our and several previous studies demonstrated a high diagnostic value
of ultrasound for carpal tunnel syndrome (CTS) [1,2]. Among the various
abnormalities within the carpal tunnel reported, the increase of the cross
-sectional area (CSA) of the median nerve is the most commonly studied
ultrasound abnormality [3]. In addition, ultrasound allows the
identification of secondary causes of CTS such as sy...
our and several previous studies demonstrated a high diagnostic value
of ultrasound for carpal tunnel syndrome (CTS) [1,2]. Among the various
abnormalities within the carpal tunnel reported, the increase of the cross
-sectional area (CSA) of the median nerve is the most commonly studied
ultrasound abnormality [3]. In addition, ultrasound allows the
identification of secondary causes of CTS such as synovitis,
tenosynovitis, calcified masses or tophaceous gout, as pointed out by Zhu
et al. We acknowledge that the diagnostic value of ultrasound is not
perfect as some patients may suffer from CTS despite a normal ultrasound
result and vice versa, abnormal ultrasound findings do not necessarily
indicate CTS [1]. In these cases, additional tests such as nerve
conduction studies (although the sensitivity and specificity of this
method are far away from 100% as shown in our and several other studies)
are required to establish the final diagnosis [1,4].
A specific aspect of our study is the determination of a relevant cut-off
for the median nerve CSA. We decided to determine two cut-offs: one
resulting in a ?90% sensitivity implying that patients with a CSA below
this limit are unlikely to suffer from CTS and a second cut-off revealing
a ?90% specificity for the diagnosis. Decreasing the cut-off certainly
increases the sensitivity (theoretically up to 100%), but at the cost of
specificity and conversely, increasing the cut-off would result in a
better specificity. A perfect cut-off providing 100% sensitivity and
specificity is unrealistic and misclassification of a proportion of
patients has, unfortunately, to be accepted [2].
Another aspect to consider is the selection of the study population. One
strength of our study is the focus on patients with suspected CTS, rather
than investigating patients with established CTS and healthy controls (as
it was performed in previous studies) [2,5]. Our results are therefore
directly applicable to daily clinical routine, whereas studies
investigating patients with known CTS and healthy controls were prone to
result in artificially high diagnostic values.
We were the first to investigate the value of intranerval Power Doppler
(PD) signals as a diagnostic criterion for CTS diagnosis systematically
[1]. We observed a reasonable sensitivity and specificity and found this
sign particularly valuable for patients with intermediate median nerve
CSA. We acknowledge, however, that the sensitivity of PD depends on the
power of the ultrasound device and that our results may not be
generalizable given that older and/or low-power machines are commonly used
[6]. Further validation studies using different devices are thus necessary
to investigate the value of PD for CTS diagnosis.
In summary, our data indicate that ultrasound is a good but not perfect
diagnostic test for patients with suspected CTS. Apart from measurement of
median nerve CSA and detection of intranerval PD signals, it provides the
possibility to identify secondary causes of CTS such as synovitis,
tenosynovitis, abnormal masses or other abnormalities within the carpal
tunnel.
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. doi:10.1136/annrheumdis-2012-202328
2 Fowler JR, Gaughan JP, Ilyas AM. The sensitivity and specificity of
ultrasound for the diagnosis of carpal tunnel syndrome: a meta-analysis.
Clin Orthop Relat Res 2011;469:1089-94. doi:10.1007/s11999-010-1637-5
3 Mallouhi A, Pulzl P, Trieb T, et al. Predictors of carpal tunnel
syndrome: accuracy of gray-scale and color Doppler sonography. AJRAmerican
J Roentgenol 2006;186:1240-5. doi:10.2214/AJR.04.1715
4 Seror P. Sonography and electrodiagnosis in carpal tunnel syndrome
diagnosis, an analysis of the literature. Eur J Radiol 2008;67:146-52.
doi:10.1016/j.ejrad.2007.06.017
5 Klauser AS, Halpern EJ, De Zordo T, et al. Carpal tunnel syndrome
assessment with US: value of additional cross-sectional area measurements
of the median nerve in patients versus healthy volunteers. Radiology
2009;250:171-7. doi:10.1148/radiol.2501080397
6 Duftner C, Sch?ller-Weidekamm C, Mandl P, et al. Clinical implementation
of musculoskeletal ultrasound in rheumatology in Austria. Rheumatol Int
Published Online First: 26 September 2013. doi:10.1007/s00296-013-2863-4 .
