Neomycin: sources of contact and sensitization evaluation in 1162 patients treated at a tertiary service

Abstract Background: Neomycin is used in several over-the-counter pharmaceutical formulations in Brazil. In Europe and Canada, where it is not freely available, its sensitization frequency is lower than in the United States, where this does not occur. Objective: To present the frequency of sensitization to neomycin observed in a tertiary hospital and the pharmaceutical formulations sold in Brazil containing neomycin. Method: Retrospective analysis of positive results to neomycin, obtained through patch tests performed in a tertiary hospital, from 2009 to 2018 and investigation of topical drugs and vaccines containing neomycin in Brazilian databases available on the internet. Results: Among 1,162 patients, 71 (6%) had positive reactions to neomycin, 65% female and 35% male individuals, 46% were over 50 years old, and 24% had a personal history of atopy. The dermatitis lasted from four months to 20 years. Lesions were located in 69% of the patients on the upper limbs, in 55% they were on the lower limbs, and in 42% they were disseminated in more than 4 sites. Polysensitization was detected in 55% of cases. Of these, 28% were linked to sensitization to rubber allergens and 27% to potassium bichromate. A total of 158 topical presentations of neomycin were found: 79 ointments, 58 creams, 10 ophthalmic solutions, seven otological solutions, one oral solution, two nasal solutions, and one antiseptic powder, in addition to 11 types of vaccines. Study limitations: Retrospective study. Conclusion: Sensitization to neomycin occurred in 6% of the studied population, affecting more females aged over 50 years, with skin lesions located mainly on the upper and lower limbs, in the context of chronic contact dermatitis. Neomycin was found in 135 formulations, most of them available over the counter, as well as in 11 miscellaneous vaccines.

Safety profile of CoviShield (ChAdOx1nCoV-19) vaccine among healthcare workers in a tertiary care hospital

Background: Coronavirus 2019 was declared as a pandemic by the World Health Organization in March 2020. Bereft of specific treatment for the disease, vaccinations and COVID appropriate behavior have come to be the main approaches to combat the pandemic. A number of vaccines have been approved after clearing clinical trials. Hence, it is essential to evaluate the safety profile of each vaccine for ensuring optimum health of the general population. This study was conducted to evaluate the adverse events following CoviShield vaccination in a tertiary care center. Aims and Objectives: The aim of the study was to describe the pattern of adverse effects, treatment given, and comorbidities seen in healthcare workers (HCW) who reported to the adverse drug reaction (ADR) monitoring center in the department of pharmacology Government T.D. Medical College, Alappuzha, following CoviShield vaccination from January 2021 to October 2021. Materials and Methods: A retrospective and descriptive study was carried out at Department of Pharmacology, GTDMCA involving all HCW who reported side effects following CoviShield vaccination in the ADR monitoring centre (AMC) in the Department of Pharmacology, GTDMCA from January 2021 to Oct 2021. Results: Out of 620 HCWs who reported adverse event following vaccination, majority (45%) were from the age group 21–30 years. About 83% of HCWs who reported adverse effect were women. Majority of the respondents (96%) experienced the adverse effects within 24 h. About 88% of respondents experienced these adverse effects after the initial dose alone. Commonly encountered adverse effects were fever (57%), headache (43%), myalgia (38%) etc. Hypertension (7%) was the most common comorbidity seen. Majority of the beneficiaries (70%) took paracetamol for the treatment of the adverse effect. Conclusion: Majority of the vaccinated HCWs experienced minor and self-limiting adverse event following immunization (AEFI) with Chimpanzee Adenovirus Oxford novel CoronaVirus-19. No serious AEFI were reported to the AMC. Despite the record speed at which the vaccine has been developed, it has shown to have a good safety profile considering the millions of doses that have been administered.

The 494th case: acute pancreatitis, acute acalculous cholecystitis and anaphylaxis / 中华内科杂志

A young male patient with abdominal pain and fever was diagnosed as acute hyper-triglyceridemicpancreatitis is clear. During the recovery of pancreatitis, the patient developed acute acalculous cholecystitis, as well as carbapenem-resistant Enterobacter infection and Cytomegaloviremia, and had anaphylaxis for several times after the use of antibiotics, which cannot be completely explained by drug allergy. This paper analyzes the possible causes of multiple diseases in the same patient in detail.

