Hereditary pancreatitis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Iqra Qamar M.D.[2]

In 1642, Johannes Wirsung of Padua first described the pancreatic duct and the concept of the pancreas as a secretory organ. In 1996, a gene for hereditary chronic pancreatitis was mapped to chromosome 7. Hereditary pancreatitis may be classified on the basis of mode of inheritance into autosomal dominant, autosomal recessive and hereditary pancreatitis with complex genetics. Hereditary pancreatitis is caused by genetic mutations in the regulatory regions present on trypsin. Mutations in PRSS1, SPINK1, CTRC, and CFTR gene result in weakening of defense mechanisms against pancreatitis. Defense mechanisms against pancreatitis include control of trypsin activity via prevention of premature activation of trypsinogen to trypsin and destruction, inhibition, or elimination of trypsin from the pancreas. Premature activation of digestive enzymes resulting in pancreatic injury, immune system activation, acute pancreatitis, and chronic pancreatitis. The incidence of hereditary pancreatitis is approximately 3.5–10 per 100,000 individuals in the USA. The median age at which the symptoms develop is 10 years. The symptoms of hereditary pancreatitis usually develop in the first or second decade of life. Patients with hereditary pancreatitis usually present with recurrent episodes of acute pancreatitis and may develop exocrine and endocrine insufficiency. If left untreated, patients with hereditary pancreatitis may progress to develop pancreatitis, biliary or pancreatic ductal dilatation, jaundice, biliary obstruction, pancreatic duct stone or stricture, pancreatic pseudocysts, and pancreatic cancer. Mortality rate is found to be increased in patients who develop pancreatic cancer. There are no established criteria for the diagnosis of Hereditary pancreatitis but the diagnosis is usually made on the basis of clinical findings, a typical medical and family history, imaging methods, and pancreatic function tests. Pancreatic function tests include direct and indirect tests. Genetic testing is generally done for the following genes; PRSS1, CFTR, SPINK1 and CTRC. Contrast enhanced CT scan may be helpful in ruling out other diseases with similar presentation such as malignancy and pseudocysts. CT scan findings suggestive of chronic pancreatitis may include dilatation of the main pancreatic duct, calcifications, pancreatic gland enlargement, changes in pancreatic size, shape, and contour, and pancreatic pseudocysts. The goals of management for hereditary pancreatitis include pain control, management of pancreatic insufficiency by pancreatic enzyme replacement and management of complications. Pain is managed in a stepwise approach of general recommendations, pancreatic enzyme replacement, analgesics and invasive procedures. General recommendations usually include smoking cessation, cessation of alcohol intake, small meals and hydration. Surgery is usually considered when pain management fails with medical and endoscopic therapies. The goals of surgery include effective pain relief, and to preserve long-term pancreatic function. Surgery for chronic pancreatitis tends to be divided into two areas – resectional and drainage procedures. Dilated pancreatic duct may be managed with lateral pancreaticojejunostomy (LPJ) and lateralpancreaticojejunostomy with localized pancreatic head resection. Nondilated pancreatic duct is usually managed with pancreaticoduodenectomy, duodenal-preserving pancreatic head resection (DPPHR), distal pancreatectomy (DP) and total pancreatectomy (TP).

In 1642, Johannes Wirsung of Padua first described the pancreatic duct and the concept of the pancreas as a secretory organ. In 1952, Comfort and Steinberg  were the first to identify a genetic background associated with hereditary pancreatitis and they found hereditary pancreatitis in six family members spanning 3 generations. In 1996, a gene for hereditary chronic pancreatitis was mapped to chromosome 7.

Hereditary pancreatitis may be classified on the basis of mode of inheritance into autosomal dominant, autosomal recessive and hereditary pancreatitis with complex genetics.

