Sawitzke et al (1) reported on the results from the GAIT study assessing the long term effects of 2-year treatment on knee osteoarthritis (OA) symptoms. The findings indicate that the effects of glucosamine hydrochloride (GHCl), chondroitin sulfate (CS), and celecoxib treatment were not better than placebo, although safe and well tolerated.
The study results are not surprising in view of the original G...
Sawitzke et al (1) reported on the results from the GAIT study assessing the long term effects of 2-year treatment on knee osteoarthritis (OA) symptoms. The findings indicate that the effects of glucosamine hydrochloride (GHCl), chondroitin sulfate (CS), and celecoxib treatment were not better than placebo, although safe and well tolerated.
The study results are not surprising in view of the original GAIT study report (2), which assessed the results from the first 6 months of the study. From the latter report a number of issues have been raised, including the unusually high level of responders in the placebo group
(60.1%). These issues have prompted many experts in the field to express concern about the validity of the study. The fact that patients were entitled to receive rescue analgesics (acetaminophen) and a large number of them had low levels of pain (symptoms) at baseline may explain why
better results were found with the combined treatment (CS + GHCl) only in patients with moderate-to-severe pain.
The current report concerns the subgroup of patients who were enrolled in the structural study (3). This study was found to be underpowered with an unusually high drop-out rate of over 50% in some treatment groups and very low pain levels at baseline (normalized WOMAC score less than or equal to 15). Under these circumstances, in addition to the limitations imposed by the original cohort, it is hard to believe that any definitive conclusion could be arrived at from these findings, as acknowledged by the investigators. Indeed, these results are in contrast to a number of
previous reports showing long term efficacy of glucosamine (4; 5) and CS (6; 7) in the treatment of knee OA pain and symptoms. Furthermore, performing intent to treat (ITT) analysis on knee OA symptoms after 2 years combined with such high drop-out rate may further dilute the potential beneficial results of active treatment over placebo. There is the distinct possibility that an unsatisfied patient may prematurely leave the study. In this instance, the ITT process of adjudication would consider such patient's treatment as a failure at 2 years of follow-up while long term administration of such products may prove to be otherwise beneficial. An according to protocol (ATP) analysis would always be performed as well to yield a broader and clearer picture of the long term efficacy of slow acting agents.
The combination of all the above factors would pose a significant threat to the reliability of data from any clinical trial. The discrepancies between the results of different DMOAD trials exploring the effect of treatment on disease symptoms and structure are a concern at this time.
Among the possible explanations, certainly the lack of uniformity between study protocols creates multiple biases. There are a number of useful recommendations to avoid this. Better homogeneity of inclusion and exclusion criteria would define more precisely the patient population
selected. The number of patients included in a trial should be carefully established to allow for sufficient power to ensure the validity of statistical analysis and for the stratification of patients, if needed.
Only patients with a clinically significant pain level (moderate-severe) should be randomized. Patient selection and management should be optimized to decrease the drop-out rate and concomitant treatment should be taken into account, especially rescue medication. This is not the first time that such advice is offered (8) and, unfortunately, is probably not the last.
In summary, the reliability of long term OA trials testing drugs and agents needs to be improved. A better standardization of study protocols would be a first step in the right direction.
References
1. Sawitzke AD, Shi H, Finco MF, et al. Clinical efficacy and safety of glucosamine, chondroitin sulphate, their combination, celecoxib or placebo taken to treat osteoarthritis of the knee: 2-year results from GAIT. Ann Rheum Dis 2010;69:1459-64.
2. Clegg DO, Reda DJ, Harris CL, et al. Glucosamine, chondroitin sulfate, and the two in combination for painful knee osteoarthritis. N Engl J Med 2006;354:795-808.
3. Sawitzke AD, Shi H, Finco MF, et al. The effect of glucosamine and/or chondroitin sulfate on the progression of knee osteoarthritis: a report from the glucosamine/chondroitin arthritis intervention trial. Arthritis Rheum 2008;58:3183-91.
4. Pavelka K, Gatterova J, Olejarova M, et al. Glucosamine sulfate use and delay of progression of knee
osteoarthritis: a 3-year, randomized, placebo-controlled, double-blind study. Arch Intern Med 2002;162:2113-23.
