Hyperlipidemic pancreatitis during pregnancy

A case of acute pancreatitis associated with type V hyperlipoproteinemia is reported. A 26-year-old-woman was referred to our department with nausea, vomiting, and severe abdominal pain at 24 weeks gestation. Elevation of pancreatic enzymes with profound hypertriglyceridemia (60 mmol/L) was noticed, and a diagnosis of hyperlipidemic pancreatitis was made on the day of admission. Because she had no history of non-gestational hyperlipidemia, the observed hyperlipidemia was thought to be gestational in origin. The treatment consisted of nasogastric decompression, intravenous hyperalimentation, insulin infusion, and plasma exchanges. Progressive abatement of the symptoms occured, and on the fifth day of admission, complete resolution was observed. On the seventh day of hospitalization, advancing preterm labor and associated fetal distress was diagnosed, which necessitated a cesarean delivery. The infant was lost due to severe immaturity. Pancreatic pseudocyst formation complicated the postpartum period, which was managed by percutaneous drainage. Early diagnosis, close monitoring, consistent supportive treatment and awareness of complications are the key points in the management of gestational pancreatitis. It is well known that hyperlipidemia can be associated with acute pancreatitis (1). Hyperlipidemic pancreatitis during gestation is a rare, but an important disorder, which carries a high maternal and fetal morbidity and mortality (2). During late gestation, the average serum very low-density lipoprotein (VLDL) cholesterol and triglyceride reach 2.5 times the non-gestational level (3). However, gestational pancreatitis is unlikely to be caused by hypertriglyceridemia less than 22 mmol/L (2000 mg/dL). This extreme hypertriglyceridemia raises the possibility of an underlying lipoprotein disorder, which might be exacerbated by pregnancy. We present a case of type V hyperlipoproteinemic acute gestational pancreatitis in a woman with no history of non-gestational hyperlipidemia. A 26-year-old woman, gravida 2, para 1, was referred to Hacettepe University Hospital with nausea, vomiting, and severe abdominal pain at 24 weeks gestation. She had no history of diabetes, alcohol abuse, gallstone, pancreatitis, drug intake, and non-gestational hyperlipidemia. Her first pregnancy had resulted in a preterm delivery at 27 weeks gestation, and she lost her premature infant as a result of respiratory distress syndrome. Unfortunately, she did not have regular follow-up during that pregnancy. On the initial examination: her height was 158 cm, her weight was 65 kg. Her blood pressure, pulse, and temperature were 110/70 mmHg, 92 beats/min and 37.5 °C, respectively. The fundal height was 23 cm above the pubic arch, consistent with the gestational age. The fetal heartbeat was positive, and no uterine contractions were noticed. The physical examination was unremarkable, with the exception of severe epigastric tenderness. Laboratory tests showed a hematocrit of 35%, white blood cell count of 13.4 × 109/L, hyperglycemia (20.3 mmol/L), decreased total serum calcium (1.88 mmol/L), and normal ionized calcium at 0.94 mmol/L (normal range, 0.9–1.3). The lipid profile consisted of an extremely high serum triglyceride concentration at 60 mmol/L (normal range, 0.5–2.8), serum total cholesterol at 31.4 mmol/L (normal value < 5.2 mmol/L), and VLDL at 9.2 mmol/L. High-density lipoprotein was found to be low, at 0.1 mmol/L (normal range, 0.8–1.8). Lipoprotein electrophoresis led us to the diagnosis of type V hyperlipoproteinemia according to the WHO classification (4) (Table I). Prompt investigation of pancreatic enzymes revealed high levels of serum amylase, pancreatic amylase, and pancreatic lipase at 487 U/L (normal range, 30–230), 184 U/L (normal range, 17–115), 786 U/L (normal range, 25–230), respectively. Renal, liver and thyroid function tests were normal. Glycosilated hemoglobin (HbA1C) was normal, at 4.8%, supporting the acute onset of a hyperglycemic state. The serum parathyroid hormone (PTH) level was normal, as well. Abdominal ultrasonography showed extensive edema of the pancreas with no evidence of cholelithiasis. Magnetic resonance (MR) imaging confirmed acute pancreatitis demonstrating a swollen pancreas