Gastroenterology and Hepatology Board Review: Pearls of Wisdom, Third Edition

Section VI GALLBLADDER, BILE DUCTS, AND PANCREAS

CHAPTER 35. Pancreatic Miscellaneous Inflammatory Diseases

Denise McCormack, MD and David W. McFadden, MD

Image True/False: An elevated amylase is always indicative of acute pancreatitis in the setting of acute calculous cholecystitis.

False. Hyperamylasemia may reflect a gangrenous gallbladder. Additionally, minor (< 2–3 times normal) elevations may be seen in acute cholecystitis without gangrene.

Image What connective tissue diseases and vasculitides may have pancreatic involvement?

Systemic lupus erythematosus, rheumatoid arthritis, polyarteritis nodosa, Henoch–Schönlein purpura, Wegener’s granulomatosis, and Behçet’s syndrome.

Image True/False: Autoimmune pancreatitis involvement of the pancreas may be either diffuse or focal.

True. Autoimmune pancreatitis is a fibroinflammatory pancreatic disease that may present with either focal or diffuse involvement. The focal form requires careful evaluation, since it may be confused with pancreatic cancer.

Image What are the four main criteria used in the diagnosis of autoimmune pancreatitis?

Pancreatic histology, radiologic features, other organ involvement, and clinical response to steroid treatment. Serum IgG4 and positive IgG4 plasma cells in pancreatic biopsies may also support its diagnosis.

Image True/False: Elevated levels of IgG4 antibodies correlate with disease severity in autoimmune pancreatitis.

True. The median serum IgG4 concentration in autoimmune pancreatitis is approximately 600 mg/dL. Elevated serum IgG4 levels may help to distinguish autoimmune pancreatitis from other conditions of the pancreas or biliary tree.

Image True/False: Treatment with corticosteroids has been shown in well-controlled clinical trials to result in rapid improvement of autoimmune pancreatitis.

False. Although treatment with steroids is a diagnostic criterion and steroid use may result in rapid improvement, there are no prospective, randomized, placebo-controlled trials of any treatment in autoimmune pancreatitis. The effect of steroids on the natural history of autoimmune pancreatitis is unclear.

Image True/False: Extrapancreatic disease occurs in about 15%–20% of patients with autoimmune pancreatitis. False. Extrapancreatitic disease occurs in 40%–90% of cases. Biliary disease is one of the most common extrapancreatic manifestations; however, organs distant from the pancreas can be involved.

Image Describe the difference between type 1 and type 2 autoimmune pancreatitis.

Type 1 is characterized by pancreas involvement as one part of a systemic IgG4-positive disease, whereas type 2 is characterized by pancreas involvement without systemic involvement or IgG4 positivity.

Image What are the HISORt criteria?

HISORt refers to diagnostic criteria for autoimmune pancreatitis and stands for Histology, Imaging, Serology, other Organ involvement, and Response to steroids.

Image What is the name of the uncommon condition characterized by fibrotic inflammation affecting the anatomical area between the head of the pancreas, the duodenum, and the common bile duct?

Groove pancreatitis.

Image True/False: Groove pancreatitis is often misdiagnosed as pancreatic malignancy or autoimmune pancreatitis because of its “pseudotumor” formation.

True.

Image Describe the inheritance pattern of hereditary pancreatitis.

Hereditary pancreatitis is usually caused by a mutation in the cationic trypsinogen gene and accounts for 2% of all cases of chronic pancreatitis. The disease has an autosomal dominant inheritance pattern with 80% penetrance.

Image True/False: The clinical presentation of hereditary pancreatitis is similar to other forms of chronic pancreatitis.

True. However, individuals usually present with recurrent acute pancreatitis in childhood, chronic pancreatitis as adolescents or young adults, and a markedly increased risk of pancreatic cancer in their fifth decade of life.

Image True/False: Mortality in hereditary pancreatitis without pancreatic cancer is the same as the general population.

True. However, mortality is significantly increased in those who develop pancreatic cancer.

Image What is the most common hereditary disease involving the exocrine pancreas?

Cystic fibrosis (CF), which affects 1 in every 2000 live births.

Image Describe the inheritance pattern of CF.

Autosomal recessive with a gene frequency of approximately 5% among Caucasians.

Image What are pancreatic manifestations of CF?

In the early stages, the pancreas may appear normal or there may be a deposition of eosinophilic concretions within ductules. Larger ductular involvement may lead to dilatation and acinar disruption. Later on, the pancreas may appear indistinguishable from chronic pancreatitis as cyst development may occur, and fat and scar may replace pancreatic lobules.

Image True/False: Pancreatic exocrine insufficiency is a common complication of CF.

