Dig Dis Sci (2015) 60:1183–1186 DOI 10.1007/s10620-015-3654-4
UNM CLINICAL CASE CONFERENCES
Recurrent Abdominal Pain in a Patient with Down Syndrome Allison Venner1 • Archana Kaza1 • Von G. Samedi2
Received: 25 March 2015 / Accepted: 27 March 2015 / Published online: 4 April 2015 Ó Springer Science+Business Media New York 2015
Case Report A 34 year-old woman with Down syndrome was seen in clinic after having two episodes of acute pancreatitis over the preceding 2 months, each requiring hospital admission. The initial episode of pancreatitis was initially manifest as severe epigastric pain radiating to her back associated with loose stools. She denied having had any fevers, nausea, or vomiting. Her medical history included hypothyroidism and a coagulation disorder that had been complicated by a cerebral vascular accident, now under treatment with anticoagulants. Her family history revealed the presence of celiac disease in several family members. She denied any use of alcohol or illicit drugs. Her medication list did not reveal any medications that are considered as possible etiologic agents [1, 2]. Physical examination revealed mild tenderness to palpation in the epigastric area but no organomegaly or palpable masses. Laboratory test results included: white blood cell count of 5.7 9 103/mm3, serum concentrations of aspartate aminotransferase 27 Unit/L (range 6–58 Unit/L), alanine aminotransferase of 34 Unit/L (range 14–67 Unit/L), alkaline phosphatase 89 Unit/L (range 38–150 Unit/L), total bilirubin 0.6 mg/dL (range 0.3–1.2 mg/dL), direct bilirubin 0.1 mg/dL (range 0.1–0.4 mg/dL), serum lipase 1695 Unit/L (range
& Allison Venner [email protected] 1
Division of Gastroenterology and Hepatology, University of New Mexico School of Medicine, 1 University of New Mexico, MSC10-5550, Albuquerque, NM 87131, USA
2
Department of Pathology, University of New Mexico School of Medicine, Albuquerque, NM, USA
66–360 Unit/L), creatinine 0.91 mg/dL (range 0.6–1 mg/ dL), serum triglycerides 95 mg/dL (range \150 mg/dL), calcium 8.2 mg/dL (range 8.4–10.4 mg/dL), and serum IgG4 22 mg/dL (range 7–89 mg/dL). A CT scan of the abdomen and pelvis with and without contrast was reported as showing mildly heterogeneous attenuation of the pancreas without frank pancreatic free fluid, no dilation of the pancreatic duct, and no pancreatic mass or pseudocyst. An abdominal ultrasound showed no cholelithiasis, pericholecystic fluid or gallbladder wall thickening, and a common bile duct that measured 4 mm with no intrahepatic bile duct dilation. An incidental note was made of a Phrygian cap of the gallbladder; the visualized portion of the pancreas appeared sonographically unremarkable. She was clinically diagnosed as having acute pancreatitis was hospitalized for 6 days of conservative management and then discharged. One month later, she was again hospitalized with similar symptoms of abdominal pain and laboratory findings of serum concentrations of lipase of 1241 Unit/L, creatinine 0.84 mg/dL, aspartate aminotransferase 23 Unit/L, alanine aminotransferase of 27 Unit/L, alkaline phosphatase 75 Unit/L, total bilirubin 0.5 mg/dL, and direct bilirubin 0.1 mg/dL. A CT scan of the abdomen and pelvis was reported as showing acute inflammatory changes in the region of the pancreatic tail and the presence of a small amount of free fluid in the left paracolic gutter. The remainder of the pancreas was without inflammatory changes or masses, although a punctate hyperattenuation was noted in the pancreatic tail that may have reflected a focus of calcification from prior pancreatitis; there was no dilation of the pancreatic duct. An abdominal ultrasound scan was unremarkable with no cholelithiasis or bile duct dilation noted. At an outpatient follow-up visit 2 weeks later, further laboratory testing revealed serum concentrations of tissue
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Dig Dis Sci (2015) 60:1183–1186
transglutaminase IgA antibody [225 Units/mL (range 0–19) and serum anti-gliadin IgA of 120 Units/mL (range 0–19), with a normal serum IgA. Additional MRI/MRCP imaging of the abdomen revealed no cholelithiasis or choledocholithiasis, a normal size pancreas and pancreatic duct, normal pancreatic signal intensity and enhancement, no persistence of peripancreatic edema, and no evidence of any congenital malformation. Esophagogastroduodenoscopy showed the presence of a small hiatus hernia, a normal esophagus and stomach, and a scalloped appearance of the mucosa of the second portion of the duodenum (Fig. 1). Duodenal biopsies were interpreted as showing villous blunting, increased intraepithelial lymphocytes, and increased lymphocytes in the lamina propria (Fig. 2). Treatment with a gluten-free diet had not been initiated prior to endoscopy and biopsy. Although she was educated about the diet and advised to use it, her compliance was questionable. One month later, she was again hospitalized with a third episode of acute pancreatitis with the similar symptoms and laboratory findings of serum concentrations of lipase 1495 Units/L, creatinine 0.83 mg/dL, aspartate aminotransferase of 169 Unit/L, alanine aminotransferase of 212 Unit/L, alkaline phosphatase
