Diseases and Conditions Self-Injection Videos

How to inject Humira, Enbrel, Simponi, and Cimzia

August 28, 2017

Humira®, Enbrel ®, Simponi ®, and Cimzia ® are medications commonly prescribed for rheumatoid arthritis, psoriatic arthritis, psoriasis, and ankylosing spondylitis. All of these come in self-injectable pens or pre-filled syringes. You will be asked to inject these yourself or by a love one, in the comfort of your home. Today, we’re going to go over how to inject these self-injectable medications.

Preparing for your injection

Keep your medication stored in the refrigerator until use
- Before injecting medication, take the autoinjector out of the refrigerator.
- Allow it to warm up to room temperature.
Pick a place in your house that is clean and has room for your materials (such as the kitchen table).
Wash your hands thoroughly with either:
- Soap & water
- Hand sanitizer
Chose an area to inject – Thigh or Stomach.
- Chose an area that is intact and clear.
- It should not have any of the following:
  - Cuts
  - Scrapes
  - Bruises
  - Psoriasis patches
  - If you have extensive psoriasis, inject between patches
  - Moles
  - Scars
- Please rotate area each time you inject (shown in picture below).

By British Columbia Institute of Technology (BCIT). Download this book for free at http://open.bccampus.ca [CC BY 4.0 (http://creativecommons.org/licenses/by/4.0)], via Wikimedia Commons

Cleanse chosen area
- Cleanse chosen area with either of the following:
  - Alcohol swab
  - Alcohol and a cotton ball
- Use the chosen alcohol material to “swipe” area
  - Can either use a circular motion or wipe in “strips”
  - Allow the area to dry

The injection

Take off the white cap, observe the medication in the window to be sure that it is clear (no cloudiness or crystals.)
- You will see a small air bubble within the window, this is normal and will not cause harm when injecting
Press down firmly on the clean area of skin, so that the pen is flush with the skin (90-degree angle).
- The pen needle will not eject unless pressed firmly to skin

For Cimzia® and other medications that come in prefilled syringes

Pinch the skin around the injection site and insert the needle at a 45-degree angle

Press in the plunger slowly

You may notice the plunger is hard to press this is due to the size of the medication, be sure to continue to inject slowly to administer all medication

Press button to inject the medication.
- You may feel a slight pinch as the needle enters your skin, and tingling as the medication is administered
- If you have trouble pressing the button try lifting the pen off your skin, and repressing the pen firmly to the area
Hold for 15 seconds.
- Window will become colored (yellow) but continue to hold dose for at least 15 seconds to ensure that all medication is administered

What to do after the injection

Lift the pen up from skin and place the whole pen into the sharps container.
- If you do not have a sharps container available, contact your pharmacy/doctor’s office about obtaining one
  - In the meantime, you may use an old coffee container with a lid
- Some hospitals take full Sharps Containers for disposal. Here at the office we do not. Contact your pharmacy for more information about the disposing of your Sharps Container.
Discard remaining materials in the trash (cap, alcohol swabs, etc.)

If you have any concerns about your medication (e.g., excessive pain, swelling, redness bruising, bleeding, fever, breathing problems), please contact your rheumatologist.

For more information

Jessica Farrell, PharmD. Clinical Pharmacist, The Center for Rheumatology/Associate Professor, Albany College of Pharmacy and Health Sciences

With the help of Autumn Koniowka. Doctor of Pharmacy Candidate Class of 2018, Albany College of Pharmacy and Health Sciences, and Megan Phillips. Doctor of Pharmacy Candidate Class of 2018, Albany College of Pharmacy and Health Sciences.

A special thanks to Tammy Garren, PhD. Instructional Designer, Center for Innovative Learning, Albany College of Pharmacy and Health Sciences.

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.

1 Comments

Diseases and Conditions Featured

Guide to living with rheumatoid arthritis: Part 2

August 2, 2017

People that suffer from rheumatoid arthritis need to exercise on a daily basis, eat healthy, and find ways to reduce stress in their lives

If you missed Part 1 of Guide to living with rheumatoid arthritis please follow the link. In part 1 we covered the basics: what is rheumatoid arthritis, the cause, symptoms, diagnosis, and treatment. In part 2, I’ll be covering how rheumatoid arthritis (RA) can affect your day-to-day living, habits that worsen RA, exercise, food, and stress reduction techniques. Without further adieu, here is Part 2 of the Guide to living with rheumatoid arthritis. I hope you enjoy!

How will rheumatoid arthritis affect my life?

Rheumatoid arthritis changes your life. Depression, anxiety, feeling overwhelmed, these are all emotions that are perfectly natural when you get diagnosed with rheumatoid arthritis or any chronic illness. These should improve with time as you learn more about the illness and with the help of family and friends.

The Arthritis Foundation is a national non-profit organization who’s mission is to help, “conquer everyday battles through life-changing information and resources, access to optimal care, advancements in science and community connections. Our goal is to chart a winning course, guiding families in developing personalized plans for living a full life – and making each day another stride towards a cure. We also publish Arthritis Today, the award-winning magazine that reaches 4.2 million readers”.

They definitely are a good group to check out and they have chapters across the country.

The physical aspect

Other than, psychological and emotional impact of the illness, there is also the physical part. There will be good days and bad days. It’s very important to work closely with your rheumatologist when you suffer from RA. It is of utmost importance to go into remission as quickly and safely as possible. There are many medications used to treat RA. Some may work for you and some may not. By working together, you can help your rheumatologist tailor the best possible treatment plan for you.

The goal is to get you back doing what you used to do with the least amount of limitations as possible.

Be aware, even in the best of situations, expect flares. Stress, infections, the weather, and hormonal changes can precipitate a flare. Another goal is to make flares a rare event. Not the norm.

