Hepatitis A Associated with Chylothorax: An Uncommon Presentation of a Common Infection

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1 VC The Author [2015]. Published by Oxford University Press. All rights reserved. For Permissions, please Journal of Tropical Pediatrics, 2015, 61, doi: /tropej/fmv059 Advance Access Publication Date: 1 September 2015 Case Report CASE REPORT Hepatitis A Associated with Chylothorax: An Uncommon Presentation of a Common Infection by Kayur Mehta, Supriya Shinde, Sylvan Rego, and Anita Shet Correspondence: Kayur Mehta, Dr. Kayur Mehta, Department of Pediatrics, St. John s Medical College Hospital, Sarjapur Road, Bangalore India. <kayur.mehta@gmail.com> ABSTRACT Extra-hepatic manifestations have seldom been described with hepatitis A, which usually manifests as mild hepatic dysfunction. We report a 3-year-old boy presenting with 3 days of fever, vomiting, abdominal distention and scleral icterus. On examination, he had tachypnea, hepatosplenomegaly, ascites and right-sided pleural. A diagnostic pleural tap yielded a milky, lymphocytepredominant exudative aspirate, with pleural fluid triglycerides of 175 mg/dl, suggestive of chylothorax. Serology for anti-hav IgM was in both blood and pleural fluid. The massive causing collapse of the underlying lung was drained by tube thoracostomy, which was followed by complete resolution within 2. This is the first reported case of chylothorax associated with hepatitis A infection. This report highlights that pleural associated with hepatitis A infection is usually a benign, self-limiting condition which should be considered in the differential diagnosis of pleural or chylothorax in a patient with acute viral hepatitis. KEYWORDS: Hepatitis A, chylothorax, pleural. INTRODUCTION Hepatitis A is the most common form of acute viral hepatitis worldwide [1]. Infection with the causative virus is generally benign and self-limiting, most commonly manifesting as mild hepatic dysfunction. Extra-hepatic manifestations have been rarely described [2 5]. Here, for the first time in literature, we report a case of chylous pleural associated with hepatitis A. CASE REPORT A 3 year old child presented to us with a 3 day history of fever, vomiting, abdominal distention and yellowish discoloration of the eyes. Fever was of high grade and intermittent type, associated with progressive abdominal distention and four to five episodes of non-bilious, non-projectile vomiting. There was no history of cough, difficulty in breathing, bleeding manifestations, loose stools and previous history of jaundice, blood transfusion or weight loss. His heart rate was 90 beats per minute, respiratory rate was 36 breaths per minute and he was febrile. Scleral icterus was evident. On abdominal examination, he had hepatosplenomegaly with ascites. On examination of the respiratory system, there was

2 Hepatitis A Associated with Chylothorax 469 Table 1. Review of literature Hepatitis A infection presenting with pleural Serial number Author and journal (reference number) Age and sex Main presenting complaints Clinical findings Imaging Pleural fluid analysis HAV serology Outcome 1 Alhan, et al., PIDJ 1999 (Case 1) [9] 2 Alhan, et al., PIDJ 1999 (Case 2) [9] 3 Gurkan, et al., Clin Microbiol and Infect, 2000 [4] 4 Tesovic, et al., PIDJ 2000 [10] 5 Vaidya, et al., Indian Pediatr, 2003 [11] 12 years, 5 years, 4 years, 3 years, 7 years, Jaundice after 6 days of fever, anorexia, malaise and myalgia. Jaundice, fever and malaise for 2 days Fever, abdominal distention and jaundice for 2 days 2 day history of fever, vomiting and jaundice. Nausea and vomiting for 2 days ascites Icterus, CXR consolidation of the right lower lobe, USG pleural in the right chest. CXR right-sided USG rightsided pleural CXR bilateral moderate pleural s on Day 6 of hospitalization; USG bilateral pleural USG right-sided pleural CXR Left-sided USG chest bilateral pleural glucose 95 mg/ dl and protein 4.2 g/dl. Cultures were sterile. glucose 85 mg/ dl and protein 4.2 g/dl. Cultures were sterile. Serum and pleural fluid anti-hav Serum and pleural fluid anti-hav transudate, staining negative, cultures sterile. Serum and pleural fluid anti-hav 1 week after liver enzyme normalization 3 days after liver enzyme normalization in 2 Death because of fulminant hepatic failure and hepatic encephalopathy in 2 (continued)

