Lupus Encyclopedia

You will learn:
- Why lupus nephritis is important for all systemic lupus patients
- How to properly collect a urine specimen
- The symptoms of lupus nephritis 
          Did you know that the most common symptom of early lupus nephritis is no symptoms at all?
- The different kinds of lupus nephritis
- How it is diagnosed
- The importance of diet, exercise, mindfulness
- How it is treated
- What happens when it is not treated
- How to get the most out of virtual online doctor visits
- An online support group for people who have lupus nephritis

Video produced by Lupus Foundation of New England and Marisa Zeppieri "Lupus Chick"

Presented by Dr. Donald Thomas, MD, author of "The Lupus Encyclopedia" and "The Lupus Secrets"

Sponsored by Aurinia Pharmaceuticals

This presentation (link below) is published on YouTube by lupus warrior Kelli Roseta of "More Than Lupus"
Moderator and questions are asked by lupus warrior Molly McCabe
Lupus questions about "The Lupus Secrets" and living with lupus are answered by Don Thomas, MD

​Topics include:
​
Hydroxychloroquine (Plaquenil) dosing, safety, how to avoid eye problems
Belimumab (Benlysta) safety and helpfulness for lupus
How long does it take for Benlysta to work?
Which lupus patients are the best candidates for Benlysta treatment
Genetics and epigenetics that can predispose people to getting lupus
Why lupus occurs more often in people of color (African descent, Hispanic, Asian, indigenous peoples)
The treatment of lupus and rheumatoid arthritis overlap, also called rhupus
What is the significance of an antinuclear antibody (ANA) test becoming negative in a lupus patient?
How to ensure that new doctors believe your diagnosis of systemic lupus made by a previous doctor
The use of hormone replacement therapy (estrogen, progesterone) in women after menopause
Steroid usage in lupus. Should it be stopped?

Please click on "Comments" above and share with us your thoughts on the topics and answers.
Share your experience.
Do you have any questions for Dr. Thomas?

The Lupus Foundation of America, in its continuous quest to advocate for better care of lupus patients, just announced a new laboratory test that can help people who have systemic lupus erythematosus (SLE).

The test is called the aiSLE DX Flare Risk Index, produced by Progentec Diagnostics, a company  that specializing in lupus. This is the first test in their "pipeline" (the yellow "01" part of the diagram above) of lab tests, designed to modernize and improve the care of SLE patients. Progentec had a press release this week about the lab test... read it here

The test measures numerous molecules of the immune system called cytokines and chemokines. Some of these cytokines increase immune system activity in SLE, while others decrease it. Studies have shown (at the Mayo Clinic and OMRF) that before lupus flares, we can predict the chances of it occurring beforehand. This is exciting. Up to now, whenever we get labs on our lupus patients, it tells us how patients are doing at this moment.  I like the way that Dr. Chaim Putterman (a lupologist) put it:

"“The management of lupus symptoms has traditionally involved a regimen of reactive protocols. A test that assesses the likely risk of the onset of a flare is one of the first proactive measures available to the rheumatological community. The empirical data derived from such a test potentially has tremendous value in helping devise the right treatment and care for lupus patients.”

- Chaim Putterman, MD, Professor of Medicine and Microbiology & Immunology at the Albert Einstein College of Medicine

I've been using the test on my patients now for a few weeks. I love it. When it comes back with a negative number result, telling me that patient has a very low risk of flaring ... it is music to my ears, and good news for them. If the test shows an increased risk for flaring, then I want that patient to ensure they are doing every thing on my - Lupus Secrets - and I'd make sure that the current treatment is maximized. I'd also check their labs more often during the next 12 -16 weeks.

Under a dozen rheumatologists have been using it up to now, but this week it has gone commercial. Rheumatologists can go to the Progentec website to sign up for the test so they can offer them to their patients. 

Share any comments below. If you have lupus, what do you think of new tests coming out such as this?

​SHARE the good news that the medical care of lupus patients is advancing!
​

Disclosure: I am on the Scientific Advisory Board of Progentec. I strongly believe in their mission and dedication to lupus patients. 

