Colitis-X

Last updated

Colitis X, equine colitis X or peracute toxemic colitis is a catchall term for various fatal forms of acute or peracute colitis found in horses, but particularly a fulminant colitis where clinical signs include sudden onset of severe diarrhea, abdominal pain, shock, and dehydration. Death is common, with 90–100% mortality, usually in less than 24 hours. The causative factor may be Clostridioides difficile , but it also may be caused by other intestinal pathogens. Horses under stress appear to be more susceptible to developing colitis X, and like the condition pseudomembranous colitis in humans, an association with prior antibiotic use also exists. Immediate and aggressive treatment can sometimes save the horse, but even in such cases, 75% mortality is considered a best-case scenario.

Contents

Clinical signs

Colitis-X is a term used for colitis cases in which no definitive diagnosis can be made and the horse dies. [1] Clinical signs include sudden, watery diarrhea that is usually accompanied by symptoms of hypovolemic shock and usually leads to death in 3 to 48 hours, usually in less than 24 hours. Other clinical signs include tachycardia, tachypnea, and a weak pulse. Marked depression is present. An explosive diarrhea develops, resulting in extreme dehydration. Hypovolemic and endotoxic shock are manifest by increased capillary refill time, congested or cyanotic (purplish) mucous membranes, and cold extremities. While there may initially be a fever, temperature usually returns to normal. [1] [2]

Clinical signs are similar to those of other diarrheal diseases, including toxemia caused by Clostridium , Potomac horse fever, experimental endotoxic shock, and anaphylaxis. [1]

Causes

To date, the precise causative factor has not been verified, and the disease has been attributed by various sources to viruses, parasites, bacteria, use of antibiotics and sulfonamides, and heavy metal poisoning. [1] [2] [3] Other possible causes include peracute salmonellosis, clostridial enterocolitis, and endotoxemia. [1] Clostridioides difficile toxins isolated in the horse have a genotype like the current human "epidemic strain", which is associated with human C. difficile-associated disease of greater than historical severity. [4] C. difficile can cause pseudomembranous colitis in humans, [5] and in hospitalized patients who develop it, fulminant C. difficile colitis is a significant and increasing cause of death. [6]

Horses under stress appear to be more susceptible to developing colitis X. [2] Disease onset is often closely associated with surgery or transport. [1] Excess protein and lack of cellulose content in the diet (a diet heavy on grain and lacking adequate hay or similar roughage) is thought to be the trigger for the multiplication of clostridial organisms. [3] A similar condition may be seen after administration of tetracycline or lincomycin to horses. [1] These factors may be one reason the condition often develops in race horses, having been responsible for the deaths of the Thoroughbred filly Landaluce, [7] [8] the Quarter Horse stallion Lightning Bar, [9] and is one theory for the sudden death of Kentucky Derby winner Swale. [7]

The link to stress suggests the condition may be brought on by changes in the microflora of the cecum and colon that lower the number of anaerobic bacteria, increase the number of Gram-negative enteric bacteria, and decrease anaerobic fermentation of soluble carbohydrates, resulting in damage to the cecal and colonic mucosa and allowing increased absorption of endotoxins from the lumen of the gut. [10]

The causative agent may be Clostridium perfringens , type A, but the bacteria are recoverable only in the preliminary stages of the disease. [3]

The suspect toxin could also be a form of Clostridioides difficile . In a 2009 study at the University of Arizona, C. difficile toxins A and B were detected, large numbers of C. difficile were isolated, and genetic characterization revealed them to be North American pulsed-field gel electrophoresis type 1, polymerase chain reaction ribotype 027, and toxinotype III. Genes for the binary toxin were present, and toxin negative-regulator tcdC contained an 18-bp deletion. The individual animal studied in this case was diagnosed as having peracute typhlocolitis, with lesions and history typical of those attributed to colitis X. [4]

