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Ehrlichial Diseases of Dogs

Benny]. Woody, DVM, MS, *


and johnny D. Hoskins, DVM, PhDt

At the outset, it is important to stress that the only consistent finding among
cases of ehrlichiosis is inconsistency.

R. LEE PYLE

Several species of the genus Ehrlichia cause clinical and subclinical


infections in dogs (Table 1). These include Ehrlichia canis, 7• 19• 34• 35 Ehrlichia
platys, 12 Ehrlichia equi, 24 and Ehrlichia risticii. 29 Of these, Ehrlichia canis
is the most common cause of clinical illness and causes the most severe
infections in dogs Y· 15
Ehrlichia canis, Ehrlichia platys, Ehrlichia equi, and Ehrlichia risticii
are obligate intracellular rickettsial organisms that parasitize circulating
leukocytes or thrombocytes of the host animal. In the dog, Ehrlichia canis
and Ehrlichia risticii primarily invade mononuclear leukocytes (predomi-
nantly monocytes), Ehrlichia equi invades polymorphonuclear leukocytes
(neutrophils), and Ehrlichia platys invades only the thrombocytes. 13
Although ehrlichial diseases were once considered rare in the United
States, this is no longer true. Diagnoses of ehrlichial diseases are being
made in the United States with increasing frequency in part because of
improving diagnostic tests, expanding geographic occurrence, and increas-
ing clinical awareness.
In the clinical situation, making a clear differentiation between acute
and chronic phases of infection in naturally occurring cases often is difficult.
Clinical presentations and laboratory findings may be similar during the
acute and chronic phases of infection, especially in Ehrlichia canis infec-
tions. 35• 39 Persistence and duration of Ehrlichia-related illness may have
been unobserved by the owner or may have occurred months to years

*Diplomate, American Board of Veterinary Practitioners; Associate Professor, Department of


Clinical Sciences, Mississippi State University College of Veterinary Medicine, Mississippi
State, Mississippi
tDiplomate, American College of Veterinary Internal Medicine; Professor of Veterinary
Clinical Medicine, Department of Veterinary Clinical Sciences, Louisiana State University
School of Veterinary Medicine , Baton Rouge, Louisiana

Veterinary Clinics of North America: Small Animal Practice-Vol. 21, No. 1, January 1991 75
76 BENNY J. WOODY AND JOHNNY D. HOSKINS

Table 1. Differential Features of Species of the Genus Ehrlichia That Occur


in Dogs in the United States ~~.

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

Illness caused by Ehrlichia canis commonly is referred to as canine


ehrlichiosis. However, it also has been known by a variety of synonyms
including tropical canine pancytopenia, canine typhus, canine hemorrhagic
fever, idiopathic hemorrhagic syndrome, Nairobi bleeding disorder, canine
rickettsiosis, and tracker dog disease.
Disease caused by Ehrlichia canis was first recognized in the United
States in 1962. By 1980, the disease had been reported in 10 states, and
by 1982, there was serologic evidence of the disease in 34 states. 18 It is
now one of the most important canine infectious diseases in the United
States. Cases occur in every state where the vector, the brown dog tick,
Rhipicephalus sanguineus, exists.
Transmission
Ehrlichia canis is transmitted among dogs primarily by the brown dog
tick, Rhipicephalus sanguineus. 11 The brown dog tick usually becomes
infected after ingesting an infected canine leukocyte. Dog-to-tick transmis-
sion is more likely to occur during the first 2 to 3 weeks of canine infection
EHRLICHIAL DISEASES OF DOGS 77
because infected leukocytes are more prevalent during the early stages of
infection. Once infected, transstadial transmission of the organism occurs
in this three-stage tick, and transmission of the disease to dogs can occur
in any stage and for at least 155 days. With this duration of infectivity, it is
possible for the tick to survive through the winter months and infect
susceptible dogs in the spring. 21 Therefore, the tick can serve as a primary
reservoir for year to year transmission of the disease even though trans-
ovarial transmission of Ehrlichia canis does not occur in the tick. Infection
of a dog occurs when an infected tick coptaminates the feeding site while
ingesting its blood meal. Because there is no intermediate host, blood
transfusion from an infected donor also can potentially transmit the disease.
Phases of Disease
Three phases of the disease, acute, subclinical, and chronic, have been
recognized on the basis of controlled laboratory studies of dogs experimen-
tally inoculated with Ehrlichia canis. The clinical signs and clinicopathologic
abnormalities associated with each phase have been documented in the
experimental studies. 6 • 16• 26 In the clinical situation with naturally occurring
cases, accurate staging of the disease is difficult if not impossible. Clinically,
it is appropriate to divide the chronic phase into mild chronic and severe
chronic phases. 39
After an incubation period of 8 to 20 days, the progression of Ehrlichia
canis infection consists of an acute phase lasting 2 to 4 weeks during which
the organisms multiply and spread throughout the body. 13 Nonspecific signs
such as fever, oculonasal discharge, anorexia, depression, weight loss, and
lymphadenomegaly may be seen during acute phases. Laboratory abnor-
malities, such as mild anemia, thrombocytopenia, and variable leukocyte
count, may be evident. The acute phase usually resolves spontaneously;
the subclinical phase then begins. During this phase, the dog's weight
normalizes and the pyrexia resolves, and the dog appears normal clinically.
Nevertheless, laboratory abnormalities may persist, especially mild throm-
bocytopenia and hyperglobulinemia. Serum antibody titers start rising 7 to
28 days after initial infection and continue to rise during the subclinical
phase. 6• 31• 36 In experimentally infected animals, the subclinical phase lasts
40 to 120 days; then the chronic phase begins. However, the subclinical
phase has the potential to persist for years in the clinical situation. 7 If
immunocompetent, infected dogs may be able to eliminate Ehrlichia canis.
If not, the chronic phase of infection can occur.
In the mild chronic phase of Ehrlichia canis infection, the clinical signs
often reappear as vague signs of illness (general unthriftiness, lethargy, or
selective appetite). The severe chronic phase may appear immediately after
the subclinical phase or after a short to extended mild chronic phase. The
factors that apparently affect the clinical severity and progression of the
disease include strain variation, breed of dog, dog's age, immunocompe-
tence of host, and concomitant disease.
78 BENNY J. WooDY AND JOHNNY D. HosKINS