Management of Adverse Reactions to Iodinated Contrast Media for Computed Tomography in Korean Referral Hospitals: A Survey Investigation

OBJECTIVE: To evaluate the current status of managing adverse reactions to iodinated contrast media (ICM) for computed tomography in referral hospitals in South Korea compared with hospitals in other countries. MATERIALS AND METHODS: This survey investigation involved 59 Korean and 15 overseas hospitals using guideline-based questionnaires consisting of 24 items in 7 main categories related to managing adverse reactions to ICM. RESULTS: Informed written consent with risk factor evaluation was appropriately performed in most of the Korean hospitals. There was considerable variability in assessing renal function across the hospitals; serum creatinine level was used as a reference in 76.4% of Korean hospitals. The Korean hospitals preferred a more stringent approach to determining normal renal function (p = 0.01), withholding metformin (p = 0.01), and fasting before ICM exposure (p < 0.001) compared with overseas hospitals. All the Korean hospitals had an emergency protocol and in-hospital system for adverse reactions to ICM. The Korean (87.7%) and overseas hospitals (100%) were similarly equipped with epinephrine (p = 0.332), but only 38.6% of Korean hospitals were equipped with a bronchodilator (p = 0.004). For patients with a previous hypersensitivity reaction to ICM, 62.3% of Korean hospitals pre-medicated with anti-histamine and corticosteroid according to the severity of the previous reaction, and changed the culprit ICM in 52.8%, while skin test was performed in 17%. CONCLUSION: In general, Korean referral hospitals were well-prepared regarding informed consent, protocol, and an in-hospital system for managing adverse reactions to ICM. Nevertheless, there was considerable variability in details and management, thus requiring standardization by reflecting current guidelines.

Drug eruption in children / 中国小儿急救医学

The epidemiology, clinical manifestations and appropriate diagnostic methods of drug eruption in children are still poorly understood.On the one hand, children′s adverse reactions to drugs are different from adults because of their weight and age characteristics.On the other hand, they can mimic many other skin diseases, especially viral exanthems, frequently appearing as a maculopapular or morbilliform rash sometimes indistinguishable from a cutaneous adverse drug reaction.Meanwhile, the tools used for drug eruption management in adults are applied also for children.Whereas this appears generally acceptable, some aspects of drug eruption and management differ with age.The pathogenesis of drug eruption in children is related to virus infection, immune state, drug and metabolic enzyme effect.Most reactions in children are still attributed to betalactams.The practicability and validity of skin test and other diagnostic procedures need further assessment in children.The key to treatment is early diagnosis, discontinuation of suspect drugs, assessment of prognosis, and specialist support.

Drug eruption in children / 中国小儿急救医学

The epidemiology, clinical manifestations and appropriate diagnostic methods of drug eruption in children are still poorly understood. On the one hand,children′s adverse reactions to drugs are dif-ferent from adults because of their weight and age characteristics. On the other hand,they can mimic many other skin diseases,especially viral exanthems,frequently appearing as a maculopapular or morbilliform rash sometimes indistinguishable from a cutaneous adverse drug reaction. Meanwhile,the tools used for drug erup-tion management in adults are applied also for children. Whereas this appears generally acceptable, some aspects of drug eruption and management differ with age. The pathogenesis of drug eruption in children is related to virus infection,immune state,drug and metabolic enzyme effect. Most reactions in children are still attributed to betalactams. The practicability and validity of skin test and other diagnostic procedures need further assessment in children. The key to treatment is early diagnosis, discontinuation of suspect drugs, assessment of prognosis,and specialist support.