5. Reginster JY, Deroisy R, Rovati LC, et al. Long-term effects of glucosamine sulphate on osteoarthritis progression: a randomised, placebo-controlled clinical trial. Lancet 2001;357:251-256.
6. Kahan A, Uebelhart D, De Vathaire F, et al. Long-term effects of chondroitins 4 and 6 sulfate on knee osteoarthritis: The study on osteoarthritis progression prevention, a two-year, randomized, double-blind, placebo-controlled trial. Arthritis Rheum 2009;60:524-533.
7. Uebelhart D, Malaise M, Marcolongo R, DeVathaire F, Piperno M, Mailleux E, Fioravanti A, Matoso L, Vignon E: Intermittent treatment of knee osteoarthritis with oral chondroitin sulfate: a one-year, randomized, double-blind, multicenter study versus placebo. Osteoarthritis Cartilage
2004;12:269-76.
8. Brandt KD, Mazzuca SA. Lessons learned from nine clinical trials of disease-modifying osteoarthritis drugs. Arthritis Rheum 2005;52:3349-59.
Dear Editor,
The recent retrospective study by Kaul et al(1) on the assessment of the 2006 revised classification criteria for definite antiphospholipid syndrome (2) sets the ground for at least three issues. a) The inclusion of “non-criteria aPL features” in the revised APS criteria is indeed a step
forward, but it appears that it requires revaluation, particularly with regards to the addition of thrombocytopenia as a dist...
Dear Editor,
The recent retrospective study by Kaul et al(1) on the assessment of the 2006 revised classification criteria for definite antiphospholipid syndrome (2) sets the ground for at least three issues. a) The inclusion of “non-criteria aPL features” in the revised APS criteria is indeed a step
forward, but it appears that it requires revaluation, particularly with regards to the addition of thrombocytopenia as a distinct clinical criteria. As known, this hematological manifestation was amongst the first clinical features recognized as part of the syndrome (3), it is actually more frequent than pregnancy morbidity in large series of APS patients (4,5) and, aCL and anti-ß2-glycoprotein-I antibodies (anti-ß2GP-I) bind strongly to activated platelets in vitro via ß2GP-I (6).
In Kaul’s series, 16 patients with aPL had thrombocytopenia (11 had a vascular event and 5 were classified as being “asymptomatic”) while 9 patients fulfilled the
pregnancy morbidity as the only criteria for APS. b) Four patients (10%) had APS according to the 2006 criteria, but not by the 1998 criteria, due to the fact that those patients fulfilled the IIc serological criteria, that is, they had anti-ß2GP-I as the only antibody. This is in agreement with earlier papers that reported the existence of aCL-negative, anti-ß2GP -I-positive patients, with or without systemic lupus erythematosus (SLE), but with otherwise clinical manifestations of the APS (7,8). Kaul´s finding also confirms that aCL (-), LAC (-), anti-ß2GP-I (+) patients account for 5-10% of patients with antiphospholipid syndrome (9,10). c) Kaul´s et al studied 82 “asymptomatic” patients, 39 of them met at least one
serological criteria for APS; assuming that the remainder 43 patients were asymptomatic and aPL negative, the sensitivity and specificity of aCL alone for APS is 0.28 and 0.67, 0.09 and 0.98 for anti-ß2GP-I alone, 0.28 and 0.59 for more than one aPL and 0.52 and 0.52 for all serological criteria, respectively. This finding confirms previous data showing that aCL have high sensitivity and low specificity for APS while anti-ß2GP-I have higher specificity and lower sensitivity than aCL for APS.
More than a decade ago, it has been our contention that antibodies toß2GP-I are comprised by at least two subpopulations, one directed against a cryptic epitope (detected by the conventional aCL ELISA) and another one
reactive with the native protein (detected by the modified ELISA with purified ß2GP-I as antigen). Thus, both immunoassays detect antibodies to ß2GP-I, while the conventional aCL ELISA also detects antibodies reactive
with cardiolipin proper (authentic aCL). This latter phenomenon may thus explain the low specificity of aCL for APS (In Kual´s series, 54% of asymptomatic patients had aCL).
The Sapporo APS criteria were developed by the experts’ opinions on the subject, while the amended criteria were born after an appraisal of the existing evidence on clinical and laboratory features of APS 1. What it is clearly needed is a large multinational study to objectively and prospectively validate the revised criteria and, why not, to challenge them with those developed 15 years ago after the systematic study of 667
patients with SLE 4
References
1. Kaul MS, Erkan D, Sammaritano L, Lockshin MD. Assessment of the 2006 revised antiphospholipid syndrome classification criteria. Ann Rheum Dis 2007.
