Rheumatoid Arthritis - Science topic

Hi,

The question is short but the answer needs more details because the topic touches not only "%". Moreover discussing biosimilars please remember that batch-to-batch of original/reference biotechnological drugs like therapeutic monoclonal antibodies are only biosimilar. So batches of original monoclonals are not identical but biosimilar as well.

Hope documents will answer your question with more details:

Best regards,

Tomasz

Hi.　I guess one interpretation of that might be helpful in the following paper.

I RECOMMEND THIS PAOER FOR U

PADI4 (rs2240340), PDCD1 (rs10204525), and CTLA4

(231775) gene polymorphisms and polyarticular

juvenile idiopathic arthritis

Please check the following references :-

thank you Malcolm Nobre for your answer and attached article,

Very vague question as it varies from region to region.

Because despite the fact that "chloroquine is efficient in limiting the transmission of SARS-CoV," the study was done in cell cultures rather than humans or animals.

Dear Mrs Gheita,

I have described the mechanism of the development and chronification of inflammation by harmful substances in a book using the example of rheumatoid arthritis in accordance with the laws of physics and have thus scientifically proven it. The book is an original work of approx. 56,000 characters including spaces. According to the laws of physics, especially thermodynamics, inflammation is primarily caused physically by heat conduction and only secondarily by harmful bacteria. A change in thinking is required.

Heat conduction, which everyone knows from everyday life, always occurs where temperature differences exist and continues to do so until the temperature difference is equalised. Heat conduction is always taken into account in science and technology, but not in medicine. This is a serious mistake, because heat conduction occurs everywhere, including in the living body. Heat conduction is a physical mechanism that always occurs with external and internal temperature differences and cannot be controlled organically. Therefore, the organism is exposed to the damage caused by heat conduction. If the temperature differences are too great, inflammation of joints and organs can occur.

The book is entitled: Physics of the Origin of Inflammation by Pollutants and subtitled: Causal Treatments that Cure Inflammation and Prevent Antibiotic Resistance.

The link to the publication by Cuvillier Publishing is:

< https://cuvillier.de/de/shop/publications/8462 >

Here you can read an abstract, a reading sample, the table of contents and the keywords for free. I will be happy to answer any questions.

Yours sincerely

Frank Mitter (Author)

99428 Weimar, Germany

Dear Azam Ali, the protocol in general looks fine to me - Particularly because it is provided by the manufacturer. Common problems with PBMC isolation are disturbing the gradient when not carefully handling it, centrifuging without break, and pipetting too much of the supernatant (= plasma) after the centrifugation step.

As an alternative, I can provide you with our protocol for PBMC isolation from RA patients using Ficoll Histopaque too. It is based on 50 ml Falcon tubes with a filter (available e.g., by Greiner bio-one). But of course, it also works with 50 ml Falcons without filter. This then only requires careful pipetting of the blood on top of the ficoll. The last to steps in our protocol are only required if you want to submit your cells to FACS analysis.

Please do not hesitate to contact me in case of further questions about it.

Abdulsatar Mathkhor Thank you very much for your help , but if our disease is rheumatoid arthritis and we want to asses the QOL depending on ADHERENCE , what do you suggest as a method ? we have the tools such as PDC,AND WHOQOL-BREF questionnaire But we are having a problem on how can we utilize these tools, when do we give them , how we will follow up , and in your answer do you mean depression as an example? but how it will correlate with adherence ? since it is our focus and our objective is that we aim that people with better adherence have a better QOL.

Wow, Barry, Renan can now go wild.

Those are the most important references.

I recall the frustrations of a US doctor who penned that as:

Death by Prescription - Dr Ray D Strand

Dear Mwihia Stephen,

Propolis has a complex composition. Many of its pharmacological affects are believed to be related to phenolic compounds. Caffeic acid phenethyl ester (CAPE) is among the most active compounds with antiinflammatory activity. Here we have reviewed of the pharmacology of CAPE and clinical trials: https://www.academia.edu/40588958

RAW 264.7 cell line.

