A 10-year-old 29.6-kg (65.1-lb) spayed female Golden Retriever was examined because of a 3-month history of lethargy and anorexia and because of stumbling often when walking. The owners reported that the dog weighed 34.0 kg (75.0 lb) 3 months earlier and that recent weight loss (4.4 kg [9.7 lb]) was obvious. The dog was receiving heartworm prophylaxis but had not received routine vaccinations for > 1 year. In addition, the dog's medical history included surgical removal of multiple subcutaneous lipomas 4.4 years ago, antimicrobial treatment for pyoderma 1.8 years ago, and surgical removal of a meibomian adenoma on an upper eyelid 1.4 years ago. On physical examination, the dog had a body condition score of 2 (on a scale of 1 to 5); however, the owners described the dog as having had a body condition score of 3 just 3 months earlier. The dog's rectal temperature was 38.5°C (101.3°F; reference range, 38.1° to 39.2°C [100.5° to 102.5°F]), and heart rate was 120 beats/min (reference range, 60 to 120 beats/min). The dog's gait appeared clinically normal, and neither joint swelling nor signs of pain were detected with palpation of the limbs. No abnormalities were noted during neurologic examination; however, the dog had numerous subcutaneous lipomas (confirmed with cytologic evaluation of fine-needle aspirate samples).
Results of hematologic evaluation indicated nonregenerative anemia (PCV, 33% [reference range, 37% to 55%]; mean corpuscular volume, 57.3 fL [reference range, 60 to 77 fL]; mean corpuscular hemoglobin concentration, 32.3 g/dL [reference range, 32 to 36 g/dL]; and reticulocyte production index < 2% [reference range to be considered regenerative, > 2%]) and leukocytosis (18,200 WBCs/μL [reference range, 6,000 to 17,000 WBCs/μL] with 14,500 neutrophils/μL [reference range, 3,000 to 11,500 neutrophils/μL]). No band neutrophils were detected. The only abnormal result on biochemical analyses was high serum CRP concentration (7.9 mg/dL; reference range, 0 to 1.0 mg/dL). Radiography of the thorax and abdomen revealed no thoracic abnormalities, but did reveal a mass in the central region of the abdomen. Results of echocardiography were unremarkable; however, abdominal ultrasonography revealed a nodular mass (approx 10 × 10 × 3 cm) with iso- to hypoechogenic areas (including areas of nonechogenicity) in the center of the spleen. No peritoneal effusion was detected with ultrasonography. Results of urinalysis were unremarkable.
To further investigate the cause of the dog's high serum CRP concentration, arthrocentesis was performed bilaterally on the carpal and stifle joints. The collected synovial fluid appeared to have normal viscosity but was white and turbid. Although synovial protein concentration was not assessed, cytologic evaluation revealed many nucleated cells (approx 10 nucleated cells/hpf), consistent with suppurative inflammation in synovial fluid (defined as > 2 nucleated cells/hpf1) in samples from each of the 4 joints. In the left and right carpal joints, lymphocytes comprised 75% and 60%, respectively, of the total nucleated cell count and nondegenerative neutrophils comprised 5% of the total. In the left and right stifle joints, nondegenerative neutrophils comprised 60% of the total nucleated cell count (neutrophils > 12% of total nucleated cells in synovial fluid is a component of suppurative inflammation1). In addition, lymphocytes comprised approximately 20% and 10% of the total nucleated cell counts in the left and right stifle joints, respectively. Radiography of the joints revealed no abnormal findings (eg, joint erosion) indicative of rheumatoid arthritis.
On the basis of findings, a splenic mass, polyarthritis, and nonregenerative anemia were diagnosed in the dog. To further investigate potential underlying causes, we submitteda,b samples of synovial fluid for bacterial culture and susceptibility testing and samples of frozen serum and EDTA-anticoagulated blood for assessments of antinuclear antibody titer, free T4 and thyroid-stimulating hormone concentrations, rheumatoid factor, and vector-borne disease agents (by PCR assays for Anplasma spp, Babesia spp, Bartonella spp, Ehrlichia spp, Hepatozoon spp, Leishmania spp, Neorickettsia risticii, and Rickettsia rickettsii). Pending results, firocoxib (5.8 mg/kg [2.6 mg/lb], PO, q 24 h) and misoprostol (3.4 mg/kg [1.5 mg/lb], PO, q 12 h]) were prescribed.
