Critical Updates on Canine & Feline Health

SYMPOSIUM PROCEEDINGS Critical Updates on Canine & Feline Health From 2011 NAVC and WVC Conferences Sponsored by: SYMPOSIUM PROCEEDINGS: Critical...
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SYMPOSIUM PROCEEDINGS

Critical Updates on Canine & Feline Health From 2011 NAVC and WVC Conferences

Sponsored by:

SYMPOSIUM PROCEEDINGS:

Critical Updates on Canine & Feline Health

Managing Chronic Enteropathies in Dogs

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Kenneth W. Simpson, BVM&S, PhD, DACVIM, DECVIM, College of Veterinary Medicine, Cornell University, Ithaca, New York Diagnostic and investigative approaches designed to help practitioners better manage dogs with chronic enteropathies

Update on Canine Cutaneous Adverse Reactions to Food

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Robert A. Kennis, DVM, MS, DACVD, College of Veterinary Medicine, Auburn University, Auburn, Alabama Current concepts regarding the pathogenesis, diagnosis, and management of dogs with cutaneous adverse reactions to food

Clinical and Research Experiences with Probiotics in Cats

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Michael R. Lappin, DVM, MS, DACVIM, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, Colorado Recent investigations into the beneficial effects of probiotics and the role of probiotic supplementation in cats

Rehabilitation & Nutrition in the Overweight/Osteoarthritic Dog Wendy Baltzer, DVM, PhD, DACVS, College of Veterinary Medicine, Oregon State University, Corvallis, Oregon The role of nutrition and rehabilitation in the daily management of chronically obese dogs with osteoarthritis

From 2011 NAVC/WVC Conferences

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Managing Chronic Enteropathies in Dogs Kenneth W. Simpson, BVM&S, PhD, DACVIM, DECVIM, College of Veterinary Medicine, Cornell University, Ithaca, New York

Dogs with chronic intestinal disease typically present for investigation of diarrhea, weight loss, or vomiting. Diarrhea lasting 3 weeks or longer is usually considered chronic. The initial approach to treating chronic diarrhea is based on determining

In patients with chronic diarrhea and no obvious cause, it is best to adopt a systematic approach as determined by the localization of diarrhea to the small or large bowel.

its nature and severity, along with specific or localized clinical findings. The onset of additional clinical signs often points to the underlying cause, such as: • Tenesmus and dyschezia — large bowel disease • Melena — upper gastrointestinal (GI) bleeding or ulceration • Abdominal pain — structural disorders, perforation, thrombosis • Abdominal distention, difficulty breathing, or peripheral edema — enteric protein loss. This information is integrated to determine whether the diarrhea is attributable to large bowel disease, as characterized by dyschezia, tenesmus, increased frequency of defecation, and small volume of feces with mucus and blood, or is a consequence of small intestinal disease or exocrine pancreatic insufficiency, as characterized by a large volume of diarrhea, weight loss, and

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Managing Chronic Enteropathies in Dogs

TABLE 1 possible vomiting. In patients with abdominal pain, dehydration, frequent vomiting, or localized findings (eg, abdominal mass), these problems are pursued ahead of an in-depth workup for chronic diarrhea. In patients with chronic diarrhea and no obvious cause, it is best to adopt a systematic approach as determined by the localization of diarrhea to the small or large bowel. Patients with signs of large and small bowel involvement are usually evaluated for diffuse GI disease. This presentation reviews the diagnosis and management of dogs with chronic enteropathies predominantly associated with small bowel diarrhea.

Investigation of Chronic Small Bowel Diarrhea

Initial Diagnostic Approach to Chronic Small Bowel Diarrhea Action

Steps to Take

Integrate signalment, history, and physical examination

Note breed predisposition, environment, diet, other clinical signs; localize findings

Detect endoparasites and enteric pathogens by conducting clinicopathologic testing • Detect non-GI disease

• Detect/characterize intestinal disease

Conduct diagnostic imaging • Detect non-GI disease

• Detect/characterize intestinal disease

Conduct CBC, profile, UA, ±TLI, ACTH stimulation, free T4/TSH, bile acids Rule out hypoproteinemia, hypocalcemia, hypocholesterolemia, leukopenia, leukocytosis; check for low serum cobalamin and/or folate

Radiography, ultrasound (liver, spleen, pancreas, lymph nodes, masses, effusions) Radiography, ultrasound (obstruction, intussusception, focal masses, thickening, loss of layering, hyperechoic striation)4

ACTH = adrenocorticotropic hormone; CBC = complete blood count; GI = gastrointestinal; T4 = thyroxine; TLI = trypsin-like immunoreactivity; TSH = thyroid-stimulating hormone; UA = urinalysis.

The initial diagnostic approach to patients with chronic small bowel diarrhea is summarized in Table 1. After exclusion of infectious and parasitic agents, non-GI disorders, exocrine pancreatic insufficiency, and intestinal structural abnormalities requiring surgery, the most common groups of intestinal diseases associated with chronic small bowel diarrhea are idiopathic inflammatory bowel disease (IBD), dietresponsive enteropathy, antibiotic-responsive enteropathy, and lymphangiectasia. The approach to these patients is usually determined by the severity of clinical signs (ie, frequent severe diarrhea, excessive weight loss, decreased activity or appetite), along with the presence of hypoalbuminemia or hypocobalaminemia and intestinal

Hypoalbuminemia is associated with a poor outcome in dogs with chronic enteropathy, and low serum cobalamin concentration is associated with a negative prognosis. thickening or mesenteric lymphadenopathy. In patients with these abnormalities, intestinal biopsy is required to define the cause (eg, lymphangiectasia, lymphoma) and to optimize therapy. The clinical severity of intestinal disease can be quantified by determining the clinical disease activity index (eg, attitude, activity, appetite, vomiting, stool consistency, stool frequency, weight loss).1 Measurement of serum C-reactive protein (CRP) has been shown to correlate with clinical disease activity (canine IBD activity index [CIBDAI]) and implies that severe clinical disease is accompanied by a systemic inflammatory response.1

Measurement of clinical disease activity or CRP can also serve as a baseline for determining response to treatment. Controlled studies have shown that hypoalbuminemia is associated with a poor outcome in dogs with chronic enteropathy.2,3 Serum concentrations of cobalamin and folate can be measured to determine whether supplementation is required and low serum cobalamin concentration (< 200 ng/L) is associated with a negative prognosis.3 Evaluation of hemostatic function is recommended to ascertain if hypo- or hypercoagulability has developed as a consequence of enteric protein loss. In stable patients with chronic diarrhea (ie, good attitude, appetite, mild weight loss, normal serum proteins, no intestinal thickening or lymphadenopathy), measurement of serum cobalamin and folate concentrations can help determine the need for intestinal biopsy, localize the site of intestinal disease (eg, cobalamin absorbed in the ileum), determine the need for vitamin B12 supplementation, and establish a prognosis. In stable patients with chronic diarrhea and normal cobalamin concentrations, the client can be given the option of empirical treatment trials with diet, followed by antibiotics if there is no response to diet (see section on Minimal change enteropathy). Failure to respond to empirical therapy or a worsening of disease is indication for endoscopy and intestinal biopsy. In stable patients with chronic diarrhea and subnormal serum cobalamin, I pursue endoscopic evaluation and intestinal biopsy rather than empirical treatment trials. Intestinal biopsy Intestinal biopsy samples can be acquired endoscopically or surgically. In patients without an indication for surgery (eg, intes-

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tinal masses, anatomic or structural disease, perforation), I prefer to perform diagnostic endoscopy to visually inspect the esophageal, gastric, and intestinal mucosa and to procure endoscopic biopsy samples. It is noteworthy that the endoscopic appearance of the small intestine correlates better with outcome than histopathologic appearance does.3 If there is a suspicion of ileal involvement (eg, low cobalamin, ultrasonographic evidence of disease), I perform a transcolonic ileoscopy in addition to the standard endoscopic examination. Guidelines for biopsy acquisition have recently been published.5 Operator experience and biopsy sample quality and number are of key importance in facilitating histopathologic evaluation. Surgical biopsy is usually performed if involvement of the submucosa or muscularis is suspected or when endoscopic biopsy findings do not adequately explain the clinical picture. Histopathologic evaluation The most common histopathologic diagnoses in dogs with chronic diarrhea are IBD, lymphangiectasia, and lymphoma. The most common histopathologic lesion found in the intestines of dogs involves increased cellularity of the lamina propria and is usually referred to as IBD. The extent of inflammation varies and ranges from focal to diffuse involvement of the small and large intestine. The degree of cellular accumulation is also variable and is subjectively categorized as normal, mild, moderate, or severe.

Increased numbers of lymphocytes and plasma cells, so-called lymphoplasmacytic enteritis, is the most frequently reported form of IBD. Unfortunately, the interpretation of GI histopathology varies considerably among pathologists.6 To address this problem, a working group established by the World Small Animal Veterinary Association (WSAVA) formulated a scheme to standardize the evaluation of intestinal histopathology.7 However, this scheme has poor agreement among pathologists, and clinical relevance of the pathologic criteria evaluated remains to be established.8 Intestinal infiltration with macrophages or neutrophils raises the possibility of an infectious process, and culture, special staining, and fluorescence in situ hybridization (FISH) are indicated. The presence of moderate-to-large numbers of eosinophils in intestinal biopsy samples, often accompanied by circulating eosinophilia, suggests possible parasitic infestation or dietary intolerance.

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Increased numbers of lymphocytes and plasma cells, so-called lymphoplasmacytic enteritis, is the most frequently reported form of IBD. Moderate-to-severe lymphoplasmacytic enteritis is often described in association with a protein-losing enteropathy. Predisposed breeds include the basenji, Lundehund, and shar-pei. However, whether the term lymphoplasmacytic enteritis is appropriate or has clinical relevance is a contentious issue. Dogs have similar numbers of CD3-positive T cells before and after clinical remission,9 and cats with and without signs of intestinal disease have similar numbers of lymphocytes and plasma cells.10 Recent studies indicate that changes in mucosal architectures, such as villous morphology and goblet cell mucus content, are related to the presence and severity of GI disease. These studies have used quantitative observer-independent variables (eg, inflammatory cytokines, intestinal mucus) to identify histopathologic correlates of disease. In cats with signs of GI disease, villus atrophy and fusion correlated with the severity of clinical signs and degree of proinflammatory cytokine upregulation in the duodenal mucosa.11 Architectural changes in the gastric mucosa also correlated with cytokine upregulation in dogs with lymphocytic gastritis.12 In the colon, loss of mucus and goblet cells correlates with the severity of disease in dogs with lymphoplasmacytic and granulomatous colitis13,14 and is inexplicably discounted as a criterion in the WSAVA scheme on the basis of possible changes related to sample collection.7 Dilation of lymphatics and the presence of crypt abscesses and cysts are most frequently encountered in dogs with protein-losing enteropathies and often are accompanied by lymphoplasmacytic inflammation of varying severity.15,16

Treatment Considerations Treatment is guided by the clinical severity of disease, presence or absence of hypoalbuminemia or hypocobalaminemia, and nature and severity of endoscopic and histopathologic lesions. Minimal change enteropathy Minimal change enteropathy is characterized by low clinical disease activity, serum albumin > 2 g/L, normal cobalamin, and normal intestinal histopathology. Empirical treatment. Empirical treatment for Giardia and endoparasitic infection involves fenbendazole at 50 mg/kg PO for 5 days. Dietary trial. Options for dietary trials are outlined in Table 2. A positive response suggests diet-responsive enteropathy, a term that includes both dietary allergy and intolerance. In dogs with GI signs related to diet, a clinical response is usually observed within 1 to 2 weeks after the diet was changed. If the response is good, the diet should be continued. Rechallenge with the original diet is required

