Drug-Induced Severe Cutaneous Adverse Reactions: Insights Into Clinical Presentation, Immunopathogenesis, Diagnostic Methods, Treatment, and Pharmacogenomics

Abstract

SCARs are rare and life-threatening hypersensitivity reactions. In general, the increased duration of hospital stays and the associated cost burden are common issues, and in the worst-case scenario, they can result in mortality. SCARs are delayed T cell-mediated hypersensitivity reactions. Recovery can take from 2 weeks to many months after dechallenging the culprit drugs. Genetic polymorphism of the HLA genes may change the selection and presentation of antigens, allowing toxic drug metabolites to initiate immunological reactions. However, each SCARs has a different onset latency period, clinical features, or morphological pattern. This explains that, other than HLA mutations, other immuno-pathogenesis may be involved in drug-induced severe cutaneous reactions. This review will discuss the clinical morphology of various SCARs, various immune pathogenesis models, diagnostic criteria, treatments, the association of various drug-induced reactions and susceptible alleles in different populations, and the successful implementation of pharmacogenomics in Thailand for the prevention of SCARs.

Eculizumab Related Drug Reaction in a Patient with Neuromyelitis Optica

“…Cutaneous adverse drug reactions usually start 12-24 hours after exposure. 4 A temporal relationship between introduction of eculizumab and development of skin rash suggests a relationship between them.…”

Graves’ disease: an uncommon cause of late sequelae following DRESS (drug reaction with eosinophilia and systemic symptoms)

“…It has many functions, such as transcriptional regulation, extracellular stimulation of inflammation, recruitment and activation of immune-competent cells. 4 Immunological alteration and A c c e p t e d A r t i c l e metabolic enzymes function in the liver, including cytochrome P450 (CYP450) enzyme, could affects the accumulation of toxin metabolites, leading to cell necrosis and apoptosis. 4) Risk factors of allopurinol induced DRESS are identified into three groups.…”

“…4 Immunological alteration and A c c e p t e d A r t i c l e metabolic enzymes function in the liver, including cytochrome P450 (CYP450) enzyme, could affects the accumulation of toxin metabolites, leading to cell necrosis and apoptosis. 4) Risk factors of allopurinol induced DRESS are identified into three groups. 6) First, time-related factors propose the typical occurrence within the first 8-9 weeks after allopurinol initiation.…”

“…Second, genetic factors are related to HLA B*58:01 which could increase a risk of allopurinol induced DRESS and other severe cutaneous adverse drug reactions (SCARs) in all ethnics. 4) Third, drug-concentration factors are potentially influence drug reactions, including initial allopurinol dose of 100 mg daily or 50 mg in chronic kidney disease, route of administration, metabolism/excretion of medication, age, renal function, and concomitant medications, particularly diuretics. 6) Our patient had multiple risk factors, such as time-related factors about 6 weeks after commencing, genetic factors of HLA B*58:01, and drug-concentration factors of initial dose 100 mg, and chronic kidney disease.…”

“…The estimated risk of DRESS syndrome is about 1:1,000 and 1:10,000 [ 1 , 2 ]. The causative agents include anticonvulsants, antimicrobial, antiviral, allopurinol, antihypertensive, antidepressant, and nonsteroidal anti-inflammatory drugs (NSAIDs) [ 1 ].…”