Acute Adverse Drug Reaction Research Articles

Positive drug patch tests and the acute cutaneous adverse drug reaction share many histopathologic features

Positive drug patch tests and the acute cutaneous adverse drug reaction share many histopathologic features

Kidney and Liver Tissue Tacrolimus Concentrations in Adult Transplant Recipients-The Influence of the Whole Blood and Tissue Concentrations on Efficiency of Treatment during Immunosuppressive Therapy.

Tacrolimus (TAC) has a narrow therapeutic index and highly variable pharmacokinetic characteristics. Close monitoring of the TAC concentrations is required in order to avoid the risk of acute rejection or adverse drug reaction. The results in some studies indicate that inter-tissue TAC concentrations can be a better predictor with regards to acute rejection episode than TAC concentration in whole blood. Therefore, the aim of the study was to assess the correlation between dosage, blood, hepatic and kidney tissue concentration of TAC measured by a validated liquid chromatography tandem mass spectrometry (LC-MS/MS) and clinical outcomes in a larger cohort of 100 liver and renal adult transplant recipients. Dried biopsies were weighed, mechanically homogenized and then the samples were treated with a mixture of zinc sulfate—acetonitrile to perform protein precipitation. After centrifugation, the extraction with tert-butyl methyl ether was performed. The analytical range was proven for TAC tissue concentrations of 10–400 pg/mg. The accuracy and precision fell within the acceptance criteria for intraday as well as interday assay. There was no correlation between dosage, blood (C0) and tissue TAC concentrations. TAC concentrations determined in liver and kidney biopsies ranged from 8.5 pg/mg up to 160.0 pg/mg and from 7.1 pg/mg up to 215.7 pg/mg, respectively. To the best of our knowledge, this is the first LC-MS/MS method for kidney and liver tissue TAC monitoring using Tac13C,D2 as the internal standard, which permits measuring tissue TAC concentrations as low as 10 pg/mg.

Treating Through Drug-Associated Exanthems in Drug Allergy Management: Current Evidence and Clinical Aspects

In the setting of an acute cutaneous adverse drug reaction there is increasing interest in selected phenotypes and hosts to continue drug therapy, especially in settings in which there are limited therapeutic options. This concept of "treating through," defined as the continued use of a drug in the setting of, in particular maculopapular exanthema, potentially avoids unnecessary drug discontinuation. A review of the recent literature, historical viewpoints, and expert opinion are provided within to form recommendations and algorithms for a "treating-through" approach.

Antipsychotics and Risk of Neuroleptic Malignant Syndrome: A Population-Based Cohort and Case-Crossover Study.

Neuroleptic malignant syndrome (NMS) is a rare and acute adverse drug reaction associated with antipsychotic therapy. However, few data on the risk and epidemiology of NMS are available. The aim of this study was to ascertain the incidence risk and all-cause mortality of NMS associated with antipsychotic use, and to assess the association of recent antipsychotic exposure and NMS. We did a population-based study using data from the Hong Kong Hospital Authority's Clinical Data Analysis and Reporting System database. Cases had a first diagnosis of NMS between 1 January 2004 and 30 November 2017. A case-crossover analysis was used to compare antipsychotic exposure 30 days before the diagnosis of NMS (index date) and a reference period 91-120 days before the index date. To adjust for potential time trends in antipsychotic exposure, we sampled from cases to match current cases and future cases, and further adjusted for select medications and acute medical conditions. 297,647 patients were prescribed antipsychotics, and the incidence risk of NMS was 0.11%. Of the 336 cases included in the case-crossover analysis, 20 (6%) died within 30 days after the index date; only one case had NMS recorded as the primary cause of death. When compared with the reference period, cases were more frequently prescribed multiple antipsychotics (15.8% vs 26.8%; standardized mean difference [SMD] 0.27) and short-acting injectable antipsychotics (3.6% vs 13.7%; SMD 0.37) during the 30 days prior to the diagnosis of NMS. Odds ratios for antipsychotic exposure in the case-crossover, case-crossover adjusted for time trend, and case-crossover adjusted for time trend and potential confounders analysis were 8.00 (95% confidence interval 3.42-18.69), 5.88 (2.46-14.04), and 4.77 (1.95-11.66). Our results suggest that recent use of antipsychotics is associated with NMS. Although a case-only design inherently controls for confounding by time-invariant factors, residual confounding by acute medical conditions with similar presentations to NMS cannot be fully excluded.

