Joints may simply be painful (arthralgia) or also inflamed (arthritis). Joint inflammation is usually accompanied by warmth, swelling (due to intra-articular fluid, or effusion), and uncommonly erythema. Pain may occur only with use or also at rest. Sometimes what is described by patients as joint pain can have an extra-articular source (eg, a periarticular structure or bone).
Polyarticular pain (polyarthralgia) involves multiple joints (pain in a single joint Pain in and Around a Single Joint Patients may report "joint" pain regardless of whether the cause involves the joint itself or surrounding (periarticular) structures such as tendons and bursae; in both cases, pain in or around... read more is discussed elsewhere). Polyarticular joint disorders may affect different joints at different times. When multiple joints are affected, the following distinction can be useful in differentiating among different disorders, particularly arthritides:
Pathophysiology of Pain in Multiple Joints
Articular sources of pain originate within the joint. Periarticular sources of pain originate in structures surrounding the joint (eg, tendons, ligaments, bursae, muscles).
Polyarticular pain caused by articular sources may result from the following:
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Inflammation (eg, infection, crystal-induced arthritis Overview of Crystal-Induced Arthritides Arthritis can result from intra-articular deposition of crystals: Monosodium urate Calcium pyrophosphate dihydrate Basic calcium phosphate (apatite) Rarely, others such as calcium oxalate crystals read more , systemic inflammatory disorders such as rheumatoid arthritis Rheumatoid Arthritis (RA) Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease that primarily involves the joints. RA causes damage mediated by cytokines, chemokines, and metalloproteases. Characteristically... read more
and psoriatic arthritis Psoriatic Arthritis Psoriatic arthritis is a spondyloarthropathy and chronic inflammatory arthritis that occurs in people with psoriasis of the skin or nails. The arthritis is often asymmetric, and some forms involve... read more 
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Mechanical or other noninflammatory disorders (eg, osteoarthritis Osteoarthritis (OA) Osteoarthritis is a chronic arthropathy characterized by disruption and potential loss of joint cartilage along with other joint changes, including bone hypertrophy (osteophyte formation). Symptoms... read more
, hypermobility syndromes)
The synovium and joint capsule are major sources of pain within a joint. The synovial membrane is the main site affected by inflammation (synovitis). Pain affecting multiple joints in the absence of inflammation may be due to increased joint laxity with excessive trauma, as in benign hypermobility syndrome.
Polyarthritis may involve peripheral joints, axial joints (eg, sacroiliac, apophyseal, discovertebral, costovertebral), or both.
Etiology of Pain in Multiple Joints
Peripheral oligoarticular arthritis and polyarticular arthritis are more commonly associated with a systemic infection (eg, viral) or systemic inflammatory disorder (eg, rheumatoid arthritis Rheumatoid Arthritis (RA) Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease that primarily involves the joints. RA causes damage mediated by cytokines, chemokines, and metalloproteases. Characteristically... read more ) than is monoarticular arthritis. A specific cause can usually be determined (see tables Some Causes of Pain in ≥ 5 Joints Some Causes of Pain in ≥ 5 Joints* Joints may simply be painful (arthralgia) or also inflamed (arthritis). Joint inflammation is usually accompanied by warmth, swelling (due to intra-articular fluid, or effusion), and uncommonly... read more and Some Causes of Pain in ≤ 4 Joints Some Causes of Pain in ≤ 4 Joints Joints may simply be painful (arthralgia) or also inflamed (arthritis). Joint inflammation is usually accompanied by warmth, swelling (due to intra-articular fluid, or effusion), and uncommonly... read more ); however, sometimes the arthritis is transient and resolves before a diagnosis can be clearly established. Axial involvement suggests a seronegative spondyloarthropathy Overview of Seronegative Spondyloarthropathies Seronegative spondyloarthropathies (seronegative spondyloarthritides) share certain clinical characteristics (eg, inflammatory back pain, uveitis, gastrointestinal symptoms, rashes). Some are... read more (also called spondyloarthritis) but can also occur in rheumatoid arthritis (affecting the cervical spine but not the lumbar spine).