The financial aspect

Finally, although no one likes to talk about it, another important impact that rheumatoid arthritis has on your life is its impact on your wallet. Rheumatoid arthritis is expensive. Frequent doctor’s appointments. Not only do you need to see your rheumatologist on a regular basis, but you may also need to see other specialists such as an ophthalmologist, nephrologist, pulmonologist, etc. So many co-pays.

Medication costs can get very expensive. Even with health insurance the out-of-pocket costs can be enormous. In my clinic, this is a daily problem. In fact, I’m lucky to work in a practice that has a dedicated patient advocate that helps my patients find solutions to get access to care without breaking the bank. I call her my “health insurance whisperer”. She kindly agreed to impart some of her knowledge in Part 3 of Guide to Living with Rheumatoid Arthritis. It’s going to be a real treat!

Other costs

These medications tend to have a long list of potential side effects. These require routine bloodwork. Yet another co-pay.

Lost work days. The less you work, the less you make.

Time. One of the most, and arguably THE most important financial costs.

I do realize that I seem to be painting a very bleak picture, but I want to make it very clear that YOU are in control. Your experience with RA will depend on how much you let it affect you. It will change you for sure but not conquer you.

Will I be able to work? How do I tell my boss?

I won’t lie. Rheumatoid arthritis can lead to work disability, abseeteeism, and presenteeism (at-work productivity loss) at a high cost to you but also to your employer. You’ve had the conversation with your family and friends but now it’s time to tell your boss.

First, you’re not legally required to disclose your RA to your employer. However, as an employer myself, I would appreciate it if my employee would disclose this information. What if your job requires heavy lifting or standing around for a very long time? Maybe I can help you and re-arrange your work duties to better accommodate you? Maybe you need a better chair or a better mouse? Every situation is different. Not everyone with RA has horrible disease but on the flip side not everyone’s employer is accommodating.

There’s also the situation with doctor’s appointments. Most people with RA see their rheumatologist every 3 to 6 months for regular checkups. Some people may need medications that only come as infusions. These infusions are given in clinic and last between 1.5 hours to half a day. That’s more time off work.

By informing your employer, you are entitled to certain legal rights, as outlined in the Americans with Disabilities Act and the Family and Medical Leave Act. For more information, please click on the following link[1].

Ultimately, the choice to tell your boss or not is yours. You are in control.

What habits worsen rheumatoid arthritis?

Smoking

At this point, I hope everyone understands that smoking is a terrible habit associated with a multitude of negative health outcomes. But did you know that smoking can also predispose people to develop antibody positive rheumatoid arthritis (seropositive)?

Costenbader et al. prospectively studied 103 818 women from 1976 to 2002. Of those women 680 developed rheumatoid arthritis. The researchers found that both past and current cigarette smoking was associated with a 40% increased risk of developing seropositive rheumatoid arthritis. Here are some of the other findings:

Increasing duration and intensity of cigarette smoking increases the risk of RA.
Greater than 10 pack years of smoking increases the risk of RA in a dose-dependent way.
It takes about 20 years of smoking cessation for the risk to return to the “never smoker” category.[2]

What if you already have rheumatoid arthritis?

Does smoking have any impact on active rheumatoid arthritis? Anecdotally, it’s a lot more difficult to control rheumatoid arthritis when someone smokes cigarettes. We end up having to cycle through more medications and use more medications at high doses. However, when you think about it, it makes logical sense.

The current paradigm of RA pathogenesis is that people with certain genetic risk factors first are exposed to environmental triggers that cause local inflammation. These people then produce autoantibodies and with time some of these people go on to develop full-blown rheumatoid arthritis. Cigarette smoking is thought to be one of these triggers by causing local inflammation in the lungs[3].

If someone already has RA and continues smoking, well that’s like trying to put out a fire with gasoline. You’re trying to put out the fire with DMARDs but you’re also adding to the fire by smoking cigarettes.

Another great reason to stop smoking when diagnosed with RA, is the fact that rheumatoid arthritis is well-known to increase the risk of cardiovascular disease.[4] Other traditional cardiovascular risk factors include high blood pressure, high cholesterol, diabetes, obesity, and physical inactivity. This brings me to my next point, “not moving”.

Not moving

Sedentary behavior is defined as any waking behavior characterized by an energy expenditure of ≤ 1.5 METs and a sitting or reclining posture. It is associated with poor health outcomes in rheumatoid arthritis. Although adopting a sedentary lifestyle won’t necessarily directly cause increased disease activity, this lifestyle can worsen muscle density, functional disability, bone mass, and cardiovascular risk.[5]

Everyone knows that life can get really busy sometimes, and going out to the gym sometimes is the last thing on your “to-do” list. Believe me, I don’t have a gym membership because getting into my car, driving to the gym, changing into workout gear, hopping on a boring treadmill, changing back into my regular clothing, and driving back home is the last thing I want to do after a long day at work.

But being active doesn’t necessarily mean going to the gym. A 30 minute walk around your neighborhood 5 days week is enough. Does walking sound boring? How about catching up on your reading while strolling about. Amazon has a ton of audiobooks via Audible. This is NOT affiliate marketing. I simply use this service on regularly during my daily walks. I walk at least 30 minutes a day AND read about a book a week. Win-win!

Now if you tend to forget to get active and need a little nudge to get you going, check out these free IFTTT recipes I made to help you stay active 30 minutes a day. You need to have a Fitbit, cell phone, and an IFTTT account (which is free) for it to work.

Periodontal disease

In recent years researchers have found a correlation between rheumatoid arthritis and periodontal disease more specifically Porhyromonas gingivalis.[6] Now the question is whether treatment of periodontal disease have any effect on rheumatoid arthritis? The answer is yes. A recent systematic review meta-analysis showed that there was a reduction in DAS 28 (this is a scale that we use to measure RA activity) in patients with rheumatoid arthritis after periodontal treatment.[7] Interestingly, treatment with DMARDs does not improve periodontal disease in people with rheumatoid arthritis.[8]

To keep up with good oral health, the American Dental Association (ADA) recommends brushing your teeth twice a day for two minutes and flossing once a day. They also recommend eating a healthy diet, limiting snacks, and of course, regular dental check-ups.[9]

Which exercises are safe with rheumatoid arthritis?

