Nicholas I. Church

Autoimmune Pancreatitis: Clinical and Radiological Features and Objective Response to Steroid Therapy in a UK Series

OBJECTIVE:Most cases of autoimmune pancreatitis (AIP) have been reported from Japan. We present data on a UK series, including clinical and radiological features at presentation, and longitudinal response to immunosuppression.METHODS:Over an 18-month period, all patients diagnosed in our center with AIP were studied. Endoscopic biliary stenting was performed as required, and patients were treated with prednisolone, with response assessed longitudinally. In cases of disease relapse following steroid reduction, azathioprine was instituted.RESULTS:Eleven patients met diagnostic criteria for AIP. Diffuse pancreatic enlargement was seen in eight patients (73%), and pancreatic duct strictures in all. Seven patients required biliary stents. Extrapancreatic involvement occurred in all, including intrahepatic stricturing and renal disease. Eight weeks after starting steroids, the median serum bilirubin level had fallen from 38 μmol/L to 11 μmol/L (P = 0.001), and ALT from 97 IU/L to 39 IU/L (P = 0.002). Stents were removed in all cases, with no recurrence of jaundice. Improvements in mass lesions and pancreaticobiliary stricturing occurred in all patients. During a median 18-month follow-up, six patients relapsed, four of whom responded to azathioprine. Two patients discontinued steroids and remained well.CONCLUSIONS:Extrapancreatic disease was an important feature of AIP in this UK series. Initial response to immunosuppressive therapy was excellent, but disease relapse was common. Optimal long-term management remains to be established.

Presentation and Management of Post-treatment Relapse in Autoimmune Pancreatitis/Immunoglobulin G4-Associated Cholangitis

BACKGROUND & AIMS Autoimmune pancreatitis (AIP) is a multisystem disorder that often has extrapancreatic manifestations such as immunoglobulin G4-associated cholangitis (IAC). Patients respond rapidly to steroids but can relapse after therapy. We assessed the clinical management of relapse in a group of patients with AIP/IAC. METHODS We performed a prospective study of patients diagnosed with AIP from 2004-2007 who received steroids. Treatment outcome was defined clinically, radiologically, and biochemically as response to steroids, remission after steroids, failure to wean steroids, and relapse. Steroids +/- azathioprine (AZA) were used to treat patients who failed, relapsed, or could not be weaned from steroids. RESULTS Twenty-eight patients with AIP were studied; 23 (82%) had IAC. All patients responded within 6 weeks to prednisolone therapy. Twenty-three patients achieved remission after a median of 5 months of treatment (range, 1.5-17 months), whereas 5 patients (18%) could not be weaned because of a disease flare. Of the patients who achieved remission, 8 of 23 (35%) subsequently relapsed. Overall, 13 of 23 patients (57%) with AIP/IAC relapsed, compared with 0 of the 5 with isolated AIP (P = .04, Fisher exact test). Steroids were increased/restarted in all patients who relapsed; 10 also received AZA. Remission was achieved and maintained in 7 patients; they remain on AZA monotherapy at a median of 14 months (range, 1-27 months). CONCLUSIONS Relapse or failure to wean steroids occurred in 46% of patients with AIP. Patients with IAC are at particularly high risk of relapse. AZA appears to be effective in patients with post-treatment relapse or who cannot be weaned from steroids. To view this articles video abstract, go to the AGAs YouTube Channel.

Endoscopic retrograde pancreatography criteria to diagnose autoimmune pancreatitis: an international multicentre study

Background Characteristic pancreatic duct changes on endoscopic retrograde pancreatography (ERP) have been described in autoimmune pancreatitis (AIP). The performance characteristics of ERP to diagnose AIP were determined. Methods The study was done in two phases. In phase I, 21 physicians from four centres in Asia, Europe and the USA, unaware of the clinical data or diagnoses, reviewed 40 preselected ERPs of patients with AIP (n=20), chronic pancreatitis (n=10) and pancreatic cancer (n=10). Physicians noted the presence or absence of key pancreatographic features and ranked the diagnostic possibilities. For phase II, a teaching module was created based on features found most useful in the diagnosis of AIP by the four best performing physicians in phase I. After a washout period of 3 months, all physicians reviewed the teaching module and reanalysed the same set of ERPs, unaware of their performance in phase I. Results In phase I the sensitivity, specificity and interobserver agreement of ERP alone to diagnose AIP were 44, 92 and 0.23, respectively. The four key features of AIP identified in phase I were (i) long (>1/3 the length of the pancreatic duct) stricture; (ii) lack of upstream dilatation from the stricture (<5 mm); (iii) multiple strictures; and (iv) side branches arising from a strictured segment. In phase II the sensitivity (71%) of ERP significantly improved (p<0.05) without a significant decline in specificity (83%) (p>0.05); the interobserver agreement was fair (0.40). Conclusions The ability to diagnose AIP based on ERP features alone is limited but can be improved with knowledge of some key features.

