392_404_FGESF_Linton.

qxp_FAB 31/03/2015 11:58 Page 392

Journal of Feline Medicine and Surgery (2015) 17, 392–404

O R I G I N A L ARtiCle

Feline gastrointestinal eosinophilic

sclerosing fibroplasia: 13 cases and
review of an emerging clinical entity

Objective: Feline gastrointestinal eosinophilic sclerosing fibroplasia (FGESF) is a recently described

Michael Linton1*
BVSc MACVSc inflammatory disease of cats affecting stomach or intestines and draining regional lymph nodes. This study
Judith S Nimmo2
presents clinical and laboratory data on 13 newly described cases from Australia (11) and the UK (two).
BSc BVSc DipPath MSc Observations: The disease was most often observed in middle-aged cats (median 7 years of age;
DipACVP PhD MRCVS interquartile range 5–9 years). Ragdolls (7/13) and males (9/13) were overrepresented. Cats generally had
Jacqueline M Norris3 a long history of vomiting and/or diarrhoea. Lesions were typically large, hard, non-painful, easily palpable
BVSc MVS PhD MASM
GradCertEd
and most commonly situated near the pylorus or ileocaecocolic junction. Lesions were heterogeneous
ultrasonographically and on sectioning at celiotomy or necropsy. Masses were hard and ‘gritty’ on
Richard Churcher4
BVSc FANZCVS fine-needle aspiration due to internal trabeculae made up of mature collagen bundles. Bacteria were
Sophia Haynes5 commonly detected within masses (9/13 cases) using either culture or conventional light microscopy and
BVSc FANZCVS a panel of special stains, and/or fluorescence in situ hybridisation (FISH), although detection often required
Agnieszka Zoltowska6 a diligent search of multiple tissue sections. A consistent bacterial morphology could not be appreciated
BVSc MRCVS among the different cases.
Sunishka Hughes7 Outcome: Patients were treated with a variable combination of cytoreduction (debulking and biopsy,
BVSc
to complete surgical resection), immunosuppressive therapy and antimicrobial agents. Many cats had
Naomi S Lessels7 a poor outcome, which was attributable to late diagnosis combined with suboptimal management. It is
BVSc
hoped that suggestions outlined in the discussion may improve clinical outcomes and long-term survival
Miranda Wright8
VetMB CertSAM MACVSc in future cases.
MRCVS
Richard Malik9
DVSc DipVetAn MVetClinStud
Feline gastrointestinal eosinophilic sclerosing in a case series of 25 cats, 24% of patients were
PhD FACVSc FASM fibroplasia (FGESF) refers to a clinical and euthanased due to the gross appearance of the
1
pathological entity of unknown cause or lesion at laparotomy.1
Eastside Veterinary
Emergency and Specialists, association defined by the presence of Although direct evidence is lacking, it has
10 Newcastle Street, Rose eosinophilic mass(es), largely confined to the been hypothesised that some cats have an, as
Bay, NSW, 2029, Australia
2
ASAP Pathology Laboratory,
gastrointestinal tract and associated lymph yet uncharacterised, genetic predisposition to
53 Glenvale Crescent, nodes.1 it has been diagnosed in cats in the develop eosinophilic inflammation in response
Mulgrave, VIC, 3170, Australia
3
USA, Japan, Europe (including the UK) and, to antigens, possibly from bacteria or parasites,
Faculty of Veterinary Science,
The University of Sydney, most recently, New Zealand.1–5 The prognosis breaching the intestinal mucosa.1 Bacteria have
NSW, 2006, Australia for affected cats is considered guarded. This been isolated from lesions in a substantial
4
North Shore Veterinary may reflect delays in treatment because the proportion of cats, but not in all cases. it is
Specialist Centre, Crows Nest,
NSW, 2065, Australia entity is not commonly considered in the unclear whether the role of bacteria is primary
5
Centre for Animal Referral differential diagnosis of intra-abdominal mass or secondary.1,4,9 other infectious agents have
and Emergency, Collingwood,
VIC 3066, Australia
lesions in cats. Without early diagnosis and been found in association with this entity
6
Your Vets, 1300 Herald Avenue, intervention, the likelihood of a successful including zygomycetes in a domestic cat and
7
Coventry, CV5 6UB, UK outcome is reduced. nematodes (most commonly Cylicospirura
Leslie Street Veterinary Clinic,
Umina, NSW, 2259, Australia Grossly, lesions can be confused with species) in pumas (Felis concolor).5,10
8
Cambridge Cat Clinic, lymphoma, granuloma or adenocarcinoma, As the pathogenesis of FGESF is not well
Fulbourn, CB21 5HE, UK while histologically lesions have been confused understood, the purpose of this study was to
9
Centre for Veterinary
Education, The University of with sclerosing mast cell neoplasia, fibro- contribute insights from additional cases from
Sydney, NSW, 2006, Australia sarcoma or extra-skeletal osteosarcoma.1,6–8 Australia and the UK. our aims were (1) to
*Corresponding author:
michael.linton@
eastsidevets.com.au