with strands of inflammation invading the peripancreatic fat (Fig. 1). Obstetric sonography revealed an appropriate for gestational age fetus, normal amniotic fluid index, and excluded a visible retroplacental hematoma. Acute pancreatitis. T2-weighted image demonstrating swollen pancreas with strands of inflammation invading the peripancreatic fat (arrow). A diagnosis of severe acute pancreatitis was made according to the Japanese criteria (5). Cessation of oral intake, nasogastric decompression, intravenous hyperalimentation, insulin infusion therapy, and plasma exchanges were employed. Three consecutive plasma exchanges within 5 days resulted in a significant reduction in plasma lipid levels. Each time 2.5 L of plasma was exchanged, and gradual abatement of clinical symptoms took place, which finally resulted in a complete resolution of pancreatitis. On the seventh day of her hospitalization, advancing preterm labor and associated fetal distress (repetitive late decelerations) was diagnosed, which necessitated a cesarean section. The birth weight was 750 g, and the Apgar scores were 4 and 5. Unfortunately, the male infant was lost 5 h after delivery as a result of severe immaturity. Fifteen days after delivery, the patient presented with recurrent abdominal pain. A pancreatic pseudocyst formation was diagnosed by abdominal computerized tomography (CT) (Fig. 2), and was managed by percutaneous drainage. She was discharged as symptom free. She has maintained normal levels of serum lipids for the past 6 months without any treatment. CT showing several pancreatic pseudocysts (arrowheads). Gestational pancreatitis is probably caused by hypertriglyceridemia exceeding 22 mmol/L (2000 mg/dL) (3). Pregnancy causes a relative increase in lipid levels especially in the third trimester. However, this mild increment does not possess a risk for pancreatitis in normal pregnancies. On the other hand, the metabolic changes of pregnancy may induce profound elevation of plasma triglycerides in women who have a pre-existing disorder of lipoprotein metabolism. The most common type of hyperlipidemia associated with acute gestational pancreatitis is type V hyperlipoproteinemia, which is followed by type I hyperlipoproteinemia (6). In the presented case lipoprotein and apolipoprotein analysis showed a marked increase in both chylomicrons and pre-β lipoproteins, along with increased apolipoprotein B, CII, CIII, and E, which led us to the diagnosis of type V hyperlipoproteinemia. The patient had no history of non-gestational hyperlipidemia. No cases of hyperlipidemia were found in her relatives, as well. Fujita et al. (7) presented a similar case of gestational acute hyperlipidemic pancreatitis without non-gestational hyperlipidemia. Because type V hyperlipoproteinemia could not be documented in our case during the non-gestation period, pregnancy itself might be the triggering factor for this hyperlipidemia and associated pancreatitis in somewhat susceptible women. Nies et al. (8), in their review of the English literature, found 11 published cases of hyperlipidemic pancreatitis during pregnancy between 1956 and 1990, and reported an additional case which was complicated with adult respiratory distress syndrome. Several reports suggested a maternal mortality rate as high as 20% in cases of acute pancreatitis secondary to hyperlipidemia during pregnancy (6, 9). Ohmoto et al. (10) reported a case of hyperlipidemic pancreatitis which was diagnosed at 35 weeks gestation, and responded to prompt initiation of intravenous hyperalimentation, protease inhibitors and antibiotics. Complete recovery of the mother and delivery of a healthy term infant was achieved. Hemodialysis, plasma exchange, immunospecific apheresis, and a combination of these have been used for the treatment of hyperlipidemic pancreatitis (3, 11). Our case further supports the beneficial effect of extracorporeal elimination of lipoproteins in this condition. Surgical approaches may include necrosectomy, peritoneal drainage and well-planned preterm cesarean delivery on demand. Nevertheless, supportive treatment is still the cornerstone of management. Finally, one should be aware of maternal and fetal risks associated with gestational pancreatitis, and anticipate possible complications.