We read the article by Aries and colleagues with great interest. The
authors describe a cohort of 8 patients with refractory Wegener’s
granulomatosis, of which 6 had no apparent response to Rituximab. Based
on this lack of response and based on the clinical disease manifestations
of the patients, the authors conclude that Rituximab may be ineffective in
patients with refractory granulomatous disease ma...
We read the article by Aries and colleagues with great interest. The
authors describe a cohort of 8 patients with refractory Wegener’s
granulomatosis, of which 6 had no apparent response to Rituximab. Based
on this lack of response and based on the clinical disease manifestations
of the patients, the authors conclude that Rituximab may be ineffective in
patients with refractory granulomatous disease manifestations. In the
discussion, the authors contrast their findings with our previous report.[1]
We would like to take this opportunity to point out that the dosing
regimen used by Aries and colleagues differs substantially from the one
used by us in our original case series and a subsequent prospective open-
label trial.[1,2] We utilized a dosing regimen of Rituximab 375mg/m2 iv
infusion weekly for 4 weeks (based on the original lymphoma treatment
regimen). The lack of significant response in the majority of patients
reported by Aries and colleagues, would suggest that the substantial
extension of the dosing intervals from one week to one month results in
underdosing. This may also allow for the formation of anti-chimeric
molecule antibodies, which may further affect efficacy. Although the
peripheral blood B cell counts dropped to zero, this may not be an
accurate reflection of effective dosing, because little is known about how
well peripheral blood B cell counts reflect tissue B cell numbers and
functional characteristics. The fact that ANCA levels did not drop as
precipitously as in most of our patients should also be interpreted with
more caution. It could also reflect the different dosing regimen rather
than that ANCA are produced by different cell types in the different
patient cohorts.
The authors further distinguish their study as including patients
with more prominent granulomatous disease manifestations, as opposed to
our series, which included more patients with predominant vasculitis
disease manifestations. We would like to clarify here that the majority of
our patients, both in our initial compassionate use series[1] and in our
subsequent pilot trial,[2] had granulomatous disease manifestations in
addition to vasculitis. Some of our patients also had retro-orbital
involvement (granted, not as advanced as the cases reported by Aries and
colleagues[3]), and this disease manifestation responded to the weekly
Rituximab regimen too.
In summary, we believe that Rituximab remains an exciting new option
for the treatment of refractory Wegener’s granulomatosis. The study by
Aries and colleagues emphasizes that deviations from the 375 mg/m2, once
weekly x 4, dosing regimen should be met with reservation, and further
careful studies of efficacy in different disease phenotypes are necessary.
This study also clearly highlights the need for further formal prospective
studies of Rituximab in ANCA-associated vasculitis. To that end, the
currently ongoing RAVE trial is a major step forward. It is a double
blind, double placebo-controlled, multicenter trial, designed to evaluate
the efficacy of Rituximab for remission induction in severe Wegener’s
granulomatosis and microscopic polyangiitis in comparison to
cyclophosphamide (www.clinicaltrials.gov). As part of the trial,
associated mechanistic studies are conducted to identify individual
patient characteristics, which influence or predict the degree and
duration of the therapeutic efficacy of B cell depletion as well as of
standard therapy.
References
1. Keogh KA, Wylam ME, Stone JH, Specks U. Induction of remission by
B lymphocyte depletion in eleven patients with refractory antineutrophil
cytoplasmic antibody-associated vasculitis. Arthritis Rheum. 2005
Jan;52(1):262-8.
2. Keogh KA, Ytterberg SR, Fervenza FC, Carlson KA, Schroeder DR,
Specks U. Rituximab for Refractory Wegener's Granulomatosis: Report of A
Prospective, Open-Label Pilot Trial. Am J Respir Crit Care Med. 2005 Oct
13; [Epub ahead of print].
The article by Gorman et al.[1], described three unusual features of
diffuse idiopathic skeletal hyperostosis (DISH). One was the young age of
the patients, the second was the familial occurrence, and the third was an
isolated involvement of the cervical spine.
We recently described a case of a young patient, 36 years of age, with
isolated involvement of the cervical spine.[2] It was estimated that a
p...
The article by Gorman et al.[1], described three unusual features of
diffuse idiopathic skeletal hyperostosis (DISH). One was the young age of
the patients, the second was the familial occurrence, and the third was an
isolated involvement of the cervical spine.
We recently described a case of a young patient, 36 years of age, with
isolated involvement of the cervical spine.[2] It was estimated that a
period of a least 10 years was needed for a complete evolvement of the
process. It is therefore likely that the pathogenetic process in the
patients described by Gorman et al had started in adolescence.
