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Zebras, Not Horses
“When you hear hoof beats, look for horses, not zebras”. This is a principle most doctors learn in medical school. What it means, basically, is that a doctor should look to the most obvious for an answer, not the exotic. This may be a sound diagnostic principle, but for a subset of people who have rare diseases, it is perhaps not the most effective approach to medical care.
I speak, of course, from personal experience. Not only did it take four years for a doctor to decide that I had lupus, but there also was a span of about twenty years when I suffered, without treatment, mysterious episodes of acute abdominal pain. A whole herd of horses was pulled out to explain these episodes. But not until an emergency room physician insisted on taking a CT scan during one episode was a clue to my gut disturbances obtained. And not until a very astute and careful gastroenterologist studied these CT images was the puzzle further unraveled. It finally took my rheumatologist, a creative and talented physician, to spot the zebra in the herd of horses: he determined that I was experiencing lupus-induced inflammation of the gut.
As idiosyncratic as lupus can be, there is still the conviction among many in the medical community that horses and not zebras predominate. In a Lupus Foundation article, for example, the transcript of a dialogue is presented. The dialogue is between Dr. David Isenberg , a noted gastroenterologist, and lupus patients. Dr. Isenberg explains to the patients the low probability that certain GI conditions will occur as a direct result of lupus. The doctor is asked about ascites (fluid in the abdomen), for example. He asserts that ascites are most likely to be caused by kidney or liver problems.
Of course, my experience refutes Dr. Isenberg’s perspective. Ascites was detected during several of my GI episodes. I did not have liver or kidney disease, although once I did have pancreatitis.
I came across another article which suggests my experience is not unique, though it certainly may not be common. In the medical journal RadioGraphics, which is dedicated to the field of radiology, I found the description of a young woman who had an acute episode of small bowel inflammation, with ascites. The woman also had systemic lupus. Her inflammation was successfully treated with high-dose steroids.
While Dr. Isenberg is an esteemed and accomplished researcher, in his interview he entertains as very remote the scenario suggested in the RadioGraphics article. Dr. Isenberg apparently not only expects to see horses, but he also recommends that everyone else does, too. This is not his “fault”; it is standard medical practice.
I have read that sometimes ten years can pass between the time lupus is first suspected to the time when it is ultimately diagnosed. Perhaps the reason for this diagnostic lag has something to do with the horse/zebra dynamic. When dealing with an idiosyncratic disease like lupus, which can confuse and confound, maybe doctors should think more often about zebras. Because something is amiss in a protocol which leaves patients, for so long, without appropriate treatment.
I know that in the ordinary course of events, hoof beats will be produced by horses. But sometimes, when the possibility, or strong suspicion, of lupus exists, a doctor might consider the extraordinary. I think a lot of unnecessary suffering and true harm could be avoided if doctors would just allow themselves to look a little bit harder at what seems to be obvious.
A Gene for Autoimmunity?
Some years ago I bought stock in a company that investigated the genetic origins of disease. The company went bankrupt and I lost all my money, but there was nothing wrong with the research–just the business plan. Hope of finding a cure–for lupus and other diseases–may rest precisely in understanding the genetic basis of illness.
It was with this idea in mind that a study–A Comprehensive Analysis of Shared Loci between Systemic Lupus Erythematosus (SLE) and Sixteen Autoimmune Diseases Reveals Limited Genetic Overlap—was undertaken. As the title suggests, the study failed to produce evidence that there is a strong genetic link between people SLE and other autoimmune diseases. The authors of the study hypothesize that the correlation may be weak between SLE and many other autoimmune diseases because SLE is so “heterogenous”. That is, there are many ways in which SLE can manifest. Perhaps each manifestation of lupus has a different genetic association.
Interestingly (according to the authors), the strongest genetic association found was between SLE and rheumatoid arthritis. The authors hypothesize that maybe this strong link has something to do with the fact that the two diseases share a major symptom: arthritis. There was another, though weaker, genetic association found between SLE and scleroderma.
The authors also noted that several established genetic links to SLE were not found in other autoimmune diseases. The authors admit that the failure to find these links may be due to a problem with the study’s methodology and that future efforts may be able to detect these associations.
So where do I think this leaves us? Well, there doesn’t seem to be an autoimmune gene, one common cause for a multiplicity of autoimmune diseases. And what the study shows, what it reinforces, is the fact that SLE, even on the genetic level, is a very complicated disease. Systemic lupus is more like several diseases than one and its cure may ultimately involve solving many genetic riddles, not just a single puzzle.
I personally think SLE might be approached the way cancer is increasingly treated: though it falls under the rubric of oncology, cancer responds to a variety of very specific therapies that have been designed for different manifestations of the disease. Something like that may evolve (is already evolving to some extent) for lupus. Though there may not be one gene that causes SLE, there may be different places on the genetic map where a susceptibility for distinct forms of lupus exist. And, just as tailored treatments are developed for different cancers, targeted treatments may need to be developed for different kinds of lupus.
