We read with great interest the report by Dejaco and co-authors
related to diagnosis of carpal tunnel syndrome (CTS) by ultrasound [1].
Dejaco et al. compared ultrasound measurement of median nerve cross-
sectional area (CSA) at different anatomical landmarks in great detail and
evaluated the value of intranerval power Doppler signals for CTS
diagnosis. It provided a good data support for the ultrasonic...
We read with great interest the report by Dejaco and co-authors
related to diagnosis of carpal tunnel syndrome (CTS) by ultrasound [1].
Dejaco et al. compared ultrasound measurement of median nerve cross-
sectional area (CSA) at different anatomical landmarks in great detail and
evaluated the value of intranerval power Doppler signals for CTS
diagnosis. It provided a good data support for the ultrasonic evaluation
of CTS. However, this study prompts questions on the three following
points:
1. CSA as an important indicator for CTS diagnosis also has
limitations. We do agree that CSA is the most commonly used for evaluation
of nerve swelling. However, some patients had typical clinical symptoms,
but those median nerves did not necessarily present obviously swelling and
compression at the carpal tunnel inlet or outlet. Instead, the
ultrasonography showed the abnormal echo of contents within carpal tunnel.
Several reports also have been published on CTS caused by space occupying
lesions including tenosynovitis [2-4], tumors[2,4,5], calcified mass[4,6]
or tophaceous gout[4,7]. We also found such cases were common in systemic
diseases such as rheumatoid arthritis, diabetes mellitus, gout and so on.
Take tenosynovitis for example, transverse sonography of the median nerve
at the level of the pisiform bone showed an ovoid hypoechoic reticular
structure without swelling. However, the deep tissue of nerve showed
swelling and hypoechoic (Fig.1A). On the longitudinal sonograms, the nerve
appeared as a consistent thickness of strip structure without a sudden
thinning or thickening (Fig.1B). However, power Doppler showed increased
blood flow signal within the nerve and carpal tunnel (Fig.1B, 1C). CSA as
a diagnostic criterion will increase the false negative rate of CTS.
2. Ultrasound also has disadvantages for diagnosis of CTS. As we
know, the diagnosis of CTS is based primarily on clinical examination and
nerve conduction studies (NCS). In the last 20 years, Ultrasound has been
employed as an important imaging tool for CTS. The value of sonographic
assessment for CTS depended mainly on three sonographic techniques:
measurement of median nerve CSA at differential locations along the carpal
tunnel, structural analysis of the median nerve and bowing of the flexor
retinaculum [8]. We agree ultrasound can evaluate morphological changes of
median nerve and provide a good data support for CTS. More specifically,
ultrasound is not much an evaluation as a diagnostic tool for CTS..
3. The term "volume" mentioned in the title was used inappropriately.
Volume of median nerve should be measured on the 3-dimensional space
image. However, Dejaco et al. [1] measured CSA of nerves on the 2D image.
In order to avoid ambiguity, we proposed to use the term "area".
References
1. Dejaco C, Stradner M, Zauner D et al. Ultrasound for diagnosis of
carpal tunnel syndrome: comparison of different methods to determine
median nerve volume and value of power Doppler sonography. Ann Rheum Dis
2013;72:1934-9.
2.Chen CH, Wu T, Sun JS et al. Unusual causes of carpal tunnel syndrome:
space occupying lesions. J Hand Surg Eur Vol 2012;37:14-9.
3.Klauser AS, Faschingbauer R, Bauer T et al. Entrapment neuropathies II:
carpal tunnel syndrome. Semin Musculoskelet Radiol. 2010;14:487-500.
4. Kang HJ, Jung SH, Yoon HK et al. Carpal tunnel syndrome caused by space
occupying lesions. Yonsei Med J 2009;50:257-61.
5. Ait Essi F, Younsi A, Abkari I et al. Diffuse tenosenovial giant cell
tumor of the wrist revealed by carpal tunnel syndrome: report of a case.
Chir Main 201;31:256-8.
6. Takada T, Fujioka H, Mizuno K. Carpal tunnel syndrome caused by an
idiopathic calcified mass. Arch Orthop Trauma Surg 2000;120:226-7.
7. Patil VS, Chopra A. Watch out for 'pins and needles' in hands--it may
be a case of gout. Clin Rheumatol 2007;26:2185-7.
8. Nakamichi K, Tachibana S. Ultrasonographic findings in isolated
neuritis of the posterior interosseous nerve: comparison with normal
findings. J Ultrasound Med 2007;26:683-687.
ELetter and Figures will be available on the Electronic Pages soon
Figure Legends
Figure 1 Transverse and longitudinal sonograms of the median nerve at the
carpal tunnel
A Transverse sonogram of the median nerve at the level of the pisiform
bone (CSA:7mm2)
B Longitudinal sonogram of the median nerve
C Transverse sonogram of the carpal tunnel with abundant blood flow signal
On behalf of the investigators of the COMORA study, we would like to
congratulate for the study you have conducted in Mexican mestizo patients.
The results observed are totally in accordance with the results observed
in the COMORA study that is: 1/ a relevant percentage of rheumatoid
arthritis patients with comorbidities and 2/ a huge inter-country
variability.
On behalf of the investigators of the COMORA study, we would like to
congratulate for the study you have conducted in Mexican mestizo patients.
The results observed are totally in accordance with the results observed
in the COMORA study that is: 1/ a relevant percentage of rheumatoid
arthritis patients with comorbidities and 2/ a huge inter-country
variability.
We would like to echo our Mexican colleagues that, in accordance to
the EULAR recommendations, these studies emphasize the need of a yearly
evaluation of such comorbidities. Such studies (the COMORA one and the one
conducted in Mexico) could facilitate the standardization of the way to
collect such comorbidities in patients with chronic inflammatory
disorders.
