Liver disease {#s0010}
=============

Liver disease is relatively common in the horse, and there are a large number of disorders that can cause hepatic disease (i.e. pathological damage to the liver) ([Table 3.1](#t0010){ref-type="table"} ) in both adult horses and foals. However, liver failure is much rarer because the liver has a large reserve capacity and good capacity to regenerate. Liver failure will not occur until 70% or more of the organ has been damaged. The distinction between liver disease and liver failure is important clinically. In view of the large reserve capacity, many horses with mild hepatic disease will make a full recovery given time and removal of the inciting cause. However, if the damage progresses to cause liver failure, then the prognosis for survival is much reduced.Table 3.1Important causes of liver disease in the horseToxic causes:•Pyrrolizidine alkaloid toxicosis.•Alsike clover.•Panicum grasses.•Iron.•Mycotoxins.Infectious causes:•Cholangiohepatitis.•Tyzzer\'s disease.•Hepatic abscess.•Equine herpesvirus (EHV-1).•Liver fluke.Inflammatory, non-infectious causes:•Chronic active hepatitis.•Neoplasia.•Granulomatous disease.Metabolic causes:•Hepatic lipidosis.•Hyperammonaemia in horses with gastrointestinal disease (no liver disease present).•Hyperammonaemia in Morgan foals.Obstructive causes:•Biliary stones.•Right dorsal colon displacement.•Papillary stricture -- foals with duodenal ulcers.•Neoplasia.•Hepatic torsion.•Portal vein thrombosis.Unknown / miscellaneous causes:•Theiler\'s disease.•Neonatal isoerthrolysis.•Senile cirrhosis.Congenital:•Portosystemic shunt.

The liver has a limited number of ways to respond to various different insults, and, therefore, the clinical and laboratory changes tend to be similar regardless of the underlying cause.

*Chronic weight loss* is the most common presenting sign of liver failure, but other presentations include dullness, anorexia, behavioural abnormalities, skin lesions, pruritus, bleeding disorders, diarrhoea and colic.

Weight loss is a common, but non-specific, finding in chronic liver disease. It is related to failure of metabolic functions of the liver and reduced food intake.

Hyperammonaemia results when ammonia from portal circulation is not metabolized to urea within the liver and enters the systemic circulation. Raised plasma ammonia affects gluconeogenesis causing utilization of branched-chain amino acids. The resultant decrease in ratio of branched-chain to aromatic amino acids affects neutrotransmission and may give rise to *hepatic encephalopathy* (see Chapter 11) or, very rarely, *peripheral neuropathy* which can lead to unusual complications such as gastric impaction (and colic) or laryngeal paralysis. Signs of hepatoencephalopathy may vary from depression to bizarre maniacal behaviour. Common signs include:•apparent blindness.•ataxia.•head pressing.•compulsive circling.•frequent yawning.

Accumulation of bilirubin in plasma may result in jaundice. There may be decreased hepatic metabolism of photodynamic phylloerythrin which, when exposed to ultraviolet light within superficial dermal circulation, results in necrotic skin lesions in white areas referred to as *photosensitization* ([Figure 3.1](#f0010){ref-type="fig"} ) (see Chapter 13). Pruritus occasionally occurs due to bile salt accumulation in the skin.Figure 3.1Photosensitization of the unpigmented areas on the face.

Altered faecal consistency is not uncommon in equine liver failure, and some affected horses may develop diarrhoea, probably caused by portal hypertension or thrombosis. Some affected horses develop abnormally firm faeces. Colic may arise due to hepatocellular swelling and obstruction of the biliary tract. A reduction in intestinal motility is a fairly frequent finding in cases of equine liver failure.

Failure of the liver to synthesize clotting factors may result in an increased *bleeding tendency*, especially after trauma. Spontaneous haemorrhage into the lungs or alimentary tract is rarely seen. Such haemorrhage usually occurs as a terminal event.

The underlying hepatic pathology is generally chronic, but clinical signs are often relatively sudden in onset when the degree of organ failure exceeds the considerable functional reserve capacities of liver. Hepatic failure occurs in a wide variety of conditions which can be difficult to differentiate, but clinical management of affected cases is often similar and directed at ameliorating hyperammonaemia and providing nutritional support.

The main differential diagnoses of equine liver failure are chronic enteropathies and chronic grass sickness.

3.1. Diagnostic approach to liver disease {#s0015}
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###### History {#s0035}

•Age -- in foals, liver failure is associated with rare disorders such as Tyzzer\'s disease or portosystemic shunt. Senile cirrhosis occurs in elderly horses.•Multiple cases affected implies ingested hepatotoxin (e.g. pyrrolizidine alkaloid) or, very rarely, liver fluke infection. Also, hyperlipaemia with associated hepatic dysfunction may occur in groups of horses under the same management, and Theiler\'s disease is seen as a group disease in North Western USA.•Duration/progression of signs -- insidious weight loss is common and non-specific for chronic hepatopathies. Neurological signs associated with hepatic encephalopathy can develop fairly suddenly in chronic advanced liver failure (e.g. pyrrolizidine toxicosis) or, more likely will be the presenting complaint in acute liver failure (e.g. Theiler\'s disease).

###### Physical examination {#s0040}

Few physical findings are diagnostic of equine liver disease. Generally the approach is to rule out other possible causes of weight loss, behavioural changes or skin lesions, e.g. signs of enteropathy, primary central nervous system (CNS) disease (Chapter 11) or primary skin disease (Chapter 13).•Jaundice occurs relatively infrequently in equine liver failure but is more likely in acute and/or cholestatic diseases. Horses commonly become mildly jaundiced from anorexia, even when the liver is not diseased.•Mucosal petechial/ecchymotic haemorrhages or bleeding due to clotting abnormalities occur uncommonly.•Peripheral oedema or ascites is rare in equine liver failure.•Photosensitization lesions occur in unpigmented skin, especially the skin of the head ([Figure 3.1](#f0010){ref-type="fig"}).

###### Laboratory investigation of liver disease {#s0045}

In the mature horse, leakage of hepatic and biliary enzymes into the circulation, failure to convert ammonia to urea and failure to conjugate bilirubin are generally recognized before failure to produce clotting factors or albumin is recognized.1.Plasma/serum liver enzymes.•*Hepatocellular damage:* glutamate dehydrogenase (GLDH) -- liver specific.sorbitol dehydrogenase (SDH) -- specific, unstable if stored (e.g. postal).lactate dehydrogenase (LDH) -- isoenzyme 5 non-specific.aspartate transferase (AST) -- non-specific.ornithine carbamoyltransferase (OCT) -- liver specific.•*Biliary tract damage or obstruction:* gammaglutamyl transferase (*γ*GT) -- specific.alkaline phosphatase (AP) -- non-specific.2.Liver function.Liver function tests only become abnormal when approximately 60-70% of liver function is lost, and these tests include elevations of bile acids, direct bilirubin, blood ammonia, prothrombin and partial thromboplastin time, serum iron, and gamma globulins (with chronic disease).•An increase in direct bilirubin is a highly sensitive and specific marker of liver failure due to either hepatocellular or hepatobiliary disease. However, mild hyperbilirubinaemia may occur in horses that are anorexic, regardless of the cause. An increase in direct bilirubin of 25% or more of the total bilirubin is suggestive of a predominant biliary disease. Clinically evident jaundice associated with marked unconjugated hyperbilirubinaemia but in the absence of other biochemical evidence of liver disease is suggestive of haemolytic anaemia. Septic foals with intestinal ileus sometimes have elevations in direct bilirubin with minimal evidence of hepatocellular dysfunction; treatment should focus on the sepsis and intestinal ileus.•There may be a decrease in blood urea nitrogen and albumin with chronic liver diseases.•Serum or plasma bile acids are elevated in horses with both hepatocellular and hepatobiliary disorders, and elevations can be an early predictor of liver failure when values rise above 30 µmol/L. Unlike for other species, fasting samples are not required in horses to interpret bile acid results, although mild elevations of bile acids (up to 20 µmol/L) may occur as a result of anorexia.•Blood ammonia can also be used as an assessment of liver function. However, rapid and careful sample handling is required. Ideally a control sample should be obtained from a healthy horse and measured simultaneously for comparative purposes.•Dye excretion tests (such as bromosulphophthalein and indocyanine green) are now very rarely used to assess liver function.3.Other analytes may be altered in hepatic disease, e.g. hypoglycaemia, hypoalbuminaemia, decreased albumin: globulin ratio, and raised concentrations of triglycerides and cholesterol.4.Clotting function -- prolonged prothrombin time. Many of the standard biochemical indices of liver function/damage possess significantly different reference ranges than adult horses. GGT, bile acids and AP, for example, are normally higher in healthy foals than adults.5.Reference ranges for many of the standard biochemical indices of liver function differ between foals and adult horses.

