Paired Oligloclonal bands and seronegativity anyone?

[MAT51]

I thought I'd update with this link and a question about seronegative SjS. I've been told by my new rheumatologist that I don't have a connective tissue disease because of my negative autoabtibodies. For a year my rheumatoid factor was a low positive and this coincided with full on RA symptoms five years ago. But the RA was non erosive - might have been chased off by Methotrexate and Hydroxichloraquine which I took for two years. Finally I became allergic to both. Now taking nothing and RA has never come back.

But the clinically diagnosed small fibre neuropathy has progressed to include both arms and legs and my face. I'm told I have Raynaud's, am hypothyroid (supposedly well controlled although I'm not sure I agree) and my blood pressure has gone steadily up so I'm now being treated for hypertension.

My eyes are very dry, my scalp itches and crawls and my feet and ankles are increasingly numb, as are my gums and lips and nostrils.

My mouth isn't particularly dry but this seems to be the only moist part now. I realise this is unusual and is why Sjogrens isn't being suggested for me. I'm not in much pain usually these days but find the numbness is now giving me disorientation problems and I'm using a cane because I often feel the ground is like quick sand if this makes any sense? My nose crusts and bleeds often with dryness. I no longer sweat at all and have lost my sense of taste and smell to an extent - apart from a bad taste often. All these symptoms, particularly the dizziness,improved dramatically while I was on steroids and I'm now suffering from reflux and constipation despite very wholesome diet and drinking masses.

So I've self diagnosed with seronegative Sjogrens because I read this article and it struck the strongest chord with me: http://www.hopkinssjogrens.org/disease-information/sjogrens-syndrome/neurologic-complications/

I had a lumbar puncture last year and the only thing that showed up were these paired Oligloclonal bands. This would tarry with my fluctuating inflammation levels and high total protein levels. The thing that flags up for almost all my symptoms is Sjogrens but my rheumatologist seems unprepared to acknowledge this without a positive Ro and La. Should I ask for a lip biopsy or change rheumatologists?

I also have microscopic haematuria.

I don't want any further immune suppression if it won't help because I've tried four so far and had horrible allergic reactions to them. Nor do I want to go back on steroids after six months of these. But I don't want to keep losing sensation and end up with increasing spatial problems. I will see a new neurologist sometime over the next few months and need to know what tests to ask for and how to slow down the progress of this small fibre neuropathy so I don't end up losing sensation completely and completely losing my sense of balance just because of my negative autoabtibodies.

[anita]

It is VERY possible for you to have sero-negative Sjogren's with your symptoms (even though you don't have dry mouth).  The paired Oligloclonal bands are associated with autoimmune disease, so that even more points in the direction of connective tissue disease (like MS, Sjogren's, SLE, etc)...regardless of what your doctor says (IMO).  I would suggest you see an immunologist...as they would be best at determining the significance of the paired bands.

That being said, you may be disappointed in what you learn because ALL the possible connective tissue diseases would address the problem in the same sort of way...immunosuppressants, steroids, Plaquenil or other DMARDs, or possibly Rituxan...none of which you wish to take or can't take.   That only leaves you with alternative and/or natural treatments...which you won't get from a regular doctor.

Personally, I would go the immunologist first and then request a lip biopsy (which the immunologist may order), just to rule out or confirm the Sjogrens.  The paired bands is the one key piece of this puzzle that has been positively identified and must be explored.  I think it will lead you to your answers...but then you will still have to address the treatment side, which will include the above mentioned options that you don't want to take.

BTW, Julius Birnbaum (who wrote the article in the link) has stated in other articles that up to 40% of patients with Sjogren's are sero-negative.  You might try googling his name for other articles to find this statement to show your rheumy.  Maybe he will believe a doctor at Johns Hopkins that patients don't need a positive Ro & La to have Sjogren's.

