The Yellow Cat: Diagnostic & Therapeutic Strategies
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Peer Reviewed THE YELLOW CAT: DIAGNOSTIC & THERAPEUTIC STRATEGIES The Yellow Cat: Diagnostic & Therapeutic Strategies Craig B. Webb, PhD, DVM, Diplomate ACVIM (Small Animal Internal Medicine) Colorado State University There is no mystery when it comes to a “yellow” cat. Icterus and jaundice—both of which describe a yellowish pigmentation of the skin—indicate hyperbilirubinemia, a 5- to 10-fold elevation in serum bilirubin concentration. However, this is where the certainty ends and the diagnostic challenge begins. The icteric cat presentation is not a sensitive or specific marker of disease, despite the visually obvious and impressive clinical sign (Figure 1).1 The objective of this article is to briefly review differentials for hyperbilirubinemia in the cat, and present a diagnostic and therapeutic strategy that will help practitioners approach this problem in an efficient and effective manner. FIGURE 1. Icteric pinna of a cat in the critical HYPERBILIRUBINEMIA: ORGANIZATION care isolation unit; prehepatic hemolysis BY LOCATION and anemia are a result of Cytauxzoon felis infection. Hyperbilirubinemia The differentials for hyperbilirubinemia should be results when organized by location: prehepatic, hepatic, and serum bilirubin posthepatic. While, in cats, it is common to find Hepatic Disease concentrations concurrent disease processes, starting from this A significant decrease, or loss, of hepatocellular reach 2 to 3 mg/dL foundation is the first step toward an effective and function effects bilirubin metabolism, and (35–50 mcmol/L). efficient diagnostic workup of icteric cats. frequently results in intrahepatic cholestasis (Table 1, page 40). Unconjugated bilirubin from damaged Prehepatic Disease hepatocytes is present, although the majority of Hemolysis releases hemoglobin, which is then bilirubin that appears in the cat’s circulation is metabolized through biliverdin to bilirubin in the conjugated, having completed the metabolic step liver. Hepatocytes in the healthy feline liver have a prior to encountering the cholestatic overflow into large capacity for uptake, conjugation, and excretion the vasculature.2 of bilirubin. Prehepatic icterus is most likely due to the Posthepatic Disease combination of a large increase in bilirubin from Extrahepatic biliary disease interferes with the hemolysis and a degree of intrahepatic cholestasis normal flow of bile and the final steps in bilirubin secondary to hypoxia.2 In dogs, the most common excretion, resulting in extrahepatic cholestasis cause of prehepatic hyperbilirubinemia is immune- (Table 1, page 40). As with intrahepatic disease, mediated hemolytic anemia (IMHA), but that both unconjugated and conjugated bilirubin appear CE condition appears to be quite rare in cats. The list in the serum, rendering the biochemical distinction of prehepatic causes of hyperbilirubinemia in cats is between conjugated and unconjugated serum ARTICLE extensive (Table 1, page 40). bilirubin of minimal diagnostic importance. 38 TODAY’S VETERINARY PRACTICE | September/October 2016 | tvpjournal.com THE YELLOW CAT: DIAGNOSTIC & THERAPEUTIC STRATEGIES Peer Reviewed COMMON CAUSES OF PREHEPATIC present in a variety of other purebred and domestic HYPERBILIRUBINEMIA shorthair cats.9 Interestingly, Abyssinian and Somali Infectious Disease breeds have also been shown to suffer from another Infectious disease is a relatively common cause of inherited cause of prehepatic hemolysis: increased prehepatic hemolysis in cats. erythrocyte osmotic fragility. Genetic testing has Mycoplasma species, particularly Mycoplasma been developed for screening cats for PK deficiency haemofelis, can cause significant erythrocyte and is commercially available (vgl.ucdavis.edu/ destruction, anemia, hyperbilirubinemia, and clinical services/pkdeficiency.php) disease. Outdoor, male, and/or shelter cats appear to be at increased risk, and coinfection with feline Other Causes of Hemolysis immunodeficiency virus (FIV) is common.3-5 Hemolysis secondary to hypophosphatemia has Concurrent diseases, immunosuppression, become rare due to heightened awareness, diligent and stress appear to impact the course and severity monitoring, and proactive intervention during the of disease and outcome of treatment. An eventual treatment of diabetic ketoacidosis. recurrence of disease is seen with some frequency in Disseminated intravascular coagulation is also those cats that show a clinical response to treatment. a rare occurrence, seen predominantly in the critical Feline leukemia virus (FeLV) infection care setting, but serving as a reminder that prehepatic can trigger a host immune response that results hemolysis can occur as a secondary consequence in a in immune-mediated prehepatic