Early detection of rheumatoid arthritis can go a long way toward reducing the risks of joint damage and disability. Accordingly, these authors offer pertinent diagnostic insights to look for in the clinical exam, patient history, lab tests and imaging modalities.

If left untreated, rheumatoid arthritis (RA) causes joint damage and often leads to disability. Accordingly, it is essential to detect early RA so one may initiate aggressive therapy to improve the potential for remission.
Rheumatoid arthritis is a systemic, chronic inflammatory condition that affects one percent of the worldwide population. While RA is the most common type of arthritis triggered by the immune system, the cause of the disease remains unknown. Genetic and environmental factors play a role and abnormalities of the cellular and humoral components of the immune system are involved.¹

Rheumatoid arthritis is two and a half times more common in females than males. The disease can occur at any age with peak onset between the ages of 40 and 60.² The progression of joint damage is highly unpredictable and varies from patient to patient.¹

The diagnosis of early RA can be difficult since it can mimic other inflammatory conditions. Although some patients present early with classic RA symptoms, others may have symptoms that are nonspecific. Unfortunately, there are no established criteria to classify or diagnose early RA.³ The current classification criteria for RA were derived from patients with longstanding disease, and established for the purpose of identifying patients for clinical studies.⁴

In the initial stages of RA, some patients may not meet all the criteria for diagnosis of the condition. In addition to obtaining a complete history of patient symptoms, combining a good joint exam with laboratory data and radiographic images is helpful in making an accurate diagnosis. Although the 1987 American College of Rheumatology (ACR) criteria have limitations as noted above, they nonetheless provide a useful framework in which to consider the major clinical manifestations of RA (see “A Guide To Diagnostic Criteria For RA”).

What To Look For In The Clinical Exam And Patient History
Rheumatoid arthritis is a symmetric peripheral polyarthritis that typically affects the small joints of the hands at the wrists, the metacarpophalangeal joints (MCPs) and the proximal interphalangeal joints (PIPs). The presence of symmetrical pain and swelling of the small joints of the hands and morning stiffness strongly suggests the possibility of RA and should lead to the appropriate diagnostic evaluation.

Joint pain and stiffness are universal in patients with RA. When interviewing a patient, first determine the location of his or her symptoms and associated functional difficulties. The pattern of joint involvement in RA is quite typical in most cases.

Patients may note swollen fingers and the need for rings to be cut off or resized. The inability to “wring out a washcloth” is common as is the need to hold a coffee cup with both hands. Patients typically report decreased grip strength. “Trigger finger” due to flexor tenosynovitis may occur. Early in the course of RA, patients frequently experience pain in the forefoot metatarsophalangeal joints (MPJs). Your patients may describe the pain as walking on gravel and be particularly symptomatic when getting out of bed in the morning.

A Guide To Diagnostic Criteria For RA

Rheumatoid arthritis also affects larger joints of the neck, shoulders, elbows, hips, knees and ankles. Spine involvement in RA is limited to the upper cervical spine. With significant involvement, patients may have symptoms of headache, neck pain, a sensation that the head might fall off, paresthesias or weakness. Shoulder involvement produces significant limitation of motion. Patients may note their elbow is stuck and that it will not straighten out or rotate completely.

Patients with RA may feel significant hip pain in the groin and medial thigh, with the pain sometimes radiating to the buttock. The knee joints may have swelling both anteriorly and posteriorly with a popliteal Baker’s cyst. A ruptured popliteal cyst can produce calf pain and swelling, which is clinically indistinguishable from deep venous thrombosis (DVT). A patient may have difficulty walking, climbing or descending stairs due to pain in the knees or ankles.

Stiffness is almost always present in patients with RA and occurs after any period of prolonged inactivity. Morning stiffness that lasts greater than one hour is typical among patients with RA. When assessing morning stiffness, ask patients what time they arise in the morning and what time the stiffness has improved to the maximum extent. They might tell you that they run hot water on their joints or wash dishes to help to loosen them up but the stiffness may reoccur after a period of inactivity. This is referred to as gelling phenomena.