Sieper et al. evaluated whether combination therapy with Infliximab (IFX)
and naproxen (NPX) was superior to treatment with NPX alone in patients
who had active moderate-to-severe early (disease duration under 3 years)
active axial spondyloarthritis (SpA) and who were naive to nonsteroidal
anti-inflammatory drugs (NSAIDs) or had only been treated with a
submaximal dose of NSAIDs (1). This study is the...
Sieper et al. evaluated whether combination therapy with Infliximab (IFX)
and naproxen (NPX) was superior to treatment with NPX alone in patients
who had active moderate-to-severe early (disease duration under 3 years)
active axial spondyloarthritis (SpA) and who were naive to nonsteroidal
anti-inflammatory drugs (NSAIDs) or had only been treated with a
submaximal dose of NSAIDs (1). This study is the first investigation of
the potential benefits of early TNF-antagonist treatment in active axial
SpA patients who are not yet refractory to NSAID therapy. Additionally,
this represents the first randomised controlled clinical trial to use the
imaging portion of the Assessment of SpondyloArthritis International
Society (ASAS) criteria for axial SpA with active inflammation of the SI
joints on MRI at baseline. Most importantly, the evidence from this study
supports early diagnosis and treatment of SpA with a full dose of NSAIDs
first, escalating to combination NSAID+TNF antagonist treatment in
patients who have insufficient response.
Moreover, this study provides important insights about the application of
the new classification criteria for axial SpA in a clinical trial.
Approximately 60 % of patients had ankylosing spondylitis (AS) fulfilling
the modified New York radiographic criteria. Thus 40% of patients had
nonradiographic axial SpA classified by MRI; it would be of interest to
know if in these patients the additional SpA features for classification
were different from AS patients. Arthritis was quite often in both
treatment arms (45.3% vs 26.9%, respectively). Importantly, the 66- joint
swollen joint count and 68- joint tender joint count was ameliorated
considerably in both treatment arms and significantly better for swollen
joints with NSAID+TNF antagonist treatment. Also in other studies testing
adalimumab against placebo and etanercept against sulfasalazine,
respectively, arthritis was found in 29% up to 52% of patients with early
axial SpA (2, 3, 4). Evidently, simultaneous peripheral symptoms are
frequent in nonradiographic and early axial SpA.
This raises the question if future studies should include together
patients fulfilling the axial and/or peripheral SpA criteria to establish
treatment evidences for SpA in general; thus would be possible to promote
approval of established and new treatments for most conditions unified
under the umbrella of SpA instead of testing for each individual diagnosis
and subgroup of clinical manifestations. However, this requires more
attention to infections associated with reactive arthritis which have been
included in the criteria for peripheral but not for axial SpA (5, 6, 7).
Preceding infection (balanitis, urethritis, cervicitis and/or acute
diarrhea) is noted in 37% of patients with peripheral SpA (8). Furthermore
35% of the patients with peripheral SpA have radiographic sacroiliitis
(8). This overlap between axial and peripheral symptoms demonstrates that
the construct of separating SpA into predominant clinical manifestations
is somewhat artificial and only partially reflect the clinical reality
given the heterogeneous character and fluctuating course of the diseases
belonging to the SpA concept. Especially in the early years of the
disease, the main target of the new classification criteria, AS progresses
by a series of flares involving localized area such as the knee, neck,
ankle, or localized area of the back (9, 10, 11). Many patients with SpA
at some time of the disease can have either prominent peripheral and axial
symptoms concurrently or peripheral and axial symptoms successively. The
classification may change from axial to peripheral and vice versa at
different times in a given study, compromising the consistency of
classification in long-term trials. Finally, the description of increased
frequency of Chlamydia-positive synovial tissue samples in patients with
chronic undifferentiated SpA, the growing insight into the etiology of
persistent chlamydial infection, and the promising treatment of Chlamydia-
induced arthritis with combination antibiotic therapy indicate the
necessity of further splitting SpA into underlying disease entities such
as reactive arthritis (c. f. 12).
References
1. Sieper J, Lenaerts J, Wollenhaupt J, et al. Efficacy and safety of
infliximab plus naproxen versus naproxen alone in patients with early,
active axial spondyloarthritis: results from the double-blind, placebo-
controlled INFAST study, Part 1. Ann Rheum Dis Published Online First: [21
May 2013] doi:10.1136/annrheumdis-2012-203201
2. Sieper J, van der Heijde D, Dougados M et al. Efficacy and safety of
adalimumab in patients with non-radiographic axial spondyloarthritis:
results of a randomised placebo-controlled trial (ABILITY-1). Ann Rheum
Dis 2013;72:815-22.
3. Haibel H, Rudwaleit M, Listing J, et al. Efficacy of adalimumab in the
treatment of axial spondylarthritis without radiographically defined
sacroiliitis: results of a twelve-week randomized, double-blind, placebo-
controlled trial followed by an open-label extension up to week fifty-two.
Arthritis Rheum 2008;58:1981-91.
4. Song IH, Hermann K, Haibel H et al. Effects of etanercept versus
sulfasalazine in early axial spondyloarthritis on active inflammatory
lesions as detected by whole-body MRI (ESTHER): a 48-week randomised
controlled trial. Ann Rheum Dis 2011;70:590-6.
5. Rudwaleit M, van der Heijde D, Landew? R, et al. The Assessment of
SpondyloArthritis international Society (ASAS) Classification Criteria for
peripheral Spondyloarthritis and for Spondyloarthritis in general. Ann
Rheum Dis 2011;70:15-21.
6. Zeidler H, Amor B. The Assessment in Spondyloarthritis International
Society (ASAS) classification criteria for peripheral spondyloarthritis
and for spondyloarthritis in general: the spondyloarthritis concept in
progress. Ann Rheum Dis 2011;70:1-3.
7. Zeidler H. The historical concept of interrelated conditions lumped
together as a family of distinct diseases is not outdated. Arthritis Rheum
2013;65:2214-5.
