Gastroenteritis Mimics: What should the emergency physician consider?

Authors: Erik J. Blutinger, MD, MSc (@UPennEM, EM Resident Physician, University of Pennsylvania Hospital) and Mira Mamtani, MD (@UPennEM, EM Attending Physician, University of Pennsylvania Hospital) // Edited by: Alex Koyfman, MD (@EMHighAK) and Brit Long, MD (@long_brit)

Case:

A 20-year-old male presents to the ED after several days of nausea, non-bloody diarrhea and vomiting. He states “all food and drink goes right through me, doc” and has felt notably weak over the past 1-2 days. He denies fevers, recent travel or abdominal distention. His vital signs include BP 120/80, HR 125 bpm, RR 20, T 97 F, SpO2 95% on room air. He appears pale, and exam demonstrates dry mucous membranes, non-focal neurological exam, non-tender/non-distended abdomen, and capillary refill > 2 seconds.

Is this gastroenteritis? What are the potential diagnoses that should still be considered on further evaluation?

Background:

Gastroenteritis is a common illness often caused by viral, bacterial, and parasitic infections that lead to inflammation of the digestive tract.[i] The disease places a heavy burden on the American health system, leading to 1.5 million visits to primary care providers each year. The disease frequently affects children worldwide, causing 1.5 to 2.5 million deaths among those aged less than five years every year.[ii] In particular, viruses account for 70% of acute gastroenteritis in children with rotavirus being the most common type.[iii] In adults, approximately 1 in 8 individuals have a lifetime risk of being diagnosed with gastroenteritis at the time of hospital discharge.[iv]

An episode of gastroenteritis often presents with watery diarrhea and vomiting attributable to inflammation of the digestive tract. Lack of appetite, nausea, malaise, and myalgias are associated symptoms. Diarrhea may be bloody or filled with mucus. Abdominal pain may be present and described as diffuse, poorly localized, associated with cramping without peritoneal signs.[v] Persistent symptoms lead to worsening functional status and significant dehydration often requiring supportive care. Labs may show hypochloremia and metabolic alkalosis with persistent vomiting and leukocytosis. Diagnosis is made clinically while accounting for other potential causes to a patient’s overall presentation given the broad differential diagnosis.

There are many mimics of gastroenteritis. We will focus on several mimics that may result in significant morbidity and mortality.

Gastroenteritis Mimics

Appendicitis: Commonly a surgical emergency, this condition can rapidly progress. Patients may present with additional signs of systemic illness including anorexia, fevers, migration of abdominal pain (from the umbilical to right lower quadrant areas), and the sudden onset of symptoms, though pain may also begin gradually. Elderly individuals are less likely to suffer from appendicitis but more commonly present atypically. Several clinical-based scoring systems exist for diagnosing appendicitis on clinical exam.[vi] Although computed tomography scanning is the gold standard, studies have demonstrated ultrasonography to be a quick and effective diagnostic option – including one study demonstrating a specificity of 81% and sensitivity of 86%.[vii] Several studies have also shown that intravenous antibiotics can treat acute nonperforated appendicitis without surgical intervention, though further study is required for IV antibiotics alone.[viii]

Bowel perforation: Often secondary to an occult intestinal disorder, perforation can present with signs of distress and exam findings consistent with abdominal distention and significant tenderness. The patient may have a history of underlying inflammatory illness (Crohn’s disease or ulcerative colitis), cancer (lymphoma), or immunological compromise (cytomegalovirus, tuberculosis, or HIV).[ix] Symptoms are often non-specific including tachycardia, fever, and loss of appetite. X-ray imaging can identify free air underneath the diaphragm raising one’s suspicion about the diagnosis. If X-ray is negative, CT should be obtained. Surgical management is time-sensitive and imperative for treatment purposes.

Mesenteric ischemia: This is an uncommon diagnosis, accounting for 0.1% of all hospital admissions though when present, but may lead to deadly outcomes (overall mortality up to 71%).[x] Key risk factors include elderly age (> 50 years old), history of cardiovascular disease, arrhythmias, and hypotension.[xi] Abdominal pain may be absent in the elderly population (unlike younger adults), and other presentations include mental status changes and tachypnea.[xii] Nausea, vomiting, and fevers are often late signs of ischemia – a condition that is most easily diagnosed using computed tomography angiography as the gold-standard radiological study.