The use of antibiotics may also be associated with some forms of colitis-X. [11] In humans, C. difficile is the most serious cause of antibiotic-associated diarrhea, often a result of eradication of the normal gut flora by antibiotics. [12] In one equine study, colitis was induced after pretreatment with clindamycin and lincomycin, followed by intestinal content from horses which had died from naturally occurring idiopathic colitis. [11] (A classic adverse effect of clindamycin in humans is C. difficile-associated diarrhea. [13] ) In the experiment, the treated horses died. [11] After necropsy, Clostridium cadaveris was present, and is proposed as another possible causative agent in some cases of fatal colitis. [11]

Diagnosis

Micrograph of a human colonic pseudomembrane in Clostridioides difficile colitis Colonic pseudomembranes low mag.jpg
Micrograph of a human colonic pseudomembrane in Clostridioides difficile colitis

At necropsy, edema and hemorrhage in the wall of the large colon and cecum are pronounced, and the intestinal contents are fluid and often blood-stained. [1] Macroscopic and microscopic findings include signs of disseminated intravascular coagulation, necrosis of colonic mucosa and presence of large numbers of bacteria in the devitalized parts of the intestine. [3] Typically, the PCV is >65% even shortly after the onset of clinical signs. The leukogram ranges from normal to neutropenia with a degenerative left shift. Metabolic acidosis and electrolyte disorders are also present. [1] There is leucopenia, initially characterized by neutropenia, which might evolve in neutrophilia. Moreover, haemoconcentration is noted with an increase in the packed cell volume; total proteins are initially increased, but changes into a lower than normal value. The most significant laboratory finding in colitis X is the increase of total cortisol concentration in blood plasma. Histopathologically, the mucosa of the large colon is hemorrhagic, necrotic, and covered with fibrohemorrhagic exudate, while the submucosa, the muscular tunic, and the local lymph nodes are edematous. [2]

Treatment

Treatment for colitis-X usually does not save the horse. The prognosis is average to poor, and mortality is 90% to 100%. [1] [2] However, treatments are available, and one famous horse that survived colitis-X was U.S. Triple Crown winner Seattle Slew, that survived colitis-X in 1978 and went on to race as a four-year-old. [7] [8] [14] Large amounts of intravenous fluids are needed to counter the severe dehydration, and electrolyte replacement is often necessary. Flunixin meglumine (Banamine) may help block the effects of toxemia. [1] Mortality rate has been theorized to fall to 75% if treatment is prompt and aggressive, including administration of not only fluids and electrolytes, but also blood plasma, anti-inflammatory and analgesic drugs, and antibiotics. Preventing dehydration is extremely important. Nutrition is also important. Either parenteral or normal feeding can be used to support the stressed metabolism of the sick horse. Finally, the use of probiotics is considered beneficial in the restoration of the normal intestinal flora. The probiotics most often used for this purpose contain Lactobacillus and Bifidobacterium . [2]

See also

Related Research Articles

<i>Clostridioides difficile</i> infection Disease caused by C. difficile bacteria

Clostridioides difficile infection, also known as Clostridium difficile infection, is a symptomatic infection due to the spore-forming bacterium Clostridioides difficile. Symptoms include watery diarrhea, fever, nausea, and abdominal pain. It makes up about 20% of cases of antibiotic-associated diarrhea. Antibiotics can contribute to detrimental changes in gut microbiota; specifically, they decrease short-chain fatty acid absorption which results in osmotic, or watery, diarrhea. Complications may include pseudomembranous colitis, toxic megacolon, perforation of the colon, and sepsis.

<span class="mw-page-title-main">Enteritis</span> Inflammation of the small intestine

Enteritis is inflammation of the small intestine. It is most commonly caused by food or drink contaminated with pathogenic microbes, such as Serratia, but may have other causes such as NSAIDs, radiation therapy as well as autoimmune conditions like coeliac disease. Symptoms include abdominal pain, cramping, diarrhoea, dehydration, and fever. Related diseases of the gastrointestinal system involve inflammation of the stomach and large intestine.

