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Type I immune-mediated polyarthritis in dogs: 39 cases (1997–2002) Dylan N. Clements, BVSc; Robyn N. A. Gear, BVSc; James Tattersall, BVSc; Stuart Carmichael, BVMS, MVM; David Bennett, BvetMed, PhD

Objective—To determine clinical signs, laboratory findings, relationship to vaccination, and response to treatment for type I immune-mediated polyarthritis (IMPA) in dogs. Design—Retrospective study. Animals—39 dogs. Procedure—Clinical records and radiographic reports from 3 university referral hospitals were reviewed. Clinical signs, laboratory and investigative findings, relationship to vaccination, and response to treatment were evaluated. Results—Clinical signs and initial laboratory and clinical investigative findings were frequently abnormal but were nonspecific and not associated with likelihood of recovery. Time of vaccination was not associated with onset of disease. Chemotherapeutic immunosuppression resulted in complete cure in 56% of dogs. Continuous medication was required in 18% (7/39) of dogs, relapses were treated successfully in 13% (5/39) of dogs, and 15% (6/39) of dogs died or were euthanatized as a result of disease. Conclusions and Clinical Relevance—The possible involvement of vaccination in type I IMPA was not made clear from this study because of the small population size. Signalment, clinical signs, and results of diagnostic tests other than multiple synovial fluid analyses were generally nonspecific. Most dogs with type I IMPA responded to initial immunosuppressive treatment, but 31% (12/39) of dogs relapsed, required further treatment, or both. (J Am Vet Med Assoc 2004;224:1323–1327)

I

diopathic, nonerosive, noninfectious arthritis was first reported in the mid 1970s as a disease of canine joints without obvious etiology.1 The condition is now referred to as canine idiopathic immune-mediated polyarthritis (IMPA) and may be differentiated into 4 subgroups according to an absence of defined associations (type I), associations with infection (type II), associations with gastrointestinal tract disease (type III), and associations with neoplasia (type IV).2 Idiopathic immune-mediated polyarthritis is now recognized as the most common immune-mediated arthritic condition in dogs3,4 and the most common cause of pyrexia of unknown origin in dogs in a referral hospital population.5,6 Only 1 published From the Department of Veterinary Clinical Studies, University of Glasgow Veterinary School, Bearsden, Glasgow, Scotland, G61 1QH, UK (Clements, Carmichael, Bennett); the Department of Veterinary Medicine, University of Cambridge, Cambridge, England, CB3 0ES, UK (Gear); and the Department of Veterinary Clinical Studies, University of Edinburgh, Edinburgh, Scotland, EH25 9RG, UK (Tattersall). Address correspondence to Mr. Clements. JAVMA, Vol 224, No. 8, April 15, 2004

report2 documents the success of treatment and long-term prognosis for dogs with IMPA. Vaccination as a trigger for immune-mediated disease in dogs and humans has frequently been suggested.7 A temporal association between canine immunemediated hemolytic anemia with vaccination has been documented.7 Recent vaccination with live feline calicivirus has been associated with feline polyarthritis.8 Type I canine IMPA associated with vaccination has been reported in 4 dogs.9 The purpose of this retrospective study was to determine the signalment, clinical signs, laboratory findings, relationship to vaccination, and response to treatment in dogs with type I IMPA. Other types of IMPA (II, III, and IV) were not included in this study because the success of their treatment depends on the initiating cause.2,4 We hypothesized that the onset of canine type 1 IMPA could be associated with recent vaccination (within 1 month) and that the prognosis for recovery with treatment could not be related to historical or laboratory findings at the time of referral. Criteria for Selection of Cases Medical records of dogs evaluated at the Glasgow University Veterinary School, Edinburgh University Veterinary School, and the University of Cambridge Veterinary School from January 1997 to July 2002 with type I immune-mediated polyarthritis were reviewed. Only dogs for which full clinical records, radiographic evaluations, details of treatment, and follow-up data (as defined by reexamination, telephone conversations with owners, or both) were available were included in the study. The diagnostic criteria for inclusion were dogs with nonerosive polyarthritis confirmed by radiographic assessment of affected joints; cytologic analysis of samples from multiple arthrocenteses; and absence of rheumatoid arthritis,10 systemic lupus erythematosus,11 polyarthritis-polymyositis,12 or polyarthritis-meningitis syndrome.4 In addition, dogs of Chinese Shar Pei and Akita breeds were excluded because of the breed-associated immune-mediated polyarthritis recognized in those dogs.4 Results of arthrocentesis were considered diagnostic if cytologic analysis of fluid from at least 2 joints in each dog revealed abnormalities (automated WBC concentration > 3 X 109cells/L or appearance of highly cellular synovial fluid with cell population > 10% neutrophils and no intra- or extracellular bacteria13). Also, dogs must not have had evidence of an infective disease process, gastrointestinal disease, or neoplasia, as determined on initial or subsequent investigations. Dogs were considered to have negative results for rheumatoid arthritis if no erosive changes were identified on examination of the radiScientific Reports: Retrospective Study

