Diagnosis and Treatment of Lyme Borreliosis in Dogs: A Case-Based Approach
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CASE BY CASE: PARASITOLOGY PEER REVIEWED CASE BY CASE: PARASITOLOGY Diagnosis and Treatment of Lyme Borreliosis in Dogs: A Case-Based Approach Alaina Moon, DVM, DACVIM (SAIM) Olympia Veterinary Specialists Internal Medicine, Olympia, Washington Lyme borreliosis is caused by the spirochete Borrelia and arthritis syndrome has been induced in dogs,5,6 no burgdorferi, which is transmitted by ticks of the Ixodes experimental model exists for Lyme (Borrelia) genus.1 In the United States, Lyme borreliosis is most nephritis,3,7,8 which limits our understanding of the commonly identified in the Northeast and upper pathophysiology. As a result, guidance for diagnosis and Midwest due to the host preferences of Ixodes ticks treatment depends largely on consensus opinion. This endemic to those regions.2 It is usually diagnosed in the case-based approach highlights best practices in spring and summer due to tick activity and human and diagnosis and treatment of Lyme borreliosis in the canine outdoor recreation.3 The most frequently context of 3 common clinical scenarios. recognized syndromes associated with Lyme borreliosis in dogs are acute polyarthritis and glomerulonephritis. CASE 1: POLYARTHRITIS Confusion surrounds the diagnosis and treatment of Case 1 was a 27-kg, 4-year-old castrated male pointer Lyme borreliosis, in part because most seropositive dogs with a 48-hour history of lethargy and unwillingness to remain asymptomatic,4 which limits veterinary walk. He was mildly febrile (39.9 °C [103.8 °F]) and Brad Whitford Photography/shutterstock.com professionals’ ability to study naturally occurring had moderate carpal effusion, mild tarsal effusion, and disease. In addition, although a Borrelia-associated fever moderate prescapular lymphadenopathy. His gait was Abstract Diagnosis of Lyme borreliosis requires a combination of diagnostic testing and clinical judgment. This article provides 3 case examples of presenting complaints, physical examination findings, and screening laboratory abnormalities that accompany Lyme borreliosis. There is no singular confirmatory test. Treatment for the clinical syndromes most commonly associated with Lyme borreliosis—polyarthritis and glomerulonephritis—is doxycycline, plus immunosuppressives for dogs with rapidly progressive glomerular disease. Asymptomatic dogs with positive serologic results do not require treatment but should be screened for proteinuria for 1 year. 18 MAY/JUNE 2023 todaysveterinarypractice.com
PEER REVIEWED CASE BY CASE: PARASITOLOGY Take-Home Points No single test can prove that Polyarthritis resulting from immunosuppression is frequently Lyme borreliosis is the cause of Lyme borreliosis is expected to necessary along with doxycycline illness; therefore, the diagnosis respond rapidly to treatment with treatment. Immunosuppression requires a combination of doxycycline; if rapid improvement is ideally based on renal diagnostic testing and clinical is not noted, other causes of histopathology, although biopsy judgment. polyarthropathy should be may not be possible for all considered. patients. A lack of reported tick exposure is not sufficient to rule out Lyme The glomerular disease Most dogs with positive borreliosis. associated with Lyme borreliosis Borrelia serologic results are can be severe, progressive, and asymptomatic; these dogs should The recommended treatment rapidly fatal. be screened for proteinuria for Lyme borreliosis in dogs is a during the first year after 4-week course of doxycycline. In dogs with severe, rapidly positive serology is identified, progressive glomerular disease and prophylactic doxycycline and positive Borrelia serology, treatment is not indicated. tentative and short strided. He had recently been taken After 48 hours, the client reported dramatic hunting, although