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

Table 2. Clinical Abno1'11Ullities Frequently Present in Retrospective Studies


of Naturally Occurring Cases of Ehrlichia canis Infection
STUDY 1* STUDY 2t STUDY 3:j: STUDY 4§
(N = 30) (N = 56) (N = 135) (N = 27) TOTAL

CLINICAL SIGN Percentage Affected N

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

Table 3. Physical Abnormalities Associated with Ehrlichia canis Infection of Dogs


INTEGUMENTARY SYSTEM . ~:.
Ticks often found during the acute infection but infrequently with chronic infection.
Petechial hemorrhages may be noted.
OPHTHALMIC SYSTEM
Purulent ocular discharge and conjunctival hemorrhages may be noted. Early fundic
lesions include tortuous retinal vessels with grayish, circular to horseshoe-shaped foci in
perivascular locations. Later lesions appear as dark gray spots in the tapetal area with
surrounding areas of hyperreflectivity. Extensive areas of retinal damage can lead to
subretinal hemorrhage and retinal detachment. Anterior uveitis, hyphema, and corneal
opacities from the deposition of cellular precipitates and/or edema occur frequently.
MUSCULOSKELETAL SYSTEM
Reduced generalized muscle mass, weakness, and occasional peripheral limb edema are
noted in the terminal stages of chronic infection. Weightbearing lameness that progresses
to reluctance to stand or walk often occurs from hemorrhage into joints, swollen painful
joints, or effusive (mostly intact neutrophils) joints.
NERVOUS SYSTEM
Arched back, severe pain in the neck or the back, unilateral or bilateral paraparesis,
cranial nerve deficits, and convulsions may occur.
CARDIOVASCULAR SYSTEM
Heart rate and pulse are generally reflective of the degree of anemia present. Cardiac
dysfunction resulting from hemorrhage into the myocardium can lead to altered breathing
patterns, tachycardia, arrhythmias, and pulse deficits. Detection of heart murmurs is an
inconsistent finding.
RESPIRATORY SYSTEM
Purulent nasal discharge and epistaxis commonly occur. Pulmonary signs occurring
secondary to Ehrlichia-induced interstitial lung disease include altered breathing patterns,
increased lung sounds, and occasional cyanosis.
DIGESTIVE SYSTEM
Pale mucous membranes, petechial hemorrhages in buccal cavity, loss of appetite, and
occasional melena may be present. Icterus and hepatomegaly accompanying other general
signs of ehrlichial infection have been noted. Vomition is an inconsistent finding.
LYMPHATIC SYSTEM
Generalized peripherallymphadenomegaly and splenomegaly are inconsistent findings.
REPRODUCTIVE SYSTEM
Petechial hemorrhages on the genital mucosa and occasional scrotal edema can occur.
Several other problems have been observed in infected bitches, including prolonged
bleeding during proestrus, inability to conceive, abortion, postparturient vaginal bleeding,
and neonatal death.
URINARY SYSTEM
Gross and microscopic hematuria commonly occurs. Reduced kidney function often is
observed in the terminal stages of chronic infection. The signs include polydipsia,
polyuria, anorexia, vomiting, and oral ulceration.

