Chapter 4. Approach to the Patient with Arthritis

Many diseases can cause arthritis. Obtaining a history and performing a physical examination are the first steps in allowing the clinician to accurately characterize the arthritis and approach the differential diagnosis in a focused, logical fashion based on the duration of symptoms, the presence or absence of joint inflammation, the number of joints affected, and the pattern of joint involvement (Table 4–1).

When evaluating a patient with joint symptoms, it is important to determine whether the symptoms are due to an articular process and not to bursitis, tendinitis, or other soft tissue conditions. The physical examination should also establish whether there are objective findings of arthritis, such as swelling, in the symptomatic joints. Arthralgias in the absence of objective arthritis commonly occur in systemic lupus erythematosus (SLE) and acute viral illnesses but have less diagnostic significance than true arthritis.

Laboratory tests cannot substitute for clinical evaluation and should never be used as a “screen” for disease. Musculoskeletal complaints are common in the general population, but the prevalence of inflammatory rheumatic diseases is relatively low. Hence, the positive predictive value of many rheumatologic tests is low when tests these are ordered indiscriminately. In general, radiographs add little to the evaluation of acute presentations of arthritis (except in cases of suspected trauma) but often are critical for the assessment of chronic arthritis.

Inflammatory versus Noninflammatory Arthritis

The distinction between inflammatory arthritis and noninflammatory arthritis is a critical bifurcation point in the differential diagnosis of arthritis. The most reliable means for making this distinction is analysis of the white blood cell (WBC) count in the synovial fluid. The synovial fluid WBC count is >2000/mcL in inflammatory arthritis and is <2000/mcL in noninflammatory arthritis (see Chapter 2). Arthrocentesis should be performed whenever feasible because although clinical features and other laboratory investigations also help distinguish inflammatory and noninflammatory arthritis, no single finding is definitive.

Patients with an inflammatory arthritis usually complain of pain and stiffness in involved joints; typically these symptoms are worse in the morning or after periods of inactivity (the so-called “gel phenomenon”) and improve with mild to moderate activity. On examination, the larger joints can be warm and, when severely inflamed as in acute gout or septic arthritis, can have erythema of the overlying skin. Laboratory investigations often reveal an elevated erythrocyte sedimentation rate (ESR) and a high C-reactive protein (CRP) level. In contrast, patients with noninflammatory arthritis have pain that worsens with activity and improves with rest. Stiffness is generally mild, lasts <30 minutes in the morning, and is not a prominent symptom. The ESR and CRP are usually normal.

Constitutional Symptoms

The presence of fever raises the possibility of infection. Most patients with septic arthritis or disseminated gonococcal infection are febrile. Fever can also accompany arthritis that is not due to active infection (Table 4–2). Indeed, intermittent high-grade fever ≥39°C is characteristic of Still disease. SLE can also cause fever ≥39°C. However, fever more often occurs when serositis, rather than polyarthritis, is the major manifestation of SLE. On the other hand, fever ≥38.3°C is unusual in rheumatoid arthritis, occurring in <1% of patients.

Significant weight loss is common at the initial presentation of reactive arthritis, systemic vasculitis, enteropathic arthritis, and paraneoplastic arthritis but is unusual in rheumatoid arthritis of recent onset. Constitutional symptoms rarely accompany noninflammatory forms of arthritis.

Extra-Articular Manifestations

Extra-articular manifestations, such as glomerulonephritis, pulmonary abnormalities, oral ulcerations, ocular inflammation, and peripheral neuropathy, may signal that arthritis is a manifestation of a systemic rheumatic disease or vasculitis. The presence of rash can be a very helpful clue to the diagnosis (Table 4–3).

Comorbid Conditions

Certain chronic conditions predispose to the development of particular musculoskeletal problems. For example, patients with long-standing, poorly controlled diabetes mellitus are at greatly increased risk for Charcot arthropathy in the feet and limited joint mobility in the hands. Certain medications can trigger drug-induced lupus, which can present as a polyarthritis, often with serositis. The resurgence in the use of hydralazine for the treatment of hypertension has led to an increase in the incidence of hydralazine-induced lupus as well as the more serious hydralazine-induced, antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Prior glucocorticoid therapy and alcohol abuse are the leading risk factors for osteonecrosis, which commonly presents as hip pain. Osteonecrosis and bone pain are common manifestations of Gaucher disease. Injection drug use carries the risk of septic arthritis; endocarditis; and infection with hepatitis B, hepatitis C, and HIV—each of which is associated with rheumatic conditions.