8. van den Berg R, van Gaalen F, van der Helm-van Mil A, Huizinga T, van
der Heijde D. Performance of classification criteria for peripheral
spondyloarthritis and psoriatic arthritis in the Leiden Early Arthritis
cohort. Ann Rheum Dis 2012;71:1366-9.
9. Wilkinson M, Bywaters EG. Clinical features and course of ankylosing
spondylitis; as seen in a follow-up of 222 hospital referred cases. Ann
Rheum Dis 1958;17:209-28.
10. Brophy S, Calin A. Definition of disease flare in ankylosing
spondylitis: the patients' perspective. J Rheumatol 2002;29:954-8.
11. Stone MA, Pomeroy E, Keat A et al. Assessment of the impact of flares
in ankylosing spondylitis disease activity using the Flare Illustration.
Rheumatology 2008;47:1213-8.
12. Zeidler H, Hudson AP. New insights into Chlamydia and arthritis.
Promise of a cure? Ann Rheum Dis 2013 (in press).
In the study recently published in the Annals of Rheumatic Diseases,
Dougados et al. [1] evaluated the prevalence of comorbidities and compared
their management in Rheumatoid Arthritis (RA) patients from different
countries. We know that RA is a chronic autoimmune disease characterized
by chronic inflammation, progressive deterioration of joint function,
increased comorbidity and mortality; RA pati...
In the study recently published in the Annals of Rheumatic Diseases,
Dougados et al. [1] evaluated the prevalence of comorbidities and compared
their management in Rheumatoid Arthritis (RA) patients from different
countries. We know that RA is a chronic autoimmune disease characterized
by chronic inflammation, progressive deterioration of joint function,
increased comorbidity and mortality; RA patients have about a 50%
increased risk of premature mortality [2]. A comorbid condition may
represent an active, past or transient illness, and may be linked to RA
process itself and/or its treatment or it may be completely independent of
them [3], the average RA patient has approximately 1.6 comorbidities [4].
We conducted an observational, cross-sectional, non-comparative study, to
describe the presence of comorbidities in RA mexican mestizo patients in a
period from January to May 2013 in a secondary care center. RA patients
fulfilled the 2010 ACR / EULAR classification criteria [5]. We collected
demographics and the disease characteristics, the history or current
evidence of comorbidities. We included 394 patients with established RA.
The baseline patient and therapy disease characteristics are shown in
Table 1. We found that 168 (42.6%) patients received disease-modifying
antirheumatic drug (DMARD) monotherapy, 175 (44.1%) used two DMARDs and 47
(12.2%) used triple therapy and 4 (1.1%) used only analgesics. We found
that 111 (28.1%) patients had no comorbidity. Comorbidities distribution
shown in Figure 1. We did not find any patient in this period or earlier
with history of myocardial infarction. The three most common comorbidities
in our study were hypertension (21.1%), diabetes (12.1%) and
hypercholesterolemia (9.9%). As noted, our results were different from
those reported by Dougados M et al, when they included patients from the
different countries but not mexican mestizo patients, they found
depression was the most common comorbidity [1], and the most prevalent
risk factors for cardiovascular disease were an increased Framingham Risk
Score, hypertension and hypercholesterolemia. Diabetes (with/without
evidence of organ damage target) was the second most prevalent comorbidity
in our cohort. The worldwide prevalence of autoimmune thyroid disease in
RA varies from 0.5 to 27% [6], we found in our cohort the presence of
thyroid disease in 7.4% . The COMORA study [5] found a prevalence of lung
disease that was less in Asia countries than in European countries and
USA, we found in our patients a prevalence of 4.8%. The RA patients have a
high risk of lymphoma and lung cancer [7], we asked to the patients the
presence of any cancer, and we found that it was 4.6%. Other comorbidities
less prevalent in our cohort were carpal tunnel syndrome, gastrointestinal
ulcer, chronic kidney disease, congestive cardiac failure and dementia.
Most of our patients were on DMARDs, and only 38 (9.6%) patients were on
biological DMARD. We observed in this mexican mestizo cohort differences
of comorbidities prevalence with the study previously published, and we
agree that it is necessary a systematic search of comorbidities in RA
patients with the objective to improve the quality of life and reduce
mortality.
Figure and table will be available on ARD Electronic Pages shortly.
References
1. Dougados M, Soubrier M, Antunez A, et al. Prevalence of comorbidities
in rheumatoid arthritis and evaluation of their monitoring: results of an
international, cross-sectional study (COMORA). Ann Rheum Dis. 2013 Oct 4.
doi: 10.1136/annrheumdis-2013-204223. [Epub ahead of print]
2. Myasoedova E, Davis JM 3rd, Crowson CS, et al. Epidemiology of
rheumatoid arthritis: rheumatoid arthritis and mortality. Curr Rheumatol
Rep. 2010;12(5):379-85
3. Gabriel SE, Michaud K. Epidemiological studies in incidence,
prevalence, mortality, and comorbidity of the rheumatic diseases.
Arthritis Res Ther. 2009;11(3):229. doi: 10.1186/ar2669. Epub 2009 May 19.
4. Wolfe F, Michaud K. The risk of myocardial infarction and
pharmacologic and nonpharmacologic myocardial infarction predictors
inrheumatoid arthritis: a cohort and nested case-control analysis.
Arthritis Rheum. 2008;58(9):2612-21.
5. Aletaha D, Neogi T, Silman AJ, et al. 2010 rheumatoid arthritis
classification criteria: an American College of Rheumatology/European
League Against Rheumatism collaborative initiative. Ann Rheum Dis.
2010;69(9):1580-8.
6. Cardenas Roldan J, Amaya-Amaya J, Castellanos-de la Hoz J, et al.
Autoimmune thyroid disease in rheumatoid arthritis: a global perspective.
Arthritis. 2012; 864907. doi: 10.1155/2012/864907. Epub 2012 Nov 18.
7. Smitten AL, Simon TA, Hochber MC, et al. A meta-analysis of the
incidence of malignancy in adult patients with rheumatoid arthritis.
