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ACG Case Reports Journal | Volume 1 | Issue 1
October 2013
An online journal of case reports edited by GI fellows
Editor-in-Chief: Mohammad Yaghoobi, MD, MSc, AFS
acgcasereports.gi.org
ACG
ABOUT THE JOURNAL
CASE REPORTS JOURNAL
acgcasereports.gi.org
EDITORIAL BOARD
PUBLICATION
Editor in Chief
Mohammad Yaghoobi, MD, MSc, AFS
Medical University of South Carolina, Charleston, SC
ACG Case Reports Journal is published online each quarter, and issues feature
images, video clips, and multimedia content in addition to case descriptions. As
an open-access publication, full-text articles are freely accessible for all readers
in both HTML and PDF format immediately upon online publication. There is no
print version of the Journal, but issue articles will be collated into an easily downloadable PDF for offline viewing and printing. ACG Case Reports Journal does not
charge submission or publication fees for authors.
Executive Editor
Manish Singla, MD
Walter Reed National Military Medical Center, Bethesda, MD
Associate Editors
Daniel E. Freedberg, MD
Columbia University Medical Center, New York, NY
Nazia Hasan, MD, MPH
New York University School of Medicine, New York, NY
Ryan Law, DO
Mayo Clinic, Rochester, MN
Kalyan Ray Parashette, MD
Indiana University School of Medicine, Indianapolis, IN
Andres J. Yarur, MD
University of Miami Miller School of Medicine, Miami, FL
EDITORIAL STAFF
Lindsey Topp
Editorial Advisor
Jenny Dunnington
Editorial Assistant
Theresa Bongorno
Graphic Designer
AIMS AND SCOPE
ACG Case Reports Journal, published by the American College of Gastroenterology and edited exclusively by GI fellows, provides a peer-reviewed publishing outlet for GI fellows, private practice clinicians, and other members of the healthcare
team to share interesting case reports. This quarterly, open-access publication
will make all content freely available online to all readers. ACG Case Reports
Journal publishes case reports, images, and letters to the editor in all topics of
gastroenterology and hepatology.
The ACG Case Reports Journal was created to help fulfill ACG’s commitment
to providing growth and learning opportunities for GI fellows, and helps fellows
meet core curriculum requirements for non-patient care activities. To this end, all
case submissions must have a GI fellow as the lead author. Cases authored by
private practice clinicians and other members of the health care team who might
traditionally face difficulty publishing with leading journals are also welcome.
PUBLISHER INFORMATION
Founded in 1932, the American College of Gastroenterology (ACG) is an organization with an international membership of more than 12,000 individuals from
86 countries. The College is committed to serving the clinically oriented digestive
disease specialist through its emphasis on scholarly practice, teaching and
research. The mission of the College is to serve the evolving needs of physicians
in the delivery of high quality, scientifically sound, humanistic, ethical, and costeffective health care to gastroenterology patients.
American College of Gastroenterology
6400 Goldsboro Road, Suite 200
Bethesda, MD 20817
Phone: 301-263-9000
Fax: 301-263-9025
[email protected]
EISSN: 2326-3253
PREPARING FOR SUBMISSION
Manuscripts must be submitted online at mc.manuscriptcentral.com/acgcr.
Questions regarding submission or site access should be sent to [email protected]. The ACG Case Reports Journal recommends that submitted
manuscripts follow the general recommendations put forth by the ICMJE Uniform
Requirements for Manuscripts.
PERMISSIONS
Authors are required to obtain permission to reproduce previously copyrighted
materials from other sources in both print and electronic form. For questions
regarding permissions for manuscripts published in ACG Case Reports Journal,
please contact [email protected].
ETHICS AND JOURNAL CONFLICT OF INTEREST
Authors must disclose all conflicts of interest, financial and otherwise, upon
manuscript submission. Each year, the Editors publicly disclose their conflicts of
interest on the ACG Case Reports Journal website.
When reporting on human or animal subjects, authors must state whether the
work was approved by a local IRB or ethics committee, or in accordance with the
Helsinki Declaration of 1975, as revised in 2008. Efforts should always be made
to guarantee protection of patient privacy in submitted cases.
OPEN ACCESS AND CREATIVE COMMONS LICENSING
Following the open-access model, ACG Case Reports Journal makes all
published content freely available to all readers immediately upon publication,
without subscription or membership fees.
ACG Case Reports Journal content is licensed according to the Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 Unported license,
under which users are free to share (copy, distribute and transmit) the contribution under the following conditions:
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For any reuse or distribution, users must make clear to others the license terms
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Manuscripts, either in whole or in part, must not be submitted to or previously
published in any other journal or as an abstract associated with any meeting.
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If your funding bodies and/or institution requires authors to self-archive articles
in publicly accessible archives, then authors are responsible for depositing the
accepted version of their manuscript into such an archive.
ACG Case Reports Journal will register for indexing on PubMed as soon as possible.
© American College of Gatstroenterology
TABLE OF CONTENTS
ACG Case Reports Journal | Volume 1 | Issue 1
October 2013
Letter
from the Editor
____________________________________________________________
1
A New ACG Journal is Born
Mohammad Yaghoobi, MD, MSc, AFS
Images
____________________________________________________________
Contrast injection through percutaneous abscess
drain showing communication between abscess,
left biliary system, and extravasation of contrast
resulting from emphysematous cholecystitis after
ERCP. (Image from Bari et al, page 51.)
2
Massive Gastric Dilatation Secondary to Internal Hernia
Obstructing the Biliary Intestinal Limb of Whipple Procedure
Pranav Patel, MD, Nisarg Patel, MD, Antwan Atia, MD, Ravindra Murthy, MD,
and Mark Young, MD
3
Small Bowel Metastasis from Renal Cell Carcinoma Identified
on Capsule Endoscopy
Daniel L. Cohen
Case
Reports
____________________________________________________________
4
7
Embedded Fishhook in the Gastric Cardia: Novel Removal Utilizing
Electrocautery Needle-Knife Dissection
Jason Colizzo, MD, Jonathan Keshishian, MD, and Patrick Brady, MD, FACG
Hemospray for Life-Threatening Ulcer Bleeding: First Case Report in the
United States
Peter J. Sargon, MD, and Timothy J. Laurie, DO
10 Endoscopic Mucosal Resection of a Large Gastric Metastasis from Renal Cell
Carcinoma
Richa Chibbar, MD, Julinor Bacani MD, and Sergio Zepeda-Gómez, MD
13 Iron Pill–Induced Gastritis
Jana G. Hashash, MD, Siobhan Proksell, MD, Shih-Fan Kuan, MD, and
Jaideep Behari, MD, PhD
16 A Case of Persistent Helicobacter pylori Infection Occurring with Anti-IgE
Immunosuppression
Daniel Zandman, MD, William Hahn, MD, and Steven Moss, MD
Massive gastric distention measuring 15 cm
transversely, 14 cm antero-posteriorly, and 35 cm
craniocaudally. (Image from Patel et al, page 2.)
19 Kaposi’s Sarcoma: An Unusual Cause of Gastric Outlet Obstruction
Sandra Rodriguez, MD, Jorge Zapatier, MD, Daniela Allende, MD, and Alison
Schneider, MD
22 Intestinal Pseudo-Obstruction and Total Villous Atrophy of the Terminal
Ileum: An Unusual Presentation of Untreated Celiac Disease
Eran C. Gwillim, BS, and Brad A. Bowyer, MD, FACG
acgcasereports.gi.org
TABLE OF CONTENTS
ACG Case Reports Journal | Volume 1 | Issue 1
October 2013
Case
Reports
____________________________________________________________
25 Nearly Fatal Case of Whipple’s Disease in a Patient Mistakenly on Anti-TNF Therapy
Christen Klochan, MD, Teresa A. Anderson, MD, Dusten Rose, MD, Rosen K.
Dimitrov, MD, and Raymond M. Johnson, MD
29 True versus Pseudo-Intestinal Malrotation: Case Series and Review
Harshit S. Khara, MD, Shivangi T. Kothari, MD, Claudia B. Gruss, MD, Alan
Langnas, DO, Daniel F. Schafer, MD, and Timothy M. McCashland, MD
33 Beware of the Patient with Thymectomy: Good’s Syndrome in a Patient
Presenting with Diarrhea
Ken Liu, MBBS, BSc, and James L. Cowlishaw, MBBS
MR abdomen of child with vsceral leishmania
demonstrates marked splenomegaly with diffuselylow intensity lesions (thick arrow). Rounded soft
tissue structures at the splenic hilum containing
numerous low intensity lesions (thin arrow). (Image from Absah et al, page 61.)
36 Giant Inflammatory Fibroid Polyp of the Descending Colon Treated with
Endoscopic Resection
Ammar Kayyali, MD, Anis Toumeh, MD, Usman Ahmad, MD, Luis E. De Las
Casas, MD, and Ali Nawras, MD, FACG
40 Not Your Everyday Case of Acute Pancreatitis: A Rare Complication of a
Common Diagnosis
Parth J. Parekh, MD, Douglas Howerton, MD, and David A. Johnson, MD, FACG
44 Portal Biliopathy Causing Recurrent Biliary Obstruction and Hemobilia
Barry Schlansky, MD, MPH, John A. Kaufman, MD, MS, Gene Bakis, MD, and
Willscott E. Naugler, MD
47 Minor Papilla Adenoma Management in Patients with Pancreas Divisum and
Familial Adenomatous Polyposis
Robert T. Lapp, MD, and Grant F. Hutchins, MD
51 Emphysematous Cholecystitis Resulting in Secondary Biliary Cirrhosis: A
Rare Complication of Endoscopic Retrograde Cholangiopancreatography
Khurram Bari, MD, Harry R. Aslanian, MD, Jeffrey Pollak, MD, Eric Reiner,
MD, Ronald R. Salem, MD, Tamar H. Taddei, MD, Sukru H. Emre, MD, and
Priya A. Jamidar, MD
55 Hepatotoxicity Associated with Herbal Tea Containing Kelp
Lavanya Viswanathan, MD, MS, and Anish Patel, DO
Electron microscopy of lymph node tissue
(43,600x magnification) of patient with advanced
Whipple’s disease. Arrow highlights a rod-shaped
bacterium consistent with Trophyrema whipplei.
(Image from Klochan et al, page 25.)
58 Tea not Tincture: Hepatotoxicity Associated with Rooibos Herbal Tea
Michael Engels, MD, Charles Wang, MD, Andres Matoso, MD, Eyal Maidan,
MD, and Jack Wands, MD
61 Visceral Leishmania as Unusual Cause of Splenic Peliosis in the United States
Youssef Ghazzawi, MD, and Imad Absah, MD
64 Conjugated Hyperbilirubinemia in a Child with Streptococcus pneumoniae
Hemolytic Uremic Syndrome
Mohini Gautam Patel, MD, and Anthony F. Porto, MD
acgcasereports.gi.org
ACG CASE REPORTS JOURNAL
LETTER FROM THE EDITOR
A new ACG journal is born.
I am very pleased to announce the launch of the ACG
Case Reports Journal. At ACG, we acknowledge the unmet need for a journal easily accessible to GI fellows and
new gastroenterologists who are eager to contribute to the
expanding field of GI literature. To fill that need, we created the ACG Case Reports Journal, the first GI journal to
be fully edited by GI fellows and open primarily to authors
still in their GI training. Our editorial board consists of a
group of brilliant GI fellows who are fully committed to the
success of this venture and to preparing themselves for
potential future leadership positions in similar fields.
It is with great pleasure that we launch this first issue of the Journal after several months
of effort by the Editorial Board, editorial office staff, our peer reviewers, and the ACG
Publications Committee. I would like to thank all involved, especially our reviewers,
who have enthusiastically volunteered to help despite their busy training schedules.
This first issue would not have been possible without your fascinating and high-quality
case submissions. We are proud that our initial announcement was extremely well received among GI trainees and others in the field. We received an impressive number
of submissions, and currently have an outstanding acceptance rate of approximately
20%.
I invite all interested GI fellows to consider submitting an interesting case report or image to the ACG Case Reports Journal or to sign up as a peer reviewer. Please explore
our website (acgcasereports.gi.org) for more information on how to get involved. I hope
you enjoy reading our very first issue, and I welcome your thoughts.
Mohammad Yaghoobi, MD, MSc, AFS
Editor-in-Chief
ACG Case Reports Journal
ACG Case Rep J 2013;1(1):1. doi:10.14309/crj.2013.1. Published online: October 8, 2013.
Copyright: © 2013 ACG Case Reports Journal. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which
permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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ACG Case Reports Journal | Volume 1 | Issue 1 | October 2013
ACG CASE REPORTS JOURNAL
IMAGE | STOMACH
Massive Gastric Dilatation Secondary to Internal Hernia
Obstructing the Biliary Intestinal Limb of Whipple Procedure
Pranav Patel, MD1, Nisarg Patel, MD3, Antwan Atia, MD1, Ravindra Murthy, MD2, and Mark
Young, MD1
Department of Gastroenterology, Quillen College of Medicine, East Tennessee State University, Johnson City, TN
Department of Gastroenterology, James H. Quillen VA Medical Center, Mountain Home, TN
3
Montgomery Family Medicine Residency Program, Montgomery, AL
1
2
Case Report
A 59-year-old woman with history of pylorus-preserving pancreaticoduodenectomy for pancreatic hamartoma
and partial colectomy for sigmoid volvulus presented with nausea, vomiting, constipation, sharp constant midabdominal pain, and abdominal distension for 2 days. She had tachycardia and diffuse mild abdominal tenderness with hypoactive bowel sounds. Lab revealed WBC of 14.1K/μL and creatinine of 2.62 mg/dL. Nasogastric
tube placement yielded 4,000 mL of bilious fluid in the first hour. Computed tomography (CT) scan of the abdomen with oral contrast demonstrated a massively distended stomach extending into the pelvis, measuring 15 cm
transversely, 14 cm antero-posteriorly, and 35 cm craniocaudally (Figure 1). Small bowel follow-through study
performed 48 hours later did not show any obstructive pathology. Patient responded to conservative management and was discharged home.
Six weeks later, the patient readmitted with similar presentation. CT scan showed partial bowel obstruction in the
mid-anterior abdomen, possibly involving multiple segments of small bowel and a portion of colon. As she did
not respond to 10 days of conservative management, laparotomy was performed, which revealed small bowel
closed loop obstruction due to internal hernia, obstructing the biliary limb of Whipple procedure adjacent to the
gastrojejunostomy. Release of small bowel obstruction was performed, followed by over-sewing of the biliary limb
serosa and closure of the internal hernia. The patient was discharged on post-operative day 7.
Disclosures
Author contributions: P. Patel designed the case report, collected the information, and is the guarantor of
the article. P. Patel, N. Patel, and A. Atia jointly interpreted the information and wrote the article. R. Murthy
and M. Young supervised and edited the article. All
authors discussed the case and commented on the
article at all stages.
Financial disclosure: The authors have no relevant
financial relationships to disclose for this article.
Figure 1. Massive gastric distention shown on CT.
Received: July 18, 2013; Accepted: August 30, 2013
ACG Case Rep J 2013;1(1):2. doi:10.14309/crj.2013.2. Published online: October 8, 2013.
Correspondence: Pranav Patel, MD, ETSU Quillen College of Medicine, 1008 Quality Cir #71, Johnson City, TN 37615 ([email protected])
Copyright: © 2013 Patel et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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ACG Case Reports Journal | Volume 1 | Issue 1 | October 2013
ACG CASE REPORTS JOURNAL
IMAGE | SMALL BOWEL
Small Bowel Metastasis from Renal Cell Carcinoma Identified
on Capsule Endoscopy
Daniel L. Cohen, MD
Gastrointestinal Diagnostic Centers, Pembroke Pines, FL
An elderly man presented with iron deficiency anemia and intermittent rectal bleeding. His past medical history
was significant for a renal cell carcinoma resected 9 years earlier. After a colonoscopy and upper endoscopy
were unremarkable, he underwent a small bowel capsule endoscopy, which revealed an ulcerated mass in the
jejunum (Figure 1 and Video 1). Surgical resection was performed, and the pathology revealed metastatic renal
cell carcinoma, clear cell type (Figure 2). The pathology was compared to the tumor from the patient’s prior nephrectomy and was found to be identical. While renal cell carcinoma only accounts for 7% of metastases to the
small bowel,1 these have occurred even up to 20 years after initial surgery.2 This case highlights the benefits of
capsule endoscopy in the diagnosis of small bowel lesions, including metastatic renal cell carcinoma.1,2
Figure 2. Histology of the jejunal mass confirms a renal cell carcinoma,
clear cell type.
Video 1. Small bowel video capsule endoscopy shows an ulcerated
mass in the jejunum, which proved to be a renal cell carcinoma metastasis. Please view video at http://acgcasereports.gi.org/?p=329.
Figure 1. An ulcerated mass is seen in the jejunum on small bowel
capsule endoscopy.
Disclosures
References
1.
2.
Vashi PG, Abboud E, Gupta D. Renal cell carcinoma with unusual metastasis to the small intestine manifesting as extensive
polyposis: Successful management with intraoperative therapeutic endoscopy. Case Rep Gastroenterol. 2011;5(2):471-8.
Vazquez C, Berrueta J, De Simone F, et al. Small-intestinalbleeding due to metastatic renal cell cancer. Endoscopy.
2011;43(suppl 2):E13.
Author contributions: D.L. Cohen completed all aspects
of article creation and is the guarantor of the article.
Financial disclosure: No financial support was received.
The author declares that there are no conflicts of interest.
Received: July 19, 2013; Accepted: August 30, 2013
ACG Case Rep J 2013;1(1):3. doi:10.14309/crj.2013.3. Published online: October 8, 2013.
Correspondence: Daniel L. Cohen, MD, 2245 N. University Drive, Pembroke Pines, FL 33024 ([email protected])
Copyright: © 2013 Cohen. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted
use, distribution, and reproduction in any medium, provided the original author and source are credited.
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ACG Case Reports Journal | Volume 1 | Issue 1 | October 2013
ACG CASE REPORTS JOURNAL
CASE REPORT | ENDOSCOPY
Embedded Fishhook in the Gastric Cardia: Novel Removal
Utilizing Electrocautery Needle-Knife Dissection
Jason Colizzo, MD1, Jonathan Keshishian, MD2, and Patrick Brady, MD, FACG2
University of South Florida Morsani College of Medicine, Department of Internal Medicine, Tampa, FL
University of South Florida Morsani College of Medicine, Department of Internal Medicine, Division of
Gastroenterology, Tampa, FL
1
2
Abstract
Foreign body ingestions often consist of benign objects that will readily pass through the gastrointestinal tract
(GI) without necessitating further intervention. While several retrieval devices and techniques are available to the
endoscopist, we present a novel method of implementing a needle-knife sphincterotome in the removal of an
ingested fishhook embedded in the gastric cardia of a 36-year-old man with underlying schizophrenia. The hook
was successfully dissected from the gastric submucosa after several unsuccessful attempts at manual extraction with forceps. To our knowledge, our case represents one in only a handful of other reports of the successful
removal of ingested foreign bodies utilizing this method.
Introduction
Foreign body ingestion is a relatively common occurrence. For most cases, a conservative approach will often
be the preferred course of management. For approximately 10–20% of cases, endoscopy will be required.1 In
such cases, removal of the object is necessary to avoid prolonged mucosal damage, perforation, obstruction,
and other potential complications.2 These complications can occur in as many as 35% of cases involving sharp
pointed objects, and will sometimes necessitate surgical intervention.2 While there are several devices available
to aid in the removal of such objects, we present a case incorporating the novel use of a needle-knife sphincterotome to free a fishhook embedded within the gastric wall.
Case Report
A 36-year-old man with a history of paranoid schizophrenia and prior foreign body ingestions presented to our
service with hematemesis shortly following the ingestion of two fishhooks. An abdominal x-ray revealed one hook
in the stomach near the gastroesophageal junction and another near the terminal ileum, which subsequently
passed without complication (Figure 1).
Esophagogastroduodenoscopy (EGD) was performed, revealing a fishhook with the barbed end firmly embedded
in the gastric cardia. The hook was rotated using rat tooth forceps so that the barb protruded into the lumen
(Figure 2). After failed attempts at manual extraction, a needle-knife sphincterotome was implemented to incise
the overlying mucosa and submucosa to free the embedded segment of the hook (Figure 3). Bleeding at the
dissection site was not adequately controlled with electrocautery provided by the sphincterotome. Hemostasis
was ultimately achieved with the Gold Probe at 20 W. Estimated blood loss was 15–20 mL. The remainder of the
stomach and duodenum were normal. The patient tolerated the procedure well and was eventually discharged
home in stable condition.
ACG Case Rep J 2013;1(1):4–6. doi:10.14309/crj.2013.4. Published online: October 8, 2013.
Correspondence: Jason Colizzo, MD, University of South Florida Morsani College of Medicine, Department of Internal Medicine, Tampa, FL 33612
([email protected])
Copyright: © 2013 Colizzo et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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ACG Case Reports Journal | Volume 1 | Issue 1 | October 2013
Colizzo et al
Needle-Knife Sphincterotome Removal of Fish Hook
servatively by allowing the object to pass naturally through
the GI tract.3 The remainder of cases can be successfully
managed endoscopically with only a minority (<1%) requiring surgery.3 For our patient, the object was firmly embedded within the gastric submucosa, which precluded extraction with more conventional methods.
The use of a needle-knife sphincterotome allowed for
successful dissection of a foreign object that would have otherwise likely required surgical intervention. While the overlying mucosal and submucosal layers were easily dissected
utilizing this technique, future cases of similarly embedded
objects may benefit from evaluation with endoscopic ultrasonography to first establish depth of penetration. The use
of submucosal injection may also add to patient safety and
minimize potential complications such as perforation.
Figure 1. X-ray revealing one hook in the stomach near the gastroesophageal junction and another near the terminal ileum.
Discussion
There are numerous techniques available to the endoscopist
in the management of foreign body ingestion. Some of the
most widely accepted devices include snares, baskets, forceps, and other grasping devices.3 Approximately 80% of
cases involving foreign body ingestion can be managed con-
Figure 3. Needle-knife sphincterotome incising the overlying mucosa and
submucosa to free the embedded segment of the hook.
Disclosures
Author contributions: J. Colizzo and J. Keshishian contributed to article content. P. Brady is the guarantor of the article.
Financial disclosure: The authors have no financial disclosures nor conflicts interest pertaining to the above study.
Received: June 6, 2013; Accepted: September 10
References
1.
Figure 2. Rat tooth forceps rotating the hook so that the barb protruded
into the lumen.
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Zhao-Shen L, Zhen-Xing S, Duo-Wu Z, et al. Endoscopic management
of foreign bodies in the upper-GI tract: Experience with 1,088 cases in
China. Gastrointest Endosc. 2006;64(4):485–492.
ACG Case Reports Journal | Volume 1 | Issue 1 | October 2013
Colizzo et al
2.
3.
Needle-Knife Sphincterotome Removal of Fish Hook
Ikenberry SO, Jue TL, Anderson MA, et al; for ASGE Standards of
Practice Committee. Management of ingested foreign bodies and food
impactions. Gastrointest Endosc. 2011;73(6):1085–91.
Liao W, Hou M, Lin H, et al. Embedded detachable endoloop after
endoscopic variceal ligation. Endoscopy. 2007;39(suppl 1):E158.
Publish your work in ACG Case Reports Journal
ACG Case Reports Journal is a peer-reviewed, open-access publication that provides GI fellows, private practice clinicians, and other members of the
health care team an opportunity to share interesting case reports with their peers and with leaders in the field. Visit http://acgcasereports.gi.org for
submission guidelines. Submit your manuscript online at http://mc.manuscriptcentral.com/acgcr.
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ACG Case Reports Journal | Volume 1 | Issue 1 | October 2013
ACG CASE REPORTS JOURNAL
CASE REPORT | ENDOSCOPY
Hemospray for Life-Threatening Ulcer Bleeding: First Case
Report in the United States
Peter J. Sargon, MD, and Timothy J. Laurie, DO
Advocate Lutheran General Hospital, Department of Medicine, Division of Gastroenterology, Park Ridge, IL
Abstract
A 13-year-old boy with metastatic rhabdomyosarcoma presented with biliary obstruction requiring ERCP for stent
placement. Re-evaluation after recurrence of symptoms revealed external migration of the stent with formation of
a contralateral wall bleeding duodenal ulcer. Endoscopic therapy was not feasible and bleeding persisted despite
medical therapy and embolization. Given his life-threatening condition, approval for the use of Hemospray (Cook
Medical, Winston-Salem, NC, USA) was obtained. Hemospray was applied to the visualized bleeding sites with
subsequent hemostasis. Patient tolerated the procedure well. This is the first use of Hemospray in the United
States outside of a clinical trial.
Introduction
Acute upper gastrointestinal hemorrhage in the United States accounts for greater than 300,000 annual hospital admissions and a mortality rate of up to 10%.1 At the current time, there are various treatment modalities
approved for the management of upper gastrointestinal bleeding, which include injection (saline, epinephrine,
sclerosants), cautery (heat probes, lasers, argon plasma coagulation, electrocautery), and mechanical therapy
(clips, band ligation).1 In some cases, hemostasis is difficult to achieve and patients may have persistent or
recurrent bleeding. Additionally, there are some instances in which the patient’s anatomy, the location of a
lesion, or severe bleeding makes it difficult to achieve hemostasis with currently available methods. Hemospray
(Cook Medical, Winston-Salem, North Carolina, USA) is an alternative method that is currently undergoing trials and the process of FDA approval. Hemospray is a granular, mineral blend nanopowder with clotting abilities
that increase the concentration of clotting factors, activate platelets, and form a mechanical plug on an injured
blood vessel.2 According to a trial conducted by Sung et al, it has been indicated that Hemospray can be used
for hemostasis of nonvariceal confirmed peptic ulcer bleeding.3 In that study, 20 patients were recruited and
acute hemostasis was achieved in 19 of the 20 patients. The other patient required arterial embolization of a
pseudoaneurysm. Additionally, 2 patients had recurrent bleeding within 72 hours, indicated by a hemoglobin
drop. No active bleeding was identified on repeat upper endoscopy.
Case Report
We report a case in which hemostatic powder was used to treat a patient with profound thrombocytopenia and
recurrent gastrointestinal bleeding secondary to duodenal ulcer disease. The patient was a 13-year-old male with
a medical history significant for metastatic rhabdomyosarcoma with pancreatic head mass. He was referred to
adult gastroenterology in 2010 for a biliary stricture requiring endoscopic retrograde cholagiopancreatography
with sphincterotomy and placement of a biliary stent. Since that time, the patient had undergone multiple stent
exchanges including placement of a fully covered self-expandable biliary metal stent in August 2011. This was
complicated by acute cholecystitis requiring the placement of a cholecystostomy tube. Since the original diagnoACG Case Rep J 2013;1(1):7–9. doi:10.14309/crj.2013.5. Published online: October 8, 2013.
Correspondence: Peter J. Sargon, MD, Advocate Lutheran General Hospital, 1775 Dempster Street,Park Ridge, IL 60068 ([email protected])
Copyright: © 2013 Sargon and Laurie. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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ACG Case Reports Journal | Volume 1 | Issue 1 | October 2013
Hemospray for Upper GI Bleeding
Sargon and Laurie
sis of metastatic rhabdomyosarcoma, the patient had undergone multiple courses of chemotherapy over a 4-year time
period and was in remission for 3 months after undergoing
his most recent course of chemotherapy. However, the patient developed recurrent jaundice, vomiting, and thrombocytopenia. Repeat endoscopic evaluation in February 2012
revealed that the biliary stent had migrated distally and was
embedded in the contralateral wall of the duodenum. A large
bleeding ulcer was identified where the stent was embedded (Figure 1). There was also diffuse erythema and edema
with oozing proximal to this area. Endoscopic therapy with
conventional measures, including epinephrine injection, clip
placement, and cautery, was not feasible secondary to the
extent of bleeding, mucosal edema, and anatomic changes.
gational device exemption for use of hemostatic powder was
appropriate. Once approved, a Cook Medical representative
was flown out to train us on the use of the Hemospray device. The entire process to obtain approval from the time the
letters were written to the time of endoscopy was five days.
Upper endoscopy was then performed revealing erythematous, edematous, friable antral mucosa with a mosaic pattern. An adherent clot was seen at the pyloric channel and
removed with irrigation and aspiration, revealing an oozing
ulcer. The duodenum was also erythematous and edematous. There was diffuse oozing in the antrum and duodenum
along with re-identification of the duodenal ulcer. A total of
25–30 g of hemostatic powder was applied to the duodenal ulcer site, the proximal duodenum, the antrum, and the
pyloric channel site. After application, there was no further
evidence of oozing or active bleeding (Figure 2). The patient
tolerated the procedure well and he was discharged home
6 days later with no further episodes of bleeding. This is the
first use of hemostatic powder for the management of upper gastrointestinal bleeding outside of a clinical trial in the
United States.
Figure 1. Bleeding duodenal ulcer.
The patient was started on intravenous drips of pantoprazole and octreotide. He underwent urgent embolization of the
gastroduodenal artery per interventional radiology. He was
transferred to the pediatric intensive care unit for further
monitoring and treatment. Over the next week, the patient
developed recurrent bleeding despite medical and interventional therapy, requiring multiple blood transfusions.
Additionally, he developed worsening thrombocytopenia requiring platelet transfusions. Surgery evaluated the patient
and deemed him a non-surgical candidate. Given his lifethreatening condition with transfusion dependency, persistent active bleeding and no feasible medical, endoscopic, or
surgical option, we attempted to obtain approval for the use
of hemostatic powder.
