Severe Cutaneous Adverse Drug Reactions: Presentation, Risk Factors, and Management

Mustafa, S. Shahzad; Ostrov, David A.; Yerly, Daniel

doi:10.1007/s11882-018-0778-6

Cited by 46 publications

(43 citation statements)

References 87 publications

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“…Main drug groups associated with EN include anticonvulsants, antibiotics and nonsteroidal anti‐inflammatory drugs (NSAIDs) (Table 2). 25–27 Research into causal drugs in an European and Israeli population indicated allopurinol as most frequent drug‐related cause 28 . Recently, novel targeted cancer drugs have been implicated in EN 29–33 …”

Section: Epidermal Necrolysis In Shortmentioning

confidence: 99%

Clinical and pathogenic aspects of the severe cutaneous adverse reaction epidermal necrolysis (EN)

Kuijper

French

Tensen

et al. 2020

Acad Dermatol Venereol

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The severe cutaneous adverse reaction epidermal necrolysis (EN) which includes toxic epidermal necrolysis and the milder Stevens‐Johnson syndrome is characterized by epidermal loss due to massive keratinocyte apoptosis and/or necroptosis. EN is often caused by a drug mediating a specific TCR‐HLA interaction via the (pro)hapten, pharmacological interaction or altered peptide loading mechanism involving a self‐peptide presented by keratinocytes. (Memory) CD8 + T cells are activated and exhibit cytotoxicity against keratinocytes via the perforin/granzyme B and granulysin pathway and Fas/FasL interaction. Alternatively drug‐induced annexin release by CD14 + monocytes can induce formyl peptide receptor 1 death of keratinocytes by necroptosis. Subsequent keratinocyte death stimulates local inflammation, activating other immune cells producing pro‐inflammatory molecules and downregulating regulatory T cells. Widespread epidermal necrolysis and inflammation can induce life‐threatening systemic effects, leading to high mortality rates. Research into genetic susceptibility aims to identify risk factors for eventual prevention of EN. Specific HLA class I alleles show the strongest association with EN, but risk variants have also been identified in genes involved in drug metabolism, cellular drug uptake, peptide presentation and function of CD8 + T cells and other immune cells involved in cytotoxic responses. After the acute phase of EN, long‐term symptoms can remain or arise mainly affecting the skin and eyes. Mucosal sequelae are characterized by occlusions and strictures due to adherence of denuded surfaces and fibrosis following mucosal inflammation. In addition, systemic pathology can cause acute and chronic hepatic and renal symptoms. EN has a large psychological impact and strongly affects health‐related quality of life among EN survivors.

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Section: Epidermal Necrolysis In Shortmentioning

confidence: 99%

Clinical and pathogenic aspects of the severe cutaneous adverse reaction epidermal necrolysis (EN)

Kuijper

French

Tensen

et al. 2020

Acad Dermatol Venereol

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“…The results are classified as very probable, probable, possible, improbable, and very unlikely; a relationship has been established with the following drugs through the application of the ALDEN score: allopurinol (odds ratio 24.51), cox-2 inhibitors (odds ratio 24.19) PPI, fluoxetine, mirtazapine, 5-aminosalicylates, lamotrigine, Nevirapine, phenobarbital, phenytoin and sulfamethoxazole. 7,8,4 Genetically, hypersensitivity reactions and variants of HLA have been associated, which are specific for populations and drugs, which indicates that these specific HLA interact closely with molecules that act as antigens in drugs, causing the activation of T cells. 9 The presence of the allele HLA-B* 1502 is related to a greater predisposition to cutaneous hypersensitivity reactions secondary to the use of carbamazepine in Asian populations and to the HLA-A* 3101 allele in North European populations.…”

Section: Etiologymentioning

confidence: 99%

“…The spectrum is represented in Table 1, with toxic epidermal necrolysis being the largest cutaneous extension. 4…”