We read with interest the editorial by Ferraccioli and Houssiau
proposing the specific targeting of long lived plasma cells (PCs) in human
lupus nephritis (LN) [1]. The authors present a cogent summary of
experiments showing that long-lived PCs alone are sufficient to induce
murine LN, and that targeting of PCs in these models is successful.
However, we believe that clinical experience with the treatme...
We read with interest the editorial by Ferraccioli and Houssiau
proposing the specific targeting of long lived plasma cells (PCs) in human
lupus nephritis (LN) [1]. The authors present a cogent summary of
experiments showing that long-lived PCs alone are sufficient to induce
murine LN, and that targeting of PCs in these models is successful.
However, we believe that clinical experience with the treatment of human
SLE indicates that plasmablasts and short-lived PCs, recently derived from
autoreactive B-cells, are more important in the generation of autoantibody
and clinical disease activity.
The literature on antibody secreting cell subsets are in some cases
difficult to interpret due to the use of the terms plasmablast and plasma
cell interchangeably, and different surface phenotypes in mouse and human
[2]. Human plasmablasts and PCs (latter labelled CD27-ve in article) both
express CD27.
Adoptive transfer of plasmablasts alone that mature into long-lived
PCs is sufficient to cause LN in Rag-/- mice, which have no B-cells [3].
This situation is analogous to therapeutic B cell depletion in human SLE,
with continued plasma cell activity in the absence of B cells. Rituximab
therapy profoundly depletes B-cells, but does not directly affect long-
lived PCs - demonstrated by the maintenance of total IgG including anti-
microbial antibodies [4,5]. Evidence of clinical efficacy of B cell
depletion in human SLE is controversial with contradictory RCTs [6,7] and
open label studies [8]. However, there is abundant evidence that anti-
dsDNA titre falls after rituximab [4-7]. We have previously shown that
reduction in anti-dsDNA was only observed in patients with complete
depletion of both B-cells and plasmablasts [5]. We also found that
clinical relapse following rituximab was strongly associated with
plasmablast repopulation [5]. Collectively, the effects of B cell
depletion therapy in SLE suggest that autoantibodies are secreted by
shorter-lived antibody secreting cells compared to those that maintain
steady state antimicrobial immunoglobulin levels. This selective effect of
B cell depletion on the antibody secreting cell pool may be crucial to its
safety.
We therefore believe that targeting of PCs in isolation would have
limited efficacy since these cells would be replenished from autoreactive
memory B-cells. It is possible that, in a subset of SLE patients
resistant to rituximab, combined targeting of long-lived plasma cells is
required. However, there would be important safety considerations for
such indiscriminate complete ablation of autoreactive and antimicrobial
antibody production.
References
1. Ferraccioli G, Houssiau FA. Which B-cell subset should we target
in lupus? Ann Rheum Dis 2013;72(12):1891-2.
2. Gordon CJ, Grafton G, Wood PM, et al. Modelling
the human immune response: can mice be trusted? Commentary. Curr Opin Pharmacol 2001;1(4):431-5.
3. Cheng Q, Mumtaz IM, Khodadadi L, et al.
Autoantibodies from long-lived 'memory' plasma cells of NZB/W mice drive
immune complex nephritis. Ann Rheum Dis
2013;72(12):2011-7.
4. Cambridge G, Leandro MJ, Teodorescu M, et al. B cell depletion
therapy in systemic lupus erythematosus: effect on autoantibody and
antimicrobial antibody profiles. Arthritis Rheum 2006;54(11):3612
-22.
5. Vital EM, Dass S, Buch MH, et al. B cell biomarkers of rituximab
responses in systemic lupus erythematosus. Arthritis Rheum
2011;63(10):3038-47.
6. Merrill JT, Neuwelt CM, Wallace DJ, et al. Efficacy and safety of
rituximab in moderately-to-severely active systemic lupus erythematosus:
the randomized, double-blind, phase II/III systemic lupus erythematosus
evaluation of rituximab trial. Arthritis Rheum 2010;62(1):222-33.
