Case report: Hepatotoxicity and nephrotoxicity induced by methotrexate in a paediatric patient, what is the role of precision medicine in 2023?

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.

Recurrent Asymptomatic Sigmoid Diverticular Perforation in a Patient with Pemphigus Vulgaris on Immunosuppressive Therapy: A Case Report.

BACKGROUND Perforation of the colon is associated with high mortality and requires early diagnosis. However, the diagnosis of perforation from atypical causes can be a diagnostic challenge. This report is of a rare case of recurrent sigmoid colonic perforation in a patient with diverticular disease who did not present with an acute abdomen but who had pemphigus vulgaris treated with immunosuppressive therapy. CASE REPORT A 57-year-old man with pemphigus vulgaris was treated with steroids, non-steroidal anti-inflammatory drugs (NSAIDS), and azathioprine. He had episodes of abdominal bloating but denied any other symptoms. He was diagnosed with spontaneous sigmoid diverticular perforation without presenting with an acute abdomen. CONCLUSIONS Diverticular perforation can be asymptomatic in patients on immunosuppressive therapy. Therefore, there should be a high index of suspicion for bowel perforation in patients with abdominal symptoms who are treated for skin diseases, such as pemphigus vulgaris, and are on steroids and other immunosuppressive treatments.

Prevalence of cerebral cavernous malformations associated with developmental venous anomalies increases with age.

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.

Prevalence of Developmental Venous Anomalies Increases With Age.

BACKGROUND AND PURPOSE: To test the hypothesis that developmental venous anomalies (DVAs) may develop in the postnatal period, we studied the age-related prevalence of DVAs on contrast-enhanced magnetic resonance imaging. METHODS: Reports from a consecutive series of head magnetic resonance images with intravenous contrast performed over a 2-year period at our institution were reviewed. Studies reporting the presence of a DVA were retrieved and reviewed by a neuroradiologist. Patients were divided into 4 age groups: (1) <1 year old (neonates/infants), (2) 1 to 5 years old (toddlers and preschoolers), (3) 6 to 17 years old (grade schoolers), and (4) ≥18 years old (adults), and DVA prevalence by age group was studied. RESULTS: A total of 18 073 individuals were included. DVA prevalence in the neonate/infant age group was 1.5% (5/335) compared with 7.1% (51/714) in the toddler/preschool age group. In both the grade-school age group and adult age group, DVA prevalence was 9.6% (150/1557 and 1483/15 467, respectively). Neonates/infants were significantly less likely to have DVAs than other age groups (P<0.001). CONCLUSIONS: We found a very low prevalence of DVAs on contrast-enhanced magnetic resonance imaging in patients <1 year old which was significantly lower than other age groups. These findings suggest that postnatal changes in venous architecture and drainage patterns may contribute to the development of DVAs.