The Positive ANA Begins the Journey
Lupus is a disease where the immune system of the affected person attacks their own body (called an autoimmune disease). If someone has symptoms suggestive of lupus (fatigue, joint pain, rash, fever, pleurisy, Raynaud's, mouth sores, etc) the doctor will usually order an antinuclear antibody (ANA, also called FANA) test as depicted in the picture above. This is what the lab technician sees under the microscope when someone's blood is positive for ANA. This is the initial test done in people who could possibly have systemic lupus erythematosus (SLE) because around 98% to 99% of adult SLE patients are positive for ANA (when both the IFA technique and ELISA lab methods are used). Children, especially young children, with SLE have higher rates of being ANA negative (as high as 15% to 20% in young children).

If positive, the patient is then often referred to a rheumatologist (the doctor who specializes in lupus)

The Visit to the Rheumatologist
The rheumatologist then does a complete history (asks about symptoms), performs a thorough physical examination, and does a whole bunch of blood work and takes a urine sample to look for lupus. However, since multiple other disorders can cause similar symptoms as lupus and can also cause a positive ANA, he or she will also look for these possibilities. These tests include labs such as anti-dsDNA, anti-Smith antibody, anti-SSA, anti-RNP, rheumatoid factor, anti-CCP antibody, complete blood counts, liver enzymes, kidney function test, C3 and C4 complements, Coombs' antibody, CH50 complement test, antiphospholipid antibodies, and a urine protein measurement. 

The list of disorders that can mimic lupus and can have a positive ANA is broad and include (not an exhaustive list):

- Other systemic autoimmune diseases (such as rheumatoid arthritis, scleroderma, Sjogren's, polymyositis, mixed connective tissue disease, undifferentiated connective tissue disease)
- Infections (such as hepatitis C, hepatitis B, parvovirus infection, Epstein Barr virus infection)
- Fibromyalgia
- Cancer
- Medications

Or, the ANA can be a normal finding. It is found in up to 20% of all women. For example, a 55-year-old woman could have joint pains due to a different type of arthritis (such as osteoarthritis, OA), be very tired and fatigued after going through menopause, and have a positive ANA as a normal finding.

If the rheumatologist diagnoses lupus or a related disorder, hopefully, you will be treated immediately. Or, the rheumatologist will find another reason for your problems and the ANA (such as the woman with OA in the above paragraph).

​

6 Years for a Diagnosis of Lupus?
Unfortunately, not everyone is so lucky. In 2014, UK Lupus did a survey of their members. Over 2500 SLE patients responded. The survey showed that it took an average of 6.4 years to get a correct diagnosis. Most ended up seeing multiple doctors before a diagnosis was reached. A few years later, the Lupus Foundation of America did a similar survey and found similar results, it took an average of 6 years. This is a travesty, and a huge unmet need. We need better ways to diagnose lupus. 

We do have better and more accurate ways, by the way, read onwards! But 1st ... why does it take so long?

There are several reasons:

SLE will often start off slowly and add symptoms and problems and blood test results very slowly over time. Someone can actually have the disease lupus, feel miserable, yet not have enough evidence using the typical labs to make the diagnosis. The person often suffers while waiting for new problems to occur before enough evidence is present to properly make the diagnosis. The best solution for this problem is if we can figure out a way to identify the disease process of lupus earlier and faster by identifying an immune system abnormality that is unique for lupus. For example, maybe this could be a certain interferon signature in the blood work.  However, we don't have this luxury yet. 

Another possible scenario is the person who has enough evidence for a systemic autoimmune disease, but there is not enough to label it as one of them (such as SLE, rheumatoid arthritis, scleroderma, Sjogren's, or polymyositis). This person has evidence of an autoimmune disease, which we also call connective tissue diseases (CTDs), but it has not "differentiated" into one of the named CTDs. So, we label this person as having an undifferentiated connective tissue disease (UCTD). 

People in the above situations could heed my advice and see a rheumatologist who does certain procedures to try to get a faster diagnosis (discussed below).

Musculoskeletal Ultrasound can look inside the Joints right in the Rheumatologist's Exam Room
Many, but not most, rheumatologists can perform an ultrasound exam of the joints right in the examination room. In the photo above, I am doing an exam of the big toe joint in a patient. You can see a very nice picture of the joint ultrasound image on the screen. The vertical blue line in the middle cuts right between the two bones of the toe (that is where the cartilage of the joint exists). The horizontal bright white line going to the right is one toe bone (the middle phalanx) and the left line that starts out as a hump is the other (the first metatarsal bone). 

