CASE STUDY
VOLUME 16/ISSUE 2
“Buddy”
Signalment:
“Buddy”, a 6 year old, 4.5 kg, neutered male domestic
short hair feline.
History:
Buddy was primarily an outside cat and was current on
FVRCP, Rabies, and FeLV vaccinations. Two months prior
to presentation, Buddy became lethargic and anorexic
with hemorrhagic diarrhea, occasional vomiting, and
weight loss. A total weight loss of 2kg had occurred since
the patient had been weighed 4 months prior. Blood work
(Table 1), urinalysis (Table 2), fecal, Feline GI pathogen
PCR (Table 3), and an abdominal ultrasound had been
accomplished by the primary care veterinarian.
Table 1
CBC
August 21, 2015
Results
Reference Range
Test
RBC
7.6 M/uL
5.50-9.93M/uL
HCT
32%
29 - 48%
HGB
10.4g/dL
9.3 -15.9 g/dL
MCV
42 fL
37 - 61 fL
MCHC
32 pg
18.5 - 30.0 pg
% RETIC
--
--
RETIC
--
10.0 - 110.0 K/uL
WBC
24.1 K/uL
5.50 - 16.90 K/uL
% NEU
16.87K/uL
2.50 – 8.50 K/uL
% LYM
5.78 K/uL
1.20 – 8.00 K/uL
% MONO
0.72 /uL
0.00 – 0.60 K/uL
% EOS
0.72 /uL
0.00 - 1.00 K/uL
% BASO
0.00 /uL
0.0 - 0.15 K/uL
PLT
432 K
200-500K/uL
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Table 1 Continued
Reference Range
Serum Biochemical Profile
Table 2
GLU
110 mg/dL
74 - 170 mg/dL
BUN
28 mg/dL
14 - 36 mg/dL
CREAT
2.0 mg/dL
0.6 – 2.4 mg/dL
PHOS
4.4 mg/dL
2.4 – 8.2 mg/dL
CA
9.0 mg/dL
8.2 – 10.8 mg/dL
TP
7.4 mg/dL
5.2 - 8.8 g/dL
ALB
2.7 mg/dL
2.5 – 3.9 g/dL
GLOB
4.7 mg/dL
2.3 – 5.3 g/dL
ALT
28 IU/L
10 - 100 IU/L
ALKP
37 IU/L
6 - 102 IU/L
GGT
3 IU/L
1 - 10 IU/L
TBIL
0.2 mg/dL
0.1 - 0.4 mg/dL
CHOL
115 mg/dL
75 - 220 mg/dL
AMYL
2483 U/L
100 - 1200 U/L
LIPA
69 U/L
0 - 205 U/L
Na
151 mEq/L
145 - 158 mEq/L
K
5.2 mEq/L
3.4 - 5.6 mEq/L
Cl
120 mEq/L
104 - 128 mEq/L
CPK
257 IU/L
56-529 IU/L
Total T4
2.6 ug/dL
0.8-4.0 ug/dL
FeLV
Negative
Negative
FIV
Negative
Negative
FCV @ 1:400
< 1:400
< 1:400
FCV @ 1:1600
Negative
Negative
Toxoplasma lgG Antibody
Negative
Negative
Toxoplasma lgM Antibody
Negative
Negative
Results
Fecal
Ova Negative
Urinalysis
August 21, 2015
Color
Dark Yellow
Giardia ELISA
Results
Positive
Appearance
Cloudy
Glucose
Negative
pH
8.0
Bilirubin
Negative
Protein
1+
Ketone
Negative
Leukocytes
0-1
Sp. Gravity
1.044
Blood
None
Bacteria
None Seen
Epithelial Cells
None Seen
Crystals
None Seen
Casts
None Seen
Fat Droplets
4-10/HPF
Microprotein
1mg/dL
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Table 3
Feline GI PCR Profile
September 17, 2015
Feline Parvovirus/Panleukopenia
Negative
Tritrichomonas foetus
Negative
Campylobacter jejuni/coli
Negative
Cryptosporidium spp
Negative
Cryptosporidium felis
Negative
Salmonella spp
Negative
Clostridium difficile toxins A/B
Negative
Clostridium perfringens enterotoxin
Negative
An abdominal ultrasound was done by the
referring veterinarian and was read by a
veterinary radiologist.
