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.
Aggregated risk of carbamazepine (CBZ)‐induced cutaneous adverse drug reactions (cADRs) with different
HLA
variants are unclear and limited in terms of the power of studies
.
This study aimed to assess the aggregated risk of CBZ‐induced cADRs associated with carrying the following
HLA
variants:
HLA‐B*15:02
,
HLA‐B*15:11
,
HLA‐B*15:21
,
HLA‐B*38:02
,
HLA‐B*40:01
,
HLA‐B*46:01
,
HLA‐B*58:01
,
HLA‐A*24:02
, and
HLA‐A*31:01
. Literature was searched in different databases following PRISMA guidelines. The outcomes were measured as odds ratio (OR) using RevMan software by a random/fixed effects model, where
p
< 0.05 was set as statistical significance. In total, 46 case–control studies met the inclusion criteria and were included in this analysis consisting of 1817 cases and 6614 controls. It was found that case‐patients who carried the
HLA‐B*15:02
allele were associated with a significantly increased risk of CBZ‐induced Stevens−Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) compared to controls (OR 26.01; 95% CI 15.88–42.60;
p
< 0.00001). The aggregated risk of cADRs was slightly higher in Asian compared to Caucasian patients (Asians: OR 14.84; 95% CI 8.95–24.61;
p
< 0.00001; Caucasians: OR 11.65; 95% CI 1.68–80.70;
p
= 0.01). Further,
HLA‐B*15:11
,
HLA‐B*15:21
, or
HLA‐A*31:01
allele was also associated with significantly increased risk of CBZ‐induced cADRs (
HLA‐B*15:11:
OR 6.08; 95% CI 2.28–16.23;
p
= 0.0003;
HLA‐B*15:21:
OR 5.37; 95% CI 2.02–14.28;
p
= 0.0008;
HLA‐A*31:01:
OR 5.92; 95% CI 4.35–8.05;
p
< 0.00001). Other
HLA
variants were not found to have any significant associations with CBZ‐induced cADRs. Strong associations between the
HLA‐B*15:02
,
HLA‐B*15:11
,
HLA‐B*15:21
, or
HLA‐A*31:01
allele with CBZ‐induced cADRs have been established in this analysis. Pharmacogenetic testing of particular
HLA
alleles before initiation of CBZ therapy may be beneficial to patients and may help to eradicate cADRs substantially.
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