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ographs of affected joints14 and negative results for systemic lupus erythematosus if there was no evidence of other body system involvement based on clinical or laboratory examinations; dogs were seronegative for antinuclear antibody when tested.15 Procedures Details of age, breed, sex, neuter status, vaccination history, clinical signs at time of referral, clinically affected joints, duration of clinical signs prior to referral, hematologic and biochemical evaluations at referral, urinalysis, radiographic and ultrasound evaluations, arthrocentesis, immunosuppressive treatment regimens, and response to treatment were obtained from the medical records. Antinuclear antibody tests were performed on all dogs with abnormalities detected via hematologic, serum biochemical, or urinalysis tests. The relationship to vaccination was evaluated via the date of vaccination relative to the date of onset of clinical signs. Mean age, time to referral, number of joints affected, highest WBC concentration, and duration of immunosuppression were calculated. Remission at follow-up examination was defined as an absence of clinical signs and synovial fluid analysis that detected WBC concentration < 3 X 109 cells/L, with a cell population that included < 10% neutrophils. Statistical analyses—The frequency of diagnosis of type 1 IMPA at the Glasgow University Veterinary School was compared with the frequency of evaluation of each breed in the general hospital population over the same time period by use of the χ2 test statistic. Breeds were considered to be at increased risk for type 1 IMPA if the odds ratio and lower bound of its 95% confidence interval were > 1. Only breeds for which more than 2 cases of type 1 IMPA were included in this analysis. The study population was divided into 4 assessment groups on the basis of treatment success (defined as complete remission with immunosuppressive therapy) versus nonsuccess (defined as recurrence, continuous treatment required, euthanasia, or death) or treatment success (defined as complete remission with immunosuppressive therapy or recurrence also treated successfully) versus nonsuccess (defined as continuous treatment required, euthanasia, or death). Variables were assessed for normality by use of the KolmogorovSmirnov test. Parametric data (age and number of joints involved) were compared among groups by use of single 2-tailed t tests, and nonparametric data (time to referral, time from routine vaccination, and highest WBC concentration) were compared by use of a Mann Whitney U test. Success of treatment was compared by use of Fisher exact tests for dichotomized data, including sex, neuter status, the presence of pyrexia, inappetance, lymphadenopathy, signs of back pain at referral, hematologic abnormalities, leucocytosis, leucopenia, anemia, thrombocytopenia, serum biochemical abnormalities, high serum activity of alkaline phosphatase, high serum activity of liver enzymes or bile acid concentration, hypoalbuminemia, hyperglobulinemia, or hypocalcemia. A value of P < 0.05 was considered significant for all comparisons. 1324 Scientific Reports: Retrospective Study