Ischemic colitis: This is the most common type of intestinal ischemia. Symptoms range from mild and transient to persistently severe abdominal pain. Studies have shown a strong association with being female, aged over 65 years old, and either IBS or COPD (potentially due to underlying small-vessel disease secondary to smoking).[xiii] In young patients, beware of underlying hypercoagulable states, use of oral contraceptives, and smoking. Symptoms of dull, diffuse abdominal pain, diarrhea, and mild lower gastrointestinal bleeding are common. Diagnosis requires a high index of clinical suspicion and often made by endoscopy although angiography often remains the diagnostic test of choice.

Clostridium difficile colitis: History of recent antibiotic use, persistent diarrhea, and healthcare setting (including nursing homes) are salient points for this diagnosis. According to a recent systematic review, the symptoms of C. difficile colitis vary significantly, from asymptomatic carriers to life-threatening toxic megacolon exhibiting abdominal guarding, leukocytosis, and pyrexia. Stool samples should be drawn on individuals experiencing diarrhea with 3 or more stool episodes daily for at least 2 days.[xiv] Inflammatory markers may be elevated including one prospective study finding pro-calcitonin levels of 2 ng/mL as an adequate cutoff for diagnosing C. difficile toxin positive patients.[xv]

AAA: Abdominal aortic aneurysms (AAA) often remain asymptomatic until vessel rupture, which is associated with high in-hospital mortality rates.[xvi] Most commonly found in the elderly, symptoms may present as sudden, severe back/flank/abdominal pain associated with vomiting, nausea, lightheadedness and cool, clammy skin sensation. The presence of underlying connective tissue disorder heightens the chances of developing AAA. Asymptomatic aneurysms may simply provide a palpable abdominal mass on exam. Rupture may quickly lead to shock and obvious distress on presentation. The literature supports ultrasonography as the initial screening tests for suspected AAA (with a sensitivity of 90%) and CT or CT angiography as imperative for further characterizing the aneurysm in hemodynamically stable patients.[xvii] In unstable patients, bedside US with surgical consult are required, and consideration should always be made to initiative massive transfusion protocol.

Volvulus: Abrupt twisting of the small intestine can lead to this life-threatening diagnosis with the majority of cases occurring within the first year of life. Notable features include bouts of intermittently sharp, severe abdominal pain associated with bilious vomiting, nausea, and irritability. Upper GI series remains the gold standard of imaging with higher sensitivity in detecting malrotation (93-100%) versus volvulus (54-74%), both requiring immediate surgical consultation.[xviii]

Bowel obstruction: Small bowel obstruction (SBO) can be due to mechanical (e.g., intrinsic blockage or extrinsic compression) or non-mechanical (e.g., neurogenic gastrointestinal paralysis) causes with the most common cause being bowel adhesions. Hernia is another important cause to consider. History of prior intra-abdominal surgeries, inconsistent bowel movements, and flatus passage are key HPI findings. Diffuse, colicky abdominal pain with vomiting and distention are common exam findings confirmable by CT scan.  US can also be used to support the diagnosis.

Intussusception: This condition is the most common cause of obstruction in children under two years of age, mostly prevalent in males with telescoping of the ileum into the colonic region.[xix] Non-specific findings of lethargy and intermittent abdominal pain are hallmark features with patients often appearing normal between pain attacks. Classic “currant jelly” dark-colored stool can be found as a late finding (due to bowel ischemia). Ultrasound is best for diagnosing children without high suspicion for intussusception. Usually within 24-48 hours, high recurrence rates (10%) often prompt physicians to admit children for air-contrast enema reduction.[xx]

Diverticulitis: Pain localized to the LLQ with distention are key features to this disease, attributable to localized inflammation of sac-like protrusions of the colon wall. Diverticulitis is more commonly left-sided. Associated symptoms include nausea, vomiting, and low-grade fevers. One study showed 50% of patients complaining of constipation while 20-35% of patients complaining of diarrhea with diverticular disease.[xxi] Antibiotics (gram-negative and anaerobe coverage) are considered the standard of care though studies show disease resolution without antibiotic treatment can occur.[xxii]  CT scan is recommended when either a prior diagnosis has not been confirmed, additional intra-abdominal pathology is suspected and/or evaluation for potential complications must be performed (e.g.. abscess).

Biliary colic/cholecystitis: The presence of gallstones (cholelithiasis) can lead to obstruction and acute inflammation of the gallbladder (cholecystitis) or intermittent – and occasionally worsening – pain (biliary colic). Jaundice is more common in children versus adults, and pain remains sharp, localized to the RUQ in most patients. Pain onset is often sudden, worse after meals, and associated with leukocytosis. One systematic review showed improved post-operative morbidity, mortality, and hospital stays with laparoscopic cholecystectomy (compared to open procedure).[xxiii]  Ultrasound is the diagnostic imaging of choice with high sensitivity and specificity for suspected gallstone disease.

