Lupus tendinitis (lupus tendonitis), lupus tenosynovitis, and lupus enthesitis: What are they?
What is lupus tendinitis (also spelled lupus tendonitis)?
Lupus tendinitis (lupus tendonitis) and tenosynovitis are common in systemic lupus erythematosus (SLE). The tendons are sinewy, inelastic fibrous tissue that connects the muscles to the bones. When muscles contract to move parts of the body, these strong tendons enable the muscles to move the much stronger bones. The movement of these tendons in unison with the body’s muscles and joints allows us to move. To demonstrate tendons to yourself, place your left fingers on the front bend of your right elbow. Then, bend your right elbow. The muscle just above this is your biceps. The hard, long structures just below the biceps that connect to the bone below the bend are the biceps tendons. If these were to become inflamed and painful, this would be “biceps tendonitis.”
Just as lupus can cause inflammation of the joints, it can also cause inflammation of the tendons (lupus tendonitis or lupus tendonitis). Tendonitis usually causes pain around and between the joints of the body. The joint pains seen in SLE are commonly due to lupus tendonitis (lupus tendonitis) rather than arthritis. One Japanese study in 2017 showed that 94% of their SLE patients with joint pains had tendon involvement (tendonitis and tenosynovitis), while 80% had joint (arthritis) involvement. Many patients had a combination of both.
The photo above shows the hands of Dr. Thomas' patients with severe damage to her tendons from lupus tendinitis and lupus tenosynovitis. We call this "Jaccoud's arthropathy." Jaccoud's arthropathy was first seen in people affected by rheumatic fever. Today, SLE is the most common cause.
Make sure to read my "Lupus Secrets" to learn to take care of and prevent problems such as lupus tendinitis.
Benlysta (belimumab) is safe and effective for lupus
Benlysta is amazing. There are very good reasons why it has achieved 3 FDA approvals for lupus (SLE, pediatric lupus, and lupus nephritis) in the past 10 years. It is safe and effective.
How the target (BLyS) of Benlysta normally works in the immune system:
BLyS is B-cell fertilizer
There is an immune system chemical messenger (a cytokine) called BLyS (B Lymphocyte Stimulator) also called BAFF (B cell activating factor). B-cells that make antibodies require this BLyS (BAFF) to stay alive.
For Example: Suppose you get pneumonia from a bacteria called Pneumococcus pneumoniae (pneumococcus). B-cells are called upon to produce pneumococcal antibodies. The immune system makes a lot of BLyS to keep the pneumococcal antibody producing B-cells alive. When the infection is gone, the immune system stop making BLyS. The B-cells then retire and die because we don't need them any more. When cells of the body retire and die a natural death when not needed, it is called apoptosis. Think of BLyS as "B-cell fertilizer." Without BLyS, B-cells go through apoptosis, which is an important process of the body so that younger, newer cells can replace old, unneeded cells.
The tiny pink things floating around are cytokines (like BLyS) ready to attach to the purple white blood cell and tell it what to do (stay alive in the case of antibody producing B-cells) photo credit: Wikipedia and Scientific Animations at https://commons.wikimedia.org/wiki/File:Cytokine_release.jpg
Benlysta (belimumab) attaches to BLyS and takes it away so B-cells can die
Lupus patients constantly make too much BLyS, so those bad B-cells that make autoantibodies that attack your own body's cells (ANA, anti-dsDNA, etc) stay alive, and can even be immortal. Benlysta binds to BLyS and takes it away. The bad B-cells can then retire, die, and go away (go through apoptosis).
Yet, during infections, the immune system can still make lots of BLyS so that the important, needed B-cells can fight off the infection.
After studying Benlysta patients for over 20 years, we are not seeing any more infections in our Benlysta patients than we do in those taking placebo plus "standard of care" therapies.
Think of Benlysta as balancing out the immune system, achieving homeostasis, rather than suppressing it.
COMMENT above. Are you on Benlysta? How are you doing on it?
Don Thomas, MD, author of "The Lupus Encyclopedia" and "The Lupus Secrets"
Doing a urine sample wrong can cause false results
Why do lupus patients need to give a urine sample every 3 months?
Around 40% of systemic lupus erythematosus patients develop kidney inflammation (nephritis).
Some groups get it more often, as high as 80% in Afro-Caribbean women and 50-55% in African American women
Finding excess protein in the urine (proteinuria) is how we identify lupus nephritis at its earliest stages.
How can the urine sample be inaccurate?
If there are white blood cells, red blood cells, and other substances contaminating it from the vagina or foreskin, this can cause an artificially high amount of proteinuria
If you collect it after exercising a lot, or in the afternoon it can be artificially high (orthostatic proteinuria)
How to collect a urine sample optimally (PRINT THIS OUT AND KEEP IT HANDY):
Why this is important: If you get into the habit of doing this correctly, you will save yourself from having to repeat it or from having to collect an unnecessary 24 hour urine collection (which is cumbersome to do)
- Always try to collect your sample first thing in the morning (either the 1st or 2nd void)
- Hydrate. Drink at least 8 glasses of water daily for a few days before the collection (unless your doctor has you on a water restriction)
- Collect a "mid-stream, clean-catch" urine sample:
- 1st wash your hands.
- Carefully remove the lid from the urine sample cup (making sure not to touch the inside of the container or cover) and lay the cover with the inside section facing up.
- If you are giving a urine culture as well to make sure you do not have a urinary tract infection, use a sterile cup.
- Place the cup on an easy-to-reach surface.
- Pull apart the labia (if you are female) or retract the foreskin (if you are a male) with one hand.
- Using your other hand, you wipe the urethra three times with three sterile wipes (front to back if you are a female). Continue to keep the labia or foreskin retracted with one hand and grab the cup with the other hand.
- You then urinate the first couple of seconds into the toilet (this gets rid of any bacteria that may have been in the urethra), and then urinate into the cup to the fill line.
- You should empty the last part of your urine into the toilet again (which is why the term “midstream”). You should immediately put the lid securely on the cup, making sure not to touch the inside of the cover or the container.
- Make sure and place the lid securely on the cup prior to flushing the toilet to prevent contamination from aerosolized droplets from the toilet (thanks to ANON for this great recommendation).
PRINT this out and keep it handy
SHARE with others who have lupus
The Lupus Encyclopedia
Fanouriakis A, Kostopoulou M, Cheema K, et al. 2019 Update of the Joint European League Against Rheumatism and European Renal Association–European Dialysis and Transplant Association (EULAR/ERA–EDTA) recommendations for the management of lupus nephritis. .Annals of the Rheumatic Diseases 2020;79:713-723.
Please come join us and register at link below
Community Resources & How to Navigate Them Successfully
10:10–10:45 a.m. CDT (11:10 EDT)
Andrew Robinson, MSW, LMSW
Heartland Chapter Patient Navigator
Our Patient Navigator will provide an overview of the resources that are available in the community and how to best access those resources. He will discuss resource assistance for insurance, utilities, transportation, prescriptions, and others. He will also share resources and programs available through the Heartland Chapter.
Bringing Lupus Nephritis Out of the Shadows
Donald E. Thomas, Jr., M.D., FACP, FACR
Associate Professor of Medicine at the Uniformed Services
University of the Health Sciences and a Rheumatologist at
Arthritis and Pain of Prince George’s County, Maryland
Join us and ALL IN™ for a virtual discussion featuring Dr. Thomas about lupus and lupus nephritis. The presentation and Q & A session are brought to you by Aurinia Pharma U.S., Inc.
COVID-19 Vaccines & Lupus Update
11:30 a.m.–12:00 p.m.
Alfred H. Kim, MD, PhD
Co-Director, Lupus Clinic at Washington University, Assistant
Professor of Medicine, Division of Rheumatology, Washington
University School of Medicine
Dr. Kim will provide an update on the Washington University School of Medicine trial evaluating the safety and effectiveness of COVID-19 vaccines in people taking immunosuppressives.
Closing the Gap on Health Disparities
Ashira Blazer, MD, MSCI
Assistant Professor of Medicine, Division of Rheumatology, NYU Langone Medical Center Bellevue Arthritis Clinic
Lupus disproportionately affects women of color, particularly black women. The implicit and explicit bias within the healthcare system may prevent them from receiving a timely diagnosis and the best care possible. Dr. Blazer will discuss ways to close this gap through education, awareness, and advocacy.
Managing Your Lupus: How You Can Take a More Active Role & Meditation Exercise
Arnita Christie, RN, BSN, MS Patient Engagement Liaison at GSK
Learn how you can take an active role in managing your lupus. You will learn more about the disease and how it affects your body, resources that can help you monitor your symptoms, how to communicate with your healthcare team, and the steps you can take to control lupus. Arnita will end with a guided meditation exercise. The presentation and Q & A Session are brought to you by GSK Us in Lupus.