An investigational device exemption was obtained to use
hemostatic powder through the appropriate process involving clearance through our institution’s IRB chairperson and
chairman of the Department of Medicine. An additional gastroenterologist, who was not involved in the patient’s care,
reviewed the case to determine whether obtaining an investi8
acgcasereports.gi.org
Figure 2. Hemostasis of bleeding duodenal ulcer after application of
Hemospray.
Discussion
Hemostatic powder is approved for use in Europe and Canada for non-variceal ulcer bleeding and is currently undergoing FDA approval for the same indication in the United
States. At this time, there are no major complications or adverse events associated with the use of hemostatic powder.
There has been concern for embolization if used in variceal
bleeding or larger vessels; however, this has not yet been
encountered. The difficulty that we encountered in using
hemostatic powder was clumping in a moist or wet environment. As part of the standard procedure, the biopsy port of
the endoscope would have to be flushed with an air-filled
ACG Case Reports Journal | Volume 1 | Issue 1 | October 2013
Sargon and Laurie
syringe to avoid clumping within the catheter. However, we
still experienced clumping within the catheter if it touched
fluid or mucosa that was not fully dry. One can imagine that
it may be difficult to have a completely dry environment in
a patient with upper gastrointestinal hemorrhage requiring
aggressive irrigation.
Based on our review of the literature and personal experience with using the device, there will likely be certain scenarios and circumstances where hemostatic powder will be
most helpful. Anatomic location of the lesion may dictate
use of hemostatic powder, such as in patients with pyloric
channel ulcers, which are difficult to treat with conventional
methods. Additionally, large areas of bleeding where it is difficult to identify lesions can be sprayed with the hemostatic
powder without the need to target the lesion directly. Applications outside of non-ulcer bleeding will also need to be
investigated. At this time, there are no published trials evaluating use of hemostatic powder in variceal bleeding or other
non-ulcer etiology of bleeding.
Holster et al recently published a case series in which 16
consecutive patients on antithrombotic therapy with upper
gastrointestinal hemorrhage were treated with hemostatic
powder at the Erasmus MC University Medical Centre in Rotterdam, The Netherlands. Hemostasis was initially achieved
in 5 of the 8 (63%) patients on antithrombotic therapy and
8 of the 8 (100%) patients not on antithrombotic therapy
(P=0.20). Rebleeding rate was similar in both groups; however, in 4 of the 5 total patients with rebleeding, hemostatic
powder was applied to arterial spurting bleeding.4 It would
be beneficial to have future trials investigating the use of
hemostatic powder with combination therapy as well as trials
investigating its use in non-ulcer bleeding, including variceal
bleeding.
Hemospray for Upper GI Bleeding
Disclosures
Author contributions: P.J. Sargon wrote and edited the manuscript, and is the article guarantor; T.J. Laurie edited the
manuscript.
Financial disclosure: No competing financial interests to disclose.
Received: June 9, 2013; Accepted: September 10, 2013
References
1.
2.
3.
4.
Adler DA, Leighton JA, Davila RE, et al. ASGE guideline: The role of
endoscopy in acute non-variceal upper-GI hemorrhage. Gastroinest
Endosc. 2004;60(4):497–504.
Giday SA. Preliminary data on the nanopowder hemostatic agent
TC-325 to control gastrointestinal bleeding. Gastroenterol Hepatol.
2011;7(9):620–622.
Sung JJ, Luo D, Wu JC, et al. Early clinical experience of the safety
and effectiveness of Hemospray in achieving hemostasis in patients
with acute peptic ulcer bleeding. Endoscopy. 2011;43(4):291–295.
Holster IL, Kuipers EJ, Tjwa ET. Hemospray in the treatment of upper gastrointestinal hemorrhage in patients on antithrombotic therapy.
Endoscopy. 2013;45(1):63–66.
Publish your work in ACG Case Reports Journal
ACG Case Reports Journal is a peer-reviewed, open-access publication that provides GI fellows, private practice clinicians, and other members of the
health care team an opportunity to share interesting case reports with their peers and with leaders in the field. Visit http://acgcasereports.gi.org for
submission guidelines. Submit your manuscript online at http://mc.manuscriptcentral.com/acgcr.
9
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ACG Case Reports Journal | Volume 1 | Issue 1 | October 2013
ACG CASE REPORTS JOURNAL
CASE REPORT | ENDOSCOPY
Endoscopic Mucosal Resection of a Large Gastric Metastasis
from Renal Cell Carcinoma
Richa Chibbar, MD1, Julinor Bacani MD2, and Sergio Zepeda-Gómez, MD1
1
2
Division of Gastroenterology, University of Alberta, Edmonton, Canada
Division of Anatomical Pathology, University of Alberta, Edmonton, Canada
Abstract
Gastric metastasis from renal cell carcinoma (RCC) occurs in less than 1% of cases. A variety of management
options have been described for this condition, however, total or partial gastrecomy is the most common therapeutic approach. We present a case of a large gastric metastatic lesion from a RCC diagnosed 10 years before.
This was treated with endoscopic mucosal resection (EMR) without evidence of residual lesion after 10 months
of follow-up.
Introduction
Renal cell carcinoma (RCC) accounts for 3% of all adult malignancies and 25–30% of RCC patients have metastatic disease at presentation.1 A low percentage of patients present with metastatic disease up to 25 years after
initial presentation and treatment. The usual sites of metastasis for RCC include lung (50–70%), liver (30–40%),
bone and soft tissue (10%), and brain (5%).2 Gastric metastasis from RCC occurs in less than 1% of cases.
A variety of management options have been described for this condition, including endoscopic resection. We
present a case of a patient with a large polypoid metastatic lesion in the stomach from RCC diagnosed 10 years
before. This lesion was treated with endoscopic mucosal resection (EMR) without evidence of residual lesion
after 10 months of follow-up.
Case Report
A 69-year-old female presented for endoscopic evaluation with recent iron-deficiency anemia. The patient had
a radical left nephrectomy as definitive treatment for a renal cell carcinoma (pT3a pN0) in 2002. She noticed
increasing fatigue and lightheadedness, but denied overt gastrointestinal bleeding. She was found to have a
hemoglobin level of 10.6 g/dL with an iron level of 5 µmol/L (normal: 8–25). The gastroscopy showed an atypical 2.5-cm sessile polypoid lesion in the gastric body. It was friable with erosions in the mucosal surface, but
without active bleeding (Figure 1). We injected the base of the polypoid lesion with saline solution, methylene
blue, and diluted epinephrine (1:10,000). There was adequate lifting and subsequent EMR was performed with
a combination of coagulation and cutting current (ENDO CUT® Q, Effect 3, ERBE Elektromedizin, GmbH, Tübingen, Germany). No immediate complications were observed at the EMR site (Figure 2). The patient reported no
symptoms after the procedure and was discharged. The histopathologic examination of the specimen showed
metastatic clear cell renal carcinoma, with free margins of resection (Figures 3 and 4).
Subsequent CT scan of the chest, abdomen, and pelvis 1 month after the procedure did not show evidence
of other site of metastasis. The patient was started on oral iron and the hemoglobin level increased to normal
range. A follow-up gastroscopy was performed 8 weeks later. This showed scar tissue at the EMR site without
ACG Case Rep J 2013;1(1):10–12. doi:10.14309/crj.2013.6. Published online: October 8, 2013.
Correspondence: Sergio Zepeda-Gómez, MD, Division of Gastroenterology, 1-20A Zeidler Ledcor Centre, 130 University Campus, University of Alberta,
Edmonton, Canada T6G2X8 ([email protected])
Copyright: © 2013 Chibbar et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
10
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ACG Case Reports Journal | Volume 1 | Issue 1 | October 2013
Chibbar et al
EMR of Large Gastric Metastasis
Figure 1. Endoscopic view of a 2.5-cm polypoid lesion in the body of the
stomach corresponding to a gastric metastasis from a RCC.
macroscopic evidence of residual disease. Biopsies from
the resection site confirmed normal gastric mucosa (Figure
5). The patient has remained asymptomatic and a follow-up
CT scan of the abdomen 10 months after the EMR showed
stable findings without evidence of metastatic disease.
Discussion
Gastric metastasis from renal cell carcinoma is a rare occurrence and confers a poor prognosis.1 It can present as
an incidental finding or associated with anemia, abdominal
pain, or gastrointestinal bleeding.3 There is no standard approach to management, but surgical excision (either total
or partial gastrectomy) is the most common therapeutic approach. Endoscopic therapy has been reported as an alternative treatment of these lesions, either with EMR or endoscopic submucosal dissection (ESD). There are 48 cases of
gastric metastasis from RCC reported in the literature; however, only 11 patients have been treated with endoscopic
resection and one with ESD.4–10 A summary of the cases that
have been treated endoscopically is presented in Table 1.
Unfortunately, in the majority of the cases reported, the endoscopic resection technique is not described in detail. In
one report, the lesion size was 3 cm, an endoloop snare
was placed at the base, and polypectomy was performed;
however, this was an incomplete resection.6 Another report
describes 3 polypoid lesions actively bleeding in the body of
the stomach. The lesions were 2–3 cm in size and resected
with epinephrine injection and snare polypectomy, but it is
unclear if this was a complete resection.10 There is one report of ESD for a 6-mm flat metastatic lesion in the stomach.9
Figure 3. Hematoxylin and eosin (H&E) of gastric polypectomy at 2x magnification. (A) Gastric mucosa with underlying submucosal metastatic clear
renal cell carcinoma (RCC) causing grossly polypoid appearance. (B) Gastric mucosal erosion and ulceration by underlying clear-cell RCC morphologically identical to prior RCC in D. (C) Well-visualized cauterized margins
without evidence of malignancy. Cauterized margin on right side denoted by
arrows is 2 mm away from closest metastatic RCC tumor front (asterisks).
(D) Prior clear-cell RCC. Normal renal parenchyma in upper left corner.
by EMR. The endoscopic resection was carried out without complications, and a repeat gastroscopy after 8 weeks
showed no evidence of residual lesion. There were no other
metastatic lesions identified on a subsequent CT scan. The
patient remains without evidence of disease by endoscopic
or radiologic criteria at almost 1 year of follow-up.
In cases with high diagnostic suspicion of invasive gastric
metastasis from RCC, prior assessment of depth of invasion
by endoscopic ultrasound would be appropriate. However,
To our knowledge, our case is the largest gastric metastasis from a RCC to be completely resected endoscopically
Figure 2. Adequate lifting of the polypoid lesion with combination of saline solution, methylene blue, and dilute epinephrine (left), and post-EMR result (right).
11
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Figure 4. H&E and confirmatory immunostains showing strong co-expression
for renal cell carcinoma markers at 40x magnification. (A) H&E of metastatic
clear cell RCC to stomach. (B) H&E primary clear cell RCC. (C) RCC immunostain. (D) Vimentin immunostain.
ACG Case Reports Journal | Volume 1 | Issue 1 | October 2013
Chibbar et al
EMR of Large Gastric Metastasis
Table 1. Summary of Case Reports of Gastric Metastatic Lesions from RCC Treated Endoscopically
Country
Cases
Age, y
Interval, y
Technique
Size
Complete
Resection
Outcome
Japan4
4
Mean: 56
Mean: 8.25
Not specified
NS
NS
2 Patients lived more than 6 mo after resection
Austria5
3
Mean: 72
Mean: 8
Standard
polypectomy + APC
Mean:
1.5 cm
NS
2 Patients died within 6 mo after resection;
The other alive after 2 y with disease
Australia6
1
65
9
Endoloop +
polypectomy
3 cm
No
Alive 6 y after resection with disease
UK7
1
71
3
EMR
1.2 cm
Yes
Alive after 15 mo
US
1
60
6 mo
Not specified
6 mm
Yes
Died 8 mo after resection
S. Korea9
1
79
At RCC diagnosis
ESD
6 mm
Yes
Alive 6 mo after resection
2–3 cm
NS
Died 6 mo after resection
2.5 cm
Yes
Alive 10 mo after resection
8
Italy10
1
78
5
Epinephrine injection
+ snare polypectomy
(3 lesions identified)
Canada*
1
69
10
EMR
*Current study. APC = argon plasma coagulation; EMR = endoscopic mucosal resection; ESD = endoscopic submucosal dissection; NS = not specified; RCC = renal cell carcinoma.
Financial disclosure: The authors disclose no financial relationship relevant to this publication.
Received: July 18, 2013; Accepted: September 19, 2013
References
1.
Figure 5. H&E follow-up post gastric polypectomy. (A) 3 benign gastric
mucosal biopsies at polypectomy site taken at 2X magnification. (B) Representative H&E 10X magnification. There is no evidence of residual metastatic RCC.
polypoid lesions that lift well with submucosal injection, such
as the one reported here, have low risk of deep mucosal and
lymphatic invasion, thus low risk of bleeding and/or perforation after EMR. Currently, there are no guidelines for the
endoscopic follow-up after a gastric metastasis resection
from RCC. Such patients should be followed closely for any
sign of recurrence. In our patient, we will perform a yearly
gastroscopy, in addition to standard oncologic surveillance.
Our experience shows that gastric metastasis from RCC that
appear to be amenable to endoscopic resection can be resected safely and effectively in expert hands.
Disclosures
Author contributions: R. Chibbar wrote the first draft, collected
the data for the article, and conducted the literature research;
J. Bacani completed the histopathological analysis and description of the histopathology, and reviewed the final draft; S.
Zepeda-Gómez reviewed and wrote the final draft, conducted
the literature research, and is the guarantor of the article.
Cohen HT, McGovern FJ. Renal-cell carcinoma. N Engl J Med.
2005;353(23):2477–90.
2. Nguyen MM, Gill IS, Ellison LM. The evolving presentation of renal carcinoma in the United States: Trends from the surveillance, epidemiology, and end results program. J Urol. 2006;176(6 pt 1):2397–400.
3. Kobayashi O, Murakami H, Yoshida T, et al. Clinical diagnosis of metastatic gastric tumors: Clinicopathologic findings and prognosis of nine
patients in a single center. World J Surg. 2004;28(6):548–51.
4. Maeda T, Kozakai N, Nishiyama T, et al. Gastric metastasis from renal
cell carcinoma 20 months after radical nephrectomy: A case report [in
Japanese]. Hinyokika Kiyo. 2009;55(3):137–40.
5. Pollheimer MJ, Hinterleitner TA, Pollheimer VS, et al. Renal cell carcinoma metastatic to the stomach: Single centre experience and literature review. BJU Int. 2008;102(3):315–9.
6. Eslick G, Kalantar J. Gastric metastasis in renal cell carcinoma: A case
report and systematic review. J Gastrointest Canc. 2011;42(2):296–301.
7. Siriwardana HP, Harvey MH, Kadirkamanathan SS, et al. Endoscopic
mucosal resection of a solitary metastatic tumor in the stomach: A
case report. Surg Laparosc Endosc Percutan Tech. 2012;22(3):e132–
e134.
8. Xu J, Latif S, Wei S. Metastatic renal cell carcinoma presenting as gastric polyps: A case report and review of the literature. Int J Surg Case
Rep. 2012;3(12):601–4.
9. Kim MY, Jung HY, Choi KD, et al. Solitary synchronous metastatic gastric cancer arising from T1B renal cell carcinoma: A case report and
systematic review. Gut Liver. 2012;6(3):388–94.
10. Pezzoli A, Matarese S, Boccia S, et al. Gastrointestinal bleeding from
gastric metastasis of renal cell carcinoma, treated by endoscopic polypectomy. Endoscopy. 2007;39(suppl):E52.
Publish your work in ACG Case Reports Journal
ACG Case Reports Journal is a peer-reviewed, open-access publication that provides GI fellows, private practice clinicians, and other members of the
health care team an opportunity to share interesting case reports with their peers and with leaders in the field. Visit http://acgcasereports.gi.org for
submission guidelines. Submit your manuscript online at http://mc.manuscriptcentral.com/acgcr.
12
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ACG Case Reports Journal | Volume 1 | Issue 1 | October 2013
ACG CASE REPORTS JOURNAL
CASE REPORT | STOMACH
Iron Pill–Induced Gastritis
Jana G. Hashash, MD1, Siobhan Proksell, MD2, Shih-Fan Kuan, MD3, and Jaideep
Behari, MD, PhD1
Division of Gastroenterology, Hepatology, and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, PA
Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA
3
Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA
1
2
Abstract
Iron-deficiency anemia is a prevalent condition treated with iron supplementation. Iron pill–induced gastritis is
an under-recognized, albeit serious potential complication of iron pill ingestion. This entity must be identified by
healthcare providers who prescribe iron. We present a case of a 59-year-old male with iron deficiency anemia on
ferrous sulfate tablets who underwent an upper endoscopy, during which a single superficial gastric ulceration in
the body was noted. Biopsies revealed heavy iron deposition confirming the ulceration was a consequence of the
iron tablets. Iron pill–induced gastritis causes corrosive mucosal injury similar to that caused by chemical burns.
Introduction
Oral iron supplementation, usually in the form of a pill or tablet, is the most common treatment of iron-deficiency
anemia. A potential complication of using oral iron supplementation is iron pill–induced gastritis. All gastroenterologists should be aware of the endoscopic findings associated with iron pill–induced gastritis, because they
play a crucial role in diagnosing this condition. Patients with iron pill–induced gastritis should have their iron
pills or tablets replaced by liquid iron. It is thought that iron pills and tablets cause a corrosive mucosal injury
and that the effect is concentration-dependant. For this reason, liquid iron does not have the same side effect
of promoting mucosal injury.
Case Report
A 59-year-old male with Child-Pugh B cirrhosis from nonalcoholic fatty liver disease and prior history of esophageal variceal bleeding presented to our gastroenterology suite for an upper gastrointestinal endoscopy for prophylactic variceal band ligation. The patient also had diabetes mellitus, hypertension, dyslipidemia, and chronic
kidney disease (serum creatinine 1.4 mg/dL and a glomerular filtration rate 52 mL/min/1.73 m2). Among his
medications were metformin, insulin glargine, ferrous sulfate, fenofibrate, and valsartan. The patient was receiving 325 mg of ferrous sulfate by mouth twice daily. The patient appeared comfortable and had no complaints.
His vital signs were within normal limits and his physical examination was significant for splenomegaly with
spleen tip palpable 5 cm below the costal margin. Blood work revealed hemoglobin 11.4 g/dL (normal: 14–18
g/dL), a normal mean corpuscular volume of 91 fL, iron saturation 14% (normal: 25–50%), ferritin 88 ng/mL
(normal: 10–282 ng/mL), and total iron binding capacity 339 µ/dL (normal: 250–420 µ/dL).
On upper endoscopy, the patient was found to have esophageal varices in the distal esophagus and mild portal
hypertensive gastropathy. One superficial 6-mm gastric ulcer was found in the gastric body (Figures 1 and 2).
Biopsies from this ulcer revealed erosive gastritis. An iron stain demonstrated heavy iron deposition consistent
ACG Case Rep J 2013;1(1):13–15. doi:10.14309/crj.2013.7. Published online: October 8, 2013.
Correspondence: Jana G. Hashash, MD, Division of Gastroenterology, Hepatology, and Nutrition, University of Pittsburgh Medical Center, 200 Lothrop Street PUH, M2, C Wing, Pittsburgh, PA 15213 ([email protected])
Copyright: © 2013 Hashash et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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ACG Case Reports Journal | Volume 1 | Issue 1 | October 2013
Hashash et al
Iron Pill–Induced Gastritis
with iron pill–induced gastritis (Figures 3 and 4). The patient
was started on an oral proton pump inhibitor and instructed
to discontinue his oral iron tablets. He was started on a liquid iron preparation instead of the iron tablets. Of note, the
patient had a liver biopsy performed a few years prior to this
presentation at an outside hospital, as part of his liver cirrhosis work-up, and this did not show any evidence of iron
overload.
Figure 3. Hematoxylin and eosin stain of the gastric ulcer at 100 magnification.
Figure 1. Endoscopic appearance of the gastric ulcer margins.
Discussion
dark stools, and gastrointestinal irritation, often in the form
of nausea.2 Iron pill gastritis is a documented complication
of iron supplementation, but is rarely encountered. Recently,
however, the topic has been garnering increasing attention.
Kaye et al published a prospective study investigating the effects of iron supplementation on patients with iron deficiency anemia.3 Of 16 patients with iron deposition confirmed by
biopsy, 6 had visible erosions on endoscopy, a significantly
greater proportion than those patients without iron supple-
According to the most recent data published by the World
Health Organization, almost 25% of the world’s population
carries a diagnosis of anemia, the majority being of the iron
deficiency type.1 Ferrous sulfate supplementation in the
pill or tablet form is a commonly prescribed treatment for
these patients with iron deficiency anemia. Common side
effects of oral iron supplementation include constipation,
Figure 4. Iron stain of the gastric ulcer revealing heavy iron deposition at
100 magnification.
Figure 2. Endoscopic appearance of the gastric ulcer bed.
14
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mentation (14/141). No significant differences were attributed to potential confounders such as age, gender, aspirin
and non-steroidal anti-inflammatory drug use. Kaye et al
also included a retrospective analysis reviewing the cases of
59 patients with iron deposition, 58 of whom were receiving
oral iron. Of this population, 31 were documented to have
erosions and ulcerations by endoscopy report.
ACG Case Reports Journal | Volume 1 | Issue 1 | October 2013
Hashash et al
Laine et al published a prospective evaluation of healthy volunteers who were separated into 2 groups, both of which
had not had previous iron supplementation.4 The first group
was assigned to receive ferrous sulfate 325 mg orally 3 times
daily for a duration of 2 weeks, while the second group took
the supplement at the same daily dose and frequency for
only 1 week. Endoscopy was performed prior to and after the
completion of iron therapy and showed a significant increase
in endoscopic abnormalities of the stomach in patients who
received iron therapy for a longer duration. Two patients had
developed gastric ulcerations after iron therapy.
Iron pill–induced gastritis is an under-recognized, albeit serious entity that merits further investigation. Many patients
who are diagnosed with iron pill gastritis have numerous comorbidities that may increase their susceptibility to this condition, though substantial investigation into this subject has
not been undertaken. Iron has been noted to cause a focal
erosive mucosal injury similar to that caused by a chemical
burn. Endoscopically, this manifests as an erosion, an ulceration, or diffuse gastritis. Iron deposits a brown–black crystalline hemosiderin that erodes the mucosa. It is thought that
iron erodes the mucosa through a direct corrosive effect that
subsequently produces a local injury to the mucosa in a concentration-dependant manner. In some patients, particularly
these with other comorbid conditions such as hemochromatosis, gastric antral vascular ectasia, and gastric adenocarcinoma, among others, the degree of iron deposition extends
to the lamina propria and even the gastric glands. Iron pill–
induced gastritis only occurs when iron supplementation is
given in the tablet or pill form likely because of the concentration effect, but has not been noted to occur in patients
who are placed on a liquid form of iron supplementation.
This case report is intended to remind gastroenterologists of
the possible risks of iron pill supplementation.
Iron Pill–Induced Gastritis
Disclosures
Author contributions: J.G. Hashash: study concept and design, acquisition of data, analysis and interpretation of data,
drafting of the manuscript; S. Proksell: acquisition of data,
drafting of the manuscript; S.F. Kuan: aquisition of data,
analysis and interpretation of data; J. Behari: study concept
and design, acquisition of data, analysis and interpretation
of data, study supervision. J.G. Hashash is the article guarantor.
Financial disclosure: No conflicts of interest or sources of
funding exist.
Received: June 9, 2013; Accepted: September 10, 2013
References
1.
2.
3.
4.
World Health Organization. Vitamin and Mineral Nutrition Information
System. Worldwide prevalence on anaemia 1993–2005. World Health
Organization web site. http://www.who.int/vmnis/database/anaemia/
anaemia_status_summary/en/index.html. Accessed June 6, 2013.
Ferrous sulfate: Patient drug information. UpToDate web site. http://
www.uptodate.com/contents/ferrous-sulfate-patient-drug-information.
Accessed June 6, 2013.
Kaye P, Abdulla K, Wood J, et al. Iron-induced mucosal pathology of
the upper gastrointestinal tract: a common finding in patients on oral
iron therapy. Histopathology. 2008;53(3):311–7.
Laine LA, Bentley E, Chandrasoma P. Effect of oral iron therapy on
the upper gastrointestinal tract. A prospective evaluation. Dig Dis Sci.
1998;33(2):172–7.
Publish your work in ACG Case Reports Journal
ACG Case Reports Journal is a peer-reviewed, open-access publication that provides GI fellows, private practice clinicians, and other members of the
health care team an opportunity to share interesting case reports with their peers and with leaders in the field. Visit http://acgcasereports.gi.org for
submission guidelines. Submit your manuscript online at http://mc.manuscriptcentral.com/acgcr.
15
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ACG Case Reports Journal | Volume 1 | Issue 1 | October 2013
ACG CASE REPORTS JOURNAL
CASE REPORT | STOMACH
A Case of Persistent Helicobacter pylori Infection Occurring
with Anti-IgE Immunosuppression
Daniel Zandman, MD, William Hahn, MD, and Steven Moss, MD
Division of Gastroenterology, Department of Internal Medicine, Rhode Island Hospital, The Warren Alpert School
of Medicine of Brown University, Providence, RI
Abstract
The increasingly widespread use of novel immunosuppressive drugs may lead to unexpected infectious complications. We report a case of persistent Helicobacter pylori (H. pylori) infection that failed to respond to antimicrobial therapy in a patient receiving omalizumab (Xolair™, Genentech USA Inc., San Francisco, CA and Novartis
Pharmaceuticals, Basel, Switzerland), an anti-IgE monoclonal antibody approved by the FDA for treatment of
severe persistent asthma. To our knowledge, this is the first case report linking an immunosuppressive regimen
containing anti-IgE biologic therapy to persistent H. pylori infection.
Introduction
Helicobacter pylori (H. pylori) infection is amongst the most prevalent infections in humans worldwide, and is a
significant source of morbidity and mortality. H. pylori is considered a carcinogen, thus treatment is standard of
care. However, there are numerous barriers to eradication, including antimicrobial resistance, patient adherence
to complex medication regimens, and, as proposed in this case, a growing array of novel immunosuppressive
medications.
Case Report
A 31-year-old female with severe, steroid-dependent asthma, morbid obesity, and type II diabetes, was found to
have iron deficiency anemia during evaluation for bariatric surgery. At upper endoscopy, there were no mucosal
abnormalities, but H. pylori infection was diagnosed via immunohistochemical staining of gastric biopsies. She
was treated with conventional first-line anti-H. pylori combination triple therapy (amoxicillin, clarithromycin, and
omeprazole) for 2 weeks. There was no test of cure until later in her pre-operative bariatric surgery evaluation,
when it was discovered that the patient was still infected with H. pylori, demonstrated by both positive fecal
antigen and urea breath testing. Her surgical team was hesitant to proceed with gastric bypass, based upon the
evidence linking persistent H. pylori infection with a higher risk for post-operative marginal ulceration.1
We therefore treated her with a standard bismuth-based quadruple therapy regimen for 14 days (tetracycline,
metronidazole, omeprazole, bismuth) as per the Maastricht guidelines (Figure 1).2 A subsequent urea breath
test was positive and she was then treated with 14 days of an amoxicillin-based quadruple therapy regimen
(amoxicillin, metronidazole, bismuth, and omeprazole). H. pylori fecal antigen performed as a test-of-cure both
3 and 7 weeks after completion of quadruple therapy was still positive. A fourth treatment consisted of a salvage
fluoroquinolone-based regimen (levofloxacin, amoxicillin, and omeprazole twice daily) for 2 weeks. However,
5 weeks following therapy, a repeat fecal antigen was again positive. A fifth “sequential” regimen consisting of
lansoprazole twice daily and amoxicillin for 5 days, followed by lansoprazole, clarithromycin, and tinidazole for
ACG Case Rep J 2013;1(1):16–18. doi:10.14309/crj.2013.8. Published online: October 8, 2013.
Correspondence: Dr. Steven Moss, APC Building 406, Rhode Island Hospital, 593 Eddy Street, Providence, RI 02903 ([email protected])
Copyright: © 2013 Zandman et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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Zandman et al
Anti-IgE Immunosuppression and H. pylori
Culturing H. pylori for in vitro antibiotic sensitivity profiling is
technically and logistically challenging in the United States.
Therefore, we attempted to treat with empiric regimens this
asymptomatic patient without significant inflammation or ulcer disease. It is possible that this patient’s failure to clear
her H. pylori infection reflected infection with an a priori resistant strain. We hypothesize that there may be a relationship between the patient’s anti-IgE therapy and the failure to
clear her H. pylori infection. Her lack of symptomatic gastritis also supports the notion that IgE may play an important
role in host inflammatory response to H. pylori infection.
Figure 1. Treatment course of patient.
5 days was therefore prescribed. This regimen is reported to
be effective for resistant strains.3 Both H. pylori fecal antigen
and urea breath tests remained positive 8 weeks after the
end of therapy.
Throughout these multiple unsuccessful attempts at H.
pylori eradication, the patient had been taking both omalizumab and prednisone continously (at least 10 mg prednisone daily, with approximately 8 booster/taper courses).
Her other chronic medications included omeprazole, citalopram, carbamazapine, lisinopril, pravastatin, montelukast, and
alendronate. The patient reported complete adherence to all
courses of H. pylori treatment and calls to her pharmacy
verified that she had filled the prescriptions as written.
