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ESFM Congress 2006 - Scientific Proceedings

feline congress 2006
ergife palace hotel rome
8–10 september
Scientific Proceedings
Sponsored by
Welcome – Dr Andy Sparkes
President’s Welcome – Dr Stefano Romagonoli
Feline pancreatitis – where are we in 2006?
Kenny Simpson, USA
Diseases of the ears, nose, throat and oral cavity of cats
Richard Malik, Australia
Medical or pedicle? - treatment of traumatic eye injuries in cats
David Gould, UK
Feline inflammatory bowel disease – moving beyond “lymphoplasmacytic
Kenny Simpson, USA
Feline leishmaniasis
Maria Grazia Pennisi, Italy
Welcome reception - Drinks and buffet at Ergife restaurant/poolside
Management of chronic enteropathies
Kenny Simpson, USA
09.30 Clinical decision making – how do we decide the best way to manage our
Richard Malik, Australia
10.30 Tea/Coffee
11.00 Case: an unusual case of a mature cat with crusted ears
Richard Malik, Australia
11.30 Nontuberculous mycobacterial syndromes in cats
Richard Malik, Australia
12.30 Should I worry about Helicobacter?
Kenny Simpson, USA
13.30 AGM
14.00 Afternoon off
Excursion to Torre Argentina Cat Sanctuary
‘Glitter & Sparkle' Congress Dinner at The Palazzo Brancaccio
Feline cryptococcosis – what do studies in koalas have to tell us about the
most common systemic mycosis of cats?
Richard Malik, Australia
Case: chronic diarrhoea in the cat
Kenny Simpson, USA
Clinical assessment of congenital heart diseases in cats
Claudio Bussadori, Italy
Case: chronic vomiting in the cat
Kenny Simpson, USA
What's your diagnosis? – case presentations in ophthalmology
David Gould, UK
Refractory ulcers on the nasal bridge of a young cat: an exercise in diagnostic
Richard Malik, Australia
Feline pancreatitis – where are we in 2006?
Diseases of the ears, nose, throat and oral cavity of cats
Medical or pedicle? - treatment of traumatic eye injuries in cats
Feline inflammatory bowel disease – moving beyond “lymphoplasmacytic enteritis”
Feline leishmaniasis
Managing chronic enteropathies
Clinical decision making
Case study: an unusual case of a mature cat with crusted ears
Nontuberculous mycobacterial syndromes in cats
Should I worry about Helicobacter?
Feline cryptococcosis – what do studies in koalas have to tell us about the most common
systemic mycosis of cats?
Case: chronic diarrhoea in the cat*
Clinical assessment of congenital heart diseases in cats
Case: chronic vomiting in the cat*
What's your diagnosis? – case presentations in ophthalmology*
Refractory ulcers on the nasal bridge of a young cat: an exercise in diagnostic reasoning
* Notes not available for these case presentations
ESFM Feline Congress 2006
Feline Pancreatitis: where are we in 2006?
Kenneth W Simpson BVM&S, PhD, MRCVS, DipACVIM, DipECVIM-CA
College of Veterinary Medicine, Cornell University Ithaca NY
Since its initial description in 1989 feline pancreatitis has emerged as an important and potentially life
threatening disease. Despite increased awareness its etiology remains unknown, diagnosis is
challenging, and surgical biopsy is often required to confirm a diagnosis, and facilitate detection of
intercurrent disease. Treatment is generally symptomatic and typically involves aggressive nutritional
support. This article reviews the current state of play in the diagnosis and treatment of acute
pancreatitis in cats.
Clinical findings
Signalment and History
Acute pancreatitis has been reported in cats aged from 4wks to eighteen years old. Domestic Shortand Long-hair cats are most commonly affected. Siamese cats have been over-represented in some
series. No sex bias has been demonstrated.
A small number of cases have been associated with trauma, Toxoplasma gondii, pancreatic and liver
flukes, FIP, calicivirus (virulent variant) and lypodystrophy. Usually there are no obvious associated
The most common clinical findings in cats with acute pancreatitis are lethargy, anorexia, and weight
loss. Vomiting diarrhea, constipation, icterus, dehydration, ascites and dsypnea are more variably
present. Polyuria and polydipsia have been encountered in some cats with diabetes mellitus and
pancreatitis. The duration of clinical signs until presentation varies from less than 3 days to 12 wks.
Physical Examination
Dehydration, and hypothermia are commonly reported. Icterus may also be present. Abdominal pain
is infrequently elicited. The presence of a palpable cranial abdominal mass or abdominal pain has
been reported in a quarter to a third of cats in some clinical series and cats with experimental and
trauma - induced pancreatitis.
Diagnostic approach and differential diagnosis
Lethargy anorexia and weight loss are the most common presenting complaints. Localizing signs or
findings such as vomiting, icterus, diarrhea, abdominal pain, abdominal mass, polyuria or polydipsia
should be pursued if present.
Where vomiting is present it is approached by pursuing localizing findings such as abdominal pain or
masses and by ruling out infectious, parasitic, metabolic and gastrointestinal causes. Hyperthyroidism
should be ruled out in cats >5yrs old by determination of serum total T4 concentration. Elevated
hepatic enzymes, hyperbilirubinemia, hyperglycemia, and glucosuria are frequently encountered in
cats with acute pancreatitis so pancreatitis should be strongly considered in these cats.
The diagnostic approach to feline icterus is to first rule out pre-hepatic causes i.e. hemolysis, and then
to pursue hepatic or post-hepatic causes. The association of acute pancreatitis and hepatic lipidosis
of increased mortality, cholangiohepatitis and inflammatory bowel disease has been shown in some
studies. A high index of suspicion should be adopted for pancreatitis in cats with hepatic, biliary or
intestinal disease. Cats with a confirmed diagnosis of hepatic lipidosis who have a peritoneal effusion
should also be strongly suspected of having pancreatitis.
Pancreatitis may be the cause of diabetes mellitus in some cats, but the true association between
these diseases is unclear. One study suggests that cats with pancreatitis and diabetes mellitus are
very sensitive to insulin. Transient euglycemia and reduced insulin requirements after removal of a
pancreatic abscess suggest that pancreatic inflammation or infection can exacerbate diabetes mellitus
in cats. Transient diabetes mellitus has also been reported in a cat that was suspected of having
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Where a high index of suspicion for pancreatitis is present ultrasonography and determination of
pancreatic markers (e.g. pancreas specific lipase) should initially be employed to help to detect
pancreatitic inflammation. However, given the spectrum of inter-current disease in cats with
pancreatitis a well performed exploratory laparotomy with biopsy of the pancreas, liver, intestines and
mesenteric lymph nodes is often required to generate an accurate diagnosis and enable feeding tube
Laboratory findings
Hematology: A mild anaemia that may be non-regenerative, and leukocytosis, often without a leftshift, are common in cats with pancreatitis. Leukopenia is present in some cats and carries a poorer
Serum biochemistry: Increased ALT, SAP, bilirubin, cholesterol and glucose, and hypokalemia and
hypocalcemia (total and ionized) are most frequently observed. Azotemia is variably present.
Hypocalcemia, present in about 50% of cases, is perhaps the most helpful finding for raising the
probability of a diagnosis of pancreatitis. Pancreatitis associated hypocalcemia may be caused by a
variety of reasons, such as saponifcation of fat, soft tissue accumulation and changes in PTH
homeostasis. The presence of ionized hypocalcemia (<1mmol/l) carries a poor prognosis.
Hypocobalaminemia is present in some cats with pancreatitis and is thought to reflect concurrent
intestinal disease, rather than exocrine pancreatic insufficiency.
Urinalysis: Enables azotemia to be characterized as renal or pre-renal. The presence of glucose or
ketonuria should prompt consideration of diabetes mellitus.
Pancreas specific enzymes: Classically, elevations in serum amylase and lipase activity have been
used as indicators of pancreatic inflammation in dogs. In cats it seems fair to state that total serum
amylase and lipase are of no utility for diagnosing acute pancreatitis.
These limitations have stimulated the development of assays for enzymes or “markers” considered
pancreatic in origin. Tests for trypsin-like immunoreactivity (TLI), trypsinogen activation peptide (TAP)
and pancreas specific lipase have been evaluated in cats.
Feline Trypsin like immunoreactivity (fTLI). Immunoreactive trypsin has been shown to be a reliable
indicator of pancreatic mass, enabling the reliable detection of feline and canine exocrine pancreatic
insufficiency. It is much less useful as an indicator of pancreatic inflammation. Its sensitivity has been
reported to be as low as 28%, and cats with fatal acute pancreatitis frequently have values within the
normal range. Specificity is better, @ 66-75%. The poor sensitivity, particularly in cats with severe
acute pancreatitis strongly suggests down regulation of TLI in the inflamed pancreas, similar to that
observed in dogs with pancreatitis. Altered renal clearance in cats with renal failure can impact the
specificity, as can the finding of normal pancreatic histology in cats with high TLI and intestinal
Pancreas specific lipase immunoreactivity (fPLI).
Given the limitations of fTLI a test to measure feline pancreas specific immunoractive lipase has
recently been developed. Its clinical utility is still being ascertained. However the initial results for fPLI
are a lot more promising than fTLI, with sensitivity for pancreatitis reported as 67%, and specificity at
Trypsinogen activation peptide (TAP), is a peptide generated by the activation of trypsiongen. In
health TAP is not detected in the circulation or urine. However the intrapancreatic acticvation of
trypisnogen liberates Tap that can be measured in EDT plasma and urine. Experimental studies have
shown that TAP generation can be detected in cats with edematous and hemorrhagic pancreatitis,
with higher levels generated in those with hemorrhagic pancreatitis. Unfortunately, clinical application
is unlikely as the assay is generally unavailable.
Radiographic findings in cats with acute pancreatitis may include loss of serosal detail, increased
opacity in the right cranial quadrant of the abdomen, displacement of the duodenum ventrally and/or
to the right, dilated hypomotile duodenum and caudal displacement of the transverse large intestine.
Although radiographic signs often are absent and non-specific radiography is a logical first choice
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imaging modality for animals with gastrointestinal signs. Negative or equivocal radiographic findings
may be followed up with ultrasonography or an upper gastrointestinal contrast study. Thoracic
radiographs may enable the detection of pleural fluid, edema or pneumonia which has been
associated with pancreatitis in dogs and cats. The high rate of pulmonary thromboembolism
associated with feline pancreatitis may explain some of the thoracic radiographic abnormalities.
Ultrasonographic findings include enlarged, hypoechoic pancreas, cavitary lesions such as abscess or
pseudocyst, dilated pancreatic duct, swollen hypomotile duodenum, biliary dilatation and peritoneal
fluid. Findings in cats indicate that ultrasound will detect from 35 to 67 % of cats with pancreatitis, with
a specificity of @ 73%. This clearly means that a normal ultrasound does not rule out pancreatitis,
and that diseases other than pancreatitis (e.g. pancreatic hyperplasia, pancreatic neoplasia) should
be considered when an abnormal pancreas is visualised.
The clinician should also be careful to consider differential diagnoses of enlarged peri-pancreatic
structures, which can have an identical ultrasonographic appearance to pancreatitis. Fine needle
aspirates of cavitary lesions may be useful to distinguish abscess from pseudocyst, neoplasia from
inflammation etc.
Computed tomography
Contrast enhanced computed tomography (CE-CT) is the diagnostic test of choice for diagnosing
pancreatitis in people. Studies in cats have been disappointing, ranging from a failure to detect the
pancreas to no differences visualized in cats with pancreatitis.
Abdominal paracentesis
Examination of peritoneal fluid may aid the detection of various causes of acute abdominal signs such
as pancreatitis, gastrointestinal perforation or ruptured bile duct. The accumulation of fluid in the
abdomen or the pleural cavity has been variably encountered in cats with acute pancreatitis. Effusion
in the abdomen or chest was present in 17/40 cats in one study, in the abdomen of 5/5 cats with
hepatic lipidosis and pancreatitis, and the abdomen of 2/8 cats another.
Stratifying the severity of pancreatitis is useful when deciding how aggressive to be with medical and
nutritional support, and in offering a prognosis. Severe pancreatitis requires aggressive support and
carries a guarded prognosis, whereas mild pancreatitis may respond to short-term symptomatic
therapy. Clinical and clinicopathological criteria can be used to predict the severity of acute
pancreatitis. The presence of shock or abnormalities such as oliguria, azotaemia, icterus, markedly
elevated transaminases, ionized hypocalcaemia (<1mmol/l), hypoglycaemia, hypoproteinaemia,
acidosis, leukopenia, falling haematocrit, thrombocytopaenia and DIC should be considered likely
indicators of severe pancreatitis in the cat.
The measurement of components of the systemic inflammatory response such as TNF- , alpha-1acid
glycoprotein, and IL-6 may also yield information about the severity of pancreatitis in cats, and in the
future might lead to the administration of specific antagonists of this response. Indicators which are
potentially useful in both the diagnosis and prognosis of pancreatitis include trypsinogen activation
peptide (TAP), trypsin complexed with inhibitors and phospholipase A2. Further validation of these
markers is required before clinical application.
Pancreatic Biopsy and Histology
The pancreas can be biopsied surgically or laparoscopically. Current recommendations, based on the
patchy distibution of pancreatic inflammation, suggest taking biopsies from parts that look or feel
abnormal, and from the left and right limbs and the body. Histological findings are variable and there
is not yet a consensus on their interpretation. In general histopathology is reported according to the
predominant features as acute necrotizing (necrosis predominates), acute suppurative (neutrophils
predominate) or non-supputative (lymphocytic/plasmacytic inflammation and fibrosis). Whether these
histologic types indicate a distinct etiology or some form of progression is unclear. The prognosis for
suppurative pancreatitis is poor.
Medical treatment is based on maintaining or restoring adequate tissue perfusion, limiting bacterial
translocation and inhibiting inflammatory mediators and pancreatic enzymes; surgical treatment
consists principally of restoring biliary outflow, removing infected necrotic pancreatic tissue, or coping
ESFM Feline Congress 2006
with sequela such as pseudocysts. No studies have critically evaluated treatment modalities in cats
with naturally occurring pancreatitis.
The initial medical management is usually initiated before a diagnosis is confirmed, and is based on
the presenting clinical findings and initial laboratory data. Dehydration or hypovolemia are supported
with intravenous fluid therapy. Lactated Ringers solution or 0.9% NaCl are common first choices.
Potassium and glucose should be supplemented where necessary. The type of fluid should be
tailored on the basis of electrolyte and pH measurements to restore normal electrolytes and acid-base
balance. Inonized hypocalcemia is a common finding in cats with acute pancreatitis and impacts
prognosis. However, it is not clear if treatment of hypocalcemia, which is not usually associated with
fasiculations, teatny or seizures, will impact outcome.
Plasma (20ml/kg i.v.) or colloids (10-20ml/kg/day i.v.). may be indicated in the presence of
hypoproteinemia or shock. Colloids such as dextran 70 and hetastarch may also have antithrombotic
effects that help maintain the microcirculation.
Insulin therapy is initiated in diabetic patients. Stress hyperglycemia has to be differentiated from
diabetes mellitus.
Where vomiting is a persistent problem antiemetics (chlorpromazine .2-0.4 mg/kg administered
subcutaneously or intramuscularly every 8 hours,) and antacids (e.g. famotidine 0.5-1mg/kg) may be
Prophylactic broad-spectrum antibiotics (e.g. amoxicillin ± enrofloxacin depending on severity) may be
warranted in patients with shock, fever, diabetes mellitus or evidence of breakdown of the GI barrier.
Bacterial translocation has been demonstrated in experimental feline pancreatitis using distinct E.coli
placed in the colon, and other sites e.g. bile, and colonization was prevented with cefotaxime
(50mg/kg TID).
Analgesia is an important aspect of caring for animals with pancreatitis. It can be provided using
injectable opioids such as buprenorphine (0.005-0.01mg/kg SC q6-12hrs) or oxymorphone (0.050.1mg/kg cats IM, SC Q 1-3hrs). It may be necessary to administer low dose sedation with
acepromazine (0.01mg/kg IM) to patients who become dysphoric after opioids. Buprenorphine is a
partial agonist and may antagonise the administration of more potent analgesics in animals with
severe pain. A transdermal fentanyl patch (Duragesic, Janssen) applied to a clipped clean area of
skin provides longer duration of analgesia (25µg/hr patch q118hrs). Adequate fentanyl levels are not
attained for between 6-48 hrs after application, so another analgesic should be administered in the
short term. This author does not use non-steroidal anti-inflammatory drugs to provide analgesia to
cats with suspected pancreatitis.
Once a diagnosis of pancreatitis is confirmed potentially more specific therapy may be employed.
The specific treatment of pancreatitis has evolved along two lines: 1. Stopping further pancreatitis
from occurring. 2. Limiting the local and systemic consequences of pancreatitis.
The lack of success with inhibiting the progression of spontaneous pancreatitis has led to increased
emphasis on damage limitation; ameliorating the effects of inflammatory mediators or pancreatic
enzymes on the patient and maintaining pancreatic perfusion.
Coagulation abnormalities should be pursued and treatment with parenteral vitamin K can be
assessed. Where a coagulopathy e.g. DIC, or hypoproteinemia are present, or the patient with
pancreatitis is deteriorating, fresh frozen plasma (10-20ml/kg) may be beneficial in alleviating the
coagulopathy, hypoproteinemia and restoring a more normal protease-antiprotease balance. The
administration of heparin (75-150IU/kg TID) may be potentially useful in ameliorating DIC, promoting
adequate microcirculation in the pancreas and clearing lipemic serum. In experimental pancreatitis
isovolemic rehydration with dextran has also been shown to promote pancreatic microcirculation in
dogs. A dopamine infusion (5µg/kg/min) had a protective effect when administered to cats within
12hrs of induction of experimental pancreatitis. H1 and H2- antagonists blocked the progression of
edematous to hemorrhagic pancreatitis in experimental cats and may be beneficial in patients.
In the future therapy to directly abrogate the systemic inflammatory response e.g. antagonists of PAF
(e.g. lexipafant), IL-1 and TNF- may prove to be beneficial.
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Oral pancreatic enzyme extracts have been reported to reduce pain in humans with chronic
pancreatitis, though this is controversial. The presence of a protease mediated negative feedback
system. Has not been described in cats.
In contrast to dogs, where vomiting and abdominal pain predominate, pancreatitis in cats is usually
associated with anorexia and weight loss. The presence of anorexia and weight loss in cats with
pancreatitis may be a significant contributing factor to their poor prognosis. Prolonged fasting (>3
days) to avoid pancreatic stimulation may only serve to compound malnutrition. The clinician is faced
with the dilemma of having to provide nutritional support to prevent or reverse malnutrition and hepatic
lipidosis, and fasting the patient to prevent “pancreatic stimulation”. Current dogma suggests that oral
intake be avoided in patients with pancreatits who are vomiting or have abdominal pain, and that
enteral nutrition should avoid nutrients that stimulate the pancreas (though the protein requirements
of cats makes this unachievable).
However, there is growing evidence in people, and animals, that enteral nutrition is superior to
parenteral nutrition in the treatment of acute pancreatitis. Jejunal feeding (distal to the site of
pancreatic stimulation) does not exacerbate acute pancreatitis in people or experimental animals.
People with acute pancreatitis fed via jejunostomy tubes (these can be oral transpyloric tubes), have
lower morbidity, shorter hospital stay, and less cost than those treated with TPN (total parenteral
nutrition). As it is now feasible to place jejunostomy tubes non-surgically in cats and dogs, through the
nose, esophagus or stomach, clinical application of this feeding strategy is not restricted by a surgical
procedure. It remains open whether cats with acute pancreatitis really require jejunal delivery of
nutrients. Good responses (approximately 70% discharge rate) have been observed at referral
centers employing esophagostomy or gastrostomy tube feeding of enteral diets (e.g. clinicare)
containing approximately 50% calories as fat. These results seem consistent with findings in people
and experimental dogs that show the major benefits of enteral support in acute pancreatitis are due to
reductions in the systemic inflammatory response and the translocation of enteric bacteria rather than
a reduction in pancreatic stimulation.
The author does not mean to imply that parenteral nutrition should be discarded, but its use should be
restricted to patients that really need it, for instance those in whom caloric intake is severely and
persistently impaired by persistent vomiting.
When parenteral nutrition is indicated a choice has to be made between total and partial parenteral
nutrition. Partial parenteral nutrition (PPN) is a more practical and manageable procedure than TPN in
most settings and has been shown to be a safe and effective way of providing nutrition to dogs with
pancreatitis and gastrointestinal disease. Interestingly dogs that received a combination of enteral and
PPN survived more often than those receiving PPN exclusively.
Patients with suspected or confirmed pancreatitis should be monitored to enable early detection of
shock or other systemic abnormalities. Minimal monitoring for stable patients includes regular
assessment of vital signs and fluid and electrolyte balance. In those with systemic abnormalities,
monitoring should be more aggressive and may include vital signs, weight, haematocrit, total protein,
fluid intake and output, blood pressure (central venous and arterial), electrolytes and glucose, acidbase status, platelets and coagulation status. Ultrasound-guided fine needle aspiration of the
pancreas may enable infected pancreatic necrosis to be detected. Ultrasonography may also enable
detection of delayed consequences of acute pancreatitis such as pancreatic abscessation,
pseudocyst formation and biliary obstruction.
Surgery is often necessary to confirm a diagnosis of acute pancreatitis in cats and also enable feeding
tube placement. The increased utility of ultrasonography and measurement of markers of pancreatic
inflammation (e.g. fPLI) may lead to a reduced dependency on surgery in cats with high fPLI and
sonographic abnormalities. However it should be stressed that cats with pancreatitis often have
concurrent abnormalities in other organ systems e.g. liver and gut, and biopsy of these organs and
the pancreas may be indicated to optimize diagnosis and treatment. Transient euglycemia and
reduced insulin requirements were noted after the removal of a pancreatic abscess in one cat suggest
that surgical intervention may be beneficial in these cases. Surgery is potentially indicated for infected
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pancreatic necrosis, abscess drainage, and to investigate and to relieve persistent biliary obstruction.
Resection or surgical drainage of pancreatic pseudocysts is not always necessary as these can
resolve spontaneously or following percutaneous drainage.
The prognosis for acute pancreatitis in cats must always be considered guarded. Extensive hepatic
lipidosis, suppurative pancreatitis, leucopenia and ionized hypocalcemia <1mmol/l are associated
with a poor prognosis.
References and further reading
Akol K, Washabau RJ, Saunders HM, Hendrick MJ. Acute pancreatitis in cats with hepatic lipidosis.
Journal of Veterinary Internal Medicine 1993; 7: 205-209.
Bhattacharya SK, Luther RW, Pate JW. Soft tissue calcium and magnesium content in acute
pancreatitis in the dog: calcium accumulation, a mechanism for hypocalcemia in acute pancreatitis.
Journal of Laboratory Clinical Research 1985; 105: 422-427.
Etue SM, Penninck DG, Labato MA, Pearson S, Tidwell A. Ultrasonography of the normal feline
pancreas and associated anatomic landmarks: a prospective study of 20 cats. Veterinary Radiology
& Ultrasound 2001; 42: 330-336.
Ferreri J, Hardam E, Van Winkle TJ, Saunders HM, Washabau RJ. Clinical differentiation of acute
and chronic feline pancreatitis. Journal of the American Veterinary Medical Association. 2003; 223:
Forman MA, Marks SL, De Cock HE, Hergesell EJ, Wisner ER, Baker TW, Kass PH, Steiner JM,
Williams DA.Evaluation of serum feline pancreatic lipase immunoreactivity and helical computed
tomography versus conventional testing for the diagnosis of feline pancreatitis. J Vet Intern Med. 2004
Gerhardt A, Steiner JM, Williams DA, Kramer S, Fuchs C, Janthur M, Hewicker-Trautwein M, Nolte I.
Comparison of the sensitivity of different diagnostic tests pancreatitis in cats. Journal of Veterinary
Internal Medicine 2001; 15: 329-333.
Harvey MH, Wedgwood KR, Reber HA. Vasoactive drugs, microvascular permeability, and
hemorrhagic pancreatitis incats. Gastroenterology 1987; 93: 1296-1300.
Head LL, Daniel GB, Tobias K, Morandi F, DeNovo R, Donnell R. Evaluation of the feline pancreas
using computed tomography and radiolabeled leukocytes. Veterinary Radiology & Ultrasound 2003;
44(4): 420-428.
Hill R, and van Winkle T. Acute necrotizing pancreatitis and acute suppurative pancreatitis in the cat.
Journal of Veterinary Internal Medicine 1993; 7: 25-33.
Hurley KE, Pesavento PA, Pedersen NC, Poland AM, Wilson E, and Foley JE. An outbreak of virulent
systemic feline calicivirus disease. Journal of the American Veterinary Medical Association 2004;
224(2): 241-249.
Karanjia ND, Lutrin FJ, Chang Y-B, et al. Low dose dopamine protects against hemorrhagic
pancreatitis in cats. Journal of Surgical Research 1990; 48: 440-443.
Karanjia ND, Widdison A, Jehanili A, Hermon-Taylor J, Reber HA. Assay of trypsinogen activation in
the cat experimental model of acute pancreatitis. Pancreas 1993; 8: 189-195.
Kimmel SE, Washabau RJ, Drobatz KJ. Incidence and prognostic significance of ionized
hypocalcemia in feline acute pancreatitis. Journal of the American Veterinary Medical Association
2001; 219: 1105-1109.
Macy DW. Feline pancreatitis. In: Kirk RW, Bonagura JD, eds. Current Veterinary Therapy X,
Philadelphia, PA: WB Saunders, 1989, 893-896.
Saunders HM, VanWinkle TJ, Kimmel SE, Washabau RJ. Ultrasonographic and radiographic findings
in cats with clinical, necropsy, and histologic evidence of pancreatic necrosis. Journal of the
American Veterinary Medical Association 2002; 221: 1724-1730.
Schermerhorn T, Pembleton-Corbett JR, Kornreich B.Pulmonary thromboembolism in cats. J Vet
Intern Med. 2004 Jul-Aug;18(4):533-5.
Simpson KW, Beechey-Newman N, Lamb CR, et al. Cholecystokinin-8-induces edematous
pancreatitis in dogs associated with short burst of trypsinogen activation. Digestive Diseases and
Sciences 1995; 40: 2152-2161.
Simpson KW, Fyfe J, Cornetta A, et al. Subnormal concentrations of serum cobalamin (vitamin B12)
in cats with gastrointestinal disease. Journal of Veterinary Internal Medicine 2001; 15: 26-32.
Simpson KW, Shiroma JT, Biller DS, Wicks J, Johnson SE, Dimski D, Chew D. Ante-mortem
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diagnosis of pancreatitis in four cats. Journal of Small Animal Practice 1994; 35: 93-99.
Steiner JM, Williams DA. Serum feline trypsin-like immunoreactivity in cats with exocrine pancreatic
insufficiency. Journal of Veterinary Internal Medicine 2000; 14: 627-629.
