Diagnosis Of Drug Hypersensitivity Reactions Research Articles

Clinical Features of Drug Allergy and Factors Affecting Drug-Related Anaphylaxis: Single-center Experience of the Tertiary University Hospital

Background-Aims: Drug hypersensitivity is defined as any unfavorable reaction that occurs after the administration of any drug. We aim to determine the frequency, etiology, and clinical features of drug hypersensitivity reactions (DHRs), and to evaluate the factors affecting drug-related anaphylaxis among the patients admitted to the outpatient allergy clinic of the tertiary university hospital.
 Materials-methods: In this cross-sectional study, medical records of the 8295 patients who visited the allergy outpatient clinic of Sivas Cumhuriyet University Hospital from 2nd July 2018 to 10th December 2019 were retrospectively reviewed by the hospital data system using the ICD-code Y57.4. The frequency, etiologies, demographic and clinical features of the DHRs were evaluated.
 Results: Among the 8295 patients who visited the allergy outpatient clinic of Sivas Cumhuriyet University Hospital, 159 patients with a mean age of 40,52± 14,85 years (129 female, 30 male) were evaluated with the diagnosis of DHRs. The frequency of DHRs among admissions was found to be approximately 2%. Accompanying allergic diseases included respiratory (17%), cutaneous (10%), venom (n=3), drug (7%), and food hypersensitivity (n=2). Multiple allergic diseases were detected in 20%. Eighty-six % (n=138) could recognize the culprit drug. The causes of drug allergy were non-steroidal anti-inflammatory drugs (NSAIDs) (27%), beta-lactams (16%), co-sensitization to beta-lactams and NSAIDs (8%), antimicrobials except beta-lactams (8%), and other kinds of drugs (39%). Type 1 reaction occurred in 80%, type 4 in 21%, non-immune mediated in 7, and mixed type composed of type 1 and 4 in 9 patients. Anaphylaxis occurred in 46,5%. Fifteen% had grade 2, 22% had grade 3, and 4 had grade 4 anaphylactic reactions. According to systematical assessment, cutaneous symptoms were observed in 93%, respiratory in 38%, cardiovascular in 29,5%, neurologic in 25%, and gastrointestinal in 11%. Allergy to NSAIDs (88,6 %) and beta-lactams (82,5%) were more frequent in type 1 reactions than in type 4 and mixed type reactions (p

Development of anaphylaxis upon oral food challenge and drug provocation tests in pediatric patients.

Background: The drug provocation test (DPT) and the oral food challenge (OFC) are considered as the criterion standard for the diagnosis of drug hypersensitivity reactions and food allergy. Severe allergic reactions may develop during these tests. Objective: To evaluate the frequency and features of anaphylaxis in pediatric patients undergoing OFCs and DPTs. Method: OFCs and DPTs performed in an open method in the pediatric allergy clinic of our institution between January 2014 and January 2021 were reviewed retrospectively. The characteristics of anaphylaxis that developed during these tests were evaluated. Results: A total of 3631 OFCs and/or DPTs were performed on 2588 pediatric patients. Reactions were recorded in 317 challenges (8.7%), including 42 (1.2%) in the form of anaphylaxis. Of the patients with anaphylaxis, 31 developed anaphylaxis during OFC and 11 during DPT. Anaphylaxis during OFCs was mostly triggered by yogurt (n = 8), hen's egg (n = 6), baked milk (n = 5), and baked egg (n = 4). Cases with anaphylaxis during DPT were recorded mostly with ibuprofen (54.5% [n = 6]). All patients who developed anaphylaxis during OFC had cutaneous manifestations, and 90.3% had respiratory symptoms. Gastrointestinal involvement was present in 32.3% of the patients. During DPT, cutaneous manifestations were observed in 90.9% in the patients who developed anaphylaxis and the respiratory tract was involved in 81.8%. In terms of concomitant allergic diseases, 51.6% of the patients who developed anaphylaxis during OFC had atopic dermatitis and 38.7% had asthma. All the patients with anaphylaxis triggered by nonsteroidal anti-inflammatory drug DPT had asthma. Of the anaphylaxis, 54.8% were mild, 35.7% were moderate, and 9.5% were severe. Severe anaphylaxis was recorded with baked milk (n = 2), baked egg and trimethoprim-sulfamethoxazole (n = 1, each). The patients did not require intensive care, and no death occurred. Conclusion: Anaphylaxis may develop during OFCs and DPTs. These tests should be carried out by experienced allergists in an appropriate setting where emergency equipment and medications, including epinephrine, are readily available.

