Diagnostic Imaging of Rheumatologic Disorders

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[edit] Diagnostic Imaging of Rheumatologic Disorders

James M. Coumas

Brian A. Howard

Eric W. Jacobson

The final diagnosis of immune-mediated rheumatologic disease is based on integration of clinical features with laboratory and imaging results.Rheumatologic screening tests should be ordered selectively based on the patient's clinical presentation.Such tests are frequently nonspecific, however, and results must be interpreted in the context of the particular clinical situation.Joint aspiration (arthrocentesis) is performed for both diagnostic and therapeutic purposes.Synovial fluid analysis is important in the evaluation of acute or chronic arthropathy of unknown cause.In general, patients with acute monoarthritis require joint aspiration to exclude joint infection (septic arthritis) or to confirm the presence of a crystal-induced arthropathy.Long-acting corticosteroid preparations can be injected directly into a noninfected joint to relieve the inflammatory arthritic symptoms.Selective imaging studies are important in the evaluation of the articular components of rheumatologic disorders.Conventional radiographs help distinguish inflammatory from noninflammatory arthropathies.Certain observed radiographic features help differentiate various arthritides.^[1][2][3]

[edit] LABORATORY TESTS

[edit] Acute-phase Response

The acute-phase response refers to the change in systemic and metabolic factors that occurs in response to inflammatory stimuli such as infection or tissue injury.The most dramatic aspect of the acute-phase response is a rapid change in the concentration of certain plasma proteins produced primarily in the liver, including increased production of fibrinogen, haptoglobin, C-reactive protein, and serum amyloid A.The erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are used most often to assess for an acute-phase response.

[edit] Erythrocyte Sedimentation Rate.

Erythrocyte sedimentation depends on the ability of red blood cells (RBC) to aggregate and form linear clumps (rouleaux).When large amounts of acute-phase proteins (e.g., fibrinogen) are produced, binding of these proteins to erythrocytes neutralizes the negatively charged, repulsive electrostatic forces and allows the erythrocytes to aggregate and thus sediment more quickly.This forms the basis of the ESR.The more rapidly the RBCs sediment, the higher the ESR.The normal range for the Westergren method is usually less than 20 mm/hour.This range may vary among laboratories.

The ESR tends to be higher in women than in men, probably because androgens in men may lower the ESR.ESRs increase steadily with age, presumably due to increased levels of fibrinogen.They also can increase in the presence of certain medications (e.g., oral contraceptives, heparin).

The ESR may be falsely lowered by any condition that interferes with the ability of RBCs to aggregate (Box 123-1), including diseases in which (1) erythrocyte shape is abnormal, thus interfering with rouleaux formation (e.g., sickle cell disease, hereditary spherocytosis, anisocytosis); (2) hepatic dysfunction is present, which impairs production of acute-phase proteins; and (3) fibrinogen is consumed (such as disseminated intravascular coagulation).Corticosteroid preparations and high-dose antiinflammatory agents may lower the ESR.Congestive heart failure and diseases associated with an extreme elevation of the white blood cell (WBC) count (e.g., chronic lymphocytic leukemia) also may be associated with low ESRs.

The ESR is a nonspecific test; it can be elevated in many conditions associated with inflammation and tissue necrosis.The disease states most often associated with dramatically elevated (more than 100 mm/hour by Westergren technique) ESRs are malignancy (10%), collagen vascular disease (25%), and infection (50% to 60%).A thorough history,physical examination, and routine laboratory screens usually suggest the correct diagnosis.

[edit] C-Reactive Protein.

CRP is one of the acute-phase proteins.The properties of CRP include the ability to bind to phosphocholine, to activate the complement cascade, and to interact with polymorphonuclear neutrophil leukocytes (PMNs).It tends to rise and fall quickly in response to acute-phase stimulation.

The CRP and ESR do not always correlate.CRP is a direct measure of one acute-phase protein, whereas the ESR reflects multiple processes.The CRP concentration rises and falls rapidly in response to inflammation or necrosis.Therefore it accurately reflects acute changes in clinical status.The ESR tends to rise more slowly and remain elevated for prolonged periods in response to acute-phase stimulation.Thus CRP level may be more indicative of a patient's clinical status at any point in time.

As with ESR, CRP can be used to assess for underlying inflammation or necrosis.It can also be used to follow the course of a disease and response to treatment.In chronic inflammatory states, CRP levels rarely exceed 6 to 8 mg/dl.Levels greater than this should suggest superimposed infection.Interestingly, CRP levels are frequently normal in active systemic lupus erythematosus (SLE).Therefore, when CRP levels are elevated, infection should be considered.

[edit] Rheumatoid Factor

Rheumatoid factor (RF) is an antibody directed against the Fc portion of human immunoglobulin G (IgG).The classic RF is an IgM antibody; however, all immunoglobulin classes of RF have been described.Only IgM RF is assayed routinely.

Several methods can be used to detect IgM RF.The most common are the latex fixation agglutination assay (LF) and the sensitized sheep RBC agglutination assay (SSCA).The LF and SSCA are considered to be positive at a dilution of 1:20 or greater.The importance of RF lies in its incidence and distribution in disease, its association with the course and severity of rheumatoid arthritis (RA), and its possible pathogenic role in RA.RF is positive in approximately 80% of patients with RA; however, it is nonspecific and is also present in many other diseases (connective tissue diseases, chronic inflammatory diseases, certain malignancies) as well as in up to 5% of the normal population, especially the elderly (Box 123-2).It is often present in high titers in mixed essential cryoglobulinemia.

The probability that a patient has RA increases in direct proportion to the titer of RF.In patients with RA, high titers of RF correlate with more severe and active joint disease, as well as rheumatoid nodules, systemic complications, and a poorer prognosis.Titers are not typically helpful in following the course of the disease over time.RF's role in the pathogenesis of RA is unclear.Possible pathophysiologic roles include (1) enhanced clearance of immune complexes, (2) increased complement fixation, (3) enhanced inflammatory response, and (4) antiviral properties.The physician should order RF test when considering a diagnosis of RA.A positive result supports the diagnosis of RA if the clinical features are consistent.

