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J Vet Intern Med 2007;21:700–708

Chronic Enteropathies in Dogs: Evaluation of Risk Factors for

Negative Outcome
K. Allenspach, B. Wieland, A. Gröne, and F. Gaschen

Hypothesis: Certain variables that are routinely measured during the diagnostic evaluation of dogs with chronic
enteropathies will be predictive for outcome and a new clinical disease activity index incorporating these variables can be
applied to predict outcome of disease.
Animals: Seventy dogs were entered into a sequential treatment trial with elimination diet (FR, food-responsive group)
followed by immunosuppressive treatment with steroids if no response was seen with the dietary trial alone (ST, steroid-
treatment group). A 3rd group consisted of dogs with panhypoproteinemia and ascites (PLE, protein-losing enteropathy) that
were treated with immunosuppressive doses of steroids.
Methods: Three years of follow-up information was available for all dogs. Clinicopathologic variables were tested for their
ability to predict negative outcome, defined as euthanasia due to refractoriness to treatment. Different scoring systems
including different combinations of these variables were evaluated using receiver operating characteristic (ROC) curves.
Results: Thirteen of 70 (18%) dogs were euthanized because of intractable disease. Univariate analysis identified a high
clinical activity index, high endoscopic score in the duodenum, hypocobalaminemia (,200 ng/L) and hypoalbuminemia
(,20 g/L) as risk factors for negative outcome.
Conclusions and clinical importance: Based on the factors identified by logistic regression and ROC curve analysis, a new
clinical scoring index (CCECAI) was defined that predicts negative outcome in dogs suffering from chronic enteropathies.
Key words: Canine; Chronic Diarrhea; Clinicopathologic variables; Prognosis.

mong the causes for chronic enteropathies (CE) in
A dogs, adverse reaction to food, idiopathic in-
flammatory bowel disease (IBD), and antibiotic-respon-
sive diarrhea (ARD) are common.1–4 These disorders are
diagnosed retrospectively by their response to treatment.
Little information is available on clinical and clinico-
pathologic markers that may help distinguish between
cases that respond to diet alone and those that require
treatment with corticosteroids. Furthermore, little in-
formation is available on risk factors associated with
refractoriness to treatment leading to euthanasia of
affected animals.5
The purpose of this prospective study therefore was
to evaluate standard tests performed during diagnostic
evaluation of CE cases for their accuracy to predict
response to therapy and outcome. Specifically, clinical
signs, CBC, serum biochemical analysis, serum co-
From the Small Animal Teaching Hospital of the University of
Bern, Department of Veterinary Clinical Medicine, Vetsuisse
Faculty, Switzerland (Allenspach, Gröne, Gaschen); and the De-
partment of Veterinary Clinical Sciences, Royal Veterinary College,
University of London, North Mymms, UK (Wieland). Dr Karin
Allenspach is currently affiliated with the Department of Veterinary
Clinical Sciences, Royal Veterinary College, University of London,
North Mymms, UK. Dr Andrea Gröne is currently affiliated with the
Department of Pathobiology, Faculty of Veterinary Medicine,
Utrecht University, Utrecht, The Netherlands. Dr Frederic Gaschen
is currently affiliated with the Department of Veterinary Clinical
Sciences, School of Veterinary Medicine, Louisiana State University,
Baton Rouge, LA. This study was presented in part at the ACVIM
Forum 2006 in Louisville, KY. May 31-June 3.
Reprint requests: Karin Allenspach DVM., Department of
Veterinary Clinical Sciences, Royal Veterinary College, University
of London, Hawkshead Lane, North Mymms, Hatfield, AL9 7TA;
e-mail: kallenspach@rvc.ac.uk.
Submitted August 16, 2006; Revised October 18, 2006 and
November 17, 2006; Accepted January 22, 2006
Copyright E 2007 by the American College of Veterinary Internal
Medicine
0891-6640/07/2104-0004/$3.00/0
balamin and folate concentrations, 2-dimensional trans-
abdominal ultrasound, endoscopy, and histopathology
were evaluated for their usefulness to predict outcome.
This study was part of a larger study with the broad goal
of investigating the pathogenesis and treatment of CE in
dogs performed at the University of Bern between 2002
and 2005. We aimed additionally to assess previously
proposed markers of disease (ie, albumin5 and C-
reactive protein [CRP]6) for their effectiveness to predict
response to treatment and outcome. We carried out
a prospective study design and obtained objective data
on clinical variables by using a previously published
clinical scoring system (CIBDAI, canine IBD activity
index),6 endoscopic scoring, and histologic scoring
before and after a standardized treatment regimen.
Materials and Methods
Over the 3-year period, 78 dogs with signs of chronic
gastrointestinal disease were referred to the Small Animal Teaching
Hospital, Vetsuisse Faculty, University of Bern, Switzerland. Four
dogs were excluded because of intestinal neoplasia (2 lymphoma, 1
colonic adenocarcinoma, and 1 intestinal histiocytic sarcoma).
Four dogs tested positive for Campylobacter spp. on fecal culture
and had clinical signs consistent with acute campylobacter
infection. In all other dogs, fecal culture results were negative for
Campylobacter spp., Salmonella spp., Yersinia spp., and entero-
pathogenic Escherichia coli. The 4 dogs with positive cultures for
Campylobacter spp. were successfully treated with erythromycin
(15 mg/kg PO q8h for 4 weeks) and were excluded from the study.
Seventy dogs were included in the prospective treatment trial.
Some information about the clinical signs in 35 of the dogs in this
study has been published elsewhere.7 Follow-up information was
available for all 70 dogs during a period of 3 years after finishing
the treatment trial. Owners of dogs were contacted every month by
telephone and the dogs were re-examined if their clinical signs were
worsening at any time point. Selection criteria for cases included
a history of chronic diarrhea with or without vomiting of at least
6 weeks duration, exclusion of identifiable underlying disorders,
and histopathologic evidence of intestinal inflammatory cellular
infiltrates. None of the dogs had been treated with antibiotics,
corticosteroids, or antacids in the 2 weeks before entering the