Hereditary pancreatitis is caused by genetic mutations in the regulatory regions present on trypsin. Mutations in PRSS1, SPINK1, CTRC, and CFTR gene result in weakening of defense mechanisms against pancreatitis. Defense mechanisms against pancreatitis include control of trypsin activity via prevention of premature activation of trypsinogen to trypsin and destruction, inhibition, or elimination of trypsin from the pancreas. Premature activation of digestive enzymes resulting in pancreatic injury, immune system activation, acute pancreatitis, and chronic pancreatitis. Hereditary pancreatitis may be associated with Shwachman-Diamond syndrome (SDS), Pearson marrow pancreas syndrome, CEL maturity-onset diabetes of the young (CEL-MODY) and Johanson-Blizzard syndrome. Gross examination may show enlarged or atrophic pancreas, Cysts, Calcifications and Fibrosis. On microscopic histopathological analysis, non-invasive dysplastic intraductal lesions, called pancreatic intraepithelial neoplasia (PanIN), may be noticed. Common risk factors in the development of Hereditary pancreatitis include smoking, alcohol consumption, lack of antioxidants, genetic mutations such as increased PRSS1 gene expression and CTRC gene mutations.  Patients with hereditary pancreatitis should be screened for pancreatic cancer as they are at markedly increased risk of pancreatic cancer.

Hereditary pancreatitis may be caused by mutation in any one of the following genes PRSS1, SPINK1, CFTR and CTRC gene.

Hereditary pancreatitis needs to be differentiated from other diseases presenting with similar complaints such as abdominal pain, diarrhea and weight loss.

The incidence of hereditary pancreatitis is approximately 3.5–10 per 100,000 individuals in Europe and the USA. In Western countries, the prevalence was found to be 0.3/100 000. Hereditary pancreatitis commonly affects younger age group. The median age at which first diagnosis is made is 19 years. The median age at which the symptoms develop is 10 years.

Common risk factors in the development of Hereditary pancreatitis include smoking, alcohol consumption, lack of antioxidants, genetic mutations such as increased PRSS1 gene expression and CTRC gene mutations.

Patients with hereditary pancreatitis should be screened for pancreatic cancer as they are at markedly increased risk of pancreatic cancer.

The symptoms of hereditary pancreatitis usually develop in the first or second decade of life. Patients with hereditary pancreatitis usually present with recurrent episodes of acute pancreatitis and may develop exocrine and endocrine insufficiency. If left untreated, patients with hereditary pancreatitis may progress to develop pancreatitis, biliary or pancreatic ductal dilatation, jaundice, biliary obstruction, pancreatic duct stone or stricture, pancreatic pseudocysts, and pancreatic cancer. Mortality rate is found to be increased in patients who develop pancreatic cancer.

There are no established criteria for the diagnosis of Hereditary pancreatitis but the diagnosis is usually made on the basis of clinical findings, a typical medical and family history, imaging methods, and pancreatic function tests.

Patients with hereditary pancreatitis usually have a positive family history of recurrent acute pancreatitis or chronic pancreatitis occurring in two first degree relatives or three or more second degree relatives, in two or more generations in the absence of precipitating factors after negative work-up for known chronic pancreatitis aetiology. The majority of patients with hereditary pancreatitis are asymptomatic. The most common presentation is recurrent acute pancreatitis.

Patients with hereditary pancreatitis may assume a characteristic position in an attempt to relieve their abdominal pain such as lying on the left side, flexing the spine, drawing the knees up toward the chest. Patients with steatorrhea or advanced disease may present as loss of subcutaneous fat, temporal wasting and sunken supraclavicular fossa. Skin findings may include  jaundice, pallor and bruises.

Serum amylase and lipase are usually normal but may be slightly elevated (neither diagnostic nor prognostic). Serum bilirubin and alkaline phosphatase levels may be elevated in case of intra-pancreatic biliary duct obstruction. Fecal tests include Sudan staining of faeces, 72-hour quantitative fecal fat, and faecal elastase measurement. Pancreatic function tests include direct and indirect tests. Genetic testing is generally done for the following genes; PRSS1, CFTR, SPINK1 and CTRC.

