Se ha denunciado esta presentación.
Utilizamos tu perfil de LinkedIn y tus datos de actividad para personalizar los anuncios y mostrarte publicidad más relevante. Puedes cambiar tus preferencias de publicidad en cualquier momento.

Autoimmune Pancreatitis

1.320 visualizaciones

Publicado el

Autoimmune pancreatitis is the pancreatic manifestation of a systemic disorder that affects various organs, including the bile duct, retroperitoneum, kidney, and parotid and lacrimal glands. It represents a recently described subset of chronic pancreatitis that is immune mediated and has unique histologic, morphologic, and clinical characteristics. A hallmark of the disease is its rapid response to corticosteroid treatment. Although still a rare disease, autoimmune pancreatitis is increasingly becoming recognized clinically, leading to evolution in the understanding of its prognosis, clinical characteristics, and treatment.

Publicado en: Salud y medicina
  • Did you try ⇒ www.HelpWriting.net ⇐?. They know how to do an amazing essay, research papers or dissertations.
       Responder 
    ¿Estás seguro?    No
    Tu mensaje aparecerá aquí
  • A Proven Drug Free Holistic System For Reversing Vitiligo And Related Skin Disorders. ☞☞☞ http://tinyurl.com/y4d5dqxj
       Responder 
    ¿Estás seguro?    No
    Tu mensaje aparecerá aquí
  • Hello! I have searched hard to find a reliable and best research paper writing service and finally i got a good option for my needs as ⇒ www.WritePaper.info ⇐
       Responder 
    ¿Estás seguro?    No
    Tu mensaje aparecerá aquí
  • Natural Breast Enlargement... The Magic Formula ➣➣➣ https://t.cn/A6Liz7kD
       Responder 
    ¿Estás seguro?    No
    Tu mensaje aparecerá aquí
  • If you have any problems with writing, feel free to ask our writers for help! HelpWriting.net is ready to help with any kind of academic writing!
       Responder 
    ¿Estás seguro?    No
    Tu mensaje aparecerá aquí

Autoimmune Pancreatitis

  1. 1. Autoimmune Pancreatitis
  2. 2. Review Article INTRODUCTION Autoimmune pancreatitis (AIP) represents a unique subset of chronic inflammatory pancreatic disease with distinct clinical, morphologic, and histopathologic features that typically responds dramatically to steroid treatment [1-3]. Named in 1995 by Yoshida and colleagues [4-5], the clinical characteristics of the disease had been described as early as 1961. It took several decades for it to be accepted as adistinctiveentity;infact,asrecentlyas2003,theAmerican Pancreatic Association still debated its existence [6]. In the last 5 years, however,AIPhas generated significant interest fromcliniciansandresearchers.Althoughstillararedisease, it is increasingly being recognized and its existence is no longer in doubt. HISTORICAL MILESTONES Sarles and colleagues [5] in 1961 were the first to describe an autoimmune phenomenon in relation to “sclerosis of the pancreas”. Although treatment with immune-modulatingtherapywasnotsuggestedatthattime, this spurred interest in this entity over the next several decades. Several terms were then used to subsequently describe the disease, including “chronic sclerosing pancreatitis,”“lymphoplasmacyticsclerosingpancreatitis,” “nonalcoholic duct-destructive pancreatitis,” “sclerosing pancreatitis,” “sclerosing pancreaticocholangitis,” and “autoimmune chronic pancreatitis” [7-9]. In 1991, Kawaguchi and colleagues [10] described a variant of cholangitis extensively involving the pancreas. This description was quickly followed by several other reports describingotherorganinvolvementinpatientswhohadAIP [7,11]. 269 Apollo Medicine, Vol. 7, No. 4, December 2010 AUTOIMMUNE PANCREATITIS Abid Sattar Consultant Gastroenterologist, Department of Gastroenterology, Apollo BGS Hospital, Kuvempu Nagar, Mysore 570 023, India. e-mail: drabidsattar@gmail.com Autoimmune pancreatitis is the pancreatic manifestation of a systemic disorder that affects various organs, including the bile duct, retroperitoneum, kidney, and parotid and lacrimal glands. It represents a recently described subset of chronic pancreatitis that is immune mediated and has unique histologic, morphologic, and clinical characteristics.Ahallmark of the disease is its rapid response to corticosteroid treatment.Although still a rare disease, autoimmune pancreatitis is increasingly becoming recognized clinically, leading to evolution in the understanding of its prognosis, clinical characteristics, and treatment. Key words:Auto immune Pancreatitis (AIP), Serum IgG4, CT Scan, MRI, Steroids. Ito and colleagues [12] subsequently described the first three cases of AIP that were successfully treated with corticosteroids. In a seminal study published in 2001, Hamano, et al.[9] reported that elevated serum IgG4 levels were associated with sclerosing pancreatitis and that treatment with corticosteroid therapy successfully decreased these levels. The first diagnostic criteria were proposed by the Japanese Pancreas Society in 2001 and subsequently modified in 2006 [13-14]. Chari, et al. [1] in 2006 proposed new diagnostic criteria, which included histologic,imaging,andserologiccharacteristicsandother organ involvement and response to corticosteroids. DEFINITION AIP has been defined as “the pancreatic manifestation of a systemic fibroinflammatory disease which affects not only the pancreas but also various other organs including bile duct, salivary glands, the retroperitoneum and lymph nodes. Organs affected by AIP have a lymphoplasmacytic infiltrate rich in IgG4 positive cells and the inflammatory process responds to steroid therapy” [1]. The systemic disease of which AIP is a manifestation has been called IgG4-related systemic disease (ISD) in recognition that all organsafflictedshowadenselymphoplasmacyticinfiltrate rich in IgG4-positive cells [15-16]. EPIDEMIOLOGY Almost all data describing the epidemiology of AIP come from Japan. In 2002, Nishimori and colleagues [17] randomly surveyed Japanese hospitals on how many patientstheyhadwhohadpancreatitisin2002whofulfilled the diagnostic criteria for AIP as proposed by the Japan
  3. 3. Apollo Medicine, Vol. 7, No. 4, December 2010 270 Review Article Pancreas Society. Based on this survey, the prevalence of patients who hadAIP in Japan was estimated to be 0.82 per 100,000. AIP was predominantly seen in men past middle age (older than 45 years). Other Japanese series have described the prevalence of disease between 5% and 6% of all patients who have chronic pancreatitis [18-19]. The prevalence ofAIPin the United States is unknown, because no extensive population-based studies have been performed. BecauseAIP often mimics pancreatic cancer in its initial presentation, the best estimates of prevalence of AIP are in patients undergoing resection for presumed pancreatic cancer because of obstructive jaundice or a pancreatic mass. In three recent studies, 43 of 1808 (2.4%) pancreatic resections were reported to have lymphoplasmacytic sclerosing pancreatitis (LPSP) on histologic examination of the resected specimen.. Another retrospective evaluation of 245 pathology specimens at the Mayo Clinic from patients who underwent resection for benign pancreatic