AUTHOR AND EDITOR INFORMATION

Section 1 of 9  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• Mri
• Ultrasound
• Multimedia
• References

INTRODUCTION

Section 2 of 9  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• Mri
• Ultrasound
• Multimedia
• References

Background

Introduction

Rheumatoid arthritis (RA) is a chronic multisystemic disease of unknown cause. The characteristic feature is persistent inflammatory synovitis usually involving peripheral joints in a symmetrical distribution. Synovial inflammation causes cartilage destruction and bone erosion. Subsequently, joint deformity occurs. The axial skeleton, with the exception of the cervical spine, is affected later and less frequently.

RA activity in the cervical spine begins early, with 83% of patients in prospective studies developing anterior atlantoaxial subluxation within 2 years of disease onset. Activity in the cervical spine progresses clinically and radiologically in tandem with the peripheral-joint involvement. In fact, the severity of the peripheral erosive damage is strongly correlated with the degree of structural damage in the cervical spine. Features of spinal involvement in RA include erosive synovitis, ligamentous subluxation, osteopenia, and vertebral-body fractures.

History

The clinical manifestations were first clearly described in 1800 by Landre-Bouvais, a physician at the Salpetriere Hospital in Paris. It was not until 1859 that Garrod formally named the disease process. There is no example of RA in the extensive pathologic collection of William Hunter (1718-1783) at the Royal Infirmary in Glasgow, Scotland.

From a historical perspective, RA appears either to have been absent, relatively rare, or present in a milder form before the 19th century. The era of intensive investigation into the immunologic aspects of RA began following the discovery of rheumatoid factor (RhF) by Waaler in 1940 and by Rose et al in 1948.

Pathophysiology

Histologic and immunologic processes

Microvascular injury and an increase in the number of synovial lining cells appear to be the earliest histologic abnormalities in rheumatoid synovitis. The etiology of these features is unknown. As the disease progresses, the synovium becomes edematous and protrudes into the joint cavity as villous projections.

The synovium in joints expresses an antigen that triggers the production of RhF, an immunoglobulin M directed against autologous immunoglobulin G. This interaction is mediated by polymorphonuclear leukocyte infiltration, complement activation, and immune complex formation and leads to the propagation of a chronic inflammatory response. Lymphokines and other inflammatory mediators initiate an aggressive cascade that culminates in synovial joint destruction with the laying down of pannus.

Rheumatoid pannus describes the granulation tissue that is formed within the synovium by proliferating fibroblasts and inflammatory cells. Mediators of joint destruction include phospholipase A2, prostaglandin E2, and plasminogen activators. Class II molecules are involved in antigen–T-cell interaction.

Genetic predisposition

Studies in families indicate a genetic predisposition. For example, severe RA occurs at approximately 4 times the expected rate in first-degree relatives of individuals with seropositive disease. Approximately 10% of patients with RA have an affected first-degree relative. The role of genetic influences in the etiology of RA was established by the demonstration of an association with HLA-DR4. As many as 70% of patients with classic or definite RA express HLA-DR4 compared with 28% of control subjects.

Frequency

United States

The prevalence of RA is approximately 1% of the adult population in Europe and North America (range, 0.3-2.1%). Some Native American groups have a higher prevalence, with lower rates in the Caribbean. The worldwide incidence is around 3 cases per 10,000 population.

International

See data for the United States above.

Mortality/Morbidity

RA is usually associated with significant morbidity, disability, and mortality.

• Spontaneous clinical remission is uncommon. After 5 years with the disease, about 33% of patients are unable to work, and after 10 years, around 50% of patients have substantial physical disability.
• Oostveen et al reported an overall mortality rate of 17% in patients with RA and radiographic evidence of cervical subluxation. This rate is similar to that found in other series of patients with severe RA and no cervical involvement.
• Poor prognostic factors include persistent synovitis, early erosive disease, extra-articular features, positive serum RhF results, male sex, family history, and advanced age.

Race

RA occurs throughout the world and affects persons of all races. Disease severity differs based on ethnic and geographical variation. For example, studies have shown that RA in Greece is milder, with less radiological joint destruction and fewer extra-articular manifestations compared with Northern European countries. The incidence and severity also seem to be lower in rural sub-Saharan Africa than in other areas.

