ANIMAL MODEL Juvenile Rheumatoid Arthritis

OF
HUMAN DISEASE

Animal Model: Rheumatoid Arthritis

in the Dog

Contributed by: Henry L. Allen, VMD, and Charles D. Newton, DVM, University of
Pennsylvania School of Veterinary Medicine, 3800 Spruce Street, Philadelphia,
Pennsylvania 19174.

Bioogic Features
Rheumatoid arthritis (RA) in the dog is a crippling, spontaneous poly-
arthritis.1-6 It affects dogs of various ages and breeds. Present data are
sufficient to determine that there is a significant preponderance of one
breed, the Shetland sheepdog. The disease occurs primarilv in dogs 3 to 8
y-ears old. No sex predeliction has vet been observed; both males and
females appear to be afflicted equally.
The clinically affected animals show signs which fulfill at least eight of
the diagnostic criteria which have been laid down bv the American Rheu-
matism Association.7 This is considered sufficient to make the diagnosis of
RA.
.Most of the dogs evidence morning stiffness, pain on motion of one or
more joints, and periarticular soft tissue swelling. Joint involvement is
typically symmetrical.
Radiographic changes are consistently present in the clinicallv affected
joints. The earliest radiographic findings are swelling of the soft tissues
around a joint or fluid within a joint. These are seen radiographically
either as joint capsule distension or minimal widening of the joint space.
Later radiographic findings are narrowing of the joint space with varying
degrees of irregular, radiolucent, cyst-like areas of destruction involving
Publication sponsored by the Registry of Comparatise Patholop- of the Armed Forces Institute
of Pathology and supported by Public Health Sernice Grant RR 00:301 from the Disision of
Research Resources. L-S Department of Health. Education and W elfare. under the auspices of
U niversities Associated for Research and Education in Pathology. Inc
Dr. Mlen s current address is 44-1 Merck Sharp and Dohme Research Laboratories. West Point,
PX 194S6.
699
700 ALLEN AND NEWTON American Journal
of Pathology

Figure 1-Anteroposterior radiograph

of the right tarsus. There is marked
joint space narrowing of the tibial-tarsal,
fibular-tarsal, and intratarsal joints.
Joint capsule distension is present.
There are multiple subchondral cysts
and erosions of the articular surfaces.
_sli

subehondral bone (Figure 1). The radiolucent areas usually are most
prominent at the attachment sites of ligaments to the bone. Progressive
rarefaction of bone occurs at the ends of bones involving the entire joint
surface.
Rheumatoid factor, when measured using a procedure designed specifi-
callv for the canine species, is almost always present.' However, it is
generally present at low levels (1:8 to 1:236). Antinuclear antibody is
usually absent.
In addition, the dogs are ill. They are often pyrectic and depressed, and
there may be a loss of appetite, particularly during exacerbations of the
symptoms. Lymphadenopathv has also been observed in occasional cases.
Histologically', there is marked papillarv proliferation of the articular
Vol. 81, No. 3 RHEUMATOID ARTHRITIS
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7U1
December 1975

~~~-

I
I

Figure 2-Photomicro-
graph of papillary syn-
ovium from a dog af-
fected with RA (H&E, x
40).

synovial membranes in the clinicallv affected joints. This is produced by

hyperplasia of synovial lining cells and the underlying connective tissue.
There is dense infiltrate of lymphocytes and plasma cells (Figures 2 and
3), and hemosiderophages in the synovium are often plentiful. Synovial
giant cells and bone production in the sy-novial membranes have not been
reported. Granulation tissue "pannus"' frequently invades the sub-
chondral bone and extends over the articular cartilage, destroying it.
The svnovial fluid has not vet been adequately studied in canine RA. In
the instances where it has been examined, there appears to be only a
minor decrease in viscosity and glucose content; mucin precipitation has
not been characterized.
To complete the clinical picture, aspirin and corticosteroids are pallia-
tive, and have been used with success in a number of cases of canine RA.
p ti2L -_~

Fgure 3-Thickened syn- I

ovium showing doubling
of mesothelial lining and
pure mononuclear infil- i
trate (H&E, x 120). I
702 ALLEN AND NEWTON American Journal
of Pathology

Cornpanson hthe Human Disease

Canine RA has many features in common with juvenile RA of man.8
Constitutional signs, such as fever and malaise are more pronounced in
children with RA than in adults. The low titers of rheumatoid factor found
in many dogs would not be significant in adults, but are acceptable for
diagnosis of the disease in children.
The rheumatoid nodule (of the subcutis) which is so diagnostic of the
disease in adults has been reported in 1 dog.3 The nodules are rare in
children affected with RA.
In its other aspects, the canine disease closely mimics rheumatoid dis-
ease of man. Because of the nature of the disease, many of the diagnostic
criteria are based on clinical observation. However, the canine RA cases
fulfill not only the clinical but also the radiographic, histopathologic, and
clinical laboratory criteria as well.
Potential Usefuless of the Model and Availabiut
The dog appears to be an excellent model for the study of RA. Dogs are
plentiful, and they live under conditions similar to those of their human
masters. Although the condition does not appear to be common, it occurs
sufficientlv often to warrant increased awareness on the part of veter-
inar clinicians and their medical counterparts to recognize the disease
when the animal is presented. An additional advantage in using the dog is
that there are large quantities of synovial fluid, synovium, etc., available
for biopsy. Likewise, the radiographic and laboratory parameters for the
dog are widely known.
References
1. Halliwell RE%, Lavelle RB, Butt KM: Canine rheumatoid arthritis: A review and a
case report. J Small Anim Pract 13:239-248, 1972
2. Lewis RM, Borel Y: Canine rheumatoid arthritis: A case report. Arthritis Rheum
14:67-74, 1971
3. Lewis RMI, Hathawav JE: Canine systemic lupus erythematosus presenting with
symmetrical polyarthritis. J Small Anim Pract 8:273-284, 196-7
4. Liu SK, Suter PF, Fischer CA, Dorfman HD: Rheumatoid arthritis in a dog. J Am
V'et Med Assoc 154:495-02 1969
5. Rudy RL, Hohn RB, Harrison JW: Rheumatoid and osteoarthritis in the dog. Gaines
Veterinary Svmposium, 1972, New York, Gaines Dog Research Center
6. Newton CD, Allen HL, Halliwell REW, Schumacher HR Jr: Juvenile rheumatoid-like
arthritis in a dog: Clinicopathologic conference. J Am Vet Med Assoc 165:459, 1974
7. McEwen C: The diagnosis and differential diagnosis of rheumatoid arthritis. Arth-
ritis and Allied Conditions, Eighth edition. Lea and Febiger, 1972 Philadelphia,
Pennsvlvania 8th Ed.
8. Robinson WD: Juvenile rheumatoid arthritis. Cecil-Loeb Textbook of Medicine,
Edited by PB Beeson, W McDermott, Philadelphia, W. B. Saunders Companv, 1971,
p 1898