7. Rovin BH, Furie R, Latinis K, et al. Efficacy and safety of
rituximab in patients with active proliferative lupus nephritis: the Lupus
Nephritis Assessment with Rituximab study. Arthritis Rheum
2012;64(4):1215-26.
8. Ramos-Casals M, Soto MJ, Cuadrado MJ, et al. Rituximab in
systemic lupus erythematosus: A systematic review of off-label use in 188
cases. Lupus 2009;18(9):767-76.
we read with great interest the article by Rasmussen et al. [1] which
compared the performance of the new ACR [2] and the AECG [3]
classification criteria for Sjogren's syndrome (SS) showing that they led
to similar results when applied to a well-characterized cohort of patients
with sicca symptoms. More specifically, no clear evidence for an increased
value of the new ACR criteria [2] over the old AEC...
we read with great interest the article by Rasmussen et al. [1] which
compared the performance of the new ACR [2] and the AECG [3]
classification criteria for Sjogren's syndrome (SS) showing that they led
to similar results when applied to a well-characterized cohort of patients
with sicca symptoms. More specifically, no clear evidence for an increased
value of the new ACR criteria [2] over the old AECG criteria [3] from the
clinical or biological perspective was suggested by the authors. In
addition, when compared to the ACR criteria, the AECG-criteria gave more
space to patients' subjective symptoms which were collected according to
an internationally validated questionnaire, thus, allowing clinicians to
precisely select those subjects who mostly deserve to be addressed to the
diagnostic work up for pSS. However, despite their differences, data from
the article by Rasmussen et al. clearly highlight that both AECG and ACR
criteria could be able to identify patients with homogeneous and
comparable features in clinical trials and observational studies. By
contrast, a crucial point rose by Rasmussen and colleagues, in our
opinion, concerned the diagnostic value of these classification criteria
in daily practice. We have the general feeling that both the AECG and the
novel ACR criteria will not cover the broad clinical and immunological
heterogeneity of pSS from the perspective of the diagnosis of the disease
in clinical settings. As a contribute to this debate we could refer to the
clinical data of our large cohort of SS patients collected in 5 Italian
referral centres for SS and already published elsewhere. [4-5] In this
cohort of 1170 patients, after excluding patients with hepatitis C virus
infection, the characteristics of both SS satisfying AECG criteria (n=859,
88.4%), and SS not satisfying AECG criteria (n=113, 11.6%) (only clinical
diagnosis) were compared. Interestingly, no differences emerged on a
clinical ground, neither on sicca symptoms (811/859 vs 102/113, p=0.08 for
dry eyes; 797/859 vs 101/113, p=0.2, for dry mouth) nor on extraglandular
involvement (212/859 vs 18/113, p=0.05), even if the prevalence of
glandular swelling (271/859 vs 23/113, p=0.01), and the most frequent use
of systemic treatments in the SS group which satisfied AECG criteria may
lead to consider this group to be at higher risk of severe complications.
Importantly, no clear-cut statistical differences were observed as regards
also the prevalence of lymphoma (42/859 vs 3/113, p=0.29). Although we are
aware that etiopathological and biological differences between these two
groups of patients exist, [7] the above observation implies that patients
with SS clinical diagnosis need the same clinical work-up as deserved to
SS patients with positive criteria and similar therapeutic options. We
agree with Rasmussen et al. that improvements in diagnostic acumen of the
existing classification criteria will require a more fundamental
understanding of SS pathogenic mechanisms as well as novel reliable
diagnostic biomarkers. To this end, deeper morphological investigations,
at ultrasound, [8, 9] histopathological [10] and "omics" levels, [11] may
be of major value to improve both SS diagnosis and classification.
References
1. Rasmussen A, Ice JA, Li H, et al.
Comparison of the American-European Consensus Group Sjogren's syndrome
classification criteria to newly proposed American College of Rheumatology
criteria in a large, carefully characterised sicca cohort. Ann Rheum Dis
2013 Oct 23. doi: 10.1136/annrheumdis-2013-203845. [Epub ahead of print]
2. Shiboski SC, Shiboski CH, Criswell L, et al. American College of Rheumatology classification criteria
for Sjogren's syndrome: a data-driven, expert consensus approach in the
Sjogren's International Collaborative Clinical Alliance cohort. Arthritis
Care Res (Hoboken) 2012;64(4):475-87.
