Page Last Modified on July 30, 2011
First Published in The Lupus Magazine
April 1, 2011
April 1, 2011
There is an immense amount of excitement and hope brewing among the SLE population with the recent FDA approval of the lupus treatment, Benlysta® (belimumab). This is the first medication the FDA has approved for SLE in over fifty years. Benlysta® (formerly called LymphoStat-BT) was developed to disrupt activation of B lymphocytes by interfering with BLyS, a protein required for B cell activity.
The active ingredient is Monoclonal antibodies (mAbs). Benlysta lowers BLyS which is thought to be a significant player in causing the disease. Benlysta has less toxic side effects and less immuno-suppression than current DMARDs (disease-modifying antirheumatic drugs). When Benlysta is given in combination with other lupus therapies; it has been clinically shown to decrease disease activity, and in many cases a reduction in steroid use. While the FDA approval of this novel DMARD is indeed a cause for celebration, it still has yet to gain the confidence of both patients and practitioners in effectively treating those with vital organ involvement.
Despite the fact that the Benlysta phase III studies did show objective measures of remittance in immunology, musculoskeletal and mucocutaneous manifestations, the studies did exclude people with active nephritis or central nervous system involvement. As a result, patient populations who are battling the more serious forms of the disease are not finding cause for immediate celebration. Interestingly, the FDA has approved Benlysta® for SLE, but the dispensing label states that it is not known if Benlysta® is safe and effective for patients with either severe active lupus nephritis or severe active central nervous system lupus.
I had the opportunity to ask Holly V. Russell, US Media Relations at Glaxo Smith Kline some questions about Benlysta® (belimumab):
What is the active ingredient in Benlysta? How does it work?
BENLYSTA is a BLyS-specific inhibitor that blocks the binding of soluble BLyS, a B-cell survival factor, to its receptors on B cells. BENLYSTA does not bind B cells directly, but by binding BLyS, BENLYSTA inhibits the survival of B cells, including autoreactive B cells, and reduces the differentiation of B cells into immunoglobulin-producing plasma cells. BLyS is a naturally occurring protein discovered by HGS in 1996. BENLYSTA (belimumab) is a human monoclonal antibody drug. Benlysta therapy is for moderate to severe SLE with active antibody production, shown through blood serum tests. Are those active antibodies, anti-dsDNA antibodies and ANA? The antibodies are ANA and/or anti-ds-DNA.
*Authors note: in clinical phase studies patients with active SLE were on stable immunosuppressive agents; Active SLE was defined as a SELENA SLEDAI disease activity score >6; at screening with H/O + ANA (1:80) and/or anti-dsDNA (>30 IU/mL) at 2 separate times.
Please explain the dosing schedule
The recommended dosage regimen is 10 mg/kg given intravenously only at 2-week intervals for the first 3 doses and at 4-week intervals thereafter. The infusion process is expected to take about an hour. Benlysta can be used along with other lupus (DMARD) medications and which would those be? Current standard therapy may include anti-malarial medicines, a variety of immunosuppressive and cytotoxic agents, NSAIDs, with corticosteroids as the mainstay of therapy. Patients in the Phase 3 clinical trials all received a background of various standard therapies, with the exception that use of other biologics and intravenous cyclophosphamide was not permitted.
Kidney and central nervous system involvement are two of the most serious forms of SLE. Can GSK explain how Benlysta® has been approved for ‘severe active lupus’, yet the Benlysta® dispensing pamphlet states that Benlysta is not recommended for people with severe active forms of kidney and CNS lupus. That being said, what severe forms of the SLE population does this medication really target?
BENLYSTA (belimumab) is a human monoclonal antibody drug that was approved by the U.S. Food and Drug Administration on March 9, 2011 for the treatment of adult patients with active autoantibody-positive, systemic lupus erythematosus (SLE) who are receiving standard therapy. The approved indication is not specific to mild, moderate or severe SLE. The label for BENLYSTA includes the following limitations of use: The efficacy of belimumab has not been evaluated in patients with severe active lupus nephritis or severe active central nervous system lupus, and has not been studied in combination with other biologics or intravenous cyclophosphamide. Use of belimumab is therefore not recommended in these situations. The Phase 3 studies were not designed or powered to determine improvement or worsening in individual organ systems. Patients with severe active lupus kidney disease or active CNS lupus were excluded from the trials because of the likelihood that these patients would require changes in medications and therefore not be considered to be on a stable SLE treatment regimen required for enrolment in the Phase 3 trial. Efficacy studies in these lupus populations would require a different primary endpoint than those for overall disease activity trials in SLE. The reduction in disease activity seen in the SRI was related primarily to improvement in the most commonly involved organ systems namely, mucocutaneous, musculoskeletal, and immunology. A lupus nephritis study is a post-approval commitment. SLE disproportionally affects African Americans and people of African descent than compared to other ethnic and racial populations. Benlysta has had a poor response rate in these populations during its studies.
The FDA has recommended that GSK continue further studies and reporting regarding the reasons to the lack of response in the African decent/African American SLE populations. Have those studies begun?