disease revealed that 27 (11%) representedAIPwith a “tumefactive” presentation. Males are nearly twice as likely as females to develop AIP and the average age of onset is in the fifth decade [17]. In fact, 85% of patients are older than 50 years of age [19]. PATHOGENESIS Currently, the pathogenesis of AIP is unknown, although it almost certainly reflects an immune-mediated process. Genetic susceptibility to AIP has been linked to both the HLA-DRB1"0405-DQB1"0401 in the class II and theABCF1 proximal to C3-2-11 telomeric of HLA-E in the classIregions[20].Inaddition,arecentreportdescribedthe genetic association of Fc receptor-like 3 polymorphisms withAIPin Japanese patients [21]. The trigger for AIP remains elusive. It is hypothesized that HLA-DR antigens on the pancreatic ductal and acinar cells may serve as antigens recognized by CD4+ producing interferon-c and CD8+ T lymphocytes, leading to subsequent inflammation. Polymorphisms of the cytotoxic Tlymphocyte-associatedantigen4,akeynegativeregulator of the T-cell immune response, have been demonstrated in patients who haveAIP [22].An etiologic role for antigenic Helicobacterpylori infectionbywayofmolecularmimicry has also been proposed. Like many immune-mediated diseases, AIP has been linked to many other autoimmune conditions, such as Sjögren syndrome, retroperitoneal fibrosis, and primary sclerosing cholangitis (PSC) [23-25]. The work by Kamisawa and colleagues, however [26], has shown that these associated conditions are in fact manifestations of a new clinicopathological entity, IgG4- relatedsystemicdisease(ISD)thatischaracterizedbytissue infiltration with abundant IgG4-positive plasma cells. For example, unlike Sjögren syndrome, Reidel thyroiditis and IgG4-associated nephritis [27]. Whether AIP is truly associated with any other distinct autoimmune disorder needs confirmation in case-control studies. Clinical features Most patients who haveAIP are male and older than 50 years[17,19,20]. The male/female predominance is approximately2:1[21].Femalepatientsaremoreprevalent in the subset of AIP associated with parotid gland involvement, however http://www.mdconsult.com/das/ article/body/225139942-12/jorg=journal&source =MI&sp=20688639&sid=1077935416/N/644914/1.html? issn=0889-8553-r08000150035.Althoughtheageofonset is typically in the sixth decade, AIP has been described in patients in their 30s [19]. The clinical presentation ofAIPmay include pancreatic or extrapancreatic manifestations: Pancreatic manifestations Obstructive jaundice Diabetes Steatorrhea Upper abdominal discomfort or pain Weight loss Acute pancreatitis (rare) Extrapancreatic manifestations Biliary strictures Sclerosing cholangitis Sialoadenitis Retroperitoneal fibrosis Hilar or abdominal lymphadenopathy Chronic thyroiditis, Interstitial nephritis The most common presentation, seen in over two thirds of patients with an acute presentation, is obstructive jaundice associated with a biliary stricture and a focal mass or diffuse enlargement of the pancreas [28]. The major differentialdiagnosisinthissituationispancreaticorbiliary cancer, often leading to surgical resection. Other pancreatic mani-festations include the presence of a pancreatic mass, diffuse or focal enlargement of the pancreas in the absence of obstructive jaundice, and new onset or worsening of existingdiabetesorsteatorrhea.Incontrasttootherformsof chronic pancreatitis, abdominal pain and attacks of acute pancreatitis are uncommon manifestations of AIP. Most patients with AIP have no or mild abdominal pain or discomfort that is controlled by nonnarcotic analgesics. Pancreaticenzymeelevationsmaybeseeninsomepatients. The pancreatic manifestations of AIP thus can mimic pancreatic cancer, acute pancreatitis, painless chronic pancreatitis, or unexplained pancreatic functional insufficiency.
  4. 4. Review Article 271 Apollo Medicine, Vol. 7, No. 4, December 2010 not seen in AIP; however, long-standing or recurrent AIP can be associated with stone formation. Classically, the predominant histologic feature of AIP has been dense infiltration of the periductal space with plasma cells and T lymphocytes. Associated with this infiltrate is acinar destruction, obliterative phlebitis involving the major and minor veins, and storiform or “whirling” fibrosis of the pancreatic parenchyma, which can extend to contiguous peripancreatic soft tissue. This constellation of histopathologic findings defines LPSP AIP has been associated with involvement of several other organs. These extrapancreatic manifestations of AIP can be seen in up to 49% of patients and include biliary strictures, sclerosing cholangitis, sialadenitis, retro- peritoneal fibrosis, hilar or abdominal lymphadenopathy, chronicthyroiditis,interstitialnephritis,andinflammatory- bowel disease. The extrapancreatic manifestations may occur concurrently with pancreatic disease, may be present before the recognition of pancreatic disease, or can occur weeks to months after their initial presentation [27,29]. Table 1 summarizes the common, atypical, and rare clinical features encountered inAIP. HISTOPATHOLOGY Ongrossexamination,thepancreasinAIPisoftennoted to be indurated and firm, the fibroinflammatory process within the pancreas can mimic pancreatic ductal adenocarcinoma because it is commonly localized in the head of the pancreas ( Fig. 1) [6]. The involved area is firm andgraytowhite;thenormallobulararchitectureislostand the fibrosis can sometimes be seen infiltrating the peripancreatic soft tissue. When AIP involves the head of the pancreas, involvement of the main pancreatic duct results in proximal stenosis or obstruction and distal dilatation;thecommonbileductisalsousuallyinvolved(in greater than 90% of the cases) and appears thickened and stenotic with proximal dilatation. Unlike other forms of chronic pancreatitis, such as alcoholic pancreatitis and hereditarypancreatitis,calcifications,ductdilatationwithin thefibroticareas,fatnecrosis,andpseudocystsaretypically Table 1. Clinical features of autoimmune pancreatitis Feature Typical (>50%) Less common (10-50%) Rare (<10%) Presenting Obstructive jaundice Abdominal pain, weight loss, Clinical acute pancreatitis, complaint diabetes, steatorrhea asymptomatic Histology LPSP IDCP Extensive fibrosis, minimal inflammation Pancreatic Diffusely enlarged gland Parenchymal atrophy, intraductal Pseudocyst imaging with delayed and rim calcification enhancement, irregular narrowed pancreatic duct Serology Elevated serum IgG4 Normal serum IgG4 levels levels Other organ Bile duct, kidneys, Retroperitoneum, salivary Mesenteritis, inflammatory involvement lymphadenopathy gland bowel disease Response to Complete Incomplete Refractory to steroids steroids Abbreviation: IDCP, idiopathic duct-centric chronic pancreatitis. Data from Lara LP, Chari ST.Autoimmune pancreatitis. Curr Gastroenterol Rep 2005;7:101–6. Fig. 1. Gross appearance of AIP. A cross section through the pancreas is shown. Dense, white fibrotic tissue has replaced the normal pancreatic parenchyma. There is enhancement of the process around the common bile duct (*). There are foci of fat necrosis present in this example (yellow flecks).