These descriptions draw the attention to a variant of the classical
clinical and radiologic features of DISH.[3] This notion suggests that
DISH might affect very young individuals with a predilection to the
cervical spine rather than the thoracic spine. It is therefore probable,
that these patients might have a different pathogenetic mechanism in which
genetic factors play a central role.
Studying this, at present small group, of young patients might help to
shed light on the pathogenesis of DISH in both young and elder population.
References
1. Gorman C, Jawad ASM, Chikanza I. A family with diffuse idiopathic
hyperostosis. Ann Rheum Dis 2005; 64:1794-1795.
2.Mader R. Diffuse idiopathic skeletal hyperostosis: isolated involvement
of cervical spine in a young patient. J Rheumatol 2004; 31; 620-21.
3.Mader R. Diffuse idiopathic skeletal hyperostosis: a distinct clinical
entity. IMAJ 2003;5:506-508.
In response to the hypothesis article ‘Is progressive osteoarthritis
an atheromatous vascular disease?’ [Conaghan, Hvanharanta, PA Dieppe Ann
Rheum Dis V64 No11 Nov 2005 1539-1541].
The hypothesis paper Atheroma and the Progression of Osteoarthritis
of Conaghan et al.[1] confuses four questions. Is progressive OA related
to local atheroma? Is it related to systemic atheroma? Do statins have
an...
In response to the hypothesis article ‘Is progressive osteoarthritis
an atheromatous vascular disease?’ [Conaghan, Hvanharanta, PA Dieppe Ann
Rheum Dis V64 No11 Nov 2005 1539-1541].
The hypothesis paper Atheroma and the Progression of Osteoarthritis
of Conaghan et al.[1] confuses four questions. Is progressive OA related
to local atheroma? Is it related to systemic atheroma? Do statins have
an effect of OA progression? Would using statins improve mortality in
osteoarthritis? For good measure a fifth consideration might be added...does osteoartrhitis cause progression of atheroma?
Each question needs different evidence and experiment. However
present knowledge about OA provides remarkably little evidence to support
the first two hypotheses. The evidence presented in the article could
easily support the counter thesis that there is no relationship between
the two conditions.
If local atheroma caused progression the mechanism is presumably
ischaemia. If this is a major or necessary condition for progression then
there should be a stronger association with conditions associated with
severe atheroma. No marked association with hyperlipidaemia, diabetes, or
those with established peripheral vascular disease has been reported. A
clear association should also be apparent in patients with premature OA or
ischaemic disease.
Joints have a remarkably good blood supply with good collateral
networks. Perfusion phase bone scan changes in OA have not been
highlighted as being abnormal and much of the change seen in MRI is non-
specific. The demonstration of focal necrosis by Bullough is the only
definite evidence there might be a problem due to ischaemia. However it
is not zonal , not associated with arterial changes and could be due to
local effects on blood perfusion in bone. The lack of more extensive
ischaemic change would suggest the opposite hypothesis…ischaemia is rarely
the cause of progression.
If systemic atheroma is somehow driving progression some suggestion
of the likely process is needed. This would not be ischaemia and indicate
a shared causative factor. The high frequency of atheroma in the aging
population will make analysis difficult, and the hypothesis improbable. It
can not be a sufficient condition to have atheroma and get progression.
Atheroma is so common it will have to relate to severity or extent of
atheroma. There would a have to be a dose related phenomena or everyone
should get progressive osteoarthritis. Equally people with non progressive
OA should have little artheroma ...but slow or no progression in OA is
common and many will have atheroma. Both processes are likely to be
linked by common factors such as age but this does not make
interdependence of cause between atheroma and oa likely. OA reducing
exercise and needing nonsterooidal treatment might indirectly increase
atheroma progression.
The third and fourth questions are very different. Statins have
multiple effects including effects on bone. They may very well influence
the development of OA. However their present widespread use makes it
unlikely any effect is large and of real life significance. Use of statins
is however likely to improve mortality in OA patients given the increased
mortality in both non and presumably ‘progressive’ OA s from
cardiovascular causes. With risks associated with use of non steroidals
and lack of exercise, a drug to reduce risk that is relatively safe and
cheap is attractive. Any study of statins should be powered to assess
this effect.
It is optimistic to hope to explain one poorly understood condition
with a second. The task is not made easier when both conditions are
difficult to measure. A hypothesis needs to generate a question that can
be answered by observation and experiment. Study of the value of statins
on OA survival does not need justification form speculation on how
atheroma may affect OA progression.
Dr Charles Hutton Derriford Hospital Plymouth UK
I have no competing interest.