Abdominal Ultrasound Report
October 23, 2015
Liver/Gallbladder: The liver was subjectively hypoechoic
causing increased conspicuity of the portal markings. The
hepatic vasculature was normal. There was an area of
focally decreased echogenicity in the ventral aspect of the
liver immediately ventral to the portal vein. The gallbladder
was mildly distended with anechoic bile. No gallbladder
wall abnormalities were observed.
Stomach: The stomach was empty and the majority of the
gastric wall was normal in layering and thickness. One
focal area of thickening of the gastric wall was seen
measuring up to 0.65 cm in thickness.
Kidneys: The left kidney was normal in size and shape
measuring up to 4.21 cm in length. Corticomedullary
definition was good and no pyelectasia was seen. One
wedge shaped hyperechoic defect was noted in the cortex
of the left kidney likely indicating chronic infarction. The
right kidney was slightly smaller, but smoothly marginated
measuring 3.59 cm in length. The right renal architecture
was normal.
Urinary Bladder: The urinary bladder was moderately
distended with nearly anechoic urine. No bladder wall
abnormalities were seen.
Small Intestine: There was subjective thickening of the
small intestinal muscularis layer of at least one segment of
small intestine. Other examined segments were normal in
appearance measuring up to 0.28 cm in thickness with
normal wall layering. No pathologic distention of the
small intestine was observed and there was evidence of
intestinal motility.
Conclusion: Focal thickening and alteration of the gastric
wall raises concern for gastric neoplasia such as lymphoma.
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Severe ulceration could also cause similar changes. Focal
muscularis layer thickening of the small intestine could
indicate inflammatory infiltration or round cell neoplasia
such as lymphoma or mast cell disease. Hepatic
hypoechogenicity was a nonspecific finding that may
indicate neoplastic infiltration (e.g. lymphoma), hepatitis,
or amyloidosis. Hepatic congestion was unlikely given the
lack of vascular distention. Mild renal degenerative
changes were seen in the left kidney where chronic renal
infarcts were noted.
Treatment: Buddy had been medicated with fenbendazole
(50mg/kg PO q24h for 7 days), metronidazole (10mg/kg
PO q 12h for 10 days) and prednisolone (1mg/kg PO q24
for 7 days, then QOD for 7 days). Although the lethargy
and anorexia were partially resolved, the diarrhea was
unchanged and weight loss was persisting. The patient
was referred to IndyVet for a second opinion and further
workup on October 26, 2015.
Physical Exam: Physical exam revealed a quiet, dull,
but responsive 2.3kg patient that was judged to be 5%
dehydrated. The patient was cachectic with a body
condition score of 2/9 and a temperature of 100.7 F. The
patient had an unthrifty appearing hair coat, debris in both
ears, moderate dental calculus, and had tachycardia
(220bpm) with equal and adequate pulses. Palpation of
the abdomen suggested a ropey feel to the intestines with
possible mesenteric lymphadenopathy. Peripheral lymph
nodes were unremarkable. A CBC, serum biochemical
profile, TLI, folate, cobalamine, and repeat abdominal
ultrasound with possible ultrasound guided aspirates were
recommended. Only authorization for the ultrasound and
aspirates was received.
Figure 1
Ultrasound
October 26, 2015
Liver/Gallbladder: The hepatic parenchyma was of
normal size, shape, and contour, and showed normal
mixed echogenicity with bright portal highlights.
The gallbladder was small and contained normal
anechoic bile.
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Kidneys: The left kidney was normal in size and shape
measuring 4.26 X 2.52cm with poor corticomedullary
definition and a hyperechoic wedge artifact in the caudal
pole. The right kidney was smaller than the left measuring
3.61 X 2.09cm with hyperechoic wedge infarcts in the
cranial and caudal poles. No pyelectasia or mineralization
was seen to either kidney.
Spleen: The splenic parenchyma was normal in size and
showed uniform hyperechogenicity. The splenic capsule
was smooth and uniform throughout its circumference.
The spleen was hyperechoic to the liver.
