Giant Cell Arteritis: a rheumatological emergency

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By Dr Irwin Lim, Rheumatologist

In rheumatology, there are few super-urgent, “life or death” situations. I like it that way.

Most times when urgency is involved, it’s usually relates to a severe side effect or to a severe infection. Rarely, it relates to the manifestations of difficult disease processes, such as vasculitis (where there is inflammation of blood vessels causing a lack of blood supply to the organs the vessel supplies).

Last week, I took an urgent call from a local GP. She’s a very astute GP and when faced with this older gentleman presenting with headaches, fever, a feeling of being unwell as well as a lot of tenderness at his right scalp, she immediately suspected this relatively rare disease.

Temporal Arteritis

Temporal Arteritis

 

Giant Cell Arteritis (read more about GCA here).

This is an emergency situation and should be treated as such.

Giant Cell Arteritis can lead to sudden, permanent loss of vision and prompt treatment can prevent it.

We discussed his case over the phone and these were organised urgently:

  • A same-day appointment with an Ophthalmologist to examine the eyes and to arrange biopsy of that very swollen, painful temporal artery -> the diagnosis was confirmed with classic pathological changes on the biopsy.
  • Immediate commencement of high dose Prednisone -> He was given 75mg daily of Prednisone and his symptoms improved dramatically over the next few days.
  • Measurement of inflammatory markers -> the blood tests did show markedly elevated ESR and CRP, blood proteins which increase in this disease due to the vasculitis.

What about my role as a rheumatologist?

Well, the good news with this disease is that the use of corticosteroid, Prednisone, helps immensely. The problem is that the antidote is Prednisone. I’ve already written about the 2-edged sword that Prednisone can be (here’s a link to posts re corticosteroid). And this is definitely the case at these higher doses.

So, in this disease, the rheumatology management consists of:

  • Managing the gradual reduction/taper of the dose of Prednisone. Steroid reduction can be difficult. Many rheumatologists, including myself, use Methotrexate to help with this steroid taper. Methotrexate acts as a “steroid-sparing” agent.
  • Predicting and trying to limit or avoid the side effects of Prednisone, for example:
    • Checking the bone density and then trying to prevent steroid-induced osteoporosis/bone loss.
    • Anticipating the weight gain and effects on metabolic syndrome and instituting measures to try and help. Attention to diet and nutrition is important as well as exercise.
    • Anticipating the weakness of the proximal muscles (thighs, upper arms) and instituting appropriate maintenance and strengthening exercise.

All this needs to be done, while trying not to reduce Prednisone too quickly to avoid a flare in the disease, as a lack of control on the inflammation causes many unwanted symptoms, and in particular, increases that risk of sudden blindness.

Have you any experience of this condition?

Dr Irwin Lim is a rheumatologist and a director of BJC Health. You should follow him on twitter here.
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Can we use TNF inhibitors early then take them away?

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By Dr Irwin Lim, Rheumatologist

I think that increasingly rheumatologists would like to be able to use TNF inhibitor medications much earlier in the course of rheumatoid arthritis (RA).

These drugs are effective in RA and the hope would be that earlier use leads to higher rates of remission, lower rates of joint damage, and ultimately better long term outcomes.

There are some patients who come into my room with quite severe arthritis at presentation and the goal is clearly to get disease control as soon as possible.

Understandably, early use of these agents in many countries, including Australia, is not government funded. This is due to their high cost and the argument is that we, the taxpayers, just can’t afford it.

What may change this?

Well, we have been waiting for clinical trials to give us insights into strategic use of these medications.

In the November 6th issue of the New England Journal of Medicine, such a trial has been published (read the abstract here).

This 3-phase trial tried to test the value of using Etanercept/Methotrexate in combination in patients with early RA (“early” in this case, meaning those with onset of symptoms within 12 months of enrolment) and then taking away the medication.

306 patients from multiple different centres in Europe and Asia were enrolled. The design was as follows:

  1. Phase 1: treat early RA with weekly 50mg Etanercept plus weekly oral Methotrexate (MTX) for a total of 52 weeks.
  2. Phase 2: those who achieved low disease activity at week 39 and remission at week 52 were then randomised to one of 3 groups. These 3 groups were:
    1. half-dose Etanercept at 25mg weekly plus MTX, or
    2. MTX alone, or
    3. Placebo treatment only.
  3. Phase 3: At week 39 after randomisation into the phase 2 groups, all those who continued to have a good response were taken off all medications and followed up to week 65 (post-randomisation).
Accessed from NEJM App 6 Nov 14

Accessed from NEJM App 6 Nov 14

 

A complicated trial. Trying to answer some important questions.

