World J Gastroenterol 2016 February 14; 22(6): 2149-2152 ISSN 1007-9327 (print) ISSN 2219-2840 (online)
Submit a Manuscript: http://www.wjgnet.com/esps/ Help Desk: http://www.wjgnet.com/esps/helpdesk.aspx DOI: 10.3748/wjg.v22.i6.2149
© 2016 Baishideng Publishing Group Inc. All rights reserved.
CASE REPORT
Pancreatitis in hand-foot-and-mouth disease caused by enterovirus 71 Yu-Feng Zhang, Hui-Ling Deng, Jia Fu, Yu Zhang, Jian-Qiang Wei Yu-Feng Zhang, Hui-Ling Deng, Jia Fu, Yu Zhang, Department Second of Infectious Diseases, Xi′an Children′s Hospital, Xi′an 710003, Shaanxi Province, China
Published online: February 14, 2016
Jian-Qiang Wei, Department of Radiology, Xi′an Children′s Hospital, Xi′an 710003, Shaanxi Province, China
Abstract Some viruses, including certain members of the entero virus genus, have been reported to cause pancreatitis, especially Coxsackie virus. However, no case of human enterovirus 71 (EV71) associated with pancreatitis has been reported so far. We here report a case of EV71-induced hand-foot-and-mouth disease (HFMD) presenting with pancreatitis in a 2-year-old girl. This is the first report of a patient with acute pancreatitis in HFMD caused by EV71. We treated the patient conservatively with nasogastric suction, intravenous fluid and antivirals. The patient’s symptoms improved after 8 d, and recovered without complications. We conclude that EV71 can cause acute pancreatitis in HFMD, which should be considered in differential diagnosis, especially in cases of idiopathic pancreatitis.
Author contributions: Fu J and Zhang Y collected the patient’s clinical data; Wei JQ provided the CT image; Zhang YF and Deng HL analyzed the data and wrote the paper. Institutional review board statement: This article was reviewed and approved by the Institutional Review Board of Xi′ an Children′s Hospital with protocol number 2015-014. Informed consent statement: We have requested waiver of informed consent from the legal guardian of the patient for this report. Conflict-of-interest statement: The authors declare no conflict of interest related to this report. Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/ licenses/by-nc/4.0/
Key words: Pancreatitis; Enterovirus 71; Hand, foot and mouth disease © The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
Core tip: Acute pancreatitis associated with enterovirus 71 (EV71) infection is extremely rare. We here report a case of EV71-induced hand-foot-and-mouth disease (HFMD) presenting with pancreatitis in a 2-year-old girl. This is the first case report of acute pancreatitis associated with EV71 infection. EV71 can cause acute pancreatitis in HFMD, which should be considered in differential diagnosis, especially in cases of idiopathic pancreatitis.
Correspondence to: Dr. Hui-Ling Deng, Department Second of Infectious Diseases, Xi′an Children′s Hospital, 69 Xijuyuanxiang, Lianhu District, Xi′an 710003, Shaanxi Province, China. [email protected] Telephone: +86-29-87692204 Fax: +86-29-87692009 Received: October 15, 2015 Peer-review started: October 15, 2015 First decision: November 5, 2015 Revised: November 18, 2015 Accepted: December 8, 2015 Article in press: December 8, 2015
WJG|www.wjgnet.com
Zhang YF, Deng HL, Fu J, Zhang Y, Wei JQ. Pancreatitis in hand-foot-and-mouth disease caused by enterovirus 71. World
2149
February 14, 2016|Volume 22|Issue 6|
Zhang YF et al . Pancreatitis in hand-foot-and-mouth disease J Gastroenterol 2016; 22(6): 2149-2152 Available from: URL: http://www.wjgnet.com/1007-9327/full/v22/i6/2149.htm DOI: http://dx.doi.org/10.3748/wjg.v22.i6.2149
INTRODUCTION Enterovirus 71 (EV71) is a human enterovirus in the Enterovirus genus of the Picornaviridae family. Many of the EV71-infected cases have occurred in AsiaPacific region, and posed a serious threat to children’s [1] health . EV71 primarily causes hand-foot-and-mouth disease (HFMD) in young children, and many neurolo gical complications such as encephalitis, brain stem encephalitis and fatal pulmonary edema occur occa [2] sionally . However, no EV71-associated pancreatitis has been reported so far. We here describe a case of EV71-induced HFMD presenting with pancreatitis in a 2-year-old girl.