no tick infestation was reported. improvement in the patient’s willingness to walk. By the next week, his tentative gait, joint effusion, and Lab work revealed mild thrombocytopenia, minimally lymphadenopathy had resolved. The client had concentrated urine, and B burgdorferi antibodies discontinued analgesics several days earlier when the (TABLE 1). The findings of polyarthropathy and dog was no longer perceived to be painful, but the positive Borrelia serology raised suspicion for doxycycline was continued for 4 weeks. Recheck polyarthritis caused by Lyme borreliosis. However, examination 3 weeks after doxycycline discontinuation because of the high prevalence of asymptomatic dogs revealed no recurrence of painful gait, joint effusion, or with positive serologic results, further investigation to lymphadenopathy. Urinalysis was monitored every rule out alternative causes of polyarthropathy was 4 months for the first year after diagnosis to screen for recommended. Carpal and tarsal radiographs revealed development of proteinuria, but no proteinuria was no erosive changes. Arthrocentesis was recommended, detected. but the client declined in favor of doxycycline with a plan to proceed with arthrocentesis if improvement was not seen. Initial treatment was doxycycline (5.5 mg/kg CASE 2: NEPHRITIS PO q12h) with gabapentin (7.4 mg/kg PO q12h) and Case 2 was a 6.8-kg, 7.5-year-old spayed female codeine (1.1 mg/kg PO q12h) for pain control. Maltese mix that was presented to her primary care TABLE 1 Laboratory Values for Case 1: Dog With Polyarthritis TEST (REFERENCE RANGE) VALUE NOTES Blood chemistry Within reference range Platelet clumping on slides noted; Platelet count, platelets/µL 167 000 platelet count estimated to be within (170 000–377 000) reference range USG (1.015–1.05) 1.053 with 1+ protein UPC (
CASE BY CASE: PARASITOLOGY PEER REVIEWED veterinarian for chronic diarrhea. A chemistry panel Doxycycline was initiated (5.7 mg/kg PO q12h) for revealed azotemia and mild hypoalbuminemia; urine 4 weeks and benazepril was continued (0.3 mg/kg PO was mildly dilute with an inactive sediment and q24h). Amlodipine (0.25 mg/kg PO q24h) was 3+ protein (TABLE 2). Treatment was initiated with initiated for treatment of hypertension and clopidogrel benazepril (0.3 mg/kg PO q24h). Three months later, (1.8 mg/kg PO q24h) was initiated for repeat lab work revealed progressive azotemia, thromboprophylaxis, based on concern for progressive hypoalbuminemia, and persistent hypercoagulability in dogs with protein-losing proteinuria. A prescription renal diet was prescribed glomerular disease,9 which may put them at risk for and the patient was referred for further diagnostics. thromboembolic complications.10,11 At the time of referral, the patient was feeling well. A At a recheck examination 2 weeks later, hypertension chemistry panel revealed stable azotemia and was improved but persistent and blood urea nitrogen progressive hypoalbuminemia. A complete blood count and creatinine were unchanged. Amlodipine was revealed marked thrombocytopenia, and the urine increased to 0.5 mg/kg PO q24h. specific gravity was within reference range but with increased protein. A urine bacterial culture was Three days after doxycycline completion, lab work negative. The urine protein:creatinine ratio (UPC) was revealed stable azotemia, persistently marked markedly elevated. SNAP 4Dx (IDEXX, idexx.com) proteinuria, persistently marked thrombocytopenia, testing was positive for antibodies to B burgdorferi. The and decreased blood pressure. C6 titer was lower but patient was markedly hypertensive, and C6 antibody still above reference range. Renal biopsy was titer was elevated. Abdominal ultrasonography revealed recommended to further characterize the a mild loss of corticomedullary definition with no other glomerulopathy but was not performed due to the risks renal or extrarenal abnormalities. posed by thrombocytopenia. Instead, empiric immunosuppressive treatment (mycophenolate mofetil TABLE 2 Laboratory Values for Case 2: Dog With Nephritis TEST 3 DAYS AFTER 3 MONTHS AFTER (REFERENCE 3 MONTHS DOXYCYCLINE IMMUNOSUPPRESSIVE RANGE) INITIAL LATER AT REFERRAL COMPLETION THERAPY INITIATION Platelet count, platelets/µL 30 000 32 000 (170 000–377 000) BUN, 66 81 79 77 68 mg/dL (9–31) Creatinine, 2.7 4.4 4.2 4.3 3 mg/dL (0.5–1.3) Albumin, 2.3 1.9 1.7 g/dL (2.7–3.9) C6 titer, 281 103 U/mL (
