4 months of pain and no answers. Negative ANA.

[PennyRoseFlow]

hello all.

I posted 4 months ago when my illness started. Joint pain and a full body rash (that went away in a few days) were my main symptoms at the time, then mostly joint pain.

I saw a rheumatologist in July (paid privately). He was very interested in what he called my malar rash which GPs told me 10 years ago was rosacea. At the point he said it could be a reactive arthritis or potentially another autoimmune thing like lupus.

I started steroids for 5 weeks in July into August. Life got a little better pain and movement wise. As soon as I stopped it got worse, chest pain came back and I’ve been riddled with mouth ulcers and now developed a rash on my abdomen and breasts since.

Saw NHS rheumatologist last week. They are a little stumped as I don’t fit neatly into one disease. They said a negative ANA was reassuring but after asking more questions both doctors said “CTD” at the same time and advised this is the group of autoimmune a like lupus etc.

I’ve got an ultrasound next week so all I’m doing is trying to manage pain as best I can, treat ulcers and look at an awful rash

I guess does anyone have similar experience? The NHS rheumatologist said it can take years to diagnose as these diseases can take a while to manifest properly in bloods and diagnostics. The fact I have a negative ANA would mean I definitely don’t have lupus which is positive but I don’t know what it all means long term.

thanks so much in advance x

[PMRpro]

A negative ANA is not conclusive evidence it isn;t lupus - it is rare, about 2% of negative ANAs are seen in lupus. But positive ANA is also not conclusive.

hopkinslupus.org/lupus-test....

Mixed and undifferentiated CTD are terms that account for you not fitting neatly into a box - and there are other options. It is less important having the "right" label really - there are no cures for any autoimmune disorders and symptom management is the aim.

Had you had the mouth ulcers before? Have you ulcers anywhere else? Any eye problems?

[PennyRoseFlow in reply to PMRpro]

So about 13 years ago when I developed the “rosacea” is also had bouts of mouth ulcers. They thought I had IBD but came back normal and it settled down. I also had gritty sore eyes for a while and GP said was related to rosacea. Haven’t had ulcers elsewhere, just mouth and tongue. The bout in September was my longest spell, and developed some more this week.

I’ve had unexplained bouts of illness including a weird liver/ bile duct thing 4 years ago. 2 years ago I had bad hand joint pain for 5/6 weeks but it passed before I saw rheumatology so didn’t think much of it till now.

[PMRpro in reply to PennyRoseFlow]

It does sound to me as if this is the early rather vague signs of whatever it is - and all you can do is be patient and keep notes on what you experience. My own experience was more obvious as it turned out - but it still took 5 years to find a doctor who recognised it.

[KayHimm]

Penny -

It sounds like you have been pretty sick and hope you improve soon. Your situation is not that uncommon. Many of us started with various diagnoses of possible autoimmune disease, lupus-like illness or undifferentiated connective tissue disease.

Some people go on to evolve into a specific autoimmune disease. We are all sort of our own unique group of symptoms.

A negative ANA usually rules out lupus but you have good doctors who see such clear signs of autoimmune disease that they are making a general diagnosis now. Your ANA could become positive later. That happened to me.

I wish everyone had a rheumatologist who explained the difficulty of diagnosis as yours did rather than being vague and leaving everything to our imagination.

I am ANA positive but called lupus like because I don’t fully meet criteria. At least in my rheumatologists practice, we undifferentiated types are ten times more common than lupus, which he says they now view as the top of the pyramid.

Hope that helps. I know they will treat your symptoms and continue to test you.

Kay

[OldTed60 in reply to KayHimm]

Kay I love your wise comments but am often struck by how your rheumatologist puts Lupus at “top of pyramid” rather than alongside RA, Vasculitis, Scleroderma, Sjogren’s, Myositis and other equally serious and debilitating systemic autoimmune diseases? Do they perhaps mean top of pyramid just for you ie your own pyramid?

I just wonder if many doctors and patients too often get diverted off the wider diagnostic path towards one more common autoimmune disease such as RA or Lupus?

I know that for myself these two were the main focus of doctors for too long. The famous zebra analogy of the dr who trained his students saying “if you hear sound of hooves expect horses rather than zebras” (or words to this effect) might apply in this CTD setting for both RA and Lupus? Certainly they was all my rheumatologists ever looked for with me for many years and consequently I was misdiagnosed and under-treated. If I didn’t have compelling signs of symptoms of these two or APS then they confident I didn’t have a CTD. They were wrong as it turned out - although right that some diseases evolve slowly - particularly limited Systemic Sclerosis, formerly known as CREST.

