Diagnosis Of Adverse Drug Reactions Research Articles

The association of degree of polypharmacy before and after among hospitalised internal medicine patients and clinical outcomes: a retrospective, population-based cohort study

ObjectivesTo determine the prevalence and incidence of polypharmacy/hyperpolypharmacy and which medications are most prescribed to patients with varying burden of polypharmacy.DesignRetrospective, population-based cohort study.SettingIceland.ParticipantsIncluding patients (≥18 years) admitted to internal...

Cutaneous Adverse Drug Reactions

An adverse drug reaction is defined as any noxious, unintended, and undesired effect of a drug that occurs at doses used in humans for prophylaxis, diagnosis, or therapy. A cutaneous eruption is one of the most common manifestations of an adverse drug reaction. This chapter reviews the epidemiology, etiology, diagnosis, clinical manifestations, and differential diagnosis of adverse drug reactions, as well as laboratory tests for them. Also discussed are the types of cutaneous eruption: exanthematous eruption, urticarial eruption, blistering eruption, pustular eruption, and others. The simple and complex forms of each type of eruption are reviewed. The chapter includes 4 tables and 12 figures. Tables present the warning signs of a serious drug eruption, clinical features of hypersensitivity syndrome reaction and serum sickness-like reaction, characteristics of Stevens-Johnson Syndrome and toxic epidermal necrolysis, and clinical pearls to identify anticoagulant-induced skin necrosis. Figures illustrate hypersensitivity syndrome reaction, a fixed drug eruption from tetracycline, pseudoporphyria from naproxen, linear immunoglobulin A disease induced by vancomycin, pemphigus foliaceus from taking enalapril, pemphigus vulgaris from taking penicillamine, toxic epidermal necrolysis after starting phenytoin therapy, acneiform drug eruption due to gefitinib, acute generalized exanthematous pustulosis from cloxacillin, coumarin-induced skin necrosis, a lichenoid drug eruption associated with ramipril, and leukocytoclastic vasculitis from hydrochlorothiazide. This chapter contains 106 references.

Cutaneous Adverse Drug Reactions

An adverse drug reaction is defined as any noxious, unintended, and undesired effect of a drug that occurs at doses used in humans for prophylaxis, diagnosis, or therapy. A cutaneous eruption is one of the most common manifestations of an adverse drug reaction. This chapter reviews the epidemiology, etiology, diagnosis, clinical manifestations, and differential diagnosis of adverse drug reactions, as well as laboratory tests for them. Also discussed are the types of cutaneous eruption: exanthematous eruption, urticarial eruption, blistering eruption, pustular eruption, and others. The simple and complex forms of each type of eruption are reviewed. The chapter includes 4 tables and 12 figures. Tables present the warning signs of a serious drug eruption, clinical features of hypersensitivity syndrome reaction and serum sickness-like reaction, characteristics of Stevens-Johnson Syndrome and toxic epidermal necrolysis, and clinical pearls to identify anticoagulant-induced skin necrosis. Figures illustrate hypersensitivity syndrome reaction, a fixed drug eruption from tetracycline, pseudoporphyria from naproxen, linear immunoglobulin A disease induced by vancomycin, pemphigus foliaceus from taking enalapril, pemphigus vulgaris from taking penicillamine, toxic epidermal necrolysis after starting phenytoin therapy, acneiform drug eruption due to gefitinib, acute generalized exanthematous pustulosis from cloxacillin, coumarin-induced skin necrosis, a lichenoid drug eruption associated with ramipril, and leukocytoclastic vasculitis from hydrochlorothiazide. This chapter contains 106 references.

Cutaneous Adverse Drug Reactions

An adverse drug reaction is defined as any noxious, unintended, and undesired effect of a drug that occurs at doses used in humans for prophylaxis, diagnosis, or therapy. A cutaneous eruption is one of the most common manifestations of an adverse drug reaction. This chapter reviews the epidemiology, etiology, diagnosis, clinical manifestations, and differential diagnosis of adverse drug reactions, as well as laboratory tests for them. Also discussed are the types of cutaneous eruption: exanthematous eruption, urticarial eruption, blistering eruption, pustular eruption, and others. The simple and complex forms of each type of eruption are reviewed. The chapter includes 4 tables and 12 figures. Tables present the warning signs of a serious drug eruption, clinical features of hypersensitivity syndrome reaction and serum sickness-like reaction, characteristics of Stevens-Johnson Syndrome and toxic epidermal necrolysis, and clinical pearls to identify anticoagulant-induced skin necrosis. Figures illustrate hypersensitivity syndrome reaction, a fixed drug eruption from tetracycline, pseudoporphyria from naproxen, linear immunoglobulin A disease induced by vancomycin, pemphigus foliaceus from taking enalapril, pemphigus vulgaris from taking penicillamine, toxic epidermal necrolysis after starting phenytoin therapy, acneiform drug eruption due to gefitinib, acute generalized exanthematous pustulosis from cloxacillin, coumarin-induced skin necrosis, a lichenoid drug eruption associated with ramipril, and leukocytoclastic vasculitis from hydrochlorothiazide. This chapter contains 106 references.

