Aravind Sugumar

Differences in Clinical Profile and Relapse Rate of Type 1 Versus Type 2 Autoimmune Pancreatitis

BACKGROUND & AIMS Autoimmune pancreatitis (AIP) has been divided into subtypes 1 (lymphoplasmacytic sclerosing pancreatitis) and 2 (idiopathic duct centric pancreatitis). We compared clinical profiles and long-term outcomes of types 1 and 2 AIP. METHODS We compared clinical presentation, relapse, and vital status of 78 patients with type 1 AIP who met the original HISORt criteria and 19 patients with histologically confirmed type 2 AIP. RESULTS At presentation, patients with type 1 AIP were older than those with type 2 AIP (62 +/- 14 vs 48 +/- 19 years; P < .0001) and had a greater prevalence of increased serum levels of immunoglobulin G4 (47/59 [80%] vs 1/6 [17%]; P = .004). Patients with type 1 were more likely than those with type 2 to have proximal biliary, retroperitoneal, renal, or salivary disease (60% vs 0; P < .0001). Inflammatory bowel disease was associated with types 1 and 2 (6% vs 16%; P = .37). During median clinical follow-up periods of 42 and 29 months, respectively, 47% of patients with type 1 and none of those with type 2 experienced a relapse. In type 1 AIP, proximal biliary involvement (hazard ratio [HR], 2.12; P = .038) and diffuse pancreatic swelling (HR, 2.00; P = .049) were predictive of relapse, whereas pancreaticoduodenectomy reduced the relapse rate (vs the corticosteroid-treated group; HR, 0.15; P = .0001). After median follow-up periods of 58 and 89 months (types 1 and 2, respectively), the 5-year survival rates for both groups were similar to those of the age- and sex-matched US population. CONCLUSIONS Types 1 and 2 AIP have distinct clinical profiles. Patients with type 1 AIP have a high relapse rate, but patients with type 2 AIP do not experience relapse. AIP does not affect long-term survival.

Treatment of relapsing autoimmune pancreatitis with immunomodulators and rituximab: the Mayo Clinic experience

Background There is a paucity of data on long-term management of type 1 autoimmune pancreatitis (AIP), a relapsing steroid-responsive disorder. Objective We describe our experience with treatment of relapses and maintenance of remission using steroid-sparing immunomodulators (IMs) and induction of remission using rituximab (RTX). Methods We obtained details of disease relapse and treatment in 116 type 1 AIP patients from clinic visits, medical records and telephone interviews. We compared relapse free survival in those treated with IMs versus those treated with steroids alone, assessed patients’ response to RTX, and identified treatment-related complications. Results During a median follow-up of 47 months, 52/116 AIP patients experienced 76 relapse episodes. The first relapse was treated with another course of steroids in 24 patients, and with steroids plus IM in another 27 patients; subsequent relapse-free survival until a second relapse was similar in the two groups (p=0.23). 38 patients received an IM for >2 months; failure or intolerance of IM therapy occurred in 17 (45%). 12 patients with steroid or IM intolerance/resistance were treated with RTX, an antiCD20 antibody; 10 (83%) experienced complete remission and had no relapses while on maintenance therapy. Treatment-limiting side effects related to RTX were uncommon. Conclusions In type 1 AIP relapses are common. Relapse-free survival is similar in those treated with steroids plus IM compared to those treated with steroids alone. Nearly half the patients on IMs will relapse during treatment. RTX is effective in the treatment of both IM resistant and steroid intolerant patients.

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.

Autoimmune Pancreatitis: Pathologic Subtypes and Their Implications for Its Diagnosis

Autoimmune pancreatitis (AIP) is a rare but treatable form of pancreatic disease that is being increasingly recognized worldwide. The diagnosis of AIP remains a clinical challenge and the difficulty is compounded by the fact that there are no internationally agreed on diagnostic criteria for AIP. One of the reasons for the lack of consensus on diagnostic criteria could be that the term “AIP” likely refers to more than one distinct disease or subtype. This may explain the divide between European and other diagnostic criteria. Recent insights into AIP subtypes should help develop an evidence-based consensus on diagnostic criteria for the disease.