Yes ANA can change and other autoimmune diseases such as Hashimoto’s, Pernicious Anaemia, primary immune deficiency or low IgG/ immunoglobulins and Hypermobile Spectrum Disorders can also be factors in fluctuating or negative results. But there are rare systemic autoimmune diseases which many rheumatologists really don’t know enough about. Mouth ulcers are fairly ubiquitous with autoimmune diseases as are rashes and hair loss. Without biopsies looking for as much as possible and keeping a very open mind, diagnoses and treatment can be much delayed and damage done. I have friends with Behcets and Dermatomyositis for example, who spent years misdiagnosed with UCTD, IBS, Fibromyalgia etc, waiting for Lupus or Systemic Sclerosis to show up at last - fobbed off untreated - until they finally managed to see a dr who specialised in one of these and was able to diagnose them correctly. A rheumatologist keeping a genuinely open mind doesn’t put just Lupus at top of pyramid surely?

[KayHimm in reply to OldTed60]

Hi OldTed,

He was only referring to undifferentiated connective tissue in contrast to lupus. I asked him many patients were like me and lupus-like, undifferentiated. His response was that we are a far greater percentage than lupus. In his practice, 10 to 1. I have read twenty percent, so this is consistent.

It would interesting to know where RA stands in relation to UCTD. RA is consistently stated as the most common connective tissue disease.

I can certainly see why they see lupus as the top of the pyramid with various undifferentiated syndromes underneath. It’s the severity, the common kidney involvement and less common life-threatening brain involvement. They are always on the look out for progression and the unusual case of UCTD that gets something very serious.

The classifiable connective tissue diseases in general seem to be more severe, right?

Hope that explains the context.

xxK

[OldTed60 in reply to KayHimm]

Yes I wasn’t questioning the statistics re commonality. But I am querying severity of Lupus compared to other rarer connective tissue diseases which can have a higher mortality than Lupus, particularly Systemic Sclerosis, some forms of Vasculitis and Myositis. And I don’t think RA is any less serious than Lupus either and is also a systemic autoimmune disease with a higher risk of lung and cardiovascular problems associated. So I would put all of these at top of CTD pyramid, if they are seropositive and full blown. And I feel this matters because so many on this forum seem to have the idea that Lupus is the most serious systemic autoimmune disease and this simply isn’t the case. All these autoimmune diseases have their own spectrums and there’s often much overlap in both symptoms and in signs. If we get the idea in early stages that we have one particular disease then we can start matching our symptoms up incorrectly with a degree of confirmation bias - and doctors can do this as well. As I’ve said, rashes, ulcers, hair loss etc with or without ANA could be a precursor to many conditions and if we only focus on one rheumatic autoimmune and place this at the top of pyramid then there are risks of other equally or more serious conditions getting missed, as happened with me.

So if it were me with UCTD or MCTD I’d want to hold onto the CTD pyramid rather than call or think of it as “Lupus-like”. I hope this explains.

[KayHimm in reply to OldTed60]

Maybe I wasn’t clear. The discussion was not in any way about comparing the discrete connective tissue diseases. I was how many of us lupus-like he treated as opposed to lupus. I always thought I was a freak with a UCTD diagnosis. Turns out we are very common.

There is a committee looking into changing diagnosis categories to a lupus spectrum disorder. That would not affect the diagnosis of the other diseases like scleroderma. But it would help to see what my doctor was talking about. Dr. Kaul describes how he sees lupus spectrum disorder in one of his talks.

We shall see.

You are correct scleroderma and Sjogren’s can be way more severe than mild lupus. And UCTD with interstitial pneumonia is not a good thing to have either. No rules with these diseases.

One way to think of the pyramid is disease expression. It is when a disease is full-blown or fully expressed.

