View source for Colitis-X

{{Short description|Fatal colitis in horses}}
'''Colitis X''', '''equine colitis X''' or '''peracute toxemic colitis''' is a catchall term for various fatal forms of acute or peracute [[colitis]] found in [[horse]]s, but particularly a [[Colitis#Severity of colitides|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 (bacteria)|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.

== Clinical signs ==
Colitis-X is a term used for colitis cases in which no definitive diagnosis can be made and the horse dies.<ref name="Merck" /> 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.<ref name="Merck">
{{cite web
| url        = http://merckveterinarymanual.com/mvm/index.jsp?cfile=htm/bc/22206.htm
| title      = Colitis-X
| work       = Merck Veterinary Manual
| publisher  = Merck & Co., Inc.W
| year       = 2008
| accessdate =2010-01-10
}}</ref><ref name="Diakakis">
{{cite journal
| author     = Diakakis, N.
| title      = Equine colitis X
| journal       = Journal of the Hellenic Veterinary Medical Society
| volume = 59
| issue      = 1
| date       = January–March 2008
| pages      = 23–28(6)
| doi = 10.12681/jhvms.14944
| doi-access= free
}}</ref>

Clinical signs are similar to those of other diarrheal diseases, including toxemia caused by ''[[Clostridium]]'', [[Potomac horse fever]], experimental endotoxic shock, and [[anaphylaxis]].<ref name="Merck" />

== 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.<ref name="Merck" /><ref name="Diakakis" /><ref name="Schiefer" /> Other possible causes include peracute [[salmonellosis]], [[Clostridium|clostridial]] [[enterocolitis]], and [[endotoxemia]].<ref name="Merck" /> ''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.<ref name="Songer" />  ''C. difficile'' can cause [[pseudomembranous colitis]] in humans,<ref name=Baron_c>{{cite book | vauthors = Wells CL, Wilkins TD | chapter = Antibiotic-Associated Diarrhea, Pseudomembranous Colitis, and ''Clostridium difficile'' | title=Baron's Medical Microbiology | editor=Baron S | display-editors=etal | edition = 4th | publisher = Univ of Texas Medical Branch | year = 1996 | pmid = 21413315 | chapter-url = https://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=mmed.section.1122 | isbn = 978-0-9631172-1-2 }}</ref> and in hospitalized patients who develop it, fulminant ''C. difficile'' colitis is a significant and increasing cause of death.<ref>{{cite journal |vauthors=Dallal RM, Harbrecht BG, Boujoukas AJ |title=Fulminant Clostridium difficile: an underappreciated and increasing cause of death and complications |journal=Annals of Surgery |volume=235 |issue=3 |pages=363–72 |date=March 2002 |pmid=11882758 |pmc=1422442 |doi=10.1097/00000658-200203000-00008|display-authors=etal}}</ref>

Horses under stress appear to be more susceptible to developing colitis X.<ref name="Diakakis" /> Disease onset is often closely associated with surgery or transport.<ref name="Merck" /> 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 [[Clostridium|clostridial]] organisms.<ref name="Schiefer" /> A similar condition may be seen after administration of [[tetracycline]] or [[lincomycin]] to horses.<ref name="Merck" /> These factors may be one reason the condition often develops in [[horse racing|race horses]], having been responsible for the deaths of the Thoroughbred [[filly]] [[Landaluce]],<ref name="Lukas" /><ref name="SI">

{{cite web
| url         = http://sportsillustrated.cnn.com/vault/article/magazine/MAG1122220/
| archive-url = https://web.archive.org/web/20110604011635/http://sportsillustrated.cnn.com/vault/article/magazine/MAG1122220/
| url-status  = dead
| archive-date = June 4, 2011
| author      = Leggett, William
| title       = Suddenly A Young Champion Is Gone
| publisher = Sports Illustrated
| date        = June 25, 1984
| accessdate  = 2010-01-13
}}</ref>
the Quarter Horse stallion [[Lightning Bar]],<ref>
{{cite encyclopedia |author       = Simmons, Diane
 |title        = Lightning Bar
 |editor       = Simmons, Diane
 |editor2      = Jim Goodhue
 |editor3      = Holmes, Frank Wakefield
 |editor4      = Phil Livingston
 |encyclopedia = Legends 2: Outstanding Quarter Horse Stallions and Mares
 |publisher    = Western Horseman
 |location     = Colorado Springs, CO
 |page         = [https://archive.org/details/legendsoutstandi00simm/page/149 149]
 |year         = 1994
 |isbn         = 978-0-911647-30-3
 |url          = https://archive.org/details/legendsoutstandi00simm/page/149
}}</ref>
and is one theory for the sudden death of [[Kentucky Derby]] winner [[Swale (horse)|Swale]].<ref name="Lukas">
{{cite book
| title      = D. Wayne: The High-Rolling and Fast Times of America's Premier Horse Trainer
| author     = DeVito, Carlo
| publisher  = McGraw-Hill Professional
| year       = 2002
| pages      = 93–94
| isbn       = 978-0-07-138737-8
| url=https://books.google.com/books?id=9OQg3Sm6BAYC&dq=landaluce+colitis&pg=PA93
}}</ref>