This is a very frequent question. What exercises are “good” and which exercises are “bad”. Personally, I don’t think that there are any good or bad exercises for rheumatoid arthritis. What really matters is whether you are you moving. You should try being active for about 30 minutes a day. Choose an activity that you enjoy and stick with it. If someone tells you swimming is excellent for RA but you really don’t like swimming, chances are you won’t stick with the program. Be active in a way that brings you joy. Here are some examples.

Walking
Swimming
Yoga
Tai chi
Jogging
Rowing
Etc

Have fun!

What types of food should I eat with rheumatoid arthritis?

This is a very common question yet there is very little quality evidence-based research about this topic. Most studies with robust quality controls focus on cardiovascular disease as opposed to rheumatoid arthritis. There is very little quality evidence to support a specific diet for RA.

What is Epigenetics?

Everyone is born with genes. Some of these genes are active and some remain dormant. Your genotype is the entire makeup of your genes. Your phenotype is the result of how your genetic material is expressed. For example, you may have the genes for blue eyes and brown eyes. If the genetic material for brown eyes is dominant, you’ll have brown eyes.

This is where it gets really interesting. Over the course of your lifetime, some of your genes are turned on and off. This is influenced by factors like aging, the environment, and lifestyle. Epigenetics is the study of how genes are turned on and off based on external influences.

Epigenetic changes can be good but can also cause harm. We think that some of these changes can result in autoimmune diseases. It’s important to remember that epigenetics is in its infancy. Researchers still are not 100% sure how this happens, let alone, how to specifically manipulate the environment to cause favorable epigenetic change.

What types of foods are good for people with rheumatoid arthritis?

First, listen to your body. If you find that your arthritis worsens when you eat nightshades, then stop eating nightshades. Look for patterns. Journaling is helpful in finding these patterns.

Since there isn’t great data supporting a specific diet for RA, I typically recommend a diet that is good for overall health. For this I recommend adhering to the principles of the Blue Zone Project, more specifically the Power 9. The Blue Zones Project initially began as a research project funded by the National Geographic. They sought to find regions in the world where people tend to live to 100 years of age and be healthy. They identified 5 zones:

Ikaria, Greece
Okinawa, Japan
Ogliastra region, Sardinia
Loma Linda, California
Nicoya Peninsula, Costa Rica

All these regions have very different cultures and geography, yet they all live by these 9 common attributes. They called them the Power 9.

Move Naturally

People that live to 100 years don’t necessarily run marathons or go the gym. They are always on the go and they move naturally. For example, they tend a garden, they walk to the market, and they use stairs instead of the elevator.

Purpose

People that live in the Blue Zones live with purpose. They wake up every morning, and they know “why I wake up in the morning”. Having a clear purpose in life can add an extra 7 years of life expectancy.

Down Shift

We all know that stress can cause inflammation. I often see people in my clinic who’s rheumatoid arthritis was in perfect control until something really bad happened, like a divorce, job loss, or a death in the family. Chronic stress leads to chronic inflammation. People in the Blue Zones develop daily habits to help reduce stress.

80% Rule

The Japanese have a saying “Hara hachi bu”. This is a mantra that Okinawans say before every meal, reminding them to stop eating when they feel about 80% full. There is a delay between feeling full and actually being full. When you feel 80% full, you are actually full. So if you stop eating when you feel full, you are overeating. People living in the Blue Zones tend to eat their largest meal at breakfast and their smallest meal at dinner.

Plant Slant

Although not all regions of the Blue Zones eat meat, their diets all mainly consist of fresh veg and beans. Lot’s of beans: fava, soy, lentils, etc. They eat meat very sparingly and servings are small, “about the size of a deck of cards”.

Wine @ 5

Thank goodness for this one! People in the Blue Zones, except for Adventists, drink alcohol moderately and regularly. Typically, they drink 1-2 glasses of wine per day with friends and family at the end of the work day. They found that people who drink regularly and moderately tend to live longer than those who don’t.

Belong

Almost all people who live until 100 tend to belong to some sort of faith-based community. They found that attending a service 4 times a month can add up to 4 – 14 years of life expectancy.

Loved Ones First

People living in Blue Zones tend to live close to their families. It’s common to have children, parents, and grandparents living under the same roof. They also tend to commit to a life partner.

Right Tribe

People in the Blue Zones keep strong social networks. Not only are these social strong, but they also foster healthy behaviors. Women in Okinawa create “moais” early on in life. These are groups of 5 friends that are completely committed to each other for life.

Does stress affect rheumatoid arthritis?

Psychological stress can trigger RA flares. A recent study looked at 274 people with RA. They found that the most frequent reasons for joint symptoms were psychological stress/mood disorder (86.1%) followed by infection.[10] Other studies have also shown similar [11] findings and I do regularly see this in clinic.

Techniques to reduce stress

Everyone experiences stress in a different way and everyone has different stress thresholds. When it comes to the best way to reduce stress in people with rheumatoid arthritis, well the data is very poor. There are a many studies that look at different methods but they have poor quality standards.

The Mayo clinic has a page on their website dedicated to stress management and techniques[12]. It’s quite good. Some techniques include:

Autogenic relaxation
Progressive muscle relaxation
Visualization
Deep breathing
Massage
Meditation
Tai chi
Yoga
Biofeedback therapy
Music and art therapy
Aromatherapy
Hydrotherapy

Try a few and see what works for you. Remember, consistency is key.

Conclusion

Thus concludes Part 2 of a Guide to living with rheumatoid arthritis. In part 3 I’ll be covering the financial aspect of rheumatoid arthritis with some help from my “health insurance whisperer”. Since you are reading this article, there’s a good chance you just were diagnosed with rheumatoid arthritis. Now the question that I know must be on your mind, “How am I going to pay for these expensive medications?”