Results A diagnosis of type I IMPA was reported in 46 dogs examined at the 3 veterinary teaching hospitals during the study period. Seven cases were excluded because of insufficient follow-up information. Labrador Retrievers (n = 7), German Shepherd Dogs (4) and cross-breeds (3) were most commonly seen, and 20 breeds were represented overall. None of these breeds had increased risk relative to the general population at the Glasgow University Veterinary School. Twenty dogs were classified as large-breed dogs (> 22 kg [48.4 lb]). Mean ± SD age at referral was 4.9 ± 2.5 years (range, 3 months to 11 years). The sex distribution was 14 sexually intact males, 3 neutered males, 9 sexually intact females, and 13 neutered females. Clinical signs commenced from 4 days to 2 years prior to referral (mean, 64 ± 112 days). Twenty-seven dogs were vaccinated; the time of vaccination was known for 21 dogs, 3 dogs were not vaccinated, and the vaccination history was not known for 9 dogs. For dogs that were vaccinated, the most recent vaccination had been administered 6.1 months (mean) before the onset of clinical signs (median, 8 ± 15 months; range, 2 weeks to 6 years). Two dogs developed clinical signs of disease within 1 month of vaccination. Prior to referral, all dogs were treated with antimicrobials (n = 22), corticosteroids (8), or nonsteroidal anti-inflammatory drugs (15). Stiffness was the most common clinical sign at referral and affected all dogs. Nearly half of the dogs had pyrexia (n = 22), lymphadenopathy (20), or inappetance (18), and 9 dogs had signs of lumbar spinal pain. Less common signs at referral included polydipsia (n = 3), signs of depression (3), exercise intolerance (2), and lethargy (2). At referral, clinical signs of joint involvement (swelling, pain, or heat) were observed in all limbs in 28 dogs, only hind limbs in 10 dogs, and only forelimbs in 1 dog. Carpal joints were most commonly affected (n = 31 dogs), followed by hock joints (28), stifle joints (28), and elbow joints (17). Thoracic radiography was performed in 20 dogs. No abnormalities were detected in 12 dogs. Cardiomegaly was observed in 3 dogs and an interstitial lung pattern was identified in 2 dogs, a bronchointerstitial pattern in 2 dogs, pleural effusion in 1 dog, and peritoneopericardial diaphragmatic hernia in 1 dog. Abdominal radiography was performed in 9 dogs, with no abnormalities detected in 6 dogs. Lumbar spondylosis was identified in 2 dogs and hepatomegaly in 1 dog. Radiographs of clinically affected joints revealed soft tissue swelling, joint effusion, or both in all dogs. Abdominal ultrasonography was performed in 11 dogs and revealed sublumbar lymphadenopathy in 6 dogs, splenomegaly in 1 dog, hepatomegaly in 1 dog, renal cysts in 1 dog, prostatomegaly in 1 dog, and no abnormalities in 1 dog. Routine hematologic and serum biochemical tests were performed on blood samples taken from 36 dogs. Most commonly, neutrophilic leucocytosis was observed (n = 18), followed by anemia (6), thrombocytopenia (3), and leucopenia (3). No hematologic abnormalities were identified in 11 dogs. Serum biochemical abnormalities were identified in 26 dogs, with high activity of alkaline JAVMA, Vol 224, No. 8, April 15, 2004


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Treatment—Twenty-six dogs were treated with prednisolone alone, initially at an immunosuppressive and anti-inflammatory dosage (1 to 2 mg/kg [0.45 to 0.9 mg/lb], PO, q 24 h, or divided equally q 12 h) for approximately 2 weeks, at which time gradual dosage reduction was initiated until an anti-inflammatory dosage (< 0.5 mg/kg [< 0.23 mg/lb], PO, q 24 to 48 h) was reached, generally after 4 to 6 weeks. The prednisolone dosage was further tapered for varying lengths of time thereafter, depending on the response to treatment. Thirteen dogs responded to a single course of prednisolone of 4 to 16 weeks’ duration (mean ± SD, 8 ± 4.5 weeks) without recurrence. One dog was initially treated for 3 months with prednisolone, followed by euthanasia as a result of recurrent clinical signs 1 year later. Two dogs required continuous low-dosage prednisolone (0.2 mg/kg [0.09 mg/lb], PO, q 24 h and 0.05 mg/kg [0.023 mg/lb], PO, q 24 h, respectively) to ameliorate clinical signs. One dog required prednisolone administration for 2 years, after which clinical remission was maintained via oral administration of aloe vera. One dog was treated with prednisolone for 4 months, followed by crystal therapy (homeopathic crystal placed in the dog’s water bowl), which coincided with remission of clinical signs. Four dogs responded to administration of prednisolone and antimicrobial agents for 8 weeks; 1 dog was euthanatized 6 months later because of recurrence of disease. Four dogs responded to prednisolone administration initially but subsequently relapsed between 3 and 12 months after treatment (mean, 7.8 ± 4.5 months). One dog responded to a further course of prednisolone of 8 weeks’ duration; 2 dogs responded to courses of prednisolone (anti-inflammatory dosage) and levamisolea (5 mg/kg [2.3 mg/lb], PO, q 48 h) of 8 and 12 weeks’ duraJAVMA, Vol 224, No. 8, April 15, 2004