Sex

Women are affected approximately 3 times more often than men. The prevalence increases with age, and sex differences diminish in the older age group.

Age

The onset is more frequent during the fourth and fifth decades of life, with 80% of all patients developing disease from age 35-50 years. The incidence of RA is more than 6 times as great in 60- to 64-year-old women compared with 29-year-old women.

Anatomy

Various phases of joint destruction are seen in RA: early RA, erosion formation, pseudocyst formation, and advanced RA.

In early RA, inflammation leads to synovial hyperemia and swelling. Synovial processes adhere to cartilage surfaces at joint periphery.

In the stage of erosion formation, marginal destruction of cartilage, granulation tissue formation, and osteoclastic resorption of nearby bone leads to tissue loss, which is radiologically depicted as erosion.

With pseudocyst formation, granulation tissue formed in continuity with the inflamed synovial membrane continues to replace bone and cartilage at circumference of articular surfaces. This tissue extends through the surfaces to form radiolucent zones called pseudocysts.

In advanced RA, the extent of synovitis and fasciitis, tendonitis, and cellulitis becomes greater than before. Adhesions between joint surfaces cause ligament and capsule laxity. This, in addition to muscle atrophy and tendonitis, allows joint subluxation to occur. Little normal articular cartilage remains. Secondary osteoarthrosis develops with osteoporosis. Fibrous ankylosis is likely with joint shortening and destruction.

Clinical Details

Clinical course

There are now believed to be 3 characteristic clinical courses of RA: course I, monocyclic; course II, polycyclic; and course III, progressive.

Course I, monocyclic

Approximately one third of all patients who develop RA undergo complete and permanent remission within 2 years of disease onset, with or without treatment. The course is benign and self-limiting.

Course II, polycyclic

This is a slow, progressive course with moderate activity interspersed with short episodes of acute arthritis. Periods of acute activity become more sustained with the passage of time. This is also known as the palindromic type of RA, and it affects around 40% of patients.

Course III, progressive

This course affects approximately 20% of patients. It represents an unrelenting, progressive, and destructive form of RA with deformity, disfigurement, and even death.

In a given patient, it is not possible to predict the future course of the disease at its outset. However, in the presence of subcutaneous nodules, high titer of RhF, and erosive x-ray changes, rapid progression and destructive changes are inevitable.

Spinal involvement

RA may affect any synovial joint in the vertebral column, but lesions are most commonly seen in the cervical spine. The disease only rarely occurs in the thoracolumbar spine.

Cervical spinal involvement

As early as 1890, Garrod reported that 36% of his patients with RA had cervical-spine involvement. After the metacarpophalangeal joints, the most common region to be involved in RA is the cervical spine. This can lead to severe pain and disability, as well as a variety of neurologic manifestations, although some patients with significant radiographic evidence of disease may be entirely asymptomatic. The frequency of radiographic signs of involvement of the cervical area is in the range of 43-86% depending on the duration of the disease.

Symptoms and signs related to cervical-spinal abnormalities develop in approximately 60-80% of patients with RA at some time during their illness. Pain is the most common clinical manifestation of cervical-spinal involvement, and it may be brief or sustained in duration. Weakness and abnormal mobility can also be evident. Neurologic manifestations occur in 11-58% of patients with RA and include paresthesias, paresis, muscle wasting, quadriplegia, and even sudden death. This finding is well correlated with elevated levels of C-reactive protein, peripheral joint involvement, and carpal collapse.

A number of RA disease- and patient-related factors may contribute to the development of cervical spine involvement. These include the following:

• Severe polyarthritis is common in patients with cervical spine involvement, most of whom also have rheumatoid nodules. Often, coexisting severe erosive destruction is present in the hands and feet and at the hips and knees.
• Patients with immunoglobulin M rheumatoid factor are at higher risk for cervical spine involvement. Moreover, seronegative disease is less severe.
• The C-reactive protein concentration at the onset of RA may predict the subsequent development of cervical spine involvement.
• Older patients are more likely to have lesions in the lower spine.
• Degenerative disk disease may contribute to the severity of cervical spine involvement and to the development of dislocation.
• The effect of disease duration on cervical spine changes is controversial. Cervical spine involvement has been described within 2 years of disease onset. In a 5-year study by Pellicci et al in 106 RA patients, radiological evidence of cervical spine involvement was present in 43% of patients at baseline and in 76% of patients at last follow-up.
• The role of long-term steroid therapy is somewhat controversial. One study suggests that this may contribute to promoting cervical spine damage by virtue of alleviating the pain that might otherwise limit neck movements. Corticosteroids are well known to induce osteoporosis, and this may decrease the mechanical strength of the cervical spine, although this theory has been challenged. In a study by Rudge et al, corticosteroid treatment was associated with an increased incidence of SAS. This was related to duration of treatment. Recent studies with the newer DMARDs have suggested that early and aggressive treatment may prevent or retard the development of cervical spine changes.

Pathoanatomy of cervical spinal involvement

The entire cervical spine is involved in the rheumatoid process. Changes may be evident as far cephalad as the base of the occiput and as far caudad as the cervicothoracic junction. More specifically, synovial and cartilaginous articulations, the joints of Luschka, tendinous and ligamentous attachments, and soft tissues of the cervical region can develop significant abnormalities.

Atlantoaxial subluxation (AAS) is the result of erosive rheumatoid synovitis in the atlantoaxial, atlanto-odontoid and atlanto-occipital joints and in the synovium-lined bursa between the anterior arch of C1, the odontoid process, and the transverse ligament. Subluxation is normally prevented by the action of several ligaments, especially the transverse ligament, which connects the lateral masses of the atlas and maintains the normal position of the odontoid process. The alar ligaments and, to a lesser extent, the apical ligaments also play a critical role in stability of this region.

Synovitis within the articulations of the cervical spine causes destruction of the articular cartilage with direct extension of rheumatoid pannus into the spinal canal. Simultaneous involvement of ligaments causes laxity and rupture, promoting instability and subluxation. These factors in combination produce compression of the spinal cord or nerve roots, and may even compress the vertebral arteries. Progressive disease can also trigger off a cascade of events causing significant bone destruction, osteoporosis, instability, and fractures of the vertebral bodies or the posterior neural arches.

Subluxation

The synovial inflammatory process within the 4 atlantoaxial articulations often results in subluxation, of which 4 major types are recognized. The anterior type of subluxation is the most common and is present in 65% of RA patients undergoing total joint replacement, although only 50% of these are symptomatic. Results of physical examination may be misleading in its assessment because of a myriad of physical signs from tendon rupture, tenosynovitis, peripheral neuropathy, and myelopathy. It is typified by abnormal separation between the anterior arch of the atlas and the odontoid process of the axis. Generally, the interosseous distance between the posterior aspect of the anterior arch of the atlas and the anterior aspect of the odontoid process should not exceed 2.5 mm in adults.

The atlantoaxial subluxation can also occur in a posterior direction; this is seen in around 7% of all rheumatoid subluxations, but it is not usually associated with spinal cord compromise. Lateral subluxation is defined as offset of the lateral masses of the atlas in relation to the axis of greater than 2 mm, and it is usually associated with a rotational deformity. An irreducible head tilt is also seen in 10% of cases.

Vertical subluxation (VS) accounts for 22% of all other subluxations, and when extensive can be fatal. It is also known as cranial settling or atlantoaxial impaction and results from the combined bone and cartilage loss in the atlantoaxial and atlanto-occipital articulations. It may coexist with the more common anterior AAS.

Rheumatoid involvement of the subaxial cervical spine is most often seen at the C3-4 and C4-5 levels where the facet joints and interspinous ligaments are involved along with the intervertebral disks. The C7-T1 level is also a common site for subluxation and radiographs of the cervical spine must include this area. Multilevel subluxations produce the characteristic stepladder configuration, which is found in 10-20% of patients. In most cases, subluxations are not fixed in the abnormal position. Rather, changes in alignment can be demonstrated on lateral radiographs taken during flexion and extension of the neck.

Changes of the spinal canal are seen as a direct consequence of the subluxations highlighted primarily by pachymeningitis, arachnoiditis, cord ischemia and CSF and cord compression. Neurologic compression is more common in the subaxial portion of the cervical spine, where the spinal canal is less capacious, than elsewhere. It may especially occur below the level of a cervical fusion and in the presence of anterior spondylodiskitis, intracanal-rheumatoid granulations, and a hyperlordotic configuration. When cervical myelopathy is present, mortality is a common outcome if untreated, but in 10% of cases, sudden death can occur owing to fatal high-cervical medullary compression.

