Increased intestinal permeability precedes the onset of Crohn's disease ina subject with familial risk

Increased intestinal permeability to several specific molecular probes has been observed in patients with Crohn's disease and their first-degree relat ives. A positive family history is also a potent risk factor for inflammato ry bowel disease. Although it has been argued that increased permeability i n relatives may confer an increased future risk of developing Crohn's disea se, longterm follow-up of such family members has been lacking We describe a 24-year-old woman with a positive family history of Crohn's disease who h ad an elevated gut permeability to Cr-51-EDTA at age 13, as part of a cross -sectional cohort study in patients and their first-degree relatives. She w as asymptomatic at the time, and extensive investigation found no evidence of microscopic or macroscopic Crohn's disease. Repeat investigation because of symptom onset at age 21 revealed ileocolonic Crohn's disease, which req uired treatment with systemic corticosteroids to induce a clinical remissio n. In this case, a permeability defect was clearly identified to precede th e onset of Crohn's disease in a subject at increased risk. This observation provides sup port for the hypothesis that increased gut permeability to ma cromolecules is an early step in the pathogenesis of this disorder.