References:
1. Is progressive osteoarthritis an atheromatous vascular disease?
PG Conaghan, Hvanharanta, PA Dieppe
Anals of Rheumatic Disease V64 No11 Nov 2005 1539-1541.
Osteoarthritis can occur at almost any joint, osteoarthritis of the
knee is the most common type. More than 10 million Americans have
osteoarthritis of the knee. Most people affected are older than 45 years.[1]
The published article by K L Bennel et al. lacks patient’s information
like patient’s age, sex, weights, heights, and family history. In this
article K L Bennel et al. concluded that p...
Osteoarthritis can occur at almost any joint, osteoarthritis of the
knee is the most common type. More than 10 million Americans have
osteoarthritis of the knee. Most people affected are older than 45 years.[1]
The published article by K L Bennel et al. lacks patient’s information
like patient’s age, sex, weights, heights, and family history. In this
article K L Bennel et al. concluded that physiotherapy trial was no more
effective than regular contact with a therapist at reducing pain and
disability. Osteoarthritis is a Multifactorial disease. Many factors
influence patient’s morbidity. Many studies had been done to see the
efficacy of treatment options in osteoarthritis of joints. Most of the
study reports really put us in a questionable position.
An article[2] “efficacy of acupuncture on osteoarthritic pain”
published in NEJM. The experimental group received treatment at standard
acupuncture points, and the control group at placebo points. Gaw A. C at
el in this study found that Thus, both experimental and control groups
showed a reduction in pain after the treatments. These results may reflect
the natural course of illness, and various attitudinal and social factors.
Many patients report symptomatic relief after undergoing arthroscopy
of the knee for osteoarthritis, but it is unclear how the procedure
achieves this result. Efficacy of arthroscopic surgery for osteoarthritis
treatment is also confusing. In a study[3] by J. Bruce Moseley et al. did
randomized, placebo-controlled trial to evaluate the efficacy of
arthroscopy for osteoarthritis of the knee. The outcomes after
arthroscopic lavage or arthroscopic débridement were no better than those
after a placebo procedure.
Even intra-articular hyaluronan injections have little benefit for
osteoarthritis (OA) of the knee and that the effect is similar in
magnitude to the superiority of nonsteroidal anti-inflammatory drugs
(NSAIDs) over acetaminophen.[4]
Dr Lo and colleagues1 concluded that intra-articular hyaluronan
injections have little benefit for osteoarthritis (OA) of the knee and
that the effect is similar in magnitude to the superiority of nonsteroidal
anti-inflammatory drugs (NSAIDs) over acetaminophen.
Aerobic exercise and resistance exercise showed a promising step in
osteoarthritis patients. In a study[5] W. H. Ettinger Jr et al. found that
Older disabled persons with osteoarthritis of the knee had modest
improvements in measures of disability, physical performance, and pain
from participating in either an aerobic or a resistance exercise program.
Their data suggest that exercise should be prescribed as part of the
treatment for knee osteoarthritis.
Reference:
1. Sharon Parmet; Cassio Lynm; Richard M. Glass
Osteoarthritis of the Knee. JAMA, Feb 2003; 289: 1068.
2. Efficacy of acupuncture on osteoarthritic pain. A controlled,
double-blind study. Gaw A. C., Chang L. W., Shaw L-C . N Engl J Med 1975; 293:375-378, Aug 21,
1975.
3. A Controlled Trial of Arthroscopic surgery for osteoarthritis of
the knee. Moseley J. B., O'Malley K., Petersen N. J., Menke T. J., Brody B. A.,
Kuykendall D. H., Hollingsworth J. C., Ashton C. M., Wray N. P. N Engl J
Med 2002; 347:81-88, Jul 11, 2002.
4. Grace H. Lo; David Felson; Michael LaValley
Intra-articular Hyaluronic Acid for Treatment of Osteoarthritis of the
Knee. JAMA, March 24/31, 2004; 291: 1441-1442.
5. W. H. Ettinger Jr; R. Burns; S. P. Messier; W. Applegate; W. J.
Rejeski; T. Morgan; S. Shumaker; M. J. Berry; M. O'Toole; J. Monu; T.
Craven. A randomized trial comparing aerobic exercise and resistance exercise with
a health education program in older adults with knee osteoarthritis. The
Fitness Arthritis and Seniors Trial (FAST). JAMA, Jan 1997; 277: 25-31.
In their recent report, Armstrong and colleagues highlight the high
prevalence of falls in patients with rheumatoid arthritis (RA)[1], show
that falls increase with functional disability and antidepressant use, and
comment that fracture prevention extends beyond the pharmacological
treatment of osteoporosis. This concurs with current guidelines for the
management of steroid induced osteoporosis[2], whi...
