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Rory M. Marks

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date: 12 August 2020

  1. A. Overview. Diagnosis for a patient presenting with joint pain from arthritis comes principally from a consideration of the anatomic pattern of joints that are affected and the time course over which symptoms have developed, and nothing more than that clinical assessment may be required. Clinical features are supplemented as needed by judicious use of imaging, looking for specifically diagnostic features, and selective laboratory testing chosen to help diagnose or exclude specific arthritic diseases that are being considered.

The initial assessment, with information from the history and physical examination, often with radiographic data and sometimes with initial laboratory data (from joint fluid aspiration and blood testing), should permit construction of a differential diagnostic list. Determining whether there is related disease in other organ systems is also an important part of the assessment because arthritis in an acutely ill patient can be part of a multisystem process caused by very different types of disease.

Pediatric and adult joint diseases share much of the same nomenclature but often have very different clinical features, and this overview of adult arthritis must not be applied to pediatric practice.

  1. 1. History taking

    1. a. What is the time course of developing joint pain? Pain developing abruptly and progressing rapidly over hours or a few days is more concerning for an acute and important medical cause such as infection than pain present for months.

    2. b. What areas are affected? Patients can describe painful joints, when in fact it may be other adjacent structures that are involved, such as bones, tendons and tendon sheaths, or bursae. While the approach to assessing these may overlap with the approach to arthritis, it may be very different. Also, patients with fibromyalgia often describe joint pain, whereas their pain is much more generalized and not related to any specific anatomic structures.

    3. c. What joints are affected? Knowing the anatomic pattern of involved joints is often the most helpful feature that leads to making a diagnosis. Pain in one or a few peripheral joints is quite likely to be caused by a crystal arthritis or bacterial infection. Pain that develops in many small peripheral joints at the same time could be from a viral arthritis (if acute) or from rheumatoid arthritis (RA) (if more chronic). Pain in axial joints can also be infective but may indicate a possible spondyloarthritis. See later section on arthritis patterning.

    4. d. What is the severity of pain? Arthritis is almost always painful, but the intensity of pain can be a helpful diagnostic feature. Rheumatoid arthritis is certainly painful but rarely causes very severe pain. Patients with very severe pain, especially if in one or a few peripheral joints, may well have a crystal arthritis, and severe pain in any joint makes consideration of bacterial infection critically important.

    5. e. What are the clinical features beyond the joints? Patients may have acute clinical features other than arthritis that can be very important for making a diagnosis of a systemic disease that includes arthritis as part of its manifestations. It is important to assess whether all the clinical features can be integrated because that may lead to a single unifying diagnosis. For example, a patient with a symmetric small joint polyarthritis could have any one of several different types of joint disease, but the same patient who also had a malar rash, pleuritic chest pain, and an active urinary sediment will very likely have systemic lupus erythematosus (SLE) rather than any other condition as a unifying diagnosis. Taking a full history is an important component of the assessment.

  2. 2. Physical examination

    1. a. Include full musculoskeletal examination. Patients may have diagnostically important involvement of joints that they are unaware of or unconcerned about, or they may be unable or unwilling to communicate their history.

    2. b. Complete comprehensive physical examination. This is important in all patients but especially so in acutely ill, hospitalized patients. Knowing whether disease is restricted to joints or whether there is concurrent, active disease in other organ systems is a key part of the assessment.

    3. c. Determine whether the joint is affected. As noted previously, complaints of joint pain may relate to adjacent structures. Physical examination is the best tool to distinguish processes affecting joints, bones, tendons, bursae, and other structures. Also, joint inflammation that has spread beyond the joint into adjacent soft tissues can be an important distinguishing feature of highly inflammatory conditions such as septic arthritis and gout.

    4. d. Joint examination. The focus is on deciding which joints are affected, whether or not it is an inflammatory process, and if it is, how intense is the inflammatory process.

      1. i. Inspection. Are individual joints swollen and/or erythematous (signs of possible inflammation)? Are they deformed (sign of chronic destructive disease)? Comparison with your own joints can help if in doubt.

      2. ii. Palpation. Determine whether the joints are tender to squeeze (no more pressure than it takes to blanch the tissues under a fingernail, which is sign of inflammation). If there is swelling, determine whether it is soft and mobile from fluid or synovial tissue (may be a sign of inflammation) or hard from bony hypertrophy.

