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Rheumatoid nodules of the spinecase report and review of the literature.

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709
BRIEF REPORT
RHEUMATOID NODULES OF THE SPINE: CASE REPORT AND
REVIEW OF THE LITERATURE
MARK E. PEARSON, MARY KOSCO, WILLIAM HUFFER, WILLIAM WINTER, JAMES A. ENGELBRECHT, and
JAMES C. STEIGERWALD
We present the case of a patient who had rheumatoid nodules of the vertebrae, which had resulted in
bony destruction of the spine at 3 levels. Although there
have been only 3 previous reports of such findings with
confirmation by histologic analysis, we believe the condition is more common than has been thought. From a
review of the literature, we found that similar clinical
and radiographic features, as well as descriptions of
rheumatoid granulation tissue invading the disc spaces,
have been described in several subjects,
Rheumatoid nodules are found in approximately 20% of patients with rheumatoid arthritis (RA).
These nodules occur most commonly on the extensor
surface of the forearm, on the Achilles tendon, and in
the olecranon bursa (1). Less commonly, they have
been found in the lungs, heart, spinal cord, meninges,
and on the vocal cords. Standard rheumatology texts,
however, make no mention of rheumatoid nodule
involvement on body structures (2,3). Autopsy studies
have demonstrated that rheumatoid nodules were the
cause of vertebral body destruction in 3 subjects with
RA (4-6). We report another case of vertebral destrucFrom the Department of Medicine, Division of Rheumatology, the Department of Pathology, and the Department of Orthopedic Surgery, University of Colorado Health Sciences Center,
Denver.
Mark E. Pearson, MD: Fellow in Rheumatology; Mary
Kosco, MD: Resident in Internal Medicine; William Huffer, MD:
Associate Professor of Pathology; William Winter, MD: Associate
Professor of Orthopedic Surgery; James A. Engelbrecht, MD;
James C. Steigenvald, MD: Associate Professor of Medicine.
Address reprint requests to James C. Steigenvald, MD,
Division of Rheumatology, Box B115, University Hospital, 4200
East Ninth Avenue, Denver, CO 80262.
Submitted for publication March 7, 1986; accepted in revised form October 22, 1986.
Arthritis and Rheumatism, Vol. 30, No. 6 (June 1987)
tion at multiple levels of the spine. This case is unique
in that, during spinal surgery, rheumatoid nodules
were found to have caused the vertebral destruction.
Case report. The patient, a 65-year-old American Indian woman, had a 17-year history of seropositive nodular RA and a 9-year history of insulindependent diabetes mellitus. The arthritis had been
treated with prednisone for most of the 17 years, and
D-penicillamine had recently been added to the regimen. Her arthritis was well controlled with these
medications until November 1984, when she noted the
onset of dull, nonradiating pain in her lower back.
The pain progressed, and in April 1985, roentgenograms were made of the patient’s spine; these
showed destruction of the L3-L4 disc space. A bane
scan was also performed, and it showed diffuse uptake
in this same area. Needle aspiration of the disc space
was performed. Cytologic results and acid-fast bacilli
(AFB) staining were negative, as were bacterial and
tuberculosis (TB) cultures. It was believed, however,
that the radiographic results were most compatible
with a diagnosis of TB of the spine, and she was
started on a regimen of isoniazid and rifampin.
The pain worsened, and by June 1985, the
patient became unable to walk. Roentgenograms of
her spine (July 1985) showed progressive destruction
of the L3-L4 disc space, with right sacroiliac (SI)joint
destruction. A computed tomography scan demonstrated marked destruction of the L4 vertebral body.
Needle aspiration of the right SI joint gave negative
results on cytologic study, AFB staining, and bacterial
and TB cultures. At that time, the patient was referred
to the University of Colorado Health Sciences Center
for further evaluation.
At the time of admission, she was taking the
710
BRIEF REPORTS
serum glucose 239 mg/dl. Results of all other blood
chemistries analyzed were within normal limits.
The chest roentgenogram performed at admission demonstrated a diffuse increase in interstitial
markings bilaterally. Roentgenograms of the lumbosacral spine revealed destruction of the L4 vertebral
body, particularly of the inferior endplate, as well as
the superior endplate of the L5 vertebral body (Figure
1). There was also widening and sclerosis of the right
SI joint. Roentgenograms of the thoracic spine revealed destruction and fusion of the T3 and T4 vertebral bodies, with obscuration of the T3-T4 disc space.
A similar process involving the T8-T9 vertebral bodies
and disc space was also observed. Roentgenograms of
the cervical spine demonstrated destruction and fusion
of the C4 and C5 vertebral bodies, with obscuration of
the C&C5 disc space (Figure 2).
Figure 1. Lateral view radiograph of the lumbosacral spine, revealing destruction of the L4 and LS vertebral bodies.
following medications: prednisone (5 mg/day), Dpenicillamine (250 mglday), neutral protamine Hagedorn (NPH) insulin (20 unitdday, subcutaneously, in
the morning), digoxin (0.25 mglday), amitriptyline HC1
(25 mg/day, at bedtime), theophylline (200 mg every 8
hours), isoniazid (300 mg/day), and rifampin (600
mg/dzty).
