Alpha-gal syndrome: when treatment of hypovolemic shock can lead to anaphylaxis.

Delayed anaphylaxis after ingestion of red meat because of galactose-alpha-1,3-galactose (alpha-gal) syndrome has increased in recent years. The mechanism involves an immunoglobulin E reaction to alpha-gal, a molecule found in mammalian meat, dairy products, medications and excipients containing mammalian-derived components, and tick salivary glycans. Sensitization occurs due to the bite of a lone star tick and the transmission of alpha-gal molecules into person's bloodstream. We describe a case of alpha-gal syndrome with severe food, drug, and perioperative allergy in which anaphylaxis with hypovolemic shock occurred immediately after an emergency surgical procedure, when a gelatin-containing drug was injected. This case study confirms that the clinical manifestations of alpha-gal syndrome could be different depending on the route of administration, with immediate reactions if an alpha-gal-containing drug is injected and delayed type allergic manifestations occurring several hours after oral intake. The purpose of this report is to highlight the importance of risk communication in case of exposure to medical products and surgical procedures of patients with alpha-gal syndrome and to encourage drug manufacturers to indicate clearly the origin of excipients in product literature.

How to Define and Manage Low-Risk Drug Allergy Labels.

Risk stratification in drug allergy implies that specific risk categories (eg, low, moderate, and high) classify historical drug hypersensitivity reactions. These risk categories can be based on reaction phenotypic characteristics, the timing of the reaction and evaluation, the required reaction management, and individual characteristics. Although a multitude of frameworks have been described in the literature, particularly for penicillin allergy labels, there has yet to be a global consensus, and approaches continue to vary between allergy centers. Immune-mediated drug allergies can sometimes be confirmed using skin testing, but a negative drug challenge is required to demonstrate tolerance and remove the allergy from the electronic health record ("delabel" the allergy). Even for quintessential IgE-mediated drug allergy, penicillin allergy, recent data reveal that a direct oral challenge, without prior skin testing, is an appropriate diagnostic strategy in those who are considered low-risk. Drug allergy pathogenesis and clinical manifestations may vary depending on the culprit drug, and as such, the optimal approach should be based on risk stratification that considers individual patient and reaction characteristics, the likely hypersensitivity reaction phenotype, the drug class, and the patient's clinical needs. This article will describe low-risk drug allergy labels, focusing on ß-lactam and sulfonamide antibiotics, nonsteroidal anti-inflammatory drugs, iodinated contrast media, and common chemotherapeutics. This review will also address practical management approaches using currently available risk stratification and clinical decision tools.

Removing penicillin allergy label in a hospitalized adolescent with a remote penicillin and recent cephalosporin allergy.

Background: ß-Lactam antibiotics are widely used with increased utilization in hospitalized patients. Of this population, as high as 10-20% report an allergy to ß-lactam antibiotics but <5% are at risk of developing clinically significant immunoglobulin E- or T-lymphocyte-mediated reactions. Most of the time, these reported allergies are present during an illness with no previous inquiry of their validity, which makes investigation and possible removal of this allergy label a challenge. Methods: We report a 16-year-old boy who presented with 1 week of night sweats, chills, headaches, and fatigue, followed by 1 day of fever and right knee swelling and who was diagnosed with septic bursitis. Due to concern of a penicillin allergy label, the patient was started on a cefepime infusion. Five minutes into the infusion, the patient reported puffy eyes and itchy throat, followed by a witnessed cascading flat nonpruritic erythematous rash from head to shoulders. This rash went away in 3 minutes after stopping the infusion and the patient being given 50 mg of intravenous diphenhydramine and 10 mg of oral dexamethasone. He was subsequently diagnosed with a cefepime allergy. Results: Allergy/immunology was the speciality consulted, and, by using a screening questionnaire, the patient's reported penicillin allergy was determined to be low risk. Subsequent 1-step oral challenge was the key to providing the patient with the necessary antibiotic course to resolve his infection. Conclusion: Multiple reported antibiotic allergies lead to poor antibiotic stewardship that causes impactful health and financial burden on the patient and health-care system. It is thus important to have an evidence-based systematic approach to de-label penicillin antibiotic allergy labels to reduce these potential harms.

