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giant cell arteritis

Diseases and Conditions When to see a rheumatologist

Signs and symptoms of polymyalgia rheumatica

May 22, 2018
Signs and symptoms of polymyalgia rheumatica

Polymyalgia rheumatica is a systemic inflammatory disease that almost exclusively affects people aged 55 and above.  How this disease occurs and why it more-or-less exclusively affects the elderly is poorly understood.  Like most autoimmune diseases, it’s thought that something in the environment be it a virus, bacteria, or in the case of polymyalgia rheumatica seasonal variation, triggers autoimmunity in a genetically susceptible person.

The hallmark symptoms of polymyalgia rheumatica include severe pain and stiffness involving the shoulder and or pelvic muscles.

However, it’s very important to understand that polymyalgia rheumatica is a diagnosis of exclusion.  It’s important to rule out other conditions before making this diagnosis.

Polymyalgia rheumatica statistics

Polymyalgia rheumatica is the second most common autoimmune condition.  It affects 2.4% of women and 1.7% of men.  It can affect people as young as 50 years, but mainly affects people aged 60 years and above. Finally, Caucasians are mainly affected.  It very rarely affects African Americans, Asians, or people of Hispanic descent.

What are the signs and symptoms of polymyalgia rheumatica?

People suffering from polymyalgia rheumatica typically describe a slow and insidious process of worsening stiffness and pain involving their shoulders and their pelvis.  Sometimes the process is quick but typically it progresses over 3 months.  Usually there is a dramatic loss of function.  This includes difficulty getting up from a seated position, difficulty getting out of bed, difficulty dressing.

“I feel 20 years older than I am”.

What are some other symptoms of polymyalgia rheumatica?

Some other symptoms include fevers, chills, drenching night sweats, and unintentional weight loss. Importantly, giant cell arteritis, a type of vasculitis, can occur in about 15% of people suffering from polymyalgia rheumatica.

People suffering from giant cell arteritis typically report very similar symptoms, as well as the following:

  • Recent onset headache
  • A cramping sensation while chewing
  • Change in vision
  • A recent change in hearing, taste, as well as smell
  • Tenderness of the scalp

I’ll go into this later, but people suffering with giant cell arteritis usually do NOT improve with 20 mg of prednisone, whereas, people with pure polymyalgia rheumatic do.

Do people with polymyalgia rheumatica get arthritis?

The simple answer is yes they can.  About 30% of people with polymyalgia rheumatica develop inflammatory arthritis that can look a lot like rheumatoid arthritis.  However, unlike rheumatoid arthritis, this type of arthritis does not cause permanent damage.

How do you differentiate polymyalgia rheumatica from rheumatoid arthritis?

This can get very tricky and sometimes can take months of observation to finally figure it out.  However, here are some distinguishing features that can help:

  • Absence of rheumatoid factor and other rheumatoid arthritis antibodies
  • Lack of involvement of small joints
  • Lack of joint damage

What are some differential diagnoses in polymyalgia rheumatica?

Diagnosis Features
Fibromyalgia Tender points and normal inflammation
Underactive thyroid (hypothyroidism) Normal thyroid tests, normal inflammation
Depression Normal inflammation
Osteoarthritis, rotator cuff, frozen shoulder Abnormal x-rays and MRI, normal inflammation
Myositis Mainly weakness, elevated muscle enzymes, abnormal nerve conduction test
Infection Clinical suspicion and positive cultures
Cancer Clinical suspicion with positive workup
Rheumatoid arthritis Positive rheumatoid factor, small joints involved
Spondyloarthritis History of psoriasis or inflammatory bowel disease[1]

How is polymyalgia rheumatica diagnosed?

The diagnosis of polymyalgia rheumatica is predominantly clinical.  It’s very important to exclude other potential diagnoses as listed above.  Levels of inflammation are typically very high but can be normal in select cases.

The American College of Rheumatology and EULAR have established criteria, but these are not the greatest in the world.  They have a sensitivity of 68% and specificity of 78%.  Finally, sometimes ultrasound studies and a PET scan can help as well.

How is polymyalgia rheumatica treated?

Steroids.  People suffering from polymyalgia rheumatica often describe a dramatic resolution or improvement of the symptoms on 15 to 20 mg of prednisone a day.  By dramatic I mean it typically take less than 24 hours for symptoms to resolve.  In about 25% of cases, the response will not be dramatic and will take a few more days or a higher dose of prednisone.

Unlike other rheumatic conditions, prednisone must be tapered very slowly in polymyalgia rheumatica.  It’s not uncommon for a person to be on steroids for over two years.  At times, we need to taper by 1 mg every month or two!

My best friend, my worst enemy

Prednisone is both your best friend and worst enemy.  Unfortunately, it remains the mainstay of therapy.  While on high doses of steroids for a prolonged period of time, it’s very important to remain active and pay attention to possible side effects such as osteoporosis, diabetes, heartburn/stomach ulcers, and infection.  Not to mention an ever expanding waist line.