[edit] Antinuclear Antibodies

Antibodies to various nuclear (or cytoplasmic) antigens are found in the serum of many patients with systemic rheumatic diseases.A search for antinuclear antibodies (ANAs) may beappropriate as a screen for autoimmune disease if the clinical situation suggests an autoimmune illness.Beside supporting a diagnosis of autoimmune disease, ANAs may define a specific subset of disease based on staining patterns and further identification of the specific target antigen.

ANAs are detected by an indirect immunofluorescent assay (IFA).Many different tissues or cell lines may be used as a substrate for this assay.If ANAs are present, the pattern and intensity of nuclear staining are documented.ANAs of all immunoglobulin classes will be detected, but IgM and IgA antibodies are detected with less sensitivity than IgG.False-positive tests are common with serum dilutions of less than 1:20; positivity at lower titers is considered a negative result.

ANAs are positive in more than 95% of patients with SLE and thus are an excellent screening test but are nonspecific for SLE.ANAs are present in other autoimmune diseases, chronic infections, certain neoplasms, chronic liver disease, pulmonary fibrosis, hypergammaglobulinemia, multiple sclerosis, and after other illnesses.ANAs can be produced transiently after viral illnesses or burns and can be induced by certain drugs, with or without associated clinical symptoms (Table 123-1).Procainamide is the medication most often associated with ANAs; up to 80% of patients taking this medication exhibit ANA.Only about 20% of these patients, however, experience a lupuslike illness.ANAs also are seen in normal people; the incidence increases steadily with age.

Table 123-1 Agents Associated With Antinuclear Antibodies (ANAs)

Four main staining patterns are observed with ANAs and suggest the etiology of the ANA.One pattern is homogeneous (or diffuse), in which the entire nucleus is fluorescent.It is produced by antibodies to deoxyribonucleoprotein (or the DNA-histone complex) and is nonspecific.In the speckled pattern the nucleus appears spotted.The speckled pattern occurs with antibodies directed against the extractable nuclear antigens (ENAs), which include Smith (Sm), ribonucleoprotein (RNP), Ro (formerly SS-A), and La (formerly SS-B).Sm is highly specific for SLE but found in only 20% to 30% of cases.RNP is nonspecific but found in high titer in mixed connective tissue disease.Ro and La are strongly associated with Sjögren's syndrome but also are nonspecific.A third pattern is rim or peripheral, a pattern produced by antibodies directed against double-stranded (native) DNA, which is specific for SLE.The outer rim of the nucleus is stained.In the last pattern, nucleolar, the nucleoli are stained.This pattern is most often seen in scleroderma (Table 123-2).

Table 123-2 Common Staining Patterns of ANAs

The physician should order an ANA when considering a connective tissue disease.As with other rheumatologic tests, the result must be interpreted in the context of the particular clinical situation.Typically, the higher the titer, the more significant is the finding of a positive ANA.Rim or nucleolar patterns are more specific, and their presence indicates SLE or scleroderma, respectively.Speckled and homogeneous patterns are less specific.A positive speckled result can be further evaluated by ordering an ENA panel.Anti–double-stranded deoxyribonucleic acid (aDNA) and complement levels can provide additional important information when pursuing a workup of a positive ANA.

[edit] Anti–double-stranded DNA

aDNA is found almost exclusively in non–drug-induced SLE.Antibody titers often correlate with clinical disease activity, although changes may precede relapse or remission by several months.aDNA also correlates with development of lupus nephritis, in which it probably plays a direct pathogenic role.

[edit] Complement

The complement system comprises a group of distinct glycoproteins involved in clearance of immune complexes and microorganisms from the circulation and promotion of the inflammatory response.The measurement of complement factors and function identifies complement-consuming diseases and hereditary complement deficiencies.A screening test for complement levels is the quantitative CH₅₀photometric assay.The dilution of the patient's serum that will induce 50% lysis of antibody-coated sheep RBCs is measured.For suspected complement deficiency, CH₅₀will be low.C₃and C₄may be measured directly if specific quantitation is desired.

Complement glycoproteins are acute-phase reactants;elevated levels may be present in several conditions, including many inflammatory diseases.Elevations also occurin noninflammatory diseases (e.g., diabetes mellitus), obstructive jaundice, and acute myocardial infarction.

Decreased levels of complement factors can result from (1) decreased production, (2) in vivo activation and consumption of complement factors, or (3) in vitro consumption (e.g., postphlebotomy).The first mechanism is seen in hereditary factor deficiencies and severe liver disease.The second mechanism occurs with classic immune complex deposition and other infectious and inflammatory conditions.In vitro activation can be the result of poor specimen handling or the presence of complement activators in the serum.Inflammatory diseases result in normal complement levels when increased production equals in vivo consumption.

Complement levels are measured to assess for immune complex–mediated diseases such as active SLE and vasculitis.When immune complexes are produced, the classic pathway is activated.As complement is consumed, levels decline.Other disease states in which complement levels may be reduced by consumption include serum sickness, chronic active hepatitis, subacute bacterial endocarditis, glomerulonephritis, malaria, and mixed essential cryoglobulinemia.In SLE and vasculitis, complement levels may correlate with disease activity.Patients with inherited complement deficiencies also have low levels of complement.Some complement deficiencies (e.g., C₄) have been associated with autoimmune diseases, possibly from the inability to clear immune complexes from the circulation.Deficiencies of factors C₅through C₉predispose to recurrent infections with encapsulated microorganisms (e.g., Neisseria species), presumably because of reduced ability to lyse these organisms.

[edit] Antiphospholipid Antibodies

Antibodies to phospholipids are a heterogeneous group of "autoantibodies" that have been associated with thrombotic events.Some of the more common antigens to which these antibodies are produced include cardiolipin, phosphatidylserine, and phosphatidic acid.They are uniformly present in the primary antiphospholipid syndrome, which is characterized by venous and arterial thrombosis, recurrent fetal loss (typically in the second or third trimester), thrombocytopenia, and Coombs-positive hemolytic anemia.These antibodies are seen frequently in SLE (20% to 30%) and may be associated with certain drugs and other chronic inflammatory and infectious diseases.

