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[4] Lederman ER, Crum NF. A case series and focused review of nocardiosis:
clinical and microbiologic aspects. Medicine 2004;83:300e13.
[5] Laurin JM, Resnik CS, Wheeler D. Vertebral osteomyelitis caused by
Nocardia. J Rheumatol 1991;18:455e8.
[6] Harm C, Graat HC, Van Ooij A, Day JA, Mac Phee IB. Nocardia farcinica
spinal osteomyelitis. Spine 2002;27:253e7.
[7] Moylett EH, Pacheco SE, Brown-Elliott AE. Clinical experience with
linezolid for treatment of Nocardia infection. Clin Infect Dis
2003;36:313e8.
Emmanuel Chatelus*
Rose-Marie Javier
Jean Sibilia
Jean-Louis Kuntz
Rheumatology Department, Hautepierre Teaching Hospital,
CHU de Hautepierre, Avenue Moliere,
67098 Strasbourg Cedex,
France
*Corresponding author.
E-mail address: emmanuel.chatelus@chru-strasbourg.fr
(E. Chatelus)
Emmanuel Forestier
Internal Medicine and Infectious and Tropical Diseases
Department, Strasbourg Teaching Hospital,
Strasbourg, France
Jeannot Gaudias
Septic Surgery Department,
Illkirch Center for Traumatology and Orthopedic Surgery,
Strasbourg, France
28 March 2006
Available online 2 February 2007
1297-319X/$ - see front matterÓ2007 Elsevier Masson SAS. All rights reserved.
doi:10.1016/j.jbspin.2006.08.003
Amyloid deposition in knee and ankle joints in the course
of multiple myeloma
Keywords: Amyloidosis; Multiple myeloma; Knee and ankle joints
1. Introduction
Multiple myeloma (MM) is a malignant hematological dis-
ease, which is characterized by the production of monoclonal
M protein and abnormal plasma cell infiltration of bone mar-
row and other tissues in some cases [1,2]. MM is sometimes
complicated by amyloidosis [3,4]. Amyloidosis may be sys-
temic or localized. Although the current classification of the
disease is based on the biochemical composition of the precur-
sor protein, unrelated to the biochemical features, clinical fea-
tures are similar and may vary correlated with the involved
tissue and organs. The most common symptoms are fatigue,
weight loss, macroglossia, orthostatic hypotension, diarrhea,
cardiomegaly, nephrotic syndrome, renal failure, congestive
heart failure, carpal tunnel syndrome and neuropathy [4]. Am-
yloid infiltration in vital organs can be fatal if left untreated.
Amyloid deposition in joints can be detected in the course
of systemic myeloma complicating with the restriction of
movements of infiltrated regions. Most common involved
joints are shoulders, wrists, knees and metacarpophalangeal
joints. Generally, arthropathy presents with bilateral symmet-
ric polyarthritis. However, amyloid deposition in bilateral
knees associated with other joint invasion has been reported
very rarely [5]. We hereby present a case with the diagnosis
of MM complicated with amyloid deposition in bilateral
knee and ankle joints under the treatment.
2. Case report
This fifty four years old male patient was referred to our
hospital because of anemia, generalized bone pain and elevated
erythrocyte sedimentation rate (ESR). He complained restric-
tion in movements of bilateral wrist joints and diagnosed as
carpal tunnel syndrome few months ago without further inves-
tigation and treatment. On his physical examination, there was
no finding except pallor. Laboratory analysis showed anemia
(haemoglobin as 7.9 g/dl), hyperuricemia (8.2 mg/dl) and
elevated ESR (67 mm/h). There was rouleaux formation on pe-
ripheral blood smear. Urinalysis revealed proteinuria more than
1 gr/day and immunofixation of urine and blood showed mono-
clonal gammopathy of lambda-light chain. No lythic lesions
were detected on his plain bone radiograms. Bone marrow as-
piration and biopsy demonstrated 30e40% lambda-positive
atypical plasma cells, confirming the diagnosis of lambda light
chain myeloma, stage IIA, according to Durie-Salmon classifi-
cation. Standard dose of VAD regimen was administered as
vincristine 0.4 mg/day D1e4, adriablastina 9 mg/m
2
/day
Fig. 1. Right knee T2-weighted sagittal plane MRI: Low signal intensity and
signal void areas are present in effusion of knee joint posteriorly.
209Letters to the editor / Joint Bone Spine 74 (2007) 205e211
D1e4 and dexamethasone 40 mg/day D1e4 and also monthly
biphosphanate treatment was applied. After completing 4th cy-
cle of therapy, he complained stiffness and joint restriction in
bilateral knee and ankle, which was developed very recently.
