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Acta Radiologica Short Reports
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DOI: 10.1177/2047981613477401
2013 2: tActa Radiologica Short Reports
Karantanas
Charalambos P Economides, Elpidoforos S Soteriades, Michalis Hadjigavriel, Ioannis Seimenis and Apostolos
Iron deposits in the knee joints of a thalassemic patient
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Case report
Iron deposits in the knee joints of a thalassemic patient
Charalambos P Economides
1,2
, Elpidoforos S Soteriades
1,3
, Michalis Hadjigavriel
4
,
Ioannis Seimenis
5
and Apostolos Karantanas
6
1
Cyprus Institute of Biomedical Sciences (CIBS), Nicosia, Cyprus;
2
Agios Therissos MRI Diagnostic Center, Department of MRI, Nicosia,
Cyprus;
3
Harvard School of Public Health, Department of Environmental Health, Environmental and Occupational Medicine and
Epidemiology (EOME), Boston, MA, USA;
4
Limassol General Hospital, Department of Internal Medicine, Limassol, Cyprus;
5
Democritus
University of Thrace, Medical School, Laboratory of Medical Physics, Alexandroupoli, Greece;
6
University of Crete, Department of Medical
Imaging, Heraklion-Crete, Crete
Correspondence to: Charalambos P Economides. Email: ceconomides@cibs.org.cy
Abstract
The overall prognosis for patients with b-thalassemia has improved considerably during the past decades
mainly due to regular blood transfusions, improvements in chelation therapy, and enhanced surveillance
with imaging studies examining iron overload and other clinical complications. However, the prolonged
survival of these patients leads to the development of other health problems including degenerative
diseases such as arthropathies, which require further attention since they have a significant impact on
the quality of life. In the current case report, we present a 45-year-old white man with b-thalassemia
complaining of non-traumatic pain and restriction in the range of motion of both knees. Magnetic resonance
imaging (MRI) revealed a tear in the medial meniscus of the left knee as well as iron deposits in both knees.
Histological findings confirmed the presence of hemosiderin in both joints. To our knowledge, this is the
first reported case of macroscopically documented iron deposits in the knee joints of a patient with
b-thalassemia using MRI.
Keywords: MR imaging, knee, arthritides, hematologic diseases
Submitted October 7, 2012; accepted for publication January 15, 2013
Patients with thalassemia constitute a significant public
health problem. Providing comprehensive care to such
patients has been viewed by many as a sensitive indicator
of the level and quality of healthcare services in each
country. Blood transfusions and iron overload of liver,
spleen, and heart and their associated complications have
received considerable attention by clinicians and researchers
alike due to their significant impact on morbidity and
mortality of these patients (1, 2). However, as the above
problems have gradually been studied and appropriate
therapies have been introduced in a relatively successful
fashion, contributing to a dramatic increase of patients’
overall survival, other health problems affecting quality
of life eventually may require further attention. Such pro-
blems may be associated with aging and/or degenerative
processes, which appear to have an accelerated pace in
patients with b-thalassemia or may also be related to iron
deposits in other organs including pancreas, pituitary
gland, and joints (3, 4).
Arthropathy is one of the emerging chronic health pro-
blems affecting a significant number of patients with
b-thalassemia, which, so far, has received limited attention
by the scientific, clinical, and public health community
(2, 5 –7). Although magnetic resonance imaging (MRI) has
been regularly utilized in assessing iron deposits in liver,
spleen, and heart and to a lesser extent in pancreas and
pituitary gland, no studies have, to date, been published
on the assessment of possible iron deposits in joints of
patients with b-thalassemia (1, 3, 4, 8).
Case report
A 45-year-old white man with b-thalassemia major was
referred for MRI of the left knee due to prominent non-
traumatic chronic medial and lateral pain (past 1–2 years),
as well as partial locking and restriction in the range of
motion. Neither previous nor recent traumatic knee injury
nor other suspicious events were reported. The patient
had been undergoing regular blood transfusions twice a
month main taining a hemoglobin level of about 9.5 mg/dl
and a ferritin level of 3000 ng/mL. The patient reported
receiving chelation therapy with only oral deferiprone for
Acta Radiologica Short Reports 2013:1. DOI: 10.1177/2047981613477401
the past 13 years at a dose of 75 mg/kg / day. Occasional
chelation with desferioxamine was also used during the
same time period. T2
measurements from previous MRI
examinations on heart and liver are presented in Table 1.