3. Vitali C, Bombardieri S, Jonsson R, et al. Classification criteria for Sjogren's syndrome: a
revised version of the European criteria proposed by the American-European
Consensus Group. Ann Rheum Dis 2002;61(6):554-8.
4. Priori R, Gattamelata A, Modesti M, et al. Outcome of pregnancy in Italian patients with primary
Sjogren syndrome. J Rheumatol 2013;40(7):1143-7.
5. Quartuccio L, Isola M, Baldini C, et al. Biomarkers of lymphoma in Sjogren's syndrome and evaluation of
the lymphoma risk in prelymphomatous conditions: Results of a multicenter
study. J Autoimmun 2013. doi:pii: S0896-8411(13)00134-0.
6. Ioannidis JP, Vassiliou VA, Moutsopoulos HM. Long-term risk of
mortality and lymphoproliferative disease and predictive classification of
primary Sjogren's syndrome. Arthritis Rheum 2002;46(3):741-7.
7. De Vita S, Lorenzon G, Rossi G,et al. Salivary gland
echography in primary and secondary Sjogren's syndrome. Clin Exp
Rheumatol 1992;10:351-6.
8. Cornec D, Jousse-Joulin S, Pers JO, et al. Contribution of salivary gland ultrasonography to the
diagnosis of Sjogren's syndrome: toward new diagnostic criteria? Arthritis
Rheum 2013;65(1):216-25. doi: 10.1002/art.37698.
9. Tavoni AG, Baldini C, Bencivelli W, et al. Minor salivary gland biopsy and Sjogren's syndrome:
comparative analysis of biopsies among different Italian rheumatologic
centers. Clin Exp Rheumatol 2012;30(6):929-33.
10. Gallo A, Baldini C, Teos L, et al.
Emerging trends in Sjogren's syndrome: basic and translational research.
Clin Exp Rheumatol 2012;30(5):779-84.
I read with interest the study by Takeuchi et al (1) looking at the role
of monotherapy golimumab in Japanese rheumatoid arthritis (RA) patients,
who had active disease despite disease modifying anti-rheumatic drug
(DMARD) therapy. Inclusion criteria for the study stipulated that patients
have 2/3 criteria which were: elevated inflammatory markers, erosions on
radiograph or positive serology, in additio...
I read with interest the study by Takeuchi et al (1) looking at the role
of monotherapy golimumab in Japanese rheumatoid arthritis (RA) patients,
who had active disease despite disease modifying anti-rheumatic drug
(DMARD) therapy. Inclusion criteria for the study stipulated that patients
have 2/3 criteria which were: elevated inflammatory markers, erosions on
radiograph or positive serology, in addition to more than 6 swollen and
tender joints despite DMARD therapy for at least 3 months. They had mean
disease duration of close to 9 years and mean swollen and tender joint
counts of roughly 16 and 13. They were then randomized to placebo,
golimumab 50 or golimumab 100 mg injections. Primary efficacy outcome was
at 14 weeks, as the authors state "due to ethical concerns about the
potential for an inadequate response to placebo". At 14 weeks both
golimumab doses showed better efficacy than placebo. In the introduction
section, the justification for looking into monotherapy was explained as
"some patients cannot tolerate MTX treatment; therefore, it is clinically
relevant to evaluate the safety and efficacy of monotherapy...".
In the discussion, authors state that 100 mg golimumab was studied as
monotherapy in a previous publication (2) but in that study primary end
point was not reached by this monotherapy arm. Various reasons are
presented to possibly explain this difference. However, in the current
study this time the 50 mg monotherapy did not show any significant
difference in radiographic inhibition from placebo and neither did the 100
mg until post hoc adjustments were made and the data were reanalyzed.
There are several serious methodological and ethical issues with this
study that are not addressed in the paper. First, the trial was registered
at the clinicaltrials.gov site in October 2008. It is unclear to me how
the ethical justification of withholding active treatment from patients
with RA, for up to 4 months, including the 4 weeks of washout before the
study medication was administered, who were failing their current therapy
and were at risk for destructive disease as reflected by the inclusion
criteria (high joint counts, serological or radiographic evidence for
higher risk for erosions) was made. In 2008 there is no more equipoise
about how patients fare when they are not given DMARDs, biologics or
combinations of these agents.