In their recent report, Armstrong and colleagues highlight the high
prevalence of falls in patients with rheumatoid arthritis (RA)[1], show
that falls increase with functional disability and antidepressant use, and
comment that fracture prevention extends beyond the pharmacological
treatment of osteoporosis. This concurs with current guidelines for the
management of steroid induced osteoporosis[2], which also recommend falls
risk assessment. However, they did not address another important risk
factor for falls i.e. visual impairment.
Older people with visual impairment are seven times more likely to
fall and sustain an injury[3] and the risk of hip fracture is doubled by
poor or moderately impaired vision.[4] Visual impairment (classified as
binocular visual acuity (VA) of <6/18[5]) affects 12.4% of the
population aged 75 years or more[6], while 30% of the over 65s have
reduced binocular VA to <6/12.[7] The latter study assessed people
wearing their spectacles, thus measuring day-to-day vision. In three
quarters of these cases vision was potentially remediable.
Visual impairment may have implications beyond fall risk, including
potentially reduced safety of medication-taking, social isolation,
depression, reduced functional status and quality of life[8], features
also well recognised in RA patients.[9] The cumulative effects of both
could be devastating.
We investigated the prevalence of impaired VA in patients with RA
attending routine outpatient clinics. 75 RA patients were examined (78.7%
female). The mean age was 58.9 years (SD 11.73), disease duration 14.8
years (range 1-48 years), HAQ 1.62 (SD 0.8). 39.7% had a VA of <6/18 in
either eye, which was corrected with the patients’ spectacles in all
except 2 patients who did not use them (1 of which had amblyopia, the 2nd
patients vision corrected with pin-hole which signifies potential for good
eyesight). 84% of patients had had an eye test within 18 months. Patients
with normal vision were less likely to have had a recent test (c2=6.15;
p<0.05).
Although uncorrected visual impairment is rare in RA and most
patients had had an eye test within the previous 18 months, we have
included in our multidisciplinary annual reviews[10] a systematic enquiry
of the latest refraction test date as part of routine falls assessment in
RA patients.
I have read the article by Kvien et al. with great interest (1). I
agree with their conclusion that PDA and other electronic media have a
future in data collection not only in clinical trials but also possibly in
routine clinical care, even in patients’ homes. However, I disagree with
some of the points they raise.
First, they state that patients were more satisfied with PDA than
paper. I...
I have read the article by Kvien et al. with great interest (1). I
agree with their conclusion that PDA and other electronic media have a
future in data collection not only in clinical trials but also possibly in
routine clinical care, even in patients’ homes. However, I disagree with
some of the points they raise.
First, they state that patients were more satisfied with PDA than
paper. I would think this would be expected since the recruitment involved
explaining what would be done and patients with interest and/or favorable
opinion about electronics in general would have been recruited. It is also
not surprising that they managed to use a PDA, it is more likely that if
they had heard of or used a PDA before that they would respond favorably
to participate. One way to see if this holds true would be to give the PDA
or paper version to the next 100 patients in a routine care setting and
see how they do.
Second, the distinction between patient questionnaires for clinical
research and routine care has to be made. An 8 page paper questionnaire
rarely succeeds in everyday rheumatology care (2). This is one of the
reasons very few clinicians utilize patient questionnaires in their
routine care, associating them with the lengthy research questionnaires
(3). Third, even though PDAs might be cheaper than before, they are still
not as cheap as pen and paper, even when you include time for a research
assistant and/or secretary to enter the data, which can easily be
maintained in a flow sheet, and does not necessarily require a computer
(personal experience).
I have implemented a system of giving patient questionnaires (MDHAQ)
to each and every patient every time they are seen in the office since
2001 (4). One of the main reasons for its success has been the ease of
giving everyone a 2 page questionnaire which includes 80% of the outcomes
measures utilized by most clinical trials.
One of our initial efforts should be to increase the use of these
very simple to administer and score questionnaires. An MDHAQ, by the
virtue of ease of use, applicability to not only RA but other diagnoses
seems like a very good candidate (5). Having a front desk in real life
patient care decide which patient can handle a PDA, which one needs a
paper version, let alone which disease specific questionnaire to give to
which patient, is only going to make the real life application of this
technology more difficult in routine care at this time. It could become
yet another impediment to the use of patient questionnaires in routine
care.
I believe the effort and time that may be devoted to establishing
wireless, fire walled, PDA environments can be better utilized using and
spreading the word on benefits of a simple pen and paper patient
questionnaire in routine clinical care.
