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Autoimmune pancreatitis and inflammatory bowel disease: Case series and review of literature

Digestive and Liver Disease, In Press, Corrected Proof, Available online 19 May 2016, Available online 19 May 2016



An association between autoimmune pancreatitis (AIP) and inflammatory bowel disease (IBD) has been documented, but its clinical significance remains unclear.


Characterize the particular phenotypes of IBD and AIP in patients with both diseases (IBD-AIP).


Retrospective study of patients with IBD-AIP followed at our IBD referral centre and literature search to identify previous reports of IBD-AIP patients.


We found 5 cases of IBD-AIP in our records and 5 prior studies reporting 47 additional IBD-AIP patients. A combined analysis showed that most IBD-AIP patients were young males with ulcerative colitis, usually extensive, and that in all Crohn's disease cases, the colon was involved. IBD severity was heterogeneous across studies, ranging from mild disease to severe disease requiring colectomy. The most frequent type of AIP was idiopathic duct-centric pancreatitis (type 2) and it most often occurred after the diagnosis of IBD. AIP presentation and treatment were similar to those in the general population.


AIP occurs rarely with IBD; in the other way around, up to 1/3 of AIP patients, especially type 2, may have concomitant IBD. IBD-AIP patients are usually males presenting extensive colitis. More data are needed on the impact of AIP, if any, in IBD course.

Keywords: Autoimmune pancreatitis, Idiopathic duct-centric pancreatitis, Inflammatory bowel disease, Lymphoplasmacytic sclerosing pancreatitis.

1. Introduction

Inflammatory bowel disease (IBD) is a systemic disorder that often affects organs outside the gastrointestinal tract. Extra-intestinal manifestations (EIMs) are present in 6–47% of IBD patients [1] and [2] and are occasionally even more debilitating than the intestinal disease itself. Some EIMs may parallel the intestinal activity, while others run an independent course of bowel disease [1] and [3]. Furthermore, certain EIMs seem to be associated with particular forms or phenotypes of IBD. For instance, patients with primary sclerosing cholangitis (PSC) and IBD more frequently have extensive colonic involvement, quiescent or mild disease activity, and predominantly right-sided distribution when compared to IBD patients without PSC [4].

Autoimmune pancreatitis (AIP) is a benign fibroinflammatory disease of the pancreas first reported in 1961. It acquired the name, “autoimmune”, later in 1995, because it was associated with hypergammaglobulinemia, was accompanied by autoantibodies and responded dramatically to corticosteroids (CS) [5]. On imaging, the pancreatic inflammatory process is classically seen as a sausage-shaped pancreas with an irregular narrowing of the pancreatic duct [6].

Two types of AIP were subsequently recognized according to clinical profile, histopathological pattern and natural history; namely, type 1 AIP or lymphoplasmacytic sclerosing pancreatitis (LPSP) and type 2 AIP or idiopathic duct-centric pancreatitis (IDCP) [5]. Box 1 summarizes the typical features of each type of AIP. Type 1 AIP occurs more often in elderly men, who present with painless jaundice, and it is the pancreatic manifestation of IgG4-systemic related disease. For this reason it is common to find in type 1 AIP patients an increase in IgG4 serum levels, and extrapancreatic symptoms due to the involvement of other organs (OOI) [7]. In type 2 AIP, by contrast, patients are younger, there is no gender predominance and the most common presentation is acute pancreatitis (AP). Type 2 is a disease limited to the pancreas [6]; however it is notable that 15–30% of patients have concomitant IBD, most often ulcerative colitis (UC) [5], [8], [9], [10], [11], and [12]. This high prevalence is in striking contrast to the 0.4% prevalence of UC in the general population [13]. These observations suggest a possible association between IBD and AIP, and several authors have proposed that AIP may be an EIM of IBD [14], [15], [16], [17], and [18].

Box 1 Comparison between the clinical profiles of type 1 and type 2 autoimmune pancreatitis.