False. Only about 15% of CF patients show clinical evidence of pancreatic exocrine insufficiency resulting from pancreatic duct obstruction.

Image What percentage of patients with CF has diabetes mellitus?

Cystic fibrosis–related diabetes (CFRD) occurs in approximately 20% of adolescents and 40%–50% of adults.

Image Describe the pathophysiology of pancreatic endocrine insufficiency that may occur in CF.

Replacement of pancreatic tissue with fibrosis and fat in severe disease leads to disruption of normal islets by autodigestion and diminution of the number of islets.

Image True/False: Gallstones are more common in CF and can lead to acute inflammatory exacerbations.

True. Cholelithiasis, sludge, and gallbladder wall thickening occur in 12%–24% of patients with CF.

Image True/False: Laparoscopic cholecystectomy should be considered for CF patients with asymptomatic gallstones detected during screening radiography.

False.

Image True/False: Pancreatitis is a rare manifestation of CF.

True. Patients with CF may develop chronic pancreatic insufficiency; however, acute pancreatitis is seen in less than 1%.

Image True/False: Microscopic pancreatic involvement is seen in the majority of patients with sarcoidosis.

False. Pancreatic involvement occurs in only 1%–6% of all affected individuals and is rarely seen before the diagnosis is made from the upper aerodigestive tract.

Image True/False: Microscopic gastrointestinal involvement is seen in the majority of patients with sarcoidosis.

True. Granulomas are seen in nearly 100% of patients with known sarcoidosis, although symptoms are described in less than 1%.

Image Briefly describe the pathophysiology of sarcoidosis.

Noncaseating granulomata occur in sarcoidosis. Enlarged lymph nodes may cause pressure-related symptoms and granulomatous infiltration may cause dysfunction or dysmotility in the gastrointestinal tract.

Image True/False: Involvement of the pancreas in Crohn’s disease is not seen in the absence of duodenal involvement.

False.

Image What are potential mechanisms underlying Crohn’s disease involvement of the pancreas?

There are four suggested mechanisms: ampullary involvement, cholelithiasis secondary to ileal disease, immunologic injury, and drug therapy.

Image Name the usual, albeit rare, manifestation of Wegener’s granulomatosis involving the pancreas.

Pancreatic mass.

Image What is the classic triad of Wegener’s granulomatosis?

Focal glomerulonephritis, vasculitis, and necrotizing granulomata.

Image Classically, Wegener’s granulomatosis affects what part of the alimentary tract?

The intestine. The associated vasculitis can lead to intestinal or colonic bleeding, ischemia, or perforation.

Image What is the most common cause of pancreatitis in childhood?

Trauma (child abuse must be considered). Systemic disease, drugs, and infection are the other major causes in children.

Image What is Shwachman’s syndrome (aka, Shwachman–Diamond syndrome)?

A disorder of pancreatic exocrine insufficiency, hematologic abnormalities, and growth retardation with normal sweat electrolytes. This autosomal recessive disorder is the second most common cause of pancreatic insufficiency in children.

Image A patient recovering from gallstone pancreatitis develops multiple painful, erythematous subcutaneous nodules. What is the diagnosis?

Pancreatic panniculitis. Subcutaneous fat necrosis occurs in 2%–3% of patients with acute pancreatitis or pancreatic cancer. The lesions may resemble erythema nodosum.

Image What are the effects of end-stage renal disease on the pancreas?

Morphologically, multiple abnormalities (acinar dilation, interlobular fibrosis) may be seen. Functionally, an elevated trypsin with a normal output of lipase and impaired bicarbonate secretion may be seen. Hyperamylasemia and hyperlipasemia may be seen due to a lack of renal clearance, even in the absence of pancreatic inflammation. Clinically, the frequency of acute pancreatitis may be increased in these patients, but the mechanisms are unclear.

Image What are the pancreatic effects of hereditary hemochromatosis?

Selective accumulation of excess iron in islet beta-cells results in a loss of endocrine granules and subsequent glucose intolerance or frank diabetes.

Image True/False: Diabetics have an increased risk of exocrine pancreatic insufficiency.

True. Nearly 40% of diabetics will have impaired pancreatic secretion. This is thought to be due to the inhibitory effects of excess glucagon and lack of stimulatory effects of insulin on the pancreas, vagal neuropathy, and nutritional wasting.

• • • SUGGESTED READINGS • • •

Detlefsen S, Löhr JM, Drewes AM, Frøkjær JB, Klöppel G. Current concepts in the diagnosis and treatment of type 1 and type 2 autoimmune pancreatitis. Recent Pat Inflamm Allergy Drug Discov. 2011 May;5(2):136-149.

Lal A, Lal DR. Hereditary pancreatitis. Pediatr Surg Int. 2010 Dec;26(12):1193-1199.