HGS and GSK are working with the FDA on the design and timetable for this post-marketing commitment. When will Benlysta be available on the US market? We expect to have BENLYSTA available to physicians and patients in the U.S. by the end of March. When will Benlysta be available in Europe, Australia, New Zealand and other countries? GSK submitted a Marketing Authorization Application (MAA) for belimumab to the European Medicines Agency (EMA) in June 2010. With usual EMA timelines, we expect to have a decision from EMA in the second half of 2011. Regulatory applications have also been submitted and are currently under consideration in Canada, Australia, Switzerland, Russia, Brazil and The Philippines. We anticipate regulatory submissions in a number of additional countries during 2011
Another interesting and positive note for lupus research, is that the Human Genome Sciences devised the SLE Responder Index (SRI) (for the Benlysta phase trials), which is used as a relatively high bar for response including tests of organ involvement (the BILAG score) and overall disease activity (SELENA SLEDAI) that FDA favors in lupus clinical trials. The Human Genome Sciences SRI is a composite of three existing objective and well-defined measures of disease activity and therapeutic response. The SRI composite was accepted by the FDA and will continue to help pave the way in other future clinical lupus trials.
The approval of Benlysta marks a much needed and encouraging milestone for those living with and those treating the disease. More precise clinical trials need to be conducted on patient populations battling active vital organ involvement and the therapeutic responses substantiated therein. Let us hope that inclusive clinical studies with Benlysta, namely in the kidney, central nervous system and blood vessel involvement populations prove to be an effective treatment as well. Benlysta is a historical event and a promising sign of therapeutic potentials for many lupus patients. Yet, while this is a large step toward the prospects of therapeutic options in SLE, many other steps will be required to move forward with the future alternatives in treating The Great Imitator.
*The author wishes to thank Holly V. Russell, US Media Relations staff, at Glaxo Smith Kline, makers of Benlysta® (belimumab) for the interview and her assistance. References: Human Genome says average annual price of Benlysta treatment $35,000: Human Genome said the price for Benlysta has been set at $443.18 for a 120 mg vial and $1,477.26 for a 400 mg vial. The average price for an annual course of treatment would be approximately $35,000. http://www.theflyonthewall.com/permalinks/entry.php/HGSIid1391853/HGSI-Human-Genome-says-average-annual-price-of-BENLYSTA-treatment-
FDA Benlysta® Press Release: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm246489.html
Benlysta® Gateway Patient Support Program:
Systemic Lupus Erythematosus Disease Activity Index SELENA Modification: http://www.rheumatology.org/practice/clinical/indexes/sledai.asp
Novel Evidence-Based Systemic LupusErythematosus (SRI) Responder Index:
© 2011 Kim Nault
The Apathy of Loved One’s
When Patients with Invisible Illness Become Invisible to Loved Ones
First Published in The Lupus Magazine
November 1, 2010
By © Kim Nault
The apathy of loved one’s toward the chronically ill person is a source of emotional pain and frustration for many people. This topic is an uncomfortable and recurring subject that I keep running into with fellow patients.
I have heard people with chronic illnesses say, “My family doesn’t get it"
"They think that I’m a whiner”
“They think that I’m exaggerating”
“My family doesn’t visit me when I’m in the hospital”
“They’re sick and tired of hearing me bitch”
“They don’t understand that I want to participate but I’m too exhausted,” ad infinitum.
It is one thing to live with an invisible illness, yet when a patient becomes invisible to their loved ones because of their disease that creates an agony far worse than the medical dilemmas caused by the illness.
Do the apathetic know we are not looking for pity parties, and do not want bleeding brownie points for courage? The loved ones that understand our predicament are compassionate without indulging us and are sources of emotional support to us. Yet, there remains this awful fact that many patients do experience apathy from some important loved ones. When someone we love is indifferent toward us because of our conditions, it becomes source of emotional anguish for many of us.
I have taken it upon myself to examine this sociological and psychological phenomenon sadly and painstakingly extricated from the bitter experience of the chronically ill patient population. I have hypothesized the following:
Apathetic Personality Types
- My Aches Are Worse than Yours Are Personality:
The description of their aches and pains are frightfully worse than ours are. They do not actually have a chronic illness, yet they always have to gain the lead over us when we try to discuss our health problems. These people are self-contained in a plastic bubble world. This group is unable to see beyond themselves. Some are hypochondriacs, while others just have too much free time on their hands. Perhaps this group would benefit from a hobby or volunteering for a charity (not illness related, of course).
- It Could Be Worse Personality:
This group always says that “it” could be worse. No matter what we discuss with them, their role in this world is to remind us of the philosophically comforting and rather nauseating words of, it could be worse!
- Your Faith Isn’t Strong Enough Personality:
Many of us have enough problems just living our daily lives, let alone answering theological or spiritual questions of agnostic or Gnostic. This well-intended blissful spiritual bunch tells us that if we only believed enough, that we could be healed of our condition. This has left some of us silently feeling guilty for maybe not believing enough.
- Hot Air Personality:
Amazingly, you discover that hot air is not just for balloons. This personality type is the overzealous helper with big plans and ambitions in the event of our medical emergency. This type may insist that you make them your healthcare proxy. In theory their plans are convincing, yet during the actual crisis, they are regrettably unavailable.
- Disappearing Act Personality:
No, this is not just a magicians performance, this is an actual group of people or “loved-ones” who disappear from the chronically ill patient's life.
I term this, “If I don’t see you, then you are not really sick,” or “Don’t inconvenience me with your illness.” This group stops all contact with us. They avoid us like the plague.