###### Liver biopsy {#s0050}

In many cases biopsy can provide a definitive diagnosis (which laboratory tests cannot). Liver biopsy is best performed after the liver has been visualized by ultrasonography on either the right or left side. Liver biopsies can be useful to determine the amount of fibrosis, inflammation, and predominant location of disease and for culture purposes. Pre-biopsy evaluation of extrinsic, intrinsic and common clotting function, by measurement of prothrombin time (PT) and activated partial thromboplastin time (APTT) is often recommended. Although prolonged clotting times are rare even with severe liver disease, the risk of haemorrhage is higher in adults with Theiler\'s disease and foals with Tyzzer\'s disease. Using a 14-cm needle, percutaneous biopsy can also be performed 'blind' in the standing horse at the 12th, 13th or 14th right-sided intercostal spaces between the level of lines drawn from the tuber coxa to the point of the olecranon and to the point of the shoulder.

###### Diagnostic ultrasound in liver disease {#s0055}

Transabdominal ultrasonography is best performed with either a 2.5-MHz or 5-MHz transducer. In neonatal foals, 7.5-MHz or 10-MHz transducers are effective. The liver is best imaged from the right, immediately caudal and ventral to the lung. Typical landmarks for imaging the liver are the 6th to 15th intercostal spaces on the right, and the 6th to 9th intercostal spaces on the ventral aspect of the abdomen. In neonatal foals, the liver can also be imaged from the ventral aspect of the abdomen. In adults, the image quality is variable, depending on such factors as the underlying disease, normal age changes (right lobe atrophy in old horses), extent of the lung fields, degree of gas distension of the colon, amount of subcutaneous fat, etc. Healthy liver tissue is less echogenic than the spleen, and has a more prominent vascular pattern. The portal veins can be distinguished from the hepatic veins by the greater amount of fibrous tissue in the walls of the portal vessels. Bile ducts are not visible in the normal liver. Discrete lesions such as abscesses/masses, choleliths, biliary sludge and dilated bile ducts can be visualized, and chronic fibrosis or hepatomegaly can be appreciated.

3.2. Pyrrolizidine toxicity {#s0060}
---------------------------

Ingestion of plants containing pyrrolizidine alkaloids is a common cause of equine liver disease and failure. The plant species most frequently include *Senecio jacobea* (ragwort), *Crotalaria* spp. (rattlebox), *Senecio* spp. (groundsel), *Amsinckia* spp. (riddleneck) and *Echium plantagineum* (Patterson\'s Curse). These plants are generally unpalatable to horses unless withered, e.g. following pasture-topping or within hay, or if grazing is severely restricted. The intoxication typically results in the delayed onset of chronic, progressive liver failure. The onset of clinical signs is usually delayed weeks to months following ingestion of pyrrolizidine alkaloid-containing plants. Not all horses that consume the plants develop clinical signs. Horses generally present with variable periods of:•depression.•anorexia.•weight loss.

Horses with areas of unpigmented skin may develop photosensitivity. The clinical course may vary from several days to several months, but when sufficient liver damage has occurred to produce functional failure, there may be an abrupt onset of profound clinical signs of hepatic encephalopathy, and in many cases death. The apparent acute onset of clinical illness generally represents the end stage of a chronic, progressive disease process ([Figure 3.2](#f0015){ref-type="fig"} ). Clinical signs and death may occur up to a year after the contaminated feed was eaten.•Elevation of liver-derived serum enzyme activities (SDH and AST) is associated with active liver damage, but activities may decrease toward normal until the later stages of the disease process when marked elevation may again be noted.•Elevation of GGT and AP activities reflects the focus of the pathological process in the periportal regions and the biliary system.•Serum bile acid concentration is generally increased.•Serum bilirubin concentrations may remain within normal limits until the horse reaches a state of functional failure.•The blood urea nitrogen concentration is generally below normal in horses with functional failure. Figure 3.2Post-mortem appearance of fibrosed, end-stage liver due to pyrrolizidine toxicity.

Definitive diagnosis can be made by percutaneous biopsy. Typical lesions include megalocytosis, periportal fibrosis, biliary hyperplasia, and occlusion of the central veins. Treatment (see 3.11 below) can be attempted; although the prognosis is poor, some cases survive.

3.3. Theiler\'s disease (acute hepatic necrosis, serum hepatitis, serum sickness) {#s0065}
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The aetiology is unknown but often there is a history of the affected horses receiving an equine-origin biological product (now most commonly tetanus antitoxin) 4--10 weeks prior to the onset of clinical signs. In some cases, the affected horses may not have received an antitoxin, but may have been in contact with another horse that had received tetanus antitoxin. It may occur as a group outbreak during autumn in North Western USA but is only rarely recognized as an entity elsewhere. Generally, affected cases develop peracute liver failure (signs of hepatic encephalopathy, jaundice, red discoloured urine, etc) but individuals may have mild or subclinical signs with raised serum liver enzyme concentrations. The history, onset, clinical signs, and histopathological findings of Theiler\'s disease are similar to hepatitis B virus in humans. However, no viral aetiology has ever been proven. The diagnosis is based on:•history.•clinical findings.•laboratory confirmation of hepatic disease and hepatic failure.•liver biopsy.

3.4. Cirrhosis {#s0070}
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This is not well documented but is not uncommon. End-stage pathology is the same as for other specific liver condition or for senile change. The most likely clinical presentation is chronic, progressive weight loss. Diagnosis is confirmed by biopsy. Supportive treatment may prolong life by weeks or months, but the prognosis is very poor.

3.5. Liver fluke {#s0075}
----------------

*Fasciola hepatica* infection is rare in the horse, but donkeys may be more susceptible. Clinical signs of liver failure can occur, and it may be a group disease. Diagnosis can be confirmed by finding fluke eggs in the faeces, but immature, migrating parasites could cause signs prior to patency. Treatment is with triclabendazole, 15 mg/kg body weight *per os* (not licensed in the horse).

3.6. Cholangiohepatitis and choledocholithiasis (biliary calculi) {#s0080}
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Cholangiohepatitis is the most commonly encountered, clinically significant form of biliary tract disease in horses. The condition probably begins as a cholangitis, but extension into the periportal region of the liver normally follows (hence the term 'cholangiohepatitis' is usually used). It is probable that many mild cases of cholangitis/cholangiohepatitis are asymptomatic, but the condition predisposes horses to chronic, active, inflammatory hepatobiliary disease and the formation of biliary calculi ([Figure 3.3](#f0020){ref-type="fig"} ). Chronic cholangiohepatitis may frequently be associated with significant intrahepatic or extrahepatic biliary calculus formation. Discrete calculi can often be visualized ultrasonographically or at post mortem examination, but some horses with cholangiohepatitis develop a sonolucent 'sludge-like' material within the biliary tract. With severe suppurative cholangiohepatitis significant periportal and bridging fibrosis can occur. Clinically significant hepatobiliary disease appears to be more common in middle-aged to old horses.Figure 3.3Large biliary calculus at post-mortem examination of a horse affected by cholangiohepatitis.

Clinical signs are non-specific, and include:•fever.•icterus.•colic.•weight loss.•encephalopathy.

Recurrent bouts of mild-to-moderate colic coincident with fever may occur. Significant weight loss will commonly accompany more chronic cases. Occasionally signs of hyperammonaemic hepatic encephalopathy can be seen when complete calculus obstruction to biliary outflow occurs or the disease process has progressed to hepatic failure. Serum biochemical abnormalities include:•increases in the hepatobiliary enzymes GGT and AP, with moderate increases in the hepatocellular enzymes (AST and SDH).•total serum bilirubin is elevated with the conjugated fraction representing more than 25 per cent of the total.•bilirubinuria may also be observed.•serum bile acids are usually elevated, and blood ammonia concentration may be raised in horses with complete calculus obstruction.

Typically, haematological changes are consistent with chronic, active inflammation and include neutrophilia and hyperfibrinogenaemia. If the condition is more than 2--3 weeks in duration, hyperglobulinaemia may also be documented. A definitive diagnosis of cholangiohepatitis requires liver biopsy.