  5. 5. Apollo Medicine, Vol. 7, No. 4, December 2010 272 Review Article (Fig. 2) [10,30]. A less common histopathologic variant termed idiopathic duct-centric chronic pancreatitis is characterized by a neutrophilic infiltrate with occasional microabscesses and rare obliterative phlebitis [9,31]. Nearly a third of patients who haveAIPdevelop pancreatic calcification and atrophy and the appearance can resemble usual chronic calcific pancreatitis. Pathologic features of autoimmune pancreatitis Characteristic findings Firm, tumor-like mass within the head of the pancreas Lymphoplasmacytic inflammation with associated fibrosis (periductal or lobular) Obliterative venulitis Increased numbers of IgG4-positive plasma cells (>10/ high-powered field) Lesscommonlyseen Diffuse fibrosis Neutrophilic infiltrate within the lobules and ducts with occasional microabscess bular fibrosis without significant inflammation Not typically seen Ductal dilatation Calcifications or stones Fat necrosis Pseudocyst formation http://www.mdconsult.com/das/article/body/225139942- 12/jorg=journal&source=MI&sp=20688639& Fig.2 Histopathologic features of AIP. (A) Low magnification showing a fibroinflammatory process diffusely involving and destroying the pancreatic parenchyma (hematoxylin-eosin, original magnification _40). (B) Periductal inflammation and fibrosis extends into the adjacent parenchyma; the ductal epithelium is relatively spared (hematoxylin-eosin, original magnification _100). (C) On higher magnification, destruction of the normal acini by plasma cells (arrows), lymphocytes, and fibroblasts can be seen; the acinar cells contain pink cytoplasmic granules (hematoxylin-eosin, original magnification _400). (D) Obliterative venulitis is a characteristic finding in AIP. Here, the vein lumen (*) is nearly obliterated by the inflammatory process; an uninvolved artery is present in the lower right corner (hematoxylin-eosin, original.
  6. 6. Review Article 273 Apollo Medicine, Vol. 7, No. 4, December 2010 sid=1077935416/ N/644914/If08000150001.fig - top Because elevated IgG4 serum levels are typically identified in patients withAIP, the presence of IgG4 plasma cells, detected by immunohistochemistry, is another characteristic histopathologic finding of AIP and can be used as a diagnostic tool in AIP and related sclerosing diseases.Adense infiltration of IgG4-positive plasma cells in the pancreas is characteristic of AIP (Fig. 3). In the Japanese literature, ‘‘dense’’ is defined as greater than 30 IgG4-positive cells per high-power field (hpf). A recent publication by the Mayo Clinic divides the IgG4-positive infiltrate into mild (<10/hpf), moderate (11–30/hpf), and marked (>30/hpf). They found that patients withAIP often had moderate or marked infiltration by IgG4-positive plasma cells in their pancreatic tissue.This was particularly true in classic LPSP, in which 16 (94%) of 17 cases showed elevated numbers of IgG4-positive cells, compared with 5 (42%) of 12 cases of IDCP, highlighting yet another difference between these two histologic variants of AIP. Both sets of researchers rarely found IgG4 staining in patients with chronic alcoholic pancreatitis and pancreatic ductal adenocarcinoma. Based on these studies of IgG4 staining in AIP, another diagnostic feature of AIP is the presence of a lymphoplasmacytic infiltrate with greater than10 IgG4-positive cells/hpf in the pancreas. Imaging features Although several distinguishing imaging features of AIP have been proposed in the literature, the lack of familiarity of this entity by radiologists and referring clinical services often results in an errant diagnosis of pancreatic carcinoma. The characteristic appearance of AIP observed by various imaging modalities is that of a diffusely enlarged pancreas, forming a sausage-shaped gland with featureless borders (Fig.4) [1,32]. Other classic features that may be present include delayed and prolonged contrast enhancement, a rimlike capsule surrounding the gland on delayed enhancement sequences (the hypoattenuation halo), a nondilated, ectatic pancreatic duct, and the absence of peripancreatic fat hypoenhancement, calcifications, stones, and pseudocysts are typically not seen. On CT, in addition to appearing diffusely enlarged (Fig.4-A),thepancreashasdelayedandprolongedcontrast enhancement and can have a capsulelike low-density rim surrounding the pancreas. In a large study by Sahani and colleagues, uniform pancreatic enlargement and isoenhancement were common features in most patients with diffuseAIP; peripancreatic infiltration, when present, was minimal. Absence of normal pancreatic clefts and a subtle rim of hypoattenuation were thought to be caused by inflammatoryexudates(Fig.2A).MorefocalAIP,typically within the head and uncinate process, was difficult to distinguish from pancreatic carcinoma. MRI characteristically reveals enlargement of the pancreas with decreased signal intensity on T1-weighted MR images, increased signal intensity onT2-weighted MR images, and, occasionally, a hypointense capsule-like rim (Fig 4 B) [30]. Magnetic resonance cholangiopancreato- graphy (MRCP) is often helpful in characterizing the pancreaticandbileducts,althoughthenarrowedsegmentof the pancreatic duct is not well visualized. Narrowing of the anterior superior pancreaticoduodenal artery, posterior superior pancreaticoduodenal artery, and transpancreatic arteryonangiographicevaluationhasalsobeendescribedin AIP patients [33]. Increasingly, endoscopic ultrasound has been used to evaluate patients for AIP [34,35]. Not only can the parenchyma and biliary and pancreatic ducts be visualized, EUS also provides an opportunity to obtain Trucut biopsy samples.Intraductalultrasoundcanalsobeusedtoevaluate indeterminate biliary strictures. Levy and colleagues [36] have reported on the diagnostic usefulness ofTrucut biopsy in three patients who had suspected pancreatic adenocarcinoma with planned surgical resection following indeterminate fine-needle aspiration. In two of the patients, AIPwasdiagnosedusingTrucutbiopsy;intheotherchronic pancreatitis was diagnosed. In all patients, unnecessary surgery was avoided. On endoscopic retrograde cholangiopancreatography (ERCP), the pancreatic duct has an irregular contour and can be either segmentally or diffusely narrowed [28]. If the Fig. 3 Numerous IgG4-positive plasma cells are present in this case of AIP (IgG4 immunostain).