Other Clinical Considerations In Diagnosing Early RA
The onset of RA is usually gradual with symptoms developing over several weeks or months in at least 50 percent of cases of RA. In 10 to 25 percent of cases, RA presents suddenly overnight or over a couple of days when the patient notices intense pain in his or her joints. Initially, only a few joints become symptomatic for a short period of time and resolve after several days. Over time, the symptom-free intervals and constant symmetric symptoms develop. Usually, patients with RA experience symptoms of pain and stiffness that are constant in multiple joints and worse in the morning.

The 1987 ACR criteria require that symptoms persist for six weeks or greater for the diagnosis of RA, although this duration is arbitrary. Acute polyarticular joint pain of less than six weeks may be a sign of a self-limited disorder such as viral arthritis. European researchers have demonstrated that most cases of “early arthritis” are not RA.⁵

Patients with RA usually have symptoms of onset profound fatigue or generalized malaise with a loss of energy. In some cases, they may have a low-grade fever. Commonly, patients have mild weight loss due to a loss of appetite.

Sicca symptoms of dry eyes or mouth frequently occur in RA patients who develop Sjogren’s syndrome. The patient may have noticed firm lumps or bumps on his or her elbows or other extensor surfaces, which would indicate subcutaneous rheumatoid nodules. Patients may experience numbness and tingling in their wrists and hands due to swelling and compression of the median nerve with development of a carpel tunnel syndrome.

Ask your patient about the effectiveness of his or her current medications for RA. Often, patients are given corticosteroids that act rapidly to control the pain, stiffness and swelling associated with RA. In some cases, patients may have tried a nonsteroidal antiinflammatory drug (NSAID) but be aware that NSAIDs are often taken at a subtherapeutic dose. Many patients can accurately and reliably report their history of symptoms, including stiffness and tenderness, prior to being treated. However, clinicians should also keep in mind that patients with RA often under-report joint swelling.⁶

A Guide To Key Aspects Of The Joint Exam
A complete joint exam is essential when assessing for early RA. Check each joint individually for pain or tenderness, palpable synovitis and range of motion. In some cases, patients may present with pain symptoms before the onset of swelling.

One may detect swelling around the joint visually and by palpation of the joint capsule. When examining your patient’s joints, observe for thickness of synovial tissue or loss of joint margins. In early RA, the swelling may be mild. If there is active synovitis, the joint may have warmth or erythema.

Gently assess the joint’s range of motion. If there is restriction in motion, there may be swelling in the joint capsule. In established RA, the distribution tends to be polyarticular and symmetrical. However, early in the course of the disease, the distribution may be asymmetrical and pauciarticular or even monoarticular.3
When it comes to RA in the hands, the MCPs and PIPs are almost always involved, especially the index and long fingers. The distal interphalangeal joints (DIPs) are usually not involved.

Note the swelling about the PIP joints of the right third finger, the right fourth finger, the left third finger and mildly in the wrists.

The ability to recognize early synovitis in the joints of the hands and feet is critical. When examining the finger joints, use a “four-point” technique. Use both index fingers and thumbs to palpate the dorsal and volar aspect of the MCP and PIP joints. Synovitis is usually present in the second MCP joint. The “valleys” between the MCPs may be filled with synovitis. Clinicians should distinguish soft tissue swelling from noninflammatory bony hypertrophy, such as Heberden and Bouchard’s nodes, which often indicate osteoarthritis.⁷

At the wrist, one may note synovial proliferation around the ulnar styloid. On the dorsal surface, tenosynovitis results in swelling just above the wrist joint. It is important to visualize and palpate all joints in the hands carefully to pick up on swelling and document actively inflamed joints.⁸

Swelling in the elbows is common among patients with RA but it may be difficult to detect. One may detect synovitis by palpating between the lateral epicondyle and the olecranon prominence. Swelling of the olecranon bursa often occurs in more severe RA and tends to be bilateral.

