DETECTION OF INTRAARTICULAR ABNORMALITIES IN OSTEOARTHRITIS OF THE
Intraarticular Dirofilaria immitis microfilariae in two dogs
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Transcript of Intraarticular Dirofilaria immitis microfilariae in two dogs
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Veterinary Parasitology 152 (2008) 167–170
Short communication
Intraarticular Dirofilaria immitis microfilariae
in two dogs
Steven Hodges a,*, Mark Rishniw b
a Michigan Veterinary Specialists, 29080 Inkster Road, Southfield, MI 48034, United Statesb Department of Biomedical Sciences, Box 11 Veterinary Research Tower, College of Veterinary Medicine,
Cornell University, Ithaca, NY 14583, United States
Received 28 September 2007; received in revised form 4 November 2007; accepted 8 November 2007
Abstract
Dirofilaria immitis microfilariae were found in the synovial fluid of two dogs. One dog had clinical and cytological evidence of
polyarthritis at the time of presentation. The second dog presented with severe effusion in a single joint and was later diagnosed with
synovial sarcoma of the affected joint. These patients were not protected with heartworm prophylaxis and lived in heartworm
endemic areas. Though there is documentation of D. immitis microfilaria in the synovial fluid of several clinically normal research
dogs with cytologically normal synovial fluid, to our knowledge these are the first documented cases of intraarticular microfilaria in
a dog with cytologically confirmed polyarthritis. Based on these unique cases, D. immitis infection should be considered a
differential diagnosis in patients with polyarthropathies. Interpretive caution must be used when intraarticular microfilaria are
present, as concurrent etiologies may also be present.
# 2007 Elsevier B.V. All rights reserved.
Keywords: Dirofilaria; Microfilaria; Intraarticular; Polyarthritis; Dog
1. Introduction
The clinical presentation of dogs with Dirofilaria
immitis infection is typically associated with complica-
tions due to the anatomic location of adult heartworms
in the right pulmonary artery and, to a lesser degree, the
right ventricle. Extra-cardiopulmonary affects second-
ary to D. immitis infection have been well documented
in dogs with canine heartworm disease. The aberrant
migration of adult worms into numerous tissues appears
throughout the veterinary literature. In such cases,
clinical signs not classically associated with canine
* Corresponding author at: Oklahoma Veterinary Specialists, 515 W
Main Street, Jenks, OK 74037, United States. Tel.: +1 918 299 4900;
fax: +1 918 299 6366.
E-mail address: [email protected] (S. Hodges).
0304-4017/$ – see front matter # 2007 Elsevier B.V. All rights reserved.
doi:10.1016/j.vetpar.2007.11.018
heartworm disease have been reported (Otto, 1974;
Blass et al., 1989; Hribernik et al., 1989; Elkins and
Berkenblit, 1990; Frank et al., 1997; Healey et al.,
2003). A thorough search of the literature revealed
minimal references to the aberrant migration of D.
immitis microfilaria, specifically intraarticular migra-
tion and associated clinical signs.
Weinberger et al. (1979) studied the effect of trauma
on the canine joint in a group of fifteen dogs from the
southern United States. Microfilaria was discovered in
the synovial fluid of one of the dogs during postmortem
examination. The dog appeared clinically well and had
grossly normal appearing joints. Synovial fluid analysis
revealed a normal cell count with no evidence of
inflammation. Systemic microfilaremia was diagnosed
with the Knott test and the acid phosphate test was used
to identify the microfilaria as D. immitis in origin. The
S. Hodges, M. Rishniw / Veterinary Parasitology 152 (2008) 167–170168
Fig. 1.1. D. immitis microfilaria discovered during cytologic exam-
ination of synovial fluid obtained from the right stifle.
significance of the intraarticular microfilaria was
unknown.
2. Case report
2.1. Case 1
An approximately 3-year-old, intact male mixed
breed dog presented to Michigan Veterinary Specialists
as a rescue from the Gulf Coast of the United States
following the 2005 Hurricane Katrina. Physical
examination did not reveal any significant abnormal-
ities. A complete blood count (CBC), biochemical
profile, urinalysis, fecal floatation and smear and
heartworm antigen test were performed. Significant
findings included hyperglobulinemia (4.1 g/dL, range
1.6–3.6 g/dL), a slight monocytosis (930/mL, range 0–
840/mL), hookworm (Ancylostoma spp.) eggs on fecal
floatation and a positive heartworm antigen test. A
Knott’s test was performed and was positive for
microfilaria.
