INVESTIGATION OF MEDICALLY INDUCED SKIN REACTIONS BASED ON THE ANALYSIS OF REPORTS OF ADVERSE DRUG REACTIONS IN THE REPUBLIC OF CRIMEA (FROM 2009 TO 2016)

Drug hypersensitivity reactions are among the most important problems that arise when using drugs. The occurrence of such reactions in the population is at least 7% and tends to a constant increase. The most frequent manifestations of drug hypersensitivity reactions are medically induced skin lesions.The aimof this research was to study and analyze the cases of development of skin drug reactions on the basis of the reports on the adverse reactions (ADRs) of the drugs, registered in the Republic of Crimea in the period from 2009 to 2016.Materials and methods.The objects of the research were report cards about the adverse reactions, registered in the regional base (registry) of spontaneous messages called ARCADe (Adverse Reactions in Crimea, Autonomic Database) for the period from 2009 to 2016. During the analysis of the report cards, 2,698 cases of the development of skin drug reactions arising in response to the use of drugs in patients were selected. The study of the frequency of occurrence of skin drug reactions in the application of various groups of drugs was carried out taking into account the codes of the Anatomical Therapeutic Chemical (ATC) Сlassification System of drugs of the World Health Organization (WHO).Results.Of the study showed that the development of skin drug reactions was most often associated with the use of antimicrobial agents for internal use, nonsteroidal anti-inflammatory drugs (NSAIDs), drugs for the treatment of diseases of the gastrointestinal tract and agents that affect the nervous system. Among the clinical manifestations of skin drug reactions, generalized and localized rashes prevailed, and itching and hyperemia of the skin were much less common in patients. The analysis of age categories showed that the most frequently medically induced reactions occurred in children from birth to 3 years, as well as in the age group of patients from 46 to 60 years. The risk factors identified in the course of the analysis, were female gender, early childhood and old age, as well as the presence of aggravated drug allergy history.Conclusion.Drug hypersensitivity reactions create certain difficulties in clinical practice related to the diagnosis, treatment and prophylaxis, and may also cause danger to health or life of patients. In this connection, the study of such adverse reactions is the most important task of practical health care and requires direct participation of doctors of all specialties.

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Drug Allergies

10.2310/fm.1127 ◽

2018 ◽

Author(s):

James L Baldwin ◽

Aimee L. Speck

Keyword(s):

Adverse Drug Reactions ◽

Skin Testing ◽

Drug Hypersensitivity ◽

Type A ◽

World Health ◽

Hypersensitivity Reactions ◽

Type B ◽

Drug Reactions ◽

Drug Hypersensitivity Reactions

Adverse drug reactions (ADRs) are an important public health problem. An ADR is defined by the World Health Organization as an unintended, noxious response to a drug that occurs at a dose usually tolerated by normal subjects. The classification of ADRs by Rawlins and Thompson divides ADRs into two major subtypes: (1) type A reactions, which are dose dependent and predictable, and (2) type B reactions, which are uncommon and unpredictable. The majority of ADRs are type A reactions, which include four subtypes: overdosage or toxicity, side effects, secondary effects, and interactions. Type B reactions constitute approximately 10 to 15% of all ADRs and include four subtypes: drug intolerance, idiosyncratic reactions, pseudoallergic reactions, and drug hypersensitivity reactions. This chapter reviews the epidemiology of ADRs, risk factors for drug hypersensitivity reactions, the classification of drug reactions, diagnostic tests, reactions to specific drugs, and management of the patient with drug allergy. Figures illustrate drugs as haptens and prohaptens, the Gell and Coombs system, the four basic immunologic mechanisms for drug reactions, the chemical structure of different β-lactam antibiotics, penicillin skin testing, sulfonamide metabolism and haptenation, nonsteroidal antiinflammatory drug effects, and patient management. Tables outline the classification of ADRs, drugs frequently implicated in allergic drug reactions, and reagents and concentrations recommended for prick and intradermal skin testing. This review contains 8 figures, 7 tables, and 60 references. Key Words: Adverse drug reactions, drug hypersensitivity reactions, overdosage, toxicity, Type A reactions, Type B reactions, human leukocyte antigen, pruritus, angioedema, urticarial, bronchospasm, laryngeal edema, rhinoconjunctivitis

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Drug Allergies

10.2310/im.1127 ◽

2018 ◽

Author(s):