Figure 1 Adominal computed tomography showed acute pancreatitis with swelling of the pancreas and peri-pancreatic exudation. No cholelithiasis or tumor occluding the common bile duct or pancreatic duct was observed (arrow).
hospitalization were performed and the results were as follows: real-time reverse transcription PCR (RT-PCR) in a stool sample was positive for EV71, but negative for Coxsackie virus A16, and antibody titer against EV71 was markedly elevated and it was quadrupled during the recovery period. Ultrasonography of the abdomen revealed neither gallstones nor biliary sludge. Abdominal computed tomography (CT) showed acute pancreatitis with swelling of the pancreas, and peri-pancreatic exudation. No cholelithiasis or tumor occluding the common bile duct or pancreatic duct was observed (Figure 1). Magnetic resonance cholangiopancreatography (MRCP) performed in another hospital revealed peri-pancreatic exudation and no anatomical abnormalities in the pancreas or pancreatic duct. The girl was treated conservatively with nasogastric suction, intravenous fluid and antivirals. She was administered Cimetidine (0.15 g b.i.d.), antibiotics (Cefminox, 0.4 g q8h, iv), and antiviral agent (Leigh Bhave Lin, 0.15 g qd, iv). The patient’s symptoms improved after 8 d, and recovered without complications. On the day of discharge, all serum biochemical tests were normal. Two months later, findings on the abdominal CT scan were normal, all laboratory values were within the normal ranges, and the rashes had disappeared, and no further damage was observed. One year after follow-up, the patient was asymptomatic and showed no evidence of pancreatitis recurrence.
CASE REPORT A 2-year-old girl was admitted to our hospital in June 2014 because of acute abdominal pain and vomiting for 2 d. Vomiting occurred about ten times a day. Moreover, 4 d before admission, maculopapular rashes had appeared on her hip and then spread to the palms of her hands and feet over the following 2 d, and she also had fever during the 4 d before admission. Her past medical history showed no record of pancreatitis and her family history was negative for pancreatic disease. A physical examination on admission revealed a normal blood pressure, temperature, pulse rate, and breathing rate. Maculopapular rashes on her hip, palms and feet and vesicles in mouth cavity membrane were observed. Breathing sounds were clear on auscultation. Abdominal examination revealed only mild abdominal tenderness. No other abnormalities were found. Of note, she had not taken any drugs before admission. On admission, her chest X-ray and electrocar diogram were both normal. A complete blood count, calcitonin and blood biochemical tests including C-reactive protein, glucose, bilirubin, triglycerides and calcium, were all within reference limits. The total levels of IgG, IgA and IgM in blood were normal. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were slightly elevated (ALT: 64 IU/L; AST: 68 IU/L; reference range: 10-35 IU/L), and serum amylase (385 IU/L; reference range: 0-220 IU/L) and urine amylase (5300 IU/L; reference range: 0-1200 IU/L) were also increased. Serological tests of various infectious agents including Epstein-Barr virus, varicella zoster virus, cytomegalovirus, HIV Ⅰ and Ⅱ, hepatitis A, B and C viruses, echoviruses, syncytial virus, flu virus A and B, parainfluenza 1, 2 and 3, and adenovirus were all negative. Tumor markers were also negative. Other relevant tests and examinations during
WJG|www.wjgnet.com
DISCUSSION We have presented a case of EV71 infection associated with pancreatitis secondary to HFMD. EV71 was established as the causative pathogen of pancreatitis in this case based on the following evidence: EV71 positivity, negative history of alcoholic and drug use, no gallstones, no anatomical abnormalities in the pancreas or pancreatic duct, normal level of triglyceride and calcium, negative serological tests for other infectious agents, and presence of characteristic rash