Treatment was administered for intestinal and
ectoparasites. Because of suspected very high worm
burdens, a treatment protocol for D. immitis was
recommended by the American Heartworm Society
specifically for heartworm positive dogs rescued from
Hurricane Katrina (American Heartworm Society,
2007). Microfilaricidal treatment consisted of oral
ivermectin (Heartguard1) administered at a dose of
6 mg/kg (preventative dose) on days 1 and 14 and every
30 days thereafter. On day 28, a one-time dose of 50 mg/
kg of ivermectin was administered orally. Two months
following the initial dose of ivermectin, adulticide
therapy was initiated using the two-step, three-dose
melarsamine (Immidicide1) protocol.
Four days after the initial treatment with ivermectin,
the dog developed a mild fever (39.3 8C) and lameness
which initially responded to treatment with a non-
steroidal anti-inflammatory (NSAID) (deracoxib (Dera-
maxx1) 2.2 mg/kg daily). Despite continued NSAID
therapy, the dog developed an intermittent, shifting limb
lameness and low-grade fever. Joint palpation revealed
mild pain, however, no joint effusion was appreciated.
Serology for Ehrlichia canis, Borrelia burgdorferi and
Rickettsia rickettsii were negative. Discontinuation of
NSAID therapy resulted in worsening of fever,
progressive lameness and anorexia within 36 h. Because
of persistent lameness and low-grade fever, arthrocent-
esis was performed.
Synovial fluid was obtained from the left radio-
carpal joint and left and right stifles. Cytological
evaluation revealed low numbers of microfilariae
(Fig.1.1) with mild mononuclear inflammation in the
right stifle and low numbers of microfilariae with mixed
inflammation consisting of macrophages, small lym-
phocytes and non-degenerate neutrophils in the left
stifle. Neither sample had red blood cells or evidence of
hemosiderin in macrophages that would be suggestive
of contamination or previous intraarticular hemorrhage.
Synovial fluid from the left carpus was within normal
limits with moderate peripheral blood contamination
and no microfilaria seen.
Molecular identification of the microfilariae
observed in the synovial fluid smear was performed
as previously described, with minor modifications
(Rishniw et al., 2005). Briefly, 75 mL lysis buffer
(25 mM NaOH, 0.2 mM disodium EDTA, pH 12) was
applied to an air-dried DiffQuick-stained smear of the
joint fluid with four microfilariae visible on the slide.
After suspending the contents of the smear in the lysis
buffer, the solution was aspirated and transferred to a
1.5 mL Eppendorf tube, heated at 95 8C for 20 min and
immediately mixed with 75 mL of neutralization buffer
(40 mM Tris–HCl, pH 5) on ice (Truett et al., 2000).
Five microliters of the resultant solution were used for
the PCR genotyping reaction as previously described,
using DIDR-F1 and DIDR-R1 primer pairs. Genotyping
confirmed the microfilariae to be D. immitis in origin.
After the arthrocentesis was performed, NSAID
therapy was reinstated and the fever and lameness
improved. Five days after the first dose of melarsamine
the dog developed a mild cough and hemoptysis. The
NSAID was discontinued and treatment initiated with
prednisone 1 mg/kg PO q12 h for suspected pneumo-
nitis. The dog was released to a rescue organization and
medical care was continued through the primary
S. Hodges, M. Rishniw / Veterinary Parasitology 152 (2008) 167–170 169
veterinarian. The dog completed the remainder of
adulticide treatment without incidence and is currently
only receiving prophylactic heartworm prevention. The
dog has shown no signs of lameness as of the date of this
manuscript.
2.2. Case 2
On 20 June 2006, a 7-year-old, castrated male
German Shepherd Dog was referred to Northwest
Indiana Veterinary Emergency Specialty Hospital
(NIVESH) for the evaluation of left rear leg lameness
of several weeks duration. Initial physical examination
findings included a grade III/IV left rear leg lameness
with profound swelling of the left stifle joint. There was
no cranial drawer instability palpated. Radiographs of
the left stifle revealed severe joint effusion but no
radiographically apparent degenerative joint disease.
The patella appeared to be elevated from the distal
femur, separated by what appeared to be a soft tissue
density.