Adverse drugs reactions (ADR) suspected through phone triage and assessed by medically staffed ambulances: A pilot study

BackgroundPrompt and definitive diagnosis of adverse drug reactions (ADRs) is a challenge for health care providers. There is a global burden of ADRs worldwide associated with a negative impact on the patient's health, in parallel with increasing costs for the community.This study aims to determine the annual incidence of ADRs in the cohort of patients requiring immediate intervention of the French prehospital emergency medical service (PEMS). The definitive diagnosis of ADR was provided by the follow-up of the entire course of hospitalization from PEMS presentation to final discharge in each suspected case. MethodsA retrospective study examining the incidence of ADR at the Paris PEMS was performed in 2015. ResultsFrom January the 1st to December the 31st, 2015, 485 cases of suspected ADR were selected. Twenty-eight patients could not be identified at the hospital and were considered as lost to follow-up. For the 457 cases with the final diagnosis and outcome available, 359 had a definitive and new diagnosis of ADR, 9 were related to substance of abuse and alcohol, 14 were duplicates and 75 were excluded by drug causality was ruled out. Long-term follow-up was performed for 359 cases. Among them, 22 patients (6.1%) died of an ADR.Twenty-five severe ADRs were notified for children ages 2 to 16 with a cluster of 9 cases (36%) resulting from an accidental outbreak of poisonings with alimemazine in a classroom. No fatality was reported among children suffering from an ADR. ConclusionThe collaboration between PEMS and in hospital Pharmacovigilance Centre is feasible from the PEMS report to the long-term follow-up. The definition of a clinical pattern for some drugs is needed to allow the medical team to anticipate the clinical outcome of the involved patient and therefore adapting the patient's support as soon as possible.

Challenges in Diagnosis and Management of Cutaneous Adverse Drug Reaction

Adverse drug reactions commonly involve the skin and represent a significant proportion of all drug‐induced illnesses. Most of the times, adverse cutaneous reactions are not severe and only a few are fatal. Real incidence of cutaneous adverse drug reaction is not known. Due to rampant and multiple drug use, there is difficulty finding the culprit drug, so diagnosis of adverse drug reaction and management becomes difficult.

Skin tests in the diagnosis of adverse drug reactions.

Adverse drug reactions (ADRs) are common and influence negatively the patient's therapeutic options. They recognize multiple pathogenic mechanisms, some of immunological origin, and the clinical manifestations involve several organs and systems, including skin and/or mucous membranes in 25-30% of patients. The identification of the trigger drug remains a medical challenge, mainly in poly-medicated patients. Anamnesis and clinical approach are crucial, but allergy work-up is the essential tool to confirm or exclude the causative role of the culprit drug. Besides in-vitro tests and drug provocation test, skin tests (ST) represent the cornerstone: patch test in delayed ADR, prick test in immediate ADR, and intradermal test in both. Nevertheless, ST are in continuous evolution and characterized by technical difficulties (concentration and vehicle) that can influence their value and specificity. In this article we review the indications and the rules in performing patch test, prick test, and intradermal test with the most commonly used drugs in Italy to determine the cause of a cutaneous and/or mucous ADR, precise the involved pathogenic mechanism, and provide a valid therapeutic alternative to the patient.

Evaluation of drug provocation tests in Korean children: a single center experience.