Acute polyarticular arthritis is most often due to the following:
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Infection (usually viral)
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Flare-up of a systemic inflammatory disorder
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Gout Gout Gout is a disorder caused by hyperuricemia (serum urate > 6.8 mg/dL [> 0.4 mmol/L]) that results in the precipitation of monosodium urate crystals in and around joints, most often causing recurrent... read more
or calcium pyrophosphate arthritis Calcium Pyrophosphate Arthritis Calcium pyrophosphate arthritis involves intra-articular and/or extra-articular deposition of calcium pyrophosphate dihydrate (CPPD) crystals. Manifestations are protean and may be minimal or... read more 
(previously called pseudogout)
Chronic polyarticular arthritis in adults is most often due to the following:
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Seronegative spondyloarthropathy Overview of Seronegative Spondyloarthropathies Seronegative spondyloarthropathies (seronegative spondyloarthritides) share certain clinical characteristics (eg, inflammatory back pain, uveitis, gastrointestinal symptoms, rashes). Some are... read more (usually ankylosing spondylitis Ankylosing Spondylitis Ankylosing spondylitis is the prototypical spondyloarthropathy and a systemic disorder characterized by inflammation of the axial skeleton, large peripheral joints, and digits; nocturnal back... read more
, reactive arthritis Reactive Arthritis Reactive arthritis is an acute spondyloarthropathy that often seems precipitated by an infection, usually genitourinary or gastrointestinal. Common manifestations include asymmetric arthritis... read more 
, psoriatic arthritis Psoriatic Arthritis Psoriatic arthritis is a spondyloarthropathy and chronic inflammatory arthritis that occurs in people with psoriasis of the skin or nails. The arthritis is often asymmetric, and some forms involve... read more , or enteropathic arthritis)
Noninflammatory polyarticular pain in adults is most often due to the following:
Chronic polyarthralgia in adults is caused most often by rheumatoid arthritis and osteoarthritis.
Chronic polyarticular arthralgia in children is most often due to the following:
Evaluation of Pain in Multiple Joints
Evaluation should determine whether the joints, periarticular structures, or both are the cause of symptoms and whether there is inflammation. Extra-articular symptoms and findings, which may suggest specific systemic inflammatory disorders, should also be sought and evaluated, particularly if there is joint inflammation.
History
History of present illness should identify characteristics of joint pain, associated joint symptoms, and systemic symptoms. Among important joint symptom characteristics are the acuity of onset (eg, abrupt, gradual), temporal patterns (eg, diurnal variation, persistent vs intermittent), duration (eg, acute vs chronic), and exacerbating and mitigating factors (eg, rest, activity). Patients should be specifically asked about unprotected sexual contact (indicating risk of infectious bacterial arthritis with disseminated gonococcal infection) and tick bites or residence in or travel to a Lyme-endemic area.
Review of systems should be complete in order to identify extra-articular symptoms that may suggest specific disorders (see tables Some Causes of Pain in ≥ 5 Joints Some Causes of Pain in ≥ 5 Joints* Joints may simply be painful (arthralgia) or also inflamed (arthritis). Joint inflammation is usually accompanied by warmth, swelling (due to intra-articular fluid, or effusion), and uncommonly... read more , Some Causes of Pain in ≤ 4 Joints Some Causes of Pain in ≤ 4 Joints Joints may simply be painful (arthralgia) or also inflamed (arthritis). Joint inflammation is usually accompanied by warmth, swelling (due to intra-articular fluid, or effusion), and uncommonly... read more , and Some Suggestive Findings in Polyarticular Joint Pain Some Suggestive Findings in Polyarticular Joint Pain Joints may simply be painful (arthralgia) or also inflamed (arthritis). Joint inflammation is usually accompanied by warmth, swelling (due to intra-articular fluid, or effusion), and uncommonly... read more ).
Past medical history and family history should identify known systemic inflammatory disorders and other conditions capable of causing joint symptoms (see tables Some Causes of Pain in ≥ 5 Joints Some Causes of Pain in ≥ 5 Joints* Joints may simply be painful (arthralgia) or also inflamed (arthritis). Joint inflammation is usually accompanied by warmth, swelling (due to intra-articular fluid, or effusion), and uncommonly... read more and Some Causes of Pain in ≤ 4 Joints Some Causes of Pain in ≤ 4 Joints Joints may simply be painful (arthralgia) or also inflamed (arthritis). Joint inflammation is usually accompanied by warmth, swelling (due to intra-articular fluid, or effusion), and uncommonly... read more ). Some systemic inflammatory disorders are more prevalent in families with specific genetic profiles.