Arthritis Res Ther. 2008;10(2):R45. doi: 10.1186/ar2404. Epub 2008 Apr 23.
We have read the letter by Bossuyt X. and Fieuws S. entitled "Detection of
anti-nuclear antibodies, added-value of solid phase assay?" with great
interest (1). In this letter the authors described a comparison between
anti-nuclear antibodies (ANA) performed by indirect immunofluorescent
assay(IIFA) and by an automated method (fluoroenzymeimmunoassay; EliA CTD
screen, Thermo Fisher) using samples obtai...
We have read the letter by Bossuyt X. and Fieuws S. entitled "Detection of
anti-nuclear antibodies, added-value of solid phase assay?" with great
interest (1). In this letter the authors described a comparison between
anti-nuclear antibodies (ANA) performed by indirect immunofluorescent
assay(IIFA) and by an automated method (fluoroenzymeimmunoassay; EliA CTD
screen, Thermo Fisher) using samples obtained from patients with systemic
lupus erythematosus (SLE), systemic sclerosis (SSc),Sj?gren's syndrome
(SS) and healthy controls. The authors concluded that the favorable method
for ANA detection is disease-dependent and that combining IIFA with solid
phase assay can increase the diagnostic accuracy.
These points, raised by Bossuyt X. and Fieuws S., may be regarded in the
perspective of the international recommendations for ANA detection that we
have recently published (2). Indeed, our recommendations support the use
of IIFA as well as alternative methods (such as EliA) to determine
antibodies of the ANA family, even stating that these new methods may
represent the future of autoimmune diagnostics. However, it should be
noted that, unlike most new methods, IIFA enables detection of numerous
cellular antigens. Furthermore, diagnostic/classification criteria of
several autoimmune diseases, like SLE, autoimmune hepatitis and juvenile
idiopathic arthritis, are based on ANA results obtained by IIFA. Thus, for
screening purposes, especially as laboratory personnel are usually unaware
of the suspected diagnosis, IIFA should remain the reference method. On
the other hand we (2) have highlighted the limitations of IIFA and
acknowledged, similarly to Bossuyt X. and Fieuws S., that certain methods
may be easier to perform and even more sensitive than IIFA regarding a
specific autoimmune disease, for instance SS or inflammatory myopathies.
However, this should be evaluated for each method regarding each
autoimmune disease and addressing different populations. More importantly,
information regarding each alternative method should be clearly
communicated with the requesting physician (i.e. method of choice and test
characteristics for the respective autoimmune diseases) to avoid erroneous
application of IIFA test characteristics to these alternative methods.
The issue of using multiple screening tests has been raised by us and
by others. We believe that this may significantly improve the accuracy of
autoimmune diagnostics, but it requires a sophisticated algorithm for
interpretation of discrepant results. Moreover, it is highly unlikely to
be cost-effective and most likely is in conflict with most national
reimbursement policies.
Notably, most requests for ANA testing are issued by general practitioners
and non-rheumatologists/immunologists and in many cases this is done in
the context of diagnosing a wide array of conditions (3). Given the poor
specificity of ANA testing by IIFA, it can be argued that in particular
ANA requests for patients with a low pre-test probability solid-phase
assays may be preferred (4). We agree with Bossuyt X. and Fieuws S. that
different diseases do require different approaches and we have recently
dealt with the issue of multiple testing algorithms for distinct
autoimmune conditions as specified in Fig. 1 (5). Furthermore, in our
international recommendations (2) we highly supported the addition of
laboratory comments that will specify further options. For instance,
adding a comment such as "If clinical suspicion of SS is high, further
studies using an alternative method such as EliA should be considered" may
guide the physician to request the additional tests in a much more
restricted way. Again, this underscores the importance of bidirectional
communication: i.e. clinical information enables appropriate choices in
the laboratory and laboratory comments direct appropriate add-on testing
to be requested by the physician.
Figure see the monthly ePage for Annals of the Rheumatic Diseases
References
1. Bossuyt X and Fieuws S. "Detection of anti-nuclear antibodies, added-
value of solid phase assay?" Current Issue.
2. Agmon-Levin N, Damoiseaux J, Kallenberg C, et al. International
recommendationsfor the assessment of autoantibodies to cellular antigens
referred to as anti-nuclear antibodies. Ann Rheum Dis 2013 Oct 14.
3. Mahler M, Hanly JG, Fritzler MJ. Importance of the dense fine speckled
pattern on HEp-2 cells and anti-DFS70 antibodies for the diagnosis of
systemic autoimmune diseases. Autoimmun Rev 2012;11(9):642-5.
4. Abeles AM, Abeles M. The clinical utility of a positive antinuclear
antibody test result. Am J Med 2013;126:342-348.
5. Damoiseaux JandAgmon-Levin N. Anti-Nuclear Antibodies: a long way to
harmonization. In: Infections, Tumors and Autoimmunity (Eds: Conrad K,
Chen EKL, Fritzler RL et al.), Autoantigens, Autoantibodies, Autoimmunity
2013;9:284-289 (E-book).
Moiseev and Novikov's comments on the Five-Factor Score (FFS) for
eosinophilic granulomatosis with polyangiitis (EGPA) provide the
opportunity to address the contribution of scores and their use. The FFS
was designed to evaluate necrotizing vasculitis prognosis and identify
manifestations associated with death: those are its only roles. Its
strength is its validation on 1,108 patients with differen...
Moiseev and Novikov's comments on the Five-Factor Score (FFS) for
eosinophilic granulomatosis with polyangiitis (EGPA) provide the
opportunity to address the contribution of scores and their use. The FFS
was designed to evaluate necrotizing vasculitis prognosis and identify
manifestations associated with death: those are its only roles. Its
strength is its validation on 1,108 patients with different vasculitides,
including 230 with EGPA, ie, sufficient to validate its use.1,2 Saying
that only cardiac involvement in FFS applies to EGPA is erroneous.