Steiner JM, Wilson BG, Williams DA. Development and analytical validation of a radioimmunoassay
for the measurement of feline pancreatic lipase immunoreactivity in serum. Can J Vet Res. 2004 Oct;
Steiner JM, Wilson BG, Williams DA. Purification and partial characterization of feline classical
pancreatic lipase. Comparative Biochemistry and Physiology, Part B, Biochemistry & Molecular
Biology 2003; 134: 151-159.
Swift NC, Marks SL, MacLachlan NJ, Norris CR. Evaluation of serum feline trypsin-like
immunoreactivity for the diagnosis of pancreatitis in cats. Journal of the American Veterinary Medical
Association 2000; 217: 37-42.
Weiss DJ, Gagne JM, and Armstrong PJ. Relationship between feline inflammatory liver disease and
inflammatory bowel disease, pancreatitis, and nephritis. Journal of the American Veterinary Medical
Association 1996; 209: 1114-1116.
Widdison AL, Alvarez C, Chang Y-B, Karanjia ND, Reber HA. Sources of pancreatic pathogens in
acute pancreatitis in cats. Pancreas 1994; 4: 536-541.
Widdison AL, Karanjia ND, Reber HA. Antimicrobial treatment of pancreatic infection in cats. British
Journal of Surgery 1994; 81: 886-889.
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Diseases of the ears, nose, throat and oral cavity of cats
Professor Richard Malik DVSc PhD FACVSc FASM
Post Graduate Foundation in Veterinary Science, Conference Centre, Building B22,
University of Sydney, NSW 2006 Australia
In human medicine, specialist clinicians deal exclusively with the diagnosis and treatment of diseases
of the ears, nose and throat (E.N.T.). In veterinary medicine, such specialisation is rare, although
individuals such as Dr Anjop Venker-van Haagen have started to develop E.N.T. medicine and
surgery to such an extent that it is beginning to become a veterinary discipline in its own right. This
talk is given from my perspective, a veterinarian mainly interested in cats, who has been forced to
better understand diseases affecting the ear, nose, throat and oral cavity to best treat the patients
under my care.
Diseases affecting these anatomical areas are commonplace in feline practice. The investigation of
most cases requires equipment available in the majority of small animal clinics, although in some
cases the availability of rigid and flexible endoscopes for examination of the external ear canal and
nasopharynx facilitates investigations considerably. In the future, use of cross-sectional imaging
modalities such as computer-assisted tomography (CT) and magnetic resonance imaging (MRI) is
likely to contribute extra information concerning diseases affecting these anatomical areas.
Diseases affecting the pinna, external ear canal and middle ear
The pinna can be affected by diseases processes which affect the skin generally. Thus, lacerations
are common in cats that fight, and ultraviolet-induced solar dermatitis typically results in the
development of squamous cell carcinoma (SCC) in cats with non-pigmented (white or ginger) ears
that spend a lot of time outdoors. This is a big problem in places like Australia and California that
receive a lot of sunlight. Cats occasionally develop aural haematomas, usually as a result of irritation
affecting the ear canal that results in scratching. Harvest mite infestations can cause severe irritation
of the head and ears of cats; the diagnosis is easily made by identification of orange or yellow lesions
on the ears of affected cats. Smears of these coloured lesions demonstrate the large, orange/yellow
mites. We have also seen a small number of cats with sarcoptic mange affecting the skin of the pinna
or the external ear canal; in these cases mites were extremely abundant, as in Norwegian scabies of
human patients.
As a rule, otitis externa is less common in cats that dogs. However, young cats, outdoor cats and cats
that live in colonies are commonly afflicted with Otodectes cyanotis, which results in an irritant/allergic
otitis externa. A crusty black discharge is said to be characteristic, but a similar discharge can occur
with other diseases of the external canal. All cats with otitis externa should be suspected of having ear
mites until proven otherwise and the availability of modern, safe and effective products like selamectin
and fipronil makes it worthwhile to treat tentatively for this disease even when mites are not detected.
Direct visualisation of mites is facilitated by the use of a video otoscope, which provides both excellent
illumination, magnification and a good depth of field. Material should also be obtained from the ear
canal for cytological examination, as some mites or eggs can be seen in smears when adult mites
have been missed using otoscopy. Mites are large, pearly white, very active and are said to ‘run away’
from the light source, although this is not my experience. A variety of modern treatments are now
available for treating Otodectes infections e.g. fipronil, ivermectin, milbemycin and selamectin. It is
important to treat the whole cat, not just the ear canal, to repeat the treatment after three weeks, and
to treat in-contact cats and dogs.
Occasionally, Demodex catii can cause parasitic otitis externa in cats. The diagnosis is made by
microscopic examination of smears from the lining of the ear canal. Usually these cats have some
underlying cause for immunosupression, for example corticosteroid therapy or FIV infection.
Treatment using topical or systemic therapy is generally successful. Bacterial otitis is rare in cats, but
does occur, and should be treated using a combination of systemic and topical therapy. Systemic
therapy is often easier and more effective in cats with irritated ears that otic therapy and this is not
cost-prohibitive as in larger canine patients. Occasional cats with allergic dermatitis get otitis externa
ESFM Feline Congress 2006
as a component of their atopy or food allergy/intolerance, and treatment should be directed at the
underlying allergic condition as well as the irritated ear canal.
Proliferative lesions can sometimes be observed in the ear canal of cats. Polyps, arising from the
middle ear cavity or external ear canal, can occur in cats of all ages. When removed together with
their stalk, these polyps may be cured using simple traction. If a pedicle is left behind, however, the
problem usually recurs, necessitating more invasive surgical interventions in order to effect a
permanent resolution. In older cats, ceruminous gland carcinomas can develop in the external ear
canal. This malignancy can be cured by timely ablation of the entire horizontal and vertical ear canal.
Invasive squamous cell carcinoma can occur in the ear canal of elderly cats. In my limited experience,
this cancer already has invaded tissues outside the ear canal by the time diagnosis is made using
cytology and cross sectional imaging.
Otitis media is not-uncommon in cats, and typically results from an ascending infection up the auditory
tube from the nasopharynx. Less frequently it occurs secondary to parasitic or bacterial otitis externa.
Cats with middle ear infections develop signs of peripheral vestibular disease, either unilateral or
bilateral. Sometimes Horner’s syndrome is present also. The diagnosis is often tentative, based on
characteristic clinical signs and response to therapy. In some cases, radiographs of the tympanic
bullae or CT of the head are used to confirm the anatomical diagnosis. Material for culture is
sometimes obtained via myringotomy or via operative bulla osteotomy. Typically, otitis media is the
result of bacterial infection with organisms that normally reside in the nasopharynx, such as
Pasteurella species and obligate anaerobes. Acute cases often respond to a two to four week course
of clindamycin, doxycycline or amoxicillin/clavulanate. Some cases, however, require surgical
drainage, through a bulla osteotomy or the external ear canal (via a myringotomy), to effect a cure.
Recently, LeCouteur’s group have shown that these infections can sometimes extend to involve the
adjacent brainstem. We have seen a very small number of cats where otitis media, and sometimes
concurrent otitis externa, is referable to cryptococcosis.
Disease of the nasal cavity, choane and nasopharynx
In young cats, viral upper respiratory tract infections are the most common cause of nasal cavity
disease. Although these infections are generally self-limiting, the author recommends prophylactic
therapy using doxycycline or clindamycin to prevent adverse sequellae such as pyothorax, ascending
infections of the auditory tube and chronic rhinosinusitis. Recent work suggests that interferon-omega
may be useful in these cases, however it is virtually cost-prohibitive at present to recommend its
routine use for this purpose. The anti-herpes agent famciclovir (1/2 125 mg tablet once a day for 7 to
14 days) deserves evaluation for the treatment of cats with acute Herpesvirus rhinosinusitis.
By far and away the most common disease of the nasal cavity of adult cats is post-viral rhinosinusitis
(synonyms: snuffler cat, snuffles, etc). This a chronic disease condition thought to occur as a
sequellae of Herpesvirus or Calicivirus infection of the nasal passages, which result in extensive
destruction of turbinates, leading to residual foci of infection with secondary bacterial pathogens.
These cats are presented for chronic nasal discharge, sneezing and epiphora. Severe cases may also
show lassitude and inappetence. Such cases are diagnosed on the basis of a history of presumptive
viral respiratory tract disease and results of endoscopic, cytologic and three dimensional imaging
studies. There are no definitive diagnostic features, and usually the diagnosis is reached by excluding
other differentials such as cryptococcosis, foreign bodies (e.g. grass awns, projectiles) and neoplasia.
Some cases can be cured by long courses of antimicrobial therapy. Because anaerobic bacteria are
likely secondary invaders in many cases, clindamycin, at an anti-anaerobic dose given for at least
eight-weeks, can be curative. Such long courses are only indicated if there is an initial and sustained
response to therapy. The rationale of continuing therapy for such a long time is based on the notion
that the infection is a deep-seated osteomyelitis/chondritis. Many cases respond to antibiotics, but
relapse during or after a long course of therapy. Some of these cases may respond to major surgical
interventions eg radical turbinectomy via a ventral rhinotomy, or implantation of antibiotic-impregnated
bone cement into the frontal sinuses. Large series of surgically managed cases have not been
published, however, suggesting that surgery may help in some cases, but not others. Many cats are
not severely affected, and owners often elect to ignore the problem or dose affected cats with
antimicrobials intermittently, as required. Again, evaluation of new treatment protocols that use
antiviral agents (interferon-omega, famciclovir) in concert with antibiotics are indicated to develop
more effective treatment options for this common and frustrating condition.
ESFM Feline Congress 2006
Mycotic rhinitis occurs in the cat, but unlike the equivalent group of infections in dogs, aspergillosis is
rare while cryptococcosis is reasonably common. Cats with cryptococcosis present for signs of rhinitis
such as sneezing, nasal discharge and epistaxis. Sometimes the mucosa within the naris is swollen,
or there is a polypoid mass protruding from the nostril(s). Some strains of Cryptococcus are invasive,
and give rise to deforming disease of nearby structures, such as the nasal planum, bridge of the nose,
hard palate, tooth roots, while in other cases there is involvement of the regional lymph node(s).
Diagnosis is readily made by cytology of nasal discharges or aspirates from swellings, and confirmed
by culture on bird seed agar or using the cryptococcal antigen agglutination test. Most cases of
localised nasal cryptococcosis can be cured using monotherapy with itraconazole or fluconazole.
Severe or refractory cases benefit from combination therapy using amphotericin B and flucytosine,
with follow-up azole therapy. In contrast to canine aspergillosis, nasal aspergillosis in the cat is often
an invasive disease, with the propensity to penetrate the overlying bones and give rise to disease of
nearby structures eg the retrobulbar space, nasal bridge, palate, nasopharynx. Topical therapy (such
as used in the dog) is inappropriate for such infections, which instead require treatment with
itraconazole and sometimes amphotericin B. The new antifungal agent posaconazole (5 mg/kg orally
with food once daily) has recently been shown to be an effective agent for this condition, offering
several advantages over itraconazole and even amphotericin B.
Nasal neoplasia gives rise to progressive signs of nasal cavity disease, often with extension of the
malignancy to adjacent structures, such as the bridge of the nose, the retrobulbar tissues, the
nasopharynx or the olfactory lobes of the brain. In our practice, lymphosarcoma is the most common
nasal malignancy, followed by squamous cell carcinoma, adenocarcinoma and tumours arising from
bone or cartilage. Of these diseases, lymphoma has the best prognosis as perhaps 50% of cases (or
more) attain durable remissions with multi-agent chemotherapy, and indeed some can be cured.
Squamous cell carcinoma is amenable to radiotherapy and some cases partially respond to
carboplatinum. Bone and cartilage tumours may be treated using sumarium and/or carboplatinum.
In some cats with nasal cavity disease, there is preferential involvement of the caudal portion of the
nasal cavity, the choane or the nasopharynx. These animals usually do not have nasal discharge,
epistaxis or sneezing. Instead, they have signs of stertor, snoring or halitosis and in extreme
circumstances they learn to breathe through their mouth. A variety of disease processes can cause
these signs. Lymphosarcoma and cryptococcosis sometimes present in this fashion. On physical
examination, a mass in the nasopharyngeal region can sometimes be palpated through the soft palate
(typically under sedation or anaesthesia), and a needle aspirate through the palate can be diagnostic.
Such masses are readily visualised using a flexible endoscope retroflexed behind the soft palate.
Alternately, a vigorous nasal flushing technique often dislodges a large portion of the offending mass,
which can then be submitted for laboratory investigations and histopathology. Other disease
processes which can involve the nasopharynx include blades of grass (which get caught behind the
soft palate after being vomited), fish bones, grass awns, polyps arising from the opening of the
auditory tube, webs of scar tissue resulting from previous viral infection (giving rise to nasopharyngeal
stenosis). Foreign material can often be dislodged by flushing using a 10 mL syringe tightly wedged in
one nostril or removed using a retroflexed endoscope. Counter intuitively, flushing through the least
obstructed nostril is often most effective in dislodging mass lesion(s) or foreign material. It is our
experience that nasopharyngeal polyps do not recur if they are removed with a substantial amount of
‘stalk’, and if antibiotics are given for two-weeks following the procedure. Recurrent nasopharyngeal
polyps generally require bulla osteotomy as well as polyp removal to effect a cure. Be warned, some
cats have bilateral polyps, and other have bifid polyps with a components in both the nasopharynx
and the ipsilateral external ear canal.
Disease of the oral cavity and pharynx
Disease of the oral cavity is common, however many lesions are missed merely because clinicians
sometimes do not take the time to properly inspect every cat’s mouth during routine physical
examination. This is a sin we have been guilty of. Feline dentistry is beyond the scope of the present
talk, however it is important to emphasise that periodontal disease is one of the most important
preventable causes of disease in domestic cats and that feeding fresh raw chicken wings, lamb
shanks and other ‘raw meaty bones’ on a regular basis is critical to the overall health of cats.
Chronic Calicivirus infection gives rise to refractory disease of the gums and fauces. In these patients,
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there is sufficient antibody-mediated response to virus to produce all the classic signs of inflammation,
however there is insufficient cell-mediated immunity to throw off the virus and thereby eliminate the
chronic carrier state. Up until recently, treatment had involved radical extraction of molar and
premolars, antibiotics such as doxycycline, metronidazole or clindamycin and (when necessary) the
minimal anti-inflammatory dose of corticosteroids required to dampen down the inflammation. Recent
work, however, suggests that some of these cats can be cured using feline interferon-omega, or
thalidomide, and these treatments can be supplemented by local administration of topical agents such
as Bonjela. The natural product slippery elm has also been used with benefit in some of these cases.
Feline resorptive lesions are an important cause of tooth and gum disease in cats, and the associated
pain can cause teeth chattering, reduced appetite and weight loss in some patients. The cause of
these lesions is controversial, however the requirement for extraction of affected teeth is not in doubt.
It should be emphasised that recent information suggests that there is no need to completely remove
the tips of tooth roots that snap-off during attempted removal of affected teeth, as these are resorbed
Intraoral collagenolytic granulomas are a bizarre feline manifestation of allergic disease. They may be
either proliferative, or ulcerative, and are typically situated on the tongue or palate, although they can
appear in any lesion within the oral cavity. I have seen one cat with a large lesion arising from the
pharynx, which also had involvement of the larynx. A very characteristic feature is the presence of
yellow or white foci within the larger lesion, these areas corresponding to microscopic areas of lytic
collagen, and the presence of such foci is virtually diagnostic of this aetiology. Often ‘rodent ulcers’ or
miliary dermatitis are present concurrently. Ideally, these cases should be treated by finding and
eliminating the underlying cause of the hypersensitivity reaction, e.g. fleas in cases where flea
antigens are the underlying immunologic trigger. When this is not possible, monotherapy using a six
to eight week course of cyclosporine is successful in many cases, and has fewer side effects than
older treatments regimens such as prednisolone/chlorambucil/ gold salts. In patients with proliferative
lesions, preliminary debulking using a scalpel can be very helpful also.
‘Menrath’s ulcer’ (synonym: bleeding palatine ulcer) refers to a unusual syndrome in which, for some
reason, cats with allergic skin disease develop life-threatening bleeding from an ulcer on the palate
immediately adjacent to the upper canine tooth. It is thought that over grooming associated with
pruritic skin disease somehow results in the papillae on the tongue abrading the hard palate until a
branch of the palatine artery is eroded. When this occurs, significant haemorrhage results, however
because the cat continues to lick the ulcer and therefore potentiate the haemorrhage. Because the
blood emanating from the bleeding ulcer is swallowed, the owner (and veterinarian!) may not
appreciate the cause of the bleeding until the cat is almost dead. By this stage, a typed blood
transfusion may be required to save the patient. On-going haemorrhage is best controlled by placing a
horizontal mattress or cruciate stich (using deep bites) across the ulcer so that ensuing pressure
stops the haemorrhage. The ulcer can be hard to appreciate when the gums are very pale as a result
of hypovolaemic shock and anaemia; for this reason, a thorough oral cavity examination is mandatory
in all cats presented for severe (and typically acute) anaemia. To prevent this problem recurring in the
future, efforts of the clinician should be directed towards treatment of the underlying skin disease e.g.
using flea control, hypoallergenic diets, antihistamines, corticosteroids or cyclosporine, as appropriate.
The tongue can be affected by a variety of disease processes, and experienced feline clinicians
routinely elevate the tongue using digital pressure in the intermandibular space to facilitate
examination of the frenulum. Doing this routinely will ensure that linear foreign bodies caught around
the lingual frenulum will never be missed! Squamous cell carcinoma (SCC) is the worse disease
process which can affect the tongue, and typically affects its base. However, inflammatory diseases
resembling lingual SCC have been encountered by the author. These lesions, which may result from
secondary infection following penetration by foreign bodies, have responded promptly to debulking
(biopsy) and antimicrobial therapy. We have been surprised recently to have diagnosed lingual
lymphoma (rather than SCC) in a cat with a grossly abnormal tongue; this patient responded
favourably to multi-agent chemotherapy.
Finally, tonsils should be examined during routine oral cavity examination. Tonsillar SCC occurs in the
cat, although most cases the author has diagnosed have been presented for unilateral mandibular
lymphadenomegaly. The cause of metastatic disease was not apparent until the oral cavity was
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Medical or pedicle?
Treatment of traumatic eye injuries in cats
David Gould BSc(Hons) BVM&S PhD DVOphthal DipECVO MRCVS
Davies Veterinary Specialists, Hertfordshire, UK
Globe prolapse (proptosis)
Proptosis describes a traumatic acute forward prolapse of the globe. It is most common in breeds with
prominent globes and shallow orbits, such as the Persian. If it occurs in other breeds, it is usually
associated with severe head trauma. Note that in proptosis the equator of the globe is displaced
anteriorly so that it lies in front of the eyelids. This differs from exophthalmos (forward displacement of
the globe usually due to an orbital infection or tumour) in which the equator of the globe remains
caudal to the eyelids.
Proptosis is a surgical emergency:
Stabilise the patient (analgesia, intravenous fluids)
Check for concurrent life-threatening injuries (e.g. other head or brain injuries, diaphragmatic
hernia, pneumothorax)
Assess globe damage (examine cornea, anterior chamber, iris and pupil, check pupillary light
reflexes). If severe damage consider enucleation.
Once the patient is stabilised, the globe must be repositioned under general anaesthesia. A lateral
canthotomy may aid replacement. Place stay sutures in the upper and lower eyelids, apply lubricant
and ease the eyelids over globe using gentle globe retropulsion. Place temporary tarsorrhapy sutures
for 10-14 days and treat with systemic analgesics and antibacterials. In cats, the prognosis for vision
is extremely poor.
Eyelid trauma: surgical preparation and repair
Eyelid skin is one of the thinnest in the body and therefore requires gentle handling, fine instruments
and a gentle technique. If there has been traumatic damage to the eyelid margin, it is important to
achieve primary closure during surgical repair, as any notches will predispose to corneal ulcers.
When preparing the eyelid skin for aseptic surgery, avoid preparations containing detergent or alcohol
as these are toxic to the cornea. Instead, use povidone-iodine aqueous solution. Dilute a 10% stock
solution 1:20 with water or normal saline to a final concentration of 0.5% povidone-iodine. For flushing
the ocular surface, use 1:50 dilution.
Good patient positioning during surgery makes all the difference, so use a deflatable bean bag (e.g.
‘Buster Vacu Op Support’ + vacuum pump) and use a good overhead light source or head loupes with
illumination. Consider use of a surgical chair with armrests.
Suitable good quality surgical instruments are also vital. An eyelid surgical kit may include:
Rat-tooth forceps (e.g. Bishop-Harmon or St Martin’s)
Scalpel handle and blade (no. 15)
Needle holders (e.g. Derf or Castroviejo needle holders)
Sharp scissors (Stevens tenotomy scissors, straight, rounded tips)
Desmarres entropion forceps
For eyelid margin repair in cats, a one-layer closure using 6/0 Vicryl is usually sufficient. Place the first
suture at the eyelid margin using a figure-of-eight pattern and ensure that the knot will not contact the
cornea post-operatively. Use simple interrupted sutures elsewhere.
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Corneal and globe trauma
Traumatic laceration or corneal ulceration is common. Cat claws often introduce bacterial
contamination (frequently Pasteurella spp) and therefore topical antibacterial medication is always
indicated. Chloramphenicol is a suitable first-line choice. It has broad-spectrum activity and is the
least epitheliotoxic of the topical antibacterials. Other suitable choices include gentamicin,
ciprofloxacin or ofloxacin.
When assessing traumatic corneal or globe lacerations it is vital to check for intraocular penetration.
Examine the iris and pupil carefully and check the pupillary light reflexes. Dilate the pupil with
tropicamide and carefully examine the lens and, if possible, the retina. In particular it is important to
identify lens capsule rupture as this can lead to a severe and often uncontrollable inflammation
(phacoclastic uveitis), necessitating removal of the lens contents by phacoemulsification surgery.
Thus if lens rupture is suspected, it is advisable to seek specialist advice. Lens rupture may
predispose to intraocular sarcoma formation in later life.
Treatment of traumatic corneal ulceration depends on the depth of the ulcer:
Depth of
Medical treatment
Surgical treatment
Topical antibiotic (e.g.
Not required
Less than
1/3 depth
Topical antibiotic ±
Contact lens or third eyelid flap
than 1/3
Topical antibiotic plus
Conjunctival pedicle graft or corneoconjunctival transposition graft
Conjunctival pedicle graft placement requires microsurgical equipment, magnification and
experience. It may also result in visual opacification, so ulcers affecting the axial portion of the
cornea may benefit from more advanced techniques such as corneo-conjunctival transposition
“Melting” corneal ulcers (liquefactive stromal necrosis)
Acute stromal collagenolysis (‘melting’ corneal ulceration) describes a rapid and progressive corneal
melt that should be treated as a medical and/or surgical emergency. It can occur when an existing
corneal ulcer:
Becomes infected with a bacterium that releases proteases
Is treated with topical corticosteroids
Corneal melts may also be associated with chemical injuries (especially alkali burns) and, rarely,
insect bites.
The bacterial species most commonly isolated from corneal melts are Pseudomonas aeruginosa and
beta-haemolytic streptococcus. They release a variety of proteolytic enzymes that dissolve the
corneal stroma and lead to progressive deepening of the ulcer. Topical corticosteroids induce corneal
melts by activating release of endogenous proteases (matrix metallo-proteases, MMP’s) from
keratocytes and neutrophils.
Signs of an early corneal melt include:
A corneal ulcer with an ill-defined gelatinous rim, which may be grey, white or yellow
Increasing ocular discomfort
Progression from serous to mucopurulent ocular discharge
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Progressive deepening of the ulcer
Secondary uveitis (miosis and iris hyperaemia)
Work-up and treatment
Melting ulcers should be classed as an emergency. Immediate referral should be considered. If not,
animals should be hospitalised and carefully monitored. If this is not possible, then it is vital that the
owner returns for regular (at least daily) check-ups, and is made aware of the risk of sudden globe
A typical work-up would consist of:
History-taking (including prior ophthalmic disease, use of topical corticosteroids, exposure to
Thorough eye examination. Proceed carefully if the ulcer is deep. If there is a risk of imminent
globe rupture it may be necessary to omit certain procedures such as STT or tonometry
PH testing of conjunctival fornices if there is a history of acid or alkali exposure
Fluorescein staining
Conjunctival or corneal swab under topical anaesthesia (care!). In-house cytology can be
used to identify bacterial rods or cocci, which may help in selection of antibacterials. The
swab can also be sent for bacterial culture and sensitivity, which may be of retrospective use
Medical treatment consists of:
Autologous serum q30-60mins. This has broad-spectrum anti-protease activity to help to stop
the melt
Topical antibacterials. Fluoroquinolones such as ciprofloxacin and ofloxacin are commonly
used (their use should be reserved for melting ulcers). They are broad-spectrum, with good
activity against Pseudomonas, but note that some streptococci species may be resistant
Systemic antibacterials
Systemic NSAID’s
Other drugs that may have anti-protease activity and might be considered include topical
acetylcysteine, topical EDTA, systemic tetracycline and vitamin C
If the melt is due to an alkali burn, then copious irrigation of the corneal surface should be
performed until the normal pH (around pH7.5) has been restored. Specialist advice should be
Surgical intervention is often required, most commonly conjunctival grafting. Conjunctival pedicle,
bridge, hood and 360o grafts may be used. Conjunctival grafts not only give physical support to the
weakened cornea, but also provide a blood supply, thus allowing direct access by serum anticollagenases and systemically administered antibacterials.
Corneal surgery: equipment and techniques
Ideally, an operating microscope is recommended for all types of corneal surgery, including
conjunctival pedicle grafts. Microscopes for ophthalmic surgery provide coaxial illumination. Their
magnification typically ranges from 3x to 20x, which in most models can be varied by means of a foot
pedal operated by the surgeon. Their working distance (focal length) is usually around 17.5cm. An
operating chair with arm rests is required for the surgeon.
Head loupes are used by some practitioners. They provide fixed magnification of 1.5x to 6x
(depending on the lens chosen), which is suitable for extraocular procedures. However, they have
some significant disadvantages when employed for corneal surgery: The magnification may not be
sufficiently high; it is not possible to change magnification during a surgical procedure; they are heavy;
and their working distance can make corneal surgery difficult.
Patient positioning
Good positioning of the eye is essential. Use of a vacuum pillow allows the head to be optimally
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positioned under the microscope. Remember that the globe rotates medioventrally under general
anaesthesia and this can make surgical access difficult. I will commonly use neuromuscular blockade
and artificial ventilation to maintain a central globe position during corneal surgery. If this is not
possible, placement of limbal stay sutures (6/0 Vicryl) or careful use of fine haemostats placed
adjacent to the limbus is acceptable.
Surgical technique
Tissue handling must be gentle and kept to a minimum. The cornea is very easily damaged. Avoid
handling adjacent healthy tissue as much as possible. Always maintain visualisation of the surgical
field when you are handling tissues. Maximize haemostasis with the use of surgical spears. Keep the
surgical field moist with the frequent application of saline.