Each session includes time for Q & A
QUESTION OF THE DAY:
Dr. T. I have lupus. I got both of my Moderna COVID vaccines. Can I take off my mask like the CDC recommends?
I am so glad you asked this question!
NO! (generally, see exceptions below)
The CDC's recommendation that vaccinated people can be outside without a mask and indoors when around other vaccinated people apply to the general public.
However, we do not know how well the vaccines work in people with autoimmune diseases?
I am so happy you got vaccinated. Until many more of us get vaccinated, life can't get back to "normal." Although, it is not guaranteed that you responded to the vaccine, if the COVID vaccine goes in line with other lupus vaccine studies, there should at least be some protection. Exceptions would include those who are heavily immunosuppressed may not have a very good response (for example, someone on rituximab who gets vaccinated a month or so after their treatment are unlikely to have a robust response).
Please continue to protect yourself with social distancing. Protect yourself at all times similar to how the CDC recommended prior to the vaccines.
Ask you friends and family to strongly consider getting vaccinated to help protect you as well (the cocoon effect)
If you have very mild lupus that has been in remission, you are young with no other health problems, and you take only hydroxychloroquine as your medication, they you could possibly do OK by not wearing a mask via the May 2021 guidelines for people who have been vaccinated.
Please ask your rheumatologist for their advice.
CDC Study answers this question
QUESTION: How effective is just one COVID-19 vaccine if you did not get the second?
Type of study? A Centers for Disease Study
Where? 33 sites in 25 states (U.S. study)
Who? Health Care Provider recipients of Pfizer and Moderna vaccines
Results? One vaccine offered an 82% protection rate (Pfizer, Moderna)
94% for 2 doses. This similar to what we saw in the clinical trials
How about people with lupus, Sjogren's and other autoimmune diseases?
- They were not studied
- However, there are active studies being done at the NIH, Johns Hopkins, etc
- If you live near Bethesda, MD, call the NIH nurses at 301-435-4489 and 301-451-4990; tell them Dr. Thomas sent you
- If you have an autoimmune disorder, especially if you are on immunosuppressant therapy, you are at higher risk of bad outcomes from COVID-19 infection.
- It is imperative you get vaccinated
- Make sure to stop your immunosuppressants appropriately for vaccination (but ask your doctor 1st to check)
Here is a link on how to stop meds for the vaccines:
- If you get vaccinated, pretend you are as vulnerable as if you did not get vaccinated
- Still practice social distancing
- Ignore the CDC guidance for others who are vaccinated... i.e. still wear your masks and socially distance from everyone and plead the unvaccinated to just stay away from you (I always worry about my patients)
REFERENCE: ACR, COVID-19 Vaccine Clinical Guidance Summary for Patients with Rheumatic and Musculoskeletal Diseases. Developed by the ACR COVID-19 Vaccine Clinical Guidance Task Force.
Pilishvili T, Fleming-Dutra KE, Farrar JL, et al. Interim Estimates of Vaccine Effectiveness of Pfizer-BioNTech and Moderna COVID-19 Vaccines Among Health Care Personnel — 33 U.S. Sites, January–March 2021. MMWR Morb Mortal Wkly Rep. ePub: 14 May 2021. DOI: http://dx.doi.org/10.15585/mmwr.mm7020e2external icon.
Learn why we want a urine sample every few months
Watch the video below to learn about lupus nephritis and why it is so important to give a urine sample every a3 months when you have systemic lupus.
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
Brought to you by Lupus LA, Aurinia, and Don Thomas, MD
Finally, the phase 3 data were published in the Lancet!
Lupkynis (voclosporin) impressively improves lupus nephritis compared to when patients get mycophenolate plus steroids alone.
We can now read the data ourselves, and it is impressive.
Here is where I break down the numbers into easier to understand language:
Here is a link to the article itself:
Treatments are getting better and better for lupus patients. Now, if only anifrolumab (Saphnelo) can get approved ASAP!
Prof Brad H Rovin, MD, et al. Efficacy and safety of voclosporin versus placebo for lupus nephritis (AURORA 1): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial. The Lancet May 07, 2021 Online; DOI:https://doi.org/10.1016/S0140-6736(21)00578-XDOI
Concise, practical video from the Sjogren's Foundation
In this short video you will find out:
- the causes of fatigue in autoimmune disorders such as Sjogren's. It also applies to systemic lupus erythematosus
- the different types of fatigue
- practical advice on how to approach and treat fatigue
- Download my free Fatigue Management and Sleep Hygiene Handouts here:
SHARE with anyone who may suffer from fatigue
COMMENT above, please share how you deal with fatigue. Are you a spoonie?
Which is better for lupus nephritis?
Data below is from the phase III clinical trial (BLISS-LN) unless otherwise stated
- Flexible options. Given both by IV (intravenous) by a nurse, or at home by self injection (SQ form).
- Has been around and used for a long time (since March 2011), so there is a lot of experience with its safety and effectiveness
- Its safety in the lupus nephritis trials was similar to its safety in the phase III clinical trials for SLE.
- You don't have to fail other drugs 1st before using it for LN
- Most patients studied had class III or class IV nephritis
- Steroids had to be tapered to 10 mg a day or less of prednisone by week 24
- Complete renal response (CRR, remission or close to remission) at 104 weeks was 30% on Benlysta plus mycophenolate (MMF) or cyclophosphamide + steroids versus only 20% on standard of care alone (MMF or cyclophosphamide + steroids). Cautionary note: the definition for CRR was stricter in the Benlysta trial than the Lupkynis trial, so you cannot assume that Lupkynis did better for CRR. The Benlysta trial required better kidney function results than the Lupkynis trial did.
- The odds ratio for the CRR was 1.74 meaning that patients who received Benlysta plus standard of care had a 74% greater odds of achieving a CRR compared to patients treated with standard of care alone (ie placebo). Again, remember that the Benlysta trial had a stricter definition for CRR. You cannot compare the 1.74 for Benlysta to 2.7 for Lupkynis.
- Patients receiving Benlysta plus standard of care had a 58% increased likelihood at any time of achieving a CRR and remaining in a CRR until week 104. Note that this timing cannot be compared to Lupkynis' timing for decreased proteinuria. These are two different measurements.
- Black patients were more likely to achieve a CRR at 104 weeks on Benlysta plus standard of care compared to standard of care alone. However, these results were not calculated in the research paper.
- Benlysta plus standard of care resulted in a 49% lower likelihood of a "renal-related event or death" up to week 104 compared to placebo plus standard of care treatment.
- Benlysta was studied combined with both mycophenolate and cyclophosphamide. Lupkynis was only studied along with mycophenolate.
- Excellent patient assistance program at www.benlysta.com.
- Both the IV form and the self-injectable SQ forms can be used to treat lupus nephritis.
- Much easier dosing than Lupkynis. IV form is the same as that for SLE. The SQ form is 2 injections (400 mg) weekly for 4 doses followed by 1 injection weekly after that.
- The package insert does not recommend use in pregnancy (was not studied). However, the pregnancy registry conducted for more than 10 years has thus far shown no signals for fetal problems. Some rheumatologists have used it safely during pregnancy.
- There was a question of possible increased suicides, suicidal thoughts, and worsened depression in previous IV Benlysta studies. However, in this lupus nephritis study, there were actually more of these problems in the placebo group. However, this was most likely not statistically significant.
- Proven in multiple phase III clinical trials that it is safe and effective for systemic lupus problems other than kidney inflammation. This especially is true for arthritis, cutaneous (skin) lupus, and patients with high anti-dsDNA and low C3 and low C4 levels. Though the FDA would not allow a fatigue mention (due to not having a validated fatigue measure for SLE), there was improvements in energy (and I note this in my own patients). Of note, it is even FDA-approved to treat children with SLE as young as 5 years old!
- Both were studied for 104 weeks
- People who don't like injections may not like it
- Only around 14% of the patients were black (under-recruitment of black patients is a continuing problem)
- On the surface, the Lupkynis numbers are more impressive regarding how fast proteinuria is decreased and the number of patients who go into a complete renal response (CRR). However, definitions for these goals were different in the two studies, so direct comparisons cannot be made. From experience, we do know that other calcineurin inhibitors, such as tacrolimus, can have markedly fast and profound effects on proteinuria, so it would not be surprising if Lupkynis were to reduce proteinuria faster than Benlysta. SEE MY INDEPTH DISCUSSION ON THE CRR BELOW.
- It is expensive. But not as expensive as Lupkynis. The ICER (Institute for Clinical and Economic Review) estimates a yearly price of $43,000 for patients who stay on Benlysta.
Data below is from the phase III clinical trial (AURORA trial) unless otherwise stated
- Oral capsule form. Not an injection.
- It is brand new with no long term data. However, it is in a class of drugs called calcineurin inhibitors (CNI) which have been around for a long time.