Physical examination
The physical examination should be reasonably complete, evaluating all major organ systems (eg, skin and nails, eyes, genitals, mucosal surfaces, heart, lungs, abdomen, nose, neck, lymph nodes, and neurologic system) as well as the musculoskeletal system. Vital signs are reviewed for fever.
Examination of the head should note any signs of eye inflammation (eg, uveitis, conjunctivitis) and nasal or oral lesions. Skin should be inspected for rashes and lesions (eg, ecchymoses, skin ulcers, psoriatic plaques, purpura, malar rash). The patient is also evaluated for lymphadenopathy and splenomegaly.
Cardiopulmonary examination should note any signs that suggest pleuritis, pericarditis, or valve abnormalities (eg, murmur, pericardial rub, muffled heart sounds, bibasilar dullness consistent with pleural effusion).
Genital examination should note any discharge, ulcers, or other findings consistent with sexually transmitted diseases.
Musculoskeletal examination should start by distinguishing articular from periarticular or other connective tissue or muscular tenderness. Joint examination begins with inspection for deformities, erythema, swelling, or effusion and then proceeds to palpation for joint effusions, warmth, and point tenderness. Passive and active range of motion should be evaluated. Crepitus may be felt during joint flexion and/or extension. Comparison with the contralateral unaffected joint often helps detect more subtle changes. Examination should note whether the distribution of affected joints is symmetric or asymmetric. Painful joints can also be compressed without flexing or extending them.
Periarticular structures also should be examined for involvement of tendons, bursae, or ligaments, such as discrete, soft swelling at the site of a bursa (bursitis) or point tenderness at the insertion of a tendon (tendinitis).
Red flags
Interpretation of findings
An important initial determination, based mainly on carefully done physical examination, is whether pain originates in the joints, in other adjacent structures (eg, bones, tendons, bursae, muscles), both (eg, as in gout), or other structures. Tenderness or swelling at only one side of a joint, or away from the joint line, suggests an extra-articular origin (eg, tendons or bursae); localized joint line tenderness or more diffuse involvement of the joint suggests an intra-articular cause. Compressing the joint without flexing or extending it is not particularly painful in patients with tendinitis Tendinitis and Tenosynovitis Tendinitis is inflammation of a tendon, often developing after degeneration (tendinopathy). Tenosynovitis is tendinitis with inflammation of the tendon sheath lining. Symptoms usually include... read more or bursitis Bursitis Bursitis is acute or chronic inflammation of a bursa. The cause is usually unknown, but trauma, repetitive or acute, may contribute, as may infection and crystal-induced disease. Symptoms include... read more 
but is quite painful in those with arthritis. Pain that worsens with active but not passive joint motion may indicate tendinitis or bursitis (extra-articular); intra-articular inflammation generally restricts active and passive range of joint motion significantly.
Another important determination is whether joints are inflamed. Pain during rest and on initiating activity suggests joint inflammation, whereas pain worsened by movement and relieved by rest suggests mechanical or noninflammatory disorders (eg, osteoarthritis Osteoarthritis (OA) Osteoarthritis is a chronic arthropathy characterized by disruption and potential loss of joint cartilage along with other joint changes, including bone hypertrophy (osteophyte formation). Symptoms... read more ). Increased warmth and erythema also suggest inflammation, but these findings are often insensitive, so their absence does not rule out inflammation.
Clinical findings of prolonged morning stiffness, stiffness after prolonged inactivity (gel phenomenon), nontraumatic joint swelling, and fever or unintentional weight loss suggest a systemic inflammatory disorder involving the joints. Pain that is diffuse, vaguely described, and affects myofascial structures without signs of inflammation suggests fibromyalgia Fibromyalgia Fibromyalgia is a common, incompletely understood nonarticular disorder characterized by generalized aching (sometimes severe); widespread tenderness of muscles, areas around tendon insertions... read more .
