Vol. 22, No.
7 July 2000
CE Refereed Peer Review
FOCAL POINT
★Canine idiopathic erosive
polyarthritis (IEP) is a presumably
immune-mediated disease of
unknown etiology resulting
in a progressive, symmetric
polyarthritis that usually
responds poorly to therapy.
KEY FACTS
■ IEP shares many characteristics
with its human counterpart,
rheumatoid arthritis, and is often
referred to by the same name.
■ The pathogenesis of IEP is
unknown, but an immune-
mediated mechanism is probable.
■ Long-term prognosis in IEP is
generally poor owing to loss of
joint function and quality of life.
■ Severe cases may result in joint
subluxation or luxation, particularly
of the carpal, carpometacarpal, and
phalangeal joints.
■ Although effective medical
treatment is not yet available,
some relief of clinical signs
may be achieved with NSAIDs,
corticosteroids, cytotoxic drugs,
or slow-acting disease-modifying
agents.
Canine Idiopathic
Erosive Polyarthritis
Gulf Coast Veterinary Specialists, Houston, Texas
S. Christopher Ralphs, DVM
Brian Beale, DVM
ABSTRACT: Canine idiopathic erosive polyarthritis (IEP) is a chronic, symmetric, progressive
disease affecting primarily the joints of the distal limbs. In advanced cases, luxations and sub-
luxations may be present and animals may be reluctant or unable to walk because of pain as-
sociated with movement. The pathogenesis of IEP is unknown, although an autoimmune
cause is probable. Generally, treatment of IEP is unrewarding. There have been reported suc-
cesses using antiinflammatory or immunosuppressive drugs, but generally these are palliative
treatments and do not alter the progression of disease. Surgical treatment using pancarpal
arthrodesis has been reported to improve ambulatory ability in dogs with severely affected
carpi. The long-term prognosis for these animals is generally poor, and animals with advanced
disease are often euthanized for quality of life reasons.
I
nflammatory joint disease may be classified as having an infectious or nonin-
fectious cause. Noninfectious arthritis is thought to be primarily an immune-
mediated condition and is commonly categorized further as erosive or
nonerosive. Reported erosive polyarthropathies in dogs include idiopathic ero-
sive polyarthritis (IEP) and erosive polyarthritis of greyhounds.1
Idiopathic erosive polyarthritis is a chronic, progressive, debilitating disease
with a wide range of clinical presentations. The rate of progression is variable
but usually slow. Because canine IEP bears many similarities to rheumatoid
arthritis (RA) in humans, many authors classify this disease as canine RA. The
pathogenesis of IEP is not well characterized. There is almost certainly an im-
mune-mediated component, but what initiates this chain of events is unknown.
No infectious organism has been identified as a causal agent. The disease does
not have a sex or breed predilection and affects animals from 2 months to 13
years of age.2 The most common clinical sign is a symmetric polyarthropathy
that progresses from intermittent stiffness and soft tissue swelling to severe ero-
sive changes of the articular cartilage and subchondral bone, with subluxations
and luxations of joints of the axial skeleton in advanced cases.
Attempts to treat IEP with immunosuppressive and antiinflammatory agents
have met with variable but generally unsatisfactory results. Surgical management
(e.g., arthrodesis) may help to alleviate pain, but no treatment that predictably
arrests or reverses the progressive nature of the disorder has been found. Because
of the pain associated with locomotion, the long-term prognosis for dogs with
Small Animal/Exotics Compendium July 2000

