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\begin{document}

\title{Jejunal obstruction caused by an intramural hematoma secondary to focal
eosinophilic enteritis}



\author[1]{Maria Vergara Ariztia}%
\author[1]{Russell Freeland}%
\affil[1]{Hagyard Equine Medical Institute}%


\vspace{-1em}



  
  \date{May 26, 2024}


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\selectlanguage{english}
\begin{abstract}
Focal eosinophilic enteritis in horses is an idiopathic disease that can
cause acute abdominal pain. It is characterized by infiltration of
eosinophils into the equine intestinal tract. Intramural hematoma of the
small intestine is also a poorly understood disease. This case report
describes a surgical colic in a 9-year-old mare that had jejunal
obstruction caused by an intramural hematoma secondary to focal
eosinophilic enteritis. Diagnosis was confirmed by histopathological
results showing eosinophilic infiltration and subserosal granulomas that
contained large numbers of hemosiderin-laden macrophages. Damage to the
mucosal barrier of the intestine may have led to an immunologic reaction
and subsequent eosinophilic enteritis. While the cause of the
eosinophilic enteritis is unknown, our hypothesis in this case was an
underlying hypersensitivity such as food allergy may have played a role
based on literature and histopathological examination.%
\end{abstract}%



\sloppy


Case report:

\textbf{Jejunal obstruction caused by an intramural hematoma secondary
to focal eosinophilic enteritis}

M. Isabel Vergara\textsuperscript{1}*, Russell
Freeland\textsuperscript{1}

\textsuperscript{1}Hagyard Equine Medical Institute, 4250 Iron Works
Pike, Lexington, KY, 40511

*Corresponding author email:\emph{ivergara@hagyard.com}

\textbf{Keywords} : horse, eosinophilic enteritis, intramural hematoma,
jejunal obstruction, colic

\emph{Summary}

Focal eosinophilic enteritis in horses is an idiopathic disease that can
cause acute abdominal pain. It is characterized by infiltration of
eosinophils into the equine intestinal tract. Intramural hematoma of the
small intestine is also a poorly understood disease. This case report
describes a surgical colic in a 9-year-old mare that had jejunal
obstruction caused by an intramural hematoma secondary to focal
eosinophilic enteritis. Diagnosis was confirmed by histopathological
results showing eosinophilic infiltration and subserosal granulomas that
contained large numbers of hemosiderin-laden macrophages. Damage to the
mucosal barrier of the intestine may have led to an immunologic reaction
and subsequent eosinophilic enteritis. While the cause of the
eosinophilic enteritis is unknown, our hypothesis in this case was an
underlying hypersensitivity such as food allergy may have played a role
based on literature and histopathological examination.

\emph{Introduction}

Focal eosinophilic enteritis in horses has been described since 1990 as
an idiopathic disease that can cause acute abdominal pain (Brosnahan,
2020). It is characterized by infiltration of eosinophils into the
equine intestinal tract . This disease has been identified in 6\% of
horses undergoing exploratory laparotomy due to colic (Bont et al.,
2016). Young horses between 0 and 5 years of age are at greatest risk of
this disease .

Eosinophilia in horses is uncommon. This may relate to tissue
predilection and the short transit time from marrow to target tissue
(Sharkey and Overmann, 2015). The principal function of eosinophils is
to destroy a target pathogen, commonly the helminth parasite; however,
they also have other roles in the gastrointestinal and respiratory
disease, skin, and other body systems which are poorly understood .

Intramural hematoma of the small intestine is also a poorly understood
disease. It has been described in less than 1\% of surgical colic.
Horses present with typical signs of intestinal obstruction (Orr et al.,
2022).

This case report describes the history, signalment, treatment,
diagnosis, and favorable outcome of a thoroughbred mare with
eosinophilic enteritis and secondary intramural hematoma obstruction.

\emph{Case details}

A 9-year-old Thoroughbred mare, three months pregnant, was referred to
Hagyard Equine Medical Institute with a history of mild to moderate
colic signs. Prior to arrival, 12 ml of flunixin meglumine was
administered. Upon arrival, the mare was quiet, alert, and responsive.
Mucous membranes were pink and moist with two seconds capillary refill
time. Vitals demonstrated a heart rate of 44 beats per minute,
respiratory rate of 16 breaths per minute, and temperature of 100.3\selectlanguage{ngerman}°F. A
nasogastric tube was placed yielding no net reflux. An intravenous
catheter was placed aseptically in the left jugular vein.