Microsurgical instrumentation
It is essential to have appropriate, good quality microsurgical instruments. General features of
microsurgical instrument design include:
Lightweight design
Handle of narrow diameter and sufficient length to rest comfortably in the hand
Presence of serrations/grooves on handle to improve tactile feedback
Absence of locking mechanism and the use of spring handles to promote smooth handling
Many ophthalmic microsurgical instruments are available in stainless steel or in titanium. Titanium
instruments are more expensive but they are lightweight, more durable, non magnetic, and nonreflective.
A typical extraocular corneal/ conjunctival kit may consist of the following:
Fine-toothed tying forceps (e.g. St Martin or Bishop-Harmon)
Fine-toothed curved forceps (e.g. Colibri)
Curved needle holder, no lock (e.g. Troutman, Barraquer, Castroviejo)
Mosquito artery forceps x2 (e.g. Halstead)
Eyelid speculum (e.g. Castroviejo, Barraquer)
Stevens tenotomy scissors, straight, rounded tips
Westcott tenotomy scissors, curved, rounded tips
Beaver scalpel handle
Bard-Parker scalpel handle
Disposable instruments and equipment include corneal set depth knives, corneal dissectors, syringes
and irrigating cannulae, ophthalmic drapes, surgical spears.
Needle and suture selection
Spatulated needles are specifically designed for lamellar tissues such as the cornea, as their flattened
shape helps to maintain the needle within the tissue plane when placing sutures. Half-curved or 3/8
curved needles are suitable for corneal and conjunctival tissues. Typical needle length is 8-12mm.
Polyglactin 910 (Vicryl) is most commonly used conjunctival and corneal suture material. Conjunctival
wounds should be sutured with 6/0 suture. Corneal wounds should be sutured with 8/0 or 9/0 suture.
Placement of corneal sutures
Use a wrist-action technique and aim for 3/4 to 4/5 depth (the normal cornea is around 0.7mm thick).
Magnification is essential.
Conjunctival grafts
Types of conjunctival graft include:
Conjunctival free island graft
Conjunctival rotational pedicle graft
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Conjunctival advancement pedicle graft
Conjunctival hood graft
360 degree conjunctival graft
Rotational pedicle graft
• Using small rounded tip scissors (e.g. Westcott tenotomy scissors), make a perilimbal incision
at the site of the distal tip of the pedicle (e.g. the 8 o’clock position in the right eye, or the 4
o’clock position in the left eye) and perform extensive blunt dissection through this site to
separate the conjunctiva from the underlying Tenon’s capsule.
• Extend the incision parallel to the limbus up towards the 12 o’clock position.
• Make a parallel incision approximately 5mm from the first (depending on the width of the graft
• Rotate the graft to the defect and ensure no tension, otherwise graft dehiscence may occur.
Trim the distal end if any tissue damage is evident.
• Prepare the ulcer site by debriding epithelium and removing necrotic debris.
• Suture the pedicle into the edges of the defect using 8/0 Vicryl simple interrupted sutures. Aim
for ¾ depth bites.
• The base of the graft can be sutured to the limbus is required.
• The donor site can be closed with 8/0 Vicryl continuous suture.
Leave the graft in place for 4-6 weeks, then section under topical anaesthesia.
Further reading
Maggs D (2002). Ophthalmic surgery: instrumentation. In BSAVA Manual of Small Animal
Ophthalmology 2nd edition. Eds S Petersen-Jones, S Crispin, BSAVA Publications, Gloucester, pp3641
Maggs D (2002). Ophthalmic surgery: basic principles. In BSAVA Manual of Small Animal
Ophthalmology 2nd edition. Eds S Petersen-Jones, S Crispin, BSAVA Publications, Gloucester, pp 4249
Nasisse MP (1997). Surgical management of ocular disease. Veterinary Clinics of North America
Small Animal Practice 27 (5), 963-1271
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Feline inflammatory bowel disease - moving beyond
“lymphoplasmacytic enteritis”
Kenneth W Simpson BVM&S, PhD, MRCVS, DipACVIM, DipECVIM-CA
College of Veterinary Medicine, Cornell University Ithaca NY
Feline inflammatory bowel disease (IBD) is the term applied to a group of poorly understood
enteropathies that are characterized by the infiltration of the gastrointestinal mucosa by inflammatory
cells. The cellular infiltrate is composed of variable populations of lymphocytes, plasma cells,
eosinophils and neutrophils, and is often distributed throughout the GI tract. The infiltrate is variably
accompanied by changes in the mucosal architecture such as villus atrophy, fusion, fibrosis and
lymphangiaectasia. IBD is likely the leading diagnosis in cats presented for the investigation of
gastrointestinal causes of vomiting, diarrhea, weight loss and anorexia. Given its importance there are
surprisingly few original studies on IBD in cats, and much of what we know is descriptive. The median
age for cats presenting with IBD is around seven years. Purebred cats such as Siamese and
Abyssinian cats may be over-represented. There is no reported predilection based on sex. The nature
of the inflammation has not been defined beyond gross histopathology and little is known about
etiology and pathogenesis, or the local and systemic consequences of IBD such as lymphoma or
Immune and inflammatory responses in IBD
Recent studies in experimental animals have shed light on the immunological environment in the
gastrointestinal tract and reveal a complex interplay between the GI microflora, the epithelium,
immune effector cells e.g. lymphocytes and macrophages, and soluble mediators such as
chemokines and cytokines. In health, this system functions to avoid active inflammation by antigen
exclusion and the induction of immune tolerance. The development of mucosal inflammation in mice
lacking the cytokines IL-10, TGF or IL-2 indicates the central importance of cytokines in damping
down mucosal inflammation. In many of these murine models GI inflammation only develops in the
presence of indigenous intestinal microflora, leading to the hypothesis that spontaneous IBD may be
the result of a loss of tolerance to the indigenous GI microflora.
The basis of the immunological response in feline IBD is unknown, and it remains to be determined if
the inflammatory response is due to the presence of undefined pathogens or an inappropriate
response to dietary antigens, intra-luminal commensal bacteria. Determining the cytokine and immune
cell population in IBD is important from both a pathological and a therapeutic standpoint as treatment
of IBD in cats is non-specific and is based on dietary modification, antibiotics, and suppression of the
immune system. Recent studies in people and experimental animals have resulted in the
development of drugs and the identification of bacteria e.g. Lactobacillus spp that modulate
inflammation, some of which are now in clinical trials e.g. infliximab, etanercept and probiotics for the
treatment of human Crohn’s disease. A further benefit of characterizing the immune and inflammatory
responses in cats with IBD would be to enable comparison with GI lymphoma. Distinguishing IBD
from lymphoma by routine histology is difficult, and the potential transformation of IBD to lymphoma
awaits critical evaluation.
One recent study (Waly et al 2004) of the immunopathology of feline IBD showed increased MHC
class II expression by leukocytes with dendritic cell or macrophage morphology in the lamina propria
in cats with IBD than in healthy cats, and MHC class II expression by enterocytes also was more
pronounced in these cats. By contrast the numbers of IgA and IgG expressing cells and CD3+ Tcell
distribution was similar in healthy and IBD cats. These findings suggest that a subtle immunologic
dysregulation occurs in spontaneously arising feline IBD.
In an ongoing study we have sought to determine the relationship of mucosa-associated bacteria to
duodenal histopathology, cytokine mRNA, and clinical disease activity in cats with inflammatory bowel
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Intestinal biopsies were collected from 17 cats undergoing diagnostic investigation of signs of
gastrointestinal disease, and 10 healthy controls. Subjective duodenal histopathology ranged from
normal (10), through mild (6), moderate (8), and severe (3) inflammatory bowel disease. The number
and spatial distribution of mucosal bacteria was determined by fluorescent in situ hybridization (FISH)
with probes to 16s rDNA. The mucosal response was evaluated by objective histopathology and
cytokine mRNA levels in duodenal biopsies.
The number of mucosa-associated Enterobacteriaceae was higher in cats with signs of
gastrointestinal disease than healthy cats. Total numbers of mucosal bacteria were strongly
associated with changes in mucosal architecture and the density of cellular infiltrates, particularly
macrophages. Enterobacteriaceae spp, E. Coli, and Clostridium spp. were associated with significant
changes in mucosal architecture (principally atrophy and fusion), upregulation of cytokines
(particularly IL-8), and the number of clinical signs exhibited by the affected cats.
These findings indicate that an abnormal mucosa-associated flora is associated with the presence
and severity of duodenal inflammation and clinical disease activity in cats. They provide a rationale
basis for future investigations to address the potential causal involvement of mucosa-associated
Our observations are perhaps most consistent with a model proposed for the mucosal response to
gram negative bacteria, whereby proinflammatory cytokines (e.g. IL-8, IL1 ), produced by epithelial
cells in response to stimuli such as gram negative bacteria, are modulated by the production of IL-10
by macrophages. Support for this concept in the canine gastrointestinal tract is provided by studies in
the small intestines of Beagle dogs, where expression of IL-10 and IFN- mRNA by lamina propria
cells and the intestinal epithelium was observed in the face of a luminal bacterial flora that was more
numerous than that of control dogs.
The nutritional consequences of IBD
Gastrointestinal disease may decrease the availability of a number of micronutrients, such as vitamins
and minerals, with important consequences for the pathogenesis, diagnosis and treatment of
gastrointestinal disease. The diagnostic utility of measuring the serum concentrations of cobalamin
and folate in cats with suspected intestinal disease has only recently been established, and the impact
of deficiencies in cobalamin and folate is largely undetermined. The following summarizes recent
research in cobalamin metabolism that impacts the diagnosis and treatment of IBD in cats.
It has become clear that cats and dogs are very different from people with respect to cobalamin
Cobalamin homeostasis is a complex, multi-step process that involves participation of the stomach,
pancreas, intestines and liver. Following ingestion, cobalamin is released from food in the stomach. It
is then bound to a non-specific cobalamin-binding protein of salivary and gastric origin called
haptocorrin. Intrinsic factor (IF), a cobalamin binding protein that promotes cobalamin absorption in
the ileum, is produced by the stomach and pancreas in dogs, and the pancreas, but not the stomach,
in the cat. Humans produce only gastric intrinsic factor, and deficiency is usually associated with
atrophic gastritis and the resultant lack of gastric IF production. The affinity of cobalamin for
haptocorrin is higher at acid pH than for IF, so most is bound to haptocorrin in the stomach. Upon
entering the duodenum haptocorrin is degraded by pancreatic proteases, and cobalamin is transferred
from haptocorrin to IF, a process facilitated by the high affinity of IF for cobalamin at neutral pH.
Cobalamin-IF complexes traverse the intestine until they bind to specific receptors (previously called
IFCR, but recently dubbed cubilin) located in the microvillus pits of the apical brush-border membrane
of ileal enterocytes. Cobalamin is then transcytosed to the portal bloodstream and binds to a protein
called transcobalamin 2(TC II) that mediates cobalamin absorption by target cells. A portion of
cobalamin taken up by hepatocytes is rapidly (within an hour in the dog) re-excreted in bile bound to
haptocorrin It is thought that cobalamin of hepatobiliary origin, in common with dietary derived
cobalamin, undergoes transfer to IF and receptor mediated absorption, thus establishing
enterohepatic recirculation of the vitamin. This situation of rapid turnover means that dogs and cats
with cobalamin malabsorption can totally deplete their body cobalamin stores within one to two
months. This is completely different from people in whom cobalamin depletion may take several
years, possibly due to the presence of long-term storage enabled by the cobalamin binding protein
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TC1, which is absent in dogs and cats.
Recent studies indicate that subnormal cobalamin concentrations are common in cats with
gastrointestinal disease or exocrine pancreatic insufficiency. In a study at Cornell University, forty-nine
of 80 serum samples submitted from cats with signs of gastrointestinal disease during the period of
January 1996-January 1998 had cobalamin concentrations below the reference range for healthy cats
(range 900 - 2,800 pg/ml ; mean ± SD = 1775 ± 535 pg/ml SD ; n=33). Cats with subnormal
cobalamin concentrations (mean ± SD = 384 ± 272 pg/ml, range 3 - 883pg/ml) were middle aged or
older and were presented for weight loss, diarrhea, vomiting, anorexia and thickened intestines.
Definitive diagnoses in 22 cats included inflammatory bowel disease, intestinal lymphoma,
cholangiohepatitis or cholangitis, and pancreatic inflammation. Serum concentrations of cobalamin
were particularly low in cats with intestinal lymphoma, 3/5 of which also had subnormal serum
concentrations of folate (< 9ng/ml). The circulating half-life of parenteral cyanocobalamin was shorter
in two cats with IBD (5 days) than in four healthy cats (12.75 days). The rapid depletion of circulating
cobalamin in cats suggests that cats may be highly susceptible to cobalamin deficiency.
Investigation of the relationship of subnormal serum cobalamin concentrations to cobalamin
deficiency and the effect of cobalamin deficiency on cats has revealed the clinical significance of
cobalamin deficiency in cats (Ruaux et al 2005). Nineteen pet cats, all with severe
hypocobalaminemia (< or =100 ng/L) and histories of gastrointestinal signs, were studied. Cats
received cobalamin, 250 microg SC once weekly, for 4 weeks. Serum methylmalonic acid (MMA)
concentrations (median; range) decreased after cobalamin supplementation. Serum homocysteine
concentrations were not significantly altered, whereas cysteine concentrations increased significantly.
Mean body weight increased significantly after cobalamin therapy, and the average body weight gain
was 8.2%. Significant linear relationships were observed between alterations in serum MMA and fTLI
concentrations and the percentage body weight change. Reduced vomiting and diarrhea were
observed in 7 of 9 and 5 of 13 cats, respectively. These results suggest that cobalamin
supplementation in cats with small intestinal disease and severe hypocobalaminemia is associated
with normalization of biochemical test results and improvements in clinical findings in most affected
There is also emerging evidence that cobalamin supplementation may result in clinical improvement
of cats with IBD, without recourse to immunosuppressive therapy. In this respect it is interesting to
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note that cobalamin deficiency is associated with altered immunoglobulin production and cytokine
levels in mice. Serum C3, IgM and IgG contents were lower in cobalamin-deficient mice than in the
control mice. On the other hand, serum IgE content was significantly higher in cobalamin-deficient
mice. CD4+CD8- cells and CD4+CD8-/CD4-CD8+ ratio in splenocytes were significantly higher in
cobalamin-deficient mice than in control mice. CD4+IFN-gamma+ cells were significantly lower in
cobalamin-deficient mice than in control mice, and CD4+IL-4+ were significantly higher in cobalamindeficient mice than in control mice. These results suggest that cobalamin- deficiency causes
CD4+CD8-T cells shift from the T helper type 1 to the T helper type 2, which participate in the IgE
production and elevates CD4+CD8-/CD4-CD8+ ratio. The impact of cobalamin deficiency on the
immune environment of cats remains to be established.
In conclusion, much remains to be learned about the complex interplay between the GI microflora,
dietary antigens, the epithelium, immune effector cells and soluble mediators in the feline
gastrointestinal tract in health and disease. The development of feline specific reagents, and a
growing realization of the nutritional consequences of IBD has precipitated a shift beyond reliance on
qualitative histology, and holds promise for improved understanding, therapy and prevention in the
Dr Simpson is supported by a grant from the Public Health Service (NIH DK 002938). I am grateful to
the Winn Feline Foundation, and the Cornell Feline Health Center for their support. I wish to thank my
collaborators Drs. Andrea Grieter, Richard Goldstein, Reinhard Straubinger, Sean MacDonough,
Yung-Fu Chang, John Fyfe, Patrick McDonough, Olivier Toulza, LaShonn McNair, David Williams and
Craig Ruaux for their help and support in studying feline gastrointestinal disease. I thank Francis
Davis for invaluable technical support.
Goldstein RE A. Greiter-Wilke, S.P. McDonough and K.W. Simpson. Quantitative evaluation of
inflammatory and immune responses in cats with inflammatory bowel disease. Proceedings of the
Amercian College of Veterinary Internal Medicine Charlotte North Carolina 2003.
Ruaux CG, Steiner JM, Williams DA. Early biochemical and clinical responses to cobalamin
supplementation in cats with signs of gastrointestinal disease and severe hypocobalaminemia. J Vet
Intern Med. 2005 Mar-Apr;19(2):155-60.
Ruaux CG, Steiner JM, Williams DA.Metabolism of amino acids in cats with severe cobalamin
deficiency. Am J Vet Res. 2001 Dec; 62(12):1852-8.
Schiffrin, EJ and Blum, S. Interactions between the microbiota and the intestinal mucosa. Eur J Clin
Nutr 2002; 56 Suppl 3:S60-S64.
Simpson K.W., Fyfe J., Cornetta A., Sachs A., Strauss-Ayali D., Lamb S., Reimers T. Subnormal
concentrations of serum cobalamin (vitamin B12) in cats with gastrointestinal disease. Journal of
Veterinary Internal Medicine. JVIM 2001b. 15, 26-32.
Waly NE, Stokes CR, Gruffydd-Jones TJ, Day MJ.Immune cell populations in the duodenal mucosa of
cats with inflammatory bowel disease. J Vet Intern Med. 2004 Nov-Dec; 18(6):816-25.
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ESFM Feline Congress 2006
Feline leishmaniasis
Maria Grazia Pennisi DVM, PhD
Full Professor Veterinary Clinical Medicine, University of Messina
The cat was commonly considered an unusual host for Leishmania spp. infection because of the
sporadic case reports from countries where the organism and different species of sand fly vectors are
endemic (Pennisi, 2002). Over the last twenty years many studies have been published concerning
serological investigations performed with different methods (IHAT, IFAT, ELISA, WB) and/or PCR test
(Pennisi, 2002): serological prevalence ranged form 0.6% (Bez, 1992) to 59% (Pennisi et al., 1998)
and 61% of blood PCR tests were positive with no significant association with positive Leishmania
serology, season, breed and a marginally significant higher prevalence in female cats and cats aged >
2 years (Pennisi et al., 2000).
By the end of 1997, we have diagnosed in Sicily five clinical cases of feline leishmaniasis (FL)
(Pennisi, 1999; Pennisi et al., 2004; Pennisi, unpublished data). Leishmania infantum has been
identified in 5 feline isolates from 4 of these cats and 3 different zymodemes were typed by
isoenzyme electrophoresis of 13 isoenzymes: ZMON1 (2 cats), ZMON72, ZMON201 (Gramiccia et
al., 2005; Maroli et al., 2006). In Europe, characterization of feline strains was also achieved
elsewhere in Italy (Poli et al., 2002) and in France (Ozon et al., 1998; Grevot et al., 2005): in all these
three cats L. infantum ZMON1 was typed.
In about the last ten years, detailed and confirmed case reports from France (Laurelle-Magalon &
Toga, 1996; Ozon et al., 1998; Grevot et al., 2005), Italy (Pennisi, 1999; Pennisi, 2002; Poli et al.,
2002; Pennisi et al., 2004; Britti et al., 2005), Spain (; Hervas et al., 2001; Leiva et al., 2005), Portugal
(Costa Durão et al., 1994) and Switzerland (Rüfenacht et al., 2005) in 17 overall cats, provided some
specific information concerning signalment, concurrent immunosuppression, clinical signs, clinical
pathology, therapy and follow up of FL in endemic areas for L. infantum. Case reports concerned
domestic shorthaired cats, twelve females and five males, aging between 3 and 15 years. Actually, 14
out of these 17 cats had been tested for FIV and FeLV infections and two cats scored positive for both
viruses, four cats had anti-FIV antibodies and eight of them were negative for both viral infections.
Four individuals in this last group had been chronically treated with corticosteroids. We can therefore
assume that 10 out 14 cats affected by FL could have been immunosuppressed.
As concerning the clinical presentation, skin lesions (nodules, hemorrhagic nodules, ulcers, alopecia)
were reported in 11 out of 17 cats. Systemic involvement was described (15 out 17 cats) in
association with enlarged lymph nodes (7 cats), weight loss (6 cats), lethargy (4 cats), anorexia (4
cats), ocular lesions (4 cats), stomatitis / faucitis (4 cats), dehydration (3 cats), pale mucous
membranes (2 cats), vomiting (2 cats), fever (2 cats), dyspnoea (1 cat), jaundice (1 cat),
hepatomegaly (1 cat), splenomegaly (1 cat), abortion (1 cat). Complete cell blood count showed
neutrophilia (4 cats), eosinophilia (2 cats), lymphocytosis (1 cat), monocytosis (1 cat) pancytopenia (2
cats), lymphopenia (1 cat). Abnormalities in serum profile were hyperglobulinemia (13 cats),
gammopathy (10 cats), hyperproteinemia (7 cats), increased BUN (3 cats), increased creatinine (2
cats), increased bilirubin (1 cat), increased ALT (1 cat), low folate (1 cat), low albumin (1 cat).
Long term allopurinol treatment (10 mg/kg BID) was considered successful (although with different
criteria of evaluation and various follow up periods) in four out of five cats (Pennisi et al., 2004; Leiva
et al., 2005; Rüfenacht et al., 2005); in one case the dose was lowered (5 mg/kg BID) because of
increases in liver enzymes (Rüfenacht et al., 2005). Fluconazole, itraconazole and spiramycin &
metronidazole were not effective in one case (Pennisi, 2002). Meglumine antimoniate was given to a
cat (5 mg/kg SID SC) combined with ketoconazole (10 mg/kg SID PO) in 3 cycles of 4 weeks and 10
days apart, leading to resolution of skin lesions (Hervas et al., 1999). Costa Durão et al. (1994)
administered in a cat 375 mg of meglumine antimoniate, each other day intramuscularly for 55 days,
registering normalization of ALT values and no relapse after a repeated surgical removal of nodular
lesions. Relapses following surgical removal of skin lesions have also been described by Rüfenacht et
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ESFM Feline Congress 2006
Post diagnosis survival and long term follow up are available in very few cases: 2 cats did not show
clinical recurrence (Rüfenacht et al., 2005); two cats were retreated with allopurinol because of the
worsening of serology and gammopathy after a 2 (Pennisi et al., 2004) or 3 month withdrawal (Leiva
et al., 2005). Chronic renal failure developed in four cats specifically monitored for a time ranging
between 22 months and 6 years (Pennisi et al., 2004; Pennisi, unpublished data). One of them (a FIV
positive cat), that did never undergo specific treatment, developed urinary signs of renal failure three
years after diagnosis and was euthanased about 2 years later (Pennisi et al., 2004).
Apart from case reports of natural infection, some experimental studies on various feline models have
been performed in order to settle susceptibility of cats to Leishmania spp. In 1984, Kirkpatrick et al.
inoculated 15 cats with L. chagasi or L. donovani amastigotes by intravenous routes and 6 cats with
promastigotes of L. donovani by subcutaneous route. None of the cats showed clinical signs in the
short-term follow up (8-24 weeks), but all of them developed elevated serum antibody titres and the
parasite was isolated from the spleen. Conversely, negative results (culture and microscopy) were
achieved by Anjli and Githure (1993) with a Kenian strain of L. donovani. More recently (SimôesMattos et al., 2005), the subcutaneous inoculation (ear and nose) of L. braziliensis in 13 cats (9 of
them were FeLV positive) led to the development of primary nodules and seroconversion in all the
cats and to dermal dissemination in 42.6% of them. Ulceration occurred in both the ear (25%) and the
nose (33.3%) lesions with a 87.5% (ear) or 100% (nose) rate of spontaneous healing at 32 (ear) or 40
(nose) weeks post infection; none of the cats had lesion recurrence at the end of the follow up (72
weeks post infection).
Susceptibility of cats to Leishmania spp. infection is supported by case reports of natural disease and
experimental studies, thereby the epidemiological role of this host species is probably the main
question arisen from this. Host feeding habit of Phlebotomus spp. includes the cat (Johnson et al.
1993; Ogusuku et al., 1994; Maroli & Pennisi, unpublished data) and the recent evidence that a
naturally infected cat was infectious to a proven L. infantum vector (xenodiagnosis) such as P.
perniciosus (Maroli et al., 2006), support the potential role of the cat as reservoir in the natural
environment. Extended studies can quantify to what extent feline infection actually affect the
epidemiology of leishmaniasis. Although the overall small number of reported cases, published data
suggest that impaired immune competence of individuals (concurrent immunosuppressive retroviral
infection or therapy) could enhance susceptibility of cats to Leishmania infection and cause the
developing of a disease similar to that seen in dogs, but it could also affect the cat’s infectiousness to
the vector such as seen in HIV patients (Alvar, 1999).
Alvar, J. (1999). Leishmania and HIV co-infection in the Mediterranean countries. Proceedings of the
International Canine Leishmaniasis Forum. Barcelona, Spain. 78-81
Anjli, C.O. & Githure, J.I. (1993). Refractoriness of domestic cats to infection with a Kenyan strain of
Leishmania donovani. East African Medical Journal, 70 (5): 322
Bez, M. (1992). La leishmaniose chez le chat. Enquete seroepidemiologique dans les AlpesMaritimes. Thèse Doct. Vet. Ecole Nationale Veterinaire de Lyon, n.46.
Britti, D., Vita, S., Aste, A., Willams, D.A., Boari, A. (2005). Sindrome da malassorbimento in un gatto
con leishmaniosi. Atti LIX Congresso SISVet, 59:281-282.
Costa Durão, J.F., Reselo, E., Peleteiro, M.C., Correia, J.J., Simôes, G. (1994). Primeiro caso de
leishmaniose em gato domestico (Felis catus) detectado em Portugal (Concelho de Sesimbra). Nota
preliminar. Revista Portuguesa de Ciencias Veterinarias, 89:140-144.
Gramiccia, M., Di Muccio, T., Vitale, F., Caracappa, S., Reale, S., Pennini, M.G. (2005). Leishmania
infantum characterization from three cases of feline leishmaniasis in Sicily (Italy). Proceedings of
Third World Congress on Leishmaniosis. Palermo-Terrasini. Sicily, Italy. 146.
Grevot, A., Jaussaud Huges, P., Marty, P., Pratlong, F., Ozon, C., Haas, P., Breton, C., Bourdoiseau,
G. (2005). Leishmaniosis due to Leishmania infantum in a FIV and FeLV positive cat with a squamous
cell carcinoma diagnosed with histological, serological and isoenzymatic methods. Parasite, 12:271-5.
Hervas, J., Chacòn-Manrique de Lara, F., Sànchez-Isarria, M.A., Pellicer, S., Carrasco, L., Castillo,
J.A.,Gòmez-Viallamandos J.C. (1999). Two cases of feline visceral leishmaniosis in Spain. Journal of
Feline Medicine and Surgery, 1:101-105.
Hervas, J., Chacòn-Manrique de Lara, F., Lopez, J., Gòmez-Viallamandos J.C., Guerrero, M-J.,
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Moreno, A. (2001). Granulomatous (pseudotumoral) iridociclitis associated with leishmaniasis in a
cat. Veterinary Record, 149: 624-625.