- It is a new and improved 3rd generation CNI. It is more potent than cyclosporine (another CNI) and is less likely to cause cholesterol problems than cyclosporine. It is much less likely to cause diabetes compared to the CNI called tacrolimus. It results in such a stable, predictable drug level that blood drug levels are not needed.
- You don't have to fail other drugs 1st before using it for LN
- Most patients studied had class IV nephritis (the type with the worst prognosis)
- Amazing steroid taper! Only 500 mg IV SoluMEDROL for 2 days (many docs use 1000 mg for 3 days) followed by 25 mg a day prednisone tapered to 5 mg a day by 2 months and 2.5 mg a day by 4 months. Many, to most docs, use 40 mg to 60 mg a day after the IV steroids. So, starting with just 25 mg is phenomenal!
- Complete renal response (CRR, remission or close to remission) at 52 weeks was 41% on Lupkynis plus mycophenolate (MMF) + steroids versus only 23% on standard of care alone (MMF + steroids).
- The odds ratio for the CRR was 2.7 meaning that patients who received Lupkynis plus standard of care had a 170% greater odds of achieving a CRR compared to patients treated with standard of care alone (ie placebo).
- Lupkynis plus standard of care resulted in low urine protein levels (urine protein to creatinine ratio of 0.5 mg/mg or less) twice as fast compared to standard of care. The median time to this goal was 172 days for Lupkynis and 372 days for standard of care! "Time is kidney," we want our treatments to work as fast as possible, so this is amazing.
- 46% of black patients on Lupkynis had a CRR by 1 year compared to 16% on standard of care. In other words, three times as many black patients achieved a CRR on Lupkynis compared to standard of care! Our black patients are harder to treat and get their disease under control, so this is promising.
- Likewise, 39% of Hispanic patients on Lupkynis had a CRR at 1 year compared to 19% on standard of care (again, they typically are harder to treat, so this is promising).
- When looking at the type of LN, the worst type, class IV diffuse proliferative-- 47% of patients had a CRR at 1 year on Lupkynis, while 25% of those did on standard of care.
- It has 2 modes of action. In addition to the immunosuppressive effects, it also stabilizes podocytes, which are essential kidney cells that ensure the kidney filters (nephrons, glomeruli) are working properly and not allowing large proteins to escape from the blood into the urine.
- Excellent patient assistance program, Aurinia Alliance. They will get medication in the patient's hands within 5 days if there is any delay in getting it while they help work on the prior authorization process: support@AuriniaAlliance.com and 833-287-4642
- It is not FDA-approved to treat SLE problems other than lupus nephritis. However, in both the phase 2 and phase 3 clinical trials, there were some numerical improvements in a lupus disease measurement called the SELENA-SLEDAI score. The lupus nephritis trials were not designed to answers this question. I hope Aurinia pharmaceuticals considers doing an SLE study.
- Although the phase III clinical trial was only 52 weeks, a press release in May 2021 stated that low urine protein levels along with stabilization of kidney function was seen through week 104 in the long term extension trial.
- Lots of pills to take daily. Most commonly 3 capsules twice daily
- Only around 9% of the patients were black (under-recruitment of black patients is a continuing problem)
- As expected for a calcineurin inhibitor, decreased kidney function and high blood pressure were the most common side effects
- However, at week 24 and week 52, there was no difference in blood pressure between patients on Lupkynis and those on placebo plus standard of care
- In those with decreased kidney function, the dose of Lupkynis was decreased as recommended in the package insert. Most patients rebounded well to normal or to their target kidney function goal. In the end, there was "no clinically meaningful differences in mean eGFR vs placebo plus standard of care."
- The next most common side effects, as expected, were gastrointestinal issues, infections, and headaches.
- Long term side effects for infections and cancer is unknown.
- Lupkynis is more expensive. The ICER estimates a yearly price of $92,000 for patients who stay on it.
- Complicated dosing. The dose should be reduced if the kidney function decreases too much, or if there is cirrhosis of the liver, or if used with drugs that affect metabolism (CYP3A4 inducers, inhibitors, and P-gp substrates)
- Numerous potential drug interactions (such as listed above). It is important to use a drug interaction program such as UpToDate.
- Blood pressure and kidney function need checked before treatment, then every 2 weeks the first month. Kidney function should be checked monthly on treatment after month 1.
- Use during pregnancy and breastfeeding not recommended.
- Benlysta was studied combined with both mycophenolate and cyclophosphamide. Lupkynis was only studied along with mycophenolate.
- More difficult to prescribe than Benlysta. Only one specialty pharmacy handles it. Must contact Aurinia Alliance for assistance 1-833-287-4642
Why is a complete renal response (CRR) so important? Our goal in treating lupus nephritis is to get it into remission. Patients who reach remission are much less likely to go into kidney failure, have less organ damage, and live significantly longer than patients who have a partial response to therapy. CRR is not called "remission" because you truly do not know if the patient is in remission unless you do a kidney biopsy, but it is the closest we have without the biopsy.
First, what did they have in common? - Both did not allow any significant increase in steroids, change in doses of ACEi's or ARBs (blood pressure medicines that lower urine protein), addition of an antimalarial if not on one already, and no addition of any other immunosuppressant drug.
The other is they both had a similar urine protein to creatinine ratio (UPCR) goal (with one slight, nonsignificant difference). Lupkynis patients had to reach a UPCR of 0.5 mg/mg or less; Benlysta patients had to be below 0.5 mg/mg.
The big difference for complete renal response was in the kidney function stabilization criteria:
Benlysta required a eGFR of 90 ml/min or higher (or within 10% of the baseline if less than 90).
Lupkynis patients could have a eGFR of 60 ml/min or more (or within 20% of the baseline if less than 60).
It is much more difficult to have an eGFR of 90 ml/min or higher when you have severe lupus nephritis. So, this was an impressive requirement.
However, this is balanced out by Lupkynis using the CRR as its primary endpoint, while Benlysta used it as a secondary endpoint. Having it as the primary endpoint is wonderful as that is truly our goal. We don't just want a "renal response," with a treatment, we want remission (CRR or close to a CRR).
INTERESTING FACT ABOUT LUPKYNIS AND PREGNANCY:
Other calcineurin inhibitors (such as tacrolimus) are safe to use in pregnancy.
Why is it recommended not to use Lupkynis in pregnancy?
Each capsule of Lupkynis contains 21 mg of alcohol.
Putting it into perspective, 5 oz of red wine contains around 4000 mg of alcohol.
However, the Centers for Disease Control states, " There is no known safe amount of alcohol use during pregnancy or while trying to get pregnant."
Neither is definitely any better or worse than the other!
They are both game changers in the treatment for lupus nephritis, and they both have their place
What would I do if I had severe lupus nephritis?
Whenever I treat a patient, I always put myself in their shoes and ask myself, "what would I want if I were the patient, knowing everything that I know?" Or, what would I recommend to my family member if they were the patient.
The problem with the treatments for lupus nephritis prior to Benlysta and Lupkynis is that most patients do NOT go into remission.
Previous therapies (called ""standard of care" in the research studies) take too long to work. While we wait for them to work, permanent damage to the kidneys occurs. Once you lose each nephron (filter) due to lupus inflammation, it is gone forever.
We end up having to use too much steroids which cause side effects in everyone when used at high doses for lupus nephritis. These high doses of steroids also cause organ damage themselves. We always want to get away from treatments that also cause damage to our bodies!
So here we have two drugs that have proven themselves to increase remission, work faster, and decrease the need for steroids.
Plus, they had excellent safety in the studies. In my opinion, they are markedly safer than steroids.
If I had lupus nephritis, I would absolutely want Benlysta or Lupkynis plus mycophenolate plus hydroxychloroquine plus an angiotensin converting enzyme inhibitor or an angiotensin receptor blocker plus vitamin D plus religious sunscreen usage immediately as my treatment.
If my nephritis were severe, I'd only want 250 mg to 500 mg IV pulse SoluMEDROL for only 2 days followed by just 20 mg to 25 mg a day of prednisone daily with a rapid taper. I want as little of steroids as possible.
I would also see if my insurance would allow me to use both Benlysta plus Lupkynis at the same time! They work in 2 different directions and if they could get me into remission faster and get me off steroids faster, why not?
What should you do if you have lupus nephritis?
- Learn as much as you can. Knowledge is Power!
- Mentally accept the fact that you will need to take numerous medications to treat the nephritis. Take all the medicines religiously. When you get tired of taking your medicine, tell yourself, "I want to do everything possible to stay off dialysis and prevent needing a kidney transplant." Each treatment has its reason behind using it. Your goal is to let the other meds (Hydroxychloroquine, vitamin D, sunscreen, mycophenolate or cyclophosphamide, Benlysta, Lupkynis, ACEi or ARB) do their magic so you can get under control faster and get down and off of those steroids! Just for example, I recently started taking care of this very nice gentleman with severe lupus nephritis who had numerous, painful, broken bones in his spine from steroids (his treatment did not include all the things I mention above). I wish I could have taken care of him from day #1. I'm confident I could have helped prevent that from happening. Don't let that be you.
