Monarthritis/Polyarthritis: Differential Diagnosis
Stephen Ray Mitchell
John F. Beary III
The number of joints involved and the time course of their involvement enable the physician to classify joint problems and to construct the appropriate differential diagnosis.
“Chronic” refers to joint symptoms that persist beyond 2 months. Oligoarthritis refers to the involvement of 2 to 4 joints, and polyarthritis is defined as the involvement of more than four joints.
Acute monarthritis can be due to infection, and septic arthritis is a rheumatologic emergency.
Gout is a classic example of acute monarthritis, but approximately 25% of gout cases present as polyarthritis, mainly in the lower extremity.
Rheumatoid arthritis (RA) is the classic example of chronic polyarthritis, but it is important to carefully confirm the diagnosis, as one occasionally encounters a patient with gout who has hand deformities that look like RA and has a relatively normal uric acid. Such a patient may even receive disease-modifying antirheumatic drugs (DMARDs) for a time, which are stopped when it is discovered that it is actually gouty tophi that are involved in the destructive hand lesions.
The importance of identifying the pauciarticular pattern in children with juvenile idiopathic arthritis (JIA) is that it is an important clue to seek, identify, and treat iridocyclitis, which is asymptomatic but can destroy the sight of children.
The number of joints and the time course during which a joint disorder develops guide the approach to differential diagnosis. Acute and severe monarthritis, especially one that presents along with fever, may represent septic arthritis, which is a rheumatologic emergency. The promptness of the diagnosis and treatment of a potentially septic process is likely to profoundly alter the outcome.
Alternatively, a single abnormal inflamed joint that persists beyond 2 months presents a different diagnostic challenge, with infection being a much less likely
disease process. In each case, one must view the overall clinical presentation, including factors such as extra-articular visceral involvement, constitutional signs and symptoms, severity of illness, limitation of function, potential foci of infection, skin lesions, hyperuricemia, and history of trauma or bleeding disorders.
Table 14-1 Differential Diagnosis of Monarthritis by Presentation
Inflammatory bowel disease
Lyme disease (recurring)
CPPD, calcium pyrophosphate dihydrate; JIA, juvenile idiopathic arthritis; PVNS, pigmented villonodular synovitis; RA, rheumatoid arthritis.
Often, an aggressive initial approach is indicated, including joint aspiration with synovial fluid analysis and occasionally, in more refractory or unexplained situations, referral for synovial biopsy or arthroscopy. Therapy will vary significantly depending on the presumptive diagnosis. Specific therapy for each disease is discussed in later chapters. Tables 14-1 and 14-2 summarize the diagnostic approach to this group of disorders.
Infectious arthritis has an abrupt onset and a marked systemic inflammatory response. Because prompt therapy is required to prevent irretrievable joint damage, it is important to diagnose bacterial infection promptly. One may be deceived, however, in a partially treated patient on oral antibiotics or in an immunosuppressed patient in whom the inflammatory response is dampened by steroid therapy. A prudent approach includes careful examination for associated infectious foci and clinical clues (e.g., cutaneous pustules with neisserial infection), prompt joint aspiration and synovial fluid analysis, synovial fluid culture and Gram stain, and empiric antibiotics (depending on age and epidemiology). A viral process is typically polyarticular and may be accompanied by rash or other viral signs and symptoms. Lyme arthritis, caused by a Borrelia spirochete in endemic areas, can present acutely in recurring episodes of knee monarthritis; but more often it presents early in the course of the disease as migratory polyarthralgias, is associated with a characteristic rash or tick bite, and has a less “toxic” presentation (see Chapter 47).