Johnson, R.N., Ngumbi, P.M., Mwanyumba, J.P., Roberts, C.R. (1993). Host feeding preference of
Phlebotomus guggisbergi, a vector of Leishmania tropica in Kenya. Medical and Veterinary
Entomology, 7:213-218.
Kirkpatrick, C.E., Farrell J.P. and Goldschmidt, M.H. (1984). Leishmania chagasi and L. donovani:
experimental infection in domestic cats. Experimental Parasitology, 58:125-131.
Laurelle-Magalon, C., Toga, I. (1996). Un cas de leishmaniose féline. Pratique Médicale Chirurgicale
de l’Animal de Compagnie, 31 :255-261.
Leiva, M., Lloret, A., Peña, T., Roura, X. (2005). Therapy of ocular and visceral leishmaniasis in a cat.
Veterinary Ophtalmology, 8: 71-75.
Maroli, M., Pennisi, M.G., Gramiccia, M., Di Muccio, T., Khoury, C., Lo Giudice, S., Gradoni, L. (2006).
First report of experimental Leishmania infection in Phlebotomus perniciosus fed on a cat with natural
acquired leishmaniasis in Italy. Parassitologia, 48: 322.
Ogusuku, E., Perez, J.E., Paz, L., Nieto, E., Monje, J., Guerra, H. (1994). Identification of bloodmeal
sources of Lutzomya spp. in Perù. Annals of Tropical Medicine and Parasitology, 88:329-335.
Ozon, C., Marty, P., Pratlong, F., Breton, C., Blein, M., Leliévre, A., Haas, P. (1998). Disseminated
feline leishmaniosis due to Leishmania infantum in Southern France. Veterinary Parasitology, 75:273277.
Pennisi, M.G., Masucci, M., Catarsini, O. (1998). Presenza di anticorpi anti-Leishmania in gatti FIV+
che vivono in zona endemica. Atti Società Italiana delle Scienze Veterinarie, 52: 265-266.
Pennisi, M.G. (1999). Case report of Leishmania spp. infection in two cats from the Aeolian arcipelago
(Italy). Proceedings of the 24th WSAVA Congress, CD
Pennisi, M.G., Maxia, L., Vitale, F., Masucci, M., Borrato, G., Caracappa, S.(2000). Studio
dell’infezione da Leishmania mediante PCR in gatti che vivono in zona endemica. Atti Società Italiana
delle Scienze Veterinarie, 54: 215-6.
Pennisi, M.G. (2002). A high prevalence of feline leishmaniasis in southern Italy. Proceedings of the
Second International Canine Leishmaniasis Forum. Sevilla, Spain. 39-48
Pennisi, M.G., Venza, M., Reale, S., Vitale, F., Lo Giudice, S. (2004). Case report of feline
leishmaniasis in four cats. Veterinary Research Communications, 28: 363-366.
Poli., A., Abramo, F., Barsotti, P., Leva, S., Gramiccia, M., Ludovisi, A., Mancianti, F. (2002). Feline
leishmaniosis due to Leishmania infantum in Italy. Veterinary Parasitology, 106:181-191
Rüfenacht, S., Sager, H., Müller, N., Schaerer, V., Heier, A., Welle, M.M., Roosje, P.J. (2005). Two
cases of feline leishmaniosis in Switzerland. Veterinary Record, 156: 542-545.
Simôes-Mattos, L., Mattos, M.R.F., Teixeira, M.J., Oliveira-Lima, J.W., Bevilacqua, C.M.L., PrataJunior, R.C., Holanda, C.M., Rondon, F.C.M., Bastos, K.M.S., Coêlho, I.C.B., Barral, A., Pompeu,
M.M.L. (2005). The susceptibility of domestic cats (Felis catus) to experimental infection with
Leishmania braziliensis. Veterinary Parasitology, 127:199-208.
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Management of chronic enteropathies
Kenneth W Simpson BVM&S, PhD, MRCVS, DipACVIM, DipECVIM-CA
College of Veterinary Medicine, Cornell University Ithaca NY
Idiopathic inflammatory bowel disease is the term used to describe a diverse group of intestinal
disorders which are characterised by cellular infiltrates of the intestinal mucosa. Diagnosis is based
on the description of histological findings in intestinal biopsies and the exclusion of known causes of
intestinal inflammation e.g. endoparasites, dietary sensitivity. The most common inflammatory
infiltrates are lymphocytes and plasma cells or eosinophils. Neutrophils or granulomatous
inflammation are encountered less commonly.
Lymphoplasmacytic enteritis
Lymphoplasmacytic enteritis is the most common type of inflammatory bowel disease in dogs and
cats. It is characterised by the accumulation of excessive numbers of lymphocytes and plasma cells
in the lamina propria of the intestine. The degree of cellular accumulation is variable and is
subjectively categorised as mild, moderate and severe. Moderate to severe lymphoplasmacytic
enteritis is often associated with a protein losing enteropathy. A severe form of the condition has been
reported in Basenjis. The extent of inflammation appears variable and ranges from the duodenum to
the small and large bowel.
Clinical findings
Chronic small bowel diarrhea accompanied by weight loss or vomiting are the most frequent findings
in dogs whereas vomiting is the most common clinical sign in cats. Vomitus often contains bile.
Hairballs are frequent in cats. Other findings include changes in appetite, excessive borborygmi and
abdominal discomfort. The severity of disease is variable, ranging from intermittent diarrhoea and
vomiting in mild cases to intractable small bowel diarrhea, inappettance and weight loss in severe
ones. The severity of the disease is thought to reflect the degree of cellular infiltrate. Physical findings
range from normal to thickened intestines ± mesenteric lymphadenopathy, marked weight loss, and
ascites or oedema in animals with severe protein losing enteropathy.
A diagnosis of idiopathic lymphoplasmacytic enteritis is made by excluding systemic, parasitic,
infectious, pancreatic and structural causes of chronic diarrhea and demonstrating excessive
numbers of lymphocytes and plasma cells in intestinal biopsies.
Treatment of IBD is usually based on dietary modification, antibiotics and immunosuppression.
Treatment is to some extent based on the severity of the disease. Mild to moderate intestinal
inflammation may be associated with dietary sensitivity or intolerance, or potentially idiopathic small
intestinal bacterial overgrowth. A therapeutic dietary trial can be performed with either:1) a highly
digestible diet which is restricted in fat and gluten-free ,2) a diet limited to a single novel protein
source or3) a diet containing protein hydrolysate, to determine if dietary sensitivity or intolerance are
present. A response is usually observed within 2 wks. Similarly a therapeutic trial (21days) with
Tylosin (10mg/kg PO TID), metronidazole (15mg/kg PO BID) or oxytetracycline (10-20mg/kg PO TID)
for antibiotic responsive enteropathy /small intestinal bacterial overgrowth may be warranted. In
patients who fail these trials and in those with moderate to severe infiltrates, or hypoproteinaemia the
administration of immunosuppressive agents is usually required to achieve a response. Oral
prednisolone (1-2mg/kg PO BID) is the initial drug of choice. It is usually administered at an
immunosuppressive dose for 2-3 wks and then decreased by 50% every 2-3wks, and then continued
on an alternate day basis for 2-3 months. If clinical response is poor or the adverse effects of
prednisolone predominate azathioprine can be added to the regimen. In dogs it is usually given every
day (2mg/kg PO SID) for five days and then on alternate days to prednisolone. Cats are more
sensitive to azathioprine (0.3mg/kg PO SID) and may be better managed with chlorambucil (6mg/m2
PO PO EOD (@2mg/5.3kg cat) and prednisone (5mg PO /cat/day). Supplemental cobalamin (1ml SC
q 2-3wks) and folate / B complex vitamins should also be given if serum concentrations are low.
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Metronidazole (15mg/kg PO BID 10-14d then SID 10-14d) can also be used in conjunction with
corticosteroids and has effects on bacteria and possibly the immune system. Successful treatment is
accompanied by a decrease in clinical signs and an increase in plasma proteins. Once a patient has
had 2-3 months remission from signs it may be possible to gradually withdraw immunosuppressive
therapy. If signs recur daily medication is continued until signs resolve then gradually reduced. In
patients who respond poorly to therapy or relapse after an initial response lymphoma should be ruled
The prognosis for lymphoplasmacytic enteritis is variable and depends on its severity. Many patients
require prolonged treatment with glucocorticoids and diet. As no accurate criteria exist for predicting
response it is wise to give a guarded prognosis.
Eosinophilic enteritis
Eosinophilic enteritis is characterised by the excessive accumulation of eosinophils in the lamina
propria. It is speculated that it may result from an immunologic reaction to parasites or diet. the
disease may also involve other areas of the gastrointestinal tract.
Clinical findings
Chronic small bowel diarrhoea accompanied by vomiting or weight loss are the principal clinical signs.
Large bowel signs or vomiting predominate in some cases. Physical findings range from normal to
focally or diffusely thickened intestines and marked weight loss.
Intestinal biopsy. Clinicopathologic abnormalities may include peripheral eosinophilia. Mast cell
neoplasms, hypoadrenocorticism and endoparasites can produce a similar spectrum of clinical signs
and should be ruled out. The degree of eosinophilia can be extreme in cats and may be associated
with eosinophillic infiltrates in the spleen, liver, lymph nodes and bone marrow. Intestinal protein loss
is less common than lymphoplasmacytic enteritis.
Some patients may respond to a strict exclusion diet, though prednisolone (2mg/kg PO SID) is
usually required. In dogs signs usually resolve within a couple of weeks and prednisolone can be
tapered. Feeding an easily digestible diet that is restricted to a single novel protein source or is
hydrolyzed may help to maintain clinical remission. Prophylactic administration of an anthelminthic
such as fenbendazole (50mg/kg PO SID 3 days) is warranted to treat potential visceral larval migrans
which has been associated with eosinophilic gastroenteritis. Cats with hypereosinophillic syndrome
often respond very poorly to treatment with immunosuppressive agents, diet and anthelminthics.
The prognosis is guarded as relapse is common. The prognosis in cats with hypereosinophilic
syndrome is poor.
Other inflammatory enteropathies
Other enteropathies which are characterised by neutrophilic or granulomatous inflammation have also
been described infrequently in small animals. Some of these may be associated with bacterial
infections such as Streptococcus, Campylobacter, Yersinia and Mycobacteria and fungal infections
such as Histoplasma. Special stains and culture of mucosal biopsies and intestinal lymph nodes and
other abdominal organs should be undertaken in cases of granulomatous enteritis to detect infectious
organisms. Serology, chest radiographs and bone marrow biopsies may help to diagnose systemic
fungal disease. The prognosis for idiopathic granulomatous or neutrophilic enteropathies is guarded
to poor.
Lymphosarcoma (LSA) is characterised by the mucosal and sub-mucosal infiltration of neoplastic
lymphocytes which cause malabsorption. Focal forms of lymphosarcoma may cause obstruction. The
tumor is often thought to be related to feline leukemia virus in cats though cats with GI lymphoma are
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usually FeLV negative, and is of unknown etiology in dogs. In cats LSA has been classified as
lymphocytic or lymphoblastic, with the lymphocytiic form responding well to chemotherapy. In some
animals lymphoplasmacytic enteritis may progress to LSA.
Clinical findings
Weight loss, chronic small bowel diarrhoea and progressive inappettance are common features of
intestinal LSA. Vomiting may also be noted. Physical examination may reveal diffusely thickened or
nodular intestines ± mesenteric lymphadenopathy. Acute abdominal pain and shock may be present if
intestinal perforation has occurred. Hepatosplenomegaly and generalised lymphadenopathy are less
frequently detected. Signs of hypoproteinemia may be evident.
Middle aged or older dogs and cats are most commonly affected. Routine biochemistry often reveals
a protein losing enteropathy in dogs with LSA. Anaemia which is either normocytic normochromic
non-regenerative or microcytic and hypochromic, and neutrophilia may also be present. Ultrasound is
useful for evaluating intestinal thickness and detecting mesenteric lymphadenopathy. Diagnosis can
be made by demonstrating neoplastic lymphocytes in aspirates or biopsies from enlarged intestinal or
peripheral lymph nodes, but is more often made by intestinal biopsy. Endoscopic biopsies may miss
the lesion or show lymphoplasmacytic enteritis. Serum concentrations of cobalamin are often very low
in cats with GI lymphoma and serum folate concentrations may also be reduced.
Treatment and prognosis
Dogs respond poorly to therapy. Cats with lymphocytic lymphoma may show a dramatic and lasting
response (av. 17-20 mo.) to treatment with chlorambucil (6mg/m2 PO PO EOD (@2mg/5.3kg cat)
and prednisone (5mg PO /cat/day). Supplemental cobalamin (1ml SC q 2-3wks) and folate / B
complex vitamins should also be given. Lymphoblastic lymphoma is much less responsive.
MA Kiselow1, KM Rassnick1, SP McDonough2, RE Goldstein1, KW Simpson.1 HN Erb.3 1. Dept of
Clinical Sciences, 2. Department of Biomedical Sciences, 3. Department of Population
Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca,
To date, there is only one study evaluating cats with low-grade lymphoma; all had disease confined to
the gastrointestinal (GI) tract. The objective of this study was to evaluate factors that influence
response to therapy, remission duration, and overall survival in cats with low-grade, lymphocytic
lymphoma of various anatomic sites.
Records and biopsies from 41 cats with histologically confirmed low-grade lymphoma were
retrospectively reviewed. Only cats treated with prednisone and chlorambucil that were available for
follow-up were included. Risk factors evaluated for prognostic significance included signalment,
clinical signs, lab work abnormalities, site affected, and response to treatment. P values ≤ 0.05 were
considered significant.
Common clinical signs were weight loss (83%), vomiting (73%), and diarrhea (59%). Eighty percent
of cats tested had low serum cobalamin. Lymphoma was confined to the GI tract in 68%, while 32%
had other organ systems affected. Response to therapy was complete in 22 cats (54%) and partial in
15 (37%). Two cats (5%) experienced no response. There was no difference between any risk factors
and response to therapy. Overall median remission duration was 948 days. Lymphoma in nongastrointestinal sites (P = 0.007), decreased serum cobalamin, and partial response to therapy (P =
0.002) were associated with shorter remission duration. Overall median survival time was 704 days.
Decreased serum cobalamin was associated with shorter survival time (P = 0.047).
Results of this study suggest most cats with lymphocytic lymphoma respond to therapy and various
host factors are associated with outcome.
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Small intestinal bacterial overgrowth (SIBO) = an abnormal accumulation of bacteria in the
small bowel.
The intestinal flora of healthy dogs and cats: Humans have total bacterial counts less than 5
(log10 cfu/ml or gram) small intestinal juice/tissue and anaerobic bacterial counts less than 4 5 (log10
cfu/ml or gram). Gram positive aerobic bacteria such as Streptococci and Staphylococci predominate;
anaerobic bacteria such as Clostridia and Bactericides are extremely uncommon.
Those findings in humans are not applicable to healthy dogs and cats.
At least 24 papers have been published which describe the small intestinal bacterial flora of healthy
dogs or cats. The majority of studies indicate that both the healthy dog and cat harbor a large number
of diverse bacteria in the small intestine. The total bacterial counts in the proximal small intestine of
healthy dogs ranges from 0-9.43 (log10 cfu/ml or gram) and anaerobes from 0 to 8.18 (log10 cfu/ml
or gram). Similarly cats have total duodenal bacterial counts ranging from 2 to 8.3 (log10 cfu/ml or
gram), and anaerobic bacteria from 2 to 8.05 (log10cfu/ml). Common aerobic bacterial species in
dogs and cats include Streptococcus species, Staphylococcus spp, Bacillus spp, Escherichia coli,
Corynebacterium spp, Enterobacter cloacea, Pseudomonas spp, and Pasturella multocida.
Clostridium spp, Bifidobacterium spp, Eubacterium spp and Bacteroides spp are common anaerobes.
Lactobacillus spp, are also common.
SIBO in dogs and cats
The syndrome of small intestinal bacterial overgrowth has been used to describe patients with signs
such as diarrhea and weight loss that are associated with a gastrointestinal abnormality which is
considered to cause small intestinal bacterial proliferation. It has also been applied to patients with
similar clinical signs without an obvious cause for bacterial proliferation that respond to antibiotics.
The literature on the normal flora of dogs and cats indicates that SIBO can be defined as: bacterial
counts > 9.43 (log10 cfu/ml or gram) in dogs, > 8.3 (log10 cfu/ml or gram) in cats OR anaerobic
bacterial counts > 8.18 (log10cfu/ml or gram) in dogs, > 8.05 (log10 cfu/ml or gram) in cats.
Interestingly a disease, which fulfills those criteria, has yet to be described in the dog and cat.
Diseases other than SIBO which may improve with antibiotic therapy
• Occult pathogens: giardia, coccidia, Salmonella, Campylobacter, enteropathogenic E. Coli?
• Unknown pathogens e.g. Helicobacter spp.
• Increased host susceptibility to endogenous flora:
1. Breakdown of immune tolerance to indigenous microflora: Conventionally reared IL-10
knockout mice develop IBD whereas germ free mice, do not. A similar loss of tolerance to a
normal bacterial flora, or increased susceptibility to the potentially harmful effects of abnormal
flora may also explain why Basenji dogs with immunoproliferative small intestinal disease
respond to antibiotic therapy.
2. Increased susceptibility to endogenous flora arising from mucosal IgA deficiency could explain
the antibiotic responsive chronic diarrhea in GSD.
3. Altered balance between damage and repair: Decreased synthesis of mucosal enzymes in the
face of increased degradation e.g. EPI
Does idiopathic SIBO occur in dogs and cats?
In 1983 Batt et al. described small intestinal bacterial overgrowth in German Shepherd dogs which
had no obvious underlying cause of SIBO. This study compared bacterial counts from German
Shepherd dogs with diarrhea, with those obtained in six healthy dogs. Those investigators proposed
that SIBO was present based on the presence of >5 (log10 cfu/ml) of bacteria in dogs with diarrhea.
Unfortunately the intestinal fluid aspirated from the dogs was variably diluted or frozen before culture.
The abnormal clinical signs and the associated intestinal mucosal changes in affected dogs were
responsive to antibiotic therapy, suggesting that the bacterial flora was an important cause of the
diarrhea. However, whether the clinical signs were caused by excessive numbers of bacteria or an
enteropathy which renders the intestine more susceptible to damage by a normal flora, is unresolved.
Subsequent investigators have used the cut-off value described by Batt et al., despite clear evidence
indicating higher bacterial numbers in healthy dogs and cats.
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Further confusion over the reality of idiopathic SIBO in dogs was caused by a report which described
a group of healthy GSD with duodenal bacterial counts >5 (log10 cfu/ml) as having SIBO. The
authors explicitly stated that 'All dogs appeared clinically normal” and '...one would not expect that
these dogs had alimentary tract disease by observing or working with them.’ The lack of clinical signs
in these dogs is in stark contrast to the syndrome of SIBO in humans, experimental animals, and the
GSD originally described by Batt et al. that was characterized by diarrhea, weight loss and altered
concentrations of cobalamin and folate. The authors refuted the suggestion that they had cultured
intestinal fluid from healthy dogs. More recently in a study of 107 dogs, 52 were diagnosed as having
idiopathic SIBO (intestinal bacteria greater than >5 (log10 cfu/ml)) and no identifiable underlying
cause. Such a high prevalence of idiopathic SIBO serves to further question the validity of the 5
(log10 cfu/ml) cut-off vale for the diagnosis of SIBO.
Treatment of suspected SIBO is directed at correcting underlying anatomic or structural
abnormalities, treating EPI, and controlling the abnormal flora with antibiotics. Suitable antibiotics
include oxytetracycline (20mg/kg TID PO), tylosin (10mg/kg TID PO), or metronidazole (15 mg/kg BID
PO). In dogs with idiopathic SIBO/ intolerance antibiotic therapy is usually given for 28 days. Dietary
modification also appears to be important and anecdotal evidence supports the use of highly
digestible, low fat diets.
Many animals with undefined antibiotic responsive enteropathies relapse when antibiotics are
stopped and require further courses, or long term maintenance therapy Prognosis for secondary
SIBO depends on the underlying disease.
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Clinical Decision Making
Professor Richard Malik DVSc PhD FACVSc FASM
Post Graduate Foundation in Veterinary Science, Conference Centre, Building B22,
University of Sydney, NSW 2006 Australia
Introduction and conceptual framework
As veterinarians in small animal practice, not a day goes by that we do not make critical decisions
about the investigation and treatment of cases under our care. Interestingly, most of us have received
very little specific training in clinical decision making as part of our undergraduate curriculum, and
most continuing education forums emphasize the acquisition of new knowledge, rather than
philosophical approached to diagnostic and therapeutic decision making.
In small animal medicine, we are frequently confronted with disease conditions we have never
encountered before. This makes life challenging and interesting, but it can also make life very
stressful! We try our best to use common sense, deductive reasoning and to work things out from first
principles using a pathophysiologic approach. Unfortunately, some things are counter-intuitive, for
example, the disease necrotizing sialoadenitis, in which patients present with signs that appear
referable to mandibular salivary gland disease, but generally respond completely to anticonvulsant
drugs such as phenobarbitone. It is therefore vital that we learn through our working life how to draw
on the experience of junior colleagues (fresh out of veterinary school), senior colleagues (with vast
experience, and special ‘local’ knowledge), textbooks, local and international experts and medical and
veterinary electronic data bases, and resources such as the Veterinary Information Network (VIN).
In relation to diagnosis, there are at least three important conceptual approaches:
(i) Pattern recognition, the recognition of characteristic combination of clues or signs (e.g. cutaneous
reaction patterns, radiologic patterns, histological patterns, hematological patterns)
(ii) Problem-based medicine, and
(iii) Diagnosis based on clinical probability (i.e. that certain diseases occur much more commonly than
The best diagnosticians can use all these approaches interchangeably, combining great
analytic skill, a systematic approach, but utilizing also good clinical intuition, which can
make the diagnostic process faster and less expensive.
Rather than continue to write abstractly about these disparate concepts, I will attempt to illustrate
them by working through what would seem to be a “very straightforward” cases. I will then challenge
different members of the audience, in relation to HOW and WHY they make clinical decisions.
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Case presentation
Magic is a two-year-old desexed female Australian Mist cat. This is an Australian bred, based on initial
crosses between Burmese (50%), Abyssinian (25%) and Australia domestic crossbred cats.
Presenting complaint
The cat may have ingested a sewing needle.
The owner observed the cat playing with a sewing needle. The needle allegedly had no thread
attached. The owner tried to intervene and stop the cat playing with the needle; however when the
owner caught the cat, there was no needle to be found. To complicate matters further, the cat then ate
100 rams of commercial tinned cat food, which the owner had been preparing.
Physical findings
No abnormalities were detected on physical examination. Coughing was not noted, nor was vomiting
or regurgitation during the duration of the physical examination. No foreign bodies or lesions were
detected within the oral cavity. A thread was not evident in the vicinity of the lingual frenulum when the
tongue was elevated by application of pressure to the intermandibular space. The abdomen was
palpated gently, however no pain, discomfort or abnormal structures were evident.
(1) What is your assessment?
(2) What would you do next?
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(this is EASY)
1. the cat may or may not have swallowed a sewing needle
2. the needle may or may not have had attached thread
3. if so, there may be as a consequence a variety of clinical problems
What are the potential problems?
1. Penetration of pharynx
2. Penetration of oesophagus
3. Migration of needle from stomach to other sites
a) which sites?
b) why THESE sites?
4. Complications related to thread i.e. intestinal plication
a) when does plication occur?
What would you do next?
(this is a BIT harder)
Haematology, biochemistry and urinalysis plus FIV and FeLV
Whole cat, in one go?
How many views?
Where is the needle?
Do we need a 2nd radiograph?
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¾ How should we manage this case?
¾ On what basis should we make decisions regarding clinical management?
(this may be CONTROVERSIAL)
Conservative - do nothing
Conservative - use drugs, other techniques
Endoscopic removal
Surgical removal
# On what basis should we make decisions regarding clinical management?
Look up text books
Ask colleagues
Ask local experts/specialists
Consult veterinary and medical databases – CAB, Medline, PubMed
Post a question on V.I.N.
# But before we do that, what are the UNIQUE considerations of the present case?
The cat has been presented EARLY
We cannot be sure if there is thread attached, or NOT
The cat has just eaten a LARGE meal
It is a young healthy patient that should cope OK with anaesthesia and surgery, if done in an
appropriate manner
5. Money is not an issue with these owners
6. There is time to THINK and RESEARCH the best course of action
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Is endoscopic removal a viable possibility?
1. In general, yes - although needles are hard to catch and hard to safely retrieve
2. You need good equipment and GREAT expertise
3. IN THIS CASE, the ingestion of food immediately prior to presentation would have made
endoscopic removal very problematic, furthermore anaesthesia would be relatively
contraindicated in this setting
What about surgery?
likely will resolve the problem
high success rate
minimum morbidity
makes more money for the clinic - $$$$$$
takes away all the possible complications associated with penetrating object and thread
1. invasive
2. costs the owner more money
3. some pain and morbidity for the patient
Ask learned colleagues
1. Dr Dick Churcher (opinionated Australian internist) STRONGLY recommended surgery based
on his experience with migrating needles in the UK; had seem them migrated liver, thoracic
cavity etc
2. V.I.N. ~ UK surgeon RECOMMENDED surgery TO BE SURE it would be OK; but said it might
pass, but couldn’t be sure this would happen
Veterinary Textbooks
Consulted a wide variety – NOT very helpful in this specific instance
EVIDENCE BASED MEDICINE using electronic databases
1. Look at veterinary data bases (most reliable)
2. Also, look at medical data bases (less reliable, but MORE information available for certain
topics, such as this one)
3. Case series MUCH MORE HELPFUL than individual case reports when looking for overall
4. (i)Year of the report and (ii) the country of origin and (iii)institution are very germane to the
quality and applicability of the data
5. Textbooks useful, but generally rated low down in the list compared to original peer-reviewed
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Veterinary Database (CAB)
In this instance, was technically difficult. Needed some patience to find the correct key words
(stomach, cat, needle). Only limited information available, both two case series.
1. Gunsser (1978) in German language Journal ‘Sewing needles and fish hooks as foreign
bodies in dogs and cats’ 57 dogs and 15 cats
- of 9 cats with gastric needles, 6/9 passed spontaneously in 3-4 days
2. Felts et al (1984) JAVMA Thread and sewing needles as GI foreign bodies in the cat: a review
of 64 cases (from the Animal Medical centre in New York City)
- most had thread and required surgery
Enough information is available to give you an impression that both good and bad outcomes were
possible, but there is insufficient quality data to be definitive in recommending treatment
strategies. Interestingly, young cats were overrepresented and the presence of thread must be
suspected, as it is the incentive for curiosity and play.
Intestinal plication from a string foreign body in a cat
What about individual case reports?