The pattern of joint involvement helps establish a diagnosis. Symmetry of joint involvement can also be a clue. Involvement tends to be symmetric in rheumatoid arthritis Rheumatoid Arthritis (RA) Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease that primarily involves the joints. RA causes damage mediated by cytokines, chemokines, and metalloproteases. Characteristically... read more , whereas asymmetric involvement is more suggestive of psoriatic arthritis Psoriatic Arthritis Psoriatic arthritis is a spondyloarthropathy and chronic inflammatory arthritis that occurs in people with psoriasis of the skin or nails. The arthritis is often asymmetric, and some forms involve... read more , gout Gout Gout is a disorder caused by hyperuricemia (serum urate > 6.8 mg/dL [> 0.4 mmol/L]) that results in the precipitation of monosodium urate crystals in and around joints, most often causing recurrent... read more , and reactive arthritis Reactive Arthritis Reactive arthritis is an acute spondyloarthropathy that often seems precipitated by an infection, usually genitourinary or gastrointestinal. Common manifestations include asymmetric arthritis... read more or enteropathic arthritis.
Examination of the hand joints may yield other clues (see table Some Suggestive Findings in Polyarticular Joint Pain Some Suggestive Findings in Polyarticular Joint Pain Joints may simply be painful (arthralgia) or also inflamed (arthritis). Joint inflammation is usually accompanied by warmth, swelling (due to intra-articular fluid, or effusion), and uncommonly... read more ) that help differentiate osteoarthritis from rheumatoid arthritis (see table Differential Features of the Hand in Rheumatoid Arthritis and Osteoarthritis Differential Features of the Hand in Rheumatoid Arthritis and Osteoarthritis Joints may simply be painful (arthralgia) or also inflamed (arthritis). Joint inflammation is usually accompanied by warmth, swelling (due to intra-articular fluid, or effusion), and uncommonly... read more ) or that may suggest other disorders.
Spinal pain in the presence of peripheral arthritis suggests a seronegative spondyloarthropathy Overview of Seronegative Spondyloarthropathies Seronegative spondyloarthropathies (seronegative spondyloarthritides) share certain clinical characteristics (eg, inflammatory back pain, uveitis, gastrointestinal symptoms, rashes). Some are... read more (ankylosing spondylitis Ankylosing Spondylitis Ankylosing spondylitis is the prototypical spondyloarthropathy and a systemic disorder characterized by inflammation of the axial skeleton, large peripheral joints, and digits; nocturnal back... read more , reactive arthritis Reactive Arthritis Reactive arthritis is an acute spondyloarthropathy that often seems precipitated by an infection, usually genitourinary or gastrointestinal. Common manifestations include asymmetric arthritis... read more , psoriatic arthritis Psoriatic Arthritis Psoriatic arthritis is a spondyloarthropathy and chronic inflammatory arthritis that occurs in people with psoriasis of the skin or nails. The arthritis is often asymmetric, and some forms involve... read more , or enteropathic arthritis) but can occur in rheumatoid arthritis Rheumatoid Arthritis (RA) Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease that primarily involves the joints. RA causes damage mediated by cytokines, chemokines, and metalloproteases. Characteristically... read more (usually with cervical spinal pain). New-onset oligoarthritis plus spinal pain is particularly likely to be a seronegative spondyloarthropathy if the patient has a family history of the same disorder. Eye redness and pain and low back pain suggest ankylosing spondylitis. Prior plaque psoriasis in a patient with new onset of oligoarthritis strongly suggests psoriatic arthritis.
Testing
The following tests are particularly important:
Arthrocentesis is mandatory in most patients with a new effusion to rule out infection and identify crystals (see How to Do Arthrocentesis How To Do Ankle Arthrocentesis Arthrocentesis of the ankle is the process of puncturing the tibiotalar joint with a needle to withdraw synovial fluid. The anteromedial approach is described. (See also Evaluation of the Patient... read more ). It can also help distinguish between an inflammatory and a noninflammatory process. Synovial fluid examination includes white blood cell (WBC) count with differential, Gram stain and cultures, and microscopic examination for crystals using polarized light. Finding crystals in synovial fluid confirms crystal-induced arthritis but does not rule out coexisting infection. A noninflammatory synovial fluid (eg, WBC count of < 1000/mcL [< 1 × 109/L]) is more suggestive of osteoarthritis or trauma. Hemorrhagic fluid is consistent with hemarthrosis. Synovial fluid WBC counts can be very high (eg, > 50,000/mcL [> 50 × 109/L]) in both infectious and crystal-induced arthritis. Synovial fluid WBC counts in systemic inflammatory disorders causing polyarthritis are most often between about 1,000 and 50,000/mcL (1 and 50 × 109/L).
If the specific diagnosis cannot be established based on the history and examination, additional tests may be needed. ESR and C-reactive protein can be done to help determine whether the arthritis is inflammatory. Elevated ESR and C-reactive protein levels suggest inflammation but are nonspecific, particularly in older adults. Findings are more specific if values are high during inflammatory flare-ups and normal between flare-ups.