Discussion
We report a case of treatment-refractory H. pylori infection
in the setting of immunosuppression, most notably with an
anti-IgE biologic (omalizumab), prednisone, and the leukotriene receptor antagonist montelukast. While H. pylori elicits a specific humoral IgG and a mucosal and serum IgA
response, the relationship between humoral immunity and
protection/clearance of H. pylori is controversial.4,5 Nevertheless, several lines of evidence suggest that IgE may play
a role in the immune response to H. pylori infection. In
samples from H. pylori-positive patients whose endoscopies
did not demonstrate active inflammation, there was a clear,
statistically significant reduction in IgE-positive mast cell
numbers.6 Investigations of H. pylori-associated gastric ulcers have co-localized IgE positive plasma cells within the ulcers.7 Furthermore, although controversial, there have been
several smaller epidemiologic investigations reporting a positive association between H. pylori infection and IgE-mediated systemic disorders, most notably chronic urticaria.8
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Several lines of evidence suggest that a robust immune response, whether mediated by IgE or other mechanisms, is
necessary for effective eradication of H. pylori.9 Mice vaccinated with various H. pylori antigens and subsequently
challenged with Helicobacter develop a more severe gastritis than in natural infection prior to clearing the bacteria.10
In a mouse model examining the role of anti-inflammatory
CD25+ T-regulatory cells in H. pylori infection, CD25 deficient mice had higher levels of inflammation and lower levels
of persistent H. pylori infection11; depletion of CTLA-4 (a costimulatory surface molecule expressed by CD25-positive Tregulatory cells) resulted in higher levels of gastritis and lower
bacterial loads than in control mice.12 In humans, biopsies
from patients with persistent H. pylori infection demonstrate
up to a 50-fold increase in CD25+ T-cells,13 suggesting an
underlying inappropriate “tolerance” to the infection.
To date, the few investigations evaluating the relationship
between immunosuppression and H. pylori infection support a role for inflammation in clearing H. pylori infection.
A case series of renal allograft patients undergoing upper
endoscopy demonstrated a higher percentage of H. pylori
positivity (63% vs. 43.6%) with a lower incidence of active
gastritis (6.9% vs. 31.3%).14 Animal models, however, are
conflicting; one mouse model of H. pylori infection failed to
demonstrate an association between corticosteroid administration and H. pylori bacterial load or gastritis,15 whereas
a gerbil model showed decreased gastritis with both tacrolimus and dexamethasone, but no significant change in H.
pylori viability.16
In summary, we speculate that concurrent anti-IgE therapy
was an important factor in the inability of our patient to clear
H. pylori infection. If this proves to be the case in larger case
series and/or animal models, it may have important implications in the pathogenesis of refractory H. pylori infection.
Disclosures
Author contributions: D.B. Zandman and W. Hahn contributed equally to the creation of the article; S.F. Moss contrib-
ACG Case Reports Journal | Volume 1 | Issue 1 | October 2013
Zandman et al
uted in an editorial, advisory, and supervisory capacity and
is the guarantor of the article.
Financial disclosure: No financial support contributed to the
creation of this article. D.B. Zandman and W. Hahn disclose
no conflicts of interest. S.F. Moss is a member of the speaker’s bureau for Otsuka America Pharmaceutical, Inc.
Received: May 23, 2013; Accepted: September 10, 2013
Anti-IgE Immunosuppression and H. pylori
7.
8.
9.
10.
11.
References
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2.
3.
4.
5.
6.
Rasmussen JJ, Fuller W, Ali MR. Marginal ulceration after laparoscopic gastric bypass: An analysis of predisposing factors in 260 patients.
Surg Endosc. 2007;21(7):1090–4.
Malfertheiner P, Megraud F, O’Morain C, et al. Current concepts in
the management of Helicobacter pylori infection: The Maastricht III
Consensus Report. Gut. 2007;56(6):772.
Vaira D, Zullo A, Vakil N, et al. Sequential therapy versus standard
triple-drug therapy for Helicobacter pylori eradication: A randomized
trial. Ann Intern Med. 2007;146:556.
Zhang S, Moise L, Moss SF. H. pylori vaccines: Why we still don’t have
any. Hum Vaccin. 2011;7(11):1153–7.
Müller A, Oertli M, Arnold I. H. pylori exploits and manipulates innate
and adaptive immune cell signaling pathways to establish persistent
infection. Cell Commun Signal. 2011;9(1):25.
Liutu M, Kalimo K, Kalimo H, et al. Mast cells and IgE-containing
cells in gastric mucosa of Helicobacter pylori-infected and non-infected patients with chronic urticaria. J Eur Acad Dermatol Venereol.
2004;18(1):69–72.
12.
13.
14.
15.
16.
Berczi L, Sebestyén A, Fekete B et al. IgE-containing cells in gastric
mucosa with and without Helicobacter pylori infection. Pathol Res
Pract. 2000;196(12):831–4.
Greaves MW. Pathophysiology of chronic urticaria. Int Arch Allergy
Immunol. 2002;127(1):3–9.
Portal-Celhay C, Perez-Perez GI. Immune responses to Helicobacter
pylori colonization: mechanisms and clinical outcomes. Clin Sci
(Lond). 2006;110(3):305–14.
Michetti P, Corthésy-Theulaz I, Davin C, et al. Immunization of BALB/c
mice against Helicobacter felis infection with Helicobacter pylori
urease. Gastroenterology. 1994;107(4):1002–11.
Stuller KA, Ding H, Redline RW, et al. CD25+ T cells induce Helicobacter pylori-specific CD25-T-cell anergy but are not required
to maintain persistent hyporesponsiveness. Eur J Immunol.
2008;38(12):3426–35.
Anderson KM, Czinn SJ, Redline RW, et al. Induction of CTLA4-mediated anergy contributes to persistent colonization in the
murine model of gastric Helicobacter pylori infection. J Immunol.
2006;176(9):5306–13.
Rad R, Brenner L, Bauer S, et al. CD25+/Foxp3+ T cells regulate
gastric inflammation and Helicobacter pylori colonization in vivo. Gastroenterology. 2006;131(2):525–37.
Hruby Z, Myszka-Bijak K, Gosciniak G, et al. Helicobacter pylori in
kidney allograft recipients: High prevalence of colonization and low
incidence of active inflammatory lesions. Nephron. 1997;75(1):25–9.
Conlan JW, KuoLee R, Webb A, et al. Immunosuppression by a corticosteroid fails to exacerbate Helicobacter pylori infection in a mouse
model of gastric colonization. Can J Microbiol. 1999;45(11):975–80.
Naka Y, Aihara T, Keto Y, Okabe S. Effects of dexamethasone and
FK506 on Helicobacter pylori-induced gastritis and bacterial viability
in Mongolian gerbils. J Physiol Paris. 2001;95(1–6):443–51.
Publish your work in ACG Case Reports Journal
ACG Case Reports Journal is a peer-reviewed, open-access publication that provides GI fellows, private practice clinicians, and other members of the
health care team an opportunity to share interesting case reports with their peers and with leaders in the field. Visit http://acgcasereports.gi.org for
submission guidelines. Submit your manuscript online at http://mc.manuscriptcentral.com/acgcr.
18
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ACG Case Reports Journal | Volume 1 | Issue 1 | October 2013
ACG CASE REPORTS JOURNAL
CASE REPORT | STOMACH
Kaposi’s Sarcoma: An Unusual Cause of Gastric Outlet Obstruction
Sandra Rodriguez, MD1, Jorge Zapatier, MD2, Daniela Allende, MD3, and Alison Schneider, MD2
Department of Internal Medicine, Cleveland Clinic, Weston, FL
Department of Gastroenterology, Cleveland Clinic, Weston, FL
3
Department of Pathology, Cleveland Clinic, Weston, FL
1
2
Abstract
Kaposi’s sarcoma (KS) is the most common AIDS-related neoplasm and is one of the AIDS-defining illnesses.
It most frequently presents with cutaneous lesions, but may also involve organ systems. Most cases of gastrointestinal (GI) involvement are clinically silent and found incidentally on imaging studies or endoscopy. Sole
involvement of the GI tract can be seen with or without cutaneous disease; however, the latter has been reported
as rare by some investigators. We report a case of a 25-year-old man with HIV who presented with gastric outlet
obstruction (GOO) and disseminated GI involvement by KS.
Introduction
AIDS-related Kaposi’s sarcoma (KS) is the most common neoplasm in patients infected with HIV. The incidence
has significantly decreased since the introduction of highly active anti-retroviral therapy (HAART). Skin involvement is the most common initial presentation, and it is seen in up to 60% of cases. Visceral involvement is also
frequent, affecting most commonly the gastrointestinal (GI) tract (40%) and lungs (30%).1,4,6 As reported in the
literature, the association between gastrointestinal KS and cutaneous disease is controversial. Some studies
report the incidence to be as high as 40–70%.1,5,9 However, other authors have found the former association
to be uncommon.3,7,8 In the GI tract, the small intestine is affected most frequently, followed by the stomach,
esophagus, and colon, and generally is considered to be more common in the upper gastrointestinal tract than
in the lower gastrointestinal tract.2,3,6
Most patients with GI involvement are asymptomatic, but may present with non-specific symptoms such as
weight loss, diarrhea, and abdominal pain. Endoscopically, lesions range from minimally elevated submucosal
vascular patches, some with central ulceration, to large polypoid defects. Obstruction, perforation, intussusception, and protein-losing enteropathy are infrequent complications associated with advance disease and high GI
burden.4,8 KS usually responds to HAART; nevertheless, systemic chemotherapy may be used for symptomatic
visceral KS.
Case Report
A 25-year-old African-American man with history of sexual encounters with men was evaluated in the emergency
department for worsening nausea, vomiting, and epigastric abdominal pain for the past 5 days. He had also experienced a 30-pound weight loss over the past 3 months. Vital signs were remarkable for a sinus tachycardia,
hypotension, and positive orthostatic blood pressure. Physical examination revealed dry mucous membranes,
decreased skin turgor, and no rashes. There was tenderness to palpation in the epigastrium and hyperactive
bowel sounds. Laboratory data showed a mild leucopenia and normocytic anemia, but was otherwise unremarkACG Case Rep J 2013;1(1):19–21. doi:10.14309/crj.2013.9. Published online: October 8, 2013.
Correspondence: Sandra Rodriguez, MD, Cleveland Clinic Florida, 2950 Cleveland Clinic Blvd, Weston, FL 33331 ([email protected])
Copyright: © 2013 Rodriguez et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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ACG Case Reports Journal | Volume 1 | Issue 1 | October 2013
Rodriguez et al
able. Contrast computed tomography (CT) of the abdomen
and pelvis revealed multiple nodules in the stomach with
marked thickening of the antrum, suggestive of a gastric
outlet obstruction (Figure 1). The patient was admitted for
conservative management of the obstruction with NPO and
intravenous hydration. Gastroenterology was consulted and
EGD and colonoscopy were performed, which revealed multiple erythematous nodules with central ulceration through-
Figure 1. CT of the abdomen showing multiple nodules in the stomach with
marked thickening of the antrum, suggestive of gastric outlet obstruction.
out the esophagus, stomach, duodenum, and colon (Figure
2). The largest lesion was located at the lesser curvature of
the stomach near the pre-pyloric region. The biopsies revealed gastric mucosa infiltrated by an atypical spindle cell
proliferation, forming slit-like vascular spaces, with focally
extravasated red blood cells and hemosiderin deposition.
The vascular proliferation was strongly and diffusely positive
for CD34 and human herpes virus-8 (HHV8; Figure 3). Such
Gastric Outlet Obstruction and HIV
histologic and immunohistochemical findings are consistent
with GI involvement by KS.
Upon further testing, he was found to have a CD4 count
of 17 cells/μL and an HIV viral load of 179,000 copies/mL.
HAART was initiated, as well as treatment with anthracycline
chemotherapy. He completed 6 cycles of taxol over a period
of 5 months post initial diagnosis. To date, he has not experienced symptomatic recurrence of his GI symptoms and has
achieved adequate virological response.
Figure 3. Immunohistochemical stains diffusely positive for human herpes
virus-8 (HHV-8) and CD-34, confirming the diagnosis of diffuse visceral
Kaposi’s sarcoma.
Discussion
We present a case of KS with diffuse gastrointestinal involvement in the absence of cutaneous disease that manifested
with acute gastric outlet obstruction. To our knowledge, this
is a very infrequent initial presentation of AIDS, as most patients with KS and GI involvement have no GI symptoms.
Our goal is to encourage clinicians maintain a high index of
suspicion in high-risk patients who present with persistent
GI symptoms, even in the post-HAART era. In addition, we
recommend early endoscopic evaluation to prevent complications associated with progression of the disease. This
will allow for proper staging and selection of the appropriate
therapeutic options.
Disclosures
Author contributions: S. Rodriguez wrote and revised the
article, performed the literature search, and is the article
guarantor; J. Zapatier wrote and revised the article, and performed the literature search; D. Allende provided the pathological descriptions, histology, and images; A. Schneider
initially conceptualized and revised the article.
Financial disclosures: None of the authors have any financial or other conflict of interest.
Figure 2. Endoscopic lesions related to Kaposi’s sarcoma.
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Received: May 17, 2013; Accepted: August 26, 2013
ACG Case Reports Journal | Volume 1 | Issue 1 | October 2013
Rodriguez et al
Gastric Outlet Obstruction and HIV
References
1.
2.
3.
4.
5.
6.
7.
8.
9.
Saltz RK, Kurtz RC, Lightdale CJ, et al. Kaposi’s sarcoma. Gastrointestinal involvement correlation with skin findings and immunologic
function. Dig Dis Sci. 1984;29(9):817–23.
Friedman SL, Wright TL, Altman DF. Gastrointestinal Kaposi’s sarcoma
in patients with acquired immunodeficiency syndrome. Gastroenterology. 1985;89(1):102–8.
Parente F, Cernuschi M, Orlando G, et al. Kaposi’s sarcoma and AIDS:
Frequency of gastrointestinal involvement and its effect on survival. A
prospective study in a heterogeneous population. Scand J Gastroenterol. 1991;26(10):1007–12.
Weprin L, Zollinger R, Clausen K, Thomas FB. Kaposi’s sarcoma:
Endoscopic observation of gastric and colon involvement. J Clin Gastroenterol. 1982;4:357–60.
Zoller WG, Bogner JR, Liess H, et al. Diagnosis and therapy of
gastrointestinal Kaposi’s sarcoma in AIDS. Bildgebung. 1994;61(suppl 1):46–52.
Reed WB, Kamath HM, Weiss L. Kaposi’s sarcoma with emphasis on
internal manifestations. Arch Dermatol. 1974;110(1):115–8.
Yee J, Wall SD. Gastrointestinal manifestations of AIDS. Gastroenterol
Clin North Am. 1995;24(2):413–34.
Gottlieb MS, Groopman JE, Weinstein WM, et al. The acquired immunodeficiency syndrome. Ann Intern Med. 1983;99(2):208–20.
Barrison IG, Foster S, Harris JW, et al. Upper gastrointestinal Kaposi’s
sarcoma in patients positive for HIV antibody without cutaneous disease. Br Med J (Clin Res Ed). 1988;296 92–93.
Publish your work in ACG Case Reports Journal
ACG Case Reports Journal is a peer-reviewed, open-access publication that provides GI fellows, private practice clinicians, and other members of the
health care team an opportunity to share interesting case reports with their peers and with leaders in the field. Visit http://acgcasereports.gi.org for
submission guidelines. Submit your manuscript online at http://mc.manuscriptcentral.com/acgcr.
21
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ACG Case Reports Journal | Volume 1 | Issue 1 | October 2013
ACG CASE REPORTS JOURNAL
CASE REPORT | SMALL BOWEL
Intestinal Pseudo-Obstruction and Total Villous Atrophy of
the Terminal Ileum: An Unusual Presentation of Untreated
Celiac Disease
Eran C. Gwillim, BS1, and Brad A. Bowyer, MD, FACG1,2
1
2
University of Illinois College of Medicine, Rockford, IL
Rockford Gastroenterology Associates, Rockford, IL
Abstract
Intestinal pseudo-obstruction (IPO) is a rare complication of celiac disease (CD) and has often resulted in laparotomy for diagnosis. We report an adult case of CD presenting as IPO with severe protein calorie malnutrition
(PCM) and negative endomysial as well as tissue transglutaminase antibodies. This is the first case report of
CD presenting with combined IPO, severe PCM, negative first-line celiac serologies, and terminal ileal atrophy
that was diagnosed without laparotomy. A non-surgical diagnosis was achieved by expanded laboratory and
endoscopic methods, including video capsule endoscopy. Extent of pathologic gut involvement and response to
treatment with budesonide and gluten-free diet is described.
Introduction
Intestinal pseudo-osbtuction (IPO), by definition, presents with signs and symptoms of bowel obstruction in the
absence of any identifiable occluding gut lesion. Not only is this condition quite unusual, but it is associated
with significant morbidity and a broad differential diagnosis. The etiology of IPO may be idiopathic or secondary
to a host of well-recognized underlying pathological conditions, including endocrine, autoimmune, neurologic,
paraneoplastic, and iinflammatory/infectious diseases. IPO has rarely been reported in adults as a manifestation
of untreated celiac disease (CD) and was first described by Inglefinger in 1943.1 Only 7 additional adult cases
have been described in the medical literature.2–6 All but one previous report underwent laparotomy to exclude
mechanical obstruction.5
Case Report
A 52-year-old man reported being treated with sporadic courses of budesonide over a 6-year period for abdominal pain, diarrhea, and gradual weight loss, presumptively on the basis of inflammatory bowel disease. Financial
restraints and non-compliance had precluded his previous gastroenterologists from thorough evaluation and
continuity of care. He had supplemented his prescriptions of budesonide from those obtained by his daughter,
who was being treated for Crohn’s disease. The patient presented to our hospital service after several weeks of
increasing diarrhea, abdominal pain, vomiting, and 6.8-kg weight loss. On physical examination, he was found to
be afebrile and hypotensive, with a systolic pressure of 93 mmHg. He weighed 65.3 kg with a calculated BMI of
21 kg/m² and appeared chronically ill with somatic muscle wasting. The abdomen was modestly distended and
diffusely tender to deep palpation without peritoneal signs. His bowel sounds were cavernous. Plain abdominal
radiographs and CT abdomen (Figure 1) revealed diffuse small and large bowel dilation with significant edema
of a large segment of the distal ileum.
ACG Case Rep J 2013;1(1):22–24. doi:10.14309/crj.2013.10. Published online: October 8, 2013.
Correspondence: Brad A. Bowyer, MD, Rockford Gastroenterology Associates, LTD, 401 Roxbury Road, Rockford, IL 61107 ([email protected])
Copyright: © 2013 Gwillim and Bowyer. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which
permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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ACG Case Reports Journal | Volume 1 | Issue 1 | October 2013
Gwillim and Bowyer
Villous Atrophy in Untreated Celiac Disease
Pan endoscopy with duodenal, terminal ileal, and universal
colon biopsies revealed endoscopic features of CD involving the duodenum. The colonic mucosa was edematous
throughout. Histology revealed total villous atrophy of the
duodenum and terminal ileum (Figure 2), with typical features of lymphocytic colitis involving the colon. A patency
capsule procedure was negative. Subsequent video capsule
endoscopy (VCE) identified stacking of folds and scalloped
mucosa (Figure 3). No obstruction was identified.
Figure 1. CT abdomen demonstrates diffuse gut dilation and significant
edema of the distal ileum.
Comprehensive laboratory interrogation was remarkable for
iron deficiency anemia (Hgb 8.1 gm/dL, iron 38 mcg/dL, ferritin 13 ng/mL) and hypoproteinemia (albumin 2.5 gm/dL,
total protein 5.1 gm/dL). Serum immunoglobulin levels were
normal. IgA tissue transglutaminase antibody (tTG) and antiendomysial antibodies (EMA) were negative; however, both
IgG deaminated gliadin peptide (DGP) antibodies (105.0
U) and IgA DGP antibodies (74.6 U) were strongly positive
(<20 U is considered negative for both indices). HLA DQ
typing was permissive for CD. Neuromuscular markers for
IPO including anti-neuronal nuclear Ab; type 1 ANNA-1, s;
striational (striated muscle) Ab, s; N-type calcium channel
Ab, acetylcholine receptor (muscle) binding Ab; AChR ganglionic neuronal Ab, s; and GAD65 Ab assay were negative.
Figure 3. Stacking of folds and scalloped mucosa as seen on video capsule
endoscopy (VCE).
The patient was placed on a gluten-free diet and prescribed
budesonide 9 mg daily for 8 weeks. He returned for followup duodenal biopsies after 9 weeks of therapy. He was
asymptomatic and had gained 4.5 kg in weight. Duodenal
pathology had markedly improved and revealed only partial
villous atrophy. The patient was seen again 5 months after
discontinuation of budesonide therapy and remained free of
gut symptoms on a gluten-free diet, with return to his premorbid weight of 85.3 kg.
Discussion
Figure 2. Histology of terminal ileum demonstrating total villous atrophy.
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Intestinal pseudo-obstruction is a rare complication of CD
and has often resulted in laparotomy for diagnosis. Pathogenesis of intestinal pseudo-instruction may involve neuromyopathic mechanisms as well as injury to the interstitial
cells of Cajal.7 Celiac disease is an autoimmune disorder
with IgA antibodies to the intestinal smooth muscle connective tissue known as the endomysium, as well as tissue
transglutaminase, which is found within the endomysium.
ACG Case Reports Journal | Volume 1 | Issue 1 | October 2013
Gwillim and Bowyer
These antibodies serve as markers for the diagnosis of celiac disease and would suggest a myopathic basis for IPO in
untreated patients. Absence of these markers in our case
would suggest an alternative mechanism(s) for the development of IPO. Perhaps direct gut injury related to the diffuse
inflammatory process, as demonstrated in our case, was responsible for the development of IPO. Whether this inflammatory-related injury was primarily neuropathic, myopathic,
or related to injury of the interstitial cells of Cajal is unknown.
In our patient, VCE excluded mechanical obstruction and
provided images highly suggestive of CD, obviating unnecessary surgery. Our case illustrates the diffuse pathologic
nature of untreated CD, in particular, total villous atrophy of
the terminal ileum, which has not been described in previous cases of celiac-induced IPO. Despite our high index of
suspicion, a confident diagnosis of CD was not supported
by positive endomysial or tissue transglutaminase antibodies. Serologic exclusion for known neuromuscular markers
of IPO allowed us to focus on the differential diagnosis of
villous atrophy, which included autoimmune enteropathy
and common variable immunodeficiency syndrome; negative anti-enterocyte antibody and normal immunoglobulins,
respectively, excluded these causes of small intestinal villous atrophy. Tropical sprue, Crohn’s disease, eosinophilic
gastroenteritis, Zollinger-Ellison syndrome, giardiasis, bacterial overgrowth, and lymphoma as causes for small intestinal
villous atrophy were reasonably excluded on clinical and/or
histopathologic grounds. Permissive HLA typing results and
positive deaminated gliadin antibodies supported our clinical diagnosis of CD as the most likely etiology of the pathologic and endoscopic findings. The diagnosis of CD was confirmed by the patient’s resolution of symptoms and normalization of duodenal histology after treatment with gluten-free
diet and tapering course of oral budesonide.
Villous Atrophy in Untreated Celiac Disease
Disclosures
Author contributions: E.C. Gwillim participated in manuscript design, acquisition of data, and draft of manuscript;
B.A. Bowyer participated manuscript design, acquisition of
data, critical revision for intellectual content, and is the guarantor of the article.
Financial support: No financial support or competing interests to report.
Received: July 18, 2013; Accepted: September 6, 2013
References
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2.
3.
4.
5.
6.
7.
Ingelfinger FJ. The diagnosis of sprue in nontropical areas. N Engl J
Med. 1943;228(6):180–184.
Cluysenaer OJ, Van Tongeren JM. Pseudo-obstruction in coeliac
sprue. Neth J Med. 1987(5–6);31:300–304.
Dawson DJ, Sciberras CM, Whitwell H. Coeliac disease presenting
with intestinal pseudo-obstruction. Gut. 1984;25(9):1003–1008.
Hirsh EH, Brandenburg D, Hersh T, Brooks WS. Chronic intestinal
pseudo-obstruction. J Clin Gastroenterol. 1981;3(3):247–254.
Koklu S, Coban S, Ertugrul I, et al. Intestinal obstruction in celiac disease: Case report. Dig Dis Sci. 2004;49(9):1485–8.
Naish JM, Capper WM, Brown NJ. Intestinal pseudo-obstruction with
steatorrhoea. Gut. 1960;1(1):62–66.
De Giorgio R, Sarnelli G, Corinaldesi R, Stanghellini V. Advances in our
understanding of the pathology of chronic intestinal pseudo-obstruction. Gut. 2004;53(11):1549–52.
Publish your work in ACG Case Reports Journal
ACG Case Reports Journal is a peer-reviewed, open-access publication that provides GI fellows, private practice clinicians, and other members of the
health care team an opportunity to share interesting case reports with their peers and with leaders in the field. Visit http://acgcasereports.gi.org for
submission guidelines. Submit your manuscript online at http://mc.manuscriptcentral.com/acgcr.
24
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ACG Case Reports Journal | Volume 1 | Issue 1 | October 2013
ACG CASE REPORTS JOURNAL
CASE REPORT | SMALL BOWEL
Nearly Fatal Case of Whipple’s Disease in a Patient Mistakenly
on Anti-TNF Therapy
Christen Klochan, MD1, Teresa A. Anderson, MD1, Dusten Rose, PharmD2, Rosen K.
Dimitrov, MD3, and Raymond M. Johnson, MD, PhD1
Department of Medicine, Indiana University School of Medicine, Indianapolis, IN
Purdue University School of Pharmacy, Indianapolis, IN
3
Department of Pathology, Indiana University School of Medicine, Indianapolis, IN
1
2
Abstract
Whipple’s disease is a rare cause of chronic diarrhea and abdominal pain that may be confused with inflammatory bowel disease. We report a Whipple’s case misdiagnosed as Crohn’s disease in which treatment with
anti-tumor necrosis factor (anti-TNF) therapy led to nearly fatal progression. Lymph node tissue obtained during laparotomy for suspected bowel necrosis stained dramatically with periodic acid–Schiff (PAS), and electron
microscopy showed a bacterium consistent with Trophyrema whipplei. The patient made a remarkable recovery
complicated only by cholestatic hepatitis, which was likely a treatment-associated inflammatory response. This
case serves as a reminder that all granulomatous infections should be considered prior to initiation of anti-TNF
therapies.
Introduction
Whipple’s disease is a rare granulomatous infection of the gastrointestinal tract, with roughly 30 cases reported
to the United States Centers for Disease Control each year. The causative agent is a fastidious, slow-growing,
gram-positive actinomycete, Trophyrema whipplei, which was finally identified in the early 1990s using molecular biology techniques based on 16S ribosomal RNA PCR amplification.1,2 The illness is seen mostly in the fourth
through sixth decades of life, typically presenting as chronic abdominal pain, diarrhea, weight loss, and joint
complaints, with or without fevers. Pathogenesis of the infection includes invasion of the gastrointestinal mucosa,
recruitment of macrophages to the lamina propria, and obstruction of local lymphatics, causing blunting of the
small intestine villi and malabsorption/malnutrition. The bacteria can disseminate regionally from the small bowel
to mesenteric lymph nodes, spleen, liver, and extraperitoneal organs including the joints, pleura, heart, and CNS.
Untreated Whipple’s disease is a fatal infection; however, once diagnosed, Whipple’s disease is readily treated
with ceftriaxone induction followed by prolonged oral trimethoprim/sulfamethoxazole therapy.3
It is common for patients with Whipple’s disease experiencing prominent joint complaints with mild gastrointestinal tract symptoms to be initially misdiagnosed with inflammatory arthritides. In a recent large survey of confirmed cases, 50% of Whipple’s patients were initially treated with immunosuppressive agents including steroids
(43%) and tumor necrosis factor (TNF)-antagonists (14%) for presumed inflammatory arthritis.4 Analogously,
there is the potential to misdiagnose Whipple’s disease as inflammatory bowel disease, as chronic diarrhea with
abdominal pain is a common presentation in gastroenterology clinics. Because Whipple’s disease is rare and
lacks a convenient diagnostic test, it may not be considered in the differential diagnosis for individual patients.
Because TNF-antagonists are highly effective for treating inflammatory bowel diseases, including Crohn’s disACG Case Rep J 2013;1(1):25–28. doi:10.14309/crj.2013.11. Published online: October 8, 2013.
Correspondence: Raymond M. Johnson, MD, PhD, Division of Infectious Diseases, Department of Medicine, Indiana University School of Medicine, 635
Barnhill Drive, MS 224, Indianapolis, IN 46202 ([email protected])
Copyright: © 2013 Klochan et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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ACG Case Reports Journal | Volume 1 | Issue 1 | October 2013
Klochan et al
ease, it is foreseeable that some Whipple’s patients misdiagnosed with inflammatory bowel disease will receive anti-TNF
therapy. We report the first known example of this clinical
scenario and the severe progression of Whipple’s disease
that developed while on anti-TNF therapy.
Table 1. Admission Laboratory Values
Admission Values
Normal Values
Sodium
138 mmol/L
135–145 mmol/L
Potassium
2.9 mmol/L*
3.5–5.5 mmol/L
Chloride
115 mmol/L*
98–108 mmol/L
Case Report
Bicarbonate
12 mmol/L*
22–29 mmol/L
Our patient is a 69-year-old female with a past history of hypothyroidism, degenerative joint disease, and restless legs syndrome admitted through the emergency room with 2.5 years
of waxing and waning abdominal pain, diarrhea, fatigue, and
weight loss. Upper endoscopy at an outside medical center
1 year prior to admission showed patchy erythema in the
duodenum. Biopsies showed villous blunting; celiac serologies were negative. Three months after the endoscopy ,she
was admitted to a local hospital with diarrhea, abdominal
pain, and dizziness. Video capsule endoscopy showed ulcerations in the small bowel consistent with Crohn’s disease.
