Natural history of children with mild Crohn’s disease

BACKGROUND: There is a small and poorly studied population of patients with mild and limited Crohn’s disease (CD), who either spontaneously enter remission and can discontinue therapy, or be maintained on milder anti-inflammatory treatment. AIM: To identify a group of children with mild CD who were not escalated to immunomodulators (azathioprine, mercaptopurine, or methotrexate) or biologics (infliximab or adalimumab) within the first two years after their Crohn’s diagnosis and outline the natural history and phenotypic features of these patients. METHODS: In a retrospective chart review of the inflammatory bowel disease database at Boston Children’s Hospital we reviewed all the mild CD patient’s clinic visits, laboratory studies, and procedures for the duration of time they were followed at the center. Patients were included if they had clear diagnosis of Crohn’s disease, and they were not escalated to immunosuppressive therapies for at least 2 years after the date of diagnosis. These mild CD patients were compared to controls diagnosed at a similar time, that were treated with immunomodulators or biologics. Data that was abstracted included: Age at diagnosis, sex, disease location utilizing the Paris classification, medical treatment, surgical treatment, endoscopic findings, histology, and hospitalizations. We also analyzed differences in the phenotypic features between those with mild CD and those with moderate to severe disease. RESULTS: Out of 1205 patients with CD diagnosed between 1990 and 2013, we identified 29 patients that met the inclusion criteria, and they were matched with 58 controls. There were no significant differences between the disease behaviors at presentation, with approximately 90% of patients in each group having inflammatory disease. However, patients with mild disease were more likely to have disease limited to the colon (31% vs 12%, P = 0.03). In contrast, patients with moderate to severe disease (aka control group) were more likely to have ileocolonic disease (70% vs 45% in the mild group, P = 0.02). Of the 29 patients, only 8 required medication escalation to immunomodulators during the period of follow-up. The primary indication for escalation to immune suppressive therapies was corticosteroid dependence. We also found that patients treated without immunomodulators or biologics for mild CD continue to exhibit histologic intestinal inflammation. Of the 29 patients, three developed significant complications of ileal disease, though only one required surgical intervention during the period of follow-up. CONCLUSION: We identified a cohort of children with mild CD, who were able to avoid the institution of immune suppressive therapies for several years, and generally had good outcomes during the period of follow-up. While a subset of these patients will eventually require either immunosuppression or surgery, the majority of them have a good quality of life despite having low-grade intestinal inflammation. Importantly, this subset of patients has managed to avoid the potential toxicities of immune suppression for several years. The majority of these patients have either colonic disease with minimal small bowel involvement or limited ileal disease.