There was a time when certain cancers carried with them very high mortality rates. Some of these, like lymphoma, today have dramatically improved cure rates. The day will surely come when people with lupus will experience the same success. They then will be able to look forward to futures that include the prospect of a complete cure.
A Handful of Pills
Image by Ayena
If you have systemic lupus, there’s a pretty good chance you have been prescribed a NSAID (example: aspirin, ibuprofen, Naproxen, etc.) over the course of your illness. Given that likelihood, I have dedicated some time to seeking an understanding of this broad class of drugs. The following essay is one of several I hope to post on the subject.
In writing this post, I have tried to be very careful in my use of language; I draw no conclusions. The available information about NSAIDs indicates that caution should be exercised in their use. Some of the reasons for the caution are explained below. Since research on these drugs continues, the recommendations of the American Heart Association and the FDA for their use reflect only what is currently known. Recommendations of both organizations will likely change over time.
The American Heart Association has issued repeated advisories about the use of NSAIDs; while the Association allows that NSAIDS may still be prescribed under certain circumstances in clinical practice, caution is required. The Association recommends that NSAID use be tempered by an awareness of associated risks. These are risks about which the patient should be informed if NSAID therapy is decided upon. As the Heart Association explains in its report, An Update for clinicians: A Scientific Statement From the American Heart Association (Feb, 2007), the issues surrounding NSAIDS “highlight” the obligation of patients and doctors to balance “the risks and benefits of medications for pain relief”.
So, what are these risks? This is a question that still has not been completely answered. Part of the answer is certainly that there is evidence of increased heart attack, heart failure, stroke and vascular events. The most recent advisory I found from the Heart Association (Sept, 2012) is entitled, “Taking painkillers increases death risk, second heart attack in survivors“. The article explains that the painkillers in question are NSAIDs. Anne-Marie Schjerning Olsen, the physician who led the relevant study, states: “It is important to get the message out to clinicians taking care of patients with cardiovascular disease that NSAIDs are harmful, even several years after a heart attack”.
According to the Heart Association’s 2007 study (cited above), not all painkillers appear to carry an equal risk of potentially lethal side effects. The Association cautions that results are suggestive and more information needs to be collected about the relative risks of each drug. With this cautionary note, they publish a chart that is meant to guide physicians in their use of NSAIDs. The chart describes a “stepped approach” to prescribing painkillers. In this approach, the least dangerous (according to Heart Association information) should be prescribed before moving on to those drugs that are seen to carry greatest risk. The Heart Association chart can be found at Figure 7, http://circ.ahajournals.org/content/115/12/1634.full.
Studies seem to suggest that NSAID risk is dose dependent, though what a safe dose is for an individual has not been established. The risk to individuals from NSAIDs (available over the counter in many cases) is considered so serious that the U. S. FDA has mandated inclusion of black box warnings in their packaging. A description of this black box warning can be found at the NIH website; APPENDIX BLACK BOX WARNINGS OF INCLUDED DRUGS
As I repeat throughout my posts on this website: I am not a doctor or a researcher. I am a patient who reads and who seeks to understand. What I get from the research about NSAIDs is that these readily available drugs are serious medicine. The fact that they are over-the-counter and easily accessed belies the danger they may present to the medical consumer. Before taking any one of these, think for a moment. Be sure that the drug is important to your care. And, consult your doctor. Between the two of you, an informed decision about taking NSAIDs can be made.
By A. G. Moore 2/16/2013
National Cancer Institute
While this essay specifically addresses the connection between sulfasalazine and lupus, the principles involved in the discussion have wider application. As an article in Pharmacological Review explains, “Individual variability in drug efficacy and drug safety is a major challenge in current clinical practice, drug development, and drug regulation” (Pharmacogenetics, Pharmacogenomics, and Individualized Medicine ). In other words, drug effectiveness varies according to the individual. The challenge is to find the most effective drug for each patient.
In the past, an appropriate patient/drug match was achieved through trial and error. Increasingly, though, science has improved the process of prescribing appropriate drugs for patients; often, a doctor can know in advance physical characteristics of patients which might make them more receptive to a drug or more likely to experience side effects.
Targeting medication to enhance effectiveness and avoid side effects is a gift to everyone: patients don’t lose precious, sometimes irreplaceable time with a therapy that doesn’t work; and dangerous, even lethal, side effects may be avoided.
Sulfasalazine is a drug therapy which can be administered today with greater confidence because of advances in genotyping–that is, identifying genetic elements which influence the way a patient processes medication. The history of this drug and its associated risks has been well-documented. In 1965 a physician from the Mayo Clinic reported that a patient he had been treating for inflammatory bowel disease went on to develop lupus. The doctor, Donato Alarcón-Segovia, attributed this development to the drug the patient had been taking: sulfasalazine. Since the 1965 case, sulfasalazine has been recognized as a drug which can induce lupus; the phenomenon is known as drug-induced lupus, or DIL. Sulfasalazine also may exacerbate disease in established lupus.