Guideline for allergological diagnosis of drug hypersensitivity reactions

Guideline for allergological diagnosis of drug hypersensitivity reactions

Psychological Distress and Drug Provocation Test-Related Anxiety Levels of Pediatric Patients and Their Parents.

Background: Drug provocation tests (DPTs) are the gold standard for the diagnosis of drug hypersensitivity reaction (DHR). To the best of our knowledge, there is no previous study reporting DPT-related anxiety levels in children and their parents. This study aimed to determine the difference in pre- and post-DPT anxiety levels of parents and children who were informed of the possibility of another DHR during the DPT, and to evaluate the relationship between parental psychological distress and anxiety levels. Methods: The study included children who underwent DPT in our clinic between July 1, 2019, and February 29, 2020, and accompanying parents who consented to participate. Age-appropriate State-Trait Anxiety Inventory scales were used to assess levels of state and trait anxiety in the patients and parents. The Symptom Checklist-90-Revised (SCL-90-R) was used to screen for psychological symptoms in parents. Results: Data were collected from the parents of 69 children who underwent DPTs. The patients' median age was 7.28 (interquartile range: 4.52-10.06) and their parents' mean age was 35.28 ± 5.38 years. Anxiety-related data were collected from 21 pediatric patients. The children and parents had higher state anxiety scores before DPT compared to after DPT. There was a positive correlation between the parents' trait anxiety and pre-DPT state anxiety scores. In addition, parental pre-DPT state anxiety scores were positively correlated with SCL-90-R general severity index, somatization, anxiety, obsessive-compulsive, and depression subscale scores. Conclusion: The risk of allergic reaction in DPT may cause anxiety. A high level of parental anxiety before DPT, which gradually decreased after negative test results, was associated with history of drug-induced anaphylaxis in their children and high trait anxiety. Appropriate evaluation of patients and parents before DPT and providing detailed information may be important to reduce this anxiety.

Detection of drug-specific immunoglobulin E (IgE) and acute mediator release for the diagnosis of immediate drug hypersensitivity reactions

The diagnosis of a drug hypersensitivity reaction (DHR) is complex. The first step after taking the clinical history is to look for a sensitization to confirm or exclude the diagnosis and to identify the culprit drug. Skin tests are the primary means of detecting sensitization in DHR, but are associated with a risk for a severe reaction and may be contraindicated. In vitro tests offer the potential to support or confirm a diagnosis of DHR and influence medical decision making. For immediate-type DHR, a few validated assays for measurement of specific IgE (sIgE) are commercially available to a limited number of drugs. In addition, several home-made sIgE radioimmunoassays have been used in other studies. The sensitivity of the sIgE assay is drug-dependant and generally low (0–85%) for betalactams and reported heterogeneous for other drugs ranging from 26% for chlorhexidine and 44% for suxamethonium to 92% for chlorhexidine. However, as all these studies included patients, in whom DHR was confirmed only by skin tests and not by provocation, the results have to be interpreted carefully and may be unreliable. Determination of mediators during an acute phase of a reaction may indirectly support the diagnosis of a DHR by demonstrating mast cell and basophil mediator release. Negative in vitro tests do not exclude a DHR or imputability of a drug, but a positive result may support causality and eliminate the necessity for a drug provocation test. Unfortunately, evidence is limited with a lack of well-controlled studies in larger numbers of well-phenotyped patients, which results in susceptibility for bias and a need for future multicenter studies.