      3. iii. Passive movement. Gently trying to put a joint through its expected range of motion can help evaluate how severely affected a joint is and whether it is being affected by a highly inflammatory process.

      4. iv. Nodules. As an extension of the joint examination, determine whether there are nodules at the elbows and other regions. Firm olecranon region nodules could be from RA or gouty tophi.

  3. 3. Imaging

    1. a. Radiographs

      1. i. Acute arthritis. Radiographs are not needed in every case of arthritis. If joints were completely normal until a few days before a patient presents with an acutely painful arthritis, radiographs will not be informative.

      2. ii. Chronic polyarthritis. In patients presenting with a chronic polyarthritis, it is usual to perform radiographs of both hands and both feet (even if asymptomatic), looking for the specific erosive and destructive changes typical of RA or a spondyloarthritis. It is not helpful or practical to perform radiographs of every affected joint in a polyarthritis patient.

      3. iii. Chronic monoarthritis or oligoarthritis. It is usual to perform radiographs of affected regions. Even though uric acid is not radiopaque, the destructive joint lesions caused by gout can have very distinctive imaging features, and any associated tophaceous deposits calcify over time and become radiopaque.

      4. iv. Acute on chronic arthritis. Joints that were previously affected by noninflammatory osteoarthritis can become complicated by calcium pyrophosphate deposition disease and present with a highly inflammatory gout-like condition (pseudogout). Radiographs can demonstrate the cartilage calcification sometimes found in this condition.

      5. v. Axial arthritis. Most patients with spine pain do not have an inflammatory arthritis, and the spine is also concerning for pain caused by infectious and neoplastic disease in a way that does not often affect peripheral joint-bearing structures. Patients suspected of having RA may have neck involvement, and cervical spine radiographs, with additional flexion-extension views to detect atlantoaxial instability, are indicated. Spondyloarthropathies very often affect the axial skeleton, usually the most distal region (i.e., sacroiliac joints) first and progressing proximally. Radiographs of affected spine regions can be diagnostic.

    2. b. Ultrasound. Musculoskeletal ultrasound, in centers where it is done by expert musculoskeletal radiologists, can be a very valuable tool in situations in which the physical examination and radiographs are inadequate to establish the diagnosis.

      1. i. Erosive and inflammatory arthritis. Ultrasound may demonstrate subtle diagnostic erosive changes affecting individual joints not apparent on radiographs and may demonstrate the hyperemia that characterizes inflammatory arthritis.

      2. ii. Joint effusions. Ultrasound can identify joint fluid and also guide aspiration in situations in which blind aspiration might be impossible.

    3. c. Magnetic resonance imaging (MRI)

      1. i. Erosive and inflammatory arthritis. This can be a sensitive modality for identifying joint erosions in polyarthritis cases, if radiographs are inadequate.

      2. ii. Septic arthritis. When bacterial infection is suspected, MRI is often used to determine involvement of the tissues in and around joints. Intravenous contrast can be given but may not be needed for this type of assessment.

      3. iii. Axial arthritis. MRI is especially useful for detecting bone marrow edema that is a subtle indicator of joint inflammation and can indicate the presence of a spondyloarthritis before radiographic changes occur. MRI is also especially useful in RA when cervical spine involvement is suspected and may demonstrate an inflammatory synovial pannus and its impact on the spinal cord and other adjacent structures.

      4. iv. Avascular necrosis. This painful process occurs adjacent to joints, can mimic arthritis, and is best diagnosed by MRI.

    4. d. Computed tomography (CT) does not have a major role in the diagnosis of arthritis.

      1. i. Subtle fractures. CT is used to diagnose suspected insufficiency and other subtle fractures that can mimic arthritis and may not be evident on plain radiograph.

      2. ii. Erosive arthritis. CT can define loss of continuity of the cortical bone that occurs in erosive or destructive arthritis when this is suspected on radiograph and needs to be confirmed.

      3. iii. Septic arthritis. Contrast CT can be helpful in situations in which MRI cannot be done in order to image the regions in and around large joints.

    5. e. Radionuclide bone scan

      1. i. Inflammatory arthritis. Bone scintigraphy has very little role in the diagnosis of arthritis and in general does not provide any more information than what can be obtained from the physical examination.

      2. ii. Avascular necrosis can be diagnosed by bone scintigraphy, although MRI has become the preferred diagnostic modality.

