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20
At the outset, it is important to stress that the only consistent finding among
cases of ehrlichiosis is inconsistency.
R. LEE PYLE
Veterinary Clinics of North America: Small Animal Practice-Vol. 21, No. 1, January 1991 75
76 BENNY J. WOODY AND JOHNNY D. HOSKINS
BLOOD
SPECIES NATURAL HOST DISEASE CELLS INFECTED
Ehrlichia canis Domestic dog and wild Canine ehrlichiosis Mononuclear cells
canidae
Ehrlichia platys Domestic dog and Infectious cyclic Platelets
possibly wild canidae thrombocytopenia
Ehrlichia equi Horse Equine ehrlichiosis Granulocytes
Ehrlichia risticii Horse Equine monocytic Mononuclear cells
ehrlichiosis (Potomac
horse fever)
earlier and therefore did not seem to be associated with the current illness.
Therefore, hematologic and serum chemistry changes observed must be
considered in light of the case history and the presenting signs of illness.
Concurrent babesiosis, haemobartonellosis, hepatozoonosis, and other op-
portunistic infections may complicate ehrlichial infection in areas where
these diseases are common.
In this article, information on history, transmission, pathogenesis, and
clinicopathologic findings of each ehrlichial disease of dogs are presented
independently. The sections on diagnosis, therapy, and prevention are
inclusive for all ehrlichial diseases of dogs. Case reports are included to
illustrate clinical presentations associated with naturally occurring cases of
Ehrlichia canis infection.
EHRLICHIA CANIS
Clinicopathologic Findings
The clinicopathologic findings in cases of natfirally occurring canine
ehrlichiosis have been studied retrospectively. 19• 34· 35• 37 Collectively, these
retrospective studies evaluated 248 cases of Ehrlichia canis infection pri-
marily from the states of Louisiana, Maryland, Mississippi, New Jersey,
Pennsylvania, and Texas. Cases that were included in each study had a
positive indirect fluorescent antibody (IFA) titer to Ehrlichia canis. The
clinicopathologic findings in canine ehrlichiosis are varied, depending on
the phase of infection. Because accurate staging of the disease is difficult,
if not impossible in the naturally occurring case, no attempt has been made
to correlate the findings in the retrospective studies to a particular phase
of infection.
The presenting complaints often were nonspecific and included depres-
sion and lethargy, weight loss, and anorexia in. over 50% of the cases (Table
2). Bleeding, vomition, and ataxia were less frequent presenting complaints.
Hemorrhagic tendencies, pyrexia, and lymphadenomegaly were the most
frequently detected abnormalities during physical examination (Table 2).
Splenomegaly, heart murmurs, vomition, and ataxia were detected in 10%
to 20% of the dogs.
Hemorrhagic tendencies in these cases most frequently included
epistaxis, petechiae, ecchymoses, melena, and prolonged bleeding from
venipuncture sites. Additional bleeding disorders included hematuria,
hyphema, hemoptysis, hemat~mesis, hemarthrosis, retinal hemorrhage,
and cerebral hemorrhage. Epistaxis was the most common bleeding disorder
reported and was present in 51 (27%) of 192 cases reporting the nature of
Depression/lethargy 53 59 70 85 67 248
Weight loss 60 39 70 44 59 248
Anorexia 60 27 64 67 56 248
Hemorrhagic tendencies 50 34 53 37 46 248
Pyrexia 50 20 48 37 40 248
Tick infestation 40 NR 39 11 35 192
Lymphadenoljlegaly 13 27 36 NR 30 221
Splenomegaly 7 14 20 37 19 248
Heart murmur NR NR 10 44 16 162
Vomition NR 9 17 11 14 218
Ataxia 7 NR 14 7 12 192
*Troy et al33
tKuehn et al19
+Woody""
§Waddle e t al34
NR = not reported.
EHRLICHIAL DISEASES OF Docs 79
the bleeding.
Neurologic signs seen with canine ehrlichiosis include ataxia, seizures,
upper and lower motor neuron deficits, and mental stupor. 39 Possible causes
include plasma cell infiltration or hemorrhage in the meninges or paren-
chyma of the spinal cord or brain. Cerebrospinal fluid from dogs with
central nervous system signs commonly shows mildly increased protein
levels and mononuclear pleocytosis, especially lymphocytes and plasma
cells.
Ocular signs seen with canine ehrlichiosis primarily are associated with
anterior uveitus and retinal disease (such as focal chorioretinitis, papille-
dema, retinal hemorrhage, retinal perivascular infiltrates, and bullous
retinal detachment). Additional findings include serous or mucopurulent
discharge, conjunctivitis, corneal opacity, hyphema, and iris petechia-
tionY· 34
Many varied physical abnormalities of other organ systems have been
recognized and associated with canine ehrlichiosis (Table 3).
