An 8 1⁄2 year old girl presented with pain abdomen with hypertriglyceremia

This article has no abstract. The first 100 words appear below:A 8 ½ year old girl, 1st issue of non-consanguineous parents, from Norshingdi immunized as per EPI  presented at the outpatient department with the history of abdominal pain for 5 days. The pain was located in the epigastric region and dull in nature. There was no aggravating or relieving factor and no radiation and persisted all the days. The pain had no relation with the food. She had also the history of vomiting for several times for the same  duration which occurred usually after feed and contained food particle and not mixed with blood or bile and it was not projectile.


Presentation of Case
Dr. Zannatul Ferdous Sonia: A 8 ½ year old girl, 1 st issue of non-consanguineous parents, from Norshingdi immunized as per EPI presented at the outpatient department with the history of abdominal pain for 5 days.The pain was located in the epigastric region and dull in nature.There was no aggravating or relieving factor and no radiation and persisted all the days.The pain had no relation with the food.She had also the history of vomiting for several times for the same duration which occurred usually after feed and contained food particle and not mixed with blood or bile and it was not projectile.She had no history of fatigue, weight loss, polyuria, polyphagia, polydypsia, respiratory distress or constipation.She had the history of similar type of attacks for repeated times for the last 7 months.The pain was so severe that she needed hospitalization for several times.Her younger brother is healthy and there is no family history of such type illness.On examination, she was afebrile, anicteric, mildly pale, and vitals were within the normal limit.Anthropometrically she was normal and the BCG mark was present.Abdominal examination showed epigastric tenderness.There was no organomegaly and ascites was absent.Other systemic examinations showed normal findings.
For her complaints she was admitted in a private hospital and underwent some investigations like serum electrolytes, amylase, lipase, alkaline phosphatase, alanine aminotransferase, calcium, random blood sugar, fasting triglyceride, ultrasonography of the whole abdomen, etc (Table I).Her reports showed severe hypertriglyceremia with raised serum amylase, lipase and blood sugar.The ultrasonography report showed a single calcification in the right lobe of liver measuring 6.6 mm.She was treated with intravenous fluid, injectable proton pump inhibitor and ceftriaxone but her condition didn't improve and was then referred to this tertiary level hospital for better management.
After admission in the Bangabandhu Sheikh Mujib Medical University, the blood was sent for complete blood count, fasting lipid profile, serum T4, TSH, plain X-ray of abdomen in erect posture, chest X-ray and Mantoux test (Table I).

Differential Diagnosis
Dr. Afsana Yasmin: As peptic ulcer diseases also present with similar type of clinical features, I thought it could be a case of peptic ulcer disease.

Peptic ulcer disease
Peptic ulcer diseases can occur in children, but it is uncommon in pediatric age group.In children, it may be due to primary or secondary causes.Among the primary causes Helicobacter pylori infection is the commonest.Other primary causes are Zollinger-Ellison syndrome, G-cell hyperplasia, systemic mastocytosis, short bowel syndrome, hyperparathyroidism, etc. Secondary ulcers are more common than primary which have bad prognosis.Secondary ulcer may develop due to stress, sepsis, trauma, burn, type 1 diabetes mellitus, drug, etc. 1 Among the drugs NSAID, steroid, immunosuppressive drugs, etc can cause ulcer. 2 Stress ulcer is more common in children of less than 4 years of age and the primary ulcer is more common above 4 years of age and primary ulcer may recur even after treatment.The common symptoms are gas, bloating, nausea, vomiting, epigastric pain, abdominal discomfort which usually increase at empty stomach or after meal. 2 Gastrointestinal bleeding may occur with long standing epigastric pain but painless bleeding may be the only manifestation of ulcer.Primary peptic ulcers in children usually presents between the ages of 8 to 17 years, commonly around 12 years, usually the cause is Cite this arti le: Nahar L, Kari ASMB, Ruku uzza a M, Yas i A. A ½ year old girl prese ted ith pai a do e ith hypertrigly ere ia.Ba ga a dhu Sheikh Muji Med U i J.

Copyright:
The opyright of this arti le is retai ed y the author s [Atri utio CC-By .] A aila le at: .a glajol.ifo In this patient, epigastric pain with no radiation along with vomiting of undigested food and epigastric tenderness goes in favor of peptic ulcer disease, but no relation with food and not relieved by antiulcerant goes against the peptic ulcer disease.
To exclude peptic ulcer disease, we have done anti-H.pylori antibody (IgG) and upper GI endoscopy.Her anti-H.pylori antibody (IgG) was negative and upper gastrointestinal endoscopy findings were normal.So, it was not a case of peptic ulcer disease.Acute pancreatitis is diagnosed by the presence of at least two of the following three criteria 14-17 :

Diabetic ketoacidosis
1. Characteristic abdominal pain of acute onset, severe dull ache, especially in the epigastric region may radiate to back, aggravated by eating or drinking, usually after taking fatty food and relieved by lean forward or knee-chest position. 18 Serum amylase and /or lipase level at least more than 3 times of upper normal limit.