It was evident from the decreasing T2
measurements of
heart and liver, that there was progressive increase in the
degree of iron deposits in the above two org ans in parallel
with clinical observations of poor adherence to chelation
therapy compatible with high levels of plasma ferritin.
Following regular assessment, the patient underwent
MRI of the left knee. Subsequent MR scanning of the right
knee was also performed for comparison purposes.
Written informed consent was obtained from the patient
for publi cation of this manuscript and accompanying
images.
MRI technique
MRI was performed with a 3.0 Tesla scanner (Achieva,
Philips Medical Systems, Best, The Netherlands) to assess
arthropathy including potential iron deposits in the knee
joints. We used the built-in quadrature radiofrequency
(RF) body coil and a phased array 8-channel knee coil for
proton excitation and signal detection, respectively. MRI
scanning protocol included several multislice pulse
sequences routinely performed for morphological imaging
Table 1 Time trends of T2
measurements of liver and heart
Organ
Mean T2
(ms)
2007 2008 2010 2011
Liver
†
3.8 4.2 1.6 1.6
Heart
‡
18 22 11.3 10.3
†
Iron deposits assessed by T2
liver measurements range from mild to
moderate severity. Liver measurements were obtained from a region of
interest prescribed in the segment V/VIII of the right liver lobe
‡
Iron deposits assessed by T2
heart measurements range from normal
to moderate severity. Heart measurements were obtained from a region of
interest prescribed in the intraventricular region
Fig. 1 A fat-suppressed, PD-w image in the coronal plane of the left knee
shows a longitudinal tear in the body of medial meniscus (long arrow) and
the displaced meniscal fragment within the intercondylar notch (short
arrow). In addition, osteoarthritic changes with minimal subcortical cyst
formations and reactive bone marrow edema are noted in the medial
tibial plateau (open arrow)
Fig. 2 (a) A T2
-w sagittal image in the left knee represents foci of iron
deposits within the supra patellae pouch right above the superior pole of
the patellae (short arrow) and also in contact with the patellae cartilage at
the upper pole (long arrow), as well as within the Hoffa’s fat pad in contact
with the patellae cartilage in its inferior pole (open arrow) and in the cartilage
surface over the trochlea (doted arrow). (b) A fat-suppressed PD-w image in
the sagittal plane in the left knee shows foci of iron deposition along the
surface of the cartilage over the lateral trochlea (short arrow). We note
the drop of signal in the area of iron deposits, which is less prominent in
comparison with the corresponding T2
-w image
2 CP Economides et al.
.................................................................................................................................................
(in each case, 28 slices were acquired with a field-of-view
of 170 mm, a section thickness of 2.8 mm, and a pixel size
of 0.6 0.7 mm); T1-weighted (T1-w) (repetition time
[TR], 674 ms; echo time [TE], 18 ms; total scan time [ST],
2.5 min) turbo spin echo (TSE) in the sagittal plane;
T2
-weighted (T2
-w) (TR, 575 ms; TE, 12 ms; ST, 2.4 min)
gradient recalled echo (GRE) in the axial plane; proton
density-weighted (PD-w) (TR, 2342 ms; TE, 35 ms; ST,
2.9 min) TSE with spectral fat suppression in the coronal
and axial planes. Three-dimensional (3D) susceptibility
weighted imaging (SWI) and ultra short echo time (UTE)
GRE pulse sequences were also prescribed in the axial
plane. The former utilizes an echo-shifting technique that
allows the employment of relatively long ec ho times (TE,
21 ms) in a time-efficient way (TR, 15 ms; ST, 1.5 min for
100 slices with an acquisition resolution of 1 1 2 mm).