What is new in beta-lactam allergy in children?

This review highlights the novelties in understanding the underlying immunologic mechanisms of drug hypersensitivity reactions (DHRs) with special reference to beta-lactams (BLs) in the pediatric population, as well as tiny changes in clinical classification and diagnosis of DHRs, in the last couple of years. BLs are still the most commonly prescribed and used antibiotics in children. Viral infections are very often in children, and they can provoke skin rashes which are difficult to differentiate from DHRs. The majority of children are incorrectly labeled as "allergic." Therefore, allergy to BLs in children is overdiagnosed. These children often receive suboptimal treatment with second-line broad-spectrum antibiotics, which are less effective, more costly, and associated with an increased risk of antibiotic-resistant infections. This prolongs hospitalization and thus more uses health care. The correct diagnosis of BL allergy in children is still an important and hot topic. This review has outlined the need for correct diagnosis of BL allergy in children and all the controversies encountered by pediatricians and pediatric allergists. It is also necessary to change the paradigm.

Advances and novel developments in drug hypersensitivity diagnosis.

A correct diagnosis of drug hypersensitivity reactions (DHRs) is very important for both the patient and health system. However, DHRs diagnosis is complex, time consuming, requires trained personnel, is not standardized for many drugs, involves procedures not exempt of risk, and in most cases lacks standardized in vivo and in vitro tests. Thus, there is an urgent need for improving the different approaches to diagnose patients with suspected DHRs. In this review, we have analyzed the advances performed in immediate and nonimmediate DHRs diagnosis during the last two years and obtained several conclusions: the significant heterogeneity in current practice among centers illustrates the need to re-evaluate, update, and standardize in vivo tests and protocols for the diagnosis and management of patients with suspected drug allergy. Regarding in vitro tests, the latest studies have focused on increasing their sensitivity or on establishing the sensitivity and specificity for the tests performed with new drugs. There seems to be a consensus about combining in vivo and in vitro tests as the best way to increase the diagnostic accuracy.

Diagnosis and management of the drug hypersensitivity reactions in Coronavirus disease 19: An EAACI Position Paper.

Coronavirus disease 2019 (COVID‐19), a respiratory tract infection caused by a novel human coronavirus, the severe acute respiratory syndrome coronavirus 2, leads to a wide spectrum of clinical manifestations ranging from asymptomatic cases to patients with mild and severe symptoms, with or without pneumonia. Given the huge influence caused by the overwhelming COVID‐19 pandemic affecting over three million people worldwide, a wide spectrum of drugs is considered for the treatment in the concept of repurposing and off‐label use. There is no knowledge about the diagnosis and clinical management of the drug hypersensitivity reactions that can potentially occur during the disease. This review brings together all the published information about the diagnosis and management of drug hypersensitivity reactions due to current and candidate off‐label drugs and highlights relevant recommendations. Furthermore, it gathers all the dermatologic manifestations reported during the disease for guiding the clinicians to establish a better differential diagnosis of drug hypersensitivity reactions in the course of the disease.

Basophil Activation Test Application in Drug Hypersensitivity Diagnosis: An Empirical Approach