Date accepted:
17 December 2014

392 JFMS CLINICAL PRACTICE

doi: 10.1177/1098612X14568170
© iSFM and AAFP 2015
392_404_FGESF_Linton.qxp_FAB 31/03/2015 11:58 Page 393
examine trends in the clinical presentation in
terms of disease associations (diet, history,
breed, gender), and salient physical and
imaging findings; (2) determine whether feline
coronavirus (FCoV), feline herpesvirus type 1
(FHV-1) or specific bacterial species play a role
in the development of this disease through the
use of special stains, immunohistochemistry
(iHC) and/or fluorescence in situ hybridisation
(FiSH); and (3) to speculate as to the underlying
pathophysiology of this enigmatic entity.
Methods
Case selection and clinical data retrieval
This study was initially retrospective, but
developed a prospective arm as eight additional
cases were encountered during case analyses. To
be included in the study, a histological diagnosis
of FGESF had to have been considered by the
original pathologist, and confirmed by a second
pathologist (JSN). Cases were acquired directly by
the authors, or via consultation with colleagues in
general, institutional or private referral practice.
in addition, we contacted veterinary pathologists
in Australia and presented abstracts to the
Australian and New Zealand College of Veteri -
nary Scientists and the annual meeting of the
Australian Society for Veterinary Pathology
to maximise case recruitment and improve
awareness of this emerging entity.
on inclusion into the study, case notes,
clinical images (photographs, radiographs,
ultrasonograms) and formalin-fixed paraffin-
embedded (FFPE) tissue blocks were retrieved.
Patient characteristics, physical findings,
clinicopathological data, procedural reports,
treatment regimens, outcomes (when
available) and necropsy findings were
tabulated into an Excel spreadsheet.
Histology and immunohistochemistry
Cases were classified as FGESF if full thickness
gastrointestinal biopsies and/or incisional
biopsies of mesenteric lymph nodes showed
typical histological features.1 The key findings
were the presence of eosinophilic inflammation
within a characteristic fibroplasia, including
broad mature organised collagen bundles.
Multiple sections were examined to exclude
poorly differentiated mast cell neoplasia and
atypical lymphoma, and to search for hair or
plant material (to exclude trichobezoars).
Special stains were employed mainly to
determine whether or not infectious agents
(bacteria, fungi, protozoa) were present within
lesions; these included Giemsa, methamine
silver, Ziehl–Neelsen (for mycobacteria and
Nocardia species), toluidine blue (for mast cells),
Gram Twort, and periodic acid Schiff (for
fungi). Trichrome stain was sometimes used to
highlight collagen in tissue sections.
O R I G I N A L A R T I C L E / Feline gastrointestinal eosinophilic sclerosing fibroplasia
iHC for FCoV and FHV-1 was performed
(4 µm) of FFPE tissue were mounted on silane-
as described previously.11,12 Briefly, sections
coated slides and dried for 24 h at 37°C to
facilitate tissue adherence to the slide. Slides
were deparaffinised and rehydrated by
submerging in 100% xylol and graded
dilutions of ethanol to water. Antigen retrieval
for FCoV iHC was achieved using working
dilutions of a commercially available antigen
retrieval solution (Target Retrieval Solution,
10 x concentrate; dakoCytomation, CA, USA)
and microwaved for 15 mins, according to
the manufacturer’s instructions.12 Antigen
retrieval for FHV-1 iHC was achieved using a
proteinase K enzymatic method.11 Thereafter
slides were placed in an automated slide
processing system (dakoCytomation Auto-
stainer Plus). Endogenous peroxidases were
blocked by incubating the slides with 0.03%
hydrogen peroxide (Peroxidase Block;
Grossly, dakoCytomation) for 15 mins at room
FGESF can be temperature. Antigen detection was then
achieved by incubating the slides for 60 mins
confused with at room temperature using either a 1/1000
dilution of monoclonal antibody against the
lymphoma, nucleocapsid of FCoV or a 1/200 dilution of
granuloma or monoclonal antibody against the gd
glycoprotein of FHV-1 (FHV7-5; Custom
adenocarcinoma; Monoclonals international, Sacramento, USA).
All slides were incubated with the secondary
histologically,
antibody (Envision Labelled Polymer-HRP
lesions have Anti-mouse; dakoCytomation) for 30 mins at
room temperature. Finally, slides were
been confused incubated for 5 mins at room temperature with
with sclerosing 3,3'-diaminobenzidine (dAB) chromogen
solution (dakoCytomation).
mast cell Slides were thoroughly rinsed with Tris-
buffered saline between each of the above
neoplasia, steps. once the Autostainer had completed the
fibrosarcoma dAB step, slides were rinsed in water,
manually counterstained with haematoxylin,
or extra-skeletal and dehydrated through graded alcohol
dilutions and xylol; a cover-slip was placed
osteosarcoma. prior to microscopic examination. Positive and
negative controls were included in every run.
Fluorescence in situ hybridisation
biopsy specimens, FFPE sections (4 µm) were
To determine if bacteria were present within
mounted on silane-coated slides and evaluated
by FiSH using a eubacterial probe (EUB-338;
GCT GCC TCC CGT AGG AGT).13 Paraffin-
embedded tissue sections were deparaffinised
by passage through 100% xylene and
rehydrated by submerging in graded dilutions
of ethanol (100% to 70%) to water. Slides were
dried at 45°C for 30 mins. FiSH probes 5'
labelled with Cy3 or 6-FAM (Sigma-Aldrich,
Australia) were reconstituted using sterile
water and diluted to a working concentration
of 5 ng/ml with hybridisation buffer (20 mM
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O R I G I N A L A R T I C L E / Feline gastrointestinal eosinophilic sclerosing fibroplasia

Tris-HCl, 0.1% sodium dodecyl sulphate,

Table 1 Historical findings in 13 cats with FGESF
hybridise with 30 µl of dNA probe mix in a
0.9% NaCl [pH 7.5]). Sections were allowed to
Owner-reported clinical signs Number (percentage) of patients
hybridisation chamber at 46°C for 14 h. Slides
were rinsed in wash buffer (hybridisation Chronic vomiting and diarrhoea 11/12 (91%)
buffer without SdS) at 48°C for 30 mins. Weight loss 10/13 (77%)
Hybridised samples were washed in Lethargy 8/13 (62%)
phosphate-buffered saline, allowed to dry, and Acute vomiting 7/13 (54%)
mounted with a ProLong Antifade Gold
Excessive grooming (5/10) 50%
reagent (Molecular Probes, oR, USA). Sections
Anorexia 6/13 (46%)
were examined under a fluorescent microscope
Acute diarrhoea 5/13 (38%)
(olympus model BX60F-3).
Control samples consisted of FFPE tissues Coughing 1/13 (8%)
prepared by making a ‘bacterial sandwich’ No clinical signs reported 1/13 (8%)
using lung tissue.14 Control bacteria in these FGESF = feline gastrointestinal eosinophilic sclerosing fibroplasia
preparations included Staphylococcus aureus,
Pseudomonas aeruginosa, Escherichia coli or
Clostridium perfringens. Probe specificity
was additionally evaluated using tissue Table 2 Physical examination findings in 13 cats with
sections treated with ribonuclease and also FGESF
using the irrelevant probe non-EUB-338 (ACT Abnormal physical exam findings Number (percentage) of patients
CCT ACG GGA GGC AGC).
Abdominal mass 11/13 (85%)
Following evaluation by FiSH with
eubacterial probes, new slides were prepared Abdominal pain 3/12 (25%)
for examination with specific probes to Pyrexia 2/11 (18%)
characterise fluorescent bacteria further as Dyspnoea 1/13 (8%)
being either Clostridium species (5' GTT ATC FGESF = feline gastrointestinal eosinophilic sclerosing fibroplasia
CGT GTG TAC AGG G-3'; 5' TTA TGC GGT
ATT AAT CTY CCT TT -3') or E coli (5' GCA
AAG GTA TTA ACT TTA CTC CC 3') using
adjusted hybridisation and wash solutions.15 Results