Although a concomitant atherosclerotic process cannot be excluded, each
patient's cardiac symptoms were reviewed to confirm that they were EGPA-
related and not attributable to preexisting atherosclerosis or
valvulopathy.1,2 Because the FFS was not designed to predict vasculitis
impact on function, peripheral neuropathy was not included. Alveolar
hemorrhage was mostly minor, thus not associated with death. That does not
mean that severe alveolar hemorrhage cannot be life-threatening; indeed,
it is often associated with renal failure, which is an FFS item
independently predictive of mortality.1,2
The second aspect of building scores is how to use them. We worked for a
decade on adapting treatment to disease severity and using the FFS to
identify patients with poorer prognoses. Moiseev and Novikov's comment on
therapeutic choices is inaccurate because many patients studied by
Comarmond et al had participated in prospective trials and received
immunosuppressant(s) based on their FFS.3-5 Furthermore, the FFS now
includes age, thereby emphasizing the severity of vasculitis in the
elderly. We agree with Moiseev and Novikov that CORTAGE trial results will
probably influence our future therapeutic strategies.6
Comparing previously reported results, among the 348 patients followed by
Comarmond et al,4 55.9% initially received corticosteroids and
immunosuppressant(s) (70.8% throughout follow-up), with 25.3% relapse and
88.9% 5 year overall survival rates; whereas Moosig et al's7 269 patients
more frequently received immunosuppressant(s) (cyclophosphamide for 71%),
with 14% major relapses and 28% minor relapses (comparable to the former)
and 97% 5-year overall survival. Azathioprine's steroid-sparing effect and
prevention of EGPA relapses are currently under investigation
(ClinicalTrials no. NCT00647166), and results should be available in late
2014.
ANCA were not retained as a poor-prognosis factor.1,2 However, cardiac
involvement, an FFS item, is more frequent in ANCA-negative EGPA
patients.4 The authors probably confused the prediction of mortality and
relapses, as the latter are more frequent in ANCA positive patients.4,8
However, relapses, even severe, are not associated with higher mortality.8
Our recently published long term analyses8 of Ribi's et al's patient
population5 demonstrated the accuracy of a therapeutic strategy based on
distinguishing between EGPA patients with baseline FFS=0 or higher.
Indeed, the long-term analysis showed comparable overall and disease free
survival rates for FFS=0 and FFS?1 EGPA patients given FFS-guided
treatment.
Certainly, a score is an evolving concept that should consider clinical,
immunological and therapeutic items. Based on prospective trial results,
we tried to determine factors predicting vasculitis-prognosis severity and
optimal treatments. The FFS, which represents part of this effort, will
continue to mature, but must remain simple and easy to use in clinical
practice, thereby limiting subtleties.
References
1. Guillevin L, Lhote F, Gayraud M, et al. Prognostic factors in
polyarteritis nodosa and Churg-Strauss syndrome. A prospective study in
342 patients. Medicine (Baltimore) 1996;75:17-28.
2. Guillevin L, Pagnoux C, Seror R, et al. The Five-Factor Score
revisited: assessment of prognoses of systemic necrotizing vasculitides
based on the French Vasculitis Study Group (FVSG) cohort. Medicine
(Baltimore) 2011;90:19-27.
3. Cohen P, Pagnoux C, Mahr A, et al. Churg-Strauss syndrome with poor-
prognosis factors: A prospective multicenter trial comparing
glucocorticoids and six or twelve cyclophosphamide pulses in forty-eight
patients. Arthritis Rheum 2007;57:686-93.
4. Comarmond C, Pagnoux C, Khellaf M, et al. Eosinophilic granulomatosis
with polyangiitis (Churg-Strauss): clinical characteristics and long-term
followup of the 383 patients enrolled in the French Vasculitis Study Group
cohort. Arthritis Rheum 2013;65:270-81.
5. Ribi C, Cohen P, Pagnoux C, et al. Treatment of Churg-Strauss syndrome
without poor-prognosis factors: a multicenter, prospective, randomized,
open-label study of seventy-two patients. Arthritis Rheum 2008;58:586-94.
6. Pagnoux C, Quemeneur T, Ninet J, et al. Treatment of systemic
necrotizing vasculitides in patients ? 65 years old: Results of the
multicenter randomized CORTAGE trial. Presse Med 2013;42:679-80.
7. Moosig F, Bremer JP, Hellmich B, et al. A vasculitis centre based
management strategy leads to improved outcome in eosinophilic
granulomatosis and polyangiitis (Churg-Strauss, EGPA): monocentric
experiences in 150 patients. Ann Rheum Dis 2013;72:1011-7.
8. Samson M, Pu?chal X, Devilliers H, et al. Long-term outcomes of 118
patients with eosinophilic granulomatosis with polyangiitis (Churg-Strauss
syndrome) enrolled in two prospective trials. Journal of autoimmunity
2013;43:60-69.
We thank Forestier and Erol for their response on our paper on Eular
recommendations for the non-pharmacological core management of hip and
knee osteoarthritis (OA). We agree that balneotherapy is a relevant non-
pharmacological intervention in hip and knee OA, and has been properly
evaluated by means of randomised clinical trials, with the evidence
summarized in systematic reviews. The topics to be in...
We thank Forestier and Erol for their response on our paper on Eular
recommendations for the non-pharmacological core management of hip and
knee osteoarthritis (OA). We agree that balneotherapy is a relevant non-
pharmacological intervention in hip and knee OA, and has been properly
evaluated by means of randomised clinical trials, with the evidence
summarized in systematic reviews. The topics to be included in the
recommendations were however, in accordance with the standard operating
procedures for the development of Eular recommendations [1], determined by
the Task Force. Starting with a long list of propositions on a wide range
of non-pharmacological interventions, the final set was selected by means
of several Delphi rounds. This procedure resulted, apart from the
exclusion of balneotherapy, in the omission of several other non-
pharmacological interventions which are relevant and for which evidence is
available.
