ttp://www.bsava.

com REVIEW

Feline chronic enteropathy

S. Marsilio1

School of Veterinary Medicine, Department of Medicine and Epidemiology, University of California, One Shields Avenue, Davis,
CA, 95616, USA
1
Corresponding author email: [email protected]

Feline chronic enteropathy is a common disorder, especially in the senior cat population, with rising
incidence over the past decade. Feline chronic enteropathy is considered an umbrella term comprising
different diseases including food-responsive enteropathy, idiopathic inflammatory bowel disease and
alimentary small cell lymphoma. However, differentiation between those diseases is often difficult in
practice. This review will discuss the clinical approach to cats with chronic enteropathy, state-of-the-
art diagnostic tests and pitfalls thereof as well as current therapeutic approaches. Although, much
of the etiopathogenesis is still unknown, increased research efforts in this field have brought new
­insights into diagnostic and therapeutic options for these cats.

Journal of Small Animal Practice (2021), 1–11

DOI: 10.1111/jsap.13332
Accepted: 05 March 2021

INTRODUCTION additional diagnostic testing such as ­immunohistochemistry

(Paulin et al. 2018) and clonality testing (Moore et al. 2005,
Feline chronic enteropathy (FCE) is amongst the most common Moore et al. 2012, Sabattini et al. 2016). Treatment options
disorders in the elderly cat population with rising incidence over include combinations of nutritional and nutraceutical support,
the past decades (Richter 2003, Louwerens et al. 2005). The dis- steroids and other immunosuppressive medication, if necessary.
order is defined as the presence of clinical signs of gastrointestinal In this review, we will discuss different diagnostic and therapeu-
disease for more than 3 weeks in the absence of extraintestinal tic approaches to cats with chronic enteropathy.
causes or infectious, obstructive or localised neoplastic intestinal
diseases (Jergens et al. 2003, Simpson and Jergens, 2011b).
Although there is no uniform classification scheme for chronic SIGNALMENT, HISTORY AND CLINICAL SIGNS
enteropathies, most authors will subclassify cases based on the
response to treatment into food-responsive enteropathy (FRE), Generally, signalment clinical, laboratory testing and even
idiopathic inflammatory bowel disease (IBD) (often used inter- abdominal ultrasound are not suitable means to differentiate dif-
changeably with steroid-responsive enteropathy) and small cell ferent subtypes of FCE. While cats with IBD tend to be younger
lymphoma (SCL) (Jergens et al. 1992, Jergens et al. 2010, Jer- with a median reported age of approximately 8 years (Waly
gens 2012, Moore et al. 2012, Barrs & Beatty 2012a, Barrs & et al. 2004, Janeczko et al. 2008, Jergens et al. 2010, Marsilio
Beatty 2012b). Although the etiopathogenesis is unknown, IBD et al. 2019b) compared to cats with SCL with an approximate
is thought to occur as the results of perturbations in the crosstalk median age of 12.5 years (Kiselow et al. 2008, Lingard et al. 2009,
between the environment, the immune system and the microbi- Stein et al. 2010) age ranges significantly overlap (IBD 1.3 to
ome in a genetically susceptible host (De Souza & Fiocchi 2016, 16 years versus SCL ranges from 4 to 20 years). In one study cats
De Souza et al. 2017). with FRE had a reported median age of 7.7 years while cats with
Progression of IBD to SCL over months to years has long been IBD had a median age of 10.4 years (Jergens et al. 2010). The
suspected based on the frequent coexistence of inflammatory and study did not compare the age of both groups statistically and
neoplastic lesions in cats with SCL and/or a previous history of thus it remains unclear whether this difference was statistically
IBD (Moore et al. 2005, Moore et al. 2012). significant. Domestic short-hair cats are most commonly affected
Clinical signs are non-specific and diagnosis and differentiation in both groups and although Siamese cats have anecdotally been
of IBD from SCL requires histopathological examination of tis- found to be overrepresented in cats with FCE (Jergens 2012),
sue biopsies. However, even with histopathological examination this has not been a consistent finding. ­Similarly, clinical signs
of tissue samples, ambiguous cases frequently occur and require are unsuitable for the differentiation between feline IBD and

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 S. Marsilio

SCL (Norsworthy et al. 2015). Weight loss is the most common Although significant protein loss and the development of pro-
clinical sign in cats with FCE (80–90%), followed by vomiting tein-losing enteropathy is very rare in cats, ­hypoalbuminaemia
(70–80%), anorexia (60–70%) and diarrhoea (50–65%) (Waly is a common finding in both disease entities with up to
et al. 2005, Burke et al. 2013, Norsworthy et al. 2015). This is in 100% of cats with severe IBD or SCL being affected (Janec-
contrast to dogs, where diarrhoea is by far the most common pre- zko et al. 2008, Burke et al. 2013). In contrast, total protein is
senting complaint. In the author’s and other’s experience (Nor- often normal or increased due to concurrent hyperglobulinae-
sworthy et al. 2013), weight loss is often overlooked due to its mia and an increased total protein concentration is part of the
very gradual progression over weeks to months. Cats often lose FCEAI (Table 1) (Jergens et al. 2010). Other laboratory tests
muscle mass first and may develop significant sarcopenia, par- with potential diagnostic as well as therapeutic and prognostic
ticularly appreciable along the spine, before adipose tissue is lost. value are serum folate, cobalamin and inorganic phosphorus
Abdominal fat pads are often preserved even in otherwise cachec- concentrations, and deficiencies have previously been associated
tic cats. Beside sarcopaenia (Cruz-Jentoft et al. 2019) and a gen- with disease severity in cats with chronic enteropathy (Simp-
erally low body condition score, physical examination may reveal son et al. 2001, Ruaux et al. 2005, Reed et al. 2007). Cobala-
segmental or diffusely thickened intestinal loops and abdominal min is a water-soluble vitamin present in dietary proteins. In
discomfort/pain often located in the cranial abdomen, possibly the small intestinal tract, it is bound to intrinsic factor which,
related to concurrent pancreatitis and/or cholangiohepatitis (Lin- in cats, stems mostly from pancreatic secretion (Fyfe 1993, Fyfe
gard et al. 2009, ­Jergens 2012, Barrs & Beatty 2012b). et al. 2004). Cobalamin is absorbed in the distal small intesti-
A study in cats with FRE and IBD established and validated a nal tract, especially the ileum through the binding of intrinsic
FCE activity index (FCEAI) through correlation of histopatho- factor to its respective receptors (Fyfe et al. 2004). Thus, hypo-
logical changes with clinical, endoscopic and laboratory param- cobalaminaemia has been documented with diffuse distal small
eters (Table 1) (Jergens et al. 2010). While the index may help intestinal disease (e.g. inflammation, neoplasia, fungal disease
to objectively assessment disease activity and clinical response etc.), exocrine pancreatic insufficiency (EPI) with intrinsic fac-
to treatment it was not established in cats with SCL and oth- tor deficiency, and receptor defects, which have so far only been
ers have found no correlation between clinical signs and a diag- documented in dogs (Table 2.). Similarly, folate is a water-solu-
nosis of IBD versus SCL (Norsworthy et al. 2013, Norsworthy ble vitamin present in a wide variety of food sources and can also
et al. 2015). be produced by certain bacteria. Folate is mainly absorbed in the
In contrast to IBD and SCL, cats with intermediate to LCL proximal small intestinal tract (Butterworth et al. 1969, Bern-
(large cell lymphoma) usually show more acute onset and rap- stein et al. 1970). Serum folate concentrations can be decreased
idly progressive clinical signs (Collette et al. 2016, Limmer due to diffuse proximal small intestinal mucosal infiltration and
et al. 2016, Gouldin et al. 2017, Finotello et al. 2018). Abdomi- subsequent malabsorption or increased as a result of bacterial
nal masses, intussusception, obstruction or even perforation is production during dysbiosis (Reed et al. 2007). The presence
mostly associated with this more aggressive form of alimentary of combined hypofolataemia and hypocobalaminaemia usually
lymphoma. represents significant small intestinal disease and malabsorption
of these and probably many other nutrients. In addition, folate
and cobalamin are essential for DNA synthesis. Besides the bone
LABORATORY ASSESSMENT marrow, enterocytes are amongst the most rapidly dividing cells
in the body with a high level of DNA turn over. Supplementa-
Previous studies have investigated the utility of minimally inva- tion of cobalamin and folate has been shown to be beneficial in
sive diagnostic tests for the differentiation of FCE subtypes. cats (Ruaux et al. 2005) and in people (Habibi et al. 2017) with
However, no single biomarker that reliably distinguishes IBD chronic enteropathies. Studies in cats with gastrointestinal signs
from SCL has been identified yet. Nevertheless, in the author’s have shown rising serum concentrations of methylmalonic acid
experience, laboratory tests and imaging studies are still helpful with cobalamin concentrations <400 ng/L, indicating ­cellular
measures to localise and characterise lesions and decide on fur- cobalamin deficiencies (Steiner, personal communication).
ther diagnostic steps. Therefore, the author recommends cobalamin supplementation