Abdominal ultrasonography revealed a gas distended stomach, one
distended loop of small intestine (6cm) with normal wall thickness
(\textless{}2mm) on ventral midline, and in the same area another loop
of small intestine associated with a circular mixed echogenicity (Fig 1
and 2). Abdominocentesis showed a mildly serosanguinous fluid, a lactate
of 4.8 mmol/L (normal reference range: \textless{}2 mmol/L) and a total
protein of 2.2 gm/dl (normal reference range:\textless{}2.5 gm/dl).
Cytology was normal, with a few white blood cells seen, primarily
polymorphonuclear (PMN) neutrophils, non-degenerated, and occasionally
macrophages. Moderate red blood cells were also seen. There was no
plant, fecal material or bacteria seen. Blood lactate was 1 mmol/L
(normal reference range: \textless{}0.7 mmol/L). Due to ultrasound exam
findings, exploratory celiotomy was recommended.

The mare was sedated with xylazine (1.1 mg/kg, IV) and butorphanol (0.02
mg/kg, IV) and then induced using ketamine (2.2 mg/kg, IV) and diazepam
(0.05 mg/kg, IV). General anesthesia was maintained using isoflurane and
100\% supplemental oxygen. The ventral abdomen was aseptically prepared.

An approximately 20 cm ventral midline skin incision was made cranially
from the umbilicus with a number 10 scalpel blade and continued through
the subcutaneous tissue and the line-alba. Abdominal exploration
revealed approximately 1.5 feet of dark red, distended loop of small
intestine in the distal one-third of the jejunum (Fig 3). Significant
orad jejunal distension was present.

Due to the nonviable appearance, an end-to-end jejunojenunostomy was
performed. First, the mesenteric vessels were double ligated using 2-0
polydioxanone proximal and distal to the affected segment. A ¼'' penrose
drain was placed surrounding the small intestinal lumen via a stab
incision through the mesentery proximal and distal to the proposed
resection location. The mesentery was transected using a Metzenbaum
scissor at the level of the ligations previously performed. After that,
the affected portion of the small intestine was transected using a
number 10 scalpel blade at approximately 60 degrees from the mesenteric
attachment, making the mesenteric portion longer than the
antimesenteric, to create a large stoma and preserve blood flow to the
antimesenteric side. Finally, the anastomosis of both ends of the small
intestine was performed using a single-layer interrupted Cushing pattern
at the mesenteric and antimesenteric borders using 2-0 polydioxanone.

A sample of the affected jejunum was submitted to the University of
Kentucky Veterinary Diagnostic Lab for histopathology (Fig 4).

.

\emph{Histopathology results}

Sections of the submitted sample of jejunum contained moderate to large
numbers of eosinophils and fewer mononuclear cells within the mucosa and
submucosa. Also present within the submucosa and between the circular
and longitudinal layers of tunica muscularis was mild to moderate edema
and moderate to marked amounts of hemorrhage, which extended into the
serosa and mesentery. The vessels within the serosa and mesentery were
markedly dilated and engorged with blood and fibrin. An area between the
longitudinal and circular layers of the tunica muscularis had
proliferative fibrovascular tissue and was partially separated. Several
small and large caliber arteries exhibited myxomatous changes and
myointimal bodies within the intima and subintimal layers of the
vessels.

\emph{Treatment}

Before surgery, the mare received 30 ml of gentamicin (6.6 mg/kg SID)
and 24 ml of penicillin G potassium (22,000 IU/kg QID) intravenously
(IV), and 1 ml of tetanus toxoid intramuscularly (IM).

The mare was hospitalized for five days post operatively, with her
vitals being constantly monitored, which remained normal throughout the
entire period. Postoperative treatment consisted of 30 ml of gentamicin
every 24 hours for four days, 22,000 IU of penicillin G potassium every
six hours for four days, 6ml of flunixin meglumine IV, every 12 hours
for six days, 1000lb dose of omeprazole for six days and altrenogest
12ml orally every 24 hours.

The mare received two days of maintenance fluid therapy intravenously.
Furthermore, a lidocaine 2\% CRI was given on the first day, starting
with 35 ml in 15 minutes and followed by 75ml per hour. Cryotherapy with
ice boots on all four legs was applied during the first two days.

Complete blood cell count, chemistry, fibrinogen, and Serum Amyloid A
(SAA) were performed on days three and five, showing normal parameters.
SAA was the only parameter affected with 2837.00 mcg/ml (normal range 0
-- 20 mg/L).

On the sixth day, the mare was discharged on normal feed with exercise
restrictions, including stall rest for three weeks, followed by small
paddock turnout for four weeks.

\emph{Outcome}

A month after surgery, the mare aborted her fetus and developed forelimb
laminitis. After five months, the laminitis deteriorated and therefore
the owner elected for human euthanasia. For the case report purpose, a
necropsy was performed. Samples of the jejunum were submitted for
histopathology and showed jejunitis and serositis. The distal jejunum
showed multiple granulomas. The histopathology results found the
submucosa to be mildly edematous with a mild increase in collagenous
tissue. Moderate to large numbers of eosinophil infiltrates were
identified within the submucosa, from immediately subjacent to the
lamina propria to the muscular tunics. The serosa was thickened, with
fibroplasia, and there were serosal and subserosal granulomas that
contained large numbers of hemosiderin-laden macrophages.