2150
February 14, 2016|Volume 22|Issue 6|
Zhang YF et al . Pancreatitis in hand-foot-and-mouth disease on hip, palms and feet. Based on these observations, it is tempting to speculate that the EV71 is the most likely pathogenic factor for pancreatitis in this case. Acute pancreatitis can be triggered by a variety of etiologies. Gallstones and alcohol are the most [3] common causes of acute pancreatitis in adults . However, the etiology in children is often drugs, infection, trauma, genetic mutation, and congenital structural abnormalities such as choledochal cysts and [4,5] abnormal union of the pancreatobiliary junction . The most common infections are mumps, viral hepatitis, [6] Coxsackie virus and echovirus . At present, among anomalies of the pancreatobiliary system, choledochal [7] cyst is the most common cause of acute pancreatitis . Some acute pancreatitis cases without a detectable [8] cause are considered as “idiopathic” . Viral etiology may be involved in idiopathic acute pancreatitis. The Enterovirus genus is part of the large Picornaviridae family, and is known to be highly cytolytic. The species are small non-enveloped RNA viruses and the most common viruses causing human diseases. EV71 belongs to the Enterovirus genus in the Picornaviridae family, and has been recognized as one of the most important viral pathogens. EV71 infection causes countless diseases ranging from mild HFMD or herpangina to fatal brain stem encephalitis complicated with pulmonary edema, and has become a serious threat to children’s health. So far, no EV71-associated pancreatitis has been reported, but Coxsackievirus A and B have been reported to be causative pathogens [9-11] [12,13] of pancreatitis and type 1 diabetic mellitus . Studies have suggested the presence of enteroviruses in pancreatic tissue including the pancreatic islets of [14] type 1 diabetic patients . Coxsackievirus has been [13] shown to replicate and destroy human β-cells . But to the best of our knowledge, EV71-induced pancreatitis is quite rare, and our patient presented no other severe complications except for acute pancreatitis. A previous study analyzing the EV71 genome obtained from an immunocompromised host showed various EV71 lineages and indicated that a mutation in the VP1 BC loop region of EV71 (L97R) may play a critical [15] role in cell tropism independent of the EV71 lineage . The mechanism of pancreatitis associated with EV71 is still unknown; EV71 might injure the pancreatic acinar cell membrane, leading to the leakage of intracellular enzymes, and at the same time, some other factors such as pancreatitis-related genetic susceptibility genes and virulence determinants in the genotype of the infecting strain should also be considered. Therefore, a multi-disciplinary approach is required to extend our understanding of this complex relationship. In conclusion, EV71 can cause acute pancreatitis in HFMD, which should be considered in the differential diagnosis, especially in cases of idiopathic pancreatitis. It is important to screen the patients with acute pancreatitis for EV71 infections.
WJG|www.wjgnet.com
COMMENTS COMMENTS Case characteristics
A 2-year-old girl presented with acute abdominal pain and vomiting for 2 d after the onset of rashes appearing on her hip, hands and feet.
Clinical diagnosis
Abdominal pain and vomiting, elevated level of urine and serum amylase concentration, magnetic resonance cholangiopancreatography (MRCP) and computed tomography (CT) findings of peri-pancreatic exudation and swelling.
Differential diagnosis
Gallstone-induced pancreatitis or pancreatic tumor.
Laboratory diagnosis
Serum amylase, 385 IU/L; urine amylase, 5300 IU/L.
Imaging diagnosis
MRCP and CT showed acute pancreatitis with swelling of the pancreas and peri-pancreatic exudation.
Treatment
The girl was treated conservatively with nasogastric suction, intravenous fluid, and antivirals.