  7. 7. Apollo Medicine, Vol. 7, No. 4, December 2010 274 Review Article proximal duct is strictured, there is often dilation of the distalpancreaticductorproximalcommonbileduct.Unlike ERCP, MRCP may not be able to detect the irregular narrowing of the main pancreatic duct, but the MRCP findings of skipped, nonvisualized main pancreatic duct lesions, in conjunction with other imaging studies, are useful in supporting a diagnosis of AIP .Cholangiography has been shown to be an accurate method to differentiate AIP from primary sclerosing cholongitis (PSC). Nakazawa and colleagues [37] reported that bandlike stricture, beaded orpruned-treeappearance,anddiverticulum-likeformation were significantly more frequent in patients who had PSC. In contrast, segmental stricture, long stricture with prestenotic dilatation, and stricture of the distal common bile duct were significantly more common in sclerosing cholangitis with AIP. Increased uptake with whole-body (18)F-fluorodeoxyglucose positron emission tomography is seen in the pancreas and extrapancreatic lesions of patients who haveAIP[38-40]. FEATURES OF AUTOIMMUNE PANCREATITIS BY VARIOUS IMAGING MODALITIES General findings Diffusely or focally enlarged pancreas With structuring of the main pancreatic duct, can see dilatation of the upstream pancreatic or common bile ducts Typically absent: calcifications, pancreatic duct stones, and pseudocysts CT Diffuse pancreatic enlargement, uniform enhancement, minimal pancreatic infiltration The focally enlarged pancreas can mimic pancreatic cancer Capsule-like low-density rim surrounding the pancreas MRI Global pancreatic enlargement decreased T1 signal, increased T2 signal, peripancreatic decreased signal intensity Fig. 4. Images from a 42-year-old woman with mild abdominal pain and history of undifferentiated connective tissue disease. (A) Contrast-enhanced CT shows global pancreatic enlargement.The pancreas enhances uniformly. (B) Fat saturation T1-weighted image shows diffuse pancreatic enlargement (asterisk). (C) Contrast-enhanced CT performed after steroid treatmentshows a decrease in size of the pancreas (compare measure bar with Fig. 1A).
  8. 8. Review Article 275 Apollo Medicine, Vol. 7, No. 4, December 2010 ERCP Segmental or diffuse irregular narrowing of the main pancreatic duct MRCP Skipped, nonvisualized main pancreatic duct lesions ± upstream dilatation Segmental or diffuse irregular narrowing of the main pancreatic duct may not be seen EUS Duringroutineevaluationofapancreaticmass,EUScan provide targeted fineneedleaspirates or core biopsies to aid in the distinction between carcinoma SEROLOGY Increased numbers of circulating immunoglobulins, specifically immunoglobulin subclass 4, are a hallmark of the disease [9,16]. In a landmark study, Hamano and colleagues [9] reported that serum IgG4 levels were highly (95%) sensitive and highly (97%) specific for AIP. In a recent study of 510 patients from the United States [16] including 45 who hadAIP, 135 who had pancreatic cancer, 62 who had no pancreatic disease, and 268 who had other pancreatic diseases, the sensitivity, specificity, and positive predictivevaluesforelevatedserumIgG4(>140mg/dL)for diagnosis of AIP were 76%, 93%, and 36%, respectively. When using a cutoff of twice the upper limit of normal for serum IgG4 (>280 mg/dL), the corresponding values were 53%,99%,and75%,respectively[16].Inthisstudy,5-10% of non-AIP patient groups, including 10% of patients who had ductal adenocarcinoma, had elevated IgG4 levels [16]. In addition, serum IgG4 levels, even in the presence of classic histologic findings ofAIP, can be normal (Table 2) [32,40]. Elevated titers of many autoantibodies have been described in AIP. Autoantibodies against carbonic anhydrase II and IV and lactoferrin are detected in most patients who haveAIP [41,42]. Involvement of antinuclear andanti–smoothmuscleantibodieshasalsobeendescribed [41]. Autoantibodies to the pancreatic secretory trypsin inhibitor have been shown to be elevated in nearly 50% of AIP patients compared with controls [43]. None of these autoantibodies have prediction characteristics that equal that of IgG4. Levels of total IgG and gamma globulins are also increased in AIP. In our experience, however, it is unusual to have elevated serum levels of IgG or gamma globulinswithoutelevationofserumIgG4levels.Although a combination of serum IgG4 levels and autoantibody titers of antinuclear antibodies and rheumatoid factor modestly increasessensitivity,italsosignificantlyreducesspecificity. The authors do not routinely use autoantibody titers to diagnoseAIP. OTHER ORGAN INVOLVEMENT Other organs are often involved in AIP; their involvement may be diagnosed before, simultaneous with, orafterthediagnosisofAIP.Biliarytractisinvolvedin60% to 100% of all patients presenting with AIP [1,44], and has recently been termed IAC http://www.mdconsult.com/das/ article/body/225139942-12/jorg=journal&source= MI&sp=20688639&sid=1077935416/N/644914/ 1.html?issn=0889-8553 - r08000150042. IAC affects both intra- and extrahepatic bile ducts, with the distal common bile duct being the most common site of involvement [48]. Biliary imaging may not necessarily reveal involvement, even when present microscopically [30]. Histologically, a lymphoplasmacytic infiltrate surrounds the bile ducts in a pattern similar to that seen in the pancreas and IgG4- positive staining is often present [24], http:// www.mdconsult.com/das/article/body/225139942-12/ jorg=journal&source=MI&sp=20688639&sid=1077935416/ N/644914/1.html?issn=0889-8553 - r08000150095. AIP coexisting with PSC has been described, although Table 2. IgG4 level in patients who have different diseases of the pancreas AIP Normal Pancreatic Benign pancreatic Chronic pancreas cancer tumor pancreatitis Numbera* 45 62 135 64 79 Mean IgG4 ± SM 550 ± 99 49 ± 6 68 ± 9 47 ± 5 46 ± 5 Range 16–2890 3–263 3–1140 3–195 3–231 Proportion elevated 76% 4.8% 9.6% 4.7% 6.3% >140 mg/dL *Basedon510patientsreferredtotheMayoClinicforevaluationofpancreaticdiseasefromJanuary2005throughJune2006.Datafrom Ghazale A, Chari ST, Smyrk TC, et al. Value of serum IgG4 in the diagnosis of autoimmune pancreatitis and in distinguishing it from pancreatic cancer.Am J Gastroenterol 2007;102(8):1646-1653.