While doctors have known for a long time that drugs can induce lupus (first case was reported in 1945 in response to Sulfadiazine), this manifestation of lupus, known as drug-induced lupus or DIL, is usually described as being “mild”. However, “mild” lupus is not always the experience of a DIL patient. For example, an article which appears in Postgraduate Medical Journal (Postgrad Med J. 1982 February; 58(676): 98–99) describes a comatose 19-year old girl with “sulphasalazine-induced cerebral lupus erythematosus”.
Sulfasalazine has its uses: among other applications, some doctors find it a good alternative for controlling inflammatory bowel disease, rheumatoid arthritis, and, ironically, discoid lupus (see: Treatment of discoid lupus erythematosus with sulfasalazine: 11 cases ). According to the Lupus Foundation, sulfasalazine may even be prescribed to someone who has lupus if symptoms of rhuematoid arthritis are evident (see Lupus and Overlap).
So, what is a patient to do with this information? Whether sulfasalazine induces a “mild” or severe case of lupus, the development is obviously one a patient would like to avoid. As it turns out, this may be possible–without completely eliminating sulfasalazine from the physician’s list of viable treatment options. There is a way for doctors to profile individual patients and approximately assess their risk for developing sulfasalazine-induced lupus. Research has shown that almost all people who develop lupus after taking sulfasalazine fall in a group known as “slow acetylators” (see my blog: Medication Alert ). Those at high risk for developing sulfasalazine-induced lupus also tend to have specific genetic markers: HLA A1, HLA B8, and HLA DR3. If a patient does not have these markers and is not a “slow acetylator”, then the risk of developing drug-induced lupus may be greatly reduced.
Of course, it‘s impossible to tell how someone will respond to a drug. A serious discussion with the physician is in order before the decision is made to take sulfasalazine, or any medication. Risk and benefits need to be assessed.
Every drug has associated risks–not taking a drug also has associated risks. The more information a patient and doctor have about a proposed course of treatment, the more confidently can they assess the relative risk. In the case of sulfasalazine, it seems patients and doctors have the opportunity to weigh the medication’s benefits with more confidence than was available in the past.
Some articles helpful in learning about sulfasalazine and sulfasalazine-induced lupus:
Sulfasalazine-induced Lupus and Hypersensitivity, by Qingping Yao, and Bevra Hahn UCLA School of Medicine
Drug-induced lupus erythematosus on DermNet NZ
By A. G. Moore 2/28/2013
by Liz West on Wikimedia Commons
Today’s blog was prompted by a question I read recently on Lupus UK.
Pancreatitis, whether related to lupus or not, is a very serious development and requires immediate medical attention. During an attack, the pancreas starts to digest itself because certain pancreatic enzymes have been released prematurely. These enzymes usually break down food in the small intestine but, since they have been put to work in the wrong place, they instead begin to break down the pancreas. The situation can quickly become life-threatening.
A doctor diagnoses pancreatitis by reviewing blood tests and abdominal scans. The reason the attack occurred, however, may not be easy to discover. Without knowing the cause, it will be difficult to design an appropriate treatment plan.
If pancreatitis is related to lupus, a specific protocol is recommended. In the medical journal Clinical and Developmental Immunology, outcomes for groups of patients with lupus pancreatitis are compared. Those patients who are treated promptly and aggressively fare far better than patients who do not receive this level of care. (See: Clinical and Developmental Immunology, Systemic Lupus Erythemtaosus-Related Acute Pancreatitis: A Cohort from South China.)
Pancreatitis occurs for a variety of reasons. In some people, the condition may be a result of lifestyle–excess consumption of alcohol is generally included in this category. For other people, medication may precipitate an attack. Azathioprine and steroids are often suspected antagonists in this scenario. Evidence about the link between pancreatitis and these two drugs is not uniformly persuasive; while azathioprine clearly may cause pancreatitis in some people, steroids are another matter. There is disagreement about whether steroid-induced pancreatitis actually exists.
Estimates vary about the risk of developing pancreatitis while on azathioprine. According to a 2003 study published in the American Journal of Gastroenterology, patients on azathioprine ran a 0.4% increased risk of developing pancreatitis. Another medical journal, Annals of Gastroenterology, reported that patients on azathioprine (or mercaptopurine, into which azathioprine is converted by the liver) who had inflammatory bowel disease stood a 3.1% increased risk of developing pancreatitis. So, if someone is on azathioprine therapy and pancreatitis develops, suspicion will first fall on the medicine as culprit. The drug will be discontinued and an alternate medication prescribed.
