Diagnostic Aids (Table 4.1)

All cases of FUO should have a laboratory database consisting of a complete blood count (CBC), urinalysis, and biochemical profile. The CBC should include morphology of red blood cells and white blood cells (WBCs), WBC differential, and fibrinogen determination.

Serum protein and albumin determinations characterize either hypoproteinemia or hyperproteinemia. Serum protein electrophoresis and immunoelectrophoresis further classify deficiencies or increased production of proteins. It is prudent to measure serum hepatocellular enzyme activities and serum bile acid concentration for evaluation of hepatocellular damage and function, respectively.

Because much of the abdomen is unavailable to rectal palpa­tion, abdominocentesis and evaluation of peritoneal fluid for protein, cellularity, and cell morphology are justified. Peritoneal fluid is obtained more consistently in horses than in ruminants with abdominal disease because of the presence of the greater omentum and the rapid formation of fibrinous adhesions in ruminants with inflammatory abdominal disease. Peritoneal fluid evaluation is usually most helpful in inflammatory diseases, but it may be diagnostic in some cases of abdominal neoplasia. Bacterial culture and sensitivity of peritoneal fluid are indicated in inflammatory diseases when WBCs show degenerative or toxic changes but are rarely positive unless gross bowel con­tamination has occurred. Polymerase chain reaction (PCR) for Streptococcus equi and/or R. equi may be warranted in horses with evidence of chronic inflammation of the abdominal cavity.

Blood cultures are best used after characterization of a remittent fever and evidence of pyogenic inflammatory disease from the laboratory database.

Serologic evaluation for infectious diseases common in the geographic area and/or patient population should be performed. Single serologic determinations are usually of value only in those diseases in which one positive titer is significant and when the disease is characterized by persistent infection such as EIA, brucellosis, or Johne's disease. In many instances vaccination history and/or accompanying clinical signs must be correlated with titer determinations. Paired samples for toxoplasmosis, babesiosis, and various mycotic diseases (espe­cially coccidioidomycosis) are indicated when the diagnosis remains obscure. Serologic determination of antibody titers to the SeM protein of S. equi can aid in the diagnosis of internal abscessation.⁶² The synergistic hemolysis inhibition (SHI) test may be helpful in the diagnosis of Corynebacterium pseudotu­berculosis infections in horses and small ruminants.^63-65 Virus isolation, PCR, and/or immunohistochemistry, particularly in persistent bovine viral diarrhea (BVD)-infected cattle, may be helpful.

Feces should be tested for the presence of occult blood. Suspicion of gastrointestinal blood or protein loss, intermittent/ chronic diarrhea, and weight loss warrants fecal cultures and

ECG, Electrocardiogram; RBC, red blood cell.

rectal biopsy for ruling out salmonella or infiltrative bowel disease in horses, whereas such signs in adult dairy cattle warrant ruling out abomasal lymphosarcoma and Johne’s disease as the cause.

Also helpful are biopsies of enlarged lymph nodes, accessible abdominal masses, and the liver and kidney when laboratory data indicate abnormalities. Liver biopsies should be cultured and evaluated histologically, because bacterial cholangiohepatitis can be a cause of FUO. Evaluation of biopsies for the presence of immunoglobulins, particularly if skin lesions are present, may add in diagnosis of immune-mediated disorders. Antinuclear antibody determinations and a Coombs test are also indicated in suspected immune-mediated diseases.

Radiographic evaluation, particularly of the thorax, should be performed in horses and small ruminants and is often possible in dairy cattle. In cattle, radiographic evaluation of the cranio- ventral abdomen can help diagnose traumatic reticuloperitonitis. Ultrasonographic examination of the heart may definitively diagnose cardiac abnormalities and may provide more complete scrutiny of other organs in the thorax and abdomen, as well as deep structures of the musculoskeletal system. Ultrasono­graphic examination also aids in percutaneous biopsy of internal structures and may help the practitioner make the decision for exploratory laparotomy.

In equine patients, exploratory laparotomy should be performed only in patients that are becoming progressively debilitated and in which all other avenues of diagnosis have been exhausted. Blind exploratory laparotomies usually do not contribute to diagnosis, are costly, and are not without risk. Standing laparotomy or laparoscopy can be a useful alternative to ventral midline exploratory celiotomy because each of them is less expensive and does not involve general anesthesia. In ruminants, especially adult cattle, exploratory laparotomy is inexpensive and low risk and should therefore be used more routinely as an aid in the diagnosis of an FUO.

Nuclear imaging and imaging using autologous WBCs labeled with technetium-99m or indium-111 are increasingly used in human and small animal medicine.⁶⁶ These procedures may be helpful in localizing abscesses, particularly osteoarticular infections. These modalities may prove to be of benefit for large animals as the modalities’ availability increases. As a note, the use of nuclear imaging in food-producing animals is strongly discouraged.

The use of therapeutic trials of antimicrobials in FUO should be restricted to cases in which strong evidence of a bacterial infection exists. The therapeutic regimen should be as specific as possible and administered for a predetermined amount of time. Inappropriate use of broad-spectrum antimicrobials for all febrile diseases contributes to interference in accurate diagnosis.