A 22-month-old boy presented with hematochezia beginning in infancy. He had a history of lymphadenitis after Bacille Calmette-Guérin vaccination. Based on absent neutrophil oxidative burst activity, absent gp91phox expression (0%), and a CYBB variant (c.252G>A), he was diagnosed with X-linked chronic granulomatous disease (X-CGD). Colonoscopy revealed ulcerative colitis-like pancolitis characterized by diffuse loss of the vascular pattern, fine mucosal granularity, and friability, without perianal fistula. Histopathology showed neither foamy histiocytes nor granulomas.
Treatment with 5-aminosalicylic acid (5-ASA) was discontinued because of intolerance. Vedolizumab (VED) was insufficiently effective, and prednisolone (PSL) and tacrolimus (Tac) were added. Although Tac induced remission at higher trough concentrations, relapse recurred as the trough concentration was lowered. After mirikizumab (MRK) was introduced, clinical remission could be maintained at lower Tac trough concentrations. However, colitis remained difficult to fully control, and prolonged Tac use led to renal dysfunction and septic shock secondary to a catheter-related infection. He therefore underwent unrelated donor bone marrow transplantation at 32 months of age. Conditioning consisted of fludarabine, dose-adjusted busulfan, antithymocyte globulin, and 3-Gy total body irradiation. For graft-versus-host disease (GVHD) prophylaxis, Tac and short-course methotrexate were used. At the start of conditioning, MRK was replaced with VED. Neutrophil engraftment was achieved on day 17 after transplantation, and hematochezia resolved. Although skin GVHD and vomiting developed, endoscopy showed improvement of colitis. Erythema in the stomach and duodenum prompted the addition of PSL while VED was continued, resulting in prompt symptom improvement. VED was discontinued 4 months after transplantation, Tac 9 months after transplantation. He remains alive without recurrence of colitis 1 year after transplantation.
Anti-tumor necrosis factor-alpha agents are generally avoided in chronic granulomatous disease-associated colitis because fatal cases have been reported. The efficacy of VED and ustekinumab, an anti–interleukin-12/23 antibody, has been described in case series, but an optimal treatment strategy for refractory cases has not been established. In this case, MRK reduced the Tac requirement, and VED was safely continued before and after transplantation as bridging therapy. Careful selection of biologic agents with attention to infection risk may facilitate bridging to transplantation in refractory X-CGD–associated colitis. Further accumulation of cases is needed to establish an optimal treatment strategy.