Background: The diagnosis of drug hypersensitivity reactions (DHRs) is based both on clinical history and in vivo tests, such as specific IgE and cutaneous tests, when available. Objectives: The aim of this work was to evaluate the basophil activation test (BAT) as a supplementary tool for drug challenges and drug allergy diagnosis. Method: We evaluated 204 outpatients reporting DHRs. Available serum-specific IgE drugs were determined and cutaneous tests were performed when appropriate. BAT was performed immediately after blood sampling. The expression of CD63 was evaluated with flow cytometry. The test was considered positive when CD63 expression was > 5% and the stimulation index (the ratio of the percentage of CD63-expressing cells with drug exposure/percentage of CD63-expressing cells with wash buffer) was > 2. Patients who reported mild to severe reactions and those with a discrepancy between clinical history and BAT underwent a challenge test. Results: The drugs that caused adverse reactions were mainly antibiotics (49%). Non-steroid anti-inflammatory drugs (NSAID) were cited as responsible for DHRs in 37%, with the remaining 14% being due to other drugs. BAT revealed a high specificity (92%) and low sensitivity for antibiotics (40%). For the suspected reactions to penicillin, both the in vitro tests supported 94% of the diagnoses. We also observed a high specificity in the case of challenge with NSAIDs (100% specificity). Conclusions: BAT is effective in discriminating adverse drug reactions, whilst only more critical cases require integrated evaluations and more complex clinical examinations. It is relevant that the concordance of anamnesis and in vitro tests reduce the need for challenge testing, limiting them to selected cases.

Epidemiology of drug hypersensitivity reactions using 6-year national health insurance claim data from Korea.

Background Drug hypersensitivity reactions (DHRs) constitute a large portion of adverse drug reactions (ADRs), but studies for DHR incidence based on national data are scarce. Objective This study aimed to estimate the incidence and patterns of DHRs in a Korean population and the associated utilization of medical resources using the national claims data. Setting The retrospective cohort study performed using the national insurance claim database of the Health Insurance Review and Assessment (HIRA) in Korea. Methods The International Classification of Disease 10th revision code was used to identify DHRs with 20 drug induced DHR codes. The claim data with a diagnosis of DHR in the 2009-2014 periods were analyzed. Main outcome and measure The annual incidence and the 6-year incidence rates were calculated. Incidence rate coefficients were analyzed by sex, age, and year. DHRs following with visits of emergency department (ED) or intensive care unit (ICU) were assessed for utilization of medical resources and risk of ER or ICU visits by sex and age Results A total of 535,049 patients with 1,083,507 claims were assessed in the HIRA database for 6years. DHR incidence was high in the elderly. The risk of ED and ICU visit with DHR was also higher in the elderly than in the young [highest relative risk, RR of ED 2.59 (1.65-4.07), ICU 5.04 (2.50-10.18)]. DHRs related to blood were high in the young age. Conclusion Incidence of DHRs in the real-world clinical practice was higher in the elderly and female. Clinical consequence was more severe in the elderly.

Outcomes of drug provocation tests in Korean children with suspected drug hypersensitivity reaction

Purpose: Drug provocation tests (DPT) are the gold standard for confirming the diagnosis of drug hypersensitivity reactions (DHRs). However, there are little studies of DPT in children. The purpose of this study was to evaluate DPT results and safety as diagnostic methods of DHR in Korean children. Methods: We reviewed the medical records of 39 children under 18 years of age with a suspected DHR and performed DPT be tween January 2010 and May 2016 at Asan Medical Center. Results: Total 110 DPT were performed in 39 children (20 boys and 19 girls) with a history of DHR. Clinical presentation of DHR in cluded skin rash (n=7), pruritus (n=3), urticaria (n=18), angioedema (n=19), dyspnea (n=5), hoarseness (n=1), hypothermia (n=1), and anaphylaxis (n=5). The median age at the time of DPT was 9 years. Positive DPT were observed in 21 of 39 children (53.8%) and 28 of 110 cases (25.5%). Drugs causing positive reactions were acetaminophen in 50% (9 of 18), nonsteroidal anti-in flammatory drugs in 29.2% (14 of 48), cephalosporin in 9.1% (1 of 11), trimethoprim/sulfamethoxazole in 50% (1 of 2), local anes thetics in 10% (1 of 10), and others (levodropropizine and idursulfase) in 15.4% (2 of 13). There was no statistical difference between children who had positive and negative results in sex, age, personal and parental history of allergic disease, eosinophil count, or to tal IgE level. Children with positive DPT did not develop anaphylaxis during the DPT procedure. Conclusion: Drug provocation test is safe, and it can be considered in children with suspected DHRs. (Allergy Asthma Respir Dis 2018;6:26-33)

