Are you suffering from recurrent attacks of pancreatitis?? What are the rare causes?? And what is Repeated attacks of pancreatitis without any cause ? (IDIOPATHIC RECURRENT PANCREATITIS)

Recurrent Attack of Pancreatitis from Unknown cause :

Acute pancreatitis is an inflammatory process of the pancreas that can affect peripancreatic tissues and distant sites. An cause can be found in most patients after an attack of acute pancreatitis, with gallstone disease and alcohol abuse most often implicated. When patients have more than one clinical episode of acute pancreatitis they are given the diagnosis of acute recurrent pancreatitis (ARP). Most causes of acute pancreatitis can lead to recurrent disease if the underlying factor remains uncorrected.

The cause of recurrent pancreatitis is found in 70–90% of patients after an initial evaluation, which includes a thorough history, physical exam, routine labs, and transabdominal ultrasound or CT. In the 10–30% of patients in whom the initial evaluation fails to reveal an etiology, the diagnosis of idiopathic ARP (IARP) is applied. The extent of the evaluation impacts the frequency with which an etiology can be found, and in turn how often the label idiopathic can be applied. Evaluation and therapy is important because >50% of untreated patients experience recurrent episodes that may lead to chronic pancreatitis.

Initital evaluation of acute recurrent pancreatitis:

Acute pancreatitis is diagnosed in the proper clinical setting with the aid of laboratory values and imaging studies. Patients may present with acute epigastric pain, nausea, vomiting, fever, and tachycardia. Laboratory analysis usually reveals elevated pancreatic enzymes and leukocytosis. Abdominal ultrasound and CT help support the diagnosis and exclude other causes. After confirmation of the presence of acute pancreatitis, the focus shifts to determining the etiology. The initial evaluation includes a search for evidence of alcohol abuse, drug-induced pancreatitis, and a family history of pancreatitis, and other clues that may suggest the origin.

The serum amylase level is used to help establish the diagnosis of pancreatitis and may be predictive of the underlying pathology. Pancreatitis resulting from gallstones, microlithiasis (small stones), or drugs is typically associated with a greater elevation in amylase than lipase . The amylase level, as compared to lipase, tends to be lower in alcoholic pancreatitis, hypertriglyceridemia-induced pancreatitis, neoplasia, and chronic pancreatitis . Lipase elevation is more specific for pancreatitis than amylase, and the level remains elevated longer, but the level is not predictive of the etiology. The ratio of lipase to amylase may help distinguish alcoholic from nonalcoholic pancreatitis, with an increased ratio suggesting alcohol-induced disease. Of note, the amylase and lipase levels do not correlate with disease severity and they are not useful for determining prognosis.

Liver function tests are routinely measured and may be elevated because of biliary obstruction resulting from gallstones, microlithiasis, a choledochocele, neoplasia of the ampulla or pancreas, or sphincter of Oddi dysfunction (SOD). Liver function tests may also increase as a result of pancreatic head edema, inflammation, or pseudocyst formation. A 3-fold or greater increase in the Liver enzyme level is generally regarded as the best indicator of gallstone-induced pancreatitis. One study, however, noted that the best indicator of bile duct stones is a serum total bilirubin > 1.35 mg/dl on the second day of hospitalization . Although it is unclear which laboratory parameter is the most predictive, both may be used to help assess the presence of gallstone-induced pancreatitis in an individual patient. Metabolic causes of pancreatitis should be excluded by checking the serum calcium and triglyceride levels. These values should be measured soon after admission, or well after resolution of the pancreatitis, because of the drop in calcium and triglyceride levels that can occur during hospitalization.

Transabdominal ultrasound is a simple, inexpensive, and highly sensitive procedure for evaluating the biliary tract . CT more accurately delineates the pancreas and may also help identify the cause, assess the severity, and detect complications of pancreatitis . Some recommend performing CT only when the first attack is severe, when the course is complicated, or in the elderly. Patients not scanned during the first episode are generally scanned with their second attack regardless of age or disease severity. However, I believe that the yield is great enough to justify a CT in all patients during their first episode.