Once a diagnosis of a systemic inflammatory disorder is clinically suspected, supportive serologic testing for antinuclear antibodies, double-stranded DNA, rheumatoid factor, anti-cyclic citrullinated peptide antibody, and antineutrophil cytoplasmic antibodies (ANCA) may assist in making the diagnosis. Specific tests should only be ordered to provide support for a specific diagnosis, such as systemic lupus erythematosus, ANCA-associated vasculitis, or rheumatoid arthritis.
If arthritis is chronic, x-rays and/or ultrasonography are typically done to look for signs of joint damage. Joint ultrasonography has many advantages over x-rays, including allowing for better identification of fluid around the joints, visualization of tendons and other periarticular structures during the physical exam, and guidance for arthrocentesis and joint injections.
Other tests may be needed to identify specific disorders (see tables Some Causes of Pain in ≥ 5 Joints Some Causes of Pain in ≥ 5 Joints* Joints may simply be painful (arthralgia) or also inflamed (arthritis). Joint inflammation is usually accompanied by warmth, swelling (due to intra-articular fluid, or effusion), and uncommonly... read more and Some Causes of Pain in ≤ 4 Joints Some Causes of Pain in ≤ 4 Joints Joints may simply be painful (arthralgia) or also inflamed (arthritis). Joint inflammation is usually accompanied by warmth, swelling (due to intra-articular fluid, or effusion), and uncommonly... read more ).
Treatment of Pain in Multiple Joints
In patients with joint pain, the underlying disorder is treated whenever possible. Systemic inflammatory diseases may require either immunosuppression or antibiotics as determined by the diagnosis. Joint inflammation is usually treated symptomatically with nonsteroidal anti-inflammatory drug (NSAIDs). Pain without inflammation is usually more safely treated with acetaminophen. Joint immobilization with a splint or sling can sometimes relieve pain. Heat or cold therapy may be analgesic in inflammatory joint diseases. Because chronic polyarthritis can lead to inactivity and secondary muscle atrophy, continued physical activity should be encouraged.
Geriatrics Essentials
Osteoarthritis Osteoarthritis (OA) Osteoarthritis is a chronic arthropathy characterized by disruption and potential loss of joint cartilage along with other joint changes, including bone hypertrophy (osteophyte formation). Symptoms... read more is by far the most common cause of arthritis in older people. Rheumatoid arthritis Rheumatoid Arthritis (RA) Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease that primarily involves the joints. RA causes damage mediated by cytokines, chemokines, and metalloproteases. Characteristically... read more (RA) most commonly begins between ages 30 and 40, but in up to one third of patients, it develops after the age of 60. Because cancers can cause paraneoplastic polyarthritis, cancer should be considered in older adults in whom new-onset RA is suspected, particularly if the onset is acute, if the lower extremities are predominantly affected, or if there is bone tenderness. Polymyalgia rheumatica Polymyalgia Rheumatica Polymyalgia rheumatica is a syndrome closely associated with giant cell arteritis (temporal arteritis). It affects adults > 55. It typically causes severe pain and stiffness in proximal muscles... read more should also be considered in patients > 50 who have hip and shoulder girdle stiffness and pain, even if patients have arthritis of peripheral joints (most often the hands). Gout Gout Gout is a disorder caused by hyperuricemia (serum urate > 6.8 mg/dL [> 0.4 mmol/L]) that results in the precipitation of monosodium urate crystals in and around joints, most often causing recurrent... read more in older women has predilection for the distal interphalangeal (DIP) joints of the hands.
Key Points
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The differential diagnosis of polyarticular joint pain can be narrowed by considering which and how many joints are affected, whether inflammation is present, whether joint distribution is symmetric, and whether any extra-articular symptoms or signs are present.
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Chronic polyarthritis is most often caused by juvenile idiopathic arthritis in children and chronic polyarthralgia is most often caused by osteoarthritis and rheumatoid arthritis in adults.
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Acute polyarticular arthritis is most often due to infection, gout, or a flare of a systemic inflammatory disease.
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Arthrocentesis is mandatory in most cases of a new effusion to rule out infection, diagnose crystal-induced arthropathy, and help distinguish between an inflammatory and noninflammatory process.