Related reports
Reports of acute pancreatitis associated with enterovirus 71 (EV71) are rare, and only Coxsackie virus-related pancreatitis has been reported.
Experiences and lessons
EV71 can cause hand-foot-and-mouth disease (HFMD) with complications of acute pancreatitis, which should be noticed in differential diagnosis, especially in cases of idiopathic pancreatitis.
Peer-review
This interesting case is the first report of acute pancreatitis associated with EV71-related HFMD. The authors describe the clinical features, physical examination, laboratory findings, and MRCP and CT imaging in this case. Although the mechanism of pancreatitis associated with EV71 is unknown, suspected cases should be confirmed and treated as early as possible.
REFERENCES 1 2
3
4
5 6
2151
Wong SS, Yip CC, Lau SK, Yuen KY. Human enterovirus 71 and hand, foot and mouth disease. Epidemiol Infect 2010; 138: 1071-1089 [PMID: 20056019 DOI: 10.1017/S0950268809991555] Solomon T, Lewthwaite P, Perera D, Cardosa MJ, McMinn P, Ooi MH. Virology, epidemiology, pathogenesis, and control of enterovirus 71. Lancet Infect Dis 2010; 10: 778-790 [PMID: 20961813 DOI: 10.1016/S1473-3099(10)70194-8] Pulkkinen J, Kastarinen H, Kiviniemi V, Jyrkkä J, Juvonen P, Räty S, Paajanen H. Statin use in patients with acute pancreatitis and symptomatic gallstone disease. Pancreas 2014; 43: 638-641 [PMID: 24632548 DOI: 10.1097/MPA.0000000000000068] Rai P, Sharma A, Gupta A, Aggarwal R. Frequency of SPINK1 N34S mutation in acute and recurrent acute pancreatitis. J Hepatobiliary Pancreat Sci 2014; 21: 663-668 [PMID: 24844923 DOI: 10.1002/jhbp.111] Pohl JF, Uc A. Paediatric pancreatitis. Curr Opin Gastroenterol 2015; 31: 380-386 [PMID: 26181572 DOI: 10.1097/MOG.00000 00000000197] Parenti DM, Steinberg W, Kang P. Infectious causes of acute pancreatitis. Pancreas 1996; 13: 356-371 [PMID: 8899796]
February 14, 2016|Volume 22|Issue 6|
Zhang YF et al . Pancreatitis in hand-foot-and-mouth disease 7
8
9 10 11
Fujishiro J, Masumoto K, Urita Y, Shinkai T, Gotoh C. Pancreatic complications in pediatric choledochal cysts. J Pediatr Surg 2013; 48: 1897-1902 [PMID: 24074664 DOI: 10.1016/ j.jpedsurg.2012.12.038] Nesvaderani M, Eslick GD, Vagg D, Faraj S, Cox MR. Epide miology, aetiology and outcomes of acute pancreatitis: A retrospective cohort study. Int J Surg 2015; 23: 68-74 [PMID: 26384834 DOI: 10.1016/j.ijsu.2015.07.701] Gooby Toedt DM, Byrd JC, Omori D. Coxsackievirus-associated pancreatitis mimicking metastatic carcinoma. South Med J 1996; 89: 441-443 [PMID: 8614892] Ozsvár Z, Deák J, Pap A. Possible role of Coxsackie-B virus infection in pancreatitis. Int J Pancreatol 1992; 11: 105-108 [PMID: 1318913] Akuzawa N, Harada N, Hatori T, Imai K, Kitahara Y, Sakurai S, Kurabayashi M. Myocarditis, hepatitis, and pancreatitis in a patient with coxsackievirus A4 infection: a case report. Virol J 2014; 11: 3
12
13
14 15
[PMID: 24410962 DOI: 10.1186/1743-422X-11-3] Liu B, Li Z, Xiang F, Li F, Zheng Y, Wang G. The whole genome sequence of coxsackievirus B3 MKP strain leading to myocarditis and its molecular phylogenetic analysis. Virol J 2014; 11: 33 [PMID: 24555514 DOI: 10.1186/1743-422X-11-33] Precechtelova J, Borsanyiova M, Sarmirova S, Bopegamage S. Type I diabetes mellitus: genetic factors and presumptive enteroviral etiology or protection. J Pathog 2014; 2014: 738512 [PMID: 25574400 DOI: 10.1155/2014/738512] Tauriainen S, Oikarinen S, Oikarinen M, Hyöty H. Enteroviruses in the pathogenesis of type 1 diabetes. Semin Immunopathol 2011; 33: 45-55 [PMID: 20424841 DOI: 10.1007/s00281-010-0207-y] Cordey S, Petty TJ, Schibler M, Martinez Y, Gerlach D, van Belle S, Turin L, Zdobnov E, Kaiser L, Tapparel C. Identification of sitespecific adaptations conferring increased neural cell tropism during human enterovirus 71 infection. PLoS Pathog 2012; 8: e1002826 [PMID: 22910880 DOI: 10.1371/journal.ppat.1002826] P- Reviewer: Hauser G, Jafari T, Meshikhes AWN, Tovey FI S- Editor: Qi Y L- Editor: A E- Editor: Ma S