Regular weight-bearing exercise, vitamin D supplementation, as well as keeping up-to-date with vaccines (flu shot, pneumonia shot, shingles shot) are essential.

Conclusion

If you think you or one of your loved ones suffers from polymyalgia rheumatica, I encourage you to make an appointment with your local rheumatologist.

Medical Disclaimer

This information is offered to educate the general public. The information posted on this website does not replace professional medical advice, but for general information purposes only. There is no Doctor – Patient relationship established. We strongly advised you to speak with your medical professional if you have questions concerning your symptoms, diagnosis and treatment.

References

Rheumatology Secrets, 3rd edition

UpToDate

[1] Adapted from Rheumatology Secrets, 3rd edition

Diseases and Conditions

Tocilizumab: the new wonder drug for giant cell arteritis

June 7, 2017
People aged 50 years and above can develop giant cell arteritis

On May 22nd 2017 the FDA approved weekly subcutaneous tocilizumab (trade name Actemra®) to treat giant cell arteritis, a type of vasculitis that can cause blindness and in some cases death.  Why is this so important and how does this change everything?  The answer is simple.  Previously there were no effective treatments.  Rheumatologists used steroids like prednisone at high doses for months on end.  Many people would get lot’s of side effects due to the steroids and even this did not guarantee success.  Typically it takes many years for a medication to get FDA approval.  Although it did take more than a year to get approval, the process in this particular situation was fast-tracked.  Before I get into how we got to where we are today, let’s start with some background.

What is giant cell arteritis?

Giant cell arteritis is a type of large vessel vasculitis that tends to affect people aged 50 years and above.

Pay attention to the spelling, a-r-T-E-r-i-t-i-s. This is completely different from a-r-T-H-r-i-t-i-s.

Giant cell arteritis is an autoimmune disease that inflames blood vessels not joints.  More specifically, it inflames the aorta and the branches of the aorta.  Sometimes it’s also called temporal arteritis, but that’s not a good name for it because the temporal arteries are one type of artery that giant cell arteritis can affect.  We call this autoimmune disease giant cell arteritis because if you biopsy an artery you will find “giant cells” also called “granulomatous inflammation”, when you look at it under a microscope.  In fact, this is one way rheumatologists make the diagnosis.

This is an image of the human arterial system. Giant cell arteritis can affect any artery coming off the aorta

By LadyofHats, Mariana Ruiz Villarreal [Public domain], via Wikimedia Commons

What are the symptoms of giant cell arteritis?

Giant cell arteritis can present in many ways.  It really depends on the affected blood vessel(s).  If there is vasculitis in a temporal artery, then people tend to have a bad headache and a cramping pain when chewing food.  Maybe the blood vessels supplying the ears has vasculitis? This can cause a change in hearing and vertigo.  If the blood vessels supplying the eyes is affected, then it can cause blindness.  In some cases, people aren’t even aware of it.  They get a CT scan for some unrelated issue and the radiologist finds a large aortic aneurysm.  Giant cell arteritis is a condition that causes inflammation throughout the body, so many people present with fevers, drenching night sweats, and weight loss.

One of the most common presentations of giant cell arteritis is polymyalgia rheumatica.  Sometimes doctors simply call it “PMR”.  While 40% of people with giant cell arteritis have polymyalgia rheumatica, 10-20% of people with polymyalgia rheumatic develop giant cell arteritis.  Polymyalgia rheumatica is an autoimmune disease that causes muscle pain and stiffness in the shoulders, neck, hips, and thighs.  Finally, like giant cell arteritis, it affects people aged 50 years and above.

How do you diagnose giant cell arteritis?

There are many ways to diagnose giant cell arteritis.  First of all, blood tests like the CRP and the sed rate are usually very high.  These are tests that measure the amount of inflammation in your body.   Ideally you want to have a biopsy of the affected blood vessel but sometimes that’s not possible.  The biopsy should show giant cells but this only occurs in about 50% of cases so having a negative biopsy does not necessarily completely exclude disease.  When a biopsy is not possible, certain imaging studies can help like ultrasound, CT angiography, and PET scans.

How is giant cell arteritis treated?

Steroids, steroids, and more steroids.  If a doctor suspects that someone has giant cell arteritis, they immediately start treatment with high doses of steroids.  This happens even before the workup!  Once the diagnosis is firmly made the steroids are slowly tapered.  This happens over months.  It’s not uncommon to still be on steroids for YEARS after the diagnosis.  In many cases, the vasculitis returns.  This can be very frustrating and upsetting.  Rheumatologists have tried to treat people with medications like methotrexate in addition to steroids, but these haven’t really worked.

That is until now…

How it began

In 1990 researchers tested the blood of 15 people who had untreated giant cell arteritis.  They found high levels of a cytokine called interleukin 6 (IL-6) in their blood.  After treatment with steroids, their interleukin 6 levels decreased except for a few people.  Which is unsurprising since many people with giant cell arteritis relapse.

At that time, we didn’t have any medications that specifically blocked interleukin 6.