IEP is poor and many ani- Animals may intermittently

mals in advanced stages are
euthanized because of poor
quality of life.
PATHOGENESIS
The exact cause and patho-
mechanism of IEP is un-
known. Most current theories
have been extrapolated from
what is known about RA in
humans. Some researchers
propose that an extrinsic anti- Figure 1—This 12-year-old spayed terrier mix presented
gen introduced into the sys- with a 1-year history of progressive lameness. The diagno-
tem closely resembles an en- sis of idiopathic erosive polyarthritis was made on the
dogenous one. The exogenous basis of characteristic clinical signs and radiographic find-
stimulus initiates an immune ings. Note the excessive laxity of the carpal and carpo-
response that cross-reacts with metacarpal joints.
the endogenous antigen and
continues even in the absence of the initiating antigen.
Another theory is that a local immune response may re-
lease cytokines to upregulate local antigen-presenting
capacity, allowing autoantigens, which are otherwise
“hidden” because of a lack of antigen-presenting capaci-
ty, to be presented to T lymphocytes.3
Although the inciting cause is unknown, it seems
that there is a triggering event that initiates an im-
munologic cascade that continues in the absence of the
initial stimulus. The search for an infectious inciting
agent for this disease has been investigated. Canine dis-
temper virus (CDV) has been implicated because ele-
vated levels of CDV antibodies (free and in immune
complexes) have been found in the synovial fluid of
dogs with IEP.4 However, a cause-and-effect relation-
ship has not been established.
Leukocytes, leukocyte enzymes, cell-mediated immu-
nity, immune complexes, complement, and even au-
toallergic reactions directed against cartilage compo-
nents play a role in the pathogenesis of this debilitating
disease.5,6 Despite an earlier focus on the role of im-
mune complex deposition, evidence from both human
and canine studies shows that this disease is primarily
perpetuated by cell-mediated immunity (i.e., T lym-
phocytes).3,4 Immunohistochemical studies have shown
that T lymphocytes are the predominant inflammatory
cells distributed through the synovial membranes.4,7
CLINICAL PRESENTATION
There appears to be no sex predilection for IEP in
dogs.1,2,5 In the early stages of the disease, animals present
with a symmetric stiffness, especially after rest. The signs
may appear sporadically, making early diagnosis difficult
and the interpretation of treatment response challenging.
present with such systemic signs
as depression, anorexia, pyrex-
ia, and lymphadenopathy.2,5,8–10
As the disease advances, lame-
ness becomes more marked
and persistent. The joints
most commonly affected are
the carpi, tarsi, and phalangeal
joints, although elbows, stifles,
and shoulders can be affected
as well. 1,2,9,11 As the disease
progresses, there is erosion of
articular cartilage and sub-
chondral bone and instability
of joints that may lead to luxa-
tion or subluxation, especially
of the carpal and phalangeal
joints1,2,9,10 (Figure 1).
RADIOGRAPHIC FINDINGS
The earliest radiographic finding in patients with IEP
is periarticular soft tissue swelling.1,5 Later changes in-
clude narrowing of joint spaces and a varying degree of
irregular, radiolucent, cystlike areas of destruction in-
volving subchondral bone.2,5,9,10 Subluxation or luxation
of carpal and phalangeal joints may be present and is
commonly associated with osteophyte formation5,10
(Figure 2). Bony ankylosis of severely affected joints
may also be present.1,9 These changes primarily affect
diarthrodial joints of the appendicular skeleton, with
apparent sparing of axial joints.8,10
GROSS, CLINICOPATHOLOGIC,
AND HISTOPATHOLOGIC FINDINGS
Routine laboratory data usually do not aid practi-
tioners in the diagnosis of IEP. Autoimmune profiles
are also inconclusive and the usefulness of tests, partic-
ularly rheumatoid factor (RF), seems uncertain. RF is
an antibody against the body’s own immunoglobulin.
Of the human RA patients, 70% to 80% are RF posi-
tive, with titers usually exceeding 1:320.12 The preva-
lence of RF-positive dogs with IEP has been reported
from 7% to 100%.6–10,13–15 Differences in testing proto-
cols and an inherent bias in case selection may account
for much of this discrepancy.16 Dogs with positive RF
titers tend to have lower titers than their human RA
counterparts, 14 although whether cross-species titer
comparisons are valid is questionable.
In addition to the questionable sensitivity of RF test in
dogs, there is also strong doubt regarding its specificity as
a diagnostic aid. Several studies that revealed an in-
creased prevalence of positive RF titers in dogs with IEP