The hematologic abnormalities identified most frequently in dogs with
ehrlichiosis were nonregenerative anemia and thrombocytope nia (Table 4).
Reticulocyte counts in 126 of 181 anemic dogs showed evidence of bone
marrow response in only 27 cases (21 %). Results of direct Coombs' testing
were positive in 17 (27%) of the 62 dogs tested. The leukocyte count was
the most variable blood cell parameter. In some cases, the lymphopenia
and eosinope nia could be attributed to previous corticosteroid usage.
Thrombocytopenia is a consistent finding in all stages of Ehrlichia canis
infection. The mechanism of thrombocytopenia is different in the acute and
chronic phases. The decrease in platelet counts in the acute phase, which
begins a few days after infection, is caused by increased platelet consump-
tion or sequestration. 17• 23 • 26 Immunologic and inflammatory mechanisms
are involved with platelet consumption. Platelet half-life is decreased ,
probably as a result of sple nic sequestration.28 • 32 In the severe chronic
phase, thrombocytopenia is caused by decreased production secondary to
bone marrow hypoplasia.
Anemia in the acute phase results from increased destruction (immu-
nologic) and decreased production. 5 • 28 Erythrophagocytosis is a common
histologic finding and a number of the patients will have positive results of
direct Coombs' test. Regenerative anemias may be evident during this
stage secondary to the immune destruction of red blood cells or when there
is extensive bleeding. The myeloid to erythroid ratio in the bone marrow
may be increased secondary to erythroid hypoplasia as a result of inflam-
matory disease. Anemia in the chronic phase usually is nonregenerative
and is a result of continued destruction, chronic blood loss, or decreased
production secondary to bone marrow hypoplasia.
A mild leukopenia may be evident in the acute phase of infection and
may be related to mechanisms similar to those causing the acute phase
thrombocytopenia. Leukocytosis also may be present. Bone marrow mye-
80 BENNY J. WOODY AND JOHNNY D. HOSKINS
gamma globulins (Fig. 1). The magnitude of the increased globulin levels
can correlate with the duration of illness. Occasionally, a narrow polyclonal
spike on serum and urine protein electrophoresis and serum hyperviscosity
is identified in patients with chronic disease. 14 Differentiation of Ehrlichia
canis infection from a multiple myeloma can be difficult. 4
Elevations of ALT and ALP levels often occur and may be accompanied
by mild hyperbilirubinemia. Proteinuria and hematuria may be detected
with or without azotemia in some dogs with chronic disease. After appro-
priate therapy, the elevated ALT and ALP levels, azotemia, and proteinuria
EHRLICHIA PLATYS
4
::l Figure 2. Percentage of para-
~ 3 sitized platelets and total platelet
counts from a dog infected with
~ 2 Ehrlichia platys. (From Greene
w
...J CE, Harvey JW: Canine ehrlichi-
w 1
osis. In Greene CE (ed): Clinical
~
a.. 0
Microbiology and Infectious Dis-
eases of the Dog and Cat. Phila-
-10 0 10 20 30 40 50 60 70 80
delphia, WB Saunders, 1984, p
DAYS 559.)
EHRLICHIAL DISEASES OF DOGS 85
EHRLICHIA EQUI
EHRLICHIA RISTICII
Ehrlichia canis
Many of the signs commonly associated ~th canine ehrlichiosis
(depression, lethargy, anorexia, and weight loss) are nonspecific. Signs that
are more likely to raise the index of suspicion for canine ehrlichiosis, such
as hemorrhagic tendencies, pyrexia, lymphadenomegaly, and tick infesta-
tion, are not present in a large percentage of patients. Nonregenerative
anemia and thrombocytopenia are the most consistent hematologic findings
but are not found in every patient. The incidence of thrombocytopenia in
naturally occurring cases is possibly overestimated in the literature, because
a platelet count often has been used as a screening test for ehrlichiosis.
Thus, a diagnosis of ehrlichiosis is less likely to have been pursued in an
animal with a normal platelet count.