An anti-Saccharomyces cerevisiae antibody (ASCA) was
positive. She was started on mesalamine and budesonide for
presumed Crohn’s disease. That therapy did not control her
symptoms, so the mesalamine was changed to adalimumab,
a monoclonal antibody specific for TNF-alpha.
Urea nitrogen
35 mg/dL
5–20 mg/dL
Creatinine
1.5 mg/dL
0.6–1.4 mg/dL
Glucose
88 mg/dL
70–99 mg/dL
Calcium
6.3 mg/dL
8.5–10.5 mg/dL
Albumin
1.4 gm/dL*
3.5–5.0 gm/dL
Protein
4.8 gm/dL*
6.7–8.6 gm/dL
Total bilirubin
0.3 mg/dL
0.0–1.0 mg/dL
Alkaline phosphatase
87 U/L
25–125 U/L
AST
20 U/L
25–45 U/L
ALT
14 U/L
Five months later, and 5 months prior to her current admission, she was readmitted to the local hospital with weakness,
fatigue, nausea, vomitting, diarrhea, and weight loss. CT
evaluation was remarkable for abdominal lymphadenopathy.
A lymph node sampled by CT-guided biopsy showed granulomata with rare fungal-like organisms suggestive of histoplasmosis. Budesonide was stopped and prednisone therapy was initiated, presumably because her diarrheal symptoms were attributed to a flare of Crohn’s disease. She was
prescribed itraconazole, but she took this for only 2 weeks
due to financial issues. Her last dose of adalimumab was
approximately 1 month prior to admission to our hospital.
The patient presented to our emergency room with complaint of diarrhea, weakness, and “just not feeling right.” On
admission the patient was strikingly cachectic in appearance, weighing 40.7 kg (body mass index 16.2); temperature 35.0°C, blood pressure 96/56 mmHg, heart rate 72
bpm, respiratory rate 16 bpm, and O2 saturation 100% on
room air. Her abdomen was distended, soft, and minimally
tender to palpation, with hypoactive bowel sounds. The remainder of her exam was unremarkable. Admission labs
were grossly abnormal, especially albumin 1.4 gm/dL (normal: 3.5–5.0) and bicarbonate 12 mmol/L (normal: 22–29;
see Table 1). Her admission non-contrast CT scan showed
marked distention of the colon with multiple air-fluid levels.
There were multiple soft tissue masses within the mesentery
and retroperitoneal lymphadenopathy. A contrast CT scan
was repeated 19 hours later because of worsening acido26
Whipple’s Disease and Anti-TNF Therapy
acgcasereports.gi.org
Laboratory Parameter
White blood cells
Hemoglobin
Platelets
0–50 U/L
10.2 k/mm
4.5–11.5 k/mm3
9.3 g/dL*
12–15 g/dL
3
346 k/mm
3
150–450 k/mm3
*Abnormal values. ALT = alanine aminotransferase; AST = aspartate aminotransferase.
sis and hypotension. It showed the bulky retroperitoneal
and mesenteric adenopathy, diffuse thickening of the entire small bowel from the duodenum to the terminal ileum,
and pneumatosis intestinalis (Figure 1). Concern for bowel
compromise led to an emergent exploratory laparotomy. The
bowel was intact with a pasty exudate covering the bowel
and peritoneal surfaces. A 3 x 2-cm mesenteric lymph node
was resected for pathology. Intraoperative brushings and
frozen sections sent to surgical pathology showed granulomatous disease (Figure 2A). Acid-fast bacteria (AFB) and
Grocott’s methenamine silver (GMS) stains were negative for
acid-fast bacilli or fungi in brushings and lymph node tissue.
The patient’s T-spot and Histoplasma capsulatum H-band
M-band/complement fixation/urine antigen were negative.
Based on her clinical history, the infectious disease service
requested a periodic acid–Schiff (PAS) stain on lymph node
tissue, which was positive (Figure 2B). Electron microscopy
Figure 1. CT scan of the abdomen with lymphadenopathy (rulers), abnormal mesenteric soft tissue (*), thickened small bowel wall (small arrow),
and pneumatosis intestinalis (large arrows).
ACG Case Reports Journal | Volume 1 | Issue 1 | October 2013
Klochan et al
Whipple’s Disease and Anti-TNF Therapy
Figure 2. (A) H&E staining of peritoneal cavity brushings (200 x magnification). (B) PAS staining of mesenteric lymph node tissue (200 x magnification).
(C) Electron microscopy of lymph node tissue (43,600 x magnification). Yellow arrow highlights a rod-shaped bacterium consistent with Trophyrema whipplei.
demonstrated aggregates of rod-shaped bacteria consistent with Tropheryma whipplei (Figure 2C). There was no
evidence of malignancy on histopathology or flow cytometry.
The patient was treated with ceftriaxone 2 gm daily for 2
weeks, followed by oral trimethroprim/sulfamethoxazole
therapy, dose-adjusted for mild renal insufficiency to 400/80
mg orally 3 times daily. The patient recovered dramatically.
She had a transient increase in alkaline phosphatase from
its admission value of 87 U/L to a peak value of 525 U/L at
3 weeks into antibiotic therapy, dropping down to 244 U/L
at 4 weeks, and 204 U/L at 6 months of antibiotic therapy. A
4-month follow-up CT scan showed a roughly 50% decrease
in the size of all intraperitoneal lesions. Her lab abnormalities
of anemia, acidosis, and hypoalbuminemia resolved. Four
months after discharge, her weight was 54.9 kg, up from
40.7 kg, close to her baseline weight 3 years earlier. Her diarrhea and joint pains resolved; her only residual complaint
was her previously diagnosed restless legs syndrome.
Discussion
While there are several case reports of Whipple’s disease
patients initially misdiagnosed with inflammatory arthritides
and receiving TNF-antagonist therapies,5–9 to our knowledge
this is the first reported case of a patient initially misdiagnosed with Crohn’s disease. Our patient had a severe case
of Whipple’s disease due to either the 10-month duration of
anti-TNF therapy preceding Whipple’s diagnosis, a significant infection at the time of anti-TNF therapy initiation, or
possibly both. Because the patient’s diarrhea and abdominal
pain syndrome resolved completely with ceftriaxone followed
by trimethoprim/sulfamethoxazole, it is highly unlikely that
she has underlying Crohn’s disease.
Though difficult to prove, it is generally thought that antiTNF therapy worsens the clinical course of Whipple’s dis27
acgcasereports.gi.org
ease. A study of non-steroidal anti-inflammatory drugs versus conventional immunosuppression (corticosteroids, azathioprine, methotrexate, etc.) in Whipple’s patients initially
treated for inflammatory arthritis showed that immunosuppressive therapy accelerated the disease in the form of earlier development of diarrhea.10 Our patient’s clinical course
is consistent with that general impression. Histopathology
suggests that macrophages are critical in the host immune
response to Trophyrema whipplei infections. TNF-alpha is
critical for macrophage killing of intracellular pathogens,11,12
and has been shown to facilitate granuloma formation for
the containment of intracellular pathogens such as Mycobacterium and Histoplasma.13,14 Disruption of granuloma
formation is one hypothesis for the infectious complications
of anti-TNF therapies.
An interesting feature of our patient’s clinical course was a
dramatic asymptomatic elevation in her alkaline phosphatase level after starting antibiotic therapy. Based on the extent of infection in her abdomen and hepatomegaly seen
on CT, it is possible that the liver was also involved with the
infection. Alternatively, treatment-induced inflammatory
syndromes can be seen in Whipple’s disease patients.15 Our
patient’s cholestatic liver injury may be a treatment-induced
inflammatory syndrome. Her alkaline phosphatase continued to decline through 6 months of trimethoprim/sulfamethoxazole therapy, largely ruling out drug-related toxicity.
However, the alkaline phosphatase was never fractionated,
gamma-glutamyl transferase was never obtained, and a liver
biopsy was not performed, so the true etiology cannot be
proven.
Advent of non-invasive endoscopy (video capsule) and serologic testing for inflammatory bowel diseases (e.g., the Prometheus® IBD7 panel [Prometheus Laboratories, Inc., San
Diego, CA]) has the potential for non-histopathology–based
ACG Case Reports Journal | Volume 1 | Issue 1 | October 2013
Klochan et al
diagnosis of inflammatory bowel diseases. However, as this
case report demonstrates, a non-histology–based diagnostic
approach is problematic. There is a long differential diagnosis for small bowel ulcerations seen on capsule endoscopy.
Positive serologic testing for inflammatory bowel disease is
helpful in cases with a high pre-test probability, and can be
helpful in distinguishing between Crohn’s disease and ulcerative colitis, but it is not diagnostic of either disease. A
retrospective study in a pediatric abdominal pain/diarrhea/
weight loss cohort showed that the IBD7 panel had a positive predictive value of 63%.16 In our case, a non-diagnostic
EGD duodenal biopsy (without PAS staining) was followed
up by video endoscopy and serology to give an errant diagnosis of Crohn’s disease. Even with biopsy-based diagnosis
of inflammatory bowel disease, there are overlapping histopathlogy findings in Crohn’s disease (non-caseating granulomatous inflammation) and Whipple’s disease (histiocytic/
granulomatous infection). PAS stains on biopsy specimens
are simple and inexpensive, but they must be specifically
requested in most hospitals on biopsy specimens to exclude
the presence of histiocytic or granulomatous inflammation to
rule out Whipple’s disease. Patients presenting with abdominal pain/diarrhea syndromes in their fourth to sixth decades
should have PAS stains performed on anti-TNF therapies.
Disclosures
Acknowledgements: We acknowledge the timely and expert
surgical care provided by Dr. Christopher Touloukian and his
staff.
Author contributions: C. Klochan, T.A. Anderson, D. Rose,
and R.M. Johnson wrote and revised the article; R.K. Dimitrov evaluated the pathology and revised the article. R.M.
Johnson is the article guarantor.
Financial disclosure: No funding sources or conflicts of interest to disclose.
Whipple’s Disease and Anti-TNF Therapy
References
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
Wilson KH, Blitchington R, Frothingham R, Wilson JA. Phylogeny of the Whipple’s-disease-associated bacterium. Lancet.
1991;338(8765):474–5.
Relman DA, Schmidt TM, MacDermott RP, Falkow S. Identification of the uncultured bacillus of Whipple’s disease. N Engl J Med.
1992;327(5):293–301.
Feurle GE, Junga NS, Marth T. Efficacy of ceftriaxone or meropenem as initial therapies in Whipple’s disease. Gastroenterology.
2010;138(2):478–86; quiz 11–2.
Lagier JC, Lepidi H, Raoult D, Fenollar F. Systemic Tropheryma whipplei: Clinical presentation of 142 patients with infections diagnosed or
confirmed in a reference center. Medicine. 2010;89(5):337–45.
Hoppé E, Masson C, Audran M, et al. Whipple’s disease diagnosed
during biological treatment for joint disease. Joint Bone Spine.
2010;77(4):335–9.
Ahmadi-Simab K, Schnitzler P. Whipple’s disease with normal duodenal histology and ankylosing spondylitis [in German]. Deutsche Med
Wochenschr. 2009;134(4):127–30.
Kneitz C, Suerbaum S, Beer M, et al. Exacerbation of Whipple’s
disease associated with infliximab treatment. Scand J Rheumatol.
2005;34(2):148–51.
Spoerl D, Bar D, Cooper J, et al. Multisegmental spondylitis due to
Tropheryma whipplei: Case report. Orphanet J Rare Dis. 2009;4:13.
Daien CI, Cohen JD, Makinson A, et al. Whipple’s endocarditis as a
complication of tumour necrosis factor-alpha antagonist treatment in a
man with ankylosing spondylitis. Rheumatology. 2010;49(8):1600–2.
Mahnel R, Kalt A, Ring S,et al. Immunosuppressive therapy in Whipple’s disease patients is associated with the appearance of gastrointestinal manifestations. Am J Gastroenterol. 2005;100(5):1167–73.
Bekker LG, Freeman S, Murray PJ, et al. TNF-alpha controls intracellular mycobacterial growth by both inducible nitric oxide synthase-dependent and inducible nitric oxide synthase-independent
pathways. J Immunol. 2001;166:6728–34.
Liew FY, Li Y, Millott S. Tumor necrosis factor-alpha synergizes with
IFN-gamma in mediating killing of Leishmania major through the induction of nitric oxide. J Immunol. 1990;145(12):4306–10.
Roach DR, Bean AG, Demangel C, et al. TNF regulates chemokine induction essential for cell recruitment, granuloma formation, and clearance of mycobacterial infection. J Immunol. 2002;168(9):4620–7.
Allendoerfer R, Deepe GS Jr. Regulation of infection with Histoplasma
capsulatum by TNF-R1 and -R2. J Immunol. 2000;165(5):2657–64.
Feurle GE, Moos V, Schinnerling K, et al. The immune reconstitution
inflammatory syndrome in Whipple disease: A cohort study. Ann Intern Med. 2010;153(11):710–7.
Benor S, Russell GH, Silver M, et al. Shortcomings of the inflammatory bowel disease Serology 7 panel. Pediatrics. 2010;125(6):1230–6.
Received: May 7, 2013; Accepted: October 1, 2013
Publish your work in ACG Case Reports Journal
ACG Case Reports Journal is a peer-reviewed, open-access publication that provides GI fellows, private practice clinicians, and other members of the
health care team an opportunity to share interesting case reports with their peers and with leaders in the field. Visit http://acgcasereports.gi.org for
submission guidelines. Submit your manuscript online at http://mc.manuscriptcentral.com/acgcr.
28
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ACG Case Reports Journal | Volume 1 | Issue 1 | October 2013
ACG CASE REPORTS JOURNAL
CASE REPORT | SMALL BOWEL
True versus Pseudo-Intestinal Malrotation: Case Series and
Review
Harshit S. Khara, MD1, Shivangi T. Kothari, MD2, Claudia B. Gruss, MD3, Alan Langnas,
DO4, Daniel F. Schafer, MD1, and Timothy M. McCashland, MD1
Department of Gastroenterology and Hepatology, University of Nebraska Medical Center, Omaha, NE
Department of Gastroenterology and Hepatology, University of Rochester Medical Center, Rochester, NY
3
Department of Gastroenterology and Hepatology, Norwalk Hospital, Norwalk, CT
4
Department of Surgery, University of Nebraska Medical Center, Omaha, NE
1
2
Abstract
Intestinal malrotation is an anomaly of fetal intestinal rotation that can present with symptoms after birth or in
early childhood, but is rarely diagnosed in adults. Patients who have symptomatic presentations require surgery.
Other entities may mimic intestinal malrotation and respond to non-surgical management. We present 2 adult
cases with the radiological diagnosis of intestinal malrotation: one with true malrotation presenting as a duodenal
mass, and another with “pseudo-malrotation” due to altered anatomy. These cases illustrate the importance of
recognizing and differentiating these rare adult presentations of true malrotation from “pseudo-malrotation” in
regards to their acute management.
Introduction
Intestinal malrotation is a congenital anomaly referring to either the lack of or incomplete rotation of the fetal intestine around the axis of the superior mesenteric artery (SMA). Symptoms usually present soon after birth or in
early childhood, but are rarely seen in adults. We present 2 adult cases with the suspected radiological diagnosis
of intestinal malrotation: one with true malrotation requiring immediate surgical management, and another of
“pseudo-malrotation” due to altered abdominal anatomy, which required only conservative management.
Case Report 1
True Malrotation: A 48-year-old Caucasian male with history of hypertension and hypercholesterolemia presented to his local hospital with complaints of nausea and vomiting for 1 week. On admission, he was found to
be dehydrated and was managed with intravenous fluids. A CT scan of his abdomen was read to suggest a 3-cm
duodenal mass, and he was transferred to our hospital for further evaluation. Upon admission to our hospital,
the patient reported that he had been having intermittent problems with nausea and vomiting throughout his
adult life, but they were much milder than his current episode. The patient’s vital signs and physical exam were
normal, except for mild epigastric abdominal tenderness. Laboratory analyses were within normal limits.
An abdominal X-ray only showed a mild ileus. An esophagogastroduodenoscopy (EGD) was normal. A CT scan of
his abdomen showed gastrointestinal (GI) malrotation with the duodenum looping into the right abdomen rather
than crossing the midline. The duodenal mass-like appearance was due to the duodenum folding upon itself. A
superior mesenteric vein (SMV) rotation sign was positive, with classic inverse relationship of the SMV to the SMA
ACG Case Rep J 2013;1(1):29–32. doi:10.14309/crj.2013.12. Published online: October 8, 2013.
Correspondence: Harshit S. Khara, MD, Department of Gastroenterology and Hepatology, Yale University School of Medicine–Norwalk Hospital, 30 Stevens
Street, Suite D, Norwalk, CT 06856 ([email protected])
Copyright: © 2013 Khara et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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ACG Case Reports Journal | Volume 1 | Issue 1 | October 2013
Khara et al
(Figure 1A). An upper GI with small bowel series showed an
intestinal malrotation, with the small bowel loops spiraling
into the right abdomen (Figure 2A).
The patient was taken for an operative repair with a Ladd’s
procedure. Congenital bands across the second and third
True versus Pseudo-Intestinal Malrotation
Case Report 2
Pseudo-Malrotation: A 36-year-old Caucasian female presented to the outpatient clinic with complaints of intermittent upper abdominal pain for the past year. She had a history of a hepatoblastoma as an infant and had undergone
a tri-segmentectomy of her liver, followed by radiation and
chemotherapy. She had been asymptomatic until this new
onset of intermittent abdominal pain, which used to occur
infrequently but now occurred several times a week. She
had no associated nausea or vomiting.
Her vital signs and physical exam were normal, except for
her abdominal exam. She had multiple well-healed scars
across her mid-abdomen, without any evidence of a hernia.
There was mild epigastric abdominal tenderness. Her bowel
sounds were normal. The right lobe of her liver was not palpable. Further evaluation included a normal EGD. An upper
GI series showed no evidence of gastric outlet obstruction
or strictures. The duodenum did not appear to cross past
the vertebral bodies, and the entire jejunal small bowel was
located in the right upper quadrant, suggestive of an intestinal malrotation (Figure 2B). A subsequent CT scan of her
abdomen showed her small bowel pushed to the right; not
due to malrotation, but due to her right hepatic lobe resection, with compensatory hypertrophy of the left lobe, which
completely filled the left upper quadrant and displaced the
spleen below it. A SMV rotation sign was negative (Figure
1B). Her abdominal pain was attributed to her altered intraabdominal anatomy as well as dyspepsia, which improved
with antacid therapy. She continued to do well on medical
therapy on follow-up.
Figure 1. CAT scan of abdomen. (A) True malrotation with positive superior
mesenteric vein (SMV) rotation sign showing classic inverse relationship of
the SMV to the superior mesenteric artery (SMA). (B) Pseudo-malrotation
with small bowel pushed to the right; not due to malrotation but from right
liver lobe resection with compensatory hypertrophy of the left lobe. SMV
rotation sign is negative.
portions of the duodenum were lysed. The small bowel was
repositioned and an appendectomy and cecopexy were performed. The patient recovered uneventfully and was doing
well on his follow-up visit 1 month after discharge.
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Figure 2. Upper GI with small bowel series. (A) True malrotation: Intestinal
malrotation with the duodenum not crossing midline and the small bowel
loops spiraling into the right abdomen. (B) Pseudo-malrotation: The duodenum did not appear to cross past the midline and the jejunal small bowel
was located in the right upper quadrant, suggestive of intestinal malrotation.
ACG Case Reports Journal | Volume 1 | Issue 1 | October 2013
Khara et al
Discussion
Malrotation is estimated to occur in between 1 in 200–500
live births, and symptomatic malrotation is estimated to
occur in 1 in 6,000 live births.1 Male predominance is observed in neonatal presentations at a ratio of 2:1. In infants,
the mortality ranges between 2–24%, and it increases tremendously with the presence of necrotic bowel at the time
of surgery. However, the true incidence in adults is difficult
to estimate, as most patients remain asymptomatic until they
are picked up incidentally during diagnosis of other unrelated abdominal complaints.
Normal intestinal embryology was first described by Meckel
in 1817.2 However, it was not until 80 years later that Mall
explained the embryology of malrotation in 1898.3 In 1923,
Dott described the relationship between the anatomy and
clinical outcomes for malrotation.4 Dr. William Ladd wrote
the classic article on treatment of malrotation, and his surgical approach—the Ladd procedure—remains the cornerstone of practice.5
The process of midgut rotation can be described in 3 stages.
Stage I comprises of physiological umbilical herniation and
rotation of the midgut loop, extending from the fifth to the
10th week of gestation. Failure of return to the abdomen
during Stage I results in the development of omphaloceles.
Stage II comprises further rotation of the midgut loop followed by reduction of the midgut hernia into the abdominal
cavity, occurring during the 10th to the 12th week of gestation. Stage II anomalies result in nonrotation, mixed rotation,
and reversed rotation. Nonrotation is the most common rotational anomaly resulting in midgut volvulus and duodenal
obstruction. Stage III involves the fixation of the mesentery to
the posterior abdominal wall extending from the 12th week of
gestation up until term. Normal rotation and fixation results
in a wide-based mesentery extending from the ligament of
Treitz in the left upper quadrant to the ileocecal valve in the
right lower quadrant. Stage III anomalies result in internal
hernias, midgut volvulus, unattached duodenum, mobile cecum, incomplete fixation of hepatic flexure of the colon, and
intermittent duodenal obstruction by Ladd bands.6
Rotational anomalies can lead to a wide variety of clinical
symptoms and atypical anatomic positioning. In newborns,
the most common presenting sign is bilious vomiting. It can
also manifest as bloody vomitus due to intestinal necrosis,
abdominal pain, peritonitis, dehydration, and shock.5 In
older children and adults, the presentation could be intermittent vomiting, abdominal pain, and duodenal obstruction
due to Ladd’s bands. Less commonly, they can also present
with enteropathy, pancreatitis, peritonitis, biliary obstruction,
motility disorders, and chylous ascites.7 Volvulus can be
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True versus Pseudo-Intestinal Malrotation
caused due to the twisting of bowel around the SMA pedicle,
and it could result in a life-threatening vascular insufficiency
to the SMA distribution.
Plain radiographs are not very helpful for diagnosis, but may
show a “double-bubble” sign due to partial obstruction of
the duodenum causing distension of the stomach and the
first part of the duodenum.8 Upper GI series can show the
abnormal position of the duodenum with a “corkscrew” appearance due to duodenal obstruction or a volvulus.9 Barium enema can be used as an adjunct to upper GI series
for a volvulus involving the transverse colon. CT scan is very
useful in revealing abnormal small bowel location and for
looking for the SMV rotation sign, which results from the inverse relationship of the SMV to the SMA.10 Ultrasound can
also show a “whirlpool” sign suggesting a midgut volvulus.11
Ladd’s procedure remains the mainstay of surgical treatment regardless of the age of presentation. This procedure
involves detorsion of the midgut volvulus, if present, followed
by lysis of adhesive Ladd’s bands, widening of the mesenteric base, and a prophylactic appendectomy and cecopexy.
Ladd’s procedure can also be performed laparoscopically as
long as there is no midgut volvulus.12
The management in adults differs depending upon clinical
presentation. If there is a symptomatic malrotation, then
prompt exploration of the acute abdomen along with Ladd’s
procedure and resection of the nonviable bowel should be
performed. If malrotation is discovered during evaluation of
an unrelated complaint, then the malrotation should only
be addressed if it does not add undue risk to the current
planned procedure. It can be repaired electively at a later
date, if possible. If malrotation is asymptomatic with incidental discovery on a radiologic examination, then intervention is
only indicated if the patient is at risk for a midgut volvulus.13
Our cases illustrate the importance of identifying and differentiating a true small bowel malrotation in an adult patient versus a pseudo-malrotation. Rarely, true malrotation
can present in adult patients with a variety of abdominal
signs and symptoms, such as the duodenal mass in our first
patient; that said, initial imaging may be misleading in patients with a pseudo-malrotation due to altered abdominal
anatomy from prior surgeries such as a tri-segmentectomy,
as in our second patient. Fortunately, we can now confirm
our suspicions with advanced imaging technology in a noninvasive manner, alerting us to the need for immediate surgical management for true malrotation versus conservative
management for pseudo-malrotation.
ACG Case Reports Journal | Volume 1 | Issue 1 | October 2013
Khara et al
Disclosures
Author contributions: All authors had significant contribution
to the conception and design; analysis and interpretation of
the data; drafting of the article; critical revision of the article for important intellectual content; final approval of the
article; and meet criteria for authorship. H.S. Khara is the
article guarantor.
Financial disclosure: No funding resources were involved in
our study. No conflicts of interest exist for any authors.
Received: May 24, 2013; Accepted: August 30, 2013
References
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Skandalakis JE, Gray SW, Ricketts R, Richardson DD. The small intestines. In: Skandalakis JE, Gray SW, eds. Embryology for Surgeons: The
Embryological Basis for the Treatment of Congenital Anomalies. 2nd
ed. Baltimore, MD: Williams & Wilkins; 1994:184–236.
Mall FT. Development of the human intestine and its position in the
adult. Bull Johns Hopkins Hosp. 1898;9:197–208.
Dott NM. Anomalies of intestinal rotation: Their embryology and surgical aspects: With report of five cases. Br J Surg. 1923;11(42):251–86.
Ladd WE. Surgical diseases of the alimentary tract in infants. N Engl J
Med. 1936;215:705–8.
Amaral L, Quintanilha R, Bernardo L, et al. Intestinal malrotation in the
elderly. Am Surg. 2009;75:631–3.
Spigland N, Brandt ML, Yazbeck S. Malrotation presenting beyond the
neonatal period. J Pediatr Surg. 1990;25(11):1139–42.
Poki HO, Holland AJ, Pitkin J. Double bubble, double trouble. Pediatr
Surg Int. 2005;21(6):428–31.
Ortiz-Neira CL. The corkscrew sign: Midgut volvulus. Radiology.
2007;242(1):315–6.
Warner, BW. Malrotation. In: Oldham, KT, Colombani, PM, Foglia, RP,
eds. Surgery of Infants and Children: Scientific Principles and Practice. Philadelphia, PA: Lippincott Williams & Wilkins; 1997: 1229–40.
Publish your work in ACG Case Reports Journal
ACG Case Reports Journal is a peer-reviewed, open-access publication that provides GI fellows, private practice clinicians, and other members of the
health care team an opportunity to share interesting case reports with their peers and with leaders in the field. Visit http://acgcasereports.gi.org for
submission guidelines. Submit your manuscript online at http://mc.manuscriptcentral.com/acgcr.
32
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ACG Case Reports Journal | Volume 1 | Issue 1 | October 2013
ACG CASE REPORTS JOURNAL
CASE REPORT | SMALL BOWEL
Beware of the Patient with Thymectomy: Good’s Syndrome
in a Patient Presenting with Diarrhea
Ken Liu, MBBS, BSc1,2, and James L. Cowlishaw, MBBS2
1
2
Sydney Medical School University of Sydney, Sydney, New South Wales, Australia
Department of Gastroenterology, Concord Hospital, Concord, New South Wales, Australia
Abstract
Good’s syndrome is a rare cause of immunodeficiency in adults associated with thymoma. We describe an
80-year-old female with chronic diarrhea, multiple opportunistic infections, and cytopenias. She underwent
a thymectomy 5 years ago for a thymoma. Laboratory tests revealed neutropenia, hypogammaglobulinaemia,
complete B-cell lymphopenia, and low CD4 T cells with inverted CD4:CD8 ratio, which is consistent with Good’s
syndrome. We recommend checking immunoglobulin levels in all patients with a history of thymoma. Good’s
syndrome should be considered as a differential diagnosis if patients present with chronic diarrhea, cytopenias,
or recurrent infections. Cytomegalovirus (CMV) infection should be considered in patients with immune deficiency as a cause of chronic diarrhea.
Introduction
Good’s syndrome (GS) is a rare cause of immunodeficiency associated with thymoma. It was first described by
Dr. Robert Good in 1954,1 yet there still exists no formal set of diagnostic criteria. GS is most consistently characterized by low circulating B-lymphocytes and hypogammaglobulinaemia, among other immunological and
hematological abnormalities. Gastrointestinal abnormalities, particularly unexplained diarrhea, are common. The
incidence of hypogammaglobulinaemia in patients with thymoma is 6–11%.2
Case Report
An 80-year-old woman was admitted to hospital with watery, non-bloody diarrhea up to 6 times per day and fever
(39.4°C). There was no history pointing to a focus of infection. Her examination was unremarkable. Five years
earlier, the patient underwent a thoracotomy to remove a 12 x 9 x 10.8-cm type AB minimally invasive thymoma
(WHO classification).3 Prior to this admission, the patient had a 4-year history of watery diarrhea and 10 kg of
weight loss. Colonoscopy 4 years ago showed indeterminate colitis, after which she was started on oral mesalazine. With the exception of one positive culture for Campylobacter jejuni, stool cultures were persistently negative
for pathogens. She previously underwent 3 hospital admissions for worsening diarrhea, which responded well to
short courses of intermediate dose prednisone (10–20 mg) and loperamide.
One month prior to admission, the patient underwent a flexible sigmoidoscopy to investigate worsening diarrhea.
