Urinary excretion of N-methylhistamine as a marker of disease activity in inflammatory bowel disease

Abstract

OBJECTIVE: Mast cells are thought to participate in the pathogenesis of inflammatory bowel disease (IBD). In this study, urinary excretion of N-methylhistamine (UMH), a stable metabolite of the mast cell mediator histamine, was evaluated as an indicator of disease activity in patients with IBD. METHODS: Urinary excretion of UMH (μg/mmol creatinine × m 2 body surface area) was measured by radioimmunoassay in 55 controls, 56 patients with Crohn’s disease, and in 36 patients with ulcerative colitis. Excretion rates were correlated with clinical, serological, and endoscopic disease activity, disease extent, and location. RESULTS: Urinary excretion of UMH was found to be significantly elevated in IBD. Patients with active Crohn’s disease (7.1 ± 4.2, p = 0.002 vs controls) and active ulcerative colitis (8.1 ± 4.8, p = 0.02 vs controls) had higher rates of UMH excretion than patients in remission (6.3 ± 3.8 and 5.2 ± 2.3, respectively) or controls (4.6 ± 1.9). In Crohn’s disease and ulcerative colitis, a significant correlation of UMH excretion with clinical disease activity was obtained (Crohn’s Disease Activity Index r 2 = 0.58, Clinical Activity Index r 2 = 0.57, p < 0.0001). Serologically, orosomucoid showed the best positive correlation with disease activity (Crohn’s Disease Activity Index r 2 = 0.80, Clinical Activity Index r 2 = 0.86, p < 0.0001), but UMH excretion was found to reflect disease activity more accurately than C-reactive protein (Crohn’s Disease Activity Index r 2 = 0.46, Clinical Activity Index r 2 = 0.42, p < 0.0001). No association between UMH excretion and disease type or localization could be found in Crohn’s disease. However, UMH excretion correlated strongly with endoscopic severity of inflammation in Crohn’s disease (Crohn’s Disease Endoscopic Index of Severity r 2 = 0.70, p < 0.0001) or disease extent in ulcerative colitis. CONCLUSIONS: Urinary excretion of the histamine metabolite UMH is enhanced in IBD. It appears to represent an integrative parameter to monitor clinical and endoscopic disease activity in IBD, which appears to be influenced most likely by mediators released from histamine-containing cells, such as intestinal mast cell subtypes.