Some musculoskeletal disorders affect primarily the joints, causing arthritis. Others affect primarily the bones (eg, fractures, Paget disease of bone, tumors), muscles (eg, myositis), peripheral nerves (eg, ulnar nerve entrapment), or other periarticular soft tissues (eg, bursitis, tendinitis, sprains, ligament injuries). Arthritis has myriad possible causes, including infection, autoimmune disorders, crystal-induced inflammation, and minimally inflammatory cartilage and bone disorders (eg, osteoarthritis). Arthritis may affect single joints (monoarthritis) or multiple joints (polyarthritis) in a symmetric or asymmetric manner, with or without involving the spine.
History in Patients With Joint Symptoms
The clinician should focus on systemic and extra-articular symptoms as well as joint symptoms (1). Many symptoms and clinical findings, including the following, can be associated with various joint disorders and provide clues to the diagnosis of a specific systemic disorder:
Fever
Chills
Malaise
Weight loss
Rash
Mucosal ulcers
Eye redness or pain
Photosensitive rashes
Dysesthesias
Gastrointestinal symptoms
Cardiopulmonary symptoms
Pain is the most common symptom of joint disorders (see Pain in and Around a Single Joint and Pain in Multiple Joints). The history should address the character, location, severity, factors that aggravate or relieve pain, and time frame (new-onset or recurrent). The clinician must determine whether pain is worse when first moving a joint or after prolonged use and whether it is present upon waking or develops during the day. Pain originating from superficial structures is usually more readily localized than pain originating from deeper structures. Pain originating in small distal joints tends to be better localized than pain originating in large proximal joints. Joint pain can be referred from extra-articular structures or from other joints. Arthritis often causes aching pain, whereas neuropathies often cause a deep, boring pain or a superficial burning pain.
Stiffness refers to difficulty in moving a joint, but to patients, stiffness also may mean weakness, fatigue, or fixed limitation of motion. The clinician must separate the inability to move a joint from reluctance to move a joint because of pain. Characteristics of stiffness may suggest a cause, as in the following:
Discomfort that occurs with motion when attempting to move a joint after a period of rest occurs in systemic rheumatic disease.
Stiffness is more severe and prolonged with increasing severity of joint inflammation.
The theater sign (short-lived knee or hip stiffness upon standing that necessitates walking slowly after sitting for several hours) is common in osteoarthritis.
Morning stiffness in peripheral joints that lasts > 1 hour can be an important early symptom of joint inflammation, such as in rheumatoid arthritis, psoriatic arthritis, or chronic viral arthritis.
In the low back, morning stiffness that lasts > 1 hour and lessens with movement may reflect spondylitis.
Fatigue is a desire to rest that reflects exhaustion. It differs from weakness, inability to move, and reluctance to move because of pain with movement. Fatigue may reflect activity of a systemic inflammatory disorder as well as other disorders. Clinicians should try to distinguish fatigue from sleepiness.
Instability (buckling of a joint) suggests an internal joint derangement or weakness of the ligaments or other periarticular structures that stabilize the joint, which are assessed by stress testing on physical examination. Buckling occurs most often in the knee.
Distinguishing Inflammatory versus Noninflammatory Joint Disease by Features
Feature | Inflammatory | Noninflammatory |
|---|---|---|
Systemic symptoms | Prominent, including fatigue | Unusual |
Onset | Insidious in rheumatoid arthritis Sudden in gout or infection | Gradual |
Morning stiffness | > 1 hour | < 30 minutes |
Worst time of day | Morning | As day progresses |
Effect of activity on symptoms (joint pain and stiffness) | Lessen with activity Worsen after periods of rest May also have pain with use | Worsen with activity Lessen with rest |
History reference
1. Guidelines for the initial evaluation of the adult patient with acute musculoskeletal symptoms. American College of Rheumatology Ad Hoc Committee on Clinical Guidelines. Arthritis Rheum. 1996;39(1):1-8. doi:10.1002/art.1780390102
Physical Examination in Patients With Joint Symptoms
Each involved joint should be inspected and palpated, and the range of motion should be estimated. With polyarticular disease, certain nonarticular signs (eg, fever, wasting, rash) may reflect systemic disorders.
The rest position of joints is noted, along with any erythema, swelling, deformity, and skin abrasions or punctures. Involved joints are compared with their uninvolved opposites or with those of the examiner.
Joints are gently palpated, noting the presence and location of tenderness, warmth, and swelling. Determining whether tenderness is present along the joint line or over tendon insertions or bursae is particularly important. Soft masses, bulges, or tissues that fill normal concavities or spaces (representing joint effusion or synovial proliferation) are noted. Palpation of swollen joints can sometimes differentiate among joint effusion, synovial thickening, and capsular or bony enlargement. Small joints (eg, acromioclavicular, tibiofibular, radioulnar, sternoclavicular) can be the source of pain that was initially believed to arise from a nearby major joint. Bony enlargement (often due to osteophytes) is noted.
