вход по аккаунту


Use of the radiograph to measure the course of rheumatoid arthritis.

код для вставкиСкачать
3 16
The Gold Standard Versus Fool’s Gold
The methods used to measure the course of
rheumatoid arthritis (RA) are almost too numerous to
count. Radiographs have been used for a considerable
period of time to measure the progression of RA. Since
the early 1970s, the radiograph has evolved into the
“gold standard” for RA progression, because it provides an accurate image of the patient’s disease state
(1). However, unless its limitations are recognized and
fully understood by the interpreting physician, the
“gold standard” can quickly become “fool’s gold.”
The radiograph has become the “gold standard” because it has been proven to be a practical
method of obtaining an objective assessment of a
patient’s condition. The treated patient may become
asymptomatic, but as long as there is radiographic
progression of the disease, the therapy used is considered ineffective (2). The radiograph is an image of the
true biologic endpoint demonstrating the result of
inflammation and enzymatic degradation of cartilage
and subchondral bone due to RA (1).
The role that radiography should play in the
assessment of disease has been debated and discussed
over the past 20 years. However, significant problems
The opinions and assertions expressed herein are those of
the author and are not to be construed as reflecting the views of the
Department of Defense or the Uniformed Services University of the
Health Sciences.
From the Department of Radiology and Nuclear Medicine,
F. Htbert School of Medicine, Uniformed Services University of
the Health Sciences, Bethesda, Maryland.
Anne C. Brower, MD.
Address reprint requests to Anne C. Brower, MD, Department of Radiology and Nuclear Medicine, Uniformed Services
University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814-4799.
Submitted for publication November 9, 1988; accepted in
revised form September 7, 1989.
Arthritis and Rheumatism, Vol. 33, No. 3 (March 1990)
continue to exist with any radiographic assessment.
These center around 1) the appropriateness of the joint
radiographed, 2) technical production and reproduction of the radiograph, 3) reader variation, 4) the
pathophysiology of the radiographic change, 5 ) the
varied clinical course of a single disease, and 6) the
radiographic lag time. A discussion of these problems
and their effects upon radiographic interpretation is
the subject of this report.
Technical variables
Specific problems are encountered in producing
quality films for interpretation. First, accurate joint
positioning is absolutely essential. In most studies,
posteroanterior (PA) and occasional oblique and lateral views of the hands and wrists are obtained.
However, not all joints can be imaged by these views:
specifically, the triquetrial-pisiform joint is not imaged. Some believe that erosive disease will be identified on a NBrgaard or supinated-oblique view before
it is demonstrated on the PA view (3,4) (Figure 1). The
value of this view has been disputed in the literature
(3-5). However, it does provide an image of the
triquetrial-pisiform joint. Erosive changes often occur
between the triquetrum and pisiform before any other
carpal involvement occurs ( 3 3 ) . Once erosive changes
are visualized on the PA view, other views may not be
The exposure of the film is another extremely
important consideration. Detection of erosive disease
is lost on both underpenetrated and overpenetrated
films. Although radiographs obtained in a private office
setting are a convenience to the patient, quality control of these radiographs, a requirement in a radiology
3 17
Figure 1. Comparison of 2 radiographic views of the metacarpaljoints and wrist in a patient with rheumatoid arthritis. A, Posteroanterior view.
Erosive disease is not demonstrated. B, Ndrgadrd view. Erosive disease is seen at the radial aspect of the base of the proximal phalanges of
the second and third digits, at the base of the fourth metacarpal joint, and between the triquetrum and pisiform (arrows).
department, is often absent. In large published series
addressing the accuracy of scoring methods used on
the hands and wrists, many of the radiographs scored
were underpenetrated or overpenetrated, raising some
questions concerning the accuracy of these published
High-resolution films are absolutely essential in
the detection of early erosive disease. High resolution
is obtained using a low system speed. The routinely
used two-screen/film combination cassettes do not
provide a low system speed. Non-screen/film combinations provide the lowest system speeds, but require
long exposures. New single-screen/film combinations
give both acceptable system speeds and exposure
times, and these should be used for detection of early
erosive disease.