90% of adult SLE patients have inflammatory arthritis. They typically have pain in the joints and stiffness that is worse when they first wake up from sleep. The middle joints of the fingers, the knuckles, elbows, and knees are some of the most common joints affected. It can be very difficult to tell on physical examination (PE) when some SLE patients have inflammatory arthritis. They often will not have swelling of the joints on the PE. An ultrasound exam can be invaluable to diagnose arthritis accurately in these individuals. I've seen quite a few patients who were told they have fibromyalgia (which is not an arthritis) or arthralgias (joint pains without inflammatory arthritis) yet turn out to actually have lupus inflammatory arthritis easily seen on ultrasound.

Below is one of my SLE patient's ultrasound results of the wrist (I have her permission to use her image). Note the horizontal white line in the center between the red and yellow arrows. Those are two bones of her wrist (bright white = bone). Just above it is an oval dark area (the red arrow points at it). That is swelling and fluid inside of her wrist joint (fluid shows up as black). This is diagnostic of arthritis. Yet, more telling is the orange blotches that are on the rim of the joint swelling (yellow arrow). That is actual lupus inflammation of the joint. This ultrasound result made it very easy to prove she has lupus inflammatory arthritis.

​(by the way, the upper orange blotch is blood in the vein just below the skin of her her hand. Look at the top of your hand. See those blue veins? Your veins would look like this under ultrasound). 

Finding a Rheumatologist Certified in Musculoskeletal Ultrasound (rhMSUS)
So, first, you can search out a rheumatologist who does ultrasound in his or her office. You can figure this out by going to the American College of Rheumatology's website and look for a rheumatologist in your area who is certified to do these exams: https://www.rheumatology.org/Learning-Center/RhMSUS-Certification/RhMSUS-Designees

You can then look up the names of doctors in your area to see if they are on the list. These rheumatologists can put the initials rhMSUS after the MD of their name (rhMSUS stands for Musculoskeletal Ultrasound Certification in Rheumatology). My partner (Dr. Yevgeniy Sheyn, MD) and I were in the very first group of doctors to earn this prestigious certification. 

The second best option is to call up rheumatology offices in your area and ask if their doctors do ultrasound exams. Most rheumatologists who perform ultrasound are not certified (and are not on this list), yet many of them are still excellent ultrasonographers. Ask the phone personnel who they would see in that office to get an US exam if they might have lupus. That is always a good question to ask. Office staff usually know who the best doctors to see in their practice are. 

Exagen Diagnostic's AVISE Lupus Test and AVISE CTD Test
The second test that can be very helpful is to get newer and more accurate labs done. A company called Exagen specializes in lupus lab tests. A type of blood test called Cell-Bound Complement Activation Products (CB-CAPs) is more sensitive and accurate than standard tests in diagnosing lupus compared to the usual commercial insurance labs (LabCorp  and Quest) that most doctors order from. Exagen put these valuable labs in two helpful tests called the AVISE Lupus Test and the AVISE CTD test. Anyone can get these tests done, yet only around 25% of rheumatologists order them.

Why do so few rheumatologists order these tests if they are so accurate in diagnosing SLE?
Previously, to order these tests, a rheumatologist had to have a lab technician in the office that could draw the blood, process it correctly, then send it to the Exagen labs in California. This is a lot of work. Most rheumatologists do not have the capability to do this, or do not want to put forth the extra effort and work to implement these tests in their office. (It can be a lot of hassle ordering new types of labs, fill out a lot of paperwork, and fight with the insurance companies to cover the lab costs for patients... so I can certainly understand why they would not want to do them!)

Below is an example of a patient who has a positive AVISE Lupus Test. The orange oval at the top left highlights this patient's positive result and the middle circle highlights it on the graph. The bottom orange oval highlights her positive CB-CAPS (EC4d and BC4d) that gave her the positive results. The value of this test is that CB-CAPS become positive due to activation of and consumption of complements (important immune system proteins). This is a key problem in SLE (complement activation and lower C3 and C4). Most rheumatologists order C3 and C4 complements on standard tests hoping to see low C3 or C4 to help diagnose SLE. However, this only occurs in 20% to 30% of SLE patients because the liver will often times produce a whole bunch more C3 and C4, which ends up normalizing the blood levels. CB-CAPS (EC4d and BC4d) results are not interfered with by this liver over production of C3 and C4.

​You can imagine how this test could simplify things. 