Table 1. Feline chronic enteropathy activity index (FCEAI) by Jergens et al. 2010
Parameter Points =Subtotal
Attitude/activity Normal: 0 Mild: 1 Moderate: 2 Severe: 3
Appetite Normal: 0 Mild: 1 Moderate: 2 Severe: 3
Vomiting Normal: 0 Mild: 1 Moderate: 2 Severe: 3
Diarrhoea Normal: 0 Mild: 1 Moderate: 2 Severe: 3
Weight loss Normal: 0 Mild: 1 Moderate: 2 Severe: 3
Endoscopic lesions No: 0 Yes: 1
Total protein Normal: 0 Increased: 1
ALT/ALP Normal: 0 Increased: 1
Phosphorus Normal: 0 Decreased: 1
Composite total score

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 Feline chronic enteropathy

Table 2. Differential diagnoses for hypocobalaminaemia in et al. 2009, Daniaux et al. 2014). Two previous studies investi-
cats with chronic enteropathy gated the utility of ultrasonography to differentiate IBD from
Differential diagnoses for hypocobalaminaemia SCL (Zwingenberger et al. 2010, Daniaux et al. 2014). While
Exocrine pancreatic • Measure fTLI older cats with thickening of the muscularis propria and cats
insufficiency (EPI) • EPI is often associated with chronic with abdominal lymphadenopathy were more likely to have a
pancreatitis in cats diagnosis of lymphoma, there was substantial overlap between
Diffuse distal small intestinal • Inflammation (IBD)
mucosal disease • Diffuse (distal) small intestinal SCL and IBD or even with findings in healthy cats (Zwingen-
neoplasia (e.g., lymphoma) berger et al. 2010, Daniaux et al. 2014). Interestingly, thicken-
• Diffuse infectious diseases (e.g., ing of the muscularis propria was not significantly associated
histoplasmosis)
Cobalamin receptor defect • Not described in cats with severe transmural disease (Zwingenberger et al. 2010).
Moreover, a recent study in 169 cats with FCE investigated the
predictive value of abdominal ultrasound for severity and loca-
in cats with signs of chronic enteropathy with serum cobalamin tion of intestinal lesions (Guttin et al. 2019). While the study
concentrations of ≤400 ng/L. found that ultrasonographic abnormalities had a high positive
Other micronutrients found to be decreased in cats with predictive value for mucosal histologic lesions, the location of
chronic enteropathy are inorganic phosphorus (Reed et al. 2007) lesions in the submucosa or muscularis propria was not predic-
and vitamin D (Lalor et al. 2014). Global metabolic derange- tive for histologic lesions in these layers. It needs to be noted
ments have been described in humans (Bjerrum et al. 2015, that the disease prevalence in this study was virtually 100% and
Kolho et al. 2017) and dogs (Minamoto et al. 2015) with IBD thus a high-positive predictive value of abdominal ultrasound for
as a consequence of inflammation-driven malabsorption. Hence, mucosal lesions is to be expected. However, that does not allow
even though supplementation of deficient micronutrients might the conclusion that abnormal ultrasonographic findings in cats
be beneficial, they should primarily be seen as surrogate mark- without clinical signs are indicative of intestinal disease and other
ers of substantial malabsorption due to a primary underlying studies have found that ultrasonographic abnormalities including
pathology. Identifying and treating the underlying disease is key muscularis propria thickening can be found in clinically healthy
to regain control of metabolic perturbations. Besides information cats (Zwingenberger et al. 2010, Daniaux et al. 2014). Despite
on malabsorption, cobalamin and folate can also provide cues on these limitations, ultrasound still plays an important role in the
disease location. In the presence of hypocobalaminaemia, ileal diagnosis of feline CE as a guidance on the best next diagnostic
biopsies may be beneficial to maximise the likelihood of collect- step. Cats with diffuse changes in the duodenum and proximal
ing samples that are representative of the disease process (Scott jejunum and/or the ileum may be good candidates for gastro-
et al. 2011). However, a recent paper contradicted this previous duodenoscopy and ileo-colonoscopy. By contrast, patients with
notion and showed that biopsies from the lower small intesti- localised and/or extramural changes, changes outside the range
nal tract rarely changed the diagnosis when biopsies underwent of the endoscope and changes in other organs should undergo
histopathology and ancillary testing with immunohistochemistry laparotomy or laparoscopy with collection of full-thickness
and clonality testing (Chow et al. 2021). In addition to serum biopsies. Patients with LCL or fungal disease often show local-
cobalamin and folate, the measurements of feline pancreatic ised mass lesions, lymphadenopathy, or hepato-or splenomegaly.
lipase immunoreactivity (fPLI), and feline trysin-like immu- In these cases, a diagnosis can often be made using fine-needle
noreactivity (fTLI) have value in cats with chronic enteropathy aspirates (Mavropoulou et al. 2010, Cook et al. 2012, Barrs &
(CE). Concurrent chronic pancreatitis is often observed in cats Beatty 2012b, Finotello et al. 2018). However, it should be noted
with CE (Weiss et al. 1996) (Simpson 2015). Thus, FCE should that fine-needle aspirates are unhelpful in differentiating IBD
be considered as a differential concurrent diagnosis in cats with from SCL.
increased fPLI. EPI is increasingly recognised in cats (Xenoulis
et al. 2016). While canine EPI is commonly caused by pancreatic Biopsy collection
acinar atrophy in young dogs, cats with EPI are often older and Every biopsy collection method has advantages and disadvan-
sometimes have a history of pancreatitis. It has been hypothesised tages and it is important to realise those in order to best advise
that EPI in cats may be a consequence of chronic pancreatitis cat owners on this crucial diagnostic step.
causing fibrosis and severe loss of functional tissue. Therefore, Main disadvantages of gastrointestinal endoscopy and biopsy
measurement of fPLI and fTLI in cats with FCE can be beneficial collection are the limitation to the mucosa and sometimes sub-
to identify of concurrent pancreatic disorders. mucosa, the limited range (i.e., lesions in the mid to distal jeju-
num and that extramural lesions are out of the endoscopic range
and cannot be biopsied). Patients with these types of lesions
ABDOMINAL ULTRASOUND should undergo laparoscopy or laparotomy and with sampling of
surgical biopsies. However, the collection of endoscopic biopsies
Ultrasonographic abnormalities frequently observed in IBD is minimally invasive and fast, recovery time is very short and
and SCL are thickened muscularis propria, loss of wall layer- therapy can be started immediately after the procedure without
ing and lymphadenopathy. A muscularis to submucosa ratio of the risk of wound dehiscence. In addition, the mucosal surface
>1 is suggestive of an abnormal bowel segment (Fig 1) (Lingard can be visualised and targeted biopsies can be obtained from

