We thank Dr Chan and collaborators for their interest in our study
and for their comments.[1] As concerns the patients’ selection, we excluded
patients with serious medical problems such as heart, and lung diseases,
as well as other ophthalmological disorders including glaucoma. Thus, none
of our patients were treated with beta-blockers and none were on hormone
replacement therapy which may exacerbate d...
We thank Dr Chan and collaborators for their interest in our study
and for their comments.[1] As concerns the patients’ selection, we excluded
patients with serious medical problems such as heart, and lung diseases,
as well as other ophthalmological disorders including glaucoma. Thus, none
of our patients were treated with beta-blockers and none were on hormone
replacement therapy which may exacerbate dry eye symptoms. For
postmenopausal osteoporosis some patients were treated with raloxifene and
some others with biphosphonates. The type of artificial tears used by our
patients was: natural tears free monodose and it was used according to
their sicca complains, as they needed.
The dose of oral pilocarpine was 5 mg at 08.00 in the morning and the same
dose at 20.00 in the evening. Patients performed the Schirmer’s I test in
the outpatient eye clinic between 09.00 and 11.00 in the morning, after
receiving pilocarpine. Thus, we do not believe that the negative results
of Schirmer’s I test are influenced by pilocarpine. We think that
Schirmer’s I test is less sensitive than Rose Bengal test and is
influenced from many factors like the body and room temperature, the
status of hydradation, the climate, etc.[2]
As regards the long-term safety of oral pilocarpine, this is exactly the
reason for excluding patients with serious medical problems and of using
small doses of pilocarpine. With 10 mg of oral pilocarpine daily we showed
a substantial clinical response and improvement of Rose Bengal test in the
majority of patients.[3] Of course local treatment for the dry eyes of
Sjogren’s syndrome patients is essential.[4] However, not all patients
responded to topical treatment. We have used cyclosporin A (since 1986)
for the treatment of sicca syndrome in Sjogren’s patients,[5] but local
cyclosporin A is not in use in many countries in Europe.
References
(1) Chan W-M et al. Comments on oral pilocarpine for ocular symptoms in Sjõgren’s syndrome [electronic response to Tsifetaki et al. Oral pilocarpine for the treatment of ocular symptoms in patients with Sjögren’s syndrome: a randomised 12 week controlled study] annrheumdis.com 2003http://ard.bmjjournals.com/cgi/eletters/62/12/1204#52
(2) Talal N, Moutsopoulos HM, Kassan SS, ed. Sjogren’s syndrome: clinical
and immunological aspects. Berlin: Springer, 1987.
(3) Tsifetaki N, Kitsos G, Paschides CA, Alamanos Y, Eftaxias V, Voulgari
PV, et al. Oral pilocarpine for the treatment of ocular symptoms in
patients with Sjogren’s syndrome: a randomised 12 week controlled study.
Ann Rheum Dis 2003;62:1204-7.
(4) Bell M, Askari A, Bookman A, Frydrych S, Lamant J, McComp J et al.
Sjogren’s syndrome: a critical review of clinical management. J Rheumatol
1999;26:2051-61
(5) Drosos AA, Skopouli FN, Costopoulos JS, Papadimitriou CS, Moutsopoulos
HM. Cyclosporin A (CyA) in primary Sjogren’s syndrome: a double blind
study. Ann Rheum Dis 1986;45:732-5.
Many thanks to Schoels et al for their very helpful systematic literature review of the evidence for treating RA to target [1]. However, I am concerned that the authors' discussion may lead readers to conclude erroneously that there is no evidence that treat to target, intensive
management has a beneficial impact on physical function. In their discussion the authors state that 'Functional outcomes, reported...
Many thanks to Schoels et al for their very helpful systematic literature review of the evidence for treating RA to target [1]. However, I am concerned that the authors' discussion may lead readers to conclude erroneously that there is no evidence that treat to target, intensive
management has a beneficial impact on physical function. In their discussion the authors state that 'Functional outcomes, reported in two trials, failed to show functional gains,' only referring to two negative trials [2-3]. However, Table 1 of their paper shows that in the TICORA
study there were substantial improvements in physical function with intensive therapy (HAQ change -0.97 0.8 versus -0.47 0.9; p=0.0025)[4].
References
1. Schoels M, Knevel R, Aletaha D, et al. Evidence for treating rheumatoid arthritis to target: results of a systematic literature search. Ann Rheum Dis 2010;69:638-43.
