The Approach to the Painful Joint 

Joint pain can be caused by diverse processes, including inflammation, cartilage degeneration, crystal deposition, infection, and trauma. The differential diagnoses of joint pain are generated in large part from the history and physical examination.^[1] Screening laboratory test results serve primarily to confirm clinical impressions and can be misleading if used indiscriminately. The initial aim of the evaluation is to localize the source of the joint symptoms and to determine the type of pathophysiologic process responsible for their presence.

Joint pain may arise from structures within or adjacent to the joint or may be referred from more distant sites. Sources of pain within the joint include the joint capsule, periosteum, ligaments, subchondral bone, and synovium, but not the articular cartilage, which lacks nerve endings. Determination of the anatomic part responsible for joint pain is often a difficult yet critical task, since it guides the approach to diagnosis and therapy. Knowledge of the anatomy of complex joints, such as the knee, shoulder, and ankle, aids in this assessment.

The evaluation of joint pain, both in terms of the history and the physical examination findings, is best achieved through an understanding of the basic pathophysiologic types of joint disease. These include synovitis, enthesopathy, crystal deposition, infection, and structural or mechanical derangements. These types of joint disease are not mutually exclusive. Examples of pathologic processes that commonly coexist include crystal deposition in osteoarthritis, synovitis in enthesopathies, and cartilage destruction in chronic synovitis.

Synovitis

The synovial membrane is the principal site of inflammation in persons with rheumatoid arthritis (RA) and many other inflammatory arthritides.^[2] Synovitis is characterized pathologically by neovascularization; infiltration of the synovium with lymphocytes, plasma cells, and macrophages; and synovial lining cell hyperplasia. These cause synovial proliferation, recognized clinically by warmth, tenderness, and a boggy consistency of the soft tissues overlying the involved joint. The inflamed synovium may infiltrate and erode intra-articular bone and cartilage.

Enthesitis

The enthesis is the transitional zone where collagenous structures such as tendons and ligaments are interwoven into bone.^[3] Other examples of entheses include the interface between cortical bone and the periosteum and between vertebral bodies and the annulus fibrosus. It is the principal site of pathology in the seronegative spondyloarthropathies. As a result of inflammation at these interfaces, the radially oriented collagen fibers undergo metaplasia, forming fibrous bone. These metaplastic transformations result in new bone formation (periostitis), gradual ossification of syndesmoses (eg, the sacroiliac joints), and syndesmophyte formation along the outer fibers of the vertebral discs. When enthesitis occurs in a diarthrodial joint, a secondary synovitis may develop.

Crystal deposition

The deposition of crystals in articular structures may lead to symptomatic joint disease. The responsible crystals include monosodium urate, calcium pyrophosphate dihydrate, basic calcium phosphate (including hydroxyapatite), and calcium oxalate.

Monosodium urate crystal deposition occurs on the surface of hyaline cartilage, within the synovium and in periarticular structures, including tendon sheaths and bursae. As a result, inflammation related to urate crystal deposits may be localized to a bursa or tendon sheath adjacent to the joint or may be widespread, involving multiple joint structures. Clinically, an acute gouty joint is inflamed, with overlying erythema, warmth, or both.^[4] Prominent periarticular inflammation may resemble cellulitis.

Calcium pyrophosphate crystal deposition is confined to hyaline cartilage, fibrocartilage, and areas of chondroid metaplasia (ie, degenerated areas of tendons, ligaments, and joint capsule) within the joint.^[5] Shedding of these crystals into the joint space may trigger an acute inflammatory arthritis, known as pseudogout.

Infectious arthritis

The synovium may become the seat of acute or chronic infections related to bacterial, fungal, or viral organisms.^[6] These infections almost always arise from blood-borne organisms and may be part of a systemic infection. The infection is based in the synovium. The cardinal pathologic findings include intense infiltration by neutrophils with resultant necrosis of the synovium and subsequent formation of granulation and scar tissue. A dense mass of fibrin, infiltrated by neutrophils, forms over the surface of the synovium. Bacterial products released within the joint are capable of producing rapid cartilage destruction.

Structural or mechanical joint derangement

Degeneration of the articular cartilage is the principal pathologic feature of osteoarthritis.^[7] It occurs in response to both local and host factors. Local factors include previous joint trauma (eg, meniscal tears), congenital or developmental joint alterations (eg, congenital hip dysplasia, slipped capital femoral epiphysis), alterations of the subchondral bone (eg, osteopetrosis, avascular necrosis, Paget disease), alterations of supporting structures (eg, hypermobility), and cartilage derangements (eg, ochronosis, crystal deposition). Host factors include genetic traits, obesity, and occupation. Damage to the articular cartilage is associated with subchondral bone sclerosis and marginal osteophyte formation. Patients with osteoarthritis may have an associated synovitis, with the formation of bland synovial effusions.