[MAT51]

Thanks very much for your considered reply Anita. Firstly to explain; it's not that I don't want to try any more medications - it's that the ones I've tried have either given me severe GI problems or Pancreatitis (Imuran) or Anaphylaxis. So I can't try them again. I haven't qualified for Rituxan because my RA symptoms have upped and gone. If the synovitis returns then I would be offered biologics under NHS guidelines -  but only ones for RA not for neuro presentation of Sjogrens. I asked my last neurologist about IViG but he said this is only available for people with inflammatory neuropathies affecting the CNS - not "a patient such as you". This was despite my paired 'o' bands and highly fluctuating CRP and ESR.

Re the immunologist - I haven't got the option on seeing one unless I do so privately - which won't be easy where I live. However in another work related context I did come across a senior professor of immunology so I could possibly ask her to recommend someone as she lived here until recently. I do feel the need for answers is overwhelming and also I want to know what my status is in autoimmune terms so that I can manage it myself better if it worsens.

I did see a maxillofacial consultant recently and he said very much they same as yourself but felt a neurologist was key. He never mentioned Sjogrens or examined my face/ mouth because he said he'd read my last neurologist's report re paired 'O' bands and high CRP/ PV and explained that I have a clinically diagnosed small fibre neuropathy which is affecting my face now. He said the fact that steroids helped my dizziness/ disorientation showed that something autoimmune is responsible. So I then cheered up but since then all I'm offered are drugs such as Pregabalin and Norotriptyline - which my rheumatologist says in all they can offer me. I refuse these because coming off Cymbalta triggered a whole host of infections last year including pneumonia and sepsis. I've tried Gaberpebtin and Amitriptyline - not good. And anyhow I am not presently in much pain - just dizzy and full of weird heat and chills and numbness - so these drugs wouldn't help me at all.

Sorry to rant here - but I'm so frustrated with it all. Thanks I will definitely look up Julias Birnbaum's other articles. However in the UK rheumatologists take their criteria from EULAR - which is somewhat different on certain diagnostic specifics to the ACR. But I'm going to keep trying and will print off the relevant articles as you suggest. Mat

[anita]

Your infection issues (whether directly or indirectly from the Cymbalta) is yet another reason to seek out an immunologist.  Highly unusual for an antidepressant (SSRI) to cause an infection, but if your immune system isn't functioning properly then an immunologist is the doctor to see.

I understand that some of the medications you can no longer take, but the steroids helped (particularly with your current symptoms) you without incident.   I am NOT for long term use of steroids, but use during flares, etc is typical practice for autoimmune conditions.

It would be great if this person could suggest an immunologist that you might be able to see.  If they can find or confirm something definitive, then wouldn't you be eligible (afterward) for more care with immunology through NHS?  Not only would the immunologist be appropriate for looking into the paired bands AND the autoimmune side of the problem, but might be able to shed light on the unusual infections from Cymbalta (which might open doors for other medications that will be helpful for you).

Rituxan is slowly being approved as an appropriate treatment for certain autoimmune conditions, so if they find something specific in you, then maybe you would be eligible...even through NHS.  I just feel (as you do) that further investigation is warranted to find out what the heck is going on.  Even the best treatments out there need to be implemented ASAP for best results.  I'd hate them to sit back and watch you get worse without looking more into this.

[MAT51]

Thanks so much for your support and advice Anita. I  am composing a letter to my current rheumatologist explaining that it's more practical for me to move to the larger hospital in a neighbouring health area. I've decided to try to get someone else to review all my symptoms and test results and hopefully be less dogmatic and antibody focussed. I will be registering with a new GP soon too so I will speak to them about seeing an immunologist about my paired o bands.

I admit I'm slightly giving up hope because I live in a relatively small country and once a rheum has made a decision it's hard for their colleagues to contradict this. I'm hoping that by moving everything to a new, much larger teaching hospital with an international reputation - they may see a bigger picture through team work across the specialisms. Maybe the neurologist will refer me to an immunologist in this hospital? I do hope so.

I'm not really sick presently but I'm just so tired all the time. Just navigating on foot without tripping up, eating food that I can't taste properly, half smelling, not sweating, dry eyes and nasal passages, cold aching legs and semi numb, cold feet, gums, lips and ever itching crawling scalp. It is all just not so great. 