There are no ECG findings associated with Hereditary pancreatitis.

Pancreatic calcification can often be seen on plain abdominal X-rays. 

Ultrasound findings suggestive of hereditary pancreatitis may include dilatation of the main pancreatic duct, calcifications, pancreatic gland enlargement, changes in pancreatic size, shape, and contour, pancreatic pseudocysts, hyperechogenicity suggesting fibrotic changes, pseudoaneurysms and ascites. 

Contrast enhanced CT scan may be helpful in ruling out other diseases with similar presentation such as malignancy and pseudocysts. CT scan findings suggestive of chronic pancreatitis may include dilatation of the main pancreatic duct, calcifications, pancreatic gland enlargement, changes in pancreatic size, shape, and contour, and pancreatic pseudocysts. The sensitivity of CT scan is 75 to 90 percent and specificity is 85 percent.

MRI findings for hereditary pancreatitis may be classified as early and late findings. Early findings may include low-signal-intensity pancreas on T1-weighted fat-suppressed images, decreased and delayed enhancement after IV contrast administration and dilated side branches. Late findings may include parenchymal atrophy or enlargement, pseudocyst formation, dilatation and beading of the pancreatic duct with intraductal calcifications giving an appearance of ‘chain of lakes’.

Other imaging findings may include MRCP, ERCP, and endoscopic ultrasonography. MRCP is the diagnostic study of choice. MRCP findings suggestive of chronic pancreatitis may include calcifications and pancreatic duct obstruction. ERCP findings diagnostic of chronic pancreatitis may include beaded appearance of the main pancreatic duct and ectatic side branches from the main pancreatic duct. Presence of stones is the most predictive finding seen on endoscopic ultrasonography. Other findings suggestive of chronic pancreatitis may include visible side branches, cysts, lobularity, an irregular main pancreatic duct, hyperechoic foci, dilation of the main pancreatic duct and hyperechoic margins of the main pancreatic duct. Pancreatic function tests may include direct tests such as secretin stimulation tests and indirect tests.

Genetic testing is generally done for the following genes PRSS1, SPINK1, CFTR and CTRC . Predictive testing is done only after expert genetic counseling and may be considered for patients who have a first-degree relative with a known PRSS1 mutation. Predictive testing is not done for patients below 16 yr age. Predictive testing is usually not recommended for patients with SPINK1 or CFTR mutations.

The goals of management for hereditary pancreatitis include pain control, management of pancreatic insufficiency by pancreatic enzyme replacement and management of complications. Pain is managed in a stepwise approach of general recommendations, pancreatic enzyme replacement, analgesics and invasive procedures. General recommendations usually include smoking cessation, cessation of alcohol intake, small meals and hydration. Medical therapy includes pancreatic enzyme supplementation, analgesics and antioxidants. Specialized approaches include celiac nerve block, endoscopic therapy, extracorporeal shock wave lithotripsy (ESWL), and radiation. Steatorrhea can be managed by dietary modification, lipase supplementation, vitamin supplementation, and medium chain triglycerides (MCTs). Diabetes is usually managed with a trial of oral hypoglycemic agents followed by insulin therapy.

Surgery is usually considered when pain management fails with medical and endoscopic therapies. The goals of surgery include effective pain relief, and to preserve long-term pancreatic function. Surgery for chronic pancreatitis tends to be divided into two areas – resectional and drainage procedures. Dilated pancreatic duct may be managed with lateral pancreaticojejunostomy (LPJ) and lateralpancreaticojejunostomy with localized pancreatic head resection. Nondilated pancreatic duct is usually managed with pancreaticoduodenectomy, duodenal-preserving pancreatic head resection (DPPHR), distal pancreatectomy (DP) and total pancreatectomy (TP).

There are no established measures for the primary prevention of hereditary pancreatitis.

