Acute Pancreatitis as an Initial Presentation of Hereditary Chronic Calcific Pancreatitis with Pancreatic Duct Stones: A Case Report

Abstract

Background:

Hereditary pancreatitis is a rare type of chronic pancreatitis that is due to an inherited germline mutation, involving pancreatic trypsin activity. This condition causes either increased trypsinogen activation or impaired trypsin inhibition/degradation, resulting in recurrent pancreatic injury and progression to chronic pancreatitis.

Case presentation:

We present the case of a young male who presented with acute pancreatitis in the setting of a positive family history of chronic pancreatitis. He had no prior similar episodes. Imaging revealed features consistent with chronic calcific pancreatitis, including diffuse dilation of the main pancreatic duct with intraductal stones. The patient underwent ERCP with pancreatic sphincterotomy and successful removal of multiple pancreatic stones resulting in symptomatic relief. Genetic testing confirmed the diagnosis of hereditary pancreatitis with identification of a pathogenic PRSS1 mutation.

Management:

Therapeutic interventions typically involve management of acute pancreatitis flares and its complications, chronic pain management, exocrine and endocrine insufficiency, and endoscopic and surgical interventions, and genetic counseling and surveillance.

Conclusion:

Our case report emphasizes the significance of taking hereditary pancreatitis into account in acute-on-chronic presentations. This helps in establishing a genetic diagnosis for directing treatment, long-term surveillance, and family screening.

Introduction

Chronic pancreatitis is defined as a long-term inflammatory state of the pancreas that results in fibrosis, and impaired exocrine and endocrine function. It can be caused by environmental, genetic and other risk factors and is characterized by irreversible changes, unlike acute pancreatitis. A rare inherited type of chronic pancreatitis, hereditary pancreatitis (HP) commonly presents in childhood or adolescence and often supported by family history. The most well known genetic variations linked to HP are mutations in PRSS1, SPINK1, CFTR, and CTRC. ¹ PRSS1 mutations (such as R122H) alter trypsinogen activity, leading to premature trypsin activation, causing pancreatic auto digestion, recurrent injury, and chronic calcification changes. ² Genetic testing can assist identifying the cause of HP, direct therapeutic treatment, and determine the risk of complications such as pancreatic cancer and pancreatic insufficiency. ³ Reporting such cases contributes to the literature on atypical presentations, genotype-phenotype relationships, and insights into diagnostic value of genetic testing in HP.

Case Presentation

A 30 year old man known to have a history of diabetes mellitus presented with an acute onset epigastric pain radiating to the back. The pain started overnight and got worse with time. It was persistent, exacerbated in the supine position, and slightly relieved by bending forward. Associated symptoms included nausea and frequent non-bilious, non-bloody vomiting. He denied the use of illicit drugs, smoking or drinking alcohol. There was no history of gallstones, biliary colic, abdominal trauma, recent infections, or prior similar episodes. No previous history of pancreatitis was reported by patient. Family history was noteworthy for a distant history of the patient’s brother of multiple episodes of pancreatitis requiring a pancreatic duct stent placement.

On presentation, the patient was hemodynamically stable. Physical examination showed mild guarding and localized epigastric discomfort, but neither rebound tenderness nor rigidity were present. Jaundice, scleral icterus, and chronic liver disease stigmata were absent. The rest of the exam was unremarkable.

Laboratory tests demonstrated a normal complete blood count and renal function Inflammatory markers were elevated with a C-reactive protein (CRP) was significantly elevated, with a level of 75.4 mg/L. Liver function tests, serum lipase, serum amylase, calcium, and triglyceride levels were within normal limits.

Contrast-enhanced computed tomography (CT) of the abdomen (Figures 1 and 2) demonstrated an edematous pancreas with peripancreatic fat stranding, diffuse dilation of the main pancreatic duct (MPD), and a suspicious dense focus within the distal MPD, without evidence of a pancreatic mass, ascites, or biliary ductal dilation. Subsequent magnetic resonance cholangiopancreatography (MRCP; Figures 3 and 4) revealed marked MPD dilation up to 10 mm with multiple intraductal filling defects consistent with pancreatic duct stones, the largest measuring approximately 10 mm in the distal MPD near the papilla, while the common bile duct and intrahepatic bile ducts appeared normal. No pancreatic or ampullary mass was identified.

Figure 1.

CT scan of the abdomen with findings of diffuse MPD dilation, with no evidence of ascites, intrahepatic ducts common bile duct dilation.

Figure 2.

CT scan of the abdomen with findings of an edematous pancreas, peripancreatic fat stranding, diffuse MPD dilation, dense focus in the distal MDP.

Figure 3.

MRCP axial cut showing a dilated MPD (10 mm) with multiple intraductal filling defects, consistent with pancreatic stones (largest measuring 10 mm in the distal MPD).

Figure 4.

MRCP coronal cut showing a dilated MPD (10 mm) with multiple intraductal filling defects, consistent with pancreatic stones (largest measuring 10 mm in the distal MPD).

As a next initial step in the diagnosis, genetic testing for hereditary pancreatitis was performed due to the patient’s young age, family history, and lack of clear etiology. Furthermore, serum IgG4 level was tested and was reported to be within the normal range, making autoimmune pancreatitis unlikely.