Thoracic and lumbar spinal involvement

Abnormalities of the thoracic and lumbar spine are relatively rare in this disease. Destructive lesions of the vertebral bodies that may histologically resemble rheumatoid nodules have been occasionally described. These granulomatous foci involve the vertebral body and may extend to the vertebral endplates and allow collapse of subchondral bone and intervertebral disk abnormalities. Rare cases of extradural rheumatoid nodules producing spinal cord compression have been described.

RA changes in the apophyseal joints of the thoracic and lumbar spine are reported only infrequently. Alterations at the discovertebral junctions have also been noted. Intervertebral disk-space narrowing, irregularity of the subchondral margins of the vertebral bodies, erosion and sclerosis can be evident on radiography. Patients with RA who are receiving corticosteroid medication are predisposed to ischemic necrosis of bone. Although the femoral head is the usual site for this, vertebral bodies in the thoracic and lumbar regions of the spine can be affected. On radiography, this may be seen as vertebral collapse and fragmentation. Radiolucent fracture lines, which may accumulate gas from surrounding tissues, are an important clue to the diagnosis.

Patient Education: For excellent patient education resources, visit eMedicine's Arthritis Center. Also, see eMedicine's patient education articles Rheumatoid Arthritis and Understanding Rheumatoid Arthritis Medications.

DIFFERENTIALS

Section 3 of 9  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• Mri
• Ultrasound
• Multimedia
• References

RADIOGRAPH

Section 4 of 9  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• Mri
• Ultrasound
• Multimedia
• References

Findings

The mainstay of imaging the rheumatoid spine remains plain radiography. Flexion/extension views are necessary to assess the level of involvement and any evidence of instability. The need for further imaging by means of CT, MRI, or myelography may also be assessed during radiography.

Anterior AAS

Only half of patients with radiographic evidence of AAS are actually symptomatic. The role of plain radiography is to establish whether there are risk factors for cord compression.

Anterior atlantodental interval

AAS is defined as an anterior atlantodental interval (AADI) of greater than 2.5 mm in adults. This distance is measured as the interosseous distance between the posterior aspect of the arch of the atlas and the anterior aspect of the odontoid process. The point of measurement of the joint is a subject of debate: the inferior point is the most popular.

There may be a slight variation in normal measurements between men and women. More importantly, it should be noted that an atlantodental interval of less than 2.5 mm, which changes considerably on flexion and extension, may also be abnormal. An AADI of 3-6 mm indicates early instability and implies transverse ligament damage. An AADI of greater than 6 mm indicates that the alar ligaments are also damaged. Some authors consider an AADI of greater than 9 mm to be an indication for surgical stabilization.

Posterior atlantodental interval

Recent literature suggests that the posterior atlantodental interval (PADI) is a better method of assessing AAS because the PADI directly measures the spinal canal and therefore shows how much is narrowed by the subluxation. The PADI is the distance between the posterior surface of the odontoid and the anterior margin of the posterior ring of the atlas. At all cervical spinal levels, the cord requires a minimum canal width of 10 mm; the CSF, 2 mm; and the dura, 2 mm. Therefore, a minimum PADI of 14 mm is required to avoid cord compression. The normal spinal canal measures 17-29 mm at C1.

In 1993, Boden et al investigated the predictive value of the PADI and found that a value of less that 14 mm on plain radiographs had a 97% ability to detect patients with neurological deficit. Also, neurological recovery from surgery was unlikely if the PADI fell beneath 10 mm. Moreover, complete motor recovery occurred if the surgery was performed while the PADI was greater than 14 mm.

Detecting VS

Regarding McGregor method, VS has been defined as the protrusion of the odontoid tip by more than 4.5 mm above the McGregor line. This is drawn between the posterosuperior aspect of the hard palate and the most caudal aspect of the occiput. However, it is not the most accurate of measurements in the rheumatoid spine due to odontoid erosion and often marked osteoporosis.