Medical Disclaimer

References

[1] https://www.dol.gov/general/topic/benefits-leave/fmla

[2] Costenbader KH, Feskanich D, Mandl LA, Karlson EW. Smoking intensity, duration, and cessation, and the risk of rheumatoid arthritis in women. Am J Med. 2006 Jun;119(6):503.e1-9.

[3] Sparks JA, Karlson EW. The roles of cigarette smoking and the lung in the transitions between phases of preclinical rheumatoid arthritis. Curr Rheumatol Rep. 2016 Mar;18(3):15. doi: 10.1007/s11926-016-0563-2.

[4] Balsa A, et al. Prevalence of comorbidities in rheumatoid arthritis and evaluation of their monitoring in clinical practice: the Spanish cohort of the COMORA study. Reumatol Clin. 2017 Jul 12. pii: S1699-258X(17)30134-1. doi: 10.1016/j.reuma.2017.06.002. [Epub ahead of print].

[5] Fenton SA, Veldhuijzen van Zanten JJ, Duda JL, Metsios GS, Kitas GD. Sedentary behaviour in rheumatoid arthritis: definition, measurement and implications for health. Rheumatology (Oxford). 2017 Apr 7. doi: 10.1093/rheumatology/kex053. [Epub ahead of print]

[6] Azzi L, et al. Periodontal microbioma and rheumatoid arthritis: The role of Porhyromonas gingivalis. J Biol Regul Homeost Agents. 2017 Apr-Jun;31(2 Suppl 1):97-103.

[7] Calderaro DC, Correa JD, Ferreira GA, Barbosa IG, Martins CC, Silva TA, Teixeira AL. Influence of periodontal treatment on rheumatoid arthritis: a systematic review and meta-analysis. Rev Bras Reumatol Engl Ed. 2017 May – Jun;57(3):238-244. doi: 10.1016/j.rbre.2016.11.011. Epub 2017 Jan 4.

[8] Ayravainen L, Leirisalo-Repo M, Kuuliala A, Ahola K, Koivuniemi R. Meurman JH, Heikkinen AM. Periodontitis in early and chronic rheumatoid arthritis: a prospective follow-up study in Finnish population. BMJ Open. 2017 Jan 31;7(1):e011916. doi: 10.1136/bmjopen-2016-011916.

[9] http://www.ada.org/en/science-research/science-in-the-news/periodontal-disease-affects-nearly-half-us-population

[10] Yilmaz V, Umay E, Gundogdu I, Karaahmet ZO, Ozturk AE. Rheumatoid arthritis: are psychological factors effective in disease flare. Eur J Rheumatol. 2017 Jun;4(2):127-132. doi: 10.5152/eurjrheum.2017.16100. Epub 2017 Jun 1.

[11] Nagano J, Sudo N, Nagaoka S. Yukioka M, Kondo M. Life events, emotional responsiveness, and the functional prognosis of patients with rheumatoid arthritis. Biopsychosoc Med. 2015 Jun 23;9:15. doi: 10.1186/s13030-015-0043-3. eCollection 2015.

[12] http://www.mayoclinic.org/healthy-lifestyle/stress-management/basics/stress-basics/hlv-20049495

Diseases and Conditions

Can small fiber neuropathy mimic fibromyalgia?

July 19, 2017

Can small fiber neuropathy (SFN) mimic fibromyalgia? The simple answer is yes, but it’s more complicated… So why does a rheumatologist care about small fiber neuropathy? The answer is very simple. Many people get referred to a rheumatologist for fibromyalgia, which is a disease that causes widespread pain, brain fog, non-restorative sleep, and various other unexplained symptoms such as headaches. While fibromyalgia IS NOT an autoimmune disease, small fiber neuropathy can present very similarly but CAN BE caused by autoimmune diseases.

There’s a lot of controversy in the medical community about fibromyalgia. One group believes that it’s a separate entity, some do not believe in its existence, and some people are somewhere in the middle. Personally, I believe that fibromyalgia likely represents many diseases that we haven’t identified yet. Until we can categorize them into distinct entities, we’re going to have a hard time understanding them, let alone come up with effective treatments.

First, let’s review the clinical criteria that doctors use to make a diagnosis of fibromyalgia.

2010 ACR criteria for fibromyalgia

Criteria A patient satisfies diagnostic criteria for fibromyalgia if the following 3 conditions are met:

Widespread pain index (WPI) ≥ 7 and symptom severity (SS) scale score ≥5 or WPI 3–6 and SS scale score ≥ 9.
Symptoms have been present at a similar level for at least 3 months.
The patient does not have a disorder that would otherwise explain the pain.

Number #1 are various validated pain scores. These are rarely used in clinic but are often used for clinical trials. It helps researchers objectively quantify pain levels at any given time. As you can see, we don’t use trigger points to check for fibromyalgia anymore.

Small fiber neuropathy in people with fibromyalgia

So is small fiber neuropathy a feature of fibromyalgia, just like it is for diseases like Sjogren’s syndrome or are patient’s with small fiber neuropathy mistakenly diagnosed with fibromyalgia?

In one study, 46 patients with fibromyalgia and 34 normal controls were tested for small fiber neuropathy with a specialized skin biopsy. I’ll talk more about this later on. The researchers measured pain intensity with a survey called the Neuropathic Pain Symptom Inventory. They found that 32.6% of patients with fibromyalgia had reduced nerve fiber density on their biopsy, i.e, they had small fiber neuropathy. Interestingly, they also didn’t find any correlation between pain scores and nerve density.

This implies three things. First of all, the level of pain and symptoms experienced by people with fibromyalgia was the same as those with small fiber neuropathy. So you can’t distinguish between fibromyalgia and small fiber neuropathy based on symptoms alone. Second, about 1/3 of people diagnosed with fibromyalgia have small fiber neuropathy. Finally, having worse nerve density doesn’t necessarily mean you’ll experience more pain. Other studies have also found similar results.

