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Pain in Multiple Joints

By Alexandra Villa-Forte, MD, MPH, Staff Physician, Center for Vasculitis Care and Research, Department of Rheumatic and Immunologic Diseases, Cleveland Clinic

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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 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:

  • Oligoarticular: Involving ≤ 4 joints

  • Polyarticular: Involving > 4 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:

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 and excessive trauma, as in benign hypermobility syndrome.

Polyarthritis may involve peripheral joints, axial joints (eg, sacroiliac, apophyseal, discovertebral, costovertebral), or both.


Peripheral oligoarticular arthritis and polyarticular arthritis are more commonly associated with a systemic infection (eg, viral) or systemic inflammatory disorder (eg, RA) than is monoarticular arthritis. A specific cause can usually be determined (see Table: Some Causes of Pain in ≥ 5 Joints* and see Table: Some Causes of Pain in ≤ 4 Joints); however, sometimes the arthritis is transient and resolves before a diagnosis can be clearly established. Axial involvement suggests a seronegative spondyloarthropathy (also called spondyloarthritis) but can also occur in RA (affecting the cervical spine but not the lumbar spine).

Acute polyarticular arthritis is most often due to the following:

Chronic polyarticular arthritis in adults is most often due to the following:

Noninflammatory polyarticular pain in adults is most often due to the following:

Chronic polyarthralgia in adults is caused most often by RA and osteoarthritis.

Chronic polyarticular arthralgia in children is most often due to the following:

Some Causes of Pain in ≥ 5 Joints*


Suggestive Findings

Diagnostic Approach

Severe, migratory pain affecting mainly the large joints in the legs, elbows, and wrists

Tenderness more severe than swelling

Extra-articular manifestations, such as fever, symptoms and signs of cardiac dysfunction, chorea, subcutaneous nodules, and rash

Prior streptococcal pharyngitis

Specific (Jones) clinical criteria

Tests for Group A streptococcal infection (eg, culture, rapid strep test, antistreptolysin O and anti-DNase B titers)

ECG and sometimes echocardiogram

Hemoglobinopathies (eg, sickle cell disease or trait, thalassemias)

Pain usually near but sometimes in joints, sometimes symmetric

Usually in children or young patients of African or Mediterranean descent, often with known diagnosis

Hb electrophoresis

Hypermobility syndromes (eg, Ehlers-Danlos, Marfan, benign hypermobility)

Polyarthralgia, rarely with arthritis

Recurrent joint subluxation

Sometimes increased skin laxity

Usually family history of joint hypermobility

For Marfan and Ehlers-Danlos syndromes, possibly a family history of aortic aneurysm or dissection at a young age or during middle age

Clinical evaluation

Infectious bacterial (septic) arthritis (more commonly monoarticular)

Acute arthritis with severe pain and joint effusions

Sometimes immunosuppression or risk factors for STDs


Infectious viral arthritis (parvovirus B19, hepatitis B, hepatitis C, enterovirus, rubella, mumps, and HIV)

Acute arthritis

Joint pain and swelling usually less severe than infectious bacterial arthritis

Other systemic symptoms depending on virus (eg, jaundice with hepatitis B, often generalized lymphadenopathy with HIV)


Viral serology testing as clinically indicated (eg, hepatitis B surface antigen and IgM antibody to hepatitis B core for suspected hepatitis B)

Childhood onset of joint symptoms

Manifestation with oligoarthritis plus uveitis, or with systemic symptoms (Still disease—fever, rash, adenopathy, splenomegaly, pleural and/or pericardial effusions)

Clinical evaluation

ANA, RF, and HLA-B27 testing

Disease-specific manifestations including specific dermatologic manifestations (dermatomyositis), dysphagia (systemic sclerosis), muscle soreness (polymyalgia rheumatica), or dry eyes and dry mouth (Sjögren syndrome)

Clinical evaluation

Sometimes x-rays and/or serologic testing (eg, anti-SSA and anti-SSB in Sjögren syndrome, anti-Scl-70 in systemic sclerosis)

Sometimes skin or muscle biopsy

One of five patterns of joint involvement, which include polyarthritis similar to rheumatoid arthritis and oligoarthritis

Extra-articular manifestations, such as psoriasis, onychodystrophy, uveitis, tendinitis, and dactylitis (sausage digits)

