Preclinical and Undiagnosed Crohn's Disease: The Submerged Iceberg

Little is known on the natural history of Crohn's disease (CD) before diagnosis. By the time the patient is diagnosed, the disease has often produced considerable damage to the intestinal mucosa and sometimes other organs. Such period before diagnosis might involve both a silent and a symptomatic phase. The silent phase, or preclinical CD, might last several years after the biological disease onset. Evidence is accumulating that the symptomatic phase might also go undiagnosed for months or years. In fact, for each established case of CD, there are probably several undiagnosed cases, a classic iceberg phenomenon of disease. Such status quo--lagging behind diagnostic standards for many other diseases--effectively hampers efforts to block disease evolution and the development of complications. This is no longer tenable because CD is a debilitating, severe, and costly affection, whose incidence is rapidly rising worldwide. Here, we will review what is currently known on preclinical and undiagnosed CD and what could be done to improve accuracy and timeliness of diagnosis.