Risks and management of antiepileptic drug induced skin reactions in the adult out-patient setting

Abstract

Adverse cutaneous reactions caused by mostly aromatic antiepileptic drugs (AED) affect 50.000 people a year in the United Kingdom (UK; incidence 75.7/100.000). Optimal management of these cases is often difficult, as the patient may report symptoms to a general practitioner, attend Accident & Emergency or inform a specialist over the telephone or via email. When clinical assessment is limited it is thought safest to withdraw offending medication and inform the patient of a new drug allergy. This may unjustifiably restrict future treatment choices, and increase cost. Most frequent offenders are aromatic AEDs: carbamazepine, oxcarbazepine, eslicarbazepine, phenytoin, lamotrigine, phenobarbitone, primidone (recently licensed lacosamide associated with lower risk) and the sulpha-derivative zonisamide. Our study provides a summary of severe delayed allergic reactions and offers a pragmatic management pathway for patients suffering a suspected drug-induced rash. We include UK pretreatment screening guidelines, step by step clinical assessment of rash and associated symptoms aiding early identification of patients at risk of developing severe allergic reactions. At the same time our manuscript reviews published data informing best choice and titration of alternative medication when allergy confirmed. Finally we summarize current knowledge on genetic predisposition and other personalized risks of AED allergies identifying gaps in our current understanding.

Diagnostic Test Criteria for HLA Genotyping to Prevent Drug Hypersensitivity Reactions: A Systematic Review of Actionable HLA Recommendations in CPIC and DPWG Guidelines

“…PPV is low (3%–44%) while NPV is consistently high (91%–98%). Due to the high incidence of MPE, the NNG is low, especially in Canadians and Europeans ( Locharernkul et al., 2008 ; GlaxoSmithKline, 2009 ; US Food and Drug Administration, 2009 ; He et al., 2012 ; Shi et al., 2012 ; Amstutz et al., 2013 ; He et al., 2013 ; Lv et al., 2013 ; Caudle et al., 2014 ; Genin et al., 2014 ; ULC MP, 2015 ; Moon et al., 2016 ; Pfizer, 2016 ; Chen et al., 2017 ; Khor et al., 2017 ; Khosama et al., 2017 ; Deng et al., 2018 ; Fowler et al., 2019 ). But NNG is also low in North India ( An et al., 2010 ) due to a relatively high sensitivity (22.2%).…”

“…The incidence of phenytoin induced SJS/TEN is assumed to be 0.24% in Asians and 0.069% in Caucasians (Fowler et al, 2019; Koninklijke Nederlandse Maatschappij ter bevordering der Pharmacie, 2020f).…”

Drug rash with eosinophilia and systemic symptoms syndrome in an adolescent - efficiency of immunoglobulin G in a corticosteroid resistant case

“…In conclusion, we join the authors [6,[10][11][12][13][14][15][16][17][18]20] of who favor the treatment of DRESS sy using IVIG, and we point out to the need to change the order of recommendations in the current treatment recommendations for DRESS sy [5,9] in favor of IVIG. IVIG should be considered as a second-line treatment as soon as possible in patients in whom corticosteroid treatment failed.…”

“…Fowler indicates clear gaps in our current understanding of DRESS sy, and points to the need for old test (patch) and new diagnostic tests to screen patients before starting the carbamazepine (interleukin 15 and microRNA 122 in the serum) and that certain authors favor IVIG and plasma exchange instead of steroids for the treatment of DRESS sy [18].…”

İşitsel Peyzaj Kavramı Üzerine Bir Mimari Tasarım Stüdyosu Deneyimi

“…Although aural architecture is not a direct tool to solve a complex issue like acoustic sustainability in urban scale, it provides an important framework regarding how to re-examine the disciplinary boundaries of architectural practice. 26 This can be theoretically achieved by interrogating the natural connections between sound/sound sources, perception and space, and Blesser and Salter 9 supports this as a need for 'auditory spatial awareness'. In the development of the theory, there is an explanation considering aural architecture as a candidate as follows:…”