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Current
Rheumatology Reviews
ISSN: 1573-3971
Current Rheumatology Reviews
Volume 3, Number 2, May 2007
Contents
Editorial Pp. 93
Endothelial Progenitor Cells: A Vascular Perspective
for Inflammatory Rheumatic Disorders Pp. 95-101
Jérôme Avouac, Georges Uzan, Fabrice Juin,
André Kahan, Catherine Boileau and Yannick Allanore
[Abstract]
Serum Procalcitonin Levels in Febrile Patients with
Systemic Autoimmune Diseases Pp. 103-111
Ernesto Trallero-Araguás, Alberto Selva-O’Callaghan
and Miquel Vilardell-Tarrés
[Abstract]
New Insights into the Pathogenesis of Fibromyalgia
Syndrome: Important Role of Peripheral and Central Pain Mechanisms
Pp. 113-121
Roland Staud
[Abstract]
The Role of Biomechanical Factors on Patellofemoral
Osteoarthritis Pp. 123-127
Patricia A. Berry, Andrew J. Teichtahl, Anita E. Wluka
and Flavia M. Cicuttini
[Abstract]
Why Should Rheumatologists Consider Vitamin D Supplementation
for their Patients? Pp. 129-134
Heike A. Bischoff-Ferrari
[Abstract]
Tendinopathy and Neovascularization in Rheumatology
Pp. 135-146
Karsten Knobloch
[Abstract]
Low Level Laser Therapy [LLLT] in Inflammatory and
Rheumatic Diseases: A Review of Therapeutic Mechanisms
Pp. 147-154
Rodrigo Álvaro B. Lopes-Martins, Sócrates
C. Penna, Jon Joensen, Vegard V. Iversen and Jan M. Bjordal
[Abstract]
Periarticular Corticosteroid Treatment of the Sacroiliac
Joint Pp. 155-157
Reijo Luukkainen
[Abstract]
Pathogenesis of SLE Dermatitis – A Reflection
of the Process in SLE Nephritis? Pp. 159-165
Silje Fismen, Ole P. Rekvig and Elin S. Mortensen
[Abstract]
Pathophysiology and Treatment of Fibromyalgia Syndrome
Pp. 167-170
Thomas Stratz, Marion Schneider, Thomas O. Joos, Hsin-Yun
Hsu and Wolfgang Müller
[Abstract]
Abstracts
[Back to top]
Editorial: At Long Last: A Viable Biomedical Model
for Fibromyalgia
Fibromyalgia (FM) is a syndrome and not a disease. Six million
people in the United States have FM and it costs society $14
billion annually in lost productivity. Since patients don’t
succumb and are rarely hospitalized for FM, its evolution
into an entity with a distinct epidemiology, etiopathogenesis,
clinical presentation, laboratory abnormalities and therapy
has lagged behind other conditions. Further compounding this
is been the debate over provenance: should the primary treating
physician for FM be in neurology, physical medicine, orthopedics,
rheumatology, internal medicine or psychiatry? For example,
the American College of Rheumatology (ACR) endorsed an ad
hoc committee’s preliminary criteria for FM, only to
have the organization’s president in his national address
posit that the syndrome should not be treated by rheumatologists.
Further, some practitioners published opinions that “feeling
out of sorts” is a nondisease which does not deserve
the cachet of even being a syndrome. The individuals who articulated
these concerns wrote editorials but never conducted any evidence
based studies validating these opinions. While the fibromyalgia
dialog has been in full intercourse since the publication
of the ACR criteria in 1990, some investigators have been
quietly working to craft a biomedical model which embraces
its pathophysiologic abnormalities and translationally apply
it to the chronic widespread pain and fatigue our FM patients
endure. Roland Staud is an outstanding example of a “bench
to bedside” Renaissance man. His prescient work elucidated
the mechanisms of the “wind up” phenomenon of
pain experienced by FM patients in the Melzack/Wall “gate
theory” context. However, he has also able to convey
to a lay audience appreciation of the syndrome with his popular
work, “Fibromyalgia for Dummies”. Dr. Staud’s
contribution to this issue of Current Rheumatology Reports
represents the most comprehensive and readable compendium
published to date on the biomedical model of FM. In his summary,
the chief autonomic, hormonal, muscular, local myofascial,
neurotransmitter, cytokine, and stress facets of the syndrome
are elegantly woven together in a reader friendly presentation
which should help crystallize a practitioner’s understanding
of what FM constitutes. We are proud to be able to offer these
insights to you.