erythrocyte variety of diseases. destruction. This may be the result of a virus-induced Feline erythrocytes are susceptible to oxidative expression of antigens on the red blood cell (RBC) stress, and a large variety of toxins and drugs surface. Immune-mediated thrombocytopenia may (including acetaminophen, benzocaine, methylene accompany IMHA in cats with underlying FeLV blue, phenazopyridine, onions/onion powder, infection.6 propylene glycol, and propylthiouracil) can cause Cytauxzoon felis is transmitted by ticks (Am- Heinz body anemia or hemolytic destruction of RBC blyomma americanum) and appears to be increasing membranes. in prevalence and geographical distribution in the United States, expanding from the southeastern COMMON CAUSES OF HEPATIC portion of the country. Risk for infection increases HYPERBILIRUBINEMIA with increased exposure to the tick vector, and the Feline Hepatic Lipidosis progression of clinical disease is rapid and often fatal. Hepatic lipidosis appears to be a unique feline Babesia felis can cause severe prehepatic phenomenon, highlighting that hepatic metabolism hemolysis and anemia in cats, but appears to be rare in the cat is different from many other species.10 outside of costal South Africa.7 Although feline hepatic lipidosis may be an idiopathic (Figure 2) and, therefore, primary problem, it quite Immune-Mediated Hemolytic Anemia frequently occurs secondary to another disease that Primary IMHA appears to be quite rare in cats. caused the cat to stop eating. It is difficult to characterize feline IMHA or determine risk factors because of the paucity of cases in the literature, but younger male cats may be overrepresented. The prognosis is guarded, with a mortality rate of 25%.8 Inherited Erythrocyte Disorders Erythrocyte pyruvate kinase (PK) deficiency is a very rare inherited disorder transmitted as an autosomal recessive trait, causing prehepatic hemolysis. Cats usually present as young adults, and the severity of the anemia and clinical signs is variable and may change over time, ranging from asymptomatic to hemolytic crisis. FIGURE 2. The liver (seen laparoscopically) of a The disease is most frequently described in cat with idiopathic hepatic lipidosis. Abyssinian and Somali breeds but may also be tvpjournal.com | September/October 2016 | TODAY’S VETERINARY PRACTICE 39 Peer Reviewed THE YELLOW CAT: DIAGNOSTIC & THERAPEUTIC STRATEGIES TABLE 1. Hyperbilirubinemia in Cats: Differential Diagnoses & Clinical Signs pain diarrhea / OTHER CLINICAL SIGNS Anorexia Lethargy Fever Lymphadenopathy Vomiting loss Weight Anemia Abdominal PREHEPATIC HYPERBILIRUBINEMIA Mycoplasma species23 Hypothermia x x x Physiologic murmur Increased heart rate/respiratory effort secondary to anemia Cytauxzoon felis24 Dehydration x x x Evidence of shock Progression to moribund dyspnea and hypothermia Feline infectious peritonitis Effusive/wet FIP: Ascites, pleural effusion x x x x Dry FIP: Ocular and neurologic signs Babesia species x x x x Feline leukemia virus Immune suppression x Secondary infection Feline immunodeficiency virus Oral inflammation x x x Secondary infection and lymphoma Immune-mediated hemolytic Signs of primary IMHA, excluding identifiable causes x x x anemia8,25 Pica Erythrocyte PK deficiency26 Pica Increased erythrocyte osmotic x x x x fragility27 Neonatal isoerythrolysis28 Cessation of nursing, failure to thrive Acute kidney injury x Disseminated intravascular coagulation Death Pigmenturia Transfusion reaction29 Erythema or pruritus Tremor, convulsion Vocalization Shock x x Dyspnea or tachypnea Cardiopulmonary arrest Tachycardia or bradycardia Hypophosphatemia30,31,a Clinical signs usually consistent with acute hemolysis x x x Weakness Tachypnea, tachycardia Microangiopathic hemolytic Clinical signs vary with condition and severity anemia32,b Hyperthermia x x x x Obtundation Cardiopulmonary arrest Drugs, toxins, envenomation, Clinical signs nonspecific and depend on underlying etiology; may include oxidative stress c clinical signs associated with Microangiopathic hemolytic anemia (above) and allergic reaction (eg, swelling, pain, redness, focal inflammation) Cholangitis COMMON CAUSES OF POSTHEPATIC In contrast to dogs—in which hepatic disease is HYPERBILIRUBINEMIA usually located in the liver parenchyma—feline liver Extrahepatic Bile Duct Obstruction disease typically targets the biliary system, and is Cholelithiasis may be obstructive and is, thus, most commonly seen as cholangitis. The World Small approached as a cause of extrahepatic bile duct ob- Animal Veterinary Association Liver Standardization struction (EHBO). Other causes of EHBO include Group clarified the terminology, defining feline tumors, nonneoplastic masses, cholecystitis, inspissat- cholangitis as neutrophilic (acute or chronic), ed bile, cholangitis, and pancreatitis.