Authors state, as mentioned previously, that
"due to ethical concerns about the potential for an inadequate response to
placebo" they were analyzed at 14 weeks and switched to active drug at 16
weeks. What is meant by "potential for an inadequate response to placebo"?
Is it only a potential or a near certainty? How is it that authors truly
believe this is not a resolved issue in this day and age of RA treatment,
that active RA patients need treatment not placebo, and how is that any
IRB would think this to be ethical? It would be of interest to see what
the informed consent document actually read and how the information that
despite available active medications that the patients could have been
switched to including other biologic agents, , instead of enrolling in
this trial, treatment was withheld for over 4 months (including the 4
weeks of washout before the study medication was administered), when
overwhelming published data suggest early and aggressive treatment is the
best way to get RA under control.
The second issue is that even though the similar intervention was tried in
an earlier study (2) , the need to try again was felt. This time there
were some differences that suggest golimumab 100 mg has radiographic (no
such benefit was seen with 50 mg, the approved dose in the US) and
clinical benefit but who is to say the reasons listed by the authors that
affected the first trials results in one way, did not affect the results
of the second trial in the other direction? Which one is the "true" study?
This is now the second study where radiographic benefit was not
demonstrated with golimumab until post hoc analysis of the data was done.
Several explanations for this state of affairs come to mind; 1) either
radiographic progression is not a clinically important outcome, as was
argued previously (3), since the actual differences are so small to have
clinical relevance 2) golimumab does not work as well as some other
biologics, which have shown effects on radiographic progression as a
primary outcome with no need for posthoc analysis, or 3) the authors would
like to think and are trying to prove golimumab is no different than any
other biologic, despite what the data show. None of these are good reasons
for withholding treatment from active RA patients for close to 4 months in
the guise of scientific experimentation.
References
1. Takeuchi T, Harigai M, Tanaka Y, et al. Golimumab monotherapy in
Japanese patients with active rheumatoid arthritis despite prior treatment
with disease-modifying antirheumatic drugs: results of the phase 2/3,
multicenter, randomized, double-blind, placebo-controlled GO-MONO study
through 24 weeks. Ann Rheum Dis. 2013;72:1488-95.
2. Keystone EC, Genovese MC, Klareskog L, et al. Golimumab, a human
antibody to tumour necrosis factor ? given by monthly subcutaneous
injections, in active rheumatoid arthritis despite methotrexate therapy:
the GO-FORWARD Study. Ann Rheum Dis 2009;68:789-96.
3. Yazici Y, Yazici H. Tumor necrosis factor alpha inhibitors,
methotrexate or both? An inquiry into the formal evidence for when they
are to be used in rheumatoid arthritis. Clin Exp Rheumatol. 2008;26:449-
52.
We read with interest the findings of the paper by Neovius et al recently
published on Annals of the Rheumatic Diseases 1 who retrospectively
studied the drug survival on TNF-alpha blockers in patients with rheumatoid
arthritis (RA) in real life settings. The primary endpoint of their
analysis was to assess the drug discontinuation rates in RA patients
starting a first ever TNF-alpha inhibitor, and to...
We read with interest the findings of the paper by Neovius et al recently
published on Annals of the Rheumatic Diseases 1 who retrospectively
studied the drug survival on TNF-alpha blockers in patients with rheumatoid
arthritis (RA) in real life settings. The primary endpoint of their
analysis was to assess the drug discontinuation rates in RA patients
starting a first ever TNF-alpha inhibitor, and to compare between-group
survival rates for the historical anti-TNF-alpha drug, namely adalimumab,
etanercept, and infliximab, during five years follow-up. Additionally,
they also evaluated the discontinuation rates of each anti-TNF-alpha drug
across calendar period. They selected patients starting the treatment
since 2003, when all three drugs were available on the market, and claimed
that it was the first study assessing adalimumab, etanercept, and
infliximab retention rates from 2003 onwards, together with the article by
Kievit et al2. Indeed, we have published a similar study in which the drug
discontinuation of first ever adalimumab, etanercept and infliximab in RA
patients starting follow-up in 2003 was compared among groups3. Our cohort
was smaller because only patients beginning the treatment in 2003 through
2004 and followed up-to 4 years were analysed. Notwithstanding, our study
yielded nearly identical results. After 4-year follow-up the survival rate
of etanercept (51 %) was significantly greater than that of infliximab
(37.6 %) or adalimumab (36.4 %; p <0.0001). Unlike the study by Neovius
et al, the Kaplan-Meier life curve of adalimumab was closer to that of
infliximab rather than etanercept (Figure 1). Of note, Neovius et al
carried out an analysis by calendar period from 2003 to 2011 and provided
evidence that discontinuation rates increased over time, maybe due to the
availability of new biologics. They also showed that discontinuation rate
was higher for adalimumab than etanercept during the 1st year. Likewise,
we observed the highest discontinuation rate of adalimumab in the 1st year
of follow-up, and the difference between etanercept and adalimumab was 13
% and 4 % in the 1st and 2nd year, respectively (data not shown).