Address correspondence to Editor-in-Chief at the David Geffen
School of Medicine at UCLA, Los Angeles, CA 90048, USA; E-mail:
dwallace@ucla.edu
[Back to top]
Endothelial Progenitor Cells: A Vascular Perspective
for Inflammatory Rheumatic Disorders
Jérôme Avouac, Georges Uzan, Fabrice Juin,
André Kahan, Catherine Boileau and Yannick Allanore
In human adults, new blood vessels may form in two ways: via
endothelial sprouting from pre-existing endothelial cells/angioblasts
(angiogenesis) or via the peripheral recruitment
of endothelial progenitor cells (EPCs) (vasculogenesis). EPCs,
which have been recently discovered, are a population of bone
marrow-derived cells capable of differentiating into mature
endothelial cells, and participating in the formation of new
blood vessels. The molecular phenotype of EPCs and processes
leading to their mobilization from bone marrow and homing
to neovascularization sites remain unclear. There is still
debate regarding methods for their quantification and isolation.
Evidence is growing for vascular involvement in inflammatory
rheumatic diseases. Recent studies suggest that EPCs in rheumatoid
arthritis are involved in synovial vascularization, and may
contribute to the increased cardiovascular morbidity and mortality,
known features of this disease. Data available in systemic
sclerosis is consistent with the hypothesis that EPCs are
recruited during active disease; however, their levels may
be depleted as the disease progresses and under chronic ischemic
conditions. Other inflammatory disorders have not yet been
investigated. EPCs are important in vasculogenesis, and may
be involved in other features of inflammatory rheumatic disorders.
There are various interesting pathophysiological aspects to
these cells, for example as pathogenic actors and/or biomarkers,
and which may have therapeutic significance.
[Back to top]
Serum Procalcitonin Levels in Febrile Patients with
Systemic Autoimmune Diseases
Ernesto Trallero-Araguás, Alberto Selva-O’Callaghan
and Miquel Vilardell-Tarrés
Procalcitonin (PCT), the precursor of the hormone calcitonin,
is a new parameter of inflammation. This acute-phase hormokine
seems to be more accurate for differentiating between bacterial
infections and viral or non-infective causes of inflammation
than other serological markers. PCT, which is induced in invasive
bacterial infections, is routinely assayed in some intensive
care, surgery, haematological units and emergency rooms to
help determine the cause of a systemic inflammatory response
syndrome (SIRS).
Patients with systemic autoimmune diseases have a higher risk
of developing severe systemic bacterial infections due to
the disease itself and to the immunosuppressive therapy received.
Distinguishing between infection and a disease flare is sometimes
difficult. Strategies to reach a precise diagnosis are decisive
to establish early, adequate patient management. Studies in
febrile patients with systemic autoimmune diseases (systemic
lupus erythematosus, antineutrophil cytoplasmic antibody-associated
systemic vasculitis, and rheumatoid arthritis) suggest that
elevated PCT concentrations offer good sensitivity and specificity
for diagnosing systemic bacterial infection. Nevertheless,
there is little published information on PCT levels in other
autoimmune diseases and inflammatory processes. In this review
we summarise the current evidence regarding the pathophysiological
basis of systemic PCT production in sepsis and the results
from current case series on the response of this peptide to
infectious and non-infectious SIRS in systemic autoimmune
diseases.
[Back to top]
New Insights into the Pathogenesis of Fibromyalgia
Syndrome: Important Role of Peripheral and Central Pain Mechanisms
Roland Staud
Clinical symptoms of chronic muscle conditions like fibromyalgia
(FM), include pain, stiffness, subjective weakness, and muscle
fatigue. Pain in FM is usually described as fluctuating and
always associated with local or generalized tenderness (hyperalgesia
and/or allodynia). This tenderness related to FM pain depends
on increased peripheral and/or central nervous system responsiveness
to peripheral stimuli which can be either noxious (hyperalgesia)
or non-noxious (allodynia). For example, patients with muscle
hyperalgesia will rate painful muscle stimuli higher than
normal controls, whereas patients with allodynia may perceive
light touch as painful, something that a "normal"
individual will never describe as painful. The pathogenesis
of such peripheral and/or central nervous system changes in
FM is unclear, but peripheral tissue changes, specifically
in muscles have been implicated. Indirect evidence from interventions
that attenuate tonic peripheral impulse input in patients
with FM suggest that overall FM pain is dependent on signals
from deep tissues. More importantly, allodynia and hyperalgesia
can be improved or abolished by removal of peripheral impulse
input. Another potential mechanism for FM pain is central
disinhibition. However, this pain mechanism also depends on
tonic impulse input even if only inadequately inhibited. Thus
a promising approach to understanding FM pain is to determine
whether abnormal activity of receptors in deep tissues is
fundamental to the development and maintenance of this chronic
pain disorder.
