Granulomatous Enteritis (GE) is a form of inflammatory bowel disease that affects predominantly the small intestine in horses. GE is most commonly seen in young horses suffering from weight loss. The blood work on these horses frequently shows hypoalbuminemia and anemia. Diagnosis is made by biopsy of the rectum or small intestine. Many treatments have been tried on horses suffering from GE, but to date, no specific treatment is known to be definitively effective. The prognosis for horses suffering from GE is guarded to poor.
Pathophysiology of Granulomatous Enteritis in Horses
Granulomatous Enteritis (GE) is a form of inflammatory bowel disease (IBD) that is caused by infiltration of macrophages or epithelioid cells into the mucosa and submucosa of the small intestine. The infiltrating cells tend to form into sheets of cells and can also form distinctive circumscribed granulomas, which give rise to the name of the disease – Granulomatous Enteritis
The ileum tends to be most severely affected by GE. The disease can cause gross thickening of the small intestine, and may also lead to villous atrophy. In severe disease, adhesions may form between affected loops of small intestine (Schumacher, 2009).
The inciting cause of inflammatory bowel disease is not yet fully known. The disease is thought to be caused by an abnormal and severe immune response to some type of antigen.
Equine GE shares some pathological similarities to Crohn’s disease in humans. Crohn’s disease is caused by Mycobacterium avium paratuberculosis.
In recent years, and with the availability of PCR technology, evidence for the involvement of the Mycobacterial species in equine GE has been growing. Mycobacterium avian spp. hominisuiss was found in 5 out of 9 horses in Finland with GE. Mycobacterium bovis and Mycobacterium genavense have also been sporadically isolated from horses with GE (Schumacher 2000).
Another inciting factor that has been considered is the presence of aluminum in the small intestine, as aluminum was found in the intestinal cells of horses with GE (Fogarty et al, 1998) and in humans with Crohn’s disease (Djouina et al, 2016). Research is ongoing.
Presentation of GE in Horses
GE tends to affect young horses, often younger than 4 years of age. Horse breeds such as the Thoroughbred and Standardbred are reported to be more frequently affected.
Weight loss is the most common symptom of GE. Other symptoms can include inappetance, depression, colic, diarrhea and dehydration. Skin lesions of the head, limb and coronet may also be present; this is a similar presentation to that seen with another inflammatory bowel disease – Multisystemic Eosinophilic Epitheliotropic Disease (MEED). MEED also affects young horses and causes weight loss (Schumacher, 2000, 2009).
Hypoalbuminemia is a very common finding in a horse with GE. There are several possible contributing factors to the development of the hypoalbuminemia. These include:
- Mucosal thickening and villous atrophy, causing malabsorption of protein (70% of ingested protein is absorbed through the small intestine);
- Loss of lymph secondary to lymphatic obstruction;
- Exudation of protein through mucosal ulceration;
- Increased intestinal permeability to protein due to structural alteration.
Of the two main proteins, albumin and globulins, globulins are produced faster than albumin, and therefore body and blood albumin concentrations fall quicker than globulin concentrations (Schumacher 2000, 2009).
Anemia is also a common finding in GE. Some anemic horses are occasionally found to be Coombs positive, indicating a possible immune-mediated component to the anemia. Other possible causes of the anemia include anemia of chronic inflammatory disease and/or a decrease in serum iron. The total iron-binding capacity of these horses is usually normal, suggesting that low serum iron concentrations may be due to malabsorption of the elements necessary for erythropoiesis (i.e. iron, cobalamin, folic acid). Blood loss through intestinal hemorrhage is another possible contributor to the anemia (Schumacher 2000).
Diagnosis of Equine Granulomatous Enteritis
GE should be considered in any horse, and particularly in young horses that are suffering from weight loss. However, as GE is a relatively uncommon disease, and accurate diagnosis of GE is not easy, it is usually not considered a possibility until many other more common diseases have first been ruled out – such as insufficient nutrition, intestinal parasitism, intestinal ulceration or dental disease.
Blood work findings in horses with GE tend to be non-specific, except that horses with GE frequently have hypoalbuminemia in combination with anemia. This combination is rare in other forms of IBD, however it may be seen with colonic ulceration, neoplasia or possibly severe gastric ulceration. Anemia may not be immediately apparent in a horse with GE if a concurrent hypoalbuminemia is causing a decrease in the plasma volume (Schumacher, 2014). The anemic horses are occasionally Coombs positive.
White blood cell count is usually normal, however both neutropenia and neutrophilia have been reported in some cases (Schumacher 2000). A derangement in the white cell count will likely reflect the severity of the disease and may indicate that the integrity of the intestinal wall has been compromised.
Abdominocentesis findings are often unremarkable, except in severe disease, if peritonitis has occurred (Schumacher 2000).
Horses with GE usually have an abnormal result to a CHO absorption test. (Schumacher 2009)
Rectal biopsy can be diagnostic if the disease has extended beyond the small intestine. Diagnostic histopathologic findings include the presence of sheets of macrophages or epithelioid cells, and circumscribed granulomas, in the mucosa or submucosa of the rectal mucosa, in the absence of other inflammatory cells. Accurate diagnosis requires an experienced pathologist (Schumacher 2000).
Exploratory laparotomy and biopsy of the small intestine is the ultimate diagnostic tool.
Treatment for Granulomatous Enteritis in Horses
Granulomatous enteritis is not easy to treat – partly due to the fact that it is not yet known what is driving the pathologic process.
The various treatments that have been tried are aimed at decreasing intestinal inflammation and combat suspected allergens. These treatments have included one or more of the following: corticosteroids, anthelminthics with larvicidal activity, anabolic steroids, antibiotics (including metronidazole), iodochlorhydroxyquin, salicylazosulfapyridine and methylsolfonymethane. The latter two drugs have been successful in treating Crohn’s disease in humans (Schumacher 2000). Some horses respond for a period of time to some of these treatments, but long-term success is not commonly reported – although it does occasionally occur.
Surgery to resect a focal area of affected bowel can be attempted, but the disease would rarely be detected as a focal disease, and even with resection the symptoms are likely to recur (Schumacher 2000).
Prevention of GE in Horses
It may be prudent to avoid breeding horses that are affected, in case there is a hereditary component to the GE. Until the underlying cause is determined, knowing how to prevent the GE is difficult
Djouina, M., et al. (2016) Toxicological consequences of experimental exposure to aluminium in human intestinal epithelial cells. Food and Chemical Toxicology, 91:108-116.
Fogarty, U., et al. (1998) A cluster of equine granulomatous enteritis cases: the link with aluminium. Veterinary and human toxicology 40.5: 297-305.
Schumacher, J. (2009) Infiltrative Bowel Diseases. In: Current Therapy in Equine Medicine 6, ed. N.E. Robinson. Saunders, St Louis, Missouri p. 441.
Schumacher, J. (2000) Chronic Idiopathic Inflammatory Bowel Disease of the Horse. J. Vet. Intern. Med. 14:258-265.