ACS: Ischemic heart disease may range from unstable angina to acute myocardial infarction, diagnoses important to consider in those patients with underlying cardiac risk factors (including age > 65 years old, known coronary artery disease, hypertension, diabetes). Often, chest or epigastrium discomfort is present, commonly described as “dull”, “heavy”, or “full.” Nausea, vomiting, and dyspnea may be present plus easy fatigability, especially in women.[xxiv] Patients that are elderly, female, and/or have diabetes may present with atypical symptoms of ACS and solely demonstrate nausea or vomiting. Diagnosis requires a high index of suspicion. Response to nitroglycerin or GI cocktail does not suggest one diagnosis in particular.

Myocarditis: Myocarditis occurs due to inflammation of heart tissue, with several causes: inflammatory, medication-associated, idiopathic, viral, and bacterial. It can lead to worsening cardiac function and ultimate heart failure. Worldwide, it remains an important cause of dilated cardiomyopathy.[xxv] Angina-type chest pain, fatigue, headache, and tachycardia are common symptoms that may also overlap with those of GI-related illness. Clinical symptoms and supportive testing are used to diagnose the disease including ECG (which may show non-specific S-T changes), echocardiography, and cardiac MRI imaging. If confirmed, treatment is largely supportive with little data supporting the use of immunosuppressive therapy (such as prednisone or azathioprine).[xxvi] Prognosis largely depends upon the clinical presentation, ejection fraction, and the pulmonary artery pressure.[xxvii]

PID/TOA: Infections of the female upper reproductive tract can lead to significant genitourinary tract inflammation, infertility, and a wide spectrum of clinical symptoms. Patient at highest risk include those with history of intravenous drug use, intrauterine device (IUD) use, and history of sexually transmitted illnesses. Pregnancy serves as a protective factor due to the natural mucus plugging of the cervical os.

Persistent pain in the lower abdomen and cervical areas are characteristic and may be associated with fevers, vaginal discharge, vomiting, and urinary discomfort. If perihepatic inflammation occurs (called Fitz-Hugh Curtis syndrome), pain most pronounced in the RUQ and jaundice may also be present. Symptoms often occur at the beginning or end of menstrual cycles and can be associated with mucopurulent vaginal discharge. Many complications can result from PID including chronic pelvic pain, ectopic pregnancy, and tubo-ovarian abscess (TOA). TOA has been found in up to one-third of women hospitalized with PID and presents with rebound abdominal tenderness.[xxviii] Diagnostic studies include pregnancy test, routine blood work, saline- and potassium hydroxide-treated wet preparations of vaginal secretions, and urinalysis. Additional studies are recommended as clinically indicated. Consider transvaginal ultrasound in cases of severe PID or suspected TOA for quick diagnostic purposes, even though MRI is more specific and sensitive than ultrasound. CT may also be considered.

Neutropenic enterocolitis: Also known as “typhlitis,” this life-threatening disease predominates in immunocompromised patients traditionally in those receiving chemotherapy (commonly with neutropenia). Direct mucosal injury often leads to inflammation, blood vessel leakage, and bacterial invasion leading to significant abdominal pain, fevers, nausea, vomiting, and abdominal distention. Severe hemorrhage and hemodynamic instability may be present, further warranting immediate imaging (including angiography with embolization) to stem potential surgery.[xxix] Symptom onset occurs within two weeks of chemotherapy (especially induction therapy) associated with a low leukocyte count and bowel wall thickening. Fevers are often present, too. CT scan with intravenous contrast is the recommended imaging study. Management requires bowel rest, broad-spectrum antibiotics, fluid resuscitation, and abdominal decompression. Surgical consultation is recommended.