Xxk

[OldTed60 in reply to KayHimm]

Yes I can see how many on here would like to see the umbrella moved to Lupus spectrum disorder, similar to the way those, including myself, who can’t get a diagnosis of EDS, are often described as having Hypermobile Spectrum Disorder or worse, Joint Hypermobility Disorder with emphasis only on the joints. But we must remember that Dr Kaul is just a Lupus specialist just as Dr E Price is a UK Sjogren’s specialist. They have their own agendas re making each full blown rheumatic disease seem less rare - so that there’s more research funding for it. Personally I think this would be a big mistake for reasons I’ve described. Connective Tissue Diseases are isolating enough to live with without picking out one aspect over the others and bigging it up. However the reason I’m here and commenting is because this post was from someone asking about symptoms and their rheumatologist saying they have Lupus-like autoimmune. Alarm bells ring for me now when I read or hear of references to Lupus-like or Rheumatoid-like rather than simply as CTD. The rarer the disease the longer it often takes to correctly diagnose and treat, the less research funding it gets and the riskier it then becomes to have these vaguer titles being applied. If there has to be an umbrella then I think Systemic Autoimmune Diseases (SAIDs) is by far the best one because it doesn’t rob the rarer SAIDs of research funding we all badly need. And, although I have Sjogren’s as well as Systemic Sclerosis and it completely sucks to live with, Systemic Sclerosis has the worst outlook of any CTD, as stated in all online literature on the subject. So I’d hate for anyone else here to sit languishing in the Lupus-like basket when it was Systemic Sclerosis and/or Dermatomyositis all along, as happened to me and several others I know of - OTxx

[KayHimm in reply to OldTed60]

For me it is important to see that no one would go in to rheumatology if they needed certainty. Unlike with most doctors, nothing stays the same with their patients. We just keep going on .

[OldTed60 in reply to KayHimm]

I totally agree. It’s just the name of the uncertainty we perhaps disagree on, not the fact that things can and do change x

[KayHimm in reply to OldTed60]

The international committee that is working on changing to a lupus spectrum disorder definition hopes to be able to diagnose patients earlier. Currently there is no lupus diagnostic criteria.

It sounds like a major undertaking that will take a long time, and they acknowledge it may not be feasible.

You are correct that when the article came out many people on the forum embraced the concept.

The UK rheumatologist leading the group is Ian Bruce.

XxK

[OldTed60 in reply to KayHimm]

I’ve not heard of Ian Bruce but I do hope my own perspective gets heeded because I do think that for, research and patient inclusuvity’s sake, SAIDs would be a much better umbrella heading. For your information there are plenty on the SRUK group with UCTD and MCTD who feel more Scleroderma -like than Lupus-like. The larger American forums are packed with them too. But SRUK is a quieter community due to rarity and the higher prevalence of primary Raynauds so they come often here for support. Meanwhile, for your possible interest, here are the newly published BSR (UK) guidelines on Systemic Sclerosis. You will see that overlap syndromes get a specific mention. OT60 x: academic.oup.com/rheumatolo...

[OldTed60 in reply to KayHimm]

”Background

Systemic sclerosis (SSc) is uncommon in the UK population, with around 1000 new cases per year in the UK [2] and is complex and diverse with limited treatment options [3]. It has the highest mortality of any of the autoimmune rheumatic diseases with approximately half of people affected by SSc eventually dying as a direct result of the disease or a related complication [4]. Around one in three people with SSc develops interstitial lung disease (ILD) and 1 in 10 may develop pulmonary hypertension and these are currently the most frequent direct causes of SSc related death [5]. One in five people with SSc develop overlap connective tissue diseases and this will require specific management in parallel with SSc [6].”

[KayHimm in reply to OldTed60]

I listened to a talk that a scleroderma at Columbia University gave to her rheumatology colleagues. I knew the seriousness but had not known the neglect in terms of research and treatment options. It saddened me.

You point to what will be a problem the spectrum diagnosis will confront: do they only include undifferentiated connective tissue disease patients who are lupus-like in presentation? Dr. Kaul mentioneded APS and UCTD in the spectrum but this was informal. They are looking to refine diagnosis. I have no idea how that will be done. Maybe have the features more clearly delineated.

It seems to me with scleroderma they have tried to do that a bit in the Crest vs SS. Maybe I am wrong.

Yes, many with UCTD have toes more in the other connective tissue diseases. I read SS is the most represented but Michael Lockshin noted more lupus-like in his practice. Who knows?

This is a major undertaking. It was begun because of the problems that have arrived for patients diagnosed with UCTD. The article is something like lupus diagnosis ambiguity and harm to patients.