Long-term (weeks to months) antimicrobial therapy is essential in the successful treatment of cholangiohepatitis and choledocholithiasis/hepatolithiasis in adult horses. In certain situations where biliary obstruction is complete, or the horse is in uncontrollable abdominal pain, surgery may be considered. The choice of specific antibiotics should be based upon both aerobic and anaerobic cultures of liver biopsy material. If biopsy culture results are either unavailable or negative, then broad spectrum antibiotics such as potentiated sulphonamides, cephalosporins, or fluoroquinolones would be appropriate choices.

3.7. Chronic active hepatitis {#s0085}
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Chronic active hepatitis is a descriptive term for a group of conditions characterized by active, progressive, inflammatory liver disease of long duration. The history is often one of depression, weight loss, and variable icterus. Signs are often intermittent and may be associated with fever. Some horses have a history of previous or active intra-abdominal disease. The disease can progress to the point of liver failure with major central nervous system involvement and death. Unusual cutaneous manifestations such as moist lesions at the coronary bands may be present. Liver lesions tend to be located in the periportal region, and the histopathological diagnosis is often cholangiohepatitis. The cause of chronic active hepatitis has not been determined, although autoimmune disease is possible. Alternatively, some cases may be a manifestation of chronic cholangitis.

Laboratory evaluation provides evidence of liver damage:•elevation of liver-derived serum enzyme activities and marked elevation GGT and AP.•serum bilirubin may be elevated with direct-reacting bilirubin comprising up to 40% of the total.•the urine is positive for bilirubin.•serum bile acids are elevated.

Haematological examination may show leukocytosis, left shift, and monocytosis. Total plasma protein concentration is generally elevated. Culture of liver biopsy specimens may be rewarding because bacterial agents may contribute to hepatitis or cholangitis.

Treatment involves general supportive care until horses regain their appetite. Corticocosteroids are often helpful; initial treatment should consist of 20--40 mg of dexamethasone given by injection. This dose rate is maintained for 3--5 days (depending on the response) and is then gradually decreased over the next 7--10 days. At this time the horse may be placed on oral prednisone at 1 mg/kg/day. Treatment may be necessary for 4--6 weeks or longer with careful monitoring of clinical signs and biochemical values. Bacterial infection may play a role, especially in horses with fever and a neutrophilic inflammatory infiltrate present on liver biopsy, and long-term (4--6 weeks) systemic administration of antibiotics is indicated.

3.8. Iron overload (haemochromatosis) {#s0090}
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Newborn foals given an oral intestinal inoculum containing ferrous fumarate during the first day or two of life can develop acute liver failure due to iron overload. This is probably associated with an inability of the newborn foal to effectively regulate intestinal absorption of iron. Clinical signs develop within a few days with rapid progression of anorexia, depression, icterus, collapse, and death. Acute iron overload with liver damage has also been reported in a few adult horses given iron supplements orally.

Iron overload or haemochromatosis associated with chronic hepatic cirrhosis has been reported in adult horses. Clinical signs include depression, anorexia, weight loss, icterus, ventral oedema, and terminal hepatic encephalopathy. Liver-derived enzyme activities and serum bilirubin are increased. Histological lesions include disruption of hepatic architecture, bridging fibrosis, and bile duct hyperplasia. Iron accumulation is noted within hepatocytes, macrophages, and Kupffer\'s cells as indicated by Prussian blue staining. Unlike the condition in human beings, there is no evidence that the disorder is inherited. Since excessive dietary iron has not been a consistent feature in these horses, it has been suggested that for unknown reasons excessive intestinal iron absorption occurs with resultant accumulation of iron in the liver. It is possible that the accumulation of iron in the liver is the result of liver damage, and may not be the cause of liver failure.

3.9. Hydatid cysts {#s0095}
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Cysts of the horse-dog tapeworm *Echinococcus granulosus equinus* are common in equine livers, but they are virtually never associated with clinical disease.

3.10. Other hepatic diseases {#s0100}
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Various other liver diseases have been documented in the horse but should be regarded as uncommon. Other diseases may affect liver function, and some of these are described elsewhere in the text.•Portosystemic shunts (Chapter 20).•Liver abscess.•Equine herpesvirus (Chapter 19).•Biliary atresia.•Mycotoxicosis.•Hyperlipaemia (Chapter 9).•Hepatic carcinoma/neoplasia.•Lymphoma (see [3.16](#s0280){ref-type="sec"}).•Tyzzer\'s disease (Chapter 20).•Right hepatic lobe atrophy.

3.11. Treatment for liver failure {#s0105}
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Treatment of liver failure is basically supportive. Treatment is most likely to be successful in acute hepatic failure and is not indicated in horses with severely cirrhotic livers. The prognosis is poor for severe hepatoencephalopathy.•Sedation may be necessary in horses with signs of hepatoencephalopathy. Xylazine or detomidine administered in small doses is usually effective. Doses of sedatives that cause lowering of the head should be avoided if possible as low-head position and hypoventilation may worsen cerebral oedema. Phenobarbital can be used, but diazepam should be avoided since it may worsen hepatoencephalopathy.•Intravenous fluids are probably the most important component of treatment for acute liver disease and hepatic encephalopathy. The intravenous fluids should consist of a balanced electrolyte solution, preferably without lactate, and should be supplemented with potassium 20--40 mEq/L, and 5--10 grams of dextrose per 100 mL. Sodium bicarbonate should be given only if blood pH is less than 7.1 and/or bicarbonate is less than 14 mEq/L. Additional potassium may be given as potassium chloride mixed in molasses and administered per os via a dose syringe. Fresh frozen plasma may be used, but hetastarch or stored whole blood should be avoided.•Attempts should be made to decrease blood ammonia concentration.▪*Mineral oil* is administered by nasogastric tube.▪*Neomycin* can be administered at 5.0 mg/kg every 8 hours orally by dose syringe for 2 days.▪*Lactulose* 0.2--0.5 mL/kg every 8--12 hours may also decrease ammonia production in the bowel and can be used concurrently with neomycin. Both lactulose and neomycin may cause diarrhoea if given in excessive dosages or for prolonged periods.▪*Vinegar* (acetic acid) may also be effective in decreasing blood ammonia when it is administered per os at 240 mL/450 kg horse.•Affected horses should be fed high-carbohydrate, high-branch-chain amino-acid (BCAA) feeds, with moderate to low total protein content. Sorghum and/or cracked corn mixed with molasses or commercially prepared BCAA paste are ideal. Carbohydrates should be fed frequently in small amounts. A grass hay with a moderate amount of protein, rather than alfalfa hay or spring-cut grass, should be fed.•Affected horses should be protected from sunlight to prevent photosensitization.•*Vitamin B* ~1~, *folic acid* and *vitamin K* ~1~ should be administered weekly.•*Anti-oxidant, anti-inflammatory and anti-oedema therapy* is indicated in acute hepatic failure. The anti-oxidant, anti-oedema treatments include dimethylsulphoxide, acetylcysteine and mannitol given intravenously and vitamin E given intramuscularly. Anti-inflammatory therapy should include flunixin meglumine and pentoxifylline.•*Antibiotics* are indicated in cases of bacterial cholangitis/cholangiotepatitis.•Hyperlipaemia may be treated by administration of insulin and heparin (see Chapter 9).

Pancreatic diseases {#s0110}
===================

3.12. Pancreatic diseases {#s0115}
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Clinical disease due to pancreatic disorders is rare in the horse. Non-specific signs of weight loss, intermittent colic, jaundice and fever can arise from either chronic pancreatitis or pancreatic adenocarcinoma. Both disorders may give rise to increased concentrations of serum amylase and lipase as well as hypocalcaemia. Pancreatic diseases may also be associated with raised liver enzymes and hyperbilirubinaemia due to either biliary obstruction or pancreatic production of gamma glutamyl transferase (γGT) which is regarded as a 'liver-specific' enzyme. Confirmation of chronic pancreatitis or pancreatic carcinoma is by either exploratory celiotomy or post-mortem examination. Acute pancreatitis is a very rare cause of severe abdominal pain and is characterized by nasogastric reflux and circulatory failure such that it must be differentiated from strangulating intestinal obstruction and anterior enteritis.

Equine grass sickness {#s9000}
=====================

3.13. Equine grass sickness (equine dysautonomia) {#s0120}
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Grass sickness is a neurological disease associated primarily with degeneration of neurons of the autonomic nervous system (in particular the enteric nervous system) (dysautonomia) which is typically manifest by gastrointestinal signs. It is hypothesized but not yet proven that the aetiology of grass sickness (*equine dysautonomia*) is a toxicity; the current leading hypothesis is that the disease results from a toxicoinfection with *Clostridium botulinum* types C and D (i.e. the toxin is produced locally within the intestinal tract by resident bacteria). The disease is fairly common in regions of UK (the North East region of Scotland has the highest prevalence of the disease) and parts of northern continental Europe. A virtually identical condition (known as *mal seco*) occurs in South America.