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.<ref name="Tuskegee">{{cite web
 |url          = http://compepid.tuskegee.edu/syllabi/clinical/large/lam/chapter1.html
 |title        = Colitis X (Peracute Toxemic Colitis)
 |author       = Srivastava, K.
 |work         = Biomedical Research and Graduate Studies Resources, Large Animal Laboratory Animal Medicine
 |publisher    = Tuskegee University
 |accessdate   = 2010-01-10
 |archive-url  = https://archive.today/20121210121951/http://compepid.tuskegee.edu/syllabi/clinical/large/lam/chapter1.html
 |archive-date = 2012-12-10
 |url-status     = dead
}}</ref>

The causative agent may be ''[[Clostridium perfringens]]'', type A, but the bacteria are recoverable only in the preliminary stages of the disease.<ref name="Schiefer">{{cite journal |author=Schiefer HB |title=Equine colitis "X", still an enigma? |journal=The Canadian Veterinary Journal |volume=22 |issue=5 |pages=162–5 |date=May 1981 |pmid=6265055 |pmc=1790040}}</ref>

The suspect toxin could also be a form of ''[[Clostridioides difficile (bacteria)|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.<ref name="Songer">{{cite journal |vauthors=Songer JG, Trinh HT, Dial SM, Brazier JS, Glock RD |title=Equine colitis X associated with infection by Clostridium difficile NAP1/027 |journal=Journal of Veterinary Diagnostic Investigation |volume=21 |issue=3 |pages=377–80 |date=May 2009 |pmid=19407094 |url=http://www.jvdi.org/cgi/pmidlookup?view=long&pmid=19407094 |doi=10.1177/104063870902100314|doi-access=free |url-access=subscription }}</ref>

The use of antibiotics may also be associated with some forms of colitis-X.<ref name="Prescott"/> In humans, ''C. difficile'' is the most serious cause of antibiotic-associated diarrhea, often a result of eradication of the normal [[gut flora]] by [[antibiotic]]s.<ref name=eMed1942>{{ cite web | url= http://www.emedicine.com/med/topic1942.htm#section~introduction | author=Curry J | title=Pseudomembranous Colitis | work=eMedicine | date=2007-07-20 | publisher=WebMD| accessdate=2008-11-17}}</ref> 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.<ref name="Prescott"/> (A classic [[adverse drug reaction|adverse effect]] of clindamycin in humans is ''C. difficile''-associated diarrhea.<ref name=Thomas>{{cite journal |vauthors=Thomas C, Stevenson M, Riley TV |title=Antibiotics and hospital-acquired Clostridium difficile-associated diarrhoea: a systematic review |journal=[[Journal of Antimicrobial Chemotherapy]] |volume=51 |issue=6 |pages=1339–50 |date=June 2003 |pmid=12746372 |doi=10.1093/jac/dkg254|doi-access=free }}</ref>) In the experiment, the treated horses died.<ref name="Prescott"/> After necropsy, ''Clostridium cadaveris'' was present, and is proposed as another possible causative agent in some cases of fatal colitis.<ref name="Prescott">{{cite journal |vauthors=Prescott JF, Staempfli HR, Barker IK, Bettoni R, Delaney K |title=A method for reproducing fatal idiopathic colitis (colitis X) in ponies and isolation of a clostridium as a possible agent |journal=Equine Veterinary Journal |volume=20 |issue=6 |pages=417–20 |date=November 1988 |pmid=3215166 |doi=10.1111/j.2042-3306.1988.tb01563.x}}</ref>

== Diagnosis ==
[[File:Colonic pseudomembranes low mag.jpg|thumb|right|[[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.<ref name="Merck" /> 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.<ref name="Schiefer" /> 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.<ref name="Merck" /> 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.<ref name="Diakakis" />

== Treatment ==
Treatment for colitis-X usually does not save the horse. The prognosis is average to poor, and mortality is 90% to 100%.<ref name=Merck/><ref name=Diakakis/>  However, treatments are available, and one famous horse that survived colitis-X was [[United States Triple Crown of Thoroughbred Racing|U.S. Triple Crown]] winner [[Seattle Slew]], that survived colitis-X in 1978 and went on to race as a four-year-old.<ref name="Lukas" /><ref name="SI" /><ref>
{{cite web
| url = http://www.thoroughbredtimes.com/stallion-directory/reference.aspx?doc=seattleslew
| author     = Sparkman, John P.
| title      = A veritable slew of sons
| publisher  = The Thoroughbred Times
| year       = 2010
| accessdate = 2010-01-13
}}</ref>
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.<ref name="Merck" /> 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]]''.<ref name="Diakakis" />

== See also ==
* [[Horse colic]]

== References ==
{{Reflist}}

[[Category:Horse diseases]]