Statistical analysis Thirteen cats met the inclusion criteria and were
Fisher’s exact tests were conducted to recruited into the study. All cases were
determine whether the observed gender or neutered. There was a preponderance of male
breed of cats with FGESF differed significantly cats (9/13 cases; P = 0.10) compared with the
from expected frequencies. Expected breed reference population in Toribio and colleagues’
frequencies were based on the Companion survey.16 The median age of cases was 7 years
Animals Register for New South Wales (NSW) (range 2–11 years; interquartile range 5–9 years).
for 2011 (containing breed data for 439,145 There were seven Ragdolls, one Persian and
registered cats). Results were considered five domestic shorthair cats. The observed
significant if P <0.05. frequency of breeds diagnosed with FGESF
differed significantly from that expected based
on the NSW Companion Animals Register
data for 2011. Ragdolls were significantly over-
represented (P <0.0001; Fisher’s exact test)
compared with the reference population (Figure
1). Cats had been fed various diets, typically a
mixture of commercial canned and extruded
dry food; raw meaty bones had not been fed
regularly to any of the patients.
The reported clinical signs and physical
examination findings are listed in Tables 1 and
2. Pertinent findings included weight loss and
a history of chronic vomiting and/or diarrhoea
Figure 1 Observed of at least 3 months’ duration (usually greater
frequency of each breed for than 12 months). When owners identified
cats with confirmed FGESF
(blue bars). Red bars show antecedent clinical signs, they were observed
expected breed frequencies between 2 days and up to 5 months prior to
based on registration data
from the Companion presentation. There was no history of previous
Animals Register, New foreign body or hairball obstruction in any of
South Wales, Australia.
DSH = domestic shorthair
the patients.

394 JFMS CLINICAL PRACTICE

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O R I G I N A L A R T I C L E / Feline gastrointestinal eosinophilic sclerosing fibroplasia

A firm, irregular, fixed abdominal mass in

the cranial and/or mid-abdomen was the most
common physical finding (Figures 2 and 3).
one cat (case 2) had an atypical presentation
with dyspnoea due to pleural effusion
(Figure 4). Two cats did not have a palpable
abdominal mass at presentation but were
lethargic, anorexic and had a history of
vomiting. Partial serum biochemistry analyses
were available for 12 cats; findings are
summarised in Table 3. Hyperproteinaemia
referable to hyperglobulinaemia was present Figure 2 Intraoperative Figure 3 Photograph of the resected jejunal mass from
photograph of the pyloric case 10. The intestinal lumen has been completely obliterated,
in 7/11 cats. Hypoalbuminaemia was present lesion in case 11. Marked resulting in signs of intestinal obstruction. The arrow denotes
in 5/11 cases, with the albumin/globulin ratio thickening of the pyloric wall a region of caseous necrosis; arrowheads identify foci of
is evident mature collagen
<0.6 in 7/11 cases. Protein serum electro-
phoresis showed a polyclonal gammopathy in
case 3, with beta–gamma bridging, the alpha 1 A firm, irregular, fixed abdominal mass in
and alpha 2 globulins being normal. Elevated
urea and creatinine concentrations were
the cranial and/or mid-abdomen was the most
identified in case 5. Two cats had common physical finding in this series of cats.
hypocalcaemia, most likely due to hypo-
albuminaemia. Hyperbilirubinaemia was
present in one patient (case 6).

Table 3 Serum biochemical findings in 13 cats with FGESF. Abnormally high values are highlighted in yellow;
abnormally low values in red
Analyte Case Case Case Case Case Case Case Case Case Case Case Case Case Reference interval
1 2 3 4 5 6 7 8 9 10 11 12 13
Sodium 151.0 144.0 146.0 149.0 205.0 N/A N/A 152.0 153.0 N/A 165.0 147.0 N/A 144.0–158.0 mmol/l
Potassium 4.1 4.2 4.9 4.4 4.7 N/A N/A 4.2 4.0 N/A 3.4 4.4 N/A 3.7–5.4 mmol/l
Chloride 118.0 113.0 116.0 112.0 178.0 N/A N/A 115.0 N/A N/A 131.0 118.0 N/A 106.0–123.0 mmol/l
Bicarbonate 15.0 21.0 21.0 25.0 N/A N/A N/A N/A N/A N/A N/A 17.0 N/A 12.0–24.0 mmol/l
Na/K ratio 36.8 34.3 29.8 30.0 45.6 N/A N/A 36.2 N/A N/A 48.5 33.4 N/A >29.0
Anion gap 22.1 14.2 13.9 16.4 N/A N/A N/A 19.1 N/A N/A N/A 16.4 N/A 15.0–31.0 mmol/l
Glucose 5.6 5.0 N/A N/A N/A N/A N/A 4.7 8.7 N/A N/A 5.3 N/A 3.2–7.5 mmol/l
(FlOx)
Glucose 6.4 4.8 5.4 5.4 4.7 6.3 N/A N/A N/A 7.3 N/A 4.7 4.9 3.2–7.5 mmol/l
(serum)
Urea 10.3 8.2 6.1 8.8 20.3 7.5 N/A 13.0 5.7 9.0 N/A 5.2 6.1 5.0–15.0 mmol/l
Creatinine 100 100 100 160 239 200 N/A 200 100 70 N/A 100 126 80–200 µmol/l
Calcium 2.4 2.0 2.2 2.4 2.4 2.1 N/A 2.4 2.3 N/A N/A 2.0 2.2 2.1–2.8 mmol/l
Phosphate 1.7 1.3 2.0 1.1 1.8 1.3 N/A 1.5 1.6 N/A N/A 1.4 1.2 1.0–2.3 mmol/l
Protein 138.0 135.0 96.0 62.0 120.0 78.0 N/A 71.0 57.0 105.0 N/A 113.0 67.0 60.0–84.0 g/l
(total)
Albumin 25.0 18.0 20.0 30.0 25.0 24.0 N/A 34.0 26.0 N/A 21.0 20.0 27.0 25.0–38.0 g/l
Globulin 113.0 117.0 76.0 32.0 95.0 55.0 N/A 37.0 31.0 N/A 61.0 93.0 40.0 31.0–52.0 g/l
A/G ratio 0.2 0.2 0.3 0.9 0.3 0.4 N/A 0.9 0.8 N/A 0.3 0.2 0.7
Bilirubin 4.0 3.0 6.0 2.0 7.0 11.0 N/A 2.0 N/A N/A N/A 3.0 5.0 <7 µmol/l
ALP 13.0 10.0 5.0 34.0 27.0 20.0 N/A 33.0 24.0 15.0 25.0 9.0 22.0 5.0–50.0 IU/l
AST 88.0 30.0 39.0 23.0 N/A N/A N/A 34.0 N/A N/A N/A 31.0 N/A 0–62.0 IU/l
ALT 26.0 20.0 14.0 48.0 10.0 <10 N/A 61.0 17.0 34.0 23.0 24.0 N/A 0–100.0 IU/l
CK 188.0 74.0 93.0 170.0 N/A N/A N/A 197.0 N/A N/A N/A 105.0 N/A 64–400.0 IU/l
Cholesterol 2.9 1.1 2.5 3.8 3.3 2.9 N/A 3.6 N/A N/A 2.8 2.8 2.8 2.2–5.5 mmol/l
GGT N/A N/A <2 N/A N/A N/A N/A 5.0 1.0 N/A <0 6.0 <0 <6.0 IU/l
FGESF = feline gastrointestinal eosinophilic sclerosing fibroplasia, N/A = not available, Na/K ratio = sodium/potassium ratio, A/G ratio = albumin/
globulin ratio, ALP = alkaline phosphatase, AST = aspartate aminotransferase, ALT = alkaline transaminase, CK = creatine kinase, GGT = gamma-
glutamyl transferase