tion, respectively; and 1 dog responded to a course of prednisolone (anti-inflammatory dose) and azathioprineb (2 mg/kg, PO, q 24 h for 7 days, then 2 mg/kg, PO, q 48 h) of 8 weeks’ duration, followed by continuous prednisolone administration at an anti-inflammatory dose. Six dogs did not respond to the initial prednisolone administration of 4 to 8 weeks’ duration. Two dogs were treated with levamisole and prednisolone (anti-inflammatory dose) for 4 weeks. Both dogs relapsed but responded to either prednisolone alone (immunosuppressive dose, 8 weeks) or prednisolone (anti-inflammatory dose) and cyclophosphamidec (50 mg/m2, PO, q 24 h for 7 days, then q 48 h) for 8 weeks. The second dog was euthanatized 8 months after diagnosis because of recurrence of clinical signs. One dog was treated successfully via administration of prednisolone (antiinflammatory dose) and azathioprine for 8 weeks. Another dog was treated with prednisolone (antiinflammatory dose), levamisole, and azathioprine for 4 weeks, followed by azathioprine and cyclosporine Ad (5 mg/kg, PO, q 24 h) continuously. One dog was treated with prednisolone (anti-inflammatory dose) and cyclophosphamide for 4 weeks. One dog was treated with prednisolone (anti-inflammatory dose) in combination with azathioprine and levamisole for 4 weeks and then with cyclosporine A for 3 months before euthanasia because of unremitting disease 6 months after diagnosis. Three dogs were initially treated with cyclosporine A (5 mg/kg, PO, q 24 h), of which none responded, and all required further immunosuppressive treatment from 2 to 12 weeks after initiation (mean, 6 weeks). One dog was subsequently treated successfully with the continuation of administration of cyclosporine and the addition of an immunosuppressive dose of prednisolone, and a second dog was successfully treated with the addition of continuously administered azathioprine. The final dog was unsuccessfully treated with combinations of prednisolone (anti-inflammatory dose) and cyclophosphamide (50 mg/m2, PO, q 24 h for 7 days, then q 48 h for 3 weeks) and then with prednisolone and azathioprine (2 mg/kg, PO, q 24 h for 7 days, then q 48 h for 2 weeks) before euthanasia because of unremitting disease. One dog died the day after diagnosis, before treatment was initiated. Three dogs were treated with prednisolone (antiinflammatory dose) in combination with levamisole (1 dog, 4 weeks of treatment), azathioprine (1 dog, 10 weeks of treatment), and cyclophosphamide (1 dog, continuous treatment). No significant differences between groups were found for signalment, time of vaccination, clinical signs at time of referral, hematologic or serum biochemical abnormalities, number of joints affected, joint fluid WBC concentration, or results of immunosuppressive treatment. When dogs that relapsed but were subsequently successfully treated were included in the successfully treated group, a significantly (P = 0.015) larger number of dogs in the unsuccessfully treated group had inappetance. Discussion The signalment of dogs in this series was similar to that described previously,2 in which German Shepherd Scientific Reports: Retrospective Study

