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Am Fam Physician. 2023;107(1):42-51

This clinical content conforms to AAFP criteria for CME.

Author disclosure: No relevant financial relationships.

Polyarticular joint pain involves five or more joints and can be inflammatory or noninflammatory. Two of the most common causes of chronic polyarthritis are osteoarthritis, especially in older patients, and rheumatoid arthritis, which affects at least 0.25% of adults worldwide. The initial evaluation should include a detailed history of the patient's symptoms, with a focus on inflammation, location of pain, duration of symptoms, the presence of systemic symptoms, and any exposures to pathogens that could cause arthritis. Redness, warmth, or swelling in a joint is suggestive of synovitis and joint inflammation. A systematic approach to the physical examination that assesses for a pattern of joint involvement and presence of synovitis can help narrow the differential diagnosis. Laboratory tests, joint aspiration, and imaging studies should be used to confirm a suspected diagnosis. Rheumatoid factor and cyclic citrullinated peptide antibody tests are helpful when there is concern for rheumatoid arthritis. Although magnetic resonance imaging is highly sensitive in identifying erosive bony changes and inflammation, conventional radiography remains the standard for the initial imaging evaluation of rheumatoid arthritis. Point-of-care musculoskeletal ultrasonography can also be a useful tool to detect findings that support a diagnosis of inflammatory arthritis.

Arthritis, defined as joint inflammation, affects nearly 1 in 4 adults in the United States.1 Two of the most common causes of chronic polyarthritis are osteoarthritis, especially in older patients, and rheumatoid arthritis (RA), which affects at least 0.25% of adults worldwide.2 Most people in the United States with arthritis have osteoarthritis, which is a noninflammatory condition. Although inflammatory arthritis is uncommon, studies show that adults presenting to primary care with musculoskeletal symptoms often report joint pain, stiffness, or swelling that could be consistent with inflammatory arthritis.3 The diagnosis of inflammatory arthritis in the primary care setting is challenging. When a patient presents with polyarticular pain (involving five or more joints), a systematic approach to the diagnosis including history, physical examination, laboratory analysis, and imaging is critical because the diagnosis is rarely made by any single measure.4

RecommendationSponsoring organization
Do not test for Lyme disease as a cause of musculoskeletal symptoms without a history of exposure and appropriate examination findings.American College of Rheumatology, American Academy of Pediatrics – Section on Rheumatology



The presence of inflammation in multiple painful joints largely differentiates inflammatory arthritis (common etiologies include RA, gout, and chronic calcium pyrophosphate deposition disease [pseudogout]) from osteoarthritis. Duration of symptoms can help narrow the differential diagnosis (Figure 1, Table 1,5,6 and Table 25,710 ). Inflammation can further be assessed by asking the patient about swelling, redness, and warmth.11 Additional evidence of joint inflammation includes prolonged morning stiffness (one hour or more), pain at night, or gelling phenomenon (stiffness after inactivity).11

