LAUSR

A 12-year-old male with chronic granulomatous disease (CGD) was evaluated at the pediatric gastroenterology clinic for diarrhea and bloody stools. He had been diagnosed with CGD in his infancy, when he was initially evaluated for a retroauricular suppurative granuloma. Growing up, he experienced several infections, including pulmonary histoplasmosis requiring prolonged course of antifungal therapy. During his evaluation for bloody stools, he tested positive for Clostridoides difficile (C. diff.) infection and received treatment with metronidazole and then vancomycin. Despite such treatments, he experienced recurrence and though he underwent fecal microbiota transfer, his symptoms did not improve. Biopsies taken at colonoscopy showed a loose collection of histiocytes with possible granuloma formation in the descending colon (Fig. 1a). There was evidence of complex crypt branching as well as cryptitis, suggesting chronic and acute inflammatory findings (Fig. 1b, c). After multiple admissions to the hospital for intravenous steroids and oral steroid dependence, he was started on mesalamine and quadruple antibiotic therapy (vancomycin 250 mg 4 times a day, amoxicillin 50 mg/kg divided by three, metronidazole 5 mg/ kg three times a day and doxycycline 2 mg/kg twice a day). He remained on mesalamine and the quadruple antibiotic regimen for about three months, after which he was evaluated acutely in the emergency room with symptoms of unsteady gait, dizziness and vomiting. Though physical examination revealed a wide-based gait, he was afebrile, and his vital signs were stable. He was admitted to the inpatient gastroenterology service where his laboratory evaluation included a complete blood count, C-reactive protein, procalcitonin, electrolytes, folic acid level, methylmalonic acid level, as well as a thiamine level, all of which were normal; Epstein–Barr virus antibody, COVID-19 PCR, respiratory pathogen panel, and blood culture were also negative. A brain MRI (Fig. 2) and axial FLAIR sequence of the brain showed bilateral symmetric hyperintense signal within the cerebellar dentate nuclei. Given that these findings were pathognomonic for metronidazole neurotoxicity, the medication was discontinued. Two days later, patient’s symptoms had resolved, and he was discharged home with mesalamine, amoxicillin, doxycycline and vancomycin. Due to recurrence of his gastrointestinal symptoms and his underlying immune deficiency, he was readmitted to the hematology/oncology service for conditioning and stem cell transplantation. His conditioning regimen consisted of rATG (rabbit anti-thymocyte globulin), clofarabine, melphalan, rituximab and fractionated total body irradiation (fTBI) of 200 cGy. His transplant was a 9/10 HLA-matched (human leukocyte antigens) from an unrelated donor that was alphaand beta-depleted. Shortly thereafter, he rejected the graft and underwent second conditioning about one month later which included rATG, fludarabine, cyclophosphamide, fTBI and rituximab. His second transplant came from his mother, and the transplant was alpha-and beta-depleted as well (dose was 6.66 × 106 CD34 + cells/kg). He engrafted on day + 15. He was then discharged home on steroids, mesalamine and vancomycin. Steroids were weaned off over a course of six months, and patient had no further diarrhea or bloody stools. Fecal calprotectin steadily improved (from 496 to 15 μg/g). Repeat colonoscopy 8 months post-transplant showed normal histology (Fig. 1d); antibiotics were discontinued. He * Yasemin Cagil [email protected]