- Mortality Denial Personality:
They cannot deal with anything remotely connected to sickness or more specifically, death. Your chronic illness forces this type to look at their mortality. They would rather change the oil in their car, or do Spring-cleaning in their house than contemplate the natural life cycle process, with or without an illness mediating it.
Comfort for the patient!
Sarcasm put aside, this is a real issue.
Real issues require real tools. To experience no emotional support from a blood relative or long time friend is stark and painful. Any serious illness unfortunately brings out either the utterly ugly side of people, or the exact opposite, that of the innately compassionate side of people. Bob Marley speaks to the complexity of human relations in this quote:
"The truth is, everyone is going to hurt you. You just got to find the ones worth suffering for."
Which of the relationships in your life are worth ‘suffering’ for? Which are not worth suffering for?
Of course, some people may just be utterly unapproachable and it is best to let this type of situation rest. Loathe or love them from a distance. Living with a chronic illness heightens a person sense of mortality and helps us choose our battles wisely. Our time becomes more valuable, as do our relationships and our choices will begin to reflect that. For the people worth our energy and attention will understand that we did not choose the plight of being sick. Through these meaningful relationships, we will discover great columns of strength, which will keep our company and encourage us while fighting the battle alongside us.
by Kim Nault ©
Hope for the Undiagnosed Patient
by ©Kim Nault
October 1, 2010
(First Published in The Lupus Magazine)
Each day an estimated 270 people worldwide are diagnosed with SLE. At this very
moment, there are individuals who have been living and struggling with lupus disease related health problems, and remain undiagnosed and untreated. It has been speculated that many patients will have seen, as many as three to six doctors before officially receiving the diagnosis of SLE. Unfortunately, many patients will have spent an estimated three to nine years undiagnosed, suffering from various health problems ,while wandering from doctor to doctor, succumbing to a variety of medical tests, and not receiving an exact name for what ails them.
The very nature of SLE is insidious and anyone having lived undiagnosed with lupus knows firsthand why it has earned the title of the Great Imitator. Many patients have spent much time in search for one doctor to put together the mysterious medical puzzle that has plagued them for perhaps years. The very manifestations of lupus are not always clear-cut; some signs are more subtle, while others may be more evident. Some studies suggest that it can take up to ten years for one individual to evolve into enough clinical signs and symptoms and actually receive the official diagnosis.
Many patients will fall through the cracks of medical communities’ inability to solve their medical mystery. Many patients will be described as whiners, lazy, depressed and hypochondriacs before the actual arrival of the long anticipated diagnosis. Sadly, many will start to feel crazy and despair of ever receiving an answer to the health problems that have been plaguing them for so long. It is beyond frustrating for any human being to live in this state of medical limbo, while still experiencing cyclic health problems and have no label or name to explain it all. Unfortunately, this is wandering undiagnosed population is more of the rule than the exception. Looking back at our own histories, many of us will admit that we really did have to pound the pavement of the medical community to secure our diagnoses. Do you have the experience of living in that hopelessly barren land of being undiagnosed and untreated?
“Living with an invisible illness sucks, but living with an undiagnosed and
untreated illness, really sucks.” - Kim Nault 2007
At the end of this International Lupus Awareness month 2010, there will be roughly 8,300 new diagnoses globally. Many of those people will have lived three to nine years with a baffling array of health problems. They will have suffered the course of longing desperately for a physician to solve the medical mystery that they have been living. For the record, not many people enjoy living the unrelenting saga of being an undiagnosed lupus patient. There are scores of veteran patients who are very mindful to the invisible population of undiagnosed patients, because they have the experience of living that very wearisome road.
In fact, the very mainspring of grassroots advocacy work within much of the global lupus community stems from people having lived such an intolerable situation first hand. Many do not want other people to experience a similar overwhelming course, and have dedicated themselves to educating other’s about the disease. Obviously, the undiagnosed and untreated population does still exist, so how can we better serve them? How can we raise our voices for this group and arm them with information to bring to their doctors? In what ways can we increase patient education? If an informed patient is an empowered patient, how can we effectively pass the torch of education and empowerment on to others? Even the most bitter of our experiences are not without reason or purpose, those experiences can be transformed into effective tools to help other bring comfort and hope, thus empowering fellow sufferers.
Lupus MCTD Foundation:
Vitamin D Therapy in SLE
It is not just about bones
by ©Kim Nault
September 1, 2010
September 1, 2010
(First Published in The Lupus Magazine)
Recent studies among lupus populations are showing that hydroxyvitamin D has actual therapeutic value and may act as a mild immunomodulating agent. This information is causing a lot of excitement among patients who are earnestly seeking to find things that will reduce pain and discomfort while increasing the quality of their lives. Let us not throw caution to the wind and run right out to the pharmacy and purchase cases of vitamin D!
Hydroxyvitamin D (1,25-hydroxyvitamin D/vitamin D3) is the most active form of vitamin D that the human body metabolizes. A standard vitamin D OTC supplement converts in the kidney into 25-hydroxy vitamin D, the active form of the vitamin D.
Vitamin D is a steroid hormone and helps control calcium and phosphate levels in the body. The 25-hydroxy vitamin D test is the most accurate way to measure how much vitamin D is in your body. The normal range is 30.0 to 74.0 nanograms per milliliter (ng/mL). Normal value ranges may vary slightly among different laboratories. Talk with your doctor about the meaning of your specific test results.