3 470 Hepatitis A Associated with Chylothorax Table 1. Continued Serial number Author and journal (reference number) 6 Selimoglu, et al., J Emer Med, 2004 [12] 7 Bulkumez, Ind J Med Micro 2008 [3] 8 Erdem, et al., Iran J Pediatr, 2010 [5] 9 Vinoth, et al., Australas Med J (Case 1) [13] Age and sex 8 years, 7 years, 12 years, 7 years, Main presenting complaints Fever, abdominal pain, jaundice, anorexia and fatigue for 10 days Fever, jaundice, abdominal distention for 6 days Nausea, vomiting, anorexia and fatigue for 7 days Abdominal pain for 2, abdominal distention, icterus and fast breathing for 3 days Clinical findings Imaging Pleural fluid analysis HAV serology Outcome Tender, ascites, icterus Icterus, CXR Consolidation of right lower lobe; USG chest not documented CXR Right lobar consolidation, USG rightsided pleural, CT thorax pleural at posterobasal segment of right lung CXR closure of right costophrenic sinus without parenchymal infiltration; USG right-sided pleural CXR bilateral pleural (right > left); USG chest not documented glucose 70 mg/ dl and protein 4.5 g/dl culture sterile. protein 20 g/dl (transudative) in 1 week in about 2 in 10 days in 3 (continued)

4 Hepatitis A Associated with Chylothorax 471 Table 1. Continued Serial number Author and journal (reference number) Age and sex Main presenting complaints Clinical findings Imaging Pleural fluid analysis HAV serology Outcome 10 Vinoth, et al., Australas Med J (Case 2) [13] 11 Dhakal, et al., Pediatric Health, Medicine and Therapeutics, 2014 [14] 10 years, 2.5 years, Fever, vomiting and abdominal pain for 7 days Abdominal pain and decreased appetite for 4 days, high-colored urine for 3 days and yellowish discoloration of the eyes for 2 days. Icterus, Icterus along with and diminished breath sounds on the right side CXR bilateral USG bilateral pleural. CXR right-sided USG bilateral (right > left) Total count 2000/ ml, 5% neutrophils, 95% lymphocytes, total protein 3.5 g/dl, LDH 434 U/l, and adenosine deaminase 28 U/l. Gram stain and Zeil Neilsen stain negative. Cultures sterile. Spontaneous resolution in 10 days HAV, Hepatitis A Virus; CXR, Chest X-Ray; USG, Ultrasonogram; CT, Computerized Tomography.

5 472 Hepatitis A Associated with Chylothorax decreased air entry on the right lower zone of the chest with stony ness on percussion. The remainder of the systemic examination was normal. On laboratory examination, his hemoglobin was 11.1 g/dl, total leukocyte count was 8350 cells/mm 3 with 31% neutrophils and 65% lymphocytes, platelet count was cells/mm 3. Liver function tests showed a total protein of 6.3 g/dl, albumin 2.8 g/dl, total bilirubin 5.34 mg/dl, conjugated bilirubin 5.24 mg/dl, Aspartate Aminotransferase (AST) 276 U/l, Alanine Aminotransferase (ALT) 332 U/l, Alkaline phosphatase (ALP) 587 U/l and Gamma Glutamyl Transferase (GGT) 108 U/l. Radiological imaging of the chest was suggestive of a gross rightsided pleural causing collapse of the underlying lung (Fig. 1). Pleural fluid analysis revealed a total count of cells/mm 3, with 99% lymphocytes, glucose 94 mg/dl, protein 7.7 g/dl, Lactate dehydrogenase (LDH) 251 U/l and adenosine deaminase U/l. Pleural fluid triglycerides measured 175 mg/dl. Gram stain, Zeil Neilsen staining and cultures on pleural fluid were all negative. Common endemic infectious etiologies like tuberculosis and dengue were ruled out with serological and nucleic acid amplification tests, respectively. Malignancy was also ruled out by immunocytochemistry on a cytospun sample. Elevated liver enzymes and evidence of hepatitis prompted an exploration of common viral pathogens; serum Hepatitis B surface antigen (HBsAg) was negative, and serum anti-hav IgM antibodies was. Anti-HAV IgM antibody on pleural fluid was also. In view of the massive right-sided causing collapse of the underlying lung, a thoracostomy was performed and a chest tube was retained in situ for a total of 5 days. An overall drain of 120 ml of milky fluid was documented. Other supportive management in the form of intravenous fluids and paracetamol was given. An intravenous combination of amoxycillin clavulanic acid was started empirically, and taken off after 5 days once the etiology was established. The child improved symptomatically and was discharged after a week of hospital stay with a diagnosis of hepatitis A with chylothorax. The child remains asymptomatic on follow-up. FIG. 1.Chest X ray anteroposterior view (supine) with chest tube in situ. This film shows a massive right-sided lamellar pleural causing collapse of the underlying lung. DISCUSSION HAV is a 27 nm diameter, RNA-containing virus that is a member of the Picornavirus family. In children, it generally causes a benign, self-limiting infection with symptoms mainly pertaining to the hepatic system. The spectrum of hepatic involvement can range from an anicteric form to fulminant hepatic failure. Rare extra-hepatic manifestations have included arthritis, renal failure, vasculitis, serositis, transverse myelitis, hemophagocytosis, pancreatitis, acute tubular necrosis, nephrotic syndrome, Guillian Barre syndrome and rarely Gianotti Crosti syndrome [6, 7]. Pleural has been rarely reported in hepatitis A. Generally presenting early in the course of the disease, it is usually self-limiting and benign. Although the precise mechanism of pleural in hepatitis A infection is unknown, various mechanisms have been postulated. These include extravasation of fluid from diaphragmatic lymphatics [4], transmigration of ascitic fluid through suspected diaphragmatic defects [4], pleural reaction following immune complex deposition [5] or viral invasion of the pleura [8]. Thus far, 11 cases of pleural accompanying hepatitis A infection in children have been reported in literature. In most cases, although the patients did not have respiratory symptoms on admission, pleural was generally detected in