References
1- Kvien TH, Mowinckel P, Heiberg T, Dammann KL, Dale O, Aanerud GJ,
Alme TN. Performance of helath status measures with a pen based personal
digital assisstan. Ann Rheum Dis 2005; 64: 1480-4.
2- Pincus T, Wolfe F. Patient questionnaires for clinical research and
improved standard patient care: is it better to have 80% of the
information in 100% of patients or 100% of the information in 5% of
patients? J Rheumatol. 2005; 32: 575-7.
3- Pincus T, Sokka T. Should contemporary rheumatoid arthritis clinical
trials be more like standard patient care and vice versa? Ann Rheum Dis.
2004; 63 Suppl 2:ii32-ii39.
4- Yazici Y. A database in private practice: the Brooklyn Outcomes of
Arthritis Rheumatology Database (BOARD). Clin Exp Rheumatol 2005; 23
(Suppl. 39): S182-S187.
5- Pincus T, Yazici Y, Bergman M. Development of a multi-dimensional
health assessment questionnaire (MDHAQ) for the infrastructure of standard
clinical care. Clin Exp Rheumatol 2005; 23 (Suppl. 39): S19-S28.
Our referral recommendations (1) for axial spondyloarthritis (SpA)
that includes ankylosing spondylitis (AS) and early preradiographic forms
of axial SpA were based on feasibility, costs, and effectiveness. Two
screening parameters have been proposed: inflammatory back pain (IBP) and
HLA-B27. According to data presented in an earlier publication (2) we
assumed for IBP a sensitivity of 75% and a specific...
Our referral recommendations (1) for axial spondyloarthritis (SpA)
that includes ankylosing spondylitis (AS) and early preradiographic forms
of axial SpA were based on feasibility, costs, and effectiveness. Two
screening parameters have been proposed: inflammatory back pain (IBP) and
HLA-B27. According to data presented in an earlier publication (2) we
assumed for IBP a sensitivity of 75% and a specificity of 76%, and for HLA
-B27 a sensitivity of 90% and a specificity of 90%, resulting in positive
likelihood ratios (LR+) of about 3 and 9, respectively. We are well aware
that the figures for HLA-B27 will be somewhat different in Non-White/Non-
Caucasian populations (discussed in ref. 2). Based on these figures and
assuming a prevalence of about 5% of axial SpA among chronic back pain
sufferers (3), a positive history of inflammatory back pain would give a
posttest probability of axial SpA of about 14-16% whereas a positive test
for HLA-B27 would yield a posttest probability of around 32% (2).
Accordingly, 1 out of 7 patients with a history of IBP and 1 out of 3
chronic back pain patients who are HLA-B27 positive can be expected to
have axial SpA.
Drs Healy and Helliwell now question the diagnostic value of HLA-B27
if appropriate controls that is patients with chronic back pain of origin
other than AS/SpA were considered, and refer to 3 studies (4-6). Two (4,
5) of the 3 studies, however, do not have the appropriate study design
and, therefore, are not valid in this context. In the study by Mau et al.
(4) no back pain controls were included at the start of the study. Rather,
patients highly suspected to have AS based on HLA-B27 positivity (overall
76% of patients suspected to have AS were HLA-B27 positive), presence of
IBP, and other clinical features of SpA but without radiographic
sacroiliitis were included. After 5 and 10 years, the frequency of
radiographic sacroiliitis rose to 36% and 59%, respectively. Among the
patients classified as AS after 10 years 91% were HLA-B27 positive
(confirming the proposed sensitivity of 90% for HLA-B27) whereas among the
12 patients who had other diagnosis after 10 years, 4 patients (33%) were
HLA-B27 positive. However, these 12 patients were initially included as
probably having SpA based on the presence of HLA-B27 and/or IBP, for
example, and therefore, cannot be considered as an appropriate control
group of patients with back pain of other origin (4). A second study (5)
referred to by Drs Healy and Helliwell is also invalid in using the data
as an argument against the diagnostic value of HLA-B27 in patients with
chronic back pain. In this study conducted by Braun et al. (5) the
frequency of clinical disease in blood donors stratified for the status of
HLA-B27 was assessed. Thus, the starting point was the HLA-B27 status
(positive or negative) in blood donors and not patients with chronic back
pain - a fundamental difference. Altogether, neither the study by Mau et
al. (4) nor the study by Braun et al. (5) can tell us the frequency of HLA
-B27 in patients with mechanical low back pain nor do these two studies
provide appropriate control groups.
