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Current Rheumatology Reviews
ISSN: 1573-3971 - Volume 2, 4 Issues, 2006
Current Rheumatology Reviews
Volume 1, Number 2, June 2005
Contents
Upgrading a Classic - Bone Scans in Rheumatology
Pp. 111-118
Robert Pichler and Karl Stieglbauer
[Abstract]
The Role of Inflammatory Mediators in Cartilage Degradation
Pp. 119-124
Kayo Masuko-Hongo and Kazuo Yudoh
[Abstract]
The Osteoclast as a New Target in the Treatment of
Rheumatoid Arthritis: A Role for the Bisphosphonates? Pp.
125-129
Jan Van Offel, Evelyne Dombrecht, Wim J. Stevens and Luc
De Clerck
[Abstract]
The Role of Apoptosis in Arthritis Pp. 131-142
Charles J. Malemud and Heather J. Gillespie
[Abstract]
The Role of Chemokines in the Pathogenesis of Rheumatoid
Arthritis Pp. 143-150
Kenji Tani, Keiko Sato and Saburo Sone
[Abstract]
The Long-Term Outcome of Juvenile Idiopathic Arthritis
Pp. 151-155
Angelo Ravelli and Alberto Martini
[Abstract]
Specific Biologic Therapy with Tumor Necrosis Factor
Inhibitors in Patients with Inflammatory Myopathy Pp.
157-165
Albert Selva-O’Callaghan, Moises Labrador-Horrillo
and Miquel V. Tarres
[Abstract]
Nociceptive Pathway and Pathology of Low Back Pain
Pp. 167-176
Shinji Imai
[Abstract]
Antigen Specificity and Clinical Relevance of Antiphospholipid
Syndrome-Related Autoantibodies Pp. 177-187
Ricardo R. Forastiero and Marta E. Martinuzzo
[Abstract]
Cyclophosphamide: Time to Say Goodnight and Goodbye?
Pp. 189-191
Catherine Edwards and David Isenberg
[Abstract]
Hyperuricemia and Coronary Artery Disease Pp.
193-197
Christine Halligan and Eric L. Matteson
[Abstract]
Syphilis: Its History and World Impact Pp.
199-204
Bruce Rothschild
[Abstract]
Abstracts
[Back to top]
Upgrading a Classic - Bone Scans in Rheumatology
Robert Pichler and Karl Stieglbauer
Bone scanning is one of the most common procedures performed
in the majority of nuclear medicine departments. Radionuclides
on 99m-Tc phosphonates initiated the widespread use of bone
scintigraphy over 40 years ago. These diagnostic methods exhibit
excellent sensitivity in the detection of local abnormalities
of bone metabolism, but specificity is lacking. Interpretation
using conventional radiological diagnostic methods coupled
with a focus on the patients´ history and clinical signs
are essential. Bone scintigraphy makes valuable contributions
to orthopedics and traumatology; in cancer patients the method
is used to detect bone metastasis and target areas for radionuclide
therapy in controlling severe osseous pain in both cancer
and polyarthritis patients. The development of inflammation
scan methods, such as the antibody-labeled granulocyte scan
and introduction of methods to detect chronic infectious processes
by 67-Ga amplified the diagnostic accuracy. Nuclear medicine
today has a broad program for diagnostic and therapeutic approaches
to diseases of bone and joints. In a vast spectrum of rheumatological
diseases, these methods contribute to early diagnosis, interpretation
of extension and are used during follow- up to define both
the inflammatory activity in arthritic joints and the therapeutic
response in osteoarthritis. Recently the use of 18-FDG by
PET camera systems to detect malignancy and infection has
provided additional information in the management of rheumatology
patients – especially considering differential diagnosis
in metastatic diseases. In the future, the excellent properties
of 18-F in bone metabolism indices for skeletal PETs may lead
to its broader use not only in Paget´s disease or SAPHO
syndrome, but also in osteoarthritis and the management of
patients with osteoporosis.