Positive imaging findings.
There are several etiologies of acute pancreatitis.Among the metabolic causes hypertriglyceremia is one of established cause of pancreatitis.The complication of HTG are pancreatitis, cardiovascular diseases, non alcoholic fatty liver disease etc. 22 HTG is a well established risk factor for pancreatitis and the risk is about 1-4%.Usually primary lipid disorder is due to genetic defect of triglyceride synthesis and metabolism. Type I hyperlipoproteinemia indicates the presence of chylomicrons, normal total cholesterol with very high level of triglyceride; whereas type V hyperlipoproteinemia is defined as the presence of chylomicrons and very low density lipoproteins with increased level of cholesterol and very high level of triglyceride.

Hypertriglyceridemia
Type 1 hyperlipoproteinemia is mainly due to genetic deficiency of lipoprotein lipase (LPL) or other related proteins as apolipoprotein C2, A5, lipase mutation factor 1 (LMF1) and glycosyl-phosphatidylinositol-anchored high-density lipoprotein binding protein 1 (GPIHBP1.It is diagnosed by genomic DNA analysis for APOA5, APOC2, LMF1 and GPIHBP1 and immunoblotting method to detect serum LPL autoantibody.
This patient presented with recuurent attacks of acute abdominal pain favorable for pancreatitis and no suggestive history for peptic ulcer diseases or diabetic ketoacidosis.Biochemically she had raised serum amylase, lipase and severe hypertriglyceremia.As there is no evidence of secondary causes of hypertriglyceremia; so, probably it is a case of primary hypertriglyceremia.
In this patient, triglyceride level was very high with normal total cholesterol and LDL couldn't be detected by Friedewald's formula, HDL was normal.She had acute pancreatitis.So, probably it is Type 1 hyperlipoproteinemia.But we couldn't confirm it due to lack of facilities to do genetic and antibody analysis.