Physical examination showed that the ranges of motion of bi-
lateral knees were restricted in flexion up to 45, and similar
findings in bilateral ankles. For this reason magnetic resonance
imaging (MRI) was planned. Multiplanar spin-echo
T1-weighted (TR: 500; TE: 12), turbo spin-echo T2-weighted
(TR: 3500; TE: 80) and turbo spin-echo T2-weighted with
fat-saturated sequences (TR: 4500; TE: 80) were performed.
T2-W images showed low signal intensity areas in bilateral
knee joints and heterogeneous signal intensity areas in effu-
sion, which were evaluated as evocative findings of amyloid
pigments (Figs. 1and S1a,b; see the supplementary material as-
sociated with this article online). MRI showed similar findings
in bilateral ankle joints and low signal intensity areas were
present in effusion of talo-calcaneal and tibiotalar joints
(Figs. 2and S2a,b). Bone marrow biopsy performed at that
time revealed AL amyloid deposition, which was positive
with congo red staining (Fig. S3) and 30% atypical plasma
cell infiltration. Renal biopsy was not performed and echo-
cardiographic examination showed normal cardiac functions.
Treatment was planned and administered as high dose chemo-
therapy with melphalan 200 mg/m
2
with the support of autolo-
gous peripheral progenitor cells (4.5 10
6
CD34þcells/kg),
which was collected after mobilization with cyclophosphamide
4 gr/m
2
and G-CSF. This treatment period was uneventful and
arthroscopic biopsy performed after completing therapy con-
firmed the diagnosis of amyloidosis in meniscus of knee joints
(Fig. S4). Clinical and laboratory findings were stable after
high dose chemotherapy regarding the amyloidosis and the pa-
tient has been in remission and still under follow up.
3. Discussion
Amyloid arthropathy is a rare complication of multiple my-
eloma. Although most cases of amyloid arthropathy are
chronic hemodialysis patients related to elevated b
2
microglo-
bulin levels [5], there are case reports with amyloid arthropa-
thy developed in the course of multiple myeloma or some
reports with myeloma patient presenting with amyloid ar-
thropathy. Most affected joints in the systemic amyloidosis
were reported as shoulders and wrists, followed by the knees
and metacarpophalangeal joints [6,7]. In the literature,
between 1978 and 1996, Fautrel et al. reported 11 patients
with amyloid arthropathy among 311 patients who had diag-
nosed multiple myeloma [8]. All patients with arthropathy
had presented with arthritis and most patients had the diagno-
sis of arthropathy within the 6 months after MM diagnosis.
Nine patients had light-chain myeloma like our patient.
They have reported that rheumatoid arthritis-like polyarthritis
and hypertrophic arthropathy were common in involved joints.
Intra-articular steroid injection was shown to be effective in
achieving complete relief. They also indicated that amyloid ar-
thropathy was not associated with decreased survival, except
for patients with concomitant cardiac involvement. In their
study, amyloid deposition was shown on magnetic resonance
images clearly and MRI was reported as effective method
for the diagnosis of amyloid arthropathy [8].
For patients in whom radiological examination of joints
shows non-specific changes, MRI is a very useful technique for
determination of the intraarticular amyloid deposition
[6,8e10]. MRI could show changes in intensity, signal void areas
and heterogeneous signal intensity in articular effusions. Syno-
vial membrane biopsy is the most important diagnostic test for
amyloid arthropathy [6,9,10]. Congo red staining of biopsy spec-
imens reveals amyloid deposition with characteristic staining.
Evaluation of the response to treatment for amyloidosis is
difficult since it is not possible to measure total amount of am-
yloid in the body even by imaging with 123I-labelled human
serum amyloid P component. Instead of this method, evaluat-
ing organ functions and measuring the monoclonal protein in
the serum and urine could be more preferable. Current therapy
modalities for systemic amyloidosis are inadequate. There are
several studies favoring the use of melphalan and prednisone.
Kyle et al. reported the results of treatment of patients with
primary systemic amyloidosis, with either colchicine alone,
or melphalan plus prednisone or combination of three drugs.
They reported that therapy with melphalan and prednisone
resulted in objective response and prolonged survival as com-
pared with colchicine [11].
Although conventional treatment of myeloma contains mel-
phalan and prednisone, randomized studies have shown that
high dose chemotherapy and autologous stem cell transplanta-
tion (ASCT) was associated with a higher survival [12,13].
Melphalan and prednisone have also been used for treatment
for patients with AL amyloidosis. Some studies showed that
these agents improved survival [12]. Another treatment option
is autologous stem cell transplantation for patients with AL
amyloidosis. A higher response rate and high transplant-
Fig. 2. Left ankle T2-weighted (fat saturated) sagittal plane MRI: Low signal
intensity areas are present in effusion of talocalcaneal joint.
