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Uncertainty and Lupus

Adapted from a presentation to the SLE Workshop at Hospital for Special Surgery

“A Rheumatologist is that doctor who lives most easily with uncertainty.” – Dr. Lockshin

There is a lot of uncertainty in the world and often you may not get the answers that you want. Uncertainty is very common in Dr. Lockshin’s world. In his discussion on this subject, Dr. Lockshin addressed the uncertainty experienced by doctors and patients and the question of how one can deal with the lack of clear answers.

Uncertainty in Autoimmune Diseases

When we talk about the diagnosis of lupus, rheumatoid arthritis (RA), scleroderma or other autoimmune diseases it is as if they are very clear entities. These diseases are not as rigidly separated as one might think. The disease a patient has in 2005 may be different in 2010 and different again in 2015. Doctors are often not schooled in the concept of a disease that has changing characteristics over time.

As we begin to analyze the components of uncertainty in autoimmune diseases, we start with what goes into making a diagnosis. Some patients may have too many symptoms and others too few.


Patients with too many symptoms

Patients who have symptoms that go beyond what is found in a textbook, are referred to as having “overlap disease.” We tend to think of lupus, RA and scleroderma as independent entities with no relationship to one another. There are, however, many overlapping symptoms among all of the autoimmune diseases. Some of these overlaps have names. “Rhupus” is not an official term, but is used to describe symptoms that are not clearly RA and not clearly lupus but fall somewhere in the middle. Mixed Connective Tissue Disease (MCTD) is an assortment of autoimmune diseases with a variety of labels attached to them. There are also other overlaps of autoimmune diseases that are not specifically named.

A large proportion of people with an autoimmune disease have multiple autoimmune diseases simultaneously. These autoimmune diseases include:

  • Thyroid diseases, including Hashimoto (underactive thyroid) and Graves' disease (overactive thyroid)
  • Inflammatory bowel diseases, including Crohn’s, ulcerative colitis and celiac disease
  • Neurologic autoimmune diseases, including multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS, also known as Lou Gehrig's disease)
  • Diabetes type 1
  • Skin autoimmune diseases, including psoriasis

How common is the overlap?

Dr. Lockshin examined data collected by the Barbara Volcker Center for Women and Rheumatic Disease. The Center specializes in women’s issues related to autoimmune diseases with a focus on pregnancy issues and special problems with autoimmune disease including overlap. Its database contains information on over 3,000 patients with a primary diagnosis. He found that over 40% of patients with Sjogren’s, 37% with lupus, 27% with Antiphospholipid Syndrome, 17% with other rheumatic diseases and 12% with RA had another autoimmune disease in addition to their primary diagnosis. Thyroid disease was most common for those with lupus.

Patients with too few symptoms

Patients who have too few symptoms are often referred to as “Forme Fruste,” a French term meaning incomplete or unfinished form, or “in evolution.” For these patients there is not enough information to make a clear diagnosis of lupus, RA or other autoimmune diseases. These patients often complain of joint pain, which is common to all autoimmune diseases, or they may have rashes that look like lupus. Despite these symptoms lab tests for these patients are not definitive and do not indicate a diagnosis. Often these patients fall under Undifferentiated Connective Tissue Disease (UCTD).

Patients with only abnormal blood tests

According to Dr. Lockshin, at this point the patient has a blood test but generally does not have an illness. For the most part treatment can be put off for weeks, months, years, even decades and nothing will happen. The blood tests generally indicate the importance of staying alert and keeping an eye out for any unusual occurrences. It’s important for these patients to let other doctors know about the abnormal blood tests in order to avoid repeating tests or treating for an illness that is not present.

According to Dr. Lockshin, diagnosis is less clear than is commonly believed. With lupus and related diseases a diagnosis is not always “yes” or “no.” These illnesses lie on a spectrum and must be organized and recognized for what may or may not need to be treated.


Dr. Lockshin discussed how the course of an autoimmune disease can change over time and the difference between acute and chronic illness.

Acute illness is dealt with immediately and generally has a clear intervention (like appendicitis or pneumonia). Once treatment is given, no further treatment is necessary. The outcome of the treatment is easily known from the results of many clinical trials.

Chronic illness is the world of lupus and RA. Symptoms may come and go. It may take months or years from the first time a patient notices their symptoms to figuring out what is actually wrong. The same thing occurs with lab test results. Often lab tests need to be repeated in order to check for any changes. In chronic illness, treatments often take a long time to have any effect. A treatment may be given for a few weeks or months and doctors will discover it is necessary to change the treatment. This cycle may continue until a correct combination is found. The illness may also differ from day to day. It is important to register if there are any changes from day to day.

Diagnosis Change in Chronic illness

Diagnosis can change over time. To illustrate this point, Dr. Lockshin presented the example of a patient who appeared in the 1970’s with a clear diagnosis of lupus. The patient went into remission, had children and her lupus seemed to be gone. She appeared in the early 2000s with a clear diagnosis of RA and no sign of lupus. She was treated for RA and once again went into remission only to reappear this last year with signs of lupus. According to Dr. Lockshin, the body does not care about labels and will do what it will do. The biggest issue is to not be too rigid and to be open to the idea that what the disease or diagnosis was a decade ago may not be what it is today.

Dr. Lockshin discussed four categories of time:

  • Instant Time is an acute illness situation in which there is no question that something is happening and must be addressed immediately, for example, a bone fracture, seizure etc.;
  • Clock Time is where there is time to figure things out. Symptoms can be watched to see what will happen over hours or days, for example, running a fever, a cough etc.;
  • Calendar Time is where there is time to work things out over several months, for example, last week the patient’s joints were swollen, this week they are not swollen, or he or she is losing weight;
  • Generational Time in which we ask what will be the result of what is done today be twenty years from now? There is a big difference from one patient to the next, for example, in terms of the effects of treatment.

