pISSN 2466-1384 eISSN 2466-1392大韓獸醫學會誌 (2016) 第 56 卷 第 1 號 Korean J Vet Res(2016) 56(1) : 47 49http://dx.doi.org/10.14405/kjvr.2016.56.1.47 <Case Report> Combination therapy of cyclosporine and prednisolone in a dog with systemic lupus erythematosus Yeon-Hee Kim, Min-Hee Kang, Hee-Myung Park* Department of Veterinary Internal Medicine, College of Veterinary Medicine, Konkuk University, Seoul 05029, Korea (Received: November 11, 2015; Revised: February 29, 2016; Accepted: March 2, 2016) Abstract : An 11-year-old, spayed female poodle presented with fever and shifting lameness. Physical examinationrevealed hyperthermia (40.6oC), and proteinuria was detected upon urinalysis. Increased neutrophils (83%) and decreasedviscosity were revealed upon synovial fluid analysis. Serum antinuclear antibody was positive at 1 : 80. Based on thesefindings, the dog was diagnosed with systemic lupus erythematosus. Immunosuppressive therapy was initiated withprednisolone and cyclosporine, and the condition was markedly improved after the treatments. This case report describesthe clinical and laboratory findings, imaging characteristics and successful outcomes after prednisolone plus cyclosporinetherapy in a canine systemic lupus erythematosus case.
Keywords : antinuclear antibody, cyclosporine, glomerulonephritis, polyarthritis, systemic lupus erythematosus Systemic lupus erythematosus (SLE) is a multisystemic dal anti-inflammatory drugs. Physical examination was unre- autoimmune disorder in which immunity is directed against markable except for hyperthermia (40.6oC). A complete blood various tissues or tissue components [1]. The most common count (CBC) revealed leukocytosis (27.1 × 103/µL; reference clinical features include shifting lameness from polyarthritis, interval, 5.05–16.7 × 103/µL) with degenerative neutrophilia ulceration of extremities caused by vasculitis, icteric and pale (26,558/µL; reference interval, 3,000–11,000/µL). A serum mucous membranes resulting from immune-mediated hemol- biochemical profile revealed elevated creatine kinase (270 U/ ysis, and peripheral edema or pleural effusion due to hypoal- L; reference interval, 100–200 U/L) and C-reactive protein buminemia secondary to glomerulonephritis. Additionally, (> 108 µmol/L; reference interval, < 20 µmol/L) (Table 1). A dermatologic lesions may be present, including crusting, alope- polymerase chain reaction (PCR) testing with a tick-borne cia, erythema, ulceration, and hyperkeratosis [8].
disease panel including Babesia spp., Haemobartonella spp., Major signs of SLE are skin lesions, non-erosive polyarthri- Anaplasma spp., Ehrlichia spp. and Borrelia burgdoferi, was tis, hemolytic anemia, glomerulonephritis, polymyositis, leuko- performed to rule out tick-borne diseases, and the result was penia, and thrombocytopenia [1]. Minor signs are fever, central negative. Radiographically, there were no evident abnormali- nervous system symptoms, oral ulcerations, lymphadenopa- ties on all four limbs (Fig. 1). Under general anesthesia, syn- thy, pericarditis, and pleuritis [2]. The antinuclear antibody ovial fluid was obtained via fine needle aspiration from (ANA) test and lupus erythematosus (LE) cell preparations are multiple joints (both stifles, carpi, and elbows). The fluid was used clinically for the diagnosis of SLE, but until recently, the transparent and had decreased viscosity. Aerobic and anaero- ANA test is considered the most sensitive [3, 14]. Immunosup- bic bacterial cultures of the synovial fluid were negative, and pression is vital to treating this abnormal immune response, the fluid cell count showed neutrophil predominance (83%).
and patients can be treated with high dose of prednisolone (1– The results characterized an inflammatory arthropathy (Fig.