Active range of motion (the maximum range through which the patient can move the joint) is assessed first; limitation may reflect weakness, pain, or stiffness as well as mechanical abnormalities. Then passive range of motion (the maximum range through which the examiner can move the joint) is assessed; passive limitation typically reflects mechanical abnormalities (eg, scarring, swelling, deformities) rather than weakness or pain. Active and passive movement of an inflamed joint (eg, due to infection or gout) may be very painful.
Inability to reproduce pain with passive or active motion or palpation of the joint suggests the possibility of referred pain.
Patterns of joint involvement should be noted. Symmetric involvement of multiple joints is common in systemic diseases (eg, rheumatoid arthritis); monarticular (involving one joint) or asymmetric oligoarticular (involving ≤ 4 joints) joint involvement is more common in osteoarthritis and psoriatic arthritis. Small peripheral joints are commonly affected in rheumatoid arthritis, and the larger joints and spine are affected more in spondyloarthropathies. However, the full pattern of involvement may not be apparent in early disease.
Crepitus, a palpable or audible grinding produced by motion of damaged joint structures, is noted. It may be caused by roughened articular cartilage or by tendons; crepitus-causing motions should be determined and may suggest which structures are involved.
Specific features should be sought at each joint. Details of the physical examination are discussed separately for the following joints:
Testing in Patients With Joint Symptoms
Laboratory testing and imaging studies often provide less information than do the history and physical examination. Although some testing may be warranted in some patients, extensive testing is often not. Testing may include
Biopsy of bone, synovium, or other tissue is occasionally done.
Blood tests
Blood tests should be selected based on history and examination findings. Some tests, although not specific, can be helpful in supporting or excluding the possibility of certain systemic rheumatic diseases, as for the following:
Antinuclear antibodies (ANA) and anti–double-stranded DNA antibodies in systemic lupus erythematosus (SLE)
Rheumatoid factor and anti-cyclic citrullinated peptide (anti-CCP) antibodies in rheumatoid arthritis (RA)
HLA-B27 in spondyloarthropathy (eg, with symptoms of inflammatory back pain and normal radiographs, or with unexplained uveitis and an inflammatory peripheral arthritis)
Tests such as white blood cell count, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) may help determine the likelihood that arthritis is inflammatory due to infectious or other systemic disorders, but these tests are not highly specific or sensitive. For example, a normocytic anemia or an elevated ESR or CRP suggests articular inflammation or may be due to a large number of nonarticular inflammatory conditions (eg, infection, cancer). Also, such markers may not be elevated in all inflammatory disorders.
Imaging studies
Imaging studies are often not necessary. Radiographs in particular reveal mainly bony abnormalities, and most joint disorders do not affect bone primarily. However, imaging may help in the initial evaluation of relatively localized, unexplained, persistent or severe joint and particularly spine abnormalities; it may reveal primary or metastatic tumors, osteomyelitis, bone infarctions, periarticular calcifications (as in calcific tendinitis), or other changes in deep structures that may escape physical examination. If chronic rheumatoid arthritis, gout, or osteoarthritis is suspected, erosions, cysts, and joint space narrowing with osteophytes may be visible. In calcium pyrophosphate arthritis (pseudogout), calcium pyrophosphate deposition may be visible in intra-articular cartilage (chondrocalcinosis).
For musculoskeletal imaging, radiographs may be obtained first, but they are less sensitive, particularly during early disease, than MRI, CT, or ultrasonography. MRI is the most accurate study for fractures not visible on radiographs, particularly in the hip and pelvis, and for soft tissues and internal derangements of the knee. CT is useful if MRI is contraindicated or unavailable. CT is also useful to detect periarticular calcification (eg, in crowned dens syndrome), which would not be detected on MRI. Dual-energy CT scanning is useful to detect uric acid deposition and diagnose gout. Ultrasonography can detect synovial proliferation and hyperemia suggestive of inflammation in the small joints of the hands and feet, and may identify urate deposition in joints affected by gout even between clinical flares. Arthrography and bone scanning may help in certain conditions.
Arthrocentesis
Arthrocentesis is the process of puncturing the joint with a needle to withdraw fluid. If there is an effusion and arthrocentesis is done correctly, fluid can typically be withdrawn. Examination of synovial fluid is the most accurate way to exclude infection, diagnose crystal-induced arthritis, and help determine the cause of joint effusions (1). This procedure is indicated for all patients with acute or unexplained monarticular joint effusions and for patients with unexplained polyarticular effusions.