[Back to top]
The Role of Biomechanical Factors on Patellofemoral
Osteoarthritis
Patricia A. Berry, Andrew J. Teichtahl, Anita E. Wluka
and Flavia M. Cicuttini
Although patellofemoral osteoarthritis is common and a frequent
cause of disability, its aetiology remains unknown. Biomechanical
factors are believed to be important in the pathogenesis of
the disease. Although the patellofemoral joint bears little
axial load during normal walking, retropatellar load increases
during knee flexion and can exceed three times body-weight
during deep knee bends. The combination of large forces being
transmitted to relatively incongruent articular surfaces during
activities of daily living may explain why patellofemoral
osteoarthritis is so common. Other patellofemoral pathologies
considered to be biomechanically mediated, such as patellofemoral
pain syndrome, may provide clues to helping understand the
aetiology of patellofemoral osteoarthritis. For instance,
patellofemoral pain syndrome is believed to be primarily due
to abnormalities in bony geometry, neuromuscular patterns
and tight fibromuscular support, which ultimately contribute
toward lateral patella translation, maltracking and pain.
Genu valgum has also been implicated as a factor that predates
lateral patella pathologies, such as the progression of patellofemoral
osteoarthritis. Nevertheless, it remains unclear whether common
patellofemoral pathologies that occur in early life, such
as subluxation/dislocation and patellofemoral pain syndrome,
are risk factors for degenerative changes, such as patellofemoral
osteoarthritis, that occur in later life. This review examines
the biomechanical factors associated with patellofemoral joint
pathology, using patellofemoral osteoarthritis as a disease
paradigm.
[Back to top]
Why Should Rheumatologists Consider Vitamin D Supplementation
for their Patients?
Heike A. Bischoff-Ferrari
Increasing evidence suggests that common musculoskeletal diseases
such as osteoporosis (OP), osteoarthritis (OA), and rheumatoid
arthritis (RA) are increased in the presence of low vitamin
D intake or low serum 25-hydroxyvitamin D (25(OH)D) levels.
In addition, individuals with OP, OA, and RA carry an increased
risk for falls and fractures, while anti-fall and anti-fracture
efficacy of vitamin D has been demonstrated in the general
older population. For patients with OA or RA, evidence suggests
that maintenance of bone density could slow disease progression,
while 25(OH)D and bone density are positively correlated among
these individuals. Finally, anti-inflammatory effects of vitamin
D have been proposed, which may contribute to decreased joint
destruction among individuals with OA or RA. In addition,
cardiovascular benefits by vitamin D may provide significant
improvement to the care of patients with inflammatory rheumatologic
diseases.
Given the low cost of vitamin D, its excellent tolerability,
combined musculoskeletal- and suggested anti-inflammatory/cardio-vascular
benefits, vitamin D supplementation holds a significant public
health potential. Thus, based on this review, a general supplementation
with vitamin D in patients with OP, OA, and RA may be warranted,
especially as a high prevalence of vitamin D deficiency has
been documented among these individuals.
[Back to top]
Tendinopathy and Neovascularization in Rheumatology
Karsten Knobloch
Tendinopathy is of distinct interest in rheumatology as it
describes a painful tendon disease with local tenderness,
swelling and pain associated with sonographic features such
as hypoechogenic texture and diameter enlargement. Recent
research elucidated microcirculatory changes in tendinopathy
using laser Doppler flowmetry. Tendon capillary blood flow
is increased at the point of pain correlating to neovascularisation.
Tendon oxygen saturation as well as tendon postcapillary venous
filling pressures, determined non-invasively using combined
Laser Doppler flowmetry and spectro-photometry, can quantify,
in real-time, how tendon microcirculation changes over with
pathology or in response to therapy.
Tendon oxygen saturation can be increased by repetitive, intermittent
short-term ice applications; this corresponds to ‘ischemic
preconditioning’, a method used to train tissue to sustain
ischemic damage. Decreasing tendon oxygenation reflects local
acidosis and deteriorating tendon metabolism.
Eccentric training, a common therapy for tendinopathy decreases
abnormal capillary tendon flow without compromising local
tendon oxygenation. Combining an Achilles pneumatic wrap with
eccentric training changes tendon microcirculation in a different
way than does eccentric training alone; both approaches reduce
pain in Achilles tendinopathy. Future research should focus
on how novel therapies, such as non-invasive nitroglycerin
application, non-invasive laser therapy, and invasive sclerosing
therapy, influence vascularisation in tendinopathy.
[Back to top]
Low Level Laser Therapy [LLLT] in Inflammatory and
Rheumatic Diseases: A Review of Therapeutic Mechanisms
Rodrigo Álvaro B. Lopes-Martins, Sócrates
C. Penna, Jon Joensen, Vegard V. Iversen and Jan M. Bjordal
Low level laser therapy (LLLT) is a promising tool for rheumatic
diseases, and a systematic Cochrane review suggests that LLLT
could be considered in rheumatoid arthritis management due
to positive outcomes for pain and morning stiffness. The possible
mechanisms behind LLLT are moving from myth to reality through
an increasing number of controlled LLLT trials. A literature
search revealed 82 laboratory trials and 11 randomized controlled
clinical trials reporting about LLLT effects in inflammatory
processes and impaired metabolism of ligament, tendons and
muscle. 71 laboratory trials provided positive outcomes for
one or more parameters, and 7 clinical trials yielded positive
results for reduction PGE2 levels, reduction of edema inflammatory
cell infiltration and reduction of ESR levels. In 4 head-to-head
comparisons with non-steroidal anti-inflammatory drugs (NSAIDs),
there were no significant difference between NSAIDs and LLLT.