Multiple laboratory assays may detect antiphospholipid antibodies.Their presence may be indicated by a false-positive Venereal Disease Research Laboratories test (VDRL) or prolongation of clotting time, as measured by the partial thromboplastin time (PTT) or Russell's viper venom time (RVVT).Antiphospholipid antibodies bind to the prothrombin activation complex (which consists of activated factor X [Xa], factor V, factor II [prothrombin], ionized calcium, and a phospholipid template) and delay the conversion of prothrombin to thrombin.Prolongation of in vitro clotting times is a paradox because these antibodies predispose to thrombosis in vivo.Antiphospholipid antibodies also may be detected by an enzyme-linked immunosorbent assay (ELISA), which identifies the specific subclass of immunoglobulin present (IgG, IgA, or IgM).Most pathogenic antiphospholipid antibodies are of the IgG variety.

The physician should consider screening for antiphospholipid antibodies when a patient presents with recurrent arterial or venous thrombi, emboli, and recurrent second-or third-trimester miscarriages.Screening may be especially important in younger patients with myocardial infarction or cerebrovascular accident in the absence of classic risk factors.

[edit] Antineutrophil Cytoplasmic Antibodies

Antineutrophil cytoplasmic antibodies (ANCAs) are directed against cytoplasmic antigens (lysosomal enzymes) of neutrophils.ANCAs may be detected using IFAs similar to those used to detect ANAs.Two different granular immunofluorescent patterns are typically described: (1) staining in granules in the peri nuclear region of the neutrophil (P-ANCA) and (2) granular staining more diffusely throughout the cytoplasm (C-ANCA).ANCAs are used to screen for the presence of vasculitis.C-ANCAs are strongly associated with Wegener's granulomatosis.P-ANCAs are less specific but have been described in patients with systemic necrotizing vasculitis associated with glomerulonephritis (e.g., polyarteritis nodosa) and idiopathic crescentic glomerulonephritis.

[edit] Lyme Antibodies

See Chapter 141 .

[edit] HLA-B27

See Chapters 133 and 137 .

[edit] ARTHROCENTESIS

Arthrocentesis is a safe and relatively simple procedure in which a needle is introduced into the joint space to remove synovial fluid.It is an essential part of the evaluation of any arthritis of unknown cause and is required to diagnose an infection in the joint.Arthrocentesis also can be used therapeutically, either to drain an inflamed joint or to introduce long-acting corticosteroids into the joint.

Joint aspiration requires sound knowledge of the joint anatomy, including the bony and soft tissue landmarks used for joint entry.Strict aseptic technique is crucial to minimize the risk of infection.The physician must practice universal precautions.The procedure is accomplished more easily when the patient is able to relax the muscles surrounding the joint.

Absolute contraindications to performing arthrocentesis include local infection of the overlying skin and severe coagulopathy.If coagulopathy is present and if septic arthritis is suspected, every effort should be made to correct the coagulopathy (with fresh-frozen plasma or alternate factors) before joint aspiration.Therapeutic anticoagulation is not an absolute contraindication, although every effort should be made to avoid excessive trauma during the aspiration.

The major complications of arthrocentesis include iatrogenically induced infection and bleeding.Both are extremely rare.The risk of infection after arthrocentesis is less than 1 in 10,000.^[1] Correction of prominent coagulopathy before arthrocentesis reduces the risk of excessive hemorrhage.

The knee is one of the most accessible joints for aspiration.The physician should describe the procedure to the patient, including risks of complications.The entry site should be cleaned with an iodine-based antiseptic solution.After the area dries, it should be wiped once with alcohol.Local anesthesia (subcutaneous lidocaine or topical ethyl chloride) may be applied.With the patient supine and the knee fully extended, the knee joint is entered medially, under the patella (Fig.123-1).The joint should be fully drained if possible.The needle is then removed, and pressure is applied to thesite until bleeding has stopped.The area is cleaned with alcohol and a bandage applied.Other joints that may be aspirated include shoulder, elbow, and ankle (Figs.123-2,123-3 through 123-4).

Figure 123-1 Technique for arthrocentesis of the knee: medial approach.

Figure 123-2 Technique for arthrocentesis of the shoulder: anterior (A) and posterior (B) approach.

Figure 123-3 Technique for arthrocentesis of the elbow.

Figure 123-4 Technique for arthrocentesis of the ankle: medial and lateral approach.

Once fluid is obtained, synovial fluid analysis is performed to distinguish noninflammatory from inflammatory fluid.Less than 2000 WBCs/mm³is consistent with noninflammatory fluid, as in osteoarthritis.Greater than 2000 WBCs/mm³indicates inflammatory fluid (Box 123-3).In addition to absolute nucleated cell count, synovial fluid is divided into various categories based on the gross appearance, viscosity, WBC differential, and culture results (Table 123-3).

Table 123-3 Joint Fluid Characteristics

Synovial fluid analysis begins with bedside observation of the fluid.Normal synovial fluid is colorless.Both noninflammatory fluid and mildly inflammatory fluid appear yellow or straw colored.Septic effusions frequently appear purulent and whitish.Hemorrhagic effusions appear red or brown.The clarity of synovial fluids depends on the number and types of cells or particles present.To test clarity, a glass tube filled with synovial fluid is placed in front of black print on a white background.If the print is easily read, the fluid is transparent, indicating normal and noninflammatory fluid.If the print is distinguishable from the background but is not clear, the fluid is translucent, indicating inflammatory effusions.Grossly inflammatory, septic, and hemorrhagic fluids are opaque, preventing any visualization through the tube.