lopoiesis usually is accelerated during the acute phase. 28 In the severe


chronic phase, leukopenia is secondary to bone marrow hypoplasia.
Abnormalities seen on bone marrow aspirates or core biopsy specimens
are dependent on the phase and severity of the infection. 13 Normal to
increased cellularity of megakaryocytic and myeloid series with a decrease
in erythroid precursors are common findings during the acute phase and
during the chronic phase of infection in some dogs. Marrow plasmacytosis,
prominent in many cases of Ehrlichia canis infection, does not depend on
EHRLICHIAL DISEASES OF DOGS 81

Table 4. Hematologic Findings in Retrospective Studies of Naturally Occurring


Cases of Ehrlichia canis Infection
STUDY 1* STUDY 2t STUDY 3:j: STUDY 4§
(N = 30) (N =56) (N = 135) (N = 27) TOTAL

CLINICAL SIGN Percentage Affected N


Anemia 90 72 68 81 73 248
Regenerative NR 15 20 40 21 126
Nonregenerative NR 85 80 60 79 126
Leukopenia 53 25 30 22 31 248
Leukocytosis 17 14 21' 30 20 248
Neutropenia 47 18 24 19 25 248
Neutrophilia NR 14 20 37 21 218
Lymphopenia NR 41 44 48 44 218
Lymphocytosis NR 7 11 11 10 218
Monocytosis 23 9 20 0 16 248
Eosinopenia NR 27 51 63 46 218
Eosinophilia NR 9 2 4 4 218
Basophilia NR 5 10 0 8 218
Thrombocytopenia 100 64 92 84 86 243
Pancytopenia NR 13 19 NR 17 191
Morulae identified 17 0 2 NR 4 221
*Troy et al33
tKuehn et aJl9
:j:Woody'"
§Waddle et al34
NR = not reported.

the phase of infection. Pancytopenia caused by hypoplasia of all bone


marrow precursor cells may occur in the severe chronic phase. Pancytopenia
was present in 33 (18%) of the 191 cases reporting the specifics of the
cytopenias (Table 4). Pancytopenia is reported to be seen more often in
German Shepherd dogs. 6
The most frequent serum chemistry abnormalities (Table 5) found in
the retrospective reviews included hyperproteinemia (33%) with hyperglob-
ulinemia (39%) and hypoalbuminemia (43%), elevated alanine aminotrans-
ferase (ALT) levels (43%), and elevated alkaline phosphatase (ALP) levels
(31 %). In some cases, the ALP elevations could be attributed to prior
corticosteroid usage.
Hyperproteinemia resulting primarily from elevated globulins com-
monly is detected after initiation of Ehrlichia canis infection. 6 In addition,
a concomitant hypoalbuminemia may occur, which may be a result of
protein malnutrition, proteinuria, blood loss, concurrent liver disease,
peripheral loss in edematous fluid secondary to vasculitis, and compensation
for hyperglobulinemia. There is no direct correlation between the levels of
serum globulins and serum antibodies (as measured by the IFA test)
produced in response to Ehrlichia canis infection, and neither is protective
against reinfection. The hype rglobulinemia suggests an exaggerated immune
response with inadequate effectiveness. Serum electrophoresis generally
shows a polyclonal hyperglobulinemia with increased alpha-2, beta, and
82 BENNY J. WOODY AND JOHNNY D. HOSKINS

Table 5. Serum Chemistry Findings in Retrospective Studies of Naturally


Occurring Cases of Ehrlichia canis Inf'I.E!ion
STUDY 1* STUDY 2t STUDY 3:j: STUDY 4§
(N = 30) (N = 56) (N = 135) (N = 27) TOTAL

CUNICAL SIGN Percentage Affected N


Hyperproteinemia 37 38 30 NR 33 213
Hypoproteinemia NR 5 4 NR 4 183
Hyperglobulinemia NR 46 39 23 39 209
H ypoglobuminemia NR 7 1 4 3 209
Hypoalbuminemia NR 36 46 42 43 209
Alanine aminotransferase (elevated) 31 36 48 44 43 234
Alkaline phosphatase (elevated) 0 39 28 58 31 235
Total bilirubin (elevated) 19 NR 10 15 12 179
Blood urea nitrogen (elevated) NR 21 20 19 20 209
Creatinine (elevated) NR 30 5 19 13 208
*Troy et al33
tKuehn et al'9
:j:Woody'"
§Waddle et al34
NR = not reported.