Drug provocation tests (DPTs) are difficult to perform in clinical practice, even though they are the gold standard for the diagnosis of adverse drug reactions (ADRs). The aims of this study were to evaluate the common causative drugs of type B ADRs and to analyze the relationships between host factors and the results of DPTs in Korean children. We retrospectively reviewed the medical records of all children younger than 19 years of age who underwent a DPT between November 1994 and November 2014. Open provocation tests were performed with non-steroidal anti-inflammatory drugs (NSAIDs), acetaminophen, aminopenicillins, cephalosporins, non-β-lactam antibiotics, antiepileptic drugs, or other drugs. Overall, 84 DPTs were performed in 56 patients whose median age was 7.5 years (range, 6 months to 18 years). DPTs were positive in 25 (29.8%) of 84 cases, which translated to 18 (32.1%) positive findings in 56 patients. Drugs that provided positive results included NSAIDs (7 cases, 28.0%), aminopenicillins (5 cases, 20.0%), acetaminophen (4 cases, 16.0%), cephalosporins (3 cases, 12.0%), and non-β-lactams (2 cases, 8.0%). Anaphylaxis was noted in 5 (20.0%) of 25 cases. There were no serious complications of DPTs in any of the subjects. The median age was 10.5 years for children who had a positive result following the DPT and 5.0 years for those with negative results (P value = 0.019). DPTs can be performed safely in children with suspected ADRs in order to achieve a correct diagnosis.

Paracetamol induced fi xed drug eruptions: A case report

To report a case of fi xed drug eruption (FDE) due to paracetamol intake. FDE is cutaneous reactions in already sensitized individuals. The characteristic of FDE is recurrence at same site on repeated insults with the off ending drug. Paracetamol induced FDE is widely reported in children and adolescents but not among elderly individuals. A 62-year-old male patient had a chief complaint of burning sensation in lips and oral cavity since 3 days. History revealed intake of paracetamol. Encrusted lesions were present on the cutaneous surfaces of lips, and erythematous areas were present on the anterior third of the hard palate. Based on Naranjo’s casualty assessment scale, provisional diagnosis of adverse drug reaction (ADR) was given. All drugs were stopped, but the patient had a similar episode of such lesions on the same site after 8 weeks. This establishes the diagnosis of FDE due to paracetamol ingestion. Though paracetamol is widely used and is considered a safe drug, ADR to it are possible and reported earlier. Clinical signifi cance: Reporting of FDE to dentist is uncommon. But on encountering such a situation, the dentist should be able to identify FDE and isolate the causative drug by means of history. A simple clinical assessment scale like Naranjo’s casualty assessment scale can establish the presence of ADR.

A Case of Acute Pulmonary Thromboembolism after Taking Tadalafil

Tadalafil is a phosphodiesterase-5 inhibitor (PDE5I), which is widely used to treat erectile dysfunction. Although PDE5Is have excellent safety profiles, and most of the side effects are mild, rare serious adverse events have been reported in association with PDE5Is. Thrombosis is one of those events, and a few previous reports have suggested the association of PDE5Is with thrombosis. We report the case of a 61-year-old male who developed pulmonary embolism combined with pulmonary infarction directly after taking tadalafil. Both the patient and the physician suspected tadalafil as the culprit drug, as the patient was in an otherwise healthy condition. However, after extensive evaluation, we noticed that factor VIII levels were elevated. Prior reports suggesting the association between thrombosis and PDEIs either lack complete information on coagulation factors, or show inconsistencies in their results. Physicians should operate caution prior to accepting the diagnosis of adverse drug reaction.

Focus on headache as an adverse reaction to drugs

There are a large number of drugs inducing headache as an adverse reaction. Nevertheless, headaches as adverse reactions to drugs have received limited attention. Non-serious adverse reactions, such as headache, are not quantified and described as accurately as serious, life threatening ones. However, non-serious reactions can also be extremely troublesome, above all when they are chronic: they can affect patients’ quality of life and contribute to non-compliance. It is absolutely possible that the number of patients with headache as an adverse reaction, which is going to increase, considering the growing use of medications. Physicians should, therefore, be aware of this issue. Indeed, it is difficult to attribute the diagnosis of adverse drug reaction to a condition, headache, which is also a very common symptom in general population.

Mechanisms of Drug Hypersensitivity Reactions and the Skin

The skin is an organ most often affected by adverse drug reactions. Because of limited reactivity of the skin, different drugs may induce the same reactions on the skin, even if the same drug may induce different adverse drug reactions. Many of these adverse drug reactions do not include immunological mechanisms, most of them are non-immunological processes. Adverse drug reactions which involve an immune system, may appear different times after drug administration. The severity of reactions is not dependent on the time at which adverse drug reaction appeared, even if some life threatening adverse drug reactions appear immediately after a drug administration. Four types of immunological reactions, (according to Cooms and Gell), may be involved in a drug adverse reaction. The first type of reaction (anaphylactic reaction) begins early after drug administration and different severities of the reactions could exist. The second type, known as cytotoxic hypersensitivity, begins after some minutes to a few hours after a drug administration. Third and fourth types of immunological reactions begin usually hours to days after drug administration. Some types of immunological reactions may begin days to weeks after drug administration. Sensitization to the drugs must be happen early, since re-exposition to the drug leads to the adverse drug reactions. The way of sensitization sometimes determines which immune mechanism will be involved and which clinical reaction will appear. Tests in vivo and in vitro can be used in the diagnosis of adverse drug reactions. All these tests are more or less limited to a false positive or false negative reaction and possibilities of serious reactions in tests. Provocations tests give the most satisfactory results but they may be dangerous and life threatening. We must carefully choose the skin tests and apply them according to the suspected pathomechanism of adverse drug reaction geneses and estimate the usefulness and the risks of the tests. Serious adverse drug reactions (i.e. Sy Steven-Johnson, lupus-like disease etc.) should not be tested. Some novel patents will have important implications in administration, diagnosis, and prevention of adverse drug reactions.

