Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2022 Apr 20:13:832048.
doi: 10.3389/fphar.2022.832048. eCollection 2022.

Drug-Induced Severe Cutaneous Adverse Reactions: Insights Into Clinical Presentation, Immunopathogenesis, Diagnostic Methods, Treatment, and Pharmacogenomics

Therdpong Tempark  1   2 , Shobana John  3   4 , Pawinee Rerknimitr  5   6 , Patompong Satapornpong  7   8 , Chonlaphat Sukasem  2   3   4   5   9   10
Affiliations
Review

Drug-Induced Severe Cutaneous Adverse Reactions: Insights Into Clinical Presentation, Immunopathogenesis, Diagnostic Methods, Treatment, and Pharmacogenomics

Therdpong Tempark et al. Front Pharmacol. .

Abstract

SCARs are rare and life-threatening hypersensitivity reactions. In general, the increased duration of hospital stays and the associated cost burden are common issues, and in the worst-case scenario, they can result in mortality. SCARs are delayed T cell-mediated hypersensitivity reactions. Recovery can take from 2 weeks to many months after dechallenging the culprit drugs. Genetic polymorphism of the HLA genes may change the selection and presentation of antigens, allowing toxic drug metabolites to initiate immunological reactions. However, each SCARs has a different onset latency period, clinical features, or morphological pattern. This explains that, other than HLA mutations, other immuno-pathogenesis may be involved in drug-induced severe cutaneous reactions. This review will discuss the clinical morphology of various SCARs, various immune pathogenesis models, diagnostic criteria, treatments, the association of various drug-induced reactions and susceptible alleles in different populations, and the successful implementation of pharmacogenomics in Thailand for the prevention of SCARs.

Keywords: PGx implementation; SCARs; Thailand; immunopathogenesis of SCARs; pharmacogenomics; risk factors.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Toxic epidermal necrolysis (TEN). Multiple macules with central dusky red (atypical target lesions) were found on the trunk (A). The lesions progressed to flaccid bullae and large sheets of skin necrosis, leading to diffuse erythema. Nikolsky’s sign was also positive (B). Facial, oral, and ocular involvements were noted (C).
FIGURE 2
FIGURE 2
Drug reaction with eosinophilia and systemic symptoms (DRESS). Diffuse maculopapular eruption involving more than 50% of body surface area. The plaques were infiltrated and exhibited follicular accentuation (A). Facial edema is a prominent feature of the syndrome (B).
FIGURE 3
FIGURE 3
Acute generalized exanthematous pustulosis (AGEP). Multiple pin-head sized, non-follicular pustules on edematous, homogenous, poorly demarcated, erythematous background. The lesions were found mainly on the folds of the body (A). The pustules can become confluent (B).
FIGURE 4
FIGURE 4
Generalized bullous fixed drug eruption (GBFDE). Multiple large and well-demarcated round to oval plaques with blisters formation. The lesions were found at different sites of the body. Fewer than two sites of the mucous membrane were involved. The patient has experienced a similar reaction in the past.
FIGURE 5
FIGURE 5
Structure of HLA classes I, II and T cell receptors (TCR).
FIGURE 6
FIGURE 6
Immune mechanisms of HLA, drug, peptide, and TCR associated drug hypersensitivity reactions.
FIGURE 7
FIGURE 7
Evolving models of immunopathogenesis of DTH.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Al-Quteimat O. M. (2016). Phenytoin-induced Toxic Epidermal Necrolysis: Review and Recommendations. J. Pharmacol. Pharmacother. 7 (3), 127–132. 10.4103/0976-500X.189662 - DOI - PMC - PubMed
    1. Alvestad S., Lydersen S., Brodtkorb E. (2007). Rash from Antiepileptic Drugs: Influence by Gender, Age, and Learning Disability. Epilepsia 48 (July 7), 1360–1365. 10.1111/j.1528-1167.2007.01109.x - DOI - PubMed
    1. Anderson M., Egunsola O., Cherrill J., Millward C., Fakis A., Choonara I. (2015). A Prospective Study of Adverse Drug Reactions to Antiepileptic Drugs in Children. BMJ Open 5 (6), e008298. 10.1136/bmjopen-2015-008298 - DOI - PMC - PubMed
    1. Asakura E., Mori K., Komori Y., Takano M., Hasegawa T., Kobayashi W., et al. (2001). The Trend of the Drug Eruptions in the Last Fifteen Years. Yakugaku Zasshi 121, 145–151. 10.1248/yakushi.121.145 - DOI - PubMed
    1. Barbaud A. (2014). Skin Testing and Patch Testing in Non-IgE-mediated Drug Allergy. Curr. Allergy Asthma Rep. 14, 442. 10.1007/s11882-014-0442-8 - DOI - PubMed