Identification of Ehrlichia canis morulae in circulating cells of Giemsa-
stained blood smears is time consuming and _is usually not rewarding (see
Table 4), because morulae are found transiently and in low numbers. The
chance of identifying an infected leukocyte may be increased by examining
huffy coat smears or thin blood smears made from a peripheral capillary
bed of the ear margin. 13 Morulae stain bluish-purple and occur in cytoplasm
of an individual cell (Fig. 3). Examination of tissue aspirates and impression
smears of biopsy samples (especially taken from lung, lymph node, or
spleen) for intracytoplasmic inclusions have been used to confirm the
diagnosis of Ehrlichia canis infection but also are low-yield diagnostic
procedures.
cline in eliminating the organism from the host and in treating the resistant
severe chronic patients. 22• 27
The response to therapy for ehrlichial disease is evaluated by noting
clinical improvement. Dogs with acute, subclinical, or mild chronic disease
often respond dramatically to therapy with improvement in attitude,
activity, and appetite within 24 to 48 hours. Clinical improvement usually
precedes hematologic improvement.
In Ehrlichia canis infections, bone marrow evaluations are not totally
reliable in predicting the interval after which a hematologic response to
tetracycline therapy will occur, although dogs with more cellular marrow
tend to respond more quickly (often within 2 to 4 days). If the bone marrow
is severely hypoplastic, as is often seen in the severe chronic disease, it
may take months for hematologic improvement to occur. Nonregenerative
anemias or pancytopenias in the severe chronic phase of Ehrlichia canis
infection are not always irreversible processes, although the prognosis is
poorer because of the risk of fatal hemorrhage or sepsis developing prior
to recovery. Many of these dogs will need tetracycline and supportive
therapy for 6 weeks or longer before improvement may occur. After
tetracycline therapy, complete bone-marrow regeneration may take as long
as 3 months. 13 Thus, some chronically infected dogs may require constant,
or at least intermittent, supportive care until they improve, which may
take 2 to 6 months. Even then, not all dogs respond. Dogs with irreversible
organ (such as liver and kidney) disease secondary to Ehrlichia canis
infection require maintenance of appropriate supportive care.
Serum IFA titers and globulin concentrations decrease gradually fol-
lowing treatment; however, a positive titer may persist for months after
therapy. Ideally, diminishing IFA antibody titers should occur with tetra-
cycline therapy. However, it is not unusual for the IFA titers to increase,
sometimes rather dramatically, after initiation of drug therapy, and then
decline over the next 3 to 6 months. Persistence of an IFA titer that is still
measurable 9 to 12 months after adequate treatment generally indicates the
presence of Ehrlichia canis organisms. This may be a persistence of the
initial Ehrlichia canis infection or a ·reinfection with Ehrlichia canis, because
successfully treated dogs are susceptible to reinfection with ehrlichial
organisms.
The prognosis for Ehrlichia canis infection depends upon the phase of
disease when therapy is initiated. The more acute the disease, the better
the prognosis should be . Despite progressive improvement, a few seemingly
recovered dogs may have a reappearance of ehrlichial organisms and
subsequently present for recurrent illness. Treatment response at this stage
is often variable, and refractory cases frequently are encountered. Infections
caused by Ehrlichia platys and Ehrlichia equi apparently respond well to
therapy.
EHRLICHIAL DISEASES OF DOGS 91
CASE REPORTS
;i;,~
Five case reports of dogs with Ehrlichia canis infection are presented
to emphasize typical clinical presentations associated with naturally occur-
ring canine ehrlichiosis. These case reports review only the most important
historical findings, abnormal physical examination findings, and abnormal
laboratory data. Brief comments regarding clinical course and therapy are
included.
Case 1
Signalment. Approximately 6-month-old female mixed-breed dog.
Chief Complaint. Patient presented for routine vaccinations.
History. The dog was found 2 weeks before admission. No abnormali-
ties had been observed by the current owner.
Physical Examination. Abnormal findings included pyrexia (103.6°F)
and lymphadenomegaly (mandibular, popliteal, and inguinal). Brown dog
ticks were present on the dog.
Laboratory Data. Abnormal hematologic findings included anemia
(PCV, 27%) and thrombocytopenia (platelet count, 85,000/j..LL). The direct
Coombs' test result was positive at 37°C. Lymph-node cytology revealed a
normal population of lymphoid cells with an increased number of plasma
cells. IFA titer to Ehrlichia canis was submitted (returned negative on day
10).
Clinical Course. Tetracycline hydrochloride therapy (22 mglkg, 3 times
a day) was initiated on day 2. The pyrexia had resolved and the dog had
gained 1.2 kg in body weight when rechecked on day 8. The owner reported
that the dog was more active and had a better appetite than before therapy
was initiated. On day 14, the hemogram was normal. IFA titer to Ehrlichia
canis was resubmitted (returned positive at 1:1280 on day22). Tetracycline
therapy was continued for a total of 4 weeks. According to the owner, the
dog was normal at 1 year follow-up.