  4. 4. Laboratory testing of joint fluid

    1. a. Indications. Examination of joint fluid can be very helpful in deciding whether a joint effusion is caused by a noninflammatory or inflammatory condition and when determining the intensity of the inflammatory process from the leukocyte count has important diagnostic implications. Polarizing light microscopy can lead to specific diagnosis of a crystal arthritis, and culture of joint fluid is critically important for diagnosing and managing septic arthritis.

    2. b. Who should perform the joint aspiration? This should only be done by physicians trained and credentialed to perform this procedure on the joint being targeted. Patient comfort from positioning, generous and expert infiltration of local anesthetic, aseptic technique, and successful entry into the joint space being targeted all require training. None of these can be provided by online videos.

    3. c. Role of ultrasound guidance. Determining whether there is joint fluid available for aspiration and positioning a needle tip in that fluid can be facilitated by ultrasound. This is done in situations in which physical examination and blind aspiration using anatomic landmarks are inadequate.

    4. d. Tests to order. In most cases, the only tests that have diagnostic utility are cell count and differential, culture, and crystal analysis.

      1. i. Leukocyte count and differential. The leukocyte count associated with different types of arthritis is listed in Table 74.1, but it is important to be aware that cell counts in all these conditions overlap considerably and are also affected by factors such as partial treatment preceding aspiration and underlying immunodeficiency states. In highly inflammatory conditions such as septic and crystal arthritis, more than 75% (and often >90%) of the leukocytes are neutrophils. Less inflammatory conditions may have lower neutrophil content.

        Table 74.1 Synovial Fluid Leukocytes in Different Types of Arthritis

        Normal synovial fluid

        Noninflammatory Arthritis

        Moderately Inflammatory Arthritis

        Highly Inflammatory Arthritis

        Arthritis type


        Rheumatoid arthritis

        Crystal arthritis

        Septic arthritis

        Leukocyte count/mm3






        % Neutrophils






      2. ii. Erythrocyte count. Aspiration is usually associated with some contamination from blood, with variable but usually minor numbers of erythrocytes. A substantial erythrocyte count should lead to consideration of possible hemarthrosis occurring with or without an associated arthritis.

      3. iii. Culture. All joint fluid should be submitted for Gram stain and culture. Most bacteria causing septic arthritis can be cultured in usual media under aerobic conditions, but it is especially important to consider the possibility of gonococcal arthritis, which will require special media and molecular-based testing. Requesting viral, fungal, mycoplasma, and mycobacterial culture and molecular studies will depend on the specific clinical features of an individual case.

      4. iv. Crystal analysis. There are many types of crystals associated with arthritis, but most cases of crystal arthritis are attributed to either gout caused by monosodium urate or pseudogout caused by calcium pyrophosphate. Both of these types of crystal can be definitively identified by polarizing light microscopy on fresh synovial fluid, and immediate examination (crystals degrade quickly) should be done when possible. It is important to understand that while this type of crystal identification is highly specific, it is not a sensitive test, and it is quite possible to have gout or pseudogout without being able to identify the responsible crystal.

  5. 5. Laboratory testing of blood

    1. a. Indications. Rheumatology laboratory testing on a patient with an arthritis syndrome may or may not be required and is determined entirely by the clinical features of an individual patient. Indiscriminate testing done in the hope of finding a result that will suggest a possible diagnosis is inappropriate and risks generating confusing false-positive results. Tests should be chosen methodically after developing an initial differential diagnosis from the clinical features and then selecting laboratory tests with significant positive or negative predictive value that will help narrow the differential diagnosis.

    2. b. General laboratory tests. Some tests can be considered to be an extension of the physical examination and can provide important background information. These tests would always be completed in an ill patient in an acute care setting and include complete blood count (CBC) with differential and platelets, comprehensive biochemical profile, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), thyroid-stimulating hormone (TSH), and urinalysis.

    3. c. Arthritis with inflammatory features. These tests include rheumatoid factor (RF), cyclic citrullinated peptide antibody (CCP Ab), hepatitis C antibody (mimic of RA), and uric acid. This very brief list will suffice for most cases in which arthritis is the sole clinical issue. If there are clinical features indicating disease beyond the joints, then additional relevant testing should be done.

