Allopurinol is frequently used for the treatment of hyperuricemia and gout. Sometimes, a life-threatening reaction develops, as is illustrated by the following case report. We describe a 60-year-old male patient who was treated with allopurinol because of asymptomatic hyperuricemia, and he was presented with fever, skin rash, eosinophilia, worsening renal function and vanishing bile duct syndrome. In this report, we discussed vanishing bile duct syndrome as a serious side effect of allopurinol, and we briefly reviewed the etiology, prevention, and treatment modalities for vanishing bile duct syndrome.
Allopurinol/*adverse effects ; Bile Duct Diseases/*etiology/pathology ; Drug Hypersensitivity/*complications ; English Abstract ; Gout Suppressants/*adverse effects ; Humans ; Male ; Middle Aged

Allopurinol ; adverse effects ; Drug Hypersensitivity ; etiology ; mortality ; Gout ; drug therapy ; Gout Suppressants ; adverse effects ; Humans ; Monitoring, Physiologic ; methods ; Nephrology ; methods ; Risk ; Treatment Outcome

With the advent of Twenty-First century, more and more genome-wide association studies (GWAS) showed that idiosyncratic adverse drug reactions (ADRs) were closely related with human leukocyte antigen (HLA) alleles, such as the associations of abacavir-HLA-B*5701, allopurinol-HLA-B*5801, and carbamazepine-HLA-B*1502, etc. To explore the mechanisms of these idiosyncratic drug reactions, hapten hypothesis, danger signal hypothesis, pharmacological interaction (P-I) concept and autoimmune mechanism are proposed. In this paper, recent GWAS studies on the HLA-mediated adverse drug reactions and underlying mechanism are reviewed in detail.
Alleles ; Allopurinol ; adverse effects ; Anti-HIV Agents ; adverse effects ; Anticonvulsants ; adverse effects ; Carbamazepine ; adverse effects ; Dideoxynucleosides ; adverse effects ; Drug Hypersensitivity Syndrome ; etiology ; immunology ; Drug-Related Side Effects and Adverse Reactions ; genetics ; immunology ; Enzyme Inhibitors ; adverse effects ; Genome-Wide Association Study ; HLA Antigens ; genetics ; HLA-B Antigens ; immunology ; HLA-B15 Antigen ; immunology ; Humans ; Stevens-Johnson Syndrome ; etiology ; immunology

BACKGROUND: Drug reaction with eosinophilia and systemic symptoms (DRESS) is a syndrome involving multiple organs. Due to a variable clinical presentation and uncertain definition, diagnosis is often delayed or misdiagnosed. OBJECTIVE: The purpose of this study was to investigate the common causative drugs of DRESS and differences according to drugs, clinical features, and prognosis of DRESS, and secondly to compare the differences between steroid use group versus non-use group. METHODS: Medical records of hospitalized patients at the Sanggye Paik Hospital from January 2001 to December 2015 were collected. DRESS patients were enrolled retrospectively using the RegiSCAR diagnostic criteria. RESULTS: A total of 65 patients were included. The four most common causative drug groups were antibiotics (27.7%), anticonvulsants (20%), antituberculosis agents (16.9%), and allopurinol (16.9%). The mean incubation period was 4 weeks, significantly shorter in antibiotics (2 weeks, p < 0.001) and significantly longer in anticonvulsants (6.5 weeks, p=0.033). Sixty-three patients fully recovered with a mean recovery time of 3.1 (standard deviation 2.2) weeks, one patient had sequelae, and one patient died. Recovery time tended to increase with longer duration of diagnosis from rash onset (p < 0.001, correlation coefficient=0.419) and higher serum aspartate aminotransferase levels (p=0.024, correlation coefficient=0.297). The mean recovery time was 1 week shorter for the systemic steroid use group, but it was not statistically significant (p=0.056). CONCLUSION: DRESS may be a heterogeneous syndrome with specific characteristics related to different drugs. The prognosis of DRESS is relatively good and the role of systemic steroid therapy is unclear. Prompt diagnosis and immediate discontinuation of the causative drug are essential for early recovery.
Allopurinol ; Anti-Bacterial Agents ; Anticonvulsants ; Aspartate Aminotransferases ; Diagnosis ; Drug Hypersensitivity ; Drug Hypersensitivity Syndrome* ; Drug-Related Side Effects and Adverse Reactions ; Exanthema ; Humans ; Medical Records ; Prognosis ; Retrospective Studies*

