Diagnostic Criteria

Diagnostic Approach

Diagnosis of rheumatoid arthritis (RA) is largely clinical, based on key historic and physical findings and serial observation of symptoms, signs and response to therapies. Observation during the first 3 months of disease will help establish the persistence of this disorder and may disclose typical patterns of joint involvement characteristic of rheumatoid arthritis. The use of certain laboratory tests and imaging may lend further support or confirm the diagnosis (Figure 4-1).

It is important that the clinician identify a pattern of symptom progression and key musculoskeletal features of the disease to firmly establish a diagnosis of RA. Patients will typically exhibit the insidious or acute onset of an oligoarthritis that, with time, will demonstrate an additive pattern of additional inflamed joints in a symmetric distribution. This inflammatory polyarthritis typically affects proximal interphalangeal (PIP), metacarpophalangeal (MCP), wrist, knee, ankle and metatarsophalangeal (MTP) joints (see Clinical Features). Features of joint inflammation (i.e., synovial effusion, swelling, warmth, erythema) should be identified. The presence of inflammatory and constitutional manifestations, such as prolonged morning stiffness, low-grade fever, anorexia, or weight loss, tends to confirm this diagnosis. Rheumatoid nodules, serum rheumatoid factor (RF), or anti– cyclic citrullinated peptide (CCP) antibody positivity would be strongly supportive evidence for the diagnosis of RA.

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Diagnostic Criteria

In 2010, the American College of Rheumatology (ACR) and European Alliance of Associations for Rheumatology (EULAR) published a new set of classification criteria for RA, designed to better classify patients with RA early in the disease course and the earlier, 1987 ARA criteria. While they are often referred to as diagnostic criteria, both the 2010 ACR/EULAR and the 1987 ARA criteria were not developed for that purpose, but to ensure homogeneity of patients with RA in clinical trials. The 2010 ACR/EULAR criteria comprise 4 domains (joint involvement, serology, acute-phase reactants, and duration of symptoms), each of which has several categories with associated point values (Table 4-1). Patients whose point scores equal 6 or higher are classified as having RA.

The utility of the 1987 American Rheumatism Association (ARA) criteria in patients with early or very early RA (between 6 weeks and 6 months of symptoms) was markedly limited by the requisite chronicity and severity that comprise these criteria. For example, they included radiographic changes which are not typically present in the earliest stages of RA. Furthermore, the only biomarker considered for classification was RF. By contrast, the 2010 ACR/EULAR criteria put more emphasis on biomarkers, including anticitrullinated protein antibody (ACPAs) and acute-phase reactants, including erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP), while the presence of rheumatoid nodules, structural damage, or a symmetric presentation is deemphasized. These changes thus enable accurate classification of RA early in disease development.

Although not primarily intended for diagnosis, the ACR criteria nonetheless serve as an important educational tool and may be helpful in distinguishing RA from other forms of inflammatory polyarthritis (e.g., gout, reactive arthritis, psoriatic arthritis, lupus). A systematic literature review of 17 full publications and 17 meeting abstracts found that the 2010 ACR/EULAR criteria have a sensitivity of 0.82 (95% CI 0.79-0.84) and specificity of 0.61 (95% CI 0.59-0.64) for the diagnosis of RA.

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Differential Diagnosis

In its acute stages, RA is often confused with reactive arthritis, viral arthritis (e.g., parvovirus B19, Epstein-Barr virus, hepatitis B, hepatitis C), Lyme disease and the polyarticular onset of other systemic rheumatic disorders (e.g., polymyositis, scleroderma, lupus). Chronically, RA needs to be distinguished from other forms of chronic, polyarticular, inflammatory arthritis, such as systemic lupus erythematosus (SLE), Lyme disease, psoriatic arthritis, tophaceous gout or pseudogout, calcium pyrophosphate disease, reactive arthritis, enteropathic arthritis, erosive/inflammatory OA, scleroderma, rheumatic fever and inflammatory myositis.