Although excellent baseline films may be obtained, reproduction of this same high quality remains
difficult because of technical variability. In addition,
even minuscule changes in the rotation of an imaged
joint will cause an erosion to appear either healed or
progressively eroded (Figure 2). Thus, accurate interpretation of radiographs depends on appropriate positioning, film exposure, screen film combination used,
and reproducibility.
Interpretation variables
Reader variation can be a problem. Recent
studies have shown that a skilled skeletal radiologist
can evaluate sequential films without any significant
deviation (1,2,6). However, all film readers find any
one of the scoring methods used to evaluate the
progression of RA to be tedious and time consuming.
Pullar et a1 (7) have recently determined that in any
meaningful assessment of trial drug therapy, one
Figure 2. Comparison of 2 posteroanterior views of the third through the fifth digits, taken 1 month apart, in a patient with rheumatoid arthritis,
demonstrating the problem produced by a slight change in rotation of ajoint. A, Soft tissue swelling and erosive disease are seen at the proximal
interphalangeal (PIP) joint of the third and the fifth digits. B, One month later, a slight change in the degree of rotation produces an apparent
increase in erosive disease involving the PIP joint of the third digit, but results in a decrease in erosive disease involving the PIP joint of the
fifth digit. (Reproduced, with permission, from Proceedings: Early Decisions in DMARD Development. Edited by KR Johnson, V Strand.
Atlanta, Arthritis Foundation, 1989.)
would need to evaluate 120 patients receiving placebo
and 120 patients receiving the trial drug over a period
of 2 years. In addition, appropriate radiographs would
be required at study entry and after 1 year and 2 years.
As patient withdrawal becomes a problem, they suggest that 3-4 times this number of patients (i.e.,
4W500 patients) would have to be enrolled in such a
study. The accurate and meaningful scoring of radiographs on all these patients would be a full-timejob for
any reader.
There is a problem with the interpretation of
radiographic progression. Most of the time, radio-
graphic progression is obvious and undisputed. However, a joint occasionally develops a new lytic lesion
that has a definable sclerotic border (Figure 3). Although the disease has obviously progressed, the
problem now arises of whether this new lesion is an
erosion or a cyst. If it is a cyst, it cannot be counted
according to the present scoring methods. If it is an
erosion, does the sclerotic border observed indicate
that the erosion has healed? If healing has occurred,
counting the erosions or grading the erosion according
to size does not reflect the state of the disease.
In addition, there is often disagreement be-
Figure 3. Comparison of 2 posteroanterior views of the third digit, taken 1 year apart, in a patient with rheumatoid arthritis. A, The baseline
radiograph shows some loss of the proximal interphalangeal joint space. B, One year later, the radiograph shows a large lytic lesion with a
well-defined sclerotic border at the base of the middle phalanx of the third digil. This radiographic series demonstrates the dilemma of assessing
disease progression on the basis ofjoint erosion count. since some would interpret this lesion to be a cyst, and therefore not countable, while
others would interpret the lesion to be an erosion, and countable toward progression. The sclerotic border suggests, however, that this erosion
has already healed. (Reproduced. with permission, from Proceedings: Early Decisions in UMARD Dcvelopmenr. Edited by KR Johnson, V
Strand. Atlanta, Arthritis Foundation, 1989.)
tween readers in interpreting a given radiograph. Although the radiograph of the hand may not show any
progression of the erosive disease, it may reveal
continued progression ofjoint space loss. Using one of
the present scoring methods, the reader should interpret the joint space loss as a progressive change of RA
(8). However, the presence of sclerosis and osteophyte formation along with joint space loss are
changes of osteoarthritis superimposed on RA, and
not just a progressive change of RA itself (Figure 4).