Many studies have been done that acknowledge the fact that many patients with different autoimmune diseases (SLE, multiple sclerosis, insulin-dependent diabetes mellitus, Crohn's disease, among others) often have sub-clinical serum levels of 1,25 hydroxyvitamin D. For some biological reason, these groups often have very low serum levels of hydroxyvitamin D.
Scientists currently understand only part of the biological role of the low hydroxyvitamin D in lupus patients. One theory is an impaired mechanism within people with autoimmune diseases making the body incapable of absorbing vitamin D compared to non-autoimmune disease populations.
Let us tackle the first and obvious information available on vitamin D. Indeed, many people with autoimmune disease do have sub-clinical levels serum hydroxyvitamin D. Does that mean that if we increase our serum levels that our illnesses will get better or even abate? I am not a scientist, nor a doctor, and what little I do understand about SLE is that there are multiple cells (some identified and many yet discovered) in the actual disease process.
This lower vitamin D serum within lupus patients does obviously have a role in the autoimmune process, but not confirmed as the cause of the disease. Understand that the lack of vitamin D does have a role in lupus but that it is only one element involved in the disease process.
Many patients are reading reports that taking mega doses of vitamin D will decrease their disease activity and other studies are suggesting that vitamin D has actual remissive properties.
Anyone considering taking doses of vitamin D above 2000 IU daily should consult their doctor or practitioner, as doses above 2000 IU daily do have the potential of damaging the kidneys. Your doctor can target the desired serum levels and monitor you through the 25-hydroxy vitamin D test.
The most notable for most patients using Vitamin D therapy is a reduction of daily fatigue. A recent cohort study confirmed that increasing serum 25-hydroxyvitamin D levels in SLE patients had reduced fatigue levels. The higher the serum vitamin D level, a significant reduction in fatigue noted. Many patients who are taking it for therapeutic value are seeing and feeling definite results.
Some patients have reported a reduction in muscular skeletal pain and symptoms. As with most therapies, it appears that it is purely an individual experience and response. It is important to emphasize that many studies only spoke of a reduction in over-all fatigue and no reduction in severity of disease or disease activity, which was measurable against the SLE Disease Activity Index.
Discuss the risks and benefits of vitamin D therapy with doctors knowledgeable on this growing topic. Have recommended serum blood tests to evaluate and prevent toxic levels that could potentially harm the kidneys. Utilize your practitioners to target daily doses and serum blood levels. Please exercise caution with taking daily mega doses without the consent and monitoring of your doctor, as in doing so you could do more harm than good.
The promising news about vitamin D as a therapeutic agent is that it is helping people. Many people will notice a decrease in fatigue and arthritis symptoms, which will enhance the quality of patient’s lives. There have been some reports about patients having a clearer mind as a direct result of vitamin D therapy. If you are benefiting from vitamin D therapy, do share your experiences with your doctor and other patients! While researchers work at answering the question of why lupus patients lack sufficient serum levels of vitamin D, we as patients can be informed and proactive patients, setting the standards for our treatment and quality of life.
SLE Disease Activity Index:
Direct Link to Article:
Understanding the Unseen Realm of Lupus Brain Fog
by ©Kim Nault
August 1, 2010
(First Published in the Lupus Magazine)
An estimated 70-90 % of SLE patients will experience the infamous lupus brain fog. This is the most common form of central nervous system involvement in SLE and can be mild to severe, and vary from person to person. The lupus brain fog is classified as a manifestation of organic brain disease and is of one of the 19 manifestations of NP-SLE/neuropsychiatric SLE that has a broad spectrum of manifestations, including psychiatric disorders and neurological syndromes of the central, peripheral, and autonomic nervous systems. Each manifestation is vast and complicating and far outside the scope of this sole article.
Sadly, the actual field of NP-SLE is still in its infancy, there is not much research done on this vast topic and not too many doctors fully understand this form of organ involvement. Many assume that the brain fog of lupus is just some quirky annoying problem, that it is not that bad, not that serious of a problem. For more than half the patients with brain fog it will be a quirky, sometimes an annoying and even at other times a comical issue, but for others it will be very disabling. In addition, lupus brain fog notably fluctuates with and without disease activity.
I have heard many heart-wrenching stories, of patients whose very own doctors have ignored or even minimized their conditions and complaints as mere irritants. Some medical practitioners do not regard the lupus brain fog as a disabling issue that reduces their patient’s quality of life. This is unacceptable. Lastly, if such large amounts of lupus patients are living and battling with the lingering consequences of brain fog, than why isn’t someone in the research field really pounding the scientific pavement for us to pinpoint the exact cause of this and yield our patient population better treatments? We deserve better diagnostic tools and therapies in our lives while we try to climb out of the trenches of the cognitively challenged.
There are also a high number of lupus patients with the secondary Antiphospholipid Antibody Syndrome/APS/Hughes Syndrome as well as those with concurrent fibromyalgia, both who seem to encounter more obvious signs of the insidious brain fog. There are many running jokes among patients regarding the effects of the brain fog monster in their lives. While we have to admit that some of the brain fog incidents are indeed hilarious and even downright entertaining to our loved ones there yet remains the silent population within the brain fog group who are overwhelmed with the mental and emotional impairments brought on by NP-SLE.