- If you want an easy to take medicine that has proven long term safety, and is less of a hassle to take, then Benlysta may be a good choice for you.
- If you think that Lupkynis may work faster and better (we do not know this 100%, however), then Lupkynis may be a good choice if you don't mind taking 6 capsules daily and getting frequent blood pressure and blood work done.
- If you want to give it everything possible (like I would) ask your doctor about taking both.
PLEASE COMMENT above. Would you add any other pros or cons? What are your questions about lupus nephritis, Benlysta, and Lupkynis?
Package inserts for both Benlysta and Lupkynis
Furie R, Rovin BH, Houssiau F, Malvar A, Teng YKO, Contreras G, Amoura Z, Yu X, Mok CC, Santiago MB, Saxena A, Green Y, Ji B, Kleoudis C, Burriss SW, Barnett C, Roth DA. Two-Year, Randomized, Controlled Trial of Belimumab in Lupus Nephritis. N Engl J Med. 2020 Sep 17;383(12):1117-1128. doi: 10.1056/NEJMoa2001180. PMID: 32937045.
Kuglstatter A, Mueller F, Kusznir E, et al. Structural basis for the cyclophilin A binding affinity
and immunosuppressive potency of E‐ISA247 (voclosporin). Acta Crystallogr D Biol Crystallogr.
Bîrsan T, Dambrin C, Freitag DG, et al. The novel calcineurin inhibitor ISA247: a more potent
immunosuppressant than cyclosporine in vitro. Transpl Int. 2005;17(12):767‐771.
Mayo PR, Huizinga RB, Ling SY, et al. Voclosporin food effect and single oral ascending dose
pharmacokinetic and pharmacodynamic studies in healthy human subjects. J Clin Pharmacol.
Gibson K, Parikh S, Saxena A, et al; AURORA Study Group. AURORA phase 3 study
demonstrates voclosporin statistical superiority over standard of care in lupus nephritis.
Presented at: National Kidney Foundation virtual 2020 Spring Clinical Meetings; March 26‐29,
Arriens C, Polyakova S, Adzerikho I, et al; AURORA Study Group. AURORA phase 3 study
demonstrates voclosporin statistical superiority over standard of care in lupus nephritis.
Presented at: EULAR European E‐Congress of Rheumatology 2020; June 3‐Sept 1, 2020
Askanase A, Randhawa S, Lisk L, et al. Efficacy of voclosporin across lupus nephritis
biopsy classes: pooled data from the AURORA 1 and AURA‐LV trials. Presented at:
National Kidney Foundation virtual 2021 Spring Clinical Meetings; April 6‐10, 2021.
Rovin BH, Parikh SW, Huizinga RB, et al; AURORA Study Group. Management of lupus nephritis with voclosporin: an
update from a pooled analysis of 534 patients. Presented at: American Society of Nephrology Kidney Week 2020
Reimagined; Oct 19‐25, 2020
Caster DJ, Solomons N, Randhawa S, et al; AURORA Study Group. AURORA phase 3 study demonstrates voclosporin
statistical superiority over standard of care in lupus nephritis. Presented at: ERA‐EDTA Virtual Congress; June 6‐9, 2020
Don Thomas, MD, author of "The Lupus Encyclopedia" and "The Lupus Secrets"
DISCLAIMER: I am on the Speaker's Bureaus for both Benlysta and Lupkynis. I do this proudly as I believe strongly in how much these medications can improve the treatment of our lupus patients, helping them live longer, better lives. I hope you can agree that the information I presented above is unbiased, using the data from the research studies. However, the opinions expressed in what I would want for treatment and what I recommend for patients are my opinions, based upon the research results.
Know your labs when you have lupus
Chromatin Antibody (Also called Anti-Chromatin Antibody; nucleosome antibody).
- Chromatin antibodies are fairly specific for people who have lupus, but can occasionally be seen in other autoimmune disorders
- They are rare in healthy people
- They may possibly increase the risk of having lupus kidney inflammation (lupus nephritis), however, having them does not mean you will get nephritis. Just make sure to have a urine sample checked regularly
- In some people, they can fluctuate with disease activity and help monitor how someone with systemic lupus erythematosus (SLE) is responding to therapy.
Chromatin refers to the complex of DNA and other proteins that form chromosomes inside the nuclei of cells. About 60% to 70% of people who have SLE are positive for these antibodies, and they appear more commonly in SLE than in other systemic autoimmune diseases. Initial studies suggested that patients with SLE who are positive for chromatin antibody may have an increased risk for developing inflammation of the kidneys (lupus nephritis); however, this has been questioned in subsequent studies.
Sometimes it can be difficult to tell if a patient may have SLE or Sjögren’s when they first come to a rheumatologist. One study showed that if that patient is positive for chromatin antibody and negative for SSA antibody, they most likely have SLE as their diagnosis. In some people with SLE, chromatin antibodies fluctuate with disease activity, decreasing in value when there is better control of lupus and increasing when it is worse. Chromatin antibodies can also occur in other systemic autoimmune diseases, including drug-induced lupus, mixed connective tissue disease, and scleroderma.
- The above excerpt comes from "The Lupus Encyclopedia" prior to printing of the second edition
- Mehra, S., & Fritzler, M. J. (2014). The spectrum of anti-chromatin/nucleosome autoantibodies: independent and interdependent biomarkers of disease. Journal of immunology research, 2014, 368274. https://doi.org/10.1155/2014/368274
World-wide shortage of rheumatologists= getting worse
The worldwide shortage of rheumatologists is getting worse: hold on to your rheumatologist!
If you have difficulty getting in to see a rheumatologist, there are good reasons why.
In 2015, there was a shortage of rheumatologists throughout the US. The American College of Rheumatology (ACR) counted 6,013 rheumatology care providers. 4,997 were full-time rheumatologists, 598 worked part-time, and the other 418 were nurse practitioners and physician assistants specializing in rheumatology. This was 13% fewer rheumatologists than needed by the population, according to the ACR. Since then, the numbers have continued to decrease. Many rheumatologists are retiring, and not enough new ones are entering the specialty. In 2020, 100 doctors who wanted to get into rheumatology training programs could not do so because there were not enough training slots.
By the year 2030, the total number of healthcare providers specializing in rheumatology in the US is predicted to drop from 6,013 to 4,133 nationwide. There will also be a greater need for rheumatologists. The number of older people with arthritis (the baby boomers) will be much higher. It is estimated that there will be only half the number of rheumatology healthcare providers that will be needed to care for rheumatologic patients, such as those with SLE.
Another problem is that many areas of the US have few to no rheumatologists. Many patients have to travel hundreds of miles to see the closest one. 21% of rheumatologists are in the Northeast while only 4% are in the Southwest, and this imbalance is predicted to get worse. There are much fewer people in the population per rheumatologist in the Northeast compared to the Southwest.
A 2019 US study showed that more than 60% of US patients had to wait more than a month to get a new patient appointment with a rheumatologist. More than a quarter of patients had to wait more than 2 months.
It’s much worse for children with rheumatic diseases (such as pediatric SLE). Only 1 of 4 children with arthritis can see a pediatric rheumatologist. Those fortunate to see one have an average of an hour’s drive. Nine states have no pediatric rheumatologists, and six states have only one.
A 2019 United Kingdom study showed that patients waited for an average of over 6 months after the onset of rheumatologic symptoms before being able to see a rheumatologist. So this is not just a US problem.
American College of Rheumatology Committee on Rheumatology Training and Workforce Issues, FitzGerald JD, Battistone M, Brown CR Jr, Cannella AC, Chakravarty E, Gelber AC, Lozada CJ, Punaro M, Slusher B, Abelson A, Elashoff DA, Benford L. Regional distribution of adult rheumatologists. Arthritis Rheum. 2013 Dec;65(12):3017-25. doi: 10.1002/art.38167. PMID: 24284967.
Battafarano DF, Ditmyer M, Bolster MB, Fitzgerald JD, Deal C, Bass AR, Molina R, Erickson AR, Hausmann JS, Klein-Gitelman M, Imundo LF, Smith BJ, Jones K, Greene K, Monrad SU. 2015 American College of Rheumatology Workforce Study: Supply and Demand Projections of Adult Rheumatology Workforce, 2015-2030. Arthritis Care Res (Hoboken). 2018 Apr;70(4):617-626. doi: 10.1002/acr.23518. PMID: 29400009.
Borenstein D. Hug your rheumatologist: the shortage is coming. The Arthritis Connection Summer 2020. Retrieved on 4/11/21 at https://www.thearthritisconnection.com/rheumatoid-arthritis/hug-your-rheumatologist-the-shortage-is-coming
Should lupus patients use medical marijuana?
