OBJECTIVE: To retrospectively evaluate safety and tolerance of leflunomide for long-term treatment of canine idiopathic immune-mediated polyarthritis (IMPA).
METHODS: 27 dogs with clinical signs and synovial fluid cytology supportive of IMPA with ≥ 6 months\' follow-up after starting leflunomide.
METHODS: Medical records were reviewed to identify dogs prescribed leflunomide for treatment of IMPA from February 2012 to May 2022. Initial leflunomide doses of 2 to 4 mg/kg once daily were prescribed and were titrated to the lowest effective dose with concurrent anti-inflammatory therapy. Complete blood count, serum chemistry, and clinical signs were monitored throughout the course of treatment.
RESULTS: Adverse effects potentially attributable to leflunomide noted in 9 of 27 dogs (33%) included vomiting, diarrhea, lethargy, decreased or absent appetite, polyuria and polydipsia, and secondary antibiotic responsive infection and were self-limiting or resolved with outpatient therapy. Alkaline phosphatase (ALP) and alanine aminotransferase (ALT) elevation were documented in all dogs prescribed leflunomide plus prednisone, with persistent liver enzyme elevation in 6 of 9 dogs (67%) and normalization after antibiotic therapy in 3 of 9 dogs (33%). The majority of dogs prescribed leflunomide plus NSAID (11/17 [65%] dogs) did not experience liver enzyme elevation; 2 of 17 (12%) dogs developed transient antibiotic-responsive liver enzyme elevations, and 4 of 17 (23%) dogs had persistent liver enzyme elevation.
CONCLUSIONS: Leflunomide was well tolerated for long-term management of IMPA. A significant difference in liver enzyme elevation was identified between dogs prescribed prednisone versus NSAID in combination with leflunomide. Leflunomide with NSAID therapy resulted in less hepatotoxicity compared with leflunomide with prednisone.

Thoracic radiography and abdominal ultrasonography are part of standard diagnostic investigations in cases of canine immune-mediated polyarthritis (IMPA). However, the clinical importance of thoracic and abdominal imaging towards the management of canine IMPA currently remains unknown. The primary aim of this study was to describe the findings documented on thoracic radiography and abdominal ultrasonography in dogs diagnosed with IMPA, and to evaluate the diagnostic utility of thoracic radiography and abdominal ultrasonography in the initial approach and management of these cases. Seventy-seven dogs diagnosed with IMPA who underwent thoracic radiography and abdominal ultrasonography at a single referral hospital between 2008 and 2022 were included. The diagnostic imaging studies of these 77 dogs were reviewed by one blinded board-certified diagnostic imaging specialist for quality assurance. The medical records, including the diagnostic imaging reports of these dogs, were then reviewed by three blinded board-certified internal medicine specialists. Using a modified version of a previous question and scoring system, the three internal medicine specialists then generated an answer for the overall diagnostic utility and a diagnostic utility score for thoracic radiography and abdominal ultrasonography for each case. The abnormal findings identified in radiography and ultrasonography were described. In the cases where the findings were considered significant enough to immediately affect the case management, the results of the further investigations that were subsequently performed were also described. No abnormalities were detected in thoracic radiography for 30 cases, and none were detected in abdominal ultrasound for 6. The majority of the internists considered thoracic radiography to be not useful in the overall case management at the time of IMPA diagnosis in 70 cases, and considered abdominal ultrasonography to be not useful in the overall case management in 57 cases. The majority of the internists agreed on the utility of thoracic radiography in 95% of the cases, and in 61% of the cases for abdominal ultrasonography. The most common finding in the thoracic radiography was a mild bronchial pulmonary pattern, and the most common in the abdominal ultrasonography was mild lymphadenomegaly. Therefore, although thoracic radiography and abdominal ultrasonography identified numerous abnormal findings in this population of dogs, in the majority of the cases, the findings were deemed not useful towards the overall case management at the time of the initial diagnosis of IMPA. Thus, the use of thoracic radiography and abdominal ultrasonography should be taken into careful consideration when considering initial diagnostic investigations for canine IMPA.

Canine immune-mediated polyarthritis (IMPA) is an idiopathic disorder encompassing both erosive and non-erosive forms of rheumatoid arthritis (RA), with a clinical picture similar to human RA. Resemblance in major histocompatibility complex (MHC)-associated risk between the two was first noted within the specific amino acid motif known as the shared epitope (SE) on human leukocyte antigen DRB1. Following further identification of amino acids conferring risk for human RA outside the SE, this study was designed to examine amino acids both within and outside the classic SE in dachshunds, a breed with reported susceptibility to IMPA in Japan. Genome-wide association studies have linked positions 11, 13 and 71 with strong risk for human RA and important roles in antigen presentation to T cells. Sequence based genotyping of 16 case and 64 control dachshunds revealed strong associations comparable to human RA between IMPA risk and valine at position 11 (Val-11), phenylalanine at 13 (Phe-13), and arginine at 71 (Arg-71) on the dog leukocyte antigen (DLA)-DRB1 molecule (OR 2.89, 95%CI 1.3-6.4, p = 0.009), while association with the classic SE was significant only regarding homozygote frequency of the QRRAA haplotype-also carrying Val 11 and Phe 13 outside the SE (p = 0.04). Moreover, limited range in possible combinations of amino acids at positions 11, 13 and 71 starting with Val-11 among all DLA-DRB1 alleles registered with the GenBank and IPD-MHC canine databases, suggested potential of further single-breed analyses in dachshunds to clarify the disorder in terms of diagnosis, treatment, and epigenetic control, while clinical and immunopathogenetic similarities between human and dachshund RA also suggested the possibility of gaining insight into RA per se through study of canine IMPA as a spontaneous model of human RA.