Perioperative anaphylactic shock caused by propofol.

Perioperative anaphylaxis is rare and the diagnosis is difficult to distinguish from normal side effects from anaesthesia. Anaesthetists should be able to diagnose anaphylaxis and treat promptly with adrenaline and fluids. Allergy investigation should be performed subsequently. This is a case report of perioperative anaphylaxis to propofol. Propofol contains refined soya oil and egg lecithin, but no connection between allergy to soy, egg or peanut and allergy to propofol has been proven, and international guidelines recommend that propofol can be used in patients with these food allergies.

Successful rapid liposomal amphotericin B desensitization in pediatric case series.

Background: Liposomal amphotericin B (LAMB) is a crucial agent in the treatment of invasive fungal diseases caused by a wide variety of yeasts and molds. In the presence of an infection caused by a fungal agent resistant to alternative antifungal drugs, desensitization may be the only option to continue treatment. However, there is insufficient information and consensus with regard to amphotericin B desensitization protocols in the pediatric age group. Objective: We present our experience with five cases of patients in whom successful desensitization protocols were applied with LAMB, along with a review of the literature on pediatric cases. We also provide a sample desensitization protocol that we successfully applied. Methods: Pediatric patients who continued their treatment with the successful rapid desensitization protocol conducted at the Paediatric Allergy and Immunology Clinic of the Ministry of Health Ankara City Hospital between September 2019 and September 2023 were examined. Desensitization protocols were applied based on Castells' desensitization protocol. Results: Five patients ages between 5 and 12 years were referred to us due to the development of anaphylaxis during their treatment with LAMB. Anaphylaxis is diagnosed clinically, according to the European Academy of Allergy and Clinical Immunology guidelines: anaphylaxis (2021 update). A 16-step desensitization protocol was prepared by using LAMB solutions at four different dilutions (0.001, 0.01, 0.1, and 1 mg/mL). Each solution consisted of four steps, with a 15-minute infusion for each step. The patients were premedicated with 1 mg/kg/dose methylprednisolone and an antihistamine. Conclusion: The data we present on the successful application of a sample protocol to five cases, particularly in a pediatric setting, are noteworthy valuable contributions to the field, which demonstrates the feasibility and success of rapid desensitization with LAMB in pediatric patients. This can provide important insights and potentially serve as a reference for medical professionals working with similar cases in the future.

Safety of Direct Drug Provocation for the Evaluation of Penicillin Allergy in Low-Risk Adults.

BACKGROUND: About 10% of patients have a penicillin allergy label, but less than 5% of them are actually allergic. Unnecessary penicillin avoidance is associated with serious medical consequences. Given the growing number of these labels, it is imperative that our diagnostic strategy for penicillin allergy be as efficient as possible. The validity of traditionally used skin tests (STs) has been questioned, whereas drug provocation testing (DPT), the criterion standard, without previous ST appears very safe in most cases. OBJECTIVE: To evaluate the safety of direct DPT without consideration for ST results and the validity of ST in the diagnosis of penicillin allergy. METHODS: In this prospective cohort study without a control group, we recruited patients consulting an allergist for penicillin allergy. Patients underwent ST followed by DPT regardless of ST results. Patients with anaphylaxis to penicillin within the past 5 years or a severe delayed reaction were excluded, as were those with significant cardiorespiratory comorbidity. RESULTS: None of the 1002 recruited patients had a serious reaction to DPT. Ten (1.0%) had a mild immediate reaction, of whom only 1 (0.1%) was considered likely IgE-mediated. The positive and negative predictive values of ST for an immediate reaction were 3.6% and 99.1%, respectively. CONCLUSIONS: In a low-risk adult population reporting penicillin allergy, ST has very poor positive predictive value. Direct DPT without ST is safe and appears to be an ideal diagnostic strategy to remove penicillin allergy labels that could be implemented in first-line practice.

Perioperative anaphylaxis and the principle of primum non nocere.