Synovial fluid viscosity, the result of hyaluronic acid content, also can be assessed at the bedside.Degradative enzymes (e.g., hyaluronidase) released from inflammatory cells produce a thinner, less viscous fluid.Viscosity can be assessed using the string sign while adhering to universal precautions.A drop of fluid is allowed to fall from the end of the needle or syringe, and an estimate is made of the length of the continuous "string" that forms.Normal fluid forms at least a 6-cm continuous string.Inflammatory fluid will not form a string; it drops like water dripping from a faucet.

After bedside assessment, the synovial fluid is sent to the laboratory for a cell count and differential, crystal analysis, Gram's stain, and culture.Cell counts approaching 100,000 WBCs/mm³suggest septic arthritis or a crystal-induced arthritis.Normally, synovial fluid has a predominance oflymphocytes.The percentage of PMNs increases with inflammatory conditions.In most circumstances an infected joint has synovial fluid with more than 75% PMNs (see Table 123-3).

All fluid should be assessed for the presence of crystals, specifically monosodium urate and calcium pyrophosphate dihydrate, using a compensated polarized light microscope (see Chapter 136 ).If the fluid cannot be examined immediately, refrigeration of the fluid helps preserve the crystals.

Gram's stain and culture should be performed on most synovial fluid specimens.Cultures for aerobic and anaerobic bacterial organisms are performed routinely.In certain patients (e.g., with chronic monoarticular arthritis), fluid may be cultured for mycobacteria and fungi.If disseminated gonorrhea is suspected, fluid should be plated directly onto chocolate agar or Thayer-Martin media.A positive culture confirms septic arthritis.Other studies on synovial fluid (glucose, protein, complement) usually are not helpful.

Arthrocentesis also is used therapeutically.In septic arthritis, serial joint aspirations are required to remove accumulated inflammatory or purulent fluid.This allows serial monitoring of the total WBC count, Gram's stain, and culture to assess response to treatment and provides complete drainage of a "closed space." Inflammatory fluid contains many destructive enzymes that contribute to cartilage and bony degradation.Removal of the fluid may slow this destructive process.

Arthrocentesis is necessary for intraarticular injection of long-acting corticosteroid preparations.Corticosteroids also are frequently injected into soft tissue sites such as bursae, tendon sheaths, and myofascial trigger points (Figs.123-5,123-6 to 123-7).The dose of corticosteroid used depends on the size of the particular joint or soft tissue site being injected (Table 123-4).Three common corticosteroid preparations are triamcinolone diacetate (e.g., Aristocort Forte, Amcort), methylprednisolone acetate (e.g., Depo-Medrol, Medralone), and triamcinolone hexacetonide (e.g., Aristospan).Triamcinolone hexacetonide has a longer duration of action than the other two preparations.It is more likely to produce tissue atrophy or tendon injury and thus is mainly used for intraarticular injections.A local anesthetic such as lidocaine is frequently mixed with the corticosteroid before injection.

Figure 123-5 Technique for injection of the subacromial bursa.

Figure 123-6 Technique for injection of the trochanteric bursa.

Figure 123-7 Technique for injection of the anserine bursa.

Table 123-4 Dose of Corticosteroid Preparation Used in Injections

In addition to infection and bleeding, other complications must be considered with injection of a corticosteroid.Lipoatrophy and skin discoloration can occur with any of the steroid preparations, especially when injecting superficial soft tissue areas.Tendon rupture also can occur when injecting tendon sheaths, possibly from a weakening effect caused by the corticosteroid.A brief postinjection "flare" has been described in up to 1% to 2% of intraarticular injections.This complication generally occurs within the first few hours after the injection.If marked inflammatory symptoms persist for more than 24 hours, the joint or soft tissue region requires reaspiration to rule out infection.Finally, systemic absorption of the corticosteroid may be associated with a transient increase in blood glucose in patients with diabetes.

Repeated injections with corticosteroid preparations into the same joint (or soft tissue region) may accelerate connective tissue degradation.Generally, at least 3 to 4months should pass before reinjecting a site.If a single site is injected regularly for more than 1 year, an alternate approach should be considered.

[edit] RADIOLOGIC EVALUATION

The common rheumatologic joint disorders (arthropathies) have a characteristic radiologic appearance.Diagnostic imaging technologies, in order of accessibility, include conventional radiography, ultrasound, nuclear scintigraphy, conventional or computed tomography (CT), and magnetic resonance imaging (MRI).Each modality has strengths and limitations.Conventional radiographic imaging (plain film) remains the most cost-effective approach to the diagnosis, evaluation, and assessment of disease progression.The history, physical examination, radiographic assessment, and laboratory results play synergistic roles in the diagnosis of joint disease.^[1] Conventional radiographs should provide standardized views of the symptomatic joint of interest and the immediate regional articulations.A structured approach to plain film analysis and interpretation provides valuable information.A typical approach involves evaluation of anatomic alignment, bony mineralization, joint space or cartilage thickness, and adjacent soft tissues changes, the ABCs of radiographic evaluation.^[2][3][4]

[edit] Rheumatoid Arthritis

RA is a common rheumatologic disorder that affects synovial-lined joints, bursae, tendon sheaths, and ligamentous and tendinous bony attachments (entheses).Abnormalities of the adjacent soft tissues, bone, and cartilaginous joints may also be seen (see Chapter 133 ).In general, a symmetric polyarticular disorder principally involving the small and large joints of the appendicular skeleton is seen.Radiographic views of the hands and wrists are obtained in posteroanterior (PA) and semisupinated oblique (Norgaard) positions.Early observable findings include the following:

• Soft tissue swelling caused by periarticular inflammation.
  
• Juxtaarticular osteopenia, diminished bony trabecular pattern, and indistinct joint margin cortex.
  
• Uniform cartilage thinning resulting in symmetric joint space narrowing, with a predilection for the metacarpophalangeal (MCP), proximal interphalangeal (IP), radiocarpal, and midcarpal joint spaces.
  
• Early focal bony erosions at the peripheral margin of the joint adjacent to the capsular insertion, often referred to as thebare area. These erosions may appear as subtle craters or cystlike changes.In the wrist, erosions of the ulnar styloid process, radial styloid process, and middle scaphoid body are common.
  