With the increasing popularity and availability of cannabis and CBD, many lupus patients are asking, "How about CBD and lupus?"
Marijuana (cannabis) and its active components (THC and CBD) has become more popular for medical treatments. As of this writing (April 2021), 42 states in the US allow the use of medical marijuana, and 11 states (and the District of Columbia) have fully legalized its use recreationally. Many of my patients ask about using it, so I think it is important to go over some important information about it.
My goal is to present the facts based on scientific evidence without bias.
Cannabinoids are the active compounds of the cannabis plant. There are over 140 different cannabis-derived cannabinoids known, and each acts differently in the body. The 2 most studied and well-known are cannabidiol (CBD) and tetrahydrocannabinol (THC). THC is the cannabinoid responsible for the “high,” intoxicating effects with recreational users. CBD does not make people “high.”
Dry mouth? Dry eyes? Dry itchy skin? Losing teeth? Severe fatigue? Pain? ... learn what you can do!
- Access to leading experts to hear the latest: You get to ask questions and hear answers live!
- Too shy to ask at a live conference? It is much easier virtually. Just type in your question!
- Around 30% of systemic lupus patients have Sjogren's!
- If you have dry mouth, dry eyes, dry itchy skin, go to www.sjogrens.org to learn more. Consider joining!
- If you are a new patient, learn the important basics
- If you are a seasoned, well-informed patient, we guarantee there will be new stuff
- Learn practical information you can take home to help with:
- Dry mouth, dry eyes, dry itchy skin
- Decrease the loss of teeth
- Lower your risk of fungal infections, thrush, etc.
- Has it been impossible to keep up with work? Understand your job and disability rights
- How did you get Sjogren's? Learn about the genetics behind it!
- How are Sjogren's patients doing during COVID-19 and what should they do?
- 15% - 20% of Sjogren's patients get inflammation of the lungs. Learn what your doctors should do
- New Guidelines published this year thanks to the Sjogren's Foundation
- Exciting, promising drugs are in the research pipeline... learn what they are and how promising they are!
- Tons of products available to improve quality of life. Learn about the latest and greatest
I hope to see you there!
A potential new drug for lupus--
here are some early facts
I received this email today, 4/18/21, announcing the brand name!
I have never seen a brand name announced before official FDA-approval.
Someone must know something I do not know ... did they get wind of a pending nod from the FDA?
This drug has impressive results from its research studies ... let me share a few so all SLE patients who have failed other medications realize that there is HOPE!
Research results "in a nut shell" in easy-to-understand language
The clinical trials for anifrolumab were called the TULIP trials
TULIP comes from the full research study name: Treatment of Uncontrolled Lupus via the Interferon Pathway
How does it work?
Most (70%) of systemic lupus erythematosus (SLE) patients have high levels of interferons
Interferons cause inflammation of organs, leading to permanent organ damage
Anifrolumab competes with interferon by attaching to the attachments (receptors) on immune system cells
Normally, when interferons bind to those receptors, the immune system cells become more active
Then they alert more immune system cells to become more active and attack body organs
Anifrolumab decreases this cascade of events from happening
This leads to less inflammation
It is a biologic monoclonal antibody, so it will be expensive!
Anifrolumab (Saphnelo) works differently than any drug used in the past to treat lupus!
1st in its class!
How is it given?
Saphnelo is given intravenously (IV), 300 mg, every 4 weeks (I suspect it will be 300 mg)
What were the research results?
There was a 90% reduction of interferons at 6 months in the patients who started off with high levels
Other labs measuring lupus inflammation improved (anti-dsDNA, C3, C4, CH50)
Low white blood cell counts and low platelet counts improved
What other good things did it do for the SLE patients?
They had less disease activity
Even patients who started with normal interferon levels overall improved
In TULIP-2: 57% (46 placebo vs 72 anifrolumab patients) more patients who started with high interferon levels met the primary endpoint with anifrolumab
... 58% more patients! Impressive!
When looking at all patients, a 51% higher number of patients responded to anifrolumab, including those with normal interferon levels!
You do not have to have high interferon levels to respond!
Close to twice as many patients were able to decrease their steroids to goal (25 placebo vs 45 on anifrolumab)
Lower steroids is important because higher doses of steroids cause organ damage
Anifrolumab reduced lupus flares
It especially worked well for cutaneous lupus
Look at the picture above from one of the studies
This patient had an amazing improvement. Many others did just as well
They measured skin activity with a CLASI score and looked for more than a 50% improvement
CLASI stands for Cutaneous Lupus Erythematosus Disease Area and Severity Index
Twice as many anifrolumab patients responded compared to placebo!
The numbers were 25% of the placebo cutaneous lupus patients responded, while 49% on anifrolumab did
How fast does it work?
Reduced disease activity was seen as early as 2 months
What were the side effects of anifrolumab
When comparing side effects, it is important to know that the placebo patients were not truly "placebo"
They were receiving standard of care therapy
In other words, most were on immunosuppressants and steroids that cause side effects themselves
The patients on anifrolumab were also on immunosuppressants and steroids
Therefore sorting out what anifrolumab may do vs the other drugs is very difficult
But, here are the numbers (combination of three different anifrolumab research studies):
Around 87% of anifrolumab patients and 80% of placebo patients had side effects
This include nuisance, mild side effects
The most common were viral upper respiratory tract (URI) and throat infections (cold-like infections)
Infusion reactions were the other most common
For example, 10% of the placebo (standard of care) patients had URIs, 18% on anifrolumab did
This is not surprising, interferon is important for fighting viral infections
Shingles occurred in around 6% of anifrolumab patients and 1%-2% of placebo patients
Again, not surprising since shingles is due to chicken pox virus
(MAKE SURE TO GET A SHINGLES VACCINE, SUCH AS SHINGRIX, BEFORE TREATMENT!)
6% of anifrolumab patients had to stop treatment due to side effects; 3% of placebo patients had to stop
What patients were not studied?
Patients with severe kidney inflammation (lupus nephritis, LN), brain, and nerve lupus (neuropsychiatric) were not
Therefore, we do not know if it works in them
However, I will go out on a limb and predict it will help LN patients
We know that interferon plays a role in LN
Just because we do not have study results for severe LN patients, this does not mean it does not work
What could possibly keep the FDA from approving it?
In the first TULIP-1 trial, it did not meet its primary endpoint (research goal called the SRI-4)
This could get some voting members to vote "no" for approval
However, lupus experts realize how hard it is to prove that lupus drugs work
They evaluated how the drug performed in the 1st trial
Patients did have significant improvements
They were able to lower their steroids and there was marked improvements in cutaneous lupus
One criticism is that some patients changed their NSAID (like ibuprofen) during the study
These patients were automatically labeled as a drug failure, though many of them had great responses
So they changed the primary endpoint for TULIP-2 based on their analysis of TULIP-1
The TULIP-2 trial did meet its primary end point
- Impressive results, especially for skin lupus
- Low rate of side effects (colds, sore throats, infusion reactions, shingles are the most important)
- Get your Shingrix shot before treatment
- I have a list of SLE patients who have failed everything who need to try this drug if it is FDA-approved!
Good luck to AstraZeneca who is the manufacturer of Saphnelo
Furie R, Khamashta M, Merrill JT, et al.; for the CD1013 Study Investigators. Anifrolumab, an anti-interferon-alpha receptor monoclonal antibody,in moderate-to-severe systemic lupus erythematosus.Arthritis Rheumatol. 2017;69(2):376–86.
Furie R, Morand EF, Bruce IN, Manzi S, Kalunian K, Vital EM, et al. Type I interferon inhibitor anifrolumab in active systemic lupus erythematosus (TULIP-1): a randomised, controlled, phase 3 trial. Lancet Rheumatol. 2019;1(4):e208–19.
Morand EF, Furie R, Tanaka Y, Bruce IN, Askanase AD, Richez C, et al.; TULIP-2 Trial Investigators. Trial of anifrolumab in active systemic lupus erythematosus. N Engl J Med. 2020;382(3): 211–21.
Tanaka Y, Takeuchi T, Okada M, Ishii T, Nakajima H, Kawai S, et al. Safety and tolerability of anifrolumab, a monoclonal antibody targeting type I interferon receptor, in Japanese patients with systemic lupus erythematosus: a multicenter, phase 2, open label study. Mod Rheumatol. 2020;30(1):101–8.
Please enter our NIH study to help us find out how the COVID-19 vaccine affects people with autoimmune disorders
We also need healthy volunteers as well!
How often does discoid lupus turn into systemic lupus?