Family History

A positive family history, particularly among first-degree relatives, increases the likelihood of certain forms of arthritis. Most notably, the risk of ankylosing spondylitis for children or siblings of a patient with ankylosing spondylitis is as much as 75-fold that of the general population. The relative risk for SLE among first-degree relatives ranges from 20 to 30. A positive family history of rheumatoid arthritis is less helpful. The relative risk for siblings may be as low as 3, and family histories of rheumatoid arthritis can be inaccurate due to confusion with osteoarthritis.

Except in cases of trauma, arthritis that is acute in onset is usually inflammatory. Septic arthritis and crystal-induced arthritis typically have an acute onset, and patients often seek medical attention within hours to days after the onset of symptoms. These disease processes, therefore, always warrant serious consideration in cases of acute arthritis. Nonetheless, the differential diagnosis of acute arthritis is broad and includes such entities as rheumatoid arthritis and the spondyloarthropathies; however, these entities more commonly present as chronic conditions.

Acute Monoarthritis

Essential Features

• Septic arthritis is the major diagnostic concern.
• Arthrocentesis is the most important diagnostic test.

Initial Clinical Evaluation

The history and physical examination should determine whether the process is acute (onset over hours to days), involves the joint rather than surrounding tissues or bone, and is truly monoarticular. The most common causes of acute monoarthritis are infection, crystal-induced arthritis, and trauma (Table 4–4). In cases of suspected trauma, it is important to ascertain whether the reported trauma was sufficiently severe to account for the joint findings. (Patients with new-onset joint effusions often attribute the joint abnormality to incidental bumps, turns, or other minor trauma.) Joint space infection is the foremost concern in patients with acute pain and swelling in a single joint not clearly due to trauma.

Laboratory Evaluation

Arthrocentesis is indicated for all cases of unexplained acute monoarthritis. Synovial fluid should be sent for culture (for bacteria, mycobacteria, and fungus), cell count, Gram stain, and examination for crystals by polarized light microscopy. Routine laboratory determinations (eg, complete blood cell count, serum electrolytes and creatinine, and urinalysis) can provide helpful ancillary information. Blood cultures should be obtained if septic arthritis is suspected.

The characteristics of the synovial fluid guide the initial differential diagnosis. Nongonococcal septic arthritis usually causes synovial fluid WBC counts >50,000/mcL and often generates very high counts (>100,000/mcL). The synovial fluid WBC count in gonococcal arthritis is generally lower than in nongonococcal septic arthritis (mean synovial fluid WBC as low as 34,000/mcL in some series). Crystal-induced arthritis is also very inflammatory, with synovial fluid WBC counts often >50,000/mcL; WBC counts >100,000/mcL, however, are uncommon.

Gram staining for bacteria in synovial fluid is relatively insensitive (false-negative rates range from 25% to 50% for nongonococcal septic arthritis and are substantially higher for gonococcal infections). On the other hand, examination of synovial fluid by polarized light microscopy is a sensitive test for urate crystals. Calcium pyrophosphate dihydrate crystals are somewhat more difficult to visualize due to their weaker birefringence, but their detection should not present difficulties for the experienced observer. Thus, the absence of crystals is a strong argument against microcrystalline disease, but a negative Gram stain does not exclude infection. Occasionally, infection and microcrystalline disease coexist; therefore, the finding of crystals in the synovial fluid does not exclude the possibility of infection.

Properly performed cultures of synovial fluid are a sensitive test for nongonococcal septic arthritis (positive in up to 90% of cases). In contrast, synovial fluid cultures are positive in only 20–50% of cases of gonococcal arthritis, and the diagnosis often depends on identification of Neisseria gonorrhoeae at other sites by culture or nucleic acid amplification tests. In some cases, however, the diagnosis of disseminated gonococcal infection rests on the response to appropriate antibiotic therapy.