Clinical evaluation

Sometimes x-rays

Symmetric arthritis of small and large joints

Sometimes initially monoarticular or oligoarticular

More common among young adults but can manifest at any age

Sometimes joint deformities at late stages

Clinical evaluation

RF and anti-CCP testing


Serum sickness

Arthralgia more often than arthritis

Fever, lymphadenopathy, and rash

Exposure to blood products within 21 days of symptom onset

Clinical evaluation

Arthralgia more often than arthritis

Systemic manifestations, such as rash (eg, malar rash), mucosal lesions (eg, oral ulcers), serositis (eg, pleuritis, pericarditis), manifestations of glomerulonephritis

More common among women

Clinical evaluation

ANA, anti-dsDNA, CBC, urinalysis, chemistry profile with renal and liver enzymes

Systemic vasculitides (eg, immunoglobulin A–associated vasculitis [formerly called Henoch-Schönlein purpura], polyarteritis nodosa, granulomatosis with polyangiitis)

Arthralgias, particularly with immunoglobulin A–associated vasculitis

Extra-articular symptoms, often involving multiple organ systems (eg, abdominal pain, renal failure, manifestations of pneumonitis, sinonasal symptoms, skin lesions that may include rash, purpura, nodules, and ulcers)

Serologic testing as clinically indicated (eg, ANCA testing with suspected granulomatosis with polyangiitis)

Biopsy as indicated (eg, of kidney, skin, or lung)

*These disorders may also manifest as oligoarticular (involving ≤ 4 joints).

Patients with joint effusion or inflammation should have arthrocentesis (with cell counts, Gram stain, cultures, and crystal examination), and usually ESR and C-reactive protein. X-rays are often unnecessary.

ANA = antinuclear antibodies; ANCA = antineutrophil cytoplasmic antibodies; anti-CCP = anti-cyclic citrullinated peptide; dsDNA = double-stranded DNA; RF = rheumatoid factor; STD = sexually transmitted disease.

Some Causes of Pain in ≤ 4 Joints


Suggestive Findings

Diagnostic Approach*

Usually axial pain and stiffness, worse in the morning and relieved with activity

Sometimes effusions in large peripheral joints

Sometimes extra-articular manifestations (eg, uveitis, enthesitis, aortic insufficiency)

More common among young adult males

Lumbosacral spine x-ray

Sometimes MRI or CT, blood tests (ESR, C-reactive protein, and CBC), and/or specific (modified New York) clinical criteria

Arthralgia or arthritis

Extra-articular manifestations, such as recurrent oral and/or genital lesions, or uveitis

Usually begins during a person's 20s

Specific (international) clinical criteria

Crystal-induced arthritis, typically caused by uric acid crystals (gout), calcium pyrophosphate crystals (calcium pyrophosphate arthritis, or pseudogout), or calcium hydroxyapatite crystals

Acute onset of arthritis with joint warmth and swelling

May be clinically indistinguishable from infectious bacterial (septic) arthritis

Sometimes fever


Arthralgia or arthritis

Systemic symptoms, such as fever, night sweats, rash, weight loss, heart murmur

Blood cultures


Chronic pain more commonly affecting the base of the thumbs, PIP and DIP joints, knees, and hips

Sometimes Heberden nodes


Reactive arthritis and enteropathic arthritis

Arthritis that is asymmetric and more common in large lower extremity joints

Reactive arthritis: GI or GU infection 1–3 wk before onset of acute arthritis

Enteropathic arthritis: Coexisting GI condition (eg, inflammatory bowel disease, intestinal bypass surgery) with a chronic arthritis

Clinical evaluation

Testing for STDs as clinically indicated

*Patients with joint effusion or inflammation should have arthrocentesis (with cell counts, Gram stain, cultures, and crystal examination), and usually ESR and C-reactive protein. X-rays are often not helpful early in the disease course.

These disorders can manifest with axial involvement.

Crystal-induced arthritis is most often monoarticular but sometimes oligoarticular.

DIP = distal interphalangeal; PIP = proximal interphalangeal; STD = sexually transmitted disease.


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 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 Table: Some Causes of Pain in ≥ 5 Joints*, see Table: Some Causes of Pain in ≤ 4 Joints, and see Table: Some Suggestive Findings in Polyarticular Joint Pain).