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###### Epidemiology {#s0140}

All equidae appear to be susceptible to grass sickness. There is no breed predisposition. Horses in good to fat body condition may be particularly at risk. The disease affects grazing horses -- it is extremely rare in horses that have no access to grass.

Regional prevalence occurs with certain localities having higher risk for the condition, and the incidence within regions varies from year to year. Horses in large number on a premise and young horses are at increased risk. Horses pastured on sandy and loam soil are at increased risk.

Age prevalence peaks between 2 and 7 years old, but the disease can occur at any age.

Seasonal prevalence exists with increased occurrence in April--July which probably relates to periods of dry, cool weather (7--11°C, 45--62°F).

Grass sickness is more prevalent in horses introduced to premises within the last 2 months and/or which are outdoors all the time and/or which are not receiving supplementary feeding. Frequently more than one horse is affected on same premises, and the risk of grass sickness is much greater if horses graze pasture on which affected horses have grazed.

Other risk factors for grass sickness include recent disturbance of the pasture (e.g. construction or mole activity), mechanical removal of faeces from the pasture, pasture cutting, and high frequency use of anthelmintics (especially use of ivermectin for the most recent treatment).

###### Pathogenesis {#s0145}

Widespread and generally severe damage to neurons of the enteric autonomic nervous system and certain somatic ganglia and nuclei of the central nervous system with resultant disruption of gastrointestinal motility.

###### Clinical signs {#s0150}

The disease is arbitrarily divided into three forms depending on the severity of the disease and the time period until death. Acute (death in \<4 days), sub-acute (4--10 days) or chronic (week to months) forms occur.

#### Acute form {#s0155}

The acute form is characterized by rapid onset and progression of clinical signs, with death often occurring in less than 48 hours.•Depression/somnolence.•Anorexia.•Dysphagia.•Colic (moderate to severe).•Absence of gut sounds.•Tachycardia (heart rate 70--80/min, or more).•Congestion and dryness of mucous membranes.•Dehydration.•± Patchy sweating.•± Muscle fasciculations/tremors.•Nasogastric reflux -- occasionally spontaneous appearance of green fluid at the nostrils or several gallons foetid yellow/green fluid obtained via stomach tube.•Gastric rupture may occur.•Crusty nasal discharge/rhinitis.•*per rectum* -- dry, tacky rectal mucosa; meagre rectal contents which are hard with mucosal casts on surface. Large intestine (especially large colon) is shrunken down onto hard, knobbly, impacted contents. Distended, fluid-filled loops of small intestine extending toward the pelvic inlet may be palpable.

#### Sub-acute form {#s0160}

The clinical signs of the sub-acute form are similar but less severe than the acute form. The duration of clinical signs is longer, and the abdomen adopts a tucked-up appearance.

#### Chronic form {#s0165}

The onset of clinical signs in the chronic form is insidious. Severity of signs varies from day to day.•Dullness/hypoaesthetic/sleepy.•Reduced intestinal motility.•Marked weight loss/emaciation ([Figure 3.4](#f0025){ref-type="fig"} ).Figure 3.4Chronic grass sickness. Emaciation and tucked-up abdomen, penile protrusion and abnormal base-narrow stance ('elephant on a tub').•Minimal faecal production -- faeces hard and dry.•Marked reduction of abdominal size -- 'greyhound-like'.•Tachycardia.•Crusty nasal discharge (*Rhintis sicca*).•± Ptosis.•± Abnormal stance -- four feet placed closely together.•± Penile protrusion.•± Patchy sweating.•± Muscle fasciculation/tremor.•± Intermittent, mild colic.

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###### Diagnosis of acute / sub-acute / chronic forms {#s0175}

•Clinical signs.•Contrast radiography: prolonged (\>5 secs) oesophageal transit time of barium given into proximal oesophagus. Also may see barium pooling or retrograde movement.•Oesophageal endoscopy -- linear ulcerations (reflux oesophagitis) ([Figure 3.5](#f0030){ref-type="fig"} ).Figure 3.5Endoscopic view of the oeseophagus of a horse with sub-acute grass sickness showing severe oesophagitis and linear ulceration due to reflux of gastric contents.•Phenylephrine eyedrops -- eyelid elevation (compare with the drooping eyelid in the contralateral eye).•Definitive diagnosis requires histopathology: neuronal vacuolation and chromatolysis with variable inflammatory infiltrate. Usual material for histopathologic examination is either coeliacomesenteric ganglion collected at post-mortem examination or ileal biopsy (at either exploratory celiotomy or post-mortem examination). Similar pathological changes occur in other autonomic ganglia as well as in brain and spinal cord.

###### Post-mortem examination {#s0180}

####### Acute and sub-acute form {#s0185}

•Gastric distension with foetid fluid.•Gastric/oesophageal mucosal ulceration.•Large colon impacted with dark, dry, hard content.

####### Chronic form {#s0190}

•Emaciated carcass.•Marked reduction of intestinal size.•Dry, firm, large intestinal content.

###### Treatment {#s0195}

•Euthanasia.•Selected chronic cases may survive given nursing/supportive therapy and use of the intestinal prokinetic agent, cisapride.

###### Prevention {#s0200}

It might help to keep equine horses indoors for at least part of every day, and/or feed supplementary roughage, during periods of peak incidence. This applies particularly to young or newly arrived horses, or when a case of grass sickness has already occurred on the premises.

Diseases of the stomach (equine dysautonomia) {#s0205}
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3.14. Gastric ulceration (equine gastric ulcer syndrome) {#s0210}
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###### Epidemiology {#s0230}

Gastric ulceration can occur in any breed or age of horse but is most common in race horses (estimated to occur in \>90%) and performance horses. Risk factors include:•High concentrate / low roughage diet.•Stress -- e.g. racing, training, showing, transport.•Other gastrointestinal diseases or illness.•Anorexia or withholding feed.•Non-steroidal anti-inflammatory drug therapy.

###### Pathogenesis {#s0235}

Hydrochloric acid is continuously secreted by the parietal cells in the gastric glandular epithelium. The gastric mucosa is typically protected from the acidic gastric contents by several mechanisms, including:•A mucus/bicarbonate barrier.•Gastric mucosal blood flow supported by prostaglandins.•Eating, which raises gastric pH due to alkaline saliva and adsorption of gastric secretions by ingested roughage.

Anything that disrupts these protective mechanisms can result in gastric ulceration. The squamous mucosa, especially that adjacent to the margo plicatus, is most commonly affected (80%); the glandular mucosa is less commonly involved (20%). Ulceration in the cardia and distal oesophagus is associated with gastro-oesophageal reflux and pyloric outflow obstructions.•High-concentrate diets, infrequent feeding and withholding of feed or anorexia result in prolonged periods of low gastric pH, resulting in damage to the poorly protected squamous mucosa.•NSAID therapy (by decreased production of protective prostaglandins).•Intense exercise and systemic illness can result in alterations in mucosal blood flow, resulting in both squamous and glandular lesions.

###### Clinical signs {#s0240}

The clinical signs of gastric ulceration in the adult are variable.•Many adult horses have no clinical signs, even with severe gastric ulceration.•Inappetence.•Colic -- usually mild and may be associated with feeding.•Bruxism or hypersalivation.•Mild depression.•Weight loss if chronic or severe ulceration.•Rough hair coat.•Behaviour and/or performance may change (not consistent feature).

###### Diagnosis {#s0245}

Diagnosis is achieved by gastroscopy ([Figure 3.6](#f0035){ref-type="fig"} ) or response to specific treatment.Figure 3.6Gastric ulceration -- endoscopic appearance of grade 1 ulcers.

A 2--3 metre flexible endoscope is necessary to fully evaluate the stomach in adult horses and most ponies. Fasting for 12--24 hours is required prior to gastroscopy to ensure sufficient visualization of the gastric mucosa.

Gastric ulcers are often graded on a scale of 0 to 3:•0 = normal (no ulceration).•1 = mild ulceration with single or multifocal hyperaemic areas or small superficial ulcers.•2 = moderate ulceration, with moderately sized single or multifocal ulcers.•3 = severe ulceration, with large multifocal, coalescing or diffuse deep, often haemorrhagic, ulcers.•Hyperkeratosis of the squamous mucosa in the absence of active ulceration is consistent with previous gastric ulceration.