Journal of Small Animal Practice • © 2021 British Small Animal Veterinary Association 3
 S. Marsilio

FIG 1. Sagittal ultrasound images of a cat with normal small intestine (left) and a cat presented for signs of chronic enteropathy (right). The mucosal,
submucosal, muscularis, and serosal layers are indicated with arrows in the far field. Compared with normal intestines, the muscularis propria is
thickened in the cat affected with SCL. Courtesy of Drs. LaPorte, McLarty, and Wanamaker, UC Davis, School of Veterinary Medicine

visually affected areas. Using appropriate endoscopic equipment, Besides technical errors at the level of biopsy collection and
advancement of the insertion tube well into the duodenum is eas- submission, other errors such as over-fixation and especially
ily accomplished, often reaching the proximal jejunum (Jergens misorientation can decrease the diagnostic value of the sample
et al. 2016). Current guidelines recommend to collect a mini- (Ruiz et al. 2016). Samples should be orientated ensuring that
mum of six mucosal biopsies of adequate quality from the feline the slides will show a transversal plane through the intestinal
duodenum and 3 to 5 from the ileum for a reliable histopatho- wall. Misorientation can lead to diagnostically suboptimal or
logical assessment (Willard et al. 2008). However, these numbers even inadequate haematoxylin and eosin (H&E) slides, despite
represent the minimum, provided all biopsies are of adequate adequately collected samples (Figs 2 and 3). Some laboratories
quality (Willard et al. 2008). Therefore, the author usually col- will orientate the samples before paraffinisation with the help
lects 10 to 15 samples per location utilising the entire endoscopic of a microscope. However, not every pathology laboratory per-
range. According to a study of Willard et al. 2008, this practice forms sample orientation. A recent study compared the diagnos-
ensures to find inflammatory lesions even if considered mild tic utility of mounting intestinal biopsies on cucumber slices or
with a confidence of at least 90%. Adequate endoscopic biop- moisturised synthetic foam sponges compared to free flotation in
sies can provide a minimally invasive method to acquire substan- formalin (Ruiz et al. 2016). Mounted biopsy specimens had sig-
tial data representative of a large portion of the small intestinal nificantly fewer artefacts and pathologists had higher confidence
mucosa. This is especially advantageous since mucosal areas can in their interpretation and diagnosis. If in doubt, the pathologists
be affected in a patchy fashion. should be contacted and biopsy reorientation requested.
In contrast, surgical biopsies, even if taken from every sec-
tion of the small intestines (i.e., the duodenum, jejunum and
ileum), are only representative of a single site within each section. PATHOLOGY
A recent, yet unpublished, study at the Gastrointestinal Labora-
tory at Texas A&M University revealed that the diagnostically Fine-needle aspirates
available mucosal surface can be substantially reduced in full- Feline IBD is mostly characterised by a mixed infiltrate com-
thickness compared to endoscopic biopsies due to the number prising (mature) lymphocytes and plasma cells. Inflammation
of specimens available (Marsilio et al. unpublished data). The is found in the lamina propria sometimes extending into the
overwhelming majority of diffuse small intestinal lesions start in epithelium and is usually accompanied by architectural changes
or involve the mucosa, and thus can be detected on adequate such as villus blunting and crypt distortion. SCL is character-
endoscopic biopsies (Waly et al. 2004, Waly et al. 2005, Moore ised by epithelial/mucosal ± transmural infiltration with well-dif-
et al. 2012). Table 3 illustrates pros and cons to be considered ferentiated lymphocytes compromising the normal architecture
and discussed with clients before biopsies are collected. and replacing most of the lamina propria. However, SCLs often
Taking samples that are representative of the disease process is show concurrent inflammatory changes in the same and/or
a key regardless of the technique; every technique is prone to fail- other parts of the intestinal tract (Dennis et al. 1992, Jergens
ure if used incorrectly. Endoscopic biopsies can be too superficial et al. 1992, Moore et al. 2005, Moore et al. 2012, Norsworthy
(often containing only crushed villi) or small, or too few. Surgical et al. 2013). Considering the histologic composition of both IBD
biopsies are taken without visualisation of the mucosa and thus and SCL it becomes obvious that fine-needle aspirates are gener-
might not be representative of the disease. Sometimes surgical ally unhelpful for the differentiation of these two disease entities.
biopsies are taken as a wedge, with a large serosal area that funnels Fine-needle aspirates lack the architectural context required for a
down through the muscularis into the mucosa and thus while the correct diagnosis and the presence of small mature lymphocytes
biopsy appears large, the most important part of the biopsy, the in whatever quantity does not allow for any conclusions as they
mucosa, is small, damaged or even absent. are hallmarks of both – IBD and SCL. Fine-needle aspirates may,

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 Feline chronic enteropathy

Table 3. Pros and cons of endoscopically or surgically acquired biopsies from cats with feline chronic enteropathy that
should be considered and discussed with clients before biopsy collection
Endoscopic biopsies Surgical biopsies
Pros Cons Pros Cons
• Minimally invasive • Limited range of • Transmural biopsies • Invasive with higher post-
• Mucosa can directly be visualised endoscope (lesions in • Sampling of lesions outside the operative morbidity
• Targeted biopsy collection the jejunum cannot be range of the endoscope (jejunum) • Risk of dehiscence and
• Multiple biopsies available that are representative reached) possible wound infection
of a larger area of the intestinal tract • No information on • Localised lesions and eccentric • Treatment is usually
• Most if not all diffuse small intestinal disease is histologic changes in lesions can be assessed postponed until complete
located in mucosa and thus endoscopic biopsies the submucosa and • Biopsies of other organs can be closure and healing of the
should be sufficient if the endoscope reaches the muscularis propria collected (e.g. liver, lymph nodes, laparotomy site
affected region spleen, etc.)
• Treatment can be started immediately after biopsy
sampling

