Canine Protein-Losing Enteropathy Approach 2024

2/16/2024 Canine Proteinlosing Enteropathy NOLIE PARNELL, DVM, DACVIM G 132 X49333 [email protected] What is Protein-losing Enteropathy (PLE)?  Most severe form of small intestinal tract diseases  Most are in the form of chronic enteropathy  Occasionally is acute enteropathy   Differential di...

2/16/2024 Canine Proteinlosing Enteropathy NOLIE PARNELL, DVM, DACVIM G 132 X49333 [email protected] What is Protein-losing Enteropathy (PLE)?  Most severe form of small intestinal tract diseases  Most are in the form of chronic enteropathy  Occasionally is acute enteropathy   Differential diagnoses for PLE mirror those of enteropathies but represent the most severe manifestation of that disease   Ex. Canine parvoviral enteropathy Ex. Inflammatory bowel disease PLE can be considered intestinal failure 1 2/16/2024 Breed Association with PLE  Yorkshire Terrier  Rottweiler  German Shepherd  Soft-coated Wheaten Terrier  Maltese  Chinese Shar Pei  Basenji  Irish Setter  Norweigen Lundehund Causes of PLE  Most Common Causes in Referral Center  Inflammatory bowel disease   New term: Steroid-responsive enteropathy  Lymphosarcoma  Intestinal lymphangiectasia  Primary  Seconday However, the above may not be the most common causes in your practice so must have a thorough diagnostic approach 2 2/16/2024 Differential Diagnoses  Food-responsive enteropathy  Antibiotic-responsive enteropathy (dysbiosis)  Intestinal neoplasia  Hypoadrenocorticism  Viral gastroenteritis (ex. parvoviral enteritis)  Parasitic enteritis (ex. hookworm)  Fungal enteropathy (ex. Histoplasmosis)  Any cause of mucosal injury (ex. NSAID, thrombocytopenia, etc)  Rarely, congestive heart failure Chronic Inflammatory Enteropathies ARE = Antibiotic-responsive enteropathy Front. Vet. Sci., 21 September 2022 Sec. Comparative and Clinical Medicine Volume 9 - 2022 3 2/16/2024 Diagnostics Approach to the hypoalbuminemic patient  First step: rule out hepatic & renal causes  Serum chemistry panel, CBC, urinalysis   Urine protein:creatinine ratio   Blood Glucose, BUN, ALT, ALP should be WNL 30%  Anorexia  OR 25.96 (95% CI) 1.00  0.75 BCS lower in PLE dogs Control 0.50  Kaplan-Meier survival estimates PLE 0.25 Hypoalbuminemia negative prognostic indicator 0.00  0 1000 P = 8 years) PLE (median survival = 701 days) 8 2/16/2024 Using nutrition in the treatment of PLE Riley Griffin 8 yr FS Cockapoo Albumin (g/dl) (2.3-3.9) 2.5 2 1.5 1 0.5 0 O2/21/13 O2/27/13 O3/27/13 9 2/16/2024 Is a therapeutic diet necessary? n= 26 Both diets from Royal Canin (HP and Intestinal Diet) 10 2/16/2024 Similar response rate in both groups (89%/88%) Test group: 87% asymptomatic Control group: 28% asymptomatic 11 2/16/2024 Nutritional Strategies for the PLE Patient  Hydrolyzed diets  Ultra-hydrolyzed diets  Ultamino (Royal Canin)  Elemental (Nestle-Purina)  Limited antigen diets  Low-fat diets  Lymphangectasia  Home-cooked diets  Elemental diets Hydrolyzed Diets  Degradation process which disrupts intact proteins  Enzymatic hydrolysis  Prevent immunologic detection  Has shown to be effective in management of refractory IBD  Vary in protein isolate  Chicken vs Soy most common  Ultamino (Royal Canin)  Kibble size for dogs can be problematic for smaller dogs  Palatability can be a problem for some patients Cave, Vet Clin NA: 2006 Marks,Vet Ther: 2002 12 2/16/2024 Limited-antigen Diets  Also called novel protein  Utilizes an intact protein which the inflamed gut has not historically seen  Has been shown to be effective in management of IBD Low-fat Diets  All therapeutic diets for