The study by Sadowska-Wróblenska et al. from Poland (6) Drs Healy and
Helliwell refer to is the only study which may allow to calculate the
diagnostic value of HLA-B27. In this study, the frequency of HLA-B27 was
83% among 70 patients with early AS (sensitivity 83%) compared to 5% among
32 mechanical back pain controls (6). Thus, a sensitivity of 83% and
specificity of 95% (LR+ 16.6) from this study results in a posttest
probability of 46% of having SpA if HLA-B27 is positive – a figure
that is even better than the 32% probability we assumed in our
calculations (1, 2).
There is even more data available supporting the diagnostic value of
HLA-B27. In an older small study from Sweden (7) 45 patients with chronic
back pain were typed for HLA-B27. 6 out of 45 (13.3%) patients were found
to be HLA-B27 positive, reflecting the population frequency of HLA-B27 in
Sweden. Of note, 2 out of these 6 (33.3%) HLA-B27 positive patients with
chronic back pain were found to have signs of ankylosing spondylitis when
examined radiographically (7). This data is strong support for our
hypothesis that 1 out of 3 patients with chronic back pain and positivity
for HLA-B27 can be expected to have AS or axial SpA.
Another study mentioned by Drs Healy and Helliwell has now been
accepted for publication (8). This study investigated primarily clinical
features of inflammatory back pain in back pain patients with established
diagnoses. In addition, the HLA-B27 status was determined in all patients
(101 AS patients and 112 patients with mechanical low back pain). The
frequency of HLA-B27 was 89.1% among AS patients and 5.5% among mechanical
back pain patients resulting in a LR+ of 16.2. Hence, this this large
study i) demonstrates convincingly that HLA-B27 is definitely not
increased in patients with mechanical back pain, and ii) confirms again
the high diagnostic value of HLA-B27 (8).
Taken these studies together, there is ample evidence that HLA-B27 is
not increased in patients with mechanical low back pain. Moreover, the
resulting LRs + in the range of 9-16 if HLA-B27 is positive represent a
major diagnostic gain according to evidence-based approaches (9, 10).
Likewise, the LRs- (in case HLA-B27 is negative) in the range of 0.11-0.18
are diagnostically helpful in ruling out the disease.
Regarding criteria for IBP we have not reduced the criteria from 5 to
2 as stated by Drs Healy and Helliwell. Instead we propose to use 2 of the
5 parameters Calin et al. (11) have developed already as obligatory entry
parameters, and offer 3 more parameters (altogether 5 parameters for IBP).
The 2 obligatory entry criteria are chronic back pain of > 3 months and
age at onset of back pain < 45 years (Calin used 40 years but this is
unlikely to make a major difference) since this group of young adults with
chronic back pain is the target group in which axial SpA is a relevant
differential diagnosis. We have further refined the 3 remaining parameters
according to our own new data (8) in that ‘pain at night/ early
morning’ has been added and ‘insidious onset’ has been
removed from the list.
The concern expressed by Dr. Helliwell that rheumatology clinics will
be overwhelmed by patients if our proposed screening recommendations come
into place is clearly a question of capacity and depends on local or
regional modalities. However, in the interest of patients, the time span
of 5 to 7 years from onset of symptoms to making the diagnosis (12) can
only be significantly reduced if a well trained rheumatologist is prepared
to diagnose patients early (13). Selecting those patients with chronic
back pain who are at a relatively high risk of having axial SpA will help
to limit the number of patients needed to be seen.
References
1. Sieper J, Rudwaleit M. Early referral recommendations for
ankylosing spondylitis (including pre-radiographic and radiographic forms)
in primary care. Ann Rheum Dis 2005;64:659-63
2. Rudwaleit M, van der Heijde D, Khan MA, Braun J, Sieper J. How to
diagnose axial spondyloarthritis early. Ann Rheum Dis 2004;63:535-43
3. Underwood MR, Dawes P. Inflammatory back pain in primary care. Br
J Rheumatol. 1995;34:1074-7
4. Mau W, Zeidler H, Mau R, Majewski A, Freyschmidt J, Stangel W, et
al. Clinical features and prognosis of patients with possible ankylosing
spondylitis. Results of a 10-year followup. J Rheumatol. 1988;15:1109-14
5. Braun J, Bollow M, Remlinger G, Eggens U, Rudwaleit M, Distler A,
et al. Prevalence of spondylarthropathies in HLA-B27 positive and negative
blood donors. Arthritis Rheum 1998;41:58-67
6. Sadowska-Wróblewska M, Filipowicz A, Garwolinska H, Michalski J,
Rusiniak B, Wróblewska T. Clinical signs and symptoms useful in the early
diagnosis of ankylosing spondylitis. Clin Rheumatol. 1983;2:37-43
7. Sandström J, Andersson GBJ, Rydberg L. HLA-B27 as a diagnostic
screening tool in chronic low back pain. Scand J Rehab Med 1984;16:27-28
8. Rudwaleit M, Metter A, Listing J, Sieper J, Braun J. Inflammatory
back pain in ankylosing spondylitis – a reassessment of the clinical
history for classification and diagnosis. Arthritis Rheum, in press
9. Jaeschke R, Guyatt GH, Sackett DL. Users' guides to the medical
literature. III. How to use an article about a diagnostic test. B. What
are the results and will they help me in caring for my patients? The
Evidence-Based Medicine Working Group. JAMA 1994;271:703-7
10. Grimes DA, Schulz KF. Refining clinical diagnosis with likelihood
ratios. Lancet 2005;365:1500-5
11. Calin A, Porta J, Fries JF, Schurmann DJ. Clinical history as a
screening test for ankylosing spondylitis. JAMA. 1977;237:2613-411.