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

Figure 1. Serum protein elec-


trophoresis pattern from a dog with
canine ehrlichiosis shows a polyclo-
nal gammopathy. In this tracing,
the globulin increases are present
I alb I " 1 I "2 I 131 I in the a 2 , ~ . and 'Y fractions.
EHRLICHIAL DISEASES OF Docs 83
often resolve. Dogs with irreversible liver or kidney damage resulting from
Ehrlichia canis infection continue to have elevated serum chemistry values
and must be maintained with supportive therapy.
In dogs with bleeding problems, prolonged bleeding times usually are
detected, but the activated coagulation time, one-stage prothrombin time
(PT), activated partial thromboplastin time (PIT), and fibrin degradation
products (FOPs) typically are normal. 13• 19• 37 Prolonged bleeding times are
evident because of thrombocytopenia or platelet malfunction. However,
the severity of hemorrhage often cannot be directly correlated to the level
of thrombocytopenia. In one study, 37 only' 15% of the dogs had petechial
hemorrhage, although 37% of these animals had thrombocyte counts less
than 40,000/mm3 • Some dogs in this study had platelet counts less than
10,000/mm3 and showed no evidence of hemorrhage. Some dogs had
hemorrhagic tendencies with normal platelet counts; however, when tested,
platelet function defects often were detected.
Pulmonary interstitial radiopacities commonly occur in cases of ehr-
lichiosis. In two reviews,8 • 37 approximately 70% of the patients had inter-
stitial lung changes. In many patients, the pulmonary lesions could not be
correlated with other diseases (such as heartworm disease and fungal
disease). Radiographic findings ranged from a mild linear pattern to marked
interstitial infiltration with peribronchial opqcities.
Pathologic findings vary with the phase of disease and the severity of
the disease process. Gross lesions often include petechial and ecchymotic
hemorrhages, generalized reticuloendothelial cell hyperplasia, and edema
of dependent tissues. The most prominent histologic lesion is plasma cell
infiltration in many organs including the meninges, kidneys, lungs, liver,
spleen, lymph nodes, and bone marrow. Meningeal lesions generally are
present histologically (especially plasma cell infiltrates) even in the absence
of neurologic signs. Early renal lesions consist of a vasculitis and phlebitis
with later infiltration of plasma cells and lymphocytes. Pulmonary changes
include an interstitial pneumonia, followed by a proliferative inte rstitial and
bronchial pneumonia in more chronic stages. Pe ribronchial and perivascular
plasma cell infiltrates and hemorrhage are common. 9• 37 Splenic lesions
include reticuloendothelial hyperplasia, plasma cell infiltration, extramed-
ullary hematopoeisis, and erythrophagocytosis. Varying degrees of infiltra-
tion of the portal triads with macrophages, lymphocytes, and plasma cells
are common hepatic lesions. 28

EHRLICHIA PLATYS

Illness caused by Ehrlichia platys commonly is referred to as infectious


cyclic thrombocytopenia. Disease caused by Ehrlichia platys was first
described in the United States in 1978. 12
Ehrlichia platys is suspected of being transmitted among dogs primarily
84 BENNY J. WOODY AND JOHNNY D. HOSKINS

by the brown dog tick. 13 Transm.ission by direct blood inoculation is possible.


Ehrlichia platys organisms infect only the platelet:~: not circulating leuko-
cytes. After an incubation period of 8 to 15 days, · acute Ehrlichia platys
infection is characterized by cyclic parasitemia of platelets followed by
thrombocytopenia and generalized lymphadenomegaly. 2 Infected dogs usu-
ally are not clinically ill and rarely show signs of significant hemorrhage
even with severe thrombocytopenias. Dual infections with Ehrlichia canis
and Ehrlichia platys are common. 15
After the first appearance of Ehrlichia-infected platelets in the periph-
eral blood occurs, there is a precipitous decrease in the total platelet count
(Fig. 2). The initial platelet counts may be 10,000 cells/~L or lower.
Thereafter, the platelet count increases rapidly, as parasitized platelets
disappear from the blood, and reach normal values within 3 to 4 days. 13
Appearance of parasitized platelets and subsequent thrombocytopenias
usually recurs at 1- to 2-week intervals. The ""Cyclic nature of the appearance
of parasitized platelets and thrombocytopenias diminishes during chronic
infections, resulting in slowly resolving thrombocytopenias in association
with sporadically occurring parasitized platelets in the blood.
Consequently, infected dogs can present with total platelet counts that
range from normal to extremely low. In some cases, transient decreases in
total leukocyte counts, absolute neutrophil counts, and packed cell volume
values have occurred concomitant with the appearance of parasitized
platelets, but these values rarely have been below the normal ranges for
dogs. Mild hypoalbuminemia and hyperglobulinemia also may be present. 1

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 equi organisms infect the circulating neutrophils of horses,


dogs, cats, sheep, goats, and nonhuman primates. Disease caused by
Ehrlichia equi infections in dogs was first described in the United States
in 1982. 24
Ehrlichia equi is thought to be transmitted to dogs primarily by ticks.
Transmission by direct blood inoculation is possible. The vector, reservoir,
incubation period, and pathogenesis of Ehrlichia equi infection in the dog
are unknown but are assumed to be similar to Ehrlichia canis. Ehrlichia
equi can cause severe illness in horses (equine ehrlichiosis) but generally
causes only mild or inapparent infections in dogs. It can cause thrombocy-
topenia and anemia in infected dogs. 24 Infection with Ehrlichia equi does
not seem to alter the susceptibility of dogs to Ehrlichia canis or to other
ehrlichial species.