(like THIS one)
1. tend to be written to highlight UNUSUAL or dramatic sequelae
2. tend not to report simple, happy, unchallenging outcomes
3. e.g. Hunt et al (1991) Suspected cranial migration of two sewing needles from the stomach of
a dog. Vet Rec - migrated into the heart! Twice!!
What about human medical databases (Medline or PubMed)
Enormous number of cases - case reports, case series, LARGE case series
Most talk about FBs generically rather than JUST sewing needles
some case series have 18,200 cases !!!
Gun et al (2003) Paediatric Surgery International which concentrates on safety pin ingestion
(49 cases) - 41% passed spontaneously; the others required endoscopy or surgery
5. Reviewing MANY of the case series available, majority of FBs that reach the stomach
continue to pass through without sequelae, prokinetic drugs NOT helpful, sites of trouble are
pylorus, duodenal flexure, ileocaecocolic valve, pins are rarely a problem because of
Jackson’s axiom i.e. the blunt weighted end passes first
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How did we manage our patient?
1. Hospitalised the patient
2. Monitored rectal temperature, demeanour and appetite (every 8 to 12 hours) - we were
watching and anticipating signs of early peritonitis, pancreatitis, ileus, partial intestinal
obstruction, etc
3. The cat was fed judiciously using commercial tinned cat food ~ small meals three times daily,
finely mashed up using a fork
4. Took another radiograph the following morning – the needle was no within the intestinal tract.
5. The cat had a good appetite for TASTY food while in hospital
6. Temperature was marginally elevated for the first 36 hours
7. No faeces was passed for 3-days
8. The cat was given amoxicillin (100 mg orally twice daily) during hospitalisation
9. She was also given some Coloxyl (50 mg orally) every 12 hours from day 3
A milestone occurred on day 4 when the needle was passed
It was attached to a segment of stool
The needle measured 3.8 cm
It had a cotton thread attached, folded in two; the thread measured 74 cm
Presumably the stool pulled the needle and thread through the rectum
Further reading
Veterinary references
1. Gunsser I. Sewing needles and fish hooks as foreign bodies in dogs and cats. Diagnosis and
therapy. [German] Berliner und Munchener Tierarztliche Wochenschrift 1978; 91: 399-403.
2. Felts, J. F. Fox, P. R. Burk, R. L. Thread and sewing needles as gastrointestinal foreign
bodies in the cat: a review of 64 cases. Journal of the American Veterinary Medical
Association 1984; 184: 56-59.
Human references
1. Wahbeh G, Wyllie R, and Kay M. Foreign Body Ingestion in Infants and Children Clin Pediatr
2002; 41:633-640
2. Cheng W, Tam PK. Foreign body ingestion in children: experience with 1,265 cases. J Pediatr
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Surg. 199; 34:1472-1476
3. Panieri E, Bass DH. The management of ingested foreign bodies in children-a review of 663
cases. Eur J Emerg Med. 1995; 2, 83-87
4. McDermott VG, Taylor T, WyattJP, et al Orogastric magnet removal of ingested disc batteries.
J Pediatr Surg. 1995;30:29-32
5. Macpherson RI, Hill JG, Othersen HB, et al. Esophageal foreign bodies in children: diagnosis,
treatment, and complications. Am J Roentgenol. 1996; 166, 919-924
6. Litovitz TL, Klein-Schwartz W, White S, et al. 1999 annual report of the American Association
of Poison Control Centres Toxic Exposure Surveillance System. Am J Emerg Med. 2000; 18,
7. Schwartz GF, Polsky HS. Ingested foreign bodies of the gastrointestinal tract. Am Surg. 1976;
42, 236-238
8. Berggreen PJ, Harrison E, Snaowski RA, et al. Techniques and complications of esophageal
foreign body extraction in children and adults. Gastrointest Endosc. 1993; 39, 626-630
9. Campbell JB, Condon VR. Catheter removal of blunt esophageal foreign bodies in children.
Survey of the Society for Pediatric Radiology. Pediatr Radiol. 1989; 19, 361-365
10. Arana A, Hauser B, Hachimi-Idrissi S, Vandenplas Y. Management of ingested foreign
bodies in childhood and review of the literature. European Journal of Paediatrics. 160(8), 46872, 2001 Aug
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Case study: An unusual case of a mature cat with
crusted ears
Professor Richard Malik DVSc PhD FACVSc FASM
Post Graduate Foundation in Veterinary Science, Conference Centre, Building B22,
University of Sydney, NSW 2006 Australia
History: A 14-year-old neutered male domestic crossbred cat living in Mittagong was presented
(15/01/2002) for crusting of the ear, apparently of acute onset. Mittagong is a small town in the
southern highlands of New South Wales (Australia) approximately 100 km from Sydney.
Initial physical findings: The dorsal margin of the right pinna and its inside surface were covered by
dry cream-coloured crusted plaques. The lesions somewhat resembled equine dermatophilosis, and
bled when scraped. Lesions were not pruritic according to the cat’s owner and in support of this there
were no obvious secondary lesions referable to self trauma. No definitive diagnosis was made and
topical antibiotic and antifungal formulations were prescribed.
More data: The cat was re-examined 40 days later. There had been no response to therapy, and
indeed more extensive lesions were now present on both ears (Figure 1A). The dorsal surfaces of
both pinnae were deeply fissured, especially towards the pinnal margins (Figure 1B). The abnormal
skin felt cold to the touch, and was clearly demarked from the more normal adjacent integument.
Lesions extended across the preauricular area of alopecia of the right forehead (Figure 1C).
Figure 1. Photographs demonstrating the lesions present in Case 1. The most
conspicuous lesion is the crusting fissured dorsal surface of the pinna (A), seen most
clearly in the second photograph (B). Similar lesions, but of lesser severity, are evident
on the ventral surface of the pinna and on the periorbital area of alopecia (C).
1. What disease processes are under consideration for a cat with
this type of history and symptomatology?
2. What is your specific differential diagnosis?
3. How would you like to investigate this case further?
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1. What disease processes are under consideration for a cat with this type
of history and symptomatology?
Using a pathoanatomic classification scheme, the causes for a severe crusting skin diseases
could be inflammatory (infectious, allergic or immune-mediated), degenerative (toxic,
traumatic) or due to a disorder of growth (cornification/keratinisation defects, neoplasia).
2. What is your specific differential diagnosis?
From a clinical perspective, the differential diagnosis would thus include allergic dermatitis
(food allergy, flea allergy, atopic dermatitis), pemphigus foliaceus, lupus, dermatophytosis,
dermatophilosis, demodecosis, notoedric mange, sarcoptic mange, ear mite infestation, a
drug eruption, atypical squamous cell carcinoma and squamous cell carcinoma in situ.
3. How would you like to investigate this case further?
In this instance, skin scraping and a skin biopsy were considered the most appropriate
investigations to pursue. A case could have been made also for obtaining material suitable for
examination for fungal elements (e.g. KOH preparations) and for dermatophyte culture.
Under heavy sedation, the crusted material was scraped away, collected and examined
microscopically at low power (Figure 2). Enormous numbers of highly mobile, round-bodied
mites (200 to 400 µm) were observed amongst the hairs and crusty keratinous debris. Adult
mites of both sexes, nymphs, hexapod larvae (Figure 3) and eggs were observed in
abundance. The adult mites had a terminal anus, a dorsal anus and shorter limb stalks.
A skin biopsy was collected from the preauricular area of alopecia (Figure 1C). Histologically,
there was a generalised, mild to marked, epidermal hyperplasia with mild to marked
hyperkeratosis that was predominantly parakeratotic in focal areas. In some sections with
particularly marked hyperkeratosis, “tunnel” formation was evident sub-corneally within the
epidermis, with sections of mites present in many tunnels (Figure 4A). In the superficial
dermis there was a mild to moderate infiltrate, predominantly of eosinophils (some
degranulating), in a perivascular pattern (Figure 4B). There were approximately 30 to 40 mast
cells per high power field (400X) and scattered lymphocytes. Epidermal transmigration
(exocytosis) was evident with mild to moderate numbers of eosinophils present in the
hyperkeratotic crust. Infiltration of the superficial dermis with eosinophils and mast cells is
consistent with an inflammatory response with a prominent Type I hypersensitivity
The presence of a crusting non-pruritic skin disease affecting the ears, with deep fissuring,
marked hyperkeratosis and enormous numbers of mites was compatible with a diagnosis of
crusted (or Norwegian) scabies. Accordingly, a more detailed history was obtained to search
for a cause for the infestation and to explore the possibilities of immune suppression or
defective grooming ability. Firstly, erythematous papules were present on the forearms of the
cat’s owners (Figure 5). Secondly, the cat was said to spend much time in a paddock
opposite the owner’s house, an area known to be frequented by foxes and “mangy” wombats.
As crusted scabies is often associated with defective cell mediated immunity in human
patients, the cat was screened for the presence of FIV antibodies and FeLV antigen; it tested
negative for both.
4. How would you treat this patient?
Treatment of crusted scabies requires physical removal of keratinous debris known to harbour
the enormous numbers of mites, followed by systemic and/or topical antiparasitic therapy. In
this case, selamectin was used as a scabicide, and also to prevent environmental
reinfestation. A 5 to 10 kg canine size “Revolution”® applicator (120 mg/mL; 0.5 mL) was
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used to administer 60 mg selamectin in the recommended manner1 every two weeks for two
months; then once monthly. Following therapy, residual scale and crusts fell off, revealing
slightly pink skin. Skin scrapings became negative and all lesions resolved.
Selamectin was applied monthly at the recommended feline dose (60 mg/mL; 0.75 mL per
cat; approx. 6 mg/kg) to prevent the infestation recurring. The cat subsequently developed
UV-related squamous cell carcinoma of both pinnae, which were surgically resected.
Hyperthyroidism was diagnosed clinically and confirmed by an elevated thyroxine value
approximately 21 months after the cat was initially presented for scabies. The owners elected
not to treat the endocrinopathy and it remained in reasonable condition for another nine
months until it developed an abdominal mass and was euthanased. A necropsy was not
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Figure 2. Low power photomicrograph
from skin scrapings obtained from case
1. Note the presence mites of both
sexes and at various stages of
development, from eggs (arrows),
hexapod larvae, nymphs, to adult male
magnification – 25X.
Figure 3. Photomicrographs of sarcoptic
magnification. A female mite, containing
an egg, is present in the top micrograph
(A). A male is identified by the large
arrow in the middle photograph (B), while
a nymph (small arrow) and hexapod larva
(arrow head) is seen in the lower most
image (C). (A) and (B) original
magnification – 100X; (C) original
magnification – 50X.
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Figure 4.
Histological sections from
Case 1, a cat with crusted scabies. Note
presence of mites in epidermal
inflammatory infiltrate in the dermis.
H&E; original magnification – 40X.
Figure 5.
Erythematous papules
present on the forearm of the owners of
Case 1 (A)
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Nontuberculous mycobacterial syndromes in cats
Professor Richard Malik DVSc PhD FACVSc FASM
Post Graduate Foundation in Veterinary Science, Conference Centre, Building B22,
University of Sydney, NSW 2006 Australia
Feline panniculitis due to rapidly growing mycobacteria
Rapidly growing mycobacteria (RGM) are a heterogeneous group of organisms that produce colonies
on synthetic media within seven-days when cultured at 24oC to 45oC. They are distributed
ubiquitously in nature. RGM include the M fortuitum group (including M fortuitum, M peregrinum and
the 3rd biovariant complex), the M chelonae/abscessus group (including M chelonae and M
abscessus), the M smegmatis group (including M smegmatis sensu stricto, M goodii and M
wolinkskyi) and a variety of other species. The taxonomy of this group has been revised recently and
because of this, the word ‘group’ is used when referring to isolates recorded in early publications.
RGM are strongly linked with localized infections of immunocompetent hosts. This is because they are
well adapted to a saprophytic existence and inherently have low virulence. Thus, they do not produce
disease unless a breakdown in normal defense barriers provides them with a portal of entry to a
favorable tissue environment. Once introduced, RGM are generally constrained by a vigorous
immune response that may or may not eradicate them, but is effective enough to prevent
haematogenous or lymphatic spread. RGM can produce widely disseminated disease, but only in
severely immunocompromised individuals.
Mycobacterial panniculitis refers to a syndrome characterized by chronic infection of the subcutis and
skin with RGM. This condition is quite common in cats, especially in Australia. RGM replicate in
mammalian tissues when introduced through some break in the skin. This typically follows penetrating
injury, especially when the wound is contaminated by dirt or soil. Preference of RGM for fat is a key
factor in the pathogenesis and results in a tendency for disease to occur in obese individuals and in
tissues rich in lipid, such as the subcutaneous panniculus and especially the inguinal fat pad.
Experimental infections cannot be induced in cats that do not have appreciable subcutaneous fat.
Adipose tissue offers a favorable environment for survival and proliferation of RGM by providing
triglycerides for growth or protecting organisms from the phagocytic and immune responses of the
host. Initial reports suggested mycobacterial panniculitis was more common in warm humid climates;
however cats from temperate regions, including parts of Australia, Canada, Finland and Germany,
have subsequently been reported. In Australia, the M smegmatis group accounts for the majority of
feline cases, whereas it is a much less common cause of equivalent infections in human patients.
Clinical signs
Infections tend to start in the inguinal region, usually following contamination of cat fight injuries, e.g.
raking wounds inflicted with the hind claws. The infection may spread to contiguous subcutaneous
tissues of the ventral and lateral abdominal wall and perineum. Penetrating injury by sticks, metallic
objects and vehicular trauma may also give rise to these infections, as can cat and dog bite injuries
contaminated with soil or dirt. Sometimes infections start in the axillae, flanks or dorsum.
Early in their course, infections resemble catfight abscesses, but without the characteristic fetid odor
and turbid pus. Instead, a circumscribed plaque or nodule is apparent. Later, there is progressive
thickening of the nearby subcutis to which overlying skin becomes adherent. Affected areas become
denuded of hair and numerous punctate fistulae appear, discharging watery exudate. Fistulae are
intermingled with focal purple depressions (thinning of the epidermis over accumulations of pus). The
‘lesion’ gradually increases in area and depth, and may eventually involve the entire ventral abdomen,
adjacent flanks or limbs. If cats are presented promptly for veterinary attention and the lesion
confused with an anaerobic cat-bite abscess, surgical drainage and administration of a β-lactam is
typically followed by wound breakdown and development of a non-healing suppurating tract
surrounded by indurated granulation tissue. Some affected cats with infections develop systemic
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signs, becoming depressed, pyretic, inappetent, losing weight and being reluctant to move.
Occasional cats develop the hypercalcaemia of granulomatous disease, although this is rarely
symptomatic. Surprisingly, other cats remain comparatively well despite extensive disease. Usually
the problem remains localized to the skin and subcutis. Although adjacent structures such as the
abdominal wall can be affected eventually, spread to internal organs or lymph nodes is very unusual.
Sample collection, Cytology and Histology
A tentative diagnosis of mycobacteriosis can be confirmed by collection of pus or deep tissue
specimens. This material is used to confirm the diagnosis using appropriately stained smears,
histological sections and culture. A histological diagnosis is unnecessary if appropriate samples for
cytology and culture have been procured. It is vital to give the laboratory warning that mycobacterial
aetiology is suspected so special procedures for processing can be adopted.
In our experience, samples of pus obtained from needle aspirates of affected tissues through intact
skin provide the best laboratory specimens. This material can be obtained from a palpably abnormal
portion of the subcutis. The overlying skin should be carefully disinfected with 70% ethanol prior to
obtaining the specimen to preclude the isolation of saprophytic mycobacteria from the skin surface. It
may be necessary to carefully move the needle in the subcutaneous space, while applying constant
negative pressure, until a pocket of purulent material is encountered. Aspirated fluid should be
submitted for cytology and mycobacterial culture, or inoculated immediately into a commercially
prepared mycobacteria culture bottle that is subsequently submitted to the laboratory. It is only
necessary to suck a small amount of liquid material into the hub of the syringe. It is easiest to submit
the entire syringe to the laboratory after replacing the needle with a sterile cover. Exudate from
draining sinus tracts is heavily contaminated secondary invaders and represents an inferior sample. If
deep biopsies are obtained, they should be triturated in brain heart infusion broth using a sterile
mortar and pestle to produce a tissue homogenate suitable for cytology and culture.
Smears prepared from aspirates or tissue homogenates should be stained using Diff Quik®, Gram
stain and a modified acid-fast procedure (decolorizing with 5% sulphuric acid for only three to five
minutes; RGM are not as acid-fast as other mycobacteria). Cytology invariably demonstrates
pyogranulomatous inflammation and it is generally possible to visualize Gram positive and/or acid-fast
bacilli (AFB) in smears, although an exhaustive search may be required. Histologically, there is
pyogranulomatous inflammation. AFB may be hard or impossible to find in Ziehl-Nielsen (ZN) stained
tissue sections and are often located in lipid vacuoles. Some US dermatologists favour Fite’s stain for
detecting AFB in tissues.
Bacteriology and antimicrobial susceptibility testing
Tissue homogenates and pus should be streaked onto blood agar plates and a mycobacterial medium
such as Lowenstein-Jensen medium or 1% Ogawa egg yolk medium and incubated aerobically at
37oC and 25oC. If available, the BACTEC system can also be utilized. Moderate to heavy growth of
pinpoint, non-hemolytic colonies is usually detected after 2-3 days (occasionally longer) on sheep
blood agar at 37oC. A useful method which can be used to differentiate RGM from contaminant flora
is by primary isolation around antibiotic sensitivity discs (first generation cephalosporins or isoxazolyl
penicillins) applied to the plate after inoculation.
There is great value in determining species identification and susceptibility data in every case, as this
has a big impact on antimicrobial strategies. Species identification can be carried out in a well
equipped veterinary bacteriology laboratory although it if often more convenient to send the strain to a
Mycobacteria Reference Laboratory following primary isolation. Identification takes into account a
number of phenotypic and biochemical features. Minimum inhibitory concentrations (MICs) for
ciprofloxacin, moxifloxacin, gentamicin, trimethoprim, clarithromycin and doxycycline can be
determined easily using the Etest (AB Biodisk, Solna, Sweden) method. This methodology is less
demanding than the ‘gold standard’ of broth microdilution. Antimicrobial susceptibility of clinical
isolates can also be determined using disc diffusion methodology.
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The management of feline mycobacterial panniculitis continues to evolve in the light of clinical
experience, availability of new anti-infective agents and the development of new surgical techniques.
There is great variation in the severity and extent of lesions from patient to patient. Difficulty in making
a prompt diagnosis is partly responsible for the chronicity, severity and refractoriness of these
infections. Briefly, treatment should commence with oral antimicrobial(s) (doxycycline, a
flouroquinolone and/or clarithromycin), initially chosen empirically, but subsequently based on in vitro
susceptibility data. Sometimes long-term administration of such an agent or agents is sufficient to
effect a cure, but in many severe cases it is eventually necessary to surgically resect recalcitrant
tissues so that oral antimicrobial therapy will be able to cure the infection permanently. Given the
extent and severity of the pathology in many of these cases, it is understandable that adequate levels
of antimicrobials may not be achieved throughout all affected tissues and that in these cases the best
chance for a successful outcome is to remove as much infected tissue as possible following
preliminary drug therapy. Residual foci of infection can then be targeted by high concentrations of
antibiotics achieved during and after surgery. Peri- and post-operative antimicrobial therapy is vital to
ensure primary intention healing of the surgical incision. In the future, drugs such as moxifloxacin and
pradofloxacin may prove even more effective that agents currently available.
Disseminated Mycobacterium avium-intracellulare complex (MAC) infection in young
cats with a putative cell mediated immunodeficiency syndrome
We have recently reported a new syndrome of disseminated MAC infection in ten young cats (1 to 5
years-of-age) from Australia or North America. A further two cats with disseminated mycobacteriosis
(precise agent not identified) were recognised also. Of the twelve, ten were Abyssinian cats, one was
a Somali cat and one was a domestic shorthair cat. None of the cats tested positive for either FeLV
antigen or FIV antibody.
The clinical course of these infections was indolent, with cats typically presenting for weight loss,
initially in the face of polyphagia, with a chronicity of up to several months. Additional clinical features
included lower respiratory tract signs and peripheral lymphadenomegaly. A marked diffuse interstitial
pattern was evident in thoracic radiographs, even in cats without overt respiratory involvement. Hair
clipped to perform diagnostic procedures tended to regrow slowly, if at all. Diagnosis was generally
made by obtaining representative tissue specimens from mesenteric lymph nodes, liver or kidney at
laparotomy, or from a popliteal lymph node. The primary antecedent event was most likely
colonisation of either the alimentary or respiratory tract, followed by local invasion and eventual
lymphatic and haematogenous dissemination.
Nine cases were treated using combination therapy with agents effective for MAC infection in human
patients. The results were generally favourable, although the disease had a tendency to recur if
insufficient treatment courses were utilised. Cats were generally treated with long courses (5 to 14
months) of clarithromycin combined with either clofazimine or rifampicin, and a fluoroquinolone or
doxycycline was sometimes given also, although in the future moxifloxacin may prove to be a superior
adjunctive agent in this setting.
Certain lines of Abyssinian and Somali cats likely suffer from a familial immunodeficiency that
predisposes them to infection with slow-growing mycobacteria such as MAC. Studies of this problem
are on-going.
Feline leprosy syndromes
Historical perspective
The term feline leprosy is used to refer to a disease in which single or multiple granulomas form in the
skin or subcutis in association with large numbers of acid-fast bacilli (AFB) which are nonculturable
using standard methods. The condition was first recorded in the literature by Australian and New
Zealand researchers in the early 1960s. Since then, the disease has been reported in Western
Canada, the Netherlands, France, the UK and USA.
Historically, the causative agent of feline leprosy was purported to be Mycobacterium lepraemurium.
This bacterium causes murine leprosy, a systemic tuberculosis-like infection of rats. Cats are thought
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to contract M lepraemurium following bite injuries from infected rodents. M lepraemurium is a
fastidious, slow-growing organism which, with difficulty, can be cultured from large inoculae on
Ogawa’s egg yolk medium under special conditions. Although a few investigators have successfully
grown M lepraemurium from infected cats, the basis of ascribing this bacterium as the etiological
agent of feline leprosy was dependent on transmission studies. Interestingly, some cats appeared
much more susceptible to experimental infection than others.
According to the literature, cats with feline leprosy are typically young adults (< 5 years-of-age),
perhaps with a preponderance of males. Presumably these patient characteristics reflect the need for
the cat to interact with a rat to become infected. The initial lesion is a focal granuloma of the subcutis.
Owners become aware of solitary, or more commonly multiple, painless, raised, fleshy, tumor-like
lesions, from a few millimeters up to 4 cm in diameter. These granulomas are freely movable over
underlying tissues. Lesions can develop rapidly and when large, may ulcerate. Infection spreads to
adjacent areas and may invade underlying tissues and drain to regional lymph nodes. Lesions can
occur anywhere, but tend to be concentrated on the head and limbs. Small lesions are occasionally
found on the tongue, lips and nasal plane. Lesions, even if multiple, tend to be initially concentrated in
one region and have the propensity to recur following excision.
Pathologically, feline leprosy was subdivided into lepromatous or tuberculoid forms based on the no.
of AFB present (multibacillary v paucibacillary) and the host immunological response (lepromatous v
tuberculoid). Because the causal mycobacteria are slow-growing organisms capable of intracellular
survival, the histologic picture actually depends on the host’s immune response. When this response
is poor, lepromatous (multibacillary) disease develops with infiltration of the dermis with large sheets
of ‘incompetent’ foamy macrophages containing enormous numbers of organisms. AFB are usually
arranged in the cytoplasm of macrophages as dense parallel accumulations which displace the
nucleus to an eccentric position. Lymphoid cells and plasma cells are virtually absent from the
lesions. If the host’s immune response is more effective, histiocytic cells are accompanied by
moderate numbers of lymphoid cells and plasma cells and multiplication of the organism is limited the so-called tuberculoid response.
AFB in smears and tissue sections appear as long slender rods. In smears stained with Romanowsky
stains such as DiffQuik or Geimsa, organisms appear as negative-staining bacilli. In smears or
sections stained with modified acid-fast stains such as ZN or Fite’s stain, organisms take up the
carbol fuschin and are acid/alcohol fast.
Molecular insights
Molecular methodologies have been used to investigate presumptive feline leprosy. Of eight cases of
invasive or disseminated cutaneous mycobacterial disease investigated by Siobhan Hughes and
colleagues using material collected largely from New Zealand cats, four were shown to have M
lepraemurium infections. Of the remaining cases, one cat had a disseminated M avium infection, the
aetiology in one cat was undetermined and in two cases infection was attributable to a novel
mycobacterial species. This information encouraged a reappraisal of Australian feline leprosy cases,
and subsequently this work has been extended to North America by groups lead by Greg Appleyard
and Janet Foley.
In Australia, cats were initially be divided into two groups based on the patients’ age, lesion histology,
clinical course and sequence of 16S rRNA PCR amplicons obtained from lesions. More recently, we
have identified a new cohort of Australian cats from the Gippsland region of Victoria which were
infected by a third novel mycobacterial species.
1. The first group consisted of young cats (typically < 4-years) which initially developed localised
nodular disease affecting the limbs. Lesions progressed rapidly and sometimes ulcerated.
Sparse to moderate numbers of AFB were identified using cytology or histology, typically in
areas of caseous necrosis and surrounded by tuberculoid inflammation. Organisms did not
stain with haematoxylin and ranged from 2-6 µm (usually 2-4 µm). M lepraemurium was
diagnosed based on the sequence of a 446 bp fragment encompassing the V2 and V3
hypervariable regions amplified from lesions using PCR and mycobacterial primers.
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2. The second group consisted of old cats (>9-years) with generalised nodular skin lesions
associated with multibacillary lepromatous histology. Some cats initially had localised disease
that subsequently became widespread, while others had generalised disease from the outset.
Disease progression was protracted, typically taking months to years, and skin nodules did
not ulcerate. Microscopically, lesions consisted of sheets of epithelioid macrophages
containing large to enormous numbers of AFB 2-8 µm (mostly 4-6µm) which stained also with
haematoxylin. A single unique sequence spanning a 557 bp fragment of the 16S rRNA gene
was identified in lesions from these patients. The sequence was characterized by a long helix
18 in the V3 region, suggesting the new species was likely to be a fastidious, slow-grower.
The 16S rRNA sequence had greatest nucleotide identity with M leprae, M haemophilum and
M malmoense, and contained an additional ‘A’ nucleotide at position 105 (the only other
mycobacterial database sequence with the same extra nucleotide being M leprae). A very
slow, pure growth of a mycobacterium species was observed on Lowenstein-Jensen medium
(supplemented with iron) and semisolid agar in one case. The environmental niche of this
new mycobacterium species has yet to be determined, although the preponderance of cases
from rural or semi-rural areas of coastal NSW suggests it is a saprophyte found more
commonly in these locations than in metropolitan environments.