[anita]

I think your plan is an excellent one.  I fresh new set of eyes/opinions from multiple doctors is the right way to go.

[MAT51]

Thanks so much Anita. You've been so helpful - i really appreciate it. Mat x

[Rgs]

Hi mat
I'm reading your post and fill like its my words, I'm also a male 34 yo, 2 years ago all those symptoms came and the main issue for me is the neuropathy thing: itching, small numbness on right feet for the Last week, dizziness.....
The thing is I went to 3 different reum and made 4 Emg/cnt tests and after the Drs see me and see the good Emg results they sending me home ...
The dryness is not so bad until now but the neuro thing is extremely hard... 
Are your Emg results also good?
Can you suggest another test?
Thx

[MAT51]

Hi - I'm actually a woman of 53 - sorry if my name gives you a different impression!

Do you have the paired Oligloclonal bands too and are your CRP, PV/ ESR and other inflammatory markers always raised and often high? If so I would ask why bother with an EMG - not sure why they would use this rather than looking into autoimmunity or even, dare I say it, malignancy? Mine have gone up quite high again and I'm having a colonoscopy on Thursday and also a lip biopsy for Sjogrens.

I'm quite worried about Multiple Myeloma but my Bence Jones has just shown negative again. If you have lots of inflammation then I would push for answers. If you have symptoms but no other signs in your blood or spinal fluid then I'm not sure what to suggest. If you haven't had blood tests for inflammation or B12 or immunoglobulins or autoabtibodies done then I'd ask for these to be done. If you want to risk it then you could ask for a lumbar puncture. Mind was fairly horrific (7 attempts to tap) but it was worth it to get something showing at last in the form of these paired o bands. I'm feeling lousy just now and my CRP is 19 and my PV is 1.98 which is high so my inflammation levels reflect the way I'm feeling as usual. Hope this helps.

[irish]

I would also make sure that the immunologist follows up on the microscopic blood in your urine. I bet that doc will check you good for Lupus also. Hope that you find some help. It is miserable to be miserable all the time. Good luck. Irish

[SJSman]

Hello,

I had paired Oligloclondal bands when I had my first lumbar puncture and was told that any infection of any kind over a long period of time in past could have caused this, so it is entirely and utterly non-specific and does not suggest, even vaguely, any diagnosis of any kind.   

ESR and/or CRP are not indicators of disease activity in Sjogren's, and in themselves are inherently non-specific for Sjogren's diagnostic purposes.  For one single example, I have severe Sjogren's and my crp and ESR have never been elevated to any meaningful degree in 12 years.  ESR and crp are more active in Rheumatoid Arthritis, and not so typically in Sjogren's.

You have a lot of symptoms of diabetes.  Have you had routine A1C tests for long-term glucose monitoring that can be used to detect and definitively diagnose Diabetes?  If not, you need routine A1C's as this single test could potentailly solve your big mystery and lead to massive relief and proper symptom treatment if you do have Type II Diabetes. 

You also have symptoms of neuropathy, fatigue, heat, and cold that could suggest a hormone imbalance - have you had those whole systems tested by a good endocrinologist?

You could have a brain tumor.  You could also have bladder cancer.   

Just wanted to mention here that "Seronegative Sjogren's" in the linked article being discussed means that the patient is seronegative for the SSA or SSB antibodies, however, they must have a positive lip biopsy. The article says it clearly enough to make that point:

"However, more than 50% of patients with neurological manifestations of Sjogrens may not have autoantibodies. In patients who have neuropathy and compelling glandular symptoms of dry eyes and dry mouth, negative blood tests for SS-A and SS-B antibodies do not exclude the diagnosis of Sjogren's syndrome. In the context of sicca symptoms, further diagnostic studies are warranted, including a Schirmer's test, and a minor salivary gland biopsy."

