HLA Association with Drug-Induced Adverse Reactions

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.

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Immunohistopathological Findings of Severe Cutaneous Adverse Drug Reactions

Journal of Immunology Research ◽

10.1155/2017/6928363 ◽

2017 ◽

Vol 2017 ◽

pp. 1-5 ◽

Cited By ~ 7

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.

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Pharmacogenomics of Allopurinol and Sulfamethoxazole/Trimethoprim: Case Series and Review of the Literature

Journal of Personalized Medicine ◽

10.3390/jpm11020071 ◽

2021 ◽

Vol 11 (2) ◽

pp. 71

Author(s):

Ogechi Ikediobi ◽

Jeremy A. Schneider

Keyword(s):

Adverse Drug Reactions ◽

Drug Targets ◽

Case Series ◽

Human Leukocyte ◽

Hypersensitivity Syndrome ◽

Outpatient Setting ◽

Stevens Johnson Syndrome ◽

Review Of The Literature ◽

Drug Reactions ◽

Drug Induced

Severe cutaneous adverse drug reactions (SCAR) such as the Stevens–Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) and drug rash with eosinophilia and systemic symptoms/drug-induced hypersensitivity syndrome (DIHS) can be induced by a plethora of medications. The field of pharmacogenomics aims to prevent severe adverse drug reactions by using our knowledge of the inherited or acquired genetic risk of drug metabolizing enzymes, drug targets, or the human leukocyte antigen (HLA) genotype. Dermatologists are experts in the diagnosis and management of severe cutaneous adverse drug reactions (SCAR) in both the inpatient and outpatient setting. However, most dermatologists in the US have not focused on the prevention of SCAR. Therefore, this paper presents a case series and review of the literature highlighting salient examples of how dermatologists can apply pharmacogenomics in the diagnosis and especially in the prevention of SCAR induced by allopurinol and sulfamethoxazole/trimethoprim, two commonly prescribed medications.

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Cutaneous Adverse Drug reactions: A Four-Year Study from Western Nepal

Journal of Gandaki Medical College-Nepal ◽

10.3126/jgmcn.v10i2.20804 ◽

2018 ◽

Vol 10 (2) ◽

pp. 21-26 ◽

Cited By ~ 1

Author(s):

S Neupane ◽

B Basnet

Keyword(s):

Adverse Drug Reactions ◽

College Teaching ◽

Clinical History ◽

Stevens Johnson Syndrome ◽

Drug Reactions ◽

Medical College ◽

Johnson Syndrome ◽

Detailed Clinical History ◽

Life Threatening ◽

History Of

Background: Cutaneous adverse drug reactions (CADRs) range from minor reactions to several life threatening complications. Objectives: To study the clinical spectrum of cutaneous adverse drug reactions, determine the causative drugs responsible for the reactions and to assess the preventability.Methods: The study was carried out in the Department of Dermatology of Gandaki Medical College Teaching Hospital from June 2011 to June 2015. All the patients attending the Dermatology Outpatient Department and the patients admitted in the wards with suspected cutaneous adverse drug reactions to systemic drugs were included in the study. A detailed clinical history, including the history of drug intake was noted. Each case was assessed for its causality by using the WHO definitions. Data analysis was done using SPSS software.Results: There were 102 patients in total. The mean age of the patient was 32 ±15.7 years. Maximum patients belonged to the 21 to 30 years age group. There were 59 female patients and 43 male patients. Severe type of cutaneous adverse drug reactions was noted in 7.8% of patients. Antibiotics were responsible for most of the cutaneous adverse drug reactions. Cefixime was the most commonly incriminated drug. Exanthematous drug reaction was the most common type seen in 45%. Stevens-Johnson syndrome was the commonest type noted among the serious adverse drug reactions. Drug preventability was noted in 6% of patients.Conclusions: The commonest type of CADR noted was exanthematous type. Antibiotics were the commonest drug group involved in CADR. Six percent of CADR were preventable. J-GMC-N | Volume 11 | Issue 01 | January-June 2018, Page: 21-26

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A Comprehensive Review of HLA and Severe Cutaneous Adverse Drug Reactions: Implication for Clinical Pharmacogenomics and Precision Medicine

Pharmaceuticals ◽

10.3390/ph14111077 ◽

2021 ◽

Vol 14 (11) ◽

pp. 1077

Author(s):

Chiraphat Kloypan ◽

Napatrupron Koomdee ◽

Patompong Satapornpong ◽

Therdpong Tempark ◽

Mohitosh Biswas ◽

...

Keyword(s):

Clinical Practice ◽

Precision Medicine ◽

Adverse Drug Reactions ◽

Drug Hypersensitivity ◽

Human Leukocyte ◽

Population Level ◽

Stevens Johnson Syndrome ◽

Drug Reactions ◽

Drug Induced ◽

Systemic Symptoms

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.

