I believe it is possible,as auto -immune diseases may be included into Aids non-related complications,that are very frequent in hiv -infected patients ttrated with ART

Dear Luigi

Thanks for your answer. I have a patients with AIDS (55 years, with undetectable viral load and high level o CD$) . She  started polyarthritis about two months with SHV of 115 mm, c-reactive protein of 10 and rheumatoid factor in high titles. I had begun corticoesteroids and I am thinking to prescribe hydroxychloroquine. What do you think about? 

Best wishes

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

Dear Shankar

Thanks for your answer!

I know that the likelihood of RA associated with AIDS is low and the reports of RA improving with AIDS, but in the case of my patient she had AIDS with indectable viral load and the pyarthritis had began 2 months ago (not 2 weeks).

I am waiting the anti-CCP

Best wishes

Dear Dr Carlos, 

I did mean 2 months but somehow typed it wrong. The logic still holds.

Lets look at it this way. Prevalence of RA is about 1% worldwide. So technically even among HIV patients , about 1 in a 100 should come up with RA. But our experience and published literature tells us otherwise. The prevalence is less than 0.1% or maybe lesser. However, It will never touch zero.

So, your patient can definitely have RA. He does seem to meet the 2010 criteria. I am sure anti CCP will help. Hydroxychloroquin is a good choice. The challenge might be long term management juggling various drugs.

Dear Shankar

(Please call me only "Carlos")

I think that hydroxychloroquin will not be sufficient...I want to try the association sulfasalazine/hydroxychloroquin...

Methotrexate probably will be not safe...

Best regards

Dear Carlos,

How active is the disease? The CDAI/DAS28 scores. 

Since you are the treating Physician, you are the best judge. SSZ + HCQ is a decent combination.

Methotrexate has been used (with or without TNF antagonists) in patients of Psoriatic arthritis with HIV and found safe. Until there is a coexisting hepatitis (HBV or HCV) or a ILD , Methotrexate too can be kept as an option

regards

Dear Carlos,

RA is indeed rarer compared to SpA group in HIV. i believe you must have ruled out other causes too. anti-ccp would definitely help. as for treatment, i would treat with SSZ + HCQ. among NSAIDs if required, i would prefer indomethacin. all these three have anti-HIV activity too by various mechanisms. methotrexate increases chances of opportunistic infections though the CD4 counts are normal and i would use it later if required. another suggestion is using Rituximab in resistant cases considering the facts that RTX is used in refractory thrombocytopenia of HIV and it is anti B- cell and not anti T-cell, though i have no personal experience of this.

Regards

Dear Bijit

Thanks for your suggestions

Best regards

Prevalence inflammatory conditions are related with increase life expectancy by use HAART therapy in AIDS patient. Last years I treated AIDS patient who suffer Rheumatoid Artrhitis (RA), Systemic Lupus Eritematosus, Psoriatric Arthiris or vulgar Psoriasis or other Spondyloartritis.

In AIDS patients treated with HAART therapy with low viral levels and controlled disease is safe use DMARDS to treat RA, if not are co-infected with hepatitis virus, and in selected cases will be able to use target therapies.

I treat for more than 12 years a female patient in remission an ovarian neoplasm since 25 years, VIH infected since more than 25 years, who suffer RA since 20 years, First in England started Sulphasalazine with unacceptable disease control and RX progression. After, without HAART therapy because patient was a long term survivor with no less than 200 CD4 and low viral load, started Methotrexate (MTX)  (medium dose around 20 mg/wk) with a good control 4 years and changed to Leflunomide 20 mg/day by hyperemesis, and patient started HAART  therapy by arise viral load. After that she started RTX+MTX for 3 cycles (around  total of  time in ACR 50 6 months in 1th cycle and  11 months in 2nd cycle), stopped treatment after   3rd cycle by poor response and persistent hypogammaglobulinemia (< 500 mg/dL IgG), Since September 2011 to actually she use Etanercept 50 mg/wk plus LFN and low steroid dose with EULAR response and AC50.

Thies patient ever use low steroid doses, without Kaposi’s sarcoma rising, patients with AIDS steroid use is associated with an increase risk KS related to replication HHV-8.

