Idiopathic Focal Eosinophilic Enteritis (IFEE) and Eosinophilic Enteritis (EE)

Idiopathic Focal Eosinophilic Enteritis (IFEE) is a rare condition that causes colic in young horses. IFEE is characterized by a focal area of eosinophilic inflammation, in the small intestine, that results in narrowing of the intestinal lumen and obstruction of ingesta flow. Horses with IFEE often have concurrent diffuse eosinophilic enteritis (EE). Diagnosis is difficult without histopathology of the affected area, which requires an exploratory laparotomy, or necropsy. The inciting cause of eosinophilic inflammation is not fully known; an abnormal immune response to antigenic stimulus is considered most likely. IFEE and EE can respond to treatment and have a fair long-term prognosis.

Introduction to Eosinophilic Infiltrative Diseases in Horses

Intestinal eosinophilic infiltrative diseases are quite rare. They can affect horses of any age, and many breed types, but tend to occur more commonly in young horses, with a reported predilection in the Standardbred breed (Schumacher 2009).
The nomenclature used with eosinophilic intestinal disease indicates the anatomical location of the lesions:

Eosinophilic Colitis Lesions of the large intestines.
Eosinophilic Enterocolitis Lesions of both the large and small intestines.
Eosinophilic Enteritis CLesions of the small intestines.
Idiopathic Focal Eosinophilic Enteritis(IFEE) Circumferential mural lesions in the small intestines (usually seen in combination with diffuse disease, like eosinophilic enteritis).
Multisystemic Eosinophilic Epitheliotrophic Disease (MEED) Lesions usually affect the gastrointestinal tract, skin, liver, pancreas and lung. These lesions are histologically different to the other eosinophilic diseases.

This article discusses specifically Idiopathic Focal Eosinophilic Enteritis (IFEE) and Eosinophilic Enteritis (EE).

Etiology and Pathogenesis of EE and IFEE

EE is caused by eosinophilic infiltrates within the wall of the small intestine. Histopathology shows all layers of the small intestine to be diffusely infiltrated with eosinophils, or an equal mixture of eosinophils and lymphocytes.

IFEE is a focal exacerbation of EE, characterized by a focal inflammatory reaction that results in narrowing of the lumen of the small intestine and obstruction to the flow of ingesta. Fibrous circumferential mural bands may form in this area. Horses with IFEE usually also have EE.

Histopathology of IFEE lesions shows accumulations of eosinophils, macrophages, and smaller numbers of lymphocytes (predominantly T lymphocytes), plasma cells and neutrophils in the wall of the small intestine. The larger numbers of macrophages, and the predominance of T lymphocytes, are thought to be the key difference between IFEE and EE (Mäkinen et al. 2008). Research is ongoing.

The precise cause of EE and IFEE is unknown, however veterinary immunologists suggest it is due to complex interplay among host genetics, immune system, intestinal microbiota, dietary constituents, or environmental triggers of inflammation (Perkins et al. 2016).

Helminth infestations have often been suspected, however there is very little evidence, from histopathology and/or necropsy examinations, to give strong support to this theory.

A study from the United Kingdom showed seasonality in the occurrence of the disease, with the greatest risk being in mid-summer to late autumn. Some geographical regions in this study were also found to be more at risk, and the presence of stagnant water was also found to be a consistent environmental factor. The horses in this study had low nematode and cestode burdens that were similar to those of normal horses (Archer et al. 2014).

In another study, from Spain, 15 young Andalusian horses developed Equine Motor Neuron Disease, and all were found to have eosinophilic enteritis. These horses had restricted access to green foliage, and giant ciliated protozoa were found in the intestine of all affected horses (Diez de Castro et al. 2016).

In rats, vitamin E and selenium deficiency are reported to cause eosinophilic enteritis. (Diez de Castro et al. 2016).

Clinical Presentation of IFEE and EE

The most common presentation of IFEE is young horses (0-5 years) with colic. The colic symptoms can be severe enough to require surgical intervention. EE lesions can also present with colic but usually lower grade. If EE lesions are diffuse and severe enough there may also be some weight loss.

Hematology and Biochemistry. There are no consistent abnormalities of the white cell count with IFEE. Hypereosinophilia is rare, and the neutrophil and lymphocyte counts will be influenced by the severity of disease, and if any bowel perforation has occurred. The horses are unlikely to be anemic, hypoproteinemic or hypoalbuminemic, unless severe diffuse EE is also present.

Abdominocentesis results will vary depending on the severity of disease. If diffuse EE is present there may be an elevated protein with a normal white cell count. If the bowel is compromised, the protein and white cell count may be elevated.

Rectal biopsies are usually not helpful, due to the focal nature of the disease, and its confinement to the small intestine.

On ultrasound, focal small intestinal lesions are difficult to identify unless they occurred in a loop of intestine close to the abdominal wall. Diffuse thickening ofthe small intestine would be a non-specific finding in many cases.

Carbohydrate absorption tests are unlikely to be abnormal unless severe diffuse EE is present.

IFEE is difficult to diagnose without visualization of the affected intestine, and histopathology. This requires an exploratory laparotomy, or a postmortem. Laparoscopy is rarely available, and requires a highly experienced surgeon.

Less severe EE and IFEE lesions are therefore likely to remain undiagnosed and are simply treated as low-grade colic (which can be effective).

Treatment for IFEE and EE

Surgical resection of fibrous mural bands, or severely affected tissue, can resolve the problem; however if diffuse EE is present then complete removal is not possible and the disease may recur.

Archer et al. (2014) describes the lesions as appearing grossly hyperemic, and they can extend circumferentially, partially or fully, around the small intestine. The intestinal tissue is palpably thick on either side of the focal lesion, with obstruction of ingesta proximal to the lesion.

IFEE may resolve over time, without surgery (Archer et al. 2014).

Oral corticosteroids over 30 days to six months may also lead to resolution of the disease. There is a possibility of recurrence after discontinuation of treatment, but this is rare.

In the absence of surgery, or with diffuse disease, the affected horse may require intermittent analgesics for abdominal pain until the lesion has time to resolve. Frequent small meals of a pelleted complete feed may also help minimize abdominal pain.

Anthelmintics with larvicidal activity are usually administered, but are unlikely to play a significant role in resolution of clinical signs.

References

Archer, D. et al. (2014) Idiopathic Focal Eosinophilic Enteritis, an emerging cause of abdominal pain in horses: the effect of age, time and geographical location on risk. PLoS One, 9:e112072.

Diez de Castro, E. et al. (2016) Eosinophilic Enteritis in Horses with Motor Neuron Disease. Journal of Veterinary Internal Medicine, 30:873-879.

Mäkinen, P.E. et al. (2008) Characterization of the inflammatory reaction in equine idiopathic focal eosinophilic enteritis and diffuse eosinophilic enteritis. Equine Veterinary Journal, 40:386-392.

Perkins, G.A. (2016) Chronic Inflammatory Bowel Disease. Equine Clinical Immunology, ed. Julia, M. et al. Wiley Publishers pp.113-119.

Schumacher, J. (2009) Idiopathic Focal Eosinophilic Enteritis. In: Current Therapy in Equine Medicine, ed. N.E. Robinson and K.A. Sprayberry. Elsevier pp. 440-441.