It is important to distinguish rheumatoid arthritis from other forms of inflammatory arthritis, including psoriatic arthritis,
systemic lupus erythematosus (SLE) and other connective tissue diseases, the relatively benign maturity-onset seronegative
synovitis (MOSS) syndrome, crystal-induced synovitis and inflammatory osteoarthritis.
The "gold" standard of good practice in rheumatoid arthritis includes early and continuous use of disease-modifying antirheumatic
drugs (DMARDs), singly or in combination, to prevent damage, deformity and disability. Although treatment may be costly and
inconvenient, the costs of medication and monitoring are minor compared with the costs to the patient and society in terms
of long-term disability.
Patients with inflammatory arthritis are a diagnostic and management challenge. When symptoms are of recent onset, the
range of possible diagnoses is great. Certain viruses including those that cause rubella, and mumps, human parvovirus B19
and some enteroviruses can cause acute polyarthritis; however, these viral arthritides normally subside within 6 weeks without
sequelae.
The prodrome of acute hepatitis B infection and infection with the Lyme disease agent, Borrelia burgdorferi, may include
polyarthritis (inflammation in more than 4 joints). The former is recognized by the ensuing hepatitis, while the latter requires
a high index of suspicion (i.e., a history of tick bite or a typical rash on a patient from an endemic area) and often involves
only 1 or 2 large joints.
In patients who are under 50 years of age with joint pain and swelling lasting longer than 6 weeks the diagnoses to be
considered include rheumatoid arthritis, psoriatic arthritis, other seronegative spondyloarthropathies and SLE.
In patients over 50 years of age, MOSS syndrome and crystal-induced synovitis should also be considered. Osteoarthritis
may also cause considerable inflammation in the affected joints.
For most of these conditions specific therapies aimed at controlling inflammation, preserving range of motion in the
joint and preventing joint damage are successful in decreasing morbidity and improving quality of life.
The patient with symptoms in many joints requires a detailed history and physical examination. If there is morning stiffness
lasting more than 30 minutes or stiffness after sitting, the joint complaints are likely to be caused by inflammation; a convincing
history of joint swelling confirms the presence of inflammation. The physician should record the onset and progression of
symptoms and the distribution of joints affected.
A history of psoriasis in the patient or a family member is an important clue to the possibility of psoriatic arthritis.
The physician should also inquire about a history of iritis or inflammatory bowel disease, both of which are associated with
seronegative spondyloarthropathies.
A recent episode of infectious diarrhea or genitourinary infection are clues to possible Reiter's syndrome.
Does the patient have symptoms suggestive of SLE (e.g., photosensitive or malar rash, alopecia or pleurisy)? Is there
a past history of acute episodes of arthritis or gout? Are the joints tender or swollen? Is movement limited? The choice of
laboratory tests that may help depend on the differential diagnosis
Onset of polyarthritis in the early postpartum period is more common with rheumatoid arthritis than with other forms
of inflammatory arthritis. The typical patient with rheumatoid arthritis has inflammation in the wrist and MCP or metatarsophalangeal
(MTP) joints, or both, that persists beyond 6 weeks. Among patients under 50 years of age more women are affected, but after
age 50 incidence is equal for men and women.
Morning stiffness and inactivity stiffness are almost always present, and swelling of affected joints is clear with careful
examination. The condition may be episodic at the onset, but within weeks to months the symptoms become persistent and more
disabling. A positive rheumatoid factor test supports the diagnosis, however, as many as 30% of those affected have negative
test results. Specificity increases with consistent results on more than 1 test and with high titre.
The presence of antinuclear antibodies at a low titre may be associated with more severe seropositive rheumatoid arthritis.
If the patient has had active polyarthritis for more than 1 year, joint erosion may be seen on radiographs of the hand or
foot.
Useful laboratory tests for patients with recent onset inflammatory polyarthritis may include complete blood count, erythrocyte
sedimentation rate or CRP, rheumatoid factor test, aspartate aminotransferase (AST) test, creatinine level and urinalysis.
Erythrocyte sedimentation rate is an inexpensive measure of disease activity in those with rheumatoid arthritis; however,
the test is not diagnostic and rates are not elevated in all patients affected.
A positive test result for rheumatoid factor is helpful but not essential to confirm the clinical impression of rheumatoid
arthritis in the setting of symmetrical inflammatory polyarthritis. If the arthritis has lasted more than a year, the physician
should consider taking radiographs of the hands and feet.
The importance of diagnosing rheumatoid arthritis is essential - early intervention with DMARDs has been shown to improve
long-term outcomes, and once joint damage has occurred erosion and joint instability are irreversible. If rheumatoid arthritis
is mild and in its early stages many rheumatologists favour using hydroxychloroquine because it is safe and convenient.
If control is suboptimal after 6 months, additional DMARDs are often prescribed. A recent study reported some efficacy
with minocycline for patients with early seropositive rheumatoid arthritis. However, long-term efficacy data for patients
treated with minocycline are not available, and radiographs show that damage progresses at the same rate as in placebo-treated
patients.