EHRLICHIA RISTICII

Dogs are susceptible to experimental infection with Ehrlichia risticii


organisms. 29 Ehrlichia risticii can cause severe illness in horses (equine
monocytic ehrlichiosis, Potomac horse fever) but causes only mild or
inapparent infections in dogs. Naturally occurring disease caused by Ehr-
lichia risticii infections in the dog has not been reported.
The vector, reservoir, mode of transmission, and pathogenesis of
Ehrlichia risticii infection in the dog are unknown. Because clinical signs
were not apparent experimentally, infected dogs may serve as carriers of
Ehrlichia risticii without having clinical illness. Serum antibody titer levels
to Ehrlichia risticii were evident as early as 6 to 12 days after initial
infection in the dogs. 29

DIAGNOSIS OF EHRLICHIAL DISEASES

Ehrlichial diseases often present diagnostic dilemmas, because many


of the clinical signs associated with ehrlichial diseases are exceedingly
nonspecific. The IFA test has become a widely used means of clinically
diagnosing ehrlichial infections. There is minimal serologic cross reaction
between Ehrlichia canis, Ehrlichia platys, Ehrlichia equi, and Ehrlichia
risticii. 15• 30 Ehrlichia canis and Ehrlichia equi have the greatest potential
for serological cross reactions. 30 Unfortunately, differences in IFA test
results can be found between diagnostic laboratories and within the same
laboratory when the test is performed on the same serum at different times.
A positive IFA titer only means the animal has been exposed. However, a
positive IFA titer coupled with compatible history, physical findings , and
additional laboratory tests helps to substantiate the clinical diagnosis.
86 BENNY J. WOODY AND JOHNNY D. HOSKINS

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.

Figure 3. Circulating monocyte (arrow) containing an Ehrlichia-like morula. (Wright


stain; original magnification X 650.)
EHRLICHIAL DISEASES OF Docs 87

Because of nonspecific clinical signs and difficulty in identifying an


Ehrlichia canis organism in the blood, a diagnosis of ehrlichiosis usually is
based on results of the IFA test. This sensitive and specific test detects
serum antibodies to Ehrlichia canis as early as 7 days after initial infection,
although some dogs may not be seropositive until 28 days after infection. 6•
26• 31 Serum antibody levels in untreated dogs peak at 80 days after infection,

and titers persist unless complete clearance of the ehrlichial organisms


occurs with drug therapy. The titer of the IFA may vary from 1:10 to
1:10,240. The lowest measurable IFA titer (1:10) is considered positive for
Ehrlichia canis; however, low false-positive titers (up to 1:80) may occur in
samples contaminated with bacteria.9 Rising titers or a persistently positive
IFA titer is considered indicative of active Ehrlichia canis infection. Sudden
decreases in or negative IFA titers have been noted in a few dogs just
before death.
Ehrlichia platys
The diagnosis of Ehrlichia platys infection can be made by the
identification of characteristic basophilic morulae in platelets of Giemsa-
stained blood smears. Detection of the morulae in platelets (Fig. 4) usually
is not rewarding because of the cyclic nature of the appearance of parasitized
platelets.

Figure 4. Ehrlichia platys organisms in platelets from an infected dog. (Wright-Giemsa


stain; original magnification X 650). (Courtesy of Dr. S.D. Gaunt, Louisiana State University,
Baton Rouge, LA.)
88 BENNY J. WOODY AND JOHNNY D. HOSKINS

Currently, the IFA test appears to be a relatively specific means of


identifying dogs that have been exposed to Ehrlichiaf).Jatys. The IFA test
detects serum antibodies to Ehrlichia platys during or shortly after the first
appearance of parasitized platelets in the acutely infected dog. The IFA
titers usually rise 7 to 17 days after initial infection to titers of 1:5120 or
greater. 2 Serum antibody titers to Ehrlichia platys, much like those of
Ehrlichia canis, probably persist in dogs. Titers greater than or equal to
1:100 by the IFA test are indicative of previous exposure but, unless
followed by a rising titer, may not indicate active infection. 15 A single titer
less than 1:200 is considered questionable; it may represent a nonspecific
fluorescent reaction rather than a low antibody titer.
Ehrlichia equi and Ehrlichia risticii
The diagnosis of Ehrlichia equi infection can be made by the identifi-
cation of Ehrlichia morulae in neutrophils and-a positive IFA test result.
Because some strains of Ehrlichia canis apparently invade neutrophils,3· 10·
33• 38 identification of Ehrlichia morulae in neutrophils does not confirm a

diagnosis of Ehrlichia equi. The IFA test appears to be a relatively specific


means of identifying dogs that have been exposed to Ehrlichia equi;
however, Ehrlichia canis and Ehrlichia equi have the greatest potential for
serological cross reactions. 30 At present, the IFA test is the preferred way
to identify dogs that have been exposed to Ehrlichia risticii.