Effective measures for the secondary prevention of Hereditary pancreatitis include low-fat diet, multiple small meals, good hydration, antioxidants, and cessation/abstinence from smoking and alcohol use.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Iqra Qamar M.D.[2]

In 1642, Johannes Wirsung of Padua first described the pancreatic duct and the concept of the pancreas as a secretory organ. In 1952, Comfort and Steinberg , were the first one to identify a genetic background associated with hereditary pancreatitis and they found hereditary pancreatitis in six family members spanning 3 generations. In 1996, a gene for hereditary chronic pancreatitis was mapped to chromosome 7.

The historical landmarks in the diagnostic evaluation and management of pancreatitis are as follows:^{[1] [2]}

• In 1642, Johannes Wirsung of Padua first described the pancreatic duct and the concept of the pancreas as a secretory organ.
• In 1737, Giovanni Santorini of Venice identified a second, accessory duct and was credited with primacy in the discovery of the ampulla of Vater.
• In 1887, Rugero Oddi published his observations of the structure and function of the choledochal sphincter in Archives Italiennes de Biologie that laid the basis for understanding its role in pancreatic and biliary disease.
• In the 16th century, Sylvius Franciscus de la Boe Sylvius found that the pancreas discharged a fluid that mixed with the partly digested food and bile in the intestine causing an effervescence (“effervescentia intestinalis”) which liquefied food.
• In the 16th century, Regnier de Graaf of Delft devised novel surgical techniques to create pancreatic fistulas (center) to collect this juice for analysis.
• In 1652, Nicholaes Tulp of Amsterdam is credited with the first description of acute pancreatitis.
• In 1761, Giovanni Morgagni described the clinical syndrome of severe upper abdominal pain, vomiting, and collapse (acute pancreatitis). He is also credited with the earliest pathological recognition of cancer of the pancreas.
• In 1652, Nicholaes Tulp was credited with the first description of acute pancreatitis
• In 1842, Karl von Rokitansky, the premier pathologist of Vienna (Wiener Allgemeines Krankenhaus) was the first one to recognize acute hemorrhagic pancreatitis.
• In late 18th century, Reginald Fitz described 3 forms of acute pancreatitis (hemorrhagic, suppurative, and gangrenous) and proposed that fat necrosis was a sequel of severe pancreatitis
• In late 18th century, Nicholas Senn of Chicago, not only addressed the mechanisms of acute pancreatitis but also provided rational insight into the validity of surgical techniques for its treatment.
• In 1952, Comfort and Steinberg , were the first one to identify a genetic background associated with hereditary pancreatitis and they found hereditary pancreatitis in six family members spanning 3 generations.^[3]
• In 1996, a gene for hereditary chronic pancreatitis was mapped to chromosome 7.^[4][5][6]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Iqra Qamar M.D.[2]

Hereditary pancreatitis may be classified on the basis of mode of inheritance into autosomal dominant, autosomal recessive and hereditary pancreatitis with complex genetics.

• Hereditary pancreatitis may be classified on the basis of mode of inheritance.
• Hereditary pancreatitis involves atleast 3 different patterns of inheritance:^{[1][2][3][4][5][6][7][8]}

Mode of inheritance	Genes involved
Autosomal dominant	Serine protease 1 gene (PRSS1)
Autosomal recessive	Serine protease inhibitor Kazal type 1 gene (SPINK1, also called pancreatic secretory trypsin inhibitor gene)
Complex genetics	A combination of genetic and environmental factors

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Iqra Qamar M.D.[2]

Hereditary pancreatitis is caused by genetic mutations in the regulatory regions present on trypsin. Mutations in PRSS1, SPINK1, CTRC, and CFTR gene result in weakening of defense mechanisms against pancreatitis. Defense mechanisms against pancreatitis include control of trypsin activity via prevention of premature activation of trypsinogen to trypsin and destruction, inhibition, or elimination of trypsin from the pancreas. Premature activation of digestive enzymes resulting in pancreatic injury, immune system activation, acute pancreatitis, and chronic pancreatitis. Hereditary pancreatitis may be associated with Shwachman-Diamond syndrome (SDS), Pearson marrow pancreas syndrome, CEL maturity-onset diabetes of the young (CEL-MODY) and Johanson-Blizzard syndrome. Gross examination may show enlarged or atrophic pancreas, cysts, calcifications and fibrosis. On microscopic histopathological analysis, non-invasive dysplastic intraductal lesions, called pancreatic intraepithelial neoplasia (PanIN), may be noticed.