[Back to top]
The Role of Inflammatory Mediators in Cartilage Degradation
Kayo Masuko-Hongo and Kazuo Yudoh
Mounting evidence points to the importance of the role played
by inflammatory mediators, such as cytokines or prostanoids,
in the degradation of cartilage, not only in inflammatory
arthritis, but also in degenerative joint diseases. In addition
to well-known mediators such as interleukin-1, recent investigations
have revealed the distinctive roles of a variety of other
mediators in the regulation of cartilage matrix turnover.
The present review focuses on the roles of inflammatory mediators
in cartilage pathology that have been revealed by experimental
evidence.
[Back to top]
The Osteoclast as a New Target in the Treatment of
Rheumatoid Arthritis: A Role for the Bisphosphonates?
Jan Van Offel, Evelyne Dombrecht, Wim J. Stevens and Luc
De Clerck
There is a lot of evidence that osteoclasts have a pivotal
role in the subchondral, periarticular and general bone loss
in rheumatoid arthritis. Bisphosphonates have a high affinity
for bone where they are strong inhibitors of osteoclast mediated
bone resorption. There is no doubt that bisphosphonates are
useful in patients with postmenopausal or glucocorticoid induced
osteoporosis certainly if these patients also suffer from
RA. Bisphosphonates appear to have beneficial effects on subchondral
bone loss and joint destruction in animal models of arthritis.
However in human studies these effects remain largely unclear
although some antiinflammatory influence seems to be confirmed.
An explanation for this discrepancy might be the possibility
that more potent agents, or higher doses of existing agents,
need to be used. Additional research is necessary to reveal
if bisphosphonates possess disease-modifying properties in
RA.
[Back to top]
The Role of Apoptosis in Arthritis
Charles J. Malemud and Heather J. Gillespie
Programmed cell death (i.e. apoptosis) plays a critical
role in the pathogenesis and progression of several arthritic
conditions and autoimmune disorders. Apoptosis induction is
dependent on the extent to which the initiating apoptotic
signal occurs via a receptor-mediated event (i.e. extrinsic
pathway) or by changes in mitochondrial membrane permeability
(i.e. intrinsic pathway). In this regard, differential activation
of downstream caspases that degrade chromatin-containing DNA
resulting in internucleosomal DNA fragmentation occurs by
one of these apoptosis pathways or by combinations of both.
In degenerative joint diseases such as osteoarthritis, interleukin-1
(IL-1), tumor necrosis factor-a (TNF-a) as well as nitric
oxide (NO) levels are significantly elevated in osteoarthritic
joint synovial fluid. Thus, IL-1, TNF-a as well as NO induced
human chondrocyte apoptosis in vitro and apoptosis frequency
is often elevated in aging and osteoarthritic cartilage compared
to young normal subjects or cartilage age-matched to the osteoarthritic
specimens, respectively. A decrease in viable chondrocytes
which could result from apoptosis induction in articular cartilage
probably has significant implications for cartilage repair
in osteoarthritis. Synovial hyperplasia with the resultant
formation of pannus suggests that apoptosis-resistance pathways
are active in rheumatoid arthritis. A resistance to apoptosis
induction is pertinent to cartilage and bone destruction as
well in rheumatoid arthritis as is the severity and progression
of rheumatoid arthritis pathology. It is noteworthy that medical
management of rheumatoid or psoriatic arthritis with anti-TNF-a
monoclonal antibodies, while limiting lymphocyte infiltration
into affected tissues does not induce apoptosis in synovial
joint tissue. Systemic lupus erythematosus is an autoimmune
disorder in which the failure to delete auto-reactive Tlymphocytes
during immune development suggests that dysfunctional T-lymphocyte
function may result from defective apoptosis. Defective T
lymphocytes are responsible for abnormal B-cell function,
autoantibody production as well as synovial joint arthropathy
in lupus. In another view, lupus may be characterized by overly
aggressive apoptosis leading to increased apoptotic cell load
coupled to a deficiency in apoptotic cell clearance. Lymphocyte
infiltration of salivary and lacrimal glands characteristic
of Sjögren’s syndrome causes gland destruction
by apoptosis with resultant gland dysfunction.