Inflammatory bowel disease: Inflammatory bowel disease (IBD) pertains to a spectrum of autoimmune disease secondary to chronic bowel inflammation. Two major forms include Crohn’s disease and ulcerative colitis (UC) which differ by anatomical location (involvement of the colon in UC versus the distal ileum for Crohn’s) and extent of disease (partial versus full thickness involvement). Symptoms include pain in the lower abdomen, persistent diarrhea (often bloody), weight loss, and rectal bleeding. Nutritional deficiencies are common due to poor absorptive capacity of the intestines. Associated symptoms may also include joint pain, spine stiffness, eye complaints (usually uveitis), and skin lesions (erythema nodosum). One study also demonstrated increased incidence of colonic cancer, cardiovascular disease, and respiratory illness in those suffering from Crohn’s.[xxx] Systemic toxicity plus total (or nonsegmental) nonobstructive colonic dilatation, known as toxic megacolon, is a potentially lethal complication of IBD. For patients without confirmed IBD, biopsies of the colon and endoscopy are effective tests for differentiating the type of inflammation. Computed tomography is preferred for detecting extra-luminal complications including abscesses, fistulas, bowel perforation, or obstruction.

Liver abscess: Potentially lethal, hepatic abscesses are defined as a “collection of suppurative material within the liver parenchyma.”[xxxi] Risk factors include diabetes mellitus, liver cirrhosis, advanced age (with one study reporting a mean age > 57 years old), and use of PPI.[xxxii]  The use of PPI medications may lead to a greater gastric pH and weaker gastric protection against bacteria.  Commonly reported signs and symptoms are abdominal pain, fevers, hypotension, and malaise. Associated lab findings include elevated WBC count, inflammatory markers (CRP, GGT), and liver function tests. Per most studies, diagnosis is confirmed by imaging 90% of the time that includes ultrasound and computed tomography (with contrast).[xxxiii] If ultrasound cannot make the diagnosis, then CT or MRI is recommended.

Management:

The content and frequency of vomiting episodes can help gauge the severity of illness with persistent bilious, bloody episodes indicating more emergent causes. Rehydration therapy remains the mainstay treatment for gastroenteritis due to significant volume loss attributable to disease. Even in severe diarrheal states, oral rehydration therapy (ORT) provides passive absorption of water by coupling the transport of sodium and glucose molecules across the intestinal epithelial cell brush border.[xxxiv] In children, a general rule is to provide one ounce (30mL) of oral rehydration solution per kilogram of body weight per hour.[xxxv] For example based on average weights for children and infants, maintenance ORT involves giving 1 oz per hour to infants, 2 oz per hour to toddlers, and 3 oz per hour to older children.[xxxvi] Rehydration through nasogastric tube is also possible.

For children and adults with severe dehydration, altered mental status (and trouble tolerating oral intake), and/or hemodynamic compromise, intravenous hydration is recommended. Among children suffering from acute gastroenteritis, one Cochrane meta-analysis comparing oral versus intravenous rehydration therapy found no important clinical differences between the two modalities, although children spent less time in the hospital with oral therapy.[xxxvii] Oral therapy can be more pleasant for children, reassuring to caregivers, and performed easily in low-resource settings.

Antiemetic therapy can be utilized for acute gastroenteritis despite there being medication side effects and lack of scientific evidence supporting widespread use. Ondansetron (Zofran) is commonly used to decrease the frequency of vomiting episodes and improves the success of oral rehydration therapy. Transient diarrhea can result from Zofran use but remains limited. Dopamine receptor agonists (eg promethazine, metoclopramide) should be avoided in children to avoid the potential of respiratory depression and extra-pyramidal reactions. Antibiotics are not routinely recommended due to predominately viral causes of gastroenteritis – except for signs of systemic inflammation including bloody diarrhea with mucus or fevers. Antibiotics may reduce the severity of disease specifically for gastroenteritis caused by strains of Shigella, Campylobacter, V. cholera, and Yersinia.

Summary:

– Acute gastroenteritis leads to significant morbidity and mortality across the world. – Patients often present with non-specific symptoms (including fevers, abdominal pain, vomiting, diarrhea and nausea) that mimic other disease processes.

– Physicians must thoroughly investigate potential causes by completing a pertinent history and full review of systems, abdominal exam and overall assessment of volume status.

– Hydration is critical for replacing fluid losses, preventing (or treating) dehydration, and maintaining nutrition especially among children who may require antiemetic therapy to allow for initiation and maintenance of oral rehydration therapy.