3. The third group consisted of 12 cats, typically young adults (2 to 8 years), with lesions located
on the head, cornea, conjunctiva or distal limbs, and lesions that were generally multibacillary
and lepromatous. The remarkable finding was that, with one exception, cases were
encountered in a very restricted part of rural Victoria. The distribution of lesions is most
compatible with a saprophytic organism being inoculated in tissues subsequent to cat scratch
The presence of tuberculoid pathology is generally marker of disease in an immune-competent host
and such infections are often initially localised. In contradistinction, the presence of a foamy histiocytic
infiltrate of the dermis and subcutis in patients with mycobacteriosis is observed almost exclusively in
association with profound immunodeficiency, such as that seen with terminal HIV infection in human
patients. Widespread dissemination of infection (rather than local invasion) suggests decreased
immunological surveillance permits the development of disease with an organism usually considered
to have limited virulence. Feline leprosy caused by the novel NSW mycobacterial species, the
Victorian novel species or more rarely M lepraemurium, may likewise represent a manifestation of
deteriorating immune competence.
For epidemiologic reasons, feline leprosy in young cats is almost invariably caused by M
lepraemurium, the novel NSW species is almost invariably seen in old (likely immunosuppressed
cats) while the novel Victorian species can occur in either immune competent or immune defective
To make matters even more complex, recent work by Appleyard and colleagues has demonstrated a
third mycobacterial syndrome in cats from western Canada and the USA (Idaho and Oregon) called
‘feline multisystemic granulomatous mycobacteriosis’. This disease is caused by a slow-growing taxa
provisionally called M visibilis or M visible. This species is capable of producing widespread
dissemination to multiple internal organs, presumably in immune deficient cats. Sequence analyses
demonstrate a number of nucleotide differences between M visibilis and both M lepraemurium and the
novel species reported by Hughes et al.
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Figure 1. Unrooted phylogenetic tree of selected Mycobacterium
species computed from concatenation of 16S rRNA gene, ITS and
hsp65 sequences by maximum likelihood.
M visibile
M. leprae
NSW novel species
M lepraemurium
M. avium
M. malmoense
M. haemophilum
M. parascrofulaceum
M. interjectum
M. genavense
M. sherrisii
M. simiae
Vic novel species
CLGS mycobacterium
Diagnosis of the ‘feline leprosy’ syndromes is usually straightforward, provided that the clinician has a
high index of suspicion for the condition. Needle aspirates, crush preparations of biopsy material and
histological sections stained with ZN or similar methods contain easily demonstrable AFB surrounded
by variable granulomatous to pyogranulomatous inflammation. In DiffQuik stained smears,
mycobacteria can be recognized by their characteristic ‘negative-staining’ appearance and location
within macrophages and giant cells.
Material should be submitted also for culture, because occasionally slowly-growing species such as
MAC and M genavense and the tubercle bacillus (M bovis or M microti) can produce an identical
clinical presentation; in such cases optimal antimycobacterial therapy can be selected more readily on
the basis of in vitro susceptibility results and information available in the literature. In the majority of
cases, however, conventional mycobacterial culture is negative due to the fastidious nature of the
causal organisms and the exact aetiology can only be proven using PCR amplification and sequence
determination of gene fragments. PCR has the additional advantage of providing a rapid diagnosis.
Fresh (frozen) tissue delivered to a mycobacterium laboratory with PCR facilities provides the optimal
sample, although freeze-dried specimens may be more conveniently sent where tissues need to
travel long distances. Sometimes PCR can be performed successfully on formalin-fixed paraffinembedded material, although fixation conditions invariably cause some DNA degradation which may
limit the success of the procedure. Recently, Hughes and colleagues have developed specific PCR
assays to diagnose infections due to M lepraemurium and the novel species; furthermore, use of a
simple restriction enzyme digest allows these assays to distinguish M visibilis strains also.
Too few cases with a documented aetiology have been reported to provide definitive treatment
guidelines. Although M lepraemurium and the novel species can be cultured in vitro with difficulty, it is
currently not routine or reliable to isolate these organisms due to their slow growth and fastidious
requirements. Determination of in vitro susceptibility data for individual isolates is therefore not
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Only limited experimental studies have been undertaken to determine effective drug therapy for M
lepraemurium in vitro or in vivo and as yet we have limited data only for the novel mycobacterial
species. Portaels and colleagues found the minimum inhibitory concentration for rifampicin of two
strains of M lepraemurium to be 4 and 8 µg/mL, levels that should be just obtainable in vivo. Other
drugs shown to have activity against M lepraemurium in vitro include ansamycin compounds
(rifabutin) and sulpha drugs. There is a good deal of clinical evidence that clofazimine has efficacy in
vivo, while it is likely that clarithromycin would be also be effective based on its wide spectrum of
activity against slow-growing mycobacterial species.
The literature suggests that when M lepraemurium infection is diagnosed early, while disease is
localized, wide surgical excision of infected tissues provides the best chance to simply and rapidly
effect a cure. Aggressive resection techniques should be adopted, with en bloc resection of all
lesions, and reconstruction of resulting tissue deficits using appropriate surgical techniques. Such an
approach should be combined with adjunct antimicrobial therapy beginning a few days prior to
surgery, so that effective levels of drugs are present in blood and tissues intra- and postoperatively to
ensure primary intention healing. Clofazimine (at a dose of up to 10 mg/kg once daily orally; typically
25 to 50 mg every 24 to 48 hours) has the best reported success rate, although it is likely that
combination therapy using two or more drugs will eventually prove superior. Drugs that could be
combined with clofazimine include rifampicin and clarithromycin, although sulpha drugs, doxycycline,
new fluoroquinolones such as moxifloxacin or pradofloxacin, or amikacin may in time also prove to be
useful. Unfortunately, clofazimine is becoming very difficult to obtain, although some compounding
pharmacies can source the dye.
In feline leprosy cases caused by novel mycobacterium species, we believe combination therapy
using two or three of clofazimine (25 to 50 mg per cat orally every day or every other day),
clarithromycin (62.5 mg twice daily) or rifampicin (10 to 15 mg/kg per day) represents optimal therapy.
However we are currently unsure of which will prove to be the best combination, and side effects in
individual cats may affect which two drugs are used in a given patient. Currently, we recommend a
combination of rifampicin and clarithromycin as initial therapy. The new quinolone moxifloxacin may
prove useful in future cases, as it has good antimycobacterial activity and is affordable. Other new
agents such as linezolid may also have a place, although currently they are prohibitively expensive for
most owners.
Further reading
1. Baral, R.M., Catt, M.J., Foster, S.F., McWhirter, C., Wigney, D.I., Martin, P., Chen, S.C.A.,
Mitchell, D.H. and Malik R. (2006) Disseminated Mycobacterium avium infection in young
cats: over-representation of Abyssinians. Journal of Feline Medicine & Surgery 8: 23-44.
2. Hunt G.B., Tisdall P. L. C., Liptak J. M., Beck J.A., Swinney G.R., Malik R. (2001) Skin-fold
advancement flaps for closing large proximal limb and trunk defects in dogs and cats.
Veterinary Surgery 30: 440-448.
3. Hughes, M.S., James, G., Taylor, M.J., McCarroll, J., Neill, S.D., Chen, S.C.A., Mitchell, D.H.,
Love, D.N., MALIK, R. (2004) PCR studies of feline leprosy cases. Journal of Feline Medicine
& Surgery 6: 235-243.
4. Hughes, M.S., Ball, N.W., Love, D.N., Canfield, P.J. Wigney, D.I., Dawson, D., Davis P.E. &
Malik, R. (1999) Disseminated Mycobacterium genavense infection in an FIV-positive cat.
Journal of Feline Medicine & Surgery 1:23-30.
5. Foster, S.F., Martin, P., Davis, W., Allan, G.S., Mitchell, D.H. & Malik R. (1999) Chronic
pneumonia caused by Mycobacterium thermoresistible in a cat. Journal of Small Animal
Practice 40: 433-438.
6. Malik R., Wigney, D.I., Dawson, D., Martin, P., Hunt, G.B., & Love, D.N. (2000) Infection of
the subcutis and skin of cats with rapidly growing mycobacteria: a review of microbiological
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and clinical findings. Journal of Feline Medicine & Surgery 2: 35-48.
7. Malik, R., Hughes M.S., James, G., Chen, S.C.A., Mitchell, D.H., Wigney, D.I., Matrin, P.,
Canfield, P.J. & Love, D.N. (2002) Feline leprosy: two different clinical syndromes. Journal of
Feline Medicine & Surgery 4:43-59.
8. Davies, J.L., Sibley, J.A., Myers, S., Clark, E.G., Appleyard, G.D. (2006) Histological and
genotypical characterization of feline cutaneous mycobacteriosis: a retrospective study of
formalin-fixed paraffin-embedded tissues. Veterinary Dermatology 17:155-162.
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Should I worry about Helicobacter?
Kenneth W Simpson BVM&S, PhD, MRCVS, DipACVIM, DipECVIM-CA
College of Veterinary Medicine, Cornell University Ithaca NY
Gastric Helicobacter
The discovery of the association of Helicobacter pylori with gastritis, peptic ulcers, and gastric
neoplasia has led to fundamental changes in the understanding of gastric disease in humans.
Investigation of the relationship of gastric disease to Helicobacter spp. in other animals has resulted in
the discovery of H. mustelae in ferrets with gastritis and peptic ulcers, H. acinonychis in cheetahs with
severe gastritis, and H. Heilmannii in pigs with gastric ulcers. The presence of gastric Helicobacterlike organisms (HLO) in the stomachs of dogs and cats has been known for many years but the
relationship of those organisms to gastric disease remains controversial.
Helicobacter spp. infecting the stomachs of dogs and cats
Helicobacter are spiral-shaped or curved, or sometimes coccoid Gram negative bacteria that inhabit
the glands, parietal cells and mucus of the stomach. The large gastric HLO are morphologically
indistinguishable by light microscopy, in which they are seen as large, 5-12µ long spirals. They have
been classified into several Helicobacter spp. on the basis of 16s rRNA sequencing, DNA
hybridization, and electron microscopic appearance. H. felis, "H. heilmannii", H. bizzozeronii, and H.
pametensis have been detected in the gastric mucosa of pet cats. H. pylori has been isolated from the
stomachs of a group of colony housed cats, but not pet cats. H. bizzozeronii, H. heilmannii, H. felii, H.
salomonis, F. rappini and H. bilis have been identified in dogs.
How common is infection with gastric Helicobacter spp.?
There is a high prevalence of gastric Helicobacter infection: HLO have been observed in gastric
biopsies from 41-100% of clinically healthy and 57-100% of vomiting cats. The prevalence of
individual Helicobacter spp. has not been thoroughly investigated, as it requires specialized
techniques. H.felis has been cultured from 3/21 Helicobacter infected cats in Finland, whereas "H.
heilmannii" was identified by PCR in 38/49 Swiss cats. PCR studies in Helicobacter infected cats in
the USA have identified 18/36 with "H. heilmannii", 6/36 with H. felis (4/36 coinfected with H. felis and
"H. heilmannii"), 2/36 H. bizzozeronii and 10 cats with unclassified Helicobacter spp. Broadly similar
results have been observed in 50 German cats, though H. bizzozeronii infected up to 30% of cats.
Electron microscopic examination of gastric biopsies from infected cats has demonstrated co-infection
with spiral organisms of differing morphology-H. felis, H. Heilmannii, H. bizzozeronii, and other large
gastric spiral organisms.
H. pylori infection has been reported in a group of laboratory cats in the USA, but has not been
reported in pet cats in the USA or Europe to date. It has been proposed that H. pylori is an
anthroponosis - an animal infection with a human pathogen.
Several studies have shown that gastric Helicobacter are common in dogs, with a prevalence ranging
from 67-100% in healthy pet dogs, 74-90% in dogs presented with vomiting and 100% in laboratory
beagles. In dogs H. bizzozeronii is the most prevalent species followed by “H. heilmannii” and
H.salomonis, with H. felis less common. Coinfection with one or more spp, usually H. bizzozeronii and
H. heilmannii, is apparent in about 15-20% of dogs. H.pylori has not been found in pet dogs.
Are cats and dogs a zoonotic risk?
“H. heilmannii”, the predominant species in pet cats, and 20-40% of pet dogs, is also found in the
mucosa of 0.4-4% of people. H. heilmannii type 1 is the principal subtype in people and is thought to
be acquired by zoonotic transmission from dogs, cats or pigs which are commonly infected with H.
heilmannii-like organisms (HHLO).
To provide a more informed estimate of the zoonotic potential of cats, gastric DNA from cats (45
American and German) infected with H. heilmannii, was amplified with primers against H. heilmannii
ureB and 16s rDNA genes and sequenced. Fluorescence in situ hybridization (FISH) with eubacterial
and H. heilmannii specific probes was employed to directly visualise H. heilmannii subtypes and their
intragastric distribution (Priestnall et al). ureB sequences of H. heilmannii amplicons clustered with
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ESFM Feline Congress 2006
human and feline isolates of H. heilmannii and were distinct from the Helicobacter heilmannii-like
organisms, H. felis, H. salomonis and H. bizzozeronii. 16S rDNA sequences in cats and dogs were
not consistent with H. heilmanii Type 1 and clustered predominantly with types 2 and 4. No obvious
differences in sequences were observed between cats from different countries. FISH failed to
definitively characterize H. heilmannii subtypes present in 14 of 15 cats. As H. heilmannii type 1 is the
dominant species in infected people, the zoonotic risk posed by cats and dogs is likely small.
In another study (Van den Bulck et al) gastric biopsy samples from humans with histological evidence
of non-Helicobacter pylori spiral bacteria (n = 123) and samples from the gastric antrum, corpus, and
cardia from dogs (n = 110) and cats (n = 43) were subjected to a multiplex PCR, enabling the
identification of Helicobacter felis, Helicobacter bizzozeronii, Helicobacter salomonis, and "Candidatus
Helicobacter suis." Single infections with "Candidatus Helicobacter suis," H. felis, H. bizzozeronii, H.
salomonis, a hitherto unknown genotype of a non-H. pylori spiral organism (Helicobacter-like
organism 135 [HLO135]), and H. pylori were identified in 30.9%, 8.9%, 2.4%, 11.4%, 7.3%, and 8.9%
of the human biopsy samples, respectively. Mixed infections (16.3%) with two or even three of these
were also found. Although the majority of human non-H. pylori organisms are Helicobacter species
naturally occurring in the stomachs of pigs, cats, and dogs, the frequent identification of H. salomonis
in human gastric biopsy samples is in contrast to its rare identification in pet carnivore samples,
suggests other sources of infection.
Do Helicobacter spp cause gastric disease?
The cause of gastritis in cats and dogs is seldom determined and is usually been attributed to dietary
allergy or intolerance, parasites, or a reaction to bacterial antigens. The association of Helicobacter
infection with gastric disease in humans, ferrets, cheetahs, pigs and experimentally infected
laboratory animals suggests that spiral organisms may have a role in the pathogenesis of gastritis in
cats. The results of studies of cats and dogs with naturally acquired gastric Helicobacter Infection can
be summarized as follows:
The relationship of infection to clinical signs: The high prevalence of gastric colonization with HLO
in healthy and sick cats indicates that there is no simple "infection = disease" relationship. An
uncontrolled treatment trial of dogs and cats with gastritis and Helicobacter infection showed that
clinical signs in 90% of 63 dogs and cats responded to treatment with a combination of metronidazole,
amoxicillin and famotidine, and that 74% of 19 animals re-endoscoped had no evidence of
Helicobacter in gastric biopsies. Controlled clinical trials are required to confirm these observations
(see treatment).
The relationship of infection to gastric histopathology:
The majority of studies in cats and dogs with naturally acquired Helicobacter infections demonstrate
that the fundus and cardia are more densely colonized with bacteria than the pylorus. Large HLO
colonize the superficial mucus and gastric glands, and may also be observed intracellularly.
Degeneration of gastric glands, with vacuolation, pyknosis and necrosis of parietal cells is more
common in infected than uninfected dogs and cats.
The gastric mucosal inflammation present in Helicobacter infected dogs and cats is generally
mononuclear, and ranges from mild to moderate in severity. A correlation between the presence of
HLO and the extent of histopathological changes in the gastric corpus has been demonstrated in cats.
The paucity of uninfected animals has hampered most investigations.
We have analyzed cytokines in gastric mucosa from 8 uninfected and 20 infected cats. Infected cats
have upregulation of IL-8 (P=0.001) and IL-1 (P=0.01), but not IFN- or IL-10.The evaluation of
cytokines complements histopathology and should be useful when evaluating grading systems for
inflammation. Gastric lymphoid hyperplasia is more common and more extensive in Helicobacter
infected, than uninfected cats. Studies in cats that have examined full thickness gastric biopsies have
demonstrated a strong association between infection and lymphoid follicle hyperplasia. In addition to
this local immune response, a systemic immune response characterized by circulating antiHelicobacter IgG has been detected in sera from naturally infected cats. To date there has been no
association made between Helicobacter infection and gastrointestinal ulcers or gastric neoplasia in
cats. However the relatively low prevalence of these diseases coupled with the small number of
animals evaluated to date means that such a relationship cannot be discounted.
Studies of the immune and inflammatory changes in 30 dogs with naturally acquired gastritis have
shown that mucosal pathology is related to cytokine mRNA expression (neutrophils to IL-8 and IFN-γ,
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macrophages and lymphocytes to IFN-γ, and fibrosis to IL-1β) (Wiinberg et al). Gastritis was
categorized as lymphoplasmacytic in all dogs, and its histological severity correlated with atrophy,
infiltration with lymphocytes and macrophages, and the expression of IL-10 and IFN-γ. Helicobacter
spp infection was associated with increased expression of TGF- , and fibrosis. Macrophages, T-cells,
and epithelial metaplasia were more frequent in uninfected than infected dogs. Circulating antiHelicobacter IgG was higher in uninfected than infected dogs. Studies in Korea have also failed to
show a relationship of Helicobacter infection to pro-inflammatory cytokine upregulation (Hwang et al).
Further defining the pathogenicity of individual Helicobacter species
Studying the effects of Helicobacter on the gastric mucosa of cats presenting with spontaneous
disease is limited by the variability in the host makeup and the infecting Helicobacter species (and
possible strain variation too). In contrast to humans, in whom H. pylori infection predominates, the
investigation of pathogenicity in cats is complicated by the fact that they can be colonized by a variety
of Helicobacter spp., and simultaneous colonization with multiple species has been frequently
observed. To overcome some of these difficulties and improve our understanding of cat-Helicobacter
interactions we have employed experimental infections with H. felis and H. pylori.
Studies of the pathogenicity of H. felis in laboratory cats have demonstrated gastritis, lymphoid
follicular hyperplasia and seroconversion. H. pylori infection in cats is associated with a moderately
severe to severe gastritis yet clinical signs associated with gastritis, such as inappetance and
vomiting, are generally absent. It serves as a model for investigating feline gastric mucosal responses
and the mechanisms of Helicobacter pylori colonization, persistence and disease.
Analyses of gastric juice and biopsies from kittens in an H. pylori-infected cat colony, using rapid
urease tests, ureB PCR and histopathology, demonstrated H. pylori in nine of 17 kittens by eight
weeks, and in 16 of these same 17 kittens by 14 weeks of age. UreB RLP patterns and sequences of
PCR products from gastric mucosa were identical in mothers and kittens. Bacterial densities were
similar in the pylorus, fundus and cardia. Infection was associated with circulating anti-Helicobacter
IgG antibodies and significant (P<0.05) gastric inflammation and lymphoid follicles; the pathology
resembled that often seen in infected human infants.
In more chronically infected cats we sought to measure the development of host inflammatory and
immune responses, and their relationship to the putative bacterial virulence factors cag pathogenicity
island (cagPAI), vacA allele and oipA in combination with bacterial colonization density in a feline
model of the early stages of H. pylori infection (Straubinger et al). Infecting H. pylori strains were
positive for vacAs1 but lacked the cagPAI and an active oipA gene. Colonization density was uniform
throughout the stomach. Up-regulation of IFN- IL-1 , IL-1 , IL-8, and increased severity of
inflammatory infiltrates and fibrosis were observed in infected cats. The median number and total area
of lymphoid aggregates were five and ten times greater, respectively, in the stomachs of infected than
uninfected cats. Secondary lymphoid follicles in uninfected cats were rare and positive for BLA.36 and
B220 but negative for CD3 and CD79 , whereas in infected cats they were frequent and positive for
BLA.36, CD79 , and CD3 but negative for B220. Cats infected with H. pylori can also develop
antigastric antibodies that cross-react with Helicobacter antigens. Changes in gastric acid secretion
and serum gastrin which are known to occur in humans with H. pylori infection have recently been
demonstrated in cats with experimental H. pylori infection.
These findings have implications for the development of gastric inflammation and possibly GI
Lymphoma. The methods developed to study these research cats are now being employed to
evaluate cast with spontaneous gastritis. Further studies are ongoing to try to determine the genetic
attributes of H. pylori that impact the host response.
Eradicating Helicobacter spp in cats and dogs
The general lack of knowledge of the pathogenicity of gastric Helicobacter spp. has meant that
veterinarians are faced with the dilemma of either treating, or ignoring, spiral bacteria observed in
biopsies from patients with chronic vomiting and gastritis. Eradication of H. pylori infection in
symptomatic humans has been associated with resolution of symptoms and gastric abnormalities. In
light of their pathogenicity in man and other animals it would seem reasonable that eradication of
gastric Helicobacter spp. is considered prior to initiating treatment with immunosuppressive agents to
control gastritis. An uncontrolled treatment trial of dogs and cats with gastritis and Helicobacter
infection lends support to this approach. Clinical signs in 90% of 63 dogs and cats responded to
treatment with a combination of metronidazole, amoxicillin and famotidine, and 74% of 19 animals reendoscoped had no evidence of Helicobacter in gastric biopsies. However, controlled therapeutic
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studies in asymptomatic cats suggest that it is difficult to eradicate gastric Helicobacter spp. in cats
with azithromycin, tinidazole, bismuth and ranitidine, or clarithromycin, metronidazole, bismuth and
ranitidine for four or seven days. After three weeks of amoxicillin, metronidazole and omeprazole, cats
with H. pylori infection were culture negative, but five out of six cats were positive in a species specific
PCR in dental plaque, saliva and/or gastric fluid samples. Amoxicillin and metronidazole does not
appear to be an effective treatment in dogs either, with a high failure rate 1 month after antibiotics.
It is unclear if in most studies antibiotic failure was due to reinfection or recrudescence, although the
persistence of Helicobacter by PCR suggests recrudescence is likely. These findings contrast
markedly with studies in H. pylori infected people where 80% cure rates with @ 1%/yr reinfection are
We have recently performed a study in H. pylori infected cats to determine if differences in H.pylori
genotype, and antibiotic sensitivity explain the difficulty in eradicating Helicobacter in cats: DNA
sequences of a variety of genes from H. pylori isolated from cat strains matched those of H. pylori
strains of human origin. Isolates from different cats differed in growth rate in culture, intrinsic
susceptibility to metronidazole and their ability to colonize stomachs of H. pylori-free cats. The pattern
of metronidazole sensitivity and the role of genes metabolizing metronidazole were similar in strains
from people and cats. Further tests showed that chronically infected cats could be cured of resident
H. pylori with amoxicillin (20mg/kg PO BID 14days), metronidazole (10-15mg/kg PO BID) and
clarithromycin (7.5mg/kg PO BID). This yielded 100% eradication in 12/12 cats 1 month post
Non- gastric Helicobacter spp.
Cholangiohepatitis / cholangitis complex in cats is an ill-defined inflammatory disorder of the
hepatobiliary tree, that is one of the most common hepatic disorders in cats .It has been subcategorized as suppurative and non-suppurative to reflect the relative proportions of neutrophils to
lymphocytes and plasma cells, and the degree of bile duct hyperplasia and fibrosis. Suppurative
cholangiohepatitis is often associated with a short duration of illness, moderate elevations of liver
enzymes, jaundice, fever, neutrophilia and being male. Non-suppurative cholangiohepatitis is similarly
characterized by jaundice and elevated hepatic enzymes, but a longer duration of clinical signs,
hepatomegaly and a protein rich abdominal effusion, hyperglobulinemia and lymphocytosis are
observed more frequently than in cats with suppurative cholangiohepatitis.
Bacterial infections, most frequently enteric species, have been implicated in acute cholangiohepatitis,
and a clinical response to antimicrobial therapy has been observed in a cat with Enterobacter
associated cholangiohepatitis. Concurrent pancreatic or intestinal inflammation and cholestasis
(intra- or extrahepatic) are also frequently diagnosed in cats with both suppurative and nonsuppurative cholangiohepatitis and may facilitate bacterial colonization, possibly by ascending
infection of the biliary tree. However, a cause and effect relationship of these potential etiologies to
cholangiohepatitis has yet to be demonstrated.
In people, rodents and dogs there is evidence that inflammation and/or neoplasia of the liver and
biliary tract are associated with infection with Helicobacter spp. Helicobacter DNA or organisms, have
been identified in the liver, bile or gallbladder of people with chronic cholecystitis, cholestatic liver
disease and hepatobiliary carcinoma and cirrhosis. In mice H. hepaticus have been associated with
hepatitis, hepatocellular carcinoma,and inflammatory bowel disease and Helicobacter bilis with
hepatitis and typhlitis. H. cholecystus has been cultured from the gallbladders and pancreas of
hamsters with cholangiohepatitis and pancreatitis. H. canis has been cultured from the liver of a
young dog with hepatitis. To date there are no reports of Helicobacter spp associated liver disease in
cats. However, as cats, like humans and other species, harbor Helicobacter in their stomachs i.e. H.
felis, H. heilmanii and H. bizzozzeronii, and H. canis, bilis, cinaedi and Flexispira have been cultured
from feces it is possible that Helicobacter species have a role in hepatic disease in cats.
It is against this background that we examined the role of Helicobacter spp. in cholangiohepatitis in
cats, by evaluating archived hepatic tissue samples from cats with and without cholangiohepatitis for
the presence or absence of Helicobacter spp using PCR, immunocytochemistry and silver staining.
Tissue blocks from 32 cats with cholangiohepatitis were identified in the pathology database for the
period 1992-2001 (Greiter-Wilke et al). Tissue blocks from a group of 13 cats with non-inflammatory
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liver disease, and 4 with normal hepatic histology served as a control group. Positive PCR results of
liver samples were obtained from 2 cats with cholangiohepatitis, and 1 cat with PSVA. Sequence
analysis indicated homology with H. nemestrinae / pylori in one Ch cat, and H. bilis in the PSVA cat.
Two amplicons of different sizes persistently detected in the third cat, were consistent with H
nemestrinae / pylori and H. fenelliae/cinaedii. PCR of gastric tissue samples yielded sequences with
close homology to gastric Helicobacter spp e.g. H. heilmannii,. No Helicobacter-like organisms were
identified in hepatic tissue by Steiner stain or immunocytochemistry.. FISH using a eubacterial probe
identified a semicurved bacterium in the intrahepatic bile duct of one cat with cholangiohepatitis.