For doctors and patients it is important to plan for all time frames simultaneously. Patients must know their own priorities (fertility, short- and long-term side effects of medications). Patients must be able to ask questions of their doctors and get as much information as possible. They must also learn to say “no,” if the solution given by their doctor does not match their priorities. Each treatment must be examined through the lens of time. One medication may work immediately but might have disastrous results six years from now. It is important for patients to keep this in mind and to remind their doctors to do the same. Dr. Lockshin encourages patients to ask questions anytime anyone wants to do something and remember that it is up to the patient to make the decision.

Code, indexes, criteria and guidelines

There are several types of criteria for diagnosis of autoimmune diseases. Terms that patients may come to hear during the process include:

  • Diagnostic criteria where the patient must meet a certain amount of criteria for diagnosis
  • Severity criteria which is based on how bad the disease activity is at that time
  • Damage criteria which looks at organs and bones and any issues that may become permanent issues altering the way a patient is treated (for example, kidney failure)
  • Treatment guidelines which are the agreed upon steps taken if a patient is diagnosed with a disease

According to Dr. Lockshin these criteria work for “classical” diseases but do not work for overlapping diseases. This can often create complications in regards to treatment guidelines and insurance billing and can impact insurance approval for treatments.

In addition, overlap diseases are not included in research studies. This is either due to researchers only selecting those patients with “classic” symptoms or to researchers not including information regarding overlap when reporting their findings. For Dr. Lockshin the biggest problem with codes, indexes (see below), criteria and guidelines is that it forces doctors to make decisions that may be inappropriate. He stresses that doctors must take into consideration the needs of individual patients and understand that overlap diseases exist.

Research on treatments always begins with testing on mice. Mouse studies can help us understand mechanisms of disease and to do preliminary testing of certain treatments. However, Dr. Lockshin points out that while there is important information gathered from mice testing, there is only so much mice can tell us about human disease. There are many human factors that must be taken into consideration when deciding upon treatment guidelines.

The SLEDAI (SLE disease activity index) only tells so much about lupus. The SLEDAI is used to assess activity of lupus. The SLEDAI measures symptoms (e.g., rash, arthritis) and lab tests (such as anti-DNA, urine). Each symptom or positive lab test is given a point, all of the points are added together to give an indication as to the level of disease activity. The SLEDAI does not measure some of the factors that are equally as important.

To address this issue, Dr. Lockshin created his own measurement called “Muddle” (MDL lupus exercise). The “Muddle” not only takes into account symptoms and labs but also takes into consideration socio-economic status and other life circumstances (children, job, beliefs, drugs, other diseases). Dr. Lockshin then calculated indexes incorporating the “Muddle.”

Dr. Lockshin provided an example of two patients. The first patient is wealthy, has easy transportation to her doctor appointments, good family support and good health habits. She also believes in her doctors and follows the rules of her treatment. Patient two, on the other hand, is poor, travels three hours to her doctor appointments, is a single mom with little family support and poor health habits. She distrusts her doctors and either runs out of her medication or does not take her medication.

Using SLEDAI, both patients will look alike, are equally eligible for clinical trials, and have similar prognoses. With “Muddle,” Patient 2 has twice the points than Patient 1, leading Dr. Lockshin to conclude that the patients should be separately analyzed and will ultimately have different prognoses. Clinical trials and data do not take into consideration these additional factors. According to Dr. Lockshin if data were reanalyzed taking these issues into consideration there would be better answers than are currently available. He further believes that predictions, treatment recommendations, and clinical trial results will be better if all of a patient’s characteristics are accounted for, not just the biological ones.

Dr. Lockshin used a poem by T.S. Eliot called The Waste Land to describe the process of looking at chronic illness in this way. The poem contains a mysterious line in French,

“Le Prince d’Aquitaine à la tour abolie”, which is translated as “The Prince of Aquataine at the ruined tower.”

No one has ever understood this line. There has been a lot written about what it means. Perhaps the best explanation offered it that the importance of the line is not in its meaning but in the music of its words. As declaimed in French, it is almost a song.

The lesson: there is always something hidden behind something obvious. It is not what seems obvious, it is what lies behind and is hidden.


Doctors are taught to look at diagnosis like a tree. The Diagnostic Tree has branches that offer only yes or no decisions. The branches get progressively smaller providing greater specificity, and the branches always end in a leaf. To a doctor, thinking of a diagnostic tree means doing more tests until an answer is found. Dr. Lockshin asks what if doctors were to look at diagnosis like a Mushroom Fairy Ring. A mushroom is at the end of a complex underground root system that can go on for acres and only at the very end does it pop up to become a visible mushroom. With the Mushroom Fairy Ring, diagnosis would be thought of in terms of the complexity of a mushroom fairy ring instead the simplicity of a tree. With rheumatic diseases one can look at the mushroom as symptoms, and the underground network as the complex diagnosis and disease process that lies beneath the symptoms. Decisions are not “yes” or “no” and moving forward does not mean getting more specific. There may not be a clear end or a clear answer. We may not get the full answer yet but we can deal with the current issue.

Doctors and patients can openly discuss what is known and is not known. It is easy to act on what we do know, but it is also important to acknowledge what we don’t know. When acting on what is not known doctors must negotiate priorities with the patient. When doctors and patients are open about what they don’t know, a dialogue between doctor and patient is established, and ultimately it becomes a way in which doctors and patients can work together.

Dr. Lockshin cited the end of Marcel Proust’s great novel, In Search of Lost Time. Proust concluded: “If at least enough time is left to me to finish my work, I would describe there how men