JFMS CLINICAL PRACTICE 395

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O R I G I N A L A R T I C L E / Feline gastrointestinal eosinophilic sclerosing fibroplasia
Figure 4 Lateral thoracic radiograph from case 2 presented for respiratory
distress. Note the pleural effusion (most evident cranioventrally) and prominent
sternal lymph node (arrow). Although this is an atypical presentation, it is
important to emphasise that some cases of FGESF can present with bicavitary
involvement, the disease process starting in the abdomen and spreading to the
thoracic cavity, presumably due to drainage of abdominal lymphatics to the
sternal lymph node. A similar observation was reported recently3
Partial haematology results were available
for 11 cats (Table 4). Peripheral eosinophilia
was present in 5/10 cases. Case 3 had
eosinophilia 2 days after initial presentation,
the eosinophil count having been within the
reference interval on presentation. Two cats
had a mild non-regenerative anaemia (cases
5 and 9), one of which also had a dis-
proportionately elevated serum urea
concentration (case 5) compared with the
creatinine concentration (Table 3), consistent
with gastrointestinal bleeding, dehydration or
concurrent renal disease; unfortunately urine
specific gravity was not recorded. Serological
testing for feline leukaemia virus antigen and
feline immunodeficiency virus antibody was
conducted in two patients and was negative
in both instances. Where haematology and
biochemistry were monitored in surviving
animals (after therapy), both eosinophilia and
hyperglobulinaemia had resolved.
Figure 6 Ultrasound image of the pyloric lesion (denoted by +) of case 11.
Note the loss of layering with the mixture of hypoechoic and hyperechoic
regions within the tissue. It is thought that the hyperechoic regions correspond
with the fibrotic zones described histologically4
396 JFMS CLINICAL PRACTICE
Figure 5 Histology of the resected lesion from case 10. The characteristic
network of coarse collagen trabeculae (staining pink) throughout the lesion
is an important distinguishing feature of FGESF. This abundance of collagen
causes the hard, gritty texture of these lesions, which is most obvious during
biopsy procedures (or during dissection at necropsy). Haematoxylin and eosin,
x 400 magnification
Histological examination was performed in
all 13 cases (Figure 5). Histopathology in all
gastrointestinal sections showed areas of
sclerosing fibroplasia characterised by broad
trabeculae of fibrous tissue interspersed by
fibroblastic cells and dotted with foci of
inflammation and necrosis. Sometimes these
necrotic areas contained bacteria. Examination
revealed that inflammation was mixed but
predominantly eosinophilic and often of
varying degrees of intensity. In 2/13 cases,
the initial histopathological diagnosis (extra-
skeletal osteosarcoma and fibrosarcoma) was
revised after review of the original sections in
concert with clinical and surgical features
(cases 2 and 5). In three cases there was some
initial debate as to whether the lesions were
due to inflammation or a fibrosarcoma;
however, all lesions were eventually classified
as being inflammatory in nature. There was
no evidence of eosinophilic enteritis or other
Figure 7 Ultrasound image from case 11, demonstrating an enlarged
mesenteric lymph node (8 mm x 14 mm)
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O R I G I N A L A R T I C L E / Feline gastrointestinal eosinophilic sclerosing fibroplasia

Case 13 Reference interval

FGESF = feline gastrointestinal eosinophilic sclerosing fibroplasia, RBC = red blood cells, MCV = mean cell volume, MCH = mean cell haemoglobin, MCHC = mean cell haemoglobin concentration,
4.9–10.0 x 1012/l

300–800 x 109/l
5.5–19.0 x 109/l

2.5–12.5 x109/l
2.0–3.0 x 109/l
0.9–7.0 x 109/l
13.0–17.0 pg
0.25-0.48 l/l

282–333 g/l
43.0–55.0 fl

<0.7 x 109/l
<1.1 x 109/l
<0.1 x 109/l
77–156 g/l

0.0–0.4%
Haematological findings in 13 cats with FGESF. Abnormally high values are highlighted in yellow; abnormally low values in red

N/A
N/A
N/A

N/A

N/A
N/A

N/A
N/A

N/A
N/A

N/A
N/A
N/A
N/A
N/A
N/A
Clumped
Case 12

<0.1
0.32

42.0

12.0

14.3

N/A
297

331
0.4

2.9
0.6
3.6
7.7

7.3
95

Clumped and
adequate
Case 10 Case 11

Figure 8 Intraoperative photograph from case 13. Note the

0.35

45.4

36.4
14.4

15.0

16.0
marked enlargement of the lymph nodes (arrow) at the root of

N/A
122

317

0.2

3.6
0.5

1.4
7.7

82

the mesentery. This is a common feature of FGESF as well as

other disease entities such as lymphoblastic B cell lymphoma5
21.16

18.16
0.30

40.0

13.0
N/A

N/A
N/A

N/A

N/A
N/A
322

322

1.4
1.3
7.3

forms of inflammatory bowel disease (iBd)

in cases where normal gastrointestinal tissue
Clumped

adjacent to the lesion was available for

Case 7 Case 8 Case 9

<0.1
0.23

49.1

53.4

21.8

26.3

microscopic assessment.
N/A

N/A

N/A

N/A
327

365
4.7

2.7
76

Lesions were situated at the ileocaecocolic

junction (eight cats), pylorus (two cats;
<0.1
9.61

0.41

42.8

12.7

N/A

N/A

N/A
296
122

Figure 6) and greater curvature of the stomach

0.1

9.1

6.9
1.7
0.2
0.3

(one cat). in two patients, the exact site could

not be established from the case notes.
N/A
N/A
N/A

N/A

N/A
N/A

N/A
Clumped and N/A

N/A
N/A

N/A
N/A
N/A
N/A
N/A
N/A

Mesenteric lymphadenomegaly was noted

in 10/13 patients (Figures 7 and 8);
microscopically, the lymph nodes exhibited
adequate

lymphoid hyperplasia and eosinophilia.

