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.
- 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.
Table 4–4. Common Causes of Acute Monoarthritis. ||Download (.pdf)
Table 4–4. Common Causes of Acute Monoarthritis.
|Bacterial infection of the joint space|
- Nongonococcal: especially, Staphylococcus aureus, β-hemolytic streptococci, Streptococcus pneumoniae, gram-negative organisms
- Gonococcal: often preceded by a migratory tenosynovitis or oligoarthritis associated with characteristic skin lesions
- Gout (monosodium urate crystals)
- Pseudogout (calcium pyrophosphate dihydrate crystals)
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.
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.
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 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.
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.
- 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.
Table 4–5. Differential Diagnosis of Acute Inflammatory Oligoarthritis. ||Download (.pdf)
Table 4–5. Differential Diagnosis of Acute Inflammatory Oligoarthritis.
- Disseminated gonococcal infectiona
- Nongonococcal septic arthritis
- Bacterial endocarditisb
- Post infection
- Reactive arthritisb
- Rheumatic fever (poststreptococcal arthritis)d
- Reactive arthritisb
- Ankylosing spondylitisb
- Psoriatic arthritisb
- Inflammatory bowel diseaseb
- Oligoarticular presentation of rheumatoid arthritis, systemic lupus erythematosus,a adult-onset Still disease, relapsing polychondritis,a or other polyarthritis
- Gout and pseudogout
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.
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.
Radiographs usually are of little help if the onset of the oligoarthritis is truly acute.
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.
- 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).
Table 4–6. Differential Diagnosis of Acute Polyarthritis. ||Download (.pdf)
Table 4–6. Differential Diagnosis of Acute Polyarthritis.
- Acute viral infections
- Early disseminated Lyme disease
- Rheumatoid arthritis
- Systemic lupus erythematosus
- Uncommon or rare
- Paraneoplastic polyarthritis
- Remitting seronegative symmetric polyarthritis with pitting edema
- Acute sarcoidosis, usually with erythema nodosum and hilar adenopathy
- Adult-onset Still disease
- Secondary syphilis
- Systemic autoimmune diseases and vasculitides
- Whipple disease
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.
Joint radiographs are rarely of value in acute polyarthritis and may be deferred until it is clear that the polyarthritis is persistent.
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).
Aletaha D, Neogi T, Silman AJ, et al. 2010 Rheumatoid Arthritis Classification Criteria: an American College of Rheumatology/European League Against Rheumatism Collaborative Initiative. Arthritis Rheum