Comments. The patient was not presented for signs related to canine
ehrlichiosis; however, fever and lymphadenomegaly were detected on
physical examination. This was probably a case of acute canine ehrlichiosis
because the IFA test result was initially negative and then was positive.
Case 2
Signalment. Two-year-old male Old English Sheepdog.
ChiefComplaint. Fever, lethargy, anorexia, and weight loss.
History. Fever, lethargy, and anorexia had been observed for 4 weeks
before admission. The dog had lost 4 kg of body weight during the past
month. Epistaxis was observed following an episode of violent sneezing 10
days prior to admission. Ticks had never been observed on the dog.
Physical Examination. Abnormal findings included mandibular lym-
phadenomegaly and loss of body condition.
EHRLICHIAL DISEASES OF Docs 93
PCV (%) 48 30 31
RBCIJLL ( x 10') 6.18 ND ND
Hgb (gldL) 16.2 10.2 10.3
Reticulocytes (%) ND 0.8 2.2
Nucleated RBC 0 0 9
WBC/JLL 33,400 64,000 21,100
Segmented neutrophils 29,893 56,320 19,412
Barid rieutrophils 334 1280 0
Lymphocytes 334 5120 1266
Monocytes 2839 1280 211
E osinophils 0 0 211
Platelets/ JLL 207,000 20,000 198,000
Plasma protein (gldL) 6.6 6.4 6. 7
ND = not determined.
94 BENNY J . WOODY AND JOHNNY D. HOSKINS
PCV (%) 19 20
RBCI!J.L (xl06) 2.78 2.76
Hgb (gldL) 6.3 6.9
Reticulocytes (%) <0.2 < 0.2
WBCI!J.L 2100 300
Segmented neutrophils 840 ND
Lymphocytes 1050 ND
Monocytes 210 ND
Platelets/j.LL . 7,000 0
Plasma protein (gldL) 7.5 6.8
ND = not determined.
creases in beta globulins (1.09 g/dL) and gamma globulins (3.34 g/dL). IFA
titer to Ehrlichia canis was submitted (returned positive at 1:1280 on day
14).
Clinical Course. Hemorrhagic tendencies observed during hospitali-
zation included epistaxis, prolonged bleeding from venipuncture sites,
hematoma formation, petechiae, and ecchymoses. Therapy initiated on day
1 included tetracycline hydrochloride (22 mg/kg, 3 times a day) and a fresh
whole blood transfusion (500 mL). Pyrexia (104°F) was present on days 2
and 3. On day 3, the hemogram revealed nonregenerative anemia, severe
neutropenia, and severe thrombocytopenia. A platelet-rich plasma transfu-
sion (250 mL) and a fresh whole blood transfusion (500 mL) were adminis-
tered. The dog died on day 3.
Necropsy Findings. Gross findings included multifocal subcutaneous
hemorrhage, pulmonary congestion, moderate splenomegaly, and reddish
bone marrow. Histologic findings included plasmacytosis in lymph node,
spleen, kidney, meninges, and small intestine; subacute interstitial pneu-
monia; focal pulmonary hemorrhage; erythrophagocytosis; and bone marrow
depletion.
Comments. The brief period of anorexia (which spontaneously resolved)
is an important part of the history because this probably was part of the
acute phase of infection. German Shepherd dogs are reported to be likely
to develop the severe chronic phase of infection more rapidly than other
breeds.
Case 5
Signalment. Seven-month-old female Great Dane.
Chief Complaint. Anemia.
History. Onset of weakness, anorexia, and weight loss was observed 2
weeks before admission. Anemia (PCV, 12%) was identified 1 day before
admission. Ticks had been observed on dog.
Physical Examination. Abnormal findings included pale mucous mem-
branes and grade 3/6 systolic heart murmur.
96 BENNY J. WOODY AND JOHNNY D. HOSKINS
PCV (%) 12 13 24 32 38
RBC/f.LL ( x lQS) 1.83 1.87 3.02 4.10 5.24
Hgb (g/dL) 4.2 4.5 7.2 10.2 12.8
Reticulocytes (%) <0.2 0.6 1.4 1.5 ND
Nucleated RBC 1 14 3 1 0
WBC/f.LL 800 970 2800 3800 2600
Segmented neutrophils 496 737 2464 3078 1742
Band neutrophils 16 0 0 0 156
Lymphocytes 224 213 224 228 520
Monocytes 16 20 28 114 52
Eosinophils 48 0 84 380 130
Platelets/ f.LL 1500 15,000 24,000 30,000 156,000
Plasma protein (g/dL) 6.8 6.9 6.3 6.2 6.3
ND = not determined.
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98 BENNY J. WOODY AND }OHNNY D. HOSKINS