Case 6

14.58

Bacteria were identified in 9/13 cases using

<0.1
0.38

50.0

19.5

N/A
292

215
111

1.0

8.9
3.3
0.8
6.4
7.6

a combination of cytology, histology using

special stains, FiSH and/or culture of
Case 4 Case 5

representative tissue specimens obtained

0.24

13.1

13.3
N/A

N/A

N/A

N/A
N/A

N/A

N/A
N/A
N/A
N/A
N/A
324
83

surgically or with a spring-loaded core biopsy

device (Table 5). in 4/13 cases, one pathologist
(JSN) identified bacteria using conventional
0.38

46.0

15.0

N/A
Clumped and N/A

N/A
N/A
330

359
124
8.2

6.5

3.6
2.7
0.1
0.2

light microscopy whereas the original

pathologist did not. in two of these four cases,
bacteria were identified using special stains,
adequate
Case 3

while they were not originally detected in

0.34

43.0

13.0
7.93

N/A

N/A

N/A
N/A
304
103

haematoxylin and eosin stained sections. in the

6.3

4.2
1.1
0.2
0.9

two other discordant cases, the discrepancy

Clumped Clumped and

may have been due to sampling bias, as the

reference pathologist examined material re-cut
adequate
Case 2

from tissue blocks supplied by the original

<0.1
0.27

50.0

15.0

N/A

N/A
296

226

laboratory.
5.4

5.2
1.1
0.5
0.8
7.6
80

in all three cases in which tissue specimens

were submitted for microbiology, bacteria were
Haematological value Case 1

0.39

39.0

isolated (Table 5). Specifically, E coli and a light

10.0

13.0

15.3
N/A

N/A
331
129

312

8.0
2.4
0.3
4.4
0.2

mixed growth of anaerobes were isolated from

the pyloric lesion in case 11; Providencia stuartii
Total white cell count

was cultured from a mesenteric lesion in case

N/A = not available

12; and a combination of E coli, a Bacteroides

Platelet count
Reticulocytes
Haemoglobin

Lymphocytes

Granulocytes

species, Enterococcus durans and a Fusobacterium

Haematocrit

Eosinophils
Neutrophils

Monocytes

Basophils
Table 4

species was cultured from pus aspirated from

Platelets
MCHC

mesenteric lymph nodes (on different

MCH
MCV
RBC

occasions) in case 3. Toxoplasma gondii tachy-

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O R I G I N A L A R T I C L E / Feline gastrointestinal eosinophilic sclerosing fibroplasia

Table 5 Summary of microbiological and gastrointestinal histopathological findings

in 13 cats with FGESF
Case Bacterial morphology Presumptive microbial Culture of tissue FISH
detected on histology diagnosis based on special
stains or histology*
1 Gram +ve bacilli Clostridium species N/A† Bacilli detected with EUB
Gram +ve cocci probe
Gram –ve bacilli Probe for Clostridium
detected
2 Gram +ve bacilli Clostridium species N/A† None detected with EUB
probe or specific probes
3 Filamentous and beaded Actinomyces species E coli, Bacilli detected with EUB
bacilli Bacteroides species, probe but not with specific
Enterococcus durans, probes
Fusobacterium
species
4 None identified N/A N/A† None detected with EUB
probe or specific probes
5 Club colony cocci Staphylococcus N/A† None detected with EUB
Bacteria have
Actinomyces probe or specific probes
been isolated
6 Gram +ve bacilli Not reported N/A† Bacilli detected with EUB
Filamentous and beaded
bacilli
probe but not with specific
probes
from lesions in
7 Coccobacilli Not reported N/A† Bacilli detected with EUB a substantial
probe but not with specific
probes proportion of
8 None identified N/A N/A† None detected with EUB
probe or specific probes cats, but not in
9 None identified N/A N/A† None detected with EUB all cases of
probe or specific probes
10 Gram +ve cocci E coli N/A† Bacilli detected with EUB FGESF. It is
Gram –ve bacilli Mixed anaerobes probe. Specific probe for
Gram +ve bacilli E coli detected unclear
11 Gram +ve bacilli Clostridium species E coli, plus a light Bacilli detected with EUB
growth of mixed probe whether the
anaerobes‡ Probe for Clostridium
detected role of bacteria
12 None identified N/A Providencia stuartii No tissue specimen available
is primary or
13 None identified N/A N/A† None detected with EUB
probe or specific probes secondary.
FGESF = feline gastrointestinal eosinophilic sclerosing fibroplasia, FISH = fluorescence in situ hybridisation,
EUB probe = eubacterial probe, N/A = not available
*Immunohistochemistry was negative for feline coronavirus (FCoV) and feline herpesvirus-type 1 (FHV-1) in 12/12
cats tested
†Insufficient tissue available
‡Culture and susceptibility testing of tissue from lumen of pylorus suggestive of bacterial contamination

zoites were identified from case 7 after the
administration of chlorambucil and pred -
nisolone; no evidence of toxoplasmosis had
been identified in the original sections. FiSH
confirmed cases 1 and 11 to have Clostridium
species present and case 10 to have E coli, while
cases 3, 6 and 7 had bacilli detected via the
eubacterial probe but no specific identification
was possible using the specific probes selected.
FiSH and histopathology (including special
stains) produced discordant findings in two
instances where histology and special stains
identified bacteria but FiSH did not (cases 2 and
5). Finally, FiSH and conventional histology
(including special stains) identified bacteria of
different morphology in case 7.
iHC was conducted on representative tissue
specimens from 12 cases. FHV-1 and FCoV
antigen could not be detected in any of the
tissue specimens examined.
Case outcome and/or results of treatment
Eight of 13 cats died or were euthanased. Three
cats died perioperatively (cases 1, 5 and 11);
two had lesions at the pylorus and one in the
ileocaecocolic region. one cat (case 1)
developed sepsis, one was found dead in its
cage 24 h post-surgery, while another (case 11)
was speculated to have died of anaesthetic
complications attributable to hypertrophic
cardiomyopathy. one cat was euthanased due
to poor response to therapy and an incorrect