James L Baldwin ◽

Aimee L. Speck

Keyword(s):

Adverse Drug Reactions ◽

Skin Testing ◽

Drug Hypersensitivity ◽

Type A ◽

World Health ◽

Hypersensitivity Reactions ◽

Type B ◽

Drug Reactions ◽

Drug Hypersensitivity Reactions

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Drug Allergies

10.2310/neuro.1127 ◽

2015 ◽

Author(s):

James L Baldwin ◽

Aimee L. Speck

Keyword(s):

Skin Testing ◽

Drug Hypersensitivity ◽

Public Health Problem ◽

Type A ◽

World Health ◽

Hypersensitivity Reactions ◽

Type B ◽

Drug Reactions ◽

Drug Hypersensitivity Reactions

Adverse drug reactions (ADRs) are an important public health problem. An ADR is defined by the World Health Organization as an unintended, noxious response to a drug that occurs at a dose usually tolerated by normal subjects. The classification of ADRs by Rawlins and Thompson divides ADRs into two major subtypes: (1) type A reactions, which are dose dependent and predictable, and (2) type B reactions, which are uncommon and unpredictable. The majority of ADRs are type A reactions, which include four subtypes: overdosage or toxicity, side effects, secondary effects, and interactions. Type B reactions constitute approximately 10 to 15% of all ADRs and include four subtypes: drug intolerance, idiosyncratic reactions, pseudoallergic reactions, and drug hypersensitivity reactions. This chapter reviews the epidemiology of ADRs, risk factors for drug hypersensitivity reactions, the classification of drug reactions, diagnostic tests, reactions to specific drugs, and management of the patient with drug allergy. Figures illustrate drugs as haptens and prohaptens, the Gell and Coombs system, the four basic immunologic mechanisms for drug reactions, the chemical structure of different β-lactam antibiotics, penicillin skin testing, sulfonamide metabolism and haptenation, nonsteroidal antiinflammatory drug effects, and patient management. Tables outline the classification of ADRs, drugs frequently implicated in allergic drug reactions, and reagents and concentrations recommended for prick and intradermal skin testing. This chapter contains 8 highly rendered figures, 3 tables, 83 references, 5 MCQs, and 1 teaching slide set.

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STUDY OF THE SAFETY OF ANTIANEMIC PREPARATIONS BY METHOD OF THE SYSTEM OF PROBLEMS RELATED TO MEDICINAL PREPARATIONS

Pharmacy & Pharmacology ◽

10.19163/2307-9266-2021-9-1-73-83 ◽

2021 ◽

Vol 9 (1) ◽

pp. 73-83

Author(s):

A. V. Matveev ◽

E. A. Egorova ◽

E. I. Konyaeva ◽

E. Yu. Bekirova ◽

L. A. Adjimamutova

Keyword(s):

Iron Deficiency ◽

Adverse Reactions ◽

Drug Hypersensitivity ◽

Clinical Manifestations ◽

Adherence To Treatment ◽

Iron Supplements ◽

Iron Protein ◽

Important Health ◽

Drug Hypersensitivity Reactions ◽

The Republic

Iron deficiency is the most common micronutrient deficiency worldwide. Prevention and treatment of iron deficiency conditions are some of the most important health problems in many countries of the world. At the same time, the main problems for it remain the timely diagnosis, elimination of the cause, as well as the choice of replacement therapy with iron-containing drugs and correction of adverse reactions (ADR) that occur during their use.The aim. This research aims to study the peculiarities of the development of antianaemic drugs ADRs in patients living in the territory of the Republic of Crimea.Materials and methods. The objects of research were cases of ADR occurrence associated with the use of a group of antianaemic drugs and revealed during the 2009-2018 period in the territory of the Republic of Crimea. The main tasks in the analysis of notification forms were the study of the ADR severity, the causality assessment for suspected drugs and ADRs, as well as analysis of particular problems associated with the use of antianaemic drugs (Drug-related problems, DRP).Results. Iron supplements in combination with other drugs became the leaders in the incidence of ADR among antianaemic drugs (28 cases, 42.4% of all cases of ADR). The largest number of cases was registered in patients aged from 18 to 30 years, with female patients prevailing. Among the clinical manifestations of ADR, the most cases were drug hypersensitivity reactions of varying severity (40 cases) and disorders of the gastrointestinal tract (18 cases). The study of the problems associated with the use of antianaemic drugs made it possible to determine that the highest rates of DRP values were observed with the use of iron preparations for parenteral use and cyanocobalamine. The minimal DRP values were observed when prescribing iron protein succinylate preparations.Conclusion. The basis of pharmacotherapy for various types of anemias is the replenishment of iron and vitamin B12 (cyanocobalamin) depots. The effectiveness of the treatment in these cases largely depends on the patient's adherence to treatment, which is, in turn, depends on the frequency and severity of ADRs that occur during the use of antianaemic drugs.