- The above photo is a classic example of discoid lupus
- Around 15% of people with systemic lupus erythematosus (SLE) will also have discoid lupus erythematosus (DLE)
- If someone develops DLE by itself, it can potentially evolve to SLE over time
- SLE will develop in 25% to 30% of children who have DLE
- In adults, it depends upon how extensive the DLE is:
- if the DLE is just above the neck (localized DLE), that person has approximately a 10% chance of SLE
- If the DLE is above and below the neck (generalized DLE), there is a 1 out of 4 chance of evolving to SLE
A ray of hope
- People who have DLE that evolves to SLE tend to have a milder form of SLE. They are less likely to have severe organ involvement, such as lupus nephritis (kidney inflammation) compared to SLE patients who do not have DLE
- However, this rule is not 100%. There are some DLE patients who will develop severe SLE. This more commonly occurs in those with severe DLE that is generalized.
- Make sure to follow all the advice in the "Lupus Secrets" to ensure you have the greatest chance of not developing severe SLE
If you have discoid lupus... what is your experience and advice for others. COMMENT above
Arkin LM, Ansell L, Rademaker A, et al. The natural history of pediatric-onset discoid lupus erythematosus. J Am Acad Dermatol. 2015;72(4):628-633. doi:10.1016/j.jaad.2014.12.028
Chong BF, Song J, Olsen NJ. Determining risk factors for developing systemic lupus erythematosus in patients with discoid lupus erythematosus. Br J Dermatol. 2012 Jan;166(1):29-35. Epub 2011 Dec 5.
Izmirly P, Buyon J, Belmont HM, et al. Population-based prevalence and incidence estimates of primary discoid lupus erythematosus from the Manhattan Lupus Surveillance ProgramLupus Science & Medicine 2019;6:e000344. doi: 10.1136/lupus-2019-000344
Pons-Estel, G. J., Aspey, L. D., Bao, G., Pons-Estel, B. A., Wojdyla, D., Saurit, V., … Drenkard, C. (2017). Early discoid lupus erythematosus protects against renal disease in patients with systemic lupus erythematosus: longitudinal data from a large Latin American cohort. Lupus, 26(1), 73–83. https://doi.org/10.1177/0961203316651740
A drug made from up to 100,000 healthy volunteers!
Intravenous Immune Globulin (IVIG)
Immune globulins (also called immunoglobulins) are antibodies. A large number of antibodies given in IVIG may help in some autoimmune disorders such as polymyositis and dermatomyositis. However, IVIG is not commonly used for SLE. It is useful in people who have a deficiency in IgG immune globulins (medically known as hypogammaglobulinemia) and have recurrent infections due to this. A person with hypogammaglobulinemia can benefit significantly from IVIG because it replaces the absent IgG globulins needed to fight infections.
Studies evaluating IVIG use in cutaneous lupus (chapter 8), lupus nephritis, muscle inflammation, low blood cell counts (to include myelofibrosis), lupus lung inflammation, myocarditis, arthritis, severe antiphospholipid syndrome, and neuropsychiatric lupus, have had encouraging results. A small 2012 study also suggested that it may help prevent congenital heart block in women with lupus who are SSA or SSB antibody positive. However, larger studies will be needed to see if IVIG should be used more often to treat lupus.
IVIG is produced from the antibodies of healthy blood donors. It takes anywhere between 1,000 and 100,000 donors for one dose. The preparation undergoes treatments to kill any potential germs and is thoroughly tested before using it for therapy.
How IVIG works: IVIG can decrease immune system overactivity.
What benefits to expect from IVIG: IVIG can decrease infections in people with low levels of IgG globulins. It can help the conditions noted in the paragraph above. In some people, it works rapidly, even within days after the first treatment.
How IVIG is given: Usually given as an intravenous (IV) infusion once or twice a month. A self-injectable form that can be given at home is available.
If you miss a dose of IVIG: Reschedule as soon as you realize that you missed your dose, then reset your schedule from that point. Consult with your prescribing doctor to double-check these instructions, but these guidelines will be enough for most people.
What needs to be monitored while you get IVIG: You will need to have periodic lab tests, including blood cell counts and kidney function tests.
Reasons not to take IVIG: Many IVIG brands are unsafe to receive if you have a deficiency in IgA globulins. Your IgA globulin level can be measured using a blood test similar to the one that measures IgG globulin levels. Gammagard S/D and Polygam brands of IVIG are generally safe to use if you are IgA deficient. Pre-existing heart disease, kidney disease, and a history of blood clots may increase your risk of having these sorts of problems on IVIG. Discuss these possibilities with your doctor.
If you have severe IgA deficiency, you should receive IVIG that does not contain IgA, or it should be provided in a hospital setting. Patients with severe IgA deficiency can sometimes develop severe allergic reactions (anaphylaxis) to IVIG containing IgA immunoglobulins.
While taking IVIG therapy: See your doctor regularly for appropriate blood tests. Seek medical attention immediately if you develop a red, painful, swollen leg; shortness of breath; chest pain; slurred speech; or arm or leg weakness.
Vaccines and IVIG: No need to stop drug or time dosing with inactivated vaccines (such as for influenza, pneumonia, and COVID-19). IVIG may decrease the response to some live vaccines. Ask your doctor about timing with any live vaccines (such as Zostavax, yellow fever, MMR, and others).
Pregnancy and breastfeeding while on IVIG: IVIG can be used for severe lupus flares during pregnancy. Some think it may help prevent congenital heart block progression due to anti-SSA antibodies.
It can be used during breast-feeding.
Older people and IVIG: There may be an increased risk for side effects such as kidney problems, heart problems, and blood clots.
What to do at the time of surgery with IVIG: IVIG can potentially increase blood clots and probably should not be used close to the time of surgery. Check with the prescribing rheumatologist and infusion doctor for more information.
Potential Side Effects of IVIG
Nuisance side effects
Mild infusion reactions (headache, muscle and joint aches, fever, hives, chills, stomach upset, nausea, abdominal pain)
Elevated liver enzymes
Anemia and low white blood cell counts
Rash, skin vasculitis
Serious side effects
High blood pressure = common, treated with blood pressure medicines
Severe allergic reaction (anaphylaxis, low blood pressure, wheezing) = uncommon, treated by the nurses during the infusion
Severe headache, aseptic meningitis = uncommon. May be prevented with antihistamines, steroids, and pain medicines. May need to stop medicine.
Kidney failure = rare
Increase in lupus flares = rare
Blood clots = rare
Side effect incidence key (approximations, as side effects can vary widely study to study): rare < 1% occurrence; uncommon 1%–5% occurrence; common > 5% occurrence
If you have been treated with IVIG, what was your experience like? Please share in the Comments section above
The above is an excerpt from "The Lupus Encyclopedia" by Johns Hopkins University Press. This is a preliminary draft for the 2nd edition, before print
Don Thomas, MD, author of "The Lupus Encyclopedia" and "The Lupus Secrets"
A Johns Hopkins Lupus Clinic study suggests so...
Sunspots related to lupus activity? Are the Johns Hopkins doctors crazy?
- They are not crazy. I know George Stojan, MD and Dr. Michelle Petri, MD well. They are two of the smartest lupologists in the world.
- Previous research in Germany suggested health changes related to magnetic storms and sunspots (specifically while studying heart attacks by Halberg F, et al.)
- The Lupus Clinic at Johns Hopkins compared disease activity in their center from 1996 to 2020 and compared it to solar cycles, sunspots, and geometric disturbances.
- They found that increased sunspots (called solar maximum in the solar cycle) was followed by lower disease activity on average in their patients.
- Increased geomagnetic activity was also associated with lower disease activity.
- This is another study suggesting how important our environment is regarding lupus.
When will there be milder lupus activity as predicted by sunspots?
- Of course, this is all hypothetical, and this research needs to be reproduced.
- If it is correct, our most recent time of fewer sunspots was DEC 2019 (the least solar activity in 100 years)
- NASA predicts that solar maximum will occur in July 2025 with 115 sunspots (179 is the average)
- The previous solar maximum was in APR 2014 with 114 sunspots. Since Dr. Stojan's research included that sun cycle, this upcoming cycle should be similar.
- Therefore, SLE patients may look forward to the Fall and Winter, Northern Hemisphere (this was a Northern Hemisphere study) of 2025 as a period of having milder lupus attacks.
Note... this is all very interesting, but I would not put my money on it until further research is done
Stojan G, Giammarino F, Petri M. Systemic lupus Erythematosus and geomagnetic disturbances: a time series analysis. Environ Health. 2021 Mar 16;20(1):28. doi: 10.1186/s12940-021-00692-4. PMID: 33722240; PMCID: PMC7962208.
Halberg F, Cornélissen G, Otsuka K, Watanabe Y, Katinas GS, Burioka N, Delyukov A, Gorgo Y, Zhao Z, Weydahl A, Sothern RB, Siegelova J, Fiser B, Dusek J, Syutkina EV, Perfetto F, Tarquini R, Singh RB, Rhees B, Lofstrom D, Lofstrom P, Johnson PW, Schwartzkopff O, the International BIOCOS Study Group. Cross-spectrally coherent ~10.5- and 21-year biological and physical cycles, magnetic storms and myocardial infarctions*. Neuro Endocrinol Lett. 2000;21(3):233-258. PMID: 11455355.