  6. B. Approach to Diagnosis. An initial differential diagnosis should be generated by (1) assessing the number and anatomic pattern of involved joints; (2) the time course, onset, and duration of the arthritis; and (3) the intensity of the associated inflammatory response. Based on this, the clinician should ask the following questions:

    1. a. Is it an inflammatory arthritis or noninflammatory osteoarthritis? This is the first question to answer in a patient presenting with joint pain. While the answer may be readily apparent from the history and physical examination, additional information from imaging and joint fluid examination may be necessary. Patients with noninflammatory osteoarthritis tend to have pain that worsens through the day and with activity and lack physical signs of joint inflammation. Patients with an inflammatory arthritis have pain that is often worse in the morning and after periods of inactivity. The pain is accompanied by persistent stiffness and signs of inflammation.

      Hot Key

      Learn to distinguish types of arthritis by onset of the disease, the pattern of presentation, and the types of joints involved.

    2. b. Is osteoarthrosis the likely cause? While osteoarthritis is the most common type of arthritis seen in ambulatory practice, it is not often a major concern in the hospital setting. The main focus is differentiating it from other, more serious causes of arthritis. Osteoarthritis tends to cause mild to moderate pain that progresses over years. It is most noticeable later in the day and is classically worsened with activity or weight bearing such that patients become more sedentary to limit pain. Physical examination often demonstrates the involvement of multiple joints. In the hands, the distal interphalangeal and thumb joints are predominantly affected. Other commonly affected peripheral joints are the hips, knees, and any area of the spine. Affected joints may be enlarged from bony hypertrophy or osteophyte formation, sometimes with associated deformities and restriction of range of motion. Effusions in large joints such as the knee may occur, but if present, they are noninflammatory (i.e., low leukocyte counts) unless complicated by a secondary process such as pseudogout or infection. Laboratory testing is generally unhelpful for osteoarthritis and is principally used to (1) assess for an underlying metabolic disorder and (2) assess for other forms of arthritis. Radiographic or other imaging is usually not needed but when performed demonstrates characteristic joint surface sclerosis, reduction in joint space from loss of cartilage, osteophyte formation, and bony cysts.

    3. c. How many joints are involved? The number of joints involved and their location and symmetry can help focus the differential diagnosis as discussed later.

  7. C. Monoarthritis. Involvement of only one joint narrows the diagnosis to specific conditions, including crystal arthropathies, infectious or septic arthritis, and trauma.

      1. i. Crystal arthritis

        1. 1. Gout results from precipitation of monosodium urate crystals in synovial fluid, leading to an acute and highly inflammatory arthritis. The classic presentation involves the first metatarsophalangeal joint in the foot (podagra). However, other joints in the feet, ankles, and knees can also be affected, as can essentially any other peripheral joint, bursa (especially the olecranon bursa of the elbow), or tendon sheath. Thus, a high index of suspicion and early consideration for an acutely inflamed joint are needed for diagnosis. In addition to acutely inflamed joints, physical examination may reveal features of a chronic destructive arthritis or tophaceous gouty deposits adjacent to joints and in soft tissues. Patients may be hyperuricemic, but not necessarily so. In fact, absence of hyperuricemia never rules out gout. Radiographs may demonstrate diagnostic destructive changes as well as calcified tophi, but these may be normal in early stages of the disease. Diagnosis is confirmed by identifying intracellular urate crystals in the setting of an inflammatory joint fluid aspirate. However, this may not be possible, and the diagnosis is often made from the clinical features.

        2. 2. Pseudogout (also called calcium pyrophosphate deposition [CPPD] disease). This is a gout-like arthritis that is secondary to underlying degenerative arthritis. The hallmark is chondrocalcinosis within the affected joint, leading to liberation of inflammatory calcium pyrophosphate (CPP) crystals. Pseudogout can be clinically distinguished from gout by which joints are affected: knees, wrists, and ankles are commonly affected in pseudogout. The history and physical examination may reveal evidence of underlying advanced osteoarthritis. Laboratory testing is not helpful in the diagnosis. Radiographs may demonstrate features of underlying osteoarthritis or chondrocalcinosis. Diagnosis is made by identifying CPP crystals in an inflammatory joint fluid aspirate. However, there are two important caveats. First, CPP crystals may be rare and hard to identify, so false-negative joint fluid examination is common and does not rule out the diagnosis. Second, CPP crystals may be released into joint fluid in other types of disease processes, especially infection. Thus, careful consideration of the clinical presentation, joint distribution, and synovial fluid is necessary when contemplating a diagnosis of pseudogout.