The differential diagnosis included acute-on-chronic pancreatitis due to obstructing main pancreatic stones, autoimmune pancreatitis, and pancreatic or ampullary neoplasia. Biliary obstruction, autoimmune disease and malignancy were successfully ruled out by imaging and test results.

Next, endoscopic retrograde cholangiopancreatography (ERCP) was done confirming a markedly dilated pancreatic duct with multiple intraductal filling defects and no evidence of ductal stricturing or mass lesions. Cannulation of the common bile duct was unremarkable, with no filling defects identified. A pancreatic sphincterotomy followed by multiple balloon sweeps of the main pancreatic duct was done. This led to the evacuation of multiple white, sand-like pancreatic stones into the duodenum. A notable improvement in distal drainage was noted.

The diagnosis was made for chronic calcific pancreatitis with several pancreatic duct stones and diffusely dilated main pancreatic duct. Therefore, the case was managed by intravenous fluids, analgesics, and supportive treatment. Moreover, as part of long-term care, pancreatic enzyme replacement therapy and nutritional supplements were planned. Genetic testing was ordered to asses for HP. Hereditary counseling was recommended in anticipation of confirmatory genetic testing results.

Within 24 to 48 hours after endoscopic intervention, the patient’s pain resolved and there were no immediate ERCP-related complications. At 2 weeks followup, the patient presented to our clinic reporting no symptoms. Genetic testing including PRSS1, SPINK1, CFTR, CTRC was pertinent for a pathogenic mutation in PRSS1 gene, confirming the diagnosis. The management strategy included counseling on avoidance of triggers, assessment of pancreatic insufficiency and long-term surveillance for pancreatic cancer due to HP’s high predisposition to malignancy.

Discussion

We present a case of a 30 year old patient with a family history of chronic pancreatitis in his sibling, presenting for acute onset epigastric pain radiating to the back. Diagnostic evaluation suggested imaging findings of chronic calcification pancreatitis (diffuse dilatation of MPD with intraductal stones). An ERCP with pancreatic sphincterotomy resulted in the evacuation of numerous pancreatic stones with post-procedure relief of symptoms. A pathogenic mutation of PRSS1 via genetic testing confirmed the diagnosis of HP. This established the final diagnosis of acute pancreatitis occurring in the context of underlying hereditary chronic pancreatitis.

Hereditary pancreatitis is a rare inherited cause of chronic pancreatitis. It is an autosomal dominant disorder with incomplete penetrance and variable expressivity. ⁴ In our case, penetrance could not be evaluated since family members were not fully genotyped. Multiple mutations have been reported to be associated with HP. PRSS1 mutations cause autosomal dominant hereditary pancreatitis, while variants in SPINK1, CFTR, CTRC act as disease modifiers. Pathogenic variants cause an increase in pancreatic trypsin activity by increasing trypsinogen activation, decreasing trypsinogen degradation, or delaying trypsin inhibition.^5,6 This ultimately leads to repeated pancreatic injury and irreversible fibrosis, resulting in chronic pancreatitis. Our case presents a young patient who has a brother with pancreatitis and tested positive for PRSS1 mutation. This demonstrates the hereditary nature of the disease.

Although HP typically presents in childhood or adolescence, there have been fewer reports of adult presentation, making our case noteworthy. Vijayakumar et al ⁷ highlighted the importance of genetic testing in unexplained adults through their case of a 29 year old male with acute pancreatitis who was found to carry a pathogenic mutation of PRSS1. Similarly, Lugo et al ⁸ documented recurrent pancreatitis in a 29 year old patient with chronic pancreatitis secondary to PRSS1-related HP, emphasizing delayed diagnosis past adulthood. Xu et al ⁹ reported a familial case involving adult relatives with PRSS1 and SPINK1 mutations, further displaying varying clinical manifestation within affected families.

Moreover, our patient presented with symptoms consistent with acute pancreatitis. However, imaging revealed findings suggestive of chronic inflammatory changes prompting an evaluation for underlying causes of chronic pancreatitis. The patient denied any prior similar episodes or hospitalizations therefore raising the possibility of previously unrecognized mild recurrent episodes of acute pancreatitis. This highlights the importance of thoroughly investigating the underlying etiology of pancreatitis. Such presentations may otherwise be misclassified as isolated acute pancreatitis leading to a missed diagnosis of chronic pancreatitis.

Our case report demonstrates an acute-on-chronic pancreatitis disease course that is well-documented via imaging findings, supported by a positive family history, and genetically confirmed by a PRSS1 mutation. However, this single-patient case report is limited by a short duration of follow-up and an incomplete family genetic testing. Moreover, our findings are only primarily applicable to PRSS1 related HP and does not necessarily represent the clinical course of other mutations causing HP.

Conclusion

In the present case report, we discuss a rare case of HP with PRSS1 mutation diagnosed in a patient with a first-time episode of pancreatitis. This case report highlights the importance of considering hereditary pancreatitis in the differential diagnosis of young patients with normal lipase level on laboratory tests and ductal changes on imaging. Calcific changes and ductal obstruction are common findings on imaging. Genetic testing is the cornerstone of diagnosis of hereditary pancreatitis and should be tested whenever there is suspicion of this condition. Early recognition is crucial to avoid possible complications and guide proper management plan.