Imaging Studies

Radiographs can demonstrate fractures in cases of trauma but usually contribute little to the diagnosis of nontraumatic monoarthritis if the process is truly acute. Radiographic evidence of chondrocalcinosis can be seen in cases of pseudogout and, when there have been recurrent attacks of gout, radiographs may reveal erosions characteristic of gout. Occasionally, imaging studies can be misleading. For example, radiographs may demonstrate osteoarthritis or other chronic conditions that predispose to the development of septic arthritis but are not the proximal cause of the acute joint inflammation.

Differential Diagnosis

Inflammatory Monoarthritis

The leading causes of acute inflammatory monoarthritis—infection and crystal-induced arthritis—are difficult to differentiate in the absence of synovial fluid analysis and culture. Patients with septic arthritis may be afebrile and may not manifest a peripheral leukocytosis. Conversely, patients with crystal-induced arthritis can have fever and an elevated peripheral blood WBC count. An elevated serum uric acid level does not establish a diagnosis of gout, and patients with gout can have a normal serum uric acid level at the time of an acute attack.

Septic arthritis indicates the presence of a potentially life-threatening infection and requires prompt treatment with appropriate antibiotics. Delay in the treatment of nongonococcal septic arthritis also causes substantial morbidity due to the rapid destruction of articular cartilage. Acute inflammatory monoarthritis should be considered septic arthritis until there is compelling evidence either against bacterial infection or in favor of an alternative diagnosis.

The differential diagnosis of acute inflammatory monoarthritis not due to septic arthritis, gout, or pseudogout is broad. Many of these entities more commonly present as subacute or chronic processes (see below). Diseases that are typically oligoarticular or polyarticular, such as the spondyloarthropathies and rheumatoid arthritis occasionally begin as an inflammatory monoarthritis (“pseudoseptic” presentation).

Noninflammatory Monoarthritis

Noninflammatory synovial fluid can be seen with internal derangements (ie, torn meniscus of the knee). Osteoarthritis of a single joint usually presents with chronic complaints but, on occasion, can cause the acute onset of pain. Similarly, neuropathic arthropathy, amyloidosis, and osteonecrosis usually cause chronic noninflammatory arthritis of one or several joints but occasionally present with acute symptoms.

Hemarthrosis

Frank blood on arthrocentesis can be indicative of a fracture or other joint trauma. Hemarthrosis also occurs in patients who are receiving anticoagulant therapy or have a clotting factor deficiency, such as hemophilia. Bloody synovial fluid can be seen in pigmented villonodular synovitis, a rare proliferative disorder of the synovium that presents as a chronic monoarthritis, typically of the knee, in young adulthood.

Acute Oligoarthritis

Essential Features

• Disseminated gonococcal infection, nongonococcal septic arthritis, and the spondyloarthropathies are leading causes of acute inflammatory oligoarthritis.
• Arthrocentesis and appropriate cultures are important diagnostic tests.

Initial Clinical Evaluation

Acute oligoarthritis is usually due to an inflammatory process (Table 4–5). Infectious causes of the arthritis need to be excluded. Disseminated gonococcal infection is the most common cause of acute oligoarthritis in sexually active young people. Nongonococcal septic arthritis is usually monoarticular but involves more than one joint in up to 20% of cases.

Spondyloarthropathies typically cause an asymmetric oligoarthritis. Of these, reactive arthritis is most likely to present with acute onset of arthritis and, early in its course, can be difficult to distinguish from disseminated gonococcal infection.

Gout is a common cause of acute oligoarthritis. Oligoarticular gout usually develops after years of antecedent attacks of acute monoarthritis, but it occasionally can be the initial manifestation.

The use of four joints as a dividing line between oligoarthritis and polyarthritis is somewhat arbitrary, and there is overlap between disorders that cause oligoarthritis and polyarthritis. For example, rheumatoid arthritis can be oligoarticular in its early stages. Erythrovirus (parvovirus B19) infection usually causes a true polyarthritis but on occasion produces an oligoarthritis. Conversely, many of the entities listed in Table 4–4 sometimes involve more than four joints.

