Abstract Immunoglobulin G4‐related disease (IgG4‐RD), which affects many organ systems, has been recognized as a distinct clinical entity in human medicine for just over a decade but has not been previously identified in dogs. In humans, IgG4‐RD is characterized by diffuse IgG4‐positive lymphoplasmacytic infiltrates that commonly lead to increased serum concentrations of IgG4 and IgE, peripheral eosinophilia, tumorous swellings that often include the parotid salivary glands, obliterative phlebitis, and extensive fibrosis. Herein we describe the diagnosis, clinical progression, and successful treatment of IgG4‐RD in an 8‐year‐old female spayed Husky mixed breed dog. Immunoglobulin G4‐related disease should be considered as a differential diagnosis for dogs with vague clinical signs, lymphoplasmacytic swellings, restricted polyclonal gammopathy, eosinophilia or some combination of these findings.
Three dogs under 12 months old were diagnosed with atypical multiple myeloma (MM), having an aggressive multifocal anaplastic round cell sarcoma in bone marrow, viscera, and/or peripheral blood, which were confirmed by cytology and immunohistochemistry to be of plasma cell origin. The intramedullary sarcomas caused myelophthisis, osteolysis, and hypercalcemia. Complete or free light chain monoclonal gammopathy in the serum and/or urine was demonstrated by protein electrophoresis and immunofixation. The polymerase chain reaction for antigen receptor rearrangement assay performed on 2 cases identified a clonally rearranged immunoglobulin gene. Neoplastic cells lacked expression of CD45, CD3, CD18, CD21, CD34, and MHCII by flow cytometry. Immunohistochemistry revealed MUM1 immunoreactivity of the neoplastic cells. Combining all data, the diagnosis was MM. An aggressive form of MM in young dogs should be a differential diagnosis for patients with an immunoglobulin-productive, B cell-clonal, CD45-negative, MUM1-positive discrete cell neoplasm arising from the bone marrow.
Abstract Background English bulldogs disproportionally develop an expansion of small B‐cells, which has been interpreted as B‐cell chronic lymphocytic leukemia (BCLL). However, clonality testing in these cases has often not been supportive of neoplasia. Hypothesis English bulldogs have a syndrome of nonneoplastic B‐cell expansion. Animals Eighty‐four English bulldogs with small‐sized CD21 + B‐cell lymphocytosis in the blood as determined by flow cytometry. Methods This is a retrospective study. We characterized this syndrome by assessing B‐cell clonality, clinical presentation, flow cytometric features, and immunoglobulin gammopathy patterns. We identified 84 cases with CD21+ lymphocytosis among 195 English bulldogs with blood samples submitted to the Colorado State University‐Clinical Immunology laboratory for immunophenotyping between 2010 and 2019. Flow cytometry features were compared to normal B‐cells and BCLL cases. PCR for antigen receptor rearrangements (PARR) by multiple immunoglobulin primers was performed to assess B‐cell clonality. A subset of cases with gammopathy were examined by protein electrophoresis, immunofixation, and immunoglobulin subclass ELISA quantification. Results Seventy percent (58/83) of cases had polyclonal or restricted polyclonal immunoglobulin gene rearrangements, suggesting nonmalignant B‐cell expansion. The median age of all dogs in the study was 6.8 years and 74% were male. The median (range) lymphocyte count was 22 400/μL (2000‐384 400/μL) and B‐cells had low expression of class II MHC and CD25. Splenomegaly or splenic masses were detected in 57% (26/46) of cases and lymphadenopathy in 11% (7/61). Seventy‐one percent (52/73) of cases had hyperglobulinemia and 77% (23/30) with globulin characterization had IgA ± IgM polyclonal or restricted polyclonal gammopathy patterns. Conclusions and Clinical Importance Polyclonal B‐cell lymphocytosis in English bulldogs is characterized by low B‐cell class II MHC and CD25 expression, splenomegaly and hyperglobulinemia consisting of increased IgA ± IgM. We hypothesize that this syndrome has a genetic basis.
Diseases affecting the upper respiratory tract, such as herpesviruses, are well described in captive chelonians worldwide, but their importance in free-ranging populations is less well known. To characterize the disease epidemiology of terrapene herpesvirus 1 (TerHV1), 409 free-ranging eastern box turtles ( Terrapene carolina carolina) in Tennessee and Illinois, US were tested for TerHV1 in 2013 and 2014 using TaqMan quantitative PCR. Whole blood and swabs of the oral mucosa were collected from 365 adults (154 females, 195 males, 16 unknown sex) and 44 juveniles. The prevalence of detection was 31.3% (n=128). Turtles were more likely to be positive for TerHV1 in July (50%; n=67) compared to September (38%; n=44) and May (11%; n=17). Turtles sampled in 2014 had a significantly higher prevalence (50%; n=98) than in 2013 (14%; n=30). In a multivariate model, only season, year, and the interaction between season and year were maintained; turtles were most likely to be positive in July (odds ratio: 30.5) and September (odds ratio: 41.8) 2014 compared to May 2013. The prevalence was not statistically different by state of collection, sex, or age class. Packed cell volume (25.5%) and total solids (4.8 mg/dL) in positive turtles were significantly higher than in negative turtles (23.0%; 4.3 mg/dL). Positive turtles had increased eosinophil concentrations, fewer lymphocytes, and fewer monocytes. No clinical sign was associated with detection of herpesvirus. Widespread DNA evidence of TerHV1 infection was detected in eastern box turtles, and knowledge of the epidemiology of this virus may aid in management of free-ranging and captive individuals.