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O R I G I N A L A R T I C L E / Feline gastrointestinal eosinophilic sclerosing fibroplasia
a had not been preserved.
Figure 9 (a) Kaplan-Meier
plot of survival for all
13 cats with FGESF.
(b) Comparison of survival
between cats treated with
and without prednisolone.
b (c) Comparison of survival
between cats treated with
complete surgical
resection and antibiotics
(no immunomodulatory
therapy) – labelled
‘Surgery’; surgical
resection (complete or
incomplete resection) with
immunomodulatory
therapy and antibiotics –
labelled ‘Combination’;
and no surgery (cases
diagnosed on incisional
biopsy and treated with
antibiotics, dietary
management ±
immunomodulatory
c therapy) – labelled
‘Medical management’
histological diagnosis (case 2). Mean survival
time for cats that died or were euthanased was
3–152 days.
Five surviving cats were alive at the time of
writing, with survival after diagnosis ranging
from 1–10 years (Figure 9a). The impact of
treatment selection on survival is summarised
in Figure 9b,c. The number of cats receiving
different treatment regimens precluded mean-
ingful statistical analysis. When information
was available, most surviving cats had com-
plete resolution of clinical signs (ie, vomiting
and diarrhoea) with no recurrence of a palpa- The tissue of FGESF lesions is hard and often
ble intra-abdominal mass. The exception was
case 3, which was subjected to multiple ‘gritty’, due to abundant trabeculae of mature
surgeries and antibiotic regimens over a 10
organised collagen. This is a useful point of
year period and only appeared to be in remis-
sion through a combination of immuno - differentiation from other common
modulatory treatment (prednisolone) and
antibiotics (amoxicillin and clavulanic acid). intra-abdominal masses of cats.
Discussion
Clinical features
FGESF is a newly recognised entity. it is being
diagnosed more often because of increased
recognition by clinicians and pathologists
following definitive diagnosis via biopsy.1 This
concept is supported by one case from 2004
being diagnosed retrospectively in the current
series, and another from 1996 which could not
be included because the detailed case notes
in this study, most cats were mature adults
(median 7 years), although cats of almost any
age (2–11 years) were affected. So far, the
entity has not been described in kittens.
Longhaired cats and specifically the Ragdoll
breed were overrepresented in this study.
Such a preponderance has not been recorded
previously. Study of the genetic relationship
between affected cats may be informative,
but pedigrees were not retrievable in most
instances. dNA from affected cats has been
archived to facilitate future molecular genetic
investigations. Alternately, there might be
another feature of Ragdolls, such as their long
hair coat (with increased ingestion of hair,
associated allergens and entrapped plant
material), which predisposes to the develop-
ment of FGESF.
Most cats had a palpable mass in the
abdomen, which was typically fixed in position
at presentation. often there was a peripheral
eosinophilia. Mass lesions often contained
bacteria. This is hardly surprising, as the
lesions were frequently ulcerated and
communicated with the lumen of the
gastrointestinal tract, as observed in this study.
Critically, when the mass lesions are subjected
to aspiration, core biopsy or excision at
laparotomy, the tissue is hard, and on many
occasions ‘gritty’ on advancing the needle,
biopsy device or scalpel blade, due to
abundant trabeculae of mature organised
collagen. This is a useful and inexpensive
point of differentiation from other common
intra-abdominal masses of cats, such as large
cell lymphoma, mast cell neoplasia and
non-scirrhous adenocarcinoma, and it is con-
ceivable that this would give a distinctive
appearance on computed tomography.
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Figure 10 Ultrasound image

of the jejunum of case 11.
Note the generalised wall
thickening (3.3 mm),
denoted by (+). Normal
layering of the intestinal wall
has been preserved. It is
thought that this cat was
also suffering from
inflammatory bowel disease,
namely eosinophilic
enteritis, although this
was not confirmed
histopathologically

The most consistent historical features were elaboration of iL-6 and MBP can result in
chronic vomiting and/or diarrhoea, which fibroplasia and fibrosis.19–22 This self-
were typically ascribed to dietary hyper- perpetuating process presumably gives rise
sensitivity, food intolerance or iBd (Figure 10). to an abdominal mass, while structural
However, in normal gastrointestinal tract alterations to the stomach, intestines,
adjacent to lesions, there was no histological mesenteric lymph nodes, enteric nervous
evidence of eosinophilic enteritis or iBd. it system and lymphatic drainage result in
Pertinent might be informative to examine other vomiting, diarrhoea and poor appetite.23,24
historical portions of the gut in future cases to confirm it would be informative to perform cytokine
or refute the presence of more widespread profiling from affected cats.25
findings in this alimentary disease. Eosinophilia, as in previous studies, was the
most consistent haematological abnormality in
series of cats Aetiopathogenesis this series of cats with FGESF, being evident in
included it has been hypothesised that affected cats 5/11 cases. Eosinophils are often specifically
suffer from immunological dysregulation linked with the presence of metazoan
weight loss, triggered by one or more factors. The trigger pathogens, fungi, viruses and sometimes
might be dietary (food allergy or intolerance), bacteria that release unusual antigens into
and chronic dysbiosis of the gut microbiota or other tissues, or diseases affecting mast cells
vomiting and/or predisposing factors (ingestion of ecto - (typically mast cell tumours and hyper-
parasites, endoparasites, excessive ingested sensitivity disorders).11,26–29 The reason why
diarrhoea of at hair or plant material). in pumas, nematodes some cats have normal eosinophil numbers in
least 3 months’ have been reported as a possible trigger, with peripheral blood remains unknown, although
these felids showing a similar histo- both endogenous and exogenous gluco-
duration pathological reaction pattern to domestic cats corticoids could play a role in reducing counts
with FGESF; it is conceivable that ascarids or to normal levels.30 FGESF should be considered
(and usually other helminths might do the same in cats.10 in cats with peripheral eosinophilia and an
greater than in one case series, lymphoma was identified abdominal mass, as cats with neoplasia tend to
at the site of an FGESF lesion.4 in the present have a stress-induced eosinopenia. Para-
12 months). study, cases were seen at different stages in the neoplastic eosinophilia can also be seen with
evolution of the lesions, which hinders an intra-abdominal lymphoma.31 Additionally,
accurate determination of disease chronology. FGESF cannot be excluded when eosinophilia
Secondary infection with bacteria, protozoa, is absent.
fungi or other infectious agents is facilitated iHC was performed to exclude the
by the abnormal tissue architecture associated involvement of FHV-1 in FGESF because
with a breach in mucosal integrity.17,18 herpetic disease is linked enigmatically with an
Secondary infections presumably further eosinophilic response in cats, specifically
perpetuate the whole process, causing a eosinophilic dermatitis, conjunctivitis and
vicious cycle of eosinophilic inflammation, keratitis.11,32 Hyperglobulinaemia was the most
fibroplasia and eventually fibrosis. common biochemical abnormality in FGESF
Eosinophilic inflammation is a defining cases. Protein electrophoresis showed a
feature of this condition. Eosinophils produce polyclonal gammopathy with beta–gamma
numerous mediators that lead to tissue bridging in one patient (case 3), non-specific
destruction (major basic protein [MBP], changes consistent with inflammation. The
transforming growth factor beta [TGF-β], secondary hypoalbuminaemia present in some
interleukin-1 beta [iL-1b], etc), while cats was presumably due to hepatic down-