Late observable changes include the following:

• Subluxation or dislocation of the MCP and IP joints caused by loss of ligamentous restraints.Classic swan-neck and boutonniére deformities and ulna deviation of the digits may be seen.At the wrist, radiocarpal and intercarpal subluxations result in various malalignment patterns.
  
• Generalized or diffuse osteopenia.
  
• Progressive articular surface erosion and destruction.
  
• Ankylosis of the carpal bones.
  
• Synovial cyst formation with dissection into the soft tissues.
  
• Soft tissue rheumatoid nodules.
  
• Superimposed degenerative arthritis.
  

Changes similar to those in the hand (Figs.123-8 and 123-9) occur in the feet in approximately 80% of patients.The knee, hip, elbow, and shoulder are the next most frequently involved joints.Approximately 60% to 70% of patients with RA develop neck symptoms (Fig.123-10).Erosions and symmetric narrowing of the posterior apophyseal joints of the cervical spine with accelerated diskal resorption lead to vertebral body subluxation at multiple levels ("staircasing") below C2.Craniocervical involvement may result in anterior or lateral atlantoaxial instability (transverse ligament insufficiency), which can be associated with cervical myelopathy.More ominously, cranial settling caused by occipitocervical joint destruction can predispose to medullary brainstem compression.^[1][5]

Figure 123-8 Rheumatoid arthritis.Early changes may be confined to juxtaarticular osteopenia (arrowheads), periarticular soft tissue swelling (arrows), and loss of normal fat fascial planes (i.e., navicular fat stripe) and superficial fat fascial border along ulna styloid.

Figure 123-9 Rheumatoid arthritis.Later changes include symmetric joint space narrowing (arrowhead), loss of subchondral cortical margin (small arrows), and marginal erosions (large arrows).

Figure 123-10 Rheumatoid arthritis of the axial skeleton.Osteopenia, "stair-casing" (multilevel subluxation), and erosion/subluxation at atlantoaxial articulation are common, with widening of atlanto-dens interval (white arrow).

Men with a high level of physical activity have a specific radiographic appearance termed robust rheumatoid arthritis, with prominent subchondral cyst formation produced by high intraarticular pressure and intravasation of synovial fluid or granulation tissue through fissures in the articular cartilage.Nuclear scintigraphy has been used to evaluate the "activity" of the inflammatory process and assess therapeutic management.More recently, MRI is used to evaluate the extent of synovial hypertrophy and pannus formation at specific targeted joints.Ultrasound is helpful in the differentiation of solid vs.fluid-filled juxtaarticular soft tissue masses.Common clinical indications for MRI include neurologic deficits, suggestive of compressive myelopathy or basilar invagination; suspicion of subarticular ischemic necrosis; and soft tissue abscess formation with or without associated osteomyelitis.

[edit] Seronegative Spondyloarthropathies

[edit] Psoriatic Arthritis.

This common skin disease may present as a monoarticular or distal interphalangeal (DIP) polyarticular disorder or spondylitis (see Chapter 137 ).Psoriatic arthritis involves the synovial-lined joints, tendon sheath, and periarticular soft tissues, with specific entheseal involvement of ligamentous and tendinous attachments to bone.Radiographic articular changes may precede the appearance of any skin disease.However, the frequency of joint disease increases with chronicity and severity of the psoriatic skin manifestations.Plain film radiographs of the hand and wrist or feet may show classic radiographic features.^[1] The distribution of joint involvement is distinct from RA.Early findings may include the following:

• Normal plain radiographs.
  
• Fusiform periarticular soft tissue swelling typically confined to a single IP joint without associated bony changes.Diffuse involvement of digits, joints, tendon sheath, and soft tissues is referred to as asausage digit.
  
• Maintenance of normal bone mineralization.
  
• Asymmetric or unilateral joint involvement.
  
• Distal phalangeal tuftal erosions.
  

Later radiographic changes include the following:

• Joint space narrowing involving the DIP and proximal interphalangeal (PIP) joints.
  
• Bone proliferation, typically adjacent to sites of articular erosion.An irregular, poorly defined marginal surface bony accretion, proliferativeenthesitis indicates reactive change at the insertion of the capsule, ligament, and tendon.
  
• Periosteal reaction along the diaphyseal shaft(periostitis).
  
• Erosions are marginal but may extend subchondrally to produce central erosions with apparent "widening of the joint."
  
• Progressive joint surface destruction.Proximal articular surface tapering results from marginal erosions.Distal articular surface central erosions and enthesitic proliferation lead to the classic pencil-in-cup radiographic deformity.
  
• Subluxation with distal-proximal telescoping of digit.
  
• Bony ankylosis of the digits.
  

Although the pattern of distribution of joint disease is variable, characteristic areas of involvement include the DIP and PIP joints (Figs.123-11 and 123-12).A high incidence of the first MCP joint involvement is noted.Wrist involvement usually follows that of the hand.Forefoot changes parallel those of the hand, with bilateral and asymmetric disease of the IP joints but a predilection for the IP joint of the great toe.In the hindfoot, characteristic erosive changes of the calcaneus are seen around the retrocalcaneal bursa.Proliferative enthesopathy, or poorly defined bony calcaneal spurs, is seen at the insertion of the plantar aponeurosis to the calcaneus^[1][4](Fig.123-13).

Figure 123-11 Psoriatic arthritis.Erosions involving distal and proximal interphalangeal joints (white arrows) with associated periosteal reaction and proliferative change (black arrows). Note pencil-in-cup configuration.

Figure 123-12 Psoriatic arthritis.Bony ankylosis (white arrows), maintenance of bone mineralization, and localization to target sites (interphalangeal involvement) help differentiate this arthritis from rheumatoid arthritis.

Figure 123-13 Psoriatic arthritis.Periostitis along plantar calcaneus (black arrows) and poorly delineated erosion (white arrow) support the diagnosis.