Managing Chronic Enteropathies in Dogs

TABLE 2 Options for Dietary Trials to confirm that clinical signs are rehave identified polymorphisms in lated to the diet. Challenge with sininnate immunity factors TLR5 and Global modification • Switch to a different diet or different manufacturer gle dietary ingredients is necessary to NOD2 that segregate with disease define the specific components that and have shown that German Optimize assimilation are eliciting an adverse response. If shepherds have increased TLR2 • Highly digestible (usually rice based) • Fat restricted (< 15% DM) dietary trials are unsuccessful, the next and decreased TLR5 expression • Easy-to-digest fats (eg, MCT oil) step is usually an antibiotic trial. relative to healthy greyhounds.25 • Restricted fiber Antibiotic trial. The antibiotic These results suggest that genetic Antigenic modification trial can include tylosin at 10 to 15 abnormalities in sensing the en• Novel protein source mg/kg PO Q 8 H, oxytetracycline teric microbiome underlie the an• Protein hydrolysate at 20 mg/kg PO Q 8 H, or metrontibiotic responsiveness of German idazole at 10 mg/kg PO Q 12 H. A shepherds. An interaction of genetImmunomodulation • Altered fat composition (eg, omega-3 or 6, fish oil) positive response suggests antibiics and diet is supported by the • Prebiotics (eg, inulin) otic-responsive enteropathy. The finding that gluten-sensitive enpatient should be maintained on DM = dry matter; MCT = medium-chain triglyceride. teropathy in Irish setters is an autoantibiotics for 28 days, after which somal recessive trait.26 they should be discontinued. If the response is good, the vetThe intestinal microenvironment. While intestinal bacteria erinarian should consider transition to probiotics. If the reare implicated frequently as a pivotal factor in the development sponse is poor, the veterinarian should reappraise the patient of IBD in humans and animals, the specific bacterial characterrecord and findings before considering other treatment options. istics that drive the inflammatory response have remained eluChronic therapy with tylosin at a dose of 5 mg/kg PO Q 24 H sive. Advances in molecular microbiology have enabled the can be used to maintain dogs that are tylosin responsive (Westanalysis of complex bacterial communities without bacterial ermarck E. Personal communication, March 2010). culture. Culture-independent analyses of bacterial 16S rDNA libraries in humans reveal that only 30% of fecal flora appears cultivable, and there is significant variation in the flora in difInflammatory bowel disease ferent GI segments and luminal contents versus the mucosa of Treatment of any disease is ideally directed at the underlying healthy individuals.27 cause, which is problematic for IBD because its pathogenesis is unclear. Application of these techniques to boxers with granulomaIBD in humans and animals is increasingly considered a contous colitis led to identification of invasive Escherichia coli that sequence of uncontrolled intestinal inflammation in response to are similar in pathotype to adherent and invasive E coli (AIEC) a combination of elusive environmental, enteric luminal conassociated with intestinal inflammation in humans.22,28 Applistituents (principally microbial and dietary), and immunoregcation of these culture-independent techniques to humans, ulatory factors in genetically susceptible individuals. dogs, and cats has revealed that intestinal inflammation is associated with a floral shift from gram-positive Firmicutes (eg, Genetic susceptibility. In humans, genetic susceptibility is Clostridiales) to gram-negative bacteria, predominantly prolinked increasingly to defects in innate immunity exemplified teobacteria, including Enterobacteriaceae.11,28-30 by mutations in the innate immune receptor NOD2/CARD15, which in the presence of enteric microflora may lead to upregInterestingly, increased numbers of Enteobacteriaceae have ulated mucosal cytokine production, delayed bacterial clearance been found to correlate with mucosal inflammation and clinical or killing, and increased bacterial translocation, thereby prosigns in cats with signs of GI disease.11 Studies in German shep17,18 moting and perpetuating intestinal inflammation. herds with antibiotic-responsive enteropathy indicated increased prevalence of Lactobacillales relative to greyhound The predisposition of certain breeds (eg, boxer, German controls and a complex and variable dysbiosis in dogs with tyshepherd), along with clinical response to such antibiotics as losin-responsive enteroapthy.25,31 It remains to be determined enrofloxacin in boxers and tylosin or oxytetracycline in German shepherds, points to a similar interaction of host suswhether alterations in luminal bacteria of dogs with lymphoceptibility and microflora in dogs.19-22 In boxers with granulomatous colitis, lasting remission correlates with eradication of Treatment of any disease is ideally directed mucosally invasive bacteria.23 Genome-wide analysis of boxers has identified disease-associated single nucleotide polymorat the underlying cause, which is problematic phisms (SNPs) in a gene (NCF2) that is involved with killing for IBD because its pathogenesis is unclear. intracellular bacteria.24 Recent studies in German shepherds

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IBD resistant Eradication of mucosally invaplasmacytic IBD are a cause or a Dysbiosis sive E coli in boxers with granuloconsequence of the inflammation, – matous colitis is associated with but their discovery has provided X • Dietary modification clinical cure, but treatment failure new opportunities for therapeutic Genetics • Antibiotics associated with antibiotic resistintervention. • Immunosuppression X ance is increasing.14,23 The prognoDietary constituents. Growing + Inflammation evidence also supports diet as an sis for idiopathic granulomatous IBD susceptible important role in the development or neutrophilic enteropathies is of canine IBD. Irish setters deoften guarded to poor if an undervelop an enteropathy that is re- Figure 1. Genetic susceptibility, intestinal inflammation, and the lying cause is not identified. lated to ingestion of gluten, and enteric microbiome are intimately related to IBD. Therapeutic insoft-coated wheaten terriers have tervention is aimed at counteracting inflammation and dysbiosis. Lymphocyte and plasma dietary responses and positive IBD = inflammatory bowel disease. cell predominant protoplasm-staining antineutrophil cytoplasmic antibodies Studies in dogs with chronic diarrhea diagnosed as lymphoplas(pANCA).32 In controlled studies of 65 dogs with diarrhea of macytic enteritis provide reasonable evidence that various subsets of dogs will respond to treatment with diet, antibiotics, or imat least 6 weeks’ duration, 39 of 65 responded to an antigenmunosuppressive therapy (Figure 1). At present, because there is restricted diet of salmon and rice (10 days of Purina Veterino reliable means for predicting which dogs will respond to which nary Diets LA Limited Antigen Canine Formulaa ).32 A treatment, treatment consists of a series of therapeutic trials. positive response to hydrolyzed soy diet (Purina Veterinary Diets HA Hypoallergenic Canine Formula Dry) has also been Response to standardized therapy. As mentioned earlier, in observed in 59% of 27 dogs with IBD.33 In this study, marked controlled studies of 65 dogs with diarrhea of at least 6 weeks’ duration, 39 of 65 responded to dietary modification, and the perturbation of the duodenal microbiome “dysbiosis” was deremaining dogs were treated with corticosteroids (2 mg/kg Q tected in a majority of dogs with IBD, including those with 24 H for 10 days, followed by a tapering dose over 10 weeks).32 a response to diet, and was likely a dietary consequence of inflammation. The CIBDAI and histopathologic scores were similar (> 70% moderate to severe in each group) in dogs that did and did not respond to diet. Dogs that responded to diet tended to be Therapeutic Approaches for younger and have higher serum albumin than did dogs that Inflammatory Bowel Disease failed to respond to diet. Dogs that did not respond to diet The overall therapeutic approach for IBD is influenced by suspiwere treated with steroids. Interestingly, intestinal histopatholcion of a breed-related problem; severity of disease as characterized ogy did not differ in either diet-responsive or steroid-responsive by clinical signs, albumin and cobalamin concentrations, and endogs before and after treatment. doscopic appearance; type of cellular infiltrate; and presence of architectural changes, such as lymphangiectasia/crypt cysts. Prospective therapeutic protocol. The approach outlined in Prospective Protocol for Dogs with Lymphoplasmacytic Inflammatory Bowel Disease has been evaluated in 27 dogs with a Granulomatous or neutrophilic histopathologic diagnosis of IBD. In this ongoing research,33 26 Enteropathies characterized by neutrophilic or granulomatous inflammation are described infrequently in dogs. Some may be of 27 (96%) dogs responded to standardized treatment as follows: associated with bacterial infections, such as from E coli (gran• Sixteen dogs were diet responsive. ulomatous colitis in boxers), Streptococcus, Campylobacter, • Three dogs were steroid responsive. Yersinia, and Mycobacteria, or with fungal or algal (eg, Pro• Three dogs were partially responsive to a combination of food totheca) infections. Special stains (eg, Gomori-Grocott and antibiotics. methenamine-silver, periodic acid-Schiff, Gram’s, modified • Three dogs were responsive to a combination of food, Steiner) are traditional cytochemical methods used to search steroids, and antibiotics. for infectious agents in fixed tissues. FISH with probes directed • One dog was responsive to antibiotics alone. against eubacterial 16S rRNA is a more contemporary method of detecting bacteria within tissues.22 It is imperative not to imIn controlled studies of 65 dogs with munosuppress patients with granulomatous or neutrophilic infiltrates until infectious agents have been excluded. diarrhea of at least 6 weeks’ duration, a The name of this diet has been changed to Purina Veterinary Diets DRM

Dermatologic Management Canine Formula.

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39 of 65 responded to dietary modification.

Managing Chronic Enteropathies in Dogs

The positive response to dietary modification alone in 59% of patients with IBD suggests that dietary change is a good therapeutic starting point. The response to diet was 67% in 21 dogs with normal serum proteins compared with 33% in 6 dogs with low serum proteins. It is noteworthy that clinical remission in response to dietary manipulation alone was observed in 2 of 6 dogs with IBD accompanied by hypoproteinemia. An unexpected positive finding was how few dogs required treatment with corticosteroids.

Prospective Protocol for Dogs with Lymphoplasmacytic Inflammatory Bowel Disease The following therapeutic protocol is based on observations and findings in an ongoing (unpublished) study33: Mild-to-moderate disease activity, mild-to-moderate histopathology (lymphocytes and plasma cells are predominant cell type), serum albumin > 2 g/L • Empirical treatment for Giardia and helminths if not already initiated. The following treatments are usually sequential but not cumulative. • Dietary trial with a hydrolyzed soy diet for 2 weeks; if the response is good, maintain patient on diet, consider rechallenge, and define basis of dietary intolerance. • Antibiotic trial with tylosin for 2 weeks; if the response is good, maintain patient on antibiotics for 28 days and then discontinue. Maintain with tylosin at a dose of 5 mg/kg Q 24 H if there is a relapse after 28 days. Also consider transition to probiotics? • Immunosuppression with glucocorticoids (dogs < 70 lb: 2 mg/kg PO Q 24 H for 21 days, 1.5 mg/kg PO Q 24 H for 21 days, 1 mg/kg PO Q 24 H for 21 days) or azathioprine (> 70 lb: 2 mg/kg PO Q 24 H for 5 days, then 2 mg/kg PO every other day). • If there is a poor response, reappraise patient before considering escalating immunosuppression (eg, add azathioprine or substitute with cyclosporine at 5 mg/kg PO Q 24 H for 10 weeks34 if already on azathioprine). • If the response is good, first taper immunosuppression and then stop antibiotics.

Eosinophil predominant Eosinophilic enteritis is characterized by excessive accumulation of eosinophils in the lamina propria. It is speculated that it may Moderate disease activity, moderate-to-severe intestinal histopathology (atrophy, result from an immunologic reaction to parfusion, lymphocytes, and plasma cells are predominant cell type), serum albumin < 2 g/L • Empirical treatment for Giardia and helminths if not already initiated. asites or diet. The disease may also involve • Dietary modification pending biopsy result; concurrent dietary modification (eg, hydroother areas of the GI tract. lyzed soy diet), antibiotics (eg, tylosin), and immunosuppressive agents (glucocorticoids Clinical findings. The principal clinical and/or azathioprine). • If the response is poor, reappraise all findings before considering escalating immunosigns are chronic small bowel diarrhea acsuppression (eg, cyclosporine). companied by vomiting or weight loss. • Consider failure to absorb oral prednisolone and switch to injectable corticosteroids. Large bowel signs or vomiting predominate • To avoid increased fluid retention, dexamethasone may be preferable to prednisolone in patients with ascites. in some cases. Physical findings range from • Concurrent therapy with ultra-low-dose aspirin (0.5 mg/kg) and judicious use of diuretics normal to focally or diffusely thickened in(Lasix and spironolactone) are often used in patients considered at risk for thrombotestines and marked weight loss. embolic disease and in those severely distended with tense ascites, respectively. Diagnosis. A diagnosis of eosinophilic • The use of elemental diets and partial parenteral nutrition may be indicated in some dogs with severe protein-losing enteropathy. enteritis is achieved by adopting a similar • If the response is good, first taper immunosuppressive agents and then stop antibiotics. approach to that described for lymphoplasmacytic enteritis. Clinicopathologic abnormalities may include peripheral eosinophilia. Mast anthelmintics. Relapse is likely unless the underlying cause is cell neoplasms, hypoadrenocorticism, and endoparasites can profound and removed. The prognosis in cats with hyperduce a similar spectrum of clinical signs and should be ruled out. eosinophilic syndrome is poor. The degree of eosinophilia can be extreme in cats and may be associated with eosinophilic infiltrates in the spleen, liver, lymph nodes, and bone marrow. Intestinal protein loss may be Lymphangiectasia/crypt cysts encountered. Intestinal lymphangiectasia is characterized by abnormal distenHistopathology is characterized by accumulation of large tion of lymphatic vessels within the mucosa. Lymphangiectasia numbers of eosinophils in the intestinal mucosa. is a consequence of a localized or generalized lymphatic abnormality or increased portal pressure (eg, right-sided heart failure, Treatment. Prophylactic administration of an anthelmintic, caval obstruction, hepatic disease). Lymphatic abnormalities are such as fenbendazole at a dose of 50 mg/kg PO Q 24 H for 3 often associated with lipogranulomatous inflammation that is days, is warranted to treat potential visceral larval migrans, visible as small white granules on the intestinal mesentery. which has been associated with eosinophilic gastroenteritis. Tumor infiltration of lymphatics or lymph nodes can also cause Some patients may respond to antigen-restricted or protein lymphangiectasia. In some cases lymphangiography reveals a hydrolysate diets, and patients failing dietary therapy are usually generalized lymphatic abnormality. Dilation of lymphatics is asstarted on prednisolone at a dose of 2 mg/kg PO Q 24 H, sociated with exudation of protein-rich lymph into the intestine tapered over an 8-week period. and severe malabsorption of long-chain fats. Crypt cysts and Cats with hypereosinophilic syndrome often respond very abscesses may also be observed in intestinal biopsies. poorly to treatment with immunosuppressive agents, diet, and

