Pancreatic Pseudocyst Complicating Hemolytic-Uremic Syndrome

INTRODUCTION Hemolytic-uremic syndrome (HUS) is the main cause of acute renal failure in young children (1). It is characterized by the association of hemolytic anemia with the presence of schizocytes, thrombocytopenia, and renal failure. Typical HUS occurs in children younger than 3 years old who have bloody diarrhea. Infection with Escherichia coli secreting verotoxin, usually of O157:H7 serotype, is found in 85% of the cases (2). Other bacteria, such as Streptococcus pneumoniae or Shigella dysenteriae, are less common etiologic agents. The availability of dialysis has virtually eliminated renal failure as a cause of death in the early stage of the disease, and extrarenal involvement is now a major contributor to morbidity and mortality (1,3). Clinically apparent pancreatitis is rare and usually self-limited (1). We report a girl with a pancreatic pseudocyst complicating the course of HUS. CASE REPORT The patient was a previously healthy 3-year-old girl who had vomited and experienced nonbloody diarrhea for 3 days. On clinical examination, she was asthenic and complained of diffuse pain. The rectal temperature was 37.7°C, and systemic blood pressure was 110/70 mmHg. Her abdomen was soft without any tenderness. Transient episodes of hypotonia were observed, but the neurologic examination was normal. Full blood count showed a haemoglobin of 91 g/L, platelet count of 82 × 109/L, and a leukocyte cell count of 13.7 × 109/L, with 65% polymorphonuclear neutrophils. There was a fivefold increase in serum alanine aminotransferase level. The blood urea nitrogen concentration was 36.3 mmol/L (103 mg/dL), and serum creatinine level was 287 μmol/L (3.2 mg/dL). The serum phosphate was 2.5 mmol/L and serum potassium was 6 mmol/L. The diagnosis of HUS was supported by the finding of schizocytes (1%) on blood smears. Neither E. coli with O157:H7 nor verotoxin were found in the stools. Shortly after admission, her condition worsened. She had a generalized seizure, became anuric, and was admitted to the intensive care unit. Recurrent seizures required profound sedation and mechanical ventilation for 6 days. A 4-week course of hemofiltration resulted in normalization of most biologic parameters with the exception of persistent renal failure (blood urea nitrogen, 15 mmol/L; serum creatinine, 110 μmol/L; creatinine clearance, 50 mL/min/1.73 m2). When feeding was resumed she experienced epigastric pain and vomiting. The serum alanine aminotransferase level was normal, as were amylase (30 IU/L) and lipase (33 IU/L) levels. Ultrasound examination of the abdomen revealed a large liquid-filled cyst (100 × 60 × 55 mm) in the head and body of the pancreas as well as bile duct dilatation. A computed tomography scan confirmed the presence of a hypodense formation consistent with the diagnosis of pancreatic pseudocyst (Fig. 1). Serum parathormone and triglyceride assays were normal; immunologic investigations for hepatitis B and C virus, cytomegalovirus, Ebstein-Barr virus, Herpes simplex virus IgG, and hepatitis A virus IgM were all negative. The child had not received any pancreatotoxic treatment, i.e. corticosteroids. On surgical drainage of the cyst, an opaque liquid with a very high concentration of amylase (12,500 IU/L) was collected. After 5 days, the drain was removed, and repeat ultrasound investigation did not reveal any recurrence of the cyst. Nonetheless, repeated attempts to refeed her were accompanied by epigastric pain and vomiting, associated with increases in serum amylase (165 IU/L) and lipase (550 IU/L). There was a gradual clinical remission with normalization of amylase and lipase levels after 1 month of total parenteral nutrition. The appearance of the pancreas on ultrasound remained normal. Chronic renal failure has persisted with a creatinine clearance of 40 mL/min/1.73 m3, and systemic hypertension requiring treatment with nifedipine.FIG. 1.: Transverse computed tomography scan of the upper part of the abdomen after infusion of contrast media demonstrates a large cystic lesion in place of the pancreas.DISCUSSION The use of dialysis has dramatically improved survival during the early stage of HUS. Extrarenal complications are now the major cause of mortality, which is approximately 5% (4). The first and foremost mortality factor (2), neurologic impairment occurs in 20% of HUS patients and is characterized