BACKGROUND/AIMS: Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS) are severe cutaneous adverse reactions (SCARs) that also affect the internal organs with high mortality. However, there has been no previous nationwide study of SCARs in Korea. METHODS: Cases of SCARs were recruited from the nationwide Korean Pharmacovigilance Research Network database, collected from June 2009 to December 2010, by a spontaneous reporting system. We analyzed age, gender, route of administration and the causative agents. We also reviewed previously published cases of SCARs in Korea. RESULTS: In total, 100 cases of SJS (66 cases), TEN (7 cases), and DRESS (27 cases) were reported. The mean age of the patients was 54.1 +/- 19.8 years and the proportion of males to females was 1:0.88. In total, 81 drugs were reported as causative agents: SJS (61 drugs), TEN (15 drugs), and DRESS (29 drugs). The most commonly reported causative drug was allopurinol (12 cases). Allopurinol (8 cases) and levofloxacin (2 cases) were the most commonly reported causative drugs for SJS and TEN, respectively. In DRESS, allopurinol (4 cases) and vancomycin (4 cases) were the two most common causative drugs. Anti-infective drugs were the most common drug category (75 cases). Carbamazepine was the most commonly reported causative drug according to published cases in Korea. CONCLUSIONS: Allopurinol in the spontaneous reporting system and carbamazepine in the published cases were the most common single causative drugs in SCARs in Korea. Anti-infectives were the most common drug category in the spontaneous reporting system.
Allopurinol ; Carbamazepine ; Cicatrix ; Drug Hypersensitivity ; Drug Hypersensitivity Syndrome ; Drug-Related Side Effects and Adverse Reactions* ; Eosinophilia ; Female ; Humans ; Korea ; Levofloxacin ; Male ; Mortality ; Pharmacovigilance ; Stevens-Johnson Syndrome ; Vancomycin

Toxic epidermal necrolysis is an unpredictable and severe adverse drug reaction. In toxic epidermal necrolysis, epidermal damage appears to result from keratinocyte apoptosis. This condition is triggered by many factors, principally drugs such as antiepileptic medications, antibiotics (particularly sulfonamide), nonsteroidal anti-inflammatory drugs, allopurinol, and nevirapine. Lamotrigine has been reported potentially cause serious cutaneous reactions, and concomitant use of valproic acid with lamotrigine significantly increases this risk. We describe a case of an 11-year-old girl with tic and major depressive disorders who developed toxic epidermal necrolysis after treatment with lamotrigine, and who was diagnosed both clinically and pathologically. Children are more susceptible to lamotrigine-induced rash than adults, and risk of serious rash can be lessened by strict adherence to dosing guidelines. Unfortunately, in our case, the patient was administered a higher dose than the required regimen. Therefore, clinicians should strictly adhere to the dose regimen when using lamotrigine, especially in children.
Adult ; Allopurinol ; Anti-Bacterial Agents ; Apoptosis ; Child* ; Depressive Disorder, Major ; Drug-Related Side Effects and Adverse Reactions ; Exanthema ; Female ; Humans ; Keratinocytes ; Nevirapine ; Stevens-Johnson Syndrome* ; Tics ; Valproic Acid

We report the case of a 36-year-old man with psoriatic arthritis and miliary tuberculosis, whose serum uric acid (SUA) level increased after the initiation of antituberculosis treatment, which included pyrazinamide. Most strikingly and paradoxically, the patient's SUA level increased after treatment with allopurinol. On cessation of allopurinol, his SUA level decreased substantially, and complete normalisation was observed following the discontinuation of pyrazinamide treatment.
Adult ; Allopurinol ; therapeutic use ; Arthritis, Psoriatic ; drug therapy ; Humans ; Hyperuricemia ; chemically induced ; Male ; Pyrazinamide ; adverse effects ; Treatment Outcome ; Tuberculosis, Miliary ; drug therapy ; Uric Acid ; blood

PURPOSE: Despite morbidities and fatalities, nationwide epidemiologic data for severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS), are not widely available. We aimed to investigate SCAR epidemiology over the last two decades in Korea. MATERIALS AND METHODS: We analyzed individual case safety reports (ICSRs) of SCARs in the Korea Adverse Event Reporting System from 1988 to 2013. Administered drugs, demographic profiles, and causality assessment according to the World Health Organization-Uppsala Monitoring Center system were analyzed. RESULTS: A total of 755 SCAR cases (508 SJS/TEN, 247 DRESS) were reported. The number of SCAR ICSRs has been increasing with increasing ICSRs for overall adverse drug events. Since 2010, the number of SCAR ICSRs has increased up to 100 cases/year. Allopurinol was the most common causative drug (SJS/TEN: 10.2%; DRESS: 11.3%; SCAR ICSRs: 10.6%), followed by carbamazepine (SJS/TEN: 8.7%; DRESS: 9.7%; SCAR ICSRs: 8.6%). Regarding drug groups, antiepileptics (19.5%) and antibiotics for systemic use (12.7%) were common causative drug groups. Twenty SCAR-related deaths were recorded. Antibacterials were the most common causes of deaths (8 cases), followed by antiepileptics (5 cases). The potential risk of SCARs was not specified in the drug information leaflet for 40.2% of drugs causing SJS/TEN and 82.5% causing DRESS syndrome in Korea. CONCLUSION: The number of SCAR ICSRs has increased rapidly with recent active pharmacovigilance programs in Korea. Allopurinol and antiepileptics are the most common individual and categorical causative agents, respectively.
Allopurinol ; Anti-Bacterial Agents ; Anticonvulsants ; Carbamazepine ; Cause of Death ; Cicatrix ; Drug Hypersensitivity Syndrome ; Drug-Related Side Effects and Adverse Reactions ; Epidemiology ; Global Health ; Korea ; Pharmacovigilance ; Stevens-Johnson Syndrome

OBJECTIVETo study the effect of retention enema of Chinese herbal medicine combined with allopurinol in treating hyperuricaemia (HUE).

METHODSSeventy-eight patients with HUE were assigned to two: groups, the 40 patients in the treated group were treated with retention enema of Chinese herbal medicine combined with oral intake of allopurinol, and the 38 patients in the control group were treated with allopurinol alone. The therapeutic course for all was 6 weeks. The clinical efficacy, changes of symptoms, blood levels of uric acid and lipids, renal function, and 24 h urinary micro-albumin were observed.

RESULTSThe total effective rate was: 92.5% in the treated group, which was significantly higher than that in the control group (68.4%, P<0.05). After treatment, the score of symptoms in the treated group decreased from 9.43+/-1.15 scores to 3.25+/-0.85 scores, significantly lower than that in the control group (9.75+/-1.43 scores vs 9.25+/-0.82 scores, P<0.01). Moreover, the post-treatment improvements in blood uric acid, blood lipids, renal function and 24h urinary micro-albumin in the treated group were all better than those in the control group (P<0.05 or P<0.01).

CONCLUSIONRetention enema with: Chinese herbal medicine combined with allopurinol could obviously reduce the uric acid level in blood, improve patients' renal function and lipid metabolism, and alleviate the clinical symptoms in patients with HUE.

Adult ; Aged ; Allopurinol ; administration & dosage ; adverse effects ; Blood Urea Nitrogen ; Drugs, Chinese Herbal ; administration & dosage ; adverse effects ; Enema ; Female ; Humans ; Hyperuricemia ; drug therapy ; physiopathology ; Lipids ; blood ; Male ; Middle Aged ; Uric Acid ; blood

BACKGROUND/AIMS: Allopurinol is a urate-lowering agent that is commonly used to prevent chemotherapy-related hyperuricemia. Allopurinol hypersensitivity syndrome (AHS) is a disorder involving multiple organs, which may be accompanied by cutaneous adverse reactions. We identified the characteristics and clinical outcomes of chemotherapy-associated AHS in patients with hematological malignancies. METHODS: This retrospective single-center study included 26 AHS patients (11 with and 15 without hematological malignancies) admitted to Seoul St. Mary's Hospital. AHS was defined using the criteria of Singer and Wallace. Comparisons were made using the Mann-Whitney U test and Fisher exact test as appropriate. RESULTS: In patients with a hematological malignancy and AHS, statistically significant differences were observed in terms of younger age at onset; shorter duration of exposure; higher starting and maintenance doses of allopurinol; lower incidence of eosinophilia, leukocytosis, and underlying renal insufficiency; and more frequent occurrence of fever compared to AHS patients without a hematological malignancy. Two AHS patients with a hematological malignancy were examined for human leukocyte antigen (HLA)-B typing, but neither patient harbored the HLA-B*5801 allele. All of the patients ceased allopurinol treatment, with most patients making a full recovery. Two patients in the study died; however, these deaths were unrelated to AHS. One patient developed serious sequelae of AHS that required hemodialysis. CONCLUSIONS: Physicians who prescribe allopurinol for the prevention of chemotherapy-related hyperuricemia should be aware of the unique risk of AHS, even in patients with hematological malignancies who do not have known risk factors for AHS. Novel urate-lowering agents should be considered alternative treatments.
Adolescent ; Adult ; Age Factors ; Aged ; Allopurinol/*adverse effects ; Antineoplastic Agents/*adverse effects ; Comorbidity ; Dose-Response Relationship, Drug ; Drug Hypersensitivity Syndrome/diagnosis/drug therapy/*etiology ; Female ; Glucocorticoids/therapeutic use ; Gout Suppressants/*adverse effects ; Hematologic Neoplasms/*drug therapy ; Humans ; Hyperuricemia/chemically induced/diagnosis/*prevention & control ; Male ; Medical Records ; Middle Aged ; Republic of Korea ; Retrospective Studies ; Risk Factors ; Treatment Outcome ; Young Adult