2. Miyakis S, Lockshin MD, Atsumi T, Branch DW, Brey RL, Cervera R et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost 2006;4:295-306.
3. Hughes GRV. Hughes' syndrome: the antiphospholipid syndrome. A historical view. Lupus 1998;2:1-4.
4. Alarcón-Segovia D, Pérez-Vázquez ME, Villa AR, Drenkard C, Cabiedes J. Preliminary classification criteria for the antiphospholipid syndrome within systemic lupus erythematosus. Semin Arthritis Rheum 1992;21:275-86.
5. Cervera R, Piette JC, Font J, Khamashta MA, Shoenfeld Y, Camps MTet al. Antiphospholipid syndrome. Clinical and immunologic manifestations and patterns of disease expression in a cohort of 1000 patients. Arthritis
Rheum 2002;46:1019-27.
6. Vázquez-Mellado J, Llorente L, Alarcón-Segovia D. Exposure of anionic phospholipids upon platelet activation permits binding of ß2-glycoprotein-I and through it IgG antiphospholipid antibodies. Studies in platelets from patients with antiphospholipid syndrome and normal
subjects. J Autoimmunity 1994;7:335-48.
7. Cabral AR, Amigo MC, Cabiedes J, Alarcón-Segovia D. The antiphospholipid/cofactor syndromes. A primary variant with antibodies to ß2-glycoprotein-I but no antibodies detectable in standard antiphospholipid assays. Am J Med 1996;101:472-81.
8. Alarcón-Segovia D, Mestanza M, Cabiedes J, Cabral AR. The antiphospholipid/cofactor syndromes. II. A variant in patients with systemic lupus erythematosus with antibodies to ß2-glycoprotein-I but no antibodies detectable in standard antiphospholipid assays. J Rheumatol 1997;24:1545-51.
9. Damoiseaux J, Wijffels M, Willems GM, Bevers EM, Spaanderman ME, van Pampus EC et al. The antiphospholipid/cofactor syndrome: results of routine screening for antibodies to ß2-GPI upon suspicion of the
antiphospholipid syndrome. Scand J Rheumatol 2004;33(6):441-2.
10. Galli M, Luciani D, Bertolini G, Barbui T. Anti-b2-glycoprotein I, antiprothrombin antibodies, and the risk of thrombosis in the antiphospholipid syndrome. Blood 2003;102:2717-23.
We would like to thank Dr. Kumar for his interest in our report. He
was very correct to point out the possibility of chronic subdural hematoma
based on the CT appearance. In fact, chronic subdural effusion was the
top differential diagnosis raised by our radiologist at that juncture.
Simultaneous and subsequent follow-up MRI scans of the brain in our
patient confirmed significant and diff...
We would like to thank Dr. Kumar for his interest in our report. He
was very correct to point out the possibility of chronic subdural hematoma
based on the CT appearance. In fact, chronic subdural effusion was the
top differential diagnosis raised by our radiologist at that juncture.
Simultaneous and subsequent follow-up MRI scans of the brain in our
patient confirmed significant and diffuse loss in brain volume, together
with a small rim of effusion in the subdural space, being more prominent
on the right side. Thus, the CT appearance was not mainly contributed by
subdural effusion alone.
The etiology and significance of this subdural
effusion was unclear and it failed to resolve after 12 months and despite
immunosuppressive therapy. However, the main focus and interest of our
case report was the progressive atrophy of the brain and the spinal cord,
which has hitherto been undescribed in Chinese patients with systemic
lupus erythematosus.
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 interest the above publication which we found to be very informative.
The article presents the results of a systemic literature review of patients with established rheumatoid arthritis (RA) (>2 years disease duration) treated with stable
and effective disease modifying anti-rheumatic drug (DMARD) therapy, with a metaanalysis to determine the effect of therapy withdrawal...
We read with interest the above publication which we found to be very informative.
The article presents the results of a systemic literature review of patients with established rheumatoid arthritis (RA) (>2 years disease duration) treated with stable
and effective disease modifying anti-rheumatic drug (DMARD) therapy, with a metaanalysis to determine the effect of therapy withdrawal vs. continuation on disease flare. We note that the authors mention 'withdrawing biological drugs
after patients have achieved sustained remission is a burning question......