The extent of evaluation required before conferring the diagnosis of Idiopathic Acute Recurrent Pancreatitis varies among studies. The purist would demand a complete and exhaustive workup before diagnosis. However, most use this diagnosis when a more limited evaluation, as detailed above, fails to reveal an etiology. A more extensive evaluation may include specialized labs, ERCP, endoscopic ultrasound (EUS), and magnetic resonance cholangiopancreatography (MRCP). This additional workup usually leads to the diagnosis of microlithiasis, SOD, or pancreas divisum . Other causes such as hereditary pancreatitis , cystic fibrosis , a choledochocele , annular pancreas , an anomalous pancreatobiliary junction , pancreatobiliary tumors , and chronic pancreatitis may be found as well. When this more extensive evaluation fails to reveal an etiology, then the diagnosis of "true" Idiopathic (without any cause) recurrent pancreatitis may be assigned.

Rare causes of Recurrent Pancreatitis:

1.Microlethiasis:

Although technically different, the terms microlithiasis and biliary sludge are often used interchangeably. Microlithiasis refers to stones of <3 mm in diameter, whereas biliary sludge is a suspension of crystals, mucin, glycoproteins, cellular debris, and proteinaceous material.

The optimum method of detecting microlithiasis is yet to be established. Transabdominal ultrasound is a noninvasive study with a sensitivity of about 50%. However, repeat examination may improve the yield. Duodenal bile aspiration is an invasive procedure that has a sensitivity of about 66%. ERCP is more invasive, but has a sensitivity of about 85%. During ERCP, the common bile duct is directly aspirated for bile. Cholecystokinin is commonly administered before duodenal drainage or ERCP, to enhance gallbladder contractility and improve the yield. In most centers, collected bile is centrifuged at 2000 revolutions/min for 10 min; the sediment is warmed to 37°C and then examined by polarized microscopy. The quantity of crystals needed to define a positive result differs among institutions, but most believe that the presence of even a small number of crystals is abnormal. EUS is increasingly being used because it offers the greatest diagnostic sensitivity. The presence of microlithiasis may also be noted at the time of MRCP.

Therapy for microlithiasis can significantly reduce the risk of recurrent pancreatitis. Several therapeutic options exist for microlithiasis. Laparoscopic cholecystectomy is nearly always curative and generally considered the procedure of choice . ERCP with sphincterotomy (incision of the bile duct sphincter) is indicated in high operative risk patients. A low-fat diet and ursodeoxycholic acid are acceptable alternatives in high surgical risk patients; however, long term therapy is required.

Sphincter of oddi dysfunction:(SOD)

The sphincter of Oddi is a 5- to 15-mm-long fibromuscular sheath that encircles the terminal common bile duct, pancreatic duct, and common channel. This sphincter regulates the flow of bile and pancreatic juice into the Intestine.

SOD is a frequent and treatable cause of IARP and is seen in roughly one third of these patients.

Patients with SOD are classified as having either biliary type or pancreatic type disease.

Sphincter of Oddi manometry (SOM) is the gold standard for diagnosing SOD. SOM employs a water-perfused catheter system, which is inserted endoscopically into the common bile duct or pancreatic duct, to measure the sphincter pressure.

Noninvasive therapies for SOD include a low-fat diet, analgesics, anticholinergics, calcium channel blockers, and nitrates. Although these noninvasive therapies may help a minority of patients, most believe them to be of limited utility in the management of SOD. Invasive therapies include endoscopic sphincterotomy, pancreatic duct stent placement, and surgical sphincteroplasty. Intrasphincteric botulinum toxin or nitric oxide injection and balloon dilation are no longer performed because they have a limited efficacy and frequent, often severe complications.

The use of pancreatic duct stenting for SOD has not been well studied, and available results have been disappointing. Stent placement may offer short term relief of symptoms and help to predict those most likely to benefit from endoscopic sphincterotomy. However, because of its lack of long-term efficacy and high rate of complications, pancreatic duct stent therapy is not recommended for these patients.