Classic involvement of the axial skeleton occurs principally in the thoracolumbar spine, with paravertebral ossification that is bulky and asymmetric.Vertically oriented, lateral paravertebral spondylophytes are different from the osteophytes of degenerative disk disease and the syndesmophyte of ankylosing spondylitis.In the cervical spine, posterior apophyseal joints narrow, erode, and ankylose.Anteriorly, however, erosive diskovertebral changes may be combined with osseous bridging, which is more typical of syndesmophytic ossification similar to other seronegative spondyloarthropathies.At the atlantoaxial articulation, erosive changes and anterolateral instability mimic RA.

Up to 50% of patients with psoriatic arthritis develop bilateral asymmetric radiographic changes at the sacroiliac (SI) joints.Superficial and deep erosions of the iliac more than the sacral joint surfaces are associated with reactive subchondral sclerosis.Erosive changes are typically confined to the synovial-lined aspect of the SI joint.SI and other pelvic ligaments may ossify from underlying enthesopathy.Psoriatic arthritis usually can be differentiated from RA on plain radiographs by the presence of periosteal and entheseal new bone formation, IP joint predilection, distal tuftal resorption, bony ankylosis, and lack of juxtaarticular demineralization.Differentiating psoriatic arthritis from other seronegative spondyloarthropathies, however, may prove difficult.As in RA, further imaging modalities may be indicated as follows:

• Total-body bone scan to screen for other sites of activity.
  
• Spinal MRI to assess neuroaxis compromise.
  
• Joint MRI to exclude complications (e.g., osteonecrosis, osteomyelitis, deep abscess, occult trauma).
  
• CT scan to assess bony destruction or confirm SI joint disease.
  
• Ultrasound to assess Baker's cyst–like masses vs.deep venous thrombosis.
  

[edit] Reiter's Syndrome.

Reiter's disease is a reactive arthritis with a typical clinical syndrome consisting of the triad of urethritis, conjunctivitis, and inflammatory arthritis.The arthritic component of this seronegative spondyloarthropathy can be identified on plain films (see Chapter 137 ).The joint disease is an asymmetric, unilateral or bilateral polyarticular disorder of synovial-lined joints, with entheses and a predilection for involvement of the feet (lower extremities).Early radiographic changes seen in the metatarsophalangeal (MTP) and IP joints of the forefoot include the following:

• Periarticular soft tissue swelling with early demineralization.Normal-appearing plain radiographs may be seen with resolution of the acute inflammatory phase.
  
• Symmetric joint space narrowing.
  
• Periostitis is often poorly defined or "fluffy" in appearance at joint margins or along the shaft.
  
• Proliferative enthesopathy at the Achilles tendon and plantar aponeurosis attachments to the calcaneus, resulting in erosions and spurs.
  
• Bursal and tendon sheath inflammation, with a predilection for the retrocalcaneal bursa.
  
• Erosions are marginal early in the disease process.Narrowing may appear asymmetric but ultimately leads to uniform joint space narrowing.
  

Late radiologic findings include the following:

• Uniform joint space loss at multiple articulations.
  
• Bulky, well-defined enthesophytes.
  
• Subluxation about the MTP joints, referred to as aLaunois deformity.
  

Reiter's syndrome may involve the larger joints of the lower extremities (e.g., knee, ankle) but tends to spare the hip.Upper extremity involvement is less common and shows a predilection for the PIP joints of the hand.The SI joints show a bilateral asymmetric involvement confined to the true synovial-lined portion of the joint, which parallels the findings of psoriatic arthritis.Changes in the axial skeleton also parallel those of psoriatic arthritis.

Differentiating Reiter's syndrome from the other seronegative spondyloarthropathies can be difficult.Reiter's arthritis typically shows less upper extremity involvement, axial skeleton involvement, and ankylosis than psoriatic arthritis or ankylosing spondylitis.Intraarticular bone production, adjacent sites of bone erosion, and poorly defined, fluffy periostitis also are hallmarks of Reiter's arthritis^[4](Figs.123-14 and 123-15).The plantar and retrocalcaneal changes are highly characteristic of Reiter's syndrome.Minimal axial skeleton involvement is helpful in differentiating Reiter's disease from peripheral ankylosing spondylitis.Nuclear scintigraphy may help detect subtle proliferative and inflammatory changes not apparent on plain radiographs.Early asymmetric, bilateral polyarticular involvement with changes involving both the hindfoot and the forefoot are helpful in establishing the early diagnosis of Reiter's syndrome.

Figure 123-14 Reiter's arthritis.Joint space narrowing, erosions (black arrows), and subluxation (arrowhead) make it difficult to differentiate Reiter's syndrome from other seronegative spondyloarthropathies.

Figure 123-15 Reiter's arthritis.Retrocalcaneal bursitis with associated erosions (black arrows) and prominent plantar calcaneal spur (white arrow) with poor cortical delineation.

[edit] Ankylosing Spondylitis.

Ankylosing spondylitis is a chronic inflammatory disorder that predominantly affects the spine but may also involve appendicular joints (see Chapter 137 ).With the onset of spinal symptoms, earlier radiographic changes may start and progress in the SI joints withsymmetric erosions, reactive sclerosis, and subsequent fusion (Fig.123-16).Early spinal involvement may occur at the thoracolumbar junction, with squaring of the vertebral body contours, corner erosions, and sclerosis, followed by formation of symmetric syndesmophytes bridging the vertebral bodies.Posterior apophyseal joint ankylosis and ligamentous ossification follow (Fig.123-17).Contiguous progression of this reactive process up and down the spine results in the end-stage ankylosed spinal changes with a bamboo appearance.Radiographic findings include the following:

• Bilateral, symmetric, apparent SI widening with loss of cortical definition of the iliac articular margin.
  
• Erosions and reactive sclerosis of the articular surfaces, especially the lower third of the SI joint.
  
• Subsequent narrowing and obliteration of the SI joint, with similar changes at the symphysis pubis.
  