Anaphylaktischer Schock nach Injektion von Solu-Decortin H

The diagnosis of adverse drug reactions is mostly a difficult job. In the reported case an anaphylactic shock was investigated which occurred during a general anaesthesia.

Headache: One of the Most Common and Troublesome Adverse Reactions to Drugs

It is difficult to attribute the diagnosis of adverse drug reaction to a condition which is also a common symptom. The decision might be arduous in the case of headache, because this disorder is very frequent in the general population. The drugs that more frequently induce headache belong to a variety of therapeutic classes with different mechanisms of action and different toxicity. In the majority of cases the headache has not a typical feature, it is dose-dependent, and is associated to other symptoms of neurotoxicity. Some drugs cause, instead, a specific headache: this is the case of NO donors, which are also used in experimental studies in order to induce headache. This review describes the classes of drugs which induce headache, analyzes the frequency of headache induction among the drugs of the same class, and discusses the possible mechanisms underlying headache induction. It is to be hoped that a better awareness of this issue would help the physician to consider it in the differential diagnosis of a recent-onset or changed headache and to avoid prescription of drugs known to cause headache to patients already suffering from this disorder.

IN VIVO AND IN VITRO TESTING FOR ADVERSE DRUG REACTIONS

The goal of providing an accurate and reliable diagnostic test for the evaluation of adverse drug reactions remains elusive. Rechallenge remains a truly conclusive method for determining the contribution of drugs to adverse effects, but there are significant disadvantages in exposing patients to drugs that may have caused serious adverse effects. Skin tests are useful for the assessment and predictive risk of serious adverse reactions for a small number of drugs, but skin tests are limited in their utility to adverse drug reactions mediated by Type 1 hypersensitivity. Skin tests must be performed with care and rigor as well. There are a number of in vitro assays that have been used for the assessment of adverse drug reactions, but many of these assays are primarily research tools and have little utility in the clinical setting. Although in vitro tests are not yet readily available for the diagnosis of adverse drug reactions, our increasing understanding of the biology of adverse drug reactions and interactions between the immune system and xenobiotics offers promise that more clinically relevant assays can be developed. At the present time, the primary diagnostic tools for the assessment of adverse drug reactions remain a careful history and physical examination and an astute, insightful physician.

Medical Knowledge: The Essential of Causality Assessment

As drug-induced disorders now occupy an increasing place in the activities of the pharmaceutical industry and the regulators, as well as in the diagnostic process of prescribers, every practitioner should ask himself whether the occurrence of an abnormality is the consequence of the treated disease or of its treatment. This is particularly true in the domains which are the main targets of drug toxicity, such as skin, blood, and liver, but it applies to all other clinical or laboratory abnormalities as well. Therefore, a physician must be aware of the most frequent causes of abnormalities and the simplest tests to detect them. Three examples of the advantages of the medical approach for diagnosis of adverse drug reactions demonstrate that quality of information and drug causality assessment are inseparable.

Macrophage migration inhibition factor release in lichenoid drug eruptions

Lichenoid drug eruption (DE) that can clinically and histologically resemble lichen planus (LP) can be induced by gold, thiazide diuretics, quinidine, and other agents. 1, 2 Lichenoid DE, which in general spares the mucous membranes, may be photodistributed or nonphotodistributed.P Common causes of photodistributed lichenoid DE are thiazide diuretics- and quinidine.': 5 The mechanism by which drugs induce a lichenoid tissue reaction is unknown. Recent observations support a critical role of helper/inducer T lymphocytes in lichenoid tissue reaction. In isolated cases of lichenoid photosensitive DE induced by hydrochlorothiazide or quinidine, positive macrophage migration inhibition factor (MIF) responses toward the offending drugs were recorded.f5 MIF is a lymphokine released from sensitized T lymphocytes by an appropriate antigen. The expression of MIF activity correlates well with delayed hypersensitivity and cellular immunity in animal models and in humans.71O Furthermore, MIF release has been recently reported to be valuable in the diagnosis of adverse drug reactions, including DE,ll-15 The present study was conducted to evaluate MIF release in patients with lichenoid DE induced by various drugs.