THERAPY FOR EHRLICHIAL DISEASES

Several effective drugs are available for the treatment of ehrlichial


infections in dogs: tetracycline, oxytetracycline, doxycycline, minocycline,
imidocarb dipropionate, and chloramphenicol (Table 6). O(these, tetracy-
cline antibiotics (such as tetracycline, oxytetracycline, and doxycycline) are
the most frequently used. The duration of therapy probably is more
important than the dosage or freqQency of administration of a particular
tetracycline drug. The treatment should be continued for a minimum of 3
to 4 weeks in the responsive cases; however, up to 8 weeks of therapy
often is required in the severe chronic disease. Doxycycline, a lipid-soluble
tetracycline, should be used in cases with compromised renal function.
Doxycycline also may be effective in some patients that were initially
unresponsive to tetracycline or oxytetracycline. Tetracycline and oxytetra-
cycline should not be given 2 to 3 hours before or after feeding, because
impaired absorption may occur. Additionally, chelation of tetracycline with
certain ions (such as calcium, magnesium, iron) within the gastrointestinal
tract decreases absorption. 22 The use of tetracycline antibiotics in puppies
and nursing or pregnant bitches is discouraged because of enamel staining.
Initially, treatment with chloramphenicol should be attempted in these
animals.
EHRLICHIAL DISEASES OF DOGS 89
Table 6. Therapeutic Agents Available for the Treatment
of Ehrlichial Infections in Dogs
THERAPEUTIC AGENT DOSE ROUTE FREQUENCY

First Line Antibiotics


Tetracycline hydrochloride 22 mglkg Oral Three times a day
Oxytetracycline 25 mglkg Oral Three times a day
Doxycycline 10 mglkg Oral or Once daily
intravenous
Minocycline 20 mglkg Oral Two times a day
Second Line Antibiotics
Chloramphenicol 50 mglkg Oral Three times a day
Imidocarb dipropionate* 5 mglkg Intramuscular or Single injection and repeat
subcutaneous injection in 2 to 3 weeks
*At this therapeutic dose, transient pain response may occur during the injection, but
there is no persistent swelling at the injection site. Within 10 minutes after injection, some
dogs show transient (30-minute duration) signs of profuse salivation, serous oculonasal
discharge, diarrhea, altered breathing, increased heart rate, and tremors. These reactions are
attributed to an anticholinesterase effect.

In addition to tetracycline therapy and good supportive care, other


therapy frequently is required, particularly for the chronically infected
dogs. Dehydration is corrected by the administration of polyionic fluids. In
animals with severe anemia or life-threatening hemorrhage, blood transfu-
sions may be required. Fresh, whole blood or platelet-rich plasma must be
used, because platelets are inactivated by commonly used storage proce-
dures. Transfusions should be repeated as needed until the bone marrow
begins to respond. Bone-marrow stimulation with androgenic steroids may
be of some benefit in dogs with depressed bone-marrow production and
pancytopenia. Oral oxymetholone (1 mg/kg, 3 times daily) or nandrolone
decanoate (1.0-1.5 mg/kg, weekly intramuscular injections) may be used.
Glucocorticoid therapy may be used early in the disease, while awaiting
serologic results, especially if thrombocytopenia is life threatening. Short-
term therapy with anti-inflammatory or immunosuppressive doses of pred-
nisolone or dexamethasone may be valuable adjunctive therapy for second-
ary immune-mediated diseases. 13• 39 Unless concurrent immune-mediated
thrombocytopenia has been confirmed, long-term or high-dose glucocorti-
coid therapy is discouraged in the treatment of ehrlichial disease, because
immunosuppression may interfere with complete elimination of the organ-
ism. Care must be exercised in the routine use of these glucocorticoids or
the other immunosuppressive drugs.
Secondary bacterial infections may occur that are resistant to tetracy-
cline. In this situation, drug compatibility and organism susceptibility must
be considered before institution of combined antibiotic therapy.
Imidocarb dipropionate therapy is an effective treatment for ehrlichi-
osis, but the drug is not approved for use in the United States. There is
evidence that imid9carb dipropionate may be more effective than tetracy-
90 BENNY J. WOODY AND }OHNNY D. HOSKINS