Now this still doesn’t answer all our questions but I think it’s safe to say that testing for small fiber neuropathy should happen when there is a clinical diagnosis of fibromyalgia. Now let’s talk about small fiber neuropathy.

What is Small Fiber Neuropathy?

Small fiber neuropathy results from damage to the small, unmyelinated nerve fibers that send pain and temperature and control autonomic functions like sweating. The following are some of the symptoms caused by SFN:

Burning pain
Numbness and tingling
Pain that is out of proportion
Cramping
Unexplained itching
Lack of sweating
Temperature dysregulation
Dryness

How to diagnose small fiber neuropathy?

The first step to diagnose small fiber neuropathy is taking a care history, reviewing risk factors, and performing a detailed physical examination. On physical exam, deep tendon reflexes (e.g., knee jerk reflex) are normal and there’s no loss of strength. If there is a suspicion for SFN your doctor may send you for electrodiagnostic tests (EMGs). These are colloquially called nerve conduction tests.

Small fiber neuropathy affects small myelinated A-delta and unmyelinated C fibers, NOT large fibers. This means that EMGs are typically negative because these are good for looking for problems affecting large fibers like carpal tunnel syndrome.

One way to diagnose small fiber neuropathy is with a skin biopsy, more specifically epidermal nerve fiber density testing (ENFD). This technique allows direct visualization, quantification, and morphologic assessment of small sensory fibers innervating the skin. This technique has a sensitivity of 88% and a specificity of 95 – 97%. In layman’s terms, the test will miss 12% of cases of small fiber neuropathy, but if the test is positive, there’s a 3 – 5% chance that it’s a mistake (false positive). These are actually pretty good values. A report by the European Federation of Neurological Societies states that ENFD is a reliable and efficient tool to assess for SFN.

How is epidermal fiber density testing done?

Epidermal fiber density testing is done by taking 2-4 three mm punch biopsies. This test happens in clinic. It’s quick and safe. Your doctor can only do these in areas that have been validated: near the ankle, upper thigh, the foot, near the wrist, and the upper arm.

The biopsy is then sent to a specialized pathologist and stained with anti-protein gene product 9.5 antibody (PGP 9.5), which stains all the axons. The pathologist can then painstakingly count all the nerves and calculate the density. The density is then compared to age and sex matched control values to decide whether it’s abnormal.

Common causes of small fiber neuropathy

Once your doctor makes a diagnosis of small fiber neuropathy, then the question is whether there is an underlying cause. About 50% of small fiber neuropathy cases are idiopathic, meaning that doctors can’t find an underlying cause. As a result that leaves us with the other 50%. Of those cases, the most common cause is diabetes mellitus. In fact, autoimmune diseases make a relatively small proportion of cases, so it’s important to look for other causes first. There are MANY other causes but these are some of the more common conditions that can cause small fiber neuropathy.

Non-autoimmune causes

Diabetes mellitus
Lyme disease
Hepatitis C infection
HIV
Celiac disease
Chronic kidney disease
Hypo/hyperthyroidism
Alcohol abuse
Medications, especially chemotherapy
Vitamin B12, B6, B1 deficiency
Paraneoplastic syndromes
Amyloidosis
Exposure to heavy metals

Autoimmune causes

Sjögren’s syndrome
Systemic lupus erythematosus
Sarcoidosis
Rheumatoid arthritis
Scleroderma
Inflammatory bowel disease (Crohn’s disease and ulcerative colitis)
Vasculitis
Psoriasis and psoriatic arthritis

Some genetic conditions can also cause small fiber neuropathy, like Fabry’s, but these are very rare.

Treatment

I won’t talk too much about treatment because it really depends on the underlying cause. If you’re dealing with an autoimmune disease… treat it. Sometimes symptomatic treatment is also necessarily. The following are some medications that are often used:

Tricyclic antidepressants
Serotonin norephinephrine re-uptake inhibitors (SNRIs)
Pregabalin
Gabapentin
Topical lidocaine
Topical capsaicin

Doctors sometimes use intravenous immunoglobulin (IVIG) in extreme situation, particularly in situations where an autoimmune disease is the culprit. The evidence supporting this type of treatment isn’t great. Sometimes it works, sometimes it doesn’t. Moreover, there are no large randomized controlled studies looking at IVIG treatment for small fiber neuropathy.

Ultimately, we’re going to need to understand why and how small fiber neuropathy happens to come up with effective treatments.

Conclusion

I hope this helps explain how small fiber neuropathy (SFN) mimics fibromyalgia and why it’s important to distinguish between both. For those who want to learn more about small fiber neuropathy and how to live with it, I’ve included a link to a great YouTube video.

Please leave your comments below!

References

Lauria G, Devigili G. Skin biopsy as a diagnostic tool in peripheral neuropathy. Nature Clinical Practice Neurology. 2007 Oct 3;3(10):546-57.

Devigili G, Tugnoli V, Penza P, Camozzi F Lombordi R, Milli G, Broglio , Granieri E, Lauria G. The diagnostic criteria for small fibre neuropathy : from symptoms to neuropathology. Brain 2008; 131; 1912-19.

Lauria G, Hsieh ST, Johansson O, Kennedy WR, Leger JM, Mellgren SI, Nolano M, Merkies IS, Polydefkis M, Smith AG, Sommer C, Valls-Sole J. European Federation of Neurological Societies/Peripheral Nerve Society Guideline on he use of skin biopsy in the diagnosis of small fiber neuropathy. Report of a joint task force of the European Federation of Neurological Societies and the peripheral nerve society. J Peripher Nerv Syst. 2010 Jun;15(2):79-92.

Giannoccaro MP, DonadioV, Incensi A, Avoni P, Liguori R. Small nerve fiber involvement in patients referred for fibromyalgia. Muscle Nerve. 2014 May;49(5):757-9.