Hereditary pancreatitis is defined as EITHER two or more individuals with pancreatitis in two or more generations of a family (i.e., an autosomal dominant pattern of inheritance) OR Pancreatitis associated with a known germline pathogenic variant.^[1]

• There are two regulatory regions present on trypsin
• Almost all of the genetic mutations associated with hereditary pancreatitis are clustered in these 2 regulatory regions

• It regulates the activation site
• It converts trypsinogen into trypsin

• It regulates the autolysis site
•  It causes destruction of trypsin

• Mutations in PRSS1, SPINK1, CTRC, and CFTR gene result in weakening of defense mechanisms against pancreatitis.^{[2] [3][4]}
• Defense mechanisms against pancreatitis include control of trypsin activity via:
  • Prevention of premature activation of trypsinogen to trypsin
  • Destruction, inhibition, or elimination of trypsin from the pancreas

• New mutations at different sites on PRSS1 gene may include:^{[3][5][6][7][8][9]}
  • Misfolding and intracellular retention of cationic trypsinogen
  • Stabilization of trypsinogen, protecting against autocatalytic degradation
  • Increases trypsin activation from trypsinogen

• Mutations in PRSS1 gene result in
  • Premature activation of digestive enzymes resulting in:
    • Pancreatic injury
    • Immune system activation
    • Acute pancreatitis
    • Chronic pancreatitis

• Hereditary pancreatitis involves atleast 3 different patterns of inheritance:^{[10][11][12][13][14][15][16][17]}

Mode of inheritance	Genes involved
Autosomal dominant	Serine protease 1 gene (PRSS1)
Autosomal recessive	Serine protease inhibitor Kazal type 1 gene (SPINK1, also called pancreatic secretory trypsin inhibitor gene)
Complex genetics	A combination of genetic and environmental factors

Hereditary pancreatitis involves mutations in the following genes:

• Serine protease 1 gene (PRSS1) encodes for trypsin-1 (cationic trypsinogen).
• 80% of patients with autosomal dominant hereditary pancreatitis have mutations in PRSS1 gene.^{[18][19][20][21][22][23]}
• The most common mutations in PRSS1 include R122H and N29I.^{[11][12][18][22]}

• The serine protease inhibitor Kazal type 1 gene (SPINK1) encodes a pancreatic secretory trypsin inhibitor, that is an acute phase reactant protein, suggesting ongoing inflammation.^{[19][24][25][8][26][27]}
• Mutations in SPINK1 may increase the risk of developing chronic pancreatitis by 12 fold when compared to general population.
• CFTR is the most common genetic variant seen with SPINK1.^[16][17]
• SPINK variants are also found to be associated with:^[28]
  • Idiopathic pancreatitis
  • Alcoholic pancreatitis
  • Familial pancreatitis
  • Tropical pancreatitis

• CFTR gene mutations may cause pancreatitis with or without cystic fibrosis.^{[29][30][31][32][16][33]}

^{[34][35][36][37]}

• The chymotrypsin C gene (CTRC) encodes for Chymotrypsin C, that is a digestive enzyme, that helps in trypsin degradation.
• Mutations in CTRC gene are found to be associated with chronic hereditary pancreatitis.^{[17][38][39][40][41]}

• Two additional genes have been found to be associated with hereditary pancreatitis.
  • CLDN2, associated with chronic alcoholic pancreatitis.^[42][43][44]
  • CPA1, associated with nonalcoholic chronic pancreatitis, especially with early age of onset.^[45]