The Ranawat index is used to assess VS by detecting settling of C1 on C2. The measurement is made from the center of the pedicles of C2 to a line connecting the midpoint of the anterior and posterior arches of C1. Normal values are 15 mm or greater for men and 13 mm or greater for women. Anything less than this confirms VS.

Confirming subaxial subluxation

The diameter of the spinal canal is actually a better predictor of the development of paralysis than the degree of subluxation of 1 vertebral body on another. The normal sagittal diameter from C3 to C7 is 14-23 mm. A spinal canal sagittal diameter of at least 14 mm is critical at all levels in the cervical spine, as this is the minimum space required for the cord, CSF, and dura.

The cervical height index (CHI) is a method for assessing subaxial subluxation that takes into account the contribution of subluxations at multiple levels, together with loss of disk height and bony collapse. The CHI is calculated by first measuring the distance from the center of the sclerotic ring of C2 (as used in the Ranawat method) to the tip of the spinous process of C2. This distance is then divided into the distance from the center of the C2 sclerotic ring to the midpoint of the inferior border of C7 vertebral body. A CHI of less than 2 has a sensitivity and specificity approaching 100% in predicting neurologic compromise.

These plain radiographic measurements, along with dynamic flexion-extension views provide a reliable and efficient means of assessing spinal involvement of rheumatoid disease and targeting at-risk patients, as well as selecting those who warrant further radiological studies with a view to surgical stabilization.

CT SCAN

Section 5 of 9  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• Mri
• Ultrasound
• Multimedia
• References

Findings

See the MRI section below.

MRI

Section 6 of 9  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• Mri
• Ultrasound
• Multimedia
• References

Findings

The major role for CT and MRI is in the preoperative assessment of the 2 main indications for surgical intervention, namely neurologic deficit and severe pain. The subluxations that are of a degree likely to result in paralysis need to be identified, as better outcomes are recorded with earlier interventions. The effect of pannus and intracanal granulations on the cord cannot be accurately assessed on plain images, despite the fact that a PADI of less than 14 mm is a sensitive indicator of paralysis risk.

Although CT scanning can document bone damage and alignment abnormalities, especially with more detailed multiplanar reconstruction, MRI has become the preferred modality for evaluation of the spinal cord and neural elements. It demonstrates the presence and effect of pannus on the spinal cord, and is useful in assessing its resolution following posterior fusion and stabilization. On MRI, the direct relationships of the odontoid to the medulla and brainstem can be documented. Spinal cord signal can be assessed; edematous changes in the cord are associated with a poor clinical status, as well as a poor prognosis and a poor postoperative outcome.

The major indications for MRI in RA are abnormal measurements on plain radiographs, unremitting suboccipital/cervical pain, progressive/severe subluxations, symptoms of cord/brainstem compression, and vertebral-artery compression.

Dynamic MRI has been used with the patient in flexed or extended positions and in the traditional neutral position. Roca et al suggested that functional (flexed position) MRIs be obtained in patients with RA in whom cervical subluxation is suspected when routine MRI findings in the neutral position are normal. Others recommend functional MRI as a preoperative examination.

Pathological series have suggested that cord atrophy in rheumatoid cervical myelopathy results from repeated traction injury as a result of compression, stretch, and movement as opposed to an inflammatory process per se. This is unsurprising considering that the atlantoaxial joint is the most mobile segment of the cervical spine.

In a study looking at those features of rheumatoid cervical myelopathy on MRI that were associated with subsequent deterioration, it was found that where axial compression or impingement was present on MRI, 60% experienced a deterioration resulting in death or surgical intervention over a median period of 12 months.

When functional imaging is performed, patient monitoring is advised, and rapid sequences are desirable because patients may find the flexed position uncomfortable. Some authors suggest that functional MRI is unnecessary and even contraindicated in patients in whom medullary or spinal cord compression is discovered on studies made in the neutral position.

Degree of Confidence

The correlation of MRI findings with symptoms is crucial before any surgical decisions can be made. There is a close correlation between the severity of cervical myelopathy and the degree of compression, as demonstrated by MRI. Besides influencing the selection of patients for spinal surgery, MRIs can help in planning surgical procedures, especially those in patients with more than 2 levels of cord compression.