Risk Factors in Canine IBD
study. Owners of dogs signed a letter of consent in which they
agreed to participate in initial and follow-up diagnostic evaluation.
All experimental procedures were approved by the Cantonal
Committee in charge of Animal Experimentation, Bern, Switzer-
land and by the Ethical Committee of the Vetsuisse Faculty,
University of Bern, Switzerland.
All dogs received treatment with fenbendazole (50 mg/kg daily
for 5 days) before being referred. Diagnostic tests performed to
exclude underlying disorders included CBC, serum biochemical
analysis, urinalysis, and analysis of fecal samples for parasites and
bacteria including examination for endoparasitic ova and Giardia
spp. by using direct smear evaluation and zinc sulfate centrifugal
flotation techniques. Additional tests included assessment of serum
concentration of trypsin-like immunoreactivity (TLI measured by
radioimmunoassay [RIA] specific for dogs) and measurements of
serum cobalamin and folate concentrations (both performed at the
Laboratory of the Royal Veterinary College, London, UK),
measurements of C-reactive protein concentrations (CRP, mea-
sured at the Texas GI Laboratorya), as well as 2-dimensional
transabdominal ultrasound examination. No underlying infectious,
pancreatic, or neoplastic disease was identified in any of the dogs.
Dogs were classified according to their predominant clinical signs
as having upper gastrointestinal disease with clinical signs such as
anorexia, weight loss, melena, increased fecal volume, normal fecal
frequency, or predominantly lower gastrointestinal disease, with
signs such as mucus, hematochezia, tenesmus, increased frequency
of defecation, and decreased fecal volume.
All dogs were given a clinical score using the CIBDAI scoring
system established by Jergens et al,6 which is based on 6
gastrointestinal variables that are routinely evaluated in affected
dogs: attitude and activity, appetite, vomiting, stool consistency, stool
frequency, and weight loss. After summation, the total composite
score is determined to be clinically insignificant (score 0–3), mild
(score 4–5), moderate (score 6–8), or severe (score 9 or greater).
Gastroscopy, duodenoscopy, and colonoscopy were performed
in all dogs except those with panhypoproteinemia. Colonoscopy
was not performed in these dogs because a 36-hour fast was
considered detrimental in these patients.
The dogs were assigned an endoscopy score for duodenum and
colon by either 2 of the authors performing the endoscopies (KA
and FG). Scores were assigned as follows: normal mucosa 5 0;
slightly friable mucosa and increased erythema 5 1; friable mucosa
with white speckling on the surface 5 2; very friable mucosa, bleeds
easily, with visible ulcers or cobble-stone appearance, difficulty in
insufflating the bowel endoscopically 5 3. Finally, mucosal biopsy
specimens from stomach, duodenum, and colon were examined
histologically and graded according to previously published guide-
lines.8 Five biopsy specimens from each site were examined
histologically. Mild lesions were those with cellular infiltrates but
without architectural distortion or mucosal epithelial immaturity.
Moderate lesions had cellular infiltrates accompanied by mucosal
epithelial immaturity, solitary epithelial necrosis, or both. Severe
lesions consisted of cellular infiltrates accompanied by multifocal
epithelial necrosis or extensive architectural distortion with
epithelial immaturity.
All dogs initially were treated with an elimination dietb for
10 days. Dogs that responded to the elimination diet in the 1st
10 days (clinical signs improved or resolved) were assigned to the
food-responsive group (FR). The dogs that did not respond in the
1st 10 days of treatment (clinical signs persisted while on the
elimination diet) were assigned to the steroid-treatment (ST) group,
and were given oral prednisolone (2 mg/kg per day PO) for 10 days
followed by a tapering dosage over 10 weeks. Thus, dogs were
separated into 2 groups according to their initial response to
treatment with elimination diet. Although it is possible that these
dogs still had IBD, we assigned them into the FR group according
to their prompt response to dietary treatment alone. The FR group
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701
was re-evaluated 4 weeks after starting treatment with the
elimination diet. At this time, the CIBDAI score was re-evaluated
and endoscopy was repeated to determine the posttreatment
endoscopy score and histopathology grade. The ST group was re-
examined a 2nd time including an endoscopy at the end of the
10-week treatment period, which was 2 weeks after complete
discontinuation of prednisolone treatment. All dogs were fed the
elimination diet exclusively for 14 weeks.
Ten dogs in the ST group were clinically classified as having
protein-losing enteropathy (PLE group) because of panhypoprotei-
nemia with severe hypoalbuminemia (mean albumin concentration,
11.3 g/L; SD 3.19; range, 10–18 g/L; reference range, 24–35 g/L) and
ascites, with or without pleural effusion or peripheral edema.
A 2nd prospective treatment trial was performed on all dogs that
did not respond to the initial 10-week course of prednisolone
(reduction of CIBDAI minimal to absent). These dogs underwent the
same clinical and laboratory examinations as described above. All of
them were completely weaned from the prednisolone treatment
before receiving cyclosporine at 5 mg/kg PO for a total of 10 weeks,c
when a 2nd endoscopy and clinical assessment was performed.
Statistical Analysis
Normally distributed data are reported as means 6SD. Data
that were not normally distributed are reported as medians (ranges)
unless otherwise indicated. Outcome was defined as good if the dog
was still alive 3 years after finishing treatment; negative outcome
was defined as the dog having been euthanized any time during the
3 years of the study because of refractoriness to treatment. A one-
way analysis of variance (ANOVA), Kruskal-Wallis test for
nonparametric data, and logistic regression models with 1 predictor
were used to evaluate differences among the groups of dogs. Cross
tabulations were performed using a Fisher’s exact or chi-square
test. Correlations were evaluated with the Spearman rank
correlation test. Odds ratios (ORs) were determined using logistic
regression models with a single predictor. Multivariate logistic
regression analysis was attempted, however, sample size was too
small in the subgroups to control for influence of more than 1
variable. Potential clinical scoring systems with different combina-
tions of the risk factors identified by univariate logistic regression
analysis were evaluated using the area under the curve (AUC) of
binomial receiver operator characteristic (ROC) curves. For each
scoring system, the optimum cut off was determined, sensitivity
and specificity estimated, and AUC was used to compare the
efficacy of the scoring systems for predicting negative outcome.
A new scoring system was named canine chronic enteropathy
clinical activity index (CCECAI), and included the lowest serum
albumin concentration measured at any time point during the study
(15–19.9 g/L, score of 1; 12–14.9 g/L, score of 2; ,12 g/L, score of
3), subjective scoring of peripheral edema and ascites (scores of 1–
3), and subjective owner assessment of severity of pruritus (scores
1–3) in addition to the composite score previously published as
CIBDAI6 (Table 1). The following scoring systems were evaluated
for their effectiveness in predicting outcome: CIBDAI as previously
described,6 CIBDAI plus serum albumin concentration, CIBDAI
plus serum cobalamin concentration, CCECAI, CCECAI plus
serum cobalamin concentration, CCECAI plus serum cobalamin
concentration and endoscopic score. Statistical significance was set
at P , .05. All statistical analyses were performed using
a commercially available statistical software system.d
Results
Breeds, Age, Sex, and Weight
Seventy dogs were included in the prospective
treatment trial. Thrity-nine dogs were included in the