        3. 3. Premature osteoarthritis, chondrocalcinosis, and pseudogout can also be caused by an underlying metabolic arthritis. The most important and common causes to consider are hereditary hemochromatosis, thyroid failure, and hyperparathyroidism. Always consider the possibility of an underlying metabolic cause when entertaining these diagnoses.

      2. ii. Infection

        1. 1. Gonococcal arthritis. While not a common cause of bacterial monoarthritis, gonococcal arthritis is especially important to consider in sexually active patients (at any age). Additionally, special culture media and molecular testing (of synovial fluid, blood, and mucosal swabs) are required to confirm the diagnosis. While the usual triad of gonococcal tenosynovitis, skin lesions, and polyarthralgias is more common, monoarthritis does occur in one-third of cases. Diagnosis is made by sending joint aspirate for culture and molecular testing.

        2. 2. Pyogenic bacterial arthritis. Bacterial arthritis is highly inflammatory. Patients are often very ill, and affected joints tend to be painful, with pain and swelling spreading into adjacent tissues. The usual causative organism is Staphylococcus aureus, followed by Streptococcus species and gram-negative organisms. This type of arthritis is especially important to recognize because of the risk for joint destruction and the implications for identifying systemic infection that may seed other parts of the body. Large, weight-bearing joints such as knees and hips are commonly affected, but any peripheral or axial joint can be involved. In particular, vertebral joint involvement should be considered when patients complain of back pain and fever. Joint fluid aspirate usually demonstrates very high leukocyte counts (>50,000 white blood cells [WBCs]/µL), and initial Gram stain may be positive for a bacterial pathogen. Radiographs are normal in early stages of the disease; thus, a negative plain film should not change suspicion. However, if the process continues unabated for several days, bony destruction may be visualized. MRI is often used to demonstrate the extent of soft tissue inflammation in and around joints and to identify infection spreading to adjacent structures. Apart from antibiotics, bacterial arthritis requires orthopedic surgery consultation because drainage or resection procedures are often part of management. When vertebral arthritis or osteomyelitis is suspected, early neurosurgical consultation is warranted because involvement of the spinal cord may lead to permanent paralysis.

          Hot Key

          When considering epidural abscess, diskitis, or vertebral osteomyelitis in a patient with back pain, always image the entire spine because thoracic vertebral involvement can present with lower back pain and may be missed on lumbosacral MRI.

        3. 3. Other infectious arthritis. Many other types of microorganisms, such as mycobacteria, fungi, and mycoplasma, can cause an infectious monoarthritis. Specific cultures and molecular studies should be ordered when clinical features raise concern for this type of infection. Infections of this type can be introduced from local trauma—even trauma perceived to be very mild. Obtaining a thorough history to include immunodeficiency states, zoonotic exposures, or relevant travel is needed to prompt studies for unusual organisms. Late Lyme disease is a rare but well-recognized cause of a monoarthritis, usually affecting the knee.

      3. iii. Distinguishing crystal from pyogenic arthritis. Although the clinical features and laboratory findings listed previously may make it seem easy to differentiate these conditions, this is not necessarily straightforward. Crystal arthritis can be mistaken for infection when patients present with systemic symptoms, high fever, and leukocytosis. Similarly, joint fluid leukocyte counts in crystal arthritis can be as high as in septic arthritis, and false-negative crystal analysis is common. Inflammation in crystal arthritis—especially gout—may also spread beyond the affected joint into adjacent soft tissues, mimicking spread of infection. Finally, some patients may have both crystal and pyogenic arthritis because arthritic joints are predisposed to infection.

      4. iv. Trauma or hemarthrosis. Hemarthrosis, either from local trauma or a coagulation disorder, can manifest as a monoarthritis. Large, peripheral joints such as the elbow and knee are usually affected. Hemarthrosis is readily recognizable based on the clinical background (e.g., trauma, coagulopathy, bleeding disorder) and joint fluid analysis that includes a high number of red blood cells.

      5. v. Other causes. Neoplasms of joints are rare but do occur. Combined surgical and oncology input is often necessary in managing these conditions.

