Drug-induced hypersensitivity syndrome following temozolimide for glioblastoma multiforme and the role of desensitization therapy

2021 ◽  
pp. 107815522110625
Author(s):  
Austin Ambur ◽  
Lindsay Ambur ◽  
Leila Khan ◽  
Rajiv Nathoo
Keyword(s):  
Glioblastoma Multiforme ◽  
Hypersensitivity Syndrome ◽  
Stevens Johnson Syndrome ◽  
Dress Syndrome ◽  
Drug Induced ◽  
Johnson Syndrome ◽  
Alternative Treatment Option ◽  
Desensitization Therapy ◽  
Cutaneous Hypersensitivity ◽  
Life Threatening

Introduction Temozolomide is an oral alkylating agent used as first line treatment of glioblastoma multiforme (GBM). It has also been used in the treatment of certain solid tumors such as metastatic melanoma. Commonly reported adverse effects include nausea and vomiting, constipation, headache, fatigue and myelosuppression. Cutaneous hypersensitivity reactions are rare and include an urticarial hypersensitivity reaction, alopecia, and Stevens–Johnson syndrome. To our knowledge, there are minimal reports of temozolomide-induced DRESS syndrome. Case Report We present a 54-year-old man with glioblastoma multiforme who presented with a fever, diarrhea and progressively worsening rash 6 weeks after starting temozolomide. Management & Outcome The patient was diagnosed recurrent DRESS syndrome and restarted on a gradual prednisone taper with resolution over the following weeks. Unfortunately, the patient was unable to be followed long-term due to relocation to a different state. Discussion To our knowledge, there are minimal reports of temozolomide-induced DRESS syndrome. The diagnosis can be life-threatening, which makes management of patients with GBM and no alternative treatment option challenging. The use of de-sensitization therapy to temozolomide has been proposed for the management of severe adverse cutaneous reactions.

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

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.

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

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.

scholarly journals HLA Association with Drug-Induced Adverse Reactions

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Wen-Lang Fan ◽  
Meng-Shin Shiao ◽  
Rosaline Chung-Yee Hui ◽  
Shih-Chi Su ◽  
Chuang-Wei Wang ◽  
...  
Keyword(s):  
Adverse Drug Reactions ◽  
Antithyroid Drug ◽  
Human Leukocyte ◽  
Stevens Johnson Syndrome ◽  
Drug Reactions ◽  
Drug Induced ◽  
Hla Association ◽  
Hla Genes ◽  
Johnson Syndrome ◽  
Life Threatening

Adverse drug reactions (ADRs) remain a common and major problem in healthcare. Severe cutaneous adverse drug reactions (SCARs), such as Stevens–Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) with mortality rate ranges from 10% to more than 30%, can be life threatening. A number of recent studies demonstrated that ADRs possess strong genetic predisposition. ADRs induced by several drugs have been shown to have significant associations with specific alleles of human leukocyte antigen (HLA) genes. For example, hypersensitivity to abacavir, a drug used for treating of human immunodeficiency virus (HIV) infection, has been proposed to be associated with allele 57:01 of HLA-B gene (terms HLA-B∗57:01). The incidences of abacavir hypersensitivity are much higher in Caucasians compared to other populations due to various allele frequencies in different ethnic populations. The antithyroid drug- (ATDs- ) induced agranulocytosis are strongly associated with two alleles: HLA-B∗38:02 and HLA-DRB1∗08:03. In addition, HLA-B∗15:02 allele was reported to be related to carbamazepine-induced SJS/TEN, and HLA-B∗57:01 in abacavir hypersensitivity and flucloxacillin induced drug-induced liver injury (DILI). In this review, we summarized the alleles of HLA genes which have been proposed to have association with ADRs caused by different drugs.

scholarly journals Immunohistopathological Findings of Severe Cutaneous Adverse Drug Reactions

2017 ◽  
Vol 2017 ◽  
pp. 1-5 ◽  
Author(s):  
Mari Orime
Keyword(s):  
Adverse Drug Reactions ◽  
Clinical Manifestations ◽  
Hypersensitivity Syndrome ◽  
Conclusive Evidence ◽  
Stevens Johnson Syndrome ◽  
Drug Reactions ◽  
Drug Induced ◽  
Cutaneous Manifestations ◽  
Johnson Syndrome ◽  
Systemic Symptoms

Diagnosis of severe cutaneous adverse drug reactions should involve immunohistopathological examination, which gives insight into the pathomechanisms of these disorders. The characteristic histological findings of erythema multiforme (EM), Stevens–Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN) provide conclusive evidence demonstrating that SJS/TEN can be distinguished from EM. Established SJS/TEN shows full-thickness, extensive keratinocyte necrosis that develops into subepidermal bullae. Drug-induced hypersensitivity syndrome (DIHS) and exanthema in drug reaction with eosinophilia and systemic symptoms (DRESS) each display a variety of histopathological findings, which may partly correlate with the clinical manifestations. Although the histopathology of DRESS is nonspecific, the association of two or more of the four patterns—eczematous changes, interface dermatitis, acute generalized exanthematous pustulosis- (AGEP-) like patterns, and EM-like patterns—might appear in a single biopsy specimen, suggesting the diagnosis and severe cutaneous manifestations of DRESS. Cutaneous dendritic cells may be involved in the clinical course. AGEP typically shows spongiform superficial epidermal pustules accompanied with edema of the papillary dermis and abundant mixed perivascular infiltrates. Mutations in IL36RN may have a definite effect on pathological similarities between AGEP and generalized pustular psoriasis.

scholarly journals Chemokines in Severe Cutaneous Adverse Reactions (SCARs)

