Inflammatory Bowel Disease
Inflammatory bowel disease (IBD) is a chronic relapsing intestinal condition. Current opinion is that IBD results from inappropriate and ongoing activation of the mucosal immune system by normal flora, possibly due to defects in the barrier function of the intestinal epithelium and the mucosal immune system.1
There are two major forms of IBD, ulcerative colitis (UC) and Crohn's disease (CD), which are distinct diseases. They differ in their histopathology, distribution in the gastrointestinal tract, and patient management but both can present with similar symptoms of diarrhoea, abdominal pain and weight loss. CD affects women and men almost equally and can appear at any age. In contrast UC occurs more frequently in women, with a peak onset at around 20 years.2, 3
Indeterminate Colitis
A definitive diagnosis of IBD is established by a combination of radiographic, endoscopic and histologic criteria with differentiation between ulcerative colitis and Crohn's disease being established in most cases. However, in 10-15% of patients, a distinction between UC and CD cannot be made with certainty even after a thorough pathological investigation. These patients are classified as having indeterminate colitis.
Correct diagnosis of ulcerative colitis and Crohn's disease has major implications on the choice of treatment, surgical procedures and long-term prognosis. This is particularly important in paediatric patients with severe symptoms and prolonged history. In such cases an earlier diagnosis may decrease long-term morbidity of IBD e.g. delayed puberty, shorter ultimate height, nutritional deficiencies etc.2 Recent studies have indicated two serological markers, anti-saccharomyces cerevisiae antibodies (ASCA) and perinuclear anti-neutrophil cytoplasmic antibodies (P-ANCA), may assist in the differentiation of ulcerative colitis and Crohn's disease in patients with indeterminate colitis.
ASCA
ASCA occur more commonly in patients with CD (50-89%) but are less frequent in UC (<10%). It has been observed that a few patients have only IgG or IgA ASCA. However the levels tend to be lower than in patients who have both classes. Results are therefore more significant when both IgG and IgA ASCA are considered.4, 6, 7
P-ANCA
A P-ANCA (myeloperoxidase (MPO) negative) pattern is found predominantly in patients with ulcerative colitis. These P-ANCA reactions localise over the nuclear periphery and typically do not cross-react with MPO and other cytoplasmic antigens.
It is believed elevated serum levels of P-ANCA in ulcerative colitis are caused by P-ANCA production in the colonic mucosa. P-ANCAs are detected in 60-80% of adult and around 83% of paediatric patients with ulcerative colitis, but are less frequent in Crohn's disease (5-30%).4,5
Combined measurement of both ASCA and P-ANCA gives a better diagnostic differentiation between Crohn's disease and ulcerative colitis than measurement of the individual markers. Both the specificity and PPV are increased to clinically useful levels.8
| Sensitivity (%) | Specificity (%) | PPV (%) | |
|---|---|---|---|
|
ASCA positive, P-ANCA negative for CD |
56 | 92 | 95 |
|
ASCA negative, P-ANCA positive for UC |
44 | 98 | 88 |
Proposed Testing Protocol
References
1. Podolsky, DK. Inflammatory bowel disease. N Eng J Med 2002;347 (6): 417-429
2. Guindi, M., Riddell, R.H. Indeterminate colitis. J Clin Pathol 2004;57:1233-1244
3. Vermeire S et al. Comparative study of ASCA (Anti-Saccharomyces cerevisiae antibody) assays in inflammatory bowel disease. Gastroenterology 2001;120: 827-33
4. Nakamura, R.M., Matsutani, M., Barry, M. Advances in clinical laboratory tests for inflammatory bowel disease. Clinical Chimica Acta 2003;335:9-20
5. Barta et al. Seroreactivity against Saccharomyces cerevisiae in patients with Crohn's disease and celiac disease. World J Gastroenterol 2003;9(10): 2308-12
6. Muratori et al. ASCA and autoimmune liver diseases. Clin Exp Immunol 2003;132:473-476
7. Walker et al. ASCA in Crohn's disease are associated with disease severity but not NOD2/CARD15 mutations. Clin Exp Immunol 2004;135:490-496
8. Rutgeerts P, Vermeire S. Serological diagnosis of inflammatory bowel disease. Lancet 2000;356;2117-8
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