Advances in the diagnosis of adverse drug reactions.

The clinician plays a key role in the detection and diagnosis of adverse drug reactions (ADRs). The diagnosis of ADRs, however, is a complex task. In the past, there were no systematically applied diagnostic criteria for ADRs, no formal methods of case analysis, no standardized epidemiologic approaches, and a limited knowledge of mechanisms. This resulted in the overdiagnosis of ADRs, which has negative consequences such as limiting treatment options. Recently, there have been various improvements in the diagnosis of ADRs, such as the development of standardized decision aids and of in vitro diagnostic tests. This article briefly reviews some of this knowledge, discusses the role of in vivo and in vitro rechallenge, and summarizes a probabilistic approach for collecting relevant information and diagnosing ADRs. The intention is to increase awareness of the different approaches for diagnosing ADRs as well as to stimulate researchers to continue to collect pharmacoepidemiologic information, study the pharmacologic, immunologic, and genetic factors involved in the pathogenesis of drug reactions, and develop and test new diagnostic instruments under various clinical conditions.

1 Criteria for the diagnosis of adverse drug reactions

In some instances it is obvious when an adverse cli drug. Often, however, this diagnosis is difficult, establishment of a cause-and-effect relationship are ambiguous (Koch-Weser et al, 1977); and in such cases a formalized evaluation, with the aid of a questionnaire or an algorithm, is useful (Busto et al, 1982; Hutchinson et al, 1983; Kramer et al, 1979; Naranjo et al, 1981; Schmidt et al, 1986). A formalized approach ensures a comprehensive evaluation, particularly when it is important not to overlook pertinent details. A guide to the procedure is given in Table 1. The adverse reaction may be classified as ‘definite’, ‘probable’, ‘possible’ or ‘unlikely’. Looking at the first of these criteria, it becomes clear that one of the most important aspects is general knowledge about the adverse reactions of specific organ systems to specific drugs. In view of the large number of drugs nowadays available, this knowledge can no longer be part of the ordinary diagnostic armamentarium of general physicians or gastroenterologistseven highly experienced physicians will have to consult reference books. The purpose of this volume of Clinical Gastroenterology is therefore to provide an up-to-date compilation of adverse reactions in this field. In contrast, the second point-the diagnostic alternatives-is part of the practice of gastroenterology and deserves no further comments. Nevertheless, the frequency of symptoms in otherwise healthy subjects-the-so-called ‘non-drug reactions’-has often been overlooked (Reidenberg and Lowenthal, 1968). It is easy to establish a satisfactory temporal relationship between a suspected adverse drug reaction and the administration of the drug, if the reaction occurs soon after the first dose and disappears rapidly upon discontinuation of therapy. This, however, may not always apply, particularly in cases of chronic therapy. For example, hepatitis may occur as late as six to eight months after initiation of therapy with isoniazid, and cholestasis may not disappear for years after cessation of treatment with ajmaline. In these instances it is helpful to verify that peculiar temporal relationships may occur with some drugs. Re-exposure to the offending agent, followed by recurrence of the clinical event, provides one of the strongest arguments in favour of the diagnosis of an

Operational criteria for adverse drug reactions in evaluating suspected toxicity of a popular scabicide.

A recently developed algorithm for the diagnosis of adverse drug reaction (ADR) was used to investigate the quality of evidence in reported cases of ADRs to 1% gamma benzene hexachloride (GBH), a popular scabicide and pediculicide currently under suspicion as a cause of central nervous system (CNS) toxicity, especially in children. Of the 53 reported cases of alleged toxicity, 37 were associated with lindane insecticide (greater than 1% GBH), which is not a pharmaceutical preparation. Of these 37 cases, 34 scored as definite or probable reactions on the algorithm. Of the 26 reports associated with the drug, 1% GBH, none scored as definite and only 6 as probable ADRs. Of these 6 probable cases, 5 represented inappropriate application or unintended ingestion. The use of rigorous operational criteria, such as those developed in this algorithm, permits a scientifically disciplined assessment of whether or not a drug has been fairly indicted, and also provides valuable clinical information about other aspects of suspected drug toxicity.