FIG 2. Histologic processing of endoscopically obtained, formalin-fixed biopsy specimens by a histologist. (A) Jejunal biopsy specimen. The specimen
is upside down with the villi facing downwards. (B) Jejunal biopsy after reorientation, villi are visible, pointing upwards. (C) The histologist is orienting
biopsy specimens in a position that allows for cutting the specimen parallel to the lamina propria. In this image, the four specimens on top have been
reoriented, whereas the two-bottom specimens are still in a tangential position. Courtesy of Kelly Mallet, Texas A&M Gastrointestinal Laboratory,
College Station, TX, USA

however, be helpful in excluding other differential diagnoses such be noted and considered when interpreting pathologists’ reports.
as LCL or fungal disease in cats with abdominal masses, lymph- One study investigating the agreement between five different
adenomegaly or organomegaly. pathologists assessing the degree of cellular infiltrates in the
intestinal mucosa of dogs and cats showed a very high interob-
Histopathology server variability (Willard et al. 2002). These results triggered
the formation of the World Small Animal Veterinary Association
While the histopathologic examination of tissue biopsy speci- (WSAVA) Gastrointestinal Standardisation Group; an attempt to
mens remains the gold standard for the diagnosis of chronic standardise histopathological assessment of gastrointestinal biop-
enteropathy, it is associated with potential pitfalls that should sies (Day et al. 2008, Washabau et al. 2010). The group published

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 S. Marsilio

Another pitfall of the current WSAVA guidelines concerns

the demographic characteristic of the group of cats that served as
examples for the definition of the “normal baseline.” These sam-
ples were collected from a group of mostly young (about 1.5 years
old), specific-pathogen-free, colony cats. However, this group is
hardly representative for the group of cats that is presented for
signs of chronic enteropathy in clinical practice. A recent study
by the author investigated histopathological findings in endo-
scopic gastric and duodenal biopsies of 20 healthy, client-owned
cats with demographic characteristics similar to those of cats pre-
sented for chronic enteropathy (median age 9.5 years, range 3
to 18 years) (Marsilio et al. 2019a). All cats showed histopatho-
logical findings considered to be abnormal based on the current
WSAVA criteria. However, only three cats went on to develop
gastrointestinal disease later on. The remaining 17 cats were
clinically unchanged after a median follow-up time of 709 days.
Despite all flaws, histopathology is still the most reliable diag-
nostic test for a diagnosis chronic enteropathy currently available.
Clinicians should pay attention to the pathologist’s description of
architectural changes as they have been recognised by the WSAVA
to be of equally importance in the assessment of chronic enter-
opathies in cats (Day et al. 2008, Washabau et al. 2010). The most
common disorders of the feline small intestine are IBD or SCL.
While IBD consists of a mixed infiltrate of lymphocytes and plasma
cells, SCL comprises a monomorphic population of small mature
lymphocytes infiltrating and effacing the lamina propria and the
epithelium (if epitheliotropic), and sometimes deeper tissue layers
of the submucosa and muscularis (transmural) (Fig 4). However, as
mentioned above SCL can have a substantial inflammatory com-
ponent and thus unsurprisingly, severe cases of LPE can be difficult
to distinguish from IBD. In addition, progression of LPE into SCL
has long been suspected. In these equivocal cases, advanced diag-
nostics such as immunohistochemistry and PCR-based methods
may be needed (Kiupel et al. 2011, Moore et al. 2012).
It is worth noting that a diagnosis of LPE is not equivalent to
a diagnosis of IBD. LPE may be associated with intestinal para-
sites, food hypersensitivity, or even hyperthyroidism. This illus-
trates why other differential diagnoses need to be excluded before
invasive diagnostics such as the collection of intestinal biopsies
FIG 3. Haematoxylin and Eosin-stained endoscopically obtained biopsy
are performed (Jergens 2012).
specimens. (A) Suboptimal sample orientation led to cutting this biopsy While architectural changes are a good indicator of the sever-
specimen tangentially, resulting in “villus slaw.” The biopsy specimen ity of intestinal disease, cellular infiltrates are still valuable as
is uninterpretable. (B and C) Examples of optimally oriented biopsy
specimens from the same slide. The images are the ×5 magnification of
they may give clues about the underling aetiology. A promi-
the red square in the slide map on the bottom right of images (B) and nent eosinophilic inflammatory component may be associated
(C). All biopsies on the slide are optimally oriented. Villi and crypts are with parasites, food hypersensitivity or T-cell lymphoma (Barrs
cut parallel to the lamina propria and the entire lamina propria is visible
for optimal interpretation
et al. 2002) or occur as a part of the hypereosinophilic syn-
drome. This systemic eosinophilic disorder is characterised by
an increased production of eosinophilic precursors in the bone
a standard form for pathologists that included a grading scheme marrow. Patients display peripheral (mature) eosinophilia and
for the cellular infiltrate as well as for architectural changes such ­eosinophilic ­infiltration in multiple tissues (e.g. gastrointestinal
as epithelial injury, villus blunting, crypt distention, fibrosis and tract, spleen, liver, lymph nodes, heart and lungs) with subse-
lacteal dilation. Findings are graded on a scale of 0 (normal) to quent organ damage (Hendrick 1981, Takeuchi et al. 2008,
3 (severe) (Day et al. 2008, Washabau et al. 2010). However, McEwen et al. 1985). Neutrophilic (suppurative) and/or histio-
subsequent studies have shown that interobserver variability still cytic infiltration may suggest an infectious cause and indicates
persists and since then other authors have attempted to simplify the need for additional testing including special staining and test-
the grading scheme (Jergens et al. 2014). ing (Simpson and Jergens, 2011a, Maunder et al. 2012).

6 Journal of Small Animal Practice • © 2021 British Small Animal Veterinary Association
 Feline chronic enteropathy

ity assays are now considered state-of-the-art to differentiate IBD

from SCL. In neoplastic lesions, lymphocytes are derived from a
single (or few) precursor cell(s) and thus the daughter cells show
the same receptor specificity, i.e. (oligo-) clonal receptor rear-
rangements. In inflammatory processes, lymphocytes are derived
from multiple precursor cells with different antigen-receptor
specificities, i.e. polyclonal receptor rearrangements. Inflam-
matory responses also usually comprise a mixture of T, B- and
possibly other immune cells. This concept is the basis of immu-
nohistochemical and PCR-based analysis.