chronic enteropathies are reduced fat  Lymphangiectasia = low-fat   ↓ lymphatic flow to reduce lacteal dilation and lymphatic pressures to decrease protein loss  MCT Concerns about palatability and energy density with some options 13 2/16/2024 Other Diet Categories Home-cooked diets Elemental  Has been shown to be effective in pruritic dogs  Use in the most severely affected patients  Subset of dogs with CE do better on HC diets  Liquid formulation   Limited ingredients Owner compliance issues   Amino acids  Glucose  < 1% fat Caution using human formulations Pharmaceutical Management  Broad-spectrum dewormer if not recently used  Fenbendazole    50 mg/kg PO x 5 days Antibiotics (for dysbiosis and )  Tylosin: 10- 20mg/kg PO BID  Metronidazole commonly used but should be avoided if possible Probiotics 14 2/16/2024 Cobalamin (Vitamin B12) Supplementation  Should be supplemented if low  Cats should be supplemented with parenteral cobalamin to maximize response to treatment   250 µg SQ per cat  Once q 7 days for 6 weeks  Then one dose after 30 days  Retest 30 days later to determine if continued use is necessary Dogs same protocol  Small dogs: 250 µg SQ  Medium: 500 µg SQ  Large: 750 µg SQ Pharmaceutical Management  Immunosuppression   Prednisone/prednisolone  2 mg/kg/day orally  20 mg/ m2 PO BID if dog is > 27 kgs Dexamethasone  Can be used successfully in some cats which are not responding to prednisolone  0.11 – 0.22 mg/kg q 48 hours 15 2/16/2024 If Prednisone Is Not Your Friend Budesonide Cyclosporine glucocorticoid analogue suppression of mucosal T cells limited systemic absorption efficacy in steroid-refractory IBD suppresses P-AC axis adequately absorbed in severe IBD minimal clinical side effects compounding for small animals $$ Dose:1 mg/cat (small dog)/day PO $$$ Dose: 5 mg/kg PO SID-BID Monitoring 3 mg/large dog/day PO Dose: 3 mg/m2 Allenspach: J Vet Intern Med, 2006 Stroup: Am J Vet Res, 2006 If Prednisone Alone is not Effective  Combination therapy can be effective  Prednisone/prednisolone + azathioprine  Azathioprine: 2 mg/kg PO once daily for 2 weeks then every other day  Not recommended in cats  Prednisone/prednisolone + cyclosporine  Prednisone/prednisolone + chlorambucil  Chlorambucil: 0.1 – 0.2 mg/kg PO once daily 16 2/16/2024 Non-responsive CE/PLE  Unknown the true incidence of nonresponsive PLE  Estimated between 1543% Novel Therapeutic for Refractory PLE  Octreotide  Somatostatin analogue  Parenteral administration only  Currently difficult to source 17 2/16/2024 Fecal Microbiota Transplantation Oral Capsules Enemas Nasoesophageal/Nasogastric Tube Donor animals need to undergo screening healthy (no parasites; no dysbiosis) deworming no antibiotics administered the previous 6 months PROGNOSIS 18 2/16/2024 Prognosis Median # cases survival (decease (days) d) 0.6-0.9 329 14 (6) 1.0-1.3 701 39 (17) 1.4-1.7 31 17 (10) 1.8-2.1 59 6 (2) >2.1 --- 49 (12) mg/dL Kaplan-Meier Graph by ALB Group 0.00 0.25 0.50 0.75 1.00 Serum alb. [ ] 0 1000 2000 analysis time 0.6-0.9 1.4-1.7 >2.1 3000 4000 (days) 1.0-1.3 1.8-2.1 P = 0.0056 Prognostic Factors for PLE  High canine inflammatory bowel disease activity index  Elevated Blood Urea Nitrogen (BUN)  Serum 25(OH)D was significantly lower in dogs with negative outcomes (defined as lived less than 4 months)  Dog: Small and large- cell lymphoma (vs inflammatory enteropathies and lymphangiectasia)  Normalization of CIBDAI and plasma albumin within 50 days was associated with a longer survival Nakashima et al. The Veterinary Journal; 2016 Allenspach et al. BMC Veterinary Research (2017) 13:96 19