Fig. 2 Duodenal biopsies showed villous blunting, increased intraepithelial lymphocytes, and increased lymphocytes in the lamina propria. a Low-power (910) magnification. b High-power (940) magnification
92 Unit/L, total bilirubin 0.6 mg/dL, and direct bilirubin 0.1 mg/dL. A chest X-ray was unremarkable, and an abdominal ultrasound showed a non-dilated gallbladder with minimal echogenic debris possibly representing sludge or cholesterol crystals, no pericholecystic fluid or gallbladder wall thickening, no biliary ductal dilation, and all visualized regions of the pancreas appeared normal. Of interest, serum aminotransferase concentrations that were normal during her first two hospitalizations were elevated during this third hospitalization for pancreatitis: The precise cause of this is unclear (see below). She received additional counseling about the importance of adhering to a gluten-free diet. She has since been compliant and has been free of further episodes of pancreatitis for over a year.
Discussion
Fig. 1 Endoscopic findings of scalloped appearance of the mucosa of the second portion of the duodenum. a Duodenum. b Duodenum with closer mucosa view
123
Celiac disease is an immune-mediated enteropathy caused by early exposure to gluten in genetically susceptible individuals. Clinical manifestations of celiac disease vary widely with many intestinal and extra-intestinal
Dig Dis Sci (2015) 60:1183–1186
manifestations that can affect many organ systems. Celiac disease is traditionally characterized by malabsorption resulting from inflammatory injury to the mucosa of the small intestine after the ingestion of wheat gluten or related rye and barley proteins. The ‘‘gold standard’’ for diagnosis typically was histologic findings in the small intestine, which revealed total villous atrophy and hyperplastic crypts, with reversal of the changes after ingesting a gluten-free diet. Since the diagnostic accuracy of minor villous abnormalities is less than the accuracy of findings typical of the fully developed disease, many regard elevation of serum tissue transglutaminase antibody concentrations as a sine qua non for diagnosis in patients in whom dietary gluten has not been restricted. While there should be clinical and histologic improvement as a result of ingesting a strict gluten-free diet, with relapse after dietary gluten is deliberately re-introduced, planned gluten challenges are now uncommon [3]. Celiac disease is increasingly diagnosed in adults with the mean age at clinical presentation in the USA *45 years [4]. Celiac disease has a wide spectrum of gastrointestinal and extra-intestinal manifestations, which include anemia, osteomalacia, neurologic symptoms, dermatologic disorders, pancreatic atrophy, endocrinologic abnormalities (including menstrual irregularities), and, recognized recently, abnormal liver tests, such as observed during this patient’s third attack, which are of uncertain pathogenesis and importance [5]. There are also increased risks of the occurrence of splenic atrophy, lymphoid proliferation including lymphoma, and extra-intestinal malignancies. Associations between celiac disease and pancreatic insufficiency or pancreatic atrophy have been well described; these are thought to be the consequences of reduced stimulation of release of cholecystokinin and other GI hormones by an atrophied intestinal mucosa, reducing pancreatic secretion, ultimately affecting pancreatic morphology, with resultant atrophy, distortion, and calcifications [6]. Although there have been reports of an increased risk of pancreatitis in the setting of celiac disease, the pathogenesis of inflammatory pancreatitis is not clearly understood. In 1963, Fitzgerald et al. [7] reported two cases of celiac disease that appeared to improve clinically, with reduction in pancreatitis, after initiation of a gluten-free diet. Patel et al. [8] reported a series of 12 patients in 1999 with celiac disease, 10 of whom had documented idiopathic recurrent acute pancreatitis with elevated serum concentrations of amylase and lipase. All had manometric evidence of papillary stenosis and histologic evidence of celiac disease. All 12 were treated with a gluten-free diet, and the 10 who had evidence of papillary stenosis also underwent sphincterotomy. All who adhered to the gluten-free diet had symptomatic and histologic improvement [8]. Given these findings, it was speculated that stenosis of the papilla of Vater related to chronic or