Laboratory Evaluation

Complete blood cell count, serum electrolytes and creatinine, and urinalysis should be obtained. Synovial fluid should be sent for culture, cell count, Gram stain, and examination for crystals. When disseminated gonococcal infection is suspected, samples from pharynx, urethra, cervix, and rectum—even when asymptomatic—should be tested for N gonorrhoeae. Cultures of pharynx, urethra, cervix, and rectum are, in aggregate, positive in 80–90% of cases of disseminated gonococcal infection. Nucleic acid amplification tests of samples from these sites and from urine have greater sensitivity than culture for detection of N gonorrhoeae. Urethral and cervical swabs also should be tested for Chlamydiae. If bacterial endocarditis is a possibility, at least 3 blood cultures should be obtained, and a transesophageal echocardiogram may be indicated. Antibodies to streptococcal antigens (eg, streptolysin O) should be determined in cases of suspected acute rheumatic fever or poststreptococcal arthritis. The presence of antibodies to cyclic citrullinated peptides (CCP) is a strong predictor of evolution to rheumatoid arthritis.

Imaging Studies

Radiographs usually are of little help if the onset of the oligoarthritis is truly acute.

Differential Diagnosis

Disseminated gonococcal infection usually presents as a migratory tenosynovitis, often with characteristic skin lesions; meningococcemia can cause a similar syndrome but is much less common. Bacterial endocarditis can cause an oligoarthritis with either septic joints (due to hematogenous spread) or sterile inflammatory synovial fluid (likely due to immune complex disease); back pain is common, particularly in acute bacterial endocarditis (Table 4–5). Reactive arthritis classically follows within 1 to 4 weeks of enteric or genitourinary tract infections, but the triggering infection is sometimes subclinical. In its presenting phase, reactive arthritis has a predilection for the lower extremities and can be associated with significant constitutional signs and symptoms including prominent weight loss and fever. Most patients with the new onset of psoriatic arthritis either have or have had psoriasis, but, in a minority (15%), the arthritis precedes the skin disease. Acute rheumatic fever produces a migratory arthritis in children; in adults, however, poststreptococcal arthritis is usually not migratory and is rarely associated with the other distinctive manifestations of rheumatic fever (eg, rash, subcutaneous nodules, carditis, and chorea). Early disseminated Lyme disease can cause an acute oligoarthritis or monoarthritis (especially of the knee) but more commonly presents as migratory arthralgias.

Acute Polyarthritis

Essential Features

• Viral infections and rheumatoid arthritis are the leading causes of acute polyarthritis.
• Observation to distinguish persistent from self-limited polyarthritis is critical.

Initial Clinical Evaluation

Viral polyarthritis typically resolves over days to a few weeks. Thus, the longer polyarthritis persists, the less likely viral polyarthritis becomes. Rheumatoid arthritis usually has an insidious onset, and patients seek medical care after weeks or months of symptoms. Nonetheless, it begins abruptly in enough patients to warrant consideration as a cause of acute polyarthritis. Acute polyarthritis can also be the initial manifestation of SLE and drug-induced lupus as well as a variety of uncommon entities, including systemic vasculitis (Table 4–6).

Laboratory Evaluation

The clinical setting should guide the decision to send tests for specific viral infections (eg, erythrovirus [parvovirus B19] or hepatitis B). If viral polyarthritis is thought unlikely, then routine laboratory studies (including complete blood cell count, serum electrolytes and creatinine, liver function tests, and urinalysis), determinations of the ESR or CRP, and tests for serum rheumatoid factor, antibodies to CCP, and antinuclear antibodies (ANAs) are indicated.

Imaging Studies

Joint radiographs are rarely of value in acute polyarthritis and may be deferred until it is clear that the polyarthritis is persistent.

Differential Diagnosis

Many acute viral infections cause joint symptoms, with polyarthralgias being considerably more common than true polyarthritis. The prevalence of polyarthritis is high, however, in adults with acute erythrovirus (parvovirus B19) infection. The pattern of viral polyarthritis often mimics that of rheumatoid arthritis. Adults with acute erythrovirus (parvovirus B19) infection, the cause of “slapped cheek fever” in children, usually have only a faint rash on the trunk or no rash at all. IgM antibodies to erythrovirus (parvovirus B19) are generally present at the onset of joint symptoms and persist for approximately 2 months. Acute hepatitis B causes an immune complex–mediated arthritis, often with urticaria or maculopapular rash, during the preicteric phase of infection; tests for hepatitis B surface antigen are positive. Effective vaccination programs in the United States have substantially reduced the incidence of acute hepatitis B and have eliminated acute rubella infection, which is also associated with acute polyarthritis.