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phosphatase in 15 dogs, high activity of alanine aminotransferase or aspartate aminotransferase in 7 dogs, hypoalbuminemia in 8 dogs, hyperglobulinemia in 4 dogs, azotemia in 3 dogs, and hypercalcemia in 2 dogs. Rheumatoid factor measurements16 were performed in 17 dogs; the results were negative in 15 dogs, 1 dog had a low titer (optical density, 2/10), and 1 dog had a high titer (optical density, 7/10). Antinuclear antibody tests17 were performed in 25 dogs; 23 dogs had negative results, and 2 dogs had a low titer (1:8). Urinalysis was performed in 13 dogs, and the results were within reference ranges in 5 dogs. Four dogs had hematuria, and 4 dogs had proteinuria. Arthrocentesis was performed on 2 to 8 joints (mean, 4 joints/dog) of each dog. In 9 dogs, the joint fluid samples were assessed by smear examination only and subjectively assessed to have high neutrophil concentrations in all instances. In 30 dogs, synovial fluid was sent for WBC analysis; the highest WBC concentration from each dog ranged from 3.7 X 109 to 130 X 109 cells/L (mean, 41.9 X 109 cells/L; reference range, < 3.0 X 109 cells/L). In most dogs, neutrophils were predominant (range, 20% to 98%; reference range, < 10%), although mononuclear cells were also high in 20 dogs (mean, 6.1 X 109 cells/L; range, 0.8 to 17.5 X 109 cells/L).


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Dogs and Labrador Retrievers were found to be overrepresented. For dogs evaluated at the Glasgow University Veterinary School, this reflected the overall frequency of these breeds within the general hospital population and was not a true over-representation. It would appear that all dog breeds may be affected by type I IMPA and that obvious sex, neutering, and age predispositions do not exist. Results of a recent study18 indicate an association between certain immunogenetic markers (major histocompatability antigens) and canine IMPA. Dogs with these antigens are more likely to develop IMPA when exposed to certain, as yet undefined, environmental factors. Bilaterally symmetrical joint involvement is typical of IMPA.2 Joints are generally swollen and painful on palpation and manipulation, but not in all dogs. Although hematologic and serum biochemical abnormalities were detected in most dogs reported here, these were often nonspecific and in some instances may have been the result of previous glucocorticoid administration. Dichotomization of dogs into treatment response categories (successful vs unsuccessful) was carried out because the ultimate goal of any treatment is resolution of disease without recurrence. Because no significant differences were observed between groups for any of the variables we assessed, a second dichotomization was performed that allocated dogs that relapsed but were subsequently treated successfully into the successfully treated group. No significant differences were evident between groups other than for inappetance, which was more common in the unsuccessfully treated group. We believe that no reliable associations with treatment outcome could be made with the variables assessed because type I IMPA is a complex disease that is frequently cyclical in nature with multiple possible etiologies, making statistical comparisons difficult. Similar nonspecific changes have been reported by Bennett2 and Jacques et al.19 The absence of rheumatoid factor and antinuclear antibody in nearly all the dogs tested in our study has also been reported by those authors. An antinuclear antibody test was not performed in dogs unless there was evidence of involvement of other body systems as judged on the basis of clinical examination, laboratory investigation, and diagnostic imaging.15 The results of thoracic, abdominal, and joint radiography (other than soft tissue changes) and abdominal ultrasonography were unremarkable in most dogs. The absence of erosive changes and presence of joint effusions were expected in cases of type I IMPA. The thoracic and abdominal changes were nonspecific, and all abnormal findings appeared incidental, with the exception of lymph node enlargement that was thought to be related to the immune-mediated nature of the disease. Results of multiple arthrocenteses for detecting involvement of several joints in a bilaterally symmetrical pattern were diagnostic in all dogs (high synovial fluid WBC concentration with predominantly neutrophils). Mononuclear cell concentrations were also high in 20 dogs, although the magnitude of their increase, compared with the reference value, was less than that observed for neutrophils. It is of interest that 1326 Scientific Reports: Retrospective Study