Recent studies of cats with lymphocytic cholangitis (Boomkens et al) detected H. pylori like
sequences in the bile of 4/15cats with lymphocytic cholangits, 8/51 cats with non-LC cholangitis and
7/12 healthy cats.
The Helicobacter sequences identified in thee studies are consistent with those associated with liver
disease in other species. Further, prospective studies are warranted to elucidate the role of
Helicobacter and other infectious agents in liver disease in cats.
Acknowledgements: Dr. Simpson is supported by a grant from the US public health service (DK
002938). I gratefully acknowledge the generous support provided by numerous graduate students,
post-docs, technicians and external collaborators- some of whom are mentioned in the references
A.Greiter-Wilke, E. Scanziani, S. Soldati, P.L. McDonough, K.W.Simpson. Are Helicobacter
associated with inflammatory liver disease in cats? JVIM 2002, 16, p328
Boomkens SY, Kusters JG, Hoffmann G, Pot RG, Spee B, Penning LC, Egberink HF, van den Ingh
TS, Rothuizen J.Detection of Helicobacter pylori in bile of cats. FEMS Immunol Med Microbiol. 2004
Nov 1; 42(3), 307-11
Hwang CY, Han HR, Youn HY.Prevalence and clinical characterization of gastric Helicobacter
species infection of dogs and cats in Korea. J Vet Sci. 2002 Jun; 3(2),123-33.
Priestnall SL, Wiinberg B, Spohr A, Neuhaus B, Kuffer M, Wiedmann M, Simpson KW. Evaluation of
"Helicobacter heilmannii" subtypes in the gastric mucosas of cats and dogs. J Clin Microbiol. 2004
May; 42(5), 2144-51.
Straubinger RK, Greiter A, McDonough SP, Gerold A, Scanziani E, Soldati S, Dailidiene D, Dailide G,
Berg DE, Simpson KW. Quantitative evaluation of inflammatory and immune responses in the early
stages of chronic Helicobacter pylori infection. Infect Immun. 2003 May; 71(5):2693-703.
Van den Bulck K, Decostere A, Baele M, Driessen A, Debongnie JC, Burette A, Stolte M, Ducatelle R,
Haesebrouck F.Identification of non-Helicobacter pylori spiral organisms in gastric samples from
humans, dogs, and cats. J Clin Microbiol. 2005 May; 43(5), 2256-60.
Wiinberg B, Spohr A, Dietz HH, Egelund T, Greiter-Wilke A, McDonough SP, Olsen J, Priestnall S,
Chang YF, Simpson KW.Quantitative analysis of inflammatory and immune responses in dogs with
gastritis and their relationship to Helicobacter spp. infection. J Vet Intern Med. 2005 Jan-Feb; 19(1), 414.
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ESFM Feline Congress 2006
Feline cryptococcosis
What do studies in koalas have to tell us about the most common
systemic mycosis of cats?
Professor Richard Malik DVSc PhD FACVSc FASM
Post Graduate Foundation in Veterinary Science, Conference Centre, Building B22,
University of Sydney, NSW 2006 Australia
Biology and epidemiology
Cryptococcosis is the most common systemic fungal infection of cats worldwide. It is seen in Europe
and North America, although it would appear to be more common in Australia and southern California.
Recently there has been a fascinating ‘outbreak’ of cryptococcosis in Vancouver Island which has
captured the imagination of infectious disease experts, and this epizootic is now spreading to involve
the mainland of British Columbia.
This audience is principally concerned with this disease as it pertains to feline patients. Most
infectious disease doctors are interested primarily in the disease as it is encountered in human
patients. In contradistinction, a biological scientist interested in really understanding infectious
diseases takes what he can glean from data available from all species, as well as specific information
about the agent of disease and the environment in which it normally lives. For saprophytic organisms
such as Cryptococcus, this involves teasing apart the interaction between the saprobe, its normal
environment, and the mammalian hosts which from time to time accidentally become infected.
Cryptococcosis is caused by two different species, C. neoformans (including two varieties, C. n. var
grubii and C.n. var neoformans) and C gattii, which together form the C neoformans complex.
Switched on feline practitioners will recall that most cats with symptomatic cryptococcosis present for
variably invasive rhinosinusitis, meningitis or meningoencephalitis or nodular skin disease. In the
majority of cases, infection starts in the nasal cavity, although very rarely one can see localised
cutaneous cryptococcosis following a cat scratch injury.
Infectious propagules of the C neoformans complex comprise basidiospores produces by haploid
fruiting or sexual reproduction between different (a and alpha) mating types, or desiccated of yeast
organisms elaborated from environmental sites. There is a strong association between C.n. var grubii
and avian (especially pigeon) guano, and between C gattii VGI strains and eucalyptus trees. No one
knows why a given cat develops cryptococcosis, but is seems most likely that infection develops
because of the unfortunate combination of a heavy inoculum from some environmental source, a local
aberration in the nasal cavity (e.g. coexistent viral respiratory tract disease) and perhaps an inherent
susceptibility to fungal organisms or infectious agents that behave as intracellular pathogens (e.g. due
to a particular MHC makeup).
The anatomic site of primary infection is the key to understanding symptomatology in the feline
cryptococcosis patient. Infection starts in the nasal cavity, and takes the form of invasive
granulomatous rhinitis. This is very different to the situation in the dog afflicted with
erosive/destructive aspergillosis, in which there is atrophy of turbinate structures due to ischaemic
necrosis secondary to vascular invasion. In cats with granulomatous rhinitis, there is inflammation and
swelling of the nasal mucosa, and invasion of overlying bony structures resulting in spread of infection
to adjacent sites such as the nasal planum, bridge of the nose and hard palate. The infection can also
extend to the nasopharynx, as either a cryptococcal granuloma or a cryptococcoma (tumour-like
aggregation of organisms without much host tissue). The most worrying sequellae of cryptococcal
rhinitis is when the infection breaches the cribriform plate to involve the meninges and central nervous
system. This results in infection of the olfactory bulbs, from where spread to the nearby optic nerves
resulting in cryptococcal optic neuritis, with bilaterally dilated pupils that respond poorly to light, and
sometimes retinitis also. Brain infection can also develop haematogenously, resulting in either
meningitis or mass lesions within the substance of the brain. Such lesions can resemble tumours
grossly and using advanced imaging, and indeed they are sometimes surgically resected on this
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basis, the diagnosis being made histologically.
Studies in the arboreal Australian marsupial, the koala, which lives in intimate association with
eucalypts, strongly suggest that colonisation of mucus in the nasal cavity and contiguous sinuses
represent the critical first step in the development of infection. In areas with a high environmental
presence of cryptococcal organisms, colonisation is common, as is asymptomatic subclinical
infection. However, progression to symptomatic disease only occurs in only a very small proportion of
animals, and there is sometimes an apparent predisposing cause, such as the stress of transportation
and translocation to an unfamiliar environment. Considerations such as this are likely to be applicable
also to the cat and human beings. Serological evidence suggests asymptomatic infections of humans
is common, resulting in small residual cryptococcal lesions in the hilar lymph nodes or subpleural
space, that may reactivate many years later as a result of immunosupression, akin to the
recrudescence of tuberculosis from a walled off pulmonary tubercle. The Canadian research team
studying cryptococcosis in the Vancouver outbreak have used similar methods to the ones we
developed for studying disease in koalas in Australia, and confirmed the importance of colonisation
and subclinical infection in cats exposed to a high environmental presence of Cryptococcus gattii.
These studies have been of great interest to cryptococcologists interested in the development of
human disease.
Over the last 20 years basic scientists have developed a deeper understanding of the organisms
which comprise the C neoformans complex, and much is known about their genome, virulence factors
(capsule, laccase, urease and phospholipase enzymes, ability to grow at mammalian body
temperature, etc). Studies of the organism in vitro, its epidemiology in different regions and races, and
especially molecular biology have given us a richer appreciation of how and why disease occurs. For
example, there appears to be a clear association between eucalyptus trees and C gattii strains of the
VGI molecular biotype. Such strains account for about 20% of feline cases encountered along the
east coast of Australia, where eucalyptus trees are common. C gattii is likely to be much less
important in Europe, except for certain parts of Greece and Spain.
The imagination of scientists, veterinarians and human infectious disease physicians has been
captured by a marked increase in the number of cryptococcosis cases in animal and humans on
Vancouver Island since about 1998 (313 animal cases between 2003 and 2006). It is of great interest
that virtually all of these new cases are attributable to the molecular type VGIIa. This outbreak shows
no sign of abating, indeed it appears to be spreading geographically, with more and more animals
become affected (Figure 1). Importantly, the epidemiology of disease has many unique features.
Whereas cryptococcosis is normally 6 times more common in cats than dogs, in the Vancouver Island
outbreak, both species appear equally affected. Furthermore, unusual species such as horses, ferrets
and marine mammals consistently appear on the list of new cases. The situation on Vancouver Island
is in marked contrast to the usual situation for cryptococcosis, which is usually considered to be a
sporadic infection. Only on very rare occasion has cryptococcosis been associated with outbreaks in
which several animals have been diagnosed simultaneously with symptomatic disease. The notable
exceptions have been outbreaks of cryptococcosis in goats in Spain, sheep in Western Australia and
small primates in a Washington zoo. It is noteworthy that all epizootics in which appropriate strains
been examined have been referable to C gattii infections.
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Crypto Dec2003-april 2006, total 313
march apr
Figure 1. Cryptococcosis cases diagnosed by the largest veterinary pathology laboratory in
British Columbia during 2005/2006. Data kindly supplied by Dr Sally Lester.
The Vancouver Island outbreak has focussed our attention on the molecular types of C gattii which
we have encountered in Australian cats over the last 18 years. Cats are of great value as a sentinel
species in this regard, as unlike human patients, they rarely travel far from their usual place of
domicile. Although VGII infections are rare in cats, we have at least 5 well documented cases from
New South Wales, and interestingly these strains show some evidence of sexual recombination when
studied using techniques of population genetics. In particular, one strain (McBride) from a Birman cat
with cryptococcal rhinitis has proved to be especially interesting, as it is a fertile VGIIa strain of
striking virulence in murine models. A reappraisal of all veterinary cases from south east Western
Australia has demonstrated that the VGII biotype is common there, having been recovered from cats,
dogs, horses, sheep and koalas with cryptococcosis. This is of great interest, and we are actively
pursuing this fascinating clue to the global epidemiology of cryptococcosis.
Clinical findings
Cryptococcosis is the most common of the systemic mycoses of cats worldwide. There is no gender
predisposition and the age range of affected cats is broad, although young adult cats (two to three
years old) appear at increased risk. It is likely that exposure and self-limiting infection occur in the first
few years of life, with disease in older cats reflecting reactivation of viable cryptococci in residual
granulomatous foci likely in the sinonasal region.
Upper respiratory tract signs are most common and include sneezing, snuffling and mucopurulent,
serous or haemorrhagic, unilateral or bilateral, nasal discharge. Signs are usually chronic and in some
cases, a polyp-like mass is evident in the nostril. In others, a firm to fluctuant subcutaneous swelling
over the bridge of the nose is present. Cats with nasopharyngeal cryptococcosis develop stertor,
inspiratory dyspnoea, a tendency to open-mouth breathing and sometimes secondary otitis media.
Often mandibular lymphadenomegaly is evident and ulcerated or proliferative lesions in the oral cavity
are seen occasionally. Sometimes there is erosion of the palatine bone, with involvement of the hard
palate. Lower respiratory tract signs are rare in cats, although occasionally one can see
bronchopneumonia, with small nodular densities in the lung fields, sometimes with cryptococcal
Neurological signs associated with cryptococcosis are variable and include depression, changes in
temperament, bizarre behaviour, seizures, circling, head pressing, ataxia, paresis, paraplegia, head
tilt and other vestibular signs, anosmia and blindness. These signs may occur alone or in association
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ESFM Feline Congress 2006
with other physical findings and may result from the presence of mass-like cryptococcoma(s) or from
meningoencephomyelitis. In people, cerebral cryptococcosis is often associated with increased
intracranial pressure and the same is likely also in cats.
Ocular abnormalities occur in some affected cats and almost always are a marker for central nervous
system (CNS) involvement. The most common sign is peripheral blindness with dilated, unresponsive
pupils due to optic neuritis, exudative retinal detachment and granulomatous chorioretinitis.
Cryptococcal uveitis can occur but is exceedingly rare.
Cutaneous lesions are common in cats with cryptococcosis, principally due to secondary involvement
of the planum nasale. Very rarely, localized cutaneous cryptococcosis can develop following
inoculation of a large dose of infectious propagules e.g. after a cat scratch. Multifocal skin lesions
occur rarely in cats as a result of haematogenous dissemination and consist of papules and nodules
that are fluctuant to firm and range from 1 to 25 mm in diameter. Larger lesions tend to ulcerate,
leaving a raw surface with a serous exudate. Cats with disseminated disease also may have
enlargement of one or more lymph nodes, with cryptococci evident in aspirates from affected nodes.
Fever is uncommon in affected cats. Cryptococcosis in cats is typically a chronic infection, causing
listlessness and weight loss due to poor appetite. Other reported signs include peripheral
lymphadenomegaly (unassociated with skin lesions), bone lysis, swollen digits, chronic cough, and
renal failure due to kidney involvement.
A lesion associated with cryptococcosis can vary from a gelatinous mass, consisting almost
exclusively of organisms, to a well-ordered cell-mediated immune response resulting in granuloma
formation. The gelatinous appearance is a reflection of the large amount of capsular polysaccharide
material present in lesions. The primary cellular response is composed of macrophages and giant
cells, with a few plasma cells and lymphocytes. Generally, the presence of a granulomatous response
reflects an immune-competent host, whereas little or absent response suggests immunodeficiency.
An exception is the centre of large lesions, where even in normal hosts there is often limited or absent
response to organisms.
In cats that die or are euthanased, granulomatous rhinitis is usually evident, and in rare instances the
lungs are affected also. Cerebral cryptococcosis consists of either primary meningoencephalitis or a
cerebral granuloma(s). Optic neuritis is a common in cats that die of cerebral cryptococcosis, and in
some cats the olfactory bulbs are replaced by a gelatinous mass of yeast cells. Other affected organs
are skin and subcutaneous tissues, kidneys and lymph nodes that drain infected areas. Renal
granulomas have been found in some cases (and result in the presence of cryptococci in urine
sediment) with disseminated disease, as have lesions in the spleen, adrenal glands, thyroid glands
and liver.
The prognosis for most cats with cryptococcosis is good to excellent, given diligent co-operative
owners prepared to dose patients for many months and pay for the costs of medication and
monitoring. Animals with long-standing extensive disease have a less favourable prognosis than
patients diagnosed early with mild signs of disease, although even long-standing severe cases can be
cured. Patients with neurological signs always have a guarded prognosis, although many (perhaps
two out of three) can be treated successfully using combination therapy including amphotericin B.
Two additional considerations apply to patients with cryptococcal meningoencephalitis. Firstly,
neurologic status often deteriorates soon after starting therapy, presumably because death of
cryptococci and the resulting inflammation give rise to a dangerous increase in intracranial pressure.
Secondly, neurologic deficits (such as blindness and gait abnormalities) may or may not persist
following successful therapy.
Cats in which a positive FeLV status is confirmed on two consecutive occasions have a poor longterm outlook and drug therapy for cryptococcosis in these cases should be considered palliative. In
contrast, many FIV-positive cats can be cured, although some need a prolonged course of treatment,
and recurrence or the development of other clinical problems remain possible.
One of the reasons for renewed veterinary interest in cryptococcosis was the availability of a new
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ESFM Feline Congress 2006
generation of triazole antifungal drugs (fluconazole, itraconazole, voriconazole, posaconazole)
suitable for long term oral administration and the development of new ways to use the old drug
amphotericin B more easily and safely. Indeed, the main problem in treating cryptococcosis cases is
currently the high cost of therapy, the requirement for continued hospital visits and medication of pets
on a regular basis for a protracted period. The anticipated reduction in cost of fluconazole when
generic formulations appear on the market will greatly reduce the cost of treatment, and thereby
improve the overall prognosis in feline patients.
Selected References
1. Malik, R., Wigney, D.I., Muir, D.B., Gregory, D.J. & Love, D.N. (1992) Cryptococcosis in cats:
clinical and mycological assessment of 29 cases and evaluation of treatment using orally
administered fluconazole. Journal of Medical & Veterinary Mycology 30: 133-144.
2. Malik, R., Medeiros, C., Wigney, D.I. & Love, D.N. (1996) Suspected drug eruption in seven
dogs during administration of flucytosine. Australian Veterinary Journal 74: 285-288.
3. Malik, R., Dill-Macky, E., Martin, P., Wigney, D.I., Muir, D. & Love, D.N. Cryptococcosis in
dogs: A retrospective study of 20 consecutive cases (1995) Journal of Medical & Veterinary
Mycology 33: 291-297.
4. Malik, R., Craig, A.J., Martin, P. Wigney, D.I. & Love, D.N. (1996) Combination chemotherapy
of cryptococcosis using subcutaneously administered amphotericin B. Australian Veterinary
Journal 73: 124-128.
5. Malik, R., McPetrie, R., Wigney, D.I., & Love, D.N. (1996) Use of the cryptococcal latex
agglutination antigen test for diagnosis and monitoring of therapy in veterinary patients with
cryptococcosis. Australian Veterinary Journal 74: 358-364.
6. Malik, R., Wigney, D.I., Muir, D. & Love, D.N. (1997) Asymptomatic carriage of Cryptococcous
neoformans in the nasal cavity of dogs and cats. Journal of Medical & Veterinary Mycology
35: 27-31.
7. Malik, R., Martin, P., Wigney, D.I., Church, D.B., Bradley, W., Bellenger, C.R., Lamb, W.A.,
Barrs, V.R., Foster, S., Hemsley, S., Canfield, P.J. & Love, D.N. (1997) Nasopharyngeal
cryptococcosis. Australian Veterinary Journal 75: 483-488.
8. Malik, R., Hunt, G.B., Bellenger, C.R., Allan, G.S., Martin, P., Canfield, P.J. & Love, D.N.
(1999) Intra-abdominal cryptococcosis in two dogs. Journal of Small Animal Practice 40: 387391.
9. Foster, S.F. Parker, G., Churcher, R.M. & Malik, R. (2001) Intracranial cryptococcal
granuloma in a cat. Journal of Feline Medicine & Surgery 3: 39-44.
10. Krockenberger, M.B., Canfield, P.J., Kozel, T.R., Shinoda T., Ikeda, R., Wigney, D.I., Martin,
P., Barnes, K. & Malik, R. (2001) An immunohistochemical method that differentiates
Cryptococcus neoformans varieties and serotypes in formalin-fixed paraffin-embedded
tissues. Medical Mycology 39: 523-533
11. Krockenberger, M.B., Canfield, P.J., Barnes J., Vogelnest L., Connolly, J., Ley, C. & Malik, R.
(2002) Cryptococcus neoformans variety gattii in the koala (Phascolarctos cinereus):
Serological evidence for subclinical cryptococcosis. Medical Mycology 40: 273-282.
12. Krockenberger, M.B., Canfield, P.J., Malik, R. (2003) Cryptococcus neoformans var gattii in
the koala (Phascolarctos cinereus): a review of 43 cases of cryptococcosis. Medical Mycology
41: 225-234.
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13. Malik, R., Alderton, B., France, M.P., Krockenberger, M.B., Martin, P., McGill, J., & Love, D.N.
(2002) Cryptococcosis in ferrets: a wide spectrum of clinical disease. Australian Veterinary
Journal 80: 749-755.
14. Malik, R., Krockenberger, M.B., Cross, G., Doneley, R., Madill, D.N., Black, D., McWhirter, P.,
Rozenwax, A., Alley, M., & Love, D.N. (2003) Avian cryptococcosis. Medical Mycology 41:
15. O’Brien, C.R., Krockenberger M.B., Wigney, D.I., Martin, P., Malik, R. (2004) A retrospective
study of feline and canine cryptococcosis in Australia from 1981 to 2001: 195 cases. Medical
Mycology 42: 449-460.
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Clinical assessment of congenital heart disease in cats
Claudio Bussadori MD, DVM, Dipl. ECVIM (Cardiology)
Clinica Veterinaria Gran Sasso Milano Italy
As for many other diseases, even for congenital heart disease, cats reveal substantial differences
regarding epidemiology, clinical manifestation and survival when compared with dogs.
A review of the existing literature shows differences in epidemiology, probably due to the different
diffusion of various breeds among countries where epidemiological studies were conducted.
The feline practitioner should be prepared to recognise all those cardiac malformation through their
clinical signs, radiographic and ecocardiographic pattern. For some complicated CHD it is at least
necessary to be able to suspect the diseases in order to refer the cat to a Veterinary cardiologist.
Furthermore the practitioner should be updated on the inheritance of any of these specific diseases,
chance of treatment and life expectancy.
In the last 10 years of our case-log, cats affected by congenital heart diseases represent almost 10%
of the total amount of cats referred for cardiac consultation. In our experience disease prevalence in
cats was different from that encountered in dogs, as previously stated by other authors.
CHD on 600 cats referred for cardiac consultation (1996-2006)
Ventricular Septal Defect (VSD)
Diaphragmatic Peritoneal Pericardial Hernia (DPPE)
Subaortic Stenosis (SAS)
AV-canal defects
Aortic Bicuspidia (AI)
Cor Triatiatum Sinister (CTS)
Tricuspid Displasia (TD)
Primary Pulmonary Hypertension
Dual Chamber Right Ventricle (DCRV)
Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC)
Patent Ductus Arteriosus (PDA)
Atrial Septal Defect (ASD)
Mitral Dysplasia (MD)
Pulmonic Stenosis (PS)
Tetralogy of Fallot (ToF)
Mid ventricular obstruction
Mitral Stenosis
Total cases of CHD
The congenital heart disease we observe more frequently is isolated Ventricular Septal Defect
The main classification of ventricular septal defect considers the anatomical location of the defect: the
first subdivision is between membranous and muscular portion. Furthermore Muscular VSD may be
distinguished in Inflow VSD, outflow VSD and of the internal muscular septum which corresponds to
endocardial cushions.
Muscular ventricular septal defect in cats is rarely observed alone, more frequently this location of
VSD is associated with other malformations like pulmonic stenosis or as a part of complex CHD like
ToF or endocardial cushions defect. It is also common to identify muscular VSD in association with
diaphragmatic peritoneal pericardial hernia or to Hypertrophic cardiomyopathy.
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The most common type of VSD is the perimembranous one, located below the non coronary cusp on
the left side and immediately below the septal tricuspid leaflet. Several classifications based on the
dimensions of the defect or quantity of shunt flow, or transventricular gradient can be adopted and
used to formulate a correct prognosis and therapy.
Based on 2D echo measurement, VSD can be considered
Small (VSD diameter smaller than 1/3 of Aortic annular diameter)
Medium (VSD diameter from 1/2 to 3/4 of Aortic annular diameter)
Large (VSD diameter equal or larger than Aortic annular diameter)
Measuring by echo Doppler cardiac output through aorta and pulmonary artery it is possible to
estimate the amount of flow that crosses the shunt (Qs/Qs ratio).
Small VSD are considered restrictive in case of Qp/Qs < 1, 4: in this case the pathophysiologic
consequences are very mild, the left ventricular volume overload is very mild and generally the
pressure inside the right ventricle and pulmonary circulation does not increase. The pressure gradient
between the two ventricles is about 80 mmHg; this value can be extrapolated measuring the velocity
of the flow through the defect by continuous wave Doppler.
In medium VSD Qp/Qs values are in the range between 1,4 to 2,2; those defects have different
clinical manifestations and diagnostic patterns depending on left ventricular volume overload and the
reaction of pulmonary vasculature. Medium VSD can be considered functionally small-medium when
only a mild left ventricular volume overload is evident at radiography and cardiac ultrasound,
functionally medium-large in case of evidence of severe volume overload and when RV systolic
pressure starts to rise up to 50% of LV pressure. In Large VSD, Qp/Qs is higher than 2,3: in those
VSD the defect do not offer any resistance to the shunt, severe LV volume overload and pulmonary
oedema are observed, even in puppies most frequently in cats we may observe Eisenmenger
physiology. In this condition during the first months of life the pulmonary arteries react to the volume
overload developing an obstructive microvascular pulmonary disease that results in a severe
pulmonary hypertension and shunt inversion.
Clinical findings
Intensity of the murmur is inversely proportional to the dimension of the VSD, in a restrictive VSD is
loud, harsh and typically best heard on the right cranial thorax. Murmur intensity and duration are
reduced in largest VSD and in case of pulmonary hypertension. In some cases of Eisenmenger
physiology the murmur may disappear but in others we have heard a systolic ejective murmur on the
right side of the thorax due to tricuspid regirgitation. Cats with restrictive VSD frequently have no
clinical signs other than murmur. In case of pulmonary hypertension, it may be possible to observe
jugular distension and pulsation, hepatomegaly and, if reversion of the shunt occurs, cyanosis and
EKG findings follow the change of heart dimensions, tall R-waves in case of left ventricular
enlargement and right axis in case of pulmonary hypertension. For those evaluations EKG has a very
low sensitivity if compared to radiology and cardiac ultrasound.
The first radiographic change that should be looked for is pulmonary overcirculation with augmented
dimension of pulmonary arteries and veins; rarely we observe pulmonary congestion and left
ventricular enlargement, in case of pulmonary hypertension the lung field start to become more
radiopaque and pulmonary arteries become more large and tortuous and the right ventricle becomes
Echocardiographic findings
Perimembranous VSD may be well identified on the right parasternal long axis just below the non
coronary cusp of the aorta; from this view it is possible to measure the VSD correctly and estimate the
pressure gradient between the two ventricles measuring the peak velocity of the shunt flow. The
presence of the defect can be very well confirmed on short axis and on the left apical 4 chambers
view. By echocardiography it is also possible to identify all signs of pulmonary hypertension and
quantify it with high sensitivity and specificity.
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Natural History and Treatment
Almost all cats with restrictive VSD live all their lives without any problems and in several cases we
have observed after 3-4 years of age a spontaneous closure of the defect by proliferation of
endocardial tissue close to tricuspid valve, that creates an occlusive sac on the right side of the defect
called “pseudoaneurysm”.
In case of medium or large defects, the decision regarding treatment is determined by the prevalence
of left ventricular volume overload or pulmonary hypertension. In the first case Furosemide 0.5 to 2
mg/Kg BID and ACEI 0.5 mg/kg SID is the first choice treatment.
In the second case surgical pulmonary banding must be considered only when PHT is in the early
stage and still reversible.
AV canal defect called also endocardial cushion defects is a complex cardiac malformation. To
understand this disease it is necessary to have a basic knowledge of the development of that area of
the heart during the foetal growth. Inside the original ventricular bulb and the atrium exists an AV
canal, the mesodermal area of this AV canal proliferate creating a circular rim folding at the centre.
This tissue compose the endocardial cushions which, growing up, divide the right and the left part of
the atrioventricular orifice and create the septum primum.