Most of the researchers preferred the human samples or animal model (Rat or Mice) for the rheumatoid arthritis research. Because, it is a bone related disease. If you need cell line related studies on RA, you can use NIH-3T3 mouse embryo fibroblast cell line or sarcoma cell line (SW982). But animal model is much better than cell line studies. Because we easily observe the bone destruction, bone re-modelling, swelling and inflammation

Mediators of modified immunity in pregnancy are the polyclonal activation of B cells, the unbalanced T cell regulation in the immune response. The lupus flares up in 40 to 60% of pregnancies. This happens at every stage of pregnancy and childbirth. With little evidence, lupus occurs more often postpartum. It is recommended to plan the pregnancy with a minimum of 6 months afterflares of nephritis. Risk indicators for the mother and fetus are

[Tayseer, G. H., Chaudhary, P., Clowse, M.E.B.: Systemic lupus erythematosus in pregnant patients an neonatal lupus. In: Rheumatology. Ed. Hochberg, M. C. et al. Elsevier Philadelphia 2019;1208-1211.]

thanks a lot Kathy.

Kindly see the following RG links and PDF attachment.

ideally.. you would think so. But there has never been a successful panel, or even an inkling of what these biomarkers could even be. There are several reasons why... and I can probably list an entire page or more of them.

While I can tell you that there are clinical trials that are looking at this question... But my own personal opinion... serum/plasma biomarkers, which are kind of static... isn't going to give you the answer. I'm more of a proponent of a function assay.

For research purpose there are bio-markers that could be studied, like lung epithelium specific proteins (associated to surfactant, mucin, clara-cell) and also chemo/cytokines MCP-1, glutathione, IL2-R. For clinical use, I don't think we have yet bio-markers for ILD in RA.

NSAIDs are not the only medication for rheumatoid arthtitis. A link to an elementary explanation of the disease, diagnosis and treatment for a start:

Best wishes, Lars-Erik

Hi Jack,

Thank you for your opinions.

We always perform WB using T-cell lysates as positive control of STAT5. We can get signal of STAT5 in T-cell lysates, but not in RASFs.

We use polyclonal antibody for STAT5 which can bind both STAT5A and B. This antibody was purchased from CST.

We checked your recommended article. However, there are not so many study to investigate the expression of STAT5 in RASF.

Best wishes,

Kunihiko

Determining a prognosis or outcome for any rheumatoid arthritis (RA) patient is difficult; seronegative patients are no different. The disease itself may start out with mild symptoms and involve into more severe ones that make treatment more difficult. Seronegative patients are often regarded as having a milder set of symptoms compared to seropositive . Generally, seronegative patients don’t develop rheumatoid nodules, which are commonly displayed in seropositive patients. This is never a certainty, however, and each patient’s individual symptoms and disease progression will differ. Treatments for seronegative RA are approached the same way as seropositive patients. The goal of treatment is to mitigate pain and prevent the disease’s progression. Focusing on reducing pressure and deterioration of joints is very important in delaying the disease. Treatment should be started as early as possible to prevent the disease from worsening.

These are all add on therapies for temporary pain relief and would work at various degrees. You definitely need non biologic DEMARDs or biologic ones guided by a rheumatologist

yes

no problem, happy to contribute patients to a case series.

amazing

Dear Michael after reading your answer i did look up to the internet and started reaading bout flouride in water.

I am now able to get some insight about the big problem the humans are facing.

Lets hope that the council for water management will take up the issue in a more seroius manner.

It also has made a difference to my understnading of the disease patterns of autoimmunity.

Thank you for the insights.

Thanks Subhash.

hallo i already worked on collagen induced arthritis in rat, if this model is want you wont to use i can help you.

arthritis onset is around 14 days after the first immunisation (there is a second immunisation on day 7) bay day 20 all the animals should develop arthritis (any animal not yet arthritic after 20 days will remain non arthritic).

if you want the prophylactic effect you should start drug administration from day 0 (a day before the immunisation). for the therapeutic effect you can start from day 14 or wait until all animals develop arthritis around day 20.

i personally recommand to start with the prophylactic effect especially if you are working with new drug, this model is a sever arthritis and if the drug have a mild effect it will not be seen in therapeutic treatment

There have been many studies looking at dietary manipulation in the treatment of RA. The first thing to be said is that diet is an adjunct to the pharmacological treatment of RA with disease-modifying drugs. It does not replace drugs.