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O R I G I N A L A R T I C L E / Feline gastrointestinal eosinophilic sclerosing fibroplasia

regulation of albumin synthesis associated
with elevated globulin levels, and
compounded by albumin loss into the
gastrointestinal lumen. The albumin/globulin
ratio was <0.6 in 7/11 cats tested.
Hyperglobulinaemia and a low albumin/
globulin ratio are frequently associated with
feline infectious peritonitis (FiP).33 This is
important because pyogranulomatous lesions
reminiscent of FGESF can occur in young
adult cats with non-effusive FiP with massive
mesenteric lymphadenomegaly or ileo-
caecocolic lesions in association with high
globulin and low albumin concentrations.34–36
FCoV iHC was, therefore, performed to exclude
FGESF should be considered in cats with peripheral
eosinophilia and an abdominal mass, but cannot be
excluded when eosinophilia is absent.
the possibility of atypical non-effusive FiP.
in 12 tissue specimens tested, iHC was
negative for both FHV-1 and FCoV/FiP viral
antigens. Therefore, it appears unlikely that
FHV-1 or FCoV contribute to the pathogenesis
of FGESF.

Microbial agents of disease

The search to find a plausible causative microbial pathogen involved in the early pathogenesis of this syndrome. T gondii
underlying FGESF has been the focus of several studies. The tachyzoites were identified in lesions obtained at necropsy from
location of most lesions in close proximity to or in actual one cat (case 7). It was likely that disseminated toxoplasmosis
communication with areas containing normal bacterial flora developed in this cat as a consequence of immunosuppression
makes establishing disease associations complicated. In one secondary to prednisolone and chlorambucil treatment, as no
study where FGESF-like lesions were identified in the abdominal tachyzoites or even bradyzoite cysts were evident in the initial
cavity, subcutaneous and cervical regions, Gram-positive cocci biopsy specimens. In this study, six other cases were treated
were identified in 23/27 cats.9 In another study, 14/25 (56%) cats using prednisolone (including one other where prednisolone was
had bacteria detected histologically in abdominal lesions, which given in concert with chlorambucil) and none of these cats
is in good agreement with 9/13 (69%) detected in this present developed toxoplasmosis.
series of cases (Table 5).1 Microscopically, inflammation was FISH is used in research to describe the composition of
focused around bacteria, suggesting that, at least in some bacterial communities using labelled oligonucleotide probes
patients, bacteria played a role in either and is an evolving tool that may become
initiating or perpetuating the disease The location of most routinely available for clinical cases.37
process.1 In this study, bacteria were The use of probes labelled with different
cultured from three cases. In case 11, FGESF lesions in close fluorochromes allows distinction between
E coli was cultured anaerobically from proximity to or in actual different genera and sometimes species of
pyloric tissue, which probably reflected intact bacteria. A limitation of this study
contamination because bacilli mor- communication with was that only specific probes for E coli and
phologically consistent with Clostridium Clostridium were used due to the
species were identified using special
areas containing normal unavailability of other target probes for
stains and FISH within the mural lesions bacterial flora makes organisms. Limited availability of specific
from this patient. FISH probes may have led to an
The process by which infectious agents establishing disease underestimation of the diversity of bacteria
penetrate gastric or intestinal mucosa is associated with this disease. Specifically,
not well understood. Foreign material
associations bacteria were identified in three cases with
(plant matter, ingested hair, partially complicated. the universal bacterial probe that could not
digested bones) could play a role because be classified further (Table 5). In case 3,
of the high prevalence of lesions at the bacterial morphology was suggestive of an
pylorus and ileocaecocolic junction.1 These are sites where Actinomyces species; however a specific actinomycete probe
ingesta propelled by peristalsis undergoes a sharp change of was not available.
direction. Thus, penetration by foreign material is more likely to Interestingly, two cases negative for bacteria using the
occur at these sites. Review of patient histories yielded no eubacterial probe could be identified using histology and special
evidence of raw bone ingestion or previous gastrointestinal foreign stains (Table 5). This observation is supported by a
body obstruction. However, 50% of cases in this series had a human review where eubacterial FISH only identified 56%
history of over-grooming, which could support the possibility that of bacteria on average (range 1–100%).37 Factors such as
irritation by hair-containing ingesta or hairballs moving though the the inability of probes to penetrate the bacteria during
alimentary tract facilitated bacterial invasion or translocation. hybridisation, nucleotide mismatching of the very specific
It is noteworthy that 4/13 patients in this study did not have oligonucleotide used or suboptimal hybridisation conditions
detectable bacteria within lesions, although insufficient tissue (reagents, temperature) may all play a part in what is a very
was available for these four cases to permit the use of all specific reaction. The diversity of bacteria involved in FGESF
diagnostic procedures. Despite this limitation, the absence of lesions might best be determined using a next generation
bacteria suggests that infectious agents are not invariably sequencing approach (pyrosequencing).