Type 1 AIP
(lymphoplasmacytic sclerosing pancreatitis)
Type 2 AIP
(idiopathic duct-centric pancreatitis)
Demographics 7th decade of life
3:1 male predominance
5th decade of life
Equal gender distribution
Clinical presentation Painless jaundice AP and abdominal pain
Painless jaundice
Association with IBD Rare May be present in up to 1/3 of patients
Pancreatic imaging Diffuse pancreatic parenchymal enlargement with delayed enhancement
Long or multiple strictures of the main pancreatic duct
IgG4 elevation Increased in 2/3 of patients Usually normal
Pancreatic histology Periductal lymphoplasmacytic infiltration
Obliterative phlebitis
Storiform fibrosis
Increased IgG4 positive cells (>10 per HPF)
Granuylocytic infiltration of duct wall
Absent or scant IgG4 positive cells (0–10 per HPF)
Involvement of other organs Proximal biliary tree, salivary glands, kidney and retroperitoneal fibrosis No
Response to steroids Excellent
Recurrence Common Rare

AP, acute pancreatitis; HPF, high power field.

Despite this suggested association, the connection between IBD and AIP is still not widely recognized, nor is the relationship between the clinical course and features of the IBD and those of the AIP [8], [11], and [14]. Hence, we have sought to describe the characteristics of both IBD and AIP when they occur together in the IBD-AIP syndrome.

2. Materials and methods

2.1. Case series

The study was conducted at The Mount Sinai Hospital, an IBD tertiary referral centre. We performed a search for patients with diagnosis of IBD and AIP who attended The Mount Sinai Hospital, between January 2003 and April 2015, using the Mount Sinai Crohn's and Colitis Registry. This Registry was created in 2013 to prospectively enrol IBD patients who attended Mount Sinai Hospital. In addition, patients prior to 2013 were retrospectively searched using Data Warehouse that contains all electronic medical records (EMR), since 2003 and 2010 for inpatient and outpatient diagnosis, respectively. IBD was searched using IBD related ICD-9 codes (Crohn's disease – 555.0, 555.1, 555.2, 555.9; and ulcerative colitis – 556.0, 556.1, 556.2, 556.3, 556.5, 556.6, 556.9). To identify patients with AIP we searched the Registry and Data Warehouse for pancreas related ICD-9 codes: 577.0 acute pancreatitis, 577.1 chronic pancreatitis, 577.2 cyst and pseudocyst of pancreas, 577.8 other specified diseases of pancreas and 577.9 unspecified disease of pancreas. A total of 120 patients were found to have IBD and pancreatic disorders. The EMR of each case, including clinical notes, imaging and pathology records, was reviewed for the following keywords: “auto-immune pancreatitis”, “sausage pancreas”, “lymphoplasmacytic infiltration”, “granulocytic infiltration”, “granulocyte epithelial lesions”, “storiform fibrosis”, “obliterative phlebitis”, “IgG4 positive cells” and “IgG4”.

An IBD diagnosis required the standard histological criteria in a patient with a compatible clinical history, endoscopic or surgical features and/or imaging abnormalities [19] and [20]. The diagnosis of AIP was based on the International consensus diagnostic criteria (ICDC) criteria, specifically, imaging, serology, histology, OOI and response to CS [21]. Additionally, other causes of pancreatitis were excluded, namely gallstones, heavy alcohol intake, medications, hypercalcemia, hypertriglyceridemia and anatomical abnormalities. Genetic testing for cystic fibrosis transmembrane conductance regulator (CFTR), serine protease inhibitor Kazal type 1 (SPINK1) or trypsinogen cationic genes (PRSS1), was not available.

A retrospective analysis of EMR was conducted to identify demographic data, clinical presentation, serological markers, histological findings, imaging features and therapy for AIP and IBD. Particularly, for IBD, we registered disease distribution, disease activity, change in disease extension and IBD-related medical and surgical therapies, hospitalizations and death. Regarding AIP, we extracted clinical presentation including OOI, complications, hospitalizations and recurrences; IgG4; imaging studies; and medical, surgical, and endoscopic treatments. AIP recurrence was defined as the recurrence of symptoms and/or radiological manifestations. Follow-up time for AIP and IBD was defined as the period between diagnosis and the last available outpatient or inpatient record.

The Mount Sinai Medical Centre Institutional Review Board approved the study protocol.

