Steatorrhea occurs due to impaired fat digestion in patients with pancreatic enzyme deficiencies, or as a consequence of impaired fat absorption. Both bile salt deficiency and small intestinal disease can lead to fat malabsorption.
Pancreatic insufficiency steatorrhea
Chronic inflammation of the pancreas (chronic pancreatitis) leads to cumulative loss of lipase-producing acinar cells. Steatorrhea occurs late in the disease process and is a manifestation of severe exocrine deficiency. Loss of over 90% of pancreatic function is required before steatorrhea becomes clinically apparent.[5]Keller J, Layer P. Human pancreatic exocrine response to nutrients in health and disease. Gut. 2005 Jul;54 Suppl 6(suppl 6):vi1-28.
https://gut.bmj.com/content/54/suppl_6/1
http://www.ncbi.nlm.nih.gov/pubmed/15951527?tool=bestpractice.com
[6]Conwell DL, Lee LS, Yadav D, et al. American Pancreatic Association practice guidelines in chronic pancreatitis: evidence-based report on diagnostic guidelines. Pancreas. 2014 Nov;43(8):1143-62.
https://journals.lww.com/pancreasjournal/Fulltext/2014/11000/American_Pancreatic_Association_Practice.6.aspx
http://www.ncbi.nlm.nih.gov/pubmed/25333398?tool=bestpractice.com
Once steatorrhea develops, it has 100% specificity for pancreatic exocrine insufficiency, but only 38% sensitivity.[7]Dumasy V, Delhaye M, Cotton F, et al. Fat malabsorption screening in chronic pancreatitis. Am J Gastroenterol. 2004 Jul;99(7):1350-4.
http://www.ncbi.nlm.nih.gov/pubmed/15233677?tool=bestpractice.com
The causes of cumulative injury include:[8]Witt H, Apte MV, Keim V, et al. Chronic pancreatitis: challenges and advances in pathogenesis, genetics, diagnosis, and therapy. Gastroenterology. 2007 Apr;132(4):1557-73.
https://www.gastrojournal.org/article/S0016-5085(07)00495-7/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/17466744?tool=bestpractice.com
Although alcohol and idiopathic causes have traditionally accounted for the majority (>80%) of cases of chronic pancreatitis, identification of mutations in genes that encode for pancreatic enzymes and protease inhibitors provide insights into the pathophysiology of a small proportion of "idiopathic" cases.[9]Király O, Boulling A, Witt H, et al. Signal peptide variants that impair secretion of pancreatic secretory trypsin inhibitor (SPINK1) cause autosomal dominant hereditary pancreatitis. Hum Mutat. 2007 May;28(5):469-76.
http://www.ncbi.nlm.nih.gov/pubmed/17274009?tool=bestpractice.com
Acute pancreatitis
Pancreatic exocrine insufficiency (EPI) may occur following severe acute pancreatitis. One meta-analysis reported EPI prevalence of 62% among patients with acute pancreatitis (all severity grades) during their initial admission.[10]Huang W, de la Iglesia-García D, Baston-Rey I, et al. Exocrine pancreatic insufficiency following acute pancreatitis: systematic review and meta-analysis. Dig Dis Sci. 2019 Jul;64(7):1985-2005.
https://link.springer.com/article/10.1007/s10620-019-05568-9
http://www.ncbi.nlm.nih.gov/pubmed/31161524?tool=bestpractice.com
Risk for EPI was higher among patients with pancreatic necrosis and alcohol etiology. Prevalence decreased during recovery.[10]Huang W, de la Iglesia-García D, Baston-Rey I, et al. Exocrine pancreatic insufficiency following acute pancreatitis: systematic review and meta-analysis. Dig Dis Sci. 2019 Jul;64(7):1985-2005.
https://link.springer.com/article/10.1007/s10620-019-05568-9
http://www.ncbi.nlm.nih.gov/pubmed/31161524?tool=bestpractice.com
Bile salt deficiency steatorrhea
Patients with primary or secondary biliary cholangitis, or prolonged biliary obstruction, experience impaired excretion of bile salts (bile acids) into the duodenum. Reduced release of bile salts into the jejunal lipid emulsion impairs the micelle formation necessary for translocation of lipids into the intestinal cells. As with pancreatic disease, significant loss of bile salt output is necessary for steatorrhea to occur.
Causes of bile salt steatorrhea include:
Primary biliary cholangitis (PBC)
Primary sclerosing cholangitis (PSC)
Bacterial overgrowth
Terminal ileum Crohn disease
Ileal resection
Primary bile acid malabsorption
PBC and PSC reduce the release of bile salts into the duodenum. Bacterial overgrowth inhibits reuptake of bile salts by increasing the proportion of unconjugated bile acids.[11]Einarsson K, Bergstrom M, Eklof R, et al. Comparison of the proportion of unconjugated to total serum cholic acid and the (14C)-xylose breath test in patients with suspected small intestinal bacterial overgrowth. Scand J Clin Lab Invest. 1992;52:425-430.
http://www.ncbi.nlm.nih.gov/pubmed/1514020?tool=bestpractice.com
Resection or inflammation of the terminal ileum also impairs the normal reuptake of bile acids into the enterohepatic circulation, thus reducing the overall bile salts available.[12]Stelzner M, Somasundaram S, Khakberdiev T. Systemic effects of acute terminal ileitis on uninflamed gut aggravate bile acid malabsorption. J Surg Res. 2001 Aug;99(2):359-64.