• Inflammatory resorption of the anulus fibrosus insertion at the corners of the vertebral end plates resulting in squaring of the vertebral body contours, marginal erosions, and reactive sclerosis.
  
• Bony proliferation at the vertebral corners, which forms delicate vertical bridges of bone that create marginal syndesmophytes best appreciated on oblique views.Occasionally, destruction of the diskovertebral joint simulates septic diskitis.
  
• Apophyseal and costovertebral joint ankylosis.
  
• Craniocervical junction disease may be associated with transverse ligament insufficiency and resultant anterolateral instability.
  
• Hips, heels, and shoulders may be affected with diffuse inflammatory narrowing, erosive destruction, and proliferative "whiskering" periostitis, respectively.
  
• The ankylosed spine is rigid and osteoporotic.Minimal trauma may produce unstable, life-threatening spinal fracture, especially at the cervicodorsal junction.
  
• The peripheral joints may undergo ankylosis.
  

Figure 123-16 Ankylosing spondylitis. A, Bilateral symmetric reactive sclerosis and erosions predominantly involving iliac wing aspect of sacroiliac joint. B, Late changes include bony ankylosis and obliteration of sacroiliac joint.Note symphysis pubis erosions (white arow).

Figure 123-17 Ankylosing spondylitis.Axial skeleton shows squaring of vertebral bodies (arrowheads), classic "shiny corners" (white arrows), and ankylosis of interarticular facet joints (black arrows).

Initial radiographic evaluation to help confirm the diagnosis of ankylosing spondylitis includes AP and lateral views of the lumbar spine and AP craniad angled view of sacroiliac joint (Hibbs-Ferguson view).A CT scan performed preferentially in the coronal plane of the SI joint may demonstrate erosive disease before findings are evident on plain films.^[6] MRI has been used to assess associated spinal cord arachnoiditis, spinal canal stenosis, and posttraumatic cord changes.

[edit] Osteoarthritis

The term osteoarthritis is typically used interchangeably with degenerative joint disease(DJD).Osteoarthritis is characterized by asymmetric joint space narrowing secondary to articular cartilage thinning, subchondral eburnation or sclerosis, subchondral cystic changes, and marginal osteophyte formation (Fig.123-18).Osteoarthritis may occur as a primary process or secondary to another joint insult or destructive joint process.Radiographic features may help in differentiating a primary from secondary process.In the appendicular skeleton, osteoarthritis is characterized as aproliferative process with predilection for osteophyte formation.Asymmetric joint involvement without erosions, osteopenia, and ankylosis helps to differentiate osteoarthritis from inflammatory arthropathies.

Figure 123-18 Osteoarthritis.Proliferative marginal osteophytes (larger arrows), narrowing of medial weight-bearing joint space, and subchondral eburnative changes (smaller arrows).

Abnormalities of the synovial lining and adjacent ligamentous and soft tissue structures occur secondarily.A predilection for hips, knees, and small DIP joints of the hand is seen (Fig.123-19).In the wrist the trapeziometacarpal and scaphotrapezial joints are typically involved.Secondary osteoarthritis tends to involve the elbow and shoulder.Early radiographic changes in the appendicular skeleton include the following:

• Asymmetric joint space narrowing accentuated with weight-bearing or stress films.
  
• Subchondral reactive sclerosis frequently seen in the large weight-bearing joints.
  
• Subchondral changes seen on both sides of the joint space.
  
• Effusions that are activity related.
  
• No juxtaarticular osteopenia.
  

Figure 123-19 A, Osteoarthritis.Asymmetric extensor and volar proliferative spurs (arrows) with associated subchondral eburnative reaction and asymmetric narrowing of joint space. B, Erosive osteoarthritis.Prominent central erosions of proximal interphalangeal joints (black arrows); gull-wing deformity, bet shown at fifth posterior interphalangeal joint (white arrow); and subluxation.

Late radiographic findings in the appendicular skeleton include the following:

• Prominent marginal osteophyte formation.
  
• Subchondral cyst formation with a corticated margin.
  
• Malalignment or angular deformity, especially in weight-bearing joints.
  
• Loose intraarticular bodies (cartilaginous or osseous).
  
• Altered mechanical stress bearing, resulting in cortical and trabecular remodeling and buttressing.
  
• Chronic effusions.
  

In the axial skeleton, osteoarthritis specifically refers to changes at the apophyseal joints.Disk space narrowing or changes of the end plates resulting from diskal resorption are more properly termed intervertebral osteochondrosis. The changes of osteoarthritis at the apophyseal joints parallel those in the appendicular skeleton.In addition to the classic radiographic findings of cartilaginous thinning, marginal proliferation, subchondral eburnation, and cystic changes, capsular and ligamentous laxity foster segmental anterior, posterior, and lateral subluxation.

Erosive or inflammatory osteoarthritis refers to a specific clinical arthritic pattern seen principally in women and characterized by central erosions of the IP joints.^[7] A predilection for the PIP and DIP joints is noted.Monoarticular erosive osteoarthritis can be confused with septic arthritis.Marginal proliferative changes characteristic of osteoarthritis in the appendicular skeleton also are present.The central erosion and marginal proliferative changes with joint space narrowing are termed gull-wing deformity. Late radiographic changes may include angulation around the joint and ankylosis.

[edit] Calcium Pyrophosphate Dihydrate Arthropathy

Calcium pyrophosphate dihydrate (CPPD) crystals are deposited in articular cartilage and fibrocartilage, ligament, tendon, capsule, synovium, and synovial fluid (see Chapter 134 ).Radiologic hallmarks of chondrocalcinosis or abnormal mineralization of hyaline and fibrocartilage are seen.Target areas for chondrocalcinosis include the menisci of the knee, triangular fibrocartilage complex of the wrist, articular cartilage of the hips, and fibrocartilage of the symphysis pubis.^[6] Plain films of the knee (AP view), wrist (posteroanterior view), and pelvis (AP view) are the standard radiographs initially ordered to evaluate calcium pyrophosphate deposition disease (CPDD).