Unfortunately there is a lack of primary research in this area, and as a consequence we were unable to address the question in the current systematic review. It is an area in which more primary research is needed.'
We would, however, like to bring to the attention of the readers data published by ourselves in 2004 [1] and in last month's ARD [2], and by Brocq et al [3] and Tanaka et al [4].
In 2004 Buch et al published long-term data from patients completing the ATTRACT study [5] in our unit. In patients with established RA on methotrexate, 100% (17/17)
flared after infliximab therapy was stopped after 2 years of therapy [1].
Our more recent data, in patients with both early and established disease (median disease duration of the established group was 10 years), demonstrated high (85%, 17
/20) flare rates in patients with established RA when tumour necrosis factor (TNF)-inhibitor therapy was stopped despite continuation of methotrexate [2].
Prior to stopping TNF inhibitor therapy, there were no differences in neither DAS28 scores nor duration of remission; but HAQ and RAQoL scores were lower and
patients had shorter disease duration in those who maintained remission. We also observed that sustained remission was associated with lower inflammation-related T cell, higher naïve T cell, and higher CD62L+ Treg frequencies when compared to patients that flared [2].
Our flare rates post discontinuation of TNF inhibitor therapy have been confirmed by Brocq et al [3]. Patients with an average duration of RA of 11 years were withdrawn
from TNF inhibitor therapy after being in DAS28-defined remission for at least 6 months. Seventy-five percent (15/20) of patients flared 12 months after the withdrawal of TNF inhibitor therapy.
A Japanese study in which infliximab was discontinued in patients who were in sustained low disease activity (>6 months), 57% of the patients had lared 1 year after
stopping therapy [4]. This better outcome may be due to the genetically different population, lower DAS28 requirement to receive infliximab and different methotrexate dosing regimes.
We agree that more research is required but believe that there are already some useful data available for rheumatologists who may be considering withdrawing or
stopping TNF inhibitor therapy. Cautious therapy reduction maybe considered [6] in patients with short disease duration and low levels of functional impairment.
References
[1] Buch MH, Marzo-Ortega H, Bingham SJ, et al. Long-term treatment of rheumatoid arthritis with tumour necrosis factor alpha blockade: outcome of ceasing and restarting biologicals. Rheumatology (Oxford) 2004;43(2):243-4.
[2] Saleem B, Keen H, Goeb V et al. Patients with RA in remission on TNF blockers: when and in whom can TNF blocker therapy be stopped? Ann Rheum Dis 2010;69(9):1636-42.
[3] Brocq O, Millasseau E, Albert C, et al. Effect of discontinuing TNF-alpha antagonist therapy in patients with remission of rheumatoid arthritis. Joint Bone Spine
2009 Apr 9.
[4] Tanaka Y, Takeuchi T, Mimori T, et al. Discontinuation of infliximab after attaining low disease activity in patients with rheumatoid arthritis: RRR
(remission induction by Remicade in RA) study. Ann Rheum Dis 2009;69(7):1286-91.
[5] Maini R, St Clair EW, Breedveld F, et al. Infliximab (chimeric anti-tumour necrosis factor alpha monoclonal antibody) versus placebo in rheumatoid arthritis
patients receiving concomitant methotrexate: a randomised phase III trial. ATTRACT Study Group. Lancet 1999;354(9194):1932-9.
Dear Editor,
W Zhang and al. in their fourth recommendation for hand osteoarthritis consider that their proposition is based on expert opinion alone.
In France, and probably other European country, spa therapy (with hot mud, water or cloud) is often used for treating hand osteoarthritis.
A French spa centre supported two randomised clinical trial: One showed positive and equivalent effect between two different types of mud...
Dear Editor,
W Zhang and al. in their fourth recommendation for hand osteoarthritis consider that their proposition is based on expert opinion alone.
In France, and probably other European country, spa therapy (with hot mud, water or cloud) is often used for treating hand osteoarthritis.
A French spa centre supported two randomised clinical trial: One showed positive and equivalent effect between two different types of mud and thermal cloud [1] (which remain unpublished but is cited in the review of
E Maheu et al[2]). The other shows superiority of thermal cloud application on topical NSAI (ibuprofen) [3].