Urinary Bladder: The urinary bladder was moderately
distended with anechoic urine. The urinary bladder wall
was uniform throughout its circumference.
Sub-Lumbar Region: The sub lumbar lymph nodes and
vasculature were normal in appearance.
Stomach/Intestines: The stomach wall showed normal
rugal folds, wall thickness, and motility. The intestines
were diffusely thickened with evidence of a thickened
focal bowel loop in the cranial left quadrant. The focal
bowel wall thickening was adjacent to significantly
enlarged mesenteric lymph nodes measuring up to
1.85cm x 0.90 cm (Figure 1).
Pancreas: The pancreas appeared sonographically normal.
Conclusion: Infiltrative GI disease with focal bowel wall
thickening and mesenteric lymphadenopathy. Differentials
include lymphoma or focal enteritis, with lymphadenopathy.
Fine needle aspirates of the mesenteric lymph nodes are
recommended with endoscopy or exploratory laparotomy
with biopsies for definitive diagnosis if cytology results
are equivocal.
Ultrasound guided aspirates of the mesenteric lymph nodes
were taken and stained in house for evaluation (Figure 2) prior
to submission for pathology services evaluation.
Figure 2
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Cytology Microscopic Description: The lymphoid
population was heterogenous with a predominance of
small lymphocytes and lesser numbers of intermediate and
large sized lymphocytes with occasional well differentiated
plasma cells seen as part of the population. Low to
moderate numbers of macrophages were also seen that
contain several to numerous small, 2-4 micron round yeast
organisms with a thin clear capsule and internal purple
granulation consistent with histoplasmosis.
Cytology Interpretation: Moderate pyogranulomatous
inflammation; Histoplasmosis; reactive lymphoid hyperplasia.
Treatment: The patient was placed on itraconazole at
20mg PO bid for 30 days, then reducing the dose to 20mg
PO daily. Buddy continued to lose weight and the
itraconazole was increased back to 20mg PO bid. Liver
values were to be re-checked in 3 weeks and then
every 2 months thereafter as long as itraconazole was
being administered.
Blood work was re-evaluated three weeks later by the
primary care veterinarian (Table 4)
Outcome: Buddy continued to lose weight to 2.2kg and
remained lethargic. The client was very dedicated and
hand fed Buddy whatever he would eat for one month,
whereupon he started to again eat his dry cat food.
Buddy’s stools remained very soft, only occasionally having
a reasonably firm stool. Despite having an improved
appetite, Buddy remained lethargic and did not gain
weight. Ten weeks after starting the itraconazole, Buddy
suddenly became active and frisky and started to gain
weight. His stools, although soft, were much improved and
he gained nearly 1kg of weight in one month. Buddy
continues to receive itraconazole and is now intermittently
having firm stools, is very active, eating dry cat food very
well, and is doing great. He will remain on itraconazole for
several more months.
Discussion: Histoplasma capsulatum is a soil borne
dimorphic fungus that prefers a moist, humid environment
and grows best in soil containing nitrogen rich organic
matter such as bird and bat excrement. Although most
affected animals are exposed to an outdoor environment,
some affected cats have been exclusively indoor cats
suggesting that house dust and indoor plant soil can be a
source of infection.
The free living mycelial stage of Histoplasma that grows in
the soil produces macroconidia and microconidia. Most
animals are thought to become infected by inhalation
of the 2-5 um sized microconidia that after a 12-16 day
incubation period convert to the yeast phase of the
organism. The yeast is phagocytized by macrophages
where they further replicate intracellularly which can
lead to hematogenous and lymphatic dissemination
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of the disease. The occurrence of gastro-intestinal
histoplasmosis without respiratory tract involvement
suggests that the GI tract may also be a primary source of
infection although this route has not been able to be
reproduced experimentally.
Cats are just as susceptible as dogs to histoplasmosis.
Most cats will present with disseminated disease and can
exhibit a wide range of non-specific clinical signs that can
include lethargy, fever, weight loss, anorexia, pale mucous
membranes, peripheral lymphadenopathy, hepatomegaly,
and splenomegaly. Although coughing is uncommon,
dyspnea, tachypnea, and abnormal lung sounds are
Table 4
reported in more than 50% of cats with histoplasmosis.