Dear Agusti

Thanks for tour answer

Best regards

AIDS & polyarthritis is a difficult diagnostic and therapeutic challenge.  As mentioned, the usual polyarthritis is of the sero-negative series.  On the other hand, as already mentioned, AIDS is often accompanied by autoantibodies of the ANA (RNA) series and less by the ANA(DNA) and RF series.  In a large South African AIDS series,  . 

In a large South African AIDS series, anti-CCP was found with or without polyarthritis (J Rheum) mostly as false positive as few if any developed chronic erosive polyarthritis.  In your patient, if anti-CCP is negative, that will rule out RA.  If anti-CCP is positive, it will not necessarily support the diagnostic of RA.  Anti-MCV (Orgentec) will give the same info as anti-CCP.  To go further, you must request an anti-Sa (cit-vimentin) ELISA (Euroimmun).  If that is positive, your patient has RA with a positive predictive value of >99% vs all other CTDs (personal serological experience and observations).  If negative, you have to rely on your clinical judgment.  Treatment-wise, I would suggest to exploit cautiously combo DMARDs (HCQ-MTX-Gold) and use steroids only p.r.n. by intra-articular injections to stay away from Pred p.o.  I have no experience with Biological  in that clinical setting.  If you use them, document it very well over several years and publish your valuable N of 1 experience as a case report .

Dear Henri

Thanks for your answer

Best wishes

Dear Carlos,

I would have a different interpretation of the tests that Dr Henri menard has mentioned. All 3 tests, namely anti CCP, anti Sa and anti MCV are characterised by high specificity (between 95-99% in various studies) and modest sensitivity. He mentioned that a negative test will rule out the disease. I don't think so.

The 2 rules of interpreting tests (with High Sensitivity or High specificity) are given by the mneumonics

SP-P-IN: Specific tests when positive rule in the disease AND

SN-N-OUT: Sensitive tests when negative rule out the disease

Please refer to http://www.cebm.net/sppin-and-snnout/

A specific test when negative or a sensitive test when positive do not have the same degree of influence in changing the pretest probability of the disease.

In the scenario of AIDS, the pretest probability of a patient having RA is on the lower side. A negative test (for any of the 3 tests above which have modest sensitivity) only marginally increases your probability that the patient does not have RA. It does NOT ruleout the disease.

However, a positive test makes the probability quite high that the patient might have RA. It might actually RULE IN the disease. Recall that all 3 tests are highly specific and are best used for ruling IN a disease and not for ruling out (SPPIN).

regards

Dr Subramanian,

tks for telling us about the mnemonics you use and reminding us about PPV, NPV and pre/post-test probability. I am in general agreement with the theory but I maintain my stated position. In this specific case of AIDS and possible RA, for sure a negative test does not exclude RA but one has to believe in the notion of sero-negative RA not to look for another explanation..  IN GENERAL, if one suspects RA because of the clinical context, a negative anti-CCP or MCV (because of their high sensitivity and intrinsic NPV) will make RA even less probable.  A negative anti-cit-vim/Sa will not help at all because anti-Sa is less sensitive than the other two.

On the flip side and contrary to the initial marketing of anti-CCP to which we were all exposed,  the three tests do not have the same specificity and prognostic value.  That is obvious when one is dealing with personalized medicine in a tertiary case center vs making decisions after population-based data from regular practice.  I still have to see a flagrant false positive anti-Sa in non-RA but there is not a month without a publication (even from the Netherlands) about the false positivity of anti-CCP in various non-RA chronic inflammatory conditions.  The three tests are definitively not interchangeable: Sensitivity: CCP>=MCV>>>Sa. Specificity: Sa>>>>MCV>=CCP.  Prognosis: anti-Sa>>MCV>>CCP.  Disease monitoring: anti-Sa>>>MCV>>CCP=0.  It may be OK to rely only on a screening test in run of the mill cases but not in tertiary care centers where cases are nothing but simple. Besides, would one diagnose SLE only with an ANA? Would you entertain that diagnosis if ANA was negative?

Best.

HM

PS.  Carlos, maybe the first question to ask is what was the result of the anti-CCP test in your patient.

Hi all

I and wainting the anti-CCP. In public service in Brazil this tests' results take too long

As soon as know I wiil informe all of you

Best wishes

Dr Henri A Menard,

I think we are talking more or less the same thing, but somehow the choice of words is making it sound different. Both agree on the importance of the tests in this condition, however, we seem to have a slight difference of opinion on the "direction of pull" of the test.