One reader may interpret such radiographic findings as
progression of the disease, while another reader may
interpret these same findings as healing of the disease
with superimposed osteoarthritis (9).
Different interpretations of the same radiographic change bring up the problem of understanding
the pathophysiology behind the radiographic change.
The scoring systems that are now used (1,6,10-13) all
employ the scoring of erosions and joint space loss.
There are other indications of worsening of disease
(i.e., progression of osteoporosis, worsening of subluxations, development of rheumatoid nodules, etc.).
Figure 4. Comparison of posteroanterior views of the hand and wrist in a patient with rheumatoid arthritis. A, The baseline radiograph shows
erosive disease and joint space loss of the metacarpophalangeal (MCP) joints and !he carpal bones. B, A radiograph obtained after 42 months
of treatment with methotrexate shows progressive loss of the MCP joint spaces and pancarpal joint spaces. In addition, subchondral sclerosis
is seen at the MCP joints and the radial carpal joint. The MCPjoint of the thumb, while showing progressive joint space loss and erosion of
the base of the proximal phalanx, also shows cortication and osteophyte formation along this same base. The erosion on the metacarpal head
has filled in and has developed an adjacent osteophyte. One reader may interpret this series of radiographic changes as progression of the
rheumatoid arthritis, while another reader may interpret these changes as healing of rheumatoid arthritis with superimposed osteoarthritis (9).
If these are not taken into consideration, error in
assessment will occur in a patient who has no progressive erosive disease or joint space loss, but has progressive subluxations (Figure 5).
Clinical and pathophysiologic variables
Radiographic assessment is usually performed
on views of the hands and wrist. Brook and Corbett
(14) reviewed the radiographic changes observed in 94
patients with early rheumatoid disease. In those with
erosive disease, 35.8% had their first erosions in the
feet, 16.4% had their first erosions in the hands, and
47.8% had their first erosions in both the hands and the
feet. These statistics suggest that we should be assessing the feet, rather than the hands. However, Brook
and Corbett did not use the Nq5rgaard view in imaging
the hands. If they had used this view, it is likely that
32 1
Figure 5. Comparison of 2 posteroanterior views of the hand in a patient with rheumatoid arthritis, showing progressive disease over a I-year
interval. A, The baseline radiograph shows juxtaarticular osteoporosis, joint space loss, and erosive disease. There is a flexion deformity of the
proximal interphalangeal joint of the fourth digit. B, A radiograph taken 1 year later shows no change in the degree of juxtaarticular
osteoporosis, erosive disease, and joint space loss. However, there is evidence of disease progression, and there is an increase in the number
and degree of subluxations. Flexion deformities of the proximal interphalangeal joints of the second through the fifth digits are seen, and there
is an extension deformity of the interphalangeal joint of the thumb. (Reproduced, with permission, from Proceedings: Eurly Decisions in
DMARD Development. Edited by KR Johnson, V Strand. Atlanta, Arthritis Foundation, 1989.)
there would have been a higher percentage of first
erosions seen in the hands.
Although it is known that the earliest radiographic changes often occur in the hands and wrists, it
is not known if these joints are representative of the
course of the disease within a particular patient. Scott
et a1 (8,15) have demonstrated a lack of correlation
between hand damage and large joint damage. It is
known that different joint groups have a different time
course of involvement. Thus, if radiographs of the
hands and wrists are not used in conjunction with
radiographs of other joints, errors will occur in our
assessment of progressive disease in the patient who
has static erosive disease in the hand and wrist, but
who also shows progressive erosive disease in the hips
over the same period of time (Figure 6).
There is always a problem when attempts are
made to evaluate changes of a single disease with a
variable clinical course. The rate of radiographic
change is not only unique to each patient, but it is also
not constant over time. Brook and Corbett (14) evaluated 94 patients with early RA over a period of 5
years from the time of diagnosis. While 71.3% had
erosive disease, 23.4% had no erosive disease. Among
those who had erosive disease, 52.2% had progression, and 47.8% did not have progression.