Shoulder involvement typically produces significant limitation of motion in all planes. A visible effusion of the glenohumeral joint is unusual but can produce a “shoulder pad” sign. Upon examination, have the patient elevate the scapula to improve range of motion for abduction and elevation. These patients will often feel shoulder pain in the proximal deltoid region.

In regard to possible RA of the knee joint, check for anterior swelling. Stroke the medial knee to move the synovial fluid cephalad. Then press on the lateral knee to produce a visible fluid wave or “bulge” on the medial knee. Swelling of the posterior knee is common. Assess the knee posteriorly by palpating the popliteal area for a “Baker’s cyst.”

Clinicians may assess the ankle joint via palpation for synovial proliferation between the medial malleolus and the tibialis anterior tendon. Note that the forefoot is a major area of rheumatoid involvement. One may note swelling in the dorsum of the foot just proximal to the toes. Early in the course of RA, patients may have tenderness to palpation of the individual MPJ joints or to squeezing of the forefoot.

While examining the joints, also check the skin for rheumatoid nodules. These subcutaneous nodules have the histological appearance of a granulomatous reaction.² One will typically locate these nodules over bony prominences and pressure points or on the extensor surfaces of the forearms or fingers. You can detect these by palpating the skin over the olecranon bursa area and Achilles tendons. The nodules vary in size from a few millimeters to several centimeters. Rheumatoid nodules occur in approximately 20 percent of patients with RA.

What You Should Know About Lab Tests
There is no single laboratory test to prove the diagnosis of RA. However, clinicians may detect several laboratory abnormalities.⁹ Laboratory data, including an IgM rheumatoid factor and anti-cyclic citrullinated peptide (anti-CCP) antibody by Enzyme-Linked Immunosorbent Assay Test (ELISA), are helpful in making the diagnosis.

The rheumatoid factor (an IgM molecule binding the Fc portion of an IgG molecule) remains the primary screening test used by general practitioners. Rheumatoid factor is present in approximately 80 percent of patients with RA. The IgM-RF is reportedly 86 percent sensitive to the diagnosis of RA but has a lower specificity at 82 percent. It is important to note that a positive rheumatoid factor may occur in patients with other autoimmune diseases such as systemic lupus erythematosis (SLE), osteoarthritis, psoriatic arthritis and undifferentiated spondyloarthropathy with articular manifestations or transplanted organs. It is commonly positive in patients who have infectious diseases such as Hepatitis C or chronic bacterial infections. Also be aware that healthy individuals may exhibit a positive RF, particularly those in the elderly population.

The advent of the cyclic citrullinated peptide antibody (Anti-CCP) has been a major advance in the diagnosis of early RA. The anti-CCP antibody test is helpful when distinguishing RA from other rheumatic diseases. The anti-CCP antibody test reportedly has a 98 percent specificity for the diagnosis of RA. The sensitivity of the test is 81 percent. The combination of a positive rheumatoid factor and anti-CCP antibody test makes the diagnosis of RA extremely likely.¹⁰

Patients with a positive anti-CCP antibody test are more likely to develop joint erosions. A patient may have a positive rheumatoid factor and/or anti-CCP antibody test for several years before the onset of joint symptoms.¹¹ The anti-CCP antibody test is highly predictive in the future development of RA in both healthy people and patients with undifferentiated arthritis.^12,13

One of the most common errors in evaluating patients with joint pain is to make a diagnosis of SLE based on a positive antinuclear antibody (ANA) test without evidence of disease in multiple systems. Often, clinicians obtain the ANA during the evaluation of joint pain. The ANA is positive in 30 to 40 percent of patients with RA, especially those with more severe disease. However, in the absence of other signs and symptoms suggesting SLE, a positive ANA test, regardless of the titer, does not have great diagnostic significance.

Other laboratory data assessed during the diagnostic workup of patients with suspected RA include acute phase reactants erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). Elevations of ESR or CRP may help in assessing activity of RA since elevated values of either test correlate to some extent with the development of joint erosions. However, these tests are general markers of inflammation and are not specific to RA. They may be useful in distinguishing RA from other noninflammatory rheumatic diseases such as osteoarthritis or fibromyalgia. However, it should be emphasized that the ESR and CRP are not always elevated in patients with RA.

