done IDT among the moderate anaphylaxis group showed negative results. There was a significant relationship between severe anaphylaxis and positive IDT results (p = 0.008). Eperisone-induced immediate-type hypersensitivity is not uncommon in Korea, and the IDT could be a useful and safe diagnostic tool, especially in severe anaphylaxis.

A practical 16-day desensitization protocol in lenalidomide-induced non-immediate hypersensitivity reactions

BackgroundDesensitization in immediate-type hypersensitivity reactions (HRs) caused by chemotherapeutics is well described and standardized for many drugs. However, there are no standardized protocols in non-immediate HRs. ObjectiveTo evaluate the effectiveness of a 16-day desensitization protocol in the non-immediate HRs induced by lenalidomide. MethodsAccording to our previously published slow desensitization protocol, we desensitized patients who had experienced non-immediate HRs attributable to lenalidomide. The protocol was started with the 1/100 of the daily-prescribed dose in milligrams of the culprit drug; then the doses were slowly increased to complete the procedure in 16 days. Demographic and clinical features of the patients were further appraised. ResultsTen patients (mean age was 64.7 ± 10.8 years; 7 male) were successfully desensitized to lenalidomide. The mean reaction time was 7.3 ± 3.9 days in the history, and the reaction types were delayed urticaria (n = 4), eczematous rash (n = 3), and maculopapular eruptions (n = 3). The desensitization was successfully completed in 16 days in 9 patients. In 1 patient, maculopapular eruptions developed on the 11th day, and the patient was treated with corticosteroids. We repeated the previous tolerated dose longer and completed with a slower dose increasement, and the targeted dose was achieved in 35 days. ConclusionThe 16-day desensitization protocol seemed to be safe and effective in the non-immediate type drug HRs caused by lenalidomide.

An EAACI position paper on the investigation of perioperative immediate hypersensitivity reactions.

Perioperative immediate hypersensitivity reactions are rare. Subsequent allergy investigation is complicated by multiple simultaneous drug exposures, the use of drugs with potent effects and the many differential diagnoses to hypersensitivity in the perioperative setting. The approach to the investigation of these complex reactions is not standardized, and it is becoming increasingly apparent that collaboration between experts in the field of allergy/immunology/dermatology and anaesthesiology is needed to provide the best possible care for these patients. The EAACI task force behind this position paper has therefore combined the expertise of allergists, immunologists and anaesthesiologists. The aims of this position paper were to provide recommendations for the investigation of immediate-type perioperative hypersensitivity reactions and to provide practical information that can assist clinicians in planning and carrying out investigations.

Immediate hypersensitivity to polyethylene glycols in unrelated products: when standardization in the nomenclature of the components of drugs, cosmetics, and food becomes necessary

BackgroundPolyethylene glycols (PEGs) and their derivatives are non-ionic polymers of ethylene oxide commercially available with numerous synonyms, such as macrogol, oxyethylene polymer, and laureth-9. Although these polymers are usually safe, mild to life-threatening immediate-type hypersensitivity reactions have been reported. Nevertheless, awareness about their allergic potential is minimal due to the non-standardization of their nomenclature.Case presentationWe present the case of a 29-years-old woman who developed several local and systemic type I hypersensitivity reactions including a severe anaphylactic reaction to different pharmacologic and cosmetic products whose excipients included PEG. Prick tests and basophil activation tests were performed to several pharmacological and cosmetic products, but only those containing PEGs and their derivatives were positive. The patient was diagnosed with immediate hypersensitivity IgE-mediated to PEGs and its derivatives.ConclusionsStandardization of the terminology used to describe the presence of PEGs in products would help patients to identify them clearly and unequivocally and thus avoid the development of hypersensitivity reactions. It is also recommended studying PEG allergy in reactions to products containing PEGs, once allergy to the active ingredients has been excluded and in reactions to multiple unrelated drugs.Clinical study protocol number PI2018/29 (registered on 24 September 2018)

Immediate-Type Hypersensitivity Cross-Reactions to Proton Pump Inhibitors: A Descriptive Study of Data from the French National Pharmacovigilance Database

Background: Proton pump inhibitors (PPIs) can trigger immediate-type hypersensitivity reactions (HSRs). Three main patterns of cross-reactivity have been identified: reactions to a single PPI, selective cross-reactions, and cross-reactions with all PPIs. Several hypotheses have been advanced, but no consensus has been reached. Objective: We sought to identify immediate-type hypersensitivity cross-reactions to PPIs using real-world data about hypersensitivity testing from French pharmacovigilance cases. Methods: Potentially relevant immediate-type HSRs reported from January 1985 to February 2015 were extracted from the French pharmacovigilance database using a standardized MedDRA query (SMQ). Cases describing skin tests or oral provocation tests (OPTs) performed with several PPIs that yielded at least one positive result were included. Results: The SMQ extracted 2,119 cases, 38 of which were included in our study. Data collected from skin tests and OPTs indicated cross-reactions with all PPIs (n = 1), reactions to a single PPI (n = 14), or selective cross-reactions (n = 23). Esomeprazole, omeprazole, and pantoprazole concerned 78% of all selective cross-reactions. In more than half of the cases (55.3%), only 2 PPIs were tested. Conclusion: To the best of our knowledge, this PPI cross-reactivity study is the largest to date in terms of population size, describing 38 immediate-type HSRs to PPIs explored by skin tests or OPTs. This paucity of data belies the lack of standardized procedures for PPI hypersensitivity testing. It is likely that PPI HSR workups in everyday clinical practice are often incomplete. Further research to gain insight into selective cross-reactions between PPIs is needed. In the meantime, thorough workups should be completed when a PPI is suspected to have triggered an HSR, instead of routine contraindication to all PPIs.