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Intravenous N-acetylcysteine in severe cutaneous drug reaction treatment: A case series

SAGE Open Medical Case Reports ◽

10.1177/2050313x20934708 ◽

2020 ◽

Vol 8 ◽

pp. 2050313X2093470 ◽

Cited By ~ 1

Author(s):

Md Jahidul Hasan ◽

Raihan Rabbani

Keyword(s):

Toxic Epidermal Necrolysis ◽

Intravenous Immunoglobulin ◽

Adverse Drug Reactions ◽

Therapeutic Option ◽

Case Series ◽

High Rate ◽

Stevens Johnson Syndrome ◽

Drug Reactions ◽

Drug Induced ◽

Johnson Syndrome

Drug-induced serious adverse reaction is an unpleasant event with high rate of mortality. Stevens–Johnson Syndrome and toxic epidermal necrolysis are most common among the serious adverse drug reactions. There is no selective drug therapy for the management of serious adverse drug reactions-associated mucocutaneous blisters. The use of N-acetylcysteine in the treatment of mucocutaneous blisters has limited evidence worldwide. Three cases of toxic epidermal necrolysis or Stevens–Johnson Syndrome-associated mucocutaneous blisters are presented in this study where intravenous N-acetylcysteine (600 mg, every 8 h) was given in early hospitalization hours for the treatment of mucocutaneous fluid-filled blisters. Here, one patient with toxic epidermal necrolysis received intravenous immunoglobulin along with intravenous N-acetylcysteine and the other two patients (toxic epidermal necrolysis/Stevens–Johnson Syndrome) received only N-acetylcysteine intravenously. In response, mucocutaneous fluid-filled blisters stopped progressing within 48 h and were healed within 2 weeks of admission in the intensive care unit. Thus, intravenous N-acetylcysteine with or without having intravenous immunoglobulin in the treatment of serious adverse drug reactions-associated mucocutaneous blisters may be an effective therapeutic option for better clinical outcome.

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Phenytoin induced Stevens-Johnson syndrome: a case report

International Journal of Basic & Clinical Pharmacology ◽

10.18203/2319-2003.ijbcp20180676 ◽

2018 ◽

Vol 7 (3) ◽

pp. 573

Author(s):

Shambhavi Kulkarni ◽

A. N. Dattatri

Keyword(s):

Case Report ◽

Toxic Epidermal Necrolysis ◽

Adverse Drug Reactions ◽

Stevens Johnson Syndrome ◽

Drug Reactions ◽

Johnson Syndrome ◽

Life Threatening ◽

Inflammatory Drugs ◽

Anti Inflammatory

Toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS) are rare but potentially life threatening cutaneous adverse drug reactions. Drugs commonly implicated are anti-microbials, anti-epileptics and non-steroidal anti-inflammatory drugs (NSAIDs). Amongst anti-epileptics, carbamazepine and phenytoin are the most common offending drugs. We report here a case of SJS due to phenytoin.

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Cutaneous reactions to drugs

Oxford Textbook of Medicine ◽

10.1093/med/9780198746690.003.0565 ◽

2020 ◽

pp. 5752-5760

Author(s):

Sarah Walsh ◽

Daniel Creamer ◽

Haur Yueh Lee

Keyword(s):

Adverse Drug Reactions ◽

Adverse Reactions ◽

Normal Function ◽

Stevens Johnson Syndrome ◽

Drug Reactions ◽

Drug Induced ◽

Drug Eruptions ◽

Fixed Drug ◽

Iatrogenic Illness ◽

Systemic Symptoms

Adverse reactions to medications are common and important cause of iatrogenic illness. Severe cutaneous adverse drug reactions include toxic epidermal necrolysis, Stevens–Johnson syndrome, drug reaction with eosinophilia and systemic symptoms, and acute generalized exanthematous pustulosis, which together constitute 2% of all adverse drug reactions and may be life-threatening. Less severe drug-induced skin reactions such as exanthems, urticaria, lichenoid drug rashes, and fixed drug eruptions are more common, sometimes termed benign cutaneous adverse reactions, and generally resolve without sequelae. Drugs may also cause adverse events due to alteration of the normal function of the skin or its appendages. This may take the form of photosensitivity, abnormal pigmentation, or disrupted growth of hair or nails.

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Trimethoprim/Sulfamethoxazole-Induced Higher-Level Gait Disorder Aggrenox-Induced Stevens-Johnson Syndrome Serum Sickness–Like Reaction to Efalizumab Fluoroquinolone-Associated Achilles Tendinitis Severe Hyperglycemic, Hyperosmolar, Nonketotic Coma in a Patient Without Diabetes Receiving Aripiprazole Antidepressant-Induced Nightmares

Hospital Pharmacy ◽

10.1310/hpj4405-379 ◽

2009 ◽

Vol 44 (5) ◽

pp. 379-382

Author(s):

Joel Shuster

Keyword(s):

Adverse Drug Reactions ◽

Serum Sickness ◽

Stevens Johnson Syndrome ◽

Gait Disorder ◽

Drug Reactions ◽

Achilles Tendinitis ◽

Johnson Syndrome ◽

The Us ◽

Hyperglycemic Hyperosmolar Nonketotic Coma

The purpose of this feature is to heighten awareness of specific adverse drug reactions (ADRs), discuss methods of prevention, and promote reporting of ADRs to the US Food and Drug Administration's (FDA's) MedWatch program (800-FDA-1088). If you have reported an interesting, preventable ADR to MedWatch, please consider sharing the account with our readers.

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