702
Table 1. Comparison of clinical activity indices
(CIBDAI versus CCECAI).
Canine inflammatory bowel dis-
ease activity index (CIBDAI)6
Attitude/activity
0 normal
1 slightly decreased
2 moderately decreased
3 severely decreased
Appetite
0 normal
1 slightly decreased
2 moderately decreased
3 severely decreased
Vomiting
0 normal
1 mild (13 per week)
2 moderate (2–33/wk)
3 severe (.33/wk)
Stool consistency
0 normal
1 slightly soft feces
2 very soft feces
3 watery diarrhea
Stool frequency
0 normal
1 slightly increased
(2–33/d) or fecal blood,
mucus or both
2 moderately increased
(4–53/d)
3 severely increased
(.53/d)
Weight loss
0 none
1 mild (,5%)
2 moderate (5–10%)
3 severe (.10%)
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Allenspach et al
FR group and 21 required prednisolone in addition to
the elimination diet (ST group). Ten dogs were clinically
classified as having protein-losing enteropathy (PLE
Canine Chronic Enteropathy group) because of panhypoproteinemia with severe
activity index (CCECAI) hypoalbuminemia (mean serum albumin concentration,
Attitude/activity 11.3 g/L SD 3.19; range, 10–18 g/L; reference range, 24–
0 normal 35 g/L) and ascites, with or without pleural effusion or
1 slightly decreased peripheral edema.
2 moderately decreased Breeds included in the study and groups assigned to
3 severely decreased the study dogs were as follows: FR group (n 5 39):
Appetite Golden Retriever (6), Mixed Breed (6), Labrador
0 normal Retriever (5), German Shepherd (3), Bernese Mountain
1 slightly decreased Dog (2), Cairn Terrier (2), Malinois (2), Alaskan
2 moderately decreased Malamute (1), Border Collie (1), Border Terrier (1),
3 severely decreased Chihuahua (1), Dachshund (1), English Setter (1), Great
Vomiting Dane (1), Greyhound (1), Jack Russell Terrier (1),
0 normal Leonberger (1), Shi Tzu (1), West Highland White
1 mild (13/wk) Terrier (1), and Whippet (1); ST group (n 5 21): Mixed
2 moderate (2–33/wk) Breed (6), Boxer (2), German Shepherd Dog (2),
3 severe (.33/wk) Yorkshire Terrier (2), Coton de Tulear (1), Dachshund
Stool consistency (1), Dalmation (1), Mastiff (1), Papillon (1), Rottweiler
0 normal (1), Shar Pei (1), Toy Poodle (1), and West Highland
1 slightly soft feces White Terrier (1); and PLE group (n 5 10): Mixed breed
2 very soft feces (4), Yorkshire Terrier (4), Dachshund (1), and West
3 watery diarrhea Highland White Terrier (1).
Stool frequency There were 34 females in the study population, of
0 normal which 22 were spayed, and 36 males, 15 of which were
1 slightly increased (2–33/d) or neutered. There was no statistically significant difference
fecal blood, mucus, or both in the sex distribution between the 2 groups. Mean age
of the total study population was 5.3 6 2.9 years (range,
2 moderately increased 6 months to 13 years). The mean age of the FR group
(4–53/d) was significantly lower than that of the ST group and
3 severely increased (.53/d) PLE group (FR group: mean 3.53 6 2.36 years, range
0.6–7.6, median 3.4 years; ST group: mean 6.52 6
Weight loss 2.94 years, range 2.1–13, median 4.8 years; PLE group:
0 none mean 7.33 6 3.93 years, range 2.5–13, median 7.6 years;
1 mild (,5%) P , .001).
2 moderate (5–10%)
3 severe (.10%)
Long-term Outcomes
Albumin levels
0 albumin .20g/L The odds ratios (ORs) for negative outcome for each
1 albumin 15–19.9 g/L of the clinicopathologic variables are presented in
2 albumin 12–14.9 g/L Table 1.
3 albumin ,12 g/L In the FR group, all dogs but 1 were still alive 3 years
Ascites and peripheral edema after ending the study. All 39 dogs were switched back to
0 none their original diet after 14 weeks of elimination diet trial.
1 mild ascites or peripheral In 31 of 39 dogs, the original signs did not recur and the
edema dogs subsequently did not develop signs of their disease
2 moderate amount of ascites/ for up to 3 years of follow up. In the remaining 8 dogs,
peripheral edema switching back to the original diet lead to a recurrence of
3 severe ascites/pleural effusion disease, and therefore, these dogs were suspected of
and peripheral edema having food allergy or food intolerance. These 8 dogs
Pruritus then were challenged orally with 4 different single
0 no pruritus proteins (beef, lamb, chicken, and milk). Only 2 dogs
1 occasional episodes of itching showed a clinical reaction, with acute vomiting and
2 regular episodes of itching, hematochezia 1 day after eating the provocative diets. In
but stops when dog is asleep 1 of these 2 dogs, we were unable to find a diet that did
3 dog regularly wakes up not elicit any signs for the next 2 years. This dog also
because of itching
was on trial treatment with corticosteroids and cyclo-
sporine, but responded only minimally. This dog
eventually was euthanized because of recurring signs.