2. Symmons D, Tricker K, Roberts C, et al. The British Rheumatoid Outcome Study Group (BROSG) randomised controlled trial to compare the effectiveness and cost-effectiveness of aggressive versus symptomatic therapy in established rheumatoid arthritis. Health Technol Assess
2005;9:iii-iv, ix-x, 1-78.
3. Verstappen SM, Jacobs JW, van der Veen MJ, et al. Intensive treatment with methotrexate in early rheumatoid arthritis: aiming for remission. Computer Assisted Management in Early Rheumatoid Arthritis (CAMERA, an
open-label strategy trial). Ann Rheum Dis 2007;66:1443-9.
4. Grigor C, Capell H, Stirling A, et al. Effect of a treatment strategy of tight control for rheumatoid arthritis (the TICORA study): a single blind randomised controlled trial. Lancet 2004; 364:263-9.
It is my hypothesis that most drugs of addiction activate DHEA
release. When DHEA declines following drug activation of DHEA, the drug
is again used to reactivate DHEA. This may be the basis of addiction.
Smoking has been demonstrated to activate DHEA release
(Neuropsychopharmacology. 2005 Sep;30(9):1751-63).
DHEA, estradiol, and testosterone have been found to "stimulate
articular cartilag...
It is my hypothesis that most drugs of addiction activate DHEA
release. When DHEA declines following drug activation of DHEA, the drug
is again used to reactivate DHEA. This may be the basis of addiction.
Smoking has been demonstrated to activate DHEA release
(Neuropsychopharmacology. 2005 Sep;30(9):1751-63).
DHEA, estradiol, and testosterone have been found to "stimulate
articular cartilage integration" ( Arthritis Rheum. 2006 Nov
28;54(12):3890-3897). I suggest long term use of drugs that activate DHEA
in an addictive manner ultimately reduce DHEA production during the life
span. I suggest the findings of Amin, et al., may be explained by long-
term reduction of DHEA levels by smoking.
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).
Toivanen [1] put forward the interesting hypothesis that, in contrast
to reactive arthritis where temporary lodging of pathogenic micro-
organisms is a causative factor, in RA a continuous seeding of degraded
bacterial products from normal intestinal flora may induce synovitis. This
hypothesis closely resembles the theory published by us one year earlier,[2] in which we also stressed a continuous seeding o...
Toivanen [1] put forward the interesting hypothesis that, in contrast
to reactive arthritis where temporary lodging of pathogenic micro-
organisms is a causative factor, in RA a continuous seeding of degraded
bacterial products from normal intestinal flora may induce synovitis. This
hypothesis closely resembles the theory published by us one year earlier,[2] in which we also stressed a continuous seeding of products of normal
bacteria in RA. However, we suggested that these micro-organisms are
lodged in closed dental foci, as especially and paradoxically found in
endodontically well treated, healthy looking teeth. A mechanical factor
(grinding the teeth) may then contribute to a continuous degradation of
the micro-organisms. This explains perhaps better the massive degradation
and intrusion into the blood stream of bacterial products than a mere
adherence of micro-organisms to the intestinal wall as Toivanen's theory
implies. It is furthermore possible to hypothesise that this factor of
endodontical state is one of Toivanen's "environmental factors" which are
responsible for the differences between people who get and who do not get
RA despite a same kind of microbial flora.
References
(1) Toivanen P, Normal intestinal microbiota in the aetiopathogenesis of rheumatoid arthritis, Ann Rheum Dis 2003;62:807-811
(2) Breebaart AC, Bijlsma JWJ, Eden W van, 16-year remission of rheumatoid arthritis after unusually vigorous treatment of closed dental
foci, Clinical and Experimental Rheumatology, 2002, 20 (4), 555-557
The article by McBeth et al. [1] demonstrated a limited association of low levels of vitamin D with musculoskeletal pain in men. Another recent study from a multi-ethnic general practice in Norway also showed a
high prevalence of hypovitaminosis D in patients with non-specific musculoskeletal pain, headache, or fatigue for whom the GP had suspected a low vitamin D level [2]. This adds to previous evide...
The article by McBeth et al. [1] demonstrated a limited association of low levels of vitamin D with musculoskeletal pain in men. Another recent study from a multi-ethnic general practice in Norway also showed a
high prevalence of hypovitaminosis D in patients with non-specific musculoskeletal pain, headache, or fatigue for whom the GP had suspected a low vitamin D level [2]. This adds to previous evidence that vitamin D deficiency is common in the general population, and perhaps more so in
chronic pain patients [3].
