Comparison of the Causes and Clinical Features of Drug Rash With Eosinophilia and Systemic Symptoms and Stevens-Johnson Syndrome

Aim: To examine gene expression in different clinical phenotypes of allopurinol-induced severe cutaneous adverse reactions (SCARs). Materials & methods: Gene expression profiling was performed using microarray on 11 RNA samples (four controls, three hypersensitivity syndrome/drug rash with eosinophilia and systemic symptoms, four Stevens–Johnson syndrome/toxic epidermal necrolysis) followed by quantitative real-time PCR in a total of 11 SCARs patients and 11 controls. Results: The biological pathways which were significantly enriched in differentially expressed genes in Stevens–Johnson syndrome/toxic epidermal necrolysis compared with hypersensitivity syndrome/drug rash with eosinophilia and systemic symptoms patients included; cell surface interactions at the vascular wall, immunoregulatory interactions at the immunological synapse and MyD88 signaling pathways. Overexpression of miR146a occurred in allopurinol-tolerant HLA-B*58:01 carriers. Conclusion: Biological pathways are identified which appear to be implicated in determining clinical phenotypes in allopurinol-induced SCARs. Overexpression of miR146a is potentially important for allopurinol tolerance in HLA-B*58:01 carriers.

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Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) or Stevens - Johnson syndrome (SJS): Does the Name Matter!

10.36959/831/374 ◽

2017 ◽

Vol 1 (1) ◽

Author(s):

Magbri Awad

Keyword(s):

Stevens Johnson Syndrome ◽

Johnson Syndrome ◽

Drug Rash ◽

Systemic Symptoms

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Fatal Drug Rash

Dermatology and Dermatitis ◽

10.31579/2578-8949/092 ◽

2019 ◽

Vol 4 (2) ◽

pp. 01-03

Author(s):

Sami L. Bahna ◽

Diana Munoz-Mendoza ◽

Neetu Godhwani

Keyword(s):

Septic Shock ◽

Drug Reaction ◽

High Risk ◽

Stevens Johnson Syndrome ◽

Johnson Syndrome ◽

T Cell Stimulation ◽

Drug Rash ◽

Systemic Symptoms ◽

Multiple Drugs ◽

Prolonged Hospital

We describe the case of a woman presenting with rash and fever 3 weeks after starting oxcarbazepine. She had a convoluted, prolonged hospital course involving reactions to multiple structurally-different medications, with a variety of severe manifestations including drug rash with eosinophilia and systemic symptoms (DRESS), and Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), and complicated with MRSA septic shock and death. This case illustrates the high risk in subjects with a drug reaction that initiated excessive T cell stimulation with subsequent reactions to multiple drugs.

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Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) or Stevens-Johnson Syndrome (SJS): Does the Name Matter!

Journal of Clinical Nephrology and Renal Care ◽

10.23937/2572-3286.1510023 ◽

2016 ◽

Vol 3 (1) ◽

Author(s):

Awad Magbri

Keyword(s):

Stevens Johnson Syndrome ◽

Johnson Syndrome ◽

Drug Rash ◽

Systemic Symptoms

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An update on HLA alleles as pharmacogenetic markers for antiepileptic drug-induced cutaneous adverse reaction

Neuroscience Research Notes ◽

10.31117/neuroscirn.v2i2.29 ◽

2019 ◽

Vol 2 (2) ◽

pp. 1-17

Author(s):

Sue-Mian Then ◽

Azman Ali Raymond

Keyword(s):

Single Gene ◽

Hypersensitivity Syndrome ◽

Allelic Frequency ◽

Stevens Johnson Syndrome ◽

Case Control Studies ◽

Drug Induced ◽

Hla Alleles ◽

Exfoliative Dermatitis ◽

Johnson Syndrome ◽

Systemic Symptoms

Epilepsy is a common neurological disorder affecting approximately 50 million people worldwide. Antiepileptic drugs (AEDs) are commonly used to treat the disease depending, mainly on the type of seizure. However, the use of AEDs may also lead to cutaneous adverse drug reactions (cADR) such as toxic epidermal necrolysis (TEN), Stevens–Johnson syndrome (SJS), exfoliative dermatitis (ED) and drug‐induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms (DIHS/DRESS), which are unwanted comorbidities in epilepsy. It was first discovered that the HLA-B*15:02 allele was strongly associated with carbamazepine (CBZ)-induced SJS/TEN among Han Chinese and this led to the discovery of other HLA alleles and cytochrome P450 (CYP) genes that were significantly associated with various AED-induced cADRs across various populations. This mini review is an update on the latest findings of the involvement of various HLA alleles and CYP alleles in cADRs caused by CBZ, phenytoin (PHT), oxcarbazepine (OXC) and lamitrogine (LTG) in different case-control studies around the world. From our review, we found that CBZ- and PHT-induced cADRs were more commonly reported than the other AEDs. Therefore, there were more robust pharmacogenetics studies related to these AEDs. OXC- and LTG-induced cADRs were less commonly reported, and so more studies are needed to validate the reported association of the newer reported HLA alleles with these AEDs. It is also important to take into account the allelic frequency within a given population before drawing conclusions about the use of these alleles as genetic markers to prevent AED-induced cADR. Overall, the current body of research point to a combination of alleles as a better pharmacogenetic marker compared to the use of a single gene as a genetic marker for AED-induced cADR.