1185
chronic active duodenitis might be an etiologic factor in patients with celiac disease, which could be partially reversible by adherence to a gluten-free diet [8]. Other studies that have suggested patients with celiac disease are at increased risk of pancreatitis include an analysis by Ludvigsson et al. [9] of the Swedish Celiac Register involving 14,239 patients. Compared to the normal population, the risk of acute pancreatitis was increased threefold in the first year of follow-up and fivefold when all subsequent follow-up was included; the long-term risk for chronic pancreatitis was increased 19-fold [9]. Further study of the national Swedish registry in 2012 by SadrAzodi et al. [10] distinguished between gallstone-related pancreatitis and non-gallstone-related pancreatitis, reporting that celiac disease patients had an overall threefold increased risk of pancreatitis (HR 2.85; 95 % CI 2.53–3.21). For non-gallstone-related pancreatitis, the excess risk was 19/100,000 person-years, and for gallstonerelated pancreatitis, the excess risk was 3/100,000 personyears. There was also an increased risk of chronic pancreatitis (HR 3.33; 95 % CI 2.33–4.76) [10]. Postulated pathogenic factors included papillary inflammation and stenosis that could sensitize the pancreas to develop pancreatitis, with persistent inflammation and irreversible structural and functional changes. They also postulated that pancreatic inflammation may be part of an autoimmune spectrum as celiac and autoimmune pancreatitis may share immunologic characteristics including elevated levels of Th1- and Th2-associated cytokines [10]. Ludvigsson et al. [9] also proposed that malnutrition associated with celiac disease might affect bile composition, inducing microlithiasis and impaired secretion of pancreatic enzymes, thus increasing the risk of biliary pancreatitis. Thus while there are much data to support the etiology of pancreatic insufficiency in celiac disease, its contribution to symptoms remains uncertain [11]. More research is needed to determine the etiology and pathogenesis of pancreatitis in this patient population [6]. Celiac disease is associated with a large number of conditions, including autoimmune disorders and several genetic HLA haplotypes [4]. Several studies have reported a high prevalence of celiac disease in patients with Down syndrome who carry increased risk for developing several autoimmune diseases and congenital heart defects. Marild et al. [12] described a sixfold increased risk of celiac disease in individuals with Down syndrome. Bhat et al. [13] in a smaller study of Indian children suggested a prevalence rate of 7 % in Down syndrome patients (compared to 1–2 % prevalence in general population) recommending screening for celiac disease in all Down syndrome patients, especially in those with anemia. In retrospect, our patient may have benefitted from screening for celiac disease at an earlier age: early
123
1186
institution of a gluten-free diet might have prevented the three episodes of recurrent acute pancreatitis that she experienced. Based on published studies, she will likely benefit from using a gluten-free diet, but, as Patel et al. [8] have suggested, scarring and papillary stenosis from recurrent pancreatitis may only minimally improve with a gluten-free diet. If so, further interventions such as biliary endoscopy may indicate in time.
Summary A young female with Down syndrome experienced recurrent acute pancreatitis. There etiology of the pancreatitis was not due to alcohol, biliary disease, implicated medications, hyperlipidemia, hypercalcemia, or autoimmunity. Laboratory testing and duodenal histology was consistent with the diagnosis of celiac disease. Given the increased risk of acute pancreatitis associated with this condition, celiac disease should be considered in the differential diagnosis of pancreatitis. In the presence of celiac disease, treatment with a gluten-free diet may reduce the incidence of acute pancreatitis. Patients with Down syndrome should be screened for celiac disease, especially if anemic or malnourished.
References 1. Draganov P, Forsmark E. Idiopathic pancreatitis. Gastroenterology. 2005;128:756–763.