• The most common disease associated mutations in PRSS1 gene include:^[11][12][46]
  • R122H^[11]
  • N29I 
  • A16V

• There are 2 genetic variants that have been found to play an important role in protecting against pancreatitis. They include:
  • PRSS2 G191R mutation^[47][48]
  • PRSS1-PRSS2 locus mutation^[49][42]

Hereditary pancreatitis may be associated with following syndromes:

• Shwachman-Diamond syndrome (SDS)^[50] 
• Pearson marrow pancreas syndrome^{[51][52] [53]}
• CEL maturity-onset diabetes of the young (CEL-MODY)^[54]
• Johanson-Blizzard syndrome^[55]

• On gross examination, following findings may be observed:
  • Enlarged or atrophic pancreas
  • Cysts
  • Calcifications
  • Fibrosis

• On microscopic histopathological analysis, non-invasive dysplastic intraductal lesions, called pancreatic intraepithelial neoplasia (PanIN), may be noticed.
• Pancreatic intraepithelial neoplasia (PanIN) lesions, are precursors of infiltrating ductal carcinoma.
•  PanINs are thought to progress from low grade dysplasia to high grade dysplasia.
  • Low grade dysplasia (PanIN-1A and PanIN-1B)
  • Moderate dysplasia (PanIN-2)
  • High grade dysplasia and or carcinoma in situ (PanIN-3)

• Other findings may include:
  • Ductal inflammation
  • Fibrosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Iqra Qamar M.D.[2]

Hereditary pancreatitis may be caused by mutation in any one of the following genes PRSS1, SPINK1, CFTR and CTRC gene.

• Hereditary pancreatitis may be caused by mutation in any one of the following genes.^{[1] [2][3][2][4][5][6][7][8]}
  • PRSS1 gene^{[9][10][11][12][13][14]}
  • SPINK1 gene^{[10][15][16][7][17][18]}
  • CFTR gene mutations^{[19][20][21][22][23][24][25][26][27][28]}
  • CTRC gene mutations^{[29][30][31][32][33]}

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Iqra Qamar M.D.[2]

Hereditary pancreatitis needs to be differentiated from other diseases presenting with similar complaints such as abdominal pain, diarrhea and weight loss.

Abbreviations: RUQ= Right upper quadrant of the abdomen, LUQ= Left upper quadrant, LLQ= Left lower quadrant, RLQ= Right lower quadrant, LFT= Liver function test, SIRS= Systemic inflammatory response syndrome, ERCP= Endoscopic retrograde cholangiopancreatography, IV= Intravenous, N= Normal, AMA= Anti mitochondrial antibodies, LDH= Lactate dehydrogenase, GI= Gastrointestinal, CXR= Chest X ray, IgA= Immunoglobulin A, IgG= Immunoglobulin G, IgM= Immunoglobulin M, CT= Computed tomography, PMN= Polymorphonuclear cells, ESR= Erythrocyte sedimentation rate, CRP= C-reactive protein, TS= Transferrin saturation, SF= Serum Ferritin, SMA= Superior mesenteric artery, SMV= Superior mesenteric vein, ECG= Electrocardiogram