If the article was saying that you could have "seronegative Sjogren's" with no positive lip biopsy, then the minor salivary gland lip biopsy would not be warranted, would it?.  Julius Birnbaum (who wrote the article in the link) has stated in other articles that up to 40% of patients with Sjogren's are sero-negative, and invariably these patients have a positive lip biopsy - this is simply his definition of what "seronegative Sjogren's" is, one that is shared by Rheumatologists worldwide as is defined in each of their own publications.

[MAT51]

Thanks SJSman (and Kitt for reposting). Firstly I was given this great link by someone on the NeuroTalk forum: http://www.clinlabnavigator.com/oligoclonal-bands-in-csf.html

When my lumbar puncture was done I was not ill with any long or short term infection. Of course it is non specific and I'm not going to request a repeat because it took the doctor 7 or 8 attempts to get tap and was pretty painful. But if you look at the table I've linked to you will see that there are a number of conditions, including Sjogrens and Lupus that are associated with paired Oligloclonal bands.

Re bladder cancer - thanks but I had a cystoscopy earlier this year and my bladder was healthy. I an to have a colonoscopy tomorrow. I do have undercarriage issues in my woman parts from bearing large babies, each with episiotomy which has left much scarring - nurse felt this was compounded by likely Sjogrens related dryness as pretty severe atrophic changes have taken place long after my early menopause. I've been put on oestrogen pessaries now.

I have already been tested for diabetes. My late father, uncle and grandfather all suffered and died from a rare type 1.5 late onset diabetes so I am highly aware of the risk in my case. The only test done in UK (or offered to me) has been a fasting glucose test and mine was negative/ within normal range a few weeks ago. A private endocrinologist I saw a few months ago (for this and my hypothyroid bloods which did not seem right to me) explained that these symptoms I have been having would only be found in end stage diabetes - and so far I'm not even pre-diabetic so this is a non starter. I am going to be seeing an NHS endocrinologist soon so will ask to be regularly monitored for this as well as my Hashimoto's hypothyroidism. But I'm assured that none of this accounts for my high CRP, ESR/PV which are all rising again despite no sign of infection or illness or active RA. I'm to have a colonoscopy tomorrow. My GP believes this might be a very relevant investigation but I'm not so sure - although I've suffered from chronic constipation since Christmas and probably have polyps, haemorrhoids or fissures now.

My new rheumatogist has requested an ultrasound of my salivary glands and advised me to have a lip biopsy. As you state SO EMPHATICALLY - this will finally rule in or out Sjogrens. I'm very much hoping that I get a positive reading, but not expecting one. The rheumatologist has echoed my previous chap in saying that he thinks the only connective tissue disease I may have is Vasculitis - and this can be very hard to diagnose. My RA is no longer active in my joints so the only other thing that might otherwise explain all my signs and symptoms is a malignancy in the form of Multiple Myeloma. I have had two negative Bence Jones test results so far and I don't believe I have cancer because my inflammatory markers have fluctuated along with symptoms for at least five years and I think I would be much sicker or dying by now if I had this type of blood borne malignancy. But, as my endocrinologist says, nothing is ever set in stone 100% with these diseases. However if my lip biopsy is negative I will strike primary Sjogren's off my list for good.

[MAT51]

PS I should explain that I have not yet had a lip biopsy. Only my autoantibodies and and Schirmer's have shown negative so far. My Rose Bengal tear flow was very low a few years ago showing Sicca. I use eye drops and ointment and the Sicca is now only mild.

[SJSman]

Hi Mats,

I was only trying to help in suggesting things you could possibly have.  I see that you are deep into the fight of trying to figure it out, and it appears to me that you are making really good decisions.  You do research and develop a theory about what could cause your symptoms, then try to get tested for whatever it is, then if the test result is negative, start the whole cycle over and move on to the next most likely thing that you can find that might explain your symptoms.

I am tired now and may have missed this, but having a head and neck MRI can sometimes provide clues to a diagnosis that might otherwise be missed.  It can't hurt, however, I had a heck of a lot trouble getting one from my uncaring doctors in the cost-minimization HMO that I belonged to at that time years ago.  In the end, my MRI provided the clues that eventually lead to my Sjogren's diagnosis.  Brain MRI results can provide clues that could potentially lead you toward many different conditions that might explain your symptoms, that might otherwise be missed.  I wish you all luck in the search!   