HOWEVER: a word of caution! ... if you happen to get this test done, please do not assume that a positive AVISE Lupus Test automatically means you have lupus. On the other hand, a negative result does not mean you do not have it. The test result increases or decreases the likelihood of having lupus. For example, if the patient with test result above started off with a low likelihood of having SLE, this result may not be enough to say she has SLE. However, if the result was much further on the right of the graph (such as a Tier 1 positive test), then that could be enough to say she has SLE.  

So how can you get this valuable test done?

How to get the AVISE Lupus Test or AVISE CTD Test
It is now much easier to get the AVISE Lupus Test done. If you are interested in doing this. Follow my advice. Doctors are much more likely to do something if you make it as easy for them to do as possible. All doctors are overworked these days. So, if you make it easy, then it is a cinch.

1. Download the order form from Exagen.: https://1rn4xv3o8v9yy7scj1xot3b1-wpengine.netdna-ssl.com/wp-content/uploads/LM1028_Universal_APN_0320-1.pdf

2. Fill out the form completely with all your information and the doctor's information.

3. In Step 2 circle the diagnosis D89.89

4. Check the boxes that say "AVISE CTD Test" and the one underneath it that says "Add AVISE SLE Prognostic regardless of AVISE Index Result" and the "Add anti-Histone"

5. On page 3 print and sign your name. Fill out the last page if appropriate (sometimes you will get the test for free)

6. Make an appointment with your rheumatologist. Very tactfully ask, "Could I possibly get this lab test done for lupus called the AVISE test? I already filled out all the paperwork and I can get it done at a local lab".  Then just have him or her write in their NPI number upper right side and sign anywhere on the first page.

Also (important) ask them to add the diagnostic code D89.89 to the clinic visit note for that day. 

7. Go to the lab locator online at: https://avisetest.com/telavise-draw-site-locator/

8. Type in your zip code to find the closest lab that can do the test. 

9. Call Exagen at 888-452-1522, option 3. Tell them you'd like to get the test done and you have the paperwork.  Ask them how much it will end up costing you with your insurance. Most people pay a copay of $0 to $45. If you have no insurance, I believe it is $100 as of 2020. Then ask them what your next steps are.

10. Go to the lab to get your lab drawn, then see your rheumatologist a couple of weeks later to discuss the results. 

BOTTOM LINE: 

I strongly believe that people get better healthcare when they are proactive in their healthcare. If you have a positive ANA, have symptoms that could potentially be caused by lupus, had a thorough workup, yet you feel like you don't have a good answer, take my advice.

- Find a rheumatologist who can do an ultrasound of your joints
- And get the AVISE CTD or AVISE Lupus test done

if you do this, then you can be confident that you have done everything that you can with today's modern technology. I hope in the future that I can report on even better tests. A lot of research is being done looking into this, and I will certainly report on it when it becomes available.

I would love to hear from you about your experience. Write comments below under "LEAVE A REPLY".  If you have lupus, how long did it take? Was it frustrating? What ended up being the key in getting your diagnosis correct? Also, if anyone has any questions, I'll also be glad to answer them.

Please SHARE with anyone who is struggling to get a proper diagnosis after being ANA positive.

NOTE: I am on the Speaker's Bureau for Exagen. I do believe strongly in how their tests improve patient care. Note, that the Lupus Foundation of America has also partnered with them to support their help for lupus patients. 

CB-CAPS became a reality partially due big efforts and funding from The Lupus Foundation of America.  Please join in you have lupus and are not a member. It is a wonderful organization fighting for your health!

​Photo #1 credit (ANA picture): from Simon Caulton on Wikipedia.com

How do we identify and treat flares in people who have systemic lupus erythematosus? 

There are things that people can do to decrease them from occurring.
There are things we can do to get them under control when they do occur.

The YouTube video below is the perspective of two rheumatologists who treat lots of lupus patients. They also hint about new lab tests that are just around the corner that can help predict lupus flares before they even happen. The immune system of lupus patients becomes more active before the person knows that a flare is going on. 

Also, make sure to click on the Lupus Foundation's Flare Plan site and download their flare plan as a practical way to monitor and report flares to your physician. Have a plan in place before you flare.

Comment below about how you prevent lupus flares. 
What symptoms do you have during a flare?
What have you found to be effective in getting your flares under control?
If you have had SLE for a long time, what do you wish you would have done differently after first diagnosed to help prevent flares?

​- Don Thomas, MD