Cats with non-erosive immune-mediated polyarthritis (IMPA) were identified from seven referral hospitals between 2009 and 2020 for a multicentre retrospective case series. Data were obtained from hospital records and referring veterinarians were contacted for follow-up. Twenty cases were identified: 12 castrated males (60%), one entire male (5%) and seven spayed females (35%). Common clinical signs included lameness (n = 20/20) and pyrexia (n = 10/18). Three cats presented with and two cats developed ligament laxity during treatment. Thirteen cats (65%) were diagnosed with non-associative IMPA and seven (35%) with associative IMPA. Comorbidities identified included chronic enteropathy (n = x/7), feline immunodeficiency virus (n = x/7) feline herpesvirus (n = x/7), bronchopneumonia (n = x/7) and discospondylitis (n = x/7). Sampling of the tarsal joints most frequently identified an increased proportion of neutrophils, consistent with IMPA. Eighteen cats (90%) received immunosuppressants. Eleven cats were started on prednisolone; eight had a poor response resulting in the addition of a second agent, euthanasia or acceptance of the persisting signs. One cat received ciclosporin and required an alternative second agent owing to adverse effects. Five cats were started on prednisolone and ciclosporin; three had a poor response and required an alternative second agent. One cat received prednisolone and chlorambucil and had a good response. Two cats (10%) received meloxicam and had a good response, although the clinical signs recurred when medication was tapered. A good outcome was achieved in 14/20 cats (70%) with IMPA. In the cats with a poor outcome 4/6 were euthanased and 2/6 had chronic lameness.
Prognosis for feline IMPA can be good. Multimodal immunosuppression was often required. IMPA should be considered in lame cats, with or without pyrexia, when there is no evidence of trauma or infection. The tarsal joints should be included in the multiple joints chosen for sampling. Ligament laxity can occur in non-erosive feline IMPA.

A 9-year-old castrated male poodle dog was presented with icterus, anorexia, and lethargy. The dog was diagnosed with hypothyroidism 1 month before and was treated with levothyroxine. Severe anaemia with spherocytes, positive saline agglutination test, and hyperbilirubinemia indicated immune-mediated haemolytic anaemia (IMHA). Therefore, immunosuppressive therapy with prednisolone, mycophenolate mofetil, and danazol was started. Although the IMHA was well controlled, during tapering of prednisolone, acute multiple joint swelling and oedema suspected immune-mediated polyarthritis occurred twice. First, clinical symptoms improved as the dosage of prednisolone increased. However, the dog showed severe adverse effects to the steroid. Second time, we added leflunomide as another immunosuppressant, and clinical signs of arthritis disappeared. About 3 weeks later, despite the immunosuppressive therapy, skin lesions resembling an autoimmune dermatologic disorder spread throughout the body. Addition of cyclosporine resolved the skin lesions. This is a case report of a dog showing several sporadic clinical signs related to multiple autoimmune syndromes and their management using different immunosuppressant drugs.

BACKGROUND: In people, Salmonella is a common agent of gastroenteritis, but it can also cause extraintestinal disease such as urinary tract infections. In addition, Salmonella is often linked to the post-infection development of reactive arthritis. In canines, cases that document extraintestinal Salmonella infections or diseases similar to reactive arthritis have not been thoroughly described.
METHODS: A case of a 5-year-old German shepherd dog with Salmonella bacteriuria during treatment for immune-mediated polyarthritis (IMPA) is described. The patient first suffered from a 3 month period of diarrhoea and presented for evaluation of a 2 month history of shifting-leg lameness. A diagnosis of IMPA was made based on cytological examination and negative synovial fluid culture. Treatment with immunosuppressive doses of prednisone lead to clinical resolution of lameness, but on a recheck abnormal urine was noted. Salmonella enterica serovar Typhimurium was isolated using standard culture methods. The patient was treated with enrofloxacin to control the bacteriuria.
CONCLUSIONS: This case report is, to the best of our knowledge, the first to describe Salmonella bacteriuria in a dog and suggests that Salmonella infection may be a potential inciting factor for IMPA.

This case study is to report the proteins detected by proteomic analysis of synovial fluid from a dog diagnosed with idiopathic immune-mediated polyarthritis, and to compare it with healthy dogs. Synovial fluid was collected via arthrocentesis from a dog diagnosed with immune-mediated polyarthritis. Protein precipitation was performed on the synovial fluid, followed by isoelectric focusing and 2-dimensional gel electrophoresis. The spots on the 2-dimensional gels were analyzed using MALDI-TOF/MS. The results were then analyzed against the MASCOT database. The results from the proteomic analysis revealed an abundance of several types of immunoglobulins together with the presence of complement C4b-binding protein alpha chain. Actin and keratin were also among the proteins detected. Proteomic studies, facilitate a better understanding of the different levels of proteins expressed during disease activity. Potential disease biomarkers can aid in the diagnosis of disease, as well as help in monitoring treatment efficacy and providing prognosis for the patient.