Endoscopic sphincterotomy is the therapy of choice and is believed to decrease the risk of recurrent pancreatitis. Biliary sphincterotomy effectively reduces the pancreatic sphincter pressure and leads to clinical improvement in roughly 80% of patients.

Pancreas divisum:

Pancreas divisum is the most common congenital malformation of the pancreas, effecting 5–8% of the population.

Although it is controversial, most hold the belief that pancreas divisum is a common cause of IARP and is implicated in about 20% of patients. The diagnosis is suspected during ERCP, when injection of contrast media into the major papilla reveals an absent or small ventral pancreatic duct . The diagnosis is confirmed by minor papilla injection, which usually demonstrates a lack of communication between the dorsal and ventral ducts. However, at times the ventral and dorsal ducts do communicate via a thin filamentous channel (incomplete pancreas divisum). The clinical presentation and response to therapy for "incomplete" and "complete" pancreas divisum are identical. EUS or MRCP may also make the diagnosis.

Endoscopic and surgical therapies decrease the rate of recurrent pancreatitis in 70–90% of patients with pancreas divisum and IARP when followed for up to 5 yr. Treatment is directed toward relieving outflow obstruction at the level of the minor papilla. Endoscopic therapy is generally favored, with surgery reserved for those in whom endoscopic approaches fail.

Hereditary (familial) pancreatitis:

Hereditary pancreatitis is a genetic disorder with an autosomal dominant means of transmission and an estimated 80% penetrance . There is no gender predominance, and symptoms typically arise in childhood but may be delayed until the mid-30s.

Hereditary (familial) pancreatitis

Hereditary pancreatitis is a genetic disorder with an autosomal dominant means of transmission and an estimated 80% penetrance. There is no gender predominance, and symptoms typically arise in childhood but may be delayed until the mid-30s.

Therapy does not differ from other causes of acute and chronic pancreatitis, nor does the management of complications. Endoscopic clearance of pancreatic duct stones and surgical pancreatic decompression (pancreaticojejunostomy with anastomosis of the pancreatic duct to the jejunum) may be beneficial.

Cystic fibrosis

Cystic fibrosis is a genetic disease with an autosomal recessive means of transmission and is the most common disorder affecting the exocrine pancreas.

Therapy does not differ from that for other causes of acute and chronic pancreatitis.

Choledochocele

Cystic dilation may occur throughout the biliary system and can involve the extrahepatic and/or intrahepatic bile ducts. Todani et al. , based on the location, first classified these cysts into five types. A type III cyst, or choledochocele, is a rare congenital or acquired condition in which the intramural segment of the distal pancreatobiliary ductal system is dilated and herniates into the duodenal lumen. They vary in size from a few millimeters to several centimeters.

Although abnormal laboratory values, transabdominal ultrasound, CT, or MRCP may suggest a choledochocele, the diagnosis is usually confirmed by ERCP.

Anomalous pancreatobiliary junction

The sphincter does not separate the bile and pancreatic ducts, and therefore pancreatic and bile juices may freely flow between ducts and lead to pancreatitis.

ERCP and injection of the major papilla reveal the long common channel and simultaneous filling of the bile duct and pancreatic duct. EUS or MRCP may also establish the diagnosis. Sphincter ablation by endoscopic sphincterotomy encourages normal flow of bile and pancreatic juice and may decrease the risk of recurrent pancreatitis.

Annular pancreas

Annular pancreas is a congenital anomaly that manifests as a band of pancreatic tissue partially or completely encircling the duodenum, usually at the level of or just proximal to the major papilla.

ERCP typically identifies the duct of the pancreatic annulus encircling the duodenum

Gastrojejunostomy (resection of the lesion with anastomosis of the jejunum and stomach) may be required to bypass the segment of obstructed bowel.

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Pancreatobiliary tumors

Five to seven percent of patients with pancreatobiliary tumors, benign or malignant, present with IARP. The presence of a neoplasia may be suggested by significant weight loss, steatorrhea, radiological evidence of a solid or cystic pancreatic mass or ductal dilation, and increased age. Although younger patients less commonly have a neoplasia, they are frequently affected by lesions such as islet cell tumors that are often amenable to curative resection. Even the elderly may have potential curable lesions such as cystic neoplasms. Although pancreatic adenocarcinoma is most often implicated, these other tumors must be considered as well.