As for steroids and pancreatitis: there is growing disagreement about this relationship. The Lupus Foundation describes steroid-induced pancreatitis, and indicates that the cessation of steroid therapy is the remedy for this condition. However, a recent article in Clinical and Developmental Immunology states: “Increasingly accumulated evidence showed that steroids do not trigger acute pancreatitis or cause increased mortality” in lupus patients. The lack of unanimity about the steroid/pancreatitis link increases the element of speculation in the diagnosis and treatment of pancreatitis.
When a situation exists where lupus has evidently caused pancreatitis, the way forward is clear for the doctor. High-dose steroids are the cure. This type of pancreatitis is called idiopathic lupus pancreatitis and is a very serious condition; it needs to be treated by experts in lupus care.
Since idiopathic lupus pancreatitis is thought to be rare, it can easily be overlooked by a physician who is not experienced in treating lupus. The complexity of treatment decisions facing a clinician increases if the lupus patient with pancreatitis is already on steroid therapy. Now the doctor has to figure out whether steroid therapy is appropriate or will make matters worse. The critical question has to be answered: Did steroids cause pancreatitis or will steroids cure pancreatitis?
An incident that occurred in a Slovenian hospital llustrates this point. A 33-year-old man evidently had pancreatitis. He also had lupus. Idiopathic lupus pancreatitis was suspected but high-dose steroid therapy did not elicit an improvement. Since the patient had been on steroid therapy, steroid-induced pancreatitis was suspected, but historically the use of steroids had not been a problem for this patient, so this theory fell out of favor. Finally, close examination of the many tests to which the patient had been subjected revealed that he had cytomegalovirus. It was this virus, the doctors concluded, which caused the pancreas to become inflamed. Treatment with Ganciclovir (an antiviral) was begun. The patient improved and eventually recovered.
The 33-year-old Slovenian patient obviously benefited from excellent medical care. The team of doctors who treated him were skilled and creative. They did not think in a box but used the latest research to problem-solve for their patient. Anyone with lupus who becomes ill wants just such a medical team in charge of their care.
Pancreatitis is a serious condition, for anyone. If you have lupus, the situation is even more perilous. If you do have lupus, know in advance who the best lupus doctors are and where the best lupus treatment facilities are located. When illness strikes, whether it’s pancreatitis or another ailment, be sure you are in a place that offers the best chance of a successful outcome.
Lupus: Signs and Tells
By A. G. Moore 4/28/2013
Public Domain Wikimedia Commons
Sometimes I don’t take my own advice. Acknowledging this helps to keep me modest. Yesterday I received a strong dose of modesty as my husband’s predictions of impending trouble were realized. The truth of his insight became obvious during the night: my body confirmed what my husband had observed for several days, what he had insisted on before we turned in the night before. A flare was upon me. The thing about catching a flare early is that it’s usually easier to chase lupus away if the disease is caught on the upswing, before it’s taken hold.
Unfortunately, for my husband and others I love, signs of the flare included a compromise of my ordinarily good nature. Today, I must apologize to people–not for the first time–because I was irritable and rude.
Then I’ll take my prednisone.
As everyone who has lupus knows, reluctance to begin an immune-suppressive regimen can seem reasonable. When lupus consists mostly of pain and lack of vigor, then taking medicine can seem self-indulgent. In my case, lupus has run a relatively mild course, so the temptation to ride out a storm without medicine is quite strong.
There are risks, though, to this laissez-faire approach. Lupus has, on occasion, turned on me and become vicious. Doctors have scratched their heads and alarm bells have gone off as I lay on a stretcher with symptoms that didn’t fit into any recognized pattern.
So I’m careful now, about guarding against vicious lupus episodes. I look for signs that tell me when a serious storm is brewing and I need to take action.
Signs of trouble for me do not always occur in a cluster. Some by themselves are compelling. For example, if I start to twitch–not just an eye or a jerk or two in my leg, but unremitting, sleep depriving, multi-site twitching–then I take action. ‘Cause there’s trouble coming.
If my gut acts up and no amount of coddling will sooth it, I take action. ‘Cause there’s surely trouble coming and I never play chicken with when my gut is involved.
I don’t have lupus nephritis, which can be active without any signs such as those I just described. Though some 40% of lupus patients present with nephritis early in the disease (first 5 years), about 5% of patients will develop kidney problems later. The material I cite below suggests that the best outcome for nephritis patients is realized with early diagnosis and treatment. Since lupus nephritis can be silent, invisible, without early signs, it’s important that all lupus patients be monitored from time to time to see if this condition is developing.
What the literature says about treating early
There is little disagreement in the research community about the wisdom of getting early treatment when lupus attacks organs. To illustrate this cautious approach, I did some reading on two common manifestations of lupus. In both these cases, lupus nephrttis and GI lupus, early diagnosis and treatment are uniformly recommended. I am assuming we can extrapolate this cautious attitude to other forms of lupus where there is organ involvement.