Flash forward to 1997.  A company based in Japan called Chugai Pharmaceuticals began research on tocilizumab to treat rheumatoid arthritis.  Tocilizumab is biologic humanized monoclonal antibody that blocks interleukin 6. Then in 2003 Genentech co-developed the medication.  Genentech’s tocilizumab is called Actemra®. Finally in 2010 the FDA approved Actemra® for to treat moderate to severe rheumatoid arthritis.

Giant cell arteritis and tocilizumab

Now remember how researchers found high levels of interleukin 6 in the blood of people with giant cell arteritis? What would happen if you treated someone who has giant cell arteritis with tocilizumab?  Would they go into remission?  Maybe you could taper off steroids more quickly?  That’s exactly what some Swiss scientists showed in 2011.  They treated 5 people with giant cell arteritis with tocilizumab.  All of them went into remission and all of them were able to taper off the steroids quickly.  The elevation and blockade of interleukin 6 appeared to be especially relevant for the treatment of giant cell arteritis.  But this was a case series with a very short follow-up time.  Was this a fluke or were they onto something?

In 2012, researchers started a larger phase 2 study.  This time they studied 30 people and they randomized them to either receive tocilizumab+prednisone or placebo+prednisone. The results were favorable:

  • 85% of the people who received tocilizumab and 40% of the people who received placebo went into remission by week 12.
  • 15 % of the people who received tocilizumab relapsed, where 80% of the people who received placebo relapsed by week 52.
  • People who received tocilizumab on average stopped prednisone 12 weeks in advance compared to people who received placebo.
  • 35% of people who received tocilizumab had a serious side effect, where 50% of people who received placebo had a serious side effect.

The last act

At last year’s American College of Rheumatology conference, Dr. John Stone presented data from the GiACTA trial, which was a randomized, double-blind, placebo-controlled trial.  This was a phase 3 study.  So they looked at more people from various locations.  There were 251 people placed into 4 different groups.

  • A short course of prednisone (26 weeks) + a weekly subcutaneous placebo
  • A long course of prednisone (52 weeks) + a weekly subcutaneous placebo
  • A short course of prednisone + weekly subcutaneous tocilizumab
  • A short course of prednisone + every other week subcutaneous tocilizumab

The results

  • 56% of people who received weekly tocilizumab achieved and stayed in remission after 12 months.
  • 53.1% of people who received every other week tocilizumab achieved and stayed in remission after 12 months.
  • 14% of people who received a short course prednisone + placebo were in remission after 12 months (p <0.0001).
  • 17.6% of people who received a long course of prednisone + placebo were in remission after 12 months (p ≤ 0.0002).
  • People who received tocilizumab received about half as much prednisone overall.
  • Adverse events were about the same in all groups and there were no deaths or vision loss.

The conclusion

Due to these extraordinary results and the dire need for effective treatment for giant cell arteritis, the FDA approved weekly subcutaneous tocilizumab.  I don’t know about you, but I’m very excited about this!  Finally a medication that works!  Mind you, it doesn’t work in every single case but this is definitely is a step forward.  And to add icing on the cake, although tocilizumab doesn’t eliminate the need for steroids, it does drastically decrease the total amount people get…another big plus.

To continue learning more about rheumatology and how to read research articles from their original source, please read on!

References

https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm559791.htm

Rheumatology Secrets, 3rd edition

Dasgupta B, Panayi GS. Interleukin-6 in serum of patients with polymyalgia rheumatica and giant cell arteritis. Br J Rheumatol. 1990 Dec;29(6):456-8.

https://www.drugs.com/history/actemra.html

Seitz M, Reichenbach S, Bonel HM, Adler S, Wermelinger F, Villiger PM. Rapid induction of remission in large vessel vasculitis by IL-6 blockade. A case series.Swiss Med Wkly. 2011 Jan 17;141:w13156. doi: 10.4414/smw.2011.13156.

Villiger PM, Adler S, Kuchen S, Wermelinger F, Dan D, Fiege V, Bütikofer L, Seitz M, Reichenbach. Tocilizumab for induction and maintenance of remission in giant cell arteritis: a phase 2, randomised, double-blind, placebo-controlled trial.Lancet. 2016 May 7;387(10031):1921-7. doi: 10.1016/S0140-6736(16)00560-2. Epub 2016 Mar 4.

Stone JH, Tuckwell K, Dimonaco S, Klearman M, Aringer M, Blockmans D, Brouwer E, Cid MC, Dasgupta B, Rech J, Salvarani C, Spiera RF, Unizony SH, Collinson N. Efficacy and Safety of Tocilizumab in Patients with Giant Cell Arteritis: Primary and Secondary Outcomes from a Phase 3, Randomized, Double-Blind, Placebo-Controlled Trial [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). http://acrabstracts.org/abstract/efficacy-and-safety-of-tocilizumab-in-patients-with-giant-cell-arteritis-primary-and-secondary-outcomes-from-a-phase-3-randomized-double-blind-placebo-controlled-trial/. Accessed May 29, 2017.