Endgames Picture Quiz

Obstructive jaundice and pancreatic disease

BMJ 2012; 345 doi: http://dx.doi.org/10.1136/bmj.e6701 (Published 15 October 2012) Cite this as: BMJ 2012;345:e6701
  1. Sunita Deshmukh, academic clinical trainee,
  2. Keith Roberts, specialty registrar, hepatobiliary surgery,
  3. Andrew M Smith, consultant, hepatobiliary surgery
  1. 1St James’s University Hospital, Leeds Teaching Hospitals NHS Trust, Leeds LS9 7TF, UK
  1. Correspondence to: A M Smith andrewmalvernsmith{at}me.com

A 72 year old man was admitted under the surgical team with a short history of upper abdominal pain associated with vomiting, pruritis, pale stools, and dark urine. Four days earlier he had presented to his general practitioner with a four week history of polydipsia and polyuria. His fasting blood glucose concentration was raised. He was clinically diagnosed with new onset type 2 diabetes and given dietary advice. He drank alcohol occasionally and was a smoker with a history of chronic obstructive pulmonary disease and cystectomy for transitional cell carcinoma of the bladder 10 years previously.

On examination he was haemodynamically stable, jaundiced, and had a normal temperature. His abdomen was soft and non-tender with no palpable masses. Liver function tests were abnormal: alanine aminotransferase 783 U/L (reference range 3-35), bilirubin 76 μmol/L (3-17; 1 μmol/L=0.06 mg/dL), and alkaline phosphatase 911 U/L (30-35). His C reactive protein was 111 nmol/L (reference value <100; 1 nmol/L=0.1 mg/L) and serum amylase was normal. With the exception of hyperglycaemia, routine blood tests were normal. He was started on an insulin sliding scale with fluid replacement.

Ultrasonography showed intrahepatic and extrahepatic biliary dilation, although no cause was identified. No obstructing or mass lesion was seen on computed tomography of the abdomen (fig 1). The cross sectional images helped confirm the diagnosis and were supported by a serum test.

Figure1

Fig 1 Computed tomogram of the abdomen (cross sectional view)

Questions

  • 1 What abnormality can be seen in fig 1 and what is the likely diagnosis given these findings and the history?

  • 2 What are the main differential diagnoses?

  • 3 How would you manage this patient?

Answers

1 What abnormality can be seen in fig 1 and what is the likely diagnosis given these findings and the history?

Short answer

Figure 1 shows a diffusely swollen pancreas with loss of normal gland lobulation. Dilation of the common bile duct is present but no mass lesion. The likely diagnosis is autoimmune pancreatitis.

Long answer

The cross sectional computed tomogram (fig 2), magnetic resonance imaging scan (fig 3), and coronal computed tomogram (fig 4) all show a diffusely swollen “sausage shaped” pancreas, with loss of the normal lobulation. The common bile duct is clearly seen and dilated, with no filling defects. Magnetic resonance imaging shows a global reduction of signal intensity in the pancreas and reduced enhancement post gadolinium (fig 3), and computed tomography shows hypodensity of the pancreas (fig 2).

Importantly there is no mass lesion or calcification within the pancreas, dilation of the pancreatic duct, or loss of gland volume.

Figure2

Fig 2 Computed tomogram of the abdomen (cross sectional view) showing a diffusely swollen “sausage shaped” pancreas, with loss of normal gland lobulation (arrow)

Figure3

Fig 3 Magnetic resonance image of the abdomen (cross sectional view) showing a diffusely swollen “sausage shaped” pancreas, with loss of normal gland lobulation (arrow). A global reduction in signal intensity of the pancreas is also seen

Figure4

Fig 4 Computed tomogram of the abdomen (coronal view) showing a dilated common bile duct (A) and further views of a diffusely swollen pancreas (B), without evidence of a pancreatic head mass or features of chronic pancreatitis

2 What are the main differential diagnoses?

Short answer

Choledocholithiasis (gallstones), pancreatic cancer, distal cholangiocarcinoma, chronic pancreatitis, sclerosing cholangitis, and autoimmune pancreatitis.