Having said that, the only dietary modifications that have been consistently shown to have a (usually very modest) effect on RA are omega-3 supplements (more omega-3 containing foods are usually associated with a Mediterranean diet) and vitamin D, especially if you are vitamin D deficient. Probiotics to modulate the gut microbiome is a more recent supplement that has been shown to improve cytokine levels but not the clinical symptoms, but more research is needed.

OA SF fibroblasts can be one controls esp if you are evaluating inflammation pathways.

If you look at the 4th paragraph of the discussion of Carter et al., 2001, Immunology and Cell Biology, doi:10.1046/j.1440-1711.2001.01019.x, they state: "Vascular cell adhesion molecule-1 is also constitutively expressed on several other non-vascular cell types including type B SLC, bone marrow-derived stromal cells, thymic macrophages, thymic epithelial cells and follicular dendritic cells in tonsils." , with references to each. Hope this helps.

Hi,

I would like to help but I don't quite understand the question.  Please elaborate on the neurological condition of your RA patient?  Why do you think paraneoplastic?

HM

This is the normal test that I order to diagnose or rule out RA:  RA Factor, HLA B27, CRP, ESR

I understand. Thanks for your contribution.

From the clinical pain of view, gout usually debuts as monoarticular disease and later on it takes a polyarticular form. initially, the joints of the lower limbs are predominantly affected.

A noninvasive usefull diagnostic tool is ultrasound, that may display double contour sign in the case of gout and some other elementary lesions in the case of rheumatoid arthritis, psoriatic arthritis or osteoarthritis. Thus, i suggest including ultrasound in the initial diagnostic work-up of this patient. 

Hey Amit, 

In my opinion, having high Ct values is not a problem as long as your housekeeping gene has a good expression (Ct~20). Make sure that the amplification reaction has a good efficiency and that there is no amplification of your negative control. 

Good luck!

Thank you for the great suggestions and all the given references. I am tempted to retry IV Rituximab but using much slower infusion in our own infusion unit instead of using rheumatology community infusion centre and have some antihistamines and steroids ready for use if necessary. If this fails, I might give it a go with Alemtuzumab monotherapy. 

Thanks for your message.

Thank you so much sir for your kind reply and suggestion.

There are many, many methods out there. This is ours: We take the flushed marrow from 4-6 bones (tibias, femurs and sometimes humerus) from 8wk mice, wash one time, (do not do any cell lysis), put into a 100mm tissue culture dish (no MCSF) overnight. The next day, we take the non-adherent cells and layer that 10ml cell suspension over 15ml Ficoll Hypaque in a 50ml conical tube and spin at RT 400xg (not RPM) 35 min with no brake. Remove cells at the interface (mostly free of RBCs, which pellet during the spin). Add PBS  or serum free media (5x volume of cells) (5ml up to 50ml) Spin 1500RPM 5min to wash, wash one more time (10ml), resuspend in MEM alpha +10% heat inactivated FBS +pen/strep + glutamine, count and plate 5000 cells/well of 96MW plate. We plate cells in 100ul, then add in our reagents. To get OCs, add MCSF 30ng/ml and RANKL 30ng/ml in 100ul, but make up at 2X. Because everyone counts a little differently and stocks of MCSF and RANKL can vary depending on your source, I would plate at 4000, 5000, 6000 and add MCSF 30 and RANKL 20, 30, 40. We feed on Day 3 by gently removing media and replacing with MEM + MCSF30ng/ml +RANKL 30ng/ml. Then watch daily for OCs at Day 4, 5 and 6. Fix in 2.5% glutaraldehyde in PBS for 10min. Can store in PBS til you TRAP stain (We use SIGMA Kit 387A) Be sure your media and water are LPS free. We use Hyclone Defined FBS and buy our media ready made to avoid LPS contamination from water filtered systems. In your picture it looks like your cells are too dense. They need room to move around in order to fuse.

Hope this helps, good-luck.