Section: Introductionmentioning

confidence: 99%

Stevens-Johnson syndrome and toxic epidermal necrolysis: a review

Ruiz¹,

Treviño²,

Mendoza³

et al. 2019

Int J Res Med Sci

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Stevens Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) are considered a single entity with variability in the extent of the lesions, characterized by erythema multiforme that may involve mucosa. Severe cutaneous reactions secondary to medications are classified according to the area of epidermal detachment. The activation of cytotoxic T cells and macrophages is mediated mainly by IL-2 and interferon gamma secreted by Th1 lymphocytes, and the activation of eosinophils and B lymphocytes in IgE is mediated by secreted IL-4, IL-5, IL-10 and IL13 by B lymphocytes. The topography of SJS is predominantly central, affecting the trunk and sometimes a generalized dissemination is shown that affects a body surface area of less than 10%, characterized by irregular violaceous erythematous macules of target shooting, which can form confluent blisters. TEN is characterized by a skin detachment greater than 30% of the body surface, whose predominant lesion is diffuse erythema with individual macules, which give rise to detachment surfaces greater than 5 cm. The treatment is symptomatic, nonspecific, and aimed at avoiding complications, carried out in specialized intensive care units, due to ignorance of the pathogenesis. Integral management with different therapeutic alternatives can represent a crucial part in the multisystemic management of SJS and TEN.

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“…Severe cutaneous adverse reactions (SCARs) are a group of delayed‐type hypersensitivity reactions to drugs, including Drug Reactions with Eosinophilia and Systemic Symptoms (DRESS), Stevens‐Johnson syndrome (SJS), Toxic Epidermal Necrolysis (TEN) and Acute Generalized Exanthematous Pustulosis (AGEP) …”

Section: Introductionmentioning

confidence: 99%

Aetiopathogenesis of severe cutaneous adverse reactions (SCARs) in children: A 9‐year experience in a tertiary care paediatric hospital setting

Liccioli

Mori

Parronchi

et al. 2019

Clin Experimental Allergy

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Background: Severe cutaneous adverse reactions (SCARs) are delayed-type hypersensitivity reactions to drugs including as follows: Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), Stevens-Johnson syndrome (SJS), Toxic Epidermal Necrolysis (TEN) and Acute Generalized Exanthematous Pustulosis (AGEP). Incidence, triggers and management of SCARs have not been investigated in large-scale epidemiological studies on children.Objective: The aim of our study was to collect epidemiological, clinical and aetiological data from children with SCARs referred to our tertiary care paediatric hospital of Florence.Methods: From 2010 to 2018 charts of children with diagnosis of SCAR were reviewed, and data collected during the acute phase and/or the subsequent allergy evaluation. Patients underwent patch tests, intradermal tests and lymphocyte transformation tests. All children were investigated for infectious diseases.Results: Incidence of SCARs in hospitalized children was 0.32% over a 9-year period.Fifty-four children were enrolled (31 M; 23 F; median age 6.5 years): 17 cases of DRESS, 30 SJS, 3 TEN, 2 AGEP, 1 linear immunoglobulin A bullous disease (LABD) and 1 pemphigus. Twenty-eight out of 54 patients underwent drug allergy investigations, and 50% of them resulted positive. Combining clinical history and results of allergy work-up, 74% SCARs seem to be caused by drugs, 18.6% by both drugs and infections, 3.7% by infections, and 3.7% remained idiopathic. No deaths occurred. Conclusions:In this study, SCARs incidence is in line with literature data. Drugs were most commonly the leading cause. Management of SCARs requires cooperation among professional figures for an early diagnosis and a prompt treatment. Mortality rate seems to be lower in children. K E Y W O R D Sacute generalized exanthematous pustulosis, aetiopathogenesis, children, drug reaction with eosinophilia and systemic symptoms, hypersensitivity drug reactions, lymphocyte | 65

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Severe Cutaneous Adverse Drug Reactions: Presentation, Risk Factors, and Management

Cited by 46 publications

References 87 publications

Clinical and pathogenic aspects of the severe cutaneous adverse reaction epidermal necrolysis (EN)

Clinical and pathogenic aspects of the severe cutaneous adverse reaction epidermal necrolysis (EN)

Stevens-Johnson syndrome and toxic epidermal necrolysis: a review

Aetiopathogenesis of severe cutaneous adverse reactions (SCARs) in children: A 9‐year experience in a tertiary care paediatric hospital setting

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