The lupus brain fog can cause:
• Cognitive Dysfunction (impaired abstract, concentration & reasoning skills)
• Short-term Memory Loss
• Verbal Fluency Dysfunction (difficulty finding words)
• Impaired Recall
Patients struggle with the cognitive impairments and the ripple effects that it has on their lives. To some patients it is embarrassing, frustrating and certainly regarded as incapacitating. I recall a forum discussion where Angie Phillips (NP-SLE/APS patient-advocate, founder/ creator of Ardent Cerebrations: Musings of Lupus Survivors!), earnestly explained that for her, the disabling effects of NP-SLE have been far more devastating than that of the pain caused by SLE. That she has incurred more disability from the cognitive issues relating to CNS lupus, that she would gladly take the pain and have her mental faculties restored to the way they used to be. I too, have described to my loved ones that I have teetered on near organ failure and have accumulated physical impairments, but not to have the consistency of my cognitive sharpness and verbal fluency has rendered me more defeated than anything else I have ever faced.
A few months ago, while at my primary doctor’s office we were discussing organic brain disease and she explained that neurologists had discovered that commencing to treat stroke patients with SSRI (selective serotonin reuptake inhibitors) antidepressants immediately following stroke promoted faster neuron repair and recovery from their strokes. She surmised that if antidepressants use was benefiting recovering stroke victims than people with organic brain diseases will also benefit from using them. Before you scoff at the idea of swallowing yet another pill, you might consider having a frank discussion with your doctor about whether you may or may not benefit from taking an antidepressant.
If you have a health insurance coverage that will cover neuropsychological testing, you may consider having that done. Once the tests are completed, the psychologist will make recommendations of activities that you can do to exercise areas of your brain that are affected by the brain fog. I know some patients who do brain games to exercise their minds and keep themselves as sharp as possible. There are very good games on the internet developed by neurologists and neuropsychologists, and a small amount of time surfing the Web may provide you with a good site to frequent. Do understand that lupus brain fog will wax and wane, some days will be better than others will. Do not be hard on yourself!
Coping and Strategizing – Lupie Cognitive Survival Tips:
• Do not multi-task (it can prove dangerous)
• Do not overbook your daily schedule
• Do not over commit yourself
• Prioritize appointments/events/activities (don’t double book things on the same day)
• Determine your peak energy time of the day (schedule needs around that time)
• Reduce background noises when needing to focus
• Use only one calendar (mark doctor’s appointments in one color)
• Set timers for reminders (cellular phones and your PC have different applications)
• Note pads (one for pocketbook, one for computer desk and one for kitchen countertop)
• Keep things simple
• Learn to say “no” (we do not have to commit to every event or activity)
Do not be hard on yourself! Explain to your loved ones about your frustrations and concerns with how lupus is affecting your cognitive abilities. Some of our loved ones may even have simple suggestions to simplify things in our lives, which may foster better memory and peace of mind. Please do not try to tough things out on your own; this will not produce great results. Be willing to ask others for assistance with things. If you are a type-A control freak of a Lupie, try the Zen Lupie practice of not being a control freak! Living with a chronic illness while life whirls about us, can be at times very stressful. How often do I forget that quality of life begins right smack between my very own ears? As in life, some days will be easier than others will and when we lose our way, another veteran patient stands ready to hand feed us morsels that will lead us out of darkness and place us back on the path of inner strength and hope.
*The best resource in your healthcare is your own doctor. The Lupus Magazine does not endorse or recommend any medication or drug company. This article is informational only and should not replace the medical care of your doctor.
The SLE/Tissue Catabolism Theory
The story of a man's remarkably simple lupus theory
By ©Kim Nault
July, 1, 2010:
(First Published in The Lupus Magazine)
Tyler Malcolm is a retired commercial diver who lives in a small suburban town in Pennsylvania. He is an animal enthusiast who provides year-round food for the wildlife that frequents his backyard and has made accommodations for the flying squirrels that have taken up residence in the Christmas storage boxes in his attic. You may be wondering who Tyler is and what role does he have with lupus?
I met Tyler while he served on the Lupus MCTD Foundation of America board of directors, as the scientific/research advisor from 2008-2009. I am among several who regard Tyler as a witty and gifted man, though he will neither confirm nor deny this.
Over the phone the wildlife aficionado sighs, “SLE/ Tissue Catabolism is a simple theory and I believe it fits. If it will help people, what can it hurt? Twenty-five years of wondering if my idea could help people is too long, Kim.”
In 1985 Tyler Malcolm, a twenty-something granite contractor read an article about SLE in the New York Times. He was intrigued as to why this serious autoimmune disease population was 90% female. He did not have a family member or loved one diagnosed with lupus. He had no scientific background, nor a medical degree; he was puzzled as to what the cause of the debilitating disease was. Tyler maintains that his ignorance of the disease better placed him in a position of objectivity and served as a powerful tool for hypothesis testing.
Having an investigative mind, he began to frequent local public libraries combing through research articles on the subject of lupus. Making notes on 3X5 inch index cards, he collected scientific data, biological mechanisms of the human body and medical terminology and reasoned out his theory based on the collected data.
A few months later, his brainchild, the theory ‘Systemic Lupus Erythematosus/Tissue Catabolism’ was born. He also authored several other theories during that same time line, each having a copyrights for their authenticity with the United States Library of Congress.