Risk Factors in Canine IBD
Fig 1. Numbers of dogs in each group presenting with signs of
predominantly small-intestinal, large-intestinal, or mixed clinical
signs. FR, food-responsive group; ST, steroid-treatment group;
PLE, protein-losing enteropathy group.
The other 7 dogs showed only minor clinical signs on the
provocative diet. These dogs subsequently were fed their
specific elimination diets and remained clinically nor-
mal.
Ten of 21 dogs in the ST group responded to the initial
treatment with immunosuppressive doses of steroids and
did not show any relapses for another 3 years after the
study was completed. Of the other 11 patients, 3 were
euthanized after the corticosteroid trial. The remaining 8
dogs were subsequently treated with cyclosporine, which
rescued 2 of 8 dogs from euthanasia.
In the PLE group, none of the dogs responded to the
initial corticosteroid treatment trial and subsequently
went on to cyclosporine treatment. This protocol
rescued 7 of 10 PLE dogs from euthanasia.
Dogs in the ST group and PLE group had
a significantly higher chance of becoming refractory to
treatment and being euthanized within 3 years after
finishing the treatment trial than did dogs in the FR
group (ST group: OR 28.5 [CI 95%: 3.3; 248.5, P , .01];
PLE group: OR 16.3 [CI 95%: 1.5; 180, P , .05]).
Predominance of Clinical Signs: Small versus Large
Intestinal Disease
The initial presenting complaint predominantly in-
volved the small intestine in 30 dogs, predominantly the
large intestine in 26 dogs (86% of dogs in the FR group),
and both the small and large bowel in 14 dogs. When
comparing the groups of FR and ST, large intestinal
signs were significantly more frequently seen in the
FR than in the ST and PLE groups (P , .001) (Fig 1).
Signs of predominantly small intestinal disease were
significantly correlated with a higher CIBDAI score (P ,
.01).
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703
Endoscopy Score
There was no difference in endoscopy score among
the FR, ST, and PLE groups. The same was true within
the same group before and after treatment (median
scores in the FR and ST groups 1.3, range 0–3, median
scores after treatment in the FR group 1.2, range 0–3,
and in the ST group 1.3, range 0–3; P 5 .27; median
scores in the PLE group before treatment: 1.8, range 0–
3, median score after treatment 1.9, range 0–3, P 5 .26).
No correlation was found between endoscopy scores and
CIBDAI or histologic scores (P 5 .12). However, an
endoscopy score of 3 in the duodenum (indicating severe
inflammation) was significantly associated with negative
outcome (OR 10.5, CI 95%: 1.7–66.1, P 5 .01).
Histologic Scoring
Histologically, all dogs showed some degree of in-
filtration with lymphocytes, plasma cells, eosinophils, or
some combination of these. In 4 dogs, mild lymphan-
giectasia was evident histologically, but the accompany-
ing inflammatory infiltrate was judged by the pathologist
(AG) to be severe enough to cause secondary lymphan-
giectasia. There was no statistically significant difference
among the 3 groups for histologic scoring (histologic
scoring in the FR group before treatment: median 1.8,
range 0–3; after treatment: median 1.9, range 0–3, P 5
.11; histologic scoring in the ST group before treatment:
median 1.4, range 0–3; after treatment: median 2.3, range
0–3; P 5 .09; histologic scoring in the PLE group before
treatment: median 1.7, range 0–3, after treatment: median
2.1, range 0–3; P 5 .12). In addition, histologic scores
were not correlated with CIBDAI, endoscopy scoring, or
outcome.
Serum Albumin Concentrations
Fifteen of 70 dogs initially presented with a hypoal-
buminemia of ,20 g/L. Of these 15 dogs, 10 were
panhypoproteinemic with severe hypoalbuminemia
(PLE group). These dogs also showed clinical evidence
of PLE, such as ascites (15 of 15), peripheral edema (1 of
15), and thoracic effusion (1 of 15).
Eight dogs with hypoalbuminemia eventually were
euthanized because of refractoriness to treatment in-
cluding 3 dogs with PLE. Serum albumin concentration
was not correlated with CIBDAI, endoscopic or
histologic scoring (CIBDAI: P 5 .12; endoscopic
scoring: P 5 .23, histologic scoring: P 5 .09). In the
univariate regression analysis, the lowest serum albumin
concentration measured at any time point during the
study was significantly associated with disease outcome
when a cut off of ,20 g/L was chosen (OR 11.4, CI 95%
2.9–44.9, P , .01).
Serum Cobalamin Concentrations
Thirteen of 70 dogs had initial hypocobalaminemia
with concentrations ,200 ng/L (6 in the ST group, 6 in
the PLE group, and 1 in the FR group). Mean
cobalamin concentration in these 13 dogs was
129.3 ng/L, SD 32.4 (range, 100–224 ng/L; reference