Past medical history and family history should identify known systemic inflammatory disorders and other conditions capable of causing joint symptoms (see Table: Some Causes of Pain in ≥ 5 Joints* and see Table: Some Causes of Pain in ≤ 4 Joints). 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

The following findings are of particular concern:

  • Joint warmth, swelling, and erythema

  • Any extra-articular symptoms (eg, fever, rigors, rash, chills, plaques, mucosal ulcers, conjunctivitis, uveitis, murmur, purpura, weight loss)

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 or bursitis 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). 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.

Symmetry of joint involvement can be a clue. Involvement tends to be symmetric in RA, whereas asymmetric involvement is more suggestive of psoriatic arthritis, gout, and reactive arthritis or enteropathic arthritis.

Examination of the hand joints may yield other clues (see Table: Some Suggestive Findings in Polyarticular Joint Pain) that help differentiate osteoarthritis from RA (see Table: Differential Features of the Hand in RA and Osteoarthritis) or that may suggest other disorders.

Spinal pain in the presence of peripheral arthritis suggests a seronegative spondyloarthropathy (ankylosing spondylitis, reactive arthritis, psoriatic arthritis, or enteropathic arthritis) but can occur in RA (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.

Some Suggestive Findings in Polyarticular Joint Pain


Possible Cause

General findings

Coexisting tendinitis

Conjunctivitis, diarrhea, skin and genital lesions


Infectious arthritis, gout, systemic inflammatory disorders (eg, SLE, rheumatoid arthritis)

Malaise, weight loss, and lymphadenopathy

Oral and genital lesions

Raised silver plaques

Recent pharyngitis and migrating arthritis

Recent vaccination or use of a blood product

Serum sickness

Skin lesions, abdominal pain, respiratory symptoms, and mucosal lesions


Asymmetric involvement of PIP and DIP joints with diffuse swelling of fingers (dactylitis) and/or nail pitting

Tophi plus asymmetric involvement of any hand joints

Bony enlargement of the PIP (Bouchard nodes) or DIP (Heberden nodes) joints

First carpometacarpal (CMC) involvement

Raynaud phenomenon

Scaling rash, often with plaque formation, over extensor surfaces of MCP and PIP joints (Gottron papules)

Laxity of multiple finger tendons that can result in reducible finger deformities (Jaccoud arthropathy)


Symmetric involvement of PIP and MCP joints, particularly with swan-neck or boutonnière deformities

Thickening of the skin over the fingers (sclerodactyly) and flexion contractures

DIP = distal interphalangeal; MCP =metacarpophalangeal; PIP = proximal interphalangeal.

Differential Features of the Hand in RA and Osteoarthritis




Joint swelling


Synovial, capsular, soft tissue


Possibly mild swelling

Bony hypertrophy

Only in late stages

Common, often with irregular spurs

DIP involvement



MCP involvement



Possibly significant MCP involvement in hemochromatosis

PIP involvement



Wrist involvement


Rare, however involvement of first carpometacarpal joint (common) sometimes perceived as wrist pain

CMC = carpometacarpal; DIP = distal interphalangeal; MCP = metacarpophalangeal; PIP = proximal interphalangeal.

Adapted from Bilka PJ: Physical examination of the arthritic patient. Bulletin on the Rheumatic Diseases 20:596–599, 1970.


The following tests are particularly important:

  • Arthrocentesis

  • Usually ESR and C-reactive protein

  • Serologic testing

  • In chronic arthritis, x-rays

Arthrocentesis is mandatory in most patients with a new effusion to rule out infection and identify crystals. It can also help distinguish between an inflammatory and a noninflammatory process. Synovial fluid examination includes 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/µL) is more suggestive of osteoarthritis or trauma. Hemorrhagic fluid is consistent with hemarthrosis. Synovial fluid WBC counts can be very high (eg, > 50,000/µL) 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/µL.

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 SLE, ANCA-associated vasculitis, or RA.

If arthritis is chronic, x-rays are typically done to look for signs of joint damage.

Other tests may be needed to identify specific disorders (see Table: Some Causes of Pain in ≥ 5 Joints* and see Table: Some Causes of Pain in ≤ 4 Joints).


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 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 is by far the most common cause of arthritis in older people. 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 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).

Key Points

  • 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.

  • Chronic polyarthritis is most often caused by juvenile idiopathic arthritis in children and chronic polyarthralgia is most often caused by osteoarthritis and RA in adults.

  • Acute polyarticular arthritis is most often due to infection, gout, or a flare of a systemic inflammatory disease.

  • 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.

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