Osteoarthritis

OA is the most common arthropathy in the adult population. This degenerative condition is easily distinguished from RA by its noninflammatory features (e.g., brief morning stiffness, lack of synovial swelling or systemic symptoms) and the pattern of joint involvement. OA typically manifests with pain and bony hypertrophy of the distal interphalangeal (DIP) (Heberden’s nodes), PIP (Bouchard’s nodes), and CMC1 (base of the thumb) joints. In contrast to RA, osteoarthritis (OA) is most prevalent in the elderly.

Gout

Gout is another common arthropathy that may masquerade as RA. Gout typically affects men and postmenopausal women with an unpredictable series of acute inflammatory attacks of monarthritis or oligoarthritis (one or few joints). Initially, the lower extremity joints are involved (e.g., MTP, ankle, knee, toe), but as the attacks become more frequent, they also become polyarticular and may involve upper extremity joints (e.g., wrist, elbow, fingers). Gouty tophi (an accumulation of urate in the soft tissues) may be found in the subcutaneous tissues or around joints and are often confused with the nodules of RA. However, the two conditions differ by the association of gouty tophi with an intermittent arthropathy (at the onset) and serum elevated uric acid levels, and a characteristic light yellow or chalky hue or appearance under the skin.

In addition, gouty tophi may erode through the skin and be exuded from their subcutaneous stores. Examination by polarized microscopy of this exudate will reveal thousands of negatively birefringent crystals. Only when gout becomes tophaceous will there be a chronic inflammatory arthritis that affects the fingers and hands in a rheumatoid-like fashion, often giving rise to rheumatoid-like deformities. In this circumstance, gout can be distinguished from RA by a different pattern of disease onset, synovial fluid analysis showing uric acid crystals, radiographic evidence of bony tophaceous deposits, elevated serum uric acid and a negative serologic test for RF and anti-CCP antibodies. In fact, there is an unexplained negative correlation between gout and RA. Patients who claim to have both are usually misdiagnosed based on the apparent similarities of these diseases.

Psoriatic Arthritis

Psoriatic arthritis may also present as an inflammatory polyarthropathy that is often confused with RA. Psoriatic arthritis has several patterns or subsets of arthritis: an asymmetric oligoarthritis; DIP and PIP arthritis with nail disease; rheumatoid-like arthritis (MCP, PIP, wrists); and arthritis mutilans (a severe destructive and deforming arthritis). Each of these variants may also be seen in RA. The diagnosis of psoriatic arthritis depends on the identification of a known pattern of articular disease, psoriatic plaques (over the elbows, scalp, legs, buttocks, penis, etc.) and nail changes (e.g., pitting, onycholysis, ridging, etc.) typical of psoriasis. In many patients, psoriatic skin disease may be minor or found in seldom-examined areas (i.e., scalp, buttocks, genitalia). Last, RA is present in only a minority of affected patients (5% to 15%). Interestingly, anti-CCP antibodies are present in about 8% of patients with psoriatic arthritis. Routine laboratory testing may disclose hyperuricemia due to the increased turnover of skin in this disorder.

Reactive Arthritis

The classic triad of reactive arthritis includes arthritis, urethritis and conjunctivitis. At the onset, over half of patients will have a postvenereal or postdysenteric onset of an acute, intermittent and sometimes chronic asymmetric oligoarticular arthritis. Uncommonly, these patients will demonstrate a symmetric polyarthritis akin to RA. The diagnosis of reactive arthritis is based on the pattern of joint involvement (i.e., asymmetric oligoarticular with or without back pain and sacroiliitis) and the identification of the extra-articular features of reactive arthritis that include inflammatory eye disease (e.g., conjunctivitis, uveitis), urethritis or cervicitis, onycholysis and keratoderma blennorrhagicum (painless, scaly, papular lesions on soles and palms). Nearly 70% of Whites with reactive arthritis are positive for HLA-B27.