Diagnosis and Treatment of Lyme Borreliosis in Dogs: A Case-Based Approach

Page created by John Wells
 
CONTINUE READING
Diagnosis and Treatment of Lyme Borreliosis in Dogs: A Case-Based Approach
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
    ƒ No single test can prove that                     ƒ 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.
    ƒ A lack of reported tick exposure
      is not sufficient to rule out Lyme                ƒ The glomerular disease                          ƒ Most dogs with positive
      borreliosis.                                        associated with Lyme borreliosis                  Borrelia serologic results are
                                                          can be severe, progressive, and                   asymptomatic; these dogs should
    ƒ 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.                     ƒ 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
You can also read