The process of development of the recommendations does not include a
registration of reasons for selection and exclusion of propositions,
however specifically for balneotherapy it could be hypothesized that this
intervention is not equally available and/or common in every country.
In general terms, the issue Forestier raises is important from the
implementation perspective. It remains to be established to what extent
the selection of topics plays a role in the uptake of the recommendations.
The exclusion of recommendations on topics which are considered relevant
in clinical practice, and likewise the inclusion of recommendations on
topics which are not supported by clinicians may play an important role in
the implementation. A study on barriers and facilitators for the
implementation of recommendations among various groups of stakeholders is
needed to further study this aspect. The outcome of such a study may not
only influence the content of an update of the current set of
recommendations, but probably also the process of guideline development as
a whole, with probably larger groups of people in the various stakeholder
groups being needed to select the topics to be included in the
recommendations.
References
1. Dougados M, Betteridge N, Burmester GR et al. EULAR standardised
operating procedures for the elaboration, evaluation, dissemination, and
implementation of recommendations endorsed by the EULAR standing
committees. Ann Rheum Dis 2004;63:1172-6
In the excellent study recently published in the Annals of the
Rheumatic Diseases [1] F.Moosig et al. evaluated the individualized and
more aggressive strategy of immunosuppressive treatment in 150 patients
with EGPA. Over the last decade we utilized the same approach in our
cohort of 117 patients with EGPA. For induction of remission the authors
used cyclophosphamide in patients not only with Five Fac...
In the excellent study recently published in the Annals of the
Rheumatic Diseases [1] F.Moosig et al. evaluated the individualized and
more aggressive strategy of immunosuppressive treatment in 150 patients
with EGPA. Over the last decade we utilized the same approach in our
cohort of 117 patients with EGPA. For induction of remission the authors
used cyclophosphamide in patients not only with Five Factor Score (FFS) of
0 but with other organ- or life-threatening manifestations, e.g. active
peripheral nervous system involvement, alveolar haemorrhage or severe
eosinophilic alveolitis. FFS was developed in 1996 as a predictor of poor
prognosis in patients with systemic vasculitides [2]. It was revised in
2009 [3]. FFS was used in several trials performed by French Vasculitis
Study Group as a guide to choosing the strategy of initial treatment in
EGPA patients (only corticosteroids if FFS=0 and addition of
cyclophosphamide if FFS?1). In our opinion such simplified approach is
incorrect, at least partly, for the following reasons.
First, FFS is not specific for EGPA as it was developed in the
heterogeneous group of patients with different vasculitides. In fact only
one item of FFS is applicable to EGPA (cardiac disease). Thus, FFS does
not account for common and clinically significant manifestations that
probably cannot predict survival but can impair response to corticosteroid
treatment and lead to disability (e.g. peripheral nervous system
involvement). It should be also noted that cardiac disorders in middle-
aged patients with EGPA may be due to accelerated atherosclerosis.
Second, FFS may be misleading. C.Comarmond et al [4] calculated FFS in the
cohort of 383 patients with EGPA. The estimated original score was 0 in
76.0% of patients while revised FFS had the same value in only 25.6% of
patients. It means that in the latter case three times more patients would
require cyclophosphamide for initial treatment. One of the items included
in the revised FFS is age older that 65. Thus, every elderly patient with
EGPA has FFS of at least 1 and should be treated with cyclophosphamide. Is
age really more important than certain relatively rare but life- or organ-
threatening visceral manifestations, e.g. severe kidney or lung disease?
Systemic necrotizing vasculitides are associated with a high mortality
rate in the elderly. But age itself apparently cannot justify more
aggressive treatment (at least prior to publication of CORTAGE or similar
studies) taking into account higher risk of serious side effects of
corticosteroids and immunosuppressants in the elderly patients.
Third, in the above mentioned French Vasculitis Study Group Cohort the
presence of ANCA was associated with the higher risk of vasculitis
relapses (35.2% versus 22.5% in ANCA-negative patients, P = 0.01) and the
lower risk of death (5.6% versus 12.5%, P < 0.05) [4]. EGPA phenotype
is not an item of FFS though its predictive value deserves evaluation in
the further studies.
Fourth, in C.Ribi et al. study [5] 42% of EGPA patients with FFS = 0
failed to respond to corticosteroid therapy or relapsed during
corticosteroid dosage tapering or after termination of therapy (peripheral
neuropathy and cutaneous lesions were present respectively in 37% and 27%
of these patients). Meanwhile in F.Moosig et al. study the rate of major
relapses in the whole cohort of patients was apparently lower (14%).
We do not challenge the predictive value of FFS but the revised score
should be revised again to be useful as a predictor of response to
immunosuppressive treatment in EGPA patients. Is it really necessary to
calculate any score to choose the best treatment in vasculitis patient? Or
maybe common sense, clinical judgement and clinical experience are better?
Real life is not clinical trial. Scales and scores are important for
evaluation of strategies of treatment but they cannot account for all
challenges that rheumatologist faces in clinical practice.
References
1. Moosig F, Bremer JP, Hellmich B, et al. A vasculitis centre based
management strategy leads to improved outcome in eosinophilic
granulomatosis and polyangiitis (Churg-Strauss, EGPA): monocentric
experiences in 150 patients. Ann Rheum Dis 2013;72:1011-7.
2. Guillevin L, Lhote F, Gayraud M, et al. Prognostic factors in
polyarteritis nodosa and Churg-Strauss syndrome: a prospective study in
342 patients. Medicine (Baltimore) 1996;75:17-28.
3. Guillevin L, Pagnoux C, Seror R, et al. The Five-Factor Score
revisited: assessment of prognoses of systemic necrotizing vasculitides
based on the French Vasculitis Study Group (FVSG) cohort. Medicine
(Baltimore) 2011;90:19-27.