6 Hepatitis A Associated with Chylothorax 473 the first week of illness and most cases resolved spontaneously and had complete recovery within 2 3 (Table 1). Chylothorax should be considered in the differential diagnosis in the evaluation of a pleural with lymphocyte predominance with high levels of triglycerides (>110 mg/dl) [15]. For the first time, we report a case of hepatitis A associated with chylothorax. A anti-hav IgM antibody on pleural fluid confirmed the etiology of hepatitis A associated with the chylothorax. Similar to most cases of pleural associated with hepatitis A infection (Table 1), our patient responded well to supportive therapy and had a complete resolution of the chylous pleural. CONCLUSION In conclusion, we present this case and review of literature to show that pleural is a rare, self-limiting complication of hepatitis A, most commonly occurring early in the course of the disease. Occasionally, the pleural could be of chylous variety. Good supportive therapy remains the cornerstone of the management of this condition, with overall good outcomes in affected children. REFERENCES 1. Franco E, Meleleo C, Serino L, et al. Hepatitis A: Epidemiology and prevention in developing countries. World J Hepatol 2012;4: Saha S, Sengupta M. Anasarca-an atypical presentation of hepatitis A. Eastern J Med 2012;17: Bukulmez A, Koken R, Melek H, et al. Pleural : a rare complication of hepatitis A. Indian J Med Microbiol 2008;26: Gürkan F. Ascites and pleural accompanying hepatitis A infection in a child. Clin Microbiol Infect 2000;6: Erdem E, Urganci N, Ceylan Y, et al. Hepatitis a with ascites and acalculous cholecystitis. Iran J Pediatr 2010;20: Amarapurkar DN, Amarapurkar AD. Extrahepatic manifestations of viral hepatitis. Ann Hepatol 2002;1: Brundage SC, Fitzpatrick AN. Hepatitis A. Am Fam Physician 2006;73: Kurt AN, Bulut Y, Turgut M, et al. Pleural associated with hepatitis A. J Pediatr Inf 2008;2: Alhan E, Yildizdas D, Yapicioğlu H, et al. Pleural associated with acute hepatitis A infection. Pediatr Infect Dis J 1999;18: Tesovic G, Vukelić D, Vuković B, et al. Pleural associated with acute hepatitis A infection. Pediatr Infect Dis J 2000;19: Vaidya P, Kadam C. Hepatitis A. An unusual presentation. Indian Pediatr 2003;40: Selimoglu MA, Ziraatci O, Tan H, et al. A rare complication of hepatitis A: pleural. J Emerg Med 2005;28: Vinoth PN, Anitha P, Muthamilselvan S, et al. Pleural an unusual cause. Australas Med J 2012;5: Dhakal A, Shakya A, Shrestha D, et al. An unusual association of pleural with acute viral hepatitis A infection. Pediatric Health Med Ther 2014;5: Tutor DJ. Chylothorax in children. Pediatrics 2014;133;722.

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