A Practical Approach to Demystifying Drug Allergy in the Intensive Care Unit. A Review Article

Drug hypersensitivity reaction (DHR) is defined as an immunologically mediated response to a pharmacology agent. Some reactions require prior sensitization and some do not. The interactions between different drugs and the immune system occur by different mechanisms leading to variable clinical features. Some reactions are simple and do not alter patient quality of life. Some are life threatening and require immediate recognition and appropriate therapy. Confirming the diagnosis of DHR is often challenging. The environment in the Intensive care units (ICU) is considered high risk place for DHR development as it offers most of the risk factors. In this review, we offer a delicate combined approach that allows an accurate diagnosis of most of the DHRs encountered in the ICU.

Correction to: Guideline for the diagnosis of drug hypersensitivity reactions

Correction to: Allergo J Int 2015 https://doi.org/10.1007/s40629-015-0052-6 Suspected drug hypersensitivity reactions require allergological investigation in order, firstly, to prevent severe reactions upon renewed exposure or, secondly, to avoid unnecessary drug restrictions. Skin tests are …

Epidemiology and Risk Factors in Drug Hypersensitivity Reactions

Data on adverse drug reactions (ADRs) is abundant, especially regarding prevalence and incidence among hospital-based populations. Most studies, however, do not differentiate between drug hypersensitivity reactions (DHRs) and other kinds of ADR, and in those ones where this information is available, the diagnosis of DHR or drug allergy is mostly based on a suspected clinical history or self-reporting as the majority of patients are not referred for an allergy diagnostic workup. Large studies in drug allergy clinics revealed that only 10 to 20% of the initial DHR suspicions are actually confirmed after investigation. Diagnosis based only on clinical histories largely overestimates drug hypersensitivity, so specific data on DHR is scarce and generally of low quality. Epidemiological data, although limited, can help researchers to identify potential risk factors for DHR. Females seem to be more susceptible than males to ADR and DHRs in adult populations, while the female gender is not a risk factor among children. ADRs have also a higher incidence among young children and among the elderly. The role of atopy as a risk factor for DHR is still debatable; however, recent evidence shows that it can actually be important considering reactions to betalactams and NSAIDs. Comorbidities as infections and underlying chronic diseases are known risk factors both for ADR in general and for DHR. The most recent investigation concentrates on the importance of genetic risk factors, and many gene polymorphisms have been identified with strong associations to particular kind of DHR and/or to reactions to specific drugs. This article will discuss general limitations of the available epidemiological data on DHR and will present an in-depth review of the main identified risk factors for drug reactions with special focus on genetic findings.

Cellular Tests for the Evaluation of Drug Hypersensitivity.

The diagnosis of drug hypersensitivity reactions (DHR) is complex, with many potential pitfalls. Although the use of clinical history and skin testing can be valuable, drug provocation testing (DPT) remains the gold standard for many DHR. However, DPT carries some potential risk and should not be performed for severe reactions. There is therefore a general consensus on the need to improve in vitro tests to achieve safe and accurate diagnosis of DHR. A range of in vitro approaches can be applied depending on the type of reaction and the immunological mechanism involved, i.e. IgE- or T-cell-mediated. However, commercially available tests only exist for a handful of drugs, and only for drugs that provoke IgEmediated DHR. Of the cellular tests that focus on the identification of the culprit drug, the best validated is the basophil activation test used for evaluating IgE-mediated reactions. For T-cell-mediated DHR, the lymphocyte transformation test and enzyme-linked immunosorbent spot appear to be the most promising. However, these tests often show low sensitivity. Despite their current drawbacks, in vitro tests can complement in vivo testing and further work in this area will be crucial to improve our current arsenal of tools for the detection and assessment of DHR. For this, the use of appropriate and relevant drug metabolites as well as other factors that can amplify the cell response as well as the use of multiple tests in concert key to improving in vitro diagnosis. Such improvements will be crucial to diagnose patients with severe reactions for whom DPT cannot be performed.