CauseDistinguishing extra-articular and systemic features
BacteriaGonorrhea – bacteremic spread occurs in 0.5% to 3% of infected patients causing arthritis-dermatitis syndrome or purulent arthritis; rash, if present, is typically short-lived, painless pustules located on the distal extremities, often with only two to 10 lesions present
Infectious endocarditis – systemic symptoms including fever/chills and weight loss; heart murmur in 85% of patients
Lyme disease – associated with erythema chronicum migrans (bull's eye rash)
Meningitis – arthritis is rare in meningitis; flulike symptoms, stiff neck, photophobia, rash
Rheumatic fever – arthritis is an early manifestation; arthritis is more common in teens and young adults (80%) than in children (65%)
Crystalline arthritisGout – rare to have extra-articular manifestations in acute/early disease
Early rheumatic diseaseInflammatory bowel disease–associated arthritis
Polymyalgia rheumatica
Psoriatic arthritis
Reactive arthritis
Rheumatoid arthritis
Systemic lupus erythematosus
SarcoidosisCutaneous manifestations (e.g., erythema nodosum) occur in about 25% of patients and are often an early finding; swelling usually occurs in the soft tissue around the joints and not in the joints themselves; hilar lymphadenopathy
VirusHIV – flulike illness, pruritic erythematous rash, mouth ulcers, swollen lymph nodes
Parvovirus B19 – slapped cheeks appearance, fever, rhinitis, headache
Viral hepatitis – jaundice, abdominal pain, elevated liver function test results
OtherAutoinflammatory disease
Inflammatory myositis
Other spondyloarthropathies
Sjögren syndrome
Systemic sclerosis
Systemic vasculitis
DiagnosisDistinguishing extra-articular and systemic featuresAge and sex predominance
Calcium pyrophosphate deposition disease (pseudogout)Associated with hemochromatosis, hyperparathyroidism, hypomagnesemia, hypophosphatemiaOlder adults, no sex predominance
GoutSubcutaneous tophi possible in joints, ears, olecranon bursae, finger pads, tendonsMen 30 to 60 years of age
Inflammatory bowel disease– associated arthritisHistory of inflammatory bowel disease, weight loss, fatigueNo specific age or sex
Polymyalgia rheumaticaAching and weakness of the shoulder girdle; flulike symptomsMore common in women than men; onset typically between 50 and 70 years of age
Psoriatic arthritisPsoriatic skin lesions (papular erythematous plaques topped with a silvery scale), nail lesions (including pits and onycholysis)No specific age or sex
Reactive arthritisOften associated with gastrointestinal or genitourinary infectionsNo specific age or sex
Rheumatoid arthritisCan involve dermatologic (nodules, lymphedema); ophthalmologic (uveitis); pulmonary (interstitial lung disease, effusion); cardiovascular (effusion, arrhythmias); gastrointestinal (xerostomia); neurologic (peripheral nerve entrapment); and hematologic (lymphadenopathy, leukopenia) systemsWomen 30 to 60 years of age
Men older than 60 years
Sjögren syndromeSicca symptomsWomen 30 to 50 years of age
Systemic lupus erythematosusArthritis in proximal interphalangeal joints and knees; variable presentationYoung women of child-bearing age
Others (autoinflammatory disease, inflammatory myositis, other spondyloarthropathies, systemic sclerosis, systemic vasculitis)

Although inflammation may be localized to the joints, in rheumatic diseases, extra-articular or systemic features are often present. Rashes are a common extra-articular finding that can provide pathognomonic support for a diagnosis such as plaques in psoriasis or erythema chronicum migrans in Lyme disease. Constitutional findings such as fatigue, fever, malaise, or weight loss are also common. Other possible extra-articular features include dry eyes or mouth, dysphagia, gastrointestinal symptoms, interstitial lung disease, lymph-adenopathy, mucosal ulceration, muscle weakness, ocular inflammation, photosensitivity, pleural or pericardial effusions, and Raynaud phenomenon11 (Table 15,6 and Table 25,710). Patients with more diffuse pain and muscle rather than joint involvement may have fibromyalgia (Figure 1).


The differential diagnosis can vary depending on the duration of symptoms; however, there is no consensus on the time frame for acute vs. chronic arthritis. With that in mind, using a symptom duration of six weeks or more is a reasonable cutoff for defining chronic symptoms because that is used in the classification criteria for RA, which is the most common autoimmune inflammatory arthritis in adults.1214 However, if the duration of symptoms is less than six weeks but the clinical scenario is suggestive of an early inflammatory polyarthritis, referral to a rheumatologist should not be delayed because early treatment in these cases can affect long-term outcomes.15


A detailed history should include questions about any potential exposures as a cause of joint pain.16 Travel history may reveal potential contact with ticks carrying Lyme disease or other regional pathogens.17 Sexual or blood exposure history can identify risk for HIV, hepatitis C infection, or other sexually transmitted infections that could cause arthropathy.16 Review of medication use, such as certain antimicrobials, dipeptidyl-peptidase-4 inhibitors, and isotretinoin, can reveal potential causes of vasculitis or drug-induced syndromes.18 Additionally, occupational history may lead to concern for chemical exposures and related conditions such as lead toxicity.19

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