Arthrocentesis of the left stifle was performed and
75 mL of a mildly translucent and viscous fluid was
removed from the joint. Cytology of the synovial fluid
revealed minimal cellularity with the primary
nucleated cell population consisting of monocytic
type cells with minimal activation as well as rarely
seen lymphoid cells. Minimal amounts of peripheral
blood were present. A single microfilaria was seen in
one sample. The patient was treated with an NSAID
and returned to the primary veterinarian for further
diagnostic testing and treatment for suspected canine
heartworm disease.
A heartworm antigen test was positive and a Knott’s
test confirmed microfilaremia. Adulticide therapy was
initiated using the two-step, three-dose melarsamine
(Immidicide1) protocol. One month following the
completion of heartworm treatment, a microfilaricidal
dose (1.9 mg/kg) of milbemycin (Interceptor1) was
given and a negative Knott’s test was obtained 2 weeks
later. Left rear leg lameness persisted after the
completion of treatment for heartworm disease.
The patient returned to NIVESH for evaluation of
persistent non-weight-bearing left rear leg lameness.
The left stifle was very swollen and painful on palpation
and muscle atrophy of the leg was present. Attempts at
arthrocentesis were unsuccessful and radiographs
revealed bony lysis of the medial femoral condyle.
Amputation of the left pelvic limb was performed and
the left stifle joint was submitted for histopatholgy.
Histopathologic examination of the joint revealed a
synovial sarcoma.
3. Discussion
Although canine heartworm disease is common in
many parts of the world, polyarthritis secondary to
intraarticular microfilaria has not previously been
described. Intraarticular microfilariae have been
reported previously but inflammation associated with
the joint and clinical signs of polyarthritis were not
present in those dogs (Weinberger et al., 1979). One of
the two cases reported here had concurrent intraarticular
microfilaria and inflammation in two different joints,
neither of which had significant blood contamination.
Furthermore, the clinical signs associated with arthritis
resolved after completion of treatment for D. immitis
infection.
The dog in the second case had a synovial cell
sarcoma of the left stifle where the intraarticular
microfilaria was discovered. It is feasible that the
sarcoma was present at the time of arthrocentesis and
the integrity of the joint was compromised, allowing
migration of microfilaria into the joint. It is also feasible
that the sarcoma was responsible for the inflammatory
component of the synovial fluid.
The method by which microfilariae entered the joints
in the dog from the first case is unknown. In cases where
adult worms have been found in aberrant locations, it
has been hypothesized that immature stages may
occlude small vessels or capillaries resulting in rupture
of the vessel and release of the larva into the aberrant
location (Otto, 1974). There the larva matures into an
adult worm where it may later cause clinical signs not
typically associated with heartworm disease.
Filarial arthropathies have been described in humans
(Waltzing and Bloch-Michel, 1971; Dorfmann and de
Seze, 1972; Jaffres et al., 1983; Kohem et al., 1994;
Gallagher et al., 2002). In most cases, treatment of the
filariasis led to resolution of the arthropathy. The exact
mechanism whereby arthritis is induced in humans with
filarial diseases is unknown. Proposed hypotheses
include local release of proteases by the worms which
might directly damage the synovial tissue (Petralanda
et al., 1986) or intraarticular deposition of immune
complexes. Immune complexes containing filarial
antigens, however, are yet to be detected in human
synovial tissue (Dissanayake et al., 1982).
The presence of intraarticular microfilaria in the dog
in Case 1, and the resolution of clinical signs after
completion of appropriate heartworm treatment, sug-
gests that canine heartworm disease should be a
differential diagnosis in patients presenting with signs
of polyarthritis. However, as demonstrated by the dog in
Case 2, careful evaluation for other causes of lameness
S. Hodges, M. Rishniw / Veterinary Parasitology 152 (2008) 167–170170
or polyarthritis should be pursued if symptoms do not
resolve after appropriate heartworm treatment.
Acknowledgements
The authors thank Dr. Elizabeth Jay, ACVP, Antech
Diagnostics, for the synovial fluid analysis, Dr. Bradley
Coolman, ACVS, Northeast Indiana Veterinary Emer-
gency and Specialty Hospital, for the submission of case
number 2 and Tracy Stokol, BVSc, PhD, DACVP (clin
path), Dept Pop Med and Diag Sci, Cornell, CVM for
obtaining the photographs of the microfilaria.
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