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Treating COVID-19: Review of Drug Hypersensitivity Reactions

Journal of Investigational Allergology and Clinical Immunology ◽

10.18176/jiaci.0588 ◽

2020 ◽

Vol 30 (6) ◽

pp. 385-399 ◽

Cited By ~ 1

Author(s):

MT Treating COVID-19: Review of Drug Hypersensitivity Reactions ◽

V Herrera-Lasso Regás ◽

J Martí-Garrido ◽

D Rodríguez Cumplido ◽

P Vázquez-Revuelta ◽

...

Keyword(s):

Adverse Reactions ◽

Drug Hypersensitivity ◽

Herd Immunity ◽

Clinical Manifestations ◽

High Rate ◽

Medical Community ◽

Hypersensitivity Reactions ◽

Global Pandemic ◽

Drug Hypersensitivity Reactions ◽

Old Drugs

The disease caused by the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), ie, coronavirus disease 2019 (COVID-19), has become a global pandemic since it was first reported in Wuhan, China in December 2019. Its severe clinical manifestations, which often necessitate admission to intensive care units, and high mortality rate represent a therapeutic challenge for the medical community. To date, no drugs have been approved for its treatment, and various therapeutic options are being assayed to address the pathophysiological processes underlying the clinical manifestations experienced by patients. New and old drugs administered as monotherapy or in combination to immunologically compromised patients may favor the development of adverse drug reactions, including drug hypersensitivity reactions, which must be identified and managed accordingly. Given the lack of herd immunity and the high rate of viral contagion, new cases are expected to emerge in the coming months. Thus, the probability of more adverse reactions or even new clinical manifestations may increase in parallel. Allergists must receive updated information on these treatments, as well as on the management of possible drug hypersensitivity reactions.

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Clinical Phenotypes of Severe Cutaneous Drug Hypersensitivity Reactions

Current Pharmaceutical Design ◽

10.2174/1381612825666191107162921 ◽

2019 ◽

Vol 25 (36) ◽

pp. 3840-3854 ◽

Cited By ~ 2

Author(s):

Hakan Guvenir ◽

Tugba Arikoglu ◽

Emine Vezir ◽

Emine Dibek Misirlioglu

Keyword(s):

Adverse Drug Reactions ◽

Drug Hypersensitivity ◽

Stevens Johnson Syndrome ◽

Facial Oedema ◽

Hypersensitivity Reactions ◽

Drug Reactions ◽

Cutaneous Manifestations ◽

Clinical Phenotypes ◽

Drug Eruptions ◽

Drug Hypersensitivity Reactions

Drug hypersensitivity reactions are clinically heterogenous ranging from mild to severe. Most drug hypersensitivity reactions are accompanied by cutaneous manifestations. Fever, mucous membrane involvement, large blisters, facial oedema, pustulosis and visceral involvement are clinical features that lead to suspicion of severe adverse drug reactions. Severe cutaneous adverse drug reactions (SCARs) include Stevens-Johnson syndrome, toxic epidermal necrolysis, drug rash eosinophilia and systemic symptoms, acute generalized exanthematous pustulosis. Serum sickness like reactions, drug induced vasculitis and generalized bullous fixed drug eruptions are less severe clinical entities. SCARs are uncommon but associated with significant morbidity and mortality. Physician should be aware of specific red flags and danger signs to immediately identify these reactions. Immediate drug withdrawal is mandatory. Early diagnosis and appropriate treatment significantly affect the prognosis of the disease. The purpose of our review is to discuss clinical phenotypes of severe cutaneous drug hypersensitivity reactions.