###### Treatment {#s0250}

•Decrease or discontinue NSAID therapy if at all possible.•Decrease or eliminate dietary concentrate and permit access to pasture if possible.•Gastric acid suppression:1.Proton pump inhibitors:•Omeprazole (4 mg/kg PO q 24 hours). Very effective (\>95% success rate).Requires up to 72 hours to effectively increase gastric pH.A lower dose (2 mg/kg PO q 24 hours) may be effective for long-term preventative therapy.2.Histamine H2-receptor antagonists.•Cimetidine (16--25 mg/kg PO or 6.6 mg/kg IV q 6--8 hours).Inhibits hepatic cytochrome p450 oxidase and thus alters metabolism of other drugs; use with caution in patients on concurrent medications.•Ranitidine (6.6 mg/kg PO or 1.5 mg/kg IV q 8 hours).•Famotidine (2.8--4 mg/kg PO or 0.23--0.5 mg/kg IV q 8--12 hours).Due to the need for more frequent administration, these agents are most useful to rapidly decrease gastric pH during the initial 72 hours of proton-pump inhibitor therapy, but may also be effective when used alone.3.Antacids (magnesium hydroxide, aluminium hydroxide) -- require frequent administration (q 2--4 hours) to have any effect on raising gastric pH, thus not recommended.•Mucosal protectants.Sucralfate (20 mg/kg PO q 6--8 hours). Adheres to ulcerated mucosa, providing protection from gastric acid and stimulates local production of protective prostaglandins and cytokines to promote mucosal healing.Misoprostol (2.5--5 µg/kg). A PGE~2~ analogue, which inhibits acid secretion, promotes mucosal blood flow, and enhances bicarbonate and mucus production. Useful in NSAID-induced gastric ulceration. Side-effects include abdominal pain and diarrhoea. Should not be used in pregnant mares.

3.15. Gastric impaction {#s0255}
-----------------------

Gastric impaction is uncommon but may occur as a result of:•Feeding poor quality roughage or certain feed stuffs like beet pulp and wheat bran, which may not be adequately hydrated by saliva and gastric fluid contents.•Poor dentition resulting in inadequate mastication.•Concurrent gastrointestinal disease, resulting in generalized decreased gastrointestinal motility.•Pyloric outflow obstruction.•Horses with acute or chronic hepatic disease have an increased incidence of gastric impaction, though the direct relationship between the two conditions is poorly understood.•Bezoar formation. Persimmon seed or hair ingestion can result in formation of a phytobezoar or trichobezoar respectively. A large bezoar may obstruct the pylorus, or a small bezoar may obstruct the duodenum, resulting in impaired gastric outflow.

Clinical signs of gastric impaction include inappetence/anorexia and colic (of variable severity). Idiopathic gastric impaction occasionally occurs as a primary cause of colic in the absence of a specific predisposing or concurrent cause ([Figure 3.7](#f0040){ref-type="fig"} ).Figure 3.7Gastric impaction -- appearance at post-mortem examination.

Definitive diagnosis is difficult and is often made during exploratory celiotomy due to protracted and unrelenting pain. Trans-abdominal ultrasonography may be helpful (caudal displacement of the gastric contour). Gastroscopy does not allow accurate determination of gastric size, although identification of feed material at the level of the cardia in a fasted horse is consistent with a gastric impaction. The persistence of a large amount of feed material on serial examinations over 24--36 hours or longer in a fasted horse is needed for a presumptive gastroscopic diagnosis of gastric impaction.

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###### Treatment {#s0275}

1.Withhold all feed and limit water intake (risk of gastric rupture)2.Medical therapy:•Promote hydration of gastric contents and breakdown of the impaction:Intravenous fluid therapy.Intragastric administration of isotonic fluids and laxatives (small volumes via gravity flow).Administration of 0.5 to 1 L of Coca-cola™ via nasogastric tube every 12--24 hours can aid the breakdown of impacted material in both feed impactions and persimmon phytobezoars.•Gastric lavage via a large bore nasogastric tube.•Analgesic therapy.•Prokinetic therapy is not recommended unless a pyloric or intestinal obstruction has been ruled out.3.Surgery. Surgical resolution of a gastric impaction or removal of a gastric bezoar via gastrotomy is extremely challenging in adult horses due to limited surgical exposure and inability to exteriorize the stomach, resulting in substantial risk for abdominal contamination at surgery.

3.16. Gastric neoplasia {#s0280}
-----------------------

Gastric neoplasia is rare. The commonest neoplasm found at this site is squamous cell carcinoma.

Typical signs include:•Chronic weight loss.•Poor appetite.•Abdominal discomfort -- recurrent colic associated with feeding may occur.•Lethargy.•Ascites or oedema may occur in some cases.•If the oesophagus or cardia is involved, dysphagia or ptyalism is the predominate sign.•Metastasis to the thoracic cavity may cause tachypnoea and dyspnoea.

Many horses with gastric squamous cell carcinoma have anaemia, leukocytosis, and hyperfibrinogenaemia. Some have hypoproteinaemia due to bowel inflammation and protein exudation, whereas other cases will have hyperglobulinaemia. Gastroscopy may reveal a mass within the stomach protruding from the mucosa. Biopsy of the mass may be possible via the endoscope. Squamous cell carcinoma originates from the squamous mucosa and typically has the appearance of an ulcerated, cobblestone or florid mass. Ultrasonography, laparoscopy, and celiotomy can be used to further evaluate the patient.

Treatment of gastric squamous cell carcinoma in the horse is rarely possible.

Intestinal disorders {#s0285}
====================

The most common clinical disorders of the gastrointestinal tract are those giving rise to signs of acute abdominal pain or colic which are dealt with in Chapter 2. There are other clinical manifestations of intestinal dysfunction in the horse of which the most important are *acute diarrhoea or chronic weight loss and/or chronic diarrhoea*. The presence of diarrhoea in an adult horse almost invariably indicates large intestinal disease whereas weight loss may be associated with disorders affecting either the small intestine or the large intestine or both.

The principal pathological processes of intestinal disease are *protein losing enteropathy and/or carbohydrate malabsorption*. If only the latter is present, the clinical presentation will usually be of insidious weight loss, whereas with protein losing enteropathy (PLE) there will usually be fairly rapid weight loss and commonly peripheral oedema will develop consequent upon hypoproteinaemia/hypoalbuminaemia. In acute disorders, fever, cardiovascular compromise and coagulopathy associated with endotoxaemia are common. Additional clinical signs which may be present in gastrointestinal disease include altered intestinal motility, anorexia, ptyalism, bruxism, dysphagia and, rarely, skin lesions.

A diverse group of gastrointestinal conditions may give rise to diarrhoea and/or weight loss but often these diseases cannot be readily differentiated on clinical findings. In practical circumstances the clinical management of such cases is often similar regardless of the diagnosis and is directed at symptomatic antidiarrhoeal medication and fluid/electrolyte/nutritional support. However, the prognosis for these conditions varies greatly, e.g. successful outcome following treatment of cases of larval cyathostominosis occurs in approximately 50% of cases whereas there is virtually 100% mortality in cases of intestinal lymphosarcoma. For this reason a specific diagnosis is preferable but unfortunately that can generally only be achieved by histopathological examination of intestinal biopsy obtained at exploratory celiotomy/laparoscopy (or rectal biopsy in a minority of cases). Horses with hypoproteinaemia secondary to protein losing enteropathy are high risk for wound dehiscence and this, together with the high cost of equine abdominal surgery, means that a specific diagnosis is often only achieved at postmortem examination.

3.17. Diagnostic approach to intestinal disease {#s0290}
-----------------------------------------------

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###### History {#s0310}

1.Age -- foals and yearlings are more susceptible to gastrointestinal infections such as rotavirus, *Lawsonia intracellularis* (proliferative enteropathy) and salmonellosis (Chapter 19). Larval cyathostominosis (Chapter 19) is more common in horses less than four years old, and grass sickness is also more prevalent in this age category. Chronic inflammatory bowel disease (CIBD) and intestinal neoplasia are more common in horses greater than ten years old.2.Multiple cases are suggestive of an infectious cause, e.g. acute enterocolitis in salmonellosis (Chapter 19) or weight loss/diarrhoea of larval cyathostominosis or proliferative enteropathy (Chapter 19).3.Duration/progression -- peracute/acute systemic illness due to endotoxaemia occurs in various enterocolitides and also peritonitis. Cyathostominosis cases tend to have sudden onset, but rarely have marked systemic illness, and tend to have a timecourse of a few weeks. CIBD and intestinal neoplasia are generally insidious, with a duration of weeks to months.