<span class="mw-page-title-main">Gastroenteritis</span> Inflammation of the stomach and small intestine

Gastroenteritis, also known as infectious diarrhea, is an inflammation of the gastrointestinal tract including the stomach and intestine. Symptoms may include diarrhea, vomiting, and abdominal pain. Fever, lack of energy, and dehydration may also occur. This typically lasts less than two weeks. Although it is not related to influenza, in the U.S. and U.K., it is sometimes called the "stomach flu".

<span class="mw-page-title-main">Toxic megacolon</span> Potentially lethal large intestine emergency

Toxic megacolon is an acute form of colonic distension. It is characterized by a very dilated colon (megacolon), accompanied by abdominal distension (bloating), and sometimes fever, abdominal pain, or shock.

<span class="mw-page-title-main">Clostridia</span> Class of bacteria

The Clostridia are a highly polyphyletic class of Bacillota, including Clostridium and other similar genera. They are distinguished from the Bacilli by lacking aerobic respiration. They are obligate anaerobes and oxygen is toxic to them. Species of the class Clostridia are often but not always Gram-positive and have the ability to form spores. Studies show they are not a monophyletic group, and their relationships are not entirely certain. Currently, most are placed in a single order called Clostridiales, but this is not a natural group and is likely to be redefined in the future.

<span class="mw-page-title-main">Neutropenic enterocolitis</span> Medical condition

Neutropenic enterocolitis, also known as typhlitis, is an inflammation of the cecum that may be associated with infection. It is particularly associated with neutropenia, a low level of neutrophil granulocytes in the blood.

<span class="mw-page-title-main">Fecal microbiota transplant</span> Process of transplantation of fecal bacteria from a healthy individual into a recipient

Fecal microbiota transplant (FMT), also known as a stool transplant, is the process of transferring fecal bacteria and other microbes from a healthy individual into another individual. FMT is an effective treatment for Clostridioides difficile infection (CDI). For recurrent CDI, FMT is more effective than vancomycin alone, and may improve the outcome after the first index infection.

<span class="mw-page-title-main">Rifaximin</span> Antibiotic medication

Rifaximin, is a non-absorbable, broad spectrum antibiotic mainly used to treat travelers' diarrhea. It is based on the rifamycin antibiotics family. Since its approval in Italy in 1987, it has been licensed in over more than 30 countries for the treatment of a variety of gastrointestinal diseases like irritable bowel syndrome, and hepatic encephalopathy. It acts by inhibiting RNA synthesis in susceptible bacteria by binding to the RNA polymerase enzyme. This binding blocks translocation, which stops transcription. It is marketed under the brand name Xifaxan by Salix Pharmaceuticals.

Antibiotic-associated diarrhea (AAD) results from an imbalance in the colonic microbiota caused by antibiotics. Microbiotal alteration changes carbohydrate metabolism with decreased short-chain fatty acid absorption and an osmotic diarrhea as a result. Another consequence of antibiotic therapy leading to diarrhea is an overgrowth of potentially pathogenic organisms such as Clostridioides difficile. It is defined as frequent loose and watery stools with no other complications.

Dysbiosis is characterized by a disruption to the microbiome resulting in an imbalance in the microbiota, changes in their functional composition and metabolic activities, or a shift in their local distribution. For example, a part of the human microbiota such as the skin flora, gut flora, or vaginal flora, can become deranged (unbalanced), when normally dominating species become underrepresented and species that normally are outcompeted or contained increase to fill the void. Similar to the human gut microbiome, diverse microbes colonize the plant rhizosphere, and dysbiosis in the rhizosphere, can negatively impact plant health. Dysbiosis is most commonly reported as a condition in the gastrointestinal tract or plant rhizosphere.

<i>Clostridioides difficile</i> toxin B Cytotoxin produced by Clostridioides difficile

Clostridioides difficile toxin B (TcdB) is a cytotoxin produced by the bacteria Clostridioides difficile. It is one of two major kinds of toxins produced by C. difficile, the other being a related enterotoxin. Both are very potent and lethal.