While not everyone with lupus has nephritis, this symptom is one of the first a doctor will look for when diagnosing the disease. The consensus about management of lupus nephritis is clear: early intervention saves lives and helps to prevent kidney failure. In 2008, the American Association of Kidney Patients issued a report about pediatric lupus nephritis. The report concluded: “Early recognition of the pediatric patient…with prompt intervention…may prevent kidney failure…”.
In 2006, an article in the The Journal of Rheumatology concluded:”…early initiation of immune-suppressive treatment might be critical for the outcome of patients with lupus nephritis”.
And, finally, a 1999 article in the American Journal of Nephrology stated: “In most patients today, there is a gratifying response to early treatment…”
The consensus about early treatment of lupus nephritis is mirrored in recommendations for treatment of gastrointestinal lupus. Most sources suggest that GI lupus is often caused by lupus vasculitis, which is a very serious, life-threatening condition. However, there are aspects of lupus expressed in the GI tract which may not be caused by vasculitis. Two of these are pancreatitis and intestinal pseudo–obstruction. Early treatment in any of these instances is essential.
A 2010 article in The World Journal of Gastroenterology described lupus mesenteric vasculitis, as “…a main cause of acute abdominal pain in SLE patients”. The authors of this posited that prompt diagnosis and “….appropriate intervention can avoid potentially fatal complications of…lupus mesenteric vasculitis”.
With regard to lupus pancreatitis, the same authors concluded: “As many as 57% of SLE-related acute pancreatitis cases may develop complications if not treated promptly.” And, finally, the authors discussed psuedo-obstruction. The recommendation for early treatment was unequivocal: “Early diagnosis and prompt treatment is critical to improve the overall outcome of SLE-related IPO (intestinal pseudo-obstruction) patients.”
As for my current lupus flare, this is small potatoes. I’m paying attention and treating early. I am confident that this flare, like so many others, will subside quickly. Then my bottle of prednisone will be retired to a dark corner in the cabinet where it will wait until the next time one of my “signs” appears.
This article is about sulfa drugs, which can be separated into two categories: antibiotic and non-antibiotic. What I hope to do in writing this post is offer some insight into the issues surrounding sulfonamide hypersensitivity.
Recently I wrote about sulfasalazine, which is a sulfonamide (sulfa drug). In that blog I report that sulfasalazine can cause drug-induced lupus. Though there always exists the possibility of adverse reaction to medication, sulfa drugs as a class seem to pose a particular threat to lupus patients.
Sulfa drugs were the first antibiotics ever discovered; in 1936 a researcher at Bayer Laboratories in Germany formulated a drug called Prontosil. One of the first patients treated with this drug was the researcher’s own daughter.
Prontosil was considered a “wonder drug” and revolutionized medical care; in time, other sulfa drugs were formulated. However, resistance to sulfa drugs soon developed as some microorganisms became immune to them. Eventually, alternative antibiotics, such as penicillin, were discovered.
Sulfonamides still have a place in the doctor’s bag of tricks. These drugs are especially effective in treating urinary tract infections. Though a doctor might be tempted to resort to a sulfa drug when susceptible organisms are detected, caution is advised, especially caution in patients who have certain conditions. These conditions include lupus and HIV. Individuals who have an established sensitivity to penicillin are also at increased risk.
There is little question today about the risk of using sulfonamide antibiotics in lupus patients—that question has been asked and answered. There is an elevated risk. The question still open is whether the sensitivity to sulfonamide antibiotics carries over to non-antibiotic sulfonamides.
Non-antibiotic sulfonamides have a different chemical structure from their antimocrobial cousins; this different structure seems to limit the number of adverse reactions. I have read a number of research articles and a few case reports about the possibility of a cross-over hypersensitivity between the antibiotic sulfonamide and the non-antibiotic. Not all researchers agree about the level of risk.
It seems that most researchers feel non-antibiotic sulfonamides are safer for lupus patients (or anyone with a sulfonamide hypersensitivity) than antimicrobial sulfonamides. However, case reports do exist which show that there can be a crossover–people can be allergic to both antibiotic and non-antibiotic sulfonamides. This is especially true in people who are allergic to penicillin.
One case illustrates the dilemma a doctor may face when sorting through the conflicting research: A Canadian physician reports that a 70-year old patient has symptoms of mild heart failure. She also has a history of antibiotic sulfonamide hypersensitivity. The doctor prescribes furosemide (Lasix), an non-antibiotic sulfonamide diuretic, despite the patient’s history of allergy. He’s not concerned about a cross-over hypersensitivity between the two types of sulfonamides.
A few hours after the patient leaves his office, the doctor receives a call from the pharmacist. He points out that the patient also has a history of hypersensitivity to hydrochlorothiazide, a non-antibiotic sulfonamide. The doctor reconsiders his prescription; he agrees that a non-sulfonamide diuretic might be wiser in this case. In a follow-up consult with his patient, the doctor recommends she wear a Medic Alert bracelet.
