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.

Local Anesthetic Hypersensitivity Reactions in Pediatric Patients: Recognition and Management.

Local anesthetics (LAs) are commonly used in all medical specialties, particularly in association with surgery, obstetrics, dentistry, and emergency departments. Most individuals, starting from young children, are exposed to LAs during life. LA hardly induces adverse events when used in recommended doses and with proper injection techniques. However, immediate anaphylactic reactions to LA injections may be a rare but life-threatening manifestation. A comprehensive report of the event and performing a specialist examination are crucial to prevent further episodes. The diagnosis should be based on history, medical records, skin and challenge tests.

Differential presentation of hypersensitivity reactions to carboplatin and oxaliplatin: Phenotypes, endotypes, and management with desensitization.

BACKGROUND: Drug hypersensitivity reactions (DHRs) to platinum-based drugs are heterogenous and restrict their access, and drug desensitization (DD) has provided a ground-breaking procedure for their re-introduction, although the response is heterogeneous. We aimed to identify the phenotypes, endotypes, and biomarkers of reactions to carboplatin and oxaliplatin and their response to DD. METHODS: Seventy-nine patients presenting with DHRs to oxaliplatin (N = 46) and carboplatin (N = 33) were evaluated at the Allergy Departments of two tertiary care hospitals in Spain. Patient symptoms, skin testing, biomarkers, and outcomes of 267 DDs were retrospectively analyzed. RESULTS: Oxaliplatin-reactive patients presented with type I (74%), cytokine release reaction (CRR) (11%), and mixed (Mx) (15%) phenotypes. In contrast, carboplatin reactive patients presented with predominantly type I (85%) and Mx (15%) but no CRRs. Out of 267 DDs, breakthrough reactions (BTRs) to oxaliplatin occurred twice as frequently as carboplatin (32% vs. 15%; p < .05). Phenotype switching from type I to another phenotype was observed in 46% of oxaliplatin DDs compared to 21% of carboplatin DDs. Tryptase was elevated in type I and Mx reactions, and IL-6 in CRR and Mx, indicating different mechanisms and endotypes. CONCLUSION: Carboplatin and oxaliplatin induced three different types of reactions with defined phenotypes and endotypes amendable to DD. Although most of the initial reactions for both were type I, oxaliplatin presented with unique CRR reactions. During DD, carboplatin reactive patients presented mostly type I BTR, while oxaliplatin-reactive patients frequently switched from type I to CRR, providing a critical difference and the need for personalized DD protocols.

Hypersensitivity reactions to proton pump inhibitors. An EAACI position paper.

Proton pump inhibitors (PPIs) are invaluable therapeutic options in a variety of dyspeptic diseases. In addition to their well-known risk profile, PPI consumption is related to food and environmental allergies, dysbiosis, osteoporosis, as well as immediate and delayed hypersensitivity reactions (HSRs). The latter, although a rare event, around 1%-3%, due to the extraordinarily high rate of prescription and consumption of PPIs are related to a substantial risk. In this Position Paper, we provide clinicians with practical evidence-based recommendations for the diagnosis and management of HSRs to PPIs. Furthermore, the unmet needs proposed in the document aim to stimulate more in-depth investigations in the topic.

A novel 2-step process for the management of inpatient beta-lactam allergy labels.