Kosmidis ML, Koutsogeorgopoulou L, Alexopoulos H, Mamali I, Vlachoyiannopoulos PG, Voulgarelis M, Moutsopoulos HM, Tzioufas AG, Dalakas MC. Reduction of intraepidermal nerve fiber density (IENFD) in the skin biopsies of patients with fibromyalgia: a controlled study. J Neurol Sci. 2014 Dec 15;347(1-2):143-7.

Chan AC, Wilder-Smith EP. Small fiber neuropathy: getting bigger! Muscle Nerve. 2016 Feb 13. [Epub ahead of print]

UpToDate 2017

Uceyler N, Zeller D, Kahn AK, Kewenig S, Kittel-Schneider A, Casanova-Molla J, Reiners K, Sommer C. Small fibre pathology in patients with fibromyalgia syndrome. Brain. 2013 Jun;136(Pt 6):1857-67.

Medical Disclaimer

2 Comments

Diseases and Conditions Overcoming Inflammation

Can UV light trigger lupus flares?

July 12, 2017

Now that summer is finally in full swing, I’d like to remind everyone to use broad spectrum sunscreen while enjoying the sun! This is especially important for people living with systemic lupus erythematosus (SLE). Ultraviolet (UV) light is a known trigger of SLE flares BOTH involving the skin and major organs. Many people also report joint pain, weakness, and headaches. These flares can be very serious.

Although we know UV light is a trigger for SLE flares, we still don’t fully know how it happens. This is what we do know.

UV light directly damages the DNA of skin cells.
The cells release inflammatory cytokines, most notably interleukin-1α and tumor necrosis factor-α.
UV light also increases interferon-α signaling. People with high levels of interferon-α signaling often develop fevers, fatigue, and low white cell count (leukopenia). Interferon-α signaling is thought to be an important part in the development of SLE.

Take home points

So while you’re enjoying the sun remember to:

Avoid the sun when UV light is strongest, between 10 AM and 3 PM. If you use IFTTT, check out this app. You will get a notification on your phone when the UV index is high… and it’s free!
Use broad spectrum UVA/UVB sunscreen. Try to aim for a SPF higher than 30.
Try wearing clothing that have vivid colors and a tight weave. The Skin Cancer Foundation has a great article regarding this topic: “What is Sun-Safe Clothing?”
Wear a broad-brimmed hat when spending time in the sun.

Be safe and please leave your comments below!

References

Fernandez D, Kirou KA. What causes lupus flares? 2016 Mar;18(3):14. doi: 10.1007/s11926-016-0562-3.

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Diseases and Conditions Featured

Guide to living with rheumatoid arthritis: Part 1

July 5, 2017

Have you recently been diagnosed with rheumatoid arthritis? RheumDoctor presents a guide to living with rheumatoid arthritis

Rheumatoid arthritis… Your rheumatologist diagnosed you with rheumatoid arthritis and you have a lot questions. What’s rheumatoid arthritis? Can I get rid of it or will I live with this disease for the rest of my life? What should I expect? How do I fight it? This week I’ll present to you Part 1 of a Guide to living with rheumatoid arthritis. I’m going to present this as a three-part series. Part 1 will cover the basics: what is rheumatoid arthritis, the cause, symptoms, diagnosis, treatment, etc. In Part 2 I’ll cover prognosis, what to expect, diet and exercise. In Part 3, I’ll be covering the financial side of rheumatoid arthritis: How to get access to medications and how to deal with insurance companies.

I hope you find this information useful. Be strong, be brave, and know that you’re not alone.

What is rheumatoid arthritis?

Rheumatoid arthritis is an autoimmune disease that causes inflammation throughout the body but mainly affect joints. Without treatment, rheumatoid arthritis can eventually lead to permanent joint destruction. Autoimmune diseases occur when the immune system loses “tolerance to self”. What this means is that the immune system can no longer distinguish between healthy cells and cells that don’t belong like bacteria or cancerous cells.

According to the CDC, about 1% of people living in the US suffer from rheumatoid arthritis. It tends to occur 2-3 times more often in women and tends to start in your sixties but it can start at any age. [1]

Some common signs and symptoms include:

Pain and swelling in the joints. Particularly small joints like the knuckles, wrists, and toes.
Morning stiffness that lasts more than one hours
Having difficulty opening jars. Weakness in the hands.
Fatigue, fevers, unintentional weight loss.

What causes rheumatoid arthritis?

We’re actually unsure. We do know that in certain cases there is a genetic link. People that have a certain HLA class II genotype (shared epitope) tend to get rheumatoid arthritis more often. Especially, if they smoke cigarettes. Moreover, we know that rheumatoid arthritis tends to run in families. However, most cases of RA happen spontaneously and not everyone who has a genetic risk factor develops RA.

There’s still a lot of work that needs to be done to fully understand what causes rheumatoid arthritis. Like most autoimmune diseases, our best guess is that people who have RA probably were born with some sort of genetic predisposition for the disease. Then they get exposed to something in the environment like a virus, trauma, stress, hormonal change, which then triggers the disease to come online.

What are the symptoms of rheumatoid arthritis?

Usually rheumatoid arthritis presents with pain, swelling, and prolonged stiffness involving small joints, like the ones in your hands or feet. When I mean prolonged, I mean more than one hour. But RA can present in many ways. These can be divided into typical (90% of cases) and atypical presentations (10% of cases).

Typical

Insidious (55% – 65%): People develop pain, swelling, and prolonged stiffness mainly involving small joints like the toes and knuckles. This progressively worsens over months.

Subacute (15% – 20%): Again small joints are painful, swollen, and stiff but the this develops over weeks. Usually people experience some fatigue.

Acute (10%): Joints suddenly become swollen and tender over days. Some people have a fever, drenching night sweats, and sometimes can lose weight without trying.