I’m sure it will be analysed and debated by the experts in detail but the initial take-home messages are:

  • A high percentage of patients in phase 1 reached remission (70%) according to DAS28 criteria.
  • In the step-down therapy phase, phase 2,
    • 40 (63%) of 63 patients in the half-dose etanercept plus MTX group vs 26 (40%) of 65 patients in the MTX-only group vs 15 (23%) of 65 patients in the placebo group achieved DAS28 remission at weeks 24 and 39.
  • Of the patients who continued to have low disease activity who entered phase 3, and who had all their active medication stopped,
    • 44% of the phase 2 combination group continued to be in DAS28 remission at week 65 after randomisation vs 29% of the MTX-only group, vs 23% of the placebo group.
  • There were not any significant changes in the progression of damage on Xrays
Accessed from NEJM App on 6 Nov 14

Accessed from NEJM App on 6 Nov 14

 

So, this trial seems to provide evidence that once we achieve remission in an early group of rheumatoid patients using combination Etanercept/MTX therapy, we are then able to reduce and even withdraw the TNF inhibitor. In some, we can even withdraw MTX.

We still don’t know how to pick which patients will be able to have their medications stopped without the disease flaring.

So, in practice, rheumatologists will just taper therapy cautiously, monitor patients carefully, and restart treatment upon flare.

Dr Irwin Lim is a rheumatologist and a director of BJC Health. You should follow him on twitter here.
Arthritis requires an integrated approach. We call this, Connected Care. Contact us.
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Why would you let this arthritis occur to you?

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By Dr Irwin Lim, Rheumatologist

When I see patients walk in with this, I’m no longer shocked.

It occurs too commonly so the “wow” factor’s been lost.

Large 3rd finger tophus

Large 3rd finger tophus

Now, I feel sad. And that’s tinged with a continued disbelief that someone could allow these things to grow and to not try to treat the underlying cause.

These are Tophi.

Lumps of urate crystals deposited into soft tissues. They occur gradually, usually taking years to accumulate.

Multiple Tophi at the Elbow

Multiple Tophi at the Elbow

And they occur in patients who get repeated warnings. In the form of gout attacks (read about gout here).

These warnings aren’t subtle. There’s often acute pain and swelling. It’s meant to be quite severe with the patients usually finding it hard to walk and typically, they’re not shy in reaching for an anti-inflammatory.

If you had some skin lump somewhere on your visible body growing and growing, I would assume you’d want to know what it is, and as importantly, you’d want it removed. Fixed.

So, I still don’t understand the psyche of patients with tophaceous gout.

Even if you were to blame poor advice from the 1st doctor they consulted, you’d expect some more self-directed investigation to take place or you’d press for another opinion.

The reason I feel sad when I see this?

Well, it’s completely preventable. Effective gout medication, when used properly, in a compliant patient stops this occurring (read gout: the most curable joint disease….)

Even after the lumps have formed, it’s not too late. We can shrink them over time. We can reduce more damage from happening.

While I assume it’s unlikely anyone with gout is reading this piece, if you are, maybe you can help answer my question.

Dr Irwin Lim is a rheumatologist and a director of BJC Health. You should follow him on twitter here.
Arthritis requires an integrated approach. We call this, Connected Care. Contact us.
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Psoriatic arthritis: Beyond TNF inhibition

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By Dr Irwin Lim, Rheumatologist

Ghent, Belgium

Ghent, Belgium

 

The 9th International Congress of Spondyloarthropathies just took place in Ghent, Belgium.

World experts, both clinical and basic researchers working in the field of spondyloarthritis (that includes psoriatic arthritis and ankylosing spondylitis) congregate to share and update each other every 2 years.

As a clinician in private practice, rather than an academic or scientist, I would be in the minority attending such a meeting (read my reflections from the 8th Congress here). A lot of the basic science is difficult for me to absorb but there’s always still so much to learn and to contemplate.

With this blog’s audience in mind, I thought I’d write about a clear theme that has evolved over the last 4-5 years.

For too long, psoriatic arthritis (PsA) has really been managed in the same ways as rheumatoid arthritis (RA), eventhough RA & PsA can be so distinct in the way they present, the different tissues they affect, and the genetic susceptibility.

The medication therapy of PsA borrows so much from RA.

Methotrexate is still the drug most rheumatologists would use. In addition, we use Sulphasalazine and Leflunomide as traditional disease-modifying agents (DMARDs).

And when these traditional DMARDs aren’t effective enough, we can then use TNF-inhibitor therapy.

These agents are effective and they have proven to be a significant advance for those with Psoriasis (Ps) and PsA over the last decade or so, but there’s still a number of unmet needs:

  • A significant number of PsA patients have to switch using the medication over the years, through loss of effect or a side effect (as shown by DANBIO registry data)
  • Some patients get good skin response but their joints do not improve, or they get good joint disease improvement while the skin remains problematic. In some, the skin disease may paradoxically become more of a problem.
  • TNF inhibitors seem more effective for enthesitis, dactylitis, and nail disease compared with the traditional DMARDs, but there’s still room for improvement
  • When clinicians talk about effective medications, we mean that they reduce the extent of disease, and reduce the symptoms and signs, and thereby, how patients function in their day-to-day activities. What patients want is a cure. And we don’t have that yet with PsA.