  8. D. Oligoarthritis. Oligoarthritis is a clinical term that refers to involvement of a small number of joints, typically four or fewer joints at the same time. While diseases causing an oligoarthritis overlap with those causing monoarthritis and polyarthritis, it is a clinically distinctive syndrome whose recognition can be diagnostically helpful. Oligoarthritis is often associated with reactive arthritis.

      1. i. Reactive arthritis. The former name for this condition, Reiter’s syndrome, was characterized by three features: arthritis, urethritis, and conjunctivitis. The term “reactive arthritis” is now used to describe a distinct syndrome in which arthritis occurs a week or more after a systemic infection. Chlamydia trachomatis is an important associated infection that may need to be treated when present. However, Clostridium difficile, Campylobacter species, and a range of other gastrointestinal (GI) pathogens have also been identified as causes of reactive arthritis after a GI illness. The classic presentation of reactive arthritis is typically sudden-onset oligoarthritis affecting lower limb joints in an asymmetric pattern. However, any peripheral joint can be affected. Additionally, axial involvement and inflammation on entheses (insertion sites of tendons into bone), as well as joints, may occur. There is nothing diagnostic about the arthritis itself, and laboratory testing and imaging in early disease are normal. Patients may develop a range of extraarticular manifestations affecting the eye, genitourinary tract, skin, and other organs. Most patients recover spontaneously, but some develop ongoing disease and require treatment with potent antirheumatic medications.

      2. ii. Spondyloarthritis. This term is used to describe a group of overlapping conditions characterized by arthritis that affects both axial and peripheral joints. Peripheral joint involvement is often in the form of an asymmetric oligoarthritis, and inflammation of entheses is common. Reactive arthritis, in fact, is a type of spondyloarthritis, as are psoriatic arthritis, ankylosing spondylitis, and inflammatory bowel disease (IBD)–associated arthritis. Axial involvement often commences in the sacroiliac joints and may progress proximally. Although the peripheral arthritis tends to affect lower limb joints such as the knee and ankle, any combination of joint involvement can occur. Painful swelling of the insertion of the Achilles tendon is a classic example of the enthesitis that may also affect tendon insertion sites. Painful swelling of entire digits (dactylitis) caused by inflammation in tendon sheaths may occur. Apart from clinical problems caused by underlying diseases (e.g., IBD, psoriasis), patients may also develop uveitis.

      3. iii. The diagnosis of spondyloarthropathies is challenging. Laboratory studies are nonspecific, and there is no definitive test. HLA-B27 testing may help in making the diagnosis of ankylosing spondylitis because the prevalence of HLA-B27 is very high (>90%) in this condition. However, the prevalence of HLA-B27 positivity is too low in other types of spondyloarthritides to have positive predictive value. Diagnosis is therefore primarily based on clinical features and imaging. Some patients with spondyloarthritis may have mild disease with no detectable imaging abnormalities. Others have subtle changes only found on MRI. Some develop progressive radiographic changes in axial and peripheral joints, with a mix of proliferative and destructive changes that are diagnostic.

      4. iv. Sarcoid. Arthritis from sarcoidosis is less frequent than manifestation of the disease in other sites (e.g., mediastinum, lung, skin, eye). Löfgren’s syndrome refers to a triad of hilar adenopathy, erythema nodosum, and an acute arthritis that usually involves both ankles. This clinically distinct syndrome resolves spontaneously, and usually no diagnostic studies (beyond chest imaging) are required. Rarely, sarcoid may cause a chronic and more widespread form of arthritis in the context of severe systemic disease affecting other organ systems. The diagnosis of sarcoid arthropathy thus requires identification of the disease process in other organs.

      5. v. Gout. Most gout presents as podagra or a related form of monoarthritis. However, it is not uncommon for gout to present as an oligoarthritis, especially in an acutely ill, hospitalized patient. Pseudogout, on the other hand, is much more likely to be restricted to a single joint.

      6. vi. Infection. Gonococcal infection can manifest with an asymmetric oligoarthritis, most commonly affecting the wrists, knees, and ankles. Pyogenic bacterial arthritis and fungal arthritis may affect multiple joints. In these cases, evaluation for a hematogenous source of infection (e.g., endocarditis) is warranted.

      7. vii. Rheumatoid arthritis (RA). RA typically manifests as a polyarthritis. However, it is such a prevalent condition that atypical presentations (such as an oligoarthritis) are common.

  9. E. Polyarthritis (more than four joints). This is the most common presentation of arthritis in the ambulatory care setting. Chronic inflammatory polyarthritis is often attributed to RA or a spondyloarthritis, but it can present acutely and be associated with other diseases.