Atypical (10% of cases)

Palindromic pattern: This type of presentation isn’t technically considered rheumatoid arthritis. It’s just that 33% to 50% of people with this type of presentation progress to full-blown rheumatoid arthritis. Typically, one joint is involved. It becomes tender and swollen for a few days then gets better on its own. Then a few weeks to a few months later it happens again. The flare can happen in the same joint but not necessarily. Treatment with hydroxychloroquine can decrease the risk of developing full-blown rheumatoid arthritis, so it’s important to start treatment as this stage.

Insidious onset of the elderly: As the name suggests this type of presentation occurs in the elderly, so people aged greater than 65 years. People experience extreme pain and stiffness shoulders and the hips. Sometimes you can see whole hand or foot swelling. Sometimes it’s very difficult to differentiate from polymyalgia rheumatica or remitting seronegative symmetrical synovitis with pitting edema (RS3PE). People with polymyalgia rheumatica and RS3PE typically do NOT have any positive antibodies.

Rheumatoid nodulosis: Rheumatoid arthritis can cause nodules and bone cysts on radiographs. Usually people also have joint pain and swelling but sometimes all they have are nodules.

Arthritis robustus: This is rather rare. I’ve only seen it once. It typically occurs in men. Essentially the person develops horrible rheumatoid arthritis hand deformities but experiences little or no pain. I know it’s hard to believe, but it’s possible!

By James Heilman, MD (Own work) [CC BY-SA 3.0 (http://creativecommons.org/licenses/by-sa/3.0) or GFDL (http://www.gnu.org/copyleft/fdl.html)], via Wikimedia Commons

How is rheumatoid arthritis diagnosed?

The diagnosis of rheumatoid arthritis, contrary to popular belief, is primarily a clinical diagnosis. Having a positive antibodies like a rheumatoid factor (RF) does not necessarily mean that you have rheumatoid arthritis because MANY conditions can have a positive rheumatoid factor. Some of these include:

Rheumatoid arthritis, mixed cryoglobulinemia types II and III, sarcoidosis, and other autoimmune diseases like Sjogren’s syndrome. Other non-rheumatology diseases that can cause someone to have a positive rheumatoid factor include infections most notably hepatitis C, tuberculosis, syphilis, HIV, and endocarditis. People suffering from cancer and people with chronic pulmonary and liver diseases, can also have a positive rheumatoid factor.

It’s also important to mention that about 5 – 25% of people aged 60 years and older have a positive rheumatoid factor without any underlying causative disease.

This is why my job as a rheumatologist is so interesting 🙂

The American College of Rheumatology classification criteria for rheumatoid arthritis is as follows:

The 2010 American College of Rheumatology/European League Against Rheumatism classification criteria for rheumatoid arthritis[2]

Who to test?

People that have at least 1 joint with definite swelling.
And the swelling cannot be better explained by another disease.

Classification criteria for RA (a score of ≥ 6/10 is needed for someone to have definite RA)

Category

Score

Joint involvement

1 large joint

2 – 10 large joints

1 – 3 small joints

4 – 10 small joints

> 10 joints (at least one small joint)

Antibodies

Negative RF and negative CCP antibodies

Low positive RF or low positive CCP antibodies *

High-positive RF or high positive CCP antibodies #

Inflammation markers

Normal CRP and normal ESR

Abnormal CRP or abnormal ESR

Duration of symptoms

< 6 weeks

≥ 6 weeks

* Low positive antibodies means any value that is above normal but less than 3 standard deviations above the upper limit of normal.

# High positive antibodies means any value that is 3 standard deviations above the upper limit of normal.

It’s important to note that these criteria were NOT meant for clinical practice but rather, were really meant for research trials. Sometimes, rheumatologists do deviate. Other conditions should be ruled out and let’s face it, not everyone fits perfectly into the mold. The criteria also does not account for musculoskeletal ultrasound testing. This imaging test can detect very subtle inflammation of a joint.[3]

Positive antibodies without RA

Now sometimes the workup is completely negative including x-rays. This is not uncommon. It can mean many things. It could mean that the rheumatoid factor is not clinically significant. 5–25% of the population can have a positive rheumatoid factor without any underlying condition or any symptoms. Typically the rheumatoid factor levels are low. It could also mean that you will develop rheumatoid arthritis in the future. Studies have shown that antibodies associated with rheumatoid arthritis can be present over a decade before onset of clinical disease. [4]Unfortunately, we don’t have the tools to precisely determine who will convert and who will not. In this situation, your rheumatologist can help you watch for any change in your condition.

How is rheumatoid arthritis treated?

We treat rheumatoid arthritis with medications called disease modifying anti-rheumatic drugs (DMARDs). These medications slow down or stop the natural progression of rheumatoid arthritis.

Except for a few special situations, EVERYONE should with rheumatoid arthritis should be treated with a DMARD as soon as possible because permanent joint damage can happen in as little as 3 months after symptoms start.[5]

The following are the medications used to treat rheumatoid arthritis in the United States. It’s important to work closely with your rheumatologist because they all have possible risks and what may be good for your neighbor may not be safe for you.

I’ve broken them down into conventional DMARDs, biologic DMARDs, and pipeline medications that have not been approved as of yet.

Conventional

Methotrexate
Leflunomide
Sulfasalazine
Hydroyxchloroquine

Biologics

Etanercept, TNF inhibitor
Adalimumab, TNF inhibitor
Golimumab, TNF inhibitor
Certolizumab pegol, TNF inhibitor
Infliximab, TNF inhibitor
Abatacept, Co-stimulation inhibitor
Tocilizumab, IL-6 inhibitor
Sarilumab, IL-6 inhibitor
Tofacitinib – JAK inhibitor
Rituximab – B cell depletion

Pipeline

ABT 494, a new JAK inhibitor
Baricitinib, another JAK inhibitor
Sirukumab, another IL-6 inhibitor

Biosimilars

It’s also important to note that we are starting to see biosimilar medications in the States. These are medications that are sort of copied from existing biologic medications. They are NOT generic medications. The problem with biosimilars is that because of their complexity, it literally is impossible to exactly copy a biologic medication. If you want to learn more about biosimilar medications, please check this article.