  9. 9. Apollo Medicine, Vol. 7, No. 4, December 2010 276 Review Article this is likely not primary sclerosing cholangitis but IgG4- associatedcholangitis.Ithasalsobeenshownthatinasmall proportion of patients who have aggressive PSC, serum IgG4 levels are elevated suggesting a possible role for corticosteroid therapy. One should be cautious in diagnosing IAC simply based on elevated serum IgG4 levels, however, because false-positive elevations may occur in true PSC. IAC differs from PSC in that there is generally less intrahepatic involvement, the strictures can be transient under observation, the strictures are usually segmental,andpatientsaretypicallypANCAnegative[46]. Inflammatory bowel disease, which is present in 70% of PSC, is less common (6%) in IAC. Analogous to the responseseenintheinflammatorycomponentofpancreatic involvement, inflammation of the biliary tree typically responds to corticosteroid treatment, although the specific response of each duct segment is still being evaluated [47]. In addition to the biliary system, multiple other organs may be involved in ISD. Hamano and colleagues reviewed the frequency, distribution, clinical characteristics, and pathologyoffiveextrapancreaticlesionsin64patientswho hadAIPand found the most frequent extrapancreatic lesion was hilar lymphadenopathy (80.4%), followed by extrapancreatic bile duct lesions (73.9%), lacrimal and salivary gland lesions (39.1%), hypothyroidism (22.2%), andretroperitonealfibrosis(12.5%).Nopatientshadallfive typesoflesions.Patientswhohadhilarlymphadenopathyor lacrimal and salivary gland lesions were found to have significantly higher IgG4 levels than those who did not. Both intrinsic (tubulointestinal fibrosis) and extrinsic (hydro-nephrosis secondary to retroperitoneal fibrosis) renal disease have been associated with AIP, as has inflammatorypneumonitisandinflammatorypseudotumor of the liver [27,44,48]. Diagnostic criteria In1995Yoshidaandcolleagues[14]reportedalistof12 features suggestive of AIP, but stopped short of providing clinicalcriteriaforitsdiagnosis.Thefirstdiagnosticcriteria were proposed by the Japan Pancreas Society in 2002 and later modified in 2006.These guidelines were developed to distinguish between AIP and pancreatic adenocarcinoma. To make the diagnosis of AIP based on the Japanese guidelines, it is mandatory that findings on radiography be consistent withAIP. These findings include the presence of diffuse or segmental narrowing of the main pancreatic duct with irregular wall diagnosed by endoscopic retrograde pancreatogram and diffuse or localized enlargement of the pancreas on abdominal ultrasonography, CT, or MRI. In addition, one of serologic (high serum c-globulin, IgG, or IgG4,orthepresenceofautoantibodies,suchasantinuclear antibodies and rheumatoid factor) or histologic (marked interlobular fibrosis and prominent infiltration of lymphocytes and plasma cells in the periductal area, occasionally with lymphoid follicles in the pancreas) criteriaarerequiredtosatisfyJapanesecriteriafordiagnosis of AIP. The Japanese criteria do not take into account that AIP has unique histologic features, characteristic findings on IgG4 immunostaining of the organs involved, other organ involvement, or response to steroids. In 2006, Chari and colleagues [1] published an alternate set of guidelines based on the Mayo Clinic experience with AIP. These criteria, known by the mnemonic HISORt, recognize characteristic features of AIP on pancreatic histology and imaging, serology, other organ involvement, and response to corticosteroid therapy. Based on the HISORtcriteriapatientscanbediagnosedasAIPiftheyfall intooneofthreegroups:(a)diagnosticpancreatichistology or presence of 10 or more IgG4-positive cells per high- power field (HPF) on immunostain of lymphoplasmacytic infiltrate with storiform fibrosis; (b) typical pancreatic imaging with elevated serum IgG4 ≥140 mg/dL, or (c) unexplained pancreatic disease with negative workup for other pancreatic diseases, especially malignancy, with elevated serum IgG4 levels ≥140 mg/dL or other organ involvement confirmed by presence of abundant IgG4- positive cells, and resolution/marked improvement in pancreatic or extrapancreatic manifestations with steroid therapy (Table 3). By including additional features, these criteriaidentifyawiderspectrumofclinicalpresentationsof AIP. ASAIAN CONSENSUS CRITERIA Histology Lymohoplasmacytic infiltration with fibrosis and abundant IgG4 –positive cell infiltration. Imaging: Both of the following Diffuse, segmental or focal enlargement of the gland, with or without a mass or hypoattenuated rim Diffuse, segmental, or focal pancreatic duct narrowing, with or with out stenosis of the bile duct Serology: one of the following High levels of total IgG or IgG4 Detection of autoantibodies (ANA, RF) Response to glucocorticoid therapy: included as optional criteria,butonlyinpatientswithbothimagingcriteriaabove with a negative workup for pancreatobiliary cancer Treatment The cornerstone of treatment of AIP is the use of
  10. 10. Review Article 277 Apollo Medicine, Vol. 7, No. 4, December 2010 Table 3. Mayo Clinic HISORt criteria for the diagnosis of autoimmune pancreatitis Diagnostic criteria Histology At least one of the following: • Periductal lymphoplasmacytic infiltrate with obliterative phlebitis and storiform fibrosis • Lymphoplasmacytic infiltrate with storiform fibrosis with abundant (≥10 IgG4 cells/HPF) Imaging • Typical: diffusely enlarged gland with delayed rim enhancement, diffusely irregular, attenuated main pancreatic duct • Other: focal pancreatic mass/enlargement, focal pancreatic ductal stricture, pancreatic atrophy, calcification, pancreatitis Serology • Elevated serum IgG4 level (normal 8–140 mg/dL) Other organ involvement • Hilar/intrahepatic biliary strictures, persistent distal biliary stricture, parotid/lacrimal gland involvement, mediastinal lymphadenopathy, retroperitoneal fibrosis Response to steroid therapy • Resolution/marked improvement of pancreatic/extrapancreatic manifestation with corticosteroid therapy Diagnostic groups* GroupA: diagnostic pancreatic histology Presence of one or more of the following criteria: • Specimen demonstrating the full spectrum of LPSP • ≥10 IgG4 cells/HPF on immunostain of pancreatic lymphoplasmacytic infiltrate Group B: typical imaging + serology Presence of all of the following criteria: • CT or MRI scan showing diffusely enlarged pancreas with delayed and rim enhancement • Pancreatogram showing diffusely irregular pancreatic duct • Elevated serum IgG4 levels Group C: response to corticosteroids Presence of all of the following criteria: • Unexplained pancreatic disease after negative workup for other causes • Elevated serum IgG4 or other organ involvement confirmed by presence of abundant IgG4-positive cells • Resolution/marked improvement in pancreatic or extrapancreatic manifestations with corticosteroid therapy *Patients meeting criteria for one or more of the groups haveAIP. Data from Chari ST, Smyrk TC, Levy MJ, et al. [1]. corticosteroids with multiple authors reporting dramatic response rates with prolonged therapy [1,9,48]. A word of caution, however, is that it is imperative to thoroughly rule out other possible causes of pancreatic disease, most notably pancreatic malignancy, before initiating corticosteroid therapy. Although spontaneous remissions do occur in AIP, the use of corticosteroids seems to hasten recovery and may prevent recurrences.There are several reasons, therefore, to initiate treatment ofAIPwith corticosteroids. For one, if the diagnosis remains in doubt and malignancy has been excluded, response to corticosteroids can be a reasonable method of diagnosing AIP. The clinical suspicion for AIP should be high before initiation of therapy, however, and patients should be followed closely for any symptoms (e.g., profound weight loss, anorexia, night sweats) more consistent with malignancy thanAIP. Treatment can also be
  11. 11. Apollo Medicine, Vol. 7, No. 4, December 2010 278 Review Article a means of reducing clinical symptoms from acute pancreatic (pancreatic endocrine insufficiency, rarely acute pancreatitis) or extrapancreatic (jaundice from biliary strictures, sialadenitis) manifestations of disease http:// www.mdconsult.com/das/article/body/225139942-12/ jorg=journal&source=MI&sp=20688639&sid=1077935416/ N/644914/1.html?issn=0889-8553 - r08000150062, [48,49]. In addition, there can sometimes be structural improvement, for example in the pancreatic duct, with corticosteroid therapy The degree of structural response depends on the extent of fibrosis versus inflammation; patients who have more inflammatory injury typically have a greater structural response and extensive fibrosis may not allow complete remission to occur [48]. The exact corticosteroid treatment protocol for patients who have AIP is not standardized; however, most practitioners initiate therapy with between 30 and 40 mg of prednisone daily.These doses are usually effective to induce remission; it is unclear if starting at lower doses would be equally effective. Resolution of symptoms is generally rapidly achieved within 2 to 3 weeks of corticosteroid initiation. It usually takes several weeks to months for evidence of serologic (normalization of IgG4) or radiologic remission. Occasionally, because of fibrotic involvement of tissue, radiologic remission is not seen, especially in proximal biliary strictures resembling cholangiocarcinoma, intrahepatic strictures resembling PSC, and retroperitoneal fibrosis. Progression toward normalization of serum IgG4 levels can be used to guide treatment in these instances. Because histologic specimens are often difficult to obtain, we generally do not use histology as a marker for remission. At the Mayo Clinic, we treat patients diagnosed with AIP with a prolonged steroid taper. Patients are started on 40 mg/d of prednisone for 4 weeks. After 4 weeks, their clinical response is gauged and repeat cross-sectional imaging and serologic evaluation are performed to check for response. If clinical, serologic, or radiographic response is documented, the prednisone dose is tapered 5 mg/wk until gone. In patients in whom a biliary stent has been placed, this usually can be removed at 6 to 8 weeks following initiation of therapy. IgG4 levels are also followed and in patients who have AIP, a decrease in IgG4 (although not necessarily normalization) should occur within 4 weeks of treatment initiation.http://www.mdconsult.com/das/article/ b o d y / 2 2 5 1 3 9 9 4 2 - 1 2 / j o rg = j o u r n a l & s o u r c e = MI&sp=20688639&sid=1077935416/N/644914/ If08000150005.fig - top Recently, in patients who present with jaundice because of biliary stricturing disease who do not wish to undergo initial endoscopic retrograde cholongiopancreatography with stent placement, we have occasionally treated with a large initial bolus of intravenous corticosteroids. Although our experience is limited and at this time anecdotal, jaundice does seem to respond rapidly to this treatment, thus obviating the need for biliary stent placement. Further prospective studies are needed to determine if large initial doses of corticosteroids are an effective alternative to initial biliary stent placement in newly diagnosedAIP. Between 30% and 40% of patients have clinical or radiographic relapse following treatment with prolonged corticosteroids requiring retreatment with a second prolonged course [1,25,48,49]. These relapses generally occur in the short term; data on long-term relapse are lacking. Relapse may be symptomatic, radiologic, serologic, or histologic. The presence of symptoms (recurrent abdominal pain, weight loss, and so forth) is often a clue to relapse within the pancreas; only in the presence of symptoms is cross-sectional imaging repeated. Serologic relapse alone can be seen in patients who do not have clinical symptoms or radiologic changes; whether or not this represents a subclinical disease relapse is unclear at this time. It is also unclear if certain types of organ involvement are more prone to relapse than others. For example, Ghazale and colleagues [25] found that in patients who had IAC treated with 11 weeks of corticosteroids, proximal biliary involve-ment (proximal extrahepatic and intrahepatic biliary strictures) relapsed with a rate of 65% compared with a 25% relapse rate in those who had intrapancreatic stricturing of the distal common bile duct. In a certain subset of patients who have relapse after a second prolonged course of steroids, either chronic prednisone therapy or use of another agent, such as azathioprine or 6-mercaptopurine, may be necessary. In Japan, it is often standard of care to continue patients on a chronic low dose (2.5–10 mg/d) of prednisone indefinitely [48,49].Although there are only case reports evaluating the efficacy of long-term treatment of AIP with immuno- modulating therapy, we have had favorable, although limited, experience with these medications [50]. As more experience is gained about the long-term pathogenesis of AIP, recommendations on the use of chronic suppressive therapy needs to be developed. In addition, because there is such a high frequency of short-term relapse, whether maintenance therapy should be used in all patients, and what type of maintenance therapy should be used, remains to be established. It is unclear at this time whether corticosteroid therapy alters the long-term natural history of disease, prevents the development of future pancreatic or extrapancreatic involvement and organ dysfunction, or is adequate as a long- term suppressive strategy.