The relationship that McBeth and colleagues found was not strong, despite the large sample size and impeccable methods; although there was a20-30% increase in risk, the lower confidence interval was only just above
1 in most analyses, and was never larger than 1.1. Such modest association cautions against leaping to conclusions of causality, however beguiling a link between low vitamin D levels and musculoskeletal pain might be.
Most observational studies confirm a tendency to lower vitamin D levels in patients with musculoskeletal pain, but clinical trials (such as there are) change from perhaps suggesting a benefit of treatment to being
quite negative as their methodological quality increases. Support is found mostly in open studies, and those not even randomised [3,4]. Randomised double blind trials are overwhelmingly negative, demonstrating no significant pain relief with vitamin D treatment [3,5].
As it stands no causal link between vitamin D deficiency and chronic pain has been established. McBeth and colleagues hint that physical activity levels and lifestyle of people with musculoskeletal pain may be
important confounders, and certainly the relationship between vitamin D levels and presence of pain diminished as those criteria were used to adjust the logistic regression [1]. It was interesting that in a survey of patients with osteoarthritis and rheumatoid arthritis, only 15 of 68 (22%)
engaged in brisk walking; 30% did no exercise, whilst all other types of exercise noted would almost certainly have been taken indoors [6]. In another survey of 5,235 patients with rheumatoid arthritis only 14% reported physical exercise three or more times per week; most patients
undertook no regular weekly exercise [7]. Given that chronic musculoskeletal pain militates against exercise and spending much time out of doors, it seems likely that any association is not causative.
The presently available evidence is not good enough to answer the clinically important question whether vitamin D helps in chronic pain, especially in which type of patient, and there is clearly a need for more and better studies in this area. Their exact design is a topic worthy of discussion at length and therefore cannot be fully elaborated on here, but obvious issues involve vitamin D preparation, dose, treatment schedule and chronic pain condition [3]. As a first step, comparison with placebo would be essential to establish or refute efficacy of vitamin D in chronic pain, with safety endpoints to enable assessment of benefit versus harm. Trial outcomes and design would need to reflect what is clinically important,
something largely missing in the presently available evidence, but there is some recent guidance for chronic pain trials [8].
References
[1] McBeth J, Pye SR, O'Neill TW, et al. Musculoskeletal pain is associated with very low levels of vitamin D in men: results from the European Male Ageing Study. Ann Rheum Dis Published Online First: 24 May
2010. doi: 10.1136/ard.2009.116053
[2] Knutsen KV, Brekke M, Gjelstad S, et al. Vitamin D status in patients with musculoskeletal pain, fatigue and headache: A cross-sectional descriptive study in a multi-ethnic general practice in Norway. Scand J Prim Health Care. Published Online First: 20 July 2010. doi:
10.3109/02813432.2010.505407
[3] Straube S, Moore RA, Derry S, et al. Vitamin D and chronic pain. Pain 2009;141:10-3.
[4] Straube S, Moore RA, Derry S, et al. Vitamin D and chronic pain in immigrant and ethnic minority patients-investigation of the relationship and comparison with native Western populations. Int J Endocrinol 2010;2010:753075.
5] Straube S, Derry S, Moore RA, et al. Vitamin D for the treatment of chronic painful conditions in adults. Cochrane Database Syst Rev 2010;(1):CD007771.
[6] Gecht MR, Connell KJ, Sinacore JM, et al. A survey of exercise beliefs and exercise habits among people with arthritis. Arthritis Care Res 1996;9:82-8.
[7] Sokka T, Hakkinen A, Kautiainen H, et al.; QUEST-RA Group. Physical inactivity in patients with rheumatoid arthritis: data from twenty-one countries in a cross-sectional, international study. Arthritis Rheum 2008;59:42-50.
[8] Moore RA, Eccleston C, Derry S, et al. for the ACTINPAIN writing group of the IASP Special Interest Group (SIG) on Systematic Reviews in Pain Relief and the Cochrane Pain Palliative and Supportive Care Systematic Review Group editors. "Evidence" in chronic pain - establishing best practice in the reporting of systematic reviews. Pain, in press. doi:10.1016/j.pain.2010.05.011
We read with interest the editorial of Ritchlin and Tausk1 about psoriasiform lesions developed in patients receiving tumour necrosis factor (TNF)α antagonists. We would like to provide additional information. Indeed, we have recently reported 6 cases of psoriasiform lesions during TNFα antagonist therapy and described common characteristics of this paradoxical reaction with 40 cases already pu...