Immunohistochemistry
Immunohistochemistry is the first step for further differentia-
tion between IBD and SCL in ambiguous cases. Specific staining
includes CD3 for T cells, CD20, CD 79a or PAX-5 for B-cells
and potentially other cells. Stainings determine whether all lym-
phocytes seen on regular H&E stain are of a single lineage or
whether the infiltrate consists of a mixture of T-cells, B- cells and
plasma cells, the former supporting a diagnosis of lymphoma,
the latter a diagnosis of inflammation, i.e. IBD (Fig 5). A com-
prehensive study on the mucosal architecture, phenotype and
clonality of feline gastrointestinal lymphoma published in 2012
by Moore et al. showed that only about 16% of alimentary lym-
phomas were of B-cell origin and of those all were considered
LCL (Moore et al. 2012). A majority of about 84% of intestinal
lymphomas were T-cell lymphomas and of those about 85% were
considered SCL. Of 11 T-cell lymphomas considered LCL, nine
were LGL lymphomas. This form may be of cytotoxic T-cell or
natural killer cell origin since both cell types display intracytoplas-
mic eosinophilic granules. The vast majority of LGL lymphomas
arise in the gastrointestinal tract, causing segmental or centrifu-
gal thickening or multiple masses within the small intestine. The
jejunum, ileum, ileo-colic junction and duodenum, and large
intestine are affected in descending order of frequency. Extra-
FIG 4. H&E-stained endoscopic biopsy specimens from cats with chronic
enteropathy. (A) Mild LPE, ×5 magnification. Mild villus stunting and
gastrointestinal involvement is common and includes abdominal
crypt hyperplasia. Mildly increased infiltration with lymphocytes and or extra-abdominal lymph nodes, liver, spleen or kidneys. LGL
plasma cells. (B) Epitheliotropic SCL, ×5 magnification. A monomorphic lymphomas are often readily diagnosed upon cytological exami-
population of small mature lymphocytes is infiltrating and effacing the
lamina propria. Severe architectural changes, including villus stunting,
nation of slides acquired by fine-needle aspiration and usually do
villus fusion, and fibrosis. The lamina propria is infiltrated by a dense not require biopsy collection. On H&E stain eosinophilic gran-
infiltrate of small lymphocytes. (C) ×10 magnification of the image in (B). ules are obvious and granzyme B can be used as a special stain for
The infiltrate is present predominantly in the lamina propria of the villi
and also forms nests and plaques in the epithelium
final diagnosis.
SCLs can often be accompanied by inflammation and thus a
diagnosis can be difficult even with IHC. Therefore, other meth-
In summary, clinicians should always interpret histopatho- ods to assess the clonality of the lymphocyte receptors have been
logic results in the light of the patients’ history and clinical find- developed (Moore et al. 2005).
ings. When reading the pathologist’s report, clinicians should
pay particular attention to description of architectural changes. Clonality testing
In cases with minimal or absent architectural changes, the sig- Clonality can be assessed in many ways including flow cytom-
nificance of cellular infiltrates, especially if mild, should be etry, southern blot analysis and PCR. PCR-for receptor antigen
questioned. rearrangement (PARR) is the most commonly used method as it
can be performed on formalin-fixed, paraffin-embedded tissue
samples (Moore et al. 2005).
ANCILLARY TESTING FOR FCE Virtually any substance can be the target of an immune
response and immune responses are mediated by the antigen
Even with adequate biopsies, ambiguous cases still exist and addi- receptor. Therefore, antigen receptors have an extremely high can
tional tests including immunohistochemistry (IHC) and clonal- diversity. In fact, the diversity of B-cell immunoglobin receptors

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 S. Marsilio

FIG 5. Endoscopically obtained small intestinal biopsy of a cat with low-grade T-cell lymphoma. (A) Haematoxylin and eosin stain shows dense
infiltrates with a monomorphic population of small mature lymphocytes in the lamina propria and the epithelium. (B) Immunohistochemistry using
antibodies against the CD3 T-cell receptor confirms that most lymphocytes seen on H&E stain positive for CD3 and thus are of T cell lineage

(Ig) or T-cell receptors (TCR) is estimated to be in the order of THERAPEUTIC MANAGEMENT AND PROGNOSIS
1018 (Actor 2012). OF IBD AND SCL
This diversity is made possible by the somatic rearrangement
of germline DNA sequences inside the lymphocytes. Clonality Therapeutic management of IBD and SCL in cats can be similar
assays permit visualisation of the diversity of the antigen recep- dependent on the state of the disease (i.e. BCS, lethargy, etc.),
tors. The presence of diverse receptors suggests the existence of cat’s temperament, and the owner’s preferences (i.e. ability to
inflammatory lesions (i.e. polyclonal), while uniform receptors pill the cat). However, common differential diagnoses for IBD
indicate neoplastic lesions (i.e. clonal). However, even though the and SCL include intermediate and LCL, eosinophilic syndrome,
primers used in the PARR assays are specific for T- or B-cells, the fungal disease and other gastrointestinal neoplasia for which
cell lineage cannot be determined by PARR. In up to 10% of therapy and prognosis are vastly different. Hence, the collection
cases, T-cells can rearrange B-cell receptor genes and vice versa in of biopsies is required for the diagnosis and exclusion of other
a process of cross-lineage rearrangement (Andrews et al. 2016). diseases. Treatment for feline IBD usually involves steroids with
Therefore, clonality assays should not be used to determine the or without a concurrent dietary trial using a novel protein or
lineage of the clone. hydrolyzed diet. Table 4 shows pros and cons of different dietary
Clonality often implies immortality and uninhibited mito- approaches in cats with IBD. Is important to assess the role of
sis as seen in cases of lymphoma. However, clonality is not food and treats in the owner-cat relationship. While often more
always equal to malignancy. Benign clonal expansions have been important in dogs, some owners positively reinforce cats with
described in various diseases in humans (Alaibac et al. 1993, treats. Dietary compliance is paramount for success and in cases
Magro et al. 2003) and dogs (Diehl et al. 1992) and it is even were the ability to give treats is important to clients a novel pro-
a well-documented phenomenon on elderly otherwise healthy tein diet may be preferrable. With novel protein diets, clients
people (Posnett et al. 1994). Similarly, recent studies evaluat- can often purchase the meat source (e.g. venison) separately
ing clonality assays in humans and cats found specificities as low and use small cooked or dried pieces as treats. Although in the
as 54.3% in humans (Kokovic et al. 2014) and 33.3% in cats author’s opinion often arbitrary, cats that respond to a food trail
(Marsilio et al. 2019a, Marsilio et al. 2020). Therefore, IHC and alone are considered to have FRE. Regardless, of the diet type,
PARR should always be interpreted together and in the context nutritional support is of utmost importance, especially since
of all available data ideally in the same laboratory. many cats suffer from malabsorption and/or are already under-
A recent study by the author’s group investigated a new tech- conditioned. Appetite stimulants such as mirtazapine ¼ of a
nology, using histology-guided mass spectrometry (HMGS) 7.5 mg tablet PO q48h or 2 mg/cat of the transdermal ointment
for the differentiation of IBD from SCL (Marsilio et al. 2020). applied to the inner pinna q24h) can be helpful. However, if the
Similar to PARR, this technique can be applied to formalin-fixed cat is consistently inappetent or even anorectic, feeding devices
paraffin-embedded tissue samples and appears to have superior such as an oesophageal feeding tube (e-tube) should be placed to
test sensitivity and specificity of 86.7% and 91.7%, respectively. ensure adequate caloric support to prevent complications such
However, this test is not yet commercially available. as hepatic lipidosis (Klaus et al. 2009, Kuzi et al. 2017). The