Evaluation of Lymphocyte Transformation Test Results in Patients with Delayed Hypersensitivity Reactions following the Use of Anticonvulsant Drugs

Background/Aim: Administration of the anticonvulsant drugs phenobarbital, phenytoin, carbamazepine and lamotrigine can be associated with severe hypersensitivity reactions. The lymphocyte transformation test (LTT) is a method to determine which drug has caused the hypersensitivity reaction. This study was done to evaluate the results of LTT in patients with delayed hypersensitivity reactions following the administration of anticonvulsants. Methods: Twenty-four patients with hypersensitivity reactions, e.g. drug-induced hypersensitivity syndrome/drug rash and eosinophilia with systemic symptoms (DIHS/DRESS), Stevens-Johnson syndrome (SJS) and toxic epidermal necrosis (TEN), following the administration of anticonvulsant drugs, and 24 patients who had used anticonvulsant drugs but did not have hypersensitivity reactions (the control group) were included in this study. Peripheral blood mononuclear cells were isolated. The cells were stimulated with the drugs, phytohemagglutinin as a mitogen and Candida as an antigen (positive controls). Lymphocyte proliferation was measured using the BrdU proliferation assay kit (Roche, Germany). The stimulation index was calculated as the mean ratio of the OD of stimulated cells divided by the OD of unstimulated cells. The results in the case and control groups were compared. Results: Of 24 patients in the test group, 14 (58.3%) had positive LTT results and 10 (41.7%) had negative results. Among patients in the control group, 1 (4.2%) had a positive LTT result and 23 (95.8%) had negative results. Among the patients who had received carbamazepine and phenytoin, there was a significant difference between the results of LTT in the case and control groups (p = 0.002 and p = 0.028, respectively). Although patients receiving lamotrigine and phenobarbital had more positive LTT results in the case group than in the control group, these differences were not statistically significant. The sensitivity, specificity, positive predictive value and negative predictive value of LTT were 58.4, 95.8, 93.3 and 69.9%, respectively. Conclusions: Considering the significant difference in LTT results between the case and control groups in patients receiving carbamazepine and phenytoin, and not observing such a difference in patients receiving phenobarbital and lamotrigine, LTT results are more valuable for the diagnosis of hypersensitivity reactions following the administration of carbamazepine and phenytoin. The LTT has good specificity but low sensitivity for the diagnosis of drug hypersensitivity reactions.

Development of nanostructures in the diagnosis of drug hypersensitivity reactions

This article provides an overview of novel nanoscale structures potentially applicable to the field of allergy, and to discuss the required properties, advantages, and disadvantages of those nanostructures for clinical application focusing on diagnosis of drug hypersensitivity reactions. Advances in the development of different nanostructures are favoring their biomedical applications. One area of interest is the interaction between nanostructures and the immune system, including their ability to emulate carrier molecules and their potential use for the diagnosis of allergic reactions. Immunoassays are the most widely used in-vitro test for evaluating immunoglobulin E (IgE)-mediated drug hypersensitivity reactions. However, they have important technical limitations affecting their sensitivity. A wide variety of nanostructures have been designed to quantify specific IgE, with the aim of diagnosing different kinds of allergies. Nanoparticles-based colloidal immunoassay employed in microdevices and/or miniaturized systems are improving IgE detection sensitivity. Dendrimers have shown immense potential for the design and development of sensor platforms for evaluating IgE-mediated drug hypersensitivity reactions, due to the increase in hapten density and IgE accessibility. In this sense, a variety of dendritic structures as well as their hybridization to different solid supports have been shown to be successful when applied in the diagnosis of drug allergy. Moreover, the knowledge of the complete antigenic determinants would allow their inclusion and therefore further improvement of the sensitivity.