Carbamazepine-induced DRESS syndrome: a case report

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a potentially life-threatening, idiosyncratic, acute adverse drug reaction. Fever, morbilliform cutaneous eruption, and eosinophilia are essential features for the diagnosis of this syndrome, along with significant multisystem involvement, hepatitis being the most common, followed by nephritis. The pathogenesis of DRESS syndrome is not yet fully understood. Several hypotheses have been proposed which support the involvement of an intricate interplay of multiple factors. We report a clinical case of DRESS syndrome with renal injury, induced by carbamazepine, in a patient with alcohol abstinence syndrome. In order to define the case, the RegiSCAR score and the Japanese Group score, used in the diagnosis of drug-induced hypersensitivity, were applied. DRESS syndrome is a potentially fatal disease, with a mortality that can reach up to 40% of cases. This condition endangers the patient's life by affecting the internal organs, mainly the liver, kidneys, heart, and lungs. Our case attempts to increase awareness among physicians about this serious disease and the importance of early diagnosis, especially since carbamazepine is a commonly used anticonvulsant drug.

Drug reaction with eosinophilia and systemic symptom induced by carbamazepine: a case report

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a severe, potentially life-threatening acute adverse drug reaction (ADR), typically characterized by a long latency period (2-6 weeks to 3 months) from drug exposure. DRESS syndrome is defined by the presence of fever, cutaneous eruption, lymphadenopathy, systemic or asymptomatic internal organ involvement (e.g. Hepatitis, carditis, interstitial nephritis, interstitial pneumonitis, etc.) and haematological abnormalities, mainly leucocytosis, eosinophilia and sometimes atypical lymphocytosis. There are around 50 culprit drugs which cause DRESS syndrome e.g. carbamazepine, phenytoin, allopurinol, sulfa derivatives, antidepressants, antiepileptics, non-steroidal anti-inflammatory drugs and antimicrobials. The incidence of DRESS syndrome has been estimated to be between 1 in 1,000 and 1 in 10,000 drug exposures. There are many reported cases of DRESS syndrome due to carbamazepine, phenytoin, vancomycin, levitiracitam, ceftriaxone etc. Author presented a case of DRESS syndrome by carbamazepin. RegiSCAR and Japanese consensus group have developed specific criteria for making the diagnosis of DRESS syndrome. The patient described here met the majority of criteria according to RegiSCAR scoring guidelines for a diagnosis of DRESS syndrome induced by carbamazepine. As per RegiSCAR diagnostic criteria author had concluded that this was a “Definite” case of DRESS (Drug Reaction with Eosinophilia and Systemic Symptom) syndrome induced by carbamazepine. Carbamazepine is most common broad-spectrum antiepileptic drugs so, this case report will raises awareness among physician to suspect DRESS syndrome in patients who present unusual complaints and skin findings after starting antiepileptic drugs.

Diclofenac Rechallange Induced Fatal Toxic Epidermal Necrolysis

Lyell’s syndrome or toxic epidermal necrolysis is an acute and severe cutaneous adverse drug reaction with a significant morbidity and mortality. It is a very rare condition but a vital emergency with a poor prognosis. The diagnosis is clinical and confirmed by a cutaneous biopsy showing a necrosis of the epidermis. It can be due to a many drugs including non steroidal anti-inflammatory drugs. We report a case of fatal Lyell’s syndrome after oral readministration of diclofenac in a patient with a history of diclofenac related Stevens-Johnson syndrome four years previously.

Premedications for infliximab infusions do not impact the risk of acute adverse drug reactions

ObjectiveThe purpose of this study was to identify the association of premedication with the adverse drug reaction (ADR) rate in infliximab infusions.DesignA retrospective chart review of 684 patients who received...

Immunocompromised Patient with Bilateral Pulmonary Infiltrates (Docetaxel Induced Hypersensitivity Interstitial Pneumonitis)

A middle-aged lady admitted with metastatic breast cancer developed acute respiratory problems with bilateral pulmonary infiltrates after five days of cytotoxic administration, as an acute adverse drug reaction to the docetaxel that resolved completely after high dosage of dexamethasone.

The Safety of Infliximab Infusions in the Community Setting

Tumour necrosis factor-alpha (TNFalpha) has an important role in the pathogenesis of inflammatory conditions such as rheumatoid arthritis, Crohn's disease, ulcerative colitis and psoriasis. Infliximab, a chimeric anti-TNFalpha monoclonal antibody, has been shown to reduce the severity of symptoms or induces remission of active disease. Infusions have generally been limited to the hospital setting due to cost and concerns for patient safety. Studies defining its efficacy and safety have, therefore, originated almost exclusively from hospital settings. To evaluate the safety of infliximab in a community clinic environment, across all types of patients. A retrospective chart review of 3161 patients who received a combined 20,976 infusions at a network of community clinics over 16.5 months was conducted. Adverse drug reaction (ADR) information was retrieved and coded for time of onset, severity and outcome. Only ADRs that occurred during or within the first 24 h of the infusion were included. A total of 524 (2.5% of all infusions) acute ADRs in 353 patients (11.2%) were recorded. Most reactions (ie, ADRs) were mild (n=263 [50.2%, 1.3% of all infusions]) or moderate (n=233 [44.5%, 1.1% of all infusions]). Twenty-eight reactions (5.3%, 0.1% of all infusions) were severe. Emergency medical services were called to transport patients to hospital for seven of the severe reactions, of which none required admission. As per pre-established medical directives, adrenaline was administered three times. Infliximab infusions are safe in the community setting. Severe ADRs were rare. None required active physician intervention; nurses were able to treat all reactions by following standardized medical directives.

Amiodarone-Induced Cutaneous Leukocytoclastic Vasculitis after Cardiac Surgery

Objective: To remind physicians and pharmacists of the potential of amiodarone to cause leukocytoclastic vasculitis (LCV) as a potentially serious acute adverse drug reaction, and that the cornerstone of treatment for LCV is identification and removal of the etiologic agent (usually a drug such as amiodarone). Case Summary: A 70-year-old white male who underwent aortic valve replacement developed cutaneous LCV (without serious systemic involvement) 2 days after treatment with amiodarone 800 mg/day was initiated. Amiodarone was discontinued and the rash almost completely resolved within 48 hours. Amiodarone 400 mg/day was restarted 13 days later and arthralgias and palpable purpuric lesions reappeared in the same distribution, but much more extensively, within 2 days. Amiodarone was discontinued and, once again, arthralgias and skin lesions resolved within 1 week. Discussion: Photosensitivity and the development of blue/grey skin pigmentation are the most commonly and classically recognized cutaneous adverse drug reactions (ADRs) of long-term use of amiodarone. LCV, the most common small-vessel necrotizing vasculitis as an acute ADR to amiodarone, is rare, but needs to be considered in day-to-day clinical practice. The Naranjo probability scale suggested a highly probable association between LCV and the use of amiodarone in our patient. Conclusions: To the best of our knowledge, this is the first case report of LCV occurring in a post–cardiac surgery setting with the use of amiodarone. Cardiothoracic surgeons, cardiologists, other treating physicians and pharmacists should be aware of this rare but potentially serious adverse event related to amiodarone.

Use of intravenous immunoglobulin for the treatment of toxic epidermal necrolysis and Stevens-Johnson/toxic epidermal necrolysis overlap syndrome. Review of 15 cases

Toxic epidemial necrolysis (TEN) is an acute adverse drug reaction, that has an unpredictableprogression and a 30% mortality. The incidence of TEN in the general population is approximately 0.4 to 1.2 cases/million/year. It is characterized pathologically by keratinocyte apoptosis which leads to epidemial detachment. Keratinocyte apoptosis is triggered by activation of the Fas-FasL, pathway and could be prevented by the use of intravenous immunoglobulin (IVIG). To report the experience with the use of IVIG in TEN. Retrospective study of 15 patients with a diagnosis of Stevens-Johnson/TEN overlap (SJS/TEN) or TEN, that received a total dose of 23 +/- 0.6 mg/kg ofIVIG over aperiod of 3 to 4 days. The infusión was initiated during thefirst 24 hours after diagnosis and was associated with standard care for burn victims. Steroids were avoided if the patient was not in chronic steroidal therapy. Allpatients responded to IVIG in a lapse of 46.4 +/- 14.2 hours from the beginning of infusión. Eighty percent of patients survived, but one developed acute renal failure due to IVIG, and another became blind due to corneal opacities, a complication of TEN. Those who survived were discharged after a lapse of 19-8 +/- 6.6 days from the beginning ofthe disease. Despite the lack of blind, multicentric and randomized triáis, we agree with some international studies that TVIG is beneficial as a treatment for SSJ/NETand TEN .

Uso de inmunoglobulina humana endovenosa en pacientes con necrolisis epidérmica tóxica y síndrome de sobreposición Stevens Johnson necrolisis tóxica epidérmica

Toxic epidemial necrolysis (TEN) is an acute adverse drug reaction, that has an unpredictableprogression and a 30% mortality. The incidence of TEN in the general population is approximately 0.4 to 1.2 cases/million/year. It is characterized pathologically by keratinocyte apoptosis which leads to epidemial detachment. Keratinocyte apoptosis is triggered by activation of the Fas-FasL, pathway and could be prevented by the use of intravenous immunoglobulin (IVIG).To report the experience with the use of IVIG in TEN.Retrospective study of 15 patients with a diagnosis of Stevens-Johnson/TEN overlap (SJS/TEN) or TEN, that received a total dose of 23 +/- 0.6 mg/kg ofIVIG over aperiod of 3 to 4 days. The infusión was initiated during thefirst 24 hours after diagnosis and was associated with standard care for burn victims. Steroids were avoided if the patient was not in chronic steroidal therapy.Allpatients responded to IVIG in a lapse of 46.4 +/- 14.2 hours from the beginning of infusión. Eighty percent of patients survived, but one developed acute renal failure due to IVIG, and another became blind due to corneal opacities, a complication of TEN. Those who survived were discharged after a lapse of 19-8 +/- 6.6 days from the beginning ofthe disease.Despite the lack of blind, multicentric and randomized triáis, we agree with some international studies that TVIG is beneficial as a treatment for SSJ/NETand TEN .

Afrontar los estragos de la heroína: evaluación de diez años de un programa integral en Barcelona

The epidemic of heroin use began in Barcelona, as in the rest of Spain, in the late 70's, to reach its peak by the end of the 80's. In a first period, responsible officers experimented difficulties to define the specific objectives of opiate control policies. This paper reviews the effects of the adoption of an explicit policy on drug dependence grounded on a wide consensus in the City of Barcelona (Catalonia, Spain). Over a period of twelve years, from 1986 to 1997, both demand and offer of care and harm reduction services were analyzed, as well as the evolution of the adverse effects of drug use, such as mortality from acute adverse drug reaction, human immunodeficiency virus (HIV) infection, aids incidence, and incidence of tuberculosis. Data for city residents was compared through four different stages in this period. Despite the lack of data in initial years, relevant changes are apparent. Treatment offer changes clearly, with significant increases in initial treatment, coverage of methadone maintenance programmes, and sterile syringes distribution. Therapeutic compliance of tuberculous intravenous drug users IVDU and risk of HIV infection improve. Emergency service use linked to heroin, overdose, or withdrawal syndrome decreases. Mortality rates decline, although this decline does not reach statistical significance. Service offer shows a clear increase, reflected in treatment initiation, while harm reduction services expand. With the development of this process, outcome indicators change, both reflecting changes in the toll of the heroin epidemic (cases of tuberculosis and aids among IVDUs, HIV infection). and changes in a more comprehensive care (better treatment compliance of IVDUs with tuberculosis). There is a lower distortion of emergency services. These changes occur although the predominance of white heroin in Barcelona favors parenteral use.

An Acute Adverse Drug Reaction Alerting Scheme Using the Saskatchewan Health Datafiles

Medical record linkage offers potential benefits for postmarketing surveillance. The Saskatchewan Health datafiles record administrative information, which is linkable using unique numbers issued to each resident. The value of these datafiles in an acute adverse drug reaction (ADR) alerting scheme has been assessed using 2 nonsteroidal anti-inflammatory drugs (NSAIDs). The first 20 000 patients who were dispensed piroxicam and the first 20 000 who were dispensed sulindac were followed over the year after their initial prescription of the relevant drug and all medical events occurring during treatment were recorded. The most frequent ADRs to NSAIDs are gastrointestinal problems. Although the rate of abdominal pain/swelling in the first month after the initial prescription was significantly greater than that in the succeeding 6 months among both drug groups, there was no strong indication of serious acute gastrointestinal ADRs in either group. Nevertheless, the results indicate that the use of administrative datafiles in a systematic evaluation of acute ADRs is a feasible and practical prospect.