A Systematic Review of the Efficacy of Domperidone for the Treatment of Diabetic Gastroparesis

BACKGROUND & AIMS Despite being widely used in more than 20 countries for the treatment of diabetic gastroparesis for several decades, domperidone is approved only on an investigational basis in the United States. However, because its use is increasing, it is important for gastroenterologists in this country to understand its effectiveness in this condition. The literature on this subject varies considerably with respect to the methods and outcome measures, making a meta-analysis unfeasible. METHODS Our objective was to systematically analyze studies of the efficacy of domperidone in diabetic gastroparesis, with a focus on their methodologic and scientific merit. Information from 28 trials (11 full articles and 17 abstracts) from 1981 to 2007 was analyzed. RESULTS The average study quality score was 8.3 out of a possible 15 and the total sample size equaled 1016. Overall, 64% of the studies showed significant efficacy of domperidone on the improvement of symptoms. Sixty percent of the studies showed an efficacy in gastric emptying and 67% of the studies proved the drug effective in reducing hospital admissions. CONCLUSIONS Overall, our assessment is that there is level 3 evidence for the efficacy of domperidone in diabetic gastroparesis, leading to a grade C recommendation for its use in this condition. These results need to be interpreted very cautiously because of significant methodologic limitations of these studies, including the fact that most positive studies lacked a control arm. It is clear that larger and better-designed studies are needed to further validate the use of this drug in diabetic gastroparesis.

Prevalence, diagnosis, and profile of autoimmune pancreatitis presenting with features of acute or chronic pancreatitis.

BACKGROUND & AIMS Little is known about how many patients with features of acute pancreatitis (AP) or chronic pancreatitis (CP) have autoimmune pancreatitis (AIP); most information comes from case reports. We explored the clinical profiles and relationship between these diseases. METHODS We evaluated 178 patients presenting to our Pancreas Clinic between January 2005 and June 2006 for evaluation of the etiology of their suspected pancreatitis; AIP was diagnosed when patients met HISORt (Histology, Imaging features, Serology, Other organ involvement and Response to steroid treatment) criteria. In a separate cohort of patients with AIP from our database, we identified patients who presented with features of AP (>/=2 of abdominal pain, increased pancreatic enzymes, pancreatic inflammation determined by imaging analyses) or CP (>/=1 of pancreatic calcification, irregular main pancreatic duct dilation, or marked atrophy) and determined their clinical profile. RESULTS Only 7/178 (3.9%) patients evaluated for etiology of suspected pancreatitis had AIP. Among 63 AIP patients in our database, 22 (34.9%) had features of AP (n = 15) or CP (n = 7) at presentation (average age 53.4 +/- 19.0 years, all males). Patients with AIP and pancreatitis were characterized by presence of obstructive jaundice (59.1%), increased levels of liver enzymes (81.8%), increased levels of serum immunoglobulin G4 (80.9%), and other organ involvement (69.1%). All 19 patients presenting with pancreatitis who were treated with steroids responded to treatment. CONCLUSIONS While AIP is an uncommon etiology for acute or chronic pancreatitis, >33% of AIP have features of acute or chronic pancreatitis at presentation.

Distinguishing Pancreatic Cancer From Autoimmune Pancreatitis: A Comparison of Two Strategies

Autoimmune pancreatitis is a rare disease which closely mimics pancreatic cancer in its presentation. It is important for clinicians to distinguish one from the other due to vastly different therapeutic and prognostic implications. We compared 2 recently proposed strategies, 1 from Japan and the other from the United States, to distinguish autoimmune pancreatitis from pancreatic cancer. While both strategies have inherent strengths and weaknesses, we believe that the best features of both need prospective validation. The strategy proposed from Japan is simple to use, but is based on a small number of patients and is heavily dependent on imaging criteria. The American strategy while based on a bigger sample of patients is complicated and is most useful in expert hands. Additionally, differences in clinical practice and local preference in the use of certain diagnostic tests need to be considered while adopting either strategy.