210 Letters to the editor / Joint Bone Spine 74 (2007) 205e211
related mortality has been reported for AL amyloidosis with
ASCT [13]. Different studies with transplanted patients
reported complete hematological responses in a range of
14e62% [13]. More intensive therapy consisting of high-
dose chemotherapy followed by rescue with peripheral blood
stem cells looks like a promising treatment modality in future.
In conclusion, big joint infiltrations by amyloid deposition
should be carefully considered and evaluated in patients with
joint complaints in the course of systemic MM. MRI is
a successful technique to demonstrate amyloid deposition
in joints. While ASCT is almost standard therapy for multi-
ple myeloma patients, it could be also treatment option for
the patients with amyloidosis developed in the course of
myeloma.
Appendix. Supplementary material
Supplementary material (Figs. S1aeS4) associated with
this article can be found at http://www.sciencedirect.com,at
doi:10.1016/j.jbspin.2006.04.009.
References
[1] Kyle RA, Rajkumar SV. Plasma cell disorders. In: Goldman L,
Ausiello DA, editors. Cecil textbook of medicine. 22nd ed. Philadelphia:
W.B. Saunders; 2004. p. 1184e95.
[2] International Myeloma Working Group. Criteria for the classification
of monoclonal gammapathies, multiple myeloma and related disorders:
a report of the International Myeloma Working Group. Br J Haematol
2003;121:749e57.
[3] Haridas A, Basu S, King A, Pollock J. Primary isolated amyloidoma
of the lumbar spine causing neurological compromise: case report and
literature review. Neurosurgery 2005;57:E196.
[4] Ansari-Lari MA, Ali SZ. Fine-needle aspiration of abdominal fat pad
for amyloid detection: a clinically useful test? Diagn Cytopathol 2004;
30:178e81.
[5] Aoki Y, Kaneda K, Miyagi N, Itoh M, Ohmoto H. Popliteal amyloidoma
presenting with leg ischemia in a chronic dialysis patient. Skeletal Radiol
2000;29:717e20.
[6] Gisserot O, Landais C, Cremades S, Terrier JP, Leyral G, Bernard P, et al.
Amyloid arthropathy and Waldenstrom macroglobulinemia. Joint Bone
Spine 2006;73:456e8.
[7] Fujishima M, Komatsuda A, Imai H, Wakui H, Watanabe W,
Sawada K. Amyloid arthropathy resembling seronegative rheumatoid
arthritis in a patient with IgD-kappa multiple myeloma. Intern Med
2003;42:121e4.
[8] Fautrel B, Fermand JP, Sibilia J, Nochy D, Rousselin B, Ravaud P.
Amyloid arthropathy in the course of multiple myeloma. J Rheumatol
2002;29:1473e81.
[9] Shim JC, Lee YW, Lee GJ, Jeon JD, Kim HK. MR finding of primary
amyloid arthropathy associated with multiple myeloma. J Comput Assist
Tomogr 1997;21:800e2.
[10] Kanoh T, Izumi T, Okuma M. Multiple myeloma presenting with amy-
loid arthropathy. Rinsho Ketsueki 1993;34:962e6.
[11] Gertz MA, Leung N, Lacy MQ, Dispenzieri A. Myeloablative chemo-
therapy and stem cell transplantation in myeloma or primary amyloidosis
with renal involvement. Kidney Int 2005;68:464e71.
[12] Kyle RA, Geretz MA, Greipp PR, Witzig TE, Lust JA, Lacy MQ, et al.
A trial of three regimens for primary amyloidosis: colchicine alone,
melphalan and prednisone and melphalan, prednisone, and colchicine.
NEJM 1997;336:1202e7.
[13] Mollee PN, Wechalekar AD, Pereira DL, Franke N, Reece D, Chen C,
et al. Autologous stem cell transplantation in primary systemic amyloid-
osis: the impact of selection criteria on outcome. Bone Marrow Trans-
plant 2004;33:271e7.
Fahri Sahin
Nur Akad Soyer
Guray Saydam*
Filiz Vural
Murat Tombuloglu
Department of Hematology,
Ege University Hospital, Bornova, Izmir, Turkey
*Corresponding author. Tel./fax: þ90 232 390 3530.
E-mail address: guray.saydam@ege.edu.tr (G. Saydam)
Mehmet Argin
Department of Radiology,
Ege University Hospital, Bornova, Izmir, Turkey
Yesim Ertan
Department of Pathology,
Ege University Hospital, Bornova, Izmir, Turkey
2 January 2006
Available online 12 February 2007
1297-319X/$ - see front matterÓ2007 Elsevier Masson SAS. All rights reserved.
doi:10.1016/j.jbspin.2006.04.009
211Letters to the editor / Joint Bone Spine 74 (2007) 205e211