To date, if you have PsA, and are in the group where TNF inhibitor therapy does not prove effective, there aren’t other good options.

That’s about to change.

The TNF pathway, a series of chemical signals involved in the immune process, is definitely disordered in Ps and PsA. This is why interfering and inhibiting this pathway does help.

But, our immune system is obviously very much more complicated and dependent on many other chemical pathways and signals.

Well, it has become increasingly clear that the IL23/IL17 pathway is critical in Ps and PsA. This is a point of differentiation between the spondyloarthropathies and RA.

This IL23/IL17 pathway is also complicated, with series of signals regulating a whole host of different chemicals involved in the immune process. It is the imbalance or the overamplification of these signals which lead to disease.

There are now numerous attempts to rein in this imbalance by targeting different components of this IL23/IL17 axis, at multiple sites both upstream and downstream. These include:

  • Ustekinumab, which blocks the p40 subunit molecule, then affecting IL12 and IL23
  • Secukinumab, an IL17A inhibitor
  • Brodalumab, which blocks the IL17A receptor
  • a number of dedicated IL23 inhibitors
  • a combination antibody that can block both TNF & IL17
  • And many others….

Results have been very encouraging.

I wanted to give those of you with PsA which may not be as controlled as we would like, cause for optimism. The future does look bright.

Dr Irwin Lim is a rheumatologist and a director of BJC Health. You should follow him on twitter here.
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How Aussie Rheumatologists are using Ultrasound

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Our clinic's ultrasound setup

Our clinic’s ultrasound setup

 

By Dr Irwin Lim, Rheumatologist

Another sunny, glorious Sydney weekend.

I spent it indoors. Being upskilled.

With a bunch of 20+ rheumatologists from around Australia discussing how ultrasound is used to enhance our practices. We also brought in many helpful patients who were happy to allow us to scan their various body parts to educate and teach each other.

This cohort of Aussie rheumatologists are increasingly using an ultrasound machine at point-of-care.

By point-of-care, I mean that we use the technology to enhance our patients experience at our rooms and during our consultations.

The rheumatologist will be there as the ultrasound is performed. In many circumstances, this has a clear advantage over sending a patient away for the scan to be performed at St.Elsewheres.

The rheumatologist already has an in depth knowledge of the complaint, has already physically examined the patient, and has a clear clinical question to hopefully be answered using the ultrasound scan.

I have written about the reasons I think ultrasound is useful in my hands (read it here).

And, it’s a win for patients and a win for us, rheumatologists.

The range of clinical situations my colleagues are finding this technology helpful for them and their patients is large, and include:

  • Assessing the degree of disease involvement. For eg, in rheumatoid arthritis, working out the extent of disease.
  • Assessing the degree of damage that has already occurred in inflammatory arthritis. For eg, we may look for erosions as these predict more aggressive disease.
  • Trying to help make a diagnosis in cases where it’s not otherwise clear. For eg, trying to differentiate between osteoarthritis and a seronegative inflammatory arthritis, trying to help make the diagnosis of psoriatic arthritis, looking for classic changes of gout.
  • Helping to make clinical decisions. For eg, attempting to judge how active the disease still is before modifying medication therapy.
  • Assessing sporting injury or mechanical problems. Commonly, we look at the rotator cuff or the gluteal (buttock) tendons or the wrist or ankle or  elbow tendinopathy.
  • Assessing various lumps, bumps and a variety of swelling. Is it fluid-filled? Is it solid? Should we worry?
  • Guiding cortisone injections to various parts of the body (watch my shoulder injection video)
  • Assessing vasculitis (autoimmune inflammation of blood vessels). I’ve not learned to do this yet but a nice case of temporal arteritis was presented.
  • Assessing nerve problems, commonly carpal tunnel syndrome with the median nerve at the wrist.
  • Helping patients understand their disease better. Some patients do seem to appreciate their problem more if they can watch on a screen what is happening to their joints, tendons or other tissues, rather than just accepting what their doctor may have told them after the usual physical examination.

It’s still early days for ultrasound use in the Australian rheumatology clinic but the tide seems to be turning. It’s a skill that more and more of us are developing.

Could you share your experience of this?

Dr Irwin Lim is a rheumatologist and a director of BJC Health. You should follow him on twitter here.
Arthritis requires an integrated approach. We call this, Connected Care. Contact us.
This blog focuses on arthritis, healthcare in general, and Connected Care. Please subscribe to keep in touch:
 
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