Diarrhea Clinical Trials, Diagnosis, and Treatment

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Diarrhea

In medicine, diarrhea, also spelled diarrhoea (see spelling differences), refers to frequent loose or liquid bowel movements.

Although for many people diarrhea is merely unpleasant, diarrhea that is both acute and severe is a common cause of death in developing countries and a major cause of infant death worldwide. It is often due to gastroenteritis.

Current Research

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Causes

Diarrhea is most commonly caused by viral infections, parasites or bacterial toxins. In sanitary living conditions where there is ample food and a supply of clean water, an otherwise healthy patient usually recovers from viral infections in a few days. However, for ill or malnourished individuals diarrhea can lead to severe dehydration and can become life-threatening without treatment.

Diarrhea can also be a symptom of more serious diseases, such as dysentery, Montezuma's Revenge, cholera, or botulism, and can also be indicative of a chronic syndrome such as Crohn's disease or severe mushroom poisoning syndromes. Though appendicitis patients do not generally have diarrhea, it is a common symptom of a ruptured appendix. It is also an effect of severe radiation sickness.

Diarrhea can also be caused by dairy intake in those who are lactose intolerant.

Symptomatic treatment for diarrhea involves the patient consuming adequate amounts of water to replace that loss, preferably mixed with electrolytes to provide essential salts and some amount of nutrients. For many people, further treatment is unnecessary. The following types of diarrhea indicate medical supervision is required:

Diarrhea in infants;
Moderate or severe diarrhea in young children;
Diarrhea associated with blood;
Diarrhea that continues for more than two days;
Diarrhea that is associated with more general illness such as non-cramping abdominal pain, fever, weight loss, etc;
Diarrhea in travelers, since they are more likely to have exotic infections such as parasites;
Diarrhea in food handlers, because of the potential to infect others;
Diarrhea in institutions such as hospitals, child care centers, or geriatric and convalescent homes.

A severity score is used to aid diagnosis in children.

Types of Diarrhea

There are at least four types of diarrhea: secretory diarrhea, osmotic diarrhea, motility-related diarrhea, and inflammatory diarrhea.

Secretory Diarrhea

Secretory diarrhea means that there is an increase in the active secretion, or there is an inhibition of absorption. There is little to no structural damage. The most common cause of this type of diarrhea is a cholera toxin that stimulates the secretion of anions, especially chloride ions. Therefore, to maintain a charge balance in the lumen, sodium is carried with it, along with water.

Osmotic Diarrhea

Osmotic diarrhea occurs when there is a loss of water due to a heavy osmotic load. This can occur when there is maldigestion (e.g., pancreatic disease or Coeliac disease), where the nutrients are left in the lumen, which pulls water into the lumen.

Motility-Related Diarrhea

Motility-related diarrhea occurs when the motility of the gastrointestinal tract is abnormally high. If the food moves too quickly, there is not enough time for sufficient nutrients and water to be absorbed. This can be due to a vagotomy or diabetic neuropathy, or a complication of menstruation.

Inflammatory Diarrhea

Inflammatory diarrhea occurs when there is damage to the mucosal lining or brush border, which leads to a passive loss of protein-rich fluids, and a decreased ability to absorb these lost fluids. Features of all three of the other types of diarrhea can be found in this type of diarrhea. It can be caused by bacterial infections, viral infections, parasitic infections, or autoimmune problems such as inflammatory bowel disease.

Infectious Diarrhea

Infectious diarrhea is diarrhea caused by a microbe such as a bacterium, parasite, or virus.

Malabsorption

These tend to be more severe medical illnesses. Malabsorption is the inability to absorb food, mostly in the small bowel but also due to the pancreas.

Causes include celiac disease (intolerance to gluten, a wheat product), lactose intolerance (Intolerance to milk sugar, common in non-Europeans), fructose malabsorption, pernicious anemia (impaired bowel function due to the inability to absorb vitamin B12), loss of pancreatic secretions (may be due to cystic fibrosis or pancreatitis), short bowel syndrome (surgically removed bowel), radiation fibrosis (usually following cancer treatment), and other drugs such as chemotherapy.

Inflammatory Bowel Disease

The two overlapping types here are of unknown origin:

Ulcerative colitis is marked by chronic bloody diarrhea and inflammation mostly affects the distal colon near the rectum.
Crohn's disease typically affects fairly well demarcated segments of bowel in the colon and often affects the end of the small bowel.