BACKGROUND: Inpatient beta-lactam allergy labels may increase the unnecessary use of aztreonam and non-beta-lactam antibiotics, which can then lead to more adverse events and increased health care costs, OBJECTIVE: To assess the impact of a novel 2-step process (medication history review followed by risk stratification) on rates of beta-lactam delabeling, aztreonam use, and desensitizations on pediatric, adult, and obstetrics inpatients at a tertiary academic center. METHODS: We prospectively collected data on 700 patients who received inpatient consultation from the Beta-Lactam Allergy Evaluation Service between August 2021 and July 2022. Patients were delabeled either by medication review alone, drug challenge alone if with a low-risk history, or penicillin skin test followed by drug challenge if with a high-risk history. Generalized linear regression modeling was used to compare aztreonam days of therapy in the intervention year with the 2 prior years. Drug desensitizations were assessed by electronic chart review. RESULTS: Most of the patients (n = 656 of 700, 94%) had more than or equal to 1 beta-lactam allergy label removed, clarified, or both; 77.9% of these patients (n = 511 of 656) had 587 beta-lactam allergy labels removed. Nearly one-third (n = 149, 27.6%) had 162 allergy labels removed solely by medication history review. All 114 penicillin skin tests performed had negative results, and 98% (8 of 381) of the patients who underwent any drug challenge passed. Only 5.7% of the delabeled patients were relabeled. There was a 27% reduction in aztreonam use (P = .007). Beta-lactam desensitizations were reduced by 80%. CONCLUSION: A full-time inpatient beta-lactam allergy service using medication history review and risk stratification can safely and effectively remove inpatient beta-lactam allergy labels, reduce aztreonam use, and decrease beta-lactam desensitizations.

Overview and Current Advances in Dapsone Hypersensitivity Syndrome.

PURPOSE OF REVIEW: As a sulfone antibacterial agent, dapsone has been widely used to treat leprosy. Moreover, dapsone is also used in many immune diseases such as herpetic dermatitis because of its anti-inflammatory and immunomodulatory effects. However, dapsone can cause several adverse effects, the most serious being dapsone hypersensitivity syndrome. Dapsone hypersensitivity syndrome is characterized by a triad of eruptions, fever, and organ involvement, which limits the application of dapsone to some extent. RECENT FINDINGS: In this article, we review current research about the interaction model between HLA-B*13:01, dapsone, and specific TCR in dapsone-induced drug hypersensitivity. In addition to the proposed mechanisms, we also discussed clinical features, treatment progress, prevalence, and prevention of dapsone hypersensitivity syndrome. These studies reveal the pathogenesis, clinical features, and prevalence from the perspectives of genetic susceptibility and innate and adaptive immunity in dapsone hypersensitivity syndrome, thereby guiding clinicians on how to diagnose, prevent, and treat dapsone hypersensitivity syndrome.

Implementation of a multidisciplinary inpatient drug desensitization program.

PURPOSE: The purpose of this project was to analyze the process of adult inpatient drug desensitization and to create a multidisciplinary standardized procedure with the aim of improving patient safety, efficiency, length of stay, and patient satisfaction. SUMMARY: A team consisting of physicians, pharmacists, nurses, critical care specialists, and operational capacity managers was created. The electronic health system was queried to evaluate the frequency of desensitizations, level of care, implicated medications, and length of stay. An electronic desensitization request form was created along with a desensitization team and email listserver for notification of key stakeholders. CONCLUSION: A standardized, safe, and efficient process for inpatient drug desensitization requires advance planning and participation from all disciplines involved. Operational and logistical aspects of desensitization are crucial components of rapid drug desensitization. A structured, multidisciplinary approach to inpatient desensitization is feasible.

Drug Hypersensitivity Reactions.

Drug hypersensitivity reactions are a diverse group of reactions mediated by the immune system after exposure to a drug. The Gell and Coombs classification divides immunologic DHRs into 4 major pathophysiologic categories based on immunologic mechanism. Anaphylaxis is a Type I hypersensitivity reaction that requires immediate recognition and treatment. Severe cutaneous adverse reactions (SCARs) are a group of dermatologic diseases that result from a Type IV hypersensitivity process and include drug reaction with eosinophilia and systemic symptom (DRESS) syndrome, Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), and acute generalized exanthematous pustulosis (AGEP). Other types of reactions are slow to develop and do not always require rapid treatment. Emergency physicians should have a good understanding of these various types of drug hypersensitivity reactions and how to approach the patient regarding evaluation and treatment.

Hypersensitivity Reaction and Rapid Drug Desensitization with Chemotherapeutics: A Tertiary Reference Center Experiences.