The latter uses a radial data sampling technique achieving
an ultra short TE of 14
m
s (TR, 7.5 ms; ST, 9.8 min; 144
slices; 1 mm
3
acquisition voxel size). The sequence used
for quantitative T2 measurements was also prescribed
in the sagittal plane. A single-slice (acquisition voxel size
of 0.5 0.5 5.0 mm) Carr Purcel Meibomm Gill (CPMG)
spin echo sequence employing 16 equidistant echoes, a
short echo spacing of 6 ms and a TR of 2s was used
(ST, 5.7 min).
MRI findings in the left knee
Left knee MR images revealed several pathological findings
compatible with the prominent clinical symptomatology.
The imaging findings included a flap tear of the medial
meniscus with a displaced meniscal fragment in the
medial intercondylar notch (Fig. 1). In addition, osteo-
arthritis was noted in the medial joint compartment with
marked attenuation of the articular cartilage, reactive
subcortical bone marrow edema in the medial tibial
plateau, and minimal subcortical cystic changes (Fig. 1).
Furthermore, there was mild attenuation of the patellar car-
tilage indicating chondromalacia patellae grade II. Foci of
iron deposits were identified macroscopically within the
supra-patellar pouch right above the superior pole of the
patellae and also in contact with the patellae cartilage at
the upper pole, as well as within the Hoffa’s fat pad in
contact with the patellae cartilage in its inferior pole and
in the cartilage surface over the trochlea (Fig. 2a). Finally,
iron deposits were also noted along the surface of the
medial plica in the supra-patellar pouch. The iron deposits
were detected as low signals intensity foci in all MRI
sequences used. However, iron deposits were less conspicu-
ous on the T1-w and PD-w sequences, with particular signal
loss on gradient echo (Fig. 2B). During the above study we
Fig. 3 This image represents four corresponding axial images from different pulse sequences of the left knee. (a) is a T2
-w image, (b) is an ultra short time echo
(UTE) image, (c) was obtained with susceptibility weighted imaging (SWI), and (d) represents PD-w imaging with a turbo spin echo sequence. In (a), we note a
large area of iron deposit in contact with the patellae and trochlea groove cartilage presented as a low signal intensity focus (arrow). In (b) and (c) we highlight a
further exaggeration of the signal loss in the area of iron deposits on the UTE and SWI sequences, respectively (arrows). In (d) we note less conspicuous signal
loss of the iron deposit area in the PD-w sequence (arrow)
Iron deposits in the knee joints of a thalassemic patient 3
.................................................................................................................................................
also noticed further exaggeration of the signal loss on the
SWI and UTE sequences (Fig. 3). In Table 2 we present
mean T2 measurements for regions of interest prescribed
in different areas of the cartilage in the left knee. The T2
measurement of normal Hoffa’s fat pad was 215 ms
(18.8 SD), while in Hoffas fat pad with iron deposits T2
measurement was 54.8 ms (11 SD) and in the supra-patellar
pouch with iron deposits T2 was 51.1 ms (4.4 SD), respect-
ively. Such findings indicate iron deposits in the above
regions with decreased T2 measurements.
MRI of the right knee was also performed mainly for
comparison purposes. Iron deposits were also noted in the
right knee (Fig. 4). Iron deposits were noted in contact
with the inferior pole of the patellar cartilage, as well as in
contact with the anterior articular surface of the lateral
femoral condyle.
Histology results
Following MRI studies, the patient underwent an arthro-
scopy of the left knee in order to explore the pathological
imaging findings and repair the meniscal tear. Biopsy
of the synovium showed edema of the basal membrane
with papillary morphology and hemosiderin deposits.
Histiocytes with hemosiderin moietie s were also noted
along with hyperplastic serous cells.
Discussion
To our knowledge, this is the first reported case of iron
deposits in the knee joint of a patient with b-thalassemia
major potentially associated with clinical symptoms. Our
case report poses an important question regarding the
prevalence of iron deposits in knee and other major joints
of patients with b-thalassemia major, especially those of
the lower extremities. In addition, this particular case
raises furthe r clinical concerns as to whether iron deposits
in joints may be associated with clinical arthropathy in
such patients. Furthermore, we pose a scientific question
on the potential association of iron deposits in joints
leading to the development of synovitis and/or cartilage
damage (2, 5–7). Finally, our findings lead to significant
clinical questions with respect to the effectiveness of the tra-
ditional chelation therapy to remove iron deposits from the
joints of patients with b-thalassemia.