Drug provocation tests in the diagnosis of drug hypersensitivity reactions

Drug provocation tests (DPTs)are considered to be not only a gold standard for the diagnosis and exclusion of drug hypersensitivity, but also a safe and efficient approach to seeking alternative medicines. The operation procedures for DPTs have not yet been internationally unified. At present, consensus has been reached that prolonged successive provocation in addition to routine daily oral provocation can improve the positive rate of DPTs. DPTs have a high negative predictive value of more than 90%, and are fairly safe. Almost all positive reactions to DPTs, even long-term DPTs in children, manifest as skin eruptions or urticaria/angioedema, which are mild and easily controlled. Many studies on the diagnostic value, safety and acceptance of SPTs among patients indicate that further researches are required to develop safer and more accurate operation procedures. Key words: Pharmaceutical preparations; Hypersensitivity; Diagnosis; Methods; Drug provocation tests

Guideline for the diagnosis of drug hypersensitivity reactions: S2K-Guideline of the German Society for Allergology and Clinical Immunology (DGAKI) and the German Dermatological Society (DDG) in collaboration with the Association of German Allergologists (AeDA), the German Society for Pediatric Allergology and Environmental Medicine (GPA), the German Contact Dermatitis Research Group (DKG), the Swiss Society for Allergy and Immunology (SGAI), the

Drug hypersensitivity reactions are unpredictable adverse drug reactions. They manifest either within 1–6 h following drug intake (immediate reactions) with mild to life-threatening symptoms of anaphylaxis, or several hours to days later (delayed reactions), primarily as exanthematous eruptions. It is not always possible to detect involvement of the immune system (allergy). Waiving diagnostic tests can result in severe reactions on renewed exposure on the one hand, and to unjustified treatment restrictions on the other. With this guideline, experts from various specialist societies and institutions have formulated recommendations and an algorithm for the diagnosis of allergies. The key principles of diagnosing allergic/hypersensitivity drug reactions are presented. Where possible, the objective is to perform allergy diagnostics within 4 weeks–6 months following the reaction. A clinical classification of symptoms based on the morphology and time course of the reaction is required in order to plan a diagnostic work-up. In the case of typical symptoms of a drug hypersensitivity reaction and unequivocal findings from validated skin and/or laboratory tests, a reaction can be attributed to a trigger with sufficient confidence. However, skin and laboratory tests are often negative or insufficiently reliable. In such cases, controlled provocation testing is required to clarify drug reactions. This method is reliable and safe when attention is paid to indications and contraindications and performed under appropriate medical supervision. The results of the overall assessment are discussed with the patient and documented in an „allergy passport“ in order to ensure targeted avoidance in the future and allow the use of alternative drugs where possible.

Use of multi-parametric flow cytometry to study patterns of immune activation in peripheral blood in patients with drug hypersensitivity reactions

Drug hypersensitivity reactions (DHR) are frequently encountered in clinical practice, and often result in significant morbidity and mortality. Diagnosis of DHR is based upon clinical signs, symptomatology and biochemical parameters, and is frequently complicated by factors including polypharmacy and difficulty excluding conditions mimicking DHR. Currently available laboratory assays employed in the work-up of DHR include evaluation of lymphocytes, basophils and other cell types in peripheral blood specimens after ex-vivo stimulation with the culprit drug in the convalescent phase, several weeks after the initial reaction. There are no robust tests available for diagnosing DHR at the time of the reaction. The ability to diagnose and differentiate between various reaction types during the acute phase would facilitate early identification and specific management of affected patients. Up-regulation of several cell surface activation markers have been described in the context of Type 4 DHR, including CD69 which becomes up-regulated in various cell types, increased expression of CD40L, HLA-DR and CD25 on T cells, and up-regulation of CD107a and cytoplasmic perforin and granzyme in NK and cytotoxic T cells. 1 We present a case-based discussion of patterns of immune activation in the peripheral blood of patients presenting with acute DHR, and describe the differential up-regulation of various cell surface and cytoplasmic markers in different DHR sub-types.