In the mind of at least this one doctor, there is now a heightened concern about cross-over sensitivity between anti-biotic and non-anti-biotic sulfonamides. He concludes his report by suggesting that in the future he will proceed more cautiously in prescribing sulfonamides of any kind to someone with a demonstrated sulfonamide hypersensitivity.
Some researchers have concluded that a cross-over sensitivity between sulfonamides is not due so much to a sulfonamide allergy as it is to a general sensitivity to all medication. This would explain why people with penicillin allergy are more likely to have a allergy to both kinds of sulfonamides.
Non-antibiotic sulfonamides are present in many prescription drugs. The names of some of these are (this is not a comprehensive list–always check with your doctor and pharmacist if sulfonamide allergy is a concern): furosemide (one brand name of this drug is Lasix), Celecoxib (one brand name is Celebrex) and hydrochlorothiazide (which is sold under a variety to names and which is also used in the preparation of a number of hypertensive drugs, including Atacand, Benicar and Zestoretic).
The names of a few antibiotic sulfonamides are (once again, this is not a comprehensive list; check with your doctor and pharmacist if sulfonamide sensistivity is a concern): Septra and Bactrim; Silvadene; Azulfadine; Gantrisin; and Erythromycin-sulfisoxazole (combination drug sold under a number of brand names).
I emphasize here, as I always do: have a conversation with your doctor if you think sulfonamide sensitivity may be an issue. Report to your doctor any history of adverse reaction to medication of any kind. Patients cannot always know the class of drugs to which a medication belongs (I didn’t know, for example, that Celebrex was a sulfonamide). Pharmacists are also good sources of information. As the example from Canada (described above) illustrates, sometimes pharmacists catch things doctors miss.
A few articles that were helpful to me in putting together this blog were:
Often, when I decide to post information on this website, it’s in response to comments I’ve read on other lupus blogs. Today I write about an aspect of lupus that affects me, although my research suggests the syndrome I experience may have implications for many other lupus patients.
Anyone familiar with my website likely knows that one manifestation of lupus I experience is gastrointestinal (GI) inflammation. GI complaints are among the most frequent reported by lupus patients; these GI issues are usually believed to be a side effect of medication. However, an interesting study looked at autopsies performed on lupus patients (Takeno M, Ishigatsubo Y. Intestinal manifestations in systemic lupus erythematosus. Intern Med. 2006;45:41–42) and found that 60 to 70 % of those examined showed evidence of peritonitis, although only 10% of these subjects had been diagnosed with the condition before their deaths. According to an article in the World Journal of Gastroenterology , the incidence of gastrointestinal lupus may be underestimated because the symptoms are indistinct and there is generally no specific antibody associated with the syndrome.
Among the kinds of GI lupus mentioned in the World Journal article are: vasculitis; thrombosis and pancreatitis. Less common forms of GI lupus are: intestinal pseudo obstruction; inflammatory bowel disease; and celiac disease.
In my case, exact diagnosis remains speculative, though it is clear I have in the past had at least one episode of acute pancreatitis and one episode of acute inflammation of the small bowel. In both instances CT images revealed the presence of ascites (excess fluid in the abdomen).
I have gone through enough acute abdominal episodes to recognize signs of an attack when it is imminent. One thing consistent in each event is that I am beset with acute anxiety, almost with a sense of doom. Another thing that happens, as the attack progresses, is that I shiver. This last “sign” I find particularly perplexing, because usually there is no obvious reason for me to feel cold–and yet I shiver.
My inclination has been to write the anxiety off as experience-based: I’m afraid I’ll have to go to the hospital and I don’t know what will happen to me. But the shivering has never made sense to me. Until a couple of weeks ago.
That’s when I began to investigate the gut/brain connection. Since then I’ve learned about the vagus nerve, which is the longest nerve in the body and which forms a direct link between the gut (and other viscera) and the hypothalamus. The hypothalamus sits at the base of the brain and is in charge of a whole bunch of things, including many involuntary responses. One of these responses is shivering.
The hypothalamus also plays a significant role in emotions. It, and other parts of the brain, are tied into the limbic system. According to a paper that came out of the Columbia University Medical Center, “Emotional responses modulate the autonomic nervous system to respond to threatening stimuli or situations…” and “…the hypothalamus and limbic system mediate these behaviors.” In other words, a perceived crisis may trigger the hypothalamus to set in motion a series of involuntary responses. One of these responses is shivering.
As I continued to read about the gut/brain connection, I began to understand more about the way these two parts of the body communicate with each other. Apparently, one of the ways we know we are full, when we eat, is because the vagus nerve transmits information to the brain; it informs the brain that certain changes have taken place in the gut . It also lets the brain know when the gut is in trouble. This process is described in an article I found on scholarpedia.com: Autonomic Nervous System. The article states: …”Different… classes of…nerves respond to inflammation or damage to the gut wall”. The message of distress triggers a reaction in the autonomic nervous system.
As I reached this point in my research I began to get a handle on the cascade of events that ensue from acute GI inflammation.