PEER REVIEWED CASE BY CASE: PARASITOLOGY at 9 mg/kg PO q12h) was elected. Telmisartan therapy A positive Borrelia antibody test in a dog with (0.6 mg/kg PO q24h) was initiated and benazepril was proteinuria suggests, but does not confirm, that discontinued. Two weeks later, hypertension was Borrelia is the cause of glomerulopathy. One study even controlled, thrombocytopenia was resolved (280 000/ suggests that proteinuria is an uncommon finding in µL), and azotemia was stable. dogs with Borrelia antibodies12; therefore, a thorough diagnostic investigation of proteinuria is warranted.13 Three months after institution of immunosuppressive Nevertheless, because glomerulonephritis caused by therapy, the patient was polyuric and polydipsic but Lyme borreliosis can be rapidly progressive, doxycycline otherwise feeling well. Proteinuria was markedly treatment should be initiated concurrently with improved, azotemia was persistent but improved, and standard therapy and investigation of glomerular hypertension remained controlled. The patient disease.7 Detailed descriptions of standard therapy and returned to her primary care veterinarian for ongoing investigation of glomerular disease are published care; however, 13 months later she was euthanized due elsewhere and typically involve a combination of to complications of progressive kidney disease. antihypertensives, angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, antithrombotics, and prescription renal diets.14 CASE 3: ASYMPTOMATIC, SEROLOGY-POSITIVE For dogs that are clinically stable and nonazotemic, Case 3 was a 10-year-old spayed female terrier initial management can involve antibiotics and presented for routine vaccinations. She was feeling well standard glomerular disease therapies. Renal biopsy and physical examination was unremarkable other than should be recommended for dogs with azotemia or a chronic grade 3/6 left apical systolic heart murmur. A rapidly progressive disease.3,7 Although renal biopsy SNAP 4Dx test performed for yearly heartworm cannot prove a cause-and-effect relationship between screening was positive for B burgdorferi antibodies but Borrelia and glomerular disease,15 one justification for negative for Anaplasma species and Ehrlichia canis renal biopsy in these dogs is to enable differentiation antibodies and negative for Dirofilaria immitis antigen. between immune-mediated glomerular disease, which would be expected to respond to immunosuppression, To follow up on the positive Borrelia serology, full and causes that would not be expected to respond to laboratory work was performed. Chemistry panel and immunosuppression. If renal biopsy is not elected or is complete blood count were within reference ranges. not safe to perform (as for Case 2), or if glomerular Urinalysis revealed specific gravity within reference disease is too severe or rapidly progressive to await range (1.033) and trace protein. A UPC ratio of biopsy results, cautious immunosuppression may be 0.1 ruled out clinically significant proteinuria. warranted along with antibiotic therapy.3,7 The recommended first-line immunosuppressive for Urinalysis was repeated every 4 months for the next glomerular disease is mycophenolate mofetil, with the 12 months. Any protein detected on urinalysis was optional short-term addition of glucocorticoids for followed up with a UPC ratio. Clinically significant severe, rapidly progressive cases.16 