a much wider range of synovial fluid WBC concentrations was observed (from 3.7 to 130 X 109 cells/L) than that reported by MacWilliams and Friedrichs13 and that these initial concentrations were not useful as predictors of outcome. Although results of examination of synovial fluid smears were diagnostic, we advocate the use of accurate WBC concentrations because smear examinations have poor specificity for differentiation of degenerative joint disease from inflammatory arthropathies.20 Among the 21 dogs for which the time of vaccination was recorded, 2 developed disease within 1 month of vaccination, which is less than the 4 of 13 dogs reported by Kohn et al.9 Kohn et al9 also reported those cases to be vaccine-associated IMPA, which resolved quickly without treatment. Disease recurred in 1 dog that was revaccinated. Both dogs in our study, in which vaccination preceded development of the disease, recovered after a single course of prednisolone therapy. Clearly, vaccination is not a prerequisite for disease because it was seen in 3 dogs that were not vaccinated; however, the possible role of vaccination in the development of immune-mediated disease in certain dogs still requires clarification. It is interesting to note that polyarthritis, poly arthropathies, and polyarthrosis are reported as suspected adverse drug reactions in only 1 dose/1.6 X 106 doses of canine vaccine administered in the United Kingdom.21 Canine distemper virus (CDV) has been implicated in inflammatory synovitis with increased concentrations of anti-CDV antibodies and complexed CDV antigens within the synovial fluid.22,23 Although CDV has not been definitively proven to cause IMPA, it is the authorsâ&#x20AC;&#x2122; policy to determine antibody titers to CDV prior to booster vaccination in all dogs that have IMPA. If protective titers are detected, the distemper component of the vaccine is not given. Although the guidelines for treatment of type I IMPA are frequently given in textbooks,3,4 they are derived from clinical experience. To the authorsâ&#x20AC;&#x2122; knowledge, no prospective trials regarding the immunosuppressive regimen of choice or duration of treatment for type I IMPA have been performed. Only 1 publication indicates treatment outcomes for immunosuppressive regimens2; prednisolone alone was used in 68% of dogs and in combination with cyclophosphamide in 32% of dogs. Newer immunosuppressive drugs, such as azathioprine (n = 6 dogs) and cyclosporine A (4), were used in a small number of dogs in our study. Levamisole, which has an immunomodulatory action, was used in only 5 dogs. Comparing the final outcome results of our study with those of Bennett,2 dogs in our study had slightly higher rates of recovery (56% vs 44%) and requirement for continuous medication (18% vs 11%) and slightly lower rates of relapse treated successfully (13% vs 21%) and euthanasia or death (15% vs 24%). Most dogs responded to immunosuppression with prednisolone (81%), although 31% of these dogs subsequently had relapsed or required continuous anti-inflammatory treatment or were euthanatized because of persistent disease. JAVMA, Vol 224, No. 8, April 15, 2004


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a

Levacide, Norbrook Laboratories (GB) Ltd, The Green, Great Corby, Carlisle, Cumbria, England. b Imuran, GlaxoSmithKline, Stockley Park West, Uxbridge, Middlesex, England. c Endoxana, Baxter Healthcare Ltd, Wallingford Rd, Compton, Newbury, Berkshire, England. d Neoral, Novartis Pharmaceuticals UK Ltd, Frimley Business Park, Frimley, Camberley, Surrey, England.

References 1. Pederson NC, Weisner K, Castles JJ, et al. Noninfectious canine arthritis: the inflammatory, nonerosive arthritides. J Am Vet Med Assoc 1976;169:304–310. 2. Bennett D. Immune-based non-erosive inflammatory joint disease of the dog. 3. Canine idiopathic polyarthritis. J Small Anim Pract 1987;28:909–928. 3. Bennett D, May C. Joint diseases in dogs and cats. In: Ettinger S, ed. Textbook of veterinary internal medicine. 4th ed. Philadelphia: WB Saunders Co, 1995;2032–2077. 4. Bennett D, Day MJ. Immune-mediated musculoskeletal and neurological disease. In: Day MJ, ed. Clinical immunology of the dog and cat. London: Manson Publishing, 1999;126–145. 5. Bennett D. Pyrexia of unknown origin. In Pract 1995;17: 470–481. 6. Dunn KJ, Dunn JK. Diagnostic investigations in 101 dogs with pyrexia of unknown origin. J Small Anim Pract 1998;39:574–580.