Long answer

Obstructive jaundice associated with new onset diabetes is suggestive of pancreatic—rather than biliary or hepatic—pathology. In the presence of jaundice secondary to a stricture of the common bile duct or mass in the head of the pancreas, a malignant process must be excluded, particularly in elderly patients. Chronic pancreatitis with stricturing of the distal common bile duct would explain jaundice with concomitant diabetes. Gallstones or a malignant lesion are unlikely to be the cause in the absence of a filling defect within the bile duct, a bile duct stricture, or mass lesion (fig 5).

Figure5

Fig 5 Magnetic resonance cholangiopancreatography showing dilation of the intrahepatic and extrahepatic bile ducts. The common bile duct is smooth and dilated (arrow), without evidence of a malignant stricture, filling defect (gallstone), or gallbladder stones

The features of a diffusely enlarged pancreas, loss of lobulation, and other findings seen on cross sectional imaging suggest a diagnosis of autoimmune pancreatitis. Raised serum IgG4 helps confirm the diagnosis.

Autoimmune pancreatitis is a distinct form of inflammatory disease of the pancreas. It has been described in several countries in Europe, the United States, Korea, and Japan, where an increasing incidence might be related to increasing recognition of the condition.1 2 Incidence in the United Kingdom is not well defined, although it is thought to be similar to that in other Western countries. Patients with autoimmune pancreatitis can have a spectrum of autoimmune manifestations related to IgG4 overexpression, including retroperitoneal fibrosis and biliary strictures. These may coexist with pancreatic inflammation, or any one of these conditions can be the sole manifestation. These conditions are not associated with other common autoimmune diseases, such as rheumatoid arthritis or Sjögren’s syndrome.

Patients may present with abdominal pain, weight loss, and jaundice, with or without a pancreatic mass. Diagnosis can be clinically challenging, with a reported 5-21% of resected pancreatic masses being incorrectly mistaken for cancer, whereas misdiagnosis of pancreatic cancer as autoimmune pancreatitis risks a delay in surgery and progression of cancer.3 Furthermore, two studies have reported the subsequent development of pancreatic cancer in patients with autoimmune pancreatitis.4 Therefore, accurate and prompt diagnosis is important to avoid inappropriate management that can potentially compromise clinical outcome.

The most important step in establishing the diagnosis is to exclude a malignant process. In the absence of a mass lesion or irregular biliary stricture, patients with the radiological findings described here should be treated with steroids. Failure to respond to treatment or inconsistent radiological features should prompt further investigation, including endoscopy to assess the ampulla and endoscopic ultrasound to assess the pancreas and to obtain tissue for analysis. Cross sectional imaging should also be repeated in these cases.

Although the current case was clear, autoimmune pancreatitis may be difficult to diagnose. International consensus diagnostic criteria were developed in 2010 by an international panel of experts to aid the recognition and diagnosis of the disease.1 The box summarises the characteristic clinical, imaging, serological, histological, and therapeutic features of the disease.

Typical features of autoimmune pancreatitis12

Clinical presentation
  • Frequent episodes of obstructive jaundice, with or without pancreatic mass

Imaging
Pancreatic parenchyma (CT or MRI)
  • Diffuse enlargement

  • Delayed enhancement

  • Rim-like enhancement (not always present)

Pancreatic duct (ERCP or MRCP)
  • Long stricture (>1/3 length of main pancreatic duct)

  • Multiple strictures in the absence of marked upstream dilatation

Serology
  • Liver function tests show an obstructive pattern

  • Raised IgG4 (>2 times normal limit), IgG, antinuclear antibody titres (not always raised)

Effects on other organs
  • Histological, physical, or radiological evidence of IgG4 autoimmune disease in other organs, including:

    • Salivary gland enlargement

    • Retroperitoneal fibrosis

    • Inflammatory biliary strictures

  • Common autoimmune diseases such as rheumatoid arthritis and Sjögren’s syndrome are not associated with autoimmune pancreatitis

Histology
  • Lymphoplasmacytic infiltrate

  • Obliterative phlebitis

  • Interstitial fibrosis

Therapeutic
  • Dramatic response to corticosteroids

  • CT=computed tomography; ERCP=endoscopic retrograde cholangiopancreatography; MRI=magnetic resonance imaging; MRCP=magnetic resonance cholangiopancreatography.