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Published by Baishideng Publishing Group Inc 8226 Regency Drive, Pleasanton, CA 94588, USA Telephone: +1-925-223-8242 Fax: +1-925-223-8243 E-mail: [email protected] Help Desk: http://www.wjgnet.com/esps/helpdesk.aspx http://www.wjgnet.com
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Submit a Manuscript: http://www.wjgnet.com/esps/ Help Desk: http://www.wjgnet.com/esps/helpdesk.aspx DOI: 10.3748/wjg.v22.i6.2149
© 2016 Baishideng Publishing Group Inc. All rights reserved.
CASE REPORT
Pancreatitis in hand-foot-and-mouth disease caused by enterovirus 71 Yu-Feng Zhang, Hui-Ling Deng, Jia Fu, Yu Zhang, Jian-Qiang Wei Yu-Feng Zhang, Hui-Ling Deng, Jia Fu, Yu Zhang, Department Second of Infectious Diseases, Xi′an Children′s Hospital, Xi′an 710003, Shaanxi Province, China
Published online: February 14, 2016
Jian-Qiang Wei, Department of Radiology, Xi′an Children′s Hospital, Xi′an 710003, Shaanxi Province, China
Abstract Some viruses, including certain members of the entero virus genus, have been reported to cause pancreatitis, especially Coxsackie virus. However, no case of human enterovirus 71 (EV71) associated with pancreatitis has been reported so far. We here report a case of EV71-induced hand-foot-and-mouth disease (HFMD) presenting with pancreatitis in a 2-year-old girl. This is the first report of a patient with acute pancreatitis in HFMD caused by EV71. We treated the patient conservatively with nasogastric suction, intravenous fluid and antivirals. The patient’s symptoms improved after 8 d, and recovered without complications. We conclude that EV71 can cause acute pancreatitis in HFMD, which should be considered in differential diagnosis, especially in cases of idiopathic pancreatitis.
Author contributions: Fu J and Zhang Y collected the patient’s clinical data; Wei JQ provided the CT image; Zhang YF and Deng HL analyzed the data and wrote the paper. Institutional review board statement: This article was reviewed and approved by the Institutional Review Board of Xi′ an Children′s Hospital with protocol number 2015-014. Informed consent statement: We have requested waiver of informed consent from the legal guardian of the patient for this report. Conflict-of-interest statement: The authors declare no conflict of interest related to this report. Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/ licenses/by-nc/4.0/
Key words: Pancreatitis; Enterovirus 71; Hand, foot and mouth disease © The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
Core tip: Acute pancreatitis associated with enterovirus 71 (EV71) infection is extremely rare. We here report a case of EV71-induced hand-foot-and-mouth disease (HFMD) presenting with pancreatitis in a 2-year-old girl. This is the first case report of acute pancreatitis associated with EV71 infection. EV71 can cause acute pancreatitis in HFMD, which should be considered in differential diagnosis, especially in cases of idiopathic pancreatitis.