Even if they have some methodological limitation, we propose that these two trials (in French language) could be analysed by ESCISIT, in future recommendations, for determining if level of evidence could be improved by
their conclusion.
References
[1] Collin JF, Constant F, Herbeth B. Evaluation of comparative efficacy of mud and Berthollet on hand osteoarthritis [evaluation de l’efficacité compare de la boue et du Berthollet sur l’arthrose des mains]. Journée pratique s”hydrologie thérapeutique, MEDEC 1993.
[2] Trèves R, Maheu E, Dreiser RL. Clinical trials in hand osteoarthritis. Critical review.[les essais thérapeutiques dans l’arthrose digitale, revue
critique] Rev Rhum 1995, 62:119S-128S.
[3] Graber Duvernay B, Forestier R, Françon A. Efficacy of the Berthollet technique at Aix Les Bains spa on fuctionnal inpairment in hand osteoarthritis. A controlled therapeutic study [Efficacité du Berthollet d’Aix Les bains sur les manifestations fonctionnelles de l’arthrose des mains - Essai thérapeutique contrôlé.]Rhumatologie 1997;49(4):151-6.
We read with interest the article by Rudwaleit et al [1]. "How to
diagnose early spondyloarthropathy" and "Comment in leading" by Barkham et al
[2]. We agree that MRI, particullary with the special techniques, could be
very helpful in detecting signs of sacroiloiitis not yet visible on
standard radiographs.
MRI is most sensitive (95 %)and superior to
Quantitative SI scintigraphy...
We read with interest the article by Rudwaleit et al [1]. "How to
diagnose early spondyloarthropathy" and "Comment in leading" by Barkham et al
[2]. We agree that MRI, particullary with the special techniques, could be
very helpful in detecting signs of sacroiloiitis not yet visible on
standard radiographs.
MRI is most sensitive (95 %)and superior to
Quantitative SI scintigraphy (48 %) or conventional radiography (19 %)[3].
Although MRI scoring system for sacroiliac and spinal pathology have
developed still remains same concern about reliability and validity of
MRI, and its implications to prognosis and outcome. High costs and
availability of MRI are limiting factors for the widespread use.
Standard
radiographs, a single x-ray of the pelvis, or barsony technique still
remain common investigational method. A single AP film of the pelvis
showing inflammatory changes in the sacroiliac joints has a 55
sensitivity for spondyloarthropathy. Where changes are equivocal
additional techniques can increase sensitivity to 80 % [4]. Unfortunatelly
additional x-ray films increase the dose of radiation and costs.
In the
last 10 years we performed diascopy method in the standing position. With
this technique we can better visualis ventral and dorsal intraarticular
space and with the greater accuracy and lower degree of the radiation, the
diagnosis of the sacroiliitis can be made. In the follow up of the
patients it is possible to perform the same position [5].
References
(1). Rudwaleit M, van der Heijde D, Khan MA, Braun J, Sieper J. How to
diagnose axial spondyloarthritis early. Ann Rheum Dis 2004;63.535-543.
(2). Barkham N, Marzo-Ortega H, Mcgonagle D, Emery P. How to diagnose axial
spondyloarthropathy early. Ann Rheum Dis 2004;63:471-472.
(3). Blum U, Buitrago-Tellez C, Mundinger A et al. Magnetic resonance
imaging (MRI) for detection of active sacroiliitis- a prospective study
comparing conventional radiograph, scintigraphy, and contrast enhanced
MRI. J Rheumatol 1996;23:2107-2115.
(4). Yelland M. Diagnostic imaging for back pain. Aus Fam Physician
2004;33:415-419.
(5). Potoèki K, Æurkoviæ B, Babic-Naglic D. Advantage of diascopy of the
sacroiliac joints versus barsony x-ray views. J Rheumatol
1998;25(suppl.54):42 (abst.)
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 .
In the paper "EULAR points to consider in the development of classification and diagnostic criteria in systemic vasculitis" [1] it is stated that microscopic polyangiitis (MPA) was described in 1948 [2]. In fact, the first description of MPA I know of is considerably older than
that, dating back to 1923 [3].
References
[1] Basu N, Watts R, Bajema I et al. EULAR points to consi...