The Vagus nerve is like a train that carries information from the gut to the brain and from the brain to the gut. A gut in trouble will communicate the emergency to the brain. The hypothalamus, nested deep in the brain, is a terminus which receives the emergency bulletin from the gut, via the vagus nerve. The hypothalamus reacts–it seeks to reestablish homeostasis (return to normal). It releases powerful chemicals into the system, which increase anxiety; the effort to achieve homeostasis also triggers shivering–possibly to raise body temperature, which has likely been lowered as a result of dehydration.
If the results of the study cited in the World Journal of Gastroenterology (see paragraph 1, above) are correct, then a high percentage of people with systemic lupus experience gut inflammation. And if this is true, it is something that perhaps both patients and doctors should keep in mind. And perhaps, as they do, they may consider the strong effect that changes in the gut can exert on emotional status (see:Think Twice: How the Gut’s “Second Brain” Influences Mood and Well-Being, from Scientific American, 2004).
Cutaneous nerves in the sole (foot)
From Gray’s Anatomy
Diagram drawn by Mysid
Gray’s Anatomy is in the public domain because of copyright expiration
Ask someone with active lupus the question, “Where does it hurt?” and the reply may be, “Just about everywhere”. Pain, with lupus and many other chronic conditions, becomes a backdrop to daily routine; only if pain spikes, or changes, is one likely to take note. In this setting, peripheral neuropathy (PN)–which often signals its presence by causing pain–can be easily misdiagnosed. An article published in the online journal, medpage today reports that though PN often occurs in conjunction with SLE, the two diseases have such similar symptoms that SLE may mask the presence of PN. It is a patient who is best able to detect early signs of neuropathy; significant changes in pain or sensation should be reported to a healthcare provider.
Peripheral Neuropathy is a disease of the nervous system. The Neuropathy Association describes PN as “…a disorder of the peripheral nerves—the motor, sensory and autonomic nerves that connect the spinal cord to muscles, skin and internal organs.” The symptoms include not only pain, but, among other things, tingling, burning, loss of sensation and muscle weakness. The disorder is often progressive and can be disabling; in some cases it leads to paralysis, loss of bowel function and even amputation. According to the Mayo Clinic, early treatment of PN offers the best chance for heading off more serious developments.
Dr. Franz Blaes, of the Grummesbach Hospital in Germany, describes the dilemma facing a physician treating someone who has both PN and an inflammatory rheumatological disorder, such as SLE or Sjogren’s Syndrome: “Patients can be classified neither as a rheumatic disease patient, nor as a patient with a neurological syndrome, but as both,” Dr. Blaes explains. The key to treatment, he suggests, is to get a clear picture of exactly what is going on. Is it PN, SLE, Sjogen’s, or a combination of conditions? Treatment is prescribed based on what this process reveals. In most cases where both the inflammatory rheumatological disease and PN exist, steroids are an effective intervention. However, regimens involving IVG therapy, plasmapherisis, cyclophosphamide and Rituximab may also be prescribed.
The most important thing SLE patients can do to help themselves, if there is a suspicion that PN is present, is to read the literature. Understand the tests that are given and what the results indicate; be aware of the kind of PN that is suspected; learn about treatment options, especially the one that is prescribed for your case. An article published in the September 2013 issue of Rheumatologist–Tips for Managing Peripheral Neuropathy in Rheumatic Disease by Timothy Collins–gives a good overview of peripheral neuropathy in SLE.
How does a doctor go about diagnosing PN, especially if someone also has an underlying inflammatory condition? According to Dr. Collins, this is not an easy task. The first step is to do a lab workup, including creatinine, complete blood count and liver enzymes. From these studies a doctor might eliminate some possible causes of the PN, such as diabetes. After getting the results from these tests, a doctor may turn to electrodiagnoistic studies. These help to determine the type of neuropathy and also may indicate the kind of underlying pathology that is causing the condition. A third kind of study that is sometimes suggested carries greater risk and often yields inconclusive results: nerve biopsy. According to Dr. Yvonne Lee of the Harvard Medical School, this “...shouldn’t be done before adequate clinical, laboratory, and electrophysiologic studies have been done.1 Results are often nonspecific, and complications, such as sensory loss and/or unpleasant abnormal sensations, are common.
Quality of life studies show that SLE patients with PN tend to score lower on quality of life metrics . This outcome is similar to other assessments of SLE patients who have central nervous system involvement.
Peripheral neuropathy is a serious condition; when it appears with SLE it may be overlooked or misdiagnosed. Sometimes PN may be the first noticeable symptom of SLE. Because the research on the relationship between PN and SLE is relatively recent, some doctors may not be alert to the issue.
The bottom line is this: if you have SLE and unexplained pain, PN is a possibility–one of many possibilities. In the past, rheumatologists believed this disorder was not likely to be seen in SLE patients; research is disproving this perception.