We read with interest the editorial of Ritchlin and Tausk1 about psoriasiform lesions developed in patients receiving tumour necrosis factor (TNF)α antagonists. We would like to provide additional information. Indeed, we have recently reported 6 cases of psoriasiform lesions during TNFα antagonist therapy and described common characteristics of this paradoxical reaction with 40 cases already published in literature.2
To date, with our series1 and recent reports3-7 pooled together, 55 cases have been described, including one case in a patient with juvenile idiopathic arthritis 2 years after initiation of etanercept.5
One of these cases concerns psoriatic arthritis.6 Interestingly, after an initial resolution of plaque psoriasis with infliximab, the
patient developed an inverse psoriasis (axillae and groin). In this context of pre-existing psoriasis, other cases have been reported: exacerbation of plaque psoriasis treated with infliximab8, development of a guttate psoriasis and a worsening of psoriasis in 2 patients with plaque psoriasis treated with etanercept9, exacerbation of underlying psoriasis (asymptomatic for many years) in 3 patients with rheumatoid arthritis (RA)receiving etanercept or infliximab10, exacerbation of palmoplantar pustulosis (PPP) and apparition of erythematopapular scaly lesions in a patient with RA treated with infliximab.11 These cases of exacerbation
thus highlight that a change in clinical aspects of psoriasis can occur.
We also observed this characteristic in a woman with spondylarthropathy with Crohn’s disease but without a personal history of psoriasis. She developed follicular skin lesions over the trunk, back, pubis, buttocks,
and scalp with infliximab, and then inflammatory lesions over the upper eyelids, neck, and inner thighs with etanercept.2
Finally, we could compare these cases with PPP relapse described recently in 2 out of 4 cases of SAPHO treated with infliximab without active cutaneous manifestations before its initiation12. The latter support the specificity of this cutaneous manifestation for TNF antagonist-induced psoriasis.
Moreover, it is difficult to establish the prevalence of the phenomenon according to diagnosis. Admittedly, RA is the most common etiology in the case reports. Nevertheless, the hypothesis that this is due to the fact that more patients receive TNF antagonists for this
condition could not explain the low representativeness of Crohn’s disease.
This last remark contributes to the mystery of this paradoxical reaction.
REFERENCES
1 Ritchlin C, Tausk F. A medical conundrum: onset of psoriasis in patients receiving anti-tumour necrosis factor agents. Ann Rheum Dis 2006;65:1541-44.
2 Cohen JD, Bournerias I, Buffard V, Paufler A, Chevalier X, Bagot M, et al. Psoriasis induced by tumor necrosis factor-α antagonist therapy: a case series. J Rheumatol 2006 Oct 1; [Epub ahead of print]
3 Sari I, Akar S, Birlik M, Sis B, Onen F, Akkoc N. Anti-tumor necrosis factor-α-induced psoriasis. J Rheumatol 2006;33:1411-4.
4 Aslanidis S, Pyrpasopoulou A, Leontsini M, Zamboulis C. Anti-TNF-α-induced psoriasis: Case report of an unusual adverse event. Int J Dermatol 2006;45:982-3.
5 Peek R, Scott-Jupp R, Strike H, Clinch J, Ramanan AV. Psoriasis after treatment of juvenile idiopathic arthritis with etanercept. Ann Rheum Dis 2006;65:1259.
6 Matthews C, Rogers S, FitzGerald O. Development of new-onset psoriasis while on anti-TNFα treatment. Ann Rheum Dis 2006;65:1529-30.
7 Pirard D, Arco D, Debrouckere V, Heenen M. Anti-tumor necrosis factor alpha-induced psoriasiform eruptions: Three further cases and current overview. Dermatol 2006;213:182-6.
8 Bovenschen HJ, Van De Kerkhof PC, Gerritsen WJ, Seyger MM. The role of lesional T cells in recalcitrant psoriasis during infliximab therapy. Eur J Dermatol 2005;15:454-8.
9 Gottlieb AB, Matheson RT, Lowe N, Krueger GG, Kang S, Goffe B, et al. A randomized trial of etanercept as monotherapy for psoriasis. Arch Dermatol 2003;139:1627-32.
10 Kary S, Worm M, Audring H, Husher D, Renelt M, Soerensen H, et al. New onset or exacerbation of psoriatic skin lesions in patients with definite rheumatoid arthritis receiving TNF-α antagonists. Ann Rheum
Dis 2006;65:405-7.