Irritable Bowel Syndrome

Another possible cause of diarrhea is Irritable Bowel Syndrome (IBS). Symptoms defining IBS: abdominal discomfort or pain relieved by defecation and unusual stool (diarrhea or constipation or both) or stool frequency, for at least 3 days a week over the previous 3 months.[4] IBS symptoms can be present in patients with a variety of conditions including food allergies, infective diarrhea, celiac, and inflammatory bowel diseases. Treating the underlying condition (celiac disease, food allergy, bacterial dysbiosis, etc.) usually resolves the diarrhea.[5] IBS can cause visceral hypersensitivity. While there is no direct treatment for undifferentiated IBS, symptoms, including diarrhea, can sometimes be managed through a combination of dietary changes, soluble fiber supplements, and/or medications.

Other Important Causes

Ischemic bowel disease. This usually affects older people and can be due to blocked arteries.
Bowel cancer: Some (but not all) bowel cancers may have associated diarrhea. Cancer of the large intestine is most common.
Hormone-secreting tumors: some hormones (e.g. serotonin) can cause diarrhea if excreted in excess (usually from a tumor).
Bile salt diarrhea: excess bile salt entering the colon rather than being absorbed at the end of the small intestine can cause diarrhea, typically shortly after eating. Bile salt diarrhea is a possible side-effect of gallbladder removal. It is usually treated with cholestyramine, a bile acid sequestrant.

Alcohol

Chronic diarrhea can be caused by chronic ethanol ingestion. Consumption of alcohol affects the body's capability to absorb water - this is often a symptom that accompanies a hangover after a heavy drinking session. The alcohol itself is absorbed in the intestines and as the intestinal cells absorb it, the toxicity causes these cells to lose their ability to absorb water. This leads to an outpouring of fluid from the intestinal lining, which is in turn poorly absorbed. The diarrhea usually lasts for several hours until the alcohol is detoxified and removed from the digestive system. Symptoms range from person to person and are influenced by both the amount consumed as well as physiological differences.

Treatment

In many cases of diarrhea, replacing lost fluid and salts is the only treatment needed. Medicines that are available without a doctor's prescription include loperamide (Imodium) and bismuth subsalicylate Pepto Bismol and Kaopectate.

(adapted from Wikipedia, the free encyclopedia http://en.wikipedia.org/wiki/Diarrhea)

Findings From Current Research

Development of a Travelers' Diarrhea Vaccine for the Military: How Much is an Ounce of Prevention Really Worth?

Authors: Riddle MS, Tribble DR, Cachafiero SP, Putnam SD, Hooper TI.

Uniformed Services University of the Health Sciences, Bethesda, MD, USA.

Infectious diarrhea is one of the many threats to the deployed military, and given limited resources, a decision to pursue a vaccine acquisition strategy should be based on best evidence that weighs costs and benefits compared to alternatives. An economic model was developed to estimate the marginal cost to avert a duty day lost due to diarrhea for a vaccine acquisition strategy compared to current clinical management, for both multiplex and pathogen-specific vaccines. Vaccines against Campylobacter and enterotoxigenic Escherichia coli appeared to be more favorable than a Shigella vaccine. This model provides an evidence-based decision tool to support prioritization in vaccine development.

Journal: Vaccine. 2008 Mar 31
Adapted from PubMed; click here to access full journal article.

Derivation of a Clinical Prediction Rule for Evaluating Patients with Abdominal Pain and Diarrhea

Authors: Chen EH, Shofer FS, Dean AJ, Hollander JE, Robey JL, Sease KL, Mills AM.

Department of Emergency Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA 19104-4283, USA. esther.chen@uphs.upenn.edu

OBJECTIVE: The objective of the study was to develop a simple prediction rule to reliably identify abdominal pain patients with diarrhea who may require surgical intervention. METHODS: We performed a secondary analysis of a prospective cohort study of adults with acute nontraumatic abdominal pain and diarrhea in an urban emergency department (ED). Structured data collection included 109 historical and 28 physical examination items, laboratory and radiographic results, and final diagnosis. The main outcome was operative intervention. RESULTS: One thousand patients were enrolled; 174 patients with diarrhea were included in this analysis. Patients had a mean age of 39 +/- 16 years and were likely to be female (64%) and black (60%). Fifteen (9%) patients received a surgical intervention from the ED. Clinical variables associated with the need for surgical intervention using univariate analysis were age older than 40 years, constant pain, and peritonitis on examination. Using recursive partitioning multivariate analysis, the derived prediction rule included 2 variables: age older than 40 years and constant pain. This rule had a sensitivity of 1.0 (95% confidence interval, 0.78-1.0) and specificity of 0.23 (95% confidence interval, 0.16-0.30). CONCLUSION: Patients older than 40 years with constant abdominal pain and diarrhea are likely to have a surgical cause of their symptoms.

Journal: Am J Emerg Med. 2008 May;26(4):450-3.
Adapted from PubMed; click here to access full journal article.

Metagenomic Analysis of Human Diarrhea: Viral Detection and Discovery

Authors: Finkbeiner SR, Allred AF, Tarr PI, Klein EJ, Kirkwood CD, Wang D.

Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri, United States of America.

Worldwide, approximately 1.8 million children die from diarrhea annually, and millions more suffer multiple episodes of nonfatal diarrhea. On average, in up to 40% of cases, no etiologic agent can be identified. The advent of metagenomic sequencing has enabled systematic and unbiased characterization of microbial populations; thus, metagenomic approaches have the potential to define the spectrum of viruses, including novel viruses, present in stool during episodes of acute diarrhea. The detection of novel or unexpected viruses would then enable investigations to assess whether these agents play a causal role in human diarrhea. In this study, we characterized the eukaryotic viral communities present in diarrhea specimens from 12 children by employing a strategy of "micro-mass sequencing" that entails minimal starting sample quantity (<100 mg stool), minimal sample purification, and limited sequencing (384 reads per sample). Using this methodology we detected known enteric viruses as well as multiple sequences from putatively novel viruses with only limited sequence similarity to viruses in GenBank.

Journal: PLoS Pathog. 2008 Feb 29;4(2):e1000011.
Adapted from PubMed; click here to access full journal article.

Clostridium Difficile-Associated Diarrhea: An Emerging Threat to Pregnant Women

Authors: Rouphael NG, O'Donnell JA, Bhatnagar J, Lewis F, Polgreen PM, Beekmann S, Guarner J, Killgore GE, Coffman B, Campbell J, Zaki SR, McDonald LC.

Division of Bacterial Diseases, Centers for Disease Control and Prevention, Atlanta, GA.

OBJECTIVE: To estimate if Clostridium difficile-associated disease (CDAD) is increasing in peripartum women. STUDY DESIGN: Peripartum CDAD was assessed through 1) passive surveillance collecting clinical and pathology data on severe cases and 2) survey among infectious disease consultants (ICDs) in the Emerging Infections Network. RESULTS: Ten severe cases were collected; most had associated antibiotic use. Seven women were either admitted to the ICU or underwent colectomy. Three infants were stillborn, and 3 women died. The epidemic Clostridium difficile strain was found in 2 cases. Among 798 ICDs, 419 (52%) participated in the survey. Thirty-seven respondents (9%) recalled 55 cases, mostly in the postpartum period with 21 complications, mainly due to relapse. CONCLUSION: Severe CDAD may be increasing in peripartum women. Clinicians should have a low threshold for testing, be aware of the potential for severe outcomes, and take steps to reduce both the risk of disease and resultant complications.

Journal: Am J Obstet Gynecol. 2008 Apr 5
Adapted from PubMed; click here to access full journal article.

Enteric Infections, Diarrhea, and Their Impact on Function and Development

Authors: Petri WA, Miller M, Binder HJ, Levine MM, Dillingham R, Guerrant RL.

Center for Global Health, Division of Infectious Diseases and International Health, University of Virginia School of Medicine, Charlottesville, Virginia, USA. Fogarty International Center, NIH, Bethesda, Maryland, USA. Yale University, New Haven, Connecticut, USA. Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland, USA.

Enteric infections, with or without overt diarrhea, have profound effects on intestinal absorption, nutrition, and childhood development as well as on global mortality. Oral rehydration therapy has reduced the number of deaths from dehydration caused by infection with an enteric pathogen, but it has not changed the morbidity caused by such infections. This Review focuses on the interactions between enteric pathogens and human genetic determinants that alter intestinal function and inflammation and profoundly impair human health and development. We also discuss specific implications for novel approaches to interventions that are now opened by our rapidly growing molecular understanding.

Journal: J Clin Invest. 2008 Apr 1;118(4):1277-1290.
Adapted from PubMed; click here to access full journal article.

Chronic Diarrhea and Facial Dysmorphism in Children--A Clue to Men 2B Syndrome: A Case Report

Authors: Khatua S, Bilodeau LL.

Department of Pediatrics, University School of Medicine, Las Vegas, Nevada 89135, USA. soumenkhatua@aol.com

Medullary thyroid cancer (MTC) is a highly malignant tumor of the thyroid gland in children, rarely diagnosed and treated by pediatric oncologists. The authors describe a 9-year-old male who presented with facial dysmorphism and history of chronic diarrhea before being diagnosed with advanced MTC. Familiarity with its clinical variants, associated RET protooncogene mutation and its clinical implication, can lead to early identification of this aggressive tumor. To date, surgery remains the only definitive therapy, with continuing dismal prognosis in metastatic disease. However, evolving newer therapeutic strategies like tyrosine kinase inhibitors and pretargeted radioimmunotherapy (pRAIT) may provide hope to children with this aggressive tumor.

Journal: Pediatr Hematol Oncol. 2008 Mar;25(2):147-53.
Adapted from PubMed; click here to access full journal article.

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