CT, magnetic resonance imaging (MRI), ERCP, and EUS are all useful for identifying pancreatobiliary neoplasms. CT imaging may be adequate to evaluate patients <40 yr of age with IARP. ERCP is usually performed, in addition to CT, in patients over 40 yr because of the increased risk of malignancy. EUS is quickly becoming a favored procedure because of the ability to diagnose, stage, and biopsy pancreatobiliary tumors. In fact, most studies have found EUS to have the highest sensitivity for identifying pancreatic neoplasm relative to other imaging modalities, especially for tumors < 2–3 cm in diameter. The diagnosis may be confirmed by CT-guided biopsy, ERCP-directed brush cytology, or EUS-guided fine needle aspiration.

rent pancreatitis

All patients with ARP should undergo an initial evaluation, which includes a thorough history, routine labs, and imaging studies. When this workup fails to reveal an etiology, then a patient can be given the diagnosis of IARP and a more extensive evaluation is indicated.

Advanced laboratory analysis for patients < 40 yr of age may include an -1-antitrypsin phenotype, CFTR gene analysis, a sweat chloride test, trypsin gene studies, and duodenal aspiration for microcrystals. The level of the tumor marker, CA 19-9, should be measured in patients > 40 yr of age. The role of genetic testing for hereditary pancreatitis and cystic fibrosis, outside of a research setting, is unclear. One can argue a need for testing because of the comfort a patient receives in knowing the diagnosis and because of the potential impact on family planning. Diagnosing hereditary pancreatitis may also be important because of the potential influence on pancreatic cancer screening. However, the need for an ideal method of screening these patients are disputed. Others may argue that it is currently premature to recommend routine genetic testing because of inadequacies in genetic analysis and the absence of established guidelines for genetic counseling. Also, there are no unique endoscopic or surgical approaches for the management of hereditary pancreatitis or cystic fibrosis versus other forms of acute and chronic pancreatitis. Therefore, genetic testing currently has negligible influence on clinical management. We recommend that when genetic testing is not employed, a physician keep a registry of patients suspected of having either disorder, so that they may benefit from newly discovered medications and gene therapy.

ERCP reveals a diagnosis in about 70% of patients with IARP after a negative initial evaluation. Because the initial episode of pancreatitis may be an isolated event and because of the risk of ERCP, most agree that this procedure is not justified after the first episode of pancreatitis. Many believe, however, that ERCP is indicated when the first episode is severe or when a patient has two or more episodes. However, there are some who advocate performing an ERCP after the first episode regardless of the patient's age or disease severity. At the time of the ERCP, bile is aspirated and examined for microcrystals, SOM is performed when SOD is suspected, and the minor papilla is cannulated when pancreas divisum is suspected.

Management:

Episodes of acute pancreatitis are treated similarly regardless of the etiology. Intravenous fluids are given, oral intake is withheld, metabolic and electrolyte disturbances are corrected, analgesics are administered, and respiratory, renal, and vascular complications are treated as necessary. Specific therapy for given disorders, when available, should be managed as outlined earlier.

Therapeutic options for patients with TIARP are limited, and little information exists regarding their care. Several centers have reported favorable results with the use of pancreatic duct stents or endoscopic sphincterotomy (biliary or pancreatic) in patients with TIARP.

Conclusion :

ARP may be caused by a number of disorders. Often, our greatest challenge is to establish the correct diagnosis in those patients without a history of gallstone disease or alcohol abuse. In the 10–30% of patients with "idiopathic" acute recurrent pancreatitis, the use of specialized laboratory analysis, ERCP, EUS (ENDOSCOPIC ULTRASOUND), and MRCP may lead to the diagnosis. These procedures may be used not only to establish the correct diagnosis, but also to direct therapy and often improve a patient's long term prognosis.