Results were negative for detection of vector-borne diseases, rheumatoid factor, and antinuclear antibody titer. In addition, bacterial culture performed on synovial fluid yielded no growth, and concentrations of thyroid-stimulating hormone (0.29 ng/mL; reference range, 0.08 to 0.32 ng/mL) and free T4 (0.9 ng/mL; reference range, 0.5 to 3.0 ng/mL) were within reference limits. On recheck examination 11 days after the initial evaluation, there had been no improvement in the dog's lethargy, anorexia, stumbling gait, nonregenerative anemia (PCV, 30%), or leukocytosis (28,400 WBCs/μL with 23,500 neutrophils/μL). Anemia of chronic disease associated with polyarthritis caused by the localized splenic mass was strongly suspected, and a splenectomy was scheduled.
On the day of the splenectomy (20 days after the initial examination), no improvements were noted in the dog's clinical signs. In addition, the dog still had a nonregenerative anemia (PCV, 31%), leukocytosis (17,500 WBCs/μL with 11,900 neutrophils/μL), high serum CRP concentration (10.0 mg/mL), and unchanged synovial fluid characteristics. The dog's prothrombin time (7.5 seconds; reference range, 7.4 to 8.4 seconds) and activated partial thromboplastin time (11.9 seconds; reference range, 12.0 to 24.0 seconds) were close to the lower reference limit; however, the plasma fibrinogen concentration (388 mg/dL; reference range, 150 to 350 mg/dL) was high. The dog was anesthetized, and a splenectomy was performed. There was an adhesion of the omentum to a part of the splenic mass. Splenectomy was performed without complication, and the dog recovered from anesthesia. Postsurgical care included hospitalization and administration of lactated Ringer solution (60.0 mL/kg/h [27.3 mL/lb/h], IV) and ampicillin (20.0 mg/kg [9.1 mg/lb], SC, q 12 h).
Results of histologic examination of the splenic mass indicated that the mass was a hyperplastic nodule and that it had not ruptured. However, adhesion of the omentum to the nodule's surface was evident.
Three days after surgery (23 days after initial examination), the dog's clinical signs of lethargy, anorexia, and stumbling gait had resolved. Given this and although the dog's PCV was 25%, fluid therapy was discontinued. The dog had no relapse of signs, and on postoperative day 5 (25 days after initial examination), the dog was discharged with a prescription of ampicillin (20.0 mg/kg, PO, q 12 h for 5 days).
Eight days after surgery (28 days after initial evaluation), the dog was returned for a recheck examination and had no clinical signs of lethargy, anorexia, or stumbling gait. The dog's PCV had increased to 27%, and its serum CRP concentration (< 0.9 mg/mL) was within the reference limits. Results of arthrocentesis indicated resolution of suppurative joint inflammation in that the nucleated cell counts of the carpal and stifle joints bilaterally had decreased to < 2 cells/hpf and that inflammatory cells were not detected.
Twenty-two days after surgery (42 days after initial evaluation), the dog was again returned for a recheck examination. The dog's body weight (30.4 kg [66.9 lb]) had improved, and PCV (38%) was within reference limits. Further, there were no abnormalities on cytologic examination of synovial fluid from any of the carpal or stifle joints.
Discussion
Polyarthropathies in dogs can occur secondary to drugs, vaccinations, distant neoplasia, or other distant immunogenic stimuli (nonjoint infectious [eg, viruses, bacteria, fungi, and protozoa] or noninfectious [eg, immune-mediated skin disease, inflammatory bowel disease, and chronic hepatitis]).2–6 Reactive arthritis is believed to occur when immune complexes develop secondary to infection, inflammation, or other stimuli at a distant site4; however, to our knowledge, there have been no reports showing a detailed association between ReA and primary disease in dogs. Neoplasia, such as pancreatic adenocarcinoma, renal carcinoma, tonsillar carcinoma, squamous cell carcinoma, mammary carcinoma, leiomyosarcoma, and lymphoma, may cause ReA in dogs because antibodies and immune complexes formed in response to the antigenic stimulus by the neoplasia deposit in joint spaces.2,3,5,7 However, the proportion of dogs with ReA caused by neoplasia may be low. For instance, a study1 of nonseptic suppurative polyarthropathy in 52 dogs shows that neoplasia remote from the affected joints was identified as the underlying cause in just 1 (2%) dog. Removal of the remote neoplasia causing ReA may improve arthritis in affected dogs.6 However, ReA from other underlying causes, such as acute pancreatitis, may persist and require immunosuppressive treatment even after resolution of the initial underlying cause. The treatment for ReA remains unclear. However, in cases where there is a primary disease, treating the primary disease should be the top priority, whether it involves surgical or pharmacological treatments. For instance, a study4 shows that 35 of 43 (81%) dogs with idiopathic, nonerosive immune-mediated polyarthritis were treated with immunosuppressive drugs, including prednisolone.