Perioperative anaphylaxis is a rare and unpredictable event that continues to cause patient harm. More work is needed to decrease the risk to patients through measures to limit sensitisation, optimise management and investigation, and ensure that patients are not inadvertently re-exposed to allergens. Robust epidemiological data such as that provided by the consecutive GERAP surveys over the past 30 yr have been invaluable in defining the problem, identifying emerging allergens, acting as a catalyst for change, and stimulating research.

A rare case of phenobarbital-induced leukocytoclastic vasculitis.

Drug hypersensitivity reactions (DHRs) manifested as vasculitis are rare. Antibiotics, non-steroidal anti-inflammatory drugs (NSAIDs), sulphonamides, diuretics, immunosupressants and anticonvulsants are the most common culprits for drug-induced leukocytoclastic vasculitis (LCV) but there is scarce information about barbiturates. We present a case of 53-year-old female with severe vasculitis after phenobarbital- and NSAIDs-containing medications use. The preliminary diagnosis of drug-induced vasculitis was made based on anamnestic and clinical data. Further examinations confirmed the diagnosis of LCV and excluded other more common causes of vasculitis. The causative significance of used medications was assessed by long-term observation of the patient after the reaction, including the drug challenge series and Naranjo's Adverse Drug Reaction Probability Scale. It was concluded that phenobarbital is the most probable culprit drug. The patient's data were included in the Armenian Registry of Patients with Severe DHRs. Since then, the patient has avoided only barbiturate-containing drugs and no reactions were noted. Thus, the case indicates that even with limited diagnostic capabilities, the final diagnosis of rare drug-induced LCV and even rarer culprit drug can be established by comparing the available data. Awareness about phenobarbital and proper recording of the case are important in the management and prevention of DHRs manifested as vasculitis.

Specific IgE and Basophil Activation Test by Microarray: A Promising Tool for Diagnosis of Platinum Compound Hypersensitivity Reactions.

Drug hypersensitivity reactions (DHRs) to platinum-based compounds (PCs) are on the rise, and their personalized and safe management is essential to enable first-line treatment for these cancer patients. This study aimed to evaluate the usefulness of the basophil activation test by flow cytometry (BAT-FC) and the newly developed sIgE-microarray and BAT-microarray in diagnosing IgE-mediated hypersensitivity reactions to PCs. A total of 24 patients with DHRs to PCs (20 oxaliplatin and four carboplatin) were evaluated: thirteen patients were diagnosed as allergic with positive skin tests (STs) or drug provocation tests (DPTs), six patients were diagnosed as non-allergic with negative STs and DPTs, and five patients were classified as suspected allergic because DPTs could not be performed. In addition, four carboplatin-tolerant patients were included as controls. The BAT-FC was positive in 2 of 13 allergic patients, with a sensitivity of 15.4% and specificity of 100%. However, the sIgE- and BAT-microarray were positive in 11 of 13 DHR patients, giving a sensitivity of over 84.6% and a specificity of 90%. Except for one patient, all samples from the non-allergic and control groups were negative for sIgE- and BAT-microarray. Our experience indicated that the sIgE- and BAT-microarray could be helpful in the endophenotyping of IgE-mediated hypersensitivity reactions to PCs and may provide an advance in decision making for drug provocation testing.

Asparaginase-specific basophil recognition and activation predict Asparaginase hypersensitivity in mice.

Background: Asparaginase (ASNase) is a crucial part of acute leukemia treatment, but immune responses to the agent can reduce its effectiveness and increase the risk of relapse. Currently, no reliable and validated biomarker predicts ASNase-induced hypersensitivity reactions during therapy. We aimed to identify predictive biomarkers and determine immune cells responsible for anaphylaxis using a murine model of ASNase hypersensitivity. Methods: Our preclinical study uses a murine model to investigate predictive biomarkers of ASNase anaphylaxis, including anti-ASNase antibody responses, immune complex (IC) levels, ASNase-specific binding to leukocytes or basophils, and basophil activation. Results: Our results indicate that mice immunized to ASNase exhibited dynamic IgM, IgG, and IgE antibody responses. The severity of ASNase-induced anaphylaxis was found to be correlated with levels of IgG and IgE, but not IgM. Basophils from immunized mice were able to recognize and activate in response to ASNase ex vivo, and the extent of recognition and activation also correlated with the severity of anaphylaxis observed. Using a multivariable model that included all biomarkers significantly associated with anaphylaxis, independent predictors of ASNase-induced hypersensitivity reactions were found to be ASNase IC levels and ASNase-specific binding to leukocytes or basophils. Consistent with our multivariable analysis, we found that basophil depletion significantly protected mice from ASNase-induced hypersensitivity reactions, supporting that basophils are essential and can be used as a predictive marker of ASNase-induced anaphylaxis. Conclusions: Our study demonstrates the need for using tools that can detect both IC- and IgE-mediated hypersensitivity reactions to mitigate the risk of ASNase-induced hypersensitivity reactions during treatment.