The examination of our case was facilitated by MRI tech-
niques based on the GRE method that allow the visualiza-
tion of small foci of iron deposits. Such techniques include
the traditional T2
-w as well as the novel UTE and SWI
methods (9). The high sensitivity of the UTE pulse sequence
to iron is due to the ultra short echo time that employs,
which allows visualization of short T2 spe cies. SWI is
also a relatively new MRI sequence, which evaluates and
exploits the magnetic properties of tissues. Paramagnetic
substances like deoxyhemoglobin, a product of blood de-
gradation, and ferritin, a non-heme iron, are known
sources of magnetic susceptibility in the tissues and they
appear as hypointense foci. Albeit the high sensitivity
of UTE and SWI sequences in the detection of iron
deposits, CPMG and GRE sequences are more suited for
quantitative imaging in tissues, since the presence of para-
magnetic species reduce regional transverse relaxation
times. Therefore, T2 and T2
measurements are widely
used for liver and heart iron load evaluation.
As UTE and SWI are much more sensitive at lower con-
centrations of iron, they can be used to detect small foci of
iron deposits that conventional spin echo and GRE pulse
sequences fail to depict. In addition, because of their 3D
nature, UTE and SWI offer the possibility of rigorous and
thorough inspection of the joint for iron. Thus, they can
effectively guide the correct prescription of the single-slice
sequences used for quantitative transverse relaxation time
measurements. Due to the negative contrast effect of iron
foci, a major challenge is to distinguish regions of signal
void due to iron from those due to low signal tissues or sus-
ceptibility artifacts. Therefore, T2 measurements were only
performed at regions which appeared hypointense in both
UTE and SWI images.
MRI and the documented pathological picture of the left
knee, excluding the meniscal flap tear, showed advanced
Fig. 4 AT2
-w sagittal image of the right knee obtained with a gradient
recalled echo (GRE) pulse sequence. Iron deposits are noted in contact
with the inferior pole of the patellae cartilage (short arrow), as well as in
contact with the anterior cartilage surface of the lateral femoral condyle
(long arrow)
Table 2 Measurements of T2 in different areas of the cartilage of the
left knee
Mean T2 (SD) (ms)
Patella
Lateral
trochlea
Articular
surface
(lateral
femoral
condyle)
Articular
surface
(lateral
tibial
plateau)
Time (ms) 60 (11.5) 79 (8.8) 63 (18.6) 40 (8.9)
4 CP Economides et al.
.................................................................................................................................................
degenerative changes, which are thought to be non-
compatible with the patient’s age and clinical history. This
is an interesting finding in view of the macroscopically
noted iron deposits and the poor adherence to chelation
therapy. Further studies are warranted in order to examine
the prevalence of iron deposits in the joints of patients
with b-thalassemia and their potential association with
accelerated degenerative chang es especially in the lower
extremities. In addition , there should be enhanced clinical
interest on the evaluation of the effectiveness of chelation
therapy for removing iron deposits from joints in a similar
fashion with other organs such as liver and heart.
Our case report, although raising important epidemiolo-
gical and clinical questions, may not be representative of
the majority of patients with b-thalassemia in the developed
countries, where patients may adhere to chelation therapy,
since the particular patient had a poor adherence to chela-
tion treatment. An additional limitation of our case may
be associated with our inability to dissociate the do-
cumented clinical pathology in the knee joint with the
degenerative changes and allocate potential partial etiology
to iron deposits. Although the case is an interesting example
of iron deposits in knee joints, the causal relationship with
arthropathy/meniscal rupture documented with MRI and
arthroscopy is purely speculative. Further epidemiological
studies with case series, case-control, and cohort studies
are warranted to explore the above scientific questions.
In conclusion, our case report highlights a new and
emerging chronic problem of patients with b-thalassemia;
namely arthropathy, which may be potentially related to
accelerated degenerative changes in the joints of the above
patients in association with iron deposits.
ACKNOWLEDGEMENTS
The authors thank Philips Medical Systems Inc., Best, The
Netherlands for their kind provision of the ultra short
TE pulse sequence.
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