###### Physical examination {#s0315}

There are virtually no characteristic physical findings for individual enteropathies, and the clinical approach is to rule out other disorders which may be associated with weight loss, e.g. liver disease with evidence of hepatic encephalopathy, then to undertake clinicopathological investigation relevant to intestinal dysfunction.

Colic, reduced borborygmi and cardiovascular compromise consequent upon endotoxaemia occur in acute enterocolitis and peritonitis which, therefore, must be differentiated from strangulating intestinal obstruction, non-strangulating infarction etc. (Chapter 2).

Various musculoskeletal signs which might be useful for differential diagnosis may be detectable in certain disorders primarily manifest as gastrointestinal in nature. In chronic grass sickness, cases often adopt a characteristic stance with all four feet placed close together under the trunk, and such horses will often exhibit intermittent muscle fasciculations. Due to parietal abdominal pain, cases of peritonitis are often reluctant to move and do so with a rather 'wooden' gait. This feature should be differentiated from endotoxaemia-associated laminitis which can complicate both peritonitis and also enterocolitis.

###### Laboratory investigation {#s0320}

####### Blood biochemistry/haematology. {#s0325}

There are no specific markers of gastrointestinal disease. The most relevant analyses to measure are total protein, albumin, globulin, alkaline phosphatase, fibrinogen and a complete blood count (CBC) and differential. In acute gastrointestinal disease, hydration status, acid-base balance and electrolyte (K, Na, Cl) disturbances should be assessed, together with renal function (creatinine, urea and phosphate). Serum protein electrophoresis is sometimes useful for differentiation of parasitic colitis (cyathostominosis) from other enteropathies. The level of abnormality of analytes such as total protein, albumin, alkaline phosphatase and neutrophil concentratons relate to the severity of chronic enteropathies such that they may be helpful in assessing prognosis.

######## Peritoneal fluid cytology/biochemistry. {#s0330}

Abdominocentesis is very useful in assessment of acute abdominal disorders (Chapter 2) but of limited value in chronic conditions. Peritonitis can be confirmed by detection of peritoneal fluid white cell count \>5 × 10^9^/L, total protein \>10 g/L and alkaline phosphatase of \>250 IU/L. Intestinal neoplasia and CIBD rarely exfoliate nucleated cells into peritoneal fluid in detectable numbers.

######## Intestinal function tests. {#s0335}

Small intestinal absorptive dysfunction can be accurately detected by monosaccharide absorption tests, usually using glucose or, less commonly xylose. The protocol for the oral glucose tolerance test is:•overnight fast and basal plasma glucose measurement time 0 min.•glucose (20% solution) by stomach tube at dose of 1 g/kg body weight.•plasma glucose measurement at times 30, 60, 90, 120, 180, 240, 360 min.

'Normal' small intestinal function is evidenced by a peak of plasma glucose at 120 min of 185-200% of basal level and return to basal levels by 360 min. A peak value of less than 120% basal value indicates total carbohydrate malabsorption and an increase of between 120 and 185% is classified as partial malabsorption.

Xylose absorption should give a similar shaped curve, but interpretation is by comparison with established reference ranges.

Detection of carbohydrate malabsorption confirms the presence of small intestinal disease, but the tests are not useful for differentiating the possible causes.

####### Histopathology. {#s0340}

Chronic enteropathies can only be definitively diagnosed on the basis of histopathological features of biopsy material obtained by either celiotomy, rectal biopsy or post-mortem examination. The surgical risk and expense are high in horses with PLE, and surgery is often not undertaken. It is possible to obtain mucosal biopsies of the proximal duodenum by endoscopy, although the value of this technique in diagnosing inflammatory bowel diseases is currently uncertain. Rectal biopsy is safe and simple from intrapelvic sites on the lateral rectum: diagnostic samples are obtained in about one third of chronic enteropathy cases.

####### Imaging modalities. {#s0345}

Ultrasonography and laparoscopy are occasionally useful for investigation of horses presented with possible gastrointestinal disease, mainly to rule out rare conditions such as splenic neoplasia or urogenital disease and to identify non-specific features such as intestinal wall thickening ([Figure 3.9](#f0050){ref-type="fig"}).

3.18. Chronic inflammatory bowel disease {#s0350}
----------------------------------------

Chronic inflammatory bowel disease (CIBD) is a collective term for a group of chronic infiltrative enteropathies with very similar clinical presentations (usually of chronic weight loss) and clinical signs. These disorders are not as clearly defined in the horse as they may be in other animal species and humans. The major clinical differential diagnoses are intestinal neoplasia and chronic hepatopathies.

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###### Epidemiology {#s0370}

Generally CIBD occurs spontaneously in individual, middle aged to old horses of any breed, but it has been suggested that granulomatous enterocolitis is more common in Standardbreds less than 5 years of age.

###### Pathogenesis {#s0375}

The aetiopathogenesis of equine CIBD is uncertain but may represent immune-mediated phenomena. Various infectious agents may play a role in these enteropathies including strongyle parasites, *Mycobacterium paratuberculosis* (granulomatous enteritis), *Rhodococcus equi* (granulomatous enteritis) and *Histoplasmum capsulatum* (granulomatous colitis).

###### Clinical signs {#s0380}

•Weight loss ([Figure 3.8](#f0045){ref-type="fig"} ).Figure 3.8Marked weight loss and ventral (preputial) oedema due to small intestinal malabsorption.•± Diarrhoea.•± Intermittent colic.•± Inappetence.•± Peripheral oedema.•± Pyrexia.•± Skin lesions.•± Mesenteric lymph node enlargement.

###### Diagnosis {#s0385}

Clinical pathological findings are non-specific but may include:•Hypoalbuminaemia.•Hyperglobulinaemia.•Neutrophilia.•Anaemia.•Hyperfibrinogenaemia.•Raised serum alkaline phosphatase.•Reduced glucose absorption (OGTT).

Trans-abdominal ultrasound may reveal diffuse or focal mural thickening of small intestine ([Figure 3.9](#f0050){ref-type="fig"} ) (sometimes with concurrent large intestinal thickening). Definitive diagnosis is based on histopathological examination of intestinal (or rectal) biopsies ([Figure 3.10](#f0055){ref-type="fig"} ). The infiltrate may constitute a mixed cellular population, or there may be a predominance of specific cell types such that CIBD may be classified as either granulomatous enteritis/colitis or eosinophilic gastroenteritis, eosinophilic granulomatous enteritis or lymphocytic plasmacytic enteritis. Similar pathological findings are commonly identified within mesenteric lymph nodes and also occasionally in skin lesions. The condition described as multisystemic eosinophilic epitheliotropic disease may have gastrointestinal involvement as well as cutaneous, hepatic and pancreatic lesions.Figure 3.9Trans-abdominal ultrasonography showing thickened loops of small intestine due to inflammatory bowel disease.Figure 3.10(a) Histological appearance of normal small intestine showing the long, finger-like villi. (b) Histological appearance of small intestine affected by granulomatous enteritis -- there is an inflammatory cell infiltrate in the mucosa and submucosa with blunting and thickening of the villi.

The major differential diagnoses for CIBD are alimentary lymphoma (lymphosarcoma), larval cyathostominosis, and chronic hepatopathies.

###### Treatment {#s0390}

Long-term therapy with corticosteroids may result in clinical improvement during the course of treatment, but clinical relapses occur commonly, but not invariably, following cessation of medication. Parenteral corticosteroid treatment is usually more effective than oral treatment at least initially -- dexamethasone (0.1 mg/kg iv or im q 24 hours) followed by oral prednisolone (1--2 mg/kg po q 24 hours). If a good response to the above therapy is observed, with improvement in serum protein concentration and weight gain, steroid therapy may be tapered slowly over 6--12 weeks, with a goal of reaching the lowest possible dosage that controls the horse\'s signs. If corticosteroids are ineffective, azothiaprine (2--3 mg/kg po q 24 hours) alone or in combination with corticosteroids may be effective. Occasionally, horses respond well to corticosteroid therapy and remain in remission following discontinuation of treatment. Unfortunately, the majority of horses, however, either do not respond sufficiently or require lifelong corticosteroid therapy.