Correspondence to: Dr. Hui-Ling Deng, Department Second of Infectious Diseases, Xi′an Children′s Hospital, 69 Xijuyuanxiang, Lianhu District, Xi′an 710003, Shaanxi Province, China. [email protected] Telephone: +86-29-87692204 Fax: +86-29-87692009 Received: October 15, 2015 Peer-review started: October 15, 2015 First decision: November 5, 2015 Revised: November 18, 2015 Accepted: December 8, 2015 Article in press: December 8, 2015
WJG|www.wjgnet.com
Zhang YF, Deng HL, Fu J, Zhang Y, Wei JQ. Pancreatitis in hand-foot-and-mouth disease caused by enterovirus 71. World
2149
February 14, 2016|Volume 22|Issue 6|
Zhang YF et al . Pancreatitis in hand-foot-and-mouth disease J Gastroenterol 2016; 22(6): 2149-2152 Available from: URL: http://www.wjgnet.com/1007-9327/full/v22/i6/2149.htm DOI: http://dx.doi.org/10.3748/wjg.v22.i6.2149
INTRODUCTION Enterovirus 71 (EV71) is a human enterovirus in the Enterovirus genus of the Picornaviridae family. Many of the EV71-infected cases have occurred in AsiaPacific region, and posed a serious threat to children’s [1] health . EV71 primarily causes hand-foot-and-mouth disease (HFMD) in young children, and many neurolo gical complications such as encephalitis, brain stem encephalitis and fatal pulmonary edema occur occa [2] sionally . However, no EV71-associated pancreatitis has been reported so far. We here describe a case of EV71-induced HFMD presenting with pancreatitis in a 2-year-old girl.
Figure 1 Adominal computed tomography showed acute pancreatitis with swelling of the pancreas and peri-pancreatic exudation. No cholelithiasis or tumor occluding the common bile duct or pancreatic duct was observed (arrow).
hospitalization were performed and the results were as follows: real-time reverse transcription PCR (RT-PCR) in a stool sample was positive for EV71, but negative for Coxsackie virus A16, and antibody titer against EV71 was markedly elevated and it was quadrupled during the recovery period. Ultrasonography of the abdomen revealed neither gallstones nor biliary sludge. Abdominal computed tomography (CT) showed acute pancreatitis with swelling of the pancreas, and peri-pancreatic exudation. No cholelithiasis or tumor occluding the common bile duct or pancreatic duct was observed (Figure 1). Magnetic resonance cholangiopancreatography (MRCP) performed in another hospital revealed peri-pancreatic exudation and no anatomical abnormalities in the pancreas or pancreatic duct. The girl was treated conservatively with nasogastric suction, intravenous fluid and antivirals. She was administered Cimetidine (0.15 g b.i.d.), antibiotics (Cefminox, 0.4 g q8h, iv), and antiviral agent (Leigh Bhave Lin, 0.15 g qd, iv). The patient’s symptoms improved after 8 d, and recovered without complications. On the day of discharge, all serum biochemical tests were normal. Two months later, findings on the abdominal CT scan were normal, all laboratory values were within the normal ranges, and the rashes had disappeared, and no further damage was observed. One year after follow-up, the patient was asymptomatic and showed no evidence of pancreatitis recurrence.