INTRODUCTION: Chemotherapy drugs have been in our lives for a long time, and all agents have the potential to develop hypersensitivity. Rapid drug desensitization is an option when hypersensitivity develops. The aim of this study was to examine the characteristics, diagnostic processes, and treatment results of patients with chemotherapeutic agent hypersensitivity who applied to our tertiary reference center. METHODS: Patients who applied to our tertiary allergy outpatient clinic between January 2016 and September 2022 due to chemotherapy-induced drug hypersensitivity were examined. Demographic data of the patients, cancer diagnoses, chemotherapy regimens, skin tests, premedication scheme, desensitization cycle were evaluated. We applied a 16-step desensitization in patients with index reaction anaphylaxis or positive skin tests. If the index reaction was not anaphylaxis or skin tests were negative, we applied a 12-step desensitization. If the prick test with chemotherapeutic drugs was negative especially with taxanes, premedication was administered. We used the montelukast, cetirizine, and methylprednisolone for premedication. RESULTS: Fifty-one patients were evaluated; 35 (68.6%) were female. The most common malignancy was colorectal cancer in 17 (33.3%) patients. The most common agent responsible for hypersensitivity was oxaliplatin in 17 (33.3%) patients, followed by paclitaxel in 13 (25.4%). When the symptoms of immediate reaction to chemotherapeutic drugs were analyzed as described in the EAACI position paper, only skin and mucosal involvement was seen in 24 (46.8%) patients; only respiratory system involvement or back pain was seen in 3 (6.2%) patients; multisystem involvement meeting the criteria for anaphylaxis was seen in 24 (47%) patients. Skin test was positive in 17 (56.6%) of 30 patients who developed a reaction with platin. Prolonged anaphylaxis was developed in 1 patient, and desensitization was not performed again. Fifty of 51 patients were able to receive the target chemotherapy dose by desensitization. In total, a 172-step desensitization was applied to 51 patients. CONCLUSION: If completing the cycle is considered a treatment success, this was achieved in 98% (50/51) patients with rapid drug desensitization. This gives us the opportunity to use first-line chemotherapy agents.

Ocular involvement in allergic drug reactions.

PURPOSE OF REVIEW: Many systemic medications have been observed to cause ocular toxicity. A subset of these reactions is thought to involve immunomodulation or a hypersensitivity reaction. As new medications are developed, ocular adverse effects are becoming increasingly prevalent. Herein we review immune-mediated drug reactions affecting they eye with special attention to the hypersensitivity mechanisms leading to ocular toxicity. RECENT FINDINGS: Recent work has focused on mechanisms and risk of immune-mediated ocular adverse drug reactions including genetic susceptibility and loss of ocular immune privilege. SUMMARY: Given the consequences of immune-mediated ocular adverse drug reactions, clinicians must be aware of these to facilitate early recognition and management. The prompt involvement of an ophthalmologist for diagnosis and management is often essential to preserve vision and avoid long-term morbidity.

Drug allergy in primary care: systematic review to support quality improvement initiative of management and optimization of healthcare pathways.

PURPOSE OF REVIEW: The aim of this study was to review the practice of general practitioners (GPs) in regard to the diagnosis and management of drug hypersensitivity reactions (DHRs) to identify major challenges and to facilitate the development of decision support tools to GPs confronted with DHRs patients. RECENT FINDINGS: DHRs are still a challenge in the GPs clinical practice, which implies difficulties in clinical decisions and referral to allergy specialists. SUMMARY: DHRs can range from mild to severe and even life-threatening. Drugs are the main cause of anaphylaxis deaths in most countries. Most DHRs are firstly seen by GPs, paediatricians or emergency doctors. However, our systematic review demonstrated difficulties in differentiating DHRs from other drug side effects. Most DHRs epidemiological data are from hospital and emergency departments, which may not reflect the real-life experience in primary care. GPs should be aware of the alert signs of DHRs: the involvement of other systems beyond the skin and/or atypical skin/ mucosal involvement, which mandated immediate referral to an emergency department. Data still stress difficulties in the recognition of DHRs clinical manifestations and highlight the need for decision aids to support their management by GPs. Structured clinical history and clinical examination are key diagnostic tools. Reasons for referring to allergy specialists based on the literature are to investigate cause, to undergo specific procedure, such as desensitization and to identify well tolerated, alternative drugs.