12. Feldtkeller E, Khan MA, van der Heijde D, van der Linden S,
Braun J: Age at disease onset and diagnosis delay in HLA-B27 negative vs.
positive patients with ankylosing spondylitis. Rheumatol Int 2003;23:61-6
13. Rudwaleit M, Khan MA, Sieper J. The challenge of diagnosis and
classification in early ankylosing spondylitis: do we need new criteria?
Arthritis Rheum 2005;52:1000-8
Aries et al. demonstrate in their study, the lack of response of
granulomatous disease in Wegener's granulomatosis to rituximab. From my
reading of the paper, this agent was given every fourth week. This is not
how this agent is usually prescribed, ie usually given as weekly pulses
for four weeks. Despite this, Bcell numbers were depleted in the
peripheral blood, though I would doubt at this low dose...
Aries et al. demonstrate in their study, the lack of response of
granulomatous disease in Wegener's granulomatosis to rituximab. From my
reading of the paper, this agent was given every fourth week. This is not
how this agent is usually prescribed, ie usually given as weekly pulses
for four weeks. Despite this, Bcell numbers were depleted in the
peripheral blood, though I would doubt at this low dose that lymph node
and or granulomatous B cells would have been depleted. This may well be
signficant reason why this study reached a negative conclusion.
It would also have been useful for the authors to have measured human
anti-chimeric antibodies. These can be induced by infliximab, and may well
have affected the efficacy of subsequent rituximab therapy.
In their article: Haematopoietic malignancies in rheumatoid
arthritis: lymphoma risk and characteristics after exposure to tumour
necrosis factor antagonists (and likewise in their subsequent article:
Risks of solid cancers in patients with rheumatoid arthritis and after
treatment with tumour necrosis factor antagonists) Askling et al. compare
occurrence rates for malignancies between different cohorts...
In their article: Haematopoietic malignancies in rheumatoid
arthritis: lymphoma risk and characteristics after exposure to tumour
necrosis factor antagonists (and likewise in their subsequent article:
Risks of solid cancers in patients with rheumatoid arthritis and after
treatment with tumour necrosis factor antagonists) Askling et al. compare
occurrence rates for malignancies between different cohorts of patients
with rheumatoid arthritis.
The authors conclude that patients treated with TNF antagonists in routine
care were not at any additional increased lymphoma risk compared with
patients with RA not treated with TNF antagonists (RR 1.1; 95%CI 0.6-2.1).
They urge us to view the, at most, marginally increased lymphoma risk
associated with TNF antagonists, in the context of higher disease activity
among patients who are offered anti-TNF treatment.
What the authors fail to note however, is that in routine care in
accordance with the labels of the different drugs, a pre-treatment
screening takes place before anti-TNF is prescribed. Rheumatologists have
long been aware of a possible increased risk for malignant lymphoma’s and
other malignancies during anti-TNF use. Product inlays and treatment
protocols also warn doctors and patients for this possible association.
Subsequently, in routine care, patients with current malignancies, a
(recent) history of a malignant disease, or a high suspicion for occult
malignancies are excluded from anti-TNF use. In the other two cohorts
studied, the Inpatient Register cohort and Early Arthritis cohort, such
exclusion is not likely to occur. Therefore the baseline risk for
malignancies might actually have been lower in the anti-TNF cohort than in
the other cohorts, in which case the detected increased lymphoma risk
might not be so marginal. We urge the authors to be careful in
interpreting their results.
