2008 Clinical and subclinical manifestations of allopurinol induced severe cutaneous adverse reactions in Vietnam

Thursday, 15 October 2015
Hall D1 Foyer (Floor 3) (Coex Convention Center)

Dinh Van Nguyen, PhD Student , Allergy and Clinical Immunology, Hanoi Medical University, Hanoi, Vietnam

Hieu Chi Chu, MD , Center of Allergology and Clinical Immunology, Bach Mai Hospital, Hanoi, Vietnam

Sy Van Than, MD student , Allergy and Clinical Immunology, Hanoi Medical University, Hanoi, Vietnam

Mui Thi Tran, MD , Allergy and Clinical Immunology, Hanoi Medical University, Hanoi, Vietnam

Sheryl Van Nunen, A/Professor , Clinical Immunology & Allergy, Royal North Shore Hospital, Sydney Medical School, Sydney, Australia

Christopher Vidal, PhD , Clinical Immunopathology, Royal North Shore Hospital, Sydney, Australia

Suran Fernando, Professor , Clinical Immunology & Allergy, HIV Services, Royal North Shore Hospital, Sydney Medical School - Northern, University of Sydney, Sydney, Australia

Background: Allopurinol, a xanthine oxidase inhibitor, has been used since the 1960s for gout, hyperuricaemia associated with treatment for malignancy and renal calculi due to  hyperuricosuria. It is known as the leading cause of severe cutaneous adverse drug reactions (SCARs) comprising Stevens-Johnson Syndrome (SJS)/Toxic Epidermal Necrolysis (TEN) and HyperSensitivity Syndrome (HSS)/Drug-Rash with Eosinophilia and Systemic Symptoms (DRESS) (Halevy et al. 2008). In Vietnam, we observed a high prevalence of allopurinol- induced SCARs, likely due to both its common use and the high prevalence of HLA-B*5801 (6.5% - Hoa et. al. 2008). The role of viral activation in SCARs is well established. We reviewed patients with allopurinol- induced SCARs to reveal possible non-genetic risk factors.

Methodology: The clinical history, examination findings and results of laboratory investigations in eighty- eight confirmed cases of SCARs caused by allopurinol seen between 2011 and 2014 were surveyed.  

Results: A total of 88 patients comprised 33 SJS (37.5%), 3 TEN (3.4%) and 52 HSS/DRESS (59.1%). The mean age was 59.9±14.4 years (median 57.5) (SJS/TEN: 57.92±15.02 vs HSS/DRESS: 61.33±13.887, p =0.284) and a male preponderance was noted (male: female =62:26). Indications for allopurinol were chronic gout (22.7%), acute gout (12.5%), asymptomatic hyperuricaemia (45.5%) and unknown (19.3%). 100% of patients commenced allopurinol at a dose of 300mg or above. Co-medications were diuretics (3.4%), anti- hypertensive agents (18.2%), colchicine (12.5%), digoxin and probenecid (1.1%). Co-morbidities consisted of hypertension (29.5%), renal insufficiency (13.6%), diabetes (9.1%), dyslipidemia (5.7%), cardiac diseases (4.5%) and liver diseases (4.5%).  The index-day was 17.5 ± 10.8 days (median 17, range: 1 - 66 days, SJS/TEN: 19.58±13.03 vs HSS/DRESS: 15.98±8.68, p <0.001). Virus serology: Human simplex virus (HSV) was positive in 34/40 (85%) with IgG and 3/40 (7.5%) with IgM; Epstein Barr Virus (EBV) was positive in 34/41 (85%) with IgG, 4/41 (9.8%) with IgM; Cytomegalovirus (CMV) was positive in 35/41 (83.3%) with IgG and 2/41 (4.9%) with IgM. An abnormal creatinine was seen in 51.9%, and an elevated AST and ALT in 44.7% and 62.7% patients respectively. Mortality rate was 2.3% (observed only in TEN). In those with SJS/TEN, the average number of natural cavities affected was 2.28 ± 0.45. Ocular lesions occurred in 25 patients (69.4%). Mean of SCORTEN was 1.69 ± 0.95. In HSS/DRESS, 38 (73.1%) had fever over 38.5 °C, 17 (32.7%) had eosinophilia with a median 1.71 G/L. Only 3 (5.8%) patients had facial oedema observed.

Conclusions: The presence of virus infection is very common in allopurinol- induced SCARs patients in Vietnam. A significant number of these SCARs could be prevented by avoiding treatment of asymptomatic hyperuricaemia and reducing the starting dose of allopurinol.