Furthermore, we found the same predictors of drug survival, as baseline
concomitant therapy with Disease Modifying Drugs (DMARDs) and longer
disease duration were associated with lower odds of drug interruption in
both studies, although different statistical analysis was used. Obviously,
also our study had similar weaknesses, being an analysis of a longitudinal
cohort followed in standard care settings, without randomization and
totally depending on own decisions of treating rheumatologist that can
still influence the clinical outcome despite of the statistical
adjustments. Therefore, our data are in agreement with the conclusions of
the article by Neovius et al, and this is of note since the two RA cohorts
become from quite far geographical areas, North and South of Europe, with
racial, genetic, and cultural differences.
Figure will be available on the Electronic Pages soon.
Figure 1.
Drug retention rate in patients with rheumatoid arthritis on TNF-?
inhibitors starting from 2003 and followed-up to four (Iannone cohort) or
five (Neovius cohort) years.
References
1 Neovius M, Arkema EV, Olsson H, et al. Drug survival on TNF inhibitors in patients with rheumatoid
arthritis comparison of adalimumab, etanercept and infliximab. Ann Rheum
Dis 2013;0:1 7. doi:10.1136
2 Kievit W, Adang EM, Fransen J, et
al. The effectiveness and medication costs of three anti-tumour necrosis
factor alpha agents in the treatment of rheumatoid arthritis from
prospective clinical practice data. Ann Rheum Dis 2008;67:1229-34.
3 Iannone F, Gremese E, Atzeni F, et al.
Longterm retention of tumor necrosis factor-? inhibitor therapy in a large
italian cohort of patients with rheumatoid arthritis from the GISEA
registry: an appraisal of predictors. J Rheumatol 2012;39:1179-84.
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).
Dear Editor,
our and several previous studies demonstrated a high diagnostic value of ultrasound for carpal tunnel syndrome (CTS) [1,2]. Among the various abnormalities within the carpal tunnel reported, the increase of the cross -sectional area (CSA) of the median nerve is the most commonly studied ultrasound abnormality [3]. In addition, ultrasound allows the identification of secondary causes of CTS such as sy...
Dear Editor,
We read with interest the editorial by Ferraccioli and Houssiau proposing the specific targeting of long lived plasma cells (PCs) in human lupus nephritis (LN) [1]. The authors present a cogent summary of experiments showing that long-lived PCs alone are sufficient to induce murine LN, and that targeting of PCs in these models is successful. However, we believe that clinical experience with the treatme...
Dear Editor,
we read with great interest the article by Rasmussen et al. [1] which compared the performance of the new ACR [2] and the AECG [3] classification criteria for Sjogren's syndrome (SS) showing that they led to similar results when applied to a well-characterized cohort of patients with sicca symptoms. More specifically, no clear evidence for an increased value of the new ACR criteria [2] over the old AEC...
Dear Editor
I read with interest the study by Takeuchi et al (1) looking at the role of monotherapy golimumab in Japanese rheumatoid arthritis (RA) patients, who had active disease despite disease modifying anti-rheumatic drug (DMARD) therapy. Inclusion criteria for the study stipulated that patients have 2/3 criteria which were: elevated inflammatory markers, erosions on radiograph or positive serology, in additio...
Dear Editor,
We read with interest the findings of the paper by Neovius et al recently published on Annals of the Rheumatic Diseases 1 who retrospectively studied the drug survival on TNF-alpha blockers in patients with rheumatoid arthritis (RA) in real life settings. The primary endpoint of their analysis was to assess the drug discontinuation rates in RA patients starting a first ever TNF-alpha inhibitor, and to...
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...
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