Ocular, dermatologic, and bone involvement is far less
common in cats.
The hematologic abnormality that is most common in cats
with histoplasmosis is a normocytic, normochromic,
nonregenerative anemia which probably results from a
combination of chronic inflammatory disease, bone
marrow involvement of the organism, and intestinal blood loss
from GI involvement. Leukocyte counts are variable in cats
with histoplasmosis with a neutrophilic leukocytosis with
monocytosis being most frequent, although leukopenia,
thrombocytopenia, and pancytopenia have been reported in
CBC
November 19, 2015
RBC
4.6 M/uL
Test
HCT
HGB
Results
23%
6.6 g/dL
Reference Range
5.50-9.93M/uL
29 - 48%
9.3 -15.9 g/dL
MCV
50 fl
37 - 61 fL
MCHC
29 pg
18.5 - 30.0 pg
% RETIC
--
--
RETIC
--
10.0 - 110.0 K/uL
WBC
33.9 K/uL
5.50 - 16.90 K/uL
% NEU
27.8 K/uL
2.50 – 8.50 K/uL
% LYM
4.74 K/uL
1.20 – 8.00 K/uL
% MONO
0.678 K/uL
0.00 – 0.60 K/uL
% EOS
0.678 K/uL
0.00 - 1.00 K/uL
% BASO
0.00
0.0 - 0.15 K/uL
PLT
839K /uL
200-500K/uL
GLU
92 mg/dL
74 - 170 mg/dL
BUN
33 mg/dL
14 - 36 mg/dL
CREAT
1.6 mg/dL
0.6 – 2.4 mg/dL
PHOS
3.8 mg/dL
2.4 – 8.2 mg/dL
CA
8.4 mg/dL
8.2 – 10.8 mg/dL
Serum Biochemical Profile
Reference Range
TP
5.8 mg/dL
5.2 - 8.8 g/dL
ALB
2.3 g/dL
2.5 – 3.9 g/dL
GLOB
3.5 g/dL
2.3 – 5.3 g/dL
ALT
26 IU/L
10 - 100 IU/L
ALKP
21 IU/L
6 - 102 IU/L
GGT
3 IU/L
1 - 10 IU/L
TBIL
0.1 mg/dL
0.1 - 0.4 mg/dL
CHOL
95 mg/dL
75 - 220 mg/dL
Na
154 mEq/L
145 - 158 mEq/L
K
4.3 mEq/L
3.4 - 5.6 mEq/L
Cl
128 mEq/L
104 - 128 mEq/L
CPK
117 IU/L
56-529 IU/L
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some cats. Hypoalbuminemia is a reasonably consistent
biochemical finding in cats with disseminated disease, with
hyperproteinemia, hyperglobulimenia, and mild elevations in
alanine aminotransferase (ALT) and serum glucose being seen.
Hypercalcemia has been reported in several cats that is
probably associated with the granulomatous component
of the disease. Interestingly, most cats with histoplasmosis
test negative for feline leukemia virus and feline
immunodeficiency virus even though compromise of
cell mediated immunity is thought to be required for
disseminated disease to occur.
Thoracic radiographs of cats with active pulmonary
histoplasmosis can show a diffuse pulmonary interstitial
pattern with infiltrates that can coalesce to become miliary or
grossly nodular in appearance. Bone involvement of
Histoplasma in cats is rare, but when seen most often affects
the metaphyses of long bones with a predilection for the
bones adjacent to the carpus and tarsus.
The diagnosis of histoplasmosis is most often
accomplished by seeing the organisms on cytology of a
transtracheal wash, bronchoalveolar lavage, endoscopic
squash preps, or brushings from the small intestine or
colon. Routine Wright’s or Giemsa’s stains used for
cytology demonstrate the organisms well as small 2-4 um
yeasts with a basophilic center and lighter halo which is
caused by shrinkage of the organism during staining.
Tissue biopsy may be necessary for diagnosis if cytology
is not forthcoming. Affected tissues will show a
pyogranulomatous or granulomatous inflammatory
infiltrate, but routine H&E stain does not stain the
organism well and special fungal stains are usually needed
to see the organisms on histopathology.
