Hye Jung Park1, James Yun2, Dong Yoon Kang3, Jung-Won Park4, Young-Il Koh5, Sujeong Kim6, Sae Hoon Kim7, Young Hee Nam8, Yi Yeong Jeong9, Cheol-Woo Kim10, Hye-Kyung Park11, Sang Hyon Kim12, Hye-Ryun Kang13, Jae-Woo Jung14. 1. Department of Internal Medicine, Gangnam Severance Hospital, College of Medicine, Yonsei University, Seoul, Korea. 2. Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia. 3. Drug Safety Monitoring Center, Seoul National University Hospital, Seoul, Korea. 4. Department of Internal Medicine, College of Medicine, Yonsei University, Seoul, Korea. 5. Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea. 6. Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Korea. 7. Department of Internal Medicine, Bundang Hospital, Seoul National University, Seongnam, Korea. 8. Department of Internal Medicine, College of Medicine, Dong-A University, Busan, Korea. 9. Department of Internal Medicine, School of Medicine, Gyeongsang National University, Jinju, Korea. 10. Department of Internal Medicine, School of Medicine, Inha University, Incheon, Korea. 11. Department of Internal Medicine, College of Medicine, Pusan National University, Busan, Korea. 12. Department of Internal Medicine, Dongsan Medical Center, Keimyung University, Daegu, Korea. 13. Division of Allergy and Clinical Immunology, Department of Internal Medicine, Seoul National University Hospital, College of Medicine, Seoul National University, Seoul, Korea. 14. Department of Internal Medicine, College of Medicine, Chung-Ang University, Seoul, Korea. Electronic address: jwjung@cau.ac.kr.
Abstract
BACKGROUND: Allopurinol is the most common cause of severe cutaneous adverse reactions (SCARs) in Korea due to the relatively high prevalence of the HLA-B*58:01 genotype (8%-13%). OBJECTIVE: We aimed to reveal the clinical characteristics and risk factors for death in allopurinol-induced SCARs in Korea. METHODS: We retrospectively reviewed the medical records of 106 subjects with allopurinol-induced SCARs and 639 subjects with other drug-induced SCARs who were enrolled in the Korean SCARs Registry (collected from 34 nationwide medical institutions) from January 2010 to December 2015. RESULTS: Subjects with allopurinol-induced Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) were older and had more comorbidities, longer latent periods, longer disease durations, more deranged laboratory findings, and increased disease severity resulting in a higher mortality rate (17.6% vs 7.6%; P = .020) compared with the subjects with other drug-induced SCARs. There was no significant difference in age or mortality in drug reaction with eosinophilia and systemic symptoms (DRESS). Subjects with allopurinol-induced SJS/TEN were older and had shorter latent periods and a higher mortality rate (17.6% vs 3.7%; P = .044) than those with allopurinol-induced DRESS. In allopurinol-induced SJS/TEN, significant risk factors for death included chronic renal insufficiency, intensive care unit (ICU) admission, increased blood urea nitrogen levels on admission day, serum peak eosinophil counts, baseline and peak creatinine levels, baseline and peak alanine aminotransferase levels, and decreased lowest platelet counts. In allopurinol-induced DRESS, significant risk factors for death included ICU admission and increased glucose levels on admission day. CONCLUSIONS: Allopurinol-induced SCARs have unique characteristics and poor prognoses with important predictive factors of death.
BACKGROUND:Allopurinol is the most common cause of severe cutaneous adverse reactions (SCARs) in Korea due to the relatively high prevalence of the HLA-B*58:01 genotype (8%-13%). OBJECTIVE: We aimed to reveal the clinical characteristics and risk factors for death in allopurinol-induced SCARs in Korea. METHODS: We retrospectively reviewed the medical records of 106 subjects with allopurinol-induced SCARs and 639 subjects with other drug-induced SCARs who were enrolled in the Korean SCARs Registry (collected from 34 nationwide medical institutions) from January 2010 to December 2015. RESULTS: Subjects with allopurinol-induced Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) were older and had more comorbidities, longer latent periods, longer disease durations, more deranged laboratory findings, and increased disease severity resulting in a higher mortality rate (17.6% vs 7.6%; P = .020) compared with the subjects with other drug-induced SCARs. There was no significant difference in age or mortality in drug reaction with eosinophilia and systemic symptoms (DRESS). Subjects with allopurinol-induced SJS/TEN were older and had shorter latent periods and a higher mortality rate (17.6% vs 3.7%; P = .044) than those with allopurinol-induced DRESS. In allopurinol-induced SJS/TEN, significant risk factors for death included chronic renal insufficiency, intensive care unit (ICU) admission, increased blood urea nitrogen levels on admission day, serum peak eosinophil counts, baseline and peak creatinine levels, baseline and peak alanine aminotransferase levels, and decreased lowest platelet counts. In allopurinol-induced DRESS, significant risk factors for death included ICU admission and increased glucose levels on admission day. CONCLUSIONS:Allopurinol-induced SCARs have unique characteristics and poor prognoses with important predictive factors of death.
Keywords:
Allopurinol; Drug reactions with eosinophilia and systemic symptoms; Severe cutaneous adverse reaction; Stevens-Johnson syndrome; Toxic epidermal necrolysis