Supplements

If you’re interested in supplementing, there is some research that suggests high dose turmeric/curcuma and high dose fish oil/omega-3 fatty acids may also be helpful.[6][7] However, supplementation should be used in combination with FDA approved medications that I listed above.

Is there a cure for rheumatoid arthritis?

I honestly wish I had better news for you. Unfortunately there is no cure for rheumatoid arthritis. Treatment primarily focuses on arresting the natural progression of the disease with the use of disease modifying anti-rheumatic agents (DMARDs). Conventional DMARDs such as methotrexate, leflunomide, sulfasalazine, and hydroxychloroquine, modulate the immune system to decrease rheumatoid arthritis activity. Biologic medications like etanercept use a targeted approach, i.e., suppress a specific cytokine.

The goal of treatment is to put rheumatoid arthritis into remission and decrease the frequency of flares.

This may seem very pessimistic, but recent advances have really improved the prognosis of people living with rheumatoid arthritis.

Nevertheless, DMARDs do not cure rheumatoid arthritis.

How do we win the war against rheumatoid arthritis? Before we can win the war and find a cure, we need to know exactly what causes rheumatoid arthritis in the first place and we need to understand its exact pathophysiology. Believe it or not, despite all our advances, we still cannot answer these two questions. Don’t despair, researchers are actively trying to answer these questions.

Can rheumatoid arthritis become fatal?

Rheumatoid arthritis is a systemic autoimmune mediated disease that primarily affect the joints. Note the primarily bit. It can affect a host of different organs including the eyes, lungs, heart, skin, and bone marrow to name a few.

Untreated or poorly controlled rheumatoid arthritis can cause serious conditions such as interstitial lung disease (i.e., inflammation of the lungs), pericarditis (i.e., inflammation of the “sac” surrounding the heart), as well as something called Felty’s syndrome (i.e., a hematologic condition that can cause white cells to dramatically decrease and causes the spleen to enlarge). These severe manifestations of rheumatoid arthritis that can lead to death are hardly ever seen anymore mainly because we have many highly effective medications called disease modifying anti-rheumatic medications (DMARDs). These medications have completely changed people’s prognosis.

Cardiovascular disease and infection

The most common cause of death in people with rheumatoid arthritis these days includes cardiovascular disease and infection – primarily from medications.[8]

Rheumatoid arthritis increases cardiovascular risk via the interplay of inflammation and lipid metabolism. Studies have shown that people who receive treatment with methotrexate and or tumor necrosis factor inhibitors reduce their cardiovascular risk.[9] A British study also demonstrated that cardiovascular was not increased regardless of the choice of DMARD provided that rheumatoid arthritis was well controlled.[10]

Infection remains an ever-present problem in the world of rheumatology. To treat autoimmunity you need to suppress the immune system. Not too much, not too little, but just right. In some cases this has the unfortunate result in causing serious infections that can lead to death in extreme cases.

Rheumatoid arthritis can become fatal in many other ways, however, for the most part it is medication induced – although the pharmaceutical companies don’t really want you to know that. Just read a package insert. They’re terrifying.

However, I’ve been talking about rheumatoid arthritis fatalities. Untreated or undertreated rheumatoid arthritis is HIGHLY debilitating leading to a significant drop in your quality of life. Early treatment with a DMARD is the best way to improve your odds. You have to fight fire with fire!

Can I stop my medications if I’m feeling better?

No. Rheumatoid arthritis is a life-long disease. If you’re feeling better, great! However, it’s probably your medications that are keeping you that way. If you stop your medications the rheumatoid arthritis will come back. Maybe not now but soon. Rheumatoid arthritis subsides spontaneously in a VERY small subset of people.

If your medication is making you feel sick, talk to your rheumatologist. They’re there to make you feel better and they want to find the perfect treatment plan tailored for you.

Do not stop your medications without consulting your rheumatologist.

Next steps

We’ve covered a lot of material today and there’s a lot more coming your way! Stay tuned for Part 2. I’ll be covering topics such as what to expect, what to eat, how to exercise, and strategies on how to reduce stress. Please leave your comments below.

References

[1] https://www.cdc.gov/arthritis/basics/rheumatoid-arthritis.html

[2] https://www.rheumatology.org/Portals/0/Files/2010_revised_criteria_classification_ra.pdf

[3] Horton SC, et al. Ultrasound-detectable grey scale synovitis predicts future fulfilment of the 2010 ACR/EULAR RA classification criteria in patients with new-onset undifferentiated arthritis. RMD Open. 2017 Mar 30;3(1):e000394. doi: 10.1136/rmdopen-2016-000394. eCollection 2017.

[4] Brink M, et al. Rheumatoid factor isotypes in relation to antibodies against citrullinated peptides and carbamylated proteins before the onset of rheumatoid arthritis. Arthritis Res Ther. 2016 Feb 9;18:43. doi: 10.1186/s13075-016-0940-2.

[5] Raza K, et al. Treating very early rheumatoid arthritis. Best Pract Res Clin Rheumatol. 2006 Oct;20(5):849-63.

[6] van der Tempel H, et al. Effects of fish oil supplementation in rheumatoid arthritis. Ann Rheum Dis. 1990 Feb; 49(2): 76–80.

[7] Ramadan G Al-Kahtani MA, El-Sayed WM. Anti-inflammatory and anti-oxidant properties of Curcuma longa (turmeric) versus Zingiber officiale (ginger) rhizomes in rat adjuvant-induced arthritis. Inflammation. 2011 Aug;34(4):291-301. doi: 10.1007/s10753-010-9278-0.

[8] https://www-ncbi-nlm-nih-gov.elibrary.amc.edu/pubmed/26472415

[9] https://www-ncbi-nlm-nih-gov.elibrary.amc.edu/pubmed/28455580

[10] https://www-ncbi-nlm-nih-gov.elibrary.amc.edu/pubmed/28160488

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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.

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.

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