8 Journal of Small Animal Practice • © 2021 British Small Animal Veterinary Association
 Feline chronic enteropathy

Table 4. Pros and cons of different dietary approaches for time was not reached for cats diagnosed with lymphoplasmacytic
cats with chronic enteropathy enteritis (Sabattini et al. 2016).
Diet type Pros Cons In conclusion, FCE is an umbrella term for multiple different
Hydrolyzed Can be used in patients Possibility of persistent disease processes including FRE, IBD and SCL. The differen-
with an extensive dietary immunogenicity tiation of feline IBD from SCL remains challenging. With the
history Limited availability of treats possibility of chronic inflammation in cats with IBD progressing
Can be used as a second
or third choice after to SCL over time, we may also look at a moving target. From a
failure of other diet trials therapeutic and prognostic point of view, differentiation might
Novel Better acceptance in As commercial cat food currently not alter either approach or outcome. However, many
protein some cats increasingly contains “exotic
Treats can be bought or meats” (e.g. duck, venison questions remain unanswered, such as the causes of a profoundly
homemade (venison, etc.), it might be difficult to increased disease incidence over time, whether there are differ-
rabbit etc.) find a meat source the cat ent forms of SCL (epitheliotropic versus lamina propria, mucosal
has not had contact with
versus transmural location within the small intestine, lymph node
involvement etc.) and if we should consider approaching those
resting energy requirement (RER) can be calculated by using differently. We need to continue to ask these questions and to
the following formula: 70×(BW in kg)0.75. Diets can be prepared study these disorders in order to further expand our knowledge,
accordingly with the daily volume divided into four to six feed- refine treatment modalities and ultimately improve outcome.
ings. If the cat requires a dry diet, kibbles can be crushed into
a powder using a blender with water subsequently added to the Conflict of interest
desired consistency. It is important to start with 25% RER for None of the authors of this article has a financial or personal
the first 24 hours and increase by 25% every day until 100% is relationship with other people or organisations that could inap-
reached. propriately influence or bias the content of the paper.
There is good evidence in people (Derwa et al. 2017), but
weak evidence in dogs (Rossi et al. 2014) that probiotics, espe- References
Actor, J. K. (2012) Elsevier’s Integrated Review Immunology and Microbiology
cially #VSL3 (now renamed Visbiome) may be helpful for the Chapter 4. T-Cell Immunity. 2nd Edition. Elsevier
treatment of chronic enteropathies. There is currently no system- Alaibac, M., Daga, A., Harms, G., et al. (1993) Molecular analysis of the gamma
delta T-cell receptor repertoire in normal human skin and in oriental cutaneous
atic study in cats documenting the efficacy of probiotics in cats leishmaniasis. Experimental Dermatology 2, 106-112
with chronic enteropathy. However, the author found probiotics Andrews, C., Operacz, M., Maes, R., et al. (2016) Cross lineage rearrangement in
feline enteropathy-associated T-cell lymphoma. Veterinary Pathology 53, 559-562
helpful in some cats as one of the treatment strategies in a gener- Barrs, V. R. & Beatty, J. A. (2012a) Feline alimentary lymphoma 2. Further diagnos-
ally multifactorial approach. Cats classified as having idiopathic tics, therapy and prognosis. Journal of Feline Medicine and Surgery 14, 191-201
Barrs, V. R. & Beatty, J. A. (2012b) Feline alimentary lymphoma: 1. Classification,
IBD are commonly treated additionally with prednisolone at risk factors, clinical signs and non-invasive diagnostics. Journal of Feline Medi-
2 mg/kg/day, which can be divided q12h dependent on the toler- cine and Surgery 14, 182-190
Barrs, V. R., Beatty, J. A., Mccandlish, I. A., et al. (2002) Hypereosinophilic para-
ance of the patient (Jergens et al. 1992, Jergens 2012). The pred- neoplastic syndrome in a cat with intestinal T cell lymphosarcoma. The Journal
nisolone dose is usually tapered by 25% every 3 to 4 weeks until of Small Animal Practice 43, 401-405
Bernstein, L. H., Gutstein, S., Weiner, S., et al. (1970) The absorption and malab-
the lowest effective dose is identified. Even though cats are usu- sorption of folic acid and its polyglutamates. The American Journal of Medicine
ally tolerant to steroid side effects, budesonide (3 mg/m2 q24h) 48, 570-579
Bjerrum, J. T., Wang, Y., Hao, F., et al. (2015) Metabonomics of human fecal
has been anecdotally used as an alternative in patients intolerant extracts characterize ulcerative colitis, Crohn’s disease and healthy individuals.
to systemic steroids (e.g., cats with diabetes mellitus). Cats with Metabolomics 11, 122-133
Burke, K. F., Broussard, J. D., Ruaux, C. G., et al. (2013) Evaluation of fecal α1-
severe malabsorption can benefit from initial treatment with sub- proteinase inhibitor concentrations in cats with idiopathic inflammatory bowel
cutaneous injections of dexamethasone until the disease is bet- disease and cats with gastrointestinal. Neoplasia 196, 189-196
Butterworth, C. E., Baugh, C. M. & Krumdieck, C. (1969) A study of folate absorp-
ter controlled. In the author’s experience, many cats with SCL tion and metabolism in man utilizing carbon-14—labeled polyglutamates syn-
lymphoma initially respond to treatment with steroids as well. thesized by the solid phase method. The Journal of Clinical Investigation 48,
1131-1142
In cases of refractory IBD or SCL chlorambucil can be added to Chow, B., Hill, S. L., Richter, K. P., et al. (2021) Comprehensive comparison of
the treatment regime. Chlorambucil can be administered con- upper and lower endoscopic small intestinal biopsy in cats with chronic enter-
opathy. Journal of Veterinary Internal Medicine 35, 190-198
tinuously at a dose of 2 mg per cat PO q48h to q72h (usually Collette, S. A., Allstadt, S. D., Chon, E. M., et al. (2016) Treatment of feline inter-
at home) or as a pulse-dose protocol at 20 mg/m2 every 2 weeks mediate- to high-grade lymphoma with a modified university of Wisconsin-Mad-
ison protocol: 119 cases (2004-2012). Veterinary and Comparative Oncology
(Kiselow et al. 2008, Lingard et al. 2009, Stein et al. 2010, Pope 14(Suppl 1), 136-146
et al. 2015). The author has also used chlorambucil pulse-dos- Cook, A. K., Cunningham, L. Y., Cowell, A. K., et al. (2012) Clinical evaluation of
urine Histoplasma capsulatum antigen measurement in cats with suspected
ing in fractious cats and/or cases where the owner is unable to disseminated histoplasmosis. Journal of Feline Medicine and Surgery 14, 512-
pill for both IBD and SCL. In those cases, we offer clients to 515
Cruz-Jentoft, A. J., Bahat, G., Bauer, J., et al. (2019) Sarcopenia: revised European
administer chlorambucil every 2 to 3 weeks at the hospital. The consensus on definition and diagnosis. Age and Ageing 48, 16-31
median survival time of cats with SCL is reported to be between Daniaux, L. A., Laurenson, M. P., Marks, S. L., et al. (2014) Ultrasonographic thick-
ening of the muscularis propria in feline small intestinal small cell T-cell lym-
1.5 and 3 years (Kiselow et al. 2008, Lingard et al. 2009, Stein phoma and inflammatory bowel disease. Journal of Feline Medicine and Surgery
et al. 2010, Pope et al. 2015). Interestingly, there is only limited 16, 89-98
Day, M. J., Bilzer, T., Mansell, J., et al. (2008) Histopathological standards for
data on the survival time of cats with IBD. In a recent study the diagnosis of gastrointestinal inflammation in endoscopic biopsy sam-
with a median follow up time of about 3 years, median survival ples from the dog and cat: a report from the World Small Animal Veterinary

Journal of Small Animal Practice • © 2021 British Small Animal Veterinary Association 9
 S. Marsilio