Indeed, I think María is right. And I think the mistake must be made by a B cell because of the epidemiology - increasing incidence with age and stochastic sporadic pattern. T cell diseases should have an incidence skewed to the age of T cell repertoire development - as the seronegative spondarthropathies do. B cells go on making random changes throughout life. RA is very neatly explained by accumulation of B cell clones that can self perpetuate through bystander T cell help and recruit further clones with time.

Inducing remission in 3 months is all very well but the real target is removal of the disease memory cells, as Jakob says. There is a very nice recent paper from the Radbruch group looking at a mechanism for deleting specific B cells using complex ligands. It may be tough to do that for diseases where auto reactive B cells recognise ubiquitous proteins like IgG Fc but somebody should be able to think up a trick for knocking them out specifically. Targeting mediators I think is unlikely to give long term remission. Metalloproteinase inhibition works in animal models of cartilage resorption but has no effect on RA. I thin that is because cartilage is resorbed in RA only when it has already been killed by intra-articular hypoglycaemia induced by TNF. I doubt metalloproteinases damage living cartilage in man.

Grazie, Ciro, sono d'accordo; saluti!

After much clinical research and clinical experience I find myself in total agreement with Dr. Edwards,  One needs measures for trials, FDA, etc, but most are not very relevant for patient care.  I agree that patients should be "doing well" and will generally tell you if they are not.  I have also found that what we consider to be "doing well" often is not the same as what a patient is thinking/feeling.  Listening and dealing with expectations vs outcomes can be very important.  

I don't think this is a matter of concentration. Rheumatoid factor assays measure binding and that depends both on concentration and a profile of affinity going from very high to not so high. One patient may have a small amount of high affinity RF and another a large amount of medium affinity RF and the same amount may bind in the assay. Binding may vary with lab conditions, so you need to calibrate against a standard. It's a bit like fishing for crabs with bacon. If the crabs are hungry you will get a good catch when there are only a few. If they are not so hungry, you need more in the sea to get the same catch. 

If you had a standardised monoclonal rheumatoid factor you could probably work out the relation of IU to concentration, but not for polyclonal RF in sera. 

You need to do a standard curve to determine the efficiency of primers. 

Another standard curve to determine if there are inhibitors in your cDNA using primers you know that work.

The role of VEGF in the pathogenesis of RS3PE syndrome (and not in the pathogenesis of PMR) would speculate that the presence of RS3PE during PMR is not only a manifestation of the same PMR.

Is PMR + RS3PE a clinical entity in its own right ?   

I don't think that there are cut-off values for CCP titers and earliness of erosions to be considered determinants of bad prognosis.

Seropositive rheumatoid arthritis and erosions are simply considered factors of poor prognosis no matter the earliness for erosions or the titer for CCP. This is both are associated with more co-morbid conditions and thus with a higher mortality risk.

Thank you

Localized inflammation in RA could be reduced by inhibiting plant products that inhibit the activity of Nf-kB transcription factor. To start, one can use curcumin, a plant product routinely used in Indian food. The plan product is very potent inhibitor of inflammation and relives symptoms of inflammation-associated human diseases in long-term.

Thank you so much.

Dear Dr. Shubhankar,

ERA appears infrequently below 5 years, and it is usually associated with: male gender, oligoarticular involvement, mostly asymmetrical, over lower limbs large joints, enthesitis, sacroiliac pain or lumbar spine limitation (this may be a late finding), dactylitis, elevation of APRs and HLA B27 positivity. Your patient does not seem to present any of these except for the HLA allele.

Polyarticular JIA, especially the Rheumatoid Factor negative type, is commonly seen during the early years of age, commonly involves large and small joints of both upper and lower limbs, upper spine (cervical), while lower spine and entheses are usually spared. Your patient resembles this latter picture. However, the HLAB27 positivity prevents us from classifying your patient as Polyarthritis, while he does not meet enough criteria for ERA (I assume his family history was negative for spondyloarthropathy or other B27-related diseases).Naturally, should find a repeatedly positive Rheumatoid Factor your patient is clearly a RF-positive Polyarthritis.

Today your patient seems to fit under the "Undifferentiated Arthritis" type of the ILAR criteria. Nevertheless, given his B27 positivity (and thus an increased risk of developing lower spine invovement later on) I would follow him closely with clinical/imaging techniques to eventually detect sacroiliac impact early.