      1. i. Infection. While an uncommon cause of an inflammatory polyarthritis, it is important to consider in patients presenting with new-onset arthritis.

        1. 1. Viral arthritis. Usually presents as part of an acute febrile illness and often causes a symmetric arthritis affecting multiple small peripheral joints. Sometimes, viral arthritis may affect more proximal joints, but the characteristic feature is that these resolve spontaneously over days to weeks. Diagnosis of viral arthritis is often made from these clinical features alone, but some cases are caused by parvovirus B19 infection, which can be confirmed by antibody or molecular testing. It is likely that many viruses associated with acute polyarthritis have not been identified.

        2. 2. Hepatitis C infection can cause a chronic polyarthritis and is especially notable because it can mimic the arthritis of RA. Additionally, chronic hepatitis C infection is one of the most common causes of a false-positive RF.

        3. 3. Some cases of viral arthritis can be linked to other viruses such as hepatitis B (as part of the prodrome of infection), HIV, mosquito-borne alphaviruses and flaviviruses, and enteroviruses. With the exception of specific microbial serology, laboratory testing is usually not helpful in diagnosing viral arthritis, and radiographic imaging is normal.

        4. 4. Other microorganisms. Bacteria that cause infective monoarthritis and oligoarthritis may cause a polyarthritis.

      2. ii. Acute rheumatic fever. Rheumatic fever in the (young) adult population is rare but does occur and needs to be kept in mind (see Chapter 53). Arthritis is a very early manifestation of rheumatic fever—often occurring within 3 weeks of group A Streptococcus infection. The characteristic feature of the arthritis is that it is transient and migratory, that is, it lasts for a few days and moves from joint to joint. Large peripheral joints are typically affected. Acute rheumatic fever should thus always be on the differential diagnosis of an acute-onset polyarthritis, especially when the distinctive combination of clinical and laboratory features appear. A related syndrome of poststreptococcal arthritis shares some features of the arthritis related to rheumatic fever.

      3. iii. RA is a common condition (1% prevalence in US) that occurs in all age groups. RA typically causes a symmetric, peripheral, small joint arthritis, but it is such a common disease that many atypical cases are seen. In addition to causing a monoarthritis and oligoarthritis, RA may also cause migratory and palindromic (intermittent) disease. The cervical spine may be affected; patients with RA should have flexion-extension spine films when considering surgical procedures that require intubation. If the hands are affected, the most common joints of involvement are the metacarpophalangeal and proximal interphalangeal joints; however, the distal interphalangeal joints are spared. Wrist involvement is also common. Corresponding regions in the ankles and feet (metatarsophalangeal, proximal interphalangeal) are also affected, as can be larger, more proximal joints.

        Physical examination may demonstrate an acute arthritis with a combination of soft tissue swelling (from synovial fluid or synovial tissue) with squeeze tenderness, and if chronic, there may also be bony hypertrophy and deformities.

        Extraarticular involvement in RA is also common. Acute inflammation in tendon sheaths (tenosynovitis) is clinically similar to the associated arthritis and is especially likely to affect the hand or wrist regions. Rheumatoid nodules are firm, nontender, discrete lesions; are usually smaller than 1 cm but can be of any size; and are most often found in the olecranon region but may occur elsewhere in the skin or internally (such as in the lungs). RA is also associated with a very large range of possible complications affecting virtually any body system.

        Laboratory testing is helpful in confirming the diagnosis of RA. RF is a moderately sensitive test (present in ~70% of RA patients) but lacks specificity; thus, false-positive results are common. The CCP Ab test is less sensitive than RF (~40%) but has the benefit of much higher specificity (>90%); false-positive results do occur but are less common. Both these tests done together can be especially helpful; therefore, a patient with a clinically RA-like arthritis, who is both RF and CCP Ab positive, is virtually certain to have RA. It is also important to note that some patients with RA (~30%) are seronegative at diagnosis and may remain seronegative indefinitely. These patients otherwise develop very typical RA signs and symptoms.

        Radiographs are normal early in the course of RA, but destructive lesions with typical juxtaarticular erosions and cartilage loss can develop quickly. Most untreated patients will have erosive disease after 2 years. Erosive changes are irreversible and represent the clinical rationale for getting patients onto effective disease-modifying treatment early in the course of the disease. Ultrasound and MRI are more sensitive than radiographs for detecting destructive disease but are not usually required.