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Early Biomarkers for Severe Drug Hypersensitivity Reactions

Current Pharmaceutical Design ◽

10.2174/1381612825666191107105440 ◽

2019 ◽

Vol 25 (36) ◽

pp. 3829-3839 ◽

Cited By ~ 1

Author(s):

Adriana Ariza ◽

Maria J. Torres ◽

Carmen Moreno-Aguilar ◽

Rubén Fernández-Santamaría ◽

Tahia D. Fernández

Keyword(s):

Drug Exposure ◽

Drug Hypersensitivity ◽

Clinical Manifestations ◽

Skin Tests ◽

Time Interval ◽

Hypersensitivity Reactions ◽

Early Biomarkers ◽

Immunological Mechanisms ◽

Drug Hypersensitivity Reactions ◽

Delayed Reactions

Drug hypersensitivity reactions (DHRs) are typically classified into immediate and delayed reactions based on the time interval between drug exposure and onset of symptoms. Clinical manifestations range from mild to severe and life-threatening reactions. The most severe clinical entities are anaphylaxis and anaphylactic shock for immediate reactions, and severe cutaneous adverse reactions such as Steven Johnson Syndrome and Toxic Epidermal Necrolysis for delayed reactions. The diagnosis is complex and challenging, as drug provocation tests and even skin tests can be very risky procedures, which makes them not recommended. Therefore, it is necessary to search for useful early biomarkers to manage the diagnosis of these reactions. These biomarkers could be useful to determine the clinical entity, but not to identify the culprit drug. Some of the currently available biomarkers are few genetic associations of drug allergy with polymorphisms of human leukocyte antigen (HLA), the detection of inflammatory and lipid mediators in serum, or the detection of cytokines, chemokines, and cytotoxic markers in skin biopsies. In this literature review, it has been summarize the immunological mechanisms involved in severe reactions, both immediate and delayed, and different early biomarkers: those currently used for the diagnosis of these reactions as well as possible early biomarkers that could be useful with further studies to standardize their clinical use.

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Non-immediate drug hypersensitivity reactions secondary to intravitreal anti-vascular endothelial growth factors

Graefe s Archive for Clinical and Experimental Ophthalmology ◽

10.1007/s00417-021-05353-3 ◽

2021 ◽

Author(s):

E. Moret ◽

A. Ambresin ◽

C. Gianniou ◽

J. Bijon ◽

C. Besse-Hayat ◽

...

Keyword(s):

Growth Factors ◽

Drug Hypersensitivity ◽

Clinical Manifestations ◽

Drug Discontinuation ◽

Vascular Endothelial Growth Factors ◽

Vascular Endothelial ◽

Hypersensitivity Reactions ◽

Anti Vegf ◽

Drug Hypersensitivity Reactions ◽

Endothelial Growth Factors

Abstract Purpose To describe a series of non-immediate drug hypersensitivity reactions after intravitreal anti-vascular endothelial growth factors (anti-VEGFs). Patients and methods Retrospective report of 6 patients with cutaneous non-immediate drug hypersensitivity reactions following intravitreal anti-VEGF injections, 4 after ranibizumab, 1 after bevacizumab and 1 after aflibercept. Results Clinical manifestations ranged from mild maculopapular rash, purpura to severe generalized erythroderma, with or without systemic involvement such as microscopic hematuria and proteinuria or fever. In two out of the six patients, reintroduction of either the same or an alternative anti-VEGF drug did induce a recurrence of the drug hypersensitivity reaction, while 4 patients showed no recurrence. Conclusion Cutaneous non-immediate drug hypersensitivity reactions secondary to intravitreal anti-VEGF may occur. Continuation of the same drug or switch to another anti-VEGF may either induce recurrence or be well supported by the patient. The decision of drug discontinuation should be guided by the severity of the disease.

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ANAMNESTIC, CLINICAL AND LABORATORY DATA ANALYSIS OF PATIENTS FOR DRUG HYPERSENSITIVITY REACTIONS

Immunology and Allergy: Science and Practice ◽

10.37321/immunology.2021.3-01 ◽

2021 ◽

pp. 5-13

Author(s):

Svitlana Zubchenko ◽

Iryna Kril ◽

Marta Lomikovska ◽

Anna Havrylyuk ◽

Kristina Lischuk-Yakymovych ◽

...

