Severe Delayed Drug Reactions

Pavlos, Rebecca; White, Katie D.; Wanjalla, Celestine N.; Mallal, S.; Phillips, Elizabeth

doi:10.1016/j.iac.2017.07.007

Cited by 25 publications

(13 citation statements)

References 214 publications

(108 reference statements)

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“…In addition to causing HSRs through immunologic mechanisms, drugs can also be implicated as the cause through coincidential association with a viral exanthem or through drug-infection interactions. [13] A notable example of a drug-infection interaction is the rash observed with Epstein-Barr virus and amino-penicillin treatment, present in at least 30% of such patients. [14] Bacterial (eg, rash and mucositis associated with Mycoplasma pneumoniae) and viral (eg, herpes simplex virus) infections are directly linked to the onset of erythema multiforme mimicking Stevens-Johnson syndrome.…”

Section: Classification Presentation and Mechanismmentioning

confidence: 99%

“…[14] Bacterial (eg, rash and mucositis associated with Mycoplasma pneumoniae) and viral (eg, herpes simplex virus) infections are directly linked to the onset of erythema multiforme mimicking Stevens-Johnson syndrome. [13] A more traditional illness that resembles Stevens-Johnson syndrome and toxic epidermal necrolysis has also been associated with viruses such as Coxsackie A6. [15] Viral reactivation to human herpesvirus (HHV) 6 and 7, cytomegalovirus, and Epstein-Barr virus has been described and thought to occur as a consequence of regulatory T-cell expansion and the immune dysregulation associated with DRESS, rather than as a trigger of DRESS syndrome.…”

Section: Classification Presentation and Mechanismmentioning

confidence: 99%

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Antibiotic allergy

et al. 2019

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Antibiotics are the commonest cause of life-threatening immune-mediated drug reactions that are considered off-target, including anaphylaxis, and organ-specific and severe cutaneous adverse reactions. However, many antibiotic reactions documented as allergies were unknown or not remembered by the patient, cutaneous reactions unrelated to drug hypersensitivity, drug-infection interactions, or drug intolerances. Although such reactions pose negligible risk to patients, they currently represent a global threat to public health. Antibiotic allergy labels result in displacement of first-line therapies for antibiotic prophylaxis and treatment. A penicillin allergy label, in particular, is associated with increased use of broad-spectrum and non-β-lactam antibiotics, which results in increased adverse events and antibiotic resistance. Most patients labelled as allergic to penicillins are not allergic when appropriately stratified for risk, tested, and re-challenged. Given the public health importance of penicillin allergy, this Review provides a global update on antibiotic allergy epidemiology, classification, mechanisms, and management.

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Section: Classification Presentation and Mechanismmentioning

confidence: 99%

Section: Classification Presentation and Mechanismmentioning

confidence: 99%

Antibiotic allergy

et al. 2019

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“…Regardless of their specific clinical phenotype, delayed immunologically mediated ADR are mostly T-cell mediated; this includes the typical morbilliform as well as urticarial eruptions, and more complicated and life-threatening reactions such as Stevens Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS) and single organ diseases such as drug-induced liver and kidney diseases (1). Although the typical way of classifying T-cell mediated reactions has been the revised Gell-Coombs classification, our knowledge of different models by which drugs activate T cells has advanced considerably over the last 10 years (Figure 1A and B) (2–5). In addition, strong HLA Class I associations between severe T-cell mediated reactions such as abacavir hypersensitivity, SJS/TEN and DRESS that have led to pre-prescription screening strategies (Table 1) (2, 6).…”

Section: Introductionmentioning

confidence: 99%

Controversies in drug allergy: Testing for delayed reactions

Phillips

Bigliardi

Bircher

et al. 2019

Journal of Allergy and Clinical Immunology

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153

167

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Controversies exist with regards to in vivo approaches to delayed immunologically mediated adverse drug reactions (ADR) such as exanthem (maculopapular eruption), drug reaction with eosinophilia and systemic symptoms (DRESS), acute generalized exanthematous pustulosis (AGEP), Stevens-Johnson syndrome/toxic epidermal necrolysis, and fixed drug eruption. In particular, widespread differences exist between regions and practice on the availability and use of intradermal testing (IDT) and patch testing, the standard drug concentrations used, the use of additional drugs in IDT and patch testing to help determine cross-reactivity, the timing of testing in relation to the occurrence of the adverse drug reaction, the use of testing in specific phenotypes, and the use of oral challenge in conjunction with delayed intradermal and patch testing to ascertain drug tolerance. It was noted that there have been advances in the science of delayed T-cell mediated reactions that have shed light on immunopathogenesis and provided a mechanism of pre-prescription screening in the case of HLA-B*57:01 and abacavir hypersensitivity and HLA-B*15:02 and carbamazepine SJS/TEN in Southeast Asians. Future directions should include the collaboration of large international networks to develop and standardize in vivo diagnostic approaches such as skin testing and patch testing combined with ex vivo and in vitro laboratory approaches.

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“…Virus-specific T-cell responses are likely to contribute to the prolonged and relapsing disease as well as multi-organ involvement in DRESS. 80 Interestingly, autoimmune diseases often occur after the resolution of DRESS. The most common of these is autoimmune thyroid disease, which has been recently independently associated with HHV6 infection.…”

Section: Understanding Immune-mediated Drug Toxicities: Mechanisms Ofmentioning

confidence: 99%

“…This ability to recognize multiple microbial epitopes with the same TCR is termed heterologous immunity. 80,83 Heterologous immunity has been proposed as a potential mechanism of IM-ADRs such that prior exposure to a pathogen elicits a response from a cross-reactive effector memory T-cell when the offending drug is administrated. The heterologous immunity model could potentially explains why so many IM-ADRs have HLA allelic associations with 100% negative predictive value (NPV) but a low positive predictive value (PPV), since the HLA allele is necessary but not sufficient to trigger the IM-ADR.…”

Section: Understanding Immune-mediated Drug Toxicities: Mechanisms Ofmentioning

confidence: 99%

Applications of Immunopharmacogenomics: Predicting, Preventing, and Understanding Immune-Mediated Adverse Drug Reactions

Karnes

Miller

White

et al. 2019

Annu. Rev. Pharmacol. Toxicol.

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Adverse drug reactions (ADRs) are a significant health care burden. Immune-mediated adverse drug reactions (IM-ADRs) are responsible for one-fifth of ADRs but contribute a disproportionately high amount of that burden due to their severity. Variation in human leukocyte antigen (HLA) genes has emerged as a potential preprescription screening strategy for the prevention of previously unpredictable IM-ADRs. Immunopharmacogenomics combines the disciplines of immunogenomics and pharmacogenomics and focuses on the effects of immune-specific variation on drug disposition and IM-ADRs. In this review, we present the latest evidence for HLA associations with IM-ADRs, ongoing research into biological mechanisms of IM-ADRs, and the translation of clinical actionable biomarkers for IM-ADRs, with a focus on T cell-mediated ADRs. Expected final online publication date for the Annual Review of Pharmacology and Toxicology Volume 59 is January 6, 2019. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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Severe Delayed Drug Reactions

Cited by 25 publications

References 214 publications

Antibiotic allergy

Antibiotic allergy

Controversies in drug allergy: Testing for delayed reactions

Applications of Immunopharmacogenomics: Predicting, Preventing, and Understanding Immune-Mediated Adverse Drug Reactions

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