Association Gastrointestinal Standardization Group. Journal of Comparative Louwerens, M., London, C. A., Pedersen, N. C., et al. (2005) Feline lymphoma in
Pathology 138(Suppl 1), S1-S43 the post-feline leukemia virus era. Journal of Veterinary Internal Medicine 19,
De Souza, H. S. & Fiocchi, C. (2016) Immunopathogenesis of IBD: current state of 329-335
the art. Nature Reviews Gastroenterology & Hepatology 13, 13-27 Magro, C. M., Crowson, A. N., Kovatich, A. J., et al. (2003) Drug-induced reversible
De Souza, H. S. P., Fiocchi, C. & Iliopoulos, D. (2017) The IBD interactome: an lymphoid dyscrasia: a clonal lymphomatoid dermatitis of memory and activated
integrated view of aetiology, pathogenesis and therapy. Nature Reviews. Gastro- T cells. Human Pathology 34, 119-129
enterology & Hepatology 14, 739-749 Marsilio, S., Ackermann, M. R., Lidbury, J. A., et al. (2019a) Results of histopathol-
Dennis, J. S., Kruger, J. M. & Mullaney, T. P. (1992) Lymphocytic/plasmacytic gas- ogy, immunohistochemistry, and molecular clonality testing of small intestinal
troenteritis in cats: 14 cases (1985-1990). Journal of the American Veterinary biopsy specimens from clinically healthy client-owned cats. Journal of Veterinary
Medical Association 200, 1712-1718 Internal Medicine 33, 551-558
Derwa, Y., Gracie, D. J., Hamlin, P. J., et al. (2017) Systematic review with meta- Marsilio, S., Pilla, R., Sarawichitr, B., et al. (2019b) Characterization of the fecal
analysis: the efficacy of probiotics in inflammatory bowel disease. Alimentary microbiome in cats with inflammatory bowel disease or alimentary small cell
Pharmacology & Therapeutics 46, 389-400 lymphoma. Scientific Reports 9, 19208
Diehl, K. J., Lappin, M. R., Jones, R. L., et al. (1992) Monoclonal gammopathy in Marsilio, S., Newman, S. J., Estep, J. S., et al. (2020) Differentiation of lympho-
a dog with plasmacytic gastroenterocolitis. Journal of the American Veterinary cytic-plasmacytic enteropathy and small cell lymphoma in cats using histology-
Medical Association 201, 1233-1236 guided mass spectrometry. Journal of Veterinary Internal Medicine 34, 669-677
Finotello, R., Vasconi, M. E., Sabattini, S., et al. (2018) Feline large granular lym- Maunder, C. L., Day, M. J., Hibbert, A., et al. (2012) Serum cobalamin concen-
phocyte lymphoma: an Italian Society of Veterinary Oncology (SIONCOV) retro- trations in cats with gastrointestinal signs: correlation with histopathological
spective study. Veterinary and Comparative Oncology 16, 159-166 findings and duration of clinical signs. Journal of Feline Medicine and Surgery
Fyfe, J. (1993) Feline intrinsic factor (IF) is pancreatic in origin and mediates ileal 14, 686-693
cobalamin (CBL) absorption. Journal of Veterinary Internal Medicine 7, 133 Mavropoulou, A., Grandi, G., Calvi, L., et al. (2010) Disseminated histoplasmosis
Fyfe, J. C., Madsen, M., Højrup, P., et al. (2004) The functional cobalamin (vitamin in a cat in Europe. Journal of Small Animal Practice 51, 176-180
B12)–intrinsic factor receptor is a novel complex of cubilin and amnionless. McEwen, S. A., Valli, V. E. & Hulland, T. J. (1985) Hypereosinophilic syndrome in
Blood 103, 1573-1579 cats: a report of three cases. Canadian Journal of Comparative Medicine 49,
Gouldin, E. D., Mullin, C., Morges, M., et al. (2017) Feline discrete high-grade 248-253
gastrointestinal lymphoma treated with surgical resection and adjuvant CHOP- Minamoto, Y., Otoni, C. C., Steelman, S. M., et al. (2015) Alteration of the fecal
based chemotherapy: retrospective study of 20 cases. Veterinary and Compara- microbiota and serum metabolite profiles in dogs with idiopathic inflammatory
tive Oncology 15, 328-335 bowel disease. Gut Microbes 6, 33-47
Guttin, T., Walsh, A., Durham, A. C., et al. (2019) Ability of ultrasonography to Moore, P. F., Woo, J. C., Vernau, W., et al. (2005) Characterization of feline T cell
predict the presence and location of histologic lesions in the small intestine of receptor gamma (TCRG) variable region genes for the molecular diagnosis of
cats. Journal of Veterinary Internal Medicine 33, 1278-1285 feline intestinal T cell lymphoma. Veterinary Immunology and Immunopathology
Habibi, F., Habibi, M. E., Gharavinia, A., et al. (2017) Quality of life in inflammatory 106, 167-178
bowel disease patients: a cross-sectional study. Journal of Research in Medical Moore, P. F., Rodriguez-Bertos, A. & Kass, P. H. (2012) Feline gastrointestinal lym-
Sciences: The Official Journal of Isfahan University of Medical Sciences 22, 104 phoma: mucosal architecture, immunophenotype, and molecular clonality. Vet-
Hendrick, M. (1981) A spectrum of hypereosinophilic syndromes exemplified by erinary Pathology 49, 658-668
six cats with eosinophilic enteritis. Veterinary Pathology 18, 188-200 Norsworthy, G. D., Scot Estep, J., Kiupel, M., et al. (2013) Diagnosis of chronic
Janeczko, S., Atwater, D., Bogel, E., et al. (2008) The relationship of mucosal bac- small bowel disease in cats: 100 cases (2008-2012). Journal of the American
teria to duodenal histopathology, cytokine mRNA, and clinical disease activity Veterinary Medical Association 243, 1455-1461
in cats with inflammatory bowel disease. Veterinary Microbiology 128, 178-193 Norsworthy, G. D., Estep, J. S., Hollinger, C., et al. (2015) Prevalence and underly-
Jergens, A. E. (2012) Feline idiopathic inflammatory bowel disease: what we know ing causes of histologic abnormalities in cats suspected to have chronic small
and what remains to be unraveled. Journal of Feline Medicine and Surgery 14, bowel disease: 300 cases (2008-2013). Journal of the American Veterinary
445-458 Medical Association 247, 629-635
Jergens, A. E., Moore, F. M., Haynes, J. S., et al. (1992) Idiopathic inflammatory Paulin, M. V., Couronne, L., Beguin, J., et al. (2018) Feline low-grade alimentary
bowel disease in dogs and cats: 84 cases (1987-1990). Journal of the Ameri- lymphoma: an emerging entity and a potential animal model for human dis-
can Veterinary Medical Association 201, 1603-1608 ease. BMC Veterinary Research 14, 306
Jergens, A. E., Schreiner, C. A., Frank, D. E., et al. (2003) A scoring index for Pope, K. V., Tun, A. E., Mcneill, C. J., et al. (2015) Outcome and toxicity assess-
disease activity in canine inflammatory bowel disease. Journal of Veterinary ment of feline small cell lymphoma: 56 cases (2000-2010). Veterinary Medi-
Internal Medicine 17, 291-297 cine and Science 1, 51-62
Jergens, A. E., Crandell, J. M., Evans, R., et al. (2010) A clinical index for disease Posnett, D. N., Sinha, R., Kabak, S., et al. (1994) Clonal populations of T cells in
activity in cats with chronic enteropathy. Journal of Veterinary Internal Medicine normal elderly humans: the T cell equivalent to "benign monoclonal gammapa-
24, 1027-1033 thy". The Journal of Experimental Medicine 179, 609-618
Jergens, A. E., Evans, R. B., Ackermann, M., et al. (2014) Design of a simpli- Reed, N., Gunn-Moore, D. & Simpson, K. (2007) Cobalamin, folate and inorganic
fied histopathologic model for gastrointestinal inflammation in dogs. Veterinary phosphate abnormalities in ill cats. Journal of Feline Medicine and Surgery 9,
Pathology 51, 946-950 278-288
Jergens, A. E., Willard, M. D. & Allenspach, K. (2016) Maximizing the diagnostic Richter, K. P. (2003) Feline gastrointestinal lymphoma. The Veterinary Clinics of
utility of endoscopic biopsy in dogs and cats with gastrointestinal disease. North America. Small Animal Practice 33, 1083-1098, vii
Veterinary Journal 214, 50-60 Rossi, G., Pengo, G., Caldin, M., et al. (2014) Comparison of microbiological, his-
Kiselow, M. A., Rassnick, K. M., Mcdonough, S. P., et al. (2008) Outcome of cats tological, and immunomodulatory parameters in response to treatment with
with low-grade lymphocytic lymphoma: 41 cases (1995-2005). Journal of the either combination therapy with prednisone and metronidazole or probiotic
American Veterinary Medical Association 232, 405-410 VSL#3 strains in dogs with idiopathic inflammatory bowel disease. PLoS One
Kiupel, M., Smedley, R. C., Pfent, C., et al. (2011) Diagnostic algorithm to differ- e94699, 9
entiate lymphoma from inflammation in feline small intestinal biopsy samples. Ruaux, C. G., Steiner, J. M. & Williams, D. A. (2005) Early biochemical and clinical
Veterinary Pathology 48, 212-222 responses to cobalamin supplementation in cats with signs of gastrointestinal
Klaus, J. A., Rudloff, E. & Kirby, R. (2009) Nasogastric tube feeding in cats with disease and severe hypocobalaminemia. Journal of Veterinary Internal Medicine
suspected acute pancreatitis: 55 cases (2001-2006). Journal of Veterinary 19, 155-160
Emergency and Critical Care 19, 337-346 Ruiz, G. C., Reyes-Gomez, E., Hall, E. J., et al. (2016) Comparison of 3 handling
Kokovic, I., Novakovic, B. J., Cerkovnik, P., et al. (2014) Clonality analysis of lym- techniques for endoscopically obtained gastric and duodenal biopsy speci-
phoid proliferations using the BIOMED-2 clonality assays: a single institution mens: a prospective study in dogs and cats. Journal of Veterinary Internal Medi-
experience. Radiology and Oncology 48, 155-162 cine 30, 1014-1021
Kolho, K. L., Pessia, A., Jaakkola, T., et al. (2017) Faecal and serum metabolomics Sabattini, S., Bottero, E., Turba, M. E., et al. (2016) Differentiating feline inflam-
in paediatric inflammatory bowel disease. Journal of Crohn’s & Colitis 11, 321- matory bowel disease from alimentary lymphoma in duodenal endoscopic biop-
334 sies. The Journal of Small Animal Practice 57, 396-401
Kuzi, S., Segev, G., Kedar, S., et al. (2017) Prognostic markers in feline hepatic Scott, K. D., Zoran, D. L., Mansell, J., et al. (2011) Utility of endoscopic biopsies of
lipidosis: a retrospective study of 71 cats. Veterinary Record 181, 512-512 the duodenum and ileum for diagnosis of inflammatory bowel disease and small
Lalor, S., Schwartz, A. M., Titmarsh, H., et al. (2014) Cats with inflammatory bowel cell lymphoma in cats. Journal of Veterinary Internal Medicine 25, 1253-1257
disease and intestinal small cell lymphoma have low serum concentrations of Simpson, K. (2015) Pancreatitis and triaditis in cats: causes and treatment. Jour-
25-hydroxyvitamin D. Journal of Veterinary Internal Medicine 28, 351-355 nal of Small Animal Practice 56, 40-49
Limmer, S., Eberle, N., Nerschbach, V., et al. (2016) Treatment of feline lymphoma Simpson, K. W. & Jergens, A. E. (2011) Pitfalls and progress in the diagnosis and
using a 12-week, maintenance-free combination chemotherapy protocol in 26 management of canine inflammatory bowel disease. The Veterinary Clinics of
cats. Veterinary and Comparative Oncology 14, 21-30 North America. Small Animal Practice 41, 381-398
Lingard, A. E., Briscoe, K., Beatty, J. A., et al. (2009) Low-grade alimentary lym- Simpson, K. W., Fyfe, J., Cornetta, A., et al. (2001) Subnormal concentrations of
phoma: clinicopathological findings and response to treatment in 17 cases. serum cobalamin (vitamin B12) in cats with gastrointestinal disease. Journal of
Journal of Feline Medicine and Surgery 11, 692-700 Veterinary Internal Medicine 15, 26-32

