Acute pancreatitis is a life-threatening inflammatory disorder with many known inciting factors, especially in children. The causes include biliary tract disease; medications; trauma; and systemic, viral, metabolic, and genetic syndromes (1). However, a sizable group of patients has idiopathic pancreatitis, ranging in reports from 15% to 25% (2–5). Celiac disease (CD) is an immune-mediated enteropathy caused by permanent insensitivity to gluten in genetically susceptible individuals (6). Whereas steatorrhea in patients with CD can be caused by luminal disease, cases of CD-induced steatorrhea due to pancreatic insufficiency have been described (7). Also, recent reports, mostly in adults, have shown an association between acute pancreatitis and CD (8–11). We report here the case of a 9-year-old boy with acute pancreatitis and CD. To our knowledge, this is one of the youngest such patients to be described. Mechanisms by which CD may cause acute pancreatitis are also discussed.
Our patient was a 9-year-old boy who presented in August 2007 with severe abdominal pain and emesis. His medical history was significant for CD, diagnosed at age 7, with a presentation of failure to thrive, elevated tissue transglutaminase immunoglobulin (Ig)A antibodies of 31 U/mL (normal <5), and characteristic duodenal biopsy results. He was afebrile, with moderate nonrebound tenderness over the epigastrium and normal vital signs. His body mass index was 17.6 kg/m2, at the 50th to 75th percentile for age. The results of complete blood count, liver function tests, total bilirubin, albumin, and electrolytes were normal, including serum Ca2+. Serum amylase and lipase levels were 351 U/L (20–100) and 1657 U/L (20–265), respectively. Although triglycerides were not determined, serum samples were nonlipemic. Both abdominal ultrasound and computed tomography demonstrated a diffusely edematous pancreas. A diagnosis of acute pancreatitis was made. There was no common bile duct dilation, stones, or sludge. Notably, there was no history of abdominal trauma or family history of pancreatitis, pancreatic cancer, or cystic fibrosis. Genetic testing for known heritable causes of pancreatitis was not done. His pancreatic enzymes subsequently normalized, and a gluten-free diet was started again. At this writing he has had no recurrence of pancreatitis for more than 6 months of follow-up.
To our knowledge, this patient is one of the youngest to be described with CD associated with acute pancreatitis. Although the diagnosis of CD can be elusive (6), in this case there was clearly both serological and histological evidence. Furthermore, although patients with CD commonly present with abdominal pain related to primary luminal disease, our patient had epigastric pain due to acute pancreatitis, and the episode was confirmed by both biochemical and radiographic testing. In the United States, acute pancreatitis is not a rare disease, with an estimated overall incidence across ages of 1 in 10,000 cases per year (12), whereas CD has a serological prevalence as high as 1 in 133 in the general population (13). Thus, although one can expect to find pancreatitis in patients with CD by chance, a recent epidemiological study by Ludvigsson et al (11) has suggested that patients with CD have a higher risk than the general population for the development of acute pancreatitis. A hazard ratio was 3.3 (95% confidence interval 2.6–4.4, P < 0.001) for pancreatitis in a Swedish registry of 14,239 patients with CD. Of 9348 patients with CD younger than 16 years old, 8 were identified with pancreatitis. The youngest was 2 years old, and clinical details were not provided. Interestingly, the hazard ratio for chronic pancreatitis was manifold higher at 19.8 (95% confidence interval 9.2–42.8; P < 0.001). This is consistent with earlier reports linking both acute and chronic pancreatitis to CD (Table 1).
Three general mechanisms have been forwarded in the literature to explain why patients with CD may be predisposed to the development of pancreatitis. The first invokes malnutrition (11). Some evidence suggests that malnutrition can cause pancreatitis (14). It is also known that intestinal malabsorption during active CD can lead to significant malnutrition (15). Thus, it is postulated that malnutrition as a result of CD predisposes to pancreatitis. However, there is no evidence to show improvement of pancreatitis, either by episode frequency or pain, after correction for malnutrition. Furthermore, our patient was not malnourished. His body mass index for age, albumin, and complete blood count were normal.
A second postulated mechanism for pancreatitis in patients with CD proposed by Patel et al (8) is papillary stenosis resulting from localized duodenal inflammation. From a cohort of 169 patients with suspected papillary stenosis and recurrent pancreatitis, they identified 12 (7%) with histologically proven CD. Of those patients, 9 had new diagnoses, and all were given a gluten-free diet. None had evidence of malnutrition; however, 10 fulfilled strict manometric criteria for papillary stenosis and underwent sphincterotomy. Although after a mean 22 months of follow-up, there was no recurrence of pancreatitis and pain episodes generally improved, it is unclear whether this was a result of gluten restriction or of sphincterotomy. Nevertheless, these data suggest that papillary stenosis may cause pancreatitis in patients with CD. The theory is also corroborated in a recent report by Sood et al (10). Although we did not ascertain in our patient the presence of papillary stenosis or duodenal inflammation during his bout of pancreatitis, we at least know that he was compliant with a gluten-free diet from the time of his CD diagnosis.
The third postulate is that T helper cell class 1 (TH1) cytokine upregulation in CD is a predisposing factor for acute pancreatitis (11). Polymorphisms in tumor necrosis factor-α, a proinflammatory TH1 cytokine, have been implicated as susceptibility markers for CD (16). Tumor necrosis factor-α also plays a role in the pathogenesis of pancreatitis (17). Thus, upregulated inflammatory cytokines in CD may predispose to pancreatitis; however, the cytokine theory requires further investigation.
In summary, we have reported one of the youngest patients with acute pancreatitis and CD. The case also underscores the importance of considering pancreatitis in the diagnosis of acute abdominal pain in patients with CD.
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