PCR of Histoplasma antigen (Miravista Laboratory) in
urine is a reliable and easy method of diagnosis in dogs
and cats.
weeks or until nephrotoxicity occurs. An alternative
subcutaneous administration regimen of amphotericin B
has been described.
This case shows an interesting albeit common situation
where the symptoms, consistent with inflammatory bowel
disease, were initially treated with anti-inflammatory
medication without a definitive diagnosis due to client
resistance to additional diagnostics. The primary care
veterinarian saw that the symptoms were not improving
on initial therapy, and strongly urged the client to proceed
with further diagnostics rather than continuing with
immunosuppressive treatment. Even though endoscopy
was not authorized, due to the urgent recommendation of
the referring veterinarian the unlikely diagnosis of
histoplasmosis was established through ultrasound guided
aspirates and cytology of the mesenteric lymph nodes.
The success of this case is due entirely to the vigilance of
the primary care veterinarian to urge further diagnostics
rather than forging forward with non-specific therapy.
Veterinarians are routinely put into the situation of having
to make choices to treat clinical signs without a definitive
diagnosis due to resistance stemming from finances
or other client considerations. This case is a great reminder
of how pursuing a diagnosis with something as simple
as ultrasound re-assessment and cytology can
lead to a specific diagnosis that can then be more
successfully treated.
Here is Buddy now. Handsome and
frisky as ever, AND is waiting for
spring to get back outside.
Itraconazole given at 10mg/kg daily is currently the drug of
choice for the treatment of histoplasmosis in cats
although pharmacologic studies in cats indicate significant
variability in absorption of the orally administered drug in
capsule formulation, and some cats may require twice
daily administration at 10mg/kg to achieve adequate
therapeutic levels. The oral solution is more consistently
absorbed than capsules in cats and more consistently
allows for once daily dosing. Fluconazole at 5mg/kg PO
SID or BID is preferred for CNS or ocular disease due to its
superior penetration to the eye and neurologic tissues.
Fluconazole is commonly used as a second choice in cats
that do not tolerate orally administered itraconazole.
Amphotericin B given singly, with or without a lipid
suspension, or in combination with itraconazole has been
used in cats with severe or fulminating pulmonary or
gastrointestinal histoplasmosis. Amphotericin B is most
often given intravenously every other day for 4 to 6
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SPRING FLING
3RD ANNUAL
SEMINAR SERIES
March 12th 2016 - 12:00pm - 5:00pm
At The Indianapolis Zoo
SPECIAL ADDED FEATURE THIS YEAR!!!!
A limited number of behind the scenes tours of the zoo will be given on the morning
of the event with a limited number tour for family members of attending doctors at
2:00pm on a first request basis until full.
A total of 3.0 hours of CE will be given.
e
Sav e
Th e!
t
Da
Tou
O f rs
T
Zo he
o!
n’t
o
D iss
M !
It
Fu
Th n For
eW
Fam hole
ily!
Zoo tickets are limited to 4 per Veterinarian or Veterinary Technician
Agenda
Lunch & Registration: 12:00pm -1:00pm
“Liver Páte: A Series of IndyVet Clinical Cases”: 1:00pm - 1:50pm
“Ophthalmic Surgery for the General Practitioner”: 1:55pm - 2:45pm
Cookie Break: 2:45pm - 3:05pm
“Diagnosis and Management of Front Limb Lameness”: 3:05pm - 3:55pm
Adjourn: Dessert/Ice Cream Social Hour With Families: 4:00pm - 5:00pm
Please RSVP to IndyVet at 317-782-4484 – Fax 317-786-4484 or email Amanda at [email protected]
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CASE STUDY
VOLUME 16/ISSUE 2
Nicolás Vecchio
DVM, DACVS, CCRT
Surgery
[email protected]
Tracey Gillespie
DVM, DACVIM-SAIM
Internal Medicine
[email protected]
Julie Trzil
DVM, MS, DACVIM-SAIM
Internal Medicine
[email protected]
Heidi Klein
DVM, MS, DACVO
Ophthalmology
[email protected]
James R. Speiser
DVM, DABVP, CCRT
Canine And Feline
Medicine And Surgery
[email protected]