I notice that this question has had over 120 views and I am sure that some of the viewers might be left confused as to what exactly is the point of contention. I have therefore made a small PPT of 15 slides and taken the effort of explaining the steps of my reasoning with the help of a small table and a probability graph. It is best viewed as a slide show so that the graphics and text appear in the way I have designed it.

Words can be misinterpreted but numbers (hopefully) tell the real story!

ANA and anti CCP/anti-Sa cannot be compared as ANA has high sensitivity and low specificity while all 3 tests that we are discussing (CCP, Sa and MCV) have a high specificity and low sensitivity. Their role is diagnosis is entirely different.

regards

Good evening,

sorry for the delay in keeping up the exchange.  I was away traveling with my 9 year-old grandson taking the train from Montreal to visit Ottawa, our nation capital.

The clinical epidemiology charabia may be confusing and I thank you for reminding the readers about its elements.  That being said  your elegant  demonstration does not reconcile our views.  Probably because you may not have had the opportunity to work  with the anti-Sa ELISA.  It is very different than the other two tests.  Is it available in your Center?

To  clarify: anti-CCP ELISA was designed by a biochemist for sensitivity to catch all polyarthritides and support a clinical diagnosis of RA.  Anti-Sa ELISA was designed by a clinician for specificity to confirm RA and  identify from onset those with bad prognosis in N=1 situations. 

It follows that the former is best used as a screening test that will catch most if not all the anti-cit-epitopes whether important or not in RA.  There are zillions of potential autogenous and exogenous cit-epitope challenges.  When RA is present, higher anti-CCP titers are, in population statistics, usually present (but with significant discordant exceptions) and that is associated with worse prognosis and erosions.  That means that one cannot predict for sure in N=1, a bad future for a patient with anti-CCP.   Sure, in population data, one will also find statistics showing that anti-CCP decrease with this or that treatment.  But, as tested in the clinic, because of the ceiling effect of that ELISA, anti-CCP cannot be used in N=1 to monitor the humoral immune process and be correlated with its inflammatory consequences (CRP and DAS28).   That is why in retrospective studies, anti-CCP is best used in pre-RA studies and RA will only appear in the next 5 years presumably following the nature and intensity of the stimulus and response. Anti-CCP are a generic measure of immune response genes to cit-epitopes presented in the context of the shared epitope(s) and they are not necessarily associated with disease.  Indeed , anti-CCP is present sometimes in high titers in 10% of normal North American Natives and in 20% of normal, first degree relatives of RA patients.  If the disease is present the titers of anti-CCP will be higher and the test will be frankly positive.  In the same clinical  situation, a positive anti-Sa test will mean a titer of anti-CCP 10-100 times higher.

Thus in a patient with AIDS (with chronic infections/inflammation) and new polyarthritis, if anti-CCP is negative, RA is for all practical purpose absent (ruled out).  If positive, it does not mean that RA is present (ruled in) because that context of chronic inflammation and immune dysfunction is very permissive to false positivity as it is for RF and ANAs.  The danger to the clinician is one of circular reasoning.  RA must then be supported proven by the evolution or  by a more specific test.  We use anti-Sa for that purpose to help clarify the situation.

Anti-Sa ELISA  is not usually present in pre-RA  (in North American natives); if it is, RA will soon appear; it is more robust as it predicts from onset (in N=1) bad prognosis at 3 years better than RF and anti-CCP put together; finally, t was  designed without a ceiling effect to allow immune monitoring like anti-dsDNA in SLE.

So,  anti-CCP is much more sensitive than specific like ANA is for SLE/CTDs.  Anti-Sa is much more specific than sensitive like anti-dsDNA in SLE,.  Anti-MCV behaves sometimes like anti-CCP, sometimes like anti-Sa because it has some of the good and bad features of both making its interpretation a bit tricky in difficult cases like this one.

Most of what I wrote is referenced in  editorials I wrote for J Rheum 2009 and 2015 (See attached files)

Thanks and best.  

HM

Dear Dr Henri Menard

Thanks for the write up. I have no personal experience with anti Sa. We will get it now in our Institution.

My arguments were entirely based on published literature that show very similar numbers for the 3 tests as shown in my PPT.

Regards