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Dig Dis Sci (2015) 60:1183–1186 2. Micromedex online DRUGDEX, POISINDEX. Warfarin: drug information including adverse reactions, sub-category: gastrointestinal. 3. Farrell RJ, Kelly CP. Celiac sprue. N Engl J Med. 2002;346:180. 4. Farrell RJ, Kelly CP. Sleisenger, & Fordtran. Gastrointestinal and liver disease. Philadelphia: Publ. Saunders Elsevier; 2010:1797–1811. 5. Sainsbury A, Sanders DS, Ford AC, et al. Meta-analysis: coeliac disease and hypertransaminasaemia. Aliment Pharmacol Ther. 2011;34:33–40. 6. Freeman HJ. Pancreatic endocrine and exocrine changes in celiac disease. World J Gastroenterol. 2007;13:6344–6346. 7. Fitzgerald O, Fitzgerald P, Fennelly J, McMullin J, Boland S. A clinical study of chronic pancreatitis. Gut. 1963;4:193–216. 8. Patel RS, Johlin FC, Murray JA. Celiac disease and recurrent pancreatitis. Gastrointest Endosc. 1999;50:823–827. 9. Ludvigson JJ, Montgomery SM, Ekbom A. Risk of pancreatitis in 14,000 individuals with celiac disease. Clin Gastroenterol Hepatol. 2007;5:1347–1353. 10. Sadr-Azodi O, Sanders D, Murray J, Ludvigsson J. Patients with celiac disease have and increased risk for pancreatitis. Clin Gastroenterol Hepatol. 2012;10:1136–1142. 11. Leeds JS, Hopper AD, Hurlstone DP, et al. Is exocrine pancreatic insufficiency in adult coelic disease a causea of persisting symptoms? Ailment Pharmacol Ther. 2007;25:265–271. 12. Marild, Stephansson O, Grahnquist L, Cnattingius S, Soderman G, Ludvigsson JF. Down syndrome is associated with elevated risk of celiac disease: a nationwide case control study. J Pediatr. 2013;163:237–242. 13. Bhat AS, Chaturvedi MK, Saini S, et al. Prevalence of celiac disease in Indian children with Down syndrome and its clinical and laboratory predictors. Indian J Pediatr. 2013;80:114–117.
UNM CLINICAL CASE CONFERENCES
Recurrent Abdominal Pain in a Patient with Down Syndrome Allison Venner1 • Archana Kaza1 • Von G. Samedi2
Received: 25 March 2015 / Accepted: 27 March 2015 / Published online: 4 April 2015 Ó Springer Science+Business Media New York 2015
Case Report A 34 year-old woman with Down syndrome was seen in clinic after having two episodes of acute pancreatitis over the preceding 2 months, each requiring hospital admission. The initial episode of pancreatitis was initially manifest as severe epigastric pain radiating to her back associated with loose stools. She denied having had any fevers, nausea, or vomiting. Her medical history included hypothyroidism and a coagulation disorder that had been complicated by a cerebral vascular accident, now under treatment with anticoagulants. Her family history revealed the presence of celiac disease in several family members. She denied any use of alcohol or illicit drugs. Her medication list did not reveal any medications that are considered as possible etiologic agents [1, 2]. Physical examination revealed mild tenderness to palpation in the epigastric area but no organomegaly or palpable masses. Laboratory test results included: white blood cell count of 5.7 9 103/mm3, serum concentrations of aspartate aminotransferase 27 Unit/L (range 6–58 Unit/L), alanine aminotransferase of 34 Unit/L (range 14–67 Unit/L), alkaline phosphatase 89 Unit/L (range 38–150 Unit/L), total bilirubin 0.6 mg/dL (range 0.3–1.2 mg/dL), direct bilirubin 0.1 mg/dL (range 0.1–0.4 mg/dL), serum lipase 1695 Unit/L (range
& Allison Venner [email protected] 1
Division of Gastroenterology and Hepatology, University of New Mexico School of Medicine, 1 University of New Mexico, MSC10-5550, Albuquerque, NM 87131, USA
2
Department of Pathology, University of New Mexico School of Medicine, Albuquerque, NM, USA