<i>Clostridioides difficile</i> toxin A Cytotoxin produced by Clostridioides difficile

Clostridioides difficile toxin A (TcdA) is a toxin produced by the bacteria Clostridioides difficile, formerly known as Clostridium difficile. It is similar to Clostridium difficile Toxin B. The toxins are the main virulence factors produced by the gram positive, anaerobic, Clostridioides difficile bacteria. The toxins function by damaging the intestinal mucosa and cause the symptoms of C. difficile infection, including pseudomembranous colitis.

<i>Clostridium butyricum</i> Species of bacterium

Clostridium butyricum is a strictly anaerobic endospore-forming Gram-positive butyric acid–producing bacillus subsisting by means of fermentation using an intracellularly accumulated amylopectin-like α-polyglucan (granulose) as a substrate. It is uncommonly reported as a human pathogen and is widely used as a probiotic in Japan, Korea, and China. C. butyricum is a soil inhabitant in various parts of the world, has been cultured from the stool of healthy children and adults, and is common in soured milk and cheeses. The connection with dairy products is shown by the name, the butyr- in butyricum reflects the relevance of butyric acid in the bacteria's metabolism and the connection with Latin butyrum and Greek βούτυρον, with word roots pertaining to butter and cheese.

<span class="mw-page-title-main">Fidaxomicin</span> Antibiotic

Fidaxomicin, sold under the brand name Dificid among others, is the first member of a class of narrow spectrum macrocyclic antibiotic drugs called tiacumicins. It is a fermentation product obtained from the actinomycete Dactylosporangium aurantiacum subspecies hamdenesis. Fidaxomicin is minimally absorbed into the bloodstream when taken orally, is bactericidal, and selectively eradicates pathogenic Clostridioides difficile with relatively little disruption to the multiple species of bacteria that make up the normal, healthy intestinal microbiota. The maintenance of normal physiological conditions in the colon may reduce the probability of recurrence of Clostridioides difficile infection.

Probiotics are live microorganisms promoted with claims that they provide health benefits when consumed, generally by improving or restoring the gut flora. Probiotics are considered generally safe to consume, but may cause bacteria-host interactions and unwanted side effects in rare cases. There is little evidence that probiotics bring the health benefits claimed for them.

Antimotility agents are drugs used to alleviate the symptoms of diarrhea. These include loperamide (Imodium), bismuth subsalicylate (Pepto-Bismol), diphenoxylate with atropine (Lomotil), and opiates such as paregoric, tincture of opium, codeine, and morphine. In diarrhea caused by invasive pathogens such as Salmonella, Shigella, and Campylobacter, the use of such agents has generally been strongly discouraged, though evidence is lacking that they are harmful when administered in combination with antibiotics in Clostridioides difficile cases. Use of antimotility agents in children and the elderly has also been discouraged in treatment of EHEC due to an increased rate of hemolytic uremic syndrome.

<i>Clostridioides difficile</i> Species of bacteria

Clostridioides difficile is a bacterium known for causing serious diarrheal infections, and may also cause colon cancer. It is known also as C. difficile, or C. diff, and is a Gram-positive species of spore-forming bacteria. Clostridioides spp. are anaerobic, motile bacteria, ubiquitous in nature and especially prevalent in soil. Its vegetative cells are rod-shaped, pleomorphic, and occur in pairs or short chains. Under the microscope, they appear as long, irregular cells with a bulge at their terminal ends. Under Gram staining, C. difficile cells are Gram-positive and show optimum growth on blood agar at human body temperatures in the absence of oxygen. C. difficile is catalase- and superoxide dismutase-negative, and produces up to three types of toxins: enterotoxin A, cytotoxin B and Clostridioides difficile transferase. Under stress conditions, the bacteria produce spores that are able to tolerate extreme conditions that the active bacteria cannot tolerate.

Serum-derived bovine immunoglobulin/protein isolate (SBI) is a medical food product derived from bovine serum obtained from adult cows in the United States. It is sold under the name EnteraGam.