Pertinent findings of the physical examination
included multiple rheumatoid deformities, but no active synovitis. Rheumatoid nodules were present over
her ears, knuckles, and the extensor surface of her
forearms. There was marked tenderness to palpation
over the L3 through L5 vertebral bodies and the right
SI joint. N o focal neurologic abnormalities were
noted. Auscultation of the lungs revealed dry crackles
at both bases. No other extraarticular manifestations
of RA were observed.
Laboratory investigations demonstrated the
following results: positive rheumatoid factor at a titer
of t :5,120, peripheral blood leukocyte count 7,900
cells/r~im~
with a normal differential cell count, hemoglobin 14 gm/dl, platelet count 403,000/mm3, Westergren
sedimentation rate 78 mm/hour* alkaline phosphatase 327 units/liter (normal 64-238), and
Figure 2. Lateral view radiograph of the cervical spine, revealing
destruction of the C4 and C5 vertebral bodies.
711
BRIEF REPORTS
An open biopsy of the lumbar spine was performed. There was a minimum of inflammation, but
marked destruction of the L4 and L5 vertebral bodies
was noted. Tissue specimens were negative for AFB,
and all cultures, including bacterial, fungal, and TB,
were negative. Sections of the vertebral bodies were
stained with hematoxylin and eosin, and multiple
granulomas were found in all sections. On close inspection, these granulomas were found to contain an
area of central necrosis surrounded by a middle layer
of palisading epithelioid cells (Figure 3). An outer third
layer, which was extremely dense in some areas,
contained lymphocytes and plasma cells. The pathologic findings were most consistent with a diagnosis of
rheumatoid nodules of the vertebral bodies, causing
bony destruction.
Fusion of the lumbar spine was performed
during a later operation. A similar procedure for the
cervical spine was planned, but because of cardiovascular instability during the lumbar spine fusion, it was
not performed. A cervical collar was applied, and the
patient was transferred to a rehabilitation hospital for
further care.
Discussion. Rheumatoid nodules of the vertebral bodies have been described in 3 previous reports
(4-6). Baggenstoss et a1 (4), in 1952, were the first to
report this finding. Their patient was a 56-year-old man
with a 3-year history of nodular RA who developed
severe, nonradiating pain of the lower back. Roentgenograms revealed destruction and anterior wedging
of the T12 vertebral body. The patient died of cardiac
causes. Autopsy revealed rheumatoid nodules involving the T I2 and L3 vertebral bodies, the myocardium, pericardium, synovial membrane, and subchondral bone.
Lorber et a1 ( 5 ) described a 47-year-old man
who presented with a I-year history of kyphosis and
pain of the lower thoracic spine. Roentgenograms
demonstrated anterior wedge compression of the T9
vertebral body and collapse of the vertebral plates of
L1 through L3. The patient subsequently developed
synovitis of his right knee, and there were biopsy-
Figure 3. Histologic appearance of a section from the vertebral body, obtained at open lumbar biopsy. Rheumatoid
nodules were found in all sections. The nodules were characterized by central necrosis, a surrounding middle layer of
palisading epithelioid cells, and an outer layer of lymphocytes and plasma cells (hematoxylin and eosin stained, original
magnification X 125).
712
proven rheumatoid nodules of both olecranon bursae.
Months later, he died of nephritis, pneumonia, and
sepsis. At autopsy, grey-white nodules were seen
infiltrating the vertebral marrow. Histologically, the
nodules consisted of granulation tissue and foci of
eosinophilic fibrinoid changes in collagen fibers, surrounded by palisading histiocytes and fibroblasts. Because of the limited central necrosis, these were
believed to represent atypical rheumatoid nodules.
Glay and Rona (6) described a 79-year-old
woman with a 6-year history of deforming RA and
biopsy-proven rheumatoid nodules over her buttocks.
The patient presented with a 3-month history of severe
low back pain, and roentgenograms revealed collapse
of the T12, L2, and L3 vertebral bodies. The patient
had a debilitating course, and she died. At autopsy,
classic rheumatoid nodules were found in the collapsed vertebral bodies. Two other patients with RA
were described by Glay and Rona. Both patients had
radiographic changes similar to those of the first
patient, but histologic confirmation was not obtained.
Two other published reports present cases suggestive of a similar process. Shichikawa et a1 (7)
described a 55-year-old woman with a 9-year history of
seropositive, nodular RA who developed low back
pain. Roentgenograms revealed destruction of the L4
and L5 vertebral bodies. The patient died of cardiac
causes, and at autopsy, a necrotic area surrounded by
granulation tissue was seen in the vertebral bodies of
L4 and L5. Although not classic for a rheumatoid
nodule, the point of its similarity to a rheumatoid
nodule was raised.