Tyler believes that effective problem solving requires only relevant facts.
He says this cautiously, “I think that it is a thoughtless reflex to generalize the lupus population by just saying that SLE must have something to do with female hormones.”
He looks askance at studies focusing only on the female hormonal as an influence in SLE. “The studies are weak, inconclusive and sometimes contradictory. After reading that New York Times article, I wondered, what else could it be? I looked at the whole biology, not just hormone levels, not just cells, not just age statistics, but everything at once.”
Tyler’s conclusion was that the higher female incidence in SLE is that females have more cell turnover than males; that estrogen drives cell turnover, which could explain - if nothing else - the higher incidence of lupus in females.
Giving me an anatomy lesson, “Did you know that the kidneys process about 200 quarts of blood a day ? This creates a prime filter for cell turnover to migrate through the body. What’s also interesting is that one of the major organs that get damaged by SLE are the kidneys.”
Tyler also ascertains, “A cure for lupus won’t be made until science uncovers the exact cause of the disease. I see a big surprise coming in the future of lupus research. The cancer people are jumping on the apoptosis (a fancy word for cell turnover) bandwagon like crazy and once they realize that their disease is linked to SLE through the same fundamental process it will trigger a huge shift in research dollars. In many areas of study, it will be impossible to do cancer research without - at the same time - producing results that are also meaningful for lupus. “
A quarter of a century ago Tyler was personally unaffected by the disease of lupus. Years later, lupus has become personal to him.
“The complexity of a person's lupus ordeal is something that I am just learning to appreciate. Back in the 1980’s when I pondered SLE, it was just as a distant and abstract puzzle. Now it's close and real - but - it's not a puzzle anymore, is it?”
Through his service position at the Lupus MCTD Foundation, he has developed relationships with lupus patients; he worries about one friend’s declining kidney function and another’s central nervous system. It does not satisfy him that there are no new advances with lupus, and that every day people are suffering and some are dying. As a patient, I understand Tyler’s frustrations and have often contemplated the disproportional injustice of science being able to put man on the moon, versus science having yet to discover the cause or cure for lupus.
Could the cause of lupus could be a malfunction in the actual cell turnover process? Tyler’s hypothesis has left me to ponder that the very mechanism that initiates the entire autoimmune response in lupus is a hyper-reaction in the cell turnover process. He suspects that if his theory is true, that cell turnover is indeed the cause of lupus, then scientists could target and counteract cell turnover, and thereby cure lupus. Twenty-five years ago, his original objective was to uncover the reason for the higher female incidence in SLE. Through the years, he has silently wrestled with the unanswered question to whether his theory could stop the anguish that people are suffering from. Indeed, Tyler, twenty-five years of wondering whether your theory could help people is too long.
*To date, W. Tyler Malcolm’s, Systemic Lupus Erythematosus/ Tissue Catabolism theory remains disproved.
Systemic Lupus Erythematosus and Tissue Catabolism
Copyright 1985 by ©William Tyler Malcolm
A 90% female incidence and a diversity of autoantigens are unusual features of the autoimmune disorder systemic lupus erythematosus (SLE). The link between estrogenic metabolites and immune stimulation is far too weak to account for SLE's overwhelming female prevalence (besides, any such causal relationship would make all other autoimmune disorders 90% female as well). The consistent occurrence of the same set of autoantigens and the existence of animal models for SLE suggest that it may be related to a fundamental process.
The immunological aspect of tissue catabolism during necrotic clean up and necrobiotic removal may be this process since most of the autoantigens of SLE are intracellular substances and because female histology is characterized by a high amount of menstrual and pregnancy-related cell turnover in many tissues (endometrium, myometrium, cervical mucus glands, vagina, ovary, mammary epithelia).
Since these processes are driven by sex steroids the studies linking linking these hormones and oral contraceptives to SLE's predisposition or progression make sense when viewed through the steroids' stimulatory or antagonistic effects on the normal hyperplastic processes, rather than through their direct influences on the immune system.
Since tissue catabolism is such a fundamental and certain process it is unlikely that a diverse immune response is generated de novo each time a cell turns over; rather, this complicated response is probably a set of concerted actions narrowly controlled, steadily maintained, and suitably modulated.
The circulating anticoagulants often increased in SLE and the other targets of autoantibody such as platelets, erythrocytes, and lymphocytes fit this hypothesis since one would expect that they function in tissue catabolism, or are normally present at the locus, or are themselves the objects of overly aggressive immune-related turnover mechanisms.
Predictably, complement would function in cell turnover and SLE, unlike most other autoimmune disorders, shows abnormalities in serum complement levels and C3b receptors. Exposure of the T antigenic determinant (MN blood group precursor) is a possible mechanism of cell turnover.
Humans maintain anti-T IgM even in the absence of disease and females have higher IgM levels than males. Normally, the T antigen is masked and the pentameric anti-T IgM is inaccessible to tissue cells. The acidic (trauma environment) or enzymatic unmasking of T followed by its complexing with anti-T IgM at a locus of microtrauma or a site of increased vascular permeability should trigger complement fixation.
It is difficult to imagine why the T antigenic determininant exists and the anti-T IgM is maintained if the resulting complex does not serve some purposeful function, such as initiating cell turnover.