This showed left-sided colitis suggestive of ulcerative colitis. She was commenced on 50 mg daily of prednisone,
which led to a significant improvement. Surprisingly, colonic biopsies revealed diffuse active chronic inflammation and atypical cells with inclusion bodies that stained positive for cytomegalovirus (CMV). A CMV DNA PCR
from blood was positive with 48,900 copies/mL. Given her improvement on steroids, it was thought the CMV
ACG Case Rep J 2013;1(1):33–35. doi:10.14309/crj.2013.13. Published online: October 8, 2013.
Correspondence: Ken Liu, Gastroenterology Department, Level 1 West, Concord Hospital, Hospital Road, Concord, NSW 2139, Australia
([email protected]).
Copyright: © 2013 Liu and Cowlishaw. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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ACG Case Reports Journal | Volume 1 | Issue 1 | October 2013
Liu and Cowlishaw
represented a coincidental bystander rather than the cause
of the patient’s colitis, and a decision was made not to start
antiviral therapy.
On admission, her prednisone had been weaned to 25 mg
daily and her diarrhea had worsened again. Admission blood
tests showed leukopenia (1.0 x 109/L), neutropenia (0.2 x
109/L), anaemia (107 g/L) and an elevated C-reactive protein
(137 mg/L). Initial blood cultures grew Enterobacter aerogenes, while urine and stool cultures were negative. A repeat
CMV viral load was 10,179 copies/mL. She was commenced
on intravenous piperacillin and tazobactam 4.5 g three times
daily, and subcutaneous granulocyte colony stimulating factor (G-CSF) 300 μg daily. Her steroids were weaned.
Over the next 2 weeks, the patient’s diarrhea, leukopenia,
neutropenia, and C-reactive protein were improving, but
her fevers persisted despite multiple courses of antibiotics
and negative cultures. During this time the patient was diagnosed with CMV retinitis and a herpes simplex virus 1 (HSV)
dendritic corneal ulcer after developing a painful right eye.
She was commenced on intravenous ganciclovir 5 mg/kg every 12 hours for 2 weeks for disseminated CMV infection as
well as intravitreal ganciclovir and topical acyclovir ointment.
Late in her admission, our patient also had Candida glabrata
isolated from her urine. Given her ongoing fevers, this was
treated with oral fluconazole 400 mg daily for 7 days.
A bone marrow aspirate and trephine showed a hypercellular
marrow, disorganised erythropoiesis, and a left shift in myelopoiesis. Blood lymphocyte subsets revealed an absence
of CD19 B cells (0.00 x 109/L; normal 0.05–0.41 x 109/L),
decreased CD4 count (0.31 x 109/L; normal 0.4–1.32 x 109/L),
with an inverted CD4:CD8 ratio (0.37; normal 0.6–2.5).
There was marked hypogammaglobulinaemia: IgA 0.21 g/L
(normal 0.7–3.12 g/L), IgG 1.78 g/L (normal 6.39–15.6 g/L),
and IgM <0.18 g/L (normal 0.5–3.0 g/L). Her HIV serology
was negative. With her history of thymoma and characteristic pattern of immunodeficiency, a diagnosis of Good’s
syndrome with disseminated CMV infection was made. She
received an infusion of intravenous immunoglobulin (IVIG)
followed by monthly maintenance infusions. She was also
started on lifelong CMV and Pneumocystis jiroveci pneumonia prophylaxis with oral valganciclovir and trimethoprimsulfamethoxazole. She became afebrile and her diarrhea
settled 2 days after receiving IVIG, 10 days after commencing ganciclovir. CT and PET scans showed no evidence of
residual thymoma.
Discussion
Good’s syndrome is a rare acquired primary immunodeficiency associated with thymoma. Up to 1–2% of patients
34
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Good’s Syndrome: A Rare Cause of Diarrhea
with primary antibody deficiency requiring immunoglobulin
replacement have a diagnosis of GS.4 The mean age of presentation is 59 years (range 25–90 years).5 Males and females are equally affected.
The pathogenesis of GS is still unknown. Two possible mechanisms for the association of hypogammaglobulinaemia and
thymoma have been suggested.2 The first is the possible
presence of a cytokine secreted by marrow stromal cells,
which may influence both thymic and B-cell precursor differentiation. The second possible mechanism is that T cells
from patients with thymoma have been shown to inhibit preB cell growth and immunoglobulin production.
The diagnosis of thymoma may precede (42.4%), follow
(19.7%), or occur simultaneously (37.9%) with the clinical
syndrome of hypogammaglobulinaemia, infections, and diarrhea.5 The interval between thymoma diagnosis and clinical manifestations of GS can be up to 18 years. Since removal of the thymoma does not reverse the immunological
abnormalities, GS has been reported after thymectomy,6,7 as
in this patient. The full manifestations of GS are usually established within 6 years of initial presentation.8
The principal immunological findings in GS are hypogammaglobulinaemia (100%), absent B cells (87%), and low CD4
T helper cells (73.2%), with a low CD4:CD8 ratio (76.1%).
Leukopenia and neutropenia occur less commonly, in 46.5%
and 15.1% of patients, respectively.5 The reduced number
of peripheral B cells differentiates GS from common variable
immunodeficiency (CVID).
Patients with GS are at increased susceptibility to infections.
The most common infections reported are recurrent sinopulmonary infections, especially from encapsulated organisms.8 As featured in our patient, the most common opportunistic pathogens include viral infections (CMV and HSV)
and candidiasis. Mycobacterium tuberculosis, Toxoplasma
gondii, and systemic fungal infections are uncommon in GS,
in contrast to acquired human immunodeficiency syndrome
(AIDS).2
Chronic diarrhea affects almost half of GS patients.8 Occasionally, pathogens such as Salmonella spp, Campylobacter
jejuni, Giardia lamblia, and CMV are isolated. In this patient,
it was initially uncertain whether the CMV found on her colonic biopsies represented a nonpathogenic bystander or a
causative factor in her colitis. The pathogenicity of CMV in
the context of inflammatory bowel disease (IBD) has been
a longstanding topic of debate.9 Although the later discovery of CMV retinitis made CMV colitis a likely cause of her
worsening diarrhea, it is unclear why she initially responded
to high-dose steroids. Inflammatory lesions similar to those
ACG Case Reports Journal | Volume 1 | Issue 1 | October 2013
Liu and Cowlishaw
seen in IBD that respond to treatment with systemic steroids
have also been described in GS, suggesting an autoimmune
cause.10 This may explain our patient’s chronic diarrhea prior to presentation.
Although thymectomy does not reverse the immunological
abnormalities in GS, it is recommended to prevent local invasion and distant metastasis of thymomas and to achieve
favourable outcomes for associated autoimmune conditions
including myasthenia gravis, pure red cell aplasia, pernicious anaemia, and thyroid disease.11 Completeness of thymoma resection is the most important indicator of long-term
prognosis in GS.5 Immunoglobulin replacement is the mainstay of therapy for immunodeficiency and results in reduced
infection rates.5,8
A diagnosis of GS carries a worse prognosis compared to
other hypogammaglobublinaemia diseases such as CVID or
X-lined agammaglobulinaemia. The 5- and 10-year survival
rates for GS are 70% and 33%, respectively.12 The principal
cause of death is infection.
Conclusion
We report a case of GS with chronic diarrhea and multiple
opportunistic infections 5 years post-thymectomy. We recommend checking immunoglobulin levels in all patients with
current or previous thymoma. A diagnosis of GS should be
considered if these patients present with unexplained diarrhea, cytopenias, or recurrent infections, as early recognition and treatment may prevent mortality. It is important to
keep a high index of suspicion for opportunistic infections,
particularly CMV, as a possible cause of chronic diarrhea.
Thymectomy, IVIG, and aggressive antimicrobial treatment
are the mainstay of treatment.
Good’s Syndrome: A Rare Cause of Diarrhea
References
1.
Good RA. Agammaglobulinaemia: A provocative experiment of nature.
Bull Univ Minn Hosp Med Found. 1954;26:1–19.
2. Kelleher P, Misbah SA. What is Good’s syndrome? Immunological abnormalities in patients with thymoma. J Clin Pathol. 2003;56(1):12–
6. 3. Travis W, Brambilla E, Muller-Hermelink H, Harris C, eds. Pathology
and Genetics of Tumours of the Lung, Pleura, Thymus, and Heart.
IARC WHO Classification of Tumours. Lyon, France: IARC Press;
2004. http://www.iarc.fr/en/publications/pdfs-online/pat-gen/bb10/index.php. Accessed: May 8, 2013.
4. International Union of Immunological Societies. Primary immunodeficiency diseases. Report of an IUIS scientific committee. Clin Exp Immunol. 1999;118(suppl 1):1–28.
5. Kelesidis T, Yang O. Good’s syndome remains a mystery after 55
years: A systematic review of the scientific evidence. Clin Immunol.
2010;135(3):347–63.
6. Ho JK, Wong MM, Tai TK, Tse DM. A rare combination of recurrent
pneumonia, diarrhoea, and visual loss in a patient after thymectomy.
Hong Kong Med J. 2010;16:493–6.
7. Leibovitz I, Zamir D, Polychuck I, et al. Recurrent pneumonia postthymectomy as a manifestation of Good syndrome. Eur J Intern Med.
2003;14(1):60–2.
8. Tarr PE, Sneller MC, Mechanic LJ, et al. Infections in patients with
immunodeficiency with thymoma (Good Syndrome). Medicine.
2001;80(2):123–33.
9. Hommes DW, Sterringa G, van Deventer SJ, et al. The pathogenicity
of cytomegalovirus in inflammatory bowel disease. Inflamm Bowel Dis.
2004;10:245–50.
10. Kirk BW, Freedman SO. Hypogammaglobulinemia, thymoma and ulcerative colitis. Can Med Assoc J. 1967;96(24):1272–77.
11. Souadjian JV, Enriquez P, Silverstein MN, Pepin JM. The spectrum of
diseases associated with thymoma. Coincidence or syndrome. Arch
Intern Med. 1974;134(2):374–9.
12. Hermaszewski RA, Webster AD. Primary hypogammaglobulinaemia: A survey of clinical manifestations and complications. Q J Med.
1993;86(1):31–42.
Disclosures
Author contributions: K. Liu drafted the article, completed
the literature review and research of case, corrected revisions, and is the article guarantor; J.L. Cowlishaw critically
revised the article and approved the final draft.
Financial disclosure: The authors deny any financial support of the manuscript, and any potential financial or other
conflicts of interest.
Received: May 11, 2013; Accepted: September 10, 2013
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ACG Case Reports Journal | Volume 1 | Issue 1 | October 2013
ACG CASE REPORTS JOURNAL
CASE REPORT | COLON
Giant Inflammatory Fibroid Polyp of the Descending Colon
Treated with Endoscopic Resection
Ammar Kayyali, MD1, Anis Toumeh, MD1, Usman Ahmad, MD1, Luis E. De Las Casas, MD2,
and Ali Nawras, MD, FACG1
1
2
Department of Internal Medicine, Division of Gastroenterology, University of Toledo Medical Center, Toledo, OH
Department of Pathology, University of Toledo Medical Center, Toledo, OH
Abstract
Inflammatory fibroid polyps (IFPs) of the colon are very rare, reactive, non-neoplastic polyps that may grow to
large sizes but do not carry any risk of malignancy. Because of their size, IFPs are usually treated with surgery;
however, size alone should not be an indication for surgery. Depending on the location and morphology of the
polyp, endoscopic resection should be considered. We here describe a case of a giant IFP that was successfully
removed with endoscopy without complication or recurrence.
Introduction
Inflammatory fibroid polyps (IFPs) are rare, reactive non-neoplastic lesions with no documented malignant potential that involve the stomach (70%), the small intestine (20%), and, rarely, the colon.1 They usually contain
blood vessels, fibroblasts, and an edematous stroma rich in eosinophils.2 Signs and symptoms depend mostly
on their location and size. Bleeding, obstruction, or abdominal pain are potential manifestations of IFP. The diagnosis is usually made by imaging studies or endoscopy. Treatment options include surgical excision, in most
cases, and endoscopic mucosal resection (Table 1).
Case Report
An 83-year-old male with a history of diabetes mellitus and coronary artery disease presented with intermittent hematochezia and abdominal pain for 6 months. Physical examination was unremarkable. Initial lab work
showed a hemoglobin of 8.6 g/dL. CT scan of abdomen revealed a hypodense heterogeneous mass within the
proximal descending colon with low internal density (Figure 1A). No other masses or significant lymphadenopathy were seen. Colonoscopy was performed and a giant 7-cm polypoid mass with a wide stalk and yellowish
surface, nearly obstructing the lumen of the descending colon, was found (Figure 1B). Biopsies revealed an
inflamed submucosal stroma with granulation tissue denuded of epithelium. Neither malignant cells nor features
of an adenoma were present. Serum CEA was 1.3 ng/mL. Surgical resection was declined by the patient. He
underwent a repeated colonoscopy with snare polypectomy. Despite using the largest snare available, we were
unable to encircle the polyp due to its size, so it was removed in a piecemeal fashion and the site was tattooed
(Figure 1C). Gross pathologic examination showed a 7.0 x 4.0 x 3.0 cm partially infarcted polypoid mass (Figure
1D). Microscopic examination revealed a polypoid lesion with a prominent fibrotic submucosal stroma, blood
vessels, and scattered eosinophils. Immunostains performed on tumor tissue sections were positive for CD34
and negative for S-100 protein, desmin, and CD117 (Figure 2A). The findings were those of IFP. The patient
tolerated the procedure well and a follow-up colonoscopy 7 months later did not show recurrence.
ACG Case Rep J 2013;1(1):36–39. doi:10.14309/crj.2013.14. Published online: October 8, 2013.
Correspondence: Ammar Kayyali, 31400 Harlo Drive, Madison Heights, MI 48071 ([email protected])
Copyright: © 2013 Kayyali et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
36
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ACG Case Reports Journal | Volume 1 | Issue 1 | October 2013
Kayyali et al
Giant IFP Treated with Endoscopic Resection
nohistochemistry studies, spindle cells of IFPs are generally
positive for CD34 and negative for S-100 protein, P53, c-kit,
and Bcl-2, which helps to differentiate IFP from gastrointestinal stromal tumor (GIST).2
A
B
C
D
Figure 1. (A) CT scan showing large hypodense hetereogenous mass measuring 5 cm (arrow), occupying most of the descending colon. (B) Endoscopic view of the large colonic mass obstructing the lumen of the descending colon. (C) Endoscopic view of the post polypectomy site (endoloop and
endoclips seen at the site). (D) Gross view of the colonic mass after endoscopic resection.
Discussion
IFPs were first described in 1920 as smooth, usually solitary,
submucosal proliferating growths with inflammatory eosinophilic (Figure 2B) and fibroblastic infiltration.3 The first case
of colonic IFP was reported by Kofler in 1952.4 The etiology
and pathogenesis are not well known. IFPs are found in all
age groups, but most commonly in adults.5 They are mostly
found in the stomach (70%) and the small intestine (20%).
Colonic IFPs are rare and are most commonly located in
the proximal colon, especially in the cecum.8 They can be
sessile or pedunculated and usually contain blood vessels,
fibroblasts, and an edematous stroma rich in eosinophils
(Figure 3). Clinical presentation depends, in general, on
their size and location.8 As they enlarge, they can cause abdominal pain, hematochezia, anemia, weight loss, diarrhea,
and intussusceptions.9 Definitive diagnosis is made by histopathologic examination of tissue specimens obtained by
surgery or endoscopy. Biopsies can be challenging because
the epicenter of the lesion is often in the submucosa and the
polyp is often covered by epithelial mucosa. Using immu-
PubMed, Medline, and Google Scholar were searched for
English articles in reference to colonic IFP. All case reports
of colonic IFP from 1952 to present were collected. The
clinicopathological features and modality of removal were
reviewed and summarized in Table 1. To our knowledge,
only 31 cases of colonic IFP were reported in the English literature (Table 1). The size ranged between (0.5–7 cm) with
a median diameter of 3.8 cm. There were 2 cases of small
(<1 cm) polyps, 19 cases of large (1–4 cm) polyps, and only
5 cases of giant (>4 cm) polyps, as in our case; cases of unspecified size were not included in our calculations. Most of
the polyps were found in the cecum (15 cases) accounting
for 44% of cases, whereas only 2 cases of descending colon IFP were reported prior to our case. Males were affected
more than females (72%). Fifteen cases (44 %) were pedunculated and 7 (20%) were sessile; the rest were unspecified.
A
B
C
A
B
Figure 2. (A) Intermediate power view of the inflammatory fibroid polyp
showing the rich vascular supply (arrows) highlighted by a CD34 immunostain. Tissue section. CD 34 immunostain. Original magnification x100. (B)
Eosinophils within the stroma. Inflammatory fibroid polyp. Tissue section,
hematoxylin, and eosin; original magnification x1,000.
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Figure 3. (A) Low power view. Submucosal stromal proliferation with superimposed hemorrhage. Inflammatory fibroid polyp, tissue section. Hematoxylin and eosin, original magnification x20. (B) High power view of the inflammatory fibroid polyp displaying a rich vascularized area with branching
capillaries surrounded by a collagenous stroma containing bland spindle
cells. Tissue section. Hematoxylin and eosin, original magnification x200.
(C) Low power view of the deep aspect of the inflammatory fibroid polyp
displaying rich vascularized areas. Tissue section. Hematoxylin and eosin,
original magnification x40.
ACG Case Reports Journal | Volume 1 | Issue 1 | October 2013
Kayyali et al
Giant IFP Treated with Endoscopic Resection
Table 1. Summary and Clinicopathological Features of Previously Reported Cases of Colonic IFP in the English Literature
Case No.
Age, y
Sex
Location
1
79
M
Cecum
Less than 1 cm
2
37
M
Cecum
6.5 cm, pedunculated
3
67
M
Cecum
3.5 cm, pedunculated
4
4
M
Transverse
5
56
M
Cecum
6
69
M
7
51
M
8
24
M
9
8
M
10–14
NS
15
16
17–20
21
Gross Description
Treatment
Ref
Year
None
4
1952
Surgery
16
1955
Surgery
17
1960
3.5 cm, pedunculated
Surgery
18
1966
7 cm
Surgery
19
1977
Transverse
5 cm, pedunculated
Surgery
20
1979
Sigmoid
3 cm, pedunculated, ulcer
Surgery
9
1979
Transverse
5 cm
Surgery
21
1983
Rectum
3 cm sessile
Surgery
22
1984
NS
4 Cecum
1 Ascending
1.5–4 cm
1 Cecum endopscopic
1 Ascending and 3 cecum surgery
23
1984
71
M
Cecum
4 cm, pedunculated
Endoscopic
24
1985
42
M
Cecum
3.5 cm
Surgery
25
1992
24–72
3 M, 1 F
3 Transverse
1 Cecum
3.6–5 cm
2 pedunculated, 2 sessile
NS
26
1992
33
F
Descending
4 cm, pedunculated
Surgery
27
1995
22
63
M
Ascending
3.5 cm, sessile, ulcer
Surgery
28
1999
23
45
F
Cecum
0.5 cm, sessile, erosive
Endoscopic
29
2000
24
66
M
Cecum
3.5 cm, sessile
Surgery
30
2004
25
40
M
Ascending
3 cm, pedunculated
Endoscopic
2
2005
26
45
M
Transverse
1.8 cm, depressed
Surgery
31
2006
27
82
M
Transverse
0.6 cm, pedunculated
None
32
2007
28
28
M
Sigmoid
4 cm, pedunculated
Endoscopic
33
2007
29
23
F
Descending
4.5 cm, pedunculated, erosive
Endoscopic
10
2008
30
66
F
Cecum
3 cm, sessile, ulcer
Endoscopic
34
2008
31
63
F
Cecum
4 cm, pedunculated
Surgery
35
2008
32
83
M
Descending
7 cm, pedunculated
Endoscopy
*
2011
*The case described in this article. NS = not specified.
Treatment approach was surgical in 20 cases (58%), while
endoscopic resection was done in only 8 (23%). In addition
to snare and cautery, other methods used for polypectomy
included needle-knife assisted endoscopic polypectomy10
and endoclip-assisted polypectomy.2 The largest polyp treated with endoscopy, apart from our case, was 4.5 cm. There
was no reported recurrence of IFP in the colon; however,
there were 2 reported cases of recurrent gastrointestinal IFP
in the small intestines7,12 and one in the stomach.13 Surgical
resection has been the most common method of treatment
for large and giant colonic IFP (Table 1). This is usually because of the technical difficulty of endoscopic polypectomy,
which could be very challenging due to polyp size causing
limited view and occupation of most of the lumen; the morphology (pedunculated with firm and wide stalk or sessile);
the location at a flexure or sharp curve; and concerns regarding the curative role of endoscopic treatment and recurrence.1,14,15 Successful endoscopic resections have been
38
acgcasereports.gi.org
reported in a smaller number of cases when the polyps were
small and pedunculated. Due to the benign nature of IFPs
and the low post-endoscopic resection recurrence rate,6 endoscopic polypectomy of an IFP could be an appropriate
approach if technically possible, considering the size, location, and the morphology of the polyp. Moreover, endoscopic
polypectomy is a valuable diagnostic method for providing
tissue specimens for accurate histological assessment, and
is a reasonable option for patients who are not surgical candidates or refuse surgery.
Disclosures
Author contributions: A. Toumeh and U. Ahmad conducted
the literature review; L. De Las Casas provided the pathology
description; A. Nawras supervised the article process; and
A. Kayyali is the article guarantor.
ACG Case Reports Journal | Volume 1 | Issue 1 | October 2013
Kayyali et al
Financial disclosure: The authors have no financial disclosures and no conflicts of interest to report.
Received: June 1, 2013; Accepted: September 6, 2013
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inflammatory fibroid polyp of the colon. Intern Med. 2000;39(1):25–7.
30. Ng C, Lam KY, Gupta TS, Ho YH. Inflammatory fibroid polyp of the
cecum in a patient with neurofibromatosis. Ann Acad Med Singapore.
2004;33(6):797–9.
31. Iwamoto K, Sakashita M, Takashashi T, et al. Depressed type
of inflammatory fibroid polyp of the colon. Int J Colorectal Dis.
2007;22(11):1409.
32. Hiraskai S, Matsubara M, Ikeda F, et al. Inflammatory fibroid polyp occurring in the transverse colon diagnosed by endoscopic biopsy. World
J Gastroenterol. 2007 21;13(27):3765–6.
33. Park YB, Cheung DY, Kim JI,et al. A large inflammatory fibroid polyp
in the sigmoid colon treated by endoscopic resection. Intern Med.
2007;46(19):1647–9.
34. Peedikayil MC, Al Hindi HN, Rezeig MA. Inflammatory fobroid polyp
of the cecum can be treated by endoscopic resection. Saudi J Gastroenterol. 2008;14(4):212–3.
35. Kan H, Suzaki H, Shinji S, et al. A case of inflammatory fibroid polyp
of the cecum. J Nihon Med Sch. 2008;75(3):181–6.
Publish your work in ACG Case Reports Journal
ACG Case Reports Journal is a peer-reviewed, open-access publication that provides GI fellows, private practice clinicians, and other members of the
health care team an opportunity to share interesting case reports with their peers and with leaders in the field. Visit http://acgcasereports.gi.org for
submission guidelines. Submit your manuscript online at http://mc.manuscriptcentral.com/acgcr.
39
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ACG Case Reports Journal | Volume 1 | Issue 1 | October 2013
ACG CASE REPORTS JOURNAL
CASE REPORT | PANCREAS/BILIARY
Not Your Everyday Case of Acute Pancreatitis: A Rare Complication
of a Common Diagnosis
Parth J. Parekh, MD1, Douglas Howerton, MD2, and David A. Johnson, MD, FACG2
1
2
Department of Internal Medicine, Eastern Virginia Medical School, Norfolk, VA
Division of Gastroenterology, Eastern Virginia Medical School, Norfolk, VA
Abstract
Pancreaticopericardial fistula is an extremely rare complication of chronic pancreatitis and is virtually unheard
of in the setting of acute pancreatitis. A 67-year-old male presented with acute pancreatitis complicated by
pancreaticopericardial fistulization. The patient’s initial presentation was consistent with tamponade physiology.
Computed tomography demonstrated a gas-containing pericardial fluid llection extending into the anterior upper abdomen and ill-defined fluid collections within the pancreas representing necrosis with probable infection.
Surgical exploration of the window revealed a pancreatic pericardial fistula and an infected window. The patient
ultimately passed away from septic shock. We present this rare complication of pancreatitis and review the
relevant literature.
Introduction
A pancreatic fistula is an abnormal communication between the pancreas and other organs, which results from
disruption of pancreatic ducts and subsequent leakage of pancreatic enzymes. Pancreatic fistulas can either be
external, in which case the communication is with the skin, or internal, with the most common sequela being the
development of a pancreatic pseudocyst. Other complications depend on the flow of secretions from a disrupted
pancreatic duct or leakage from a pseudocyst. If a pancreatic duct is disrupted such that pancreatic enzymes
leak anteriorly into the peritoneal cavity, the result is pancreatic ascites. Similarly, in the event of a posterior
disruption, pancreatic enzymes leak into the mediastinum via either the aortic or esophageal hiatus, resulting in
a mediastinal pseudocyst if contained. If uncontained, however, pancreatic enzymes would leak into the mediastinum, pleural space, or, rarely, into the pericardium, resulting in enzymatic mediastinitis, pleural effusion, or
pericardial effusion, respectively.1,2
Case Report
A 67-year-old male with a complicated past medical history notable for severe rheumatoid arthritis, for which he
was receiving tocilizumab, presented with increasing dyspnea and chest pain. Upon presentation, the patient
was tachycardic, tachypneic, and hypotensive. His lab values were notable for an elevated white blood cell
(WBC) count of 48.6 x 103/uL, lactic acid of 8.9 mmol/L, and liver enzymes with an SGOT (AST) of 2,552, SGPT
(ALT) of 5,198. Electrocardiography showed sinus tachycardia with low voltage. The patient was emergently
intubated in the emergency department (ED) after becoming unresponsive. Out of concern for tamponade, the
patient underwent emergent pericardiocentesis with removal of 800 mL of cloudy, milky fluid with speckled white
flecks. The patient was admitted to the intensive care unit (ICU) with a provisional diagnosis of rheumatoid pericardial effusion resulting in cardiac tamponade and septic shock in an immune-compromised host.
ACG Case Rep J 2013;1(1):40–43. doi:10.14309/crj.2013.15. Published online: October 8, 2013.
Correspondence: Parth J. Parekh, MD, Eastern Virginia Medical School, Department of Internal Medicine, 825 Fairfax Avenue, Hoffheimer Hall, Suite 445,
Norfolk, VA 23507 ([email protected]).
Copyright: © 2013 Parekh et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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ACG Case Reports Journal | Volume 1 | Issue 1 | October 2013
Parekh et al
Acute Pancreatitis: A Rare Complication
The patient was aggressively resuscitated, requiring pressor
support, and started on broad-spectrum antibiotics. After
blood and urine cultures were negative, an indium scan delineated marked WBC accumulation within the upper abdomen, favoring involvement of the pancreas (Figure 1). The
patient responded to broad-spectrum antibiotics and aggressive resuscitation and was discharged to a skilled nursing facility.
Figure 1. WBC Scan. Marked white blood cell accumulation within the upper abdomen. The anatomic distribution favors involvement of the transverse colon, pancreas, or stomach/proximal duodenum.
A few weeks following discharge, the patient returned to the
ED with recurrent shortness of breath and was noted to have
a moderate pericardial effusion on echocardiography without tamponade. A decision was made to place a pericardial
window. Shortly after the procedure, the patient began to
experience generalized abdominal and back pain with recurrent leukocytosis. Analysis of the pericardial fluid showed
an elevated lipase at 24,000 U/L. A subsequent CT demonstrated a gas-containing fluid collection anterior to the heart,
contiguous with the anterior upper abdomen. There were
fluid collections within the pancreatic head and neck, raising the possibility of necrosis and superimposed infection
(Figure 2). Surgical exploration of the subxiphoid window
revealed a pancreaticopericardial fistula and an infected
pericardial window (Figure 3). A decision was made not to
close the fistula but rather irrigate the pericardial space and
place a drain.
The patient became increasingly jaundiced and the wound
began to show signs of infection and enzymatic breakdown.
Subsequently, a wound vacuum was placed and somatostatin started. An EGD and subsequent ERCP revealed organized necrosis with communication to the lumen (Figure 4)
and side branch disruption at the head with filling of the
lesser sac; ultimately, an 11-cm stent was placed into the
pancreatic duct (Figure 5).
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A
B
C
D
Figure 2. CT Abdomen. (A and B) Gas-containing fluid collection anterior
to the heart contiguous with a pericardial effusion and extending into the
anterior upper abdomen as well as fluid collections (C and D) within the
pancreatic head and neck with possibility of pancreatic necrosis and superimposed infection.
The patient became hypotensive and was unable to maintain
adequate perfusion despite aggressive pressor support. An
emergent family meeting was held to discuss the patient’s
poor prognosis and goals of care. At this point a decision
was made to limit treatment to comfort measures only and
the patient expired shortly thereafter.
The etiology of the patient’s acute pancreatitis was never
fully understood. The common culprits such as gallstone,
ethanol, or hypertriglyceridemia-induced pancreatitis were
excluded relatively quickly. Tocilizumab has been implicated
in the setting of necrotizing pancreatitis, although the literature available is extremely limited.3 It is possible that tocilizumab played a role in this patient; however, there is insufficient evidence to implicate tocilizumab.