66–360 Unit/L), creatinine 0.91 mg/dL (range 0.6–1 mg/ dL), serum triglycerides 95 mg/dL (range \150 mg/dL), calcium 8.2 mg/dL (range 8.4–10.4 mg/dL), and serum IgG4 22 mg/dL (range 7–89 mg/dL). A CT scan of the abdomen and pelvis with and without contrast was reported as showing mildly heterogeneous attenuation of the pancreas without frank pancreatic free fluid, no dilation of the pancreatic duct, and no pancreatic mass or pseudocyst. An abdominal ultrasound showed no cholelithiasis, pericholecystic fluid or gallbladder wall thickening, and a common bile duct that measured 4 mm with no intrahepatic bile duct dilation. An incidental note was made of a Phrygian cap of the gallbladder; the visualized portion of the pancreas appeared sonographically unremarkable. She was clinically diagnosed as having acute pancreatitis was hospitalized for 6 days of conservative management and then discharged. One month later, she was again hospitalized with similar symptoms of abdominal pain and laboratory findings of serum concentrations of lipase of 1241 Unit/L, creatinine 0.84 mg/dL, aspartate aminotransferase 23 Unit/L, alanine aminotransferase of 27 Unit/L, alkaline phosphatase 75 Unit/L, total bilirubin 0.5 mg/dL, and direct bilirubin 0.1 mg/dL. A CT scan of the abdomen and pelvis was reported as showing acute inflammatory changes in the region of the pancreatic tail and the presence of a small amount of free fluid in the left paracolic gutter. The remainder of the pancreas was without inflammatory changes or masses, although a punctate hyperattenuation was noted in the pancreatic tail that may have reflected a focus of calcification from prior pancreatitis; there was no dilation of the pancreatic duct. An abdominal ultrasound scan was unremarkable with no cholelithiasis or bile duct dilation noted. At an outpatient follow-up visit 2 weeks later, further laboratory testing revealed serum concentrations of tissue
123
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Dig Dis Sci (2015) 60:1183–1186
transglutaminase IgA antibody [225 Units/mL (range 0–19) and serum anti-gliadin IgA of 120 Units/mL (range 0–19), with a normal serum IgA. Additional MRI/MRCP imaging of the abdomen revealed no cholelithiasis or choledocholithiasis, a normal size pancreas and pancreatic duct, normal pancreatic signal intensity and enhancement, no persistence of peripancreatic edema, and no evidence of any congenital malformation. Esophagogastroduodenoscopy showed the presence of a small hiatus hernia, a normal esophagus and stomach, and a scalloped appearance of the mucosa of the second portion of the duodenum (Fig. 1). Duodenal biopsies were interpreted as showing villous blunting, increased intraepithelial lymphocytes, and increased lymphocytes in the lamina propria (Fig. 2). Treatment with a gluten-free diet had not been initiated prior to endoscopy and biopsy. Although she was educated about the diet and advised to use it, her compliance was questionable. One month later, she was again hospitalized with a third episode of acute pancreatitis with the similar symptoms and laboratory findings of serum concentrations of lipase 1495 Units/L, creatinine 0.83 mg/dL, aspartate aminotransferase of 169 Unit/L, alanine aminotransferase of 212 Unit/L, alkaline phosphatase
Fig. 2 Duodenal biopsies showed villous blunting, increased intraepithelial lymphocytes, and increased lymphocytes in the lamina propria. a Low-power (910) magnification. b High-power (940) magnification
92 Unit/L, total bilirubin 0.6 mg/dL, and direct bilirubin 0.1 mg/dL. A chest X-ray was unremarkable, and an abdominal ultrasound showed a non-dilated gallbladder with minimal echogenic debris possibly representing sludge or cholesterol crystals, no pericholecystic fluid or gallbladder wall thickening, no biliary ductal dilation, and all visualized regions of the pancreas appeared normal. Of interest, serum aminotransferase concentrations that were normal during her first two hospitalizations were elevated during this third hospitalization for pancreatitis: The precise cause of this is unclear (see below). She received additional counseling about the importance of adhering to a gluten-free diet. She has since been compliant and has been free of further episodes of pancreatitis for over a year.
