“…AGEP is induced by spider bite, viral infection (Coxsackie B4, cytomegalovirus, parvovirus B19) and bacterial infection (Mycoplasma pneumoniae, Chlamydial pneumoniae, Escherichia coli) and parasitic infestation [52,53]. AGEP commonly occur as a sudden onset, mostly has time interval from drug ingestion within 24-48 h (hour to 25 days) [52,54]. The onset of this condition is variable depend on different drug.…”
“…The recent studies about genetic predisposing identified mutation IL-36RN in AGEP patients [58]. These mutations lead to increase expression of various pro-inflammatory cytokines and chemokines such as IL-36 signaling, up-regulating IL-1, IL-6, CXCL 8/IL-8 production and neutrophil recruitment [54,59]. Etiology, pathology and treatments of SCARs have been extensively described as reviewed by other authors [60][61][62].…”
Human leukocyte antigen (HLA) encoded by the HLA gene is an important modulator for immune responses and drug hypersensitivity reactions as well. Genetic polymorphisms of HLA vary widely at population level and are responsible for developing severe cutaneous adverse drug reactions (SCARs) such as Stevens–Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), maculopapular exanthema (MPE). The associations of different HLA alleles with the risk of drug induced SJS/TEN, DRESS and MPE are strongly supportive for clinical considerations. Prescribing guidelines generated by different national and international working groups for translation of HLA pharmacogenetics into clinical practice are underway and functional in many countries, including Thailand. Cutting edge genomic technologies may accelerate wider adoption of HLA screening in routine clinical settings. There are great opportunities and several challenges as well for effective implementation of HLA genotyping globally in routine clinical practice for the prevention of drug induced SCARs substantially, enforcing precision medicine initiatives.
“…AGEP is induced by spider bite, viral infection (Coxsackie B4, cytomegalovirus, parvovirus B19) and bacterial infection (Mycoplasma pneumoniae, Chlamydial pneumoniae, Escherichia coli) and parasitic infestation [52,53]. AGEP commonly occur as a sudden onset, mostly has time interval from drug ingestion within 24-48 h (hour to 25 days) [52,54]. The onset of this condition is variable depend on different drug.…”
“…The recent studies about genetic predisposing identified mutation IL-36RN in AGEP patients [58]. These mutations lead to increase expression of various pro-inflammatory cytokines and chemokines such as IL-36 signaling, up-regulating IL-1, IL-6, CXCL 8/IL-8 production and neutrophil recruitment [54,59]. Etiology, pathology and treatments of SCARs have been extensively described as reviewed by other authors [60][61][62].…”
Human leukocyte antigen (HLA) encoded by the HLA gene is an important modulator for immune responses and drug hypersensitivity reactions as well. Genetic polymorphisms of HLA vary widely at population level and are responsible for developing severe cutaneous adverse drug reactions (SCARs) such as Stevens–Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), maculopapular exanthema (MPE). The associations of different HLA alleles with the risk of drug induced SJS/TEN, DRESS and MPE are strongly supportive for clinical considerations. Prescribing guidelines generated by different national and international working groups for translation of HLA pharmacogenetics into clinical practice are underway and functional in many countries, including Thailand. Cutting edge genomic technologies may accelerate wider adoption of HLA screening in routine clinical settings. There are great opportunities and several challenges as well for effective implementation of HLA genotyping globally in routine clinical practice for the prevention of drug induced SCARs substantially, enforcing precision medicine initiatives.
“…The results showed no change in the lung pathology (calcification). As reported in the literature, patients with latent TB who received no chemoprophylaxis could be safely treated with secukinumab ( 1 , 2 ).…”
Section: Discussionmentioning
confidence: 97%
“…As it is, treatment is mainly potent topical or systemic steroids. However, a minority of cases fail to respond to them, highlighting the need for additional treatment options for these refractory cases ( 1 ). Secukinumab is an interleukin (IL)-17 inhibitor that is approved to treat psoriasis.…”
Acute generalized exanthematous pustulosis is a severe, usually drug-related reaction, characterized by an acute onset of mainly small non-follicular pustules on an erythematous base. Most cases of acute generalized exanthematous pustulosis (AGEP) clear quickly with a systemic corticosteroid, but severe or recalcitrant cases may need other systemic therapies. In this case, a man in his 40 s with a history of psoriasis consulted a physician about widespread erythema, pustules, target lesions, and fever after the administration of a quadruple antituberculosis drug. Routine laboratory testing revealed elevated white blood cell count and C-reactive protein. The histopathology showed subcorneal pustules, spongiosis as well as lymphocyte and eosinophils infiltration in the dermis. The patient was diagnosed with definitive AGEP according to the diagnostic score from the EuroSCAR study. Cutaneous lesions especially pustules and erythema multiforme-like lesions on the upper arms and palms are crucial for distinguishing AGEP from Generalized pustular psoriasis. The patient was treated with secukinumab as a result of his failure to respond to topical corticosteroids and constrain of systemic steroids. Remission with secukinumab therapy was safe without increased risks of infections. This case indicates that secukinumab is a potential therapy that can rapidly improve the clinical symptoms of AGEP.
“…There is often obvious edema in the papillary dermis and surrounding blood vessels, accompanied by infiltration of neutrophils and eosinophils, as well as vasculitis or necrosis of individual cells of keratinocytes. Of note, this is different from the histopathology of psoriasis [ 73 ]. Fig.…”
Adverse drug reactions involving the skin are commonly known as drug eruptions. Severe drug eruption may cause severe cutaneous adverse drug reactions (SCARs), which are considered to be fatal and life-threatening, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), acute generalized exanthematous pustulosis (AGEP), and drug reaction with eosinophilia and systemic symptoms (DRESS). Although cases are relatively rare, approximately 2% of hospitalized patients are affected by SCARs. There is an incidence of 2 to 7 cases/million per year of SJS/TEN and 1/1000 to 1/10,000 exposures to offending agents result in DRESS. However, the mortality rate of severe drug eruptions can reach up to 50%. SCARs represent a real medical emergency, and early identification and proper management are critical to survival. The common pathogenesis of severe drug eruptions includes genetic linkage with HLA-and non-HLA-genes, drug-specific T cell-mediated cytotoxicity, T cell receptor restriction, and cytotoxicity mechanisms. A multidisciplinary approach is required for acute management. Immediate withdrawal of potentially causative drugs and specific supportive treatment is of great importance. Immunoglobulins, systemic corticosteroids, and cyclosporine A are the most frequently used treatments for SCARs; additionally, new biologics and plasma exchange are reasonable strategies to reduce mortality. Although there are many treatment methods for severe drug eruption, controversies remain regarding the timing and dosage of drug eruption. Types, dosages, and indications of new biological agents, such as tumor necrosis factor antagonists, mepolizumab, and omalizumab, are still under exploration. This review summarizes the clinical characteristics, risk factors, pathogenesis, and treatment strategies of severe drug eruption to guide clinical management. Keywords Severe drug eruption • Stevens-Johnson syndrome • Toxic epidermal necrolysis • Acute generalized exanthematous pustulosis • Drug reaction with eosinophilia and systemic symptoms Abbreviations AGEP Acute generalized exanthematous pustulosis ALT Alanine aminotransferase APCs Antigen-presenting cells AST Aspartate aminotransferase CBZ Carbamazepine CCR CC-chemokine receptor COVID-19 Coronavirus disease 2019 CTL Cytotoxic T cells CXCR CXC chemokine receptor DiHS
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