Hypersensitive Reactions During Hemodialysis Treatment: What Do We Need to Know?

Kidney replacement therapies (KRTs) including hemodialysis (HD) are one of the treatment options for most of the patients with end-stage kidney disease. Although HD is vital for these patients, it is not hundred percent physiological, and various adverse events including hypersensitivity reactions may occur. Fortunately, these reactions are rare in total and less when compared to previous decades, but it is still very important for at least two reasons: First, the number of patients receiving kidney replacement treatment is increasing globally; and the cumulative number of these reactions may be substantial. Second, although most of these reactions are mild, some of them may be very severe and even lead to mortality. Thus, it is very important to have basic knowledge and skills to diagnose and treat these reactions. Hypersensitivity reactions can occur at any component of dialysis machinery (access, extracorporeal circuit, medications, etc.). The most important preventive measure is to avoid the allergen. However, even with very specific test, sometimes the allergen cannot be found. In mild conditions, HD can be contained with non-specific treatment (topical creams, antihistaminics, corticosteroids). In more severe conditions, treatment must be stopped immediately, blood should not be returned to patient, drugs must be stopped, and rules of general emergency treatment must be followed.

A nurse-driven penicillin allergy risk score in the preoperative setting was associated with increased cefazolin use perioperatively.

STUDY OBJECTIVE: To characterize and assess the effects of a preoperative, nurse-driven penicillin allergy risk stratification tool on rates of perioperative cefazolin and second-line antibiotic use. DESIGN: Quasi-experimental quality improvement study of penicillin-allergic surgical patients undergoing procedures for which cefazolin is indicated. SETTING: Outpatient Perioperative Care Clinic (PCC) for preoperative surgical patients at a tertiary care center. PATIENTS: 670 and 1371 adult penicillin-allergic PCC attendants and non-attendants, respectively. INTERVENTION: A paper penicillin allergy risk stratification questionnaire was administered during the PCC visit. Nurses were educated on its use. MEASUREMENTS: Antibiotic (cefazolin, clindamycin, vancomycin) use rates in the 24 months before and 17 months after intervention implementation in November 2020 (November 2018 - April 2022) were assessed in penicillin-allergic PCC attendants with statistical process control charts. Multivariable logistic regression assessed antibiotic use rates pre- and post-intervention adjusting for age, sex, surgical specialty and penicillin allergy history severity. Similar analyses were done in penicillin-allergic PCC non-attendants. MAIN RESULTS: Of 670 penicillin-allergic PCC attendants, 451 (median [IQR] age, 66 (Sousa-Pinto et al., 2021 [14])) were analyzed pre-intervention and 219 (median [IQR] age, 66 (Mine et al., 1970 [13])) post-intervention. One month after implementation, process measures demonstrated an upward shift in cefazolin use for PCC attendants versus no shift or other special cause variation for PCC non-attendants. There were increased odds of cefazolin use (aOR 1.67, 95% CI [1.09-2.57], P = 0.019), decreased odds of clindamycin use (aOR 0.61, 95% CI [0.42-0.89], P = 0.010) and decreased odds of vancomycin use (aOR 0.56, 95% CI [0.35-0.88], P = 0.013) in PCC attendants post-intervention. This effect did not occur in PCC non-attendants. There was no increase in perioperative anaphylaxis post-intervention. CONCLUSIONS: A simple penicillin allergy risk stratification tool implemented in the preoperative setting was associated with increased use of cefazolin and decreased rates of second-line agents post implementation.