Disease Clinical manifestations Diagnosis Comments Symptoms Signs Abdominal Pain Fever Rigors and chills Nausea or vomiting Jaundice Constipation Diarrhea Weight loss GI bleeding Hypo- tension Guarding Rebound Tenderness Bowel sounds Lab Findings Imaging Chronic pancreatitis Epigastric − − ± ± − + + − − − − N Increased amylase / lipase Increased stool fat content Pancreatic function test CT scan Calcification Pseudocyst Dilation of main pancreatic duct Predisposes to pancreatic cancer Pancreatic carcinoma Epigastric − − + + − + + − − − − N ↑ Alkaline phosphatase ↑ serum bilirubin ↑ gamma-glutamyl transpeptidase ↑ CA 19-9  MDCT with  PET/CT MRI Skin manifestations may include: Bullous pemphigoid Cicatricial pemphigoid Migratory superficial thrombophlebitis (classic Trousseau’s syndrome) Pancreatic panniculitis Dumping syndrome Lower and then diffuse − − + − − + + − + − − Hyperactive Glucose challenge test Hydrogen breath test Upper GI series Gastric emptying study Postgastrectomy Inflammatory bowel disease Diffuse ± − − ± − + + + − − − Normal or hyperactive Anti-neutrophil cytoplasmic antibody (P-ANCA) in Ulcerative colitis Anti saccharomyces cerevisiae antibodies (ASCA) in Crohn’s disease String sign on abdominal x-ray in Crohn’s disease Extra intestinal findings: Uveitis Arthritis Irritable bowel syndrome Diffuse − − − − ± ± + − − − − N Normal Normal Symptomatic treatment High dietary fiber Osmotic laxatives Antispasmodic drugs Whipple’s disease Diffuse ± − − ± − + + − ± − − N Thrombocytopenia Hypoalbuminemia Small intestinal biopsy for Tropheryma whipplei Endoscopy is used to confirm diagnosis. Images used to find complications Chest and joint x-ray CT MRI Echocardiography Extra intestinal findings: Uveitis Endocarditis Encephalitis Dementia Hepatosplenomegaly Arthritis Ascites Disease Abdominal Pain Fever Rigors and chills Nausea or vomiting Jaundice Constipation Diarrhea Weight loss GI bleeding Hypo- tension Guarding Rebound Tenderness Bowel sounds Lab Findings Imaging Comments Tropical sprue Diffuse + − − − − + + − − − − N Fat soluble vitamin deficiency Hypoalbuminemia Fecal stool test Barium studies: Dilation and edema of mucosal folds Steatorrhea– 10-40 g/day (Normal=5 g/day) Celiac disease Diffuse − − − − − + + − − − − Hyperactive IgA endomysial antibody IgA tissue transglutaminase antibody Anti-gliadin antibody Small bowel biopsy US: Bull’s eye or target pattern Pseudokidney sign Gluten allergy Colon carcinoma Diffuse/localized − − − − ± ± + + ± − − Normal or hyperactive if obstruction present CBC Carcinoembryonic antigen (CEA) Colonoscopy Flexible sigmoidoscopy Barium enema CT colonography  PILLCAM 2: A colon capsule for CRC screening may be used in patients with an incomplete colonoscopy who lacks obstruction Viral hepatitis RUQ + − + + − Positive in Hep A and E + − Positive in fulminant hepatitis Positive in acute + N Abnormal LFTs Viral serology US Hep A and E have fecal-oral route of transmission Hep B and C transmits via blood transfusion and sexual contact. Liver abscess RUQ + + + + − ± + − + + ± Normal or hypoactive CBC Blood cultures Abnormal liver function tests US CT Mesenteric ischemia Periumbilical Positive if bowel becomes gangrenous − + − − + + + Positive if bowel becomes gangrenous Positive if bowel becomes gangrenous − Hyperactive to absent Leukocytosis and lactic acidosis Amylase levels D-dimer CT angiography SMA or SMV thrombosis Also known as abdominal angina that worsens with eating Acute ischemic colitis Diffuse + ± + − − + + + + + + Hyperactive then absent Leukocytosis Abdominal x-ray Distension and pneumatosis CT scan Double halo appearance, thumbprinting Thickening of bowel May lead to shock

To review the differential diagnosis of Abdominal pain, click here.

References

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Iqra Qamar M.D.[2]

The incidence of hereditary pancreatitis is approximately 3.5–10 per 100,000 individuals in Europe and the USA. In Western countries, the prevalence was found to be 0.3/100 000. Hereditary pancreatitis commonly affects younger age group. The median age at which first diagnosis is made is 19 years. The median age at which the symptoms develop is 10 years.