\emph{Discussion}

Eosinophilic enteritis is an uncommon disease in horses. The number of
case reports described in the literature is scant. The disease is
characterized by the infiltration of eosinophils into the equine
intestinal tract, producing one or several circumferential mural bands
in the small intestine that cause obstruction .

In this case report, ultrasonography showed distended loops of small
intestine and an unknown structure associated with a small intestine
lumen with a mixed echogenicity material. The surgical findings
indicated the mixed echogenicity was a mural hematoma, focally present,
and collapsing the lumen of the involved jejunum. The few case reports
in the literature showed surgical findings of striking hyperemic,
circumferential bands with histological evidence of submucosal edema,
mucosa swelling, and hemorrhage (Bont et al., 2016).

The intramural hemorrhage found in this case had caused an obstruction
and necrosis in the affected segment. The cause of the hemorrhage is
unknown, and it is believed that it is secondary to eosinophilic
enteritis. The necrosis of the affected segment has not been described
in literature as a characteristic of focal eosinophilic enteritis .
However, the intramural hemorrhage and the consequent obstruction caused
necrosis in this case due to the decreased blood flow into the affected
segment. Intramural hematomas in humans are not frequent, but the few
cases described are often attributable to a complication of
anticoagulant therapy and less common bleeding diatheses, abdominal
trauma, infarction, and vasculitis (Yoldas et al., 2013).

Eosinophilia in horses has been attributed to internal parasitism,
cutaneous habronemiasis, systemic hypersensitivity reaction,
lymphosarcoma, and eosinophilic leukemia (Sharkey and Overmann, 2015).
Internal parasitism is the leading cause of eosinophilia in horses ; but
in this case, no specimen was detected. Eosinophilic enteritis has been
associated with geographical regions and seasons, most commonly between
late spring and early fall. In the United States, the seasonal
distribution of cases corresponds to the grazing period, suggesting a
dietary association .

Eosinophilic enteritis has been attributed to food allergies in humans.
Patients report intense pain in the abdomen that did not respond to
treatment. Biopsies of these patients were sent to histopathology,
confirming eosinophilia in the ileum and unspecific colitis. After the
results, the patients were treated with corticosteroids and mesalamine
(5-aminosalicylic acid (5-ASA), medication used to treat ulcerative
colitis and showed significant improvement (Laud et al., 2020).

Food allergies in horses can produce immunologic reactions. The allergen
must breach the intestinal mucosal barrier to expose it to the immune
system. An abnormal immune response can lead to hypersensitivity.
Typically, the gastrointestinal system has different mechanisms to avoid
this breach. However, in some cases, such as in older horses where the
mucosal barrier has begun to degenerate, or in animals with
gastrointestinal diseases that have damaged the intestinal barrier,
macromolecules can pass through and reach the immune system .

Finally, while the underlying cause of the enteritis and subsequent
hematoma is unknown in this case, we hypothesize that due to the age of
the mare and the season in which the disease developed, an underlying
hypersensitivity such as food allergy may have played a role based on
literature and histopathological examination. Damage to the mucosal
barrier of the intestine may have led to an immunologic reaction and
subsequent eosinophilic enteritis. Enteritis led to a loss of integrity
of the associated vasculature as indicated by the myxomatous change seen
on histopathology. Ultimately these vessels began leaking into the wall
of the jejunum, subsequently causing mural hematoma and obstruction
resulting in necrosis of the segment. Furthermore, the last
histopathology report showed that the mare continued to produce
eosinophilic infiltration in the submucosa and granulomas that contained
hemosiderin-laden macrophages in the serosa. In conclusion, as
hypothesized previously, due to a possible hypersensitivity, it is
suspected that the mare would have developed eosinophilic enteritis and
secondary intramural hematoma again.

\emph{Authors' declaration of interests}

No conflicts of interest have been declared.

\emph{Acknowledgements}

We thank the owner Elise Handler for giving us all the opportunity to
work with the mare when needed, submit the samples to histopathology and
bringing her to the clinic for euthanasia and further diagnostics.

\emph{Ethical animal research}

Ethical review not applicable for this case report.

\emph{Source of funding}

None.

\emph{ORCID}

Isabel Vergara\emph{https://orcid.org/0009-0006-0805-2173}

Russell Freeland\emph{https://orcid.org/0009-0003-2939-7056}\selectlanguage{english}
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Fig 1. Distended loop of orad small intestine (normal diameter (d) range
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Fig 2. Distended small intestine showing a mixed unknown echogenicity\selectlanguage{english}
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3. Intraoperative image showing affected jejunum segment with associated
hematoma.

Fig 4. Opened sample of affected jejunum with hemorrhagic gelatinous
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