Eosinophilia and Allergic Disorders in Autoimmune Pancreatitis

OBJECTIVES:In autoimmune pancreatitis (AIP), the prevalence, interrelationships, and significance of peripheral eosinophilia, allergic disorders, and eosinophil infiltration in the pancreas remain unclear.METHODS:From medical records, we obtained data on peripheral eosinophil counts at presentation and follow-up, and clinical diagnoses of allergic disorders in 97 AIP patients (78 type 1 and 19 type 2), which were compared with matched healthy controls. Available pancreatic histologic specimens were graded for eosinophils. Peripheral eosinophilia was defined as counts >0.5 × 109 per liter. We examined nature of and association between these parameters in AIP.RESULTS:Among 78 type 1 AIP patients (mean age 62±14 years, 77% men), peripheral eosinophilia at presentation was diagnosed in 12% and allergic disorders in 15% (vs. 0 and 4% in controls, P=0.0004 and 0.006, respectively). Allergic disorders were observed in 27 and 11% of type 1 AIP with and without eosinophilia, respectively (P=0.08). Patients with and without peripheral eosinophilia were similar in clinical profile. Moderate-to-severe eosinophil infiltration was present in 67% of pancreas resection specimens and did not correlate with peripheral eosinophilia. Type 2 AIP did not differ from type 1 AIP in any of these parameters.CONCLUSIONS:Peripheral eosinophilia, allergic disorders, and pancreatic eosinophil infiltration are associated with AIP. Eosinophilia in AIP may not reflect an allergic phenomenon, but appears to be consistent with autoimmune mechanism.

Autoimmune pancreatitis: an update

Autoimmune pancreatitis (AIP) is the pancreatic manifestation of a systemic fibroinflammatory disorder. It has been recognized as a distinct clinical entity, only recently. Multiple organs, such bile ducts, salivary glands, kidneys and lymph nodes, can be involved either synchronously or metachronously. It is one of the few autoimmune conditions that predominantly affects male subjects in the fifth and sixth decades of life. Obstructive jaundice is the most common presenting symptom but the presentation can be quite nonspecific. There are established diagnostic criteria to diagnose AIP, most of which rely on a combination of clinical presentation, imaging of the pancreas and other organs (by CT scan, MRI and endoscopic retrograde pancreatography), serology, pancreatic histology and response to steroids to make the diagnosis. It is imperative to differentiate AIP from pancreatic cancer owing to the vastly different prognostic and therapeutic implications. AIP responds dramatically to steroid treatment but relapses are common. Relapse of AIP can often be retreated with steroids. As the collective experience with this condition increases, a better understanding of the natural history of this disease is emerging.

Autoimmune pancreatitis: Autoimmune pancreatitis

The purpose of this review is to provide a concise view of the existing knowledge of autoimmune pancreatitis (AIP) for practicing clinicians. AIP is a rare disease whose recognition and understanding are evolving. It is a type of chronic pancreatitis that often presents as obstructive jaundice, has a distinctive histology, and is exquisitely sensitive to steroid therapy. This form of chronic pancreatitis has a unique clinical, biochemical, and radiological profile. The term “AIP” encompasses two subtypes: types 1 and 2. Type 1 AIP is the pancreatic manifestation of a systemic fibro‐inflammatory disease called immunoglobulin G4‐associated systemic diseases. Type 2 AIP has been shown to be associated with inflammatory bowel disease. Existing criteria are geared towards the diagnosis of type 1 AIP. At present, pancreatic histology is a requirement for the definitive diagnosis of type 2 AIP. AIP can mimic most other pancreatic diseases in its presentation, but in clinical practice, it often has to be differentiated from pancreatic cancer. There are established criteria and algorithms not only to diagnose AIP, but also to differentiate it from pancreatic cancer. The utility of these algorithms and the approach to management are discussed here.