Seaman and Wells (8) described radiographic
findings in 2 patients with RA; both exhibited destruction of intervertebral disc spaces, as well as the
neighboring vertebral endplates. These abnormalities
were observed at the C6 and C7 level in 1 patient, and
at the T8 and T9 level in the other. Followup roentgenograms demonstrated a “healing stage,” with
fusion of the neighboring vertebral bodies and
obscuration of the disc space. These findings are
remarkably similar to those in our patient; however,
the findings in those 2 patients were not confirmed
histologically.
Some researchers have shown that rheumatoid
granulation tissue involves the intervertebral disc
spaces. Ball (9,lO) and Bland (11) examined the
cervical spines of autopsy subjects with RA and found
granulation tissue, which arose from the synovial-lined
neurocentral joints nearby, invading the disc spaces.
BRIEF REPORTS
The changes were present despite radiographic evidence of minimal or no abnormalities of these areas.
Bywaters (12) demonstrated that granulation tissue
had spread from the costovertebral and zygapophyseal
joints and had invaded the thoracic and lumbar disc
spaces, respectively, in a patient with RA.
Shichikawa et a1 (7) demonstrated that granulation tissue had invaded the cervical and thoracic disc
spaces of 2 patients with RA. A rheumatoid nodule
was also observed in the peridiscal area of the cervical
spine in 1 of the patients. In contrast to the thinking of
other investigators, it was those authors’ impression
that this inflammatory tissue arises from the surrounding ligaments and areolar tissue and then extends to
the adjacent vertebral body and disc space, as occurs
in ankylosing spondylitis.
Others have refuted these findings, questioning
whether all inflammatory tissue in a patient with RA
should be deemed secondary to the RA (12). Martel
(13) and Resnick (14) have argued that discovertebral
lesions in RA are a result of trauma at the discovertebral junction. It is their opinion that the lesions
might result from spinal instability caused by zygapophyseal synovitis and ligament laxity. Martel’s
evidence to support this concept includes the following: (a) Schmorl node-like erosion and disc space
narrowing often precede vertebral endplate destruction; (b) Zygapophyseal joint destruction precedes,
and occurs at the same level as, disc-cartilage destruction; (c) Histologic examination of an involved disc
and the adjacent vertebrae in 1 patient did not reveal
inflammation; and (d) This destruction is absent in
children, in whom ankylosis of the cervical zygapophyseal joints is a frequent occurrence.
In summary, we have described a patient with
seropositive nodular RA who was found to have
rheumatoid nodules of the vertebrae, which resulted in
bony destruction at 3 levels of the spine. The diagnosis
was confirmed by histologic methods. Similar clinical
and radiographic findings, in addition to the invasion
of disc spaces by rheumatoid granulation tissue, have
been reported in other patients. Histologic confirmation of such findings has been reported in only 3 of
those patients. We believe that vertebral involvement
in RA may be more common than has previously been
realized.
REFERENCES
1. Kaye BR, Kaye RL, Bobrove A: Rheumatoid nodules:
review of the spectrum of associated conditions and
BRIEF REPORTS
2.
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6.
proposal of a new classification, with a report of four
seronegative cases. Am J Med 76:279-292, 1984
H a m s ED Jr: Rheumatoid arthritis: the clinical spectrum, Textbook of Rheumatology. Second edition. Edited by WN Kelley, ED Harris Jr, S Ruddy, CB Sledge.
Philadelphia, WB Saunders, 1985, pp 915-950
Decker JL, Plotz PH: Extra-articular rheumatoid disease, Arthritis and Allied Conditions. Tenth edition.
Edited by DJ McCarty. Philadelphia, Lea & Febiger,
1985, pp 620-642
Baggenstoss AH, Bickel WH, Ward LE: Rheumatoid
granulomatous nodules as destructive lesions of vertebrae. J Bone Joint Surg 34A:601-609, 1952
Lorber A, Pearson CM, Rene RM: Osteolytic vertebral
lesions as a manifestation of rheumatoid arthritis and
related disorders. Arthritis Rheum 4514-532, 1961
Glay A, Rona G: Nodular rheumatoid vertebral lesions
versus ankylosing spondylitis. AJR 94:631-638, 1965
713
7. Shichikawa K, Matsui K, Oze K, Ota H: Rheumatoid
spondylitis. Int Orthop 253-60, 1978
8. Seaman WB, Wells J: Destructive lesions of the vertebral bodies in rheumatoid disease. AJR 86:241-250, 1961
9. Ball J: Pathology of the rheumatoid cervical spine (letter). Lancet I:86, 1958
10. Ball J: Enthesopathy of rheumatoid and ankylosing
spondylitis. Ann Rheuni Dis 30:213-223, 1971
1 1 . Bland JH: Rheumatoid arthritis of the cervical spine. J
Rheumatol 1:31%342, 1974
12. Bywaters GL: Rheumatoid discitis in the thoracic region
due to spread from costovertebral joints. Ann Rheum
Dis 33:408409, 1974
13. Martel W: Pathogenesis of cervical discovertebral destruction in rheumatoid arthritis. Arthritis Rheum 20:
1217-1225, 1977
14. Resnick D: Thoracolumbar spine abnormalities in rheumatoid arthritis. Ann Rheum Dis 37:38%392, 1978
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