Difficulties in the Antemortem diagnosis of FIP (cytology, immunology, histology).

Difficulties in the antemortem diagnosis of FIP (cytology, immunology, histology ) Saverio Paltrinieri, DVM, PhD, dipl ECVCP Dipartimento di Patologia Animale, Igiene e Sanità Pubblica Veterinaria, Università di Milano, Italy Feline Infectious Peritonitis (FIP) is a lethal disease of felids due to a feline coronavirus (FcoV). FCoVs are widely distributed in feline populations. The large part of FCoV strains, known as Feline Enteric Coronavirus (FECV) is usually responsible of mild enteritis. FCoVs are genetically unstable and new quasispecies are quite continuously generated in FCoV-endemic environment and even in the same cat, and pathogenic strains of FCoVs, known as Feline Infectious Peritonitis Viruses (FIPV) can be generated by a series of mutation during FECV replication. The FIPV is able to infect macrophages and within macrophages it is distributed throughout the body. The immune reaction of the host determines the appearance of granulomatous lesions (dry FIP) or of a diffuse vasculitis which induces cavitary effusions (wet form). To date, FECV and FIPV cannot be distinguished by serology or PCR tests. As a consequence, the diagnosis of FIP must only be based on the identification of clinico-pathological or pathological changes in blood and tissues of affected cats. Specifically, cats with FIP had non regenerative normocytic normochromic anemia, elevated white blood cell counts with neutrophilia and lymphopenia, elevated globulin levels with hypoalbuminemia, increased 2- and -globulins and elevated 1-acid glycoprotein levels. Unfortunately, most of these changes can be detected also during diseases other than FIP. More specific tests are thus needed to correctly identify affected cats. In the case of suspect wet FIP, the analysis of the effusions is the best diagnostic method. Specifically, protein and globulin determination, cytology and bacterial cultures should be performed on the effusion: high proteins and/or globulin concentrations in a sterile effusion with cytologic signs of a non-specific inflammatory process are strongly suggestive of FIP. Bacterial cultures and cytology might help us to rule out septic effusions and neoplasia (lymphomas, epithelial tumors), while the detection of macrophages bearing FCoVs in their cytoplasms is required to rule out the suspicion of feline cholangiohepatitis and to confirm the diagnosis of FIP. On this perspective, immunocytochemistry or immunofluorescence on cytocentrifuged effusions are the best diagnostic techniques. In dry forms, a list of possible differential diagnoses (any possible cause of Fever of Unknown Origin, uveitis, neurological alterations, hepatic or renal failure) must be considered to suggest the best diagnostic approach. As previously stated, hematology and serum protein analysis can be strongly suggestive of FIP: the presence of multiple alterations in cats with symptoms suggestive of FIP might highly increase the probability of correctly diagnosing the disease. Nevertheless, the detection of histologic lesions consistent with FIP is considered the only conclusive test for FIP. Special stains can also be used to rule out some possible diagnostic doubt (e.g. Zihel-Neelsen for mycobacterioses). On the contrary immunofluorescence or immunohistochemistry for FCoV can further confirm the diagnosis. Unfortunately, surgical biopsies cannot frequently taken during FIP, due to the poor general conditions of the affected cats. Histologic lesions or FCoV-positive macrophages can be found in ultrasound-guided tru-cut biopsies (TCB), while fine needle aspiration biopsies (FNA) from liver and kidney might allow us to detect a cytological diagnosis of pyogranulomatous inflammation or, again, to perform immunocytochemistry to detect FCoVs within macrophages. In conclusion, the diagnosis of FIP must be obtained by the detection of FCoVs within macrophages. This approach would require to cytocentrifuge the effusion or to perform surgical biospies or ultrasound-guided tru-cut or fine needle aspiration biopsies. If such an approach cannot be followed, the presence of multiple clinico-pathological changes in blood might only support a clinical diagnosis of FIP in both wet and dry forms.