  12. 12. Review Article 279 Apollo Medicine, Vol. 7, No. 4, December 2010 Misdiagnosis Increasingly, we are evaluating patients in whom AIP has been inaccurately diagnosed. The misdiagnosis occurs in the setting of patients who have other unrelated conditions, such as pancreatic adenocarcinoma, being treated inappropriately with corticosteroids. We have also seen several patients who had functional abdominal pain complaints treated with prolonged courses of high-dose corticosteroids without evidence of AIP. Conversely, multiple patients have undergone therapies, such as pancreatic head resections or partial hepatectomy, without consideration of an autoimmune cause. It is therefore important that AIP be considered in the differential diagnosis of patients who have chronic pancreatitis or biliary strictures. It is imperative, however, that a thorough evaluation be performed for other causes of disease,withhistopathologicanalysisifpossible,beforethe initiation of corticosteroid therapy. Once corticosteroid therapy has been initiated, patients should be followed closely for signs of worsening or refractory disease symptoms; it is highly unusual for AIP not to quickly respond to appropriate corticosteroid therapy. In addition, cliniciansmustbecognizantthatAIPisararedisease,andin patients who do not meet the Japanese Pancreas Society or Mayo HISORt guidelines, corticosteroid therapy is likely not advisable. Prognosis There are limited data about the long-term outcome of patientswhohaveAIP.Hiranoandcolleagues publishedthe most comprehensive report on prognosis when they evaluated 42 patients who had AIP, 19 of whom received corticosteroid treatment at the time of diagnosis. In the 23 patients who did not have corticosteroid treatment initially, 16 developed unfavorable events, including obstructive jaundice attributable to distal bile duct stenosis in 4, growing pseudocyst in 1, and sclerogenic changes of extrapancreatic bile duct in 9, over an average observation periodof25months.Afteranaverageobservationperiodof 23 months in the initial treatment group, 6 patients developed unfavorable events consisting of interstitial pneumonia in 3 and recurrence of obstructive jaundice in 3. Their conclusions were that early introduction of corticosteroids is important to prevent subsequent disease complications. Mostpatientstreatedwithcorticosteroidsdevelop“burn out” of disease, rendering the pancreas usually somewhat atrophic following treatment [9]. The degree of residual pancreatic exocrine or endocrine insufficiency is likely related to the degree of gland fibrosis at the time of treatment [48]. At this time, given the relatively recent description and active investigation of AIP, there are no data regarding the long-termmortalityrateofpatientswhohavethisdisease.In addition, it has not been investigated whether life expectancy is altered by the course of this disease. Future directions There are several lines of investigation that need to be addressedinregardtoAIP.Continuedworktodeterminethe cause of this disease and its relationship with IgG4 is imperative. Specifically, the antigenic trigger of CD4 and CD8 T-cell activation needs to be identified. Clinically, investigationshouldfocusonthenaturalhistoryofAIPwith specific attention to the wide-ranging effects of IgG4- related systemic disease. It is not currently known whether different manifestations of IgG4-related disease have unique or alternate prognoses. The role of corticosteroids, specifically their role in changing the natural history of disease,needstobeinvestigated.Inasymptomaticpatients, it will be important to determine if treatment helps to prevent future organ dysfunction. Furthermore, the role of chronic suppressive therapy, either with corticosteroids or another immune-modulating drug, in preventing relapse and affecting long-term prognosis is yet to be determined. SUMMARY AIP is a unique subtype of recently identified chronic pancreatitis that is immune mediated and represents one manifestation of a systemic IgG4-related disease process. Although a rare condition, it is important to recognize because it responds often dramatically to immune system– modulating treatment. Diagnosing AIP can sometimes be challenging, however, and it is imperative that clinicians be cautious when considering this diagnosis in patients suspected of having a pancreatic malignancy. As clinical experience with AIP increases, refinement of diagnostic criteria and development of standardized therapeutic protocols should allow further optimization of care for our patients. REFERENCES 1. Chari ST, Smyrk TC, Levy MJ, et al. Diagnosis of autoimmune pancreatitis: the Mayo Clinic experience. Clin Gastroenterol Hepatol 2006; 4 (8): 1010-1016. [Abstract ]. 2. Kamisawa T. IgG4-positive plasma cells specifically infiltrate various organs in autoimmune pancreatitis. Pancreas 2004; 29 (2): 167-168 [Citation]. 3. Kamisawa T, Egawa N, Nakajima H. Autoimmune pancreatitis is a systemic autoimmune disease. Am J Gastroenterol 2003; 98 (12): 2811-2812 [Citation]. 4. Yoshida K, Toki F, Takeuchi T, et al. Chronic pancreatitis caused by an autoimmune abnormality. Proposal of the
  13. 13. Apollo Medicine, Vol. 7, No. 4, December 2010 280 Review Article concept of autoimmune pancreatitis. Dig Dis Sci 1995; 40 (7): 1561-1568. [Abstract]. 5. Sarles H, Sarles JC, Muratore R, et al. Chronic inflammatory sclerosis of the pancreas–an autonomous pancreatic disease?. Am J Dig Dis 1961; 6. 688-698. 6. Pearson RK, Longnecker DS, Chari ST, et al. Controversies in clinical pancreatology: autoimmune pancreatitis: does it exist?. Pancreas 2003; 27 (1): 1-13. [Citation]. 7. Sood S, Fossard DP, Shorrock K. Chronic sclerosing pancreatitis in Sjogren’s syndrome: a case report. Pancreas 1995; 10 (4): 419-421 [Citation]. 8. Weber SM, Cubukcu-Dimopulo O, Palesty JA, et al. Lymphoplasmacytic sclerosing pancreatitis: inflammatory mimic of pancreatic carcinoma. J Gastrointest Surg 2003; 7 (1): 129-137 [Abstract]. 9. Hamano H, Kawa S, Horiuchi A, et al. High serum IgG4 concentrations in patients with sclerosing pancreatitis. N Engl J Med 2001; 344 (10): 732-738 [Abstract]. 10. Kawaguchi K, Koike M, Tsuruta K, et al. Lymphoplasmacytic sclerosing pancreatitis with cholangitis: a variant of primary sclerosing cholangitis extensively involving pancreas. Hum Pathol 1991; 22 (4): 387-395 [Abstract ]. 11. Ichimura T, Kondo S, Ambo Y, et al. Primary sclerosing cholangitis associated with autoimmune pancreatitis. Hepatogastroenterology 2002; 49 (47): 1221-1224 [Abstract]. 12. Ito T, Nakano I, Koyanagi S, et al. Autoimmune pancreatitis as a new clinical entity. Three cases of autoimmune pancreatitis with effective steroid therapy. Dig Dis Sci 1997; 42 (7): 1458-1468 [Abstract]. 13. Kim KP, Kim MH, Kim JC, et al. Diagnostic criteria for autoimmune chronic pancreatitis revisited. World J Gastroenterol 2006; 12 (16): 2487-2496 [Abstract]. 