CASE REPORT A 2-year-old girl was admitted to our hospital in June 2014 because of acute abdominal pain and vomiting for 2 d. Vomiting occurred about ten times a day. Moreover, 4 d before admission, maculopapular rashes had appeared on her hip and then spread to the palms of her hands and feet over the following 2 d, and she also had fever during the 4 d before admission. Her past medical history showed no record of pancreatitis and her family history was negative for pancreatic disease. A physical examination on admission revealed a normal blood pressure, temperature, pulse rate, and breathing rate. Maculopapular rashes on her hip, palms and feet and vesicles in mouth cavity membrane were observed. Breathing sounds were clear on auscultation. Abdominal examination revealed only mild abdominal tenderness. No other abnormalities were found. Of note, she had not taken any drugs before admission. On admission, her chest X-ray and electrocar diogram were both normal. A complete blood count, calcitonin and blood biochemical tests including C-reactive protein, glucose, bilirubin, triglycerides and calcium, were all within reference limits. The total levels of IgG, IgA and IgM in blood were normal. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were slightly elevated (ALT: 64 IU/L; AST: 68 IU/L; reference range: 10-35 IU/L), and serum amylase (385 IU/L; reference range: 0-220 IU/L) and urine amylase (5300 IU/L; reference range: 0-1200 IU/L) were also increased. Serological tests of various infectious agents including Epstein-Barr virus, varicella zoster virus, cytomegalovirus, HIV Ⅰ and Ⅱ, hepatitis A, B and C viruses, echoviruses, syncytial virus, flu virus A and B, parainfluenza 1, 2 and 3, and adenovirus were all negative. Tumor markers were also negative. Other relevant tests and examinations during
WJG|www.wjgnet.com
DISCUSSION We have presented a case of EV71 infection associated with pancreatitis secondary to HFMD. EV71 was established as the causative pathogen of pancreatitis in this case based on the following evidence: EV71 positivity, negative history of alcoholic and drug use, no gallstones, no anatomical abnormalities in the pancreas or pancreatic duct, normal level of triglyceride and calcium, negative serological tests for other infectious agents, and presence of characteristic rash
2150
February 14, 2016|Volume 22|Issue 6|
Zhang YF et al . Pancreatitis in hand-foot-and-mouth disease on hip, palms and feet. Based on these observations, it is tempting to speculate that the EV71 is the most likely pathogenic factor for pancreatitis in this case. Acute pancreatitis can be triggered by a variety of etiologies. Gallstones and alcohol are the most [3] common causes of acute pancreatitis in adults . However, the etiology in children is often drugs, infection, trauma, genetic mutation, and congenital structural abnormalities such as choledochal cysts and [4,5] abnormal union of the pancreatobiliary junction . The most common infections are mumps, viral hepatitis, [6] Coxsackie virus and echovirus . At present, among anomalies of the pancreatobiliary system, choledochal [7] cyst is the most common cause of acute pancreatitis . Some acute pancreatitis cases without a detectable [8] cause are considered as “idiopathic” . Viral etiology may be involved in idiopathic acute pancreatitis. The Enterovirus genus is part of the large Picornaviridae family, and is known to be highly cytolytic. The species are small non-enveloped RNA viruses and the most common viruses causing human diseases. EV71 belongs to the Enterovirus genus in the Picornaviridae family, and has been recognized as one of the most important viral pathogens. EV71 infection causes countless diseases ranging from mild HFMD or herpangina to fatal brain stem encephalitis complicated with pulmonary edema, and has become a serious threat to children’s health. So far, no EV71-associated pancreatitis has been reported, but Coxsackievirus A and B have been reported to be causative pathogens [9-11] [12,13] of pancreatitis and type 1 diabetic mellitus . Studies have suggested the presence of enteroviruses in pancreatic tissue including the pancreatic islets of [14] type 1 diabetic patients . Coxsackievirus has been [13] shown to replicate and destroy human β-cells . But to the best of our knowledge, EV71-induced pancreatitis is quite rare, and our patient presented no other severe complications except for acute pancreatitis. A previous study analyzing the EV71 genome obtained from an immunocompromised host showed various EV71 lineages and indicated that a mutation in the VP1 BC loop region of EV71 (L97R) may play a critical [15] role in cell tropism independent of the EV71 lineage . The mechanism of pancreatitis associated with EV71 is still unknown; EV71 might injure the pancreatic acinar cell membrane, leading to the leakage of intracellular enzymes, and at the same time, some other factors such as pancreatitis-related genetic susceptibility genes and virulence determinants in the genotype of the infecting strain should also be considered. Therefore, a multi-disciplinary approach is required to extend our understanding of this complex relationship. In conclusion, EV71 can cause acute pancreatitis in HFMD, which should be considered in the differential diagnosis, especially in cases of idiopathic pancreatitis. It is important to screen the patients with acute pancreatitis for EV71 infections.