For most people with SLE, pain is simply a fact of life. But pain can be an important symptom and if there is a change in how it is experienced, then that should be noted. Perhaps the source of pain will not be discovered; perhaps the pain will not be alleviated. This may be a reality that a patient has to accept. However, one reality no one ever should accept is that pain, when reported, is disregarded. That course is irresponsible and even dangerous
Does mineral oil cause lupus? That’s not a question I, or anyone, can answer with absolute certainty. What I can say is this: mineral oil is a hydrocarbon and exposure to hydrocarbons has been associated with the development of lupus. Also, although mineral oil is a refined form of hydrocarbons, it retains elements that have been associated with the development of lupus autoantibodies.
According to the US EPA, hydrocarbons are “ubiquitous in the environment”. Something that distinguishes mineral oil from other hydrocarbons is that it is considered to be “safe” and is routinely added to personal care items, food wraps, medicines (such as vaccines)–and food.
Mineral oil is distilled from petroleum. “Food grade” mineral oil is a preferred food additive (preferred by some, anyway) because it is cheaper to use than the alternative, vegetable oil. Concern about mineral oil in the food supply is not confined to a small fringe of environmental extremists–the European Food Safety Authority (EFSA) has been accumulating data on the risks posed by mineral oil and has described some of the potential hazards. What the Authority seeks to establish is an acceptable level below which these hazards might not be expected to occur. The hazards include: the potential to accumulate in human tissue, and the mutagenicity (ability to cause cancer, among other problems) of mineral oil.
In its 2012 advisory, the EFSA came to the conclusion that sources of mineral oil in the diet are many and that there might be “concern for some consumers: specifically, customers who are brand loyal or who often buy the same food product from the same shop“. EFSA’s concern is that the total amount consumed in a diet would exceed the level considered to be “safe” by the authority.
EFSA’s carefully worded concern about mineral oil is not an isolated opinion in the scientific community. Responsible research has demonstrated that hydrocarbons–mineral oil among them–have the ability to induce the production of a variety of autoantibodies. Different hydrocarbons elicit different types of autoantibodies, autoantibodies that have been implicated in the development of lupus.
As described by the Oxford Journal, “certain mineral oil components… induce lupus-related anti-nRNP/Sm or –Su autoantibodies in nonautoimmune mice”. While the Journal does not state that a direct causal relationship between mineral oil exposure and lupus has been proven, the Journal is comfortable making the broad statement that, “There is some evidence that mineral oil exposure may be associated with human disease”.
The Journal article goes on to describe specifically conditions that have been attributed to mineral oil exposure: cutaneous lipogranulomas; chronic pneumonitis and systemic lipogranulomas. Data on the potential hazards of mineral oil have been persuasive to experts in the UK. These experts called for a ban on mineral oil as a food additive. Consequently, use of the oil in the UK is more restricted than it is in the US and Canada
One of the problems with mineral oil studies is that most of these have used mice as test subjects; outcomes in mice studies are not reliable predictors of human outcomes. An objection to using the results of these studies is that the amount of mineral oil administered to the mice is many times that most humans would be exposed to. However, the Oxford Journal article points out that if an individual uses mineral oil as a daily supplement (which many people do for its laxative effect), then, over time, the amount consumed would equal or exceed the amount administered to mice in an experimental setting.
Mineral oil is just one of a number of hydrocarbons in the environment. So many uses have been found for petroleum by products that it would be difficult to trace the exposures. However, when exposures are traced, it becomes obvious that hydrocarbons are implicated in the development of a variety of diseases. Lupus is one with a proven association and systemic sclerosis is another.
A study carried out in New Mexico demonstrated just how serious the risk from hydrocarbon exposure is. The study was carried out in a small subdivision in which residents were diagnosed with lupus at very high rates. The subdivision had been built over a retired oil field. When samples of vapor and dust within these homes were examined, very elevated levels of two contaminants were detected: pristane (a hydrocarbon that may be found in mineral oil) and mercury. Researchers hypothesized that it was a “synergy” between mercury and pristane that caused the extraordinary rate of lupus. Pristane, by itself, has been shown in prior studies to be a lupus antagonist .
It’s difficult to write a post like this and not imagine the criticism with which it may be received. Hydrocarbons are everywhere. Avoiding them would probably be impossible. Risks from hydrocarbon exposure will certainly be downplayed by those who find their use convenient, or cost effective. As for mineral oil–this product is considered benign by most consumers. It’s in baby oil and petroleum jelly. It’s in candy and baked goods. It’s used to coat paper and eggs. Reasonable people may charge me with alarmism because I write this post. But I write about what I discover and I have discovered some interesting facts about mineral oil.
Personally, I’m going to check labels more carefully when I buy. Baby oil, wax paper, petroleum jelly–these will not be in my home. Soft candy, shiny candy, baked goods–labels on these products will be carefully scrutinized to ascertain if the producers have chosen to use mineral over vegetable oil.