Answering your question: HLA-B27 frequency in Polyarthritis seems to be similar to the one in the general population: 3-10 % (Thompson et al. Juvenile idiopathic arthritis classified by the ILAR criteria: HLA associations in UK patients. Rheumatology 200241:1183-1189). The frequency in the patient´s particular ethnic background could give you a better estimation.

Best wishes,

thank you so much Alan!

Dear Satyaprasad,

I think you are asking for the frequency of coexistence of true rheumatoid arthritis with psoriasis, rather than psoriatic arthropathy? There may be literature on this but the problem is that ascertaining the existence of true RA in the presence of psoriasis is not straightforward. Rheumatoid factors and ACPA occur in a small percentage of normals so could occur alongside psoriatic arthropathy. 

The only time I have been convinced that I knew that an arthritis was true RA in the presence of psoriasis was in a case with typical rheumatoid nodulosis and RF. I only saw the one case in thirty odd years.

In practical terms relating to hydroxychloroquine, I think you are entitled to go on probabilities. If an inflammatory arthritis is associated with RF and or ACPA and does not have DIP involvement then if you feel hydroxychloroquine is a reasonable choice for RA (I was never very convinced) then it is probably still reasonable if the patient also has psoriasis. Without autoantibodies or nodules the chances must be that you are dealing with psoriatic arthropathy and I know of no theoretical or practical evidence for hydroxychloroquine being useful there.

dear Shima Rezaei 

i hope next research help you

best regared

hamdy

As a referral centre for interstitial lung diesease we are regularly confronted with this dilemma. The differential diagnostic possibilities in patients with rheumatic disease developing an interstitial lung disease (ILD) during treatment with MTX include infection (especially PCP), MTX associated lung disease, RA-associated ILD and MTX-associated lymphoproliferative disorder. According to the ATS/ERS guidelines, IPF in terms of UIP can be confirmed or excluded based on clinical presentation and HRCT only. The possibility of an infectious disease requires microbiological analyses of e.g. BAL fluid. In addition FACS analysis of peripheral blood may reveal a decrease in CD4+ T-cells indicating MTX-induced immunsuppression. To my experience it is difficult to distinguish MTX-associated ILD from RA-associated ILD based on clinical-radiological data only. In such cases an open lung biopsy is helpful to tell the difference: EAA-like pattern with or without fibrosis is compatible with MTX induced ILD, whereas RA-associated ILD is characterized by NSIP/OP-like pattern with or without rheuma nodules. MTX-induced lymphoproliferative disorders can be diagnosed either on periprheral lung tissue and /or by demonstrating increased EBV virusload in peripheral blood.

Physical exercises are necessary for the Rheumatoid patients as the joints remain flexible and soft tissues mobile. Despite this it will be better to do them when the inflammation is better (so better not during acute inflammatory phases where the patient will be benefitted by rest). Medication has to be monitored and controlled by having regular follow up reviews and the regime has to be changed accordingly.

Patients with RA, male or female in the same degree, will be benefited with exercises that are improving the ROM of the joints and fight against the stiffness. These are wrist rotational movements, wrist resisting (palms and dorsal areas of the hands against each other), side to side movements, stretching exercises and the use of a ball in the palm and squeeze it. Some people apply Yoga exercises.

ANCA positivity can be seen in SLE patients, 10-20 percent incidence, including our own clinical experience. A positive ANCA can also be drug-induced, as can be antiphospholipid antibodies. A positive ANA by itself is rather non-specific, and can be seen in an number of conditions, including seemingly not autoimmune entities, e.g., IPF, sickle cell disease, etc, 

Dear Chetan,

please go through this link. 

http://www.ors.org/Transactions/61/0081.pdf. 

here the dose mentioned is 150 microgram.

This might be useful for your research study.