If a patient has moderate or severe rheumatoid arthritis, especially if the rheumatoid factor is positive, methotrexate
may be the preferred DMARD. Methotrexate is convenient and well tolerated. Sulfasalazine is safe as a second-line agent and
can be used in combination with methotrexate and other DMARDs. Many new DMARDs (Biologics) are becoming available.
Often,there is a delay between the presentation of inflammatory arthritis and the confirmed diagnosis, and there is always
a delay before a prescribed DMARD has the expected benefit. When optimal DMARD therapy or a combination of DMARDs does not
control synovitis, low-dose prednisone can provide symptom relief, acceptable low toxicity and joint protection.
Bisphosphonate, either cyclical tidronate or daily alendronate, reduces the risk of steroid-induced osteoporosis and
should be prescribed when the daily dose of prednisone is 7.5 mg or more.
Patients with active rheumatoid arthritis should be assessed and monitored by a rheumatologist on a regular basis,
and clinical and laboratory evaluations should be repeated to measure the efficacy and toxicity of treatment. The aim of therapy
is to minimize pain, stiffness and joint swelling; retard joint damage; and reduce future disability. Is the treatment therapy
working?
Psoriatic arthritis is almost as common as rheumatoid arthritis. This condition should be suspected when the patient
or the patient's family has a history of psoriasis, when distal interphalangeal joints are affected or when there is a history
of unexplained chronic or recurring back pain with prolonged inactivity. Another feature of psoriatic arthritis and the spondyloarthropathies
is bursitis or enthesitis (i.e., inflammation of the muscular or tendinous attachment to bone).
Typical examples of bursitis, tendinitis and enthesitis include trochanteric bursitis, Achilles tendinitis and lateral
epicondylitis. Heel pain or plantar fasciitis are commonly associated with psoriatic arthritis, and nails may show pitting
and onycholysis. Careful examination may reveal psoriatic plaques on the scalp or ears that the patient has not noticed. Interestingly,
the severity of psoriasis has little correlation with the presence or severity of psoriatic arthritis.
Psoriatic arthritis may be indistinguishable from rheumatoid arthritis in onset and progression, and there are no diagnostic
laboratory tests for psoriatic arthritis. However, it more typically is asymmetrical oligoarticular or monoarticular. Most
cases of psoriatic arthritis are controlled with NSAIDs; for those whose arthritis is not satisfactorily controlled with NSAIDs
and for those who are experiencing joint damage the DMARDs used for the treatment of rheumatoid arthritis are effective.
Seronegative spondyloarthopathies such as reactive arthritis and Reiter's syndrome most commonly present as asymmetric
oligoarthritis affecting the lower extremity joints. Reactive arthritis is a sterile inflammatory arthritis that occurs as
a consequence of infection at a remote site. It should be suspected when there is a recent history of diarrhea, chlamydial
infection, unexplained genitourinary symptoms, prostatitis, cystitis or conjunctivitis.
Reiter's syndrome is a reactive arthritis that occurs within 3 weeks of a chlamydia infection of the genitourinary tract
or after an intestinal infection, typically caused by Salmonella, Shigella, Campylobacter,or Yersinia. Extra-articular symptoms
associated with the full-blown syndrome include conjunctivitis, circinate balanitis and hyperkeratotic skin lesions on the
soles called keratoderma blennorrhagica.
The triggering infection should be treated as appropriate; screening of contacts at risk must be included in the management
of patients with genitourinary reactive arthritis and selected patients with enteropathic Reiter's syndrome. Management of
the arthritis must be individualized and may include NSAIDs, oral or intra-articular steroids and, in resistant cases, DMARDs.
Patients with SLE (female:male ratio is about 10:1) frequently present with polyarthritis - typically a peripheral polyarthritis
with symmetric involvement of both small and large joints. The physician should question the patient in detail about symptoms
that reflect multisystem involvement, particularly photosensitivity, unexplained rashes, malar rash, pleuritic chest pain,
history of seizures, oral ulcers, hair loss, Raynaud's phenomenon, fevers and sweats.
Deformities including subluxation at the MCP joints, ulnar deviation, "swan neck" and boutonniere deformities (Jaccoud's
arthropathy) may develop in about approximately 15% of patients with SLE, but these are not associated with joint erosion,i.e.,
arthritis is usually,of the non-erosive type.
If, on the basis of the history and the physical examination, SLE is suspected the physician should order an antinuclear
antibody test, this is a useful screening test because a negative test result will virtually exclude SLE. If the test is positive
and there is clinical suspicion of multisystem disease, the physician should consider further serologic tests and refer the
patient to a rheumatologist.
For SLE patients without serious internal organ involvement hydroxy chloroquine (HCQ) is the drug of choice
because it has been shown to improve disease control, prevent flares and improve long-term outcomes.
Arthritis and pleurisy respond to NSAIDs. Steroid medications may also be required in low and moderate doses either intermittently
or continuously. For those with with serious internal organ involvement, immunosuppressant drugs are required.