The significance of erosive disease is an impoitant consideration. Scott et al (15) demonstrated a
poor correlation of erosive disease with hand function.
A question that needs to be addressed is what is more
important to the patient-function or erosion? It has
been shown in multiple-drug therapy trials that while
clinical parameters improve, radiographic changes almost always progress (16-18). Scott et a1 (16) showed
that even when drug therapy reduced the acute synovitis and the acute-phase response, radiographic progression continued. Zvaifler (17) has demonstrated
discrete steps or sequences in the pathogenic mechanisms for joint destruction in RA. Innuzzi et al (18)
point out that the acute phase of inflammation in RA is
mediated through the polymorphonuclear cells and
immune complexes found in the superficial layers of
the synovium. In addition, they indicate that the
chronic phase of inflammation is related to interactions
among the lymphocytes and monocytes in the deep
layers of the synovium. They suggest that it is the
chronic phase that leads to destruction of cartilage and
bone. Present-day drug therapy may modify the acute
Figure 6. Comparison radiographic views of the wrist (A and B) and the hip (C and D)in a patient with rheumatoid arthritis. A, The baseline
radiograph shows pancarpal erosive changes and pancarpal loss ofjoint space. B, View of the same wrist 1 year later. Allowing for differences
in the processing of the film, neither progressive erosive changes nor progressive joint space loss is observed. C, Baseline radiograph, taken
at the same time as the wrist shown in A, showing the hip to have a normal appearance. D, View of the same hip 1 year later, taken at the same
time as the wrist shown in B, showing progressive change in the hip with uniform loss of the joint space and juxtaarticular osteoporosis.
phase only, and not the chronic phase. This would
explain the progressive, destructive radiographic
changes observed, despite clinical improvement.
Joint space loss occurs independently of erosive disease. What is the pathophysiology behind this
observation? How much cartilage loss is related to the
disease itself and how much loss is related to progressive mechanical stress (Figure 4)? Pullar and Capell
(19) have suggested that perhaps with symptomatic
relief resulting from drug therapy, the patient increases the activity around the joint and thus produces
radiographic progression.
Finally, the last problem associated with the
assessment of the radiograph is that radiographic
change lags behind pathologic change. This is true of
all bone diseases. Because of this lag, it becomes very
difficult to assess how far out of sequence a given
radiograph is in relation to the true pathologic change.
In conclusion, the radiograph is certainly useful
in measuring disease outcome in RA. Although it is
considered the “gold standard,” the problems associated with it must be recognized in order to prevent it
from becoming “fool’s gold.” Finding solutions to
these problems will require the investigation and development of other modalities that will provide a more
accurate evaluation of the actual pathologic change(s)
involved. For example, bone scintigraphy will demonstrate active joints and will predict which joints will
become eroded and which ones will not (20). As
magnetic resonance imaging (MRI) continues to develop, our expertise and interpretation of MRI will
also improve. However, advancements in the understanding of the pathophysiology of RA will also be
required. These developments will result in a more
accurate and objective assessment of drug therapy on
the outcome of RA.
The author thanks Martha Ross for manuscript preparation.
Fries JF, Bloch DA, Sharp JT, McShane DJ, Spitz P,
Bluhm GB, Forrester D, Genant H, Gofton P, Richman
S, Weissman B, Wolfe F: Assessment of radiologic
progression in rheumatoid arthritis: a randomized, controlled trial. Arthritis Rheum 29: 1-9, 1986
Weisman MH: Use of radiographs to measure outcome
in rheumatoid arthritis. Am J Med 83:!36-100, 1987
Nbrgaard F: Earliest roentgenological changes in poly-
arthritis of the rheumatoid type: rheumatoid arthritis.