Note that a complete blood count often reveals anemia of chronic disease. The white blood cell count may be elevated if a patient has been treated with steroids.

In some cases, one may assess synovial fluid if an arthrocentesis of a large joint effusion is possible. Analysis of the fluid should include cell count with differential, crystal analysis and culture if indicated. Leukocytosis with WBCs in the range of 3,000 to 50,000 per mm3 and a predominance of neutrophils (greater than 75 percent) is common.⁷ Occasionally, one may see very high synovial fluid white counts in the “septic” (50,000 to 100,000 per mm3) range in cases of RA.

Pertinent Pearls On Radiographic Imaging
When it comes to assessing the structural damage of RA, it is best to use radiographs.14 In regard to early RA, radiographic changes include soft tissue changes of symmetrical swelling in the hands around the MCP and PIP joints and wrists. Bone density decreases in early RA. Accordingly, one would see bony demineralization of juxtaarticular osteoporosis on plain film x-ray.^14,15 Joint damage occurs early in the course of RA.

In these X-rays, there is periarticular osteopenia and soft tissue swelling about the PIP’s, MCP’s, and wrists. Note the multiple erosions at the left second and third PIP joints, the base of the proximal phalanx of the fourth finger, the head of the second metacarpal and the head of the fourth proximal phalanx.

Approximately 75 percent of patients develop joint erosions in the first two years of the onset of RA symptoms.¹⁴ Radiographs may show early aggressive erosions in the carpal bones, MCPs and PIPs, and in the wrist at the ulnar styloid. However, these patients will usually maintain the joint spaces. One will not see subluxation in early RA cases.¹⁵ When it comes to early RA, it is more common to see erosions in foot X-rays than in X-rays of the hand.¹⁶ Radiographs are also useful in determining if the disease is progressing.

Joint erosions and joint space narrowing, which are visible by plain X-ray, are evidence of permanent structural damage. However, radiographs may not show any abnormality in the first three to six months of the onset of arthritis. This has lead to the use of both ultrasound and magnetic resonance imaging techniques (MRI) to detect early articular changes in RA.

Clinicians sometimes utilize MRI and ultrasound to detect soft tissue swelling and early erosions, which are too small to see on plain film X-rays. Magnetic resonance imaging is significantly more sensitive than conventional radiography at detecting early inflammatory soft tissue and destructive joint process before radiographic damage becomes evident.¹⁴ One may consider ultrasound for studying joint tendon and bursal involvement in RA.9 However, the roles for ultrasound and MRI in the diagnosis of early RA are controversial, and there is currently no consensus regarding the use of these imaging modalities.

In Conclusion
There is no single test used to diagnose early RA. Clinicians commonly make this diagnosis based on a combination of patient symptoms, physical exam findings, laboratory data and radiographic changes. Whenever there is clinical suspicion of RA, it is important to look for all the clues.

Early diagnosis is needed to facilitate early treatment in order to prevent structural damage of joints and disability, even if the 1987 ACR criteria are not fully satisfied. Diagnosing RA during the early inflammatory stages and initiating treatment with disease-modifying antirheumatic drugs (DMARDs) improves patient outcomes and the long-term quality of life.¹⁴ Increasingly, rheumatologists are initiating DMARDs when they clinically suspect RA but prior to a firm diagnosis of the disease.³

Once the primary caregiver has made the diagnosis of RA, prompt referral to a rheumatology practitioner is recommended. In an ideal circumstance, the generalist and specialist work as a team in the care of a patient with RA in order to prevent permanent joint damage and a reduced quality of life.

Dr. Brasington is the Director of Clinical Rheumatology and an Associate Professor of Medicine at the Washington University School of Medicine in St. Louis. Ms. Unk is a Nurse Practitioner within the Division of Rhuematology at the Washington University School of Medicine.