704 Allenspach et al
Fig 2. Canine inflammatory bowel disease activity index (CIB-
DAI) scores for dogs in the FR, ST, and PLE group. FR, food-
responsive group; ST, steroid-treatment group; PLE, protein-losing
enteropathy group.
range, 249–733 ng/L). Dogs with low serum cobalamin
concentrations were treated with weekly cobalamin
injections (dogs #15 kg body weight: 500 mg per
injection; dogs .15 kg body weight: 1000 mg per
injection), which successfully corrected the cobalamin
concentrations into the normal range within 10 weeks in
all dogs. Seven of 13 dogs with initial hypocobalamine-
mia were subsequently euthanized because of refracto-
riness to treatment. Dogs with initial serum cobalamin
concentration below the cut off value of 200 ng/L had
a highly significant higher chance for a negative out-
come (OR 9.5, CI 95% 2.5–39.4, P , .01) in the
univariate analysis. In addition, there was a highly
significant association between a low serum albumin
concentration and a low serum cobalamin concentration
(chi square 29.21, P , .001).
Serum CRP Concentrations
In 33 of 70 dogs, serum CRP concentration was
measured before and after treatment. Based on established
reference ranges, serum CRP was increased in 7 of these 33
dogs before treatment and in none of the dogs after treat-
ment (0.55 6 1.67 mg/L; reference range, 0–7.6 mg/le).
Serum CRP concentration did not correlate with CIB-
DAI, endoscopic, or histologic scoring, or outcome.
Severity of Disease and Clinical Disease Activity Index
The CIBDAI was significantly lower in the FR group
than in the ST group and the PLE group before starting
treatment (P , .01). Clinical signs improved during
therapy in all groups, but the magnitude of improve-
ment was significantly greater in the FR group than in
the ST or the PLE group (FR group: median initial
CIBDAI 6.3 [range: 2–12] versus 1.2 [range, 0–7] after
treatment; P , .01; ST group: median CIBDAI 8.3
[range, 2–15] before versus 5.5 [range, 0–16] after
19391676, 2007, 4, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/j.1939-1676.2007.tb03011.x by Cochrane Slovakia, Wiley Online Library on [18/10/2022]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
treatment; P , .01; PLE group median 10.8 before
[range, 3–16] versus 5.1 (range 0–16) after treatment, P
, .01). Details on the CIBDAI score are presented in
Figure 2. There was no significant association between
the CIBDAI and the histologic or endoscopic scores.
However, outcome was significantly associated with
CIBDAI (OR 1.48, CI 95% 1.06–2.06, P 5 .02).
Evaluation of Scoring Systems for CE
With univariate screening, potential risk factors for
negative outcome were identified (Table 2). Some
clinical variables seemed to be important predictors of
outcome in the FR and PLE group. However, these
factors were not identified to be statistically significant
in the regression analysis because of insufficient
numbers in the subgroups. In the FR group, pruritus
was the only factor that impacted on a negative outcome
for the dog that had to be euthanized in this group. In
the PLE group, serum albumin concentration was not
a very strong negative predictive factor, but the clinical
signs associated with disease, such as ascites and
peripheral edema, impacted more on the outcome in
this group. These 2 clinical variables were added to the
new scoring system to make it applicable to all dogs with
CE. Six different scoring systems based on the pre-
viously published CIBDAI6 were defined and evaluated
for their usefulness in predicting negative outcome, as
described in the Materials and Methods section. All
scoring systems based on the newly defined CCECAI
performed at similar level with an AUC above 0.93. For
the CCECAI a cutoff value of 12 was shown to be the
best predictor for negative outcome, with a sensitivity of
0.91 and a specificity of 0.83 (Fig 3; Table 3). Similar to
the CIBDAI, 4 categories of severity were defined for
the CCECAI: insignificant disease, 0–3; mild disease, 4–
5; moderate disease, 6–8; severe disease, 9–11; very
severe disease, $12. Details of numbers of dogs grouped
in the different categories of severity are shown in
Figures 2 and 4.
Discussion
In this prospective study of 70 dogs with CE,
standard tests and previously proposed markers of
disease were evaluated for their usefulness in predicting
response to therapy (either food-responsive disease or
steroid-responsive disease) as well as for predicting
outcome (ie, euthanasia due to refractoriness to treat-
ment).
The number of cases with intractable disease was 13
of 70 dogs (18%), which is comparable to 13 of 80 dogs
(16%) as recently reported in a retrospective study.5 The
mean age of our study population was 5.3 years, which
concurs with previously reported age ranges in dogs with
chronic intestinal disease.1,5 The mean age of the dogs
with food-responsive disease was significantly lower
than that of dogs that had to be treated with steroids in
addition to the elimination diet. Diet-responsive CE in
dogs occurs predominantly in younger dogs.3 Food
allergy associated with dermatologic signs also is
 19391676, 2007, 4, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/j.1939-1676.2007.tb03011.x by Cochrane Slovakia, Wiley Online Library on [18/10/2022]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
Risk Factors in Canine IBD 705