4. Comarmond C, Pagnoux C, Khellaf M, et al. Eosinophilic granulomatosis
with polyangiitis (Churg-Strauss): clinical characteristics and long-term
followup of the 383 patients enrolled in the French Vasculitis Study Group
cohort. Arthritis Rheum 2013;65:270-81.
5. Ribi C, Cohen P, Pagnoux C, et al. Treatment of Churg-Strauss syndrome
without poor-prognosis factors: a multicenter, prospective, randomized,
open-label study of seventy-two patients. Arthritis Rheum 2008;58:586-94.
We appreciate that EULAR is preparing a specific recommendation on
non-pharmacological treatment of knee osteoarthritis but we are also very
surprised to discover that crenobalneotherapy was not even mentionned in
the analysed treatments.
Crenobalneotherapy (also called balneotherapy or spa therapy) is a very
common treatment for knee osteoarthritis in South and Eastern Europe,
Middle Asia, Japan, Sou...
We appreciate that EULAR is preparing a specific recommendation on
non-pharmacological treatment of knee osteoarthritis but we are also very
surprised to discover that crenobalneotherapy was not even mentionned in
the analysed treatments.
Crenobalneotherapy (also called balneotherapy or spa therapy) is a very
common treatment for knee osteoarthritis in South and Eastern Europe,
Middle Asia, Japan, South America and North Africa. The common point of
crenobalneotherapy procedures is the use of mineral water for the
treatment. While, it can sometimes be a passive bath only, more often it
is a combined treatment with underwater massages, mud applications, water
exercises, baths and showers. We think that crenobalneotherapy is a non-
pharmacological treatment.
In 2008, we conducted a systematic review [1] and we concluded that
"although the consistency of the results suggests a therapeutic effect of
crenobalneotherapy in limb osteoarthritis, available studies are
methodologically inadequate and sample sizes too small to allow definitive
conclusions". Later, in 2010 we published a multicenter randomized trial
on 462 patients suffering from knee osteoarthritis in Annals of Rheumatic
Diseases [2]. The results showed a clinically important improvement in
pain and function for the balneotherapy group when compared with the
control group doing home exercise alone. We suggest that, since
crenobalneotherapy is a well evaluated treatment, these non-
pharmacological treatment guidelines should also analyse this and some
other trials published in this field [3-4].
References
1. R Forestier, A Francon. Crenobalneotherapy for limb osteoarthritis: systematic literature
review and methodological analysis. Joint Bone
Spine 2008 ;75(2):138-48.
2. Forestier R, Desfour H, Tessier JM, et al. Spa therapy in the treatment of knee osteoarthritis: a large
randomised multicentre trial. Ann Rheum Dis. 2010;69(4):660-5.
3. Fioravanti A, Iacoponi F, Bellisai B, et al. Short-and long-term effects of spa therapy in knee osteoarthritis. Am J Phys
Med Rehabil 2010;89(2):125-32.
4. Nguyen M, Revel M, Dougados M. Prolonged effects of 3 week therapy in a spa resort on lumbar spine,
knee and hip osteoarthritis: follow-up after 6 months. A randomized
controlled trial. Br J Rheumatol 1997;36(1):77-81.
The article published by Landewe et al. (1) offers novel insights to
assess the benefits of new therapeutic strategies in rheumatoid arthritis
(RA) which focus more on [the visualization of] structural integrity
rather than the inhibition of radiographic progression (1). The authors
clearly outline the three major problems of the common superiority study
designs: I. Differences in progression are...
The article published by Landewe et al. (1) offers novel insights to
assess the benefits of new therapeutic strategies in rheumatoid arthritis
(RA) which focus more on [the visualization of] structural integrity
rather than the inhibition of radiographic progression (1). The authors
clearly outline the three major problems of the common superiority study
designs: I. Differences in progression are too small, II. Effective
Disease Modifying Antirheumatic Drugs used in the control group results in
levels of radiographic progression which are too low, III. The length of
placebo treatment is limited to 3 months preventing an exploration of
radiological progression of up to 12 months, which often overestimates the
true progression. Furthermore, no alternative for radiographs as a gold
standard imaging technique exists to quantify radiological progression in
Randomized Controlled Trials (RCT). Radiological progression is precisely
assessed by established scoring methods using the quantification of
erosions and joint space narrowing. Magnetic Resonance Imaging (MRI) as an
innovative and sensitive imaging technology has the potential to evaluate
RA related joint damage and structural integrity but only for early stages
of RA: As pointed out by Landewe et al., we also fully agree that MRI is
limited by the differing technical configurations as well as in the
quantification of joint space narrowing, especially for long-term
observations in RCT.
As discussed by Landewe et al. one possible solution could be the
initiation of non-inferiority trials or the use of enriched study
populations to overcome the above mentioned limitations and to achieve the
value of significance. Other solutions to detect smaller changes in
radiological progression and quantification of structural integrity might
include the introduction of computer-assisted techniques for
quantification of erosions (2), metacarpal bone mineral density (3) and
for measurement of joint space width (4). Computer-based quantifications
of metacarpal bone mineral density and joint space narrowing have
demonstrated the ability to detect very small change (5, 6). In a head-to-
head comparison between the Sharp score and computer-assisted joint space
analysis the computer- based technique was able to verify smaller changes
in joint space width independent of the severity of RA (7). Additionally,
the computer based quantification of metacarpal bone mineral density by
digital x-ray radiogrammetry has been able to quantify therapeutic effects
based on the PREMIER study and the BesT study (8, 9). In this context,
computer-assisted joint space analysis was also able to verify therapy
associated changes of joint space width in RA-patients (7).
Quantitative data derived from computer-based techniques seems to support
and validate established scoring methods. Thus optimal individual
therapeutic strategies in daily clinical practice can be designed with
less uncertainty, and the quantification of structural integrity in RCT
poses an additional benefit. The more widespread use of computer-based
methods will help close the gap between visualization of structural damage
and inhibition of radiographic progression. Despite remaining issues of
complexity, quantitative data derived from computer-based techniques
support and validate established scoring methods.