A possible explanation of the reciprocal incidences of breast cancer and SLE between black and white women is that a more active and efficient cell turnover process may reduce the risk of a fully progressed malignancy but increase the chance of SLE. This cell turnover concept is also useful in understanding the gender differences in the incidences of many other malignancies.
The National Kidney and Urologic Diseases Information Clearinghouse - How your kidneys work
Parenting with the Great Imitator
by ©Kim Nault
(First Published in The Lupus Magazine)
June 1, 2010
June 1, 2010
Having lupus or any other chronic illness and being a parent does not come with instructions or a manual. Let’s face it, we have to reinvent ourselves more often than the healthy population.
We have to make accommodations and revise the way we live in ways that is conducive to our bodies and health issues, while performing the delicate balancing act of being the nucleus of our family life.
How can we be involved parents when the disease causes fatigue that siphons our energy and brainpower? How can we accept the waning and waxing of our medical conditions whilst parenting? How do we live to good purpose with this illness, while performing ongoing balancing acts in our family lives? These are not philosophical questions, they are the qualms of many a patient who has lost the ability to be who they used to be as a direct result of lupus.
After being diagnosed many of us run the course of denial, over-doing things, pushing ourselves and still living with high expectations driven by a need for perfection. This denial is usually smashed by a series of crashes, which require more valuable time to recover from. Cleaning the house can render a patient exhausted and fatigued, not to mention being unintentionally crabby to our family members. Our loved ones may appear somewhat unaware of our inner struggles, but we have to ask ourselves what we have done to allow them to think that we are still the super human powers prior to diagnosis? How many of us can readily admit that we can allow others to help and assist us with chores and tasks?
Moreover, how many of us can accept that help without going back and fixing things the way we like them? My sister suggested to me five years ago, that I was a perfectionist with my house cleaning, to gain some sense of control in my otherwise out of control life. Ouch! This leads me to contemplate the domestic mysteries such as, why can’t my kid turn the dirty laundry right side out, or how is it humanly possible for one person to use six cups in five hours?
Then there is the guilty parent syndrome, which occurs when we are ill and our minds are busy making us feel bad for not being able to completely participate in the lives of our children. Many of us know that while we obviously fight for the experience of each new day we also have the certain nagging guilt in the back of our minds that our illness is preventing us from being a more involved parent.
How many of us have felt guilty for having to take needed naps?! How many of us have guilt about not being able to attend our child’s school or sports events because we were too sick? How many of us have landed in a flare right in the middle of a big family event? How many of us have struggled with the frustrations for normalcy in parenting while dodging the bullets of inflammation? How do we find the right balance for our family unit?
How do we learn to say no to certain things and yes to things that yield deeper family bonds?
There too are the worries of our children, especially that of mommy or daddy dying from lupus.
I cannot exclude the fact of some of our children might act out in varying ways behind our illness. After my first hospitalization this year, my nine year old was extremely snappy and angry with me. It occurred to me one night, that her anger was really fear in reverse. I decided ask her if she was angry at my disease or me. She stormed out of the room, in a pre-hormonal outburst, only to return seconds later sobbing. I explained to her that it was very acceptable for her to be angry at my illness, but it was not acceptable for her to take that anger out on me.
Quelling her fears of me dying has initiated many profound conversations with her. I am available for her emotionally, guide her in admitting and discussing her apprehensions with me, which validate her feelings and tighten our emotional connection.
Opposite of the thoughts of guilt and frustrations and worries are the thoughts that motivate us to live each day to the fullest. Some of us have discovered a real freedom in saying” No,” to unnecessary requests. Many of us are reaping the rewards of not being able to rush about and receive pleasure from the simple day-to-day things in life with our kids.
To our children, life is not about schedules or formalities. The role that we have in our children’s lives is vital. They will not look back and measure us by superficial things; they will measure us on the time we gave them and the bonds that we share. Fight fiercely for those moments!
Migrations of Lupus Patients
by ©Kim Nault
May 1, 2010:
(First published in The Lupus Magazine)
May 1, 2010
May 1, 2010
In recognition of the annual World Lupus Day, May 10, 2010, I think it is very befitting to pay tribute to the efforts of the multitude of individuals who are part of vastly growing populations of patients on the internet. Many who are passionate forces in the effort of raising public awareness and education.
Their presence on various websites is not only fulfilling the goal of public education, but most importantly, has created a conduit of peer support to fellow fighters. It is important to acknowledge the efforts of the thousands of patients worldwide who are catalysts of hope to equally as many others.
Is it not an amazing thing how the Great Imitator has drawn us to one another?
It appears that we are cultivating a network rooted in the human spirit. It is very comforting to have another person living with the same illness that you have, knowing exactly what you are going through. It creates a profound sense of belonging.
Through sharing our own stories, we find kinship and empathetic ears. Of course, we vent about the many doctors, the tests, the new manifestations of the disease, the treatments, the side effects of therapies and our joys and frustrations of trying to live a “normal” life in an otherwise not normal body.
Through individual experience, many are able to support, offer suggestions and educate a frightened peer about a new therapy, test, or ongoing health problem. At any given time, one frightened patient is petitioning their peers for information on something lupus-related. An outpouring of information, assistance and experience is gladly shared. We rally around each other and keep cheering one another along the way.