Discussion
Fig. 1 Endoscopic findings of scalloped appearance of the mucosa of the second portion of the duodenum. a Duodenum. b Duodenum with closer mucosa view
123
Celiac disease is an immune-mediated enteropathy caused by early exposure to gluten in genetically susceptible individuals. Clinical manifestations of celiac disease vary widely with many intestinal and extra-intestinal
Dig Dis Sci (2015) 60:1183–1186
manifestations that can affect many organ systems. Celiac disease is traditionally characterized by malabsorption resulting from inflammatory injury to the mucosa of the small intestine after the ingestion of wheat gluten or related rye and barley proteins. The ‘‘gold standard’’ for diagnosis typically was histologic findings in the small intestine, which revealed total villous atrophy and hyperplastic crypts, with reversal of the changes after ingesting a gluten-free diet. Since the diagnostic accuracy of minor villous abnormalities is less than the accuracy of findings typical of the fully developed disease, many regard elevation of serum tissue transglutaminase antibody concentrations as a sine qua non for diagnosis in patients in whom dietary gluten has not been restricted. While there should be clinical and histologic improvement as a result of ingesting a strict gluten-free diet, with relapse after dietary gluten is deliberately re-introduced, planned gluten challenges are now uncommon [3]. Celiac disease is increasingly diagnosed in adults with the mean age at clinical presentation in the USA *45 years [4]. Celiac disease has a wide spectrum of gastrointestinal and extra-intestinal manifestations, which include anemia, osteomalacia, neurologic symptoms, dermatologic disorders, pancreatic atrophy, endocrinologic abnormalities (including menstrual irregularities), and, recognized recently, abnormal liver tests, such as observed during this patient’s third attack, which are of uncertain pathogenesis and importance [5]. There are also increased risks of the occurrence of splenic atrophy, lymphoid proliferation including lymphoma, and extra-intestinal malignancies. Associations between celiac disease and pancreatic insufficiency or pancreatic atrophy have been well described; these are thought to be the consequences of reduced stimulation of release of cholecystokinin and other GI hormones by an atrophied intestinal mucosa, reducing pancreatic secretion, ultimately affecting pancreatic morphology, with resultant atrophy, distortion, and calcifications [6]. Although there have been reports of an increased risk of pancreatitis in the setting of celiac disease, the pathogenesis of inflammatory pancreatitis is not clearly understood. In 1963, Fitzgerald et al. [7] reported two cases of celiac disease that appeared to improve clinically, with reduction in pancreatitis, after initiation of a gluten-free diet. Patel et al. [8] reported a series of 12 patients in 1999 with celiac disease, 10 of whom had documented idiopathic recurrent acute pancreatitis with elevated serum concentrations of amylase and lipase. All had manometric evidence of papillary stenosis and histologic evidence of celiac disease. All 12 were treated with a gluten-free diet, and the 10 who had evidence of papillary stenosis also underwent sphincterotomy. All who adhered to the gluten-free diet had symptomatic and histologic improvement [8]. Given these findings, it was speculated that stenosis of the papilla of Vater related to chronic or
1185
chronic active duodenitis might be an etiologic factor in patients with celiac disease, which could be partially reversible by adherence to a gluten-free diet [8]. Other studies that have suggested patients with celiac disease are at increased risk of pancreatitis include an analysis by Ludvigsson et al. [9] of the Swedish Celiac Register involving 14,239 patients. Compared to the normal population, the risk of acute pancreatitis was increased threefold in the first year of follow-up and fivefold when all subsequent follow-up was included; the long-term risk for chronic pancreatitis was increased 19-fold [9]. Further study of the national Swedish registry in 2012 by SadrAzodi et al. [10] distinguished between gallstone-related pancreatitis and non-gallstone-related pancreatitis, reporting that celiac disease patients had an overall threefold increased risk of pancreatitis (HR 2.85; 95 % CI 2.53–3.21). For non-gallstone-related pancreatitis, the excess risk was 19/100,000 person-years, and for gallstonerelated pancreatitis, the excess risk was 3/100,000 personyears. There was also an increased risk of chronic pancreatitis (HR 3.33; 95 % CI 2.33–4.76) [10]. Postulated pathogenic factors included papillary inflammation and stenosis