2.2. Literature review of published cases

A literature query was conducted to identify studies reporting epidemiology, phenotype and treatment of IBD and/or AIP in IBD-AIP patients. A broad PubMed/Medline search was performed from inception to 31st of July 2015 using the following keywords: autoimmune pancreatitis, type 1 autoimmune pancreatitis, lymphoplasmacytic sclerosing pancreatitis, type 2 autoimmune pancreatitis or idiopathic duct-centric pancreatitis combined with inflammatory bowel disease, Crohn's disease, ulcerative colitis or IBD. Additionally, we hand-searched the references of the most recent (≥2010) review papers published on AIP to identify additional relevant titles.

3. Results

3.1. Case series

In total, our search identified 8 IBD patients who were suspected of having AIP. Three cases were excluded because they were lost to follow-up before diagnostic investigation was completed (IgG4 serum levels, imaging showing resolution of pancreatic abnormalities after steroid therapy and/or investigation of OOI). Hence, our study population comprised 5 adult patients with IBD and a diagnosis of AIP (Table 1 and Table 2). The median IBD follow-up time was 72 months, ranging from 11 to 108 months.

Table 1 Demographics and clinical characteristics of IBD in patients with coexistent AIP: current series.

Case 1 Case 2 Case 3 Case 4 Case 5
Age at diagnosis 13 32 33 46 35
Gender Male Male Female Male Male
Extension N/A Proctitis Left-sided Pancolitis Left-sided
Change in extensiona No Pancolitis No No No
Medical therapy 5-ASA 1 course CS
5-ASA 1 course CS
Hospitalizations No No No No No
Bowel/perianal surgery No No No No No
Follow-up (months) 12 108 11 12 72

a Macroscopic findings.CS, corticosteroids; EIM, extraintestinal manifestations; IBD, inflammatory bowel disease; PSC, primary sclerosing pancreatitis; UC, ulcerative colitis.

Table 2 Clinical presentation and diagnostic criteria of AIP in patients with IBD: current-series.

Case 1 Case 2 Case 3a Case 4a Case 5a
Type AIP (ICDC) Definitive type 1 Probable type 1 Probable type 2 Probable type 2 Probable type 2
Age at diagnosis (Calendar year) 17 (4 years after IBD; 2009) 33 (1 year after IBD; 2007) 33 (2 months after IBD; 2013) 46 (6 months after IBD; 2012) 35 (simultaneous IBD; 2009)
Smoking/heavy drinking No/No Former/No Former/No No/No Former/No
Presentation Abdominal pain Recurrent AP Recurrent AP AP Recurrent AP
Pancreatic imaging MRCP:
 - Body and tail enlargement with rim-like delayed enhancement
 - Body MPD focal interruption without upstream dilatation
 - Diffuse pan-parenchymal enlargement
 - Diffuse mild narrowing of MPD
 - Head and uncinate enlargement; body and tail parenchymal atrophy
 - MDP body and tail beading without upstream dilatation
 - Head and neck enlargement with delayed enhancement
 - Normal MPD
 - Head and neck enlargement
 - MPD mild beading
EUS Not performed Not performed Without features suggestive of malignancyb
Histology Not obtained Not obtained Not obtainedb Pancreatic FNA (4 passages, 19G procore) with benign findingsd Not obtainedb
Serum IgG4 2.1 × upper limit 1.2 × upper limit Normalc Normal Normal
OOI No No No No No
Steroid response Only symptoms Yes Yes Yes Yes
Treatment CS CS; AZA after recurrence CS CS; AZA after recurrence CS; 6-MP; rituximab
Recurrence Yes Yes Yes Yes Yes
Follow-up (months) 12 96 9 6 72

a Patients 3, 4 and 5 were categorized as probable type 2 AIP due to the presence of IBD and inexistence of OOI. A definitive diagnosis of type 2 AIP is not possible without histology.

b In cases 3 and 5 FNA was not performed considering the young age, absence of constitutional symptoms and benign endosonographic features. All patients responded to prednisolone and on follow-up none turned out to have cancer.

c Levels determined after a steroid course for UC.

d The procedure was complicated by mild acute pancreatitis.AIP, autoimmune pancreatitis; AP, acute pancreatitis; 5-ASA, aminosalicylates; AZA, azathioprine; CBD, common bile duct; CP, chronic pancreatitis; CS, corticosteroids; FNA, fine needle aspiration; ICDC, International consensus diagnostic criteria; EUS, endoscopic ultrasound; MPD, main pancreatic duct; MRCP, magnetic resonance cholangiopancreatography; OOI, other organ involvement.