Hay and fibrous feed may be poorly tolerated in many horses with CIBD. Maintainence on good quality pasture and a well-balanced complete pelleted feed with high protein supplementation may be effective.

In other species, allergy testing and exclusion diets can be helpful in determining the role dietary antigens may play in CIBD. In horses, designing an effective yet nutritionally balanced exclusion dietary regime is very difficult.

Other symptomatic treatments which may be useful include antidiarrhoeal agents such as codeine phosphate and/or anthelmintics and/or probiotics.

###### Prognosis {#s0395}

Sustained clinical improvement is rarely achieved, and many cases require euthanasia on humane grounds.

3.19. Alimentary lymphoma {#s0400}
-------------------------

Alimentary lymphoma is more common than either thoracic or cutaneous lymphoma (see Chapters 6 and 13Chapter 6Chapter 13), and most cases are presented with insidious weight loss, such that the major differential diagnoses are other chronic hepatopathies or chronic enteropathies.

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###### Epidemiology {#s0420}

The disease may occur in young adults (2 to 6 years) but is apparently more common in horses more than 10 years old.

###### Pathogenesis {#s0425}

No infectious agent has been incriminated in equine lymphoma. Diffuse infiltration of the small intestinal (sometimes large intestinal) wall is the most frequent manifestation. The disease can result in both small intestinal carbohydrate malabsorption and/or protein losing enteropathy. In some cases, discrete masses of the intestinal wall or associated mesentery may occur, resulting in focal intestinal obstruction.

###### Clinical signs {#s0430}

•Weight loss.•± Inappetence.•± Intermittent/recurrent colic.•± Peripheral oedema.•± Diarrhoea.•± Pyrexia.•± Colic.•± palpable mesenteric lymph node enlargement.

###### Diagnosis {#s0435}

Clinical pathological findings are non-specific but may include:•Hypoalbuminaemia.•Hyperglobulinaemia.•Neutrophilia.•Anaemia.•Hyperfibrinogenaemia.•Raised serum alkaline phosphatase.•Reduced glucose absorption (OGTT) and xylose absorption.•Peritoneal fluid cytology -- rarely detect tumour cells.•Hypercalcaemia in some cases.•Decreased serum concentrations of IgM (and less commonly IgA or IgG) in some cases.

Abdominal ultrasonography and exploratory celiotomy/laparoscopy may be helpful. Definitive diagnosis is based on histopathology of intestinal (or rectal) biopsies.

###### Treatment {#s0440}

Temporary improvement can be achieved with palliative, symptomatic medication with either orally or systemically administered corticosteroids (dexamethasone, prednisolone), and antidiarrhoeic agents, such as codeine phosphate. Cytotoxic therapy for treatment of equine alimentary lymphoma has not been reported.

Surgical excision of focal lymphoma masses within the intestinal wall may occasionally be curative ([Figure 3.11](#f0060){ref-type="fig"} ).Figure 3.11Intra-operative view of a focal small intestinal lesion due to lymphoma.

###### Prognosis {#s0445}

The prognosis is extremely poor -- most cases are euthanased on humane grounds within 6--12 months of onset of signs.

3.20. Sand enteropathy {#s0450}
----------------------

Accumulation of sand in the gastrointestinal tract is a well-recognized but fairly uncommon cause of diarrhoea and/or colic.

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###### Epidemiology {#s0470}

The horses at risk of developing sand enteropathy are those grazing areas of sandy soil with little pasture cover (or horses turned out into sand arenas), and the risk is exacerbated if grain is fed from the ground to such horses. There is a relatively high prevalence in certain geographical regions, e.g. California, New Jersey.

###### Pathogenesis {#s0475}

Sand accumulates within the large colon and gives rise to either colonic irritation and/or physical obstruction which results in diarrhoea and/or colic.

###### Clinical signs {#s0480}

•Inappetence.•± Diarrhoea.•± Colic.•± (Rarely) weight loss.

###### Diagnosis {#s0485}

•Per rectum detection of sand impaction.•Visualization of sand sediment from faecal solution.•'Pouring sand' sounds on abdominal auscultation of ventral abdomen.•Abdominal radiography.•Abdominal ultrasonography.

###### Treatment {#s0490}

•Bulk laxatives (especially psyllium hydrophilia), initially via nasogastric tube and then in-feed.•Mineral/vegetable oils via nasogastric tube.•Parenteral fluid therapy.•(Rarely) surgical removal of impacted sand.

###### Prognosis {#s0495}

The prognosis is generally good following aggressive laxative therapy, although not all cases respond. Recurrence and/or cases in other horses under the same management can be prevented by avoiding overgrazing of pastures on sandy soil and feeding from fixed troughs.

3.21. Idiopathic chronic diarrhoea {#s0500}
----------------------------------

In the horse, the cause of chronic diarrhoea often remains undiagnosed despite extensive investigative procedures.

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###### Epidemiology {#s0520}

Some cases of idiopathic diarrhoea may be consequent upon earlier infectious enteropathies and/or fermentation disorders. Particularly in foals and yearlings, diarrhoea may persist for several months before resolution which can be associated with a change to a pasture-based diet.

###### Pathogenesis {#s0525}

By definition the pathogenesis of these cases is not known.

###### Clinical signs {#s0530}

•Diarrhoea.•± Weight loss.

###### Diagnosis {#s0535}

Diagnosis is by exclusion of identifiable causes of diarrhoea.

###### Treatment {#s0540}

Symptomatic therapy can be used with variable clinical effect -- recurrence of diarrhoea is not uncommon. Symptomatic antidiarrhoeals (e.g. codeine phosphate, iodochlorohydroxyquin) administered concurrently with either probiotics or natural yoghurt or transfaunated caecal contents are appropriate. Absorbents such as chalk, kaolin or activated charcoal are only useful in foals.

###### Prognosis {#s0545}

The prognosis is generally good for survival, but recurrent, chronic diarrhoea may persist.

3.22. Acute enterocolitis {#s0550}
-------------------------

The term incorporates a variety of large intestinal disorders with very similar presenting and clinical signs of acute onset diarrhoea and colic. Causes of enterocolitis include salmonellosis (also see Chapter 19), Potomac horse fever (i.e. *Neorickettsia risticii* infection, Chapter 19), clostridiosis (see Chapter 19), colitis X, antimicrobial therapy, non-steroidal anti-inflammatory drug (NSAID) therapy, and toxicities such as either monensin/salinomycin or heavy metals. These disorders cannot be readily differentiated on the basis of clinical features, and often there is rapid clinical progression with predisposition to sequelae of endotoxaemia and systemic inflammatory response syndrome, including circulatory collapse, laminitis and thrombophlebitis.

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###### Epidemiology {#s0570}

•Salmonellosis -- increased risk in foals, stressed/hospitalized horses and those receiving antimicrobials: 'outbreaks' may occur.•Potomac horse fever -- regional occurrence -- Eastern USA. Probably involves an insect vector.•Clostridiosis -- associated with *Clostridium difficile* or *Clostridium perfringens* infection. Initiating factors similar to salmonellosis, especially antimicrobial therapy for *C. difficile*.•Colitis X -- peracute colitis, endotoxaemia and anaphylaxis of unknown aetiology. Typically involves single isolated cases rather than outbreaks.•Antimicrobial therapy -- disruption of intestinal flora leading to diarrhoea has been associated with either lincomycin or tetracycline therapy, but other antibiotics can have similar effects.•NSAID toxicity -- excessive or prolonged dosages and/or dehydrated horses.•Monensin/salinomycin toxicity -- ingestion of contaminated feedstuff.•Heavy metal toxicity -- rare.

###### Pathogenesis {#s0575}

•Salmonellosis -- invasion of the primary pathogen; intestinal mucosal colonization results in inflammatory protein losing enteropathy (PLE) and endotoxaemia.•Potomac horse fever -- invasion of a primary pathogen; initial infection of peripheral monocytes and macrophages with later phase of infection within small intestinal and colonic mucosa. As a result there may be several days of fever and colic prior to onset of diarrhoea.•Clostridiosis -- overgrowth by potentially pathogenic normal inhabitants of the intestinal tract (normally present in low numbers); marked colonic oedema and PLE.•Colitis X -- the cause remains unknown although an infectious or toxic aetiology is assumed. Some cases may be forms of clostridiosis. Intestinal anaphylaxis to an unidentified antigen may be involved.•Antimicrobial therapy -- altered fermentation by disruption of normal intestinal microflora can give rise to diarrhoea. In addition, antibiotic therapy predisposes to both salmonellosis and clostridiosis.•Monensin/salinomycin -- ionophores alter ionic transport across cell membranes: gastrointestinal, cardiovascular and neurological effects occur.