The diagnostic criteria describe clinical profiles for two subtypes of autoimmune pancreatitis according to histological patterns—type 1 (lymphoplasmacytic sclerosing pancreatitis) and type 2 (idiopathic duct centric pancreatitis).1 2 Type 1 disease probably represents a pancreatic manifestation of IgG4 related systemic disease with an underlying autoimmune mechanism of pathogenesis. Patients are typically elderly and male, presenting with obstructive jaundice, raised serum IgG4, and effects on other organs. In contrast, type 2 disease lacks a serological biomarker, does not seem to have a clear autoimmune component, and can be associated with inflammatory bowel disease. A recent large cohort study reported raised serum IgG4 in 80% of patients with type 1 disease but in only 17% of those with type 2 disease.5

Diagnosis is based on a combination of cardinal features (box). Clinical presentation and imaging findings may be atypical. In clinical practice histology is not routinely sought and is often not available.1 All the serological markers described may be falsely raised in pancreatic cancer, primary sclerosing cholangitis, and other diseases. A recent retrospective UK study over 24 months reported that serum IgG4 greater than 1.3 g/L had a positive predictive value of 79.2% (chance of confirming that the patient had autoimmune pancreatitis (using histology or radiological imaging, or both) rather than cancer).6

The guidelines of the International Association of Pancreatology provide diagnostic algorithms for typical and indeterminate (including atypical) presentations.1

3 How would you manage this patient?

Short answer

Corticosteroids form the mainstay of treatment of autoimmune pancreatitis.

Long answer

Management comprises establishing the diagnosis, excluding pancreatic cancer, and supporting pancreatic exocrine and endocrine function. Obstructive jaundice or the presence of a pancreatic mass (or both) are the most common signs at acute clinical presentation, and symptoms such as anorexia or pain that requires opioid analgesia are rare.1

A steroid trial, starting with prednisolone 0.6-1 mg/kg daily for two weeks, should be instigated, and an improvement in imaging abnormalities and a fall in CA19-9 (carbohydrate antigen 19-9—a marker of biliary obstruction) are expected.1 Improvement in presenting symptoms and IgG4 levels should not be relied on to assess response because they may also improve with steroids in patients with pancreatic cancer and other conditions.1 Symptoms of obstructive jaundice should improve with steroid treatment but temporary placement of a plastic biliary stent can be considered. Diabetes should be treated aggressively and symptoms of pancreatic exocrine insufficiency sought. Steatorrhoea is a sign of severe insufficiency, whereas more subtle symptoms include bloating and abdominal cramps after eating meals. Oral pancreatic enzyme supplements should be started when appropriate and the dose titrated to clinical response.

It can be difficult to distinguish between autoimmune pancreatitis and pancreatic cancer and difficult to diagnose cases must be referred to a specialist multidisciplinary team.

Patient outcome

Our patient responded well to steroids but owing to poor glycaemic control needed to be referred to the diabetes specialist team for support with insulin administration, monitoring of blood glucose, and advice about driving insurance notification.

At two weeks of follow-up, liver function tests and plasma glucose had normalised. At four weeks after discharge he was responding well to steroid treatment. We decided to continue treatment with a tapering dose of prednisolone. The disease is ameliorated with one course of steroids in 30-40% of patients. Other patients may need long term steroid sparing immunosuppressant therapy. Retinal screening showed bilateral drusen deposits, in keeping with age related macular degeneration.

Notes

Cite this as: BMJ 2012;345:e6701

Footnotes

  • Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

  • Provenance and peer review: Not commissioned; externally peer reviewed.

  • Patient consent obtained.

References