Radiology 85:325-329, 1965
Hartley RM, Liang MH, Weissman BN, Sosman JL,
Katz R, Charlton JR: The value of conventional views
and radiographic magnification in evaluating early rheumatoid arthritis. Arthritis Rheum 27:744-751, 1984
Mewa AAM, Pui M, Cockshott WP, Buchanan WW:
Observer differences in detecting erosions in radiographs of rheumatoid arthritis: a comparison of posteriorhnterior, Ndrgaard and Brewerton views. J Rheumato1 10:216-221, 1983
Sharp JT, Bluhm GB, Brook A, Brower AC, Corbett M,
Decker JL, Genant HK, Gofton JP, Goodman N, Larsen
A, Lidsky MD, Pussila P, Weinstein AS, Weissman BN,
Young DY: Reproducibility of multiple-observer scoring
of radiologic abnormalities in the hands and wrists of
patients with rheumatoid arthritis. Arthritis Rheum 28:
16-24, 1985
Pullar T, Hunter JA, Capell HA: Does second-line
therapy affect the radiological progression of rheumatoid
arthritis? Ann Rheum Dis 43.18-23, 1984
Scott DL, Coulton BL, Popert AJ: Long term progression ofjoint damage in rheumatoid arthritis. Ann Rheum
Dis 45:373-378, 1986
Weinblatt ME, Trentham DE, Fraser PA, Holdsworth
DE, Falchuk KR, Weissman BN, Coblyn JS: Long-term
prospective trial of low-dose methotrexate in rheumatoid arthritis. Arthritis Rheum 31:167-175, 1988
Sharp JT,Lidsky MD, Collins LS, Moreland J: Methods
of scoring the progression of radiologic changes in
rheumatoid arthritis: correlation of radiologic, clinical,
and laboratory abnormalities. Arthritis Rheum 14:
706-720, 1971
Larsen A: Radiological grading of rheumatoid arthritis.
Scand J Rheumatol 2: 136-138, 1973
Nance EP Jr, Kaye JJ, Callahan LF, Carroll FE, Winfield AC, Earthman WJ, Phillips KA, Fuchs HA, Pincus
T: Observer variation in quantitative assessment of
rheumatoid arthritis. 1. Scoring erosions and joint space
narrowing. Invest Kadiol 21:922-927, 1986
Kaye JJ, Nance E P Jr, Callahan LF, Carroll FE, Winfield AC, Earthman WJ, Phillips KA, Fuchs HA, Pincus
T: Observer variation in quantitative assessment of
rheumatoid arthritis. 11. A simplified scoring system.
Invest Radiol 22:41, 1987
Brook A, Corbett M: Radiographic changes in early
rheumatoid disease. Ann Rheum Dis 36:71-73, 1977
Scott DL, Coulton BL, Bacon PA, Popert AJ: Methods
of x-ray assessment in rheumatoid arthritis: a reevaluation. Br J Kheumatol 24:31-39, 1985
Scott DL, Grindulis KA, Struthers GR, Coulton BL,
Popert AJ, Bacon PA: Progression of radiological
changes in rheumatoid arthritis. Ann Rheum Dis 43:
8-17, 1984
Zvaifler NJ: Overview of etiology and pathogenesis,
Rheumatoid Arthritis. Edited by PD Utsinger, NJ Zvaifler, GE Ehrlich. Philadelphia, Lippincott, 1985
18. Innuzzi L, Dawson N , Zein N , Kushner I: Does drug
therapy slow radiographic deterioration in rheumatoid
arthritis? N Engl J Med 309:1023-1028, 1983
19. Pullar T, Capell HA: Can treatment really influence the
radiological progression of rheumatoid arthritis? Br J
Rheumatol 25:2-6, 1986
20. Mottonen IT,Hannonen P, Toivanen A, Kekonen A,
Oka M: Value of joint scintigraphy in the prediction of
erosions in early rheumatoid arthritis. Ann Rheum Dis
47: 183-197, 1988
Без категории
Размер файла
687 Кб
course, radiographic, arthritis, measures, use, rheumatoid
Пожаловаться на содержимое документа