References/Further Reading:

[i]  “Gastroenteritis.” Healthy WA – Health Information for Western Australians. Government of Western Australia, Department of Health, Accessed 22 July 2017. http://healthywa.wa.gov.au/Articles/F_I/Gastroenteritis

[ii] Chow, Chung Mo. “Acute gastroenteritis: from guidelines to real life.” Clinical and Experimental Gastroenterology (2010): 97. Accessed 19 July 2017.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3108653/

[iii] Long, Brit, and Kann Kristen. “”All that wheezes is not asthma” – an evaluation of asthma mimics.” EmDOCs.net – Emergency Medicine Education. Ed. Koyfman Alex. EmDocs.net, 12 July 2017. Accessed 18 July 2017.

http://www.emdocs.net/wheezes-not-asthma-evaluation-asthma-mimics/

[iv] Bresee, JS., Marcus R, Venezia RA, et. al: “The Etiology of Severe Acute Gastroenteritis Among Adults Visiting Emergency Departments in the United States.” The Journal of Infectious Diseases205.9 (2012): 1374-381. Accessed 15 July 2017.
https://academic.oup.com/jid/article/205/9/1374/2192242/The-Etiology-of-Severe-Acute-Gastroenteritis-Among

[v] “Pediatric Gastroenteritis.” CDEM Curriculum. N.p., 17 July 2015. Access 25 July 2017

[vi] McKay R, Shepherd J. The use of the clinical scoring system by Alvarado in the decision to perform computed tomography for acute appendicitis in the ED. American Journal Emergency Medicine (2007). 25, 5, 489-493.

[vii] Humes DJ. “Acute appendicitis.” BMJ333.7567 (2006): 530-34. Accessed 10 July 2017. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1562475/

[viii] Wilms, Ingrid Mha, Dominique Enm De Hoog, et. al: “Appendectomy versus antibiotic treatment for acute appendicitis.” Cochrane Database of Systematic Reviews (2011): n. pag. Web.

[ix] Freeman HJ. “Spontaneous free perforation of the small intestine in adults.” World Journal of Gastroenterology20.29 (2014): 9990. Accessed 09 July 2017. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4123378/

[x] Kazanowski M, Smolarek S, Kinnarney F, et. al: “Clostridium difficile: epidemiology, diagnostic and therapeutic possibilities—a systematic review.” Techniques in Coloproctology18.3 (2013): 223-32. Accessed 12 July 2017. http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2036.2005.02269.x/full

[xi] Brandt LJ, Boley SJ.Intestinal ischaemia. In: Feldman, M, Friedman, LS, Sleisenger, MH, eds. Sleisenger and Fordtran’s Gastrointestinal and Liver Disease, Philadelphia, PA, USA: WB Saunders, 2002: 2321–40.

[xii] Finucane PM, Arunachalam T, O’Dowd J, et al. Acute mesenteric infarction in elderly patients. J Am Geriatr Soc 1989; 37: 355–8.

[xiii] Sreenarasimhaiah J. “Diagnosis and management of ischemic colitis.” Current Gastroenterology Reports7.5 (2005): 421-26. Accessed 12 July 2017. https://link.springer.com/article/10.1007%2Fs11894-005-0013-1?LI=true

[xiv] Kazanowski M, Smolarek S, Kinnarney F, et. al: “Clostridium difficile: epidemiology, diagnostic and therapeutic possibilities—a systematic review.” Techniques in Coloproctology18.3 (2013): 223-32. Accessed 12 July 2017. http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2036.2005.02269.x/full

[xv] Bernal, Vanesa, and Fernando Gomollón. “Diagnosis of Clostridium difficile-associated diarrhea.” Journal of Crohns and Colitis 3.2 (2009): 137. Web. 10 July 2017. https://www.ncbi.nlm.nih.gov/pubmed/28513121

[xvi] Lefevre, Michael L. “Screening for Abdominal Aortic Aneurysm: U.S. Preventive Services Task Force Recommendation Statement.” Annals of Internal Medicine161.4 (2014): 281. Accessed 08 July 2017.

[xvii] Reis SP, Majdalany BS, Aburahma AF, et. al: “ACR Appropriateness Criteria ® Pulsatile Abdominal Mass Suspected Abdominal Aortic Aneurysm.” Journal of the American College of Radiology14.5 (2017): n. pag. Accessed 07 July 2017.

[xviii] Sizemore AW, Rabbani KZ, Ladd A, and Applegate KE: Diagnostic performance of the upper gastrointestinal series in the evaluation of children with clinically suspected malrotation. Pediatr Radiol 38: 518, 2008. [PMID: 18265969]

[xix] Fischer TK, Bihrmann K, Perch M, et al: Intussusception in early childhood: a cohort study of 1.7 million children. Pediatrics 114: 782, 2004. [PMID: 15342854]

[xx] Daneman A, Alton DJ, Lobo E, Gravett J, Kim P, Ein SH: Patterns of recurrence of intussusception in children: a 17-year review. Pediatr Radiol 28: 913, 1998. [PMID: 9808629]

[xxi] Konvolinka CW. Acute diverticulitis under age forty. Am J Surg. 1994 Jun; 167(6):562-5.