Keyword(s):

Clinical Laboratory ◽

Drug Hypersensitivity ◽

Laboratory Data ◽

Clinical Manifestations ◽

Basophil Activation Test ◽

Progressive Increase ◽

Hypersensitivity Reactions ◽

Treatment Protocols ◽

Test Execution ◽

Drug Hypersensitivity Reactions

The current development of the pharmaceutical industry in the synthesis of new chemical compounds, standardized treatment protocols, and disease prevention can lead to a progressive increase in drug hypersensitivity reactions, which often have serious consequences for human health. Increasing evidence of involvement of infections, including Herpesviridae viruses, in the development of drug hypersensitivity reactions is known.The method of flow cytometry can be used, in particular, the basophil activation test to diagnose drug hypersensitivity reactions. The anamnestic, clinical, andlaboratory data of 368 people were analyzed for the selection of patients at risk of drug hypersensitivity for the basophil degranulation test execution. It was found that among patients hypersensitivity reactions were most often detected to antibiotics (50.0%), radiopaque substances (27.7%), perioperative drugs, local anesthetics - 13.6% each. Clinical manifestations of these reactions were urticaria with angioneurotic edema (40.6%), urticaria (28.1%), anaphylaxis (21.9%), obstructive bronchitis chenges (9.37%). According to anamnestic and clinical-laboratory data, patients with a high risk of drug hypersensitivity reactions revealed frequent manifestations of herpesvirus infection HSV1 (34.4%), active chronic persistence of EBV (59.4%), accompanied by manifestations of EBV-associated secondary immune disorders and prevalence of chronic EBV infection in all patients.

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ANALYSIS OF ADVERSE DRUG REACTION REPORT FORMS ON THE MEDICINES, USED FOR AIDS TREATMENT (REGISTERED IN THE REPUBLIC OF CRIMEA IN THE PERIOD FROM 2011 TO 2016)

Pharmacy & Pharmacology ◽

10.19163/2307-9266-2018-6-6-568-583 ◽

2019 ◽

Vol 6 (6) ◽

pp. 568-583

Author(s):

A. V. Matveev ◽

A. Е. Krasheninnikov ◽

E. A. Egorova ◽

E. I. Konyaeva

Keyword(s):

Quality Of Life ◽

Adverse Drug Reaction ◽

Drug Reaction ◽

Antiretroviral Therapy ◽

Adverse Reactions ◽

Clinical Manifestations ◽

Public Health Problem ◽

World Health ◽

The Republic

According to the data of the World Health Organization (WHO), human immunodeficiency virus (HIV) remains a major global public health problem.The mainmethod of treating HIV is using highly active antiretroviral therapy (HAART), which is the use of multiple medicines acting on different viral targets. The timely onset of HAART can suppress the replication of the virus in the human body and helps to strengthen its immune system and restore its ability to fight infections. At the same time, the choice of medicines to improve the quality of life and patients’ compliance during antiretroviral therapy should be based on their effectiveness and safety. The aim of this research was to analyze and study the adverse reactions that occur in patients with HIV living in the territory of the Republic of Crimea, when using HAART.Materials and methods.The objects of research were 274 report cards about the adverse reactions, registered in the regional base (registry) of spontaneous messages called ARCADe (Adverse Reactions in Crimea, Autonomic Database) for the period from 2011 to 2016.Results.The results of the study showed that the most often adverse reactions were observed when using medicines of the group of Nucleoside Reverse Transcriptase Inhibitors (NRTI). This is explained by the inclusion of NRTI medicines as the main medicine in the method of HAART. Efavirenz (EFV) and Nevirapine (NVP) were absolute leaders among these groups of antiretroviral medicines. Among the combined antiviral medicines active against HIV, the most frequently adverse reactions were associated with the use of a combination of Lamivudine (3TC) and Zidovudine (ZDV). The main clinical manifestations of adverse reactions in the use of combination medicines for treating HIV were a decrease in the level of hemoglobin and the development of anemia. At the same time, in 85% of cases, the patients needed medication in order to correct the resulting adverse drug reaction (ADR). The combination of antiretroviral therapy has often been associated with the development of serious ADR. In case of monotherapy, the main clinical manifestations of adverse reactions were disorders of the central nervous system (dizziness, hallucinations, sleep disorders) and allergic reactions of varying severity (including 1 case of angioedema to “Eferven” (Efavirenz (EFV)),600 mg). Hereby, in almost half of the cases, the usage of antiretroviral medicines of the NRTI group and protease inhibitors caused the development of serious side effects. This confirms the necessity to study and analyze adverse reactions in order to increase the safety of patients’ pharmacotherapy and improve their quality of life.Conclusion.The study of adverse reactions to the medicines used for treatment of HIV is of a paramount importance in improving the safety and compliance of HIV patients to lifelong pharmacotherapy.

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