The incomplete formation of endocardial cushions determine the AV canal defect; this includes
several malformations caused by varying degrees of incomplete development of the inferior portion of
the atrial septum (ASD), the inflow portion of the ventricular septum (VSD) and the AV valves.
The clinical findings are variable depending on the severity of the malformations. A murmur of mitral
regurgitation is the most common finding. There is often growth retardation. In severe cases young
cats may arrive at our observation with cardiac failure symptoms or with sign of pulmonary
This large defect may interfere with the anatomy of the conduction tissue and we may observe some
Right Bundle branch Block and first degree AV block.
On X-ray we may observe a generalized cardiomegaly prevalent for right atrium and ventricle,
evidence of overcirculation and signs of left-sided CHF pulmonary edema, pleural effusion. The
combination of right side dilatation and overcirculation is not common in other CHD and when
observed must be considered strongly suggestive for endocardial cushions defect.
Cor triatriatum sinister is a well-described congenital abnormality rarely seen in the canine
population but which is more frequent in cats. In classical cor triatriatum sinister, a common
pulmonary venous chamber (the proximal or posterior superior chamber) is separated from the true
left atrium (the distal or anterior inferior chamber, containing the left atrial appendage and the mitral
orifice) by a fibromuscular membrane. Communications between the proximal and distal chambers
consist of one or more fenestrations or holes in the intervening membrane, the total size of which
determines the resulting physiology and clinical presentation. Some cats do not reveal any clinical
symptoms for a long time, in case of very stenotic membrane the clinical major pattern is pulmonary
oedema; furthermore the slowed velocity of the flow in the proximal chamber may become one of the
cause of thrombus formation, a very dangerous complication. The definitive diagnosis even for this
malformation is done by echocardiography; it is also possible to evaluate the severity of
hemodynamic consequences by Doppler.
Isolated Pulmonic Stenosis is rare in cats and its anatomical pattern resemble type A pulmonic
stenosis frequently observed in dogs with valvular leaflet fusion, systolic doming and post stenotic
dilatation of the main pulmonary artery and right ventricular hypertrophy; those signs are evident both
at echo and chest X-ray. Even this congenital heart disease in cats is better tolerated than in dogs,
most of the cats with severe pulmonic stenosis survive well without developing right heart failure or
effort syncope.
A challenging for cardiology specialist is the differential diagnosis between PS and Dual Chamber
Right Ventricle. In this malformation the murmur is exactly the same of the PS murmur, loud, harsh
and ejective and located on the left base. On radiograph it easy to note RV enlargement in both
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diseases but main pulmonary artery dilatation which is common in many cases of pulmonary stenosis
can’t be observed in DCRV. The definitive diagnostic of DCRV can be done only by 2D
echocardiography the area around the trabecola marginalis which correspond at the border between
the inflow and the outflow part of the right ventricle in that area it is possible to identify a trasversal
muscular wall perpendicular to the tricuspid plane that divides the two chamber that usually
communicate through a fibrous tunnel that create an intraventricular gradient with an high pressure
chamber (inflow) and a low pressure chamber (outflow).
Tricuspid dysplasia (TD) is a complex malformation of the right AV apparatus with various degree of
thickening of the valve leaflets, abnormally short or long chordae tendineae, abnormal papillary
muscles and abnormally low implanted atrioventricular valves, if this last condition is evident and it
determines a reduction of dimension of the RV inflow chamber and “atrialization” of proximal part of
the RV we can describe the anomaly as “Ebstein disease”.
The murmur of TD is a systolic plateau murmur and is determined by tricuspid regurgitation. In cases
of severe TD the regurgitant flow might become laminar and no murmur will be audible. Signs of rightsided congestive heart failure are the clinical presentation of severe cases. Ascites is less common in
cats with right side congestive heart failure than in dogs.
At the thoracic radiography we may observe right atrial enlargement, widened caudal vena cava,
hepatomegaly, pleural effusion, in some cases of very severe right atrial dilatation the trachea may
appear displaced dorsally just by this dilatation.
By echocardiography it is possible to quantify the RV and RA dilatation and evaluate the downward
displacement of the tricuspid annulus. Colour flow and Pulsed wave Doppler is useful to asses the
quantity of regurgitant flow.
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Refractory ulcers on the nasal bridge of a young cat
An exercise in Diagnostic Reasoning
Professor Richard Malik DVSc PhD FACVSc FASM
Post Graduate Foundation in Veterinary Science, Conference Centre, Building B22,
University of Sydney, NSW 2006 Australia
Presenting complaint and history: An eight-month-old castrated male domestic crossbred cat is
presented for multiple non-healing ulcers on the bridge of its nose.
Physical findings: The lesions do not appear to be pruritic. There are no lesions like this on the
nasal planum or one the digital pads. There is no suppuration from the lesions. There are no current
signs of nasal cavity disease such as sneezing or nasal discharge. The cat is constitutionally well.
The lesions did not respond to a four week course of cephalexin, and have persisted while the cat has
been boarding in the clinic for seven days.
What is your assessment?
How would you investigate this case further?
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Background concepts to be explored
When we trained up as clinicians in Vet School, the major focus was on giving us an overview of the
many disease conditions that can affect the different body systems in disparate animal species. This
was underpinned by “Problem-orientated medicine”, a conceptual approach which was has been
well accepted in veterinary medicine since the 1970s, and is taught in most veterinary colleges in
North America and Australia.
In problem-orientated medicine, presenting complaints, clinical signs, abnormal laboratory test results,
information from imaging modalities and so forth can all be entered as “Problems” in a Problem List.
This Problem List forms the cornerstone of the patient’s medical record. These problems are
then resolved, if possible, into a smaller number of entities which reflect the key underlying disease
processes giving rise to the patient’s symptoms. The advantage of this approach is that it can be
applied to any disease, simple or complex, and it works (or should work) even for disease conditions
that the clinician has never seen before, or not even heard about! The trouble with this system is that
it is cumbersome, tedious for simple cases, and not well suited to the majority of software systems
used in veterinary practice. It is VERY USEFUL, however, in developing a conceptual framework to
explain logic pertaining to diagnostic reasoning to undergraduates, and it should form the cornerstone
for clinical decision making when combined with information from textbooks and electronic data
Sherlock Holmes - a great
believer in Problem based
analysis. Dr Watson can be
seen suffering from passive
smoking on the right.
Experienced clinicians, if they are honest, will admit that much of the time they can recognise the
cause of many patients’ problems by recognizing a characteristic pattern of historical clues and
clinical signs. Such “pattern recognition” is traditionally frowned upon, especially by academic
clinicians. This is counterintuitive, as in my experience the best academic internists have the most
sophisticated pattern recognition skills! The reason why this intuitive style of diagnostic
reasoning is so disdained is that it can let you down, sometimes in a spectacular fashion. In
particular, some patients do not have the classic pattern, and other patients with “a classic pattern”
can have a completely different disease, or a concurrent significant other problem. (Indeed, the
presence of multiple concurrent diseases is a real problem when dealing with complex cases,
especially when preliminary treatments have been given by other veterinarians.) This is why medicine
is so tricky. Unfortunately this has resulted in ‘throwing out the baby with the bathwater’, because an
intuitive, thoughtful clinician can harness both pattern recognition AND analytic diagnostic
reasoning to sort out challenging internal medicine cases.
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This cat has stiffness and
unyielding rigidity of ONE
thoracic limb. The cat is
otherwise well. There may
be clues in the history that
HELP establish the
A further critical component of diagnostic reasoning relates to probability theory, or if you will, a “form
guide approach” to diagnosis. This can be summed up by the expression “common things occur
commonly”. Thus, when confronted by a characteristic combination of clinical findings, or an anatomic
diagnosis, then based on chance certain diseases are much likely to be encountered than
others. For example, it is possible to say that of the many potential causes of polydipsia/polyuria in
dogs, most patients in a general practice setting will have diabetes mellitus, hyperadrenocorticism or
renal insufficiency (The exact order may vary from country to country, or region to region). Other
diseases, such as diabetes insipidus are much less likely to be encountered.
This cat has multifocal
lesions on the nasal bridge
region. They have failed to
response to antibiotics and
The trouble with “pattern recognition” and “probability” is that you must either have a lot of experience,
or do a lot of rote learning, to make these diagnostic considerations work for you. Local knowledge
and a lot of astute clinical experience can be very helpful in this setting, which is unhelpful for new
graduates or locums, and sometimes a good veterinary nurse with long corporate history can be
helpful! Another important theme is that the patterns can be COMPLETELY DIFFERENT in different
species; for small animal clinicians this is of key importance because diseases in cats and dogs
present in different ways, and occur with different frequencies. Hence the expression, “cats are not
small dogs”. This is less of a problem for people that are less reliant on a problem-based approach.
Another thing that almost no-one talks about is that certain individual veterinarians are intuitive
clinicians. Probably such individuals would have made good medicos, or indeed good criminal
investigators, as there is without doubt an art as well as a science in diagnostic medicine. I have no
doubt Robert Goren would have made at outstanding veterinary internist, as he would be have been a
sophisticated exponent of pattern recognition, problem orientated medicine and also clinical intuition.
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ESFM Feline Congress 2006
Robert Goren – a GREAT
exponent of Problem-based
medicine and pattern
Can YOU be a vetective??
This talk will flesh out some of these issues by proving that WE ALL USE A COMBINATION of
problem solving, pattern recognition and probability to work out what is wrong with our patients.
Importantly, I will try to convince you there is nothing wrong with developing YOUR OWN clinical style,
which takes into account (i) the way you learn, (ii) the way you think and (iii) whether or not you have
a certain type of retentive memory, or not, and whether you have reliable clinical intuition.
I will also try to demonstrate that there are many patterns; including imaging patterns (e.g. air
bronchogram, alveolar pattern), dermatological patterns (‘cutaneous reaction patterns’), hematological
patterns (e.g. stress response), clinical chemistry patterns (e.g. high ALT with hyperthyroidism,
increased ALP without jaundice in Cushing’s disease), cytological patterns (e.g. capsulated yeast with
narrow necked budding with cryptococcosis) – and that there is nothing wrong with using all of them.
For example, we are all comfortable that the combination of dysuria, haematuria, pollakiuria and
stranguria are together suggestive of lower urinary tract disease; once we have make this connection,
it is easy to sort out the specific diagnosis (infection, stones, neoplasia, etc). Likewise, we are
comfortable about recognizing clinical syndromes. For some reason this has never been frowned
upon. Clinical syndromes are really just patterns, e.g. Horner’s syndrome (ptosis, meiosis, third eyelid
prolapse) is a sophisticated pattern that tells us something is interfering with sympathetic innervation
of the eyeball; we then just need to remember the corresponding anatomic pathway to work out the
complete differential diagnosis (T1-T3 spinal cord disease, brachial plexus disease, cervical disease
and middle ear disease). The presence of Horner’s syndrome and concurrent ipsilateral facial nerve
paralysis is an even more complex pattern, and strongly suggestive of middle era disease. But you
still need diagnostics to work out whether the problem is an infectious, polypoid or neoplastic in origin.
This dog presented for masticatory muscle
atrophy, absence of blink reflex (ipsilateral)
but normal menace reflex and dazzle
What is your pattern recognition
What is your problem-based diagnosis?
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The importance of using ALL TECHNIQUES will be emphasized in the accompanying presentation.
Many clinical examples will be used. This will include some common and well recognised patterns,
some more arcane patterns, and also cases where pattern recognition must be tempered by a
problem orientated approach.
Differential diagnosis of diseases affecting the nasal
bridge of cats
Infections affecting the skin and subcutis of the naso-ocular region are seen from time to time in feline
practice. We have investigated in excess of 20 of these cases since 1987 and the likely pathogenesis
of these infections has become apparent over the years. The key finding is that infections affecting
this anatomic region develop through two different mechanisms.
Cases with infection of the naso-ocular region but without concurrent nasal signs
These cases likely result from contaminated cat-scratch injuries. Presumably the claw(s) of the feline
perpetrator are contaminated by viable, potentially-pathogenic, saprophytic organisms. These are
inoculated in such large numbers that non-specific defense mechanisms (bleeding, inflammation,
neutrophilic phagocytosis, lysozyme) of the victim are overwhelmed. This results in a localised,
variably invasive infection of an otherwise immunocompetent host. A wide range of microorganisms
can be cultured from such cases including a variety of bacteria and fungi normally residing in soil,
rotting vegetation, humus or dirt. Lesions are typically on the bridge of the nose, but they may also
occur more laterally or involve the nasal planum.
In our referral centre in eastern Australia, opportunistic pathogens isolated from such cases (a total of
7 cats between 1987 and 2003) have comprised the bacteria Corynebacterium pseudotuberculosis (1
case), Mycobacterium avium (1 case) and Nocardia nova (1 case), and the fungi Cryptococcus
neoformans (1 case), Exophiala jeanselmei (2 cases) and Paecilomyces lilacinus (1 case).
Mycobacterium avium, Exophiala jeanselmei, Alternaria species and Sporothrix schenckii have been
reported to produce similar lesions by others. Conceptually similar mycobacterial infections or mycotic
lesions can develop on the cornea following cat scratch abrasions. The biologic behaviour of these
infections depends on the virulence of the pathogen, the initial dose of organisms inoculated, the
subsequent host response, the effect of subsequent medical and surgical interventions and the
chronicity of the lesion.
Although the precise location and appearance of lesions is quite variable from case to case, the
relatively consistent anatomic distribution of lesions which will be apparent from this presentation is
strongly suggestive of a cat-scratch-aetiology. One differential diagnosis for florid disease at this
anatomic site is insect-bite hypersensitivity. However, the punctate nature of the primary lesions,
frequent concurrent involvement of the ears and toes and characteristic eosinophilic histology
distinguishes the underlying allergic basis. A further important diagnostic possibility is ulcerative
dermatitis due to feline herpesvirus type 1, which is associated with eosinophilic inflammation, mild
concurrent upper respiratory signs and in some cases characteristic viral inclusion bodies in biopsy
specimens; definitive diagnosis depends on amplification of Herpesvirus amplicons using PCR, ideally
on fresh tissue specimens. This infection may respond to topical agents used to treat cold sores in
people, or the systemic anti-herpes agent famciclovir.
The main focus of this short note is to alert clinicians to the likely pathogenesis for infections of this
anatomic region. Importantly, even though saprophytic organisms generally considered to be of low
virulence are isolated from these patients, in most cases there is no predisposing immunodeficiency
state. Thus, the infection merely reflects a breach in the integrity of normal cutaneous barriers and an
especially heavy inoculum of infectious agent. Unfortunately these infections may be difficult to cure,
as some causal strains are locally invasive and the region does not have an especially rich blood
supply or mobile skin nearby to facilitate reconstructive surgical procedures. Furthermore, many of
these saprophytic organisms demonstrate resistance to commonly used antimicrobials both in vitro
and in vivo, and this can be especially problematic for the fungal pathogens.
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ESFM Feline Congress 2006
One may speculate as to why cat scratch-related infections occur at this site rather than elsewhere.
Firstly, it is a very commonly involved site. Secondly, it is a location that cats cannot reach with their
tongue, whereas scratch wounds elsewhere may be cleansed of potentially pathogenic microbes
before an infection is established. Thirdly, the predilection area is sparsely covered by hair, so injuries
from claws may penetrate more deeply into the subcutis compared to areas afforded the protection of
a longer hair coat. Finally, growth of many saprophytic species may be favored at the lower
temperatures encountered at this anatomic prominence. It must be emphasized, however, that lesions
attributable to a similar range of pathogenic saprophytes can develop on the body wall or distal
extremities following contamination by soil or dirt of cat fight lacerations or abrasive injuries to the
pads or interdigital spaces. Likewise, contaminated penetrating wounds of the caudoventral
abdominal region often result in mycobacterial panniculitis of the inguinal fat pad.
Diagnostic work-up
Investigation of these cases typically involves obtaining representative material for cytology, histology
and appropriate culture. Cytology and histology generally show pyogenic or pyogranulomatous
inflammation and usually causal organisms can be visualised using special stains (DiffQuik, Gram,
Ziehl-Neelsen, periodic acid Schiff, silver stains). A variety of staining techniques may be required,
and in some cases an exhaustive search of smears or histologic sections is required to detect the
infectious agents. Mycobacteria, fungi and Nocardia species may sometimes be detected in DiffQuikstained smears because of a negative, rather than positive, staining reaction. The laboratory should
be warned of the possibility of a fastidious saprophytic pathogen, as these organisms often have
specific growth requirements (e.g. special culture media, reduced temperature of incubation,
requirement for high carbon dioxide concentration etc) and/or require several days or even weeks to
become detectable as visible colonies in vitro. Ideally, a small portion of the biopsy specimen should
also be frozen in case polymerase chain reaction techniques or additional culture studies are required
at a later date.
Many authorities would also recommend obtaining a minimum data base consisting of a complete
blood count, serum biochemistry profile, urinalysis and possibly tests for feline immunodeficiency
virus (FIV) and feline leukaemia virus before embarking on therapy. Concurrent metabolic problems
such as renal insufficiency or diabetes mellitus may render the cat somewhat immunodeficient, while
the presence or liver or kidney dysfunction may affect the selection of the most appropriate
antimicrobial agent(s) or limit doses that can be safely given (e.g. amphotericin B in cats with preexisting renal insufficiency). A positive FIV-status does not preclude a satisfactory response to
appropriate therapy, as it is generally impossible to discern the stage and impact of the FIV infection
until after the cat has received appropriate therapy. Indeed, in the authors’ experience, concurrent FIV
infection is most often an epiphenomenon in this cohort of patients reflecting the cats’ outdoor lifestyle
and propensity to fight.
The treatment of these cases involves long courses of carefully selected antimicrobials based on
accurate species identification, in vitro susceptibility data (ideally from a specialist reference
laboratory) and information from the human and veterinary literature available through electronic
databases. Additionally, many of these patients require complete surgical excision of grossly infected
tissues to assist the host’s non-specific immune response. Given the severity of the pathology in longstanding cases and the diffusion barriers resulting from tissue necrosis and fibroplasia, it is
understandable that adequate levels of antimicrobials may not be achieved throughout all affected
tissues. Thus, the best chance for a successful outcome for certain cats is to use an approach
reminiscent of oncologic surgery, by removing as much infected tissue as possible using en bloc
resection following preliminary antimicrobial therapy which is extended into the intra-operative period
and continued post-operatively. Residual microscopic foci of infection can then be targeted by the
high concentrations of antibiotics achieved during and after surgery.
This may be done at the outset (for convenience and to minimise the number of procedures to which
the patient must be subjected), or after a microbiological diagnosis has been made e.g. by aspiration
biopsy or resection of a small representative tissue specimen. In the latter scenario, it is possible to
ensure that effective levels of appropriate antimicrobial agents are obtained in the peri-operative
period. This may be advantageous if a major reconstructive procedure is required to remove an
extensive lesion with clear margins. In some cases, surgery alone may be effective in resolving the
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infection (e.g. Bostock et al 1982), although routine use of follow-up antimicrobials is strongly
recommended to guard against the possibility of the surgical margin being seeded with infectious
material. Generally speaking, in the absence of complete surgical excision, these infections require
treatment with long courses of antimicrobials, at least for several weeks, and typically for many
months, depending on exactly which organism is involved and how much infected tissue can be safely
resected at the outset. In some cases, combination therapy with two or more antimicrobial is superior
to monotherapy with a single agent. Infections caused by organisms capable of intracellular survival
(e.g. Mycobacteria spp, Nocardia spp) and fungi require the longest courses of therapy, and should
ideally be treated not only until the lesion appears grossly normal, but for an additional period
exceedingly the lifespan of macrophages in the tissues i.e. a further two months. Additional
information on diagnosis and treatment of representative infections of this type can be found in the
Although the vast majority of cat scratch injuries to the face heal without any untoward sequelae, the
possibility of opportunistic infections developing should be borne in mind when recommending
treatment for feline patients with cat scratch injuries seeking veterinary advice by telephone or by
consultation. Thorough cleansing of contaminated scratch wounds using saline or a dilute antiseptic
(e.g. 0.05% chorhexidine) would seem prudent, followed by instillation of an ointment containing both
antibacterial and antifungal agents (and without corticosteroids) and possibly a short course of an
antibiotic such as doxycycline monohydrate (5mg/kg twice daily for 3 to 5 days). Although it is
impossible to choose an agent with a spectrum sufficiently broad to cover all potentially-pathologic
saprophytes, doxycycline has useful activity against many saprophytic mycobacteria, some Nocardia
species, oropharyngeal organisms such as Pasteurella spp and obligate anaerobes that may have
been inoculated simultaneously via bite wounds. Additionally, it is generally well tolerated, devoid of
significant toxicity (e.g. retinotoxicity, nephrotoxicity) and available in conveniently sized tablet and
paste formulations in Australia, New Zealand and South Africa (VibraVet®; Pfizer Animal Health),
which facilitates dosing and owner compliance. The use of a formulation containing the monohydrate
salt is strongly recommended, as it is less irritant to the stomach and oesophagus than conventional
human formulations utilising the hydrochloride salt.
Cases with naso-ocular infection and concurrent signs of nasal cavity disease
These cases are not the main focus of this communication, but are included for completeness. In
these patients, the primary problem starts with infection of the nasal cavity by infectious propagules
(typically spores) of saprophytic fungi filtered by the nasal passages. This may be facilitated by a preexisting cause of nasal injury. Involvement of the naso-ocular region develops subsequent to the
infection spreading to the nasal planum or penetrating the overlying bones to reach the subcutis over
the nasal bridge. Most of these cases are attributable to cryptococcosis and in many of these patients
the nasal planum is affected prominently. We have also seen this type of disease progression with
invasive aspergillosis and rhinitis caused by the termite mycoparasite Metarhizium anisopliae. Similar
findings have also been reported in a cat with invasive bacterial rhinitis caused by an Actinomyces
These cases can be investigated either by directing attention to the primary site of infection i.e. the
nasal cavity, by cytological examination of nasal swabs or washings (e.g. for budding, capsulate
yeasts), serum cryptococcal antigen titre determinations, anterior/posterior rhinoscopy, crosssectional imaging and biopsy of affected turbinates. Alternatively, needle aspirates or incisional
biopsies can be obtained from the subcutaneous lesions and submitted for cytologic and histologic
investigations and culture. Invasive mycotic rhinosinusitis is generally treated with one or a
combination of antifungal agents administered systemically. Although monotherapy with azoles such
as itraconazole or fluconazole is convenient for owners and effective in many patients, some cases do
not respond and require amphotericin B e.g. as twice weekly subcutaneous infusions, to effect a cure.
Unusual fungal infections may sometimes be more susceptible to other classes of antifungal agent
such as terbinafine, or newer azoles such as voriconazole or posaconazole. Although topical therapy
using clotrimazole ‘soaks’ has been used by others to treat cases such as this, the authors believe
systemic therapy is preferable due to the invasive, granulomatous nature of the infection and the
propensity in cats for bony erosion (including the cribriform plate) to occur in association with these
The major differential diagnosis in these cases is invasive nasal neoplasia which can also breach the
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ESFM Feline Congress 2006
integrity of overlying nasal bones to invade the subcutaneous tissues of the nasal bridge and/or
forehead. In our practice, lymphoma is the commonest sinonasal malignancy in the cat, followed by
adenocarcinoma and osteosarcoma, whereas solar-induced squamous cell carcinoma is the most
common cancer of the nasal planum.
Further reading
1. Bostock DE, Cohoe PJ, Castellani PJ (1982) Phaeohyphomycosis caused by Exophiala
jeanselmei in a domestic cat. Journal of Comparative Pathology 92,479-482.
2. Deykin AR, Wigney DI, Smith JS, Young BD (1996) Corneal granuloma caused by
Mycobacterium intracellulare in a cat. Australian Veterinary Practitioner 26, 23-26.
3. Hargis AM, Ginn PE, Mansell JEKL, Garber RL (1999) Ulcerative facial and nasal dermatitis
and stomatitis in cats associated with feline herpesvirus 1. Veterinary Dermatology 10, 267274.
4. Hughes MS, Ball NW, Love DN, Canfield PJ, Wigney DI, Dawson D, Davis PE, Malik R
(1999) Disseminated Mycobacterium genavense infection in a FIV-positive cat. Journal of
Feline Medicine & Surgery 1, 23-29.
5. Kennis RA, Rosser EJ, Dunstan RW (1994) Difficult dermatologic diagnosis. [Sporotrichosis
in a cat]. Journal of the American Veterinary Medical Association 204, 51-52
6. Love DN, Malik R, Norris JN (2000) Bacteriological warfare amongst cats: what have we
learned about cat bite infections? Veterinary Microbiology 74, 179-193.
7. McKay JS, Cox CL, Foster AP (2001) Cutaneous alternariosis in a cat. Journal of Small
Animal Practice 42, 75-78.
8. Malik R, Gabor L, Martin P, Mitchell DH, Dawson DJ (1998) Subcutaneous granuloma caused
by Mycobacterium avium complex infection in a cat. Australian Veterinary Journal 76, 604607.
9. Malik R, Wigney DI, Dawson D, Martin P, Hunt GB, Love DN. (2000) Infection of the subcutis
and skin of cats with rapidly growing mycobacteria: a review of microbiological and clinical
findings. Journal of Feline Medicine & Surgery 2, 35-48.
10. Malik R, Martin P, Davis PE, Love DN (1996) Localised Corynebacterium pseudotuberculosis
infection in a cat. Australian Veterinary Practitioner 26, 27-3.
11. Malik R, Wigney DI, Muir DB (1994) Phaeohyphomycosis due to Exophiala jeanselmei in a
cat. Australian Veterinary Practitioner 24, 27-31.
12. Mason KV, Evans AG (1991) Mosquito bite-caused eosinophilic dermatitis in cats. Journal of
the American Veterinary Medical Association 198, 2086-2088.
13. Miller DM, Blue JL, Winston SM (1983) Keratomycosis caused by Cladosporium sp in a cat.
Journal of the American Veterinary Medical Association 182, 1121-1122.
14. Muir D, Martin P, Kendall K, Malik R. (1998) Invasive hyphomycotic rhinitis in a cat due to
Metarhizium anisopliae. Journal of Medical & Veterinary Mycology 36, 51-54.
15. Nuttal W, Woodgyer A, Butler S (1990) Phaeohyphomycosis caused by Exophiala jeanselmei
in a domestic cat. New Zealand Veterinary Journal 38:123.
16. O’Brien CR, Krockenberger MB, Wigney DI, Martin P, Malik R (2004) A retrospective study of
feline and canine cryptococcosis in Australia from 1981 to 2001: 195 cases. Medical
Mycology, in press.
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ESFM Feline Congress 2006
17. Stewart LJ, White SD, Kennedy FA, Pavletic MM (1993) Cutaneous Mycobacterium avium
infection in a cat. Veterinary Dermatology 4, 87-90.
18. Yovich JC, Read RA (1995) Nasal Actinomyces infection in a cat. Australian Veterinary
Practitioner 25,114-117.
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