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Key Take-Home Points • In patients with chronic diarrhea and no obvious cause, it is best to adopt a systematic approach as determined by the localization of diarrhea to the small or large bowel. • Hypoalbuminemia, hypocobalaminemia, and abnormal endoscopic appearance are associated with a poor outcome in dogs with chronic enteropathy. • Interpretation of GI histopathology varies considerably among pathologists, and clinical relevance of the pathologic criteria evaluated remains to be established. • Treatment is guided by the clinical severity of disease, presence or absence of hypoalbuminemia or hypocobalaminemia, and nature and severity of endoscopic and histopathologic lesions. • Studies in dogs with chronic signs of GI disease and a diagnosis of minimal change enteropathy or lymphoplasmacytic enteritis provide reasonable evidence that various subsets of dogs will respond to sequential treatment with diet, antibiotics, and immunosuppressive therapy. • It is imperative not to immunosuppress patients with granulomatous or neutrophilic infiltrates until infectious agents have been excluded. • In patients with hypoproteinemia associated with lymphangiectasia or crypt cysts, the response to therapy is highly variable, with some dogs staying in remission for several years and others pursuing a path toward fulminant hypoproteinemia or thromboembolic disease.

The Yorkshire terrier (10-fold relative risk), soft-coated wheaten terrier (concurrent proteinuria), and Norwegian Lundehund seem to be overrepresented, supporting a familial cause in some dogs.6,15,35 Clinical findings. Clinical findings are essentially a consequence of the intestinal loss of protein and range from weight loss to chronic diarrhea, ascites, edema, and chylothorax. Diagnosis. Lymphangiectasia usually presents as a proteinlosing enteropathy, with endoscopic appearance of white blebs on the mucosa (dilated lymphatics). Endoscopic biopsies are often adequate. Surgical biopsy should be undertaken carefully, with appropriate precautionary measures to avoid dehiscence. Treatment. The cause of lymphangiectasia is usually not determined. Treatment is supportive and symptomatic. Dietary recommendations are similar to those for other causes of

Lymphangiectasia usually presents as a protein-losing enteropathy, with endoscopic appearance of white blebs on the mucosa. small bowel diarrhea, but fat restriction may have to be more severe. Medium-chain triglyceride (MCT) oil, usually in the form of coconut oil at 0.5 to 2 mL/kg body weight per day, can be added to the diet, or a diet already containing MCT can be fed to provide a source of calories that is, in theory, easy to assimilate. Prednisolone is often necessary at a dose of 1 to 2 mg/kg PO Q 12 H and may work by decreasing lipogranulomatous in-

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flammation or concurrent mucosal inflammation. Prednisolone is tapered to the lowest effective dose once remission has been achieved. In patients with severe malabsorption, parenteral glucocorticoids may be required, and a switch to dexamethasone may be made in patients with ascites or edema. Escalation of immunosuppression (eg, by administration of 5 mg/kg cyclosporine PO Q 24 H) may be tried if the patient is unresponsive. However, patients with lymphangiectasia appear more prone to sepsis than do patients with other forms of IBD, so it is imperative not to over-immunosuppress these patients; concurrent therapy with metronidazole or tylosin is often initiated to decrease the risk for bacterial translocation through the markedly impaired gut. Aspirin at 0.5 mg/kg PO Q 24 H is frequently given to dogs with low ATIII if they are considered at risk for thromboembolism. Diuretics are used if ascites is problematic (IBD with albumin < 2 g/L). Response to therapy is variable, with some dogs staying in remission for several years and others pursuing a path toward fulminant hypoproteinemia or thromboembolic disease. The prognosis is always guarded. ■ Acknowledgments The support of The Morris Animal Foundation and Nestlé Purina in ongoing studies of inflammatory bowel disease in dogs is greatly appreciated. Disclosure: Dr. Simpson is a member of the Nestlé Purina Advisory Council.

References 1. A scoring index for disease activity in canine inflammatory bowel disease. Jergens AE, Schreiner CA, Frank DE, et al. J Vet Intern Med 7(3):291-297, 2003. 2. Canine inflammatory bowel disease: retrospective analysis of diagnosis and outcome in 80 cases (1995-2002). Craven M, Simpson JW, Ridyard AE, Chandler ML. J Small Anim Pract 45(7):336-342, 2004. 3. Chronic enteropathies in dogs: evaluation of risk factors for negative outcome. Allenspach K, Wieland B, Gröne A, Gaschen F. J Vet Intern Med 21(4):700708, 2007. 4 Comparison of ultrasonographic findings with clinical activity index (CIBDAI) and diagnosis in dogs with chronic enteropathies. Gaschen L, Kircher P, Stüssi A, et al. Vet Radiol Ultrasound 49(1):56-64, 2008. 5. Effect of sample quality on the sensitivity of endoscopic biopsy for detecting gastric and duodenal lesions in dogs and cats. Willard MD, Mansell J, Fosgate GT, et al. J Vet Intern Med 22(5):1084-1089, 2008. 6. Protein-losing enteropathy associated with cystic mucoid changes in the intestinal crypts of two dogs. Willard MD, Zenger E, Mansell JL. JAAHA 39(2):187-191, 2003. 7. Histopathological standards for the diagnosis of gastrointestinal inflammation in endoscopic biopsy samples from the dog and cat: a report from the World Small Animal Veterinary Association Gastrointestinal Standardization Group. Day MJ, Bilzer T, Mansell J, et al. J Comp Pathol 138(Suppl)1:S1-S43, 2008. 8. Effect of tissue processing on assessment of endoscopic intestinal biopsies in dogs and cats. Willard MD, Moore GE, Denton BD, et al. J Vet Intern Med 24(1):84-89, 2010. 9. Clinical signs, histology, and CD3-positive cells before and after treatment of dogs with chronic enteropathies. Schreiner NM, Gaschen F, Gröne A, et al. J Vet Intern Med 22(5):1079-1083, 2008.

Managing Chronic Enteropathies in Dogs

10. Immune cell populations in the duodenal mucosa of cats with inflammatory bowel disease. Waly NE, Stokes CR, Gruffydd-Jones TJ, Day MJ. J Vet Intern Med 18(6):816-825, 2004. 11. The relationship of mucosal bacteria to duodenal histopathology, cytokine mRNA, and clinical disease activity in cats with inflammatory bowel disease. Janeczko S, Atwater D, Bogel E, et al. Vet Microbiol 128(1-2):178-193, 2008. 12. Quantitative analysis of inflammatory and immune responses in dogs with gastritis and their relationship to Helicobacter spp. infection. Wiinberg B, Spohr A, Dietz HH, et al. J Vet Intern Med 19(1):4-14, 2005. 13. Unpublished data. Simpson KW, McDonough SP. Ithaca, NY: Cornell University; 2009. 14. Remission of histiocytic ulcerative colitis in boxer dogs correlates with eradication of invasive intramucosal Escherichia coli. Mansfield CS, James FE, Craven M, et al. J Vet Intern Med 23(5):964-969, 2009. 15. Protein-losing enteropathies. Peterson PB, Willard MD. Vet Clin North Am Small Anim Pract 33(5):1061-1082, 2003. 16. Interobserver variation among histopathologic evaluations of intestinal tissues from dogs and cats. Willard MD, Jergens AE, Duncan RB, et al. JAVMA 220(8):1177-1182, 2002. 17. Interplay of commensal and pathogenic bacteria, genetic mutations, and immunoregulatory defects in the pathogenesis of inflammatory bowel diseases. Packey CD, Sartor RB. J Vet Intern Med 263(6):597-606, 2008. 18. Direct bacterial killing in vitro by recombinant Nod2 is compromised by Crohn’s disease-associated mutations. Perez LH, Butler M, Creasey T, et al. PLoS One 5(6):e10915, 2010. 19. Response of the jejunal mucosa of dogs with aerobic and anaerobic bacterial overgrowth to antibiotic therapy. Batt RM, McLean L, Riley JE. Gut 29(4):473-482, 1988. 20. Tylosin-responsive chronic diarrhea in dogs. Westermarck E, Skrzypczak T, Harmoinen J, et al. J Vet Intern Med 19(2):177-186, 2005. 21. Comparison of direct and indirect tests for small intestinal bacterial overgrowth and antibiotic-responsive diarrhea in dogs. German AJ, Day MJ, Ruaux CG, et al. J Vet Intern Med 17(1):33-43, 2003. 22. Adherent and invasive Escherichia coli is associated with granulomatous colitis in boxer dogs. Simpson KW, Dogan B, Rishniw M, et al. Infect Immun 74(8):4778-4792, 2006. 23. Antimicrobial resistance impacts clinical outcome of granulomatous colitis in boxer dogs. Craven M, Dogan B, Schukken A, et al. J Vet Intern Med 24(4): 819-824, 2010.

24. Genome-wide analysis of granulomatous colitis in the boxer dog. Craven M. Proc ACVIM Forum:2010. 25. Evaluation of mucosal bacteria and histopathology, clinical disease activity and expression of Toll-like receptors in German shepherd dogs with chronic enteropathies. Allenspach K, House A, Smith K, et al. Vet Microbiol May 2010 [Epub ahead of print]. 26. Inheritance of gluten-sensitive enteropathy in Irish setters. Garden OA, Pidduck H, Lakhani KH, et al. Am J Vet Res 61(4):462-468, 2000. 27. Diversity of the human intestinal microbial flora. Eckburg PB, Bik EM, Bernstein CN, et al. Science 10;308(5728):1635-1638, 2005. 28. Culture independent analysis of ileal mucosa reveals a selective increase in invasive Escherichia coli of novel phylogeny relative to depletion of Clostridiales in Crohn’s disease involving the ileum. Baumgart M, Dogan B, Rishniw M, et al. ISME J 1(5):403-418, 2007. 29. Molecular-phylogenetic characterization of microbial communities imbalances in the small intestine of dogs with inflammatory bowel disease. Xenoulis PG, Palculict B, Allenspach K, et al. FEMS Microbiol Ecol 66(3):579-589, 2008. 30. Molecular analysis of the bacterial microbiota in duodenal biopsies from dogs with idiopathic inflammatory bowel disease. Suchodolski JS, Xenoulis PG, Paddock CG, et al. Vet Microbiol 142(3-4):394-400, 2010. 31. The effect of the macrolide antibiotic tylosin on microbial diversity in the canine small intestine as demonstrated by massive parallel 16S rRNA gene sequencing. Suchodolski JS, Dowd SE, Westermarck E, et al. BMC Microbiol 9:210, 2009. 32. Perinuclear antineutrophilic cytoplasmic antibody and response to treatment in diarrheic dogs with food responsive disease or inflammatory bowel disease. Luckschander N, Allenspach K, Hall J, et al. J Vet Intern Med 20(2):221-227, 2006. 33. High throughout pyrosequencing reveals reduced bacterial diversity in the duodenal mucosa of dogs with IBD (Abstract 158). Craven M, Dowd SW, McDonough S, Simpson KW. Proc ACVIM Congr :2009. 34. Pharmacokinetics and clinical efficacy of cyclosporine treatment of dogs with steroid-refractory inflammatory bowel disease. Allenspach K, Rüfenacht S, Sauter S, et al. J Vet Intern Med 20(2):239-244, 2006. 35. Hypomagnesemia and hypocalcemia associated with protein-losing enteropathy in Yorkshire terriers: five cases (1992-1998). Kimmel SE, Waddell LS, Michel KE. JAVMA 217(5):703-706, 2000.