NASA: What Will Solar Cycle 25 Look Like?
Latest evaluation and recommendations:
Lupus Science & Medicine
SARS-CoV-2 vaccines in patients with SLE
Link and reference below to the research studies
Summary of some main points (but I encourage you to read the article):
- This article is written by some of the world's experts in lupus
- Dr. Joan Merrill, Dr. Anca Askanase, Dr. Wei Tang, and Dr. Leila Khalili
"... the risks of not receiving the vaccine are far greater at the present time."
- The lupus experts also state,
"Patients with autoimmune rheumatic diseases should receive the COVID-19 vaccines and should be prioritized before the general population."
- Other vaccines have been shown to be safe in lupus patients.
- They recommend temporarily stopping or changing the dosing schedule on some drugs, such as cyclophosphamide, methotrexate, mycophenolate (CellCept, Myfortic), rituximab (Rituxan), abatacept (Orencia), JAK inhibitors (Xeljanz, Olumiant, Rinvoq), NSAIDs, and Tylenol.
- They recommend following the recommendations of the American College of Rheumatology (click on link)
- They recommend that doctors may want to consider monitoring antibody levels after the vaccine.
- Since we do not know how well lupus patients, patients with other autoimmune diseases, and immunosuppressed patients will respond to the vaccines, they should continue strict social distancing.
- The above recommendations are made without research regarding specifically these RNA vaccines. However, after evaluating all the data, The American College of Rheumatology and these lupus experts recommend vaccination in patients with autoimmune rheumatic diseases.
What are the risks of COVID-19 infection when lupus patients get infected?
- They are not at higher risk for infection from the novel SARS-CoV-2 Coronavirus.
- However, they are at higher risk of hospitalization than the general population.
- COVID-19 infection may even increase lupus flares.
Please get your vaccine. I got mine and I recommend it to all my patients.
This is not a substitute for your doctor's advice. Please check with your physician first.
Tang W, Askanase AD, Khalili L, et al. SARS-CoV-2 vaccines in patients with SLE. Lupus Science & Medicine 2021;8:e000479. doi: 10.1136/lupus-2021-000479
American College of Rheumatology (ACR) COVID-19 Vaccine Clinical Guidance Task Force. COVID-19 vaccine clinical guidance summary for patients with rheumatic and musculoskeletal diseases, 2021www.rheumatology.org/Portals/0/Files/COVID-19-Vaccine-Clinical-Guidance-Rheumatic-Diseases-Summary.pdf. Available: https://www.rheumatology.org/Portals/0/Files/COVID-19-Vaccine-Clinical-Guidance-Rheumatic-Diseases-Summary.pdfGoogle Scholar
There is no evidence that it is unsafe in lupus: read on!
Why do people with lupus think it is unsafe to take melatonin?
It is because there are outdated websites and patient education pages that state this. It even occurs on highly-acclaimed sites such as the Mayo Clinic.
How can the Mayo Clinic be wrong?
Most likely: there are tons of patient education pages that were produced a long time ago.
There is probably no one who polices and up dates them.
Certainly the doctors are way too busy to do this: they are taking care of patients and doing research.
Theoretically, melatonin may improve the immune system in lupus
and other autoimmune diseases
- One problem in lupus is that there are lower numbers of important white blood cells called Tregs (regulatory T-cells).
- Tregs help to normalize the immune system and prevent overactivity.
- With less Tregs, bad B-cells that make dangerous lupus autoantibodies (such as anti-dsDNA) can live a very long time (and even forever, "immortal").
- Melatonin does effect the immune system. One of the things it can do is increase these important Tregs that could be helpful in lupus and other autoimmune diseases
- The 2013 research article referenced below by Lin GJ et al and the 2019 article by Zhao et al go into detail about this
What happens to lupus mice when they are given melatonin
- When melatonin is given to female mice that are prone to getting lupus, it prevents them from getting lupus!
- This was shown in a 2010 study by Zou LL et al and another in 2008 by Jimenez-Caliani AJ et al (referenced below)
How about humans?
- There are no studies of using melatonin in people with lupus.
- This is a huge reason why it is incorrect to tell people with lupus not to use melatonin. There is no evidence to support that recommendation.
- However, there is a study in people with rheumatoid arthritis (a related autoimmune disease).
- Melatonin did NOT worsen rheumatoid arthritis in these patients (Maestroni et al, referenced below)
I do not ask my patients with lupus to avoid melatonin.
There is actually more evidence that it may be beneficial rather than harmful.
Lupus patient education websites should remove their recommendations to avoid melatonin.
These sites and pages are outdated.
What is anti-SSA antibody?
Know your labs!
I recommend that all lupus patients get copies of their labs every time they are done. Look up any abnormal results from a reliable source to know what they mean. If you cannot find a reliable source, then ask your doctor.
Remember... Knowledge is Power!
So, let's talk about anti-SSA (also called anti-Ro).
Why is anti-SSA also called anti-Ro?
Anti-SSA and anti-SSB antibodies were first discovered in 1961 in people who had Sjögren’s syndrome. This systemic autoimmune disorder attacks the body's moisture-producing glands, commonly causing dry eyes and dry mouth. The medical terms for them are “Sjögren’s syndrome-A” and “Sjögren’s syndrome-B” antibodies (or SSA and SSB for short). In 1969, another laboratory described antibodies in people who had lupus and named them anti-Ro and anti-La. “Ro” and “La” were the first two letters of the last names of the lupus patients in whom the antibodies were initially found (Robert and Lane respectively, according to Dubois’ Lupus 9th edition). Researchers later showed that anti-SSA was the same as anti-Ro and that anti-SSB was the same as anti-La. These terms are now interchangeable, with anti-SSA meaning the same thing as anti-Ro and anti-SSB meaning the same thing as anti-La.
How often does it occur?
Anti-SSA is more commonly positive in SLE patients than anti-SSB. SSA is positive in 20% to 60% of people who have SLE (depending on the patient population and the laboratory method used to detect the antibodies). Anywhere from 75% to 95% of people who have Sjögren’s syndrome are positive for this antibody. It can be present in any of the systemic autoimmune diseases and nonautoimmune conditions.
People who have SLE (systemic lupus erythematosus) and are anti-SSA positive have an increased risk of developing rashes with sun exposure (especially subacute cutaneous lupus), inflammation of the lungs (pneumonitis), shrinking lung syndrome, inflammation of the liver (hepatitis), inflammation of the pancreas (pancreatitis), inflammation of the heart (myocarditis), low platelet counts (thrombocytopenia), low lymphocyte counts (lymphopenia), and an overlap syndrome with Sjögren’s.
IMPORTANT NOTE: From the list above, the most important ones are sun-sensitive rash and Sjögren’s. Most do not develop the other problems, but are listed for your knowledge. Your doctor will monitor your liver enzymes and blood counts (hopefully every 3 months) and make sure to let your doctor know if you get chest pain, shortness of breath, bruising, rash, dry mouth or dry eyes.
Anti-SSA positive patients should particularly avoid ultraviolet light and become UV protection fanatics. Please download and follow my UV protection handout from this page:
ANA-negative SLE patients and anti-SSA
Although it is rare, some people who have SLE and are negative for ANA are positive for SSA antibody. If someone is thought to have SLE, but their ANA is negative, doctors should check for SSA antibodies. A newer ANA test, called “HEp-2000 ANA” (by a laboratory called Immuno Concepts in Sacramento, California), may be better at showing ANA positivity in these patients who are SSA antibody positive.
Anti-SSA can become positive years before SLE occurs
SSA antibody can be positive in someone many years before they develop lupus or Sjögren’s. It is one of the earliest antibodies to appear in many patients. This was figured out from blood samples of Army soldiers at the old Walter Reed Army Medical Center (Washington, DC) where I did my rheumatology fellowship.
It is essential that people found to have a positive SSA antibody (but not have evidence of having lupus, Sjögren’s, or any associated disease) be checked regularly by a doctor. I recommend that people in this situation learn what the symptoms of lupus and Sjögren’s are, and if any occur, to see a rheumatologist right away. Also, it is a good idea to see a rheumatologist regularly (such as once or twice a year) to have a proper physical examination and labs done. SLE can be potentially diagnosed by blood work (such as finding low blood counts or protein in the urine), yet the person may feel perfectly fine. The faster a proper diagnosis is made, the better the person usually does. Of course, someone who is SSA antibody positive may never develop any disease with it, but it better to be safe. I’d also recommend that someone in this category (antibody positive but no disease) avoid all potential triggers that may cause lupus (see table 3.1).
