Tick-Borne Disease Case Challenges The Saga of Leia 8 year old, female, intact German Shepherd dog Presented to the referring veterinarian for an acute onset of lethargy, anorexia and panting Medical History Diagnosed bilateral pannus two weeks prior to this presentation Topical prednisolone acetate 1%, q8h Optimmune ointment (0.2% cyclosporine) q12h Recent estrus cycle Physical Exam Findings Rectal Temp. 103.5 0 F Mild discomfort in caudal abdomen HR normal Capillary refill time was normal Mild petechiation was noted on gums No vaginal discharge noted
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Tick-Borne Disease Case Challenges
The Saga of Leia
8 year old, female, intact German Shepherd dogPresented to the referring veterinarian for an acute onset of lethargy, anorexia and panting
Medical History
Diagnosed bilateral pannus two weeks prior to this presentation
Physical Exam FindingsRectal Temp. 103.50FMild discomfort in caudal abdomenHR normalCapillary refill time was normalMild petechiation was noted on gumsNo vaginal discharge noted
Work-Up
CBCBiochemical profileAbdominal radiographs
CBCHCT 39.5% (37.0 – 54.0)RBC 5.93 x 106 (5.4 – 7.8)RBC indices WNLPLT 32.0 x 103 (150 – 430)MPV 21.8 fl (8.0 – 16.0)WBC 15.69 x 103 (6.0 – 17.0)Neutrophils 12.54 x 103 (3.9 – 8.0)Band 0.100 x 103 (< 0.3)Lymphs 1.1 x 103 (1.3 – 4.1)Eosin 0.0 x 103
Monos 1.98 x 103 (0.2 – 1.1)
Blood Film Evaluation
Moderate rouleauxNo other erythrocyte abnormalities noted
Most lymphocytes and monocytes reactivePlatelets reduced in number (no clumping)
Some large
Interpretation
Stress leukogramEvidence of nonspecific antigenic stimulationThrombocytopenia
Biochemical Profile
Elevated blood glucose (129 mg/dl; N= 76-119)
Attributed to stress
Hyperglobulinemia (5.3 g/L; N= 2.7 – 4.4)No other significant abnormalities
Abdominal Radiographs
Mild to moderate hepatosplenomegalyGas-filled loops of SI (enteritis?)No radiographic evidence of pyometraLumbar spondylosis
DDx for ThrombocytopeniaBone marrow production
Unlikely, with no other cytopenias(neutropenia or nonregenerative anemia)
Physical Exam FindingsPanting, anorexic, rectal temp 103.50FBilateral epistaxisPeripheral lymphadenopathy, most prominent in submandibular nodesNo obvious petechiation
CBC FindingsHCT 34.0% (37.0 – 54.0)RBC 5.10 x 106 (5.4 – 7.8)MCV 67.5 fl (66 – 75)MCHC 34.0 g/dl (34.0 – 36.0)PLT 105.0 x 103 (150 – 430)MPV 18.0 fl (8.0 – 16.0)WBC 17.50 x 103 (6.0 – 17.0)Neutrophils 14.18 x 103 (3.9 – 8.0)Band 0.87 x 103 (< 0.3)Lymphs 1.05 x 103 (1.3 – 4.1)Monos 1.4 x 103 (0.2 – 1.1)
Reticulocytes (1.7%) 86,700 (>80,000)
Blood Film Evaluation
Moderate anisocytosis and polychromasia
Occasional NRBC
Most lymphocytes and monocytes reactivePlatelets mildly reduced in number (no parasites seen)
Problem List
FeverMild thrombocytopenia
Bilateral epistaxis, more in left nostril??
Generalized lymphadenopathy (mild) Very prominent submandibular lymph nodes especially on left side
Plan?
PlanAspirate left submandibular LN
PlanAspirate left submandibular LN
New Plan
Remember what you learned from E.B.B.Sick dog with a history of TBD (A. platys) that responded to doxy only to relapse when discontinuedEpistaxis without significant thrombocytopeniaGranulomatous/pyogranulomatous lymphadenitis
New PlanSend serum to NCSU Vector Borne Disease Diagnostic LaboratoryBartonella vinsonii subsp. berkhoffii and Bartonella henselaeAzithromycin
5-10mg/kg PO Q24 for 5 to 7 daysSame dose every other day for 5 more weeks
Follow-up
72 hours laterTemperature normalEpistaxis resolvedPlatelet count normal
SerologyPositive for B. henselae (1:256)
Leia had uneventful recovery
Co-InfectionsAP and Lyme
Same vector and co-infections common in upper Midwest and Northeastern USCo-infected animals more likely to have severe diseaseTreatment same
AP and Bartonella spp. ( Diroff et al. JVIM 2006, 20:762)
Dogs in Northeastern US that were Bartonella positive on serology
25% also AP positive; no significant association with LymeBartonella but not AP associated with peripheral lymphadenopathyDoxy ineffective in treatment of Bartonellosis
Co-InfectionsLiterature full of data regarding co-infections with tick-transmitted organismsE. canis and epistaxis
Epistaxis has not been reported in experimental E. canis infectionsEpistaxis associated with Bartonella infection
Thrombocytopenia or not (endothelial cell invasion)Vasculitis, vascular weakness
Warrants testing for co-infection
Non-responders or relapses after appropriate therapy
L.S.U. Butterfly
Dog Case - Coco6 year oldfemale spayedmixed breedVomited 2 days agoPresented to rDVM
Is it a tumor?Is it infection?Immune-mediated disease?
Additional Tests
Serum protein electrophoresisMonoclonal gammopathy
Bone marrow aspirateLymphoplasmacytic infiltrate
Lymphocytes: 56% (<10%)Plasma cells: 8% (< 2%)
Tick-borne disease titerSNAP 3Dx positive
Additional Tests
Serum protein electrophoresisMonoclonal gammopathy
Bone marrow aspirateLymphoplasmacytic infiltrate
Lymphocytes: 56% (<10%)Plasma cells: 8% (< 2%)
Tick-borne disease titerSNAP 3Dx positiveEhrlichia canis positive IFA tier (1:10,240)
Additional Tests Outcome
Treatment with Doxycycline10 mg/kg BID for 30 days
Dog recovered uneventfullyStill positive??
Lost to follow-up
Canine Monocytic Ehrlichioses
Intracellular agents that reside in the monocytes and lymphocytes of infected hostsCan cause clonal proliferation of lymphocytsesMost often E. canis and E. chaffeensis (HME)Diagnosis problematic due to scarcity of circulating organisms
DiagnosisPresumptive diagnosis based on clinical and routine laboratory findings
+/- history of tick exposureConfirmed with serology or PCR analysisPCR used to speciate infectious agents
Not as sensitive as serology
PCR
False negative, particularly in chronically infected dogs
Must do PCR analysis on splenic aspirates or bone marrow aspirates to evaluate therapy
Snap3Dx (IDEXX Laboratories Inc.)Uses P30 and P30-1 antigens of E. canisHigh specificity (100%), but low sensitivity (79.2%)(Bélanger et al., J. Clin Microbiol, 2001
High positive and negative predictive values in low prevalence populationsCannot differentiate between E. canis and E. chaffeensis infections
Treatment and PrognosisDoxycycline (5 mg/kg PO bid for 21 -30 days) or tetracycline (20 mg/kg PO tid)Eliminates clinical signs (titers may persist)Prognosis excellent in acute cases and mild chronic casesPrognosis guarded in dogs with severe pancytopenia or aplastic bone marrow