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Robert A. Kennis, DVM, MS, DACVD, College of Veterinary Medicine, Auburn University, Auburn, Alabama

Update on Canine Cutaneous Adverse Reactions to Food Food allergy is a common term used to describe the myriad of adverse reactions dogs may experience after exposure to certain food items. Gastrointestinal (GI) ab-

The role of type I hypersensitivity as a cause of canine food allergy has been investigated with the use of an atopic dog model.

normalities, including vomiting, diarrhea, change in frequency of bowel movements, and pica, are only a few of the clinical signs that may occur independently or concurrently with cutaneous reactions,1 including pruritus, urticaria, otitis, and skin infections. This presentation reviews and evaluates current concepts regarding the pathogenesis, diagnosis, and management of dogs with suspected cutaneous adverse reactions to food (CARF).

Pathogenesis The pathogenesis of the development of CARF is poorly defined. True food allergic causes, however, may exist and can be represented by three of the four hypersensitivity reaction types (Table 1): I, III, or IV.

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Update on Canine Cutaneous Adverse Reactions to Food

TABLE 1 Oral allergy syndrome, which is a localized immunoglobulin E (IgE)-mediated type I reaction, has been reported in dogs. Mixed IgE-mediated, non-IgEmediated, and late-phase reactions may also be implicated.2

Hypersensitivity Reaction Types and Canine Cutaneous Adverse Reactions to Fooda Type

Key Characteristics

Food Related?

Type I

Immediate hypersensitivity; mediated by immunoglobulin E (IgE) attached to mast cells

Yes

Type II

Cytotoxic hypersensitivity; immune response destroys normal cells

No

Immunoglobulin Type III Immune complex hypersensitivity; antigens and antibodies Yesb E-mediated reactions form and cause inflammation when deposited in large Oral allergy syndrome was described in amounts in tissue a dog with Japanese cedar allergy3 characType IV Delayed hypersensitivity; antigens in skin cause slowly Yes terized by cross-reactivity between developing inflammatory response mediated by T cells and tomato allergens and Japanese cedar. natural killer cells When fresh tomato was offered to the a Compiled from Tizzard I. Veterinary Immunology, 8th ed. Philadelphia: Saunders Elsevier, 2009, pp 329-379. dog, it exhibited clinical signs consisting b Type III reactions may occur when antigenic milk replacer is fed to very young calves and the foreign antigen may of salivation, swelling of the lips, and be absorbed and stimulate antibody formation. quivering of the tongue. However, the same model, it was shown that oral challenge with soy- or cornsigns were not seen when the tomato was cooked before being based diets did not produce cutaneous or GI changes even fed to the dog. Therefore, this study demonstrated both crossthough dogs were sensitized to these foods.6 It appeared that the reactivity between allergens and oral allergy syndrome, which might partially explain why some dogs with CARF develop timing of the subcutaneous food allergen “booster” as these dogs acute muzzle pruritus after eating. Because many cross-reacmatured may have played a greater role in maintaining high IgE tions between food allergens and environmental allergens have levels than oral exposure through feeding. Further investigations 4 been implicated in humans with oral allergy syndrome, one using this model are warranted, with consideration given to a mechanism that can help induce the breakdown of oral tolerance. could postulate that dogs with atopy could be exacerbated by A spontaneous dog model of IgE-mediated food hypersensioral challenge with these cross-reacting antigens. tivity has also been investigated.7 These dogs exhibited relative Furthermore, the role of type I hypersensitivity as a cause of canine food allergy has been investigated with the use of an increases in serum IgE for corn antigen compared with control atopic dog model.5 Dogs were selected as being high IgE prodogs. Clinical signs were exacerbated when study dogs were challenged with oral consumption of corn. Serum IgE levels ducers and were purposely bred accordingly. The puppies were also increased after corn had been fed. This model may prove administered whole-food allergens subcutaneously soon after to be superior to the atopic dog model for investigating type I birth. A modified-live virus vaccine was used as an immune food hypersensitivity reactions. stimulant to encourage production of IgE antibodies to the food allergens. Early findings demonstrated that these dogs could be used to investigate the role of IgE in canine food alImmunologic and nonimmunologic reactivity lergy as a subset of CARF. These studies also demonstrated the In the intestinal tract, a single epithelial layer separates innate genetic predisposition for the development of high levels of IgE and adaptive immune-effector cells from a vast amount of antiantibody. This canine model, however, had limitations in algens.8 Immune tolerance is maintained by an intact barrier and lowing extrapolation of data to the canine population at large. a complex interaction of immune responses.9 Oral tolerance is Further investigations with this model led to contradictory a state of immunologic unresponsiveness. Therefore, a breakdata. Some reports indicated that oral challenges led to clinical down of tolerance can lead to the development of immunologic signs, including GI changes and pruritus. However, using the reactivity with localized and systemic clinical signs.10 A full review of the immunologic processes is beyond the scope of this review. However, human and murine research has led to A spontaneous dog model of IgE-mediated some interesting findings regarding the roles of TCR-alpha-beta food hypersensitivity may prove to be CD8-positive and TCR-gamma-delta intraepithelial lymphocytes and unconventional T-cell subsets (ie, regulatory T cells superior to the atopic dog model for [Tregs]) in the pathogenesis of common human GI diseases.8 investigating type I food hypersensitivity Nonimmunologic CARF can also occur in dogs with similar reactions. clinical signs. Food intolerance is an abnormal physiologic re-

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sponse to an ingested food item or additive. GI changes are likely seen. Toxic reactions from the ingestion of bacterial- or fungal-contaminated food may also occur. It is evident that the pathogenesis of the development of CARF is not linear and that many factors, including genetics, diet, concurrent health status, and immune status, may all play a role. Human and murine research provides interesting portals for investigation, but data from these studies may not be applicable to canine patients because of differences in the human, murine, and canine immune systems. Further studies are, therefore, warranted using dogs.

present with recurrent infections of the skin and ear canals. Interestingly, only one ear might be affected.

Diagnostic options In human medicine, the gold standard for the diagnosis of food allergy is the double-blind placebo-controlled food challenge (DBPCFC). Individual food items are administered orally in a blinded manner, and the patient is evaluated on clinical signs. Patients with oral allergy syndrome may experience a tingling sensation in the mouth or on the tongue. Sometimes tinnitis is present. Skin prick testing of whole-food extracts has been used as a screening tool for IgE-mediated food allergy.14 It appears to have good negative predictive value but is only useful in patients Diagnosis experiencing type I hypersensitivity.15,16 There does not appear to be a sex predilection for canine CARF. However, there is some evidence that certain canine breeds have In canine medicine, the elimination test diet is considered to an increased risk for developing food allergy, but that evidence be the diagnostic tool of choice. Skin prick testing and intraderhas not yet been validated. The age of onset likewise is variable, mal skin testing using whole-food items has been shown to be and the true prevalence remains unknown.11 of little diagnostic value. Intradermal testing in dogs has shown low sensitivity and high specificity (few false-positive results) similar to skin prick testing in humans.17 The difficult and inconsistent methods Endoscopic-guided injections of food allergens into the mucosa of diagnosing CARF make the true of the stomach have been investigated as a diagnostic tool.18 Time, the repeatability of the procedure, and the expertise needed to prevalence of this problem unknown. conduct such a test demonstrate its limitations. In addition, this procedure is only useful in evaluating type I hypersensitivity reactions. One can argue that the stomach is not necessarily an imporClinical findings tant organ of immunity in a dog exhibiting food allergy or CARF. Clinical signs may be seen in dogs younger than 6 months of It is assumed that a type I hypersensitivity reaction is the most age or older than 10 years of age. The most common clinical common cause of CARF in dogs and humans. There is recent evfinding with CARF is pruritus, but papules and erythema are idence that when human patients are challenged with offending also seen.12,13 The distribution pattern may include (Figure 1) allergens in a blinded manner, changes in serum IgE levels are not the face (ie, chin, muzzle, periorbital), feet, ears, axillae, significantly different than what occurs in control patients. The forelegs, or perianal region. Any or all of these regions may be IgE reactions occurred locally in the GI tract.19 affected. Occasionally, generalized pruritus is noted. Dogs may Such evidence may partially explain why skin testing and serum testing for food allergy are inaccurate in dogs.20 In one study, 13 dogs with food allergy were evaluated with an elimination test diet, ELISA testing, and intradermal testing of food allergens. Skin and serum tests were unable to adequately predict positive or negative reactions compared with the results of an elimination test diet.21 Figure 1A Figure 1B Serum evaluation for IgE levFigure 1. A dog with atopy and suspected cutaneous adverse reaction to food. (A) Trauma-induced alopecia els to food items by conductand erythema of the muzzle and (B) intense erythema with secondary infection of the foot, both due to pruritus. ing a radioallergosorbent test

12

Update on Canine Cutaneous Adverse Reactions to Food

Elimination Test Diets: Key Points to Remember (RAST) or an ELISA is available from some laboratories. The repeatability of these tests has been shown to be insufficient.22 Therefore, it is not recommended that serum testing be used as a sole method of diagnosing the underlying cause of CARF. Elimination test diet Selection of an elimination test diet is based on dietary history (see Elimination Test Diets: Key Points to Remember). It is generally recommended to feed the test diet for a minimum of 8 weeks.23 Some cases may respond to the dietary test in fewer than 8 weeks, whereas others may require longer for clinical signs to abate. Once the patient has clinically improved, the original diet may be fed to demonstrate induction of clinical signs. Reactions may occur very quickly on challenge, especially if there is a type I hypersensitivity component to the CARF. Most adverse signs occur in fewer than 14 days on challenge. Once CARF has been “proven,” the owner may elect to introduce individual food items as a challenge to attempt to identify the source of the reaction. It has been shown that most dogs with CARF have reactions to one or two individual food items.24 Although the product selection is based on dietary history, the best approach to elimination test diets remains controversial, as there are advantages and disadvantages associated with homeprepared or commercial diets containing limited antigens and with hydrolyzed protein-source diets. The ideal test diet should be free of preservatives and additives, although documented adverse reactions to these items in dogs are rare.12 A home-prepared diet consisting of a single protein source and a single carbohydrate has been recommended, whereas commercial limited-antigen diets containing novel protein sources are an alternative.25 It has been suggested that the preparation of commercial diets may have an impact on allergenicity,26 and other studies have suggested that commercially prepared diets are not as accurate in diagnosing food allergy as home-prepared diets.23,24 Of importance to note, commercial diets are usually complete and balanced. In contrast, home-prepared diets may not be balanced and may lack minerals, especially calcium.27 Balanced home-prepared menus, however, are available through several resources. Hydrolyzed diets provide an alternative to novel protein elimination test diets. It has been shown that hydrolyzed diets are beneficial in humans with known allergic reactions.28 These diets have

Realizing a more definitive diagnosis and treatment may lie in investigating the relationship between canine atopic dermatitis and CARF as hypothesized by some investigators.

• The test diet should be fed a minimum of 8 weeks. • Reactions may occur swiftly on challenge, especially with type I hypersensitivity; most reactions occur in fewer than 14 days. • Hydrolyzed diets are an alternative to novel protein elimination test diets. • Owner compliance can be challenging and may prevent successful completion of a test diet and challenge. • Some dogs may require more than one food trial with different diets to confirm CARF.

also been demonstrated as useful for investigating dogs suspected of having food allergy.29 In one study, 34 of 36 dogs improved when fed a soy hydrolysate diet and relapsed on challenge.30 Some of the limitations of hydrolyzed diets include cost and palatability, but these are subjective, depending on the client and patient. Recently, an extensive review investigated the use of hydrolyzed diets and CARF in dogs.31 It was suggested that these diets are best used in dogs suspected not to be hypersensitive to the individual components. I have documented a sole case in which a 10-year-old, spayed golden retriever suspected of having CARF improved when fed a hydrolyzed soy diet (Purina Veterinary Diets HA Hypoallergenic brand Canine Formula) and relapsed when orally challenged with fresh tofu. Owner compliance can be a challenge. In a recent study of 28 dogs started on a home-cooked elimination diet, 10 dogs did not complete the diet as prescribed.32 There are many possible reasons for poor compliance, including but not limited to: • Time of preparation • Limitation of treat items • Reduced appetence or adverse reactions to the test diet • Cost • Poor communication between the owner and the veterinarian • Clients stopping the test diet prematurely because of a disbelief that their dog may have CARF.