WJG|www.wjgnet.com
COMMENTS COMMENTS Case characteristics
A 2-year-old girl presented with acute abdominal pain and vomiting for 2 d after the onset of rashes appearing on her hip, hands and feet.
Clinical diagnosis
Abdominal pain and vomiting, elevated level of urine and serum amylase concentration, magnetic resonance cholangiopancreatography (MRCP) and computed tomography (CT) findings of peri-pancreatic exudation and swelling.
Differential diagnosis
Gallstone-induced pancreatitis or pancreatic tumor.
Laboratory diagnosis
Serum amylase, 385 IU/L; urine amylase, 5300 IU/L.
Imaging diagnosis
MRCP and CT showed acute pancreatitis with swelling of the pancreas and peri-pancreatic exudation.
Treatment
The girl was treated conservatively with nasogastric suction, intravenous fluid, and antivirals.
Related reports
Reports of acute pancreatitis associated with enterovirus 71 (EV71) are rare, and only Coxsackie virus-related pancreatitis has been reported.
Experiences and lessons
EV71 can cause hand-foot-and-mouth disease (HFMD) with complications of acute pancreatitis, which should be noticed in differential diagnosis, especially in cases of idiopathic pancreatitis.
Peer-review
This interesting case is the first report of acute pancreatitis associated with EV71-related HFMD. The authors describe the clinical features, physical examination, laboratory findings, and MRCP and CT imaging in this case. Although the mechanism of pancreatitis associated with EV71 is unknown, suspected cases should be confirmed and treated as early as possible.
REFERENCES 1 2
3
4
5 6
2151
Wong SS, Yip CC, Lau SK, Yuen KY. Human enterovirus 71 and hand, foot and mouth disease. Epidemiol Infect 2010; 138: 1071-1089 [PMID: 20056019 DOI: 10.1017/S0950268809991555] Solomon T, Lewthwaite P, Perera D, Cardosa MJ, McMinn P, Ooi MH. Virology, epidemiology, pathogenesis, and control of enterovirus 71. Lancet Infect Dis 2010; 10: 778-790 [PMID: 20961813 DOI: 10.1016/S1473-3099(10)70194-8] Pulkkinen J, Kastarinen H, Kiviniemi V, Jyrkkä J, Juvonen P, Räty S, Paajanen H. Statin use in patients with acute pancreatitis and symptomatic gallstone disease. Pancreas 2014; 43: 638-641 [PMID: 24632548 DOI: 10.1097/MPA.0000000000000068] Rai P, Sharma A, Gupta A, Aggarwal R. Frequency of SPINK1 N34S mutation in acute and recurrent acute pancreatitis. J Hepatobiliary Pancreat Sci 2014; 21: 663-668 [PMID: 24844923 DOI: 10.1002/jhbp.111] Pohl JF, Uc A. Paediatric pancreatitis. Curr Opin Gastroenterol 2015; 31: 380-386 [PMID: 26181572 DOI: 10.1097/MOG.00000 00000000197] Parenti DM, Steinberg W, Kang P. Infectious causes of acute pancreatitis. Pancreas 1996; 13: 356-371 [PMID: 8899796]
February 14, 2016|Volume 22|Issue 6|
Zhang YF et al . Pancreatitis in hand-foot-and-mouth disease 7
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February 14, 2016|Volume 22|Issue 6|
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