Figure 3. Pancreatic necrosis along with pancreaticoduodenal fistula.
ACG Case Reports Journal | Volume 1 | Issue 1 | October 2013
Parekh et al
Acute Pancreatitis: A Rare Complication
Discussion
A pancreatic pseudocyst is a collection of fluid lacking an epithelial lining arising either within or adjacent to
the pancreas, developing in up to 50% of cases of acute
pancreatitis.4 Typically comprised of pancreatic secretions, pseudocysts tend to form in the lesser sac or extend
evaluate left ventricular function in patients with acute pancreatitis. Pezzilli et al concluded the presence of pericardial effusion or left ventricular asynergy may be observed
in the setting of acute pancreatitis; however, these findings
seem to be unrelated to the severity of the disease in contrast to the presence of pleural and abdominal effusions.9
In a patient with a suspected pancreaticopericardial fistula,
CT imaging is a useful technique for the overall assessment
of pancreatitis and its complications. ERCP or MRCP may be
helpful in delineating ductal anatomy. In the presence of a
fistula, serum amylase levels are of little or no benefit, as they
may or may not be elevated, as was the case in our patient.10
A
B
Figure 4. ERCP. (A) Pancreatic stricture (genu). (B) Side branch disruption
(head) with large filling of large cyst cavity (lesser sac).
through planes of least resistance, including the aortic and
oesophageal hiatus, the foramen of Morgagni, and the diaphragm.5 Internal pancreatic fistulas presenting as pleural
effusions are a well-known complication of pancreatitis,2
but a pericardial effusion that presents as cardiac tamponade in the setting of acute pancreatitis is extremely rare.
The pathophysiology behind the development of a pericardial effusion in acute pancreatitis is poorly understood.
There have been several proposed theories that attempt to
explain the possible mechanism, including chemical pericarditis as a result of lymphatic or hematologic transport of
pancreatic enzymes and necrosis of vascular walls in the
areas of fat necrosis in the subpericardium.6 Maringhini
et al performed an echocardiogram on 100 patients with
a diagnosis of acute pancreatitis, 24 of whom had severe
pancreatitis and 3 of whom eventually succumbed to their
illness. Maringhini et al noted 17% of patients with acute
pancreatitis do have a pericardial effusion; however, the effusion in all 97 survivors dissipated spontaneously.7 Viyam et
al studied 15 patients with alcohol-induced pancreatitis by
M-mode echocardiography and noted 47% to have a pericardial effusion compared to 11% in the control population,
which he attributed to left ventricular dysfunction as a result
of chronic alcohol abuse.8 Pezzilli et al studied 21 patients
with M-mode and B-mode echocardiography to establish
the prevalence of pericardial effusion and simultaneously
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Conservative approaches may lead to closure rates of up
to 50%, thus an initial 2–4 week trial of conservative management is indicated. Bowel rest and somatostatin or its
analogue octreotide can be used to reduce pancreatic sections. A surgical approach, most commonly with a Roux-enY with or without partial pancreatic resection, is warranted
if the fistula does not close within 2–4 weeks. The role of
ERCP and stenting to bridge the site of duct disruption
serves as an alternative to surgery. Current recommendations are that the stent remain in situ for 6 weeks; however,
long-term data is necessary to determine the role for stenting in the management of internal pancreatic fistulas.10
Figure 5. Pancreatic sphincerotomy performed with insertion of 7 Fr 11 cm
pancreatic duct stent (Freeman).
Lamparter et al recently published the first case of a successful endoscopic treatment of a pancreaticopericardial
fistula. Their patient was a 57-year-old with a diagnosis of
acute alcoholic pancreatitis complicated by pericardial fistula and tamponade. Their patient underwent emergent
pericardiocentesis and was initially treated with intrapericardial triamcinolone and octreotide, which was unsuccessful. Next, they performed an ERCP and were able to
identify and successfully stent the culprit disrupted pancreatic duct, resulting in eventual resolution of the pancre-
ACG Case Reports Journal | Volume 1 | Issue 1 | October 2013
Parekh et al
aticopericarial fistula.11 The role of ERCP and pancreatic
duct stenting in the setting of a pancreaticopericardial fistula is not completely understood; however, this case illustrates its success and argues the necessity for further data.
Disclosures
Author contributions: P.J. Parekh and D.A. Johnson conceptualized, initiated, and wrote the article; D. Howerton initiated and wrote the article. P.J. Parekh is the article guarantor.
Financial disclosure: No funding source or conflicts of interest are reported.
Received: May 20, 2013; Accepted: August 26, 2013
References
1.
2.
Cameron JL, Kieffer RS, Anderson WJ, Zuidema GD. Internal pancreatic fistulas: Pancreatic ascites and pleural effusions. Ann Surg.
1976;184(5):587-93.
Iacono C, Procacci C, Frigo F, et al. Thoracic complications of pancreatitis. Pancreas. 1989;4(2):228-36.
Acute Pancreatitis: A Rare Complication
3.
Takeuchi T, Tanaka Y, Amano K, et al. Clinical, radiographic and functional effectiveness of tocilizumab for rheumatoid arthritis patients: REACTION 52-week study. Rheumatology (Oxford). 2011;50(10):190815.
4. Grace PA, Williamson RC. Modern management of pancreatic pseudocysts. Br J Surg. 1993;80(5):573-81.
5. Overbeck-Zubrzycka D, Lochan RJ, Balupuri S, et al. Pancreaticobronchial fistula: A complication of acute pancreatitis. JOP.
2011;12(1):59-61.
6. Withrington R, Collins P. Cardiac tamponade in acute pancreatitis.
Thorax. 1980;35(12):959-60.
7. Maringhini A, Ciambra M, Patti R, et al. Ascites, pleural, and pericardial effusions in acute pancreatitis. A prospective study of incidence,
natural history, and prognostic role. Dig Dis Sci. 1996;41(5):848-52.
8. Variyam EP, Shah A. Pericardial effusion and left ventricular function in patients with acute alcoholic pancreatitis. Arch Intern Med.
1987;147(5):923-5.
9. Pezzilli R, Billi P, Bertaccini B, Gullo L. Pericardial effusion and
left ventricular function in acute pancreatitis. Am J Gastroenterol.
1996;91(5):997-1000.
10. Ching SS, Rao MM, Ali A, et al. Chronic pancreatitis complicated by
pancreaticopericardial fistula. Surgical Practice. 2007;11(3):130-133.
11. Lamparter S, Sundermann H. Swinging heart in acute pancreatitis.
Am J Med Sci. 2013;346(2):160-1.
12. Bhatt VR, Koirala A, Wetz RV, et al. Cardiac tamponade in acute pancreatitis. BMJ Case Rep. 2011.
Publish your work in ACG Case Reports Journal
ACG Case Reports Journal is a peer-reviewed, open-access publication that provides GI fellows, private practice clinicians, and other members of the
health care team an opportunity to share interesting case reports with their peers and with leaders in the field. Visit http://acgcasereports.gi.org for
submission guidelines. Submit your manuscript online at http://mc.manuscriptcentral.com/acgcr.
43
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ACG Case Reports Journal | Volume 1 | Issue 1 | October 2013
ACG CASE REPORTS JOURNAL
CASE REPORT | PANCREAS/BILIARY
Portal Biliopathy Causing Recurrent Biliary Obstruction and
Hemobilia
Barry Schlansky, MD, MPH1, John A. Kaufman, MD, MS2, Gene Bakis, MD1, and
Willscott E. Naugler, MD1
1
2
Division of Gastroenterology and Hepatology, Oregon Health and Science University, Portland, OR
Dotter Interventional Institute, Oregon Health and Science University, Portland, OR
Abstract
A 63-year-old man with extrahepatic portal vein thrombosis presented with biliary obstruction and hemobilia
after a liver biopsy. Balloon sweep of the common bile duct removed clotted blood, and cholangiogram showed
a common bile duct narrowing, treated with biliary stenting. A percutaneous biliary catheter was later required
for recurrent biliary obstruction and hemobilia, and repeat cholangiogram confirmed portal biliopathy—a large
peri-biliary varix was compressing the common bile duct, causing biliary obstruction and intermittent portal
hypertensive hemobilia. A transjugular intrahepatic portosystemic shunt was inserted, followed by embolization
of the peri-biliary varix. Delayed diagnosis of portal biliopathy may lead to significant patient morbidity.
Introduction
Though chronic obstruction of the extrahepatic portal vein in the absence of cirrhosis is frequently associated
with bile duct abnormalities due to the formation of prominent collateral veins, symptomatic biliary disease is
uncommon. We report a case of extrahepatic portal vein obstruction due to portal vein thrombosis causing recurrent biliary obstruction and hemobilia that was effectively treated with variceal embolization and insertion of
a transjugular intrahepatic portosystemic shunt (TIPS).
Case Report
A 63-year-old man presented with 4 weeks of intermittent fever, dark urine, and pruritus, and 2 days of yellowed
skin and eyes and abdominal pain, unimproved with empiric antibiotics. Two years prior, he had been diagnosed
with extrahepatic portal vein (PV) thrombosis associated with the factor V Leiden mutation, and was receiving
chronic anti-coagulation. Two weeks before presentation, abnormal liver tests had prompted serologic testing for
infectious and metabolic etiologies of liver disease that were unrevealing. He then underwent a transjugular liver
biopsy 1 week before presentation that showed mild non-specific inflammation and no fibrosis. Simultaneous
venography revealed patent hepatic veins and a normal hepatovenous pressure gradient of 2 mmHg.
On physical examination, the patient was alert and afebrile, with blood pressure 102/59, heart rate 72, icteric
sclerae, jaundice, epigastric abdominal tenderness, and no abdominal distension. Laboratory studies revealed
white blood cells 7,300/mL, hemoglobin 14.2 g/dL, platelets 218,000/mL, aspartate aminotransferase (AST) 108
IU/L, alanine aminotransferase (ALT) 115 IU/L, total bilirubin 5.5 mg/dL, alkaline phosphatase 618 U/L, and
international normalized ratio 1.8. An abdominal ultrasound showed mild intrahepatic biliary dilation, a 6-mm
diameter common bile duct (CBD), and cholelithiasis. Because he had biliary dilation, cholestatic liver test
ACG Case Rep J 2013;1(1):44–46. doi:10.14309/crj.2013.16. Published online: October 8, 2013.
Correspondence: Barry Schlansky, MD, MPH, Division of Gastroenterology and Hepatology, Oregon Health and Science University, 3181 SW Sam Jackson
Park Road, L-461, Portland, OR 97239 ([email protected])
Copyright: © 2013 Schlansky et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
44
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ACG Case Reports Journal | Volume 1 | Issue 1 | October 2013
Schlansky et al
abnormalities, and no evidence of intrahepatic disease on
serologic testing or liver biopsy, endoscopic retrograde cholangiography (ERC) was pursued. After biliary sphincterotomy, balloon sweep of the CBD removed old blood and clots.
Cholangiogram showed an irregularly narrowed mid CBD
(Figure 1A, arrow), and a plastic biliary stent was inserted
proximally. The etiology of the obstruction was thought to
be bleeding into the CBD secondary to the transjugular liver
biopsy, but it was unclear what might be causing the cholangiographic abnormality. Symptoms and liver test abnormalities gradually improved, and the biliary stent was uneventfully removed 8 weeks later.
Portal Biliopathy and Hemobilia
Several weeks later, massive hemobilia recurred during endoscopic removal of the biliary stents, and a percutaneous
biliary catheter was inserted. Cholangiogram through the biliary catheter confirmed portal biliopathy—a large varix was
compressing the CBD, causing intermittent obstruction and
portal hypertensive hemobilia (Figure 1C, arrow). A transjugular intrahepatic portosystemic shunt (TIPS) was inserted,
followed by embolization of the large peri-biliary varix, and
biliary compression resolved on subsequent cholangiogram
(Figure 1D, arrow). Nearly 2 years later, hemobilia and biliary obstruction have not recurred, and his liver tests are
within the normal range.
Discussion
Figure 1. (A) Initial cholangiogram of a narrowed common bile duct (arrow).
(B) Computerized tomography of the abdomen obtained after insertion of
common bile duct stents revealed a peri-biliary varix (small arrows) adjacent to the stented common bile duct (large arrow). (C) After removal of the
biliary stents, cholangiogram demonstrated compression of the common
bile duct by the peri-biliary varix (arrow) that resolved after insertion of a (D)
transjugular intrahepatic portosystemic shunt (TIPS; arrow).
Four months later, he reported recurrent pruritus and jaundice. The total bilirubin was 6.8 mg/dL and alkaline phosphatase 316 U/L. ERC with balloon sweep of the CBD
caused rapid hemobilia that continued despite insertion of
side-by-side plastic biliary stents in an attempt to tamponade hemorrhage thought to be occurring from a luminal
CBD lesion. A covered metallic stent was considered but
not inserted due to brisk bleeding and inadequate visualization. Abdominal computerized tomography revealed the biliary stents (Figure 1B, large arrow) with a 1.2-cm diameter
varix coursing adjacent to the CBD without active contrast
extravasation, consistent with a diagnosis of portal biliopathy (Figure 1B, small arrows). Chronic superior mesenteric,
splenic, and PV thromboses with cavernous transformation
were unchanged. Hemobilia resolved after transhepatic PV
puncture with main PV stenting and mechanical thrombectomy; a portal venogram showed markedly diminished flow
through a large biliary collateral vein thought to be the bleeding culprit. The patient was discharged several days later.
45
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Chronic extrahepatic PV obstruction is common in the developing world and rare in Western nations.1 The most common etiologies of extrahepatic portal vein obstruction are
shown in Table 1. Development of collaterals is common
and often involves the epicholedochal and pericholedochal
venous plexuses. “Portal biliopathy” describes the development of portal hypertensive collaterals impinging on the
biliary tract lumen. By cholangiogram, portal biliopathy may
be identified in >80% of persons with chronic extrahepatic
PV obstruction. However, symptomatic biliary obstruction is
uncommon.2 Portal biliopathy should be considered in the
differential diagnosis of hemobilia and CBD obstruction in
any patient with known portal hypertension, especially when
chronic PV thrombosis without underlying cirrhosis is recognized.
Table 1. Most Common Etiologies of Extrahepatic Portal Vein
Obstruction
Children (N=275)a
Adults (N=356)b
1. Idiopathic (55%)
1. Idiopathic (54%)
2. Abdominal infections (36%)
2. Abdominal infections (20%)
3. Umbilical catheterization (6%)
3. Trauma/other (15%)
4. Trauma/other (3%)
4. Prothrombotic disorders (9%)
5. Pancreatitis (1%)
5. Pancreatitis (1%)
Pooled results from 7 studies published from 1962 to 1994.
b
Pooled results from 6 studies published from 1979 to 1997.
Table modified from Sarin SK, Agarwal SR. Extrahepatic portal vein obstruction.
Semin Liv Dis. 2002;22:43-58.
a
Although endoscopic treatment of choledocholithiasis
with biliary sphincterotomy and stenting is indicated when
stones are present,3 caution is warranted when portal biliopathy is coincident. Portal hypertensive hemobilia is rare
with sphincterotomy alone, despite the frequent presence
of adjacent ampullary collaterals, but it may be precipitated
by transient pressure elevation in the distal portion of biliary
varices during balloon sweeping.4 Endoscopic interventions
for symptomatic biliary narrowing due to portal biliopathy
have limited effectiveness and may cause major hemorrhage. Consequently, we advise a decompressive shunting
ACG Case Reports Journal | Volume 1 | Issue 1 | October 2013
Schlansky et al
procedure such as TIPS if technically feasible, particularly
if symptomatic biliary obstruction or hemobilia recur after
an initial attempt at endoscopic treatment. As in this case,
delays in diagnosis may lead to significant morbidity or even
mortality for the patient.
Disclosures
Author contributions: B. Schlansky drafted, critically revised,
and edited the article; J.A. Kaufman, G. Bakis, W.E. Naugler
critically revised and edited the article; all authors approved
the final draft submission. W.E. Naugler is guarantor of this
article.
Portal Biliopathy and Hemobilia
References
1.
2.
3.
4.
Sarin SK, Agarwal SR. Extrahepatic portal vein obstruction. Semin Liv
Dis. 2002;22:43–58.
Dhiman RK, Behera A, Chawla YK, Dilawari JB, Suri S. Portal hypertensive biliopathy. Gut. 2007;56:1001–1008.
Dumortier J, Vaillant E, Boillot O, et al. Diagnosis and treatment
of biliary obstruction caused by portal cavernoma. Endoscopy.
2003;35:446–450.
Sharma M, Ponnusamy RP. Is balloon sweeping detrimental in portal
biliopathy? A report of 3 cases. Gastrointest Endosc. 2009;70:171–
173.
Financial disclosure: The work contained in this article was
not supported by any external funding source. No authors
report any competing or financial interests in any aspect of
the article.
Received: May 28, 2013; Accepted: August 30, 2013
Publish your work in ACG Case Reports Journal
ACG Case Reports Journal is a peer-reviewed, open-access publication that provides GI fellows, private practice clinicians, and other members of the
health care team an opportunity to share interesting case reports with their peers and with leaders in the field. Visit http://acgcasereports.gi.org for
submission guidelines. Submit your manuscript online at http://mc.manuscriptcentral.com/acgcr.
46
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ACG Case Reports Journal | Volume 1 | Issue 1 | October 2013
ACG CASE REPORTS JOURNAL
CASE REPORT | PANCREAS/BILIARY
Minor Papilla Adenoma Management in Patients with
Pancreas Divisum and Familial Adenomatous Polyposis
Robert T. Lapp, MD, and Grant F. Hutchins, MD
Department of Gastroenterology and Hepatology, University of Nebraska Medical Center, Omaha, NE
Abstract
Several case reports on endoscopic resection of minor papilla adenomas exist in the literature. However, there
are no reported cases of endoscopic resection in patients with minor papilla adenomas with associated familial
adenomatous polyposis (FAP) and pancreas divisum. We report a case of a minor papilla adenoma in a patient
with FAP and pancreas divisum. The case demonstrates a new association between these disease processes.
Defining pancreatic ductal anatomy prior to endoscopic intervention is essential. In addition, we demonstrate
the safety and feasibility of endoscopic management of minor papilla tumors in patients with FAP and associated
pancreas divisum.
Introduction
Tumors of the minor papilla are uncommon and, to date, are only described in case reports.1–7 In contrast, tumors of the major papilla account for approximately 5% of gastrointestinal (GI) neoplasms.8 Duodenal adenomas
may occur as sporadic lesions or in patients with familial adenomatous polyposis (FAP). In the subset of patients
with FAP, up to 90% of adult patients will develop duodenal adenomas.9 For many years, surgical resection was
considered the mainstay of therapy for adenomas involving the major or minor papilla. In more recent years,
advances in endoscopic papillectomy of ampullary adenomas has been shown to have a high success rate, low
complication rate, and, importantly, a low recurrence rate.10 We report a case of endoscopic treatment of a minor
papillary adenoma in a patient with FAP and associated pancreas divisum, a condition not previously reported
with suggested algorithmic work-up.
Case Report
A 36-year-old woman with personal and family history of FAP, status post-total abdominal proctocolectomy with
rectal mucosectomy and ileoanal pouch anastomosis (IPAA) performed at the age 18 after she was diagnosed
with colon cancer, was found to have an adenoma involving her minor papilla. Her baseline upper endoscopy
exam for evaluation of gastric and duodenal polyps was performed at age 30. On her initial endoscopy she had
multiple 3–4-mm polyps in her duodenum, which were managed with endoscopic resection. No duodenal polyps were associated with the major or minor papilla at this time. In addition, she had multiple 3–4-mm fundic
gland polyps in her stomach.
On follow-up surveillance endoscopy 2 years later, she was found to have a 1-cm adenoma involving her minor
papilla. A biopsy of this polyp was consistent with a tubular adenoma without high-grade dysplasia. At EUS, the
lesion was confined to the mucosal layers and was without ductal or duodenal wall involvement. A suspicion of
pancreas divisum at EUS prompted a non-invasive MRCP, which confirmed pancreas divisum anatomy (Figure 1).
ACG Case Rep J 2013;1(1):47–50. doi:10.14309/crj.2013.17. Published online: October 8, 2013.
Correspondence: Robert T. Lapp, MD, Department of Gastroenterology and Hepatology, University of Nebraska Medical Center, 982000 NMC, Omaha, NE
68198 ([email protected])
Copyright: © 2013 Lapp and Hutchins. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
47
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ACG Case Reports Journal | Volume 1 | Issue 1 | October 2013
Lapp and Hutchins
During ERCP, a pancreatic spincterotomy was performed,
followed by placement of a 5F x 5-cm dorsal pancreatic duct
stent (Figures 2 and 3). Next, endoscopic snare resection of
the duodenal lesion was performed, followed by fulgation of
the remaining area of adenomatous-appearing tissue with
APC (Figure 4). Six months later at follow-up endoscopy,
Minor Papillary Adenoma in FAP
biopsies of the minor papilla were negative for adenomatous
tissue.
Discussion
There are several case reports on endoscopic resection of
minor papilla tumors; however, this case represents the first
report describing endoscopic minor papilla resection in a
patient with FAP and pancreas divisum anatomy. Periampullary and duodenal tumors are reported to be present in up
to 80% of patients with FAP, with the cancer risk 100-fold
greater than that of the general population.11 No known association of FAP and pancreas divisum exists in the literature.
Prior to the acceptance of endoscopic papillectomy as a safe
and feasible technique, surgical removal was the standard of
care. However, surgical removal has considerable morbidity
and mortality.12 In contrast, endoscopic resection is a safe
and effective treatment of these patients in the absence of
ductal involvement and is the standard of care in most highvolume advanced endoscopy centers. Complications of endoscopic papillectomy are similar to those encountered with
ERCP, including pancreatitis, perforation, bleeding, sedation
complications, and cholangitis.13
Figure 1. MRCP demonstrating the dorsal pancreatic duct draining through
the minor papilla consistent with pancreas divisum.
Figure 3. Dorsal pancreatic duct stent placement during ERP prior to adenoma removal.
Figure 2. Contrast injection into the minor papilla demonstrates filling of the
dorsal pancreatic duct, but not the ventral pancreatic duct.
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Accurate evaluation prior to attempted endoscopic resection
often involves a cross-sectional imaging study and performance of endoscopic ultrasound to rule out ductal involvement. EUS is a highly sensitive, effective modality for staging
ampullary neoplasms involving both the major and minor
papillary regions. EUS is our standard of practice to perform
staging prior to ampullary resection in all but select cases
ACG Case Reports Journal | Volume 1 | Issue 1 | October 2013
Lapp and Hutchins
Minor Papillary Adenoma in FAP
formed every 3 years thereafter, given her history of FAP.15
We report the first case of minor papillary adenoma involvement in a patient with FAP and previously undiagnosed
pancreas divisum anatomy. Based on our experience, MRI/
MRCP in addition to EUS examination of the ampulla to exclude ductal involvement seems a prudent, non-invasive
cross-sectional imaging procedure given the high degree of
potential complications involving the major and minor endoscopic papillectomy. Our case demonstrates that endoscopic resection appears to be a feasible and safe alternative
to surgery for management of minor papillary adenomas in
patients with FAP and pancreas divisum anatomy.
Disclosures
Author contributions: All authors contributed equally to the
creation of this manuscript. R.T. Lapp is the guarantor of the
article.
Financial disclosures: All authors have nothing to disclose
and no conflicts of interest.
Received: August 1, 2013; Accepted: September 23, 2013
Figure 4. Minor papilla adenoma snare resection with dorsal pancreatic
duct stent in place.
of adenomatous involvement of the ampulla. Complementing our endoscopic evaluation, performance of a secretinenhanced magnetic resonance cholangiopancreatography
(MRCP) has become a valuable adjunct given its non-invasive nature and its improved sensitivity in the diagnosis of
many pancreaticobiliary disorders, including pancreas divisum. ERCP remains the gold standard for diagnosis of pancreas divisum, but it is invasive and associated with many
complications including pancreatitis. Following EUS examination and review of diagnostic imaging, ERCP with sphincterotomy of the minor papilla is usually performed. The preferred method at endoscopy is en bloc resection of a given
lesion, though piecemeal resection is sometimes employed
when lesions are larger than 2 cm. Resection in lesions of
this size or greater may leave residual tissue.14 Argon plasma
coagulation is often then performed to ablate residual tissue,
as was the case in our patient.
Complete adenoma resection is the goal of papillectomy, but
recurrence rates after endoscopic snare papillectomy have
been reported at 0–26%.15 Our patient demonstrated tumorfree margins on histological evaluation and surveillance endoscopy, with biopsy demonstrating no tumor recurrence at
the resection site. Follow-up for our patient will include endoscopy with side-viewing duodenoscopy every 6 months for
a minimum of 2 years, and endoscopic surveillance per-
49
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References
1.
Sugiyama M, Kimura W, Muto T, et al. Endoscopic resection of adenoma of the minor papilla. Hepatogastroenterology. 1999;46(25):189192. P
2. Lucena JF, Alvarez OA, Gross GW. Endoscopic resection of heterotropic pancreas of the minor duodenal papilla: Case report and review
of the literature. Gastrointest Endosc. 1997;46(1):69–72.
3. Nakamura Y, Tajiri T, Uchida E, Aimoto T, et al. Adenoma of the minor
papilla associated with pancreas divisum. Hepatogastroenterology.
2007;54(78):1841–1843.
4. Loew BJ, Lukens FJ, Navarro F, et al. Successful endoscopic resection
of gangliocytic paraganglioma of the minor papilla in a patient with
pancreas divisum and pancreatitis (with video). Gastrointest Endosc.
2007;65(3):547–550.
5. Itoi T, Sofuni A, Itokawa F, et al. Endoscopic resection of carcinoid of
the minor duodenal papilla. World J Gastroenterol. 2007;13(27):3763–
3764.
6. Trevino JM, Wilcox CM, Varadarajulu S. Endoscopoic resection of minor papilla adenomas (with video). Gastrointest Endosc.
2008;68(2):383–386.
7. Kanamori A, Kumada T, Kiriyama S, et al. Endoscopic papillectomy of
minor papillary adenoma associated with pancreas divisum. World J
Gastroenterol. 2009;15(9):1138–1140.
8. Scarp A, Capelli P, Zamboni G, et al. Neoplasia of the ampulla of Vater.
Am J Path. 1993;142:1163–1172.
9. Bulow S, Björk J, Christensen IJ, et al. Duodenal adenomatosis in
familial adenomatous polyposis. Gut. 2004;53(3):381–384.
10. Bohnacker S, Seitz U, Nguyen D, et al. Endoscopic resection of
benign tumors of the duodenal papilla without and with intraductal
growth. Gastrointest Endosc. 2005;62(4):551–560.
11. Burke C, Beck GJ, Church JM, van Stolk RU. The natural history of
untreated duodenal and ampullary adenomas in patients with familial
adenomatous polyposis followed in an endoscopic surveillance program. Gastrointest Endosc. 1999;49(3):358–64.
12. Katsinelos P, Paroutoglou G, Kountouras J, et al. Safety and long-term
ACG Case Reports Journal | Volume 1 | Issue 1 | October 2013
Lapp and Hutchins
Minor Papillary Adenoma in FAP
follow-up of endoscopic snare excision of ampullary adenomas. Surg
Endosc. 2006;20(4):608–613.
13. Ito K, Fujita N, Noda Y, et al. Preoperative evaluation of ampullary
neoplasm with EUS and transpapillary intraductal US: A prospective and histopathologically controlled study. Gastrointest Endosc.
2007;66(4):740–7.
14. Cheng C, Sherman S, Fogel EL, et al. Endoscopic snare papillectomy for tumors of the duodenal papillae. Gastrointest Endosc.
2004;60(5):757–764.
15. Pandolfi M, Martino M, Gabbrielli A. Endoscopic treatment of ampullary adenomas. JOP. 2008;9(1):1–8.
Publish your work in ACG Case Reports Journal
ACG Case Reports Journal is a peer-reviewed, open-access publication that provides GI fellows, private practice clinicians, and other members of the
health care team an opportunity to share interesting case reports with their peers and with leaders in the field. Visit http://acgcasereports.gi.org for
submission guidelines. Submit your manuscript online at http://mc.manuscriptcentral.com/acgcr.
50
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ACG Case Reports Journal | Volume 1 | Issue 1 | October 2013
ACG CASE REPORTS JOURNAL
CASE REPORT | PANCREAS/BILIARY
Emphysematous Cholecystitis Resulting in Secondary Biliary
Cirrhosis: A Rare Complication of Endoscopic Retrograde
Cholangiopancreatography
Khurram Bari, MD1, Harry R. Aslanian, MD1, Jeffrey Pollak, MD2, Eric Reiner, MD2, Ronald
R. Salem, MD3, Tamar H. Taddei, MD1, Sukru H. Emre, MD4, and Priya A. Jamidar, MD1
Department of Digestive Diseases, Yale University School of Medicine, New Haven, CT
Department of Interventional Radiology, Yale University School of Medicine, New Haven, CT
3
Department of Surgery, Yale University School of Medicine, New Haven, CT
4
Yale New Haven Transplantation Center, Transplantation and Immunology, New Haven, CT
1
2
Abstract
A 48-year-old female developed acute emphysematous cholecystitis after an endoscopic retrograde cholangiopancreatography (ERCP) for evaluation of sphincter of Oddi dysfunction. Cholecystectomy was performed 2 days
later. Cultures grew Clostridium perfringens. The patient received broad-spectrum antibiotics but developed recurrent cholangitic abscesses and intra- and extra-hepatic biliary necrosis. She was managed by percutaneous
transhepatic biliary drains. For next 3 years, patient had recurrent episodes of biliary obstruction, cholangitis,
and sepsis, resulting in secondary biliary cirrhosis requiring a liver transplantation. Emphysematous cholecystitis
is a rare complication of ERCP. Prompt diagnosis and surgical management can prevent further spread of infection to biliary tree.