Closing Remarks The diagnosis of food allergy as a component of canine CARF continues to be a challenge. It has become increasingly difficult to find novel protein and carbohydrate sources because of the plethora of commercial diets available. Hydrolyzed protein diets provide an alternative but are not without their own limitations. Simple diagnostic tools, such as intradermal or skin prick testing and serum ELISA testing alone, have not been shown to be useful. Novel diagnostic procedures, such as gastroscopicassisted injections into the gastric mucosa and/or colon, are unlikely to be of clinical importance. The future of realizing a more definitive diagnosis and treatment may lie in investigating the relationship between canine atopic dermatitis and CARF as hypothesized by some investigators.33,34 The evaluation of cross-reactivity between food aller-

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gens and pollens continues to be investigated in humans, but similar studies in dogs are also needed. One major challenge is in implementing a canine DBPCFC, as dogs typically do not articulate when and how they are experiencing clinical signs until the signs become severe. The role of probiotics as a treatment for CARF has been investigated, but the immunoregulatory effects are not well understood.35 As our understanding of the immunopathogenesis of food allergy in dogs improves, we may be able to detect cellular changes indicative of adverse reactions before they become clinically significant. ■

References 1. Food hypersensitivity in 20 dogs with skin and gastrointestinal signs. Paterson S. J Small Anim Pract 36(12):529-534, 1995. 2. Food allergy in dogs and cats: a review. Verlinden A, Hesta M, Millet S, Janssens GPJ. Crit Rev Food Sci Nutr 46(3):259-273, 2006. 3. Oral allergy syndrome induced by tomato in a dog with Japanese cedar (Cryptomeria japonica) pollinosis. Fujimura M, Ohmori K, Masuda K, et al. J Vet Med Sci 64(11):1069-1070, 2002. 4. Current understanding of cross-reactivity of food allergens and pollen. Vieths S, Scheurer S, Ballmer-Weber B. Ann NY Acad Sci 964:47-68, 2002. 5. The atopic dog: a model for food allergy. Ermel RW, Kock M, Griffey SM, et al. Lab Anim Sci 47(1):40-49, 1997. 6. Use of atopic dogs to investigate adverse reactions to food. Kennis RA. JAVMA 221(5):638-640, 2002. 7. Evaluation of the clinical and allergen specific serum immunoglobulin E responses to oral challenge with cornstarch, corn, soy and a soy hydrolysate diet in dogs with spontaneous food allergy. Jackson HA, Jackson MW, Coblentz L, Hammerberg B. Vet Derm 14(4):181-187, 2003. 8. T cell-mediated immunoregulation in the gastrointestinal tract. Saurer L, Mueller C. Allergy 64(4):505-519, 2009. 9. Intestinal barrier function: molecular regulation and disease pathogenesis. Groschwitz KR, Hogan SP. J Allergy Clin Immunol 124(1):3-20, 2009. 10. Food allergy: when mucosal immunity goes wrong. Sampson HA. J Allergy Clin Immunol 115(1):139-141, 2005. 11. Systematic review of evidence for the prevalence of food sensitivity in dogs. Chesney CJ. Vet Rec 148(14):445-448, 2001. 12. Food allergy. Reedy LM. In: Reedy LM, Miller WH, Willemse T (eds): Allergic Skin Diseases of Dogs and Cats—Philadelphia: WB Saunders, 1997, pp 173-188. 13. Food hypersensitivity in 30 dogs. White SD. JAVMA 188(7):695-698, 1986. 14. Utility of food-specific IgE concentrations in predicting symptomatic food allergy. Sampson HA. J Allergy Clin Immunol 107(5):891-896, 2001. 15. Intradermal skin tests in the diagnostic evaluation of food allergy. Sampson HA, Rosen JP, Selcow JE, et al. J Allergy Clin Immunol 98(3):714, 1996. 16. Food allergy. Part 2: diagnosis and management. Sampson HA. J Allergy Clin Immunol 103(6):981-989, 1999.

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17. Validity of skin testing for diagnosis of food allergy in dogs. Kunkle G, Horner S. JAVMA 200(5):677-680, 1992. 18. Development of gastroscopic food sensitivity testing in dogs. Guilford WG, Strombeck DR, Rogers Q, et al. J Vet Intern Med 8(6):414-422, 1994. 19. Local allergic reaction in food-hypersensitive adults despite a lack of systemic food-specific IgE. Lin XP, Magnusson J, Ahlstedt S, et al. J Allergy Clin Immun 109(5):879-887, 2002. 20. Serum IgE and IgG responses to food antigens in normal and atopic dogs, and dogs with gastrointestinal disease. Foster AP, Knowles TG, Moore AH, et al. Vet Immunol Immunopathol 92(3-4):113-124, 2003. 21. Diagnostic testing of dogs for food hypersensitivity. Jeffers JG, Shanley KJ, Meyer EK. JAVMA 198(2):245-250, 1991. 22. Canine food hypersensitivity dermatitis: diagnostic possibilities. Wilhelm S, Favrot C. Schweiz Arch Tierheild 147(4):165-171, 2005. 23. Diagnosis of food allergy in dogs. Rosser EJ Jr. JAVMA 203(2):259-262, 1993. 24. Responses of dogs with food allergies to single ingredient dietary provocation. Jeffers JG, Meyer EK, Sosis EJ. JAVMA 209(3):608-611, 1996. 25. Study of the chemical and nutritional characteristics of commercial dog foods used as elimination diet for the diagnosis of canine food allergy. Ricci R, Berlanda M, Tenti S, Bailoni L. Ital J Anim Sci 8:328-330, 2009. 26. Rare, medium, or well done? The effect of heating and food matrix on food protein allergenicity. Nowak-Wegrzyn A, Fiocchi A. Curr Opin Allergy Clin Immunol 9(3):234-237, 2009. 27. Hypoallergenic diets for dogs and cats. Roudebush P. In: Bonagura JD (ed): Kirk’s Current Veterinary Therapy, XIII—Philadelphia: WB Saunders, 2000, pp 530-535. 28. Use of hydrolysates in the treatment of cow’s milk allergy. Terracciano L, Isoardi P, Arrigoni S, et al. Ann Allergy Asthma Immunol 89(6):86-90, 2002 29. A retrospective analysis of case series using home-prepared and chicken hydrolysate diets in the diagnosis of adverse food reactions in 181 pruritic dogs. Loeffler A, Soares-Magalhaes R, Bond R, Lloyd DH. Vet Derm 17(4):273279,2006. 30. Diagnosis of adverse reactions to food in dogs: efficacy of a soy-isolate hydrolysate-based diet. Biourge VC, Fontaine J, Vroom MW. J Nutr 134(8): 2062S-2064S, 2004. 31. A systematic review of the evidence of reduced allergenicity and clinical benefit of food hydrolysates in dogs with cutaneous adverse food reactions. Olivry T, Bizikova P. Vet Derm 21(1):32-41, 2010. 32. Comparison of a commercial limited antigen diet versus home prepared diets in the diagnosis of canine adverse food reaction. Tapp T, Griffin CE, Rosenkrantz W, et al. Vet Ther 3(3):244-251, 2002. 33. The ACVD task force on canine atopic dermatitis (X): is there a relationship between canine atopic dermatitis and cutaneous adverse food reactions? Hillier A, Griffin CE. Vet Immunol Immunopathol 81(3-4):227-231, 2001. 34. Food for thought: pondering the relationship between canine atopic dermatitis and cutaneous adverse food reactions. Olivry T, Deboer DJ, Prelaud P, Bensignor E. Vet Derm 18(6):390-391, 2007. 35. The role of the immune system in the use of probiotic lactic acid bacteria in eventing and treating allergic diseases. Chung KUO, Nguyen HH, Kwak IS. Korean J Food Sci Anim Resource 30(1):1-12, 2010.

Update on Canine Cutaneous Adverse Reactions to Food

Michael R. Lappin, DVM, PhD, DACVIM, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, Colorado

Clinical and Research Experiences with Probiotics in Cats Probiotics are live microorganisms that, when administered in adequate amounts, can confer health effects on the host.1 Many studies of the effects of probiotics on the health of humans have been conducted, but very few have involved small

Because infectious diseases are common in small animals, the potential beneficial effects of probiotics could significantly impact the practice of veterinary medicine.

animals. This presentation examines research findings on the role of probiotics in human medicine in general and, specifically, the beneficial effects of one probiotic as investigated in three recent studies of Enterococcus faecium strain SF68 (also known as E faecium NCIMB 10415) in cats. Notably, a recent review of human studies on probiotics2 described the “well-established probiotic effects” as follows: • “Prevention and/or reduction in the duration and complaints of rotavirus-induced or antibiotic-associated diarrhea and alleviation of complaints attributed to lactose intolerance • Reduction of the concentration of cancer-promoting enzymes and/or putrefactive (bacterial) metabolites in the gut

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The biologic effects of individual probiotics can vary, and each probiotic introduced should be rigorously evaluated in a controlled fashion to define its potential for clinical value. • Prevention and alleviation of nonspecific and irregular complaints of the gastrointestinal tracts in healthy human adults • Notable beneficial effects on microbial aberrancies, along with complaints about inflammation and other complaints in connection with inflammatory diseases of the gastrointestinal tract, Helicobacter pylori infection, or bacterial overgrowth • Normalization of passing stool and stool consistency in subjects suffering from obstipation or an irritable colon • Prevention or alleviation of allergies and atopic diseases in infants • Prevention of respiratory tract infections (eg, common cold, influenza) and other infectious diseases as well as treatment of urogenital infections.”2 Because infectious diseases are common in small animals, the potential beneficial effects of probiotics could significantly impact the practice of veterinary medicine. All mechanisms of immunomodulation have not been characterized, and it is likely that these effects vary by the probiotic. However, it is known that many probiotics in the lactic acid bacteria group help balance endogenous microbiota and some can inhibit replication of pathogenic bacteria.2 The proposed mechanisms of action include competition for essential nutrients or receptor sites, binding with pathogenic bacteria, and production of inhibitory substances. In addition, it is now known that some probiotics can beneficially influence innate and acquired immunity systemically by a variety of proposed mechanisms, including inducing cytokine production, natural killer cell activity, and both specific and nonspecific immunoglobulin (Ig) production.2

Effects of Individual Probiotics Several considerations should be evaluated when selecting individual probiotics, including the role of biologic effects as evidenced by human research findings.3-5 In addition, the source of probiotic should be considered, as evidenced in a recent canine study conducted in Canada in which a majority of diets claiming to contain probiotics generally did not meet the label claims when evaluated.6 Human study findings Based on several recent review articles in human medicine, the biologic effects of individual probiotics can vary and each probiotic introduced should be rigorously evaluated in a controlled

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fashion to define its potential for clinical value.3-5 These articles also suggested that evidence for the beneficial effects of individual probiotics on various conditions affecting humans, such as Clostridium difficile diarrhea and hospital-acquired pneumonia, is minimal, thereby indicating that larger, more rigorously controlled multicenter studies should be conducted. Puppy study findings E faecium strain SF68 was originally isolated from the feces of a healthy baby and initially shown to inhibit the growth of a number of enteropathogens.7 In one canine study, E faecium strain SF68 was fed to a group of puppies vaccinated with canine distemper virus (CDV) and compared over time with a control group that was similarly vaccinated but was not fed the probiotic.8 A number of findings suggested an immunomodulating effect of the probiotic. The puppies supplemented with SF68 had increased serum and fecal total IgA concentrations, increased CDV-specific IgG and IgA serum concentrations, and an increased percentage of circulating B lymphocytes compared with control puppies. The effect on CDV-specific IgG and IgA antibodies in serum materialized only after the puppies had been supplemented for 31 and 44 weeks, and it was believed that SF68 prevented the decline in antibody titers observed in the control group by maintaining high levels of antibodies in the supplemented puppies.

Collaborative Study: Role of SF68 in Healthy Kittens Methodology and evidence collection After the puppy study was published, our research group at Colorado State University collaborated with Nestlé Purina PetCare on a similar study conducted in healthy kittens.9 Of note, E faecium strain SF68 is the probiotic of choice in the company’s FortiFlora veterinary product (purinaveterinarydiets.com). In this study, we hypothesized that feeding E faecium SF68 to kittens would enhance their nonspecific immune responses; humoral immune responses to feline herpesvirus-1 (FHV-1), feline calicivirus (FCV), and feline panleukopenia virus (FPV); and FHV-1-specific cell-mediated immune responses. Twenty, 6-week-old specific pathogen-free (SPF) kittens were purchased from a commercial vendor and divided into two groups: One group was fed SF68 daily, and the other was fed the palatability enhancer starting at 7 weeks of age. At 9 and 12 weeks of age, a commercially available FVRCP modified-live vaccine was admin-

Hypothesis: Feeding E faecium SF68 to kittens would enhance nonspecific, humoral, and cell-mediated immune responses.