Table 2. Results of the univariate logistic regression analysis of each clinicopathologic variable with outcome, which
was defined as euthanasia because of refractoriness to treatment at any time point during the study.
ST and FR Group ST, FR, and PLE Group

Risk Factors OR CI 95% P OR CI 95% P

Predominant clinical presentation of disease
Small intestinal 5.6 0.9–33.2 .06 5.7 1.1–29.8 .04
Small and large intestinal 3.7 0.5–25.2 .18 3.7 0.5–25.2 .18
Large intestinal 1 1 1 1 1 1
Clinical group
IBD 28.05 3.3–248.5 ,.01 28.5 3.2–248.5 ,.01
PLE 16.3 1.5–180 .02
FRD 1 1 1 1 1 1
Albumin ,2g/L 49 4.7–506.6 ,.01 11.4 2.9–44.9 ,.01
CRP . 0 0.48 0.1–3 .43 11.4 0.5–27.1 .12
Cobalamin ,200ng/L 10.4 1.9–58.4 ,.01 9.9 2.5–39.4 ,.01
Endoscopy Duodenum
Score 0 1 1 1 1 1 1
Score 1 2.8 0.5–17.3 .27 2.8 0.5–17.3 .27
Score 2 0.9 0.1–10.7 .91 0.7 0.1–8.4 .8
Score 3 15.8 1.6–157.6 .02 10.5 1.7–66.1 .01
Endoscopy Colon
Score 0 1 1 1 1 1 1
Score 1 0.4 0.1–3.5 .37 0.4 0.1–3.5 .37
Score 2 0.6 0.1–6 .65 0.6 0.1–6 .65
Score 3 5.2 0.6–49 .14 5.2 0.6–49 .14
Histology Duodenum
Score 0 + 1 1 1 1 1 1 1
Score 2 2.8 0.3–24.7 .36 2.9 0.3–25.3 .33
Score 3 6.5 0.5–91.9 .17 9.8 0.8–121.8 .08
Histology Colon
Score 1 1 1 1 1 1 1
Score 2 1.1 0.2–6.7 .89 1.l 0.2–6.7 .89
Score 3 1.6 0.1–16.9 .72 1.6 0.1–16.9 .72
CIBDAI 1.5 1.1–2.1 .02 1.4 1.1–1.8 ,.01