Endoscopic Retrograde Cholangiography Does Not Reliably Distinguish IgG4-Associated Cholangitis From Primary Sclerosing Cholangitis or Cholangiocarcinoma

BACKGROUND & AIMS Distinction of immunoglobulin G4-associated cholangitis (IAC) from primary sclerosing cholangitis (PSC) or cholangiocarcinoma is challenging. We aimed to assess the performance characteristics of endoscopic retrograde cholangiography (ERC) for the diagnosis of IAC. METHODS Seventeen physicians from centers in the United States, Japan, and the United Kingdom, unaware of clinical data, reviewed 40 preselected ERCs of patients with IAC (n = 20), PSC (n = 10), and cholangiocarcinoma (n = 10). The performance characteristics of ERC for IAC diagnosis as well as the κ statistic for intraobserver and interobserver agreement were calculated. RESULTS The overall specificity, sensitivity, and interobserver agreement for the diagnosis of IAC were 88%, 45%, and 0.18, respectively. Reviewer origin, specialty, or years of experience had no statistically significant effect on reporting success. The overall intraobserver agreement was fair (0.74). The operating characteristics of different ERC features for the diagnosis of IAC were poor. CONCLUSIONS Despite high specificity of ERC for diagnosing IAC, sensitivity is poor, suggesting that many patients with IAC may be misdiagnosed with PSC or cholangiocarcinoma. Additional diagnostic strategies are likely to be vital in distinguishing these diseases.

Autoimmune Pancreatitis: Optimal Therapy Has Not Been Determined

TO THE EDITOR: We would like to thank Matsushita et al. for their interest in our article. They raise specific points concerning the type of steroid therapy for acute autoimmune pancreatitis (AIP) and the use of azathioprine in disease relapse. These points are part of the broader question: What is the optimum therapy for autoimmune pancreatitis (AIP)? This question remains unanswered, as published data include only small case series and case reports. No randomized controlled data exist.

PTU-061 Utility of endoscopic retrograde cholangiography to diagnose IgG4-associated cholangitis: an international, double blind, randomised, multicentre study

Introduction IgG4 associated cholangitis (IAC) may have similar radiographic appearances to primary sclerosing cholangitis (PSC) and cholangiocarcinoma (CCA). Making the diagnosis is important as IAC usually responds favourably to steroids (in contrast to PSC) and erroneous treatment for presumed CCA may be avoided. We assessed whether specialists familiar with these diseases could reliably distinguish between them based on endoscopic retrograde cholangiograms (ERC). Methods ERCs (n=104) of patients with a definitive diagnosis of IAC, PSC and CCA from centres in the US, Japan and UK were screened for quality by an experienced endoscopist unaware of clinical diagnoses. A final set of 48 ERCs (20 IAC, 10 PSC, 10 CCA and 8 duplicates) were arranged in random order and presented to 18 reviewers unaware of the diagnosis. Reviewers noted presence or absence of key ERC features and provided their three most probable diagnoses given as per cent confidence (95%, 75%, 50%, 25% and 5%, totalling 100%). We used a ≥75% confidence in the diagnosis of IAC to determine sensitivity and specificity for that condition. The κ statistic for intra- and inter-observer agreement was also calculated. Results The specificity of ERC for detecting IAC was high and did not differ significantly between centres (Abstract 061), but sensitivity was uniformly low. Neither reviewer speciality (endoscopist, radiologist, HPB physician) nor years of experience had any statistically significant effect on reporting success. Although intraobserver agreement was generally very good, interobserver agreement was poor (Abstract 061). Abstract PTU-061 All USA UK Japan n=18 n=4 n=8 n=6 Sensitivity for IAC (CI) 45% (36 to 54%) 51% (25 to 78%) 42% (25 to 59%) 44% (24 to 64%) Specificity for IAC (CI) 88% (83 to 93%) 88% (68 to 100%) 86% (77 to 95%) 90% (82 to 98%) Interobs agreement for IAC (κ) 0.18 −0.02 0.18 0.17 Conclusion High specificity for diagnosing IAC using ERC suggests that particular cholangiographic features support the diagnosis. However, poor sensitivity suggests that, based on ERC, many patients with IAC, who might benefit from steroid therapy, may be misdiagnosed with PSC or CCA. Additional diagnostic strategies, including pathological sampling, are likely to be vital in distinguishing these diseases.