References
1. Landewe R, Strand V, van der Heijde D. From inhibition of
radiographic progression to maintaining structural integrity: a
methodological framework for radiographic progression in rheumatoid
arthritis and psoriatic arthritis clinical trials. Ann Rheum Dis
2013;72(7):1113-7.
2. Langs G, Peloschek P, Bischof H, et al. Model-based erosion
spotting and visualization in rheumatoid arthritis. Acad Radiol
2007;14(10):1179-88.
3. Boettcher J, Pfeil A, Rosholm A, et al. Digital X
-ray radiogrammetry combined with semiautomated analysis of joint space
widths as a new diagnostic approach in rheumatoid arthritis: a cross-
sectional and longitudinal study. Arthritis Rheum 2005;52(12):3850-9.
4. Pfeil A, Haugeberg G, Hansch A, et al. Value of digital X-ray radiogrammetry in the assessment of
inflammatory bone loss in rheumatoid arthritis. Arthritis Care Res
(Hoboken) 2011;63(5):666-74.
5. Hoff M, Haugeberg G, Odegard S, et al. Cortical hand bone loss after 1 year in early
rheumatoid arthritis predicts radiographic hand joint damage at 5-year and
10-year follow-up. Ann Rheum Dis 2009;68(3):324-9.
6. Sharp JT, Angwin J, Boers M, et al. Multiple computer-based methods of measuring joint space width
can discriminate between treatment arms in the COBRA trial -- Update of an
ongoing OMERACT project. J Rheumatol 2009;36(8):1825-8.
7. Pfeil A, Oelzner P, Bornholdt K, et al. Joint damage in rheumatoid arthritis: assessment of a
new scoring method. Arthritis Res Ther 2013;15(1):R27.
8. Hoff M, Kvien TK, Kalvesten J, et al. Adalimumab
therapy reduces hand bone loss in early rheumatoid arthritis: explorative
analyses from the PREMIER study. Ann Rheum Dis 2009;68(7):1171-6.
9. Guler-Yuksel M, Allaart CF, Goekoop-Ruiterman YP, et al. Changes in hand and generalised bone mineral density
in patients with recent-onset rheumatoid arthritis. Ann Rheum Dis
2009;68(3):330-6.
Dear Editor,
We read with great interest the report by Dejaco and co-authors related to diagnosis of carpal tunnel syndrome (CTS) by ultrasound [1]. Dejaco et al. compared ultrasound measurement of median nerve cross- sectional area (CSA) at different anatomical landmarks in great detail and evaluated the value of intranerval power Doppler signals for CTS diagnosis. It provided a good data support for the ultrasonic...
Dear Editor,
On behalf of the investigators of the COMORA study, we would like to congratulate for the study you have conducted in Mexican mestizo patients. The results observed are totally in accordance with the results observed in the COMORA study that is: 1/ a relevant percentage of rheumatoid arthritis patients with comorbidities and 2/ a huge inter-country variability.
We would like to echo our Me...
Dear Editor,
Sieper et al. evaluated whether combination therapy with Infliximab (IFX) and naproxen (NPX) was superior to treatment with NPX alone in patients who had active moderate-to-severe early (disease duration under 3 years) active axial spondyloarthritis (SpA) and who were naive to nonsteroidal anti-inflammatory drugs (NSAIDs) or had only been treated with a submaximal dose of NSAIDs (1). This study is the...
Dear editor,
In the study recently published in the Annals of Rheumatic Diseases, Dougados et al. [1] evaluated the prevalence of comorbidities and compared their management in Rheumatoid Arthritis (RA) patients from different countries. We know that RA is a chronic autoimmune disease characterized by chronic inflammation, progressive deterioration of joint function, increased comorbidity and mortality; RA pati...
Dear Editor,
We have read the letter by Bossuyt X. and Fieuws S. entitled "Detection of anti-nuclear antibodies, added-value of solid phase assay?" with great interest (1). In this letter the authors described a comparison between anti-nuclear antibodies (ANA) performed by indirect immunofluorescent assay(IIFA) and by an automated method (fluoroenzymeimmunoassay; EliA CTD screen, Thermo Fisher) using samples obtai...
Dear Editor,
Moiseev and Novikov's comments on the Five-Factor Score (FFS) for eosinophilic granulomatosis with polyangiitis (EGPA) provide the opportunity to address the contribution of scores and their use. The FFS was designed to evaluate necrotizing vasculitis prognosis and identify manifestations associated with death: those are its only roles. Its strength is its validation on 1,108 patients with differen...
Dear editor,
We thank Forestier and Erol for their response on our paper on Eular recommendations for the non-pharmacological core management of hip and knee osteoarthritis (OA). We agree that balneotherapy is a relevant non- pharmacological intervention in hip and knee OA, and has been properly evaluated by means of randomised clinical trials, with the evidence summarized in systematic reviews. The topics to be in...
Dear Editor,
In the excellent study recently published in the Annals of the Rheumatic Diseases [1] F.Moosig et al. evaluated the individualized and more aggressive strategy of immunosuppressive treatment in 150 patients with EGPA. Over the last decade we utilized the same approach in our cohort of 117 patients with EGPA. For induction of remission the authors used cyclophosphamide in patients not only with Five Fac...
Dear Editor,
We appreciate that EULAR is preparing a specific recommendation on non-pharmacological treatment of knee osteoarthritis but we are also very surprised to discover that crenobalneotherapy was not even mentionned in the analysed treatments. Crenobalneotherapy (also called balneotherapy or spa therapy) is a very common treatment for knee osteoarthritis in South and Eastern Europe, Middle Asia, Japan, Sou...
Dear Editor,
The article published by Landewe et al. (1) offers novel insights to assess the benefits of new therapeutic strategies in rheumatoid arthritis (RA) which focus more on [the visualization of] structural integrity rather than the inhibition of radiographic progression (1). The authors clearly outline the three major problems of the common superiority study designs:
I. Differences in progression are...
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