11 Michaëlsson G, Kajermo U, Michaëlsson A, Hagforsen E. Infliximab can precipitate as well as worsen palmoplantar pustulosis: possible linkage to the expression of tumour necrosis factor-α in the normal
palmar eccrine sweat duct? Br J Dermatol 2005;153:1243-4.
12 Massara A, Cavazzini PL, Trotta F. In SAPHO syndrome anti-TNF-alpha may induce persistent amelioration of osteoarticular complaints, but may exacerbate cutaneous manifestations. Rheumatol 2006;45:730-3.
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.
It was interesting to read the recent report of systemic lupus
erythematosus associated with atrophy of brain and spinal cord.[1]
However, I would like to make certain observations.
Computerised tomography (CT) of brain presented in the report showed
bilateral hypodense lesions in the frontal and parietal regions. Though
Mok et al attribute this CT appearance to diffuse cerebral atrophy; othe...
It was interesting to read the recent report of systemic lupus
erythematosus associated with atrophy of brain and spinal cord.[1]
However, I would like to make certain observations.
Computerised tomography (CT) of brain presented in the report showed
bilateral hypodense lesions in the frontal and parietal regions. Though
Mok et al attribute this CT appearance to diffuse cerebral atrophy; other
possibilities too need to be considered in this setting. Chronic subdural
haematoma (SDH) is the foremost among these. In a recent report, all
chronic SDH appeared hypodense on CT, and were predominantly located in
the parietal and frontal regions,[2] which is similar to the case
presented by Mok et al. Hypodensity in chronic SDH could occur due to
gradual absorption of erythrocytes from the haematoma, typically with
haemoglobin concentration falling below 15 mg/dl.[3] Another mechanism
responsible for differing densities of acute and chronic SDH could be
related to their varying compositions. In a pathological study, hyperdense
picture on CT resulted with haematomas predominantly consisting of
erythrocytes and erythrocyte-fibrin component, whereas hypodense picture
resulted with haematomas consisting of fibrin and inflammatory cells.[4]
It should also be noted that bilateral chronic SDH is a recognized
complication of vasculitic syndromes and could even be a presenting
symptom.[5] Moreover, SLE too could produce focal angiitis of a cerebral
artery with secondary aneurysm formation, rupture of which leads to SDH.[6]
In conclusion, though I agree with Mok et al. that cerebral atrophy is
a known finding in patients with SLE, chronic SDH is a distinct
possibility in patients with bilateral fronto-parietal hypodense lesions
on CT.
References
1. Mok CC, Mak A, Tsui EYK. Shrinking central nervous system in
systemic lupus erythematosus. Ann Rheum Dis. 2004; 63:603-4.
2. Agunloye AM, Adeyinka AO, Obajimi MO, Malomo A, Shokunbi MT.
Computerised tomography of intracranial subdural haematoma in Ibadan. Afr
J Med Med Sci. 2003; 32:235-8.
3. Ito H, Maeda M, Uehara T, Yamamoto S, Tamura M, Takashima T.
Attenuation values of chronic subdural haematoma and subdural effusion in
CT scans. Acta Neurochir (Wien). 1984; 72:211-7.
4. Poljakovic Z, Petrusic I, Kalousek M, Brzovic Z, Jadro-Santel D.
Correlative pathology of subdural hematoma with computerized tomography.
Neurol Croat. 1991; 41:21-32.
5. Shiotani A, Mukobayashi C, Oohata H, Yamanishi T, Hara T, Itoh H,
et al. Wegener's granulomatosis with dural involvement as the initial
clinical manifestation. Intern Med. 1997; 36:514-8.
6. Sakaki T, Morimoto T, Utsumi S. Cerebral transmural angiitis and
ruptured cerebral aneurysms in patients with systemic lupus erythematosus.
Neurochirurgia (Stuttg). 1990; 33:132-5.
Thank you for your letter, and the possibility to reply. We fully appreciate the favorable HAQ outcomes of the intensive strategy arm in the TICORA study [1]. However, based on the systematic literature search for the Treat to Target Initiative, the impact of strategic
treatment on functional outcome was controversial: of the four trials that assessed functional outcome[1-4], three [2-4] stated no ben...
