Joel Baines & Cheryl Balkman -- IDR -- Case Presentation -- (12-6-2024) PDF

Ceefer: A Case Presentation Jaimeson Kass, MVB Cheryl Balkman, DVM 12/1/2023  Ceefer Domestic Shorthair (DSH) cat Female, Spayed Young adult Chief Complaints: ○ Decreased Appetite ○ Weight Loss ○ Decreased activity level Patient medical histor...

Ceefer: A Case Presentation Jaimeson Kass, MVB Cheryl Balkman, DVM 12/1/2023  Ceefer Domestic Shorthair (DSH) cat Female, Spayed Young adult Chief Complaints: ○ Decreased Appetite ○ Weight Loss ○ Decreased activity level Patient medical history Adoption Found as a stray about 6 months ago Other Pets 5 other cats → 3 barn, 2 indoor/outdoor Ceefer 2 dogs, 4 horses Breed : DSH Vaccine Status Age : Unknown Vaccinated about 3 months ago against Panleukopenia/calicivirus/herpes-1 & Rabies Lifestyle : Indoor/Outdoor Gender : Female Retroviral Status Weight : 4.8kg Unknown/Never Tested What other history information do you want from the owner? Further History How Long? Previous issues? About a month, getting Occasional sneezing progressively worse Diarrhea? Vomiting? Don’t think so, but she No sometimes goes outside Hydration? Diet? No increased drinking or Fancy Feast dry, some wet urinating, no decrease What kind of appetite did either she have before illness? Physical examination Demeanor Quiet, Alert, Responsive Thoracic Auscultation HR 180, no murmur or arrhythmia RR 28, increased bronchovesicular sounds Temperature 101.2°F Normal stool on thermometer Physical examination Oral Exam MM pale pink and tacky, CRT 2-3s Gingiva erythematous with multiple focal oral ulcers Abdominal Palpation Comfy, not nauseous. Both kidneys feel irregular on palpation, normal to slightly enlarged in size. Problem List Decreased appetite Weight loss Lethargy Mild dehydration (tachy MM, longer CRT) Oral ulcers/stomatitis Abnormal lung sounds Irregular kidneys Differential Diagnosis D Degenerative A Anomalous M Metabolic N Neoplasia I Inflammatory/Infections/Immune-mediated T Trauma/Toxin Differential Diagnosis V Vascular I Infectious N Neoplasia D Degenerative I Inflammatory C Congenital A Autoimmune T Toxin/Trauma E Endocrine/Metabolic What diagnostic tests would you like to perform? Diagnostic Tests Complete Blood Count (CBC) Chemistry profile (Chem) Urinalysis Retroviral testing ○ FeLV, FIV FeLV/FIV Snap Test Positive Control FIV FeLV Negative Control What patient samples can you use to run an FeLV test? Whole Blood, Serum, Plasma What is the snap test? ELISA for antigen What is the snap test detecting? Soluble p27 viral antigen So we have a positive snap test… Now what? Confirm positive results - IFA (immunofluorescent assay) - Detects antigen within leukocytes What would be another option if this were part of a routine wellness exam and the patient was healthy? Retest in 3 months Consequences of Infection Classification Abortive Viral replication terminated by effective cell mediated and humoral immune response Likely occurs when viral exposure is low Probably a rare event Cats are neither viremic nor contagious (no viral shedding) All FeLV testing is negative Pathogenesis is not observed Vaccine presumed useful. Consequences of Infection Classification Regressive/Latent Cats are contagious during transient viremia (can test positive on ELISA (snap) early after exposure) Virus replication/viremia eliminated prior to or shortly after bone marrow infection ○ Viral shedding only happens during transient viremia or after reactivation Viremia clears - remain negative for all tests that detect antigen (ELISA/IFA) Pathogenesis is uncommon, but possible (reactivation) ○ If provirus DNA is present in bone marrow stem cells (Positive PCR) Vaccine not useful Consequences of Infection Classification Progressive Cats persistently contagious (viral shedding) Positive on ELISA, IFA, PCR FeLV-associated disease common Pathogenesis usually observed within 3 years (median PFI 2.5-3yrs) Poor prognosis Vaccine not useful  How might you explain discordant results (such as ELISA