Differential diagnosis	Distinguishing features	Diagnostic approach
Adult-onset Still disease	Arthralgia, fever, lymphadenopathy, splenomegaly	Elevated erythrocyte sedimentation rate, elevated ferritin level, leukocytosis, and anemia
Behçet syndrome	Aphthous ulcers, arthralgia, uveitis	Recurrent oral ulcers plus two of the following: eye lesions, genital ulcers, skin lesions
Chronic fatigue syndrome	Persistent and unexplained fatigue that significantly impairs daily activities	Perform the following tests to rule out other diseases: complete blood count, erythrocyte sedimentation rate, C-reactive protein level, complete metabolic panel, thyroid-stimulating hormone, urinalysis
Endocarditis	Arterial emboli, arthralgia, fever, heart murmur, myalgia	Positive echocardiography findings with vegetation on heart valve; positive blood culture
Fibromyalgia	Poorly localized musculoskeletal pain with hyperalgesia and allodynia	Digital palpation of soft tissue tender points: gluteal, greater trochanter, knee, lateral epicondyle, low cervical, occiput, second rib, supraspinatus, trapezius
HIV infection	Arthralgia, fever, lymphadenopathy, malaise, myalgia, peripheral neuropathy, rash	Western blot assay for detection of HIV antibodies
Inflammatory bowel disease	Diarrhea, peripheral arthritis, rectal bleeding, tenesmus	Perform colonoscopy to assess disease activity; measure C-reactive protein level, platelets, and erythrocyte sedimentation rate; test for anemia
Lyme disease	Arthritis, carditis, erythema migrans, neuritis	Perform serologic testing for Lyme disease
Mixed connective tissue disease	Arthralgia, myalgia, puffy fingers, Raynaud phenomenon, sclerodactyly	Elevated erythrocyte sedimentation rate and hypergammaglobulinemia; positive anti-U1RNP antibodies
Psoriatic arthritis	Psoriasis before or after joint disease, nail changes in fingers and toes	Inflammatory articular disease and more than three of the following: dactylitis, nail changes, negative rheumatoid factor, psoriasis, radiographic evidence of new bone formation in hand or foot
Reactive arthritis	Acute nonpurulent arthritis from infection elsewhere in the body; evaluate for infectious urethritis or colitis	Clinical diagnosis to identify triggers; serologic findings of recent infections may be present
Rheumatoid arthritis	Morning joint stiffness lasting more than one hour; affected joints are usually symmetrical, tender, and swollen	Positive test results for rheumatoid factor and anti-cyclic citrullinated antibodies; synovial fluid reflects inflammatory state
Sarcoidosis	Cough, dyspnea, fatigue, fever, night sweats, rash, uveitis	Perform chest radiography; bilateral adenopathy with biopsy revealing noncaseating granuloma; elevated angiotensin-converting enzyme level
Systemic sclerosis	Arthralgia, decreased joint mobility, myalgia, Raynaud phenomenon, skin induration	Perform tests for specific autoantibodies
Thyroid disease	Dry skin, fatigue, feeling cold, weakness	Measure thyroid-stimulating hormone