Testes in vivo nas reações de hipersensibilidade a medicamentos - Parte I: testes cutâneos / In vivo tests in hypersensitivity drug reactions - Part I: skin tests

As reações de hipersensibilidade a medicamentos são frequentes na prática clínica e são consideradas problema de saúde pública. O diagnóstico inclui, após detalhada história clínica, a realização de testes in vivo: cutâneos ou de provocação. Recentemente, estes testes foram aprovados pela Câmara Técnica da Associação Médica Brasileira para inclusão tanto no SUS, como na Saúde Suplementar, o que facilitará o acesso dos pacientes a estas ferramentas. Nesta revisão, abordaremos com mais detalhes as indicações, técnica e impacto da utilização dos testes cutâneos com fármacos na prática clínica.

Hypersensitivity drug reactions are frequent in clinical practice and are considered an important public health issue. Diagnosis includes a detailed clinical history, followed by in vivo tests, such as skin tests and drug provocation tests. Those tests were recently approved by the Brazilian Medical Association Technical Board to be included in both public and private practice, which will facilitate investigation with those tools. In this review paper, we will address in more detail the indications, technique, and impact of the use of skin tests to drugs in clinical practice.

Specific questionnaire detects a high incidence of intra-operative hypersensitivity reactions

OBJECTIVE: To assess the incidence of intra-operative immediate hypersensitivity reactions and anaphylaxis. METHODS: A cross-sectional observational study was conducted at the Department of Anesthesiology, University of São Paulo School of Medicine, Hospital das Clínicas, São Paulo, Brazil, from January to December 2010. We developed a specific questionnaire to be completed by anesthesiologists. This tool included questions about hypersensitivity reactions during anesthesia and provided treatments. We included patients with clinical signs compatible with immediate hypersensitivity reactions. Hhypersensitivity reactions were categorized according to severity (grades I-V). American Society of Anesthesiologists physical status classification (ASA 1-6) was analyzed and associated with the severity of hypersensitivity reactions. RESULTS: In 2010, 21,464 surgeries were performed under general anesthesia. Anesthesiologists answered questionnaires on 5,414 procedures (25.2%). Sixty cases of intra-operative hypersensitivity reactions were reported. The majority patients (45, 75%) had hypersensitivity reactions grade I reactions (incidence of 27.9:10,000). Fifteen patients (25%) had grade II, III or IV reactions (intra-operative anaphylaxis) (incidence of 7:10,000). No patients had grade V reactions. Thirty patients (50%) were classified as ASA 1. The frequency of cardiovascular shock was higher in patients classified as ASA 3 than in patients classified as ASA 1 or ASA 2. Epinephrine was administered in 20% of patients with grade III hypersensitivity reactions and in 50% of patients with grade II hypersensitivity reactions. CONCLUSIONS: The majority of patients had hypersensitivity reactions grade I reactions; however, the incidence of intra-operative anaphylaxis was higher than that previously reported in the literature. Patients with ASA 3 had more severe anaphylaxis; however, the use of epinephrine was not prescribed in all of these cases. Allergists and anesthesiologists should implement preventive measures to reduce the occurrence of anaphylaxis.

A pediatric case of anaphylactic shock induced by tipepidine hibenzate (Asverin)

Tipepidine hibenzate (Asverin) is commonly used as an antitussive drug for acute and chronic cough in various age groups and is generally safe and well-tolerated. However, we experienced a case of tipepidine hibenzate-induced anaphylactic shock in a 1-year-old boy. After ingesting cold medication including tipepidine hibenzate, the patient presented with generalized erythema and urticaria, swollen face, coughing, wheezing and vomiting, together with hypotension and a decreased level of consciousness. To identify the culprit drug, we performed skin prick tests (SPTs) and oral drug provocation tests (DPTs). SPTs revealed a negative reaction for all drugs, but DPTs caused a positive reaction only for a full therapeutic dose of tipepidine hibenzate. Physicians need to consider tipepidine hibezate as a culprit drug when anaphylaxis occurs after taking anticough or common cold medication.

