A Practical Approach To Polyarthropathies
Dr. Anthony Carr, DACVIM (internal medicine)
Polyarthropathies demand a thorough work up. Once it has been determined that an animal is suffering from inflammatory joint disease, it is necessary to determine whether the disease is caused by infectious agents or is a result of an idiopathic immune mediated disease. If an infection is present it isn’t necessary for the causative organism to be present in the joint itself. However, antigen antibody immune complex formation can occur with deposition in the joint. This then induces inflammation. When dealing with a case of polyarthritis, every effort to eliminate infectious disease as the underlying etiology should be made since the treatment of inflammatory arthropathies involves the use of immunosuppressive drugs. This could be disastrous if an infectious disease was present. Often the underlying cause of immune mediated arthritis remains undetermined.
Serologic testing may be indicated if appropriate
physical examination or historical information are present. These
include titers for rickettsial and fungal organisms. Heartworm status
of the dog should also be established since heartworm infection can lead
to chronic immune stimulation. In cats, testing for feline leukemia
virus and FIV is of great interest. Polyarthritis has often been
associated with the presence of rickettsial organisms. Presentation
of these dogs generally is that of a febrile and lame dog. Both
neutrophilic ehrlichia (such as E. ewingii) and monocytic ehrlichia (such
as E. canis) occur. It would be wrong to assume that we know all the ehrlichial
organisms that can cause joint disease, more and more are being discovered
with advanced genetic testing techniques. The drug of choice for rickettsial
organisms is a tetracycline antibiotic, whereby I prefer doxycycline at
5 mg/kg BID for 10 to 14 days. A cure seems less likely based upon current
research, however clinical improvement is seen and is usually rapid. Many
dogs without ehrlichial polyarthritis will get better with doxycyline
(possible anti-inflammatory effect), however in a dog with ehrlichiosis
clinical signs should cease rapidly and completely.
Infection of a joint occurs either hematogenously or by direct penetration (wound). For polyarthropathies hematogenous dissemination is more likely. Joints that have been traumatized are more susceptible to infection. Surgery and arthrocentesis are two potential ways to introduce infectious agents into a joint. Organisms most commonly isolated include Staphylococci, Streptococci, E. coli and anaerobes. The spectrum of clinical signs can range from severe fulminating to mild and slowly progressive. Radiography may be able to detect changes in bone and cartilage consistent with infectious disease (bone erosion, joint space collapse, osteosclerosis). Aggressive therapy is needed. With a joint infection essentially an abscess can form. With severe disease, surgical management often becomes necessary.
These organisms represent cell wall deficient bacteria. Antibiotic therapy and host immune response can cause this change. Repeated passages in special culture medium may allow reversion to the original form. They have been implicated in cats as pathogens, are however rare. Abscesses, fever, anorexia and inflammatory joint disease can occur. These organisms also respond to therapy with tetracyclines.
Mycoplasma spp. have been implicated as the cause of joint disease in many species. They can be part of the normal flora as well. In both cats and dogs it has been suspected that they can cause joint disease. Our understanding of this is limited. The organisms should be responsive to tetracyclines.
Polyarthritis associated with fungal disease is almost always immune mediated phenonema. Rarely the organisms can gain entrance to the joint in the process of hematogenous dissemination. Osteomyelitis is commonly present with certain systemic fungal infections and the joint can be invaded by direct extension from these lesions. Radiography is especially valuable in this case as the lesions present would be highly aggressive. Cryptococcus, Blastomyces and Coccidioides have been reported to have joint involvement.
PATHOPHYSIOLOGY AND CLINICAL FINDINGS:The clinical signs in dogs and humans vary greatly. Whereas humans have the typical skin reaction this is uncommon (or unseen) in dogs. In humans seroconversion can occur after clinical signs have become apparent. This was not seen in dogs experimentally infected with Lyme disease. All dogs had titers by the time they became ill. Serious complications in people are common and usually associated with the chronic disease state. In dogs this has been suspected, but not proven. In none of the experimentally infected dogs was kidney or heart disease seen. Arthritis was variably present, generally mild, waxed and waned and was most prominent in those dogs exposed at a very young age. Disease signs disappeared without therapy. Recently a novel form of Lyme related kidney disease has been identified. The majority of dogs involved were Labs or Golden Retrievers. It is thought that genetic makeup has an influence on disease course in humans so that the same may apply in dogs. The nephritis was progressive with all dogs dying in a relatively short time span from the disease. Many dogs also had peripheral edema which is rare with most other causes of renal failure.
DIAGNOSIS: Titers often cannot differentiate between
vaccine and natural exposure. Some Borrelia titers may relate to non-pathogenic
Borrelia that do occur. Additionally it appears that only 5% of infected
animals have signs consistent with the disease. Western blot can differentiate
between vaccination and natural disease. Diagnosis should depend upon
appropriate clinical signs, positive serology as well as a rapid response
to antibiotic therapy.
THERAPY: In experimental natural challenge, antibiotics did not appear to change the duration or magnitude of antibody titers, probably meaning that the spirochetes persisted in the host. Additionally, dogs seemed to spontaneously “cure” of clinical signs in 7-10 days. Duration of treatment is also unknown though 30 days is suggested. Primary antibiotic choices are doxycyline or a penicillin. I prefer doxycycline as co-infection with other tick-borne organisms (such as Ehrlichia) is possible and this would not respond to a penicillin. It is important to remember that if the dog does not respond well and rapidly to antibiotics it is much less likely to be Lyme and other causes for the clinical signs should be investigated.
PREVENTION: At present there are several vaccines are available. The original vaccine was by Fort Dodge. Both the Fort Dodge and Galaxy Lyme are bacterin products. The newest entrant into the field is a recombinant product. In natural challenge studies the use of a recombinant Osp A or B was effective in protection. First and foremost tick prevention should be practiced. There are many products on the market for this. Vaccination should be reserved for those animals at risk. It is important to remember that in endemic regions upward of 70% of dogs may be seropositive but only 3 to 4 % have clinical signs. There has been the suggestion that the vaccines themselves could cause disease.
TAKE HOME MESSAGEA thorough physical exam is vital. As much as possible a complete database should be gathered to try to find the underlying etiology. The main causes of joint disease will be responsive to tetracyclines so that trial therapy with this type of antibiotic should be a part of the “work up” of joint disease. The other main differential is true idiopathic immune-mediated disease. The thoroughness of the work-up done will be the factor that minimizes the chances of immune suppression having negative consequences because of an underlying infectious disease.