Although the radiologic findings simulate those of a degenerative process, an atypical pattern of distribution is noted.Chondrocalcinosis of the large weight-bearing joints and smaller non-weight-bearing joints with associated capsular and soft tissue mineralization indicates a systemic process of calcium crystal deposition arthropathy.Unicompartmental or bicompartmental involvement of the knee with isolated or severe patellofemoral disease is a common radiologic presentation.A characteristic notching (erosion) of the anterior distal femur also is seen frequently (Fig.123-20).Subtle articular mineralization involving the small joints of the wrist and hand and mineralization of the triangular fibrocartilage complex suggest the diagnosis (Fig.123-21).Early radiographic changes include the following:

• Normal plain radiograph.
  
• Subtle chondrocalcinosis in one or more target areas (knee, wrist, pelvis).
  
• Mild symmetric joint space narrowing.
  
• Subtle subchondral cyst formation.
  
• Effusion.
  

Figure 123-20 Calcium pyrophosphate deposition disease (CPDD).Chondrocalcinosis of menisci, best shown anteriorly (black arrow), and characteristic distal femoral cortical notching (open arrow).

Figure 123-21 Calcium pyrophosphate dihydrate arthropathy, or CPDD.Chondrocalcinosis of triangular fibrocartilage (white arrow) and large subchondral cyst formation (black arrows).

Later radiographic findings include the following:

• Prominent chondrocalcinosis.
  
• Mineralization of ligaments, tendons, capsule, synovium, and periarticular soft tissues.
  
• Prominent symmetric joint space narrowing.
  
• Prominent subchondral cyst formation with disproportionately large cysts.
  
• Subchondral eburnation.
  
• Disproportionately small amount of osteophyte formation for the degree of joint space narrowing and subchondral change.
  
• Bilateral weight-bearing and non-weight-bearing joint involvement, suggesting a systemic disorder.
  

The AP view of the pelvis is radiologically helpful because early or subtle chondrocalcinosis may be seen in the superolateral articular cartilage of the hips, in the synovial-lined SI joints, or at the level of the symphysis pubis.

In the axial skeleton, multilevel peripheral anular and central nuclear diskal calcification are clues.The radiographic features mimic those of a degenerative arthritic process, except for more florid and widespread involvement.Calcification of associated paraspinal ligaments is characteristic.Currently, nuclear scintigraphy and MRI are not helpful in the evaluation of this disorder.CT scan characterizes thediskal calcification of paravertebral calcific deposits.The diagnosis is most frequently suggested by plain films and corroborated through crystal isolation from joint aspirate.

[edit] Gout

Gout is a crystal deposition arthropathy secondary to deposition of monosodium urate crystals in soft tissues, synovium, cartilage, and joint capsule (see Chapter 136 ).Soft tissue changes and subsequent osseous remodeling characterize the radiologic findings of primary gouty arthritis (Fig.123-22).Radiographs of initial episodes of gouty arthritis do not show articular abnormality.Juxtaarticular soft tissue swelling is the typical presenting finding.Bony demineralization is not noted.Less than 50% of patients with documented gouty arthritis show osseous change.Radiologic findings of bony change, which typically requires more than 5 years, document the chronicity of the disease process.The first MTP joint is the articulation most often involved (Fig.123-23).Besides the feet, the ankle, knees, hands, and elbows can be affected.Bilateral olecranon bursitis is a clinical and radiologic clue to the diagnosis of gouty arthritis.Tophaceous deposits may occur juxtaarticularly, causing pressure erosion to the underlying bone.Deposits are seen in tendons, ligaments, capsule, and bursa.Extraarticular deposits are seen in the helix of the ear, palm of the hand, sole of the foot, and fingertip.Deposits may simulate the amyloid arthropathy seen in chronic renal failure patients, especially those on long-term hemodialysis.^[5] Involvement of the axial skeleton is uncommon.In rare cases of SI joint involvement, changes are similar to those in other articulations, including large cystic or erosive changes of the true synovial-lined joint in an asymmetric unilateral or bilateral pattern of involvement.

Figure 123-22 Gouty arthritis.Prominent soft tissue tophi (white arrows) and associated bony erosion with geographic sclerotic margination (black arrow).

Figure 123-23 A, Gouty arthritis. B, Progressive erosion of first metatarsal head with loss of subchondral cortical delineation over 8 months (black arrows).

Early radiologic findings of gouty arthritis include the following:

• Normal mineralization.
  
• Soft tissue swelling without articular abnormality.
  
• Asymmetric monoarticular or polyarticular involvement.
  

Late radiologic findings include the following:

• Soft tissue tophi with or without mineralization.
  
• Chondrocalcinosis.
  
• Osseous erosions with a characteristic overhanging bony margin.
  
• Geographic sclerotic margination to bony erosion.
  
• Intraosseous mineralization.
  

Gouty arthritis is differentiated from RA by the absence of juxtaarticular osteopenia, symmetric joint space loss, and symmetric polyarticular involvement.The peripheral distribution of joint involvement is also different in these two joint diseases.Differentiating a seronegative spondyloarthropathy such as psoriatic arthritis from gout may be more difficult due to the overlap of target sites (e.g., first MTP joint).Periosteal reaction, progressive bony erosive destruction without an associated soft tissue mass or tophus, and ankylosis of an articulation make gouty arthritis less likely.The high incidence of axial skeleton involvement in ankylosing spondylitis and its low occurrence in gouty arthritis help distinguish these two disorders.Differentiating gout fromother crystal deposition arthropathies (e.g., CPDD) can be challenging, especially early in the disease process.Joint fluid aspiration and crystal evaluation are most helpful.Radiologic findings of extensive chondrocalcinosis, joint space narrowing, and large subchondral cyst formation without associated soft tissue tophi are helpful in excluding gouty arthritis.

Alternate radiologic imaging modalities do not provide diagnostic or therapeutic advantage in the evaluation of gouty arthritis.The diagnosis is most often suggested by plain radiographs and corroborated by crystal isolation from joint and periarticular sites.

[edit] REFERENCES