RESUMO
Methotrexate is an immunosuppressant and chemotherapeutic agent used in the treatment of a range of autoimmune disorders and cancers. Its main serious adverse effects, bone marrow suppression and gastrointestinal complications, arise from its antimetabolite effect. Nevertheless, hepatotoxicity and nephrotoxicity are two widely described adverse effects of methotrexate. Its hepatotoxicity has been studied mainly in the low-dose, chronic setting, where patients are at risk of fibrosis/cirrhosis. Studies of acute hepatoxicity of high dose methotrexate, such as during chemotherapy, are scarce. We present the case of a 14-year-old patient who received high-dose methotrexate and subsequently developed acute fulminant liver failure and acute kidney injury. Genotyping of MTHFR (Methylene tetrahydrofolate reductase gene), ABCB1 (codes for P-glycoprotein, intestinal transport and biliary excretion), ABCG2 (codes for BCRP, intestinal transporter and renal excretion) and SLCO1B1 (codes for OATP1B1, hepatic transporter) identified variants in all the genes analysed that predicted a reduced rate of methotrexate elimination and thus may have contributed to the clinical situation of the patient. Precision medicine involving pharmacogenomic testing could potentially avoid such adverse drug effects.
RESUMO
BACKGROUND AND PURPOSE: To test the hypothesis that the prevalence of cerebral cavernous malformation (CCM) associated with developmental venous anomalies (DVAs) increases with age, we studied the age-related prevalence of DVA-associated CCM among patients with DVAs. MATERIALS AND METHODS: Patients with DVAs on contrast-enhanced MRI exams performed over a 2-year period were included in this study. A single neuroradiologist reviewed all imaging exams for the presence of CCMs. Baseline demographic data collected included age, gender, presence of CNS neoplasm, history of cranial radiation, and history of seizure. Patients were divided into age groups based on decade of life. Cochran-Armitage trend tests were performed to determine if increasing age was associated with CCM prevalence. RESULTS: A total of 1689 patients with DVAs identified on contrast-enhanced MRI were included. Of these patients, 116 (6.9%) had a cavernous malformation associated with the DVA. There was a significant positive association between age and the prevalence of DVA-associated CCM (P = 0.002). The prevalence of DVA-associated CCM was 0.8% for the 0-10 age group, 1.6% for the 11-20 age group, 7.5% for the 21-30 age group, 9.5% for the 31-40 age group, 6.1% for the 41-50 age group, 6.3% for the 51-60 age group, 7.4% for the 61-70 age group, and 11.6% for the >70 age group (P < .0001). CONCLUSIONS: Our study demonstrated an age-related increase in prevalence of DVA-associated cavernous malformations among patients with DVAs. These findings suggest that DVA-associated cavernous malformations are acquired lesions.