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Genetic susceptibilities and prediction modeling of carbamazepine and allopurinol-induced severe cutaneous adverse reactions in Vietnamese

Pharmacogenomics ◽

10.2217/pgs-2019-0146 ◽

2020 ◽

Author(s):

Dinh van Nguyen ◽

Hieu Chi Chu ◽

Christopher Vidal ◽

Richard B Fulton ◽

Nguyet Nhu Nguyen ◽

...

Keyword(s):

Adverse Reactions ◽

Surrogate Marker ◽

Hypersensitivity Syndrome ◽

Stevens Johnson Syndrome ◽

Strongly Correlated ◽

Drug Induced ◽

Johnson Syndrome ◽

Severe Cutaneous Adverse Reactions ◽

Systemic Symptoms ◽

Cutaneous Adverse Reactions

Aims: To determine genetic susceptibility markers for carbamazepine (CBZ) and allopurinol-induced severe cutaneous adverse reactions (SCARs) in Vietnamese. Methods: A case control study was performed involving 122 patients with CBZ or allopurinol induced SCARs and 120 drug tolerant controls. Results: HLA-B*58:01 was strongly associated with allopurinol-induced SCARs and strongly correlated with SNP rs9263726. HLA-B*15:02 was associated with CBZ-induced Stevens–Johnson syndrome/toxic epidermal necrolysis but not with drug-induced hypersensitivity syndrome/drug rash with eosinophilia and systemic symptoms. No association was found between HLA-A*31:01 and CBZ-induced SCARs. HLA-B*58:01 and rs3909184 allele A with renal insufficiency were shown to increase the risk of allopurinol-induced SCARs. Conclusion: HLA-B*58:01 and HLA-B*15:02 confer susceptibility to allopurinol-induced SCARs and CBZ-induced SJS/TEN in Vietnamese. Single nucleotide polymorphism rs9263726 can be used as a surrogate marker in identifying HLA-B*58:01.

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Beta-lactam allergy in the paediatric population

Paediatrics & Child Health ◽

10.1093/pch/pxz179 ◽

2020 ◽

Vol 25 (1) ◽

pp. 62-62 ◽

Cited By ~ 7

Author(s):

Tiffany Wong ◽

Adelle Atkinson ◽

Geert t’Jong ◽

Michael J Rieder ◽

Edmond S Chan ◽

...

Keyword(s):

Paediatric Population ◽

Outpatient Setting ◽

Stevens Johnson Syndrome ◽

Beta Lactam ◽

Antibiotic Resistant ◽

Beta Lactam Antibiotics ◽

Johnson Syndrome ◽

Ige Mediated ◽

Systemic Symptoms ◽

Exanthematous Pustulosis

Abstract Beta-lactam allergy is commonly diagnosed in paediatric patients, but over 90% of individuals reporting this allergy are able to tolerate the medications prescribed after evaluation by an allergist. Beta-lactam allergy labels are associated with negative clinical and administrative outcomes, including use of less desirable alternative antibiotics, longer hospitalizations, increasing antibiotic-resistant infections, and greater medical costs. Also, children with true IgE-mediated allergy to penicillin medications are often advised to avoid all beta-lactam antibiotics, including cephalosporins, which is likely unnecessary in greater than 97% of those reporting penicillin allergies. Most patients can be safely treated with penicillin or amoxicillin if they do not have a history compatible with IgE-mediated or systemic, delayed reactions such as Stevens-Johnson syndrome (SJS), serum sickness-like reactions, drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome, or acute generalized exanthematous pustulosis (AGEP). Guidance is provided on how to stratify risk of beta-lactam allergy, and on test dosing and monitoring in the outpatient setting for patients deemed low risk. Guidance for patients at higher risk of beta-lactam allergy includes criteria for appropriate referral to allergists and the use of alternative antimicrobials, such as cephalosporins, while awaiting specialist assessment.

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Overlapping DRESS and Stevens-Johnson Syndrome: Case Report and Review of the Literature

Case Reports in Dermatology ◽

10.1159/000475802 ◽

2017 ◽

Vol 9 (2) ◽

pp. 1-7 ◽

Cited By ~ 4

Author(s):

Aneline Casagranda ◽

Mariano Suppa ◽

Florence Dehavay ◽

Véronique del Marmol

Keyword(s):

Diagnostic Criteria ◽

Adverse Reactions ◽

Stevens Johnson Syndrome ◽

Drug Induced ◽

Johnson Syndrome ◽

Systemic Symptoms ◽

The Right ◽

Exanthematous Pustulosis ◽

Cutaneous Adverse Reactions

Drug-induced severe cutaneous adverse reactions (SCARs) include acute generalized exanthematous pustulosis, drug reaction with eosinophilia and systemic symptoms (DRESS), and epidermal necrolysis (Stevens-Johnson syndrome [SJS], toxic epidermal necrolysis). The identification of the causal drug is crucial in order to avoid further exposure, but making the right differential diagnosis of the type of SCAR is equally important since treatment, follow-up, and prognosis of different SCARs are not the same. These syndromes are distinct entities with different clinical, biological, and histological patterns, but sometimes the early distinction between 2 SCARs can be extremely challenging, and overlapping conditions could therefore be taken into consideration, although true overlapping SCARs are very rare when using strict diagnostic criteria (described by the RegiSCAR group). Only a better understanding of the physiopathology of the SCARs could possibly explain these ambiguities and overlaps. We report a case of SCAR in an 86-year-old patient probably induced by allopurinol and simultaneously fulfilling the diagnostic criteria for DRESS and SJS, thus considered as an overlapping case of SCARs.

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