ACVIM consensus statement on the treatment of immune thrombocytopenia in dogs and cats.

Management of immune thrombocytopenia (ITP) in dogs and cats is evolving, but there are no evidence-based guidelines to assist clinicians with treatment decisions. Likewise, the overall goals for treatment of ITP have not been established. Immunosuppressive doses of glucocorticoids are the first line treatment, but optimal treatment regimens beyond glucocorticoids remain uncertain. Additional options include secondary immunosuppressive drugs such as azathioprine, modified cyclosporine, and mycophenolate mofetil, usually selected based on clinician preference. Vincristine, human IV immunoglobulin (hIVIg), and transfusion of platelet or red blood cell-containing products are often used in more severe cases. Splenectomy and thrombopoietin receptor agonists are usually reserved for refractory cases, but when and in which patient these modalities should be employed is under debate. To develop evidence-based guidelines for individualized treatment of ITP patients, we asked 20 Population Intervention Comparison Outcome (PICO) format questions. These were addressed by 17 evidence evaluators using a literature pool of 288 articles identified by a structured search strategy. Evidence evaluators, using panel-designed templates and data extraction tools, summarized evidence and created guideline recommendations. These were integrated by treatment domain chairs and then refined by iterative Delphi survey review to reach consensus on the final guidelines. In addition, 19 non-PICO questions covering scenarios in which evidence was lacking or of low quality were answered by expert opinion using iterative Delphi surveys with panelist integration and refinement. Commentary was solicited from multiple relevant professional organizations before finalizing the consensus. The rigorous consensus process identified few comparative treatment studies, highlighting many areas of ITP treatment requiring additional studies. This statement is a companion manuscript to the ACVIM Consensus Statement on the Diagnosis of Immune Thrombocytopenia in Dogs and Cats.

Bacterial culture and immunohistochemical detection of bacteria and endotoxin in cats with suppurative cholangitis-cholangiohepatitis syndrome.

OBJECTIVE: To characterize the frequency and type of bacterial infection by culture- and immunohistochemical (IHC)-based methods and determine the impact of infection on clinical features and survival time in cats with suppurative cholangitis-cholangiohepatitis syndrome (S-CCHS). ANIMALS: 168 client-owned cats with S-CCHS (cases). PROCEDURES: Clinical features, bacterial culture results, culture-inoculate sources, and survival details were recorded. Cases were subcategorized by comorbidity (extrahepatic bile duct obstruction, cholelithiasis, cholecystitis, ductal plate malformation, biopsy-confirmed inflammatory bowel disease, and biopsy-confirmed pancreatitis) or treatment by cholecystectomy or cholecystoenterostomy. Culture results, bacterial isolates, Gram-stain characteristics, and IHC staining were compared among comorbidities. Lipoteichoic acid IHC staining detected gram-positive bacterial cell wall components, and toll-like receptor expression IHC reflected pathologic endotoxin (gram-negative bacteria) exposure. RESULTS: Clinical features were similar among cases except for more frequent abdominal pain and lethargy in cats with positive culture results and pyrexia, abdominal pain, and hepatomegaly for cats with polymicrobial infections. Bacteria were cultured in 93 of 135 (69%) cats, with common isolates including Enterococcus spp and Escherichia coli. IHC staining was positive in 142 of 151 (94%) cats (lipoteichoic acid, 107/142 [75%]; toll-like receptor 4, 99/142 [70%]). With in-parallel interpretation of culture and IHC-based bacterial detection, 154 of 166 (93%) cats had bacterial infections (gram-positive, 118/154 [77%]; gram-negative, 111/154 [72%]; polymicrobial, 79/154 [51%]). Greater frequency of bacterial isolation occurred with combined tissue, bile, and crushed cholelith inoculates. Infection and gram-positive bacterial isolates were associated with significantly shorter long-term survival times. CLINICAL RELEVANCE: S-CCHS was associated with bacterial infection, pathologic endotoxin exposure, and frequent polymicrobial infection in cats. Combined tissue inoculates improved culture detection of associated bacteria.

Clinical, clinicopathologic, and hepatic histopathologic features associated with probable ketoconazole-induced liver injury in dogs: 15 cases (2015-2018).

OBJECTIVE: To characterize clinical, clinicopathologic, and hepatic histopathologic features and outcome for dogs with probable ketoconazole-induced liver injury. ANIMALS: 15 dogs with suspected ketoconazole-induced liver injury that underwent liver biopsy. PROCEDURES: Medical record data were summarized regarding signalment, clinical signs, clinicopathologic and hepatic histopathologic findings, concurrent medications, ketoconazole dose, treatment duration, and outcome. RESULTS: Median age and body weight were 8.2 years (range, 5 to 15 years) and 13.0 kg (28.6 lb; range, 8.2 to 38.0 kg [18.0 to 83.6 lb]), respectively. The most common breed was Cocker Spaniel (n = 5). All dogs received ketoconazole to treat cutaneous Malassezia infections. Median daily ketoconazole dose was 7.8 mg/kg (3.5 mg/lb; range, 4.4 to 26.0 mg/kg [2.0 to 11.8 mg/lb]), PO. Treatment duration ranged from 0.3 to 100 cumulative weeks (intermittent cyclic administration in some dogs); 6 dogs were treated for ≤ 10 days. Common clinical signs included lethargy, anorexia, and vomiting. All dogs developed high serum liver enzyme activities. Hepatic histopathologic findings included variable lobular injury, mixed inflammatory infiltrates, and conspicuous aggregates of ceroid-lipofuscin-engorged macrophages that marked regions of parenchymal damage. Five dogs developed chronic hepatitis, including 3 with pyogranulomatous inflammation. Of the 10 dogs reported to have died at last follow-up, survival time after illness onset ranged from 0.5 to 165 weeks, with 7 dogs dying of liver-related causes. CONCLUSIONS AND CLINICAL RELEVANCE: Findings for dogs with hepatotoxicosis circumstantially associated with ketoconazole treatment suggested proactive monitoring of serum liver enzyme activities is advisable before and sequentially after initiation of such treatment.

Characterization of aminoaciduria and hypoaminoacidemia in dogs with hepatocutaneous syndrome.

OBJECTIVE To characterize aminoaciduria and plasma amino acid concentrations in dogs with hepatocutaneous syndrome (HCS). ANIMALS 20 client-owned dogs of various breeds and ages. PROCEDURES HCS was definitively diagnosed on the basis of liver biopsy specimens (n = 12), gross and histologic appearance of skin lesions (4), and examination of skin and liver biopsy specimens (2) and presumptively diagnosed on the basis of cutaneous lesions with compatible clinicopathologic and hepatic ultrasonographic (honeycomb or Swiss cheese pattern) findings (2). Amino acid concentrations in heparinized plasma and urine (samples obtained within 8 hours of each other) were measured by use of ion exchange chromatography. Urine creatinine concentration was used to normalize urine amino acid concentrations. Plasma amino acid values were compared relative to mean reference values; urine-corrected amino acid values were compared relative to maximal reference values. RESULTS All dogs had generalized hypoaminoacidemia, with numerous amino acid concentrations < 50% of mean reference values. The most consistent and severe abnormalities involved glutamine, proline, cysteine, and hydroxyproline, and all dogs had marked lysinuria. Urine amino acids exceeding maximum reference values (value > 1.0) included lysine, 1-methylhistidine, and proline. CONCLUSIONS AND CLINICAL RELEVANCE Hypoaminoacidemia in dogs with HCS prominently involved amino acids associated with the urea cycle and synthesis of glutathione and collagen. Marked lysinuria and prolinuria implicated dysfunction of specific amino acid transporters and wasting of amino acids essential for collagen synthesis. These findings may provide a means for tailoring nutritional support and for facilitating HCS diagnosis.

Hepatocutaneous syndrome in Shih Tzus: 31 cases (1996-2014).

OBJECTIVE: To characterize findings in Shih Tzus with progressive superficial necrolytic dermatitis and degenerative vacuolar hepatopathy consistent with hepatocutaneous syndrome. DESIGN: Retrospective case series. ANIMALS: 31 Shih Tzus. PROCEDURES: Medical records were reviewed to obtain information on signalment, history, treatment, outcome, and results of clinicopathologic testing, abdominal ultrasonography, and histologic examination of skin and liver specimens. A pedigree analysis was performed. RESULTS: There were 16 males and 15 females. Median age at the time of diagnosis was 8 years (range, 5 to 14 years). Common clinical signs included lethargy, inappetence, weight loss, and lameness. Twenty-five dogs had cutaneous lesions consistent with hepatocutaneous syndrome; the remaining 6 initially only had hepatic abnormalities, but 3 of the 6 subsequently developed cutaneous lesions. Common clinicopathologic abnormalities included microcytosis (15/24 [63%] dogs) and high serum alkaline phosphatase activity (24/24 [100%] dogs). Hepatic ultrasonographic findings included a hyperechoic or heteroechoic appearance to the parenchyma with innumerable hypoechoic nodules. Histologic hepatic lesions consisted of degenerative vacuolar (glycogen and lipid) hepatopathy associated with minimally fibrotic to nonfibrotic, noninflammatory, proliferative nodules. Pedigree analysis confirmed a common ancestry in 12 of 18 dogs. Median survival time was 3 months (range, 1 to 36 months). CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that HCS may have a heritable component in Shih Tzus, although the condition may also be identified in Shih Tzus without affected relatives. Clinical, clinicopathologic, ultrasonographic, and histologic abnormalities in affected Shih Tzus were similar to those previously reported for dogs of other breeds with HCS.