Thank you for your letter, and the possibility to reply. We fully appreciate the favorable HAQ outcomes of the intensive strategy arm in the TICORA study [1]. However, based on the systematic literature search for the Treat to Target Initiative, the impact of strategic
treatment on functional outcome was controversial: of the four trials that assessed functional outcome[1-4], three [2-4] stated no benefit of a targeted treatment approach, including the only study in which function was the primary outcome [4]. For these reasons, the results were interpreted by the T2T committee to be insufficient to claim functional benefits of a strategic treat-to-target approach, although we agree that the TICORA study indicates that the last word on this might not yet be spoken.
References
[1]Grigor C, Capell H, Stirling A, et al. Effect of a treatment strategy of tight control for rheumatoid arthritis (the TICORA study): a single-blind randomised controlled trial Lancet 2004;364:263-9.
[2]Verstappen SM, Jacobs JW, van der Veen MJ, et al. Intensive treatment with methotrexate in early rheumatoid arthritis: aiming for remission. Computer Assisted Management in Early Rheumatoid Arthritis (CAMERA, an open-label strategy trial). Ann Rheum Dis 2007;66:1443-9.
[3] Fransen J, Bernelot Moens H, Speyer I, et al. Effectiveness of systematic monitoring of rheumatoid arthritis disease activity in daily practice: a multicentre, cluster randomised control trial. Ann Rheum Dis 2005;64:1294-8.
[4] Symmons D, Tricker K, Roberts C, et al. The British Rheumatoid Outcome Study Group (BROSG) randomised controlled trial to compare the effectiveness and cost-effectiveness of aggressive versus symptomatic therapy in established rheumatoid arthritis. Health Technol. Assess 2005; 9:iii-iv, ix-x, 1-78.
Dear Editor
We thank Dr Chan and collaborators for their interest in our study and for their comments.[1] As concerns the patients’ selection, we excluded patients with serious medical problems such as heart, and lung diseases, as well as other ophthalmological disorders including glaucoma. Thus, none of our patients were treated with beta-blockers and none were on hormone replacement therapy which may exacerbate d...
Dear Editor,
Many thanks to Schoels et al for their very helpful systematic literature review of the evidence for treating RA to target [1]. However, I am concerned that the authors' discussion may lead readers to conclude erroneously that there is no evidence that treat to target, intensive management has a beneficial impact on physical function. In their discussion the authors state that 'Functional outcomes, reported...
Dear Editor
It is my hypothesis that most drugs of addiction activate DHEA release. When DHEA declines following drug activation of DHEA, the drug is again used to reactivate DHEA. This may be the basis of addiction. Smoking has been demonstrated to activate DHEA release (Neuropsychopharmacology. 2005 Sep;30(9):1751-63).
DHEA, estradiol, and testosterone have been found to "stimulate articular cartilag...
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
Toivanen [1] put forward the interesting hypothesis that, in contrast to reactive arthritis where temporary lodging of pathogenic micro- organisms is a causative factor, in RA a continuous seeding of degraded bacterial products from normal intestinal flora may induce synovitis. This hypothesis closely resembles the theory published by us one year earlier,[2] in which we also stressed a continuous seeding o...
Dear Editor,
The article by McBeth et al. [1] demonstrated a limited association of low levels of vitamin D with musculoskeletal pain in men. Another recent study from a multi-ethnic general practice in Norway also showed a high prevalence of hypovitaminosis D in patients with non-specific musculoskeletal pain, headache, or fatigue for whom the GP had suspected a low vitamin D level [2]. This adds to previous evide...
Dear Editor,
We read with interest the editorial of Ritchlin and Tausk1 about psoriasiform lesions developed in patients receiving tumour necrosis factor (TNF)α antagonists. We would like to provide additional information. Indeed, we have recently reported 6 cases of psoriasiform lesions during TNFα antagonist therapy and described common characteristics of this paradoxical reaction with 40 cases already pu...
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
It was interesting to read the recent report of systemic lupus erythematosus associated with atrophy of brain and spinal cord.[1] However, I would like to make certain observations.
Computerised tomography (CT) of brain presented in the report showed bilateral hypodense lesions in the frontal and parietal regions. Though Mok et al attribute this CT appearance to diffuse cerebral atrophy; othe...
Dear Editor,
Thank you for your letter, and the possibility to reply. We fully appreciate the favorable HAQ outcomes of the intensive strategy arm in the TICORA study [1].
However, based on the systematic literature search for the Treat to Target Initiative, the impact of strategic treatment on functional outcome was controversial: of the four trials that assessed functional outcome[1-4], three [2-4] stated no ben...
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