Clinical and Research Experiences with Probiotics in Cats

45 – Percentage of Lymphocytes (%)

Placebo istered subcutaneously, and the kittens 40 – Treatment were followed until 27 weeks of age. 35 – The attitudes and behavior of the 30 – kittens were monitored daily 25 – throughout the study, and body weight was measured weekly. Blood, 20 – * saliva, and feces were collected from 15 – all cats before probiotic or palatability 10 – enhancer supplementation was initiated at 7 weeks of age, followed by 5– collections at 9, 15, 21, and 27 weeks 0– 7 9 15 21 27 of age. In addition, feces were colAge (weeks) lected from kittens in the treatment * = Time points at which the treatment group was significantly higher than the placebo group (P = .0220) group at 28 weeks of age. For each group of kittens, five fecal Figure 1. Percentage of gated lymphocytes positive for CD4 in peripheral blood by flow cytometry. samples per day were randomly se(From Effect of supplementation with Enterococcus faecium (SF68) on immune functions in cats. Veir JV, Knorr R, Cavadini C, et al. Vet Ther 8:229, 2007; with permission.) lected from the shared litter box and scored using a standardized graphic scoring card; fecal extracts taken at 9 and 27 weeks of ages were analyzed for total IgA and IgG levels. Interpretation of findings Other parameters monitored included randomly amplified polyThe cats readily ingested the probiotic or palatability enhancer. morphic DNA (RAPD)-PCR on feces to determine if viable Body weight and fecal scores were not statistically different beE faecium SF68 was in the stools of treated cats and to assess tween the two groups over time or at any individual time points. whether the probiotic was accidentally transmitted from the Complete blood counts and biochemical profiles were within treated kittens to the control kittens. Commercially available normal limits for the age group for all cats at all time points. ELISAs were used to determine whether Clostridium perfringens The results suggested that SF68 was safe for long-term use in enterotoxins or C difficile toxins A/B were present in the feces of cats. Feces from seven of nine treatment kittens were positive for the kittens. Routine aerobic fecal cultures for Salmonella and SF68 on at least one time point during the study, whereas feces Campylobacter were also conducted. Complete blood counts, from all control kittens were negative for SF68 at all time points, serum biochemical panels, and urinalyses were done to assess suggesting there was no cross-over of SF68 into the control group whether any adverse events were induced by the probiotic. cats. SF68 DNA was not amplified from feces of any treated kitten one week after supplementation was stopped (week 28), thereby showing that the probiotic did not colonize the kittens. The results of a collaborative study in healthy All samples from placebo kittens were negative for SF68 by kittens suggested that SF68 was safe for RAPD-PCR. Neither Salmonella nor Campylobacter organisms were grown from feces. The number of positive samples for long-term use in cats. C difficile toxins A/B or C perfringens enterotoxins was not significantly different between the groups over the course of the Antigen-specific humoral immune responses were estimated study. by measuring serum FHV-1-specific IgG, FHV-1-specific IgA, At 21 and 27 weeks of age, the mean levels of FHV-1-specific FCV-specific IgG, and FPV-specific IgG in sera, as well as IgA in serum and saliva were numerically greater in the treatFHV-1-specific IgG and IgA levels in saliva using adaptations ment group compared with the placebo group. Furthermore, of previously published ELISAs. Total IgG and IgA concentrathe mean FHV-1-specific serum IgG levels were numerically tions in sera, fecal extracts, and saliva were estimated using greater in the treatment group compared with those in the commercial ELISAs or radial immunodiffusion (RID) assays. placebo group at 15, 21, and 27 weeks of age. However, these Cellular immune responses were assessed via flow cytometry differences in FHV-1 antibody levels did not reach statistical and whole blood proliferation assays. Lymphocytes were stained significance. No FHV-1-specific IgG was detected in saliva. for expression of CD4, CD8, CD44, MHC Class II, and B FCV-specific IgG levels in serum were similar for both cells. In addition, lymphocyte proliferation in response to congroups. At 15 weeks of age, the mean FPV-specific IgG serum canavalin A and FHV-1 antigens was assessed. levels in the treatment group kittens were numerically greater

Critical Updates on Canine & Feline Health • 2011 NAVC/WVC Proceedings

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Percentage of Conjunctivitis (%)

noted at 31 weeks and 44 than levels in the placebo group weeks.8 In addition, inclusion kittens, but the differences were not statistically significant. Conof greater numbers of cats centrations of total IgG and IgA may have led to detection of in serum also were similar for additional statistical differboth groups. Total IgG was not ences between groups for detected in saliva, and total IgA those parameters with nuconcentrations in saliva were simmeric trends. ilar between groups. Total IgA and IgG concentrations in fecal exFollow-up Studies tracts also were similar between Effects of SF68 on groups. FHV-1 in cats Figure 2. A cat infected with feline herpesvirus-1 (FHV-1). Proliferation assays using either The results of the first study concanavalin A or FHV-1 antigen prompted a follow-up study preparation did not produce sigon FHV-1.10 This virus is ex– 35 nificantly different mean maxitremely common in cats and mum counts between groups at is frequently associated with SF68 30 – any time points. There were no morbidity because of recurPlacebo statistical differences between the rent ocular and respiratory – 25 groups for any cell surface markers clinical signs of disease (Figure at the first four time points. How2). In addition, there is no 20 – ever, at 27 weeks of age (Figure 1), known drug therapy that conthe treatment group had a signifisistently eliminates the carrier 15 – cantly higher percentage of gated state and vaccination does not P < .0001 lymphocytes positive for CD4 provide sterilizing immunity. 10 – (mean, 13.87%) than did the We hypothesized that feedplacebo group (mean, 10.61%; ing SF68 would decrease 5– P = .0220). clinical disease, episodes of In this study, we concluded that FHV-1 shedding, and num0– SF68 was safe to administer to cats bers of FHV-1 DNA copies Supplementation/Stress Period and the increase in CD4+ cell shed over time in cats with Figure 3. Cumulative conjunctivitis scores in feline herpesvirus-1counts in the treatment group chronic FHV-1 infection. infected kittens with and without SF68 supplementation over time. compared with the placebo group In this study, 12 cats with (From Pilot study to evaluate the effect of oral supplementation of Enwithout a concurrent increase in chronic FHV-1 infection terococcus faecium SF68 on cats with latent feline herpesvirus 1. Lappin MR, Veir JK, Satyaraj E, Czarnecki-Maulden G. J Feline Med Surg CD8+ counts at 27 weeks of age were administered either 11:650, 2009; with permission.) demonstrated a systemic imSF68 or the palatability enmunomodulating effect by the hancer as a placebo, moniprobiotic. Because we did not show a significant increase in lymtored for clinical signs of disease, monitored for FHV-1 phocyte stimulation by FHV-1 or an increase in the expression shedding, and evaluated for FHV-1-specific humoral and cellof the memory cell marker CD44 on the CD4+ lymphocytes in mediated immune responses and fecal microbiome stability. the treatment group, the increase in CD4+ T lymphocytes may After an equilibration period, mild stress was induced over time have been nonspecific, as the cells appeared to be unprimed. by changing the housing of the cats from cages to gang housing However, because the CD4+ T lymphocytes of kittens in this repeatedly over a 5-month period. study were not additionally characterized via cytokine production profiles or additional cell surface marker characterization, Hypothesis: Feeding SF68 would decrease it could not be determined whether a Th1 or Th2 (helper T cells) response predominated. We believed that sample size or clinical disease, episodes of FHV-1 the duration of the study may have precluded detection of stashedding, and numbers of FHV-1 DNA tistical differences between the groups in regards to FPV, FCV, copies in cats with chronic FHV-1 infection. and FHV-1 antibody titers. In the puppies, those effects were

18

Clinical and Research Experiences with Probiotics in Cats

SF68 supplementation was well tolerated by all study cats. Fecal microbial diversity was maintained throughout the study in cats supplemented with SF68 but decreased in cats fed the placebo, indicating a more stable microbiome in cats fed SF68. Upper respiratory signs of disease were not exacerbated in this model of stress, so the use of a glucocorticoid stress model in future studies should be considered. Although the study results varied among cats, those receiving SF68 had fewer episodes of conjunctivitis than did cats in the placebo group during the supplementation period, suggesting that administration of the probiotic lessened morbidity associated with chronic FHV-1 infection (Figure 3). The results of this study also suggested that the immunomodulated effects of SF68 demonstrated in the healthy cat study may induce clinically beneficial results for this viral infection. Additional data should be collected from cats in the field to further substantiate these findings. SF68 effects on nonspecific diarrhea in an animal shelter In previous work, mice administered SF68 and then infected with Giardia intestinalis shed fewer trophozoites and less Giardia antigen than did the placebo group.11 In addition, supplemented mice had increased CD4+ cells in Peyer’s patches and the spleen as well as increased anti-Giardia intestinal IgA and serum IgG when compared with untreated mice. This work prompted our next study on the SF68 effects on nonspecific diarrhea in cats and dogs housed in an animal shelter.

Hypothesis: Cats and dogs housed in an animal shelter and fed SF68 would have decreased episodes of diarrhea and improved fecal scores compared with untreated dogs and cats when housed in the same environment. We hypothesized that cats and dogs housed in an animal shelter and fed SF68 would have decreased episodes of diarrhea and improved fecal scores compared with untreated cats and dogs in the same environment.12 In a northern Colorado animal shelter, cats were housed in two different rooms and dogs were housed in two different rooms. All study cats and dogs were fed the same species-specific standardized diet. In the animals in one room, the diet was supplemented daily with FortiFlora, whereas the animals in the alternate room received daily supplementation of a FortiFlora carrier without SF68. Otherwise, the management of animals in both rooms was identical for the duration of the study. However, to minimize any risk that room selection could influence the study results, the rooms were switched after one month

(ie, cats and dogs supplemented with FortiFlora and those receiving the carrier without SF68 switched rooms). During the study, routine shelter cleaning and disinfectant protocols were followed. At the time of the room switch, the study was discontinued for one week to lessen the possibility that SF68 surviving in the environment could influence study results. Before the rooms were cleaned each morning, feces in the cage of each animal were scored by one of the investigators (see Purina Fecal Scoring System). This person was blinded to the treatment groups. At the conclusion of scoring, feces from dogs or cats with a score of 4 to 7 were collected and transported to Colorado State University for infectious disease testing, which

Purina Fecal Scoring System Fecal consistency is primarily a function of the amount of moisture in the stool and can be used to identify changes in colonic health and other problems. Ideally, in a healthy animal, stools should be firm but not hard, pliable and segmented, and easy to pick up (Score 2). Score 1 Stool very hard and dry Much effort required to expel feces from body No residue left on the ground when feces picked up Often expelled as individual pellets Score 2 Stool firm but not hard Pliable and segmented in appearance Little or no residue left on the ground when picked up Score 3 Stool log-like No segmentation visible Moist surface Leaves residue but remains firm when picked up Score 4 Feces very moist (soggy) Distinct log shape Leaves residue and loses form when picked up Score 5 Feces very moist Distinct shape (piles rather than log shape) Leaves residue and loses form when picked up Score 6 Feces has texture but no defined shape’ Occurs in piles or looks like spots Leaves residue when picked up Score 7 Feces watery, flat, with no texture Occurs as puddles Leaves residue when picked up

Critical Updates on Canine & Feline Health • 2011 NAVC/WVC Proceedings

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Percentage of Cats (%)

25 – 20 –

20.7

Placebo SF68

15 – 10 –

Current research is evaluating the effect of SF68 on the outcome of shelter animals that have diarrhea and are being treated with metronidazole.

7.7

5– 0– Diarrhea >2 Days’ Duration

Significant difference at P = .0297

Figure 4. Percentage of diarrhea of greater than 2 days’ duration in cats with and without SF68 supplementation over time. (From Effect of Enterococcus faecium SF68 supplementation on diarrhea in cats housed in a northern Colorado Animal Shelter. Bybee SN, Scorza V, Lappin MR. Proc ACVIM Annu Conf :June 2010; with permission.)

included microscopic examination for parasite eggs, cysts, and oocysts after zinc sulfate centrifugation flotation and immunofluorescent antibody (IFA) testing for Cryptosporidium oocysts and Giardia cysts (Merifluor Cryptosporidium/Giardia, www. meridianbioscience.com). The percentages of dogs or cats with diarrhea of greater than 2 days’ duration were calculated over the course of the study. A generalized linear mixed model using a binomial distribution with treatment being a fixed effect and the room being a random

effect was used to assess for statistical differences between treatment groups. The presence of parasites was included as a covariate, and significance was defined as P < .05. Because diarrhea prevalence rates were low for all dogs in the study, statistical differences were not detected. However, the percentage of cats with diarrhea lasting longer than 2 days was 7.7% for the probiotic group and 20.7% for the placebo group (Figure 4). This result was significantly different (P = .0297). The results suggest that administration of SF68 to cats housed in shelters may lessen the numbers of days with diarrhea. However, because this was a short-term study, the effect was likely from probiotic influences on intestinal flora rather than systemic immune-enhancing effects.