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7. Duval D, Giger U. Vaccine-associated immune-mediated hemolytic anemia in the dog. J Vet Intern Med 1996;10:290–296. 8. Dawson S, McArdle F, Bennett D, et al. Investigations of vaccine reactions and breakdowns after feline calicivirus vaccination. Vet Rec 1993;132:346–350. 9. Kohn B, Garner M, Lubke S, et al. Polyarthritis following vaccination in four dogs. Vet Comp Orthop Traumatol 2003;16:6–10. 10. Bennett D. Immune-based erosive inflammatory joint disease of the dog. 1. Clinical, radiological and laboratory investigations. J Small Anim Pract 1987;28:779–797. 11. Bennett D. Immune-based erosive inflammatory joint disease of the dog. 1. Pathological investigations. J Small Anim Pract 1987;28:799–819. 12. Bennett D, Kelly DF. Immune-based non-erosive inflammatory joint disease in the dog. 2. Polyarthritis/polymyositis syndrome. J Small Anim Pract 1987;28:891–908. 13. MacWilliams PS, Friedrichs KR. Laboratory evaluation and interpretation of synovial fluid. Vet Clin North Am Small Anim Pract 2003;33:153–178. 14. Bennett D. Immune-based erosive inflammatory joint disease of the dog: canine rheumatoid arthritis. 1. Clinical, radiological and laboratory investigations. J Small Anim Pract 1987;28:779–797. 15. Bennett D. Immune-based non-erosive inflammatory joint disease of the dog. 1. Canine systemic lupus erythematosus. J Small Anim Pract 1987;28:871–889. 16. Bell SC, Carter SD, May C, et al. IgA and IgM rheumatoid factors in canine rheumatoid arthritis. J Small Anim Pract 1993;34: 259–264. 17. Bennett D, Kirkham D. The laboratory identification of serum antinuclear antibody in the dog. J Comp Pathol 1987;97: 523–539. 18. Ollier WE, Kennedy LJ, Thompson W, et al. Dog MHC alleles containing the human RA shared epitope confer susceptibility to canine rheumatoid arthritis. Immunogenetics 2001;53: 669–673. 19. Jacques D, Cauzinille L, Bouvy B, et al. A retrospective study of 40 dogs with polyarthritis. Vet Surg 2002;31:428–434. 20. Gibson NR, Carmichael S, Li A, et al. Value of direct smears of synovial fluid in the diagnosis of canine joint disease. Vet Rec 1999;144:463–465. 21. Gaskell RM, Gettinby G, Graham SJ, et al. Veterinary Products Committee working group report on feline and canine vaccination. Vet Rec 2002;150:126–134. 22. Bell SC, Carter SD, Bennett D. Canine distemper viral antigens and antibodies in dogs with rheumatoid arthritis. Res Vet Sci 1991;50:64–68. 23. May C, Carter SD, Bell SC, et al. Immune responses to canine distemper virus in joint diseases of dogs. Br J Rheumatol 1994; 33:27–31. 24. Grundy SA, Barton C. Influence of drug treatment on survival of dogs with immune-mediated hemolytic anemia: 88 cases (1989–1999). J Am Vet Med Assoc 2001;218:513–546.

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In 1 study,2 no single treatment regimen was completely successful. Hence, it is not surprising that a wide variety of treatment regimens were observed in our study. Similar observations have been reported in the treatment of immune-mediated hemolytic anemia, in which there were no significant differences in mortality rate when using multiple immunosuppressive drug treatments, compared with single immunosuppressive drugs.24 The small number of dogs in our study made meaningful comparisons of treatment regimens impossible. Cyclosporine A, when used alone, did not have any efficacy in treating type I IMPA. The possible involvement of vaccination in type I IMPA was not made clear from this study because of the small population size, but no association was made with onset of disease and timing of vaccination. Signalment, clinical signs, and results of diagnostic tests other than multiple synovial fluid analyses were generally nonspecific. Most dogs with type I IMPA responded to initial immunosuppressive therapy, but 28% of dogs did relapse and required further treatment.


Type I immune mediated polyarthritis in dogs_39 cases