[xxii] Shaheen NJ, Hansen RA, Morgan DR, et. al: The burden of gastrointestinal and liver diseases, 2006. Am J Gastroenterol. 2006 Sep; 101(9):2128-38.

[xxiii] Coccolini F, Catena F, et al. “Open versus laparoscopic cholecystectomy in acute cholecystitis. Systematic review and meta-analysis.” International Journal of Surgery18 (2015): 196-204. Accessed 05 July 2017.

[xxiv] Canto JG, Goldberg RJ, Hand MM, et al: Symptom presentations of women with acute coronary syndromes. Arch Intern Med 167: 2405, 2007. [PMID: 18071161]

[xxv] Schultz, Jason C., Anthony A. Hilliard, Leslie T. Cooper, and Charanjit S. Rihal.”Diagnosis and Treatment of Viral Myocarditis.” Mayo Clinic Proceedings 84.11 (2009): 1001-009. Accessed 02 July 2017.

[xxvi]  Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 8th Edition. Chapter 55: Cardiomyopathies and Pericardial Disease. Niemann JT. Tintinalli JE, et al. eds. Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 8e New York, NY: McGraw-Hill; 2016. http://eresources.library.mssm.edu:2744/content.aspx?bookid=1658&sectionid=109430493 Accessed July 20, 2017.

[xxvii] Schultz, JC, Hilliard AA, Cooper LT, et. al: “Diagnosis and Treatment of Viral Myocarditis.” Mayo Clinic Proceedings84.11 (2009): 1001-009. Accessed 02 July 2017.

[xxviii] Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 8th Edition. Chapter 103: Pelvic Inflammatory Disease. Shepherd SM, Weiss B, Shoff, WH. Tintinalli JE, et al. eds. Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 8e New York, NY: McGraw-Hill; 2016. http://eresources.library.mssm.edu:2744/content.aspx?bookid=1658&sectionid=109430493 Accessed July 20, 2017.

[xxix] Meyerovitz MF, Fellows KE. Typhlitis: a cause of gastrointestinal hemorrhage in children. AJR Am J Roentgenol. 1984;143:833–835.

[xxx] Canavan C, Abrams KR, Mayberry J. Meta-analysis: colorectal and small bowel cancer risk in patients with Crohn’s disease. Aliment Pharmacol Ther. 2006;23:1097–1104.

[xxxi] “The Evolving Nature of Hepatic Abscess: A Review.” Journal of Clinical and Translational Hepatology4.2 (2016): n. pag. Accessed 10 July 2017. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4913073/

[xxxii] Tian LT, Yao K, Zhang XY, et. al: Liver abscesses in adult patients with and without diabetes mellitus: an analysis of the clinical characteristics, features of the causative pathogens, outcomes and predictors of fatality: a report based on a large population, retrospective study in China. Clin Microbiol Infect. 2012 Sep; 18(9): E314-30.

[xxxiii] Lardière-Deguelte S, Ragot E, Amroun K, et. al: Hepatic abscess: Diagnosis and management. J Visc Surg. 2015 Sep; 152(4):231-43.

[xxxiv] King CK, Glass R, Bresee JS, et. al: Centers for Disease Control and Prevention: Managing acute gastroenteritis among children: oral rehydration, maintenance, and nutritional therapy. MMWR Recomm Rep 52 (RR16): 1, 2003. [PMID: 14627948]

[xxxv] Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 8th Edition. Chapter 128: Vomiting, Diarrhea, and Dehydration in Infants and Children. Freedman SB, Thull-Freedman JD. Tintinalli JE, et al. eds. Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 8e New York, NY: McGraw-Hill; 2016. http://eresources.library.mssm.edu:2744/content.aspx?bookid=1658&sectionid=109430493 Accessed July 22, 2017.

[xxxvi] Canavan, Amy, and Jr. Billy S. Arant. “Diagnosis and Management of Dehydration in Children.” American Family Physician. N.p., 01 Oct. 2009. Accessed 30 July 2017.

[xxxvii] Hartling L, Bellemare S, Wiebe N, Russell K, Klassen TP, et. al: Oral rehydration versus intravenous rehydration for treating dehydration due to gastroenteritis in children. Cochrane Database Syst Rev. 2006 Jul 19; (3):CD004390.