[Back to top]
The Role of Chemokines in the Pathogenesis of Rheumatoid
Arthritis
Kenji Tani, Keiko Sato and Saburo Sone
Rheumatoid arthritis (RA) is a chronic, multisystem autoimmune
disease characterized by persistent accumulation of leukocytes
in the synovial compartment. The influx of the leukocytes
is important as a critical step in the pathogenesis of RA.
Chemotactic cytokines (chemokines) play a critical role in
the pathogenesis of RA not only by inducing the migration
of inflammatory cells but also by enhancing the production
of inflammatory mediators and angiogenesis. The production
of chemokines is regulated by proinflammatory cytokines such
as tumor necrosis factor-a and interleukin-6 produced in the
inflamed joint suggesting that the efficacy of anti-cytokine
therapy is mediated at least partly by the reduction of chemokine
production. Th1- type T cells have a role in the joint inflammation
of RA because Th1-related chemokine receptors are predominantly
expressed on RA synovial tissue T cells. The present review
summarizes current knowledge on the role of chemokines and
their receptors in the pathogenesis of RA. The authors also
review the important relevance of chemokines for therapeutic
intervention.
[Back to top]
The Long-Term Outcome of Juvenile Idiopathic Arthritis
Angelo Ravelli and Alberto Martini
Over the past decades, a number of studies have evaluated
the long-term outcome of juvenile idiopathic arthritis (JIA)
and some of them have also attempted to identify early prognostic
factors. The available data indicate that JIA is not a benign
disease because a substantial number of patients still enter
adulthood with persistently active disease and may develop
severe physical disability. Although a great deal of data
are accumulating on prognostic factors in JIA, prediction
of long-term outcome early after disease presentation is still
difficult because comparisons among existing studies are hindered
by a number of reasons. To increase comparability of future
analyses and obtain generalizable information on the prognosis
of JIA and its prediction, a great deal of effort should be
directed toward standardizing the study design and the measurement
of predictors and outcomes.
[Back to top]
Specific Biologic Therapy with Tumor Necrosis Factor
Inhibitors in Patients with Inflammatory Myopathy
Albert Selva-O’Callaghan, Moises Labrador-Horrillo
and Miquel V. Tarres
Tumor necrosis factor (TNF) and TNF receptors are members
of a family of molecules with important regulatory functions
that include cellular activation and apoptosis. Neutralization
of TNFa has proven to be effective in a variety of inflammatory
disorders and autoimmune diseases such as rheumatoid arthritis
and Crohn's disease. Treatment of inflammatory myopathies
remains a challenge, especially in the case of refractory
disease. Elevation of soluble tumor necrosis factor observed
in patients with polymyositis/dermatomyositis has led to the
suggestion that biologic therapies may be useful in these
patients, although experience with anti-TNF agents is still
limited. The aim of this mini-review is to summarize the biological
bases for treatment of these patients with TNFa inhibitors,
to look at the risks and benefits of this therapy -malignancy
in patients with a recognized paraneoplastic association and
infection versus therapeutic response in refractory myositisand
to review the results of the currently reported cases.
[Back to top]
Nociceptive Pathway and Pathology of Low Back Pain
Shinji Imai
Despite the various classical works, the mechanism of chronic
low back pain has not been fully understood. Recent improvement
of neuroanatomical techniques has enabled discrimination of
fine neural elements as well as exact tracing of the neural
projection. Use of these techniques to elucidate the fine
innervation of the vertebral column has provided numerous
original findings. The present article reviews those studies
that contributed to the improvement of our understanding on
the mechanism of chronic low back pain. Meanwhile, recent
development of molecular biological techniques has also elucidated
participation of cellular mediators in the local and central
sensitization of nociceptors. The cellular components as well
as their chemical mediators may represent an attractive therapeutic
target of near future.