Diseases such as primary Sjögren's syndrome, polymyositis-dermatomyositis, limited and diffuse scleroderma and mixed
connective tissue disease may also manifest as polyarthritis. Primary Sjögren's syndrome may be extremely difficult to differentiate
from rheumatoid arthritis when the main feature is polyarthritis. Prominent muscle weakness is a clue to myositis, and patients
with scleroderma almost always have sclerodactyly and Raynaud's phenomenon.
Mixed connective tissue disease may present with features of rheumatoid arthritis in conjunction with those of other
connective tissue diseases (secondary disease). Maturity-onset seronegative synovitis syndrome is distinguished from
rheumatoid arthritis on the basis of a negative rheumatoid factor, a markedly elevated erythrocyte sedimentation rate, usual
age of onset over 60 years and marked improvement in response to low doses of steroids.
Although it is uncommon it is not rare. Onset is often sudden, and there is typically swelling of the wrists and pain,
stiffness and restriction of the shoulder joints. The clinical course of MOSS syndrome closely resembles polymyalgia rheumatica
in its sudden onset and response to prednisone.
Polymyalgia rheumatica typically presents with shoulder and pelvic girdle involvement and an absence of clinically detectable
synovitis; MOSS syndrome presents with peripheral synovitis that may be indistinguishable from seronegative rheumatoid arthritis
except in its response to prednisone and its course over time. The synovitis disappears with 10-15 mg/day of prednisone, and
the condition is nonprogressive and nonerosive.
Once the disease is under control the dose of prednisone can be lowered every 1-3 months, aiming for the lowest dose
that will control symptoms. Strategies to prevent steroid-induced osteoporosis, specifically bisphosphonates, are required.
If the prednisone dose cannot be lowered or if pain and swelling persist in spite of low-dose prednisone, the physician
should reassess the patient and consider alternative diagnoses, such as rheumatoid arthritis, psoriatic arthritis, temporal
arteritis and other vasculitides.
Since this condition is difficult to differentiate from seronegative rheumatoid arthritis and because of the morbidity
associated with long-term steroid use in the elderly, it is best to refer these patients to a rheumatologist.
Although uncommon, gout or pseudogout (often referred to as false gout) can result in inflammatory polyarthritis. The
typical patient with polyarticular gout has had acute attacks of monoarthritis and typical attacks of gout for many years.
Any joint may be affected and, in severe cases, the patient may be febrile and have leukocytosis; tophi are commonly found
on careful examination.
Patients are usually over 50 years of age or have identifiable risk factors for gout such as diuretic use, renal disease
or alcohol abuse. Although serum uric acid level is often high this is not always the case. Synovial fluid aspiration will
demonstrate the typical urate crystals.
Pseudogout may also cause polyarthritis. Patients are usually over 60 years of age, and this condition commonly coexists
with osteoarthritis. The presentation may resemble rheumatoid arthritis - typical distribution of joint inflammation includes
the wrists, knees, shoulders, hips and finger joints.
Radiographs of affected joints commonly show chondrocalcinosis, but the diagnosis is confirmed when calcium pyrophosphate
dihydrate crystals are found in the synovial fluid of inflamed joints.
Osteoarthritis affecting DIP, PIP and CMC joints may be associated with symptoms and signs of inflammation. Onset is
common in perimenopausal women, and there is often a family history of Heberden's osteoarthritis. Patients complain of joint
tenderness and episodes of swelling usually in 1 or several finger joints at a time.
Examination discloses Heberden's and Bouchard's nodes in finger and sometimes toe joints; MCP and MTP joints are not
affected. Radiographs of affected joints show narrowing, osteophytes, sclerosis and, in the advanced stages, PIP or DIP joint
erosions.
Because of the prominent involvement of DIP joints, it may be difficult to distinguish inflammatory osteoarthritis from
psoriatic arthritis, which may also develop in older patients. It is important to remember that rheumatoid arthritis can occur
in patients who also have osteoarthritis.
Degenerative osteoarthritis is associated with the so-called,"wear and tear" arthritis,where the majority of seniors
will have. Some people will not be aware that they have it. "Live long enough and most people will have some form of it."says
most physicians.
Summary: Patients with inflammatory polyarthritis are a challenge to diagnose and manage. Diagnosis and management are
usually based on a detailed history and a focused physical examination of the patient, but it is essential to inquire about
family history of diseases (e.g., psoriasis, colitis, arthritis conditions and gout) as well.
Key symptoms of inflammation are morning stiffness that lasts longer than 30 minutes, worsening of symptoms with rest
and improvement with mild exercise.
In patients with persistent inflammatory polyarthritis, diagnostic considerations include rheumatoid arthritis,
psoriatic arthritis and other seronegative spondyloarthropathies, systemic lupus erythematosus, maturity-onset seronegative
synovitis, crystal-induced synovitis and osteoarthritis.
Laboratory tests, such as those for rheumatoid factor and antinuclear antibodies, have value in increasing or decreasing
the probability of a specific diagnosis. With early diagnosis specific therapies aimed at controlling inflammation, preserving
range of motion and preventing joint damage can decrease morbidity and improve a patient's quality of life.