OR, odds ratio; CI, confidence interval; CRP, C-reactive protein; CIBDAI, canine inflammatory bowel disease activity index6; ST group,
steroid-treatment group; FR group, food-responsive disease group; PLE, protein-losing enteropathy group.

observed at a relatively young age.9 This study confirms
the results obtained in a smaller group of dogs from the
same population.7 Breed distribution in the 3 groups
indicated increased numbers of small breeds such as
Yorkshire Terriers, West Highland White Terriers, and
Dachshunds in the ST and PLE groups. Yorkshire
Terriers previously have been reported to be at risk for
developing PLE from lymphangiectasia.10 Dogs with
food-responsive disease were more likely to present with
complaints related to the large intestine than were those
in the ST group. The observation that large-bowel
clinical signs were more common in dogs in the FR
group than in those of the ST and PLE groups is an
original finding. Moreover, the severity of clinical signs
was significantly lower in food-responsive dogs. These
observations suggest that younger dogs with less severe
disease, and a predominance of large intestinal signs are
more likely to respond to elimination diet alone. Our
data also imply that a dog responding relatively quickly
to treatment with elimination diet alone (ie, within 1–
2 weeks) will most likely have a good long-term
prognosis. Most dogs in the FR group could be switched
back to their original diet without recurrence of clinical
signs for 3 years after initial diagnosis. To the contrary,
middle-aged to older dogs with more severe disease and
predominantly small-intestinal diarrhea are more likely
to require steroid treatment to improve. In addition,
they also are more likely to be euthanized because of
intractable disease.
The presence of severe mucosal lesions in the
duodenum was significantly associated with negative
outcome in the univariate analysis. No such association
could be identified for endoscopic score in the colon.
Hence, endoscopic identification of severe mucosal
lesions in the duodenum of a dog with CE may warrant
initiation of more aggressive treatment early in the
course of disease.
Surprisingly, in the 70 dogs of the present study,
histologic score was not associated with outcome. This is
consistent with observations made in a recent retrospec-
tive study, in which severity of histologic changes was
not associated with outcome.5 It also has recently been
 19391676, 2007, 4, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/j.1939-1676.2007.tb03011.x by Cochrane Slovakia, Wiley Online Library on [18/10/2022]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
706 Allenspach et al

histopathology in the assessment of dogs with CE, other

Fig 3. Receiver operator characteristic (ROC) curves comparing
the ability to predict negative outcome of the 2 scoring systems,
canine inflammatory bowel disease activity index (CIBDAI6) and
the new proposed canine enteropathy clinical activity index
(CCECAI). Odds ratios of different scoring systems (5 chance
for negative outcome when score goes up 1 point): CIBDAI: OR
1.4, P , .01, CI 95%: 1.1–1.8, CCECAI: OR 1.8, P , .01, CI 95%:
1.3–2.4. Cut off for CIBDAI: 9; cut off for CCECAI: 12. (A) ROC
curves for CIBDAI (binomial and empirical values). (B) ROC
curves for CCECAI curves (binomial and empirical values).
demonstrated that the histopathologic evaluation of
canine intestinal biopsies strongly depends on the
quality of biopsy specimen and the individual subjective
assessment of the pathologist.11 This is especially
important in the case of endoscopic biopsies, for which
the quality of the specimens can be very variable. In the
present study, a single pathologist performed all
assessments according to criteria proposed in a previous
study,1 and was blinded as to the identity of the samples.
Taken together, these data question the value of
than being useful to exclude certain other intestinal
diseases such as neoplasia or histiocytic ulcerative
colitis. Clearly, other variables seem to be more helpful
for the clinician, such as clinical grading of disease
severity and assessment of therapeutic response in dogs
with CE.
Hypoalbuminemia previously has been reported to be
associated with refractoriness to treatment.5 Serum
albumin concentration obviously is related to the
hydration status of the animal and may change over
the course of treatment, especially during and after fluid
therapy. We therefore selected the lowest serum albumin
concentration measured at any time during the study for
each individual dog for statistical analysis. Hypoalbu-
minemia with concentrations ,20 g/L was found to be
strongly associated with negative outcome in the
univariate analysis. This suggests that it may be helpful
to include this variable in the overall clinical assessment
of dogs with CE.
Low serum cobalamin concentration is a variable that
has been associated with refractoriness to treatment in
cats with CE.12,13 In dogs with CE, hypocobalaminemia
has been predominantly described in antibiotic-respon-
sive diarrhea or in dogs with exocrine pancreatic
insufficiency,14–16 in which classically a low serum
cobalamin concentration is seen in combination with
hyperfolatemia. In our study, a cobalamin concentration
,200 ng/L was significantly associated with negative
outcome, although all hypocobalaminemic dogs received
vitamin B12 supplementation for 6 weeks. These data
suggest that low serum cobalamin concentration at the
time of diagnosis may predict refractoriness to treat-
ment, as has been reported in cats. Cobalamin and
albumin however were strongly correlated, and both
parameters should be assessed together in each dog.
In a recent study, CRP was described as a marker of
disease severity in dogs with CE,6 because serum CRP
concentrations were indirectly correlated with CIBDAI
and histologic scoring. This finding is in disagreement
with the findings of the present study, in which CRP was
only high in 7 of 33 dogs. The 33 dogs that had CRP
measured had moderate severity of disease and repre-
sented a wide range of clinical severity of disease
(CIBDAI in dogs in which CRP was measured: median
5.5 mg/L, range 1–15 mg/L). High CRP concentrations
may have been missed in several animals because CRP

