1. Veterinary Specialists of South Florida Presents…

2. Anaphylaxis Veterinary Specialists of South Florida Karina Tam, DVM

3. Darci - Signalment & History 5 years old FS Miniature Schnauzer mix Acute vomiting and hematochezia few hours before presentation No known chemicals, toxins or foreign body At rDVM – PCV 62%, TP 7.2mg/dl, melena Received fluid bolus, referred here for HGE

4. Physical exam QAR Pale mucous membrane 5% dehydrated Nausea on abdominal palpation Rectal exam – anatomically normal, no feces present

5. Diagnostics CBC/CHEM HCT 57.1%, ALT >5000 IU/L, GGT 23 IU/L Coagulation tests PT – 19 sec (12-17) PTT 127 sec (71-102) cPLI – positive Blood pressure – 75-80mmHg Thoracic & abdominal radiographs - wnl

6. Initial approach Treat it as liver toxicity Hospitalization Plasmalyte bolus Plasmalyte CRI with KCl and Vitamin B Ondensetron N Acetylcystine Famotidine Metronidazole Blood pressure and PCV/TS monitoring

7. The next day: PE More bright and alert Rectal exam – melena Blood pressure – wnl Liver panel: ALT >5000 IU/L, GGT 22 IU/L PCV 38%, TS 6.4g/dl Fecal - negative

8. Additional diagnostics Abdominal ultrasound Both kidneys: decreased internal architecture – R/O: chronic renal disease Gallbladder: Thickened and hyperechoic wall with normal size and shape – R/O: cholecystitis and ??? The rest – wnl

9. Gallbladder wall thickening and elevated ALT Anaphylaxis!! Original study: Quantz JE et al. Elevation of alanine transaminase and gallbladder wall abnormalities as biomarkers of anaphylaxis in canine hypersensitivity patients. JVECC 19(6) 2009: 536-544

10. Quick review of hypersensitivity Type I - immediate, IgE dependent Atopy, feline asthma, anaphylaxis etc Type II – cytotoxic, IgG and IgM dependent IMHA, ITP, pemphigus foliaceous etc Type III – immune complexes, IgG and IgM complex dependent Glomerulonephritis, systemic lupus erythematosus etc Type IV – delayed (T cell dependent) Polymyositis, immune-mediated thyroiditis etc

11. Type I Hypersensitivity http://arapaho.nsuok.edu/~castillo/TypeI(anaphylaxis).html

12. Quick review of hypersensitivity Antigens that trigger anaphylaxis NSAIDs Antibiotics Glucocoridcoids Opiates Vaccines Foods Insect, venoms Others

13. Type I Hypersensitivity Acute allergic reactions Local, cutaneous (erythema, pruritis, urticaria, angioedema), no systemic signs Mild systemic hypersensitivity reactions More generalized, cutaneous +/- fever Moderate systemic hypersensitivity reactions Two or more organs involved, normotensive Severe systemic hypersensitivity reactions Collapse/syncope, hypotension

14. Quantz’s study Evaluate ALT and gallbladder wall in dogs with anaphylaxis Primary target organs of anaphylaxis in dogs: GI tract Liver Primary target organ of anaphylaxis in cats: Respiratory tract

15. Quantz’s study - ALT Type I hypersensitivity reaction  histamine release from GI  portal vein  hepatic arterial vasodilation (in 7 seconds!)  constrict hepatic venous sphincters @ hepatic veins and inferior vena cava  changes in blood flow  ischemia and hypoxia  hepatocellular damage  inflammatory mediators  hepatocellular damage ALT (leakage enzyme) – indicator of hepatic damage

16. Quantz’s study - ALT Half life – 60 hours (5 days) Rapid elevation with anaphylaxis– within 12 hours Back to normal in 2-3 weeks

17. Quantz’s study – Gallbladder wall Normal gallbladder wall – poorly visualized, 2-3mm in thickness Abnormal gallbladder wall – multiple striations, thickness >3mm R/O – 1 o liver disease, portal hypertension, blockage of venous drainage of the gallbladder Anaphylaxis causes hepatic venous outflow obstruction Decreased venous drainage of the gallbladder See multiple striations or thickening Sometimes see gallbladder changes much earlier than ALT changes

18. Darci GI signs – vomiting, hematochezia Elevated ALT Thickened gallbladder wall Hypotension  Anaphylaxis

19. Darci Improved really well in the next 2 days ALT >5000 IU/L on the 3 rd day Sent home Recheck liver panel in 3 weeks

20. We would like to thank you for your continued support and referrals.

21. References Castillo R. 2005. Type I (Anaphylaxis). Immunopathology. http://arapaho.nsuok.edu/~castillo/TypeI(anaphylaxis).html http://arapaho.nsuok.edu/~castillo/TypeI(anaphylaxis).html Cote E. 2007. Anaphylaxis. Clinical Veterinary Advisor: Dogs and Cats. Mosby. St. Louis. 1 st Ed. P.60-62. Nelson RW & Couto CG. 2009. Pathogenesis of Immune- Mediated Disorders. Small Animal Internal Medicine. Mosby. St. Louis. 4 th Ed. P. 1389-1392 Quantz JE et al. 2009. Elevation of alanine transaminase and gallbladder wall abnormalities as biomarkers of anaphylaxis in canine hypersensitivity patients. JVECC 19(6): 536-544 Silverstein DC & Hooper K. 2009. Anaphylaxis. Small Animal Critical Care Medicine. Mosby. St. Louis. P. 727-730 Thrall et al. 2006. Laboratory elvaluation of the liver. Veterinary Hematology and Clinical Chemistry. Blackwell. Iowa. P. 358-360