Biomolecules ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 847
Author(s):  
Fumi Miyagawa ◽  
Hideo Asada
Keyword(s):  
Adverse Reactions ◽  
Human Herpesvirus ◽  
Hypersensitivity Syndrome ◽  
Stevens Johnson Syndrome ◽  
Drug Induced ◽  
Johnson Syndrome ◽  
Severe Cutaneous Adverse Reactions ◽  
Migratory Patterns ◽  
Systemic Symptoms ◽  
Cutaneous Adverse Reactions

Although the incidence of severe cutaneous adverse reactions (SCARs) to medications is very low, SCARs can result in disability or even death if they are not diagnosed and treated properly. As the rapid recognition of SCARs is essential, it is necessary to develop diagnostic markers for them that can also be used to assess severity and predict outcomes in the early phase. In addition, it is important to identify novel therapeutic targets for SCARs. Chemokines are chemotactic cytokines that control the migratory patterns and locations of immune cells and usually exhibit markedly specific associations with certain human diseases. In Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN), the Th1-associated chemokines chemokine (C-X-C motif) ligand 9 (CXCL9) and CXCL10 predominate, while in drug-induced hypersensitivity syndrome (DIHS)/drug reaction with eosinophilia and systemic symptoms (DRESS), the levels of the Th2-associated chemokines chemokine (C-C motif) ligand 17 (CCL17) and CCL22 are markedly elevated. We suggest that the distinct chemokine profiles of SJS/TEN and DIHS/DRESS can be used to aid their differential diagnosis. CXCL10 has also been reported to be associated with the development of long-term sequelae in DIHS/DRESS. This review focuses on the chemokines involved in the pathogenesis and adjuvant diagnosis of SCARs, particularly SJS/TEN and DIHS/DRESS, but also provides a brief overview of SCARs and the chemokine superfamily. As it is being increasingly recognized that an association exists between human herpesvirus 6 (HHV-6) and DIHS/DRESS, the possible roles of the chemokine/chemokine receptor homologs encoded by HHV-6 in the pathogenesis of DIHS/DRESS are also discussed.

scholarly journals The Roles of Immunoregulatory Networks in Severe Drug Hypersensitivity

2021 ◽  
Vol 12 ◽  
Author(s):  
Yun-Shiuan Olivia Hsu ◽  
Kun-Lin Lu ◽  
Yun Fu ◽  
Chuang-Wei Wang ◽  
Chun-Wei Lu ◽  
...  
Keyword(s):  
Checkpoint Inhibitors ◽  
Drug Hypersensitivity ◽  
Human Leukocyte ◽  
Hypersensitivity Syndrome ◽  
Stevens Johnson Syndrome ◽  
Hypersensitivity Reactions ◽  
Drug Induced ◽  
Johnson Syndrome ◽  
Signaling Receptors ◽  
Systemic Symptoms

The immunomodulatory effects of regulatory T cells (Tregs) and co-signaling receptors have gained much attention, as they help balance immunogenic and immunotolerant responses that may be disrupted in autoimmune and infectious diseases. Drug hypersensitivity has a myriad of manifestations, which ranges from the mild maculopapular exanthema to the severe Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms/drug-induced hypersensitivity syndrome (DRESS/DIHS). While studies have identified high-risk human leukocyte antigen (HLA) allotypes, the presence of the HLA allotype at risk is not sufficient to elicit drug hypersensitivity. Recent studies have suggested that insufficient regulation by Tregs may play a role in severe hypersensitivity reactions. Furthermore, immune checkpoint inhibitors, such as anti-CTLA-4 or anti-PD-1, in cancer treatment also induce hypersensitivity reactions including SJS/TEN and DRESS/DIHS. Taken together, mechanisms involving both Tregs as well as coinhibitory and costimulatory receptors may be crucial in the pathogenesis of drug hypersensitivity. In this review, we summarize the currently implicated roles of co-signaling receptors and Tregs in delayed-type drug hypersensitivity in the hope of identifying potential pharmacologic targets.

scholarly journals A case series of cefixime induced Steven’s Johnson Syndrome

2018 ◽  
Vol 7 (8) ◽  
pp. 1648
Author(s):  
Arikeri Vasu Deva Rao ◽  
Imran Khan ◽  
Srinivas Velupula ◽  
Jayababu N. ◽  
Samarasimha Reddy L. ◽  
...  
Keyword(s):  
Case Series ◽  
Stevens Johnson Syndrome ◽  
Allergic Reactions ◽  
Drug Induced ◽  
Major Health Problem ◽  
Johnson Syndrome ◽  
Eye Problems ◽  
Patient State ◽  
Life Threatening ◽  
Hyper Sensitivity

Drug induced adverse reactions are a major health problem. Drug hyper sensitivity reactions manifest themselves in many diseases, of which some are very severe. The most common allergic reactions occur in the skin. Stevens-Johnson syndrome is mainly caused by drugs (antimicrobials e.g.: penicillin’s, sulphonamides and cephalosporin’s e.g.: cefixime, antiepileptic’s, NSAIDS), infections and also by other risk factors not yet identified. The most common allergic reactions occur in the skin. These reactions ranging from simple pruritic eruptions to potentially life threatening events are a significant cause of iatrogenic morbidity and mortality. Identification of the cause, withdrawal of the trigger and supportive management is crucial to improve the patient state. Despite of all therapeutic efforts, mortality is high and increases with disease severity, patient’s age and underlying medical conditions. Survivors may suffer from long-term squeal such as strictures of mucous membranes including severe eye problems.

Sign in / Sign up

Export Citation Format

Share Document