A Practical Approach To Polyarthropathies

Dr. Anthony Carr, DACVIM (internal medicine)
Associate Professor

University of Saskatchewan, Saskatoon, Canada

 

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.   

DIAGNOSTIC WORKUP

A good history is a valuable source of important information. The possibility of tick contact (vector for disease) as well as the recent administration of vaccinations and the use of medications has to be determined. Vaccination and drug administration have been associated with the development of inflammatory arthropathies, though infrequently. This is something however to be aware of as vaccinations become more controversial in veterinary medicine. Some breeds such as Weimeraners are supposedly very predisposed to post vaccinal reactions, though scientific proof to date is lacking. Heartworm status also needs to be determined, since this is a systemic infestation that results in a strong immune mediated response in some animals.

As with all diseases, a good physical examination is vital. Palpation and manipulation of all joints should be performed to determine which are affected.  Polyarthropathies tend to more commonly involve the small joints such as the carpal and tarsal joints.  They can at times involve the vertebral joints so that at times the main sign may be neck pain. It is however also possible for concomitant meningitis to be present causing neck pain. When palpating the joints, special attention should be paid for the presence of swelling, warmth or pitting edema.  In addition, every attempt should be made to localize potential sources of chronic infection or inflammation (i.e. prostate, uterus, abscesses). The heart and lungs need to be carefully ausculted. Chronic lung infections or endocarditis are a potential source of infection or antigen antibody complexes. The spinal column should be carefully palpated for the presence of pain that might be suggestive of discospondylitis. An ocular exam is also to be recommended, granuloma formation can be seen with fungal disease (especially blastomycosis) or uveitis can be a part of a generalized immune-mediated process.

LABORATORY DIAGNOSIS


Since systemic disease can be the underlying stimulus for the development of a non-erosive polyarthropathy, a CBC, chemistry screen and urinalysis are indicated. Toxic changes in the neutrophils might be indicative of infection. Anemias or thrombocytopenias might be associated with the presence of other immune mediated disease. A chemistry screen might reveal potential dysfunction in other organs. Urinalysis is absolutely indicated, since many polyarthropathies are immune mediated and can result in glomerulonephritis or amyloidosis. The presence of proteinuria with a benign sediment could be significant. If proteinuria is present, this can be quantified with a urine protein to urine creatinine ratio. In addition, urinary tract infection might be found. In certain cases blood or urine culture may also be indicated.  The most important diagnostic test is arthrocentesis. Arthrocentesis allows the taking of a sample for both cytological and microbiological evaluation.  Joints that are easy to tap include the carpus and tarsus, elbow and stifle. Synovial fluid analysis should be consistent with inflammatory joint disease before initiating therapy.  This means that nucleated cell count should be elevated, generally with greater than 5,000 nucleated cells per milliliter. Usually there is also a shift from a strictly mononuclear population to a more neutrophilic cell population. Other signs of inflammatory joint disease include decreased viscosity and increased turbidity.  Wright stain or with Gram stain can be used to identify infectious organisms. If indicated, aerobic, anaerobic and Mycoplasma culture should be obtained.  Occasionally, synovial membrane biopsies can be taken if the diagnosis is uncertain, though this is rarely necessary.  Synovial membrane can be a good sample for culture and sensitivity examination as well as histopathologic examination, it does however involve an arthrotomy.  Radiography can also be of value, though usually quite limited.  Generally, early changes with most joint diseases will be nonspecific if present.  Chronic and long-term cases of bacterial arthritis may eventually cause changes consistent with erosive arthritis.  These signs consist of destruction of articular cartilage and subchondral bone with an irregular joint space, bone erosions, periosteal new bone, osteosclerosis and osteophyte production. 

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. 

SEPTIC ARTHRITIS


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.

BACTERIAL L-FORMS


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.

MYCOPLASMAL ARTHRITIS


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.

FUNGAL ARTHRITIS


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.

VIRAL ARTHRITIS

Calicivirus, both infection and vaccination, has been associated with polyarthropathies in cats. This can be seen after vaccination as well, usually within in a few days after infection or vaccination. Disease is self-limiting. Cytology is usually not strongly inflammatory.

LYME DISEASE

Borrelia burgdorferi
has been associated with joint manifestations in humans. Experimentally infected dogs have shown signs of a neutrophilic inflammatory polyarthropathy. Signs of infection decreased in severity the older the dogs at age of initial infection. Unfortunately it is virtually impossible to definitively diagnose Lyme disease. Antibody titer levels are of little use since they merely reflect exposure. In endemic areas a large percentage of animals will be positive. The titer level also is of little value since there is considerable overlap between healthy and afflicted animals. Previous “diagnostic” criteria employed have been the presence of a titer, suggestive signs of Lyme disease and response to antibiotic (often tetracycline or chloramphenicol) therapy. However many other organisms (rickettsial, mycoplasma, L-forms) already identified would have a similar course. As a result though Borrelia may cause disease the diagnosis is at best one of suspicion.

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 MESSAGE

A 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.