Important pregnancy information about anti-SSA
One of the most important potential problems is that this antibody can cross through the placenta and enter the fetus of a woman who is positive for this antibody. These antibodies can potentially cause tissue damage in the unborn baby's heart or skin (called neonatal lupus) whose mother is anti-SSA positive. Fortunately, this occurs in only about one out of fifty mothers who are positive for anti-SSA.
However, suppose a mother with SSA antibody has one child with neonatal lupus. In that case, her chances of each subsequent baby having neonatal lupus are approximately 20%.
Source of text: from "The Lupus Encyclopedia" preliminary write up for the upcoming 2nd edition, by Don Thomas, MD and Johns Hopkins University Press
References for the above can be found under chapter 4 here:
Photo credit (1st photo of lab test HeP immunofluorescence of anti-SSA test = from www.wikipedia.com article on Anti-SSA/anti-Ro antibodies, photo by Simon Caulton
Patient Information in easy-to-understand language
- LN affects 40% of SLE patients
- People with LN do not feel badly until it becomes severe
- This is why your rheumatologist asks you to do a urine sample every 3 months (hopefully)
- This is why you should do a frequent urine sample. The faster it is diagnosed, the faster it is treated, the higher the chances for remission
- These are unprecedented times for LN. We have the 1st two ever FDA-approved drugs for LN
Lupkynis (voclosporin, 1/22/21) and Benlysta (belimumab, 12/17/20)
- Both of these drugs greatly increase the chances for remission, allowing less usage of steroids
- WATCH THE VIDEO TO LEARN MORE ABOUT LUPUS NEPHRITIS!
- Brought to you by Aurinia, Lupus Chick, The Lupus Foundation of New England, and Don Thomas, MD
Results from 64,900 vaccines: Allergy Risk?
Journal of the American Medical Association Research Study: March 2021
(reference and link to the study are at the bottom of the page)
Easy-to-Read Results Summary:
- Researchers did this study based on the fact that many are nervous to get the vaccines due to having allergies themselves and all the media-hype regarding allergic reactions causes some people to avoid the vaccines.
So... what is the truth?
- Study was done at Massachusetts General Brigham (the Original Harvard hospital!)
- Studied what happened the 3 days after the first vaccine (the time of highest chances for allergy symptoms)
- 40% got Pfizer, 60% Moderna
Mild allergic reactions
- 1 out of every 50 vaccines caused mild allergic reactions (itch, hives, swelling)
- Moderna (2.2% of the shots caused mild allergy) vs Pfizer (2% of the shots): not much difference
- 98% of all people had no allergic reactions at all (that is a nice, safe number)
Significant allergic reactions (anaphylaxis)
- Occurred in 1 out of every 3700 Pfizer shots (i.e. .027% of the shots)
- Occurred in 1 out of every 4300 Moderna shots (i.e. .023% of the shots)
- In total, there were 5 anaphylactic reactions per 20,000 vaccines (that is a really safe number compared to many other drugs)
Timing for significant allergic reaction (anaphylaxis)
- An average of 17 minutes after the shot
- The range was from immediately after the shot up to 2 hours later at the latest
- 7 of the 16 patients had mild skin reactions
- 9 of the 16 patients had "measurable" but not life-threatening reactions
- 3 did not seek any medical attention
- 1 went to the ICU and recovered
- 9 out of 16 patients needed an epinephrine shot (EpiPen) and all recovered
- There were no severe anaphylactic reactions (having shock or requiring intubation)
Who was most likely to get anaphylaxis?
- Out of 16 patients in total, 5 (31%) had a history of anaphylaxis
- 10 out of 16 (61%) had a history of allergies (probably not significantly different than the usual population)
"I have a history of anaphylaxis, what is my risk?"
- Assuming there were 4000 individuals with severe food or drug allergies in this group (this is the expected #)
- Only 5 out of 4000 people with a history of anaphylaxis get an anaphylactic reaction (1 out of every 800)
- Knowing that this is a group of people who are used to planning for anaphylaxis and should have an EpiPen, and who know they have to use it when exposed to a known allergen (like me when I accidentally eat shrimp), that is an incredibly low number.
- I took my EpiPen with me when I got mine. No problems! Only 1 out of every 800 times would someone need to use it
- Since the results were reported by the employees themselves, and not confirmed by doctors, we cannot ensure that these were truly anaphylactic reactions (people do tend to overestimate such responses = my opinion)
- The researchers, Harvard-famous allergy experts, stated, "... the overall risk of anaphylaxis to an mRNA COVID-19 vaccine remains extremely low"
If you have had an anaphylactic reaction in the past (like I have), I recommend:
- Just take your EpiPen and wait a while after your shot if you have had anaphylaxis before. However, don't sweat it.
You have a higher chance of getting into a car accident on the way to the shot than you do of getting an anaphylactic reaction
Did you get your vaccine? How did you do?
COMMENT BY CLICKING ON "Comments" ABOVE
Reference: Blumenthal KG, Robinson LB, Camargo CA, et al. Acute Allergic Reactions to mRNA COVID-19 Vaccines. JAMA. Published online March 08, 2021. doi:10.1001/jama.2021.3976
10.5% of lupus and rheumatic disease patients died
Much higher rate than infected people without rheumatic disease
People with lupus and rheumatic diseases are at risk...
What is the bottom line? What should you do?
- Earlier reports in early 2020 suggested that lupus patients may not have been at higher risk of COVID-19 complications. This report (referenced below) questions this.
- This report looked at 3729 patient. It included patients with systemic lupus, but it did not specify how many lupus patients nor how they did compared to other patients. However, it looked at the risk for death in patients receiving various drugs, patients with certain comorbidities, disease activity risks, sex, and countries of residence.
Rheumatic disease patients at highest risk for death after infected with COVID-19 (listed in order)
(these results will be given in odds ratios.
To figure out how to word this (odds ratio findings):
Subtract 1 from the number, move the decimal point 2 to the right, then say "___ greater odds of dying from COVID-19."
For example, for an 80 year old with a rheumatic disease, they have a 518% greater odds of dying from COVID-19. A man with a rheumatic disease has a 68% greater odds of dying from COVID-19 infection than a woman does.")
- Age >75 years old, OR 6.18
- Rituximab (Rituxan) treatment, OR 4.04
- Sulfasalazine treatment, OR 3.60 (see commentary below)
- Age 66-75, OR 3.00
- Immunosuppressant treatments listed below, OR 2.22
(tacrolimus, mycophenolate, cyclosporine, cyclophosphamide, azathioprine)
- Not on a disease modifying agent immunosuppressant, OR 2.11 (compared to patients on methotrexate)
- Moderate to high disease activity, OR 1.87 (compared to patients in remission and low disease activity)
- High blood pressure plus heart disease, history of stroke, or hardening of the arteries, OR 1.89
- Prednisone more than 10 mg daily (or more than 8 mg methylprednisolone), OR 1.69 (compared to no steroids)
- Chronic lung disease (like COPD, asthma, interstitial lung disease, pulmonary fibrosis), OR 1.68
- Men, OR 1.46 (compared to women)
United Kingdom had the highest death rate followed by Germany
Commentary about sulfasalazine (SSZ): Do not take away from this that SSZ increases deaths from COVID-19. SSZ is often prescribed by rheumatologists to sicker patients who are at higher risk for infections in the first place. For example, there were more smokers in the SSZ group. SSZ does not suppress the immune system. Also, SSZ is a weak drug (most often used to treat rheumatoid arthritis). Patients on just SSZ are less likely to be in remission or low disease activity (and therefore at higher risk of death from a COVID-19 infection). I suspect that this is an "association" and not a "causality."
- Hydroxychloroquine (Plaquenil) and belimumab (Benlysta) treatments were not associated with higher death
- TNF inhibitor, leflunomide, abatacept (Orencia), tocilizumab treatments were not associated with higher death
- The United States had the lowest death rate of all countries in the study
- After the US, countries (in order) of lowest death rates = Germany, then France, then Spain
- It is most important to keep your lupus under control. Do NOT stop any medications.
- Abide by all nondrug ways to lower lupus disease activity so you don't need as many steroids.
- Work hard with your doctor to control your disease better so you can lower your steroid dose.
- Get vaccinated against COVID-19!
- Ask everyone around you to get vaccinated (the cocoon strategy)
- Even after vaccination, abide by all isolation, separation, social distancing strategies
Reference: Strangfeld A, Schäfer M, Gianfrancesco MA, et al. Factors associated with COVID-19-related death in people with rheumatic diseases: results from the COVID-19 Global Rheumatology Alliance physician-reported registry. Annals of the Rheumatic Diseases Published Online First: 27 January 2021. doi: 10.1136/annrheumdis-2020-219498
DONALD THOMAS, MD
Complementary Alternative Medicine
COVID 19 And Lupus
COVID-19 And Lupus
Diet And Lupus
Flares In Lupus
Infections And Lupus
Kidneys & Bladder
Labs Used In Lupus
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Remission And Other Disease Activities
Symptoms In Lupus
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