snap positive but IFA negative) Early in disease process, Lab error, Patient cleared infection, transient viremia VCNA 2020 What’s New in FeLV Hartman et al. Consequences of Infection Classification Abortive Snap -ve IFA -ve Proviral FeLV DNA (PCR) -ve Anti-FeLV antibodies (various tests) +ve (variable titres) Replicating virus (virus isolation) in whole blood -ve Viral RNA (RT-PCR) whole blood -ve Consequences of Infection Classification Regressive/Latent Snap -ve (only +ve during transient viremia or after reactivation) IFA -ve (only +ve during transient viremia or after reactivation) Proviral FeLV DNA (PCR) +ve Anti-FeLV antibodies (various tests) +ve (high titres) Replicating virus (virus isolation) in whole blood -ve (only +ve during transient viremia or after reactivation) Viral RNA (RT-PCR) whole blood -ve (usually) Consequences of Infection Classification Progressive Snap +ve IFA +ve (~3 weeks after snap) Proviral FeLV DNA (PCR) +ve Anti-FeLV antibodies (various tests) -ve (or low titres) Replicating virus (virus isolation) in whole blood +ve Viral RNA (RT-PCR) whole blood +ve Back to our patient Updated Problem List Decreased appetite Left shift (increased Weight loss band neutrophils) Lethargy Monocytosis Dehydration Hyperglobulinemia Oral ulcers Hypercalcemia Abnormal lung sounds FeLV - Snap positive Irregular kidneys Differential Diagnosis N Neoplasia I Inflammatory/Infections/Immune-mediated Does the hypercalcemia help us to prioritize one over the other?  What are your top differentials for feline hypercalcemia? SHIRT: Spurious, Hyperparathyroidism, Idiopathic, Renal, Tumor What additional diagnostic tests would you like to perform? Diagnostic Tests Imaging! ○ Thoracic radiographs ○ Abdominal ultrasound Thoracic Radiographs (normal L lateral for reference) Thoracic Radiographs Thoracic Radiographs Abdominal Ultrasound - normal feline kidneys for reference Abdominal Ultrasound Updated Updated Problem List Decreased appetite Left caudal lung lobe mass Weight loss Bilateral renal masses Lethargy Dehydration Oral ulcers Abnormal lung sounds Irregular kidneys Left shift (increased band neutrophils) Monocytosis Hyperglobulinemia Hypercalcemia FeLV - Snap positive Updated Differential Diagnosis N Neoplasia → Lymphoma, Carcinoma I Infection → Pneumonia, renal abscesses  What diagnostic tests can help us to differentiate neoplasia from infection? Fine needle aspiration (FNA) and cytology Cytology NOT OUR PATIENT! Necropsy example FeLV and Lymphoma ~30% of cats with progressive FeLV infections develop lymphoid malignancies (lymphoma, leukemia) ○ 60X greater risk of developing lymphoma 25-50% of cats with renal LSA are FeLV+ Before the 1980’s, >70% of cats with LSA were FeLV+ From 1983 - 2003 ~ 15% of cats with LSA were FeLV+ ○ Half of these cases were seen before 1991 JVIM 2005 Louwerens et. al. So, What do you think of the vaccine? FeLV and Lymphoma How does being FeLV+ increase the risk of developing lymphoma? Insertional mutagenesis: integrated provirus may activate a proto-oncogene or disrupt a tumor suppressor gene U3-LTR region has potential to enhance the transcription of adjacent cellular genes Common integration sites for FeLV identified in six loci with feline lymphoma: ○ c-myc ○ fit-1 ○ flvi-1 ○ pim-1 ○ flvi-2 (contains bmi-1) ○ flit-1 Viral Insertion into Cellular Oncogene Viral Insertion into Cellular Oncogene Aberrant Oncogene Expression There is no virus that causes cancer; FeLV is participating, to a small degree, in a complex process Hallmarks of Cancer; adapted from Hanahan and Weinberg, 2011 Lymphoma is a systemic cancer. In broad terms, how do we treat systemic cancers? Chemotherapy Treatment/Prognosis Multidrug protocol gives the best chance for achieving remission CHOP ○ Cyclophosphamide ○ Doxorubicin ○ Vincristine ○ Prednisolone FeLV positive status may result in a shorter remission duration and survival time Patient Outcome Ceefer is currently being treated with chemotherapy and responding well. Plenty to think about… Questions?