In the dog of the present report, resolution of polyarthritis following splenectomy suggested that ReA developed in response to the dog's nonneoplastic splenic hyperplastic nodule. Hyperplasia, which increases tissue volume, refers to cellular proliferation in response to an external stimulus and is distinct from neoplasia and inflammation.8 We believe that the nonneoplastic splenic hyperplastic nodule alone in the dog of the present report was unlikely to have induced an immune response and was therefore unlikely to have caused the dog's ReA. However, previous inflammation was suggested on the basis of adhesion of the omentum to the nodule as observed during surgery and on histologic examination. This finding, combined with the dog's 3-month history of abnormal clinical signs, suggested that another splenic hyperplastic nodule or portion of the one evident on splenectomy likely had ruptured before onset of clinical signs and that the resulting omental adhesion and inflammation may have caused ReA and anemia of chronic disease in the dog of the present report. Alternatively, the dog could have mounted an immune response to the nonneoplastic splenic hyperplastic nodule, given the fact that resolution of polyarthritis occurred after splenectomy.
Because there are few vector-bone diseases in the area we serve and there has been no report of polyarthritis caused by vector-bone diseases in our country (Japan), testing for such diseases was not performed with the first examination. However, because initial findings did not identify an underlying cause and because we had frozen remaining samples of blood obtained from the dog, we submitted frozen serum and EDTA-anticoagulated blood to a commercial diagnostic laboratory to perform PCR assays to detect vector-borne diseases. Although the results were negative for the dog in the present report, we recommend that veterinarians evaluate for vector-borne diseases in dogs with polyarthritis.
In addition, measurement of serum concentrations of CRP (an acute-phase protein produced in the liver in response to an increase in the release of pro-inflammatory cytokines [eg, interleukin-1, interleukin-6, and tumor necrosis factor] during inflammation) is useful in diagnosing and monitoring systemic inflammatory diseases in dogs.9 The serum CRP concentration is high in most dogs with immune-mediated polyarthritis.10 In the dog of the present report, a high serum CRP concentration alerted us to further investigate for polyarthritis, which we later diagnosed. The findings of a decrease in serum CRP concentration to within reference limits along with resolution of polyarthritis in the dog of the present report supported results of a previous study11 that indicates plasma CRP concentration may be a marker of synovial inflammation from polyarthritis in dogs.
To our knowledge, this was the first report of ReA associated with a nonneoplastic splenic hyperplastic nodule in a dog. Therefore, veterinarians should investigate for nonneoplastic splenic hyperplastic nodules in addition to other typical underlying causes when treating dogs with polyarthritis.
Acknowledgments
The authors declare that there were no conflicts of interest.
ABBREVIATIONS
| CRP | C-reactive protein |
| ReA | Reactive arthritis |
References
1. Rondeau MP, Walton RM, Bissett S, et al. Suppurative, nonspetic polyarthropathy in dogs. J Vet Intern Med 2005;19:654–662.
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. Kohn B. Canine immune-mediated polyarthritis. Eur J Companion Anim Pract 2007;17:119–124.
4. Stull JW, Evason M, Carr AP, et al. Canine immune-mediated polyarthritis: clinical and laboratory findings in 83 cases in western Canada (1991–2001). Can Vet J 2008;49:1195–1203.
5. Johnson KC, Mackin A. Canine immune-mediated polyarthritis: part 1: pathophysiology. J Am Anim Hosp Assoc 2012;48:12–17.
6. Stone M. Immune-mediated polyarthritis and other polyarthrides. In: Ettinger SJ, Feldman EC, Cote E, eds. Textbook of veterinary internal medicine: disease of the dog and cat. 8th ed. St Louis: Elsevier, 2017;861–866.
7. Gear RN, Bacon NJ, Langley-Hobbs S, et al. Panniculitis, polyarthritis and osteomyelitis associated with pancreatic neoplasia in two dogs. J Small Anim Pract 2006;47:400–404.
8. Ehrhart EJ, Kamstock DA, Powers BE. The pathology of neoplasia. In: Withrow SJ, Vail DM, Page RL, eds. Small animal clinical oncology. 5th ed. St Louis: Elsevier, 2013;51–67.
9. Ceron JJ, Eckersall PD, Martýnez-Subiela S. Acute phase proteins in dogs and cats: current knowledge and future perspectives. Vet Clin Pathol 2005;34:85–99.
10. Hillström A, Bylin J, Hagman R, et al. Measurement of serum C-reactive protein concentration for discriminating between suppurative arthritis and osteoarthritis in dogs. BMC Vet Res 2016;12:240.
11. Foster JD, Sample S, Kohler R, et al. Serum biomarker of clinical and cytologic response in dogs with idiopathic immune-mediated polyarthropathy. J Vet Intern Med 2014;28:905–911.