The Burden of Self-Reported Antibiotic Allergies in Health Care and How to Address It: A Systematic Review of the Evidence.

BACKGROUND: Antibiotics are the first-line treatment for bacterial infections; however, overuse and inappropriate prescribing have made antibiotics less effective with increased antimicrobial resistance. Unconfirmed reported antibiotic allergy labels create a significant barrier to optimal antimicrobial stewardship in health care, with clinical and economic implications. OBJECTIVE: A systematic review was conducted to summarize the impact of patient-reported antibiotic allergy on clinical outcomes and various strategies that have been employed to effectively assess and remove these allergy labels, improving patient care. METHODS: The review was undertaken using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A critical appraisal was conducted on all studies and a narrative synthesis was performed to identify themes. RESULTS: Four themes emerged: the prevalence of antibiotic allergy, impact of antibiotic allergy on antimicrobial prescribing, impact of antibiotic allergy on clinical outcomes, and delabeling strategies to improve clinical outcomes. Of the 32 studies, including 1,089,675 participants, the prevalence of reported antibiotic allergy was between 5% and 35%. Patients with a reported antibiotic allergy had poorer concordance with prescribing guidelines in 30% to 60% of cases, with a higher use of alternatives such as quinolone, tetracycline, macrolide, lincosamide, and carbapenem and lower use of beta-lactam antibiotics. Antibiotic allergy delabeling was identified as an intervention and recommendation to advance the state of the science. CONCLUSIONS: There is substantial evidence within the literature that antibiotic allergy labels significantly impact patient clinical outcomes and a consensus that systematic assessment of reported antibiotic allergies, commonly referred to as delabeling, improves the clinical management of patients.

Desensitization in children allergic to drugs: Indications, protocols, and limits.

Any drug can potentially induce a hypersensitivity reaction. If after the allergological work-up the drug hypersensitivity reaction is confirmed, in most cases, the simple avoidance of the culprit drug and a suggestion of an unrelated alternative is enough. However, there are circumstances where the choice to stop the treatment affects the survival, the safety and/or the quality of life of the patient and the global outcome of the disease in question. When this occurs, drug desensitization can be the answer and should not be viewed as an extravagance, nor the pediatric age should be considered a contraindication. Drug desensitization in children can be safely and successfully performed, having a positive impact on the survival and overall prognosis. In general, the indications for DDS are the same in adults as in children. However, in this age group there are specificities that this paper aimed to describe, reviewing the mechanisms behind drug hypersensitivity and rapid drug desensitization, types of protocols, indications, and contraindications, as well as several technical aspects that are specific to the pediatric age.

Hypersensitivity reaction during enzyme replacement therapy in lysosomal storage disorders. A systematic review of desensitization strategies.

Lysosomal storage diseases (LSDs) are rare genetic metabolic disorders that cause the accumulation of glycosaminoglycans in lysosomes due to enzyme deficiency or reduced function. Enzyme replacement therapy (ERT) represents the gold standard treatment, but hypersensitivity reaction can occur resulting in treatment discontinuation. Thus, desensitization procedures for different culprit recombinant enzymes can be performed to restore ERT. We searched desensitization procedures performed in LSDs and focused on skin test results, protocols and premedication performed, and breakthrough reactions occurred during infusions. Fifty-two patients have been subjected to desensitization procedures successfully. Skin tests, with the culprit recombinant enzyme, deemed positive in 29 cases, doubtful in two cases, and not performed in four patients. Moreover, 29 of the 52 desensitization protocols used at the first infusion were breakthrough reaction free. Different desensitization strategies have proved safe and effective in restoring ERT in patients with previous hypersensitivity reactions. Most of these events seem to be Type I hypersensitivity reactions (IgE-mediated). Standardized in vivo and in vitro testing is necessary to better estimate the risk of the procedure and find the safest individualized desensitization protocol.