To Cari, RA drug trials don't consider just symptoms in the final evaluation of the potential efficacy or lack of it thereof of a given drug; there are validated measuring instruments such as the ACR20, 50, and 70, DAS28, etc, and these include objective measures such as swollen joint count and blood inflammatory markers, e.g., sed rates and CRP. Almost all biologic drug trials also include radiographic data of involved joints over time,

To Daniel: the treatment of RA and of any disease for that matter is best done on a individual basis, stemming from and based on an optimal doctor-patient relationship. Healthcare mandates and huge databases should have no place in the evaluation and treatment of individual patients. We are presently being inundated with non-sense health mandates that add nothing to the quality of the care provided; insurance companies for years have been trying to practice medicine without a license. I understand trying to save money; however, the real value of a given medical approach should be discussed and evaluated with the patient in front of you, based on individual patient response. Different people react differently to different medications. It is the treating physician who would know best that a given individual patient responds better to this particular TNF inhibitor and not to the next one or a biosimilar. Clinicians deal with this problem on a daily basis. I understand that administrators and CEOs of insurance companies would not know this (do they care?), but then again, they are not physicians treating patients. In the end, we don't treat just diseases; we treat human beings suffering from diseases; not two patients are the same,    

Dear Shadab,

see the following paper…

Biggs M, Yap C. The effect of high-intensity strength training as compared to standard medical care on muscle strength, physical function and health status, in patients with Rheumatoid Arthritis Functional Class II (2014). PT Critically Appraised Topics. Paper 44. http://commons.pacificu.edu/cgi/viewcontent.cgi?article=1039&context=ptcats

Best wishes from Germany

Martin

Good evening Dr Kechida,

first, I would like to recognize the thoughtful contribution of Dr M Khoury to rule out viral or amebic infections in the clinical problem you raised.  I further want to assure her of our best wishes during the hardship and turmoil that her country is going through.  We all hope for a solution if that is still a possibility.

Ulcerative keratitis is not part of run-of-the-mill RA in an adult.  So the first thing to establish is that the patient really has RA and second, if so, that the keratitis is due to RA.  So, be sure of the correct rheum and ophthalm diagnoses.

If the patient has RA,

1.  Clinically, severe keratitis may be part of either RA vasculitis, secondary sicca or associated with peripheral ulcerative keratitis (see PUK in Google for differential diagnosis).  In the former, scleromalacia perforans is more expected than deep keratitis and in the first two, there should be evidence of vasculitis and severe sicca elsewhere, respectively. To be noted, that arthritis and vasculitis are often reciprocally active/inactive in RA.  So here, the "MTX-controlled arthritis" does not necessarily mean that the rheumatoid process is controlled.

2.  Serologically,  the only (high titer) specific marker for RA vasculitis is the Euroimmun anti-Sa (citrullinated-vimentin) ELISA and that for severe sicca, the more likely, if not entirely specific, is anti-La/SS-B.  RF, anti-CCP and other ANA-sub-specificities can be positive in both.  PUK is a clinical diagnosis that can be either sero-RA +, sero-SS + or sero-negative.  ANCA and APLA should be negative.

3.  Local treatment is best left to Ophthamologists.  I would not push for any kind of medicated drops like steroids or cyclosporine and favour natural tears or gels with/without antibiotics.  Just for comfort!  R/O infection...

4.  Systemic treatment is that of vasculitis: IV or PO cyclophosphamide, IV and/or PO corticosteroid boluses and RTX.  ANTI-TNF ARE BEST AVOIDED IN RA VASCULITIS OR SS.

5.  Empirically, once, I used successfully in PKU, long term (1y) treatment with a low dose daily tetracycline (for its anti-collagenase action).  It allowed the acceptance of a corneal graft after an unsuccessful attempt.

That is a complex problem and for everybody to learn, you should give us 6-mth follow-ups. 

Sorry for the length of that response but most of it is not found in textbooks.  Bonne chance!

Henri A. Ménard MD, FRCP (C)

Emeritus Professor of Medicine, McGill U.

This article might be of value to your question that looks at community prevalence (>51000 people from 12 sites) of RA in India and pegs it closer to 0.34% in India.

Chopra A. Disease burden of rheumatic diseases in India:COPCORD perspective. Indian journal of Rheumatology 10 (2015) 70-77

The hygiene/biome theory might still hold.