Dr Ferrari has suggested that Whiplash Associated Disorders (WAD), is a
systemic illness in the September Annals of Rheumatic Disesases[1],
rather than an anatomically defineable lesion. They correctly quote that
in 90% of patients with WAD no pathology can be found. Dr Ferrari
reaches his conclusion from the acute subjective symptoms that describes
involvement of multiple systems. It is not too surpr...
Dr Ferrari has suggested that Whiplash Associated Disorders (WAD), is a
systemic illness in the September Annals of Rheumatic Disesases[1],
rather than an anatomically defineable lesion. They correctly quote that
in 90% of patients with WAD no pathology can be found. Dr Ferrari
reaches his conclusion from the acute subjective symptoms that describes
involvement of multiple systems. It is not too surprising that multiple
symptoms occur in “multiple trauma”, especially in the first 23 days.
What is very surprising and an extremely important omission, is that the
literature does not routinely report the precise location of multiple
symptoms, and even in this study, neck and shoulder pain are grouped
together.
We along with many others have found that one of the most common
locations of “neck pain” is not in the anatomical neck per se, nor even in
the shoulder, but nearby at the superior medial scapula. Indeed, there
are many reports that Whiplash Associated Disorders localized here are
diagnosed as Trapezius spasm, trigger points, etc. The problem is that in
addition to the absence of pathology, these conditions are generally
intractable to treatment.
We have considered that presentation of pain at this location is
related to the rotator cuff muscle origin, which is found here, and have
described a new cause of “neck pain” originating in the shoulder, which is
eminently treatable.[2] We now believe that many patients with “neck
pain” actually suffer from shoulder trauma, and that an anatomically
defined lesion does frequently exist, in the shoulder. Serendipitously
published at the exact time as our article, Turner et al.[3] showed that
many patients with neck pain had concurrent shoulder symptoms, and
consider this validation of the Referred Shoulder Impingement Syndrome.
Jerrold Gorski MD
Winthrop University Hospital
Mineola, New York
1. A re-examination of the whiplash associated disorders (WAD) as a
systemic illness R Ferrari, A S Russell, L J Carroll, J D Cassidy, Ann
Rhem Dis 2005; 64:1337-1442.
2. Shoulder Impingement Presenting as Neck Pain J M Gorski, L H
Schwartz, J Bone J Surg 85-American 2003;4: 635-638.
3. Impingement syndrome associated with whiplash injury S K Chauhan, T
Peckham, R Turner, J Bone J Surg 85-British 2003;3:408-410.
Dear Editor,
We read the article by Aries and colleagues with great interest. The authors describe a cohort of 8 patients with refractory Wegener’s granulomatosis, of which 6 had no apparent response to Rituximab. Based on this lack of response and based on the clinical disease manifestations of the patients, the authors conclude that Rituximab may be ineffective in patients with refractory granulomatous disease ma...
Dear Editor,
The article by Gorman et al.[1], described three unusual features of diffuse idiopathic skeletal hyperostosis (DISH). One was the young age of the patients, the second was the familial occurrence, and the third was an isolated involvement of the cervical spine. We recently described a case of a young patient, 36 years of age, with isolated involvement of the cervical spine.[2] It was estimated that a p...
Dear Editor,
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Dear Editor,
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Dear Editor
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Dear Editor
Our referral recommendations (1) for axial spondyloarthritis (SpA) that includes ankylosing spondylitis (AS) and early preradiographic forms of axial SpA were based on feasibility, costs, and effectiveness. Two screening parameters have been proposed: inflammatory back pain (IBP) and HLA-B27. According to data presented in an earlier publication (2) we assumed for IBP a sensitivity of 75% and a specific...
Dear Editor
Aries et al. demonstrate in their study, the lack of response of granulomatous disease in Wegener's granulomatosis to rituximab. From my reading of the paper, this agent was given every fourth week. This is not how this agent is usually prescribed, ie usually given as weekly pulses for four weeks. Despite this, Bcell numbers were depleted in the peripheral blood, though I would doubt at this low dose...
Dear Editor
In their article: Haematopoietic malignancies in rheumatoid arthritis: lymphoma risk and characteristics after exposure to tumour necrosis factor antagonists (and likewise in their subsequent article: Risks of solid cancers in patients with rheumatoid arthritis and after treatment with tumour necrosis factor antagonists) Askling et al. compare occurrence rates for malignancies between different cohorts...
Dear Editor,
Dr Ferrari has suggested that Whiplash Associated Disorders (WAD), is a systemic illness in the September Annals of Rheumatic Disesases[1], rather than an anatomically defineable lesion. They correctly quote that in 90% of patients with WAD no pathology can be found. Dr Ferrari reaches his conclusion from the acute subjective symptoms that describes involvement of multiple systems. It is not too surpr...
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