You present potential downsides that that group may want to know about. You should write to Ian Bruce. This project was partially driven by patients’ dissatisfaction and confusion of UCTD. So they would welcome patient input.

xxK

[KayHimm in reply to KayHimm]

* scleroderma expert

[OldTed60 in reply to KayHimm]

Thanks I may do this although I’ve never heard of Dr Ian Bruce so not sure where I’d write to him. Having come under heading of Overlap CTD/ Syndrome for years - with “Sjogren’s predominant” as adjunct - I’ve noticed that letters all now state Systemic Sclerosis at top with Sjogren’s described as Sicca Syndrome, presumably because it’s viewed as secondary now and don’t carry the Sjogren’s antibody? Prior to this change in diagnoses my dermatologist called it MCTD and surgeons refer to it “her connective tissue disorder. So I do understand and have been subjected to the same confusion and feeling of symptoms being minimised.

Nowadays I’m currently struggling to find ways to get the gold standard annual monitoring for SSc patients back on track post pandemic here in my university teaching hospital - so have other priorities where volunteering work is concerned. I also need to ask my rheumatologist, a Lupus specialist, for her thoughts on the former issue before asking her what she feels about this Lupus Spectrum Disorder idea. It would be interesting to discuss properly with her if we ever had enough time during consultations - but sadly we really don’t!

However the more I think of what my SRUK UCTD friends have and are still going through - particularly in here Scotland - the more strongly I feel that Systemic Autoimmune Diseases / SAIRDs would be a much more appropriate and inclusive term than Lupus Spectrum Disorder/LSD. SAIDs/ SAIRDs also leaves more room for possible progression towards RA or the rarer diseases than LSD - which has other associations of a psychedelic nature as an acronym! Life with rare diseases is surreal and psychedelic enough surely?!

Anyway we’ve hijacked this poor person’s post enough Kay but do please feel free to message me here instead if you have any further concerns about my ideas. X

[KayHimm in reply to OldTed60]

OT60 -

I think you would be interested in Ian Bruce’s work. I didn’t realize he was the one who studied UCTD and quality of life. He and others have a study from 2022 on UCTD that will take me a long time to read. But interesting he states that rheumatologists should have access to a particular antibody to diagnose early SS. Does that mean the tests have not been available?

I get the sense Professor has a big interest in UCTD and in getting a handle on patients early for proper treatment.

[OldTed60 in reply to KayHimm]

I am really glad there’s a rheumatologist taking this kind of interest in UCTD. I’m not sure if you read the link I sent but the big UK experts in Systemic Sclerosis are Prof Chris Denton at Royal Free in London and Prof Del Gardo in Leeds. They both quite regularly see people diagnosed with UCTD I know - two of whom it turns out actually had Dermatomyositis. One has found the UCTD diagnosis and being discharged by local rheumatologists untreated particularly distressing. The other has literally had to travel the length of UK and see Prof in Leeds privately to get correctly diagnosed and treated with DM - and is still having to pay for both because her Scottish GPs won’t work with this Leeds professor on NHS when she was diagnosed and discharged with UCTD by Glasgow rheumatologists. Another friend who’s UCTD points most to Systemic Sclerosis travelled privately to Royal Free to see Prof Denton a few years ago. He confirmed UCTD but requested from her GP that she had urgent gastro input which I believe has really helped her a lot. This is why I feel so strongly now that Lupus-like or LSD do not really cover or support those with other rarer CTDs x

[KayHimm in reply to OldTed60]

Yes, I have heard of Professor Denton. I did some research for a forum member who has severe Raynaud’s and one of the SS antibodies. I wish she had seen him. She is an example of a complicated case with features of several CTDs.

Will read your article. I have found another of Ian Bruce’s papers. He uses shared symptoms to determine quality of life in those of us with autoimmune disease. So important. It isn’t always the most serious symptom that ruins a person’s life. How many people have been told they have mild UCTD? But their life sucks?

Interesting there is also the term SS spectrum used in the Bruce paper. So I do think the whole field of rheumatology is trying to better categorize people. I love that a rheumatologist so focused on quality of life of us with autoimmune disease was just promoted to vice chancellor of faculty at his medical school. We need advocates like Dr. Bruce at high levels.