        There are published formal criteria for the diagnosis of RA (2010 American College of Rheumatology/European League Against Rheumatism). These are important for consistency in clinical research studies but have limited clinical utility. In general, these criteria depend on excluding other possible causes of arthritis; making a finding of definite joint inflammation; and composite scoring from consideration of the pattern and number of joints affected, serology, an acute phase reaction, and disease for more than 6 weeks (to exclude the viral arthritis cases). Discussion of comprehensive RA treatment is outside the scope of this chapter. However, two related but distinct aspects of management merit highlighting.

        Symptom control. Apart from use of analgesics, painful arthritis can be suppressed in the short term with nonsteroidal antiinflammatory drugs (but these may be contraindicated in many patients because of comorbidities), corticosteroid injection into one or a few affected joints, or systemic corticosteroids (given in the lowest possible effective dose).

        Disease-modifying antirheumatic drugs (DMARDs). All patients with RA need to be established on one or more DMARDs to suppress RA disease activity to the extent possible. This may consist of established treatments (such as hydroxychloroquine or methotrexate), new combinations of old drugs (such as hydroxychloroquine-methotrexate-sulfasalazine), or any of the newer medications that are based on interfering with specific immunologic/inflammatory pathways. Physical therapy and occupational therapy also have a very important role in helping to prevent disability in patients with chronic arthritis.

      4. iv. Spondyloarthritis. Spondyloarthropathies are often diagnosed through their unusual combination of axial and peripheral joint disease, but some patients may have subtle or no axial disease, so other causes of peripheral polyarthritis such as RA will need to be investigated. This is particularly an issue in psoriatic arthritis and the arthritis of inflammatory bowel disease. If patients with these conditions have polyarthritis, it tends to be less symmetric and with more proximal joint involvement than is observed in RA. Involvement of the distal interphalangeal joints of the hands (which does not occur in RA) can be a useful pointer. Finding an enthesitis is also helpful because this is an important feature of a spondyloarthritis. However, spondyloarthritic polyarthritis can exactly mimic the clinical pattern of RA joint involvement.

        Extraarticular clinical features can also be diagnostically helpful. GI symptoms or an established diagnosis of IBD would point toward IBD-associated spondyloarthritis. Similarly, a psoriatic rash (that may have to be sought) or a background or family history of psoriasis can point toward psoriatic arthritis. Uveitis occurs in patients with spondyloarthritis (but also in RA).

        Laboratory studies and imaging were discussed previously, but it is worth reiterating that there are no diagnostic laboratory tests for any peripheral spondyloarthritis and specifically that HLA-B27 testing is of little value. Radiographic imaging can be very helpful because it may demonstrate features unique to spondyloarthropathies. There is also a role for ultrasound of peripheral joints and for MRI of axial joints to reveal subtle disease.

      5. v. Gout. Polyarticular gout is much less common than monoarticular or oligoarticular disease but accounts for about 20% of cases. It tends to occur in patients with untreated gout secondary to other conditions and is associated with relatively higher uric acid levels. Patients can be systemically ill with pseudoseptic clinical features, leading to diagnostic confusion.

      6. vi. Systemic diseases. These are considered in Chapter 75. Many systemic autoimmune diseases have arthritis as part of their clinical manifestations, but in only some of them is arthritis a major feature. This is most often the case in SLE, but in SLE, as in these other conditions, it is not the specific features of the arthritis that are distinctive but the combination of an arthritis with multiple other clinical features that suggests a systemic disease process.

Suggested Further Readings

Aletaha D, Neogi T, Silman AJ, et al. 2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum 2010;62:2569–81.Find this resource:

Lim S, Lu N, Oza A, et al. Trends in gout and rheumatoid arthritis hospitalizations in the United States, 1993–2011. JAMA 2016;315:2345–7.Find this resource:

Mulay SR, Anders H-J. Crystallopathies. N Engl J Med 2016;374:2465–76.Find this resource:

Ritchlin CT, Colbert RA, Gladman DD. Psoriatic arthritis. N Engl J Med 2017;376:957–70.Find this resource:

Rosenthal AK, Ryan LM. Calcium pyrophosphate deposition disease. N Engl J Med 2016;374:2575–84.Find this resource: