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Epidemiology of Severe Cutaneous Drug Reactions
Published in Kirsti Kauppinen, Kristiina Alanko, Matti Hannuksela, Howard Maibach, Skin Reactions to Drugs, 2020
Maja Mockenhaupt, Erwin Schöpf
A different method for risk evaluation of drugs is provided by the case-control design. An international case-control study on severe cutaneous adverse reactions (SCAR) has been performed in France, Germany, Italy, and Portugal between 1989 and 1995.42 To date, phase I of the SCAR study, comprising data until the middle of 1993, has been analyzed and published. Altogether, 245 hospitalized patients with SJS, SJS/TEN overlap, and TEN, as well as 1147 controls were compared in terms of their drug use prior to the onset of the disease.43 The controls used in mat study were hospitalized patients admitted for reasons other than severe skin reactions or conditions related to previous drug use, mainly patients with trauma or acute infections not based on a chronic condition.42 Drugs usually taken for a short time period, and those usually given for a longer time period, e.g., months or years, were analyzed separately. Concerning drugs usually taken for a short time, the risk was increased for co-trimoxazole and other anti-infective sulfonamides, aminopenicillins, quinolones, cephalosporines (Table 2), and chlormezanone. In terms of drugs with a longer period of intake, the crude relative risk was increased for carbamazepine, phenobarbital, phenytoin, valproic acid, oxicam-NSAIDS, allopurinol, and corticosteroids. For these drugs, the risk seems to be higher during the first two months of treatment.43
Diagnostic Approach to Rash and Fever in the Critical Care Unit
Published in Cheston B. Cunha, Burke A. Cunha, Infectious Diseases and Antimicrobial Stewardship in Critical Care Medicine, 2020
Lee S. Engel, Charles V. Sanders, Fred A. Lopez
The spectrum of SJS and TEN represents the most common and most lethal of the severe cutaneous adverse reactions [101]. The mortality rate for these entities reaches 40%. The causes of SJS and TEN are similar to the etiologies of EM (Table 8.7). Unlike EM, SJS and TEN are more frequently associated with drug reactions than with viral infections. The drug classes most frequently associated with SJS and TEN are antibiotics, antivirals, anticonvulsants, and agents that affect uric acid metabolism [101]. There is often a 4- to 28-day interval between the beginning of the causative drug and the onset of signs and symptoms. The mechanism is thought to be a delayed hypersensitivity reaction mediated by Th1 cells [102]. Predisposing factors include polypharmacy, concomitant use of radiotherapy and anticonvulsants, genetic susceptibility, HIV infection, and other immunocompromised states [97,102].
Dermatological manifestations of malignancies and dermatological emergencies due to malignancy
Published in Biju Vasudevan, Rajesh Verma, Dermatological Emergencies, 2019
Drug reactions are among the most common reasons for which the dermatologist's opinion is sought by a treating hemato-oncologist, and the drugs range from trial drugs to older drugs like imatinib. The severe cutaneous adverse reaction (SCAR) pattern, drug list, and concomitant differential count in peripheral blood help narrow the causes. The Naranjo score and algorithm of drug causality in epidermal necrolysis are considered the standard assessment tools to evaluate the causality of adverse drug reactions and Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), respectively.
A real-world pharmacovigilance study of severe cutaneous adverse reactions associated with antiepileptic drug combination therapy: data mining of FDA adverse event reporting system
Published in Expert Opinion on Drug Safety, 2023
Chunyan Wei, Jingyi Zhang, Wanhong Yin, Aidou Jiang, Yin Liu, Bin Wu
Severe cutaneous adverse reactions (SCAR) are rare and life-threatening hypersensitivity reactions [1–3]. Acute generalized exanthematous pustulosis (AGEP), drug reaction with eosinophilia and systemic symptoms (DRESS), Steven-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are included in SCAR [4], all are non-immunoglobulin E (IgE)-mediated, delayed type IV hypersensitivity reactions [5]. The global incidence of SCAR is 0.4 to 1.2 cases per million per year [6], but the mortality of all SCAR ranges from 4% for AGEP, 2% to 6% for DRESS, and up to 48% for TEN [4]. The SJS and TEN are thought to be variants of the same condition [7], and the distinction between them is determined by the affected body surface area, with TEN affecting more [8]. However, the incidence of SCAR from the same drug varies in different populations, and may be more likely to occur in people aged from 40 to 56 [9,10].
Managing the ADR of Stevens-Johnson syndrome/toxic epidermal necrolysis
Published in Expert Opinion on Drug Safety, 2022
Bertrand Sheng-Yang Lian, Haur Yueh Lee
SJS/TEN, in some cases, is preventable. Firstly, 25% of severe cutaneous adverse reactions (SCARs) are a result of inappropriate prescriptions that were not consistent with good medical practice and could have been avoided [65]. For eg, allopurinol, which is the most common cause of SJS/TEN worldwide, is often prescribed without clear indications, eg. asymptomatic hyperuricemia, infrequent gout attacks, or non-specific joint pains [66,67]. Allopurinol-related cases would be reduced if treatment guidelines were adhered to. Secondly, it is now known that HLA associations with SJS/TEN exists. However, this is ethnic and drug specific. In Han Chinese, and various South-east Asian populations, there is a strong genetic association of HLA-B*1502 with Carbamazepine SJS/TEN [68–72]. Studies in these at-risk populations have demonstrated that screening of HLA-B*1502 before initiation of carbamazepine can reduce the incidence of SJS/TEN and this has been successfully integrated into routine practice [59,63]. Besides Carbamazepine, Allopurinol related severe cutaneous adverse reactions have been associated with HLA-B*5801 [70,71]. Pre-prescription screening has been advocated but cost-effectiveness limits wide implementation [73]. Although pharmacogenetic screening is promising, its utility remains limited to very few drugs in selected populations.
The democratization of de-labeling: a review of direct oral challenge in adults with low-risk penicillin allergy
Published in Expert Review of Anti-infective Therapy, 2020
Morgan Thomas Rose, Monica Slavin, Jason Trubiano
In a prospective case series over 12 months, Li et al. identified 70 adult inpatients with low-risk penicillin AALs at an Australian center with an infective diagnosis requiring beta-lactam therapy. Low-risk allergy phenotypes were defined as (I)Type A ADRs, and (II) all immune-mediated reactions excluding – (i) anaphylaxis (within 10 years), (ii) hemolytic anemia, (iii) serum sickness, and (iv) severe cutaneous adverse reactions (SCAR). Sixty-three proceeded to 3-stage graded oral challenge with amoxicillin (2.5 mg/25 mg/250 mg-30 min interval, 2 h total observation post-last dose) and completed a 3-day course of the target dose. Of these, 56 had described a suspected immune-mediated allergy history. Fifty-four of 56 completed the challenge without complication, 2 (3.6%) described delayed rash without systemic symptoms after 3 and 4 days of beta-lactam therapy, respectively. In comparison to historical controls, statistically significant reductions were seen in the length of stay, cost of antimicrobials, and overall admission costs, in addition to a reduction in the rate of readmission [48].