[OldTed60 in reply to KayHimm]

Sorry - forgot to answer your question about Scleroderma antibodies - which most commonly overlap with Myositis ones. I believe Systemic Sclerosis is the most heterogeneous systemic autoimmune disease with the most antibodies. Some of these are rare and some smaller/ regional hospitals around the world only test the most common ones which are anti centromere/ ACA (limited SSc) and Scl-70 (diffuse). I believe that, so far, there are 13 known Scleroderma antibodies. I know less about Myositis but I believe it also falls into two broad headings of neurological and rheumatic autoimmune. My own antibody, U3 RNP, often overlaps with Myositis and I have features associated with Dermatomyositis ie calcinosis in my feet rather than hands, muscle weakness is legs etc and have just started Rituximab. Prof Del Gardo is the one who has rescued my two UCTD-diagnosed friends from the Lupus-like pond and rediagnosed them both with Dermatomyositis - although Systemic Sclerosis is his expertise. I’ll try and find a link to him so you can read more. Like Prof Denton he works under the heading of “Experimental Rheumatology” which I think you’ll like a lot as a term! google.com/gasearch?q=profe...

leedsth.nhs.uk/consultants/...

[KayHimm in reply to OldTed60]

Professor des Gado looks excellent. Very important for SS patients to see rheumatologists who have expertise in the illness. We seem to have a number of them in New York and would hope patients are referred these centers. They have multi-disciplinary teams that include dermatologists and gastroenterologists.

I don’t think lupus-like is an official diagnosis but one used to help “differentiate” the UCTD a bit. My doctors don’t write it in the billing statement.

With me, all treatment is experimental. 😵 No good research.

[OldTed60 in reply to KayHimm]

Unfortunately the devolved nations eg Wales. Scotland and N.Ireland don’t have centres of excellence and nor are we able to get referrals on the NHS. There are many less Scleroderma and Myositis specialists in UK than Lupus and none in Scotland. My excellent rheumatologist is a Lupus specialist and covers a large area of Scotland - lucky for those with Lupus here as she’s wonderful. I know she’d understand my perspective on SAIRDS over LSD now. She takes guidance from Prof Denton by email on me but the others don’t and I’m her only SSc patient. Most see a rheumatologist who is less open minded and seems to prefer working with RA patients - I guess because there are so many treatments for them x

[Jaydhalia]

I'm at the beginning of the diagnostics after years of joint issues and mouth ulcers. All I can do is send you love and hope you take some comfort in not being alone ❤️

[Hoofprints]

I'm sorry you are having a tough time getting a diagnosis and help. As others have said, it's sadly not uncommon.

In addition to the good advice you have already had, can I suggest you check whether they have tested your C3 and C4 blood complements and also run a test for the anti-C1q antibody test?

I have a form of small vessel vasculitis that was missed for years until these blood tests were run and pieced together. (Urticarial vasculitis syndrome). I had similar symptoms to those you describe and a presentation like lupus, but without any of the typical positive blood tests.

I hope you get good support and clearer answers 🍀

[dg70]

I have negative ana and have lupus. The only positive test I got was double stranded dna. So that along with symptoms - joint pain, mouth sores, neck and sometimes face rash, constant fatigue, all got the Lupus diagnosis. Dsdna can also be negative at times and positive other as inflammation goes up and down. Took 10 years to get lupus/sjogrens diagnosis. I agree your rhuemy is saying the right thing. You have what looks like connective tissue disorder but you don't have enough markers to get a diagnosis of something concrete yet. Hopefully they'll start you on hydroxychloroquine anyway which after a few months should help a lot. Trouble is once you start hydroxy it lowers inflammation and now my dsdna is negative most of the time. There are more negative bloods Lupus/sjogrens patients out there than you think, Dr kaul at Tooting has recognised this recently in an article. On now 12 years on from first having regular bloods do I have a positive RF blood test. Be patient, work with your rheumy and hopefully things will manifest more clearly soon.

[Willow7733]

I have always had a high positive ANA, and it took over 24 years to be diagnosed. I seems to be a very hard disease to get answers for. But everyone is different. Wishing you luck in finding what is going on.

[Squirrel007]

Hi. I get rashes over my arms, lower legs, upper back and upper chest area. I occasionally get small rash areas on my face, but not obviously in the ‘butterfly’ pattern. My joints ache particularly when my rash is active. My ANA is also negative. It took about 3 years of my GP trying to work out what was going on, but after being referred to a derm consultant I was finally diagnosed with SCLE and also Urticaria Vasculitis. Like others have suggested, keep a photo diary and a few notes of how you feel ( and possible triggers). It’s been really useful for me.

Good luck