Gout classically presents as “podagra” with the abrupt and intense onset of pain and inflammation in the first metatarsophalangeal joint; it often affects the midfoot and ankle, but can involve any joint or bursa. Typically, a man in his fifties with
hypertension, obesity, diabetes, and coronary artery disease presents with monarthritis of the lower extremity. However, approximately 25% present with polyarticular synovitis. Between episodes, the joints return to normal unless chronic disease develops. A careful check for tophi on the ears, elbows, hands, or feet is required. At a younger age of onset of gout, one must think of lymphoma or other disorders associated with rapid cell turnover. The finding of negatively birefringent, needle-shaped crystals within the white blood cells in the synovial fluid is diagnostic. Note that gout can coexist with pseudogout, and both can coexist with infection (see Chapter 43).
Table 14-2 Differential Diagnosis of Polyarthritis by Presentation
Acute rheumatic fever
Lyme disease (early)
CTD and overlap syndromes
CTD, connective tissue disease; JIA, juvenile idiopathic arthritis; OA, osteoarthritis.
Calcium pyrophosphate dihydrate (CPPD) deposition disease (pseudogout) is an acute or subacute process in the elderly with involvement of large or small joints (including the second and third metacarpophalangeal joints). Chondrocalcinosis can often be defined radiographically in the knee, symphysis pubis, or triangular cartilage of the wrist. Crystals found within synovial fluid white blood cells are rhomboid-shaped and positively birefringent. In those patients who present at a younger age, other diagnostically important, treatable medical conditions, such as hemochromatosis or hyperparathyroidism must be considered (see Chapter 44).
Hemarthrosis is defined through the aspiration of bloody joint fluid.
Trauma usually is associated with a relevant history of injury. A layer of fat (from the bone marrow) seen on top of bloody fluid implies intra-articular fracture even in the presence of negative radiographs.
Internal derangement. Meniscal tears involving avascular portions of knee fibrocartilage may not be bloody but can cause intermittent locking, giving way, and a positive MacMurray’s maneuver (a painful click produced by extending the knee when the foot is internally or externally rotated). Instability of the collateral and cruciate ligaments is also a clue to this condition (see Chapter 24).
Nontraumatic hemarthrosis may be seen in the setting of anticoagulation, after the use of heparin during dialysis, or with benign neoplasms such as pigmented villonodular synovitis, synovial osteochondromatosis, or hemangioma of the synovium. Diagnosis of the latter three disorders is confirmed with synovial biopsy, arthroscopy, or magnetic resonance imaging (MRI).
Periarticular syndromes. Any of the tissues surrounding the joint can be involved in an inflammatory or traumatic process. A careful musculoskeletal examination can distinguish between tendinitis, bursitis, overuse syndromes, and surrounding cellulitis. Erythema nodosum is often seen with drug reaction, inflammatory bowel disease, or acute sarcoidosis. It often causes a periarthritis about the ankles and can result in an associated joint effusion. Osteomyelitis or neoplasia should be considered
with focal bone pain. Severe nighttime periarticular pain in a child is uncommon with juvenile arthritis and should always suggest leukemia.
Noninfectious inflammatory conditions
Spondyloarthropathies. Because of the highly inflammatory, monarticular nature of some episodes of joint inflammation associated with reactive arthritis (ReA) or psoriatic arthritis, the clinical presentation may be indistinguishable from that of infection. The diagnosis may be supported by the presence of characteristic extra-articular features, such as a psoriasiform rash, eye inflammation, or urethritis. A history of low-back symptoms or tenderness over the sacroiliac joints suggests the diagnosis of spondyloarthritis and is an indication for radiographic study of the sacroiliac joints (see Chapter 39).
Juvenile idiopathic arthritis (JIA). The child who presents with monarthritis, often subacute in character, and a negative infectious workup may well have pauciarticular (fewer than four joints) JIA (see Chapter 36). Transient synovitis of the hip characteristically presents as a monarthritis of the hip in a child following a viral illness. The child is nontoxic in appearance and has a culture-negative joint effusion. This self-limited disorder is felt to be mediated by a virus or immune complexes and responds to bed rest and anti-inflammatory medications.
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