About RA being a newly described disease, I am not too sure of that. Though European and Greek medical literature before Sydenham's time may have confused gout and other forms of polyarthritis as manifestations of the same disease, but Indian literature does have excellent description of RA from Atharva Veda (1000 BC)

Caraka described the site of manifestation of rheumatoid arthritis in the following

words. (I have attached an article and highlighted the description in page 3, reads in Sanskrit with translation)

"The sites of its manifestation are hands, feet, fingers, toes and all the joints. It establishes its base first in the hands and feet and then spreads in the entire body"

I would also refer you to the article in Arthritis and Rheumatism that touches upon this issue

Sturrock, R. D., Sharma, J. N. and Buchanan, W. W. (1977), Evidence of rheumatoid arthritis in ancient india. Arthritis & Rheumatism, 20: 42–44. doi: 10.1002/art.1780200107

Is it possible that the chosen patient selection method have selected a more educated sample and thus one living in better sociocultural standards? - ResearchGate. Available from: https://www.researchgate.net/post/Is_it_possible_that_the_chosen_patient_selection_method_have_selected_a_more_educated_sample_and_thus_one_living_in_better_sociocultural_standards [accessed Sep 25, 2015].

In fact, I think the theoretical arguments are too weak to guide clinical decision here, Bijit. We know almost nothing about immunosurveillance of tumours and in patients who have or have had overt cancer adaptive immune responses have failed anyway. There is a theoretical issue with blocking TNF since it can cause tumour cell death under  certain experimental conditions but that is not enough to base clinical practice on. There is limited evidence from post marketing surveillance that TNF inhibition is indeed a problem for some cancers. What I think is also important in practice is that TNF inhibitors have been marked as contraindicated in cancer patients and if cancer occur or re-occurs during TNF blockade there can be serious problems with feelings of guilt and anger for patients. If TNF inhibitor trials had not excluded cancer patients at the outset things might be easier.

When I introduced rituximab for RA in 1998 I made sure that we did not exclude cancer patients. As far as I know that has proved the right policy. 

In fact we have found that rituximab gives best results for patients with moderate (not high) autoantibody levels - probably because with very high levels it is harder to clear away enough antibody and disease is more severe and more difficult to get into complete remission. As far as I am concerned all RA is B cell driven. The few completely seronegative cases probably have different diseases - they rarely get a useful response to rituximab.

Thankyou for sharing this case. What is her ethnic origin? Has sustained Colchicine plus Aza allowed you to taper the steroids successfully?

I have found Anakinra to induce ISRs and other local skin reactions commonly. In the 3 weeks during which you used it, did you note any response or was it too difficult to tell? Use of alternate daily or thrice weekly Anakinra plus or minus concomitant antihistamines or potent topical corticosteroids may help attenuate the adverse skin response. Canakinumab might be better tolerated, but it is very expensive. Rilonacept development has unfortunately been discontinued.

Immunoglobulins. These patients have reversal of A/G ratio. Serum Protein Electrophoresis is advised.

NSAIDS, Hydroxychloroquine, Sulphasalazine and prednisolone

if biologics needed TNF inhibitors may be used

Dear Dr Carlos Augusto De Andrade,

Though RA is possible, the likelihood is a bit low.  A number of rheumatic manifestations have been described with HIV infection .These include arthralgia, painful articular syndrome, Psoriatic arthropathy, Reiter’s syndrome, reactive arthritis, HIV-associated arthritis, undifferentiated spondyloarthropathy, soft tissue rheumatism, septic arthritis, avascular bone necrosis, osteomyelitis, hypertrophic osteoarthropathy, myalgias, polymyositis, dermatomyositis, Sjogren’s like syndrome – DILS, vasculitis like Schonlein-Henoch purpura, polyarteritis nodosa (PAN), giant cell arteritis (GCA), Wegener’s granulomatosis (WG), Raynaud’s phenomenon, and Behcet’s syndrome. RA is conspicuous by its near absence.

There are actually reports of RA improving with development of HIV. This has been our experience too in a big cohort of over 6000 patients which we followed up at Pune, India, I do not recall a single RA patient, though many had other musculoskeletal complaints. 