Introduction
Endoscopic retrograde cholangiopancreatography (ERCP) is a widely used technique for evaluation and treatment of pancreatic and biliary tract disease. Procedure-specific complications occur in up to 7% of patients,
and mortality is estimated to be around 0.3%.1 Common complications include pancreatitis, bleeding, sepsis,
perforation, aspiration, and cardiac arrhythmias.1 Emphysematous cholecystitis is a rare form of cholecystitis
characterized by infection of the gallbladder by gas-forming bacteria such as Clostridium perfringens, Pseudomonas, Klebsiella, or E. coli.2 Cholecystitis as a complication of ERCP is rare, and to date, only 3 cases of
emphysematous cholecystitis after ERCP have been reported.3–5 We present a case of a woman who not only
developed emphysematous cholecystitis after ERCP, but also sustained intra- and extra-hepatic biliary ductal
injury resulting in recurrent cholangitis and liver abscesses.
Case Report
A 48-year-old female presented for an elective outpatient ERCP for evaluation of sphincter of Oddi dysfunction.
The indication for the procedure was recent acute pancreatitis and episodic abdominal pain. Using a Lehman
perfusion aspiration manometry catheter (Cook Medical, Winston-Salem, NC), the common bile and pancreatic
ducts were cannulated and basal sphincter pressures were measured and found to be normal (<40 mmHg).
Cholangiography and pancreatography were normal. The cystic duct was cannulated and after cholecystokinin
infusion, bile was aspirated and sent for microlithiasis analysis. No immediate complications were appreciated.
ACG Case Rep J 2013;1(1):51–54. doi:10.14309/crj.2013.18. Published online: October 8, 2013.
Correspondence: Khurram Bari, MD, 3912 Taubman Center, 1500 E. Medical Center Dr., SPC 5362, Ann Arbor, MI 48109-5362 ([email protected])
Copyright: © 2013 Bari et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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Bari et al
Due to mild post-procedure discomfort, the patient was
admitted to the hospital for overnight observation. The patient developed chest pain several hours after the procedure. Blood work revealed white blood cell count of 14.5
x 1,000/µL, hematocrit 32.9%, aspartate aminotransferase
(AST) 176 U/L, alanine aminotransferase (ALT) 32 U/L, total bilirubin 0.46 mg/dL, serum lipase 93 U/dL, and serum
troponin 2.3 ng/mL. A cardiology evaluation was requested
and the patient was found to have a non-ST elevation myocardial infarction, which was treated medically. The following
day, approximately 24 hours after the procedure, the patient
developed abdominal pain with peritoneal signs. Laboratory
tests revealed an AST 250 U/L, ALT 55 U/L, total bilirubin
3.34 mg/dL, direct bilirubin 2.85 mg/dL, and lipase of 192
U/dL. A computerized tomography (CT) scan of the abdomen identified a large amount of air within and around the
gallbladder. Extensive free air was noted in the lesser sac,
retroperitoneum, intraperitoneal cavity, and the bile duct
(Figure 1). In the posterior segment of the right hepatic lobe,
a loculated area of air that did not conform to the biliary
tree was seen. A presumptive diagnosis of emphysematous
cholecystitis was made with suspicion of bowel perforation,
given the large amounts of intra-abdominal air. The patient
was started on broad spectrum antibiotics (ampicillin/sulbactam).
Emphysematous Cholecystitis as Complication of ERCP
dence of bowel perforation. Cholecystectomy was performed
with no gallstones present. Examination of the common bile
duct (CBD) was without any abnormalities; however, the
common hepatic duct (CHD) was markedly inflamed with
possible gangrene. Histopathologic examination of the gallbladder revealed gangrenous cholecystits with gram-positive
rods invading the gallbladder wall. Cultures from the gallbladder and blood grew Clostridium perfringens. The patient
continued to improve and was discharged home 14 days
after her surgery.
One week after discharge, the patient presented with abdominal pain and fever. An abdominal CT scan revealed 2
large abscesses, one in the left lobe and the other in the
right lobe of the liver. One percutaneous drainage catheter
was placed in each abscess by interventional radiology.
The catheter in the left lobe abscess started to drain bilious
fluid. Cholangiography via percutaneous drain a few days
later showed communication of the left lobe abscess with
the left intrahepatic biliary system along with extravasation
of contrast in the peribiliary area, indicating disruption and
necrosis of intrahepatic ducts (Figure 2). The CHD and CBD
demonstrated necrosis and infarction with intramural tracking of contrast. A trans-hepatic 8F locking loop draining
A laparotomy performed 2 days after the initial ERCP revealed a completely gangrenous gallbladder without any evi-
Figure 2. Contrast injection through percutaneous abscess drain showing
communication between abscess, left biliary system, and extravasation of
contrast.
Figure 1. Computed tomography (CT) image showing extensive gas in gallbladder, gallbladder wall, and intraperitoneal cavity.
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catheter was placed through the peripheral left bile duct,
with the loop in the cavity of the disrupted common hepatic
duct. The patient was continued on antibiotics and supportive measures. A couple of weeks later the CHD drain was
exchanged for an internal external percutaneous drain. The
patient was discharged home; however, she presented to the
emergency room 4 weeks later with worsening abdominal
pain and fever, and was found to have a serum creatinine
of 3.5 mg/dL and leukocytosis of 20,000/µL. She required
treatment of septic shock with broad spectrum antibiotics,
supportive measures, and revision of biliary drain catheters.
ACG Case Reports Journal | Volume 1 | Issue 1 | October 2013
Bari et al
Emphysematous Cholecystitis as Complication of ERCP
Over the next 3 years, the patient had recurrent hospital
admissions due to cholangitis; recurring hepatic abscesses,
sepsis with Enterococcus, Pseudomonas, Klebsiella, and
Candida; and severe hypotension, renal failure and respiratory failure managed by percutaneous drains, antibiotics,
and supportive care. Most of these episodes within the first
year required medical care in intensive care units. An ERCP
was done 15 months after the index ERCP, which revealed
formation of multiple strictures and beading in the intra- and
extra-hepatic biliary tree. The hepatic abscesses resolved,
but the biliary strictures required management by placement
and exchange of biliary stents every 3 months. The patient,
however, continued to show evidence of progressive sclerosing cholangitis and developed end-stage liver disease. Three
years after the initial insult, the patient underwent successful living donor liver transplantation. Explant histopathology
revealed secondary biliary cirrhosis, bile duct necrosis, fungal hyphae, and bacterial organisms. The patient has maintained normal hepatobiliary function and has overall been
feeling well in 3 years of follow-up after liver transplantation.
Discussion
Emphysematous cholecystitis is a rare but well-described
variant of acute cholecystitis. It is characterized by the presence of gas in the gallbladder wall; infection by gas-producing organisms including Clostridia species, Klebsiella, E. coli;
a higher incidence of gangrene and perforation; higher incidence of acalculous disease; and higher mortality. Emphysematous cholecystitis is more common in males, and more
than one-third of patients with this condition have diabetes
mellitus.2,6 The exact etiology of emphysematous cholecystitis is unknown, but an initial ischemic insult with secondary infection from gas-forming bacteria has been proposed
based on histopathologic findings.7 Although a diagnosis can
be made on plain films revealing air in the gallbladder wall,
a CT scan provides further evaluation for biliary enteric com-
munication, and the presence of gallstones or perforation.
The standard management of emphysematous cholecystitis
is emergent cholecystectomy.
Emphysematous cholecystitis as a complication of ERCP has
been described in only 3 prior case reports.3–5 A comparison
of these 3 cases and our patient is described in Table 1. Our
patient differed in multiple ways, including younger age, female gender, non-diabetic, and significant intra- and extrahepatic biliary injury.
Cholangiopathy with biliary inflammation and necrosis has
been recognized as a result of post-liver transplantation
ischemic injury, particularly with livers donated after cardiac
death (DCD),8 surgical complication of laparoscopic cholecystectomy,9 advanced HIV/AIDS cholangiopathy,10 after radiofrequency ablation for hepatocellular carcinoma,11 and in
patients with hemophagocytic syndrome.12 However, to our
knowledge, this is the first report of infectious biliary necrosis
and cholangiopathy as a complication of ERCP. The mechanism seems to be an initial ischemic insult during ERCP
and contrast injection with superimposed bacterial infection
causing cholecystitis and rapid spread of infection to the
biliary system. Our patient developed myocardial infarction
after the initial ERCP, which delayed cholecystectomy and
may have promoted the spread of infection to the biliary tree.
Unlike the other reported cases of post-ERCP emphysematous cholecystitis, cystic duct was cannulated for direct
aspiration of gallbladder bile in our case, which, theoretically, could increase the chance of bacterial colonization.
Aspiration of bile from common bile duct or duodenum after
stimulation by cholecystokinin is another effective but less
invasive method to evaluate for microlithiasis.13 Surprisingly,
our patient had none of the risk factors of emphysematous
cholecystitis, such as advanced age, diabetes mellitus, and
male gender. Our patient did not receive pre-procedure antibiotics. Recent data and American Society of Gastrointesti-
Table 1. Comparison Between 4 Reported Cases of Post-ERCP Emphysematous Cholecystitis
Prophylactic
Antibiotics Use/
Gallstones
Biliary
Injury
Procedure
Indication
Sex
Diabetes
Mellitus
Baker et al
ERCP with cholangiogram
NR
Male
Yes
No / No
No
Died despite emergent
cholecystectomy and
supportive measures
Alvarez et al4
ERCP with cholangiogram
and pancreatogram; no
sphincterotomy
Double duct
sign, pancreatic
head mass
Male
No
No / No
No
Died despite emergent
cholecystectomy and
supportive measures
Itah et al5
ERCP with cholangiogram
and sphincterotomy
Cholangitis
Male
NR
NR/ Yes
No
Uneventful recovery after
cholecystectomy
ERCP with cholangiogram,
pancreatogram, and sphincter
pressure measurement
Recent
pancreatitis
Female
No
No / No
Yes
Emergent cholecystectomy,
recurrent hepatic abscesses,
liver transplantation
Case Report
3
Current case
Outcome
ERCP = endoscopic retrograde cholangiopancreatography; NR = not reported.
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ACG Case Reports Journal | Volume 1 | Issue 1 | October 2013
Bari et al
Emphysematous Cholecystitis as Complication of ERCP
nal Endoscopy (ASGE) recommendations suggest a benefit
of pre-ERCP antibiotics in only those patients with known
or suspected biliary obstruction in which complete drainage
may not be achieved.14,15
4.
Though current guidelines do not recommend routine antibiotic use given the low likelihood of infection, infectious
complications of ERCP can occur even in low-risk patients
undergoing diagnostic procedure without any biliary obstruction. Prompt diagnosis of the complication and treatment is
important to prevent long-term complications and mortality.
7.
5.
6.
8.
9.
10.
Disclosures
Author contributions: K. Bari, H. Aslanian, and P. Jamidar
conceptualized, initiated, and wrote the article; J. Pollak, R.
Salem, S. Emre, and P. Jamidar revised the article for critical
intellectual content and approved the final version for publication; and E. Reiner and T. Taddei performed the literature
review and conceptualized the article and figures. P. Jamidar is the article guarantor.
11.
12.
13.
Financial disclosure: No financial support or conflicts of interest to disclose.
14.
Received: August 3, 2013; Accepted: September 25, 2013
15.
References
1.
2.
3.
Alvarez C, Hunt K, Ashley SW, Reber HA. Emphysematous cholecystitis after ERCP. Dig Dis Sci. 1994;39(8):1719–1723.
Itah R, Bruck R, Santo M,et al. Gangrenous cholecystitis: A rare complication of ERCP. Endoscopy. 2007;39(suppl 1):E223–4.
Rosoff L, Meyers H. Acute emphysematous cholecystitis: An analysis
of ten cases. Am J Surg. 1966;111(3):410–423.
May RE, Strong R. Acute emphysematous cholecystitis. Br J Surg.
1971;58(6):453–8.
Taner CB, Bulatao IG, Willingham DL,et al. Events in procurement as
risk factors for ischemic cholangiopathy in liver transplantation using
donation after cardiac death donors. Liver Transpl. 2012;18(1):100–
11.
de Santibáñes E, Ardiles V, Pekolj J. Complex bile duct injuries: Management. HPB (Oxford). 2008;10(1):4–12.
Devarbhavi H, Sebastian T, Seetharamu S, Karanth D. HIV/AIDS cholangiopathy: Clinical spectrum, cholangiographic features and outcome in 30 patients. J Gastroenterol Hepatol. 2010;25(10):1656–60.
Schneider A, Türck J, Helmberger T,et al. Radiofrequency ablationassociated necrosis of the hepatic duct confluence: Re-establishing biliary continuity with percutaneous cholangiographic-peroral
cholangioscopic rendezvous (with videos). Gastrointest Endosc.
2011;74(5):1163–6.
Li H, Li X, Liao XX, et al. Drug associated vanishing bile duct syndrome
combined with hemophagocytic lymphohistiocytosis. World J Gastrointest Endosc. 2012;16;4(8):376–8.
Elta GH. Sphincter of Oddi dysfunction and bile duct microlithiasis in
acute idiopathic pancreatitis. World J Gastroenterol. 2008;14(7):1023–
1026.
Banerjee S, Shen B, Baron TH, et al; for ASGE Standards of Practice
Committee. Antibiotic prophylaxis for GI endoscopy. Gastrointest Endosc.
2008;67(6);791–798.
Harris A, Chan AC, Torres-Viera C, et al. Meta-analysis of antibiotic
prophylaxis in endoscopic retrograde cholangiopancreatography
(ERCP). Endoscopy. 1999;31:718–24.
Andriulli A, Loperfido S, Napolitano G,et al. Incidence rates of postERCP complications: A systematic survey of prospective studies. Am J
Gastroenterol. 2007;102(8):1781–8.
Mentzer RM, Golden GT, Chandler JG, Horsley JS III. A comparative appraisal of emphysematous cholecystitis. Am J Surg. 1975;129(1):10–5.
Baker JP, Haber GB, Gray RR, Handy S. Emphysematous cholecystitis complicating endoscopic retrograde cholangiography. Gastrointest
Endosc. 1982;28:184–186.
Publish your work in ACG Case Reports Journal
ACG Case Reports Journal is a peer-reviewed, open-access publication that provides GI fellows, private practice clinicians, and other members of the
health care team an opportunity to share interesting case reports with their peers and with leaders in the field. Visit http://acgcasereports.gi.org for
submission guidelines. Submit your manuscript online at http://mc.manuscriptcentral.com/acgcr.
54
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ACG Case Reports Journal | Volume 1 | Issue 1 | October 2013
ACG CASE REPORTS JOURNAL
CASE REPORT | LIVER
Hepatotoxicity Associated with Herbal Tea Containing Kelp
Lavanya Viswanathan, MD, MS1, and Anish Patel, DO2
Division of Internal Medicine, Brooke Army Medical Center, San Antonio Uniformed Services Health Education
Consortium (SAUSHEC), Fort Sam Houston, TX
2
Division of Gastroenterology/Hepatology, Carl R. Darnall Army Medical Center, Fort Hood, TX
1
Abstract
A 40-yr-old Sri Lankan female presented to the gastroenterology clinic with jaundice. Further work-up revealed
extrahepatic cholestasis with a hepatocellular component; however, subsequent work-up revealed no significant
findings. Hospitalization revealed hepatotoxicity associated with ingestion of a homemade herbal tea containing
kelp (Laminaria), which was confirmed with further history. Hepatotoxicity associated with herbal tea ingestion is
rare, but should be a consideration in patients with unexplained jaundice. Inquiries into dietary or herbal supplements should always be made during routine history taking, as it may be useful in achieving the diagnosis.
Introduction
Dietary and herbal supplements are a popular alternative therapy option in the United States. However, regulation of herbal supplements has not kept up with the growing demand due to limited oversight by the FDA. Patients are often hesitant to admit to the use of alternative medicine and herbal supplements to their physicians.
As use of herbal supplements continues to rise, it becomes more important to obtain complete medication
histories from patients. We present the first reported case of kelp (Laminaria) hepatotoxicity in a patient drinking
homemade Chinese rice tea.
Case Report
A 40-year-old Sri Lankan female presented to the outpatient gastroenterology clinic with jaundice and pruritus,
but complained of no other significant symptoms. Her past medical history was significant for type 2 diabetes
mellitus. She reported stopping her medications at least 1 month prior to her visit due to failure to refill her prescription. Her medication only included metformin therapy, which she had been using for at least 2 years. The
patient denied any new medications, blood transfusions, drug/alcohol abuse, herbal supplementation, or recent
travel upon initial evaluation.
On physical exam, she was icteric and jaundiced with no organomegaly or abdominal tenderness. The initial
laboratory studies revealed elevated bilirubin (total 9.2 mg/dL and direct 7.4 mg/dL), alkaline phosphatase (435
IU/L), transaminases (AST 219 IU/L and ALT 435 IU/L), and gamma glutamyl transpeptidase (416 IU/L). Hemoglobin and hematocrit were 13.6 g/dL and 40%, respectively. Hospitalization was recommended for further
work-up. Further hepatic work-up, including viral serologies, iron panel, alpha-1 antitrypsin, ceruloplasmin, and
ANA/ASMA were negative. Ultrasound of the right upper quadrant was significant for minor common bile duct
dilation without gallstones. Abdominal CT to better evaluate the pancreaticobiliary system was benign without
any masses. ERCP revealed a minor amount of sludge with a slightly dilated common bile duct (CBD). Liver
biopsy revealed intrahepatic centrilobular cholestasis with discrete microvesicular steatosis, but with few eosinoACG Case Rep J 2013;1(1):55–57; doi:10.14309/crj.2013.19. Published online: October 8, 2013.
Correspondence: Anish Patel, Carl R. Darnall Army Medical Center, 36000 Darnall Loop, Ft. Hood, TX, 76544 ([email protected])
Copyright: © 2013 Vishwanathan and Patel. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which
permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
55
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ACG Case Reports Journal | Volume 1 | Issue 1 | October 2013
Viswanathan and Patel
Hepatotoxicity Associated with Herbal Tea
phils and no significant lymphocyte infiltrate.
As the patient’s hospitalization progressed, bilirubin and
transaminase levels began to normalize (Table 1). A more
detailed history taken later on during her hospitalization revealed the use of homemade Chinese rice tea, which was
used as a natural remedy for her diabetes. Further discussion revealed that ingredients included long grain white rice,
herbal tea blend (flavoring without significant tea component), kelp, and boiled water. The patient reported drinking
up to 3 cups per day for over the past 2 months. She did not
drink any herbal tea during her hospitalization and was advised to stop using it upon discharge. Follow-up in 1 month’s
time after discontinuation of the herbal tea revealed normalization of bilirubin (total 2.0 mg/dL and direct 1.3 mg/dL),
transaminases (AST 17 IU/L and ALT 26 IU/L), and alkaline
phosphatase (161 IU/L).
Discussion
Neutraceuticals are used by 158 million Americans who
spent $17 billion in 2000 and increasingly more every year.1
A large number of herbal remedies have been found to
damage the liver from mild liver enzyme elevations to severe damage leading to death.2 As several herbal and dietary supplements can cause harmful and sometimes fatal
results, it is imperative to obtain a complete medication history that includes supplements.
Under the Dietary Supplements Health and Education Act
of 1994 (DSHEA), herbal supplements are not to be marketed using specific medical claims. Herbal supplements,
therefore, do not fall under any regulation. Many patients
are not aware of this, and have learned that even natural
substances can cause adverse symptoms and events under
the right conditions. Patients may be reluctant to mention
herbal supplements to their physicians due to fear that doctors may not approve of herbal supplements, or fail to mention over-the-counter medications and supplements during
routine history taking. Alternatively, providers may not ask
about non-prescription preparations during the initial or subsequent visits.3
Tea has historically been an important part of the Sri Lankan
culture and Chinese rice tea has been used to control diabetes. Kelp or Laminaria, one of the main ingredients in rice
tea, is primarily used for weight loss and thyroid disorders,
due to its rich source of iodine. Kelp has been associated
with adverse reactions with levothyroxine and other thyroid
replacements leading to hyperthyroidism.4 To our knowledge, kelp has not been shown to have a significant adverse
effect on the liver.
The mechanism by which kelp leads to a cholestatic syndrome has not yet been elucidated. One theory involves a
pseudo-inflammatory process in the liver due to hypothyroidism from excessive kelp consumption. The high iodine
content in kelp has been found to decrease normal thyroid
function, leading to hypothyroidism.5 Burnett et al observed
an association between elevated liver enzymes and hypothyroidism. They concluded that hypothyroidism involves an
undetermined rise in muscle enzymes, which include AST
and ALT.6 Thyroid hormone naturally increases metabolism
and oxygenation to tissues.7 In the hypothyroid patient, liver
metabolism is diminished, causing the improper breakdown
of products such as bilirubin, potentially leading to jaundice. However, as no definitive mechanism has been agreed
upon, more research is needed to elucidate the link between
kelp and hepatotoxicity.
To our knowledge, this is the first reported case of hepatotoxicity linked to the use of Chinese rice tea with kelp. Our
patient did not report a history of herbal remedy use during
the initial evaluation. Her liver enzyme and bilirubin levels
slowly declined since Chinese rice tea was absent from the
patient’s diet during hospitalization. This case underscores
the importance of obtaining all forms of iatrogenic supplementation in patients, including any herbal preparations,
during routine history taking.
Disclosures
Author contributions: L. Viswanathan and A. Patel contributed equally to article creation and editing. A. Patel is the
article guarantor.
Financial disclosure: There is no financial support or conflict
of interest to disclose for this article.
Table 1. Bilirubin, Transaminase, and Alkaline Phosphatase Levels During and After Hospital Stay
Test
Day 1
Day 3
Day 5
Day 8
Day 10
Day 20
Day 30
T. Bilirubin (mg/dL)
9.2
14.2
11.3
9.0
7.2
3.2
2.0
D. Bilirubin (mg/dL)
7.4
11.2
9.6
7.4
5.6
2.3
1.3
AST (IU/L)
219
103
99
73
50
25
17
ALT (IU/L)
408
269
201
141
110
34
26
ALP (IU/L)
435
448
400
327
290
195
161
ALP = alkaline phosphatase; ALT = alanine aminotransferase; AST = aspartate aminotransferase.
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Viswanathan and Patel
Hepatotoxicity Associated with Herbal Tea
Disclaimer: The view(s) expressed herein are those of the
author(s) and do not reflect the official policy or position of
Brooke Army Medical Center or Carl R. Darnall Army Medical Center, the U.S. Army Medical Department, the U.S.
Army Office of the Surgeon General, the Department of the
Army, Department of Defense or the U.S. Government.
Received: June 6, 2013; Accepted: August 30, 2013
References
1.
2.
3.
4.
5.
6.
7.
Eisenberg DM, Kessler RC, Foster C, et al. Unconventional medicine
in the United States. Prevalence, costs, and patterns of use. N Engl J
Med. 1993;328(4):246–52.
Stickel F, Egerer G, Seitz HK. Hepatotoxicity of botanicals. Public
Health Nutr. 2000;3(2):113–24.
Langer S. Herbal medicines are potent healers. In: Better Nutrition
1990: 4–5.
Miller LG. Herbal medicinals: Selected clinical considerations focusing on known or potential drug-herb interactions. Arch Intern Med.
1998;158(20):2200–11.
Clark CD, Bassett B, Burge, MR. Effects of kelp supplementation on
thyroid function in euthyroid subjects. Endocr Pract. 2003;9(5):363–
9.
Burnett JR, Crooke MJ, Delahunt JW, Feek CM. Serum enzymes in
hypothyroidism. NZ Med J. 1994;107(985):355–6.
Ganong, W. Review of Medical Physiology. 22nd ed. New York, NY:
McGraw-Hill Companies; 2005.
Publish your work in ACG Case Reports Journal
ACG Case Reports Journal is a peer-reviewed, open-access publication that provides GI fellows, private practice clinicians, and other members of the
health care team an opportunity to share interesting case reports with their peers and with leaders in the field. Visit http://acgcasereports.gi.org for
submission guidelines. Submit your manuscript online at http://mc.manuscriptcentral.com/acgcr.
57
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ACG Case Reports Journal | Volume 1 | Issue 1 | October 2013
ACG CASE REPORTS JOURNAL
CASE REPORT | LIVER
Tea not Tincture: Hepatotoxicity Associated with Rooibos
Herbal Tea
Michael Engels, MD1, Charles Wang, MD2, Andres Matoso, MD3, Eyal Maidan, MD1, and
Jack Wands, MD2
Department of Internal Medicine, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RI
Department of Gastroenterology, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RI
3
Department of Pathology, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RI
1
2
Abstract
A 52-year-old male presented with signs of acute hepatitis and liver failure. Laboratory investigations for common
etiologies were unrevealing, but history suggested liver injury secondary to ingestion of a traditional South African
herbal tea made with rooibos and buchu. Livery biopsy confirmed a toxin-mediated liver injury. The patient recovered liver function after stopping the herbal tea. Although hepatotoxicity associated with rooibos and buchu
has rarely been reported, anecdotal correspondence with South African physicians confirmed suspected cases.
Hepatotoxicity may be due to the heterogeneous composition of herbal teas due to small-batch manufacturing.
Our case clearly outlines the need to suspect herbal causes of idiopathic liver injury.
Introduction
Drug-induced liver injury is a common etiology of hepatotoxicity, but the diagnosis is often delayed or missed
when patients and clinicians do consider herbal supplements as drugs. The following case of acute hepatitis
and liver failure in a 52-year-old male with recent daily ingestion of rooibos and buchu herbal tea illustrates the
importance of a careful herbal drug history when presented with a case of hepatotoxicity.
Case Report
We describe a patient with hepatotoxicity related to herbal tea and highlight the importance of reviewing herbal
consumption in such cases. A 52-year-old man presented to the emergency room with new-onset jaundice and
malaise. He had scleral icterus, diffuse pruritus, dark urine, and had sought consultation with his physician,
who drew labs showing acute hepatitis prior to referral. He had a history of hyperlipidemia and stage III chronic
kidney disease secondary to IgA nephropathy. Medications included oral steroids and long-term statin use, but
no other hepatotoxic drugs. He noted rare alcohol consumption, but he had daily ingestion of buchu and rooibos
tea from South Africa in the last month.
On examination he was afebrile and jaundiced, with icteric sclera, dermal excoriations, and a non-tender abdomen. He had no asterixis, spider angiomas, hepatosplenomegaly, or ascites. Laboratory tests included alanine amino transferase (ALT) of 2,589 IU/L, aspartate amino transferase (AST) of 1,438 IU/L, total bilirubin of
12.1 mg/dL, direct bilirubin of 8.3 mg/dL, and alkaline phosphatase of 359 IU/L. His albumin was 3.0 g/dL
with normal platelet count and INR. An abdominal ultrasound showed a normal liver without ascites. Tests for
hepatitis A, B, C, E, as well as HSV, CMV, EBV, HIV, VZV, anti-nuclear antibody, anti-mitochondrial antibody,
ACG Case Rep J 2013;1(1):58–60 doi:10.14309/crj.2013.20. Published online: October 8, 2013.
Correspondence: Charles Wang, MD, Department of Gastroenterology, Rhode Island Hospital, Alpert Medical School of Brown University, 593 Eddy Street,
Providence, RI 02903 ([email protected])
Copyright: © 2013 Wang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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Wang et al
and anti-smooth muscle antibody were negative. On hospital
day 6, a liver biopsy showed predominantly centrolobular
cholestasis without evidence of large duct obstruction, bile
ductular proliferation, or portal edema. There was focal mild
portal chronic inflammation and rare apoptotic cells (Figure
1). Peri-portal plasma cells were absent and there was no
significant steatosis. Immunohistochemical staining for HSV
I and II was negative. The results were consistent with druginduced liver injury (DILI) secondary to herbal tea ingestion.
Although statin-related hepatotoxicity was considered, a review of the literature showed long-term statin use to be a rare
cause of liver failure.1 Our case met all the diagnostic criteria
Rooibos-Associated Hepatotoxicity
of DILI attributed to rooibos and buchu herbal tea, but the
exact mechanism has not been elucidated. The rarity of rooibos and buchu tea DILI may be due to small-batch production, which allows for variability in the exact components of
each tea after processing.9 Other teas with reported hepatotoxicity include chaparral, kava, germander, and Camellia
sinensis (green tea).10
Published reviews showed herbs to be a causative or contributing agent in 9–11% of DILI cases, but diagnosis is often difficult when patients do not report herbal consumption.11–13 This may be due to lack of clinician understanding
of the adverse effects or medical interactions of herbs. In our
case, tea consumption was elicited only after admission to
the hospital, which delayed diagnosis. Our report highlights
the importance of education and review of herbal drugs and
supplements in cases of hepatotoxicity.
Disclosures
Author contributions: M. Engels, C. Wang, and E. Maidan
wrote the manuscript; A. Matoso created the slides. C. Wang
is the author guarantor. C. Wang and M. Engels share first
authorship of this article.
Financial disclosure: There is no financial support, financial
conflicts, or conflicts of interest to disclose.