Closing Remarks

Key Points

In a recent study, administration of SF68 alone to dogs shedding Giardia cysts had no measurable effect on cyst shedding.13 In a previous study of nutritional supplementation in dogs with giardiasis, however, those treated with silymarin and an antiGiardia drug had improved clinical outcomes in some categories compared with those in other treatment groups.14 Therefore, in our current work, we are evaluating the effect of SF68 on the outcome of shelter animals with diarrhea and concurrently being treated with metronidazole. ■

• The potential beneficial effects of probiotics could significantly impact the practice of veterinary medicine.

References

• Because the biologic effects of individual probiotics can vary, each probiotic introduced should be rigorously evaluated in a controlled fashion. • Enterococcus faecium strain SF68 was initially shown to inhibit the growth of a number of enteropathogens when isolated from the feces of a healthy baby. This finding was subsequently confirmed in a canine study of puppies vaccinated with canine distemper virus (CDV). • Findings in a feline study conducted at Colorado State University suggested that SF68 was safe for long-term use in cats. • In a study conducted in cats with chronic feline herpesvirus-1 (FHV-1) infection, those receiving SF68 had fewer episodes of conjunctivitis than did cats in the placebo group. • In a study conducted in a Colorado animal shelter, administration of SF68 to cats with nonspecific diarrhea lessened their number of days with diarrhea. • Current research being conducted at Colorado State University is evaluating the effect of SF68 on the outcome of shelter animals with diarrhea and concurrently being treated with metronidazole.

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1. Probiotics, prebiotics, and synbiotics—approaching a definition. Schrezenmeir J, de Vrese M. Am J Clin Nutr 73:361S, 2001. 2. Probiotics, prebiotics, and synbiotics. De Vrese M, Scherezenmeir J. Adv Biochem Eng Biotechnol 111:1-66, 2008. 3. Probiotics for the prevention of nosocomial pneumonia: current evidence and opinions. McNabb B, Isakow W. Curr Opin Pulm Med 14:168, 2008. 4. Probiotic therapy for the prevention and treatment of Clostridium difficileassociated diarrhea: a systematic review. Dendukuri N, Costa V, McGregor M, Brophy JM. Can Med Assoc J 173:167, 2005. 5. Probiotics for preventing and treating nosocomial infections: review of current evidence and recommendations. Isakow W, Morrow LE, Kollef MH. Chest 132:286, 2007. 6. Bacteriological evaluation of dog and cat diets that claim to contain probiotics. Weese JS, Arroyo L. Can Vet J 44:212, 2003. 7. Biological properties of SF68, a new approach for the treatment of diarrhoeal disease. Lewenstein A, Frigerio G, Moroni M. Curr Ther Res 26:967, 1979. 8. Supplementation of food with Enterococcus faecium (SF68) stimulates immune functions in young dogs. Benyacoub J, Czarnecki-Maulden GL, Cavadini C, et al. J Nutr 133:1158, 2003. 9. Effect of supplementation with Enterococcus faecium (SF68) on immune functions in cats. Veir JV, Knorr R, Cavadini C, et al. Vet Ther 8:229, 2007.

Clinical and Research Experiences with Probiotics in Cats

10. Pilot study to evaluate the effect of oral supplementation of Enterococcus faecium SF68 on cats with latent feline herpesvirus 1. Lappin MR, Veir JK, Satyaraj E, Czarnecki-Maulden G. J Feline Med Surg 11:650, 2009. 11. Enterococcus faecium SF68 enhances the immune response to Giardia intestinalis in mice. Benyacoub J, Perez PF, Rochat F, et al. J Nutr 135:1171, 2005. 12. Effect of Enterococcus faecium SF68 supplementation on diarrhea in cats housed

in a northern Colorado Animal Shelter. Bybee SN, Scorza V, Lappin MR. Proc ACVIM Annu Conf:June 2010. 13. Influence of Enterococcus faecium SF68 probiotic on giardiasis in dogs. Simpson KW, Rishniw M, Bellosa M, et al. J Vet Intern Med 23:476-81, 2009. 14. Evaluation of silymarin in the treatment on asymptomatic Giardia infections in dogs. Chon SK, Kim NS. Parasitol Res 97:445-451, 2005.

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Wendy Baltzer, DVM, PhD, DACVS, College of Veterinary Medicine, Oregon State University, Corvallis, Oregon

Rehabilitation & Nutrition in the Overweight/ Osteoarthritic Dog Obesity is a common problem in dogs in the United States, and the incidence in

A realistic goal for owners and their dogs is to reduce the current caloric intake to achieve a loss of 0.5% to 1% of body weight per week.

other countries is reported to be as high as 41%.1,2 Approximately 20% of adult dogs suffer from osteoarthritis (OA) in one or more diarthrodial joints,3 including the shoulder, elbow, carpus, hip, stifle, tarsus, and spinal articulations. Unfortunately, progression of this disease can only be slowed but never completely stopped. Of importance in managing OA in obese dogs is restriction of caloric intake, which necessarily requires strict adherence and compliance by owners. The role of nutrition and rehabilitation in obese dogs that also suffer from OA is the focus of this presentation.

Nutrition, Obesity, and Osteoarthritis The incidence of knee and hand OA is increased in obese people,4,5 with most researchers

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Rehabilitation & Nutrition in the Overweight/Osteoarthritic Dog

Increased Adipokine Levels Linked to Osteoarthritis in Humans

theorizing that this was due to extoo fast, which can result in loss of Evidence now suggests that obesity in humans may be cessive body mass placing excessive lean tissue and an unhealthy nutria direct cause of OA due to fat cell release of the force on joints and articular cartitional state. A rate of weight loss adipokines leptin and adiponectin.8,9 These hormones lage. In addition, an increased body greater than 2% of body weight per have receptors on chondrocytes and may stimulate OA mass index is linked in humans week is considered too fast. To in joints in the hands of people, where excessive weightbearing does not play a role in the development of OA.10 to increased cartilage loss on the maintain owner interest and comAdipose tissue produces adipokines that affect many patella.6 The relationship of knee pliance in continuing the dog’s tissues, including endocrine and immune tissue.8 Two of weight loss and exercise program, OA to excessive body weight, excesthese adipokines have been identified as mediators of inflammation in the joint: leptin and adiponectin.9,11 some researchers recommend adhersive biomechanical load, and rigorLeptin induces proinflammatory cytokine expression ing to a weekly weight loss rate of at ous repeated use of the joint has (interleukin-1, matrix metalloproteinase-13 and 9) and 9 least 0.5%.20 been identified in humans and is inhibits the growth of chondrocytes. Adiponectin 7 induces chondrocytes to produce interleukin-6, matrix likely to occur in dogs as well. In most dogs, improvement in metalloproteinases-3 and 9, and nitric oxide, resulting in lameness will be noticeable after a However, other factors related to the cartilage degradation.11 6% to 9% loss in body weight.14,19 effects of obesity on the progression What the association of these cytokines is to the of OA may not be as obvious (see Achieving this noticeable loss safely disease in dogs is unknown at this point. However, research is continuing to progress in this field, and the Increased Adipokine Levels Linked without changing the dog’s exercise relationship of obesity to OA in dogs is developing as to Osteoarthritis in Humans). level takes 6 to 18 weeks. outlined here. Hip OA in dogs has been most More profound improvement in commonly linked to hip dysplasia. lameness and gait may be seen in However, obesity may play an important role in progression of dogs with forelimb lameness than in dogs with bilateral hip this disease. Genetically predisposed Labrador retriever litterOA,19 possibly due to the symmetry of lameness that occurs in mates that were fed 25% less than ad libitum developed OA of dogs with bilateral hip OA and the fact that dogs carry more the hip joints 50% less often than their free-fed littermates body weight on the forelimbs than the hindlimbs, resulting in 12 did. These same dogs had a decrease in the severity of shoulmore obvious changes in gait patterns with weight loss.19 Reder OA and a decrease in the severity, but not incidence, of gardless, improvement in lameness is seen in dogs with both elbow OA over their lifetime.12 The dogs fed ad lib developed hindlimb and forelimb OA when an ideal body weight is reached, which may take some time to achieve in obese dogs radiographic signs of hip OA at 6 years of age versus the rethat are 20% to 30% above their ideal weight.15 stricted-fed dogs, which developed radiographic signs at 12 13 years of age. Clearly, preventing obesity can have a significant effect on Caloric intake and resting energy requirement the progression of OA in dogs, but what about dogs that deA realistic goal for owners and their dogs is to reduce the curvelop the disease and are already overweight? Can weight loss rent caloric intake to achieve a loss of 0.5% to 1% of body help by improving their lameness and slowing the progression weight per week. Diets vary widely in caloric density, even of deterioration in their joints? when they are labeled for weight management, weight loss, overweight, or calorie restriction. Caloric density for these diets can range from 217 to 440 kcal per cup of dry food and 189 Safe weight reduction to 398 kcal per can of wet food.21 Researchers have found that overweight dogs with hip OA and pain have a significant decrease in lameness following weight reIn addition, the amount of food to be fed varies greatly as duction.14,15 Many believe that keeping affected dogs slightly unspecified on the dog food packages, with the recommended caloric intake for weight loss in dogs ranging from 0.73 to 1.47 derweight can help slow progression and severity of the disease.16,17 times the resting energy requirement.21 The resting energy reThe problem with getting affected dogs to lose weight is in keeping clients motivated. That is not an easy task. First, owners quirement is calculated as22: have to recognize that the dog is overweight, as defined by ac70 × [kg of lean body mass] 0.75 = kcal/day ceptable body condition scoring (see Nestlé Purina Body Condition System chart), after which they need to appreciate how weight can affect joint pathology. One approach is assuring owners that weight loss will improve their dog’s mobility14,15,18,19 A 6% to 9% loss of body weight in obese and then keeping owners motivated as they see their dog lose dogs will have a noticeable improvement in weight. lameness that most owners can appreciate. Of importance is ensuring that the dog does not lose weight

Critical Updates on Canine & Feline Health • 2011 NAVC/WVC Proceedings

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TOO THIN

Ribs, lumbar vertebrae, pelvic bones and all bony prominences evident from a distance. No discernible body fat. Obvious loss of muscle mass.

1

Ribs, lumbar vertebrae and pelvic bones easily visible. No palpable fat. Some evidence of other bony prominence. Minimal loss of muscle mass. Ribs easily palpated and may be visible with no palpable fat. Tops of lumbar vertebrae visible. Pelvic bones becoming prominent. Obvious waist and abdominal tuck.

IDEAL

]

]

Ribs easily palpable, with minimal fat covering. Waist easily noted, viewed from above. Abdominal tuck evident. Ribs palpable without excess fat covering. Waist observed behind ribs when viewed from above. Abdomen tucked up when viewed from side.

]

5

T O O H E AV Y

Ribs palpable with slight excess fat covering. Waist is discernible viewed from above but is not prominent. Abdominal tuck apparent. Ribs palpable with difficulty; heavy fat cover. Noticeable fat deposits over lumbar area and base of tail. Waist absent or barely visible. Abdominal tuck may be present.

