Inflammatory Bowel Disease Serology
Inflammatory bowel disease (IBD) is a descriptive term that encompasses Crohn’s disease (CD) and ulcerative colitis (UC). The American College of Gastroenterology Practice Parameters Committee recommends a combination of clinical, endoscopic, histologic, radiographic and surgical findings to differentiate between CD and UC.
In approximately 20% of cases, overlapping symptoms, radiographic and histologic features make the differential diagnosis difficult. It is important to accurately differentiate between these two diseases because they have different prognoses and treatments. Patients with UC are at increased risk of developing colon cancer. When medical treatment fails to control the inflammatory process, colectomy is indicated as curative therapy. In contrast, surgery is not curative and can lead to further complications in patients with CD. Also, CD patients may benefit from treatment with infliximab, an anti-tumor necrosis factor antibody.
Some commercial laboratories have promoted the routine use of an IBD serology panel to help distinguish between CD and UC. The panel includes:
- Perinuclear anti-cytoplasmic antibody (pANCA)
- Saccharomyces cerevisiae IgA and IgG antibodies (ASCA)
Because pANCA is more prevalent in UC and ASCA is more prevalent in CD, these laboratories provide simplified interpretive tables, such as the one below, to distinguish UC from CD.
|
pANCA |
ASCA |
Interpretation |
|
Positive |
Negative |
UC |
|
Negative |
Positive |
CD |
However, careful review of the literature reveals that the clinical value of ANCA and ASCA testing in IBD is limited because of insufficient sensitivity and specificity.Approximately 30-80% of patients with UC have elevated levels of perinuclear anti-neutrophil cytoplasmic antibody (pANCA) compared to 5–40% of patients with CD. ANCA are also present in patients with small vessel vasculitides, primary sclerosing cholangitis and autoimmune hepatitis. They are detectable in 2% of healthy controls and 11% of diseased controls.
Approximately 40-60% of patients with CD have measurable IgA and/or IgG ASCA, compared to 5-15% of patients with UC. ASCA are not specific for CD, but are detectable in patients with other diffuse intestinal diseases such as gluten sensitive enteropathy (celiac disease). They are also present in 3% of healthy controls and 11% of diseased controls. The presence of ASCA in patients with IBD may be due to an immune response against a Saccharomyces antigen or to an unidentified crossreactive antigen.
A retrospective audit of 2,754 consecutive IBD serology panels submitted to Mayo Medical Laboratories revealed definitive results for CD or UC in only 18% of tests (Mayo Communique, Sep 2006;31:1-4). These results suggest that serologic testing is being ordered prior to or without the recommended clinical, endoscopic, histologic and radiographic studies. Because of these limitations, Mayo Medical Laboratories has published the following IBD serologic test guidelines. Serologic testing is not recommended in the following situations:
- Screening patients with nonspecific GI symptoms
- Screening patients who are strongly suspected of having IBD
- Distinguishing between CD and UC in patients who have not undergone standard diagnostic tests.
- Determining the extent of disease in patients with IBD
- Monitoring response to disease specific therapy
An IBD serology panel is recommended only as an adjunct to differentiate CD and UC in patients with a clinical diagnosis of IBD and nondiagnostic histology and radiologic findings. Mayo Medical Laboratory has determined that IBD serology can provide definitive diagnostic results in approximately 40% of patients with IBD who have overlapping findings for CD and UC.
Mayo’s recommendations are in accordance with the American College of Gastroenterology Practice Parameters Committee, which stated that pANCA and ASCA “may be useful in the patient in whom all other clinical features do not allow a distinction between UC and CD” (Amer J Gastroenterol 2004;99:1371-85). Physicians ordering IBD serology panels should make certain that they are complying with these guidelines.