proteinuria did not develop during the 12-month monitoring period. At the next annual screening, the The recommended first-line antibiotic treatment for SNAP 4Dx result remained positive for B burgdorferi Lyme borreliosis is doxycycline, although optimal dose antibodies but the patient remained healthy. and duration of treatment are not known. The current recommendation is to continue treatment for 4 weeks.3 For Lyme borreliosis–associated polyarthritis, a robust DISCUSSION response is expected within 48 hours; a lack of response According to the American College of Veterinary within this time frame should prompt investigation for Internal Medicine’s (ACVIM) consensus statement on other causes of polyarthropathy.8 Controversy exists Lyme disease in dogs, diagnosis requires basing clinical around using C6 antibody titers to guide treatment judgment on evidence of exposure, consistent clinical duration. Measuring C6 titers before and 6 months signs, consideration of other differentials, and response after starting treatment may be useful as a decrease of to treatment.8 The cases discussed here highlight the 50% or more likely indicates decreased antigenic load variability of clinical presentations associated with as a result of effective treatment. On the other hand, Lyme borreliosis. evidence that the magnitude of C6 titer correlates to the todaysveterinarypractice.com MAY/JUNE 2023 21
CASE BY CASE: PARASITOLOGY PEER REVIEWED magnitude of current disease or the likelihood of 2. Companion Animal Parasite Council. Parasite prevalence maps. Accessed October 28, 2022. https://capcvet.org/maps developing future disease is lacking.3 In addition, the 3. Littman MP, Gerber B, Goldstein RE, Labato MA, Lappin MR, Moore GE. magnitude of the decrease tends to be smaller with ACVIM consensus update on Lyme borreliosis in dogs and cats. J Vet lower initial C6 values, in which case the threshold of a Intern Med. 2018;32(3):887-903. doi:10.1111/jvim.15085 4. Levy SA, Magnarelli LA. Relationship between development of decrease of 50% or more might not be achieved despite antibodies to Borrelia burgdorferi in dogs and the subsequent effective treatment. Nevertheless, some clinicians development of limb/joint borreliosis. JAVMA. 1992;200:344-347. prolong doxycycline treatment until clinical resolution 5. Appel MJG, Allan S, Jacobson RH, et al. Experimental Lyme disease in dogs produces arthritis and persistent infection. J Infect Dis. is achieved or until the C6 antibody titer decreases into 1993;167(3):651-654. doi:10.1093/infdis/167.3.651 the target range.3,7 6. Summers BA, Straubinger AF, Jacobson RH, Chang Y-F, Appel MJG, Straubinger RK. Histopathological studies of experimental Lyme disease in the dog. J Comp Pathol. 2005;133(1):1–13. doi:10.1016/j. Most serology-positive dogs are asymptomatic.4 A jcpa.2004.11.006 recommended approach is to screen for development of 7. Goldstein RE, Brovida C, Fernandez-Del Palacio M, et al. Consensus recommendations for treatment for dogs with serology positive proteinuria every 3 to 4 months for the first year after glomerular disease. J Vet Intern Med. 2013;27(Suppl 1):S60-66. doi:10.1111/jvim.12232 seropositivity is identified,3,8 which enables early 8. Littman MP, Goldstein RE, Labato MA, Lappin MR, Moore GE. ACVIM intervention for proteinuria, potentially preventing small animal consensus statement on Lyme disease in dogs: diagnosis, ongoing glomerular damage. For asymptomatic, treatment, and prevention. J Vet Intern Med. 2006;20(2):422-434. doi:10.1111/j.1939-1676.2006.tb02880.x serology-positive dogs, measurement of C6 antibody 9. Lennon EM, Hanel RM, Walker JM, Vaden Sl. Hypercoagulability in dogs titers is not recommended and there is no evidence that with protein-losing nephropathy as assessed by thromboelastography. J Vet Intern Med. 2013;27(3):462-468. doi:10.1111/jvim.12067 prophylactic doxycycline treatment is beneficial.3 10. Cook A, Cowgill L. Clinical and pathological features of protein-losing glomerular disease in the dog: a review of 137 cases (1985-1992). Prevention of Lyme disease is multimodal. JAAHA. 