CANINE DISTEMPER VIRUS ■ SUBCHONDRAL BONE ■ RHEUMATOID FACTOR

Compendium July 2000 Small Animal/Exotics

found a similar or higher prevalence of The history of chronic, progressive,

positive RF titers in dogs with other symmetric, peripheral polyarthropathy
diseases such as osteoarthritis, cranial combined with unremarkable routine
cruciate ligament rupture, leishmania- laboratory data should increase suspi-
sis, heartworm disease, and pyome- cions for IEP. RF does not seem to be
tra.6,14 Recognizing that unrelated dis- a consistently useful test because of the
eases may cause a transient increase in absence of RF in dogs affected by IEP.
RF in humans without RA, the Euro- Synovial fluid should show an eleva-
pean League Against Rheumatism has tion in leukocytes with nondegenerate
recommended that three consecutive neutrophils predominating. There
positive RF tests over a 3-month period should be no evidence of an infectious
be required before an individual can be agent in culture or histopathology. Ra-
considered RF positive.17 Similar mea- diographic changes should support the
sures may need to be adopted for dogs diagnosis. The difficulty for veterinari-
if the RF titer is to be considered a ans in diagnosing this disease is that
valid part of the diagnostic criteria. the early signs are variable and non-
Synovial fluid analysis in dogs with specific and treatment is difficult once
IEP typically reveals an elevated leu- the disease has become severe.
kocyte count (i.e., 10,000 to 100,000
×103/mm3).2,5,11 The majority of these TREATMENT
cells are usually nondegenerate neu- The inability to determine the incit-
trophils, although some animals may ing cause of IEP results in a therapeu-
have a predominance of mononuclear tic plan that is symptomatic rather
cells.2,10 However, the cyclic nature of than curative. Because of the cyclic na-
the disease and small amount of syn- ture of this disease, response to treat-
ovial fluid present in many dogs make ment is difficult to quantitate. No
this an imperfect test for IEP. Synovial treatment regimen has yet been found
fluid analysis is most rewarding when Figure 2—Craniocaudal radiograph of that is consistently successful. This
performed during an active phase of the same dog as in Figure 1. Note the may be due, in part, to the fact that the
disease when joint swelling is present. severe erosive nature of the radiograph- disease is rarely diagnosed before severe
Gross pathologic examination of the ic changes and the multiple subluxa- changes have occurred. Treatment may
joints of severely affected dogs is char- tions and luxations of the carpal, car- prove more efficacious if initiated in
acterized by synovial proliferation and pometacarpal, and metacarpopha- the early stages. Recommended non-
langeal joints.
pannus (with articular cartilage and drug therapy includes physiotherapy
subchondral bone erosion) as well as with range-of-motion exercises and
periarticular fibrosis.8,11 These findings correlate with weight reduction.9,18 Arthrodesis, especially of the carpi
typical radiographic findings. Synovial biopsies usually and tarsi, has shown some value in helping animals re-
reveal villous synovial proliferation with plasma cell and gain ambulatory ability and improve quality of life in se-
lymphocyte infiltration.7,9,11,13 vere cases.1,19 The drugs used to treat IEP fall into three
main categories: antiinflammatory, slow or disease mod-
DIAGNOSIS ifying, and immunosuppressive. Although there are a
Diagnosis of canine IEP has been based on the criteria few published case reports, many of the treatment
for RA originally proposed for humans by the American guidelines are based on experience with human RA pa-
Rheumatoid Association (Table I). If four of these seven tients. Before using any of these drugs, practitioners
criteria are fulfilled, the patient is considered to have should be familiar with the associated side effects.
RA.3 However, because of the differences between ca- Nonsteroidal antiinflammatory drugs are used for
nine IEP and human RA, it may not be appropriate to their analgesic and antiinflammatory properties (Table
diagnose IEP based on the guidelines established for hu- II). Aspirin doses sufficient to produce a blood salicy-
man RA. As in RA, however, the diagnosis of IEP is a late concentration of 20 µg/dl (or the highest tolerated
clinical one.3 Because there is no specific diagnostic test dose) have been used to treat early RA in humans.12,18
for the disease, diagnosis is made by observation of char- In dogs, NSAIDs such as carprofen or etodolac are pre-
acteristic clinical signs, synovial fluid analysis, radio- ferred. However, the efficacy of NSAIDS in canine IEP
graphic findings, and ruling out other diseases. is questionable. If effective at all, NSAIDs tend to give