• The incidence of hereditary pancreatitis is approximately 3.5–10 per 100,000 individuals in Europe and the USA.^[1][2]

• In Western countries, the prevalence was found to be 0.3/100 000.

• Hereditary pancreatitis commonly affects younger age group.
• The median age at which first diagnosis is made is 19 years.^[3][4]
• The median age at which the symptoms develop is 10 years.^[3][4]
• In some patients, the disease may develop before 5 years of age.^[5][6]

• There is no racial predilection to Hereditary pancreatitis.

• Hereditary pancreatitis affects men and women equally.
  

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Iqra Qamar M.D.[2]

Common risk factors in the development of Hereditary pancreatitis include smoking, alcohol consumption, lack of antioxidants, genetic mutations such as increased PRSS1 gene expression and CTRC gene mutations.

Common risk factors in the development of Hereditary pancreatitis include smoking, alcohol consumption, lack of antioxidants, genetic mutations such as increased PRSS1 gene expression and CTRC gene mutations.

• Common risk factors in the development of Hereditary pancreatitis may be occupational, environmental, and genetic.
• Common risk factors in the development of Hereditary pancreatitis include:^[1][2][3][4]
  • Smoking^[5]
  • Alcohol consumption
  • Lack of antioxidants
  • Increased PRSS1 gene expression^[6]
  • CTRC gene mutations^{[7][8][9][10][11]}

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Iqra Qamar M.D.[2]

Patients with hereditary pancreatitis should be screened for pancreatic cancer as they are at markedly increased risk of pancreatic cancer.

• Patients with hereditary pancreatitis should be screened for pancreatic cancer as they are at markedly increased risk of pancreatic cancer.^{[1][2][3][4][5][6]}
• According to 2001 guidelines, screening for pancreatic cancer should begin at age 40.^[1]
• In 2007, The Fourth Annual Symposium of Inherited Diseases of the Pancreas recommended the screening age for pancreatic cancer in patients with hereditary pancreatitis or those at increased risk to be (whichever is at the earliest age)^[2]
  • 45 year old or
  • Starting 15 years earlier than the youngest age of pancreatic cancer in the family (whichever is at the earliest age)

• Patients with hereditary pancreatitis are usually recommended for yearly screening for pancreatic exocrine and endocrine insufficiency.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Iqra Qamar M.D.[2]

The symptoms of hereditary pancreatitis usually develop in the first or second decade of life. Patients with hereditary pancreatitis usually present with recurrent episodes of acute pancreatitis and may develop exocrine and endocrine insufficiency. If left untreated, patients with hereditary pancreatitis may progress to develop pancreatitis, biliary or pancreatic ductal dilatation, jaundice, biliary obstruction, pancreatic duct stone or stricture, pancreatic pseudocysts, and pancreatic cancer. Mortality rate is found to be increased in patients who develop pancreatic cancer.

• The symptoms of hereditary pancreatitis usually develop in the first or second decade of life.
• Patients with hereditary pancreatitis usually present with recurrent episodes of acute pancreatitis and may develop exocrine and endocrine insufficiency.
• If left untreated, patients with hereditary pancreatitis may progress to develop
  • Pancreatitis
  • Biliary or pancreatic ductal dilatation
  • Jaundice
  • Biliary obstruction
  • Pancreatic duct stone or stricture
  • Pancreatic pseudocysts
  • Pancreatic cancer.

• Diabetes^[1]
• Pseudocysts
• Bile duct or duodenal obstruction
• Pancreatic ascites^[2][3]
• Pleural effusion
• Splenic vein thrombosis^[4][5][6]
• Pseudoaneurysm of splenic artery^[7][8][9]
• Pancreatic cancer^[10]

• Mortality rate is found to be increased in patients who develop pancreatic cancer.^[11]
• The overall mortality is not increased in patients with hereditary pancreatitis who do not develop pancreatic cancer compared with the general population.
• The median survival age is 74.^[11]

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