The pathophysiology of equine enterocolitis has not been defined in detail. The mechanisms which are likely to be involved include:•Loss of the colonic mucosal barrier allows intraluminal bacteria and bacterial toxins to invade the colonic wall, stimulating mural inflammation.•Raised local concentrations of prostaglandins, prostacyclin and leukotrienes.•Stimulation of fluid/electrolyte secretion and protein exudation into the bowel lumen.•Compromised colonic absorptive capacity.•Increased permeability of intestinal microvasculature.•Endotoxaemia and stimulation of the systemic inflammatory response syndrome.

###### Clinical signs {#s0580}

The clinical signs are somewhat variable, especially in Potomac horse fever, but generally cases of enterocolitis are extremely ill with rapid progression of:•Markedly dull attitude.•Fever.•Inappetence.•Decreased intestinal motility (may be gross abdominal distension in some cases).•Colic.•Explosive watery diarrhoea (occasionally acute onset of severe colic signs and rapid systemic deterioration in the absence of diarrhoea). Diarrhoea may be bloody in clostridiosis, colitis X and salmonellosis (especially in foals).•Endotoxaemia and hypovolaemic shock -- tachycardia, prolonged capillary refill time, injected or cyanotic mucous membranes, cold extremities, etc.•± Peripheral oedema.•± Laminitis.•Rapid weight loss in survivors.

Some severe per-acute cases may be found dead with no recognized clinical signs.

###### Diagnosis {#s0585}

The peracute nature of enterocolitis necessitates emergency treatment before a definitive, specific diagnosis is available. Successful intensive care of horses with enterocolitis is ideally monitored by use of biochemical and haematological findings which are extremely dynamic in this condition. Typical clinical pathological features are:•Dehydration/haemoconcentration -- raised packed cell volume (PCV) and total protein (TP), but as the disease progresses there may be progressive decrease in TP due to intestinal protein loss; raised plasma creatinine and urea.•Electrolyte imbalances -- usually hyponatraemia and/or hypochloraemia and/or hypokalaemia.•Azotaemia -- due to pre-renal or renal causes.•Metabolic acidosis and high plasma lactate concentration due to impaired tissue perfusion.•Leucopenia.•± Thrombocytopenia or disseminated intravascular coagulopathy in Potomac horse fever. Abdominal ultrasonography can be used to demonstrate fluid contents of the caecum and colon, and increased mural thickness (\>5 mm).•Peritoneal fluid is usually normal in acute colitis, but secondary septic peritonitis may occur in horses with persistent colic or fever (secondary to translocation of intestinal bacteria or infarction of the colonic vasculature).

Specific diagnosis may be obtained by:•Salmonellosis -- culture or polymerase chain reaction (PCR); may require multiple sequential faecal samples or post-mortem tissue/intestinal contents.•Clostridiosis -- faecal toxin assays for *Clostridium difficile* and *Clostridium perfringens* (serial samples may be required); culture/Gram stain of faeces/intestinal content with quantitative count of colony forming units.•Potomac horse fever -- serology (IFA or ELISA), PCR.

Gross post-mortem and/or histopathological findings vary depending on the time-course of the disease. Necropsy findings usually include:•Serosal discoloration; petechiae purple to black.•Mucosal discoloration; haemorrhagic or necrotic black/brown.•Mucosal oedema/thickening and sloughing of fibronecrotic debris (mucosal oedema may be especially marked in colitis X).•Watery, foul-smelling intestinal contents.•Mesenteric lymph node enlargement.•Hyperaemia and/or petechial haemorrhages of lungs, liver and adrenal glands.•Changes consistent with proximal enteritis (Chapter 2) may be present in some cases of clostridiosis.

###### Treatment {#s0590}

•Intravenous fluid therapy with correction of specific electrolyte and acid--base disturbances, and consider use of colloidals or plasma. Initial fluid resuscitation with hypertonic saline solution may be necessary in severely hypovolaemic patients.•Flunixin meglumine at anti-endotoxic dose of 0.25 mg/kg three times daily.•Endotoxin antisera/purified immunoglobulin products.•Intestinal adsorbents e.g. di-tri-octahedral smectite.•Frog supports.•Antibiotics.▪generally contraindicated but appropriate in neonatal salmonellosis.▪metronidazole may be helpful in clostridiosis.▪oxytetracycline is drug of choice in Potomac horse fever.•Nutritional support.•Critical care (see Chapter 26).

Horses with colitis are particularly prone to thrombophlebitis. Long-term polyethylene intravenous catheters should be used, and removed at the first sign of a problem with the catheter or vein.

###### Prognosis {#s0595}

Mortality rate is high even after aggressive, expensive, intensive care, and there is a high prevalence of complications. Cases which are diarrhoeic for more than 7 days are unlikely to survive. Acute enterocolitis does *not* usually result in chronic intestinal/digestive dysfunction in surviving cases.

3.23. Non-steroidal anti-inflammatory drug toxicity {#s0600}
---------------------------------------------------

Any non-steroidal anti-inflammatory drug (NSAID) can potentially lead to either gastrointestinal and/or renal disease. Mucosal ulceration may occur at any site of the alimentary tract from the mouth to the rectum, but the most common sites of damage are the stomach and the right dorsal colon. such that right dorsal colitis is a recognized clinical entity.

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###### Epidemiology {#s0620}

Long-term treatment and/or overdosing with NSAIDs, which may arise from owner ignorance, often underlie NSAID toxicity. Horses with cardiovascular compromise and/or dehydration will are more prone to NSAID toxicity.

###### Pathogenesis {#s0625}

Inhibition of mucosal prostaglandins E~1~ and E~2~ which have a mucosal protective effect within the stomach, intestine and kidneys. Loss of mucosal protection can result in either protein losing enteropathy as a result of gastrointestinal ulceration or protein losing nephropathy.

###### Clinical signs {#s0630}

Variable severity of:•Inappetence/anorexia.•Peripheral oedema.•Oral mucosal ulceration.•Diarrhoea.•Colic.•Endotoxaemia.•Laminitis.•Decreased urine output and/or dilute urination.

###### Diagnosis {#s0635}

Usually a presumptive diagnosis is made from the history. Laboratory assessment of fluid/electrolyte and acid-base disturbances is useful to assist fluid therapy, and monitoring of renal function and plasma proteins concentrations is appropriate.

Endoscopy can allow visualization of oesophageal or gastric ulceration.

###### Treatment {#s0640}

•Discontinue NSAID therapy.•Intravenous fluid/electrolyte therapy.•Frog supports.•Proton pump inhibitors (e.g. omeprazole) or histamine receptor type -- two antagonists (H~2~ antagonists) (e.g. ranitidine) and sucralphate for gastric ulceration.•Analgesia with butorphanol tartrate and/or alpha-2 agonists for colic (and laminitis).•Misoprostol (synthetic analogue of prostaglandin E2) (5 µg/kg; q 12 hours or 2 µg/kg; q 6 hours po) -- may cause diarrhoea.

###### Prognosis {#s0645}

Guarded in severe cases, e.g. diarrhoea, colic and laminitis, but slow recovery if signs are mild. Biochemical evidence of severe renal compromise generally indicates a poor prognosis.

3.24. Other gastrointestinal disorders {#s0650}
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Many other conditions of the gastrointestinal tract occur with low prevalence in the horse. In addition, various disorders of other body systems may give rise to gastrointestinal signs and some of these are described elsewhere in the text.•Equine proliferative enteropathy (*Lawsonia intracellularis*) (Chapters 19 and 20Chapter 19Chapter 20).•Foal heat diarrhoea (Chapter 20).•Rotavirus (Chapters 19 and 20Chapter 19Chapter 20).•Coronavirus (Chapter 20).•*Rhodococcus equi* (Chapters 6 and 20Chapter 6Chapter 20).•*Ehrlichia coli* (Chapter 20).•*Campylobacter spp.*•*Strongyloides westeri* (Chapter 19).•Strongylosis (Chapter 19).•Cyathostominosis (Chapter 19).•Cryptosporidiosis.•Coccidiosis.•Giardiasis.•Histoplasmosis.•Cardiac failure (Chapter 7).•Cushing\'s disease (Chapter 9).•Hyperlipaemia (Chapter 22).•Peritonitis (Chapter 4).•Intestinal lymphangectasia.•Cantharadin (blister beetle) toxicosis (Chapter 22).