Anaphylaxis following intralesional triamcinolone acetonide (Kenacort) injection

Intralesional triamcinolone acetonide injection is indicated for multiple skin conditions such as keloid scars, alopecia areata, and hypertrophic lichen planus. Immediate hypersensitivity reaction remains uncommon. We report on a 24-year-old woman who had received multiple intralesional injections with triamcinolone acetonide (Kenacort) plus lidocaine for keloid scar treatment without any reaction for the previous 10 years. The immediate reaction occurred 15 minutes after injection, with numbness on her face and 5 minutes later with urticaria on her chest wall and upper extremities, together with hypotension (blood pressure of 90/60 mmHg). Allergology workup revealed positive skin prick test for triamcinolone acetonide (Kenacort). Skin tests for other corticosteroids (hydrocortisone, methylprednisolone, and dexamethasone), excipients (carboxymethylcellulose, benzyl alcohol, and polysorbate 80) and lidocaine were negative, including subcutaneous challenge for lidocaine and oral challenge for carboxymethylcellulose. IgE-mediated hypersensitivity reaction must be considered in cases of multiple applications of triamcinolone acetonide injection.

In Vitro Diagnostic Testing for Antibiotic Allergy

Allergy to antibiotics is an important worldwide problem, with an estimated prevalence of up to 10% of the population. Reaction patterns for different antibiotics have changed in accordance with consumption trends. Most of the allergic reactions to antibiotics have been reported for betalactams, followed by quinolones and macrolides and, to a lesser extent, to others, such as metronidazole clindamycin and sulfonamides. The diagnostic procedure includes a detailed clinical history, which is not always possible and can be unreliable. This is usually followed by in vivo, skin, and drug provocation tests. These are not recommended for severe, potentially lifethreaten reactions or for drugs that are known to produce a high rate of false positive results. Given the limitations of in vivo tests, in vitro test can be helpful for diagnosis, despite having suboptimal sensitivity. The most highly employed techniques for diagnosing immediate reactions to antibiotics are immunoassays and basophil activation tests, while lymphocyte transformation tests are more commonly used to diagnose non-immediate reactions. In this review, we describe different in vitro techniques employed to diagnose antibiotic allergy.

Knowledge, attitudes, and practices survey of drug allergy among healthcare practitioners in central China: a multicenter study

BACKGROUND: Drug allergy (DA) is one of the most important contributors to iatrogenic morbidity and mortality. Currently DA remains a major challenge for healthcare practitioners (HCPs). OBJECTIVE: To assess the knowledge, attitudes and practices of DA among HCPs in Central China. METHODS: A 25-item self-administered DA questionnaire were developed and applied in our study. The questionnaire covered 3 domains: knowledge, attitudes, and practice patterns. From July 2015 to October 2015, HCPs in 7 cities of Central China anonymously participated in the cross-sectional study. RESULTS: A total of 350 HCPs participated the study, 91 questionnaires uncompleted and 259 were analyzed. Among the respondents, 166 (64.1%) were doctors, 55 (21.2%) were nurses and 38 (14.7%) were medical students. The mean knowledge precision was 59.8%. HCPs agreed that drug induced immediate allergic reactions were IgE mediated (83.4%) and happened within 6 hours after drug administration (89.6%), and epinephrine was the first choice for drug induced anaphylaxis (79.5%). They also agreed that penicillin skin test was valuable to predict allergic reaction (88.4%). However, high proportion of HCPs (66.0%) believed glucocorticoids had an impact on drug skin test rather than antihistamines (4.2%), 47.1% never performed positive and negative control during skin test. More than 90% of the respondents would take patients' allergic history before drug administration, 98.8% agreed that they should receive advanced training of DA knowledge and practice. CONCLUSION: The HCPs demonstrated a low level of knowledge regarding DA. Advanced education is urgently needed for better understanding and filling the gaps exist in knowledge and clinical practice of DA.