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O R I G I N A L A R T I C L E / Feline gastrointestinal eosinophilic sclerosing fibroplasia
Diagnostic imaging and exploratory
laparotomy
Non-invasive tests such as imaging (radiology,
ultrasonography, computed tomography)
combined with needle aspiration are required
to make a provisional diagnosis of FGESF
and exclude alternative possibilities such
as neoplasia and non-effusive FiP. Ultra-
sonographic changes are non-specific,
consisting of solitary masses with mural
thickening and loss of layering in the stomach,
duodenum, jejunum or colon.4 one report
suggests that endoscopy may be insensitive
where lesions fail to extend to the mucosa.3
Given the extent of the disease process, size
of the lesions (up to 10 cm diameter) and the
heterogeneous nature of the pathological
processes within lesions (especially the
distribution of bacteria), definitive staging and
therapy requires laparotomy in most instances.
Possibly this is not the case when disease is
detected earlier, as lesions are more focal and
thus limited in extent.
Histopathology
inflammation in gastrointestinal tissue was
generally mixed but predominantly eosino-
philic. The extent that other inflammatory cells
were admixed might be affected by factors such
as the presence or absence of (secondary)
bacteria, and indeed which bacteria were
involved. Histology, although typically
characteristic, can be misleading. For example,
in one study, five cases were initially diagnosed
as mast cell tumours, two as osteosarcomas and
one as a haematopoietic neoplasm.1 in this
series, case 2 was initially misdiagnosed as an
extra-skeletal osteosarcoma and case 5 as a
fibrosarcoma. The differentiation of FGESF
from sclerosing mast cell tumours is still
debated.6–8 in our series, toluidine blue staining
failed to show any consistency in the number or
distribution of mast cells. Mast cells varied from
scant to moderately numerous, but were always
in a multifocal inflammatory distribution, and
never formed mass lesions. Furthermore, the
biological behavior of FGESF is not consistent
with a mast cell malignancy. For this reason, it
is prudent that clinician and pathologist liaise
to ensure special stains are employed to make
a definitive diagnosis in patients with atypical
intra-abdominal mass lesions.
Optimal therapy
due to the largely retrospective nature of this
study, a variety of therapeutic regimens were
trialled: surgery, and various combinations of
antimicrobial agents, corticosteroids, alky -
lating agents, gastrointestinal protectants and
analgesics. it is, therefore, difficult to make
definitive statements concerning which
regimens worked best.
402 JFMS CLINICAL PRACTICE
in spite of these limitations, there was a trend
It is prudent towards improved survival times when
that clinician prednisolone was included in the therapeutic
regimen and when surgery was not the sole
and pathologist mode of therapy (Figure 9b,c). However, this
latter statement is logically flawed because not
liaise to ensure all surgical cases survived sufficiently long to
special stains receive systemic medications. Specifically, one
case died in the perioperative period due to an
are employed unrelated comorbidity (cardiomyopathy), one
case developed postoperative sepsis and was
to make a
euthanased, one case treated in general
definitive practice was found dead 24 h postoperatively
and one case was euthanased due to having
diagnosis in been given an incorrect diagnosis. Addition -
cats with ally, a standardised treatment protocol was not
in place and so treatment was at the discretion
atypical intra- of the individual clinician; thus, different cats
received different doses of a variety of
abdominal antimicrobial and immunosuppressive agents.
mass lesions. in our opinion a multimodal approach to
therapy is ideal, consisting of prednisolone,
additional immunomodulatory agents and
antibiotics following surgical resection (see box
on page 403).
Prognosis
due to the largely retrospective nature of the
study, cases were presented at variable stages
of disease and treatment regimens were
inconsistent. For this reason, survival data
must be appraised cautiously. What is clear,
however, is that, if treated appropriately,
survival times can be good, with most cats
surviving the perioperative period remaining
well for several years (Figure 9a).
With appropriate treatment, survival times
can be good.
KEY POINTS
< FGESF is primarily a condition of middle-aged cats with a chronic
history of vomiting, diarrhoea and weight loss.
< Ragdolls were significantly overrepresented in the 13 cases
investigated in this study.
< Abdominal lesions were usually palpable and localised to
the ileocaecocolic region or stomach.
< There is no evidence that FCoV, FHV-1 or a single specific
bacterial species played a role in the development of
this disease.
< A multimodal approach to therapy of FGESF would
seem ideal.
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O R I G I N A L A R T I C L E / Feline gastrointestinal eosinophilic sclerosing fibroplasia

Recommendations for multimodal therapy

Therapy needs to target the current extent and nature of disease limited, a combination of amoxicillin clavulanate plus
(many cases benefit from surgical debulking), any identifiable metronidazole would appear to be a good empirical choice;
underlying cause, perpetuating factors (specifically the strongly use of marbofloxacin plus metronidazole would also be
associated secondary infections) and the propensity towards defensible. Because antibiotics are administered in concert with
immune dysregulation attributable to eosinophilic inflammation. glucocorticoids and other immunosuppressive drugs, long
Although we currently consider surgical intervention to be a courses of antimicrobial therapy, extending to several months,
critical early component of therapy, it might turn out that it is would seem appropriate.
actually more feasible after lesions have Finally, blunting the hyperactive
been reduced in size by aggressive A multimodal approach eosinophilic response is necessary to
preliminary medical therapy. reduce the risk of ongoing fibrosis. To this
In some cases, the disease process to therapy would seem end, it seems likely that the effects of
(marked fibrosis leading to partial or ideal, consisting of glucocorticoids can be enhanced by the
complete gastrointestinal obstruction) concurrent use of ciclosporin A,
must be addressed urgently at the outset prednisolone, additional chlorambucil, hydroxyurea or lomustine.
through surgery (complete excision where Treatment with one of these agents in
possible). Medical therapy is used
immunomodulatory addition to prednisolone will likely
subsequently as an adjunct, to further agents and antibiotics enhance efficacy, be ‘steroid sparing’ and
reduce the size of non-resectable disease thereby reduce the risk of complications
and prevent new lesions developing. following surgical such as diabetes mellitus. Critically, these
Glucocorticoids such as prednisolone agents will more specifically target the
interfere with cytokines and other factors
resection. underlying immune dysregulation than
promoting survival of eosinophils.30 glucocorticoids. The instance of likely
Additionally, glucocorticoids dampen the release of eosinophil recrudescent toxoplasmosis in our series of cases provides a
granules, reduce eosinophil numbers and suppress tissue warning of this potential adverse sequela of immunosuppressive
inflammation.30 therapy. There may be a case for prophylactic administration of
Routine use of antibiotics is recommended, given the high trimethoprim sulphadiazine on a weekly basis or clindamycin on
percentage of lesions where bacteria have been cultured or a daily basis, especially in Australia where exposure to T gondii
visualised. Although data on the range of bacteria involved are is high due to the common practice of feeding uncooked meat.

Acknowledgements References

The authors thank the following veterinary practices for
contributing cases: Castle Hill Veterinary Hospital,
Hampton Park Veterinary Clinic, Fountain Gate Veterinary
Clinic, Cambridge Cat Clinic UK, Your Vets, UK, Peninsula
Animal Hospital, Hobart Animal Hospital, Greencross
Vets Sandringham, North Shore Veterinary Specialist
Centre, Rose Bay Veterinary Hospital, Leslie Street
Veterinary Hospital, University of Melbourne Veterinary
Clinic and Hospital, and Ferntree Gully Veterinary
Hospital. Professor Niels Pedersen kindly donated mono-
clonal antibody against the nucleocapsid of FCoV.
Professor Kenny Simpson generously taught Jacqui Norris
the FiSH technique during sabbatical leave. The authors
also thank Tal Bergman for creating the Kaplan-Meier plot
for survival data. Richard Malik is supported by the
Valentine Charlton Bequest of the Centre for Veterinary
Education, University of Sydney.
Funding
This research received no specific grant from any funding agency
in the public, commercial or not-for-profit sectors.
Conflict of interest
The authors do not have any potential conflicts of interest to
declare.
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