SYNOVIAL FLUID ANALYSIS ■ RADIOGRAPHIC FINDINGS ■ POLYARTHROPATHY

Small Animal/Exotics Compendium July 2000

only symptomatic relief but TABLE I corticosteroid (e.g., pred-

the progressive degenerative Revised Criteria for the Diagnosis nisone).18 Inclusion of glu-
aspects of the disease con- of Rheumatoid Arthritis in Humans22 cosamine hydrochloride and
tinue. low-molecular-weight chon-
Slow-acting or disease- American Rheumatoid Association/ a droitin sulfate should also be
American College of Rheumatology Criteria
modifying drugs such as considered. However, the
gold salts, penicillamine, Morning stiffness lasting at least 1 hr and up to 6 wk treatment regimen must be
chloroquinone, and hydrox- Arthritis affecting at least three areas or soft tissue chosen after careful examina-
ychloroquinone have been swelling or exudation lasting 6 wk or longer tion of the patient to rule out
used with some success in Arthritis affecting the hand joints (i.e., wrist, other diseases. In addition, it
metacarpophalangeal, or proximal interphalangeal)
human patients with RA. lasting more than 6 wk is vital that the dog’s owners
Approximately 50% of hu- Symmetric arthritis (of at least one area) lasting more are educated immediately re-
man patients have experi- than 6 wk garding the reasons and risks
enced some benefits from Rheumatoid nodules observed by a physician involved when treating this
these drugs, but weeks or Serum rheumatoid factor assessed by a method that is disease as well as the poor
months may be required be- positive in less than 5% of control subjects prognosis generally associated
fore a response is noted. 12 Radiographic changes viewed on anterioposterior films with it. At this point, the
Treatment costs can be con- of wrists and hands most effective drug combina-
siderable, and there are aIf four of these criteria are present, the diagnosis of rheuma- tion treatment of IEP is sim-
many associated side effects. toid arthritis is made. ply not known.
Gold salts have been used in Surgical procedures can
veterinary medicine but with poor or transient success.2 also be used to improve joint stability and reduce pain.
Penicillamine and the antimalarial drug hydroxychloro- Arthroscopic synovectomy, arthroplasty, total joint re-
quinolone have both demonstrated some therapeutic placement, or arthrodesis can be used to alleviate pain
effectiveness in one report, but this has not been veri- and improve function.
fied by other studies.9 Purified glucosamine hydrochlo-
ride and low-molecular-weight chondroitin sulfate have
been shown to reduce the severity of disease in a pol-
yarthritis model.20
Immunosuppressive agents such as methotrexate, aza-
Interested in
thioprine, chlorambucil, and cyclophosphamide are gen-
erally used for patients that have not responded to slow-
writing for
acting agents.12,18 In humans, methotrexate in particular
has been used with some success and is now one of the
COMPENDIUM?
favored methods of treatment.12 Cyclophosphamide has
been used in combination with azathioprine and pred-
For small animal articles, please contact
nisone in some animals with limited success. 10
Dr. Douglass Macintire (email macindk@
Despite their antiinflammatory and immune-mediat-
ing effects, systemic corticosteroids have not shown any
vetmed.auburn.edu; phone 334-844-6032).
12,18
effect on the long-term progression of RA in humans.
This experience has been corroborated by the veterinary
literature.2,9,10,18 Prednisone is the corticosteroid of choice
For exotics articles, please contact
2,9
for long-term therapy. Intraarticular steroid injections Dr. Branson Ritchie (phone 706-542-6316;
provide short-term relief by decreasing inflammation.
However, they do not appear to slow the disease and
email britchie@vet.uga.edu).
may promote articular cartilage degeneration owing to
inhibition of the chondrocyte’s ability to produce proteo-
glycan and collagen. Therefore, corticosteroids should be
used as adjunctive therapy and not as a primary form of
treatment.9
It has been recommended that treatment of IEP in
dogs begin aggressively, with a combination of an im-
munosuppressive agent (e.g., cyclophosphamide) and a

ARTHRODESIS ■ IMMUNOSUPPRESSIVE AGENTS

Small Animal/Exotics Compendium July 2000

TABLE II
Drug Regimens Used to Treat Idiopathic Erosive Polyarthritisa
Drug Dose Route Frequency

Aspirin8,18 25 mg/kg PO Three times/day for 2 wk, then taper

Azathioprine8,18 2 mg/kg PO Once daily, adjusted to produce mild leukopenia

Chlorambucil 0.2 mg/kg PO Once daily

Cyclophosphamide8 1.5–2.5 mg/kg PO or IV 4 days/wk, then 3 days off

50 mg/m2 PO or IV 4 days/wk, then 3 days off

Gold sodium thiomolate8,18 1 mg/kg IM Once/wk

Methotrexate21 0.5–0.8 mg/kg IV Every 7–14 days

2.5 mg/m2 PO Every 48 hr

Phenylbutazone18 14 mg/kg PO Three times/day

Prednisone8,10,18 1–2 mg/kg PO Twice/day, then taper to lowest effective dose

a
Clinicians should familiarize themselves with these drugs and their side effects before using them on idiopathic erosive
polyarthritis patients.
IM = intramuscular; IV = intravenous; PO = oral.

ARE IDIOPATHIC EROSIVE POLYARTHRITIS
AND CANINE RHEUMATOID ARTHRITIS
INTERCHANGEABLE TERMS?
Most articles published about IEP classify this disease
as canine RA. There are certainly many similarities be-
tween the diseases, but differences do exist. We believe
that idiopathic erosive polyarthritis is a more accurate term
for the disease in dogs.
Clinical presentations of IEP and RA are similar. Both
present with a wide range of clinical signs dominated by
a symmetric, progressive, erosive polyarthropathy affect-
ing mainly the distal limb joints. However, women are
2.5 times more likely to suffer from RA than are men,12
whereas IEP shows no sex predilection. RA has been re-
ported to occur in 1% to 2% of humans,12 but the
prevalence of IEP in dogs is much lower. There are
many extraarticular manifestations of RA in humans
that have rarely, if ever, been documented in dogs with
IEP. Humans are much more likely to have a positive
antinuclear antibody test3 or a positive RF test. In RF-
positive dogs, the RF titer is typically lower and has a
predominance of IgG, whereas human RF is predomi-
nantly IgM.14,15 In addition, the distinctive lymphoid
follicles often seen in RA are seldom seen in IEP and if
present lack an obvious germinal center.5,7
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About the Authors
When this article was submitted for publication, Drs.
Ralphs and Beale were affiliated with Gulf Coast Veteri-
nary Specialists in Houston, Texas. Dr. Ralphs is current-
ly affiliated with the College of Veterinary Medicine, Uni-
versity of Minnesota, St. Paul. Dr. Beale is a Diplomate of
the American College of Veterinary Surgeons.