ObjectiveThe aim of this study was to investigate the pathogenesis of AED-induced SJS/TEN across the spectrum of HLA-A, -B and -DRB1 alleles, and to explore the different clinical characteristics of patients with and without the HLA-B*15:02 allele in the SJS/TEN group. MethodsA total of twenty-three patients exhibiting AED-induced SJS/TEN (16 CBZ-SJS/TEN, seven LTG-SJS/TEN) and fifty-two patients who exhibited tolerance to AEDs were recruited. High-resolution HLA genotyping was performed to estimate the prevalence of the HLA-A, -B and -DRB1 alleles for each subject. Patients in the SJS/TEN group were further divided to positive HLA-B*15:02 allele group and negative HLA-B*15:02 allele group depending on whether carrying the HLA-B*15:02 allele, and the clinical feathers were compared between the two groups. ResultsNine of twenty-three patients (39%) in the SJS/TEN group were male, and the mean age of this group was 32 (8-68) years old. Twenty-eight of fifty-four (54%) patients in the tolerant group were male, and the mean age of the tolerant group was 28 (9-64) years old.Fourteen subjects in the SJS/TEN group carried the HLA-B*15:02 allele, whereas only four subjects (7.7%) in the AED-tolerant group carried this allele; the carrier rate of HLA-B*15:02 was significantly different between the groups (P<0.001). Among the fourteen patients who carried the HLA-B*15:02 allele in the SJS/TEN group, composing the positive HLA-B*15:02 allele group, eight patients (57.1%) were female, whereas six of nine patients in the negative HLA-B*15:02 allele group were female. The difference of the gender didn't have statistical significance between the two groups, nor did the other clinical characteristics, including mean age, the dosage of the AEDs, the interval from the drug administration to the onset of the SJS/TEN, fever, allergic history, abnormal MRI and abnormal EEG results. ConclusionsThe pathogenesis of AED-induced SJS/TEN is a complex process, which may involve one or more alleles. The HLA-B*15:02 allele may be a genetic susceptibility factor of the AED-induced SJS/TEN. However, we didn't find significant difference of the clinical characteristics of SJS/TEN between the patients with and without the HLA-B*15:02 allele. Notably, further studies using larger samples are required to confirm these conclusions.
Objective To summarize the genotypes associated with Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) induced by methazolamide and to provide references for the diagnosis and treatment of SJS and TEN induced by methazolamide. Methods Databases including PubMed, EMbase, CNKI, and WanFang Data were electronically searched from database inception to September 2021. Two reviewers independently screened literature and extracted data, and then a systematic review was performed. Results A total of 18 studies involving 49 patients were included. HLA genetic testing was performed on 37 patients. HLA-B*59:01 was detected in 27 patients, HLA-C*01:02 was detected in 15 patients, and 14 patients carried both genes. Statistical analysis showed that the positive rate of HLA-B*59:01 was 73% (95% CI 0.58 to 0.88) and that of HLA-C*01:02 was 40.5% (95%CI 0.24 to 0.57). The latent time until the symptoms were observed was 14.08 ± 8.77 days, and the mean dosage of methazolamide administered was 88.95±39.45 mg/d. Glucocorticoid and immunoglobulin were the main treatments prescribed. Conclusion Methazolamide can cause SJS and TEN. As the presence of HLA-B*59:01 or HLA-C*01:02 has been reported as a genetic risk factor for these adverse drug reactions, the implementation of genetic screening can effectively reduce their occurrence. Glucocorticoid and immunoglobulin, anti-infectives, should be administered to control the symptoms.