2 mg/kg, per oral [PO], q12h) and cytotoxic drugs, such as 2), and the ANA test was positive (1/80). Moderate pro- azathioprine, cyclosporine, and cyclophosphamide [4, 5]. This teinuria (100 mg/dL) without urinary tract infection was case report describes successful treatment using prednisolone detected on urine dipstick and sediment examination. Uri- and cyclosporine in a dog with SLE.
nary specific gravity was 1.025 (Table 2). Both aerobic and An 11-year-old, 6.1 kg, spayed female poodle dog pre- anaerobic bacterial cultures from the urine sample were per- sented with fever, lethargy, anorexia, and shifting lameness.
formed, and the results were negative. Therefore, the pro- The dog had a history of reluctance to stand up and walk, teinuria was caused by glomerular damage, not lower urinary which was intermittent and partially responsive to non-steroi- *Corresponding authorTel: +82-2-450-4140, Fax: +82-2-444-4396

Yeon-Hee Kim, Min-Hee Kang, Hee-Myung Park Table 1. A complete blood count and serum biochemical results in a dog with systemic lupus erythematosus Reference interval Creatinine (mg/dL) Total protein (g/dL) Creatine kinase (U/L) C-reactive protein (µmol/L) D, days after first examination; WBC, white blood cells; RBC, red blood cells; PCV, packed cell volume; Hb, hemoglobin; PLT, platelets;ALT, alanine aminotransferase; AST, aspartate aminotransferase; ALP, alkaline phosphatase; BUN, blood urea nitrogen; ND, not determined.
Table 2. Urinalysis in a dog with systemic lupus erythematosus Reference interval USG, urine specific gravity; UPCR, urine protein creatinine ratio. *5–10 cells/µL. †100 mg/dL. ‡30 mg/dL.
Fig. 1. Radiographs of four limbs in a dog with systemic lupus Fig. 2. Synovial fluid from the left stifle of a dog with systemic erythematosus. No evidence of bone density loss was found in the lupus erythematosus. Nucleated cell counts were increased (A), limbs. (A) Left stifle joint. (B) Right stifle joint. (C) Both carpal and non-degenerative neutrophils (B, arrows) showed predom- inance (83%). Diff-Quik stain. 400× (A) and 630× (B).
This dog satisfied the criteria for a definite SLE condition, with two major signs (polyarthritis and glomerulonephritis) detected on the 15th day after treatment began. These and a positive ANA assay; therefore, a diagnosis of definite changes suggested secondary hepatocellular damage due to SLE was made. Prednisolone (1 mg/kg, PO, q12h; Yuhan, prednisolone administration. To prevent further hepatocellu- Korea) and cyclosporine (8 mg/kg, PO, q24h; Novatis, Swit- lar damage, a liver protectant (Zentonil 0.1 T/kg divided; zerland) were initiated, and the dog's clinical signs including Vétoquinol, France) was additionally prescribed. As the dos- lameness, fever, and anorexia were improved over the next age of prednisolone administration was tapered every two two days. However, markedly increased liver enzymes were weeks, the liver enzymes also decreased.
Combination therapy of systemic lupus erythematosus The patient was monitored every 15 days, including physi- kg, PO, q12h), but proteinuria was not controlled [9].
cal examination, CBC, serum biochemical profile, urinaly- The patient in the current case received treatment with sis, and urine protein creatinine ratio (UPCR). The clinical cyclosporine and prednisolone for definite SLE. Cyclospo- signs improved rapidly with this treatment, whereas the C- rine was considered first in this case since the main side reactive protein levels and UPCR gradually improved over a effect of azathioprine is myelosuppression. Because combi- period of months (Tables 1 and 2). Plasma cyclosporine con- nation therapy of cyclosporine and prednisolone was applied centration reached the therapeutic level (310 ng/mL; thera- in the case, the dose of prednisolone used was much lower peutic range, 100–500 ng/mL) two weeks after treatment. The than was reported in previous case studies. The clinical signs initial dosage of prednisolone was 1 mg/kg, PO, q12h for 15 improved, and recurrence of the condition was not observed.
days, which was then reduced by half every 15 days. Finally, This case showed a diagnosis of definite SLE in a dog that the prednisolone medication was discontinued 60 days after satisfied the criteria of two major signs with a positive ANA the first treatment. Plasma cyclosporine concentration was test result. Unlike in previous treatment results, improve- monitored on days 30 and 60, and reached therapeutic levels ment of proteinuria was marked with the administration of each time. The dosage of cyclosporine (8 mg/kg, PO, q24h) prednisolone with cyclosporine in this dog. Thus, the use of was maintained depending on the dog's response and her prednisolone and cyclosporine is worthwhile to try in SLE plasma cyclosporine concentration. No recurrence of the con- patients with proteinuria.
dition was observed during three months of follow-up.
In conclusion, definite SLE with proteinuria was well-con- SLE is characterized by a broad spectrum of clinical symp- trolled by using prednisolone and cyclosporine in this dog.
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