Figure 1. Histopathologic findings. (A) Low-power view of central vein (arrow) with pericentral cholestasis (arrowhead). (B) Low-power view of a portal area with mild chronic inflammation. Note absence of bile pigment in
periportal area. (C and D) High-power view of two central veins (arrows)
surrounded by pericentral cholestasis (arrowheads, yellow pigment).
for liver injury secondary to herbal supplements as outlined
by Navarro VJ et al, except for hepatotoxicity after toxin reexposure.2 The patient’s liver function tests improved and he
was discharged home. He showed continued improvement
in liver function tests 2 weeks later.
Discussion
Rooibos and buchu herbal tea is a common South African
beverage. Rooibos is derived from the dried needles of Aspalathus linearis, which is native to South Africa. Commonly
referred to as red tea, it is used as a traditional remedy for infantile colic and dermatologic conditions.3 Rooibos tea consumption has reported antioxidant activity, with one study
showing hepatoprotective effects in rats exposed to CCl4;
however, hepatotoxicity has also been reported.4,5 Buchu tea
is derived from Agathosma betulina or Agathosma crenulata
and has diuretic and antimicrobial effects.6 Buchu tea hepatotoxicity has never been reported, but one of its traditional
components, pennyroyal oil, is hepatotoxic.7,8 Consultation
with a South African hepatologist revealed anecdotal cases
59
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Received: July 14, 2013; Accepted: September 25, 2013
References
1.
Björnsson E, Jacobsen EI, Kalaitzakis E. Hepatotoxicity associated
with statins: Reports of idiosyncratic liver injury post-marketing. J
Hepatol. 2012;56(2):374–80.
2. Navarro VJ, Senior JR. Drug-related hepatotoxicity. N Engl J Med.
2006;354(7):731–9.
3. Joubert E, Gelderblom WC, Louw A, de Beer D. South African herbal
teas: Aspalathus linearis, Cyclopia spp, and Athrixia phylicoides—A
review. J Ethnopharmacol. 2008;119(3):376–412.
4. Ulicná O, Greksák M, Vancova O, et al. Hepatoprotective effect of rooibos tea (Aspalathus linearis) on CCl4-induced liver damage in rats.
Physiol Res. 2003;52(4):461–6.
5. Sinisalo M, Enkovaara AL, Kivistö KT. Possible hepatotoxic effect of
rooibos tea: A case report. Eur J Clin Pharmacol. 2010;66(4):427–8.
6. Moola A, Viljoen AM. ‘Buchu’—Agathosma betulina and Agathosma
crenulata (Rutaceae): A review. J Ethnopharmacol. 2008;119(3):413–9.
7. Moorthy B, Madyastha P, Madyastha KM. Hepatotoxicity of pulegone in rats:
Its effects on microsomal enzymes, in vivo. Toxicology.1989;55(3):327–337.
8. Anderson IB, Mullen WH, Meeker JE, et al. Pennyroyal toxicity: Measurement of toxic metabolite levels in two cases and review of the
literature. Ann Intern Med. 1996;124(8):726–734.
9. Stanley S, Winterton P, Marnewick J, et al. Influence of processing
stages on antimutagenic and antioxidant potentials of rooibos tea. J
Agric Food Chem. 2001;49(1):114–117.
10. Stickel F, Patsenker E, Schuppan D. Herbal hepatotoxicity. J Hepatol.
2005;43(5):901–910.
11. Chalasani N, Fontana RJ, Bonkovsky HL, et al. Causes, clinical features, and outcomes from a prospective study of drug-induced liver injury in the United States. Gastroenterology. 2008;135(6):1924–1934.
ACG Case Reports Journal | Volume 1 | Issue 1 | October 2013
Wang et al
Rooibos-Associated Hepatotoxicity
12. Ghabril M, Chalasani N, Bjornson E. Drug-induced liver injury: A clinical update. Curr Opin Gastroenterol. 2010;26(3):222–226.
13. Eisenberg DM, Davis RB, Ettner SL, et al. Trends in alternative medicine use in the United States, 1990–1997: Results of a follow-up national survey. JAMA. 1998;280(18):1569–1575.
Publish your work in ACG Case Reports Journal
ACG Case Reports Journal is a peer-reviewed, open-access publication that provides GI fellows, private practice clinicians, and other members of the
health care team an opportunity to share interesting case reports with their peers and with leaders in the field. Visit http://acgcasereports.gi.org for
submission guidelines. Submit your manuscript online at http://mc.manuscriptcentral.com/acgcr.
60
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ACG Case Reports Journal | Volume 1 | Issue 1 | October 2013
ACG CASE REPORTS JOURNAL
CASE REPORT | PEDIATRICS
Visceral Leishmania as Unusual Cause of Splenic Peliosis
in the United States
Youssef Ghazzawi, MD, and Imad Absah, MD
Division of Pediatric Gastroenterology and Hepatology, Department of Pediatrics and Adolescent Medicine,
Mayo Clinic College of Medicine, Rochester, MN
Abstract
A 3-year-old female presented with splenomegaly and hypersplenism manifestations, including anemia, thrombocytopenia, and abdominal pain/distention. All common metabolic, hematologic, gastrointestinal, and infectious etiologies for splenomegaly were excluded. Diagnosis of idiopathic splenic peliosis was made and splenectomy was recommended. History revealed that the patient’s mother had acquired a nonspecific skin infection
during a visit to the Middle East 2 years prior. Serum antibodies and confirmatory PCR testing for visceral leishmaniasis were positive. After treatment with liposomal amphotericin, at 6-month follow-up her hypersplenism
manifestations had resolved and her splenomegaly had significantly decreased. Visceral leishmaniasis should
be considered in cases of marked splenomegaly, anemia, and thrombocytopenia, especially with a history of
visiting an endemic area.
Introduction
Leishmaniasis is a neglected tropical disease (NTD) that is rarely encountered in the United States; therefore,
it is not considered a common cause of splenomegaly. There are several clinical presentations of this parasitic
infection. The most common is cutaneous and characterized by skin sores or visceral leishmaniasis that affects
internal organs (usually spleen, liver, and bone marrow) and presents with systemic manifestations such as fever,
lymphadenopathy, and hepatosplenomegaly. People from unaffected areas may contract the disease after visiting endemic areas, so detailed history can be very helpful in making the diagnosis.
Case Report
A 3-year-old Caucasian female was referred for evaluation of splenomegaly. History revealed that symptoms
started 6 months ago with a febrile illness, cough, mouth sores, cervical lymphadenopathy, and splenomegaly.
A bacterial infection was suspected, for which she was prescribed a course of amoxicillin and cefdinir, followed
by azithromycin. Antibiotics resulted in resolution of the fever and malaise, but the splenomegaly persisted. Her
splenomegaly progressed causing abdominal distention, pain, and evidence of hypersplenism (anemia and
thrombocytopenia).
Initial evaluations for infectious agents such as HIV, CMV, and EBV, and proliferative etiologies such as leukemia
or metastatic malignancy were negative. Gastrointestinal and metabolic causes were also excluded. Imaging
by ultrasonography and magnetic resonance radiography showed mildly prominent liver with diffuse multiple
hypoechoic lesions and a markedly enlarged spleen with non-enhancing structures at the splenic hilum (Figure
1). Due to these findings, a diagnosis of splenic peliosis was considered and a splenic biopsy with splenectomy
proposed. A second opinion was sought at our institution.
ACG Case Rep J 2013;1(1):61–63. doi:10.14309/crj.2013.21. Published online: October 8, 2013.
Correspondence: Imad Absah, MD, 200 First Street SW, Rochester, MN 55901 ([email protected])
Copyright: © 2013 Ghazzawi and Absah. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which
permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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Ghazzawi and Absah
On presentation, the patient was playful without signs of distress. Physical exam was normal except for distended abdomen, splenomegaly extending to the superior iliac crest, and
an umbilical hernia. Outside evaluation excluded hemolytic
etiology with normal hemolytic anemia panel, hemoglobin
Pediatric Visceral Leishmaniasis
ergy level improved and her hypersplenism manifestations
(anemia and thrombocytopenia) resolved.
Discussion
Peliosis is a rare condition characterized by multiple cystlike, blood-filled spaces within the parenchyma of solid organ. Isolated splenic peliosis is a unique phenomenon most
commonly affecting the liver and, less frequently, the spleen
and other hematolymphoid organs. Patients with this con-
Figure 2. Splenomegaly with diffuse innumerable hypoechoic foci.
Figure 1. MR abdomen demonstrates marked splenomegaly with diffusely
low intensity lesions (thick arrow). Rounded soft tissue structures at the
splenic hilum containing numerous low intensity lesions (thin arrow).
electrophoresis, red blood cell enzymes, and osmotic fragility tests. Malignant infiltration was excluded by bone marrow aspirate/biopsy and brain/spine MRI. Medical genetics
work-up excluded metabolic etiology with normal karyotype
46, XX, urine/serum organic acids, serum amino acids,
plasma acylcarnitine profile, and arylsulfatase B activity (a
test for mucopolysaccharidosis VI). A lysosomal disease
panel was normal. Immune deficiency disorders and other
infectious etiologies like Toxocara, Brucella, Bartonella, and
M. tuberculosis were excluded. Finally, portal hypertension
and splenic vein thrombosis were excluded by a Doppler
abdominal ultrasound (US) showing patency of vessels. The
US also confirmed splenomegaly with diffuse hypoechoic lesions (Figure 2).
Further detail regarding travel history revealed that the patient visited Aleppo, Syria, and Dubai, United Arab Emirates,
about 2 years ago. At that time, the patient’s mother had a
nonspecific skin infection that resolved spontaneously. The
area they visited in the Middle East is endemic for Leishmania. Therefore, serological testing for Leishmania antibodies was performed and was positive. Confirmation with PCR
testing was performed and a diagnosis of visceral leishmaniasis was made. Our patient was treated with liposomal amphotericin B with rapid reduction in her spleen size. Her en62
acgcasereports.gi.org
dition are often asymptomatic. However, it can be a lethal
condition if spontaneous organ rupture occurs.1 Studies
showed that peliosis can be due to injury of endothelial lining of sinusoids. Factors involved in peliosis are malignancy,
tuberculosis, acquired immune deficiency, diabetes, drugs
and parasites.2–4
Splenic peliosis is usually found incidentally by finding splenomegaly on routine physical examination or by laboratory
work showing changes consistent with hypersplenism. In the
United States splenomegaly in children is most commonly
due to the body’s response to different infectious agents.
Other common etiologies include disorders of immune regulation or abnormal destruction of red blood cells. Less common etiologies include infiltration with neoplastic diseases,
storage diseases, portal hypertension, or space-occupying
lesions, which also must be considered. The differential diagnosis includes liver fibrosis, abnormal blood flow due to
splenic vein thrombosis or portal vein obstruction, and liver
cirrhosis due to chronic viral hepatitis B or C, fatty liver, and
alcohol use. All the common etiologies were excluded in our
patient, but her travel history triggered an extended work-up
to investigate parasitic etiologies such as Leishmania, which
are otherwise unusual to the United States.
Leishmaniasis is a parasitic disease endemic to the tropics, subtropics, and southern Europe. It is classified as a
ACG Case Reports Journal | Volume 1 | Issue 1 | October 2013
Ghazzawi and Absah
neglected tropical disease (NTD). Leishmaniasis is caused
by infection with Leishmania parasites, which are spread
by phlebotomine sand flies. Leishmaniasis is rarely encountered in the United States; therefore, it is not considered a
common cause of splenomegaly. There are several clinical
presentations of this parasitic infection. The most common
is cutaneous and characterized by skin sores or visceral
leishmaniasis, also known as Kala-azar. This also affects internal organs (usually spleen, liver, and bone marrow) and
presents with systemic manifestations such as fever, lymphadenopathy, and hepatosplenomegaly.5,6 People from unaffected areas may contract the disease after visiting endemic
areas. Factors that increase the risk of clinical development
of the disease include malnutrition, immunosuppression,
and HIV infection.7 The clinical presentation of visceral leishmaniasis lacks specificity, thus the diagnosis is based on a
high index of suspicion and serological and PCR confirmatory testing. The best diagnostic test is organism isolation
from the patient tissue (lymph node or spleen). The risk of
bleeding from a splenic biopsy may preclude the need for
organism isolation and therefore reliance on antibody testing
is safer. A 30% false positive rate of antibody testing necessitates confirmation with PCR for organism identification. A
correct diagnosis is essential to avoid administration of potentially toxic therapeutic agents.8,9
Pediatric Visceral Leishmaniasis
References
1.
2.
3.
4.
5.
6.
7.
8.
9.
Celebrezze JP Jr, Cottrell DJ, Williams GB. Spontaneous splenic rupture due to isolatedsplenic peliosis. South Med J. 1998;91(8):763.
Tsokos M, Püschel K. Isolated peliosis of the spleen: Report of 2 autopsy cases. Am J For Med Pathol. 2004;25(3):251–4.
Diebold J, Audouin J. Peliosis of the spleen. Report of a case associated with chronic myelomonocytic leukemia, presenting with spontaneous splenic rupture. Am J Surg Pathol. 1983;7(2):197–204.
Garcia RL, Khan MK, Berlin RB. Peliosis of the spleen with rupture.
Hum Pathol. 1982;13(2):177–9.
Desjeux P. Human leishmaniases: Epidemiology and public health aspects. World Health Stat Q. 1992;45(2-3):267–75.
Guerin PJ, Olliaro P, Sundar S, et al. Visceral leishmaniasis: Current
status of control, diagnosis, and treatment, and a proposed research
and development agenda. Lancet Infect Dis. 2002;2(8):494–501.
Murray HW. Kala-Azar: Progress against a neglected disease. N Engl J
Med. 2002;347(22): 1793–1794.
Chappuis F, Sundar S, Hailu A, et al. Visceral leishmaniasis: what are
the needs for diagnosis, treatment and control? Nat Rev Microbiol.
2007;5(11):873–82.
Buyukasik Y, Ileri NS, Haznedaroglu IC, et al. Fever, hepatosplenomegaly and pancytopenia in a patient living in the Mediterranean region. Postgrad Med J. 1998;74(870):237–9.
Conclusion
The diagnosis of visceral leishmaniasis was made in this setting due to the careful history of travel. As human population travel and migration increase worldwide, it is essential
to consider infection by unusual organisms from endemic
areas in the differential diagnosis of splenomegaly and hypersplenism.
Disclosures
Author contributions: Y. Ghazzawi gathered data and completed the initial draft. I. Absah reviewed the paper, completed the literature search and citations, and is the article
guarantor.
Financial disclosure: Neither author received support for this
article, and neither has financial disclosures to report.
Received: May 10, 2013; Accepted: September 10, 2013
Publish your work in ACG Case Reports Journal
ACG Case Reports Journal is a peer-reviewed, open-access publication that provides GI fellows, private practice clinicians, and other members of the
health care team an opportunity to share interesting case reports with their peers and with leaders in the field. Visit http://acgcasereports.gi.org for
submission guidelines. Submit your manuscript online at http://mc.manuscriptcentral.com/acgcr.
63
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ACG Case Reports Journal | Volume 1 | Issue 1 | October 2013
ACG CASE REPORTS JOURNAL
CASE REPORT | PEDIATRICS
Conjugated Hyperbilirubinemia in a Child with Streptococcus
pneumoniae-associated Hemolytic Uremic Syndrome
Mohini Gautam Patel, MD, and Anthony F. Porto, MD
Department of Pediatric Gastroenterology and Hepatology, Yale-New Haven Children’s Hospital, New Haven, CT
Abstract
Conjugated hyperbilirubinemia is a rare complication of hemolytic uremic syndrome (HUS). We report a case of
a 2-year-old female with Streptococcus pneumonia-associated HUS (SP+ HUS) who developed severe cholestasis. It is important for pediatric gastroenterologists to be aware of manifestations of HUS, and that although rare,
cholestasis can be one of the early findings in patients with SP+ HUS.
Introduction
Hemolytic uremic syndrome (HUS) is characterized by microangiopathic hemolytic anemia, thrombocytopenia,
and acute renal failure. Cholestasis in the setting of HUS is rare. However, it is important that clinicians evaluating patients with HUS be aware of this complication. We report a case of a 2-year-old female with Streptococcus
pneumonia-associated HUS (SP+ HUS) who developed severe cholestasis.
Case Report
A 2-year-old female with no past medical history was transferred to our institution for further management of her
respiratory distress. One week prior to admission she developed an upper respiratory infection with rhinorrhea,
cough, and tactile fever. She worsened over 24 hours, developed a fever to 39.4°C, had decreased oral intake
and urine output, and had 2 episodes of non-bloody, non-bilious emesis. She was initially brought to an outside
hospital, where initial labs revealed a Hb 9.8 g/dL, hematocrit 29.5%, and platelets 31,000/µL. One hour later,
her labs decreased to a Hb 8.4 g/dL, hematocrit 25.2%, and platelets 14,000/µL. Chest X-ray showed consolidation of the right upper lobe. She was given intravenous doses of ceftriaxone and vancomycin, and transferred to
our institution for further management.
Her family reported travel to Jamaica 3 weeks prior to presentation, but she had no illness during her visit there.
The patient was not on any medications. She was born full term by normal spontaneous vaginal delivery in Jamaica. Her immunizations were up to date, except her fourth pneumococcal dose was not administered, which
should have been given between 12 and 15 months of age. The family history was noncontributory.
On presentation to our institution, vital signs showed a temperature of 36.8°C, heart rate 158 bpm, respiratory
rate 44 bpm, blood pressure 105/62 mmHg, and O2 saturation 100% on 2 liters nasal canula. Patient had scleral
icterus bilaterally and moist mucus membranes. She had suprasternal and subcostal retractions, and diminished breath sounds of the right lung and left lower lung. Her liver was palpable 2 cm below the costal margin,
but no splenomegaly was noted. She was jaundiced down to her abdomen. There was no bruising, petechiae,
rash, or pitting edema of her extremities. Capillary refill time was less than 2 seconds.
ACG Case Rep J 2013;1(1):64–67. doi:10.14309/crj.2013.22. Published online: October 8, 2013.
Correspondence: Mohini Gautam Patel, Department of Pediatric Gastroenterology and Hepatology, Yale-New Haven Children’s Hospital, 333 Cedar Street, PO
Box 208064, New Haven, CT 06520 ([email protected]).
Copyright: © 2013 Patel and Porto. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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Cholestasis and Streptococcus pneumonia HUS
Patel and Porto
Her labs over 48 hours showed a drop in her Hb to 3.9 g/
dL, hematocrit to 12%, and platelets to 5,000/µL. Her WBC
count was 6.6 with 49% bands, 4% metamyelocytes, 35%
neutrophils, 8% lymphocytes, and evidence of schistocytes.
Chemistry panel showed sodium 130 mmol/L, BUN 55 g/dL,
creatinine 1.3 g/dL, bicarbonate 17.3 mmol/L, and calcium
7.9 mg/dL. Liver panel showed albumin 2.5 g/dL, aspartate
aminotransferase (AST) 290 U/L, alanine aminotransferase
(ALT) 25 U/L, and total and direct bilirubin 18.48 mg/dL and
17 mg/dL, respectively. Lactate dehydrogenase was 6,890
U/L. Urinalysis showed 3+ protein, large bilirubin and positive ichotest (used to test for the presence of bilirubin in the
urine). Coagulation studies showed elevated prothrombin
time of 12.1, partial thromboplastin time 79.9, INR 1.18,
fibrinogen >740 mg/dL, and d-dimer 5.32 mg/L. Flow cytometry showed no loss of CD46. Right upper quadrant
ultrasound showed evidence of diffuse gallbladder sludge
with wall thickening and edema, but no intrahepatic or extrahepatic biliary duct dilatation or gallstones; pancreas and
liver were normal; right kidney parenchyma was noted to be
echogenic. With evidence of liver dysfunction, her antibiotics were changed to cefotaxime and vancomycin. Within 24
hours, the patient’s blood culture was positive for pan-sensitive Streptococcus pneumonia. Patient’s antibiotic coverage
at that time was narrowed to IV penicillin.
The diagnosis of Streptococcus pneumonia-associated hemolytic uremic syndrome (SP+ HUS) was made based on
the patient’s laboratory data of hemolytic anemia, thrombocytopenia, and acute renal failure. The patient became oliguric, developed renal failure and underwent peritoneal dialysis catheter placement on hospital day 2, and peritoneal di-
alysis was started on hospital day 2. The patient’s creatinine
peaked on hospital day 14 to 5.4 g/dL. Peritoneal dialysis
was discontinued on hospital day 26. The patient received
IV penicillin for a total of 14 days and received 6 packed red
blood cell transfusions and 5 platelet transfusions. She did
not have worsening hemolytic anemia after the transfusions,
though the recommendation to prevent hemolytic transfusion reactions is to use washed blood products or fresh frozen plasma.1 She was placed on a nicardipine drip on hospital day 2 and was weaned off on hospital day 9, at which
point her blood pressures remained stable.
Ursodiol was started on hospital day 2, when total and direct
bilirubin peaked at 36.74 mg/dL and 34.5 mg/dL, respectively. At that time, AST and ALT were 603 U/L and 96 U/L,
respectively. Ursodiol was discontinued on hospital day 9.
Liver enzymes at that time had normalized, with the exception of the direct bilirubin being slightly elevated at 0.62 mg/
dL. Direct bilirubin normalized on hospital day 15. The patient was kept nothing by mouth on admission and started
on total parenteral nutrition (TPN) on hospital day 3. TPN
was continued for 12 days until she was taking adequate
calories by mouth.
The patient was discharged on hospital day 31 with normal
liver function and mild renal impairment. At the time of discharge her BUN and creatinine were 32 g/dL and 1.5 g/
dL, respectively. Three months after discharge, the patients
BUN had normalized to 17 g/dL, and she had only mild elevation in her creatinine of 1.0 g/dL. At 1-year follow-up, her
BUN remains normal and her creatinine has normalized.
Table 1. Data of Patients with Conjugated Hyperbilirubinemia and Streptococcus pneumonia-associated Hemolytic Uremic Syndrome
12
22
32
43
5*
Age (mo)
21
10
17
10
24
Sex
F
M
M
F
F
Hgb (g/dL)
8
6.1
3
5.4
3.9
Platelets (1,000/µL)
11
19
12
7
5
Creatinine (mg/dL)
1.5
2.5
2.1
2.8
5.4
Albumin (g/dL)
2.3
2.7
2.4
2.5
1.5
Total bilirubin
11.8
20
11.6
27
36.7
Direct bilirubin (mg/dL)
9.9
18.4
10.3
18.5
34.5
390/124
506/59
1,633/278
431/117
938/250
568
545
298
428
>740
AST/ALT (U/L)
Fibrinogen (mg/dL)
Normalization of bilirubin
(hospital d)
9
5
10
8
15
Duration of dialysis (d)
12
10
28
26
25
Normal at 6 mo
Normal at 10 d
Unknown
Mild impairment at 1 y
Normal at 1 y
Renal function (RF)
Pan CG, Leichter HE, Werlin SL. Hepatocellular injury in Streptococcus pneumoniae-associated hemolytic uremic syndrome in children. Pediatr Nephrol. (1995);9:690–693.
3
Chen J, Chen S, Sheu J. Unusual manifestation of severe conjugated hyperbilirubinemia in an infant with Streptococcus pneumonia-associated hemolytic uremic syndrome. J Formos Med Assoc.
2007;106(2): 517–522.
*Case presented in this article.
2
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Cholestasis and Streptococcus pneumonia HUS
Patel and Porto
Discussion
HUS is defined by a triad of hemolytic anemia, thrombocytopenia, and acute renal failure.4 The 2 subgroups include
diarrhea-associated HUS (D+ HUS) and HUS without diarrhea (D− HUS). With D+ HUS, E. coli 0157.H7 is the most
common pathogen. D+ HUS usually develops abruptly with
the onset of diarrhea, and patients are typically younger
than 5 years and have a better prognosis.5 D− HUS occurs
at any age, has a relapsing course, and a worse prognosis.
Multiple genes have been attributed to atypical HUS; one of
them is CD46, a complement regulatory protein. This was
found to be negative in our patient. HUS can present with
many gastrointestinal manifestations. Most commonly, these
include abdominal pain, diarrhea, emesis, rectal prolapse,
colonic strictures, colonic perforation, intussusception, elevated hepatic enzymes, pancreatitis, and indirect hyperbilirubinemia.1 The liver manifestations have been thought
to be secondary to hemolysis, and rarely do patients develop
cholestasis.6 There are only 4 other cases in the literature
that presented with cholestasis in the setting of SP+ HUS.2,3
Our patient presented with hemolytic anemia, thrombocytopenia, worsening renal function, and a significant conjugated hyperbilirubinemia. On hospital day 2, her total bilirubin peaked to 31 times the upper limit of normal (highest
level of 36.74 mg/dL) and direct bilirubin to 173 times the
upper limit of normal (highest level of 34.5 mg/dL). At that
time, her AST and ALT also peaked, to an AST of 59 times
the upper limit of normal (peak of 938 U/L), and ALT of 7
times the upper limit of normal (peak 250 U/L). The patient’s prothrombin time, partial thromboplastin time, and
international normalized ratio remained normal, but she did
have hypoalbuminemia. This, however, was likely secondary
to nutritional causes rather than hepatic synthetic dysfunction. In addition, antibiotics were used in our patient and are
recommended in all cases of invasive pneumococcal infection. Coverage with vancomycin and an extended spectrum
cephalosporin is recommended before culture and antibiotics sensitivities are back.7 This is in contrast to treatment for
E. coli 0157.H7, where antibiotics may cause more verotoxin
production, therefore increasing the risk of HUS.
Other patients in the literature had elevated AST, ALT, and
bilirubin, though not as significantly elevated as our patient.2,3 Table 1 compares the peak lab findings in all 5 patients (including ours) reported in the literature. Our patient’s
labs normalized within 9 days after hospitalization. As compared with all the other cases, our patient required dialysis
for 25 days, while the other cases ranged from 10 to 28
days. In all 5 patients, the cholestasis improved prior to the
discontinuation of dialysis. Therefore, the liver dysfunction is
likely due to multiple phenomena.
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Different infectious processes can cause jaundice. Elevated
bilirubin levels are also often seen in invasive pneumococcal
infections. However, in these cases the bilirubin is usually
minimally elevated, so there is most likely another component causing elevated levels in these patients. In addition,
the transaminitis that occurs with bacterial infections is usually minimal.1,2,4 In HUS there is a significant hemolytic component, and RBC hemolysis is likely the cause for the greater
rise in AST compared to ALT. Significant hemolysis leads to
hepatic congestion and cholestasis, and this can also lead
to further increases in transaminases and hepatic dysfunction.2
Cholestasis can also occur with lack of enteral nutrition during the initial period of illness. It is thought that the lack of
oral intake thwarts hormone stimulation of the hepatobiliary
system, thus leading to cholestasis.6 However, in our patient
liver function normalized prior to her taking full enteral feeds,
so this cannot fully explain her liver dysfunction.
SP+ HUS is an extremely rare entity compared to D+ HUS,
and very little is known about the true pathogenesis of liver dysfunction. In our patient, multiple factors most likely
played a role in the development of cholestasis. Our case
highlights the importance of close vigilance in these patients
to monitor for cholestasis and elevated liver enzymes so appropriate treatment can be initiated. It is not clear whether
the urosdiol or dialysis had a greater impact in improving the
cholestasis in this patient, as both treatments were started
at the same time.
It is important to note that none of the reported cases had
synthetic liver dysfunction and all of the patients’ liver complications resolved. Nonetheless, it is important for pediatricians to be aware of manifestations of HUS, and understand
that although rare, cholestasis can be one of the early manifestations in patients with SP+ HUS.
Disclosures
Author contributions: M.G. Patel drafted the initial article,
reviewed and revised the article, approved the final article,
and is the article guarantor. A.F. Porto reviewed and revised
the article, and approved the final article.
Financial disclosure: No external funding was secured for
this study. None of the authors have financial relationships
conflicts of interest relevant to this article to disclose.
Received: May 6, 2013; Accepted: September 17, 2013
ACG Case Reports Journal | Volume 1 | Issue 1 | 2013
Patel and Porto
Cholestasis and Streptococcus pneumonia HUS
References
1.
2.
3.
4.
5.
6.
7.
Grodinsky S, Telmaesani A, Robson WL, et al. Gastrointestinal manifestations of hemolytic uremic syndrome: Recognition of pancreatitis.
J Pediatr Gastroenterol Nutr. 1990;11:518–524.
Pan CG, Leichter HE, Werlin SL. Hepatocellular injury in Streptococcus pneumoniae-associated hemolytic uremic syndrome in children.
Pediatr Nephrol. (1995);9:690–693.
Chen J, Chen S, Sheu J. Unusual manifestation of serve conjugated
hyperbilirubinemia in an infant with Streptococcus pneumonia-associated hemolytic uremic syndrome. J Formos Med Assoc. 2007;106(2):
517–522.
De Buys Rossingh AS, Lagausie P, Vaudoin V, et al. Gastrointestinal
complications of post-diarrheal hemolytic uremic syndrome. Eur J Pediatr Surg. 2007;17:328–334.
Siegler RL. Postdiarrheal shiga toxin-mediated hemolytic uremic syndrome. JAMA. 2003;290:1379–1381.
Jeffrey G, Kibbler CC, Baillod R, et al. Cholestatic jaundice in the
haemolytic-uremic syndrome: A case report. Gut. 1985; 26: 315–319.
Spinale JM, Ruebner RL, Kaplan BS, Copelovitch L. Update on Streptococcus pneumonia-associated hemolytic uremic syndrome. Curr
Opin Pediatr. 2013;25(2):203–8.
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