3.2. IBD phenotype in patients with AIP

All 5 IBD patients had UC, established by the combination of clinical, endoscopic and histological features. Four were male and the median age at IBD diagnosis was 33 years (Table 1). None of the patients had a family history of IBD or other autoimmune conditions. At presentation, UC was left-sided in 2 patients and involved the entire colon in a third case. Disease spread proximally from proctitis to pancolitis in a fourth patient. In the fifth case disease extension was not available. Two patients had PSC, diagnosed at the same time as UC. The diagnosis of PSC was based on typical intrahepatic biliary tree beading observed in endoscopic retrograde cholangiography in one patient and magnetic resonance cholangiopancreatography in the other. On follow-up, IgG4 related cholangitis was ruled out since the biliary tree strictures did not resolve after therapy with CS.

Regarding medical therapy, 2 patients required an oral course of CS to induce IBD remission, while the remaining 3 patients had responded to 5-aminosalycilates (5-ASA). All patients were treated with 5-ASA as maintenance therapy. Of note, one patient had an UC flare coincidental with AIP recurrence and both entities responded to a second steroid course. During follow-up, there were no hospitalizations or surgeries related to UC and there were no deaths.

3.3. AIP phenotype in patients with IBD

Three cases were classified as probable type 2 AIP, one as probable type 1 and one patient as definitive type 1 AIP (Table 2). In the 3 cases of probable type 2 AIP an endoscopic ultrasound (EUS) ruled out malignancy (Fig. 1) and the diagnosis of AIP was confirmed after clinical and radiologic response to CS. In 4 cases, AIP was diagnosed after IBD, with a median interval of 9 months (from 2 to 48 months). In one patient AIP and UC were diagnosed simultaneously. At AIP diagnosis, 5-ASA was the only current medication and no patient was under immunosuppressive therapy. AP was the most frequent presentation of AIP (n = 4) and it was mild in all cases. Of note, three of these patients had a prior history of AP episodes. The fifth patient presented with abdominal pain. None of the patients developed jaundice. Medications, including 5-ASA were ruled out as the aetiology of pancreatitis.


Figure 1 Case 3. Endoscopic ultrasound findings of autoimmune pancreatitis. Enlarged pancreatic neck/body with diffuse hypoechogenicity (asterix) with surrounding fluid rim (arrows). The pancreatic duct is poorly visualized.

All patients were successfully treated with CS at AIP diagnosis. During follow-up (median 24 months), all patients experienced recurrence (symptoms and/or imaging) that responded to CS, after which immunosuppressive therapy was initiated in 3 cases. In two patients immunosuppression was started for AIP only and in one case for AIP recurrence and a UC flare. In addition, rituximab was started in one patient due to AIP recurrence and need for CS while the patient was on thiopurine therapy. Three patients were found to have imaging features of pancreatic atrophy on follow-up; two of these 3 were asymptomatic while the third patient had recurrent upper abdominal pain. None of the patients needed endoscopic or surgical therapy related to AIP.

3.4. Literature review

The initial PubMed/Medline search yielded 140 citations, of which 32 were found potentially relevant based on the title and abstract. Review papers, editorials, symposiums and case-reports were excluded. After reading the full text, 12 studies were selected for review.

3.5. Epidemiology

The reported prevalence of IBD in patients with AIP varied between 2% and 33% and most cases of AIP were type 2 AIP [5], [9], [10], [22], [23], [24], and [25]. UC was the most common subtype of IBD in patients with AIP being present in 2–30% of AIP cases. In contrast Crohn's disease (CD) was reported in only 1–4% of AIP patients [5], [9], [10], [22], [23], [24], and [25].

On the other hand, only two studies examined the prevalence of AIP in IBD patients [8] and [14]. Ueki and colleagues reported a crude prevalence of 0.3% in CD (total of 2 cases, one with colonic disease and the second with ileocolonic disease), 0.5% in UC and 0.4% in IBD overall [14]. In the second study, the prevalence of AIP in a Korean UC cohort was 0.54% [8]. Although data are scarce, the prevalence of AIP in IBD seems to be substantially higher than that of the general population, estimated from <0.001% [6] to 0.004% [26].