Acute-onset rheumatoid arthritis can be difficult to distinguish from virally induced acute polyarthritis, and many rheumatologists are hesitant to make a diagnosis of rheumatoid arthritis in the acute setting. The joint American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) 2010 Rheumatoid Arthritis Classification Criteria are weighted toward polyarthritis, the involvement of “small joints” (metacarpophalangeal [MCP] joints, proximal interphalangeal [PIP] joints, second through fifth metatarsophalangeal [MTP] joints, thumb interphalangeal joints, and wrists), the presence of either anti-CCP antibodies or rheumatoid factor, particularly in high titer.

Testing for ANA has sensitivity for SLE but low specificity. When ANAs are detected by indirect immunofluorescence assays using human cell lines (eg, HEp-2 cells), the sensitivity for SLE approaches 100%. False-negative results, however, can occur when ANAs are measured by enzyme-linked immunoabsorbent assays (ELISA) or by high throughput assays using multiplex beads. In a patient with polyarthritis or polyarthralgias, a positive assay for ANA should prompt a careful evaluation for other manifestations of SLE and additional serologic tests (see Chapter 3).

Chronic Monoarthritis

Essential Features

• Distinguishing between inflammatory and noninflammatory arthritis is a key step toward establishing a diagnosis.
• Arthrocentesis and imaging studies are important diagnostic tests.

Initial Clinical Evaluation

It is important to determine whether the symptoms and signs point to an inflammatory or noninflammatory process. Indolent infections are a concern with inflammatory monoarthritis of weeks to even months in duration. The particular joint involved influences the differential diagnosis.

Laboratory Evaluation

A critical step is to determine whether the monoarthritis is inflammatory or noninflammatory, preferably by analysis of synovial fluid. Synovial fluid should be sent for culture (for bacteria, mycobacteria, and fungus), cell count, and Gram stain and should be examined for crystals by polarized light microscopy.

Routine laboratory studies (eg, complete blood cell count, serum electrolytes and creatinine, and urinalysis) and determinations of the ESR or CRP can provide helpful ancillary information. Patients with inflammatory monoarthritis and negative bacterial cultures should be tested for Lyme disease and for reactivity to purified protein derivative (PPD).

Imaging Studies

In contrast to acute monoarthritis, radiographs can be helpful in the evaluation of processes present for weeks or more and can point to the correct diagnosis in cases of infection, osteoarthritis, osteonecrosis, neuropathic joints, and other entities.

Differential Diagnosis

Inflammatory

A wide range of disease processes can cause inflammatory arthritis in a single joint for several weeks or longer (Table 4–7). Most patients with septic arthritis and gonococcal arthritis experience significant pain in the infected joint and seek medical attention within hours to days of the onset of symptoms. However, patients occasionally seek medical care after a delay of several weeks, particularly if symptoms have been partially masked by the use of nonsteroidal anti-inflammatory drugs, antibiotics, or glucocorticoids (systemic or intra-articular).

Untreated indolent infections, on the other hand, commonly present after weeks or more of symptoms. These are associated with negative synovial fluid cultures for bacteria and require additional diagnostic tests and cultures to establish the correct diagnosis. Chronic Lyme disease can cause an inflammatory monoarthritis, often of the knee, with synovial fluid WBC typically in the 10,000–25,000/mcL range. Tuberculous infection of a joint can present after days, weeks, or months of symptoms. Smears for acid-fast bacilli are positive in only 20% of cases; cultures for mycobacteria are positive in 80% but take weeks. Synovial biopsy can greatly expedite the diagnosis of tuberculous arthritis and is also indicated in suspected cases of fungal arthritis.