[Back to top]
Antigen Specificity and Clinical Relevance of Antiphospholipid
Syndrome-Related Autoantibodies
Ricardo R. Forastiero and Marta E. Martinuzzo
The presence of antiphospholipid antibodies (aPL) combined
with venous or arterial thrombosis, and/or obstetric complications
defines the antiphospholipid syndrome (APS). Lupus anticoagulants
(LA) and anticardiolipin antibodies (aCL) were the first described
aPL. It has been shown that aPL, despite their name, are not
directed against anionic phospholipids, as had previously
thought, but are a part of a large family of autoantibodies
against phospholipid-binding plasma proteins. The most important
and relevant antigenic targets involved in APS are b2 glycoprotein
I (b2GPI) and prothrombin. However, an increasing number of
other phospholipid-binding proteins with crucial functions
in the regulation of blood coagulation and fibrinolysis are
also targeted by APS-related autoantibodies. For clinical
purposes, it is important to find which aPL markers has the
best prognostic value. While it has been clearly demonstrated
that LA and, to a lesser extent, aCL represent a risk for
thrombosis, the role of antibodies directed against b2GPI,
prothrombin as well as other targets is still uncertain and
controversial. Data from a prospective study showed the presence
of antibodies to prothrombin and/or b2GPI is a predictor of
first or recurrent thromboembolic events in patients with
LA and/or aCL. This review intends to highlight the antigen
specificity and clinical relevance of APSrelated aPL.
[Back to top]
Cyclophosphamide: Time to Say Goodnight and Goodbye?
Catherine Edwards and David Isenberg
For over 20 years cyclophosphamide, either intravenous or
oral, has been widely used in the treatment of patients with
lupus nephritis, cerebritis and vasculitis. Although clearly
beneficial for many patients, its propensity to cause haematological
complications and reduced fertility has made it unpopular
with both patients and physicians.
The introduction of mycophenalate mofetil, and the exciting
potential for other forms of therapy including B cell depletion,
the B cell toleragen LJP394 and anti-BlyS antibodies, now
makes it possible to consider the future of the treatment
of patients with lupus without resorting to cyclophosphamide.
This review considers how close we are to achieving this goal.
[Back to top]
Hyperuricemia and Coronary Artery Disease
Christine Halligan and Eric L. Matteson
Hyperuricemia is strongly associated with several known
risk factors for cardiac disease including hypertension, diabetes
mellitus, hypercholesterolemia and obesity. Despite this association
between hyperuricemia and these coronary artery disease risk
indicators, most studies have failed to demonstrate a direct
causal relationship between hyperuricemia itself and cardiovascular
disease. It has been suggested that insulin resistance and
endothelial dysfunction may be a common denominator in linking
cardiovascular disease and hyperuricemia.
[Back to top]
Syphilis: Its History and World Impact
Bruce Rothschild
The history of syphilis is one of irresponsibility, mythology
and more recently, scientific insight. Pseudo-Descartian (defined
as ‘I think, therefore I publish’) mythology has
until now precluded any cogent discussion of where the disease
originated and who was responsible for its spread. Evidence-based
research now allows clear separation of syphilis from others
in its class of treponematosis. Examination of skeletons from
populations with clinically diagnosed bejel and yaws revealed
bone alterations distinctive to those diseases and clearly
separating them from syphilis. These insights allowed confident
identification, for the first time, of the New World origin
of syphilis and indeed, the ‘smoking gun’ in the
Dominican Republic. Thus, the role of Columbus’ crew
in transmitting syphilis from the New World to the Old is
confirmed. Finally, the impact of syphilis on history is explored,
ranging from character assassination to potential effect on
artistic expression and on the madness that enveloped the
third to fifth decades of the last century.
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