Journal of Pediatric Gastroenterology & Nutrition:
Department of General Pediatrics, University of Heidelberg, Heidelberg, Germany.
Address correspondence and reprint requests to Guido Engelmann, MD, Department of General Pediatrics, University of Heidelberg, INF 430, D-69120 Heidelberg, Germany (e-mail: email@example.com).
Received 21 March, 2012
Accepted 22 April, 2012
The author reports no conflicts of interest.
See “Investigative MRI Cholangiopancreatography for Primary Sclerosing Cholangitis–type Lesions in Children” by Alexopoulou et al on page 308.
In the present issue of JPGN, Alexopoulou et al (1) present data on the frequency of primary sclerosing cholangitis (PSC)–like lesions on magnetic resonance cholangiopancreatography (MRCP) obtained in children with inflammatory bowel disease (IBD). PSC is usually suspected in children when liver-function tests show cholestasis in children with IBD, in the majority of cases without symptomatic liver disease. Rarely are children first diagnosed as having PSC in the situation of clinical cholangitis (fever, fatigue, hyperbilirubinemia, right upper quadrant pain) (2).
By using MRCP, a surprisingly high number of patients with PSC-like lesions were detected in the study presented in this issue of JPGN. Physicians not routinely perform MRCP on patients with IBD because this is not mentioned in our guidelines (3). The data from Alexopoulou et al suggest that there needs to be a new approach in these children. Many patients with subclinical PSC are missed today as MRCP is performed only in children with suspected PSC; however, are there data on sensitivity and specificity of MRCP in patients with PSC and is there evidence that changes in MRCP detected in patients with IBD point to clinically relevant disease and therefore contribute to a better treatment of these patients?
The criterion standard in diagnosing PSC is endoscopic retrograde cholangiopancreatography, but a recent meta-analyses from Dave (4) comparing MRCP results with endoscopic retrograde cholangiopancreatography, histology, and laboratory data of 456 patients with PSC suggest that sensitivity and specificity are equally good using modern magnetic resonance imaging scans (86% and 94%, respectively). In patients with low clinical suspicion (eg, in children with IBD without signs of PSC), the posttest probability of having a PSC if MRCP was negative was 5%. Therefore, it can be concluded that in the first approach to a patient with suggested PSC, MRCP is the diagnostic procedure of choice.
What consequences arise from the diagnoses of subclinical PSC? A Cochrane meta-analysis concludes that UDC positively influences liver enzymes, but there is no evidence that UDC positively influences the course of the disease or the histology of the liver (5). A higher dosage of UDC in a study of 150 adult patients with PSC has led to a higher mortality and more liver transplantations, causing an untimely end of the study (6). A subgroup analysis of the study population later revealed that those patients with normal bilirubin and early histologic stages were at significant risk for reaching the study endpoints death or transplantation compared with those receiving placebo (7). This raises the question whether we have enough evidence to safely treat patients detected by MRCP with UDC. From the recently published studies, we, in our center, have concluded not to treat early stages of PSC but to watch and wait.
Recent work by Ordonez et al (8) suggests a better prognosis for ulcerative colitis in patients with PSC (the majority of patients in that study were diagnosed by MRCP) irrespective of the treatment. The authors postulate that a distinct disease causes ulcerative colitis and PSC (or other autoimmune phenomena). Therefore, diagnosing PSC may give us a better understanding of the prognosis of the associated bowel disease.
Screening for PSC by MRCP in all of the newly diagnosed patients with IBD seems promising concerning our understanding of the course of the disease; however, today's data on long-term outcome of patients under treatment with UDC do not justify therapy with UDC in these children with subclinical PSC.
1. Alexopoulou E, Xenophontos PE, Economopoulos N, et al. Investigative magnetic resonance cholangiopancreatography for primary sclerosing cholangitis (PSC)-type lesions in children with inflammatory bowel disease (IBD): results from a cross-sectional study. J Pediatr Gastroenterol Nutr 2012;55:308–313.
2. Ibrahim SH, Lindor KD. Current management of primary sclerosing cholangitis in pediatric patients. Paediatr Drugs 2011; 13:87–95.
3. Van Assche G, Dignass A, Panes J, et al. The second European evidence-based consensus on the diagnosis and management of Crohn's disease: definitions and diagnosis. J Crohns Colitis 2010;4:7–27.
4. Dave M, Elmunzer BJ, Dwamena BA, et al. Primary sclerosing cholangitis: meta-analysis of diagnostic performance of MR cholangiopancreatography. Radiology 2010; 256:387–396.
5. Chen W, Gluud C. Bile acids for primary sclerosing cholangitis. Cochrane Database Syst Rev 2003;2:CD003626.
6. Lindor KD, Kowdley KV, Luketic VAC, et al. High-dose ursodeoxycholic acid for the treatment of primary sclerosing cholangitis. Hepatology 2009; 50:808–814.
7. Imam MH, Sinakos E, Gossard AA, et al. High-dose ursodeoxycholic acid increases risk of adverse outcomes in patients with early stage primary sclerosing cholangitis. Aliment Pharmacol Ther 2011; 34:1185–1192.
8. Ordonez F, Lacaille F, Canioni D, et al. Pediatric ulcerative colitis associated with autoimmune diseases: a distinct form of inflammatory bowel disease? Inflamm Bowel Dis 2012 (Epub ahead of print).