that could sensitize the pancreas to develop pancreatitis, with persistent inflammation and irreversible structural and functional changes. They also postulated that pancreatic inflammation may be part of an autoimmune spectrum as celiac and autoimmune pancreatitis may share immunologic characteristics including elevated levels of Th1- and Th2-associated cytokines [10]. Ludvigsson et al. [9] also proposed that malnutrition associated with celiac disease might affect bile composition, inducing microlithiasis and impaired secretion of pancreatic enzymes, thus increasing the risk of biliary pancreatitis. Thus while there are much data to support the etiology of pancreatic insufficiency in celiac disease, its contribution to symptoms remains uncertain [11]. More research is needed to determine the etiology and pathogenesis of pancreatitis in this patient population [6]. Celiac disease is associated with a large number of conditions, including autoimmune disorders and several genetic HLA haplotypes [4]. Several studies have reported a high prevalence of celiac disease in patients with Down syndrome who carry increased risk for developing several autoimmune diseases and congenital heart defects. Marild et al. [12] described a sixfold increased risk of celiac disease in individuals with Down syndrome. Bhat et al. [13] in a smaller study of Indian children suggested a prevalence rate of 7 % in Down syndrome patients (compared to 1–2 % prevalence in general population) recommending screening for celiac disease in all Down syndrome patients, especially in those with anemia. In retrospect, our patient may have benefitted from screening for celiac disease at an earlier age: early
123
1186
institution of a gluten-free diet might have prevented the three episodes of recurrent acute pancreatitis that she experienced. Based on published studies, she will likely benefit from using a gluten-free diet, but, as Patel et al. [8] have suggested, scarring and papillary stenosis from recurrent pancreatitis may only minimally improve with a gluten-free diet. If so, further interventions such as biliary endoscopy may indicate in time.
Summary A young female with Down syndrome experienced recurrent acute pancreatitis. There etiology of the pancreatitis was not due to alcohol, biliary disease, implicated medications, hyperlipidemia, hypercalcemia, or autoimmunity. Laboratory testing and duodenal histology was consistent with the diagnosis of celiac disease. Given the increased risk of acute pancreatitis associated with this condition, celiac disease should be considered in the differential diagnosis of pancreatitis. In the presence of celiac disease, treatment with a gluten-free diet may reduce the incidence of acute pancreatitis. Patients with Down syndrome should be screened for celiac disease, especially if anemic or malnourished.
References 1. Draganov P, Forsmark E. Idiopathic pancreatitis. Gastroenterology. 2005;128:756–763.
123
Dig Dis Sci (2015) 60:1183–1186 2. Micromedex online DRUGDEX, POISINDEX. Warfarin: drug information including adverse reactions, sub-category: gastrointestinal. 3. Farrell RJ, Kelly CP. Celiac sprue. N Engl J Med. 2002;346:180. 4. Farrell RJ, Kelly CP. Sleisenger, & Fordtran. Gastrointestinal and liver disease. Philadelphia: Publ. Saunders Elsevier; 2010:1797–1811. 5. Sainsbury A, Sanders DS, Ford AC, et al. Meta-analysis: coeliac disease and hypertransaminasaemia. Aliment Pharmacol Ther. 2011;34:33–40. 6. Freeman HJ. Pancreatic endocrine and exocrine changes in celiac disease. World J Gastroenterol. 2007;13:6344–6346. 7. Fitzgerald O, Fitzgerald P, Fennelly J, McMullin J, Boland S. A clinical study of chronic pancreatitis. Gut. 1963;4:193–216. 8. Patel RS, Johlin FC, Murray JA. Celiac disease and recurrent pancreatitis. Gastrointest Endosc. 1999;50:823–827. 9. Ludvigson JJ, Montgomery SM, Ekbom A. Risk of pancreatitis in 14,000 individuals with celiac disease. Clin Gastroenterol Hepatol. 2007;5:1347–1353. 10. Sadr-Azodi O, Sanders D, Murray J, Ludvigsson J. Patients with celiac disease have and increased risk for pancreatitis. Clin Gastroenterol Hepatol. 2012;10:1136–1142. 11. Leeds JS, Hopper AD, Hurlstone DP, et al. Is exocrine pancreatic insufficiency in adult coelic disease a causea of persisting symptoms? Ailment Pharmacol Ther. 2007;25:265–271. 12. Marild, Stephansson O, Grahnquist L, Cnattingius S, Soderman G, Ludvigsson JF. Down syndrome is associated with elevated risk of celiac disease: a nationwide case control study. J Pediatr. 2013;163:237–242. 13. Bhat AS, Chaturvedi MK, Saini S, et al. Prevalence of celiac disease in Indian children with Down syndrome and its clinical and laboratory predictors. Indian J Pediatr. 2013;80:114–117.