Dr. Nahar's Diagnosis
Acute pancreatitis due to primary hypertriglyceremia

Discussion
Dr. A. S. M. Bazlul Karim: The term "recurrent acute pancreatitis" was first introduced in 1948 in medical literature by Henry Doubilet. 25According to INSPIRE criteria it is defined by at least two separate episode of acute pancreatitis with absence of irreversible, structural changes in the pancreas.
The patient must have to meet the criteria of acute pancreatitis after the first attack. 26st common causes of recurrent acute pancreatitis are bile duct stone or sludge, sphincter of oddi dysfunction, anatomical abnormality of pancreatic tree or ductal stone, genetic mutation, hyperlipidemia, hypercalcemia, ascariasis, autoimmune pancreatitis, drug such as azathioprine, mercaptopurine, sulphonamide, etc.Even organophosphorus compounds can cause acute pancreatitis.The girl had similar type of attacks before admission but there is no biochemical proof of pancreatitis.From history it is assumed that she could have previous attacks of pancreatitis.Then the case can not categorized as acute recurrent pancreatitis.
Treatment of acute recurrent pancreatitis is the same as acute pancreatitis.Initial treatment include rest to pancreas by limiting oral intake, aggressive intravenous hydration, and pain management; along with treatment of underlying cause and complications. 20. Md.Rukunuzzaman: Type 1 hyperlpoproteinemia also called familial hyperchylomicronomia.It may be due to environmental influence or may be genetic.The disorder tends to run in families.We have done fasting lipid profile of patient's mother and it was near normal limit.
The presentation of type 1 hyperlipoproteinemia are recurrent acute pancreatitis, eruptive xanthomas, lipema retinalis, hepatosplenomegaly, abnormal liver enzymes, etc. 30 When patient presents with severe hypertriglyceremia, serum turn to creamy appearance which is called lipemic serum. 31pema retinalis is a transient change of retina as creamy appearance of retinal blood vessels due to lipid infiltration and may decrease visual acuity.Lipid lowering therapy may turn to normal fundus and visual acuity.
This patient attended to us on 3 rd day.She had lipemic serum (Figure 1) and eye findings were normal Dr. Md.Wahiduzzaman Mazumder: Hypertriglyceremia lead to triglyceride rich chylomicron sludge in the capillary bed which cause ischemia of pancreas and pancreatic lipase release from damaged pancreatic acini.Further production of FFA leads to free radical damage and inflammation which cause premature activation of trypsinogen to trypsin and activation of other enzymes resulting pancreatitis.Noncompliance of low fat diet may cause recurrent pancreatitis in type 1 hypertriglyceremia.Recurrent pancreatitis can cause chronic exocrine and endocrine pancreatic insufficiency. 19ere may have relationship with some genetic predisposition to hypertriglyceremia induced pancreatitis as like mutations in cationic trypsinogen (PRSS1), serine protease inhibitor Kazal type 1 (SPINK1), cystic fibrosis transmembrane conductance regulator (CFTR), and tumor necrosis factor superfamily member 2 (TNF2). 20. Karim: Acute management of severe hypertriglyceremia is done by fasting, insulin or heparin infusion or plasmapheresis. 32patient of severe hypertriglyceremia should be kept nothing by mouth with intravenous fluid.Diet increases further chylomicron production and exacerbate hypertriglyceremia.So, fasting initially prevent chylo-micron production and is helpful for gradual clearance of chylomicron and significant reduction of hypertriglyceremia within one or two days.When triglyceride level is at 1,000 mg/dL and there is no abdominal pain then fat free oral diet can be started. 32sulin infusion reduce the triglyceride level rapidly, it can be given by continuous or subcutaneous infusion.Intravenous insulin infusion along with fasting will reduce triglyceride level up to 80% in first 24 hours.Continuous insulin can be given at 0.1-0.3U/kg/hours in dextrose infusion to maintain blood glucose level between 140-180 mg/dL.In diabetic patient continuous insulin infusion at 0.5 to 1 IU/kg/hours can be used with others supportive management. 32case report of nondiabetic adolescent patient with severe hypertriglyceremia, subcutaneous infusion bolus dose of regular insulin at 0.1 U/kg decreased triglyceride level rapidly. 33parin also release lipoprotein lipase from muscle, adipose tissue and endothelium to circulation and hydrolyze the triglyceride.This effect is short lived and is quickly followed by increased hepatic LPL degradation.Therefore heparin is not routinely recommended to treat hypertriglyceremia in children.Long-term management of hypertriglyceremia needs lifestyle changes including dietary restriction of fat <10-15% along with weight reduction, increasing physical activity and pharmacotherapy.
Fibrate (gemfibrozil and fenofibrates) are the first line drugs to treat hypertriglyceremia.Gemfibrozil 600 mg twice daily can be used.Adverse effect may be cholesterol gall stone.Fibrate is contraindicated in renal impairment and gall bladder diseases.Dr. Nahar: We advised to restrict dietary intake of fat, increase physical activity along with pharmacotherapy as fibrate, niacin, omega 3 fatty acid, cholestyramine and anti-oxidant.
Dr. Mohua Mondol: What is the explanation of hepatic calcification in this case?
Dr. Nahar: The most common cause is hepatic tuberculosis.Others etiologies are sarcoidosis, hemangioma, echinococcal cyst, hepatic adenoma, etc.She had no history of fever, weight loss, contact with TB patient and her chest X-ray was normal and Mantoux test was negative.Hepatic calcification in this case may be due to a dilated intrahepatic bile ductule.
Dr. Kamrun Nahar: Why there is gall bladder sludge and is it may the cause of pancreatitis?
Dr. Nahar: This patient was initially kept nothing by mouth.So, less contraction of gall bladder may the cause for gall bladder sludge.She received injectable Ceftriaxone for two days in a private clinic.Ceftriaxone also may be responsible it.She had also severe hypertriglyceremia.So, I think sludge is not the underlying cause.Dr. Nahar: Though acute pancreatitis is a stressful condition.Human body regulates the stress response by hypothalamic pituitary adrenal axis and releases more adrenaline, catecholamine, cortisol to reduce the mortality.At the same time, body maintains glucose intolerance and insulin resistance.So, this patient had hyperglycemia and no measures were taken to reduce glucose level.On subsequent follow-up, it was within normal limit.

Follow-up
Acute recurrent pancreatitis need long-term followup.Our plan to follow-up the patient 2, 4 and 8 weeks after discharge by doing fasting lipid profile (Figure 2).

Final Diagnosis
Acute pancreatitis due to primary hypertriglyceremia Dr. Habibur Rahman: Why initially patient had hyperglycemia and what measures were taken?BSMMU J 2018; 11: 161-167

Figure 2 :
Figure 2: Triglyceride level (upper), random blood sugar (middle) during hospital period and triglyceride during follow-up after discharge (lower)

3-4
Cushing ulcer associated with brain tumor or brain injury which are typically single, deep which are prone to perforation.Stress and spicy food don't cause ulcer but exacerbate the symptoms.

5
Diagnostic examinations include urease breath test, stool tests for H. pylori detection, anti-HP antibody (IgG) and upper gastrointestinal tract endoscopy.

Table I Laboratory investigations of patient on admission
13ute pancreatitis: Acute pancreatitis is a reversible process characterized by the histological evidence of inflammation of pancreatic parenchyma, interstitial edema, infiltration of inflammatory cells with variable degrees of cellular apoptosis, necrosis and hemorrhage.13

32, 33
Plasmapheresis is another option to treat severe hypertriglyceremia.In children, there are only few