by cerebral edema and petechial hemorrhages at autopsy (5). Generalized seizures are common and may be the initial manifestation of the disease. Encephalopathy also can lead to ataxia, aphasia, nystagmus, hemiparesia, blindness, coma, or even decerebration (1). Myocardial ischemia, pulmonary edema, or hemorrhage, although less common, also can influence survival in HUS. The colon is the primary organ involved in classic postdiarrheal HUS. Severe colitis mimicking ulcerative colitis or regional enteritis, acute appendicitis, intussusception and peritonitis are all reported manifestations of the disease (1,6). Colitis eventually may lead to bowel necrosis requiring colectomy and thus is a substantial cause of acute morbidity and death (4,7). It also is predictive of neurologic involvement and prolonged renal failure when severe (8). Pancreatic involvement has gradually been recognized to be relatively common, with elevated serum amylase or lipase levels occurring in approximately 20% of cases (4,9). Nevertheless, clinically apparent pancreatitis is rarely mentioned in most series (4,6,10). A pancreatic pseudocyst was revealed by epigastric pain and vomiting in our patient and confirmed on ultrasound examination of the abdomen. The surprisingly normal serum amylase and lipase levels could be explained by the hemofiltration procedure that can eliminate pancreatic enzymes with the same efficiency as creatinine or bilirubin (11). Diabetes mellitus occurs in 4% to 15% of patients with HUS (9,12,13) and may be transient (14) or permanent (12). It is important to be aware of the risk of severe hyperglycemia in children with glucose intolerance who require dialysis because the dialysate contains high concentration of dextrose. The pathophysiology of pancreatitis is related to endotoxin release which triggers endothelial damage, microthrombus formation, and ischemic necrosis in a number of other organs involved in HUS (15). Pancreatic thrombotic microangiopathy has been found at autopsy in patients with fatal HUS (3,16), which results in necrosis of the islets of Langerhans (17). The exocrine pancreas seems less sensitive to damage, so chronic pancreatic exocrine insufficiency is uncommon (18). To our knowledge, pancreatic pseudocyst has not been reported in patients with HUS. The main cause of pseudocysts is traumatic injury of the pancreas, although this complication has also been observed during acute (infectious, toxic) or chronic (malformation of the biliopancreatic ducts) pancreatitis (19). Although spontaneous resolution may occur, drainage of persistent pancreatic pseudocysts generally is recommended because of the risk of complications, such as infection, bleeding, rupture, fistulation, jaundice, compression of adjacent structures, or chronic pain (20,21). Surgical drainage, as performed in the patient reported here, traditionally has been considered the most appropriate therapy (22,23). During the past 2 decades, refinements in ultrasound imaging and endoscopic techniques have permitted percutaneous or endoscopic transgastric internal draining procedures (21,24). Several cases of successful endoscopic drainage of pancreatic pseudocysts have been reported in children (25–27). No serious complications have been reported after such endoscopic procedures in children, but experience remains limited in the pediatric population. In fact, bleeding, infection, peritoneal leak, and recurrence of cysts can be expected in 20% of cases in adults (20). Bosman-Vermeeren et al. (28) reported a traumatic pancreatic pseudocyst in a 10-year-old boy that resolved with total parenteral nutrition and somatostatin. Somatostatin may be beneficial directly by inhibiting the pancreatic secretion (29) or indirectly by inhibiting the secretion of gastrointestinal hormones (30). Nonetheless, treatment with somatostatin was ineffective in another child with pancreatitis caused by pancreas divisum (31). Rushforth et al. (32) reported the development of a pseudocyst in a child undergoing somatostatin treatment for pancreatic ascites. CONCLUSION Epigastric pain and feeding intolerance must increase our index of suspicion for pancreatic involvement in children with HUS. An ultrasound examination of the abdomen should be performed as the first test to detect pseudocyst. The risk of severe complications justifies cyst drainage, whereas the use of somatostatin requires additional studies.