Noninflammatory

Osteoarthritis is the leading cause of chronic noninflammatory monoarthritis, particularly when the hip, knee, first carpometacarpal joint, or acromioclavicular joint is involved (Table 4–8). Internal derangements, such as a torn meniscus in the knee, often produce mechanical symptoms and characteristic findings on physical examination. Pain is frequently a prominent feature of osteonecrosis, which can produce large knee effusions when the distal femur is involved. Radiographs are often normal early in the course of osteonecrosis, and diagnosis may require MRI. Hip pain with a normal radiograph should raise the possibility of early osteonecrosis, particularly if the patient is relatively young and has a risk factor for osteonecrosis. Diabetes mellitus is the most common underlying cause of neuropathic arthropathy, which should be considered in a diabetic patient with foot, ankle, or knee arthritis. The involved joint may be warm and painful, but the joint fluid is typically noninflammatory. Radiographs usually show characteristic neuropathic changes.

Chronic Oligoarthritis

Essential Features

• Careful delineation of the arthritis and detection of extra-articular disease facilitate accurate diagnosis.
• Radiographs are often of diagnostic value.

Initial Clinical Evaluation

Spondyloarthropathies are the most common cause of chronic inflammatory oligoarthritis (Table 4–9). For months or longer, however, it may be difficult to distinguish spondyloarthropathies from early-onset rheumatoid arthritis. Osteoarthritis commonly presents as a noninflammatory oligoarthritis of the hips or knees and usually does not present diagnostic difficulties.

Laboratory Evaluation

Synovial fluid should be analyzed for crystals and cultured. The distinction between inflammatory and noninflammatory chronic oligoarthritis often can be made on clinical grounds but is confirmed by the synovial fluid WBC count.

Antibodies to CCP and rheumatoid factor have similar sensitivity in identifying rheumatoid arthritis, but the antibodies to CCP have greater specificity and can help establish the diagnosis in the proper clinical context. Testing for HLA-B27 has usefulness in certain circumstances.

Imaging Studies

Radiographs can be of considerable value. An experienced radiologist or rheumatologist often can distinguish among the erosions of the spondyloarthropathies, rheumatoid arthritis, and gout. Radiographic demonstration of sacroiliitis points to a spondyloarthropathy and narrows the differential diagnosis considerably.

Differential Diagnosis

Although spondyloarthropathies typically cause an asymmetric oligoarthritis and rheumatoid arthritis is usually a symmetric polyarthritis, it can be difficult to differentiate these entities in patients with early disease. Several features are helpful in making this distinction. Ankylosing spondylitis always, and the other spondyloarthropathies often, produce inflammatory axial skeleton disease with sacroiliitis that causes pain and stiffness in the low back, particularly in the morning. Sacroiliitis is not a feature of rheumatoid arthritis, which involves the cervical spine but no other part of the axial skeleton. The prominent tenosynovitis of the spondyloarthropathies can produce dactylitis (“sausage digits”) of the toes or fingers. Dactylitis is not seen in rheumatoid arthritis. (Dactylitis is not specific for the spondyloarthropathies; it also occurs in sarcoidosis and gout). Reactive arthritis and the arthritis of inflammatory bowel disease have a predilection for the lower extremities. Rheumatoid arthritis invariably involves the hands, and >90% of cases eventually have wrist arthritis.

Many of the entities that cause chronic oligoarthritis have extra-articular manifestations that point to the correct diagnosis but that are easily overlooked. For example, psoriasis may be subtle, and the patient may be unaware of psoriatic lesions, particularly in the umbilicus, the external auditory canal, the scalp, and the anal cleft. The oral ulcers of reactive arthritis are painless and usually not detected unless specifically sought by the examining physician. Patients with inflammatory bowel disease may not volunteer that they have chronic diarrhea, particularly if bowel symptoms are intermittent. Antecedent anterior uveitis can be an important clue to the presence of a spondyloarthropathy, but patients generally do not associate ocular inflammation with arthritis and may not mention a past episode of anterior uveitis unless asked directly.

Chronic Polyarthritis

Essential Features

• Rheumatoid arthritis and osteoarthritis are the leading causes of chronic polyarthritis.
• Careful delineation of the joints involved, particularly in the hands, can help point to the correct diagnosis.

Initial Clinical Evaluation

Rheumatoid arthritis is the leading cause of chronic inflammatory polyarthritis, and osteoarthritis is the most common cause of chronic noninflammatory polyarthritis. Nonetheless, polyarthritis that persists for weeks or more has many possible etiologies and warrants careful diagnostic evaluation (Table 4–10). As is the case with other forms of arthritis, the distinction between inflammatory and noninflammatory processes is critical.