The Basophil Activation Test Is Safe and Useful for Confirming Drug-Induced Anaphylaxis

The basophil activation test (BAT) has been suggested as a complementary method for diagnosing drug allergies. The aim of this study was to evaluate the clinical utility of this test in patients with drug-induced anaphylaxis. In total, 19 patients, all of whom had a history of moderate to severe anaphylaxis, were enrolled. None of the causative drugs had available in vitro tests or reliable skin tests; these drugs included, among others, first and second-generation cephalosporins, H2 blockers, and muscle relaxants. The BAT yielded positive results in 57.9% of the cases, which was similar those results of skin prick and intradermal tests (42.1% and 57.9%, respectively). When basophils were double labelled with CD63 and CD203c, both of which are basophil activation markers, the positive rate was increased from 57.9% to 73.7%. Therefore, the results of this study confirm that the BAT is a quick, reliable, and safe diagnostic tool for patients with drug-induced anaphylaxis.

Mastocitosis local, sistémica y alergia medicamentosa / Local and systemic mastocytosis anddrug allergy

Se exponen datos relacionados con la histología, fisiología y patología de los mastocitos, tanto normales como patológicos, y el papel de la alergia medicamentosa en la mastocitosis, así como las repercusiones psicopatológicas de la enfermedad y las bases neuroquímicas de dichos trastornos.

Data concerning the biological aspects of mastocytes, its pathology and the importance of childhood and adult mastocytosis are described. The role of drug allergy in mastocytosis is discussed. The psychopathological and neurochemical aspects of these conditions are exposed.

Value of interleukin 4 and immunoglobulin E levels monitoring in diagnosis of drug allergy reaction / 中国生化药物杂志

Objective To explore interleukin 4 and immunoglobulin E levels indicators monitoring value in diagnosis of drug allergy reaction . Methods The way of intravenous injection and conventional intraperitoneal injection was used, with the corresponding drugs such as saline, horse serum sensitized, and in different time interleukin -4 and total immunoglobulin E index were recorded in guinea pig serum.Results Injection of saline and Chuankezhi injection, interleukin-4 and total immunoglobulin E protein content , the difference was not statistically significant, but in other drug induced sensitive D8, D14 and D21, interleukin-4 and total immunoglobulin E protein content increased significantly.Conclusion Interleukin 4 and immunoglobulin E levels index detection is the diagnosis of drug allergy is an effective and fast way .

Seven Steps to the Diagnosis of NSAIDs Hypersensitivity: How to Apply a New Classification in Real Practice?

Frequent use of non-steroidal anti-inflammatory drugs (NSAIDs) has been paralleled by increasing occurrence of adverse reactions, which vary from mild local skin rashes or gastric irritation to severe, generalized symptoms and even life-threatening anaphylaxis. NSAID-induced hypersensitivity reactions may involve both immunological and non-immunological mechanisms and should be differentiated from type A adverse reactions. Clinical diagnosis and effective management of a hypersensitive patient cannot be achieved without identifying the underlying mechanism. In this review, we discuss the current classification of NSAID-induced adverse reactions and propose a practical diagnostic algorithm that involves 7 steps leading to the determination of the type of NSAID-induced hypersensitivity and allows for proper patient management.

Intradermal Tests for Diagnosis of Drug Allergy are not Affected by a Topical Anesthetic Patch

The use of topical anesthesia to perform intradermal tests (IDTs) for drug allergy diagnosis was never investigated. We aimed to determine the effects of a topical anesthetic patch containing prilocaine-lidocaine on wheal size of IDT with drugs. Patients who had positive IDT as part of their investigation process of suspected drug hypersensitivity were selected. IDT were performed according to guidelines. Anesthetic patch (AP) was placed and the same prior positive IDT, as well as positive histamine skin prick test (SPT) and negative (saline IDT) controls, were performed in the anesthetized area. Patients with negative IDT were also included to check for false positives with AP. Increase in wheals after 20 minutes both with and without AP was recorded and compared. 45 IDT were performed (36 patients), of which 37 have been previously positive (14 antibiotics, 10 general anesthetics, 6 non-steroidal anti-inflammatory drugs, 3 iodinated contrasts, 3 anti-Hi-histamines and 1 ranitidine). Mean histamine SPT size without the AP was 4.7 mm [95%CI (4.4-5.1]), and 4.6 mm [95%CI(4.2-5.0)] with anesthesia. Mean wheal increase in IDT for drugs without the anesthesia was 4.5 mm [95%CI(3.3-5.7)] and with anesthesia was 4.3 mm [95%CI(2.8-5.8)]. No statistical significant differences were observed between skin tests with or without AP for histamine SPT (P=0.089), IDT with saline (P=0.750), and IDT with drugs (P=0.995). None of the patients with negative IDT showed positivity with the AP, or vice-versa. The use of an AP containing prilocaine-lidocaine does not interfere with IDT to diagnose drug allergy, and no false positive tests were found.