Autoimmunity is common in HIV and over 20% of all patients might be positive for RF. Your patient has early arthritis of just 2 weeks with raised acute phase reactants. It might be worth looking for Sjogrens (both clinically and with autoantibodies ) as it can mimic RA. A post viral arthritis syndrome (where the fever might not be remembered vividly) too is a possibility. RA of course can occur but the pretest probability is low. 

I would be curious to know the outcome of your patient over time.

regards

HI Phil

I suggest you to select some major rheumatic diseases to study.  As the diseases are different you have different physioterapic options... Best regards

In Rheumatoid arthritis, the inflammatory cytokines (TNF alpha, IL1, IL17 etc)  inhibit osteoblast proliferation and promote osteoclast differentiation. This causes bone erosions & periarticular osteopenia locally and generalised osteoporosis at distant sites.

The effect of inflammation in negatively affecting bone loss is very high. Almost all DMARDs have a salutatory effect on bone health by reducing this inflammation. Though invitro studies show that there is some deleterious effect on osteoblast proliferation, this effect is very small compared to the deleterious effects of inflammation itself. Thus, in clinical terms, the net effect is positive by stopping the bone loss or at least reducing the rate significantly.

The newer Biologic DMARDs like the TNF inhibitors (Infliximab, etanercept etc) have even shown reversal of bone erosions in a few studies (by MRI imaging) and possibly have a more positive effect on bone health than the non Biologic DMARDs like methotrexate. 

Hope this helps

There are 3 dimensions to this question1. Does the patient indeed have RA? Over 70% of HCV patients are positive for Rheumatoid factor. HCV itself can cause a form of non erosive arthritis. Cryoglobulinemia , often associated with HCV can present with arthritis. If the patient does not have RA, the arthritis will actually resolve with IFN.

2. Choice of RA therapy on HCV: One needs to avoid methotrexate, lefluniomide and NSAIDs. Hydroxychloroquin and Sulphasalazine might be acceptable DMARDs. In case of choosing biologics, TNF inhibitors are by and large not recommended. Rituximab, though not recommended, is sometimes given as it does have benefial effects on cryoglobulinemia related arthritis of HCV and might cause lesser harm. Abatacept might be an alternative worth exploring.

3. Effect of DAA interferon/ribavirtin on RA: This is a tough one. IFN/ribavirin is known to precipitate autoimmune diseases including RA. 4 cases of RA have been described with IFN therapy. The best I can say is, make your own judgement and monitor patient more frequently.

all the best

My protocol includes injection of a fine suspension (not a solution) 500 µg/25µL/paw Sigma Zimosan in saline. Homogenize carefully between animals.

Toxicity can be measure by cell death by annexine V staining flow cytometry and stimulation of your antigen can be measure by increasing /decreasing of specific cytokines.

Although generally DMARDs and TNFi do not affect the lipid profile, tocilizumab and tofacitinib do adversely affect the lipid profile. But whether this effect is significant, or whether the anti-inflammatory effect is more important, is not known. So the whether the CV risk is increased for those 2 agents is unknown. Below is a recent review:

Arthritis Rheumatol. 2015 Jan;67(1):117-27. doi: 10.1002/art.38894.

Lipid profile changes in patients with chronic inflammatory arthritis treated with biologic agents and tofacitinib in randomized clinical trials: a systematic review and meta-analysis.

Souto A1, Salgado E, Maneiro JR, Mera A, Carmona L, Gómez-Reino JJ.

http://www.ncbi.nlm.nih.gov/pubmed/25303044 

Thank you all for responding with your invaluable insights and perspectives!  In regards to the testing of all the isotypes of RF, the Banchuin et al article investigated the epidemiology of IgM RF, IgA RF, IgG RF, IgD RF and IgE RF. The Hermann et al article only reported on IgM and the IgE RF factor titers. Thank you very much, Maria for your potential explanations / mechanisms for an association between IgE and extraarticular manifestations. Some RA patients self-report sensitivity to various compounds that affect their joint flexibility, tenderness, and inflammation. I wonder if IgE RF could potentially contribute to the phenomena.

Thanks for your insights!  Kathy

Hello Samra,

You may find this protocol in the below link useful, because I used the same company's protocol for CIA induction in Wistar rats successfully... 

Although I also purchased the collagen from the same company as well, I believe that this may work irrespective of the source of collagen..