10 Journal of Small Animal Practice • © 2021 British Small Animal Veterinary Association
 Feline chronic enteropathy

Stein, T. J., Pellin, M., Steinberg, H., et al. (2010) Treatment of feline gastrointes- in cats. Journal of the American Veterinary Medical Association 209, 1114-
tinal small-cell lymphoma with chlorambucil and glucocorticoids. Journal of the 1116
American Animal Hospital Association 46, 413-417 Willard, M. D., Jergens, A. E., Duncan, R. B., et al. (2002) Interobserver varia-
Takeuchi, Y., Matsuura, S., Fujino, Y., et al. (2008) Hypereosinophilic syndrome in tion among histopathologic evaluations of intestinal tissues from dogs and
two cats. The Journal of Veterinary Medical Science 70, 1085-1089 cats. Journal of the American Veterinary Medical Association 220, 1177-
Waly, N. E., Stokes, C. R., Gruffydd-Jones, T. J., et al. (2004) Immune cell popula- 1182
tions in the duodenal mucosa of cats with inflammatory bowel disease. Journal Willard, M. D., Mansell, J., Fosgate, G. T., et al. (2008) Effect of sample quality on
of Veterinary Internal Medicine 18, 816-825 the sensitivity of endoscopic biopsy for detecting gastric and duodenal lesions
Waly, N. E., Gruffydd-Jones, T. J., Stokes, C. R., et al. (2005) Immunohistochemical in dogs and cats. Journal of Veterinary Internal Medicine 22, 1084-1089
diagnosis of alimentary lymphomas and severe intestinal inflammation in cats. Xenoulis, P. G., Zoran, D. L., Fosgate, G. T., et al. (2016) Feline exocrine pancreatic
Journal of Comparative Pathology 133, 253-260 insufficiency: a retrospective study of 150 cases. Journal of Veterinary Internal
Washabau, R. J., Day, M. J., Willard, M. D., et al. (2010) Endoscopic, biopsy, and Medicine 30, 1790-1797
histopathologic guidelines for the evaluation of gastrointestinal inflammation in Zwingenberger, A. L., Marks, S. L., Baker, T. W., et al. (2010) Ultrasonographic
companion animals. Journal of Veterinary Internal Medicine 24, 10-26 evaluation of the muscularis propria in cats with diffuse small intestinal lym-
Weiss, D., Gagne, J. & Armstrong, P. (1996) Relationship between inflammatory phoma or inflammatory bowel disease. Journal of Veterinary Internal Medicine
hepatic disease and inflammatory bowel disease, pancreatitis, and nephritis 24, 289-292

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