14. Choi EK, Kim MH, Kim JC, et al.The Japanese diagnostic criteria for autoimmune chronic pancreatitis: is it completely satisfactory?. Pancreas 2006; 33(1): 13-19. [Abstract]. 15. Kamisawa T: IgG4-related sclerosing disease. Intern Med 2006; 45(3): 125-126 [Citation]. 16. GhazaleA, Chari ST, SmyrkTC, et al. Value of serum IgG4 in the diagnosis of autoimmune pancreatitis and in distinguishing it from pancreatic cancer. Am J Gastroenterol 2007; 102 (8): 1646-1653. [Abstract]. 17. Nishimori I, Tamakoshi A, Otsuki M. Prevalence of autoimmune pancreatitis in Japan from a nationwide survey in 2002. J Gastroenterol 2007; 42 (Suppl 18): 6-8 [Abstract]. 18. Kim KP, Kim MH, Lee SS, et al.Autoimmune pancreatitis: it may be a worldwide entity. Gastroenterology 2004; 126 (4): 1214. [Citation]. 19. Kamisawa T, Wakabayashi T, Sawabu N. Autoimmune pancreatitis in young patients. J Clin Gastro-enterol 2006; 40 (9): 847-850. 20. Ota M, Katsuyama Y, Hamano H, et al. Two critical genes (HLA-DRB1 andABCF1) in the HLAregion are associated with the susceptibility to autoimmune pancreatitis. Immunogenetics 2007; 59 (1): 45-52 [Abstract]. 21. Umemura T, Ota M, Hamano H, et al. Genetic association of Fc receptor-like 3 polymorphisms with autoimmune pancreatitis in Japanese patients. Gut 2006; 55 (9): 1367-1368 [Citation]. 22. Kountouras J, Zavos C, Gavalas E, et al. Challenge in the pathogenesis of autoimmune pancreatitis: potential role of helicobacter pylori infection via molecular mimicry. Gastroenterology 2007; 133 (1): 368-369 [Citation]. 23. Kitagawa S, Zen Y, Harada K, et al. Abundant IgG4- positive plasma cell infiltration characterizes chronic sclerosing sialadenitis (Kuttner’s tumor). Am J Surg Pathol 2005; 29 (6): 783-791 [Abstract ]. 24. Bjornsson E, Chari ST, Smyrk TC, et al. Immunoglobulin G4 associated cholangitis: description of an emerging clinical entity based on review of the literature. Hepatology 2007; 45 (6): 1547-1554. [Citation]. 25. Ghazale A, Chari ST, Zhang L, et al. IgG4-associated cholangitis: clinical profile and response to therapy. Gastroenterol 2008; 134: 706-715. 26. Kamisawa T, Funata N, Hayashi Y, et al. A new clinicopathological entity of IgG4-related autoimmune disease. J Gastroenterol 2003; 38 (10): 982-984 [Abstract] . 27. Saeki T, Nishi S, Ito T, et al. Renal lesions in IgG4-related systemic disease. Intern Med 2007; 46(17): 1365-1371 [Abstract]. 28. Finkelberg DL, Sahani D, Deshpande V, et al. Autoimmune pancreatitis. N Engl J Med 2006; 355(25): 2670-2676. [Citation]. 29. Kamisawa T, Egawa N, Nakajima H, et al. Extrapancreatic lesions in autoimmune pancreatitis. J Clin Gastroenterol 2005; 39 (10): 904-907 [Abstract]. 30. KamisawaT, Chen PY, TuY, et al. MRCPand MRI findings in 9 patients with autoimmune pancreatitis. World J Gastroenterol 2006; 12 (18): 2919-2922 [Abstract]. 31. Chari ST, Echelmeyer S. Can histopathology be the “Gold Standard” for diagnosing autoimmune pancreatitis?. Gastroenterology 2005; 129 (6): 2118-2120 [Citation]. 32. Chari ST. Diagnosis of autoimmune pancreatitis using its five cardinal features: introducing the Mayo Clinic’s HISORt criteria. J Gastroenterol 2007; 42 (Suppl 18): 39- 41 [Abstract]. 33. Kamisawa T. Angiographic findings in patients with autoimmune pancreatitis. Radiology 2005; 236 (1): 371. [Citation]. 34. Farrell JJ, Garber J, Sahani D, et al. EUS findings in patients with autoimmune pancreatitis. Gastrointest Endosc 2004; 60 (6): 927-936.
  14. 14. Review Article 281 Apollo Medicine, Vol. 7, No. 4, December 2010 35. Salla C, Chatzipantelis P, Konstantinou P, et al. EUS- FNA contribution in the identification of autoimmune pancreatitis: a case report. JOP 2007; 8 (5): 598-604. [Abstract]. 36. Levy MJ, Reddy RP, Wiersema MJ, et al. EUS-guided Trucut biopsy in establishing autoimmune pancreatitis as the cause of obstructive jaundice. Gastrointest Endosc 2005; 61 (3): 467-472. 37. Nakazawa T, Ohara H, Sano H, et al. Cholangiography can discriminate sclerosing cholangitis with autoimmune pancreatitis from primary sclerosing cholangitis. Gastrointest Endosc 2004; 60 (6): 937-944. 38. Nakajo M, Jinnouchi S, Fukukura Y, et al. The efficacy of whole-body FDG-PET or PET/CT for autoimmune pancreatitis and associated extrapancreatic autoimmune lesions. Eur J Nucl Med Mol Imaging 2007; 34: 2088- 2095 [Abstract ]. 39. Hirano K, Kawabe T, Yamamoto N, et al. Serum IgG4 concentrations in pancreatic and biliary diseases. Clin Chim Acta 2006; 367 (1–2): 181-184. [Abstract]. 40. Choi EK, Kim MH, Lee TY, et al. The sensitivity and specificity of serum immunoglobulin G and immunoglobulin G4 levels in the diagnosis of autoimmune chronic pancreatitis: Korean experience. Pancreas 2007; 35 (2): 156-161. [Abstract ]. 41. Okazaki K, Uchida K, Ohana M, et al. Autoimmune- related pancreatitis is associated with autoantibodies and a Th1/Th2-type cellular immune response. Gastroenterology 2000; 118 (3): 573-581 [Abstract]. 42. Kawa S, Hamano H. Clinical features of autoimmune pancreatitis. J Gastroenterol 2007; 42 (Suppl 18): 9-14. [Abstract]. 43. Asada M, NishioA, Uchida K, et al. Identification of a novel autoantibody against pancreatic secretory trypsin inhibitor in patients with autoimmune pancreatitis. Pancreas 2006; 33 (1): 20-26 [Abstract]. 44. Hamano H, Kawa S, Ochi Y, et al. Hydronephrosis associated with retroperitoneal fibrosis and sclerosing pancreatitis. Lancet 2002; 359 (9315): 1403-1404 [Abstract]. 45. Nishino T, Toki F, Oyama H, et al. Biliary tract involvement in autoimmune pancreatitis. Pancreas 2005; 30 (1): 76-82 [Abstract ]. 46. Ohara H, Nakazawa T, Ando T, et al. Systemic extrapancreatic lesions associated with autoimmune pancreatitis. J Gastroenterol 2007; 42 (Suppl 18): 15-21 [Abstract]. 47. Horiuchi A, Kawa S, Hamano H, et al. Sclerosing pancreato-cholangitis responsive to corticosteroid therapy: report of 2 case reports and review. Gastrointest Endosc 2001; 53 (4): 518-522. 48. Kamisawa T, Yoshiike M, Egawa N, et al. Treating patients with autoimmune pancreatitis: results from a long-term follow-up study. Pancreatology 2005; 5 (2-3): 234-238 [Abstract ]. 49. Kamisawa T, Okamoto A. Prognosis of autoimmune pancreatitis. J Gastroenterol 2007; 42 (Suppl 18): 59-62 [Abstract]. 50. van Buuren H R, Vleggaar FP, Willemien Erkelens G, et al. Autoimmune pancreatocholangitis: a series of ten patients. Scand J Gastroenterol 2006; Suppl 243: 70-78 [Abstract].
  15. 15. Apollohospitals:http://www.apollohospitals.com/ Twitter:https://twitter.com/HospitalsApollo Youtube:http://www.youtube.com/apollohospitalsindia Facebook:http://www.facebook.com/TheApolloHospitals Slideshare:http://www.slideshare.net/Apollo_Hospitals Linkedin:http://www.linkedin.com/company/apollo-hospitals Blog:Blog:http://www.letstalkhealth.in/

×