Table 3. Receiver operator characteristic (ROC) curve analysis for different clinical scoring systems.
Sensitivity Specificity
Test AUC Standard error AUC CI 95% Best cut-off (%) (%)
CIBDAI 0.75 0.069 0.58–0.86 8 74 63
CIBDAI + albumin 0.76 0.073 0.57–0.87 9 67 71
CIBDAI + cobalamin 0.80 0.068 0.61–0.90 9 69 72
CCECAI 0.93 0.029 0.84–0.97 12 91 82
CCECAI + cobalamin 0.94 0.029 0.84–0.97 13 86 87
CCECAI + cobalamin +
endoscopy score duodenum 0.94 0.029 0.84–0.97 14 87 86

AUC, area under the curve; CI, confidence interval; CCECAI, canine chronic enteropathy clinical activity index; CIBDAI, Canine
inflammatory bowel disease activity index.6

Risk Factors in Canine IBD
Fig 4. Canine chronic enteropathy activity index (CCECAI)
scores for dogs in the FR, ST, and PLE group. FR, food-
responsive group; ST, steroid-treatment group; PLE, protein-losing
enteropathy group.
was measured in less than half of the dogs described.
Additional studies elucidating the role of CRP as
a marker in dogs with CE are warranted.
CIBDAI previously has been described in a large
prospective study with short-term follow up, but no
information about long-term outcome was available.6 In
the present study, we showed that severity of disease as
assessed by clinical scoring is also associated with long-
term disease outcome. However, adding low serum
albumin concentrations, and assessment of ascites and
pruritus to the CIBDAI to define the new clinical
scoring system CCECAI was much more powerful to
accurately predict negative outcome. Including low
cobalamin concentrations and results of more invasive
tests such as endoscopy to the scoring system did not
add any additional benefit regarding predictive ability of
the scoring system. Because serum albumin concentra-
tion is more widely available in routine small animal
practice, we chose to use this variable in the CCECAI.
Cobalamin is equally powerful as a predictive factor but
may not be as readily available for practitioners. Jergens
et al6 excluded dogs with food-responsive disease as well
as PLE dogs from their trial, whereas in our study the
prospective nature of a step-wise treatment protocol
made it possible to include food-responsive dogs, dogs
that needed steroid treatment, as well as PLE dogs.
Therefore, this new score may be valuable for all dogs
with chronic intestinal disease after exclusion of
endoparasites and enteropathogens, and could be used
widely under such circumstances.
In conclusion, the results of this study suggest that
several clinical as well as clinicopathologic variables are
useful to predict response to treatment and outcome in
dogs with CE. Dogs with food-responsive disease
generally are younger, are presented with less severe
clinical signs and predominantly have large-intestinal
diarrhea. Dogs that need to be treated with steroids are
middle-aged to older, are presented with more severe
19391676, 2007, 4, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/j.1939-1676.2007.tb03011.x by Cochrane Slovakia, Wiley Online Library on [18/10/2022]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
707
clinical signs, and predominantly have small-intestinal
diarrhea. Based on the results of this study, we devised
a new clinical scoring system that may be used for all
dogs with CE. The CCECAI scoring index includes
hypoalbuminemia (serum concentrations ,20 g/L), as-
sessment of ascites, peripheral edema and pruritus in
addition to the CIBDAI scores.
Footnotes
a
Tridelta PHASE RANGE Canine C-Reactive Protein Assay,
Tridelta, Wicklow, Ireland
b
Purina L/A salmon and rice, Nestlé Purina, Udine, Italy
c
Atopica, Novartis Animal Health, Basel, Switzerland
d
NCSS Statistical Software version 2005, Kaysville, Utah
e
Berghoff N et al. Canine CRP: Determination of a reference range
and its stability in serum samples. ACVIM Forum, 2006
Louisville, KY, (abstract)
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