3.6. Demographic features and subtypes of IBD and AIP

We identified five studies that reported this information, comprising 47 AIP-IBD patients (Supplementary Tables 1 and 2) [8], [11], [14], [27], and [28]. There were 36 cases of UC, 9 with CD and 2 cases of IBD unclassified. In two studies there was a male predominance, in one study 4 out of 6 patients were males, while in the other all 4 patients were also males [8] and [11]. In a third study most patients were females (6 out of the 7 cases) [14]. The most frequently reported type of AIP was type 2 AIP [8], [11], [14], [27], and [28] and in the majority of cases (23 out of 36 cases) AIP was diagnosed after IBD [8], [11], [14], and [27].

3.7. IBD phenotype in patients with AIP

Four studies, comprising 36 IBD-AIP patients, reported the clinical features of IBD when associated with AIP (Supplementary Table 1) [8], [11], [14], and [27]. The age at IBD diagnosis ranged from 23 to 33 years. In the UC group, the majority of patients had extensive or pancolitis (52.6–75%) [8], [11], and [27]. In only one study was left sided colitis the most frequent disease distribution [14]. Isolated rectum involvement occurred in 7.1% of cases [14] and [27]. In the CD subgroup all patients had colonic involvement (isolated in 4 cases and associated with ileal disease in the remaining 2 patients) [8], [11], [14], and [27].

In three studies IBD presentation and behaviour were detailed [8], [14], and [27]. Park et al. found that UC-AIP patients (n = 6) had a lower body mass index and a higher C-reactive protein and Mayo score at diagnosis (8 versus 5.5 points, p 0.006), when compared to the UC-only group (n = 24). Conversely, there were no significant differences in terms of disease extension, white blood count or erythrocyte sedimentation rate at diagnosis between the two groups. The use of immunomodulators was higher in UC-AIP than the UC-only group (67 versus 33%), although not statistically significant. While none of the UC-alone patients needed surgery, 2 UC-AIP patients underwent colectomy for disease “refractory to medical treatment”, though there is no mention to biologic therapy in these cases [8]. In the study by Ueki et al. there were no significant differences in age or gender; disease extent, activity or severity; or treatment between UC-AIP patients (n = 5) and UC-only (n = 691). Of note, 5 patients (71%) had active IBD at the time of AIP diagnosis [14]. Lastly, Hart et al. reported a subgroup of 19 patients with type 2 AIP and IBD, of whom 6 required biologic therapy and 6 patients underwent proctocolectomy for refractory disease (including 3 who failed biologics). Additionally, 10 patients had at least one IBD relapse that required CS during follow-up [27].

Overall, immunomodulators were used in 29–67% of patients [8] and [14] and biologic therapy was started in 14–32% of cases [14] and [27]. Colectomy rates ranged from 0% [14] to 50% [11]. In two patients colectomy preceded the diagnosis of AIP [11] while in the remaining cases the timing of colectomy was not specified [8] and [27].

3.8. AIP phenotype in patients with IBD

Four case-control studies concerning 28 AIP-IBD cases were included (Supplementary Table 2) [8], [11], [14], and [28]. The median age at AIP diagnosis ranged from 26 to 54 years (minimum 17 and maximum 84). AP (86%) [14] and abdominal pain (50 and 64%) [11] and [28] were the most common presentations. The majority of patients presented with diffuse pancreatic enlargement and MPD narrowing on imaging studies [8] and [14]. Serum IgG4 levels were increased in 12.9% of 31 patients who were tested [8], [11], [14], and [28].

Two studies performed a case-control analysis of IBD-AIP and AIP alone [8] and [11]. Both groups had a male preponderance and there were no differences in gender, race or clinical presentation [8] and [11]. In one of the studies IBD-AIP patients presented at a younger age compared to AIP-alone cases (26 versus 61 years) [8] while in the second study the median age at diagnosis was similar between the two groups [11].

The therapeutic management was similar to that of the general population, and included CS [8], [11], [14], and [28] and pancreatic resection [11] and [28] as first line therapies.

