Severe Ulcerative Colitis After Rituximab Therapy

Abstract

B-cell-depletion therapy with rituximab is efficacious against steroid-dependent nephrotic syndrome (NS) in children and adults. Safety data are limited. Results of small studies have suggested that rituximab is usually well tolerated but that adverse events (such as severe mucocutaneous reactions, fatal infusion reactions, progressive multifocal leukoencephalopathy, and bowel perforation) can occur. We report here the first case (to our knowledge) of a pediatric patient with refractory minimal-change NS who developed severe immune-mediated ulcerative gastrointestinal disease 42 days after rituximab therapy. The disease was characterized by deep ulcers throughout the intestines and predominantly affected the colon. The child presented with severe abdominal pain, bloody diarrhea, weight loss, and fever. Her inflammatory markers were significantly elevated. Extensive evaluation revealed no evidence of infections and no characteristics of defined inflammatory bowel disease or Behçet disease. Colonoscopy revealed severe intestinal inflammation with deep ulcers. Histology of the colonic biopsy specimens revealed extensive infiltrates predominantly composed of CD8(+) T lymphocytes and evidence of high forkhead box P3 (FOXP3) expression. During this significant gastrointestinal disease, the NS remained quiescent. Corticosteroid therapy successfully controlled the severe immune-mediated intestinal inflammation after rituximab therapy. NS relapsed subsequently when CD19(+) and CD20(+) B-cell populations recovered.

Novel Drug Therapies for the Treatment of Crohn's Disease

“…The rate of induction of remission was similar in the rituximab compared to placebo [74]. However; rituximab was observed to exacerbate the symptoms of UC in one case [75] and de novo UC developed in some patients treated with rituximab due to other conditions like nephrotic syndrome [76]; follicular lymphoma [77] and Grave's disease [78]. Due to the adverse events; rituximab was not tested further in IBD.…”

The Changing Face of Inflammatory Bowel Disease: Etiology, Physiopathology, Epidemiology

“…In 2010, the first report (18) was published of a 4-yearold boy, who, receiving regular doses of rituximab for his steroid-dependent nephritic syndrome, developed gut symptoms, at around 6 weeks after therapy was started. After excluding other causes, colonoscopy revealed a UClike pancolitis, with histologic cryptitis.…”

Oral tolerance is inducible during active dextran sulfate sodium-induced colitis

“…In addition to autoimmune and allergic diseases, intestinal inflammation is also regulated by Breg functions, a relationship that has been confirmed by several studies using mouse models of colitis [4] . Additionally, in humans, the depletion of B cells using anti-CD20 (rituximab) for various disorders has been reported to either exacerbate colitis or result in spontaneous colitis [5,6] . Oral tolerance is a phenomenon in which systemic immunity is suppressed relative to orally administered antigens.…”