We are discovering that we have more than lupus in common. We are spouses, significant others, parents, family members, employees, and friends. We also realize that we share common interests and values. Many of us have found old friends in new faces, and are benefiting from relationships with other patients.
There too is the ‘sick’ humor that we share among peers which has become wonderful doses of medicine along with the daily regiments of the pharmaceuticals we take. The bonds we have formed with other fighters have become vital resources to our quality of life and sense of well being. It is most moving is to witness some of the great life events occurring in a fellow patient’s personal life, and the outpouring of heartening support and encouragement from fellow patients extended to that person.
World Lupus Day is not only about elevating our voices through education to the public. It is about effecting a change in people’s lives, producing hopefulness in the minds and hearts of others. Our contributions do not have to be grand scale and no contribution ever too small! Every simple and kind act that extends hope to another is a gift to the human spirit, and does influence both the giver and receiver.
There is the old saying, ‘we teach that which we must learn’ and I have a sense that is exactly what we do with each other - sing the lyrics of the perseverance song back to one another when we ourselves have forgotten the words. We keep passing the light of hope back and forth to one another, illuminating the path for a weary friend when they have lost their inner strength. The moment we reach our hand out to a fellow fighter in support and commonality, we bridge a gap and fill it with solace and reassurance.
In celebration of each of you, in your own little corners of the world, as little butterflies, dedicated to cultivating and inspiring fellow fighters.
The World of Lupus DMARDs
By ©Kim Nault
April 1, 2010:
(First published in The Lupus Magazine)
April 1, 2010
April 1, 2010
DMARDs (Disease Modifying Anti-rheumatic Drugs) are a class of drugs used to treat lupus patients. Of the listed DMARDs, plaquenil has been the mainstay of FDA approved treatment (shoulder to shoulder with aspirin and prednisone) of lupus for several decades. The other DMARDs are in fact, drugs prescribed “off-label” for the treatment of lupus. These off label drugs, often cancer drugs at lower doses, have proven to work at targeting certain cells involved in the underlying disease process of lupus. Though not curing the actual disease, these drugs have been effective in many patients by slowing the progression of the disease and preventing further organ damage.
Some patients respond well to just NSAIDs for their arthritis, yet other patients do not respond well to NSAIDs alone, might be prescribed plaquenil in conjunction with an NSAID to their therapy. Some lupus patients with refractory arthritis prescribed a low dose two or three-medicine therapeutic plan, for example, a combination of NSAID, plaquenil and Methotrexate/MTX, or an NSAID, Methotrexate and Azathioprine.
Some researchers and doctors believe that medication combinations target multiple cells involved in the inflammatory response, thus treating the illness more effectively.
It is not unheard of for a patient to experience breakthroughs, during the course of treatment, where a medication that was once effective is not as effective as it once was, requiring stronger medications, or a combination of medications to stop inflammation and disease progression. It is not uncommon for patients to have to try several DMARDs before they find the right one.
Often times the disease flares or progresses manifesting into vital organs, and may require a steady course of prednisone coupled with a stronger DMARD. Steroids, especially its oral form, prednisone, have been a mainstay in the treatment of lupus for decades. They are very effective in treating inflammation and have proven to be very effective in treating lupus in a combination with other DMARDs.
Many times, patients may receive a new DMARD along with a high to moderate dose of prednisone to help things “cool off” and give the patient’s body time to respond to the new DMARD. Many patients know the frustrations of trying to wean down to a lower dose of prednisone, only to experience the return of symptoms. Many people do become steroid dependant over time. Doctors ideally want patients on the lowest dose possible, and for the short periods.
Unfortunately, in the real world of lupus, this does not always happen…
Patients that experience more severe organ involvement will require more powerful immunosuppressing agent’s such as Imuran, Cyclosporine, CellCept or Cytoxan that target the insidious cells causing the inflammatory reactions that attack and damage internal organs.
Some lupus patients with internal organ involvement respond very well to Azathioprine (Imuran), yet some do not and have better success with a more potentate drug such as CellCept. Some patients may receive Cytoxan for severe organ involvement, along with oral steroids. These powerful immunosuppressants do come with a double edge sword, side effects, and sometimes a laundry list of other scary health possibilities. Remember, when prescribed these medications, the benefit of taking them far outweighs the risk.
DMARDs are maintenance medications that need to be taken for a long time. The sole purpose of DMARDs is to halt the disease process, and slow the progression of the disease. In an ideal situation, DMARDs would succeed in remission. Many of these drugs to provide relief and slow disease progression in large parts of the lupus population.
An MS friend of mine has a great layperson explanation for disease modifying drugs, “They are preventatives. They do not cure the illness, only slow its progression.”
There is a lot of hope brewing in the lupus community about novel DMARD drugs specifically for the treatment of lupus that are making steps toward FDA approval. One of these drugs is Benlysta (belimumab), formerly LymphoStat-B, and may become the first FDA approved therapeutic option for lupus in 50 years. Benlysta may become FDA approved for treating mild to moderate lupus by late 2010.
Another reason for excitement about this medication is that it has shown in clinical research phases to have no serious or deadly side effects. The response rates of patients during clinical study have been very promising. Promise of better health outcomes equates quality life and that is exactly what lupus patients deserve.
* Lupus and the use of drugs and treatments should be discussed with your health professional.
by ©Kim Nault