The observed LLLT effects occurred locally and distinct dose-response
patterns and therapeutic windows were found for anti-inflammatory
effects (1 to 12 Joules), fibroblast stimulation (0.2 to 4
Joules) and fibroblast inhibition (above 6 Joules). A possible
systemic effect cannot be ruled out, but with the application
techniques and doses used in the published material, the effect
size seem small and of doubtful clinical value. Bearing in
mind, that the laboratory trials were performed mainly in
rats and mice, clinical use of LLLT should take into account
energy loss if depth from skin surface is larger than 2-3
mm and that most of the pathological organ needs to be irradiated.
Given the dual possibility of reducing inflammation alongside
with the promotion of tissue repair and the superior safety
of LLLT over NSAIDs, LLLT can be adopted in the clinical management
of rheumatic diseases.
[Back to top]
Periarticular Corticosteroid Treatment of the Sacroiliac
Joint
Reijo Luukkainen
The efficacy of periarticular corticosteroid treatment of
the sacroiliac (SI) joint was investigated in patients with
chronic low back pain in the region of the SI joint in two
double-blind, controlled studies. Twenty consecutive patients
with spondylarthropathy (SpA) entered one study and correspondingly
the other involved 24 consecutive non-spondylarthropathic
patients with chronic pain in the SI joint region. The patients
in both studies were randomised to receive a periarticular
injection of methylprednisolone and lidocaine or isotonic
sodium chloride and lidocaine to one affected SI joint. Clinical
assessment at the onset and after the follow-up included the
patient`s estimation of pain in the SI joint region on a visual
analogue scale (VAS) and by a pain index calculated from tenderness
and stressing tests on the SI joint. For SpA patients the
follow-up was 2 months and for non-spondylarthropatic patients
1 month. At the follow-up examination in both studies the
VAS and pain index had improved significantly in patients
treated with methylprednisolone compared to those receiving
isotonic sodium chloride. These results suggest that periarticular
injection of methylprednisolone may be effective in the treatment
of pain in the region of the SI joint in this kind of patients.
[Back to top]
Pathogenesis of SLE Dermatitis – A Reflection
of the Process in SLE Nephritis?
Silje Fismen, Ole P. Rekvig and Elin S. Mortensen
Systemic lupus erythematosus (SLE) is an inflammatory autoimmune
syndrome that may affect most organs in the body. Anti-dsDNA
antibodies represent a classification criterion for SLE and
are involved in lupus nephritis. Recently, the structures
that bind lupus-related nephritogenic autoantibodies in
vivo have been characterized by transmission electron
microscopy (EM), immune-EM and co-localization immune-EM.
By these methods, glomerular in vivo-bound autoantibodies
were shown to co-localize with loci for binding of different
experimental anti-chromatin antibodies, pointing at glomerular
basement membrane-associated nucleosomes as target antigens.
Lupus dermatitis has not been investigated in as much detail
as lupus nephritis, but data indicate similarities between
these two organ manifestations. The presence of granular antibody
deposits at the dermo-epidermal junction suggests that the
tissue injury is mediated by immune complexes. The deposits
may be constituted by nucleosomes or chromatin and antibodies
bound to them. The nucleosomes may be released locally or
systemically from apoptotic cells; i.e. a process similar
to that established for lupus nephritis. In this review we
summarize current knowledge on immuno-pathological processes
that are central in lupus nephritis, and discuss whether they
may be similar to those occurring in lupus dermatitis.
[Back to top]
Pathophysiology and Treatment of Fibromyalgia Syndrome
Thomas Stratz, Marion Schneider, Thomas O. Joos, Hsin-Yun
Hsu and Wolfgang Müller
Fibromyalgia syndrome is not a diagnosis in itself,
but merely represents a set of classification criteria. It
is possible to distinguish between different subgroups. Such
a distinction can be made on the basis of psychopathological,
clinical and laboratory tests. One subgroup reveals elevated
level of different cytokines. The treatment of primary fibromyalgia
can be optimized by taking these subgroups into consideration
since one group responds better to 5-HT3 receptor antagonists,
whereas another benefits more from antidepressants and a third
group from psychotherapy. In so-called secondary fibromyalgia,
5-HT3 receptor antagonists may be used in the attempt to manage
pain that might still persist after treatment of the primary
disease.
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