ULTRASOUND

Section 7 of 9  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• Mri
• Ultrasound
• Multimedia
• References

Findings

Ultrasonography is not used in the evaluation of cervical spine disease due to RA.

MULTIMEDIA

Section 8 of 9  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• Mri
• Ultrasound
• Multimedia
• References

Media file 1:  Plain lateral radiograph of the normal cervical spine taken in extension shows measurement of anterior atlantodental interval (yellow line) and posterior atlantodental interval (red line).
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Media file 2:  Lateral flexion view of the cervical spine shows atlantoaxial subluxation.
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Media file 3:  Lateral view of the cervical spine in a patient with rheumatoid arthritis shows erosion of the odontoid process.
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Media file 4:  T1-weighted sagittal MRI of the cervical spine shows basilar invagination with cranial migration of an eroded odontoid peg. There is minimal pannus. The tip of the peg indents the medulla, and there is narrowing of the foramen magnum due to the presence of the peg. Inflammatory fusion of several cervical vertebral bodies is shown.
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Media type:  MRI

Media file 5:  Sagittal T2-weighted MRI of the cervical spine in the same case as in Image 4. The compromised foramen magnum is easily appreciated, and there is increased signal intensity within the upper cord; this is consistent with compressive myelomalacia. Further narrowing of the canal is seen at multiple levels.
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Media type:  MRI

Media file 6:  Lateral radiograph of the same patient as in Images 4-5. Midcervical vertebral-body fusions are shown. The eroded peg is difficult to visualize, but inferior subluxation of the anterior arch of C1 is shown.
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Media file 7:  Lateral radiograph of a normal cervical spine shows the McGregor line. The odontoid tip should not protrude more than 4.5 mm above the line, which is drawn from the posterior edge of the hard palate to the most caudal point of the occiput.
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Media file 8:  Normal lateral magnified radiograph of the cervical spine shows the Ranawat method of detection of cranial settling. This method is used to measure the distance from the center of the pedicles (sclerotic ring) of C2 to a line drawn connecting the midpoints of the anterior and posterior arches of C1. (Normal values are 15 mm or greater for males and 13 mm or greater for females.)
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Media type:  X-RAY

Media file 9:  Lateral radiograph of the cervical spine shows how the cervical height index (CHI) is calculated. The distance from the center of the sclerotic ring of C2 to the tip of the spinous process of C2 (dotted line) is measured. This is then divided into the distance from the center of the sclerotic ring of C2 to the mid-point of the inferior border of the body of C7. A CHI of less than 2 mm is a sensitive predictor of neurologic deficit.
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Media type:  X-RAY

REFERENCES

Section 9 of 9

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• Mri
• Ultrasound
• Multimedia
• References

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• Cassar-Pullicino VN. The Spine in Rheumatological Disorders. Imaging. Vol 11. 1999: 104-18.
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• Neva MH, Kauppi MJ, Kautiainen H, et al. Combination drug therapy retards the development of rheumatoid atlantoaxial subluxations. Arthritis Rheum. Nov 2000;43(11):2397-401. [Medline].
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• Pellicci PM, Ranawat CS, Tsairis P, Bryan WJ. A prospective study of the progression of rheumatoid arthritis of the cervical spine. J Bone Joint Surg Am. Mar 1981;63(3):342-50. [Medline].
• Resnick D, Kyriakos M, Greenway GD. Rheumatoid arthritis. In: Diagnosis of Bone and Joint Disorders. Vol 2. 4th ed. Philadelphia: WB Saunders;. 2002: 891-974.
• Roche CJ, Eyes BE, Whitehouse GH. The rheumatoid cervical spine: signs of instability on plain cervicalradiographs. Clin Radiol. Apr 2002;57(4):241-9. [Medline].
• Weissman BN, Aliabadi P, Weinfeld MS, et al. Prognostic features of atlantoaxial subluxation in rheumatoid arthritispatients. Radiology. Sep 1982;144(4):745-51. [Medline].
• Winfield J, Young A, Williams P, Corbett M. Prospective study of the radiological changes in hands, feet, and cervical spine in adult rheumatoid disease. Ann Rheum Dis. Dec 1983;42(6):613-8. [Medline].

Article Last Updated: Mar 8, 2006