Laboratory Evaluation

If arthrocentesis is feasible, synovial fluid should be obtained and sent for cell count and analysis for crystals. Routine laboratory investigations (complete blood cell count, serum electrolytes and creatinine, and urinalysis) should be done. If the process appears inflammatory, studies also should include determinations of the ESR or CRP and tests for serum rheumatoid factor, anti-CCP antibodies, ANA, and hepatitis B and C infection.

Imaging Studies

Radiographs are indicated in most cases of chronic polyarthritis of the hand. Radiographs of the hand usually show characteristic changes at the time of presentation of primary generalized osteoarthritis, hemochromatosis, calcium pyrophosphate deposition disease, and chronic tophaceous gout. In cases of rheumatoid arthritis and the spondyloarthropathies, however, the likelihood of radiographic joint erosions and other characteristic findings increases with the duration of the polyarthritis; hand radiographs may be normal or demonstrate nonspecific changes only, for months or longer. Radiographs of the feet can reveal rheumatoid erosions even when hand films are unrevealing. The polyarthritis of SLE, drug-induced lupus, and chronic hepatitis C is usually nonerosive and does not produce characteristic radiographic findings.

Differential Diagnosis

Osteoarthritis and rheumatoid arthritis have different patterns of joint involvement in the hand. Osteoarthritis involves the distal interphalangeal (DIP) and PIP joints and the first carpometacarpal joint. Rheumatoid arthritis, in contrast, involves the PIP and MCP joints and the wrists.

Osteoarthritis and rheumatoid arthritis typically spare certain joints. Osteoarthritis usually does not involve the MCP joints, wrists, elbows, glenohumeral joints, and ankles; degenerative arthritis of these joints raises the possibility of antecedent trauma, calcium pyrophosphate deposition disease, underlying osteonecrosis, or neuropathic arthropathy. Rheumatoid arthritis usually spares DIP joints, the thoracic and lumbosacral spine, and sacroiliac joints.

In generalized osteoarthritis, interphalangeal joints, particularly the DIPs, may appear to be inflamed (“inflammatory osteoarthritis”) and thus cause some diagnostic uncertainty. Radiographs, however, usually show typical degenerative changes (irregular joint-space narrowing, sclerosis, and osteophytes). Psoriatic arthritis also commonly involves the DIP joints, usually with radiographic changes distinct from those of osteoarthritis. Psoriatic changes of the fingernail on the same digit often occur concomitantly with psoriatic involvement of a DIP joint.

Many diseases can mimic rheumatoid arthritis, but several warrant particular emphasis (Table 4–11). Features that distinguish rheumatoid arthritis and the spondyloarthropathies are discussed above. Chronic infection with hepatitis C can produce a symmetric polyarthritis and a positive test for rheumatoid factor (but not for anti-CCP antibodies). The polyarthritis of SLE is nonerosive but can lead to reducible “swan neck” deformities of the fingers. On occasion, chronic tophaceous gout is a remarkable mimic of rheumatoid arthritis, with tophi mistaken for rheumatoid nodules. Gout is not associated with rheumatoid factor (virtually all cases of nodular rheumatoid arthritis are seropositive), and the erosions of gout and rheumatoid arthritis have different radiographic characteristics. Analysis of synovial fluid for urate crystals is the definitive diagnostic test. Hemochromatosis and other causes of calcium pyrophosphate deposition disease lead to arthritis of the MCPs (especially the second and third) and wrists; radiographs often reveal “hook-like” osteophytes of the MCPs and degenerative changes, usually with chondrocalcinosis, of the wrist.

Although rheumatoid arthritis is the leading cause of chronic inflammatory polyarthritis, physicians must be certain that rheumatoid arthritis accounts for the full clinical picture. Rheumatoid arthritis is not a plausible explanation for the following: fever >38.3°C, substantial weight loss, significant adenopathy, rashes (apart from subcutaneous nodules), hematuria, and proteinuria. Failure to account for these additional clinical findings can lead to a failure to diagnose SLE, Still disease, subacute bacterial endocarditis, paraneoplastic syndromes, vasculitides, and the like.