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

PREVENTION OF EHRLICHIAL DISEASES

Attempts to control ticks should be made by frequently treating the


environment and dipping the animals. When spraying for ticks with a yard
and kennel spray, particular attention should be given to places where the
animals sleep. Spray at least 3 to 4 feet up any vertical objects such as
buildings, fences, trees, and woodpiles. Before spraying the yard, it should
be raked and mowed. Because most outdoor pesticides have a 7- to 14-day
residual effect, the premise should be sprayed every 2 weeks for three
treatments and then sprayed monthly during the heavy tick season. Dogs
should be dipped every 2 to 3 weeks with a commercially prepared pesticide
dip according to the instructions of the manufacturer.
New dogs should be isolated and ticks removed before introducing
them into an established group of dogs. Dogs with positive IFA antibody
titers for ehrlichial infections should be treated, and test results for dogs
should be negative before they are allowed to mingle. The success of a
control program is best assessed by repeated serologic testing at 6- to 9-
month intervals. Dogs intended to be used for blood donors should initially
test negative for ehrlichial infections on two separate IFA tests run 4 weeks
apart and then be retested at least once yearly.
When it is not economically feasible to test all animals serologically or
when it is impossible to control tick exposure, dogs can be treated with
long-term tetracycline prophylaxis so that ticks will pass through a genera-
tion cycle and the ehrlichial infections will be eliminated. The recom-
mended oral dose for tetracycline is 6. 6 mg/kg given once daily. 39
No vaccine is presently available for the prevention of ehrlichial
infections in dogs.

PUBLIC HEALTH CONSIDERATIONS

Human infection with Ehrlichia canis or another closely related ehrli-


chial species was described in the United States in 1986. 25 Since this initial
report, 45 additional cases of human ehrlichiosis have been identified by
various investigators. 20 Patients were exposed to infection in 11 states, the
majority of which were in the southeastern and south central areas of the
United States. Symptoms reported by patients were nonspecific and similar
to those reported by patients with Rocky Mountain spotted fever. Most
patients had a history of tick exposure in the 4-week period before the
onset of illness. Preliminary findings suggest that human ehrlichiosis is tick
transmitted. There is no evidence that human ehrlichiosis is transmitted
directly from dogs to people. 20
92 BENNY J. WOODY AND JOHNNY D. HOSKINS

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

Laboratory Data. Abnormal hematologic findings included anemia


(PCV, 29%) and thrombocytopenia (platelet count, 54,000/j.LL). Urinalysis
and serum chemistry profile were normal. The result of direct Coombs'
test was negative. Lymph node cytology revealed a normal population of
lymphoid cells with an increased number of plasma cells. Bone marrow
cytology revealed an adequate number of megakaryocytes and a mye-
loid:erythroid ratio of 1:1 with normal maturation of the cell lines. IFA
titer to Ehrlichia canis was submitted (returned positive at 1:5120 on day
12).
Clinical Course. Oxytetracycline therapy (22 mglkg, 3 times a day) was
initiated on day 2. By day 4, the dog was alert and active with a normal
appetite. On day 5, the hemogram revealed resolution of the thrombocy-
topenia (platelet count, 232,000/ j.LL) and improving anemia (PCV, 31 %).
Tetracycline therapy was continued for a total of 4 weeks. According to the
owner, the dog was clinically normal at 1- and 2-year follow-ups.
Comments. This patient did not have a history of tick exposure.
Case 3
Signalment. Nine-year-old neutered female Miniature Schnauzer.
Chief Complaint. Back injury.
History. Acute onset of paraparesis developed after jumping from chair
1 day before admission. Steroids had been administered by the referring
veterinarian.
Physical Examination. Abnormal findings included exaggerated spinal
reflexes and proprioceptive deficits in the hindlimbs. Pain perception was
diminished but present in the hindlimbs.
Laboratory Data. Abnormal hematologic findings included a neutro-
philic leukocytosis (Table 7). Urinalysis and serum chemistry profile were
normal.
Clinical Course. Spinal radiographs and myelogram on day 1 revealed