http://www.ncbi.nlm.nih.gov/pubmed/11469911?tool=bestpractice.com
Although such bile acid malabsorption initially causes watery diarrhea, severe loss leads to steatorrhea. Patients with PBC may also have bacterial overgrowth and pancreatic exocrine insufficiency that contribute to steatorrhea.[13]Ros E, García-Pugés A, Reixach M, et al. Fat digestion and exocrine pancreatic function in primary biliary cirrhosis. Gastroenterology. 1984 Jul;87(1):180-7.
http://www.ncbi.nlm.nih.gov/pubmed/6724261?tool=bestpractice.com
Fat malabsorption usually occurs with concurrent malnutrition in patients with cirrhosis of any cause.[14]Romiti A, Merli M, Martorano M, et al. Malabsorption and nutritional abnormalities in patients with liver cirrhosis. Ital J Gastroenterol. 1990 Jun;22(3):118-23.
http://www.ncbi.nlm.nih.gov/pubmed/2131941?tool=bestpractice.com
Malabsorption steatorrhea
Diseases of the small intestine cause impaired function of the surface intestinal epithelium, leading to impaired global absorption of lipids, carbohydrates, proteins, and minerals. Clinical features in patients with malabsorption and diarrhea include steatorrhea, liquid stools, nutritional deficiency, and weight loss. Steatorrhea is rarely the predominant symptom; approximately 50% of patients with diarrheal disease have abnormal stool fat levels, but only half of these describe steatorrhea.[15]Koch J, Garcia-Shelton YL, Neal EA, et al. Steatorrhea: a common manifestation in patients with HIV/AIDS. Nutrition. 1996 Jul-Aug;12(7-8):507-10.
http://www.ncbi.nlm.nih.gov/pubmed/8878143?tool=bestpractice.com
[16]Ung KA, Kilander AF, Lindgren A, et al. Impact of bile acid malabsorption on steatorrhoea and symptoms in patients with chronic diarrhoea. Eur J Gastroenterol Hepatol. 2000 May;12(5):541-7.
http://www.ncbi.nlm.nih.gov/pubmed/10833098?tool=bestpractice.com
There are numerous causes for malabsorption, including:[17]Rubio-Tapia A, Hill ID, Semrad C, et al. American College of Gastroenterology guidelines update: diagnosis and management of celiac disease. Am J Gastroenterol. 2023 Jan 1;118(1):59-76.
https://journals.lww.com/ajg/Fulltext/2023/01000/American_College_of_Gastroenterology_Guidelines.17.aspx
http://www.ncbi.nlm.nih.gov/pubmed/36602836?tool=bestpractice.com
[18]Quigley EMM, Murray JA, Pimentel M. AGA clinical practice update on small intestinal bacterial overgrowth: expert review. Gastroenterology. 2020 Oct;159(4):1526-32.
https://www.gastrojournal.org/article/S0016-5085(20)34928-3/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/32679220?tool=bestpractice.com
[19]Ebert EC, Nagar M. Gastrointestinal manifestations of amyloidosis. Am J Gastroenterol. 2008 Mar;103(3):776-87.
http://www.ncbi.nlm.nih.gov/pubmed/18076735?tool=bestpractice.com
Miscellaneous causes of steatorrhea
Several other etiologies have been reported as case reports or case series:[20]Corsini G, Gandolfi E, Bonechi I, et al. Postgastrectomy malabsorption. Gastroenterology. 1966 Mar;50(3):358-65.
http://www.ncbi.nlm.nih.gov/pubmed/5905355?tool=bestpractice.com
[21]Shimoda SS, Saunders DR, Rubin CE. The Zollinger-Ellison syndrome with steatorrhea. II. The mechanism of fat and vitamin B 12 malabsorption. Gastroenterology. 1968 Dec;55(6):705-23.
http://www.ncbi.nlm.nih.gov/pubmed/5715664?tool=bestpractice.com
[22]Ebert EC. The thyroid and the gut. J Clin Gastroenterol. 2010 Jul;44(6):402-6.
http://www.ncbi.nlm.nih.gov/pubmed/20351569?tool=bestpractice.com
[23]Goswami R, Tandon RK, Dudha A, et al. Prevalence and significance of steatorrhea in patients with active Graves' disease. Am J Gastroenterol. 1998 Jul;93(7):1122-5.
http://www.ncbi.nlm.nih.gov/pubmed/9672342?tool=bestpractice.com
[24]Balasekaran R, Porter JL, Santa Ana CA, et al. Positive results on tests for steatorrhea in persons consuming olestra potato chips. Ann Intern Med. 2000 Feb 15;132(4):279-82.
http://www.ncbi.nlm.nih.gov/pubmed/10681282?tool=bestpractice.com
[25]Moeller DD. Steatorrhea associated with meclofenamate sodium therapy. Am J Gastroenterol. 1987 Dec;82(12):1320-1.
http://www.ncbi.nlm.nih.gov/pubmed/3687910?tool=bestpractice.com
[26]Grigg AP, Angus PW, Hoyt R, et al. The incidence, pathogenesis and natural history of steatorrhea after bone marrow transplantation. Bone Marrow Transplant. 2003 Apr;31(8):701-3.
http://www.ncbi.nlm.nih.gov/pubmed/12728924?tool=bestpractice.com
Postgastrectomy
Zollinger-Ellison syndrome
Graves disease
Diarrhea-predominant irritable bowel syndrome
Nonabsorbable fat substitutes (olestra)
Meclofenamate sodium
Lipase inhibitors - for example, tetrahydrolipstatin (orlistat)
Graft-versus-host disease (pancreatic involvement)
Surgical resection of the pancreas such as Whipple operation, pylorus-preserving pancreatectomy, or total pancreatectomy for benign or malignant neoplasms.