In the paper "EULAR points to consider in the development of classification and diagnostic criteria in systemic vasculitis" [1] it is stated that microscopic polyangiitis (MPA) was described in 1948 [2]. In fact, the first description of MPA I know of is considerably older than
that, dating back to 1923 [3].
References
[1] Basu N, Watts R, Bajema I et al. EULAR points to consider in the development of classification and diagnostic criteria in systemic vasculitis. Ann Rheum Dis 2010;69:1744-1750.
[2] Davson J, Ball J, Platt R. The kidney in periarteritis nodosa. Q J Med 1948;17:175-202.
[3] Wohlwill F. Ueber die nur mikroskopisch erkennbare Form der Periarteritis nodosa [About the purely microscopic form of polyarteritis nodosa]. Virchows Arch Pathol Anat Physiol 1923;246:377-411.
We have read with interest the article recently published by Matsui et al (1). They study a large cohort of patients with rheumatoid arthritisfrom 33 hospitals in Japan and conclude that the modified Disease Activity Score including 28-joint count and using C-reactive protein (DAS28-CRP) gives mean values lower than the same index using ESR (DAS28-ESR). They find a mean difference of 0.72 and state that DAS...
We have read with interest the article recently published by Matsui et al (1). They study a large cohort of patients with rheumatoid arthritisfrom 33 hospitals in Japan and conclude that the modified Disease Activity Score including 28-joint count and using C-reactive protein (DAS28-CRP) gives mean values lower than the same index using ESR (DAS28-ESR). They find a mean difference of 0.72 and state that DAS28-CRP underestimates thedisease activity if the criteria of evaluation for DAS28-ESR are applied.
The patients included in clinical trials and multicentre studies may be not representative of the usual patients attended in clinical practice. Since 2002 we have registered all the data from all our patients directly
into computers using software that calculates different clinical indexes and also enables reports to be given to them when they are still at the office. The analysis of the data from the 266 patients with rheumatoid arthritis treated by one of us in 2006 confirms the same findings reportedby Matsui. In the 242 patients with complete data available, DAS28-CRP waslower than DAS28-ESR (mean difference 0.49). Our results are also similar to those recently published by Inoue, from another large Japanese data base (2). Table I shows the characteristics of our patients and the results of the statistical analysis. It includes a regression line that strongly correlates DAS28-ESR and DAS28-CRP, as well as the proposed cut-off points of DAS28-CRP values that correspond to DAS28-ESR scores of 2'6, 3'2 and 5'1, obtained by means of Receiver Operating Characteristic (ROC) curves and defining remission, low disease activity and high disease activity, respectively. Unlike Matsui, we have not observed larger differences between DAS28-ESR and DAS28-CRP when DAS28 increases. However, the correlation of both indexes is stronger at high values of DAS28, a finding also reported by Inoue.
Our results support the conclusions of Matsui and Inoue that DAS28-CRP should be evaluated using different criteria from that for DAS28-ESR and extend them to daily practice.
REFERENCES
1. Matsui T, Kuga Y, Kaneko A, Nishino J, Eto Y, Chiba N et al. Disease activity score (DAS28) using CRP underestimates the disease activity and overestimates the EULAR response criteria compared with DAS28 using ESR in a large observational cohort of rheumatoid arthritis patients
in Japan. Ann Rheum Dis published online 16 mar 2007.
2. Inoue E, Yamanaka H, Hara M, Tomatsu T, Kamatani N. Comparison of Disease Activity Score (DAS)28-erythrocyte sedimentation rate and DAS28-C-reactive protein threshold values. Ann Rheum Dis 2007;66:407-409.
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Dear Editor,
In the paper "EULAR points to consider in the development of classification and diagnostic criteria in systemic vasculitis" [1] it is stated that microscopic polyangiitis (MPA) was described in 1948 [2]. In fact, the first description of MPA I know of is considerably older than that, dating back to 1923 [3].
References
[1] Basu N, Watts R, Bajema I et al. EULAR points to consi...
Dear Editor,
We have read with interest the article recently published by Matsui et al (1). They study a large cohort of patients with rheumatoid arthritisfrom 33 hospitals in Japan and conclude that the modified Disease Activity Score including 28-joint count and using C-reactive protein (DAS28-CRP) gives mean values lower than the same index using ESR (DAS28-ESR). They find a mean difference of 0.72 and state that DAS...
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