Anaphylaxis induced by lysozyme in Green cough

Lysozyme is a small protein composed of 129 amino acids with a molecular weight of 14.3 kD. In human, it is in the eye drop, saliva, nasal secretion, and gastric juice. Because of its bactericidal properties, this protein is used as an additive in various food and drug products. A 34-year-old female patient had visited at emergency room for generalized urticaria, angioedema, and dyspnea a few minutes after taking Green cough capsule which contains lysozyme. Her serum tryptase level measured by florescence enzyme immunoassay was 11 mg/mL. Skin prick tests with Green cough itself, and then with its 10 ingredients including lysozyme chloride showed strong positive reaction to Green cough and lysozyme chloride. Base on her symptoms and the results obtained from high level of serum trypase and skin prick tests, we have concluded her conditions to be an anaphylaxis induced by lysozyme.

Munchausen Stridor-A Strong False Alarm of Anaphylaxis

The diagnosis of anaphylaxis is often based on reported symptoms which may not be accurate and lead to major psychosocial and financial impacts. We describe two adult patients who were diagnosed as having recurrent anaphylaxis witnessed by multiple physicians based on recurrent laryngeal symptoms. The claimed cause was foods in one and drugs in the other. We questioned the diagnosis because of absent documentation of objective findings to support anaphylaxis, and the symptoms occurred during skin testing though the test sites were not reactive. Our initial skin testing with placebos reproduced the symptoms without objective findings. Subsequent skin tests with the suspected allergens were negative yet reproduced the symptoms without objective findings. Disclosing the test results markedly displeased one patient but reassured the other who subsequently tolerated the suspected allergen. In conclusion, these 2 patients' symptoms and evaluation were not supportive of their initial diagnosis of recurrent anaphylaxis. The compatible diagnosis was Munchausen stridor which requires psychiatric evaluation and behavior modification, but often rejected by patients.

Social Burden of Drug Allergy and its Prevention / 대한내과학회지

Drug allergy exhibits a wide range of clinical features that partly reflect the diversity of the underlying responsible mechanisms. These range from non-immunologic idiosyncratic reactions to Gell and Coombs type 1, 2, 3, and 4 reactions. Consequently, a drug allergy may be difficult to differentiate from an adverse drug reaction. The prevalence of drug allergy varies but is assumed to account for 30% of all adverse drug reactions. In the U.S., 3.1-6.2% of all ward patients are admitted because of adverse drug reactions, and 5-10% of all out-patients or ward patients have suffered an adverse drug reaction. Nonsteroidal anti-inflammatory drugs (NSAIDs), antibiotics, and radiocontrast media are the most common causes of drug allergy, but with the recent introduction of molecular anti-cancer agents, the number of drug allergy cases by these agents is soaring. Drug allergy is an important cause of mortality in admitted patients, and 1 out of every 10,000 admitted patients will die because of a drug allergy. Approximately 30% of adverse drug reactions can be prevented if previous reactions have been monitored and managed adequately. In 2006, a regional pharmacovigilance program was launched in Korea. In addition, the Korean Institute of Drug Safety and Risk Management plans to develop a nationwide drug utilization review program to monitor adverse drug reactions and to provide relevant information from the program to health professionals working in hospitals and clinics, with the aim of preventing drug allergies. Recent studies have shown a strong association between human leukocyte antigen genotypes and the severe cutaneous adverse reactions (SCARs) induced by certain drugs. Genotype prescreening may contribute to the prevention of SCARs induced by culprit drugs such as carbamazepine, allopurinol, and abacavir.