]

7

Ribs not palpable under very heavy fat cover, or palpable only with significant pressure. Heavy fat deposits over lumbar area and base of tail. Waist absent. No abdominal tuck. Obvious abdominal distention may be present. Massive fat deposits over thorax, spine and base of tail. Waist and abdominal tuck absent. Fat deposits on neck and limbs. Obvious abdominal distention. The BODY CONDITION SYSTEM was developed at the Nestlé Purina Pet Care Center and has been validated as documented in the following publications:

3

]

9

Mawby D, Bartges JW, Moyers T, et. al. Comparison of body fat estimates by dual-energy x-ray absorptiometry and deuterium oxide dilution in client owned dogs. Compendium 2001; 23 (9A): 70 Laflamme DP. Development and Validation of a Body Condition Score System for Dogs. Canine Practice July/August 1997; 22:10-15 Kealy, et. al. Effects of Diet Restriction on Life Span and Age-Related Changes in Dogs. JAVMA 2002; 220:1315-1320 Call 1-800-222-VETS (8387), weekdays, 8:00 a.m. to 4:30 p.m. CT

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Rehabilitation & Nutrition in the Overweight/Osteoarthritic Dog

To lose weight, most pets require a daily caloric intake less than the calculated resting energy requirement at the current body weight, with some researchers suggesting feeding 40% to 60% the maintenance energy requirement, that is, 1.2–1.88 × resting energy requirement.23,24 Another approach is to reduce the amount of caloric intake by 40%, which in overweight to obese dogs can result in a reduction of 11% to 18% in body weight over approximately 4 to 5 months.14 When calculating the exact amount that owners should feed their dog, veterinarians must take into account all foods ingested, including treats and table scraps, to ensure success with the weight loss plan. One computerized feeding program allows veterinarians to calculate the dog’s food intake required to lose a certain percentage of body weight per week. The weight loss is based on the dog’s current body weight, and at the recheck examination, the software program determines a new weight loss recommendation based on the dog’s current weight and the time since the last examination.25

Diet, Nutraceuticals, and Osteoarthritis The number of nutraceuticals on the market today are too numerous to discuss in their entirety. Therefore, only the agents most commonly used for the treatment of OA in dogs are addressed here. Eicosapentaenoic acid and omega-3 fatty acids Matrix metalloproteinases are enzymes with increased levels in joints affected by OA, and their inhibition, at least experimentally in dogs, may slow the progression of degenerative joint disease.26-28 The production of arachidonic acid generates precursors to inflammatory mediators, including prostaglandin E2, which increases in joints with OA, resulting in joint pain and inflammation in dogs.29,30 Both arachidonic acid and prostaglandin E2 levels decrease in normal joints after oral administration of fish oil, specifically eicosapentaenoic acid found in omega-3 fatty acids.31 Several canine diets (eg, Purina Veterinary Diet JM Joint Mobility Canine Formula, Hill’s Prescription Diet j/d Canine, Eukanuba Senior Plus) include eicosapentaenoic acid. Unfortunately, according to one study in dogs,31 eicosapentaenoic acid does not decrease metalloproteinases or arachidonic acid levels in injured cranial cruciate ligament joints following surgical treatment. However, supplements, including capsules and diets containing omega-3 fatty acids, are capable of reducing lameness and improving clinical signs in dogs with OA.32,33 A recent evaluation of omega-3 fatty acids fed to dogs with OA found improvement in their ability to rise from rest and to play.28 In addition, switching dogs to these diets following cruciate ligament injury to one stifle may be able to prevent rupture in the contralateral stifle.34 Although these diets may not prevent increased degenerative

Adding glucosamine and chondroitin supplements to the diet may not improve lameness in dogs but does have the potential to slow OA progression. proteins in the joints of dogs following surgery, they can improve weight bearing and limb use in dogs with naturally occurring OA.32,33 When a diet high in omega-3 fatty acids is fed to dogs before and after experimental cranial cruciate ligament transection and repair, affected dogs have not only better ground reaction forces but also fewer radiographic changes in their stifles following surgery.16 Antioxidants Antioxidants such as vitamin E, vitamin C, and selenium have not been definitively proven to be beneficial to humans or dogs with OA, but many conflicting reports exist.35-39 Therefore, they are not recommended at this time. Methyl-sulfonylmethane (MSM) may improve function and decrease pain in humans, but no clinical trials have been conducted in dogs.16 Glucosamine–chondroitin sulfate Glucosamine and chondroitin sulfate are components of normal joint cartilage that may be capable of rebuilding damaged cartilage.40 A prospective double-blind study of the effects of carprofen, meloxicam, and glucosamine–chondroitin sulfate (Cosequin DS, www.nutramaxlabs.com) on ground reaction forces of dogs with established OA found that Cosequin had no effect and only carprofen and meloxicam improved lameness in the study dogs.41 Dasuquin, one of the new formulations of Cosequin, may have a more profound effect on lameness because it contains unsaponifiables of avocado and soybeans, which have been shown, at least experimentally in humans with OA, to reduce inflammation and promote cartilage aggrecan synthesis.42,43 While these nutraceuticals may not lessen pain associated with canine OA, they can decrease matrix metalloproteinases (believed to degrade cartilage in arthritis) and synovial membrane fibrosis, which could slow progression of the disease.44,45 In combination, glucosamine and chondroitin may restore a more normal synovial fluid environment, thereby helping slow OA progression.46 Different formulations of these nutraceuticals have different bioavailability, which must be considered when recommending these supplements. As little as 50% of nutraceutical products on the market today meet their label claims.46 A recent review of OA treatments found a moderate level of comfort for the effectiveness of glucosamine and chondroitin.47,48

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Low-impact exercises that focus on the development of muscles supporting joints with OA may help slow progression of the disease. Polysulfated glycosaminoglycan Polysulfated glycosaminoglycan (PSGAG; Adequan, Novartis; www.adequancanineus.com) can protect articular cartilage from degradative enzymes as well as stimulate chondrocytes to produce normal components of articular cartilage and thus prevent OA.49-52 Puppies from dysplastic parents were given 5 mg/kg IM twice a week from 6 weeks to 8 months of age and had a reduction in coxofemoral subluxation and improved Norberg angles (measure of hip joint congruity).53 The drug inhibits the intrinsic clotting system and can increase coagulation and buccal mucosal bleeding times. Conflicting reports exist as to whether PSGAG is beneficial in slowing OA progression, but the drug does appear to have a greater beneficial effect the earlier it is administered and, therefore, may be best as a preventative.40,54 A recent review of OA treatments found a moderate level of comfort for the effectiveness of PSGAG.47,48,55 Pentosan sulfate Pentosan sulfate, a derivative of PSGAG, is used similarly. It can be given intraarticularly, intramuscularly, or subcutaneously and can decrease the amount of degradative products present in osteoarthritic cartilage.40 Given once weekly at 3 mg/kg SC for 4 weeks following extracapsular repair of a ruptured cranial cruciate ligament, pentosan caused faster recovery of breaking ground reaction forces and decreased collagen degradation products if a partial meniscectomy was performed.56 General observation of the dogs’ gaits following surgery was not different from dogs receiving placebo injections and, therefore, owners may not see the benefit of using this drug postoperatively.56 Other research has shown no effect with pentosan sulfate administration, while one study showed improvement.57,58 Further studies are needed to determine whether administration of pentosan sulfate can slow long-term progression of OA in dogs. Hyaluronan Hyaluronan is produced by chondrocytes and fibroblasts in articular cartilage and synovial fluid to act as a shock absorber and lubricant in the joint. Hyaluronan is given intraarticularly but lasts only a short time in synovial fluid. Its effects are believed to last longer than its actual presence in the joint.59 Therefore, hyaluronan injection does not restore the normal concentration

26

of hyaluronan in the joint or reduce the volume of synovial fluid.59 Hyaluronan may decrease metalloproteinases, stimulate chondrocyte proliferation, and decrease degenerative cytokines, such as tumor necrosis factor-alpha and interleukin-1.60 There are conflicting reports about the effectiveness of hyaluronan in preventing or slowing the progression of OA.47,61,62 Therefore, its use cannot be definitively recommended at this time. High molecular weight with cross-linking of hyaluronan may be a formulation with better efficacy, but further study is needed.60 Additional nutraceuticals Green-lipped mussel (GLM) has PSGAGs and acts as an antiinflammatory through tetraenoic acid. Stabilized lipid preparations may decrease joint swelling and lameness, but there are no definitive studies of its effects.47,63 As part of a formulated diet, GLM has been found to be somewhat beneficial for dogs with OA; however, further studies are needed.55,63 P54FP, an extract of curcuma (a turmeric), has been shown to decrease lameness but not peak vertical force on a force plate system.64 Rarely this nutraceutical can cause a malodor of the skin, urine, and feces.65 Again, further studies are warranted, but its use may help OA patients clinically.34,64 Elk velvet antler has been shown in one objective placebocontrolled study to improve weight bearing in the arthritic limbs of dogs.66 Two of 38 dogs developed Addison’s disease; however, no other dogs were affected, and it was unlikely related to elk velvet antler.66 There is moderately strong evidence that elk velvet antler is effective in treating OA.55

Exercise The type of exercise activities that dogs are engaged in can also affect the progression of OA. For example, strength training

Key Points to Remember • Restriction of caloric intake requires strict owner adherence and compliance. • The rate of weight loss needs to be monitored throughout the weight reduction program. • The role of nutraceuticals in managing OA varies, depending on the specific agent. • Strength training and controlled exercise are important in managing OA progression. • In dogs with OA, transcutaneous electrical nerve stimulation (TENS) is an important component of any joint rehabilitation program. • Recheck examinations should be done every 1 month to 6 months to encourage ongoing progress in the management of OA and to make changes in the patient’s therapeutic protocol as needed. • Owners need to accept that OA is not curable but their dog can live a productive life with a combination therapeutic program that involves nutrition, diet, exercise, and rehabilitative measures.

Rehabilitation & Nutrition in the Overweight/Osteoarthritic Dog

Points to Discuss with Owners • The progression of OA cannot be stopped but can be vent further injury to joints by can reduce progression of the disslowed with the right diet and exercise plan as well as building muscle strength and stimease in human knees compared adherence to the plan for the rest of the dog’s life. ulating conscious proprioception in with passive range-of-motion exer• OA in dogs is managed similarly to how the disease is 67 the injured limb. Proprioception is cises. handled in people. • Determining the right caloric intake for an individual often lost following injury to a The appropriate exercise can dedog is a difficult challenge and may require some time. limb, which can result not only in crease pain associated with mildUsing a computerized weight loss program, such as muscle atrophy but also to further to-moderate OA as well.68,69 The exNestlé Purina’s software program, helps make this challenge easier while tracking the dog’s progress. injury from stumbling, twisting, ercise, however, must be controlled • As with people, a dog’s weight loss takes time. Thus, and abnormal use of the limb. and continued indefinitely or the improvement in lameness may not be achieved until There are several ways to increase beneficial effects will not be longthe dog is at its ideal body weight for managing OA. • Treats and table scraps are necessarily included in the proprioception in dogs; one of the lasting. By controlling exercise, total caloric intake. easiest is engaging in water activity excessive force on the joint and ar• The diet selected for an individual dog may include to increase resistance, thereby alticular cartilage is avoided while some key nutraceutical agents known to have some lowing the dog to feel where its leg building muscle strength. Examples beneficial properties in managing OA. • Success means commitment to a long-term program is in relation to the rest of its body. of controlled exercises include swimthat involves adherence to diet, proper exercise Underwater treadmills stimulate ming, jogging, or walking on nonactivities, and owner compliance. proprioception, build muscle, and slick surfaces (eg, grass lawns) and encourage limb use while reducing treadmill activities. the body weight load on the osteoarthritic joint. If the dog and I recommend that dogs with an increased risk for developing owner cannot participate in underwater treadmill therapy, OA avoid activities that place undue stress on joints, such as other modalities include resistance bands, cavalettis, and balhigh-impact activities on hard or slick surfaces. For example, ance boards.70 dogs that fetch a ball can still do so after a joint injury, but the ball should be rolling slowly on the ground or stopped by the Passive range-of-motion can help maintain joint mobility but time the dog retrieves it. The dog should not retrieve the ball is not a substitute for strength training in dogs with OA. Deon asphalt, and if there are predominantly hardwood, tile, or velopment of muscle in the entire body helps the overweight linoleum floors in the home, area rugs need to be placed where dog by minimizing the stress and strain on arthritic joints and the dog walks. reducing the overall body fat content. When instituting an exercise/rehabilitation program for an overweight osteoarthritic patient, realistic goals must be set Rehabilitation and accepted by the owner (see Points to Discuss with Owners). Increased muscle strength can result in increased stability to A therapy program that is too intense can result not only in joints, thereby reducing pain and slowing the progression of 18 progression of OA in the primarily affected joint but also in OA. Participation in regular exercise, along with weight loss, trauma to other joints, including rupture of the cranial cruciresults in improved function and quality of movement.18 ate ligament, collateral ligament instability, biceps tendonitis, In one study, twice-weekly physiotherapy sessions in a veteriand others.71 nary clinic coupled with weight loss and exercises performed at home reduced lameness in obese dogs with OA within 30 days Continued maintenance of the exercise program is also imof treatment.18 Dogs participating in the study were treated with perative to the long-term outcome of these patients. I usually recommend recheck examinations every 6 months to promote transcutaneous electrical nerve stimulation (TENS), using skin ongoing progress and think it is important for the owner to unelectrodes that send an electrical current to the underlying and derstand that although OA is a disease without a cure, proper intervening muscles, stimulating them to contract. The intensity management allows affected dogs to live a full and productive can be modified to maintain comfort for the patient while inlife, especially if an ideal body weight is maintained. ■ creasing the strength of muscle contractions. Rehabilitation and physical therapy exercises may also pre-

References

I recommend that dogs with an increased risk for developing OA avoid activities that place undue stress on joints, such as highimpact activities on hard or slick surfaces.

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Rehabilitation & Nutrition in the Overweight/Osteoarthritic Dog

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