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Antibodies against Saccharomyces cerevisiae and early surgery for Crohn’s disease

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Medical therapies for Crohn’s disease (CD) range from the relatively benign and less effective (5-aminosalicylates and antibiotics) to the more toxic but more effective (steroids, immunomodulators, and anti-tumour necrosis factor antibodies). Despite such treatments about 80% of patients need surgery within 20 years of diagnosis and 20–40% within three years. Earlier more aggressive medical treatment might reduce rates of surgery but better methods of assessing prognosis are needed so that early effective but potentially toxic treatments can be reserved for patients who might benefit most. Anti-Saccharomyces cerevisiae antibodies (ASCA) are found in 60% of patients with CD and are nearly 95% specific for the diagnosis. There is evidence that ASCA are indicative of poorer prognosis. Now researchers in New England, USA, have reported an association between ASCA and early need for surgery.

A cohort study at 16 centres included 345 patients with CD diagnosed between 1991 and 1999 and followed for at least three years. Sixty nine of these patients required major surgery for CD (excluding surgery at diagnosis) within three years of diagnosis. The case control study included 35 cases (major surgery within three years) and 35 controls (no major surgery within three years), 30 of them matched for age, sex, disease location, and smoking behaviour. Blood was taken for ASCA testing after surgery or, in controls, more than three years after diagnosis. ASCA tests were positive in 23/35 cases (66%) and 7/35 controls (20%). Positive IgA ASCA increased the risk of early surgery eightfold, positive IgG ASCA increased it 5.5-fold, and positive IgA and IgG ASCA increased it fivefold. The significant association between IgA ASCA and early surgery applied to ileocaecal resection and complex intra-abdominal abscess drainage but not to colon resection or complex perianal surgery. Measuring antibody titres did not add to the value of the results. Other markers of inflammatory bowel disease (perinuclear antineutrophil cytoplasmic antibodies and Escherichia coli outer membrane porin C were not associated with early surgery. ASCA titres were not related to time after surgery or time since diagnosis.

Patients with CD who have had surgery within three years of diagnosis are more likely to be ASCA positive than are patients who have not had surgery within three years of diagnosis. More work is needed to demonstrate whether ASCA status at diagnosis is predictive of more aggressive disease and whether more intensive treatment for ASCA positive patients would give better long term results.

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