4. Discussion

We studied the phenotype of IBD and AIP in IBD-AIP patients by examining cases retrospectively identified in our institution and available data in the literature.

The overall reported prevalence of AIP in IBD patients is 0.4% [8] and [14], considering the only two studies in the literature specifically examining this issue, and that concern Asian populations. This 0.4% figure is 100–400 times greater than the prevalence estimated for the general population [26]. Nonetheless, this is based on Asian studies, and we do not know if this elevated prevalence would apply to other populations. In fact, in our study regarding a Western population we only found 5 cases in the study's 12-year time span, all diagnosed between 2007 and 2015. This may suggest that AIP was underdiagnosed, considering the relatively novelty of the disease and complexity and variety of diagnostic criteria used across countries until 2011, when the first international consensus of AIP diagnostic criteria was published [21]. Prospective multicenter studies are needed to clarify the true prevalence of AIP in IBD patients.

A possible pathophysiological explanation for the observed association between IBD and AIP is that shared antigenic molecules between the colon and the pancreas trigger an immune response in both organs [24]. It is also interesting to note some histological resemblances between type 2 AIP and UC [14]. In UC, neutrophils involve colonic crypt epithelium (cryptitis) and lumen (crypt abscess) [29]. Similarly, in type 2 AIP, neutrophils are found in the epithelium and lumen of pancreatic acini and small and medium-sized ducts [30]. In none of the series of AIP-IBD, was the coexistence of factors known to be associated with acute recurrent and chronic pancreatitis, namely, genetic mutations (PRSS1, SPINK1, CFTR), alcohol and smoking acknowledged [31] and [32]. However, this may be worth exploring since PRSS1 and CFTR mutations have been identified in AIP patients [33] and [34]. In turn, smoking (>10 packs year) has been associated with more frequent pancreatic damage on imaging and higher prevalence of associated diabetes [22].

Based on our case series and literature review it seems that most IBD-AIP patients are males (64%), young and have UC (80%). Almost 50% of UC patients have extensive or pancolonic disease, and all patients with CD have colonic involvement. IBD does not seem to impact the course of the AIP and vice versa. Although the available data are still limited, it is interesting to note some striking similarities between IBD-AIP and IBD-PSC patients. First, IBD-PSC is also are more common in young males [4] and [15]. Second, like in IBD-AIP, UC is the most frequent type of IBD and patients usually have extensive disease involvement; and in the rare subgroup who had CD the disease is generally colonic or ileocolonic [4] and [15].

AIP does not seem to have an impact on IBD course or to parallel disease activity, although in terms of IBD severity data is conflicting. In our series and that reported by Ueki the course of IBD was relatively benign and none of the patients underwent surgery related to IBD [14]. On the other end of the spectrum, biologics were started in up to 1/3 of patients [27] and colectomy rates reached 30–50% in other series [8], [11], and [27]. EIM were only reported in our case-series, in which 40% of cases had an EIM, particularly PSC. In this context, it is important to differentiate PSC from IgG4 associated cholangitis, a form of OOI in type 1 AIP (the bile duct manifestation of IgG4 related disease). Clinically the main difference is that in IgG4-cholangitis there is a rapid and complete response to steroids with stricture disappearance. On the contrary, neither imaging nor serum IgG4 levels (increased in 10% of PSC cases) can safely distinguish both diseases [30].

Overall, the majority of IBD-AIP patients had type 2 or IDCP AIP, rather than type 1, although the different criteria used in the studies may have caused a diagnosis bias. Of note, in our case series, only 1 patient had a definitive diagnosis of type 1 AIP, and none had a histological confirmation. Furthermore, in the single patient, with probable type 2 AIP, where fine needle aspiration (FNA) was performed the pathology findings were not consistent with type 2 AIP. This may be accounted by the patchy nature of granulocytic epithelial lesions [10], the histological hallmark of type 2 AIP, and the 50 and 80% diagnostic yield reported for pancreatic biopsies with Tru-cut and 22 gauge needles, respectively [35] and [36].