1996;32(4):313-322. doi:10.5326/15473317-32-4-313 11. White CR, Langston C, Hohenhaus AE, Lamb K, Hackner S, Fox Ectoparasiticides are recommended to prevent tick PR. Evaluation of the relationship between clinical variables attachment or to kill ticks quickly after attachment as and thromboelastographic findings in dogs with protein-losing nephropathy. J Vet Emerg Crit Care (San Antonio). 2016;26(1):74-79. the likelihood of Borrelia and other tick-borne doi:10.1111/vec.12409 pathogen transmission increases with longer attachment 12. Goldstein RE, Cordner AP, Sandler JL, Bellohusen BA, Erb HN. Microalbuminuria and comparison of serologic testing time.17,18 Recreation habits and landscaping can be for exposure to Borrelia burgdorferi in nonclinical Labrador modified to minimize exposure to tick habitat.3 Dogs and golden retrievers. J Vet Diagn Invest. 2007;19(3):294-297. doi:10.1177/104063870701900312 should be examined after exposure to tick-infested areas 13. Littman MP, Daminet S, Grauer GF, Lees GE, van Dongen AM. and ticks should be removed promptly. Vaccination is Consensus recommendations for the diagnostic investigation of dogs effective against both experimental19 and natural20 with suspected glomerular disease. J Vet Intern Med. 2013;27(Suppl 1):S19-26. doi:10.1111/jvim.12223 infection. The ACVIM consensus update on Lyme 14. Brown S, Elliott J, Francey T, Polzin D, Vaden S. Consensus borreliosis in dogs and cats did not report a consensus recommendations for standard therapy of glomerular disease in dogs. J Vet Intern Med. 2013;27(Suppl 1):S27-43. doi:10.1111/jvim.12230 on whether vaccination is recommended.3 The decision 15. Hutton TA, Goldstein RE, Njaa BL, Atwater DZ, Chang Y-F, Simpson to vaccinate should be made on an individual basis KW. Search for Borrelia burgdorferi in kidneys of dogs with suspected “Lyme nephritis.” J Vet Intern Med. 2008;22(4):860-865. doi:10.1111/ while considering patient risk factors. j.1939-1676.2008.0131.x 16. Segev G, Cowgill LD, Heiene R, Labato MA, Polzin DJ. Consensus recommendations for immunosuppressive treatment of dogs with glomerular disease based on established pathology. J Vet Intern Med. References 2013;27(Suppl 1):S44-54. doi:10.1111/jvim.12228 1. Burgdorfer W, Hayes SF, Corwin D. Pathophysiology of the Lyme 17. des Vignes F, Piesman J, Heffernan R, Schulze TL, Stafford III KC, Fish disease spirochete, Borrelia burgdorferi, in ixodid ticks. Rev Infect Dis. D. Effect of tick removal on transmission of Borrelia burgdorferi and 1989;11(Suppl 6):S1442-1450. doi:10.1093/clinids/11.supplement_6.s1442 Ehrlichia phagocytophila by Ixodes scapularis nymphs. J Infect Dis. 2001;183(5):773-778. doi:10.1086/318818 18. Piesman J. Dynamics of Borrelia burgdorferi transmission by nymphal Ixodes dammini ticks. J Infect Dis. 1993;167(5):1082-1085. doi:10.1093/ infdis/167.5.1082 19. LaFleur RL, Callister SM, Dant JC, et al. One-year duration of immunity induced by vaccination with a canine Lyme disease bacterin. Clin Alaina Moon Vaccine Immunol. 2010;17(5):870-874. doi:10.1128/CVI.00524-09 Dr. Moon is an internist in small animal clinical practice. 20. Eschner AK, Mugnai K. Immunization with a recombinant subunit She is a graduate of the University of Wisconsin-Madison OspA vaccine markedly impacts the rate of newly acquired Borrelia and completed her residency at Oregon State University burgdorferi infections in client-owned dogs living in a coastal in 2018. Her clinical interests include hematology, community in Maine, USA. Parasit Vectors. 2015;8:92. doi:10.1186/ s13071-015-0676-x infectious disease, and the intersections of human and animal health. 22 MAY/JUNE 2023 todaysveterinarypractice.com
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