The Clostridial Cytotoxin (CCT) Family is a member of the RTX-toxin superfamily. There are currently 13 classified members belonging to the CCT family. A representative list of these proteins is available in the Transporter Classification Database. Homologues are found in a variety of Gram-positive and Gram-negative bacteria.

References

  1. 1 2 3 4 5 6 7 8 9 10 11 "Colitis-X". Merck Veterinary Manual. Merck & Co., Inc.W. 2008. Retrieved 2010-01-10.
  2. 1 2 3 4 5 6 Diakakis, N. (January–March 2008). "Equine colitis X". Journal of the Hellenic Veterinary Medical Society. 59 (1): 23–28(6). doi: 10.12681/jhvms.14944 .
  3. 1 2 3 4 Schiefer HB (May 1981). "Equine colitis "X", still an enigma?". The Canadian Veterinary Journal. 22 (5): 162–5. PMC   1790040 . PMID   6265055.
  4. 1 2 Songer JG, Trinh HT, Dial SM, Brazier JS, Glock RD (May 2009). "Equine colitis X associated with infection by Clostridium difficile NAP1/027". Journal of Veterinary Diagnostic Investigation. 21 (3): 377–80. doi: 10.1177/104063870902100314 . PMID   19407094.
  5. ↑ Wells CL, Wilkins TD (1996). "Antibiotic-Associated Diarrhea, Pseudomembranous Colitis, and Clostridium difficile". In Baron S, et al. (eds.). Baron's Medical Microbiology (4th ed.). Univ of Texas Medical Branch. ISBN   978-0-9631172-1-2. PMID   21413315.
  6. ↑ Dallal RM, Harbrecht BG, Boujoukas AJ, et al. (March 2002). "Fulminant Clostridium difficile: an underappreciated and increasing cause of death and complications". Annals of Surgery. 235 (3): 363–72. doi:10.1097/00000658-200203000-00008. PMC   1422442 . PMID   11882758.
  7. 1 2 3 DeVito, Carlo (2002). D. Wayne: The High-Rolling and Fast Times of America's Premier Horse Trainer. McGraw-Hill Professional. pp. 93–94. ISBN   978-0-07-138737-8.
  8. 1 2 Leggett, William (June 25, 1984). "Suddenly A Young Champion Is Gone". Sports Illustrated. Archived from the original on June 4, 2011. Retrieved 2010-01-13.
  9. ↑ Simmons, Diane (1994). "Lightning Bar". In Simmons, Diane; Jim Goodhue; Holmes, Frank Wakefield; Phil Livingston (eds.). Legends 2: Outstanding Quarter Horse Stallions and Mares. Colorado Springs, CO: Western Horseman. p.  149. ISBN   978-0-911647-30-3.
  10. ↑ Srivastava, K. "Colitis X (Peracute Toxemic Colitis)". Biomedical Research and Graduate Studies Resources, Large Animal Laboratory Animal Medicine. Tuskegee University. Archived from the original on 2012-12-10. Retrieved 2010-01-10.
  11. 1 2 3 4 Prescott JF, Staempfli HR, Barker IK, Bettoni R, Delaney K (November 1988). "A method for reproducing fatal idiopathic colitis (colitis X) in ponies and isolation of a clostridium as a possible agent". Equine Veterinary Journal. 20 (6): 417–20. doi:10.1111/j.2042-3306.1988.tb01563.x. PMID   3215166.
  12. ↑ Curry J (2007-07-20). "Pseudomembranous Colitis". eMedicine. WebMD. Retrieved 2008-11-17.
  13. ↑ Thomas C, Stevenson M, Riley TV (June 2003). "Antibiotics and hospital-acquired Clostridium difficile-associated diarrhoea: a systematic review". Journal of Antimicrobial Chemotherapy . 51 (6): 1339–50. doi: 10.1093/jac/dkg254 . PMID   12746372.
  14. ↑ Sparkman, John P. (2010). "A veritable slew of sons". The Thoroughbred Times. Retrieved 2010-01-13.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.