AIP was diagnosed most frequently in the third and fourth decades of life and AP and abdominal pain were the most common presentations. As result, AIP should be considered in the differential diagnosis of AP in IBD patients, alongside other more common causes, such as medications and gallstones [37]. Obstructive jaundice, back pain and new onset diabetes were less frequent presentations. Indeed, the clinical presentation was similar between patients with and without IBD [8] and [11]. On the contrary, an asymptomatic increase in pancreatic enzymes, which occurs in up to 14% of IBD patients, is not usually associated with pancreatic disease in the absence of positive findings in clinical history and physical examination [37]. A diagnosis of AIP requires a high index of suspicion and an abdominal computed tomography or magnetic resonance imaging (MRI) are valid initial tests to identify features consistent with AIP (diffuse pancreatic enlargement with loss of normal lobulated contour – “sausage-pancreas”) or pancreatic cancer [6]. If performed with cholangiopancreatography sequences MRI has the advantage of providing information on the pancreatic duct, that in AIP presents with diffuse or segmental irregularity or narrowing [6]. In addition, IgG4 serum levels should be obtained and extra-pancreatic manifestations sought for. In patients with atypical features, such as anorexia or cachexia and a pancreatic mass, pancreatic duct dilatation or pancreatic atrophy, a diagnostic EUS with FNA is necessary to rule out cancer [21]. Aside from ruling out malignancy, pancreatic histology is the gold standard for the diagnosis of AIP and mandatory for a definitive diagnosis of type 2 AIP, in which the disease is restricted to the pancreas and IgG4 levels are usually normal. This is particularly relevant in IBD patients, in whom type 2 AIP seems to be more frequent than type 1 AIP. However, FNA may have complications and so the diagnostic yield is variable as mentioned above [35] and [38]. Moreover, in a patient with typical imaging findings, a positive steroid trial is sufficient to make the diagnosis of probable type 2 AIP. Thus, in daily clinical practice, the decision to obtain a histological sample should be made on a case-by-case basis and as part of a multidisciplinary approach, including, the radiologist, the EUS operator and the gastroenterologist. CS and thiopurines are the therapies of choice in AIP with and without IBD [8], [11], [14], and [27]. In IBD-AIP patients recurrence rates were higher in type 1 (75–100%) versus type 2 AIP (15–20%) [8], [11], [14], and [28] as occurs in the general population with AIP (20–60% in type 1 AIP; <10% in type 2 AIP) [6].

The major limitations of our series are its retrospective nature; the small number of patients and that none of AIP cases were histologically proven. Another drawback is the short follow-up time, a limitation shared with the other studies on this subject. A longer follow-up may disclose the impact on disease course, as well as, any permanent pancreatic damage [39]. Nevertheless, by complementing our data with that of the literature, we were able to summarize and better characterize the available evidence regarding the phenotype of IBD and AIP in IBD-AIP patients.

In summary, although IBD is common in patients with AIP, this entity is currently considered a rare cause of pancreatitis in the IBD population. Further research is needed to ascertain the true prevalence of AIP in IBD patients and if AIP is being under recognized in this population. The development of specific guidelines and diagnostic criteria for AIP will likely raise awareness for the disease and lead, in the following years, to an increase in the number of recognized cases. Patients with IBD-AIP are usually male, young adults and have UC, frequently involving the entire colon. The impact of AIP in the course of IBD is still elusive with conflicting results in the literature. Although a rare disease, AIP may be more frequent in IBD patients compared to the general population and should be considered in the differential diagnosis of acute, recurrent and chronic pancreatitis in this subgroup of patients. Finally, this association does not seem to alter the clinical presentation and therapeutic response of AIP when comparing patients with IBD and the general population. Further research is needed to understand if AIP is in fact an EIM of IBD and if it influences any long-term outcome in IBD.

Conflict of interest

None declared.


The authors want to thank Khushbu Rupani and Sinai AppLab ( for supporting data extraction and validation from Mount Sinai Crohn's and Colitis Registry.

Appendix A. Supplementary data

The following are the supplementary data to this article:

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Table S1 IBD features in patients with concomitant AIP: literature review and current series.

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Table S2 Clinical features of AIP in patients with IBD: literature review and current study.


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a Gastroenterology Department, Hospital Garcia de Orta, Almada, Portugal

b Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, United States

Corresponding author. Tel.: +1 212 241 0150; fax: +1 212 241 4218.