Table 7. Hematologic Findings in Case 3


DAY 1 DAY 10 DAY 17

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

a compressive lesion of the spinal cord at T12 to T13. Hemilaminectomy


and decompression were performed on day 2. Posllii]Jrgical recovery was
uneventful, and the paraparesis gradually improved. On day 10, the dog
was anorexic and had a rectal temperature of 103.5°F. Petechiae and
splenomegaly were present. The hemogram revealed a nonregenerative
anemia, a neutrophilic leukocytosis with a left shift, and thrombocytopenia
(Table 7). Serum chemistry profile was normal except for hypoalbuminemia
(total protein, 5.4 g/dL; albumin, 2.2 g/dL) and elevated hepatic enzymes
(ALT, 113 U/L; ALP, 348 U/L). Coagulation profile (i.e., PT, PTT, and
FOPs) was normal. Bone marrow cytology was normal except for plasma-
cytosis. The direct Coombs' test result was negative. IFA titer to Ehrlichia
canis was submitted (returned positive at 1:5120 on day 24). Tetracycline
hydrochloride therapy (22 mg/kg, 3 times a day) was initiated on day 11.
On day 15, the pyrexia and anorexia resolved. The splenomegaly was no
longer palpable on day 17. A repeat hemogram on day 17 revealed a
regenerative anemia and neutrophilic leukocytosis. Tetracycline therapy
was continued for a total of 4 weeks. According to the owner, the dog was
clinically normal at 1-year follow-up.
Comments. The patient was presented for a problem unrelated to
canine ehrlichiosis, and initially, no clinical or laboratory findings suggested
canine ehrlichiosis. It is likely that the stress related to the surgery and
concomitant steroid therapy compromised the patient's immune system to
allow a subclinical or mild chronic phase of canine ehrlichiosis to become
clinically apparent.
Case 4
Signalment. One-year-old male German Shepherd dog.
Chief Complaint. Depression and anorexia.
History. The dog was in a vigorous 5-day-a-week training program.
Anorexia, weight loss, and depression had been observed 1 week before
admission. A 3-day period of anorexia (which spontaneously resolved) had
been observed approximately 2 months before admission. Ticks had been
observed on dog.
Physical Examination. Abnormal findings included pale mucous mem-
branes, petechiae, and edematous lower extremities.
Laboratory Data. Abnormal hematologic findings included nonregen-
erative anemia, leukopenia, and thrombocytopenia (Table 8). No Ehrlichia
morulae were seen on a huffy coat examination. Urinalysis was normal.
Serum chemistry profile was normal except hypoalbuminemia and hyper-
globulinemia (total protein, 7. 7 g/dL; albumin, 2.1 g/dL). Coagulation
profile (i.e., PT, PTT, FOPs, and fibrinogen) was normal except for
hyperfibrinogenemia (900 mg/dL). The result of direct Coombs' test was
negative . Bone marrow cytology revealed numerous marrow particles
composed only of stromal cells, fat cells, lymphocytes, and plasma cells.
Serum electrophoresis revealed a polyclonal gammopathy caused by in-
EHRLICHIAL DISEASES OF Docs 95
Table 8. Hematologic Findings in Case 4
DAY 1 DAY3

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

Table 9. Hematologic Findings in Case 5


DAY l DAY5 DAY 15~;. DAY 20 DAY60

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.

Laboratory Data. Abnormal hematologic findings included nonregen-


erative anemia, leukopenia, and thrombocytopenia (Table 9). The serum
chemistry profile was normal except for hypoalbuminemia (total protein,
6.1 g/dL; albumin, 2.3 g/dL). Bone marrow cytology revealed marrow
particles composed primarily of stromal cells, fat cells, and lymphocytes.
No megakaryocytes were observed, and only an occasional myeloid or
erythroid stem cell was observed. IFA titer to Ehrlichia canis was submitted
(returned positive at 1:160 on day 12).
Clinical Course. Tetracycline hydrochloride therapy (22 mg/kg, 3 times
a day) was initiated day 1. Nandrolone decanoate therapy (1. 0 mglkg,
weekly intramuscular injections) was initiated on day 2. By day 7, the dog
was alert, active, and had normal appetite. By day 15, the cardiac murmur
was no longer auscultable. Tetracycline therapy was continued for a total
of 6 weeks. Nandrolomi decanoate therapy was continued for a total of 4
weeks. On day 60, the hemogram revealed resolution ofthe anemia and
thrombocytopenia; however, the leukopenia and neutropenia persisted
(Table 9). Doxycycline therapy (10 mg/kg, once daily) was initiated for 2
weeks. Follow-up laboratory data by the referring veterinarian on day 90
and day 150 revealed persistence of the leukopenia and neutropenia. No
additional laboratory data were obtained; however, according to the owners,
the dog was still clinically normal 2 years following discharge.
Comments. Even though the bone marrow cytology was similar to that
of case 4, this animal did partially respond to therapy. A prognosis should
not be established based on clinical or laboratory findings until therapy has
been attempted.
Key Points Derived from the Case Studies
1. Lethargy, weight loss, anorexia, hemorrhagic tendencies, and py-
rexia are the most common clinical abnormalities reported in canine
ehrlichiosis.
EHRLICHIAL DISEASES OF Docs 97

2. Thrombocytopenia, nonregenerative anemia, elevated ALT, hypo-


albuminemia, and hyperglobulinemia are the most common laboratory
abnormalities reported in canine ehrlichiosis.
3. Clinical signs and laboratory abnormalities may be detected during
the acute phase of infection before an IFA titer is positive.
4. In areas where canine ehrlichiosis is endemic, it often is appropriate
to initiate therapy for suspected canine ehrlichiosis based upon clinical and
laboratory findings prior to obtaining a positive IFA test result for Ehrlichia
canis.
5. Improvement in clinical signs following therapy often is apparent
before laboratory improvement is shown. Although long-term clinical im-
provement may occur, laboratory parameters may improve only partially in
some patients.
6. Therapy in addition to tetracycline administration often is appro-
priate and required.
7. Plasmacytosis in various tissues is a common cytologic and histologic
finding.

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Address reprint requests to


Benny J. Woody, DVM, MS
Department of Clinical Sciences
College of Veterinary Medicine
Mississippi State University
Mississippi State, MI 39762

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