And yes, the correct definition of what "seronegative Sjogren's" is, and what criteria must be used in a correct diagnosis of Sjogren's - meaning a correct understanding of what Sjogren's is and what it is not, are very important to me as you gathered lol.

[MAT51]

Thanks for clarifying. Yes I had a brain and cervical MRI at the same time as nerve conduction tests and lumbar puncture last year. The only thing that showed up was some arthritis in my neck - which was not impacting on my spinal cord in a way that could explain my widespread small fibre neuropathy apparently. My RA has been blamed for damaging my small nerve fibres permanently when it was active.

But I'm very unusual in that my rheumatoid factor has gone from being weakly positive five years ago, to negative - and I no longer meet the criteria for seronegative RA because I have no eroded or swollen synovial joints. I was on injectable methotrexate, Hydroxichloraquine and Sulfasalazine for two years so this  aggressive DMARD treatment might have nipped it in the bud in time apparently.

However, as my other symptoms have continued to wax and wain I have been on a very hard and twisting journey to try and educate myself and understand as many autoimmune and related diseases and comorbidities as I am able to, as a non-medic and non scientist. One of the things I have learned on this journey is that the disease criteria, which you obviously feel represent you and others with Sjogrens well, can never be 100% reliable. Of course I understand why we need criteria and have a reasonable grasp of health economics too. But there will always be a small, perhaps minuscule, amount of people who do not meet any of the criteria but still do have the disease. After all no one actually tells our cells what criteria they have to comply with in order to meet certain targets. And there are always crossovers. So I might possibly have a rare form of Sjogrens which mainly affects my peripheral nervous system so far, and a non erosive form of seronegative RA which makes my inflammatory markers raised or high simultaneously to seronegative Sjogrens. This may be very unlikely but it is not impossible.

For example I found out about this forum from someone who is thought to have Sjogrens as cause of her very rare autoimmune ganglionopathy. Her lip biopsy was negative and her mouth and eyes are only just starting to become dry many years after the small fibre neuropathy/ ganglionopathy were confirmed. As two rheumatologists have explained to me - rheumatology is a very inexact area of medicine.

So, having been using this and other health forums for a number of years, I have come across people who have many, if not all of the clinical manifestations of Scleroderma or Lupus or Behcets or Sjogren's, but because they do not meet the criteria in autoantibody terms, they are left undiagnosed and untreated while their bodies deteriorate painfully and horribly - and yet they are unable to get the support they need - each set of failing organs ir joints or dying nerves or central nervous system is treated in isolation as a problem. Terms like "functional" or "psychological" are applied to the more unquantifiable/ idiopathic symptoms.  Acute or chronic symptoms such as kidney failure, heart failure, atherosclerosis, Pernicous Anaenia etc are not put in any wider context. This is because the international medical community have not yet learned enough to explain the sufferer's dire symptoms or make a connection between multiple symptoms and one overarching disease process. So rather than blaming themselves there is a tendency to for doctors to blame the sufferer - until one day Ulcerative Colitis (for example), is recognised as a disease of itself rather than as a manifestation of an anxiety disorder.

I speak here as someone only partly in the shadowlands, having been diagnosed with RA five years ago, having acknowledged autoimmunity and never having been given a diagnosis of ME or Fibromyalgia or IBS - (yet!). But I do feel tremendous empathy for those who suffer in the shadowlands without a diagnosis simply because their bodies have had the temerity not to comply with any specific disease criteria.

I'm sure you don't really need this rant but you have accidentally trodden on my own pet ants nest with your own passion for sticking to SjS criteria. I do respect this but disagree with the rigidity. I do hope you feel less exhausted soon. I'm confined to home (and nearby toilet) today, fasting and drinking laxative in prep for tomorrow's  colonoscopy. Not much fun!