Arthrocentesis of the Shoulder, Arthrocentesis of the Elbow, and Arthrocentesis of the Knee). Ultrasound guidance has been shown to increase the likelihood of a successful aspiration.
Synovial fluid examination
At the bedside, gross characteristics of the fluid are assessed, such as its color and clarity.
Gross characteristics allow many effusions to be tentatively classified as noninflammatory, inflammatory, or infectious (see table Classification of Synovial Effusions). Effusions can also be hemorrhagic. Each type of effusion suggests certain joint diseases (see table Differential Diagnosis Based on Synovial Fluid Classification). So-called noninflammatory effusions are often mildly inflammatory and suggest diseases such as osteoarthritis and osteonecrosis, in which inflammation is not severe.
Classification of Synovial Effusions
Examination | Normal | Hemorrhagic | Infectious | Inflammatory | Noninflammatory |
|---|---|---|---|---|---|
Gross examination | |||||
Appearance | Clear | Bloody | Turbid or purulent | Yellow, cloudy | Straw-colored, clear |
Routine laboratory examination | |||||
Culture | Negative | Negative | Often positive | Negative | Negative |
Polymorphonuclear leukocyte %* | < 25 | — | Usually >85 | > 50 | < 25 |
White blood cell count* | <200/mcL | Affected by amount of blood | 5,000–>100,000/mcL | 1,000–50,000/mcL | 200–1000/mcL |
* White blood cell (WBC) count and polymorphonuclear leukocyte % in infectious arthritis are lower if the organism is less virulent (eg, in gonococcal, Lyme, tuberculous, or fungal arthritis) or partially treated. Some effusions in systemic lupus erythematosus and other systemic rheumatic diseases are only equivocally inflammatory, with a WBC count of 500–2000/mcL. Noninfectious effusions rarely have up to 100,000 WBC/mcL. | |||||
Laboratory tests commonly done on joint fluid include cell count, leukocyte differential, Gram stain and culture (if infection is a concern), and wet drop examination for cells and crystals. However, the exact tests often depend on which diagnoses are suspected.
Differential Diagnosis Based on Synovial Fluid Classification*†
Type of Effusion | Possible Causes |
|---|---|
Hemorrhagic | Anticoagulants Hemangioma Neurogenic (neuropathic) arthropathy Pigmented villonodular synovitis Thrombocytopenia (rarely) Trauma with or without fracture Tumor |
Infectious | Various organisms depending on patient characteristics (see table Organisms That Commonly Cause Acute Infectious Arthritis) |
Inflammatory | Acute crystal synovitis (gout and calcium pyrophosphate arthritis [pseudogout]) Partially treated or less virulent bacterial infections Systemic lupus erythematosus (mild inflammation) Synovial infarction (eg, caused by sickle cell disease) |
Noninflammatory | Hypertrophic pulmonary osteoarthropathy (including clubbing) Metabolic diseases causing osteoarthritis Neurogenic (neuropathic) arthropathy Osteochondritis dissecans Osteonecrosis (including osteonecrosis caused by sickle cell disease) Subsiding or early inflammation Trauma |
Also see table Classification of Synovial Effusions. This differential diagnosis is only a partial listing. | |
† Some disorders span classifications (eg, neuropathic arthropathy can be hemorrhagic or noninflammatory; systemic sclerosis can be inflammatory or noninflammatory). | |
Microscopic examination of a wet drop preparation of synovial fluid for crystals (only a single drop of fluid from a joint is needed) using polarized light is essential for definitive diagnosis of gout, calcium pyrophosphate arthritis, and other crystal-induced arthritides. A polarizer over the light source and another polarizer between the specimen and the examiner’s eye allow visualization of crystals with a shiny white birefringence. Compensated polarized light is provided by inserting a first-order red plate, as is found in commercially available microscope kits that can be adapted to standard light microscopes.
The most common crystals seen are those diagnostic of gout (monosodium urate, negatively birefringent needle-shaped crystals) and calcium pyrophosphate arthritis (calcium pyrophosphate, rhomboid- or rod-shaped crystals that are positively birefringent or not birefringent). If crystals appear atypical in a wet drop, several less common crystals (cholesterol, liquid lipid crystals, oxalate, cryoglobulins) or artifacts (eg, depot corticosteroid crystals) should be considered.
Other synovial fluid findings that occasionally make or suggest a specific diagnosis include the following:
Specific organisms (identifiable by Gram or acid-fast stain)
Marrow spicules or fat globules (caused by fracture)
Amyloid fragments (identifiable by Congo red stain)
Sickled red blood cells (caused by sickle cell hemoglobinopathies)
Testing reference
1. Brannan SR, Jerrard DA: Synovial fluid analysis. J Emerg Med 30(3):331-339, 2006. doi:10.1016/j.jemermed.2005.05.029