Background Oclacitinib is a selective Janus kinase inhibitor for the treatment of canine allergic pruritus and atopic dermatitis in dogs. Glucocorticoids and ciclosporin increase urinary tract infection ( UTI ) frequency in dogs with inflammatory skin disease. Objective Prospective study to evaluate the frequency of UTI and subclinical bacteriuria in dogs with allergic dermatitis receiving oclacitinib. Methods Client‐owned dogs ≥2 years of age with a history of allergic dermatitis without apparent history of urinary tract disease or predisposition to UTI were included. Prior to enrolment, urinalysis and quantitative urine culture were performed after a washout period of at least 14 days from systemic antimicrobial drugs and 28 days for ciclosporin and systemic glucocorticoids. Dogs received oclacitinib at labelled dosing for an intended period of 180–230 days with a follow‐up urinalysis and urine culture performed regardless of urinary tract signs. Systemic antimicrobial and immune‐modulating drugs were not administered during the study. Results None of the 55 dogs in this study developed UTI while receiving oclacitinib based on follow‐up urinalysis and urine culture performed during a range of 58–280 days (mean 195 days). Two dogs developed self‐limiting abnormal urinary tract signs without urine culture or urinalysis findings consistent with UTI . Conclusions and clinical importance These findings indicate that bacteriuria is not an expected adverse effect in dogs treated with oclacitinib without a prior history of UTI or predisposing condition during this treatment period. Therefore, routine urine culture is not indicated for such dogs in the absence of abnormal urinalysis or clinical signs of urinary tract disease.
Canine vector-borne diseases (VBDs) induce non-specific dysproteinemias, detectable by serum protein electrophoresis (SPE). VBDs have been reported to induce a monoclonal gammopathy pattern. Monoclonal gammopathies are commonly the result of paraprotein (M-protein) produced by an immunoglobulin-secreting neoplasm.
A 1.5-year-old 1.5-kg (3.3-lb) castrated male Pomeranian was examined because of a 10-month history of diarrhea characterized by hematochezia and weight loss and an acute onset of respiratory distress (ie, tachypnea and dyspnea). A presumptive diagnosis of inflammatory bowel disease had been made previously, and the dog had been treated with budesonide and tylosin but continued to have diarrhea and weight loss.On initial examination, the dog was weak and slightly obtunded. Thoracic radiography revealed a moderate to severe, diffuse, unstructured interstitial pattern. Serum biochemical abnormalities consisted of mild hypoalbuminemia, hypoglycemia, hypocalcemia, hypomagnesemia, and hypocholesterolemia that were likely secondary to chronic gastrointestinal disease and malnutrition. Pyuria and moderate bacteriuria with a single live larva were found on microscopic evaluation of the urine sediment. Fecal examination revealed numerous nematode larvae; the morphology was consistent with first-stage, rhabditiform larvae of Strongyloides stercoralis.A diagnosis of disseminated S stercoralis infection was made. The dog was treated with fenbendazole and ivermectin but developed respiratory collapse approximately 12 hours later and was euthanized because of the poor prognosis. Postmortem examination revealed S stercoralis in the lungs, small intestine, and kidney.Findings illustrated the importance of performing diagnostic testing, including routine fecal examination, to rule out infectious causes of diarrhea before beginning empirical treatment with glucocorticoids such as budesonide. Further, repeated fecal examinations, including Baermann tests, should be considered if a positive response to glucocorticoids is not observed.
Population-based reference intervals (RIs) are vital tools used to characterize health and disease based on laboratory values. The science and statistical basis for RI generation have evolved over the past 50 yr. Current veterinary-specific guidelines by the American Society of Veterinary Clinical Pathology exist for establishing RIs from nondomestic and wild animals. A list of 35 items that should be included during generation and publication of reference data was distilled from the currently available RI guidelines. The archives of five peer-reviewed journals were searched and 106 articles presenting laboratory reference data from nondomestic or wildlife species were identified and each reviewed by two authors to determine compliance with the list of 35 items. A compliance score was calculated as the number of articles that fulfilled the item out of the number where it would have been appropriate to fulfill the item. Most articles reported the number of reference individuals (compliance score 0.98), their partitioning demographics (compliance score 0.95), and sample collection and handling practices (compliance scores 0.97 and 0.96, respectively). Common deficiencies included omitting discussion of the validation status of the analytical methods for the species being evaluated (compliance score 0.12), documentation of use of exclusion criteria (compliance score 0.51), outlier detection (compliance score 0.43), appropriate statistical methods for the reference population (compliance score 0.34), and calculation and presentation of confidence intervals around the reference limits (compliance score 0.35). Compliance scores were not statistically different when stratified on the number of individuals in the largest and smallest evaluated group or the format of the article (full vs short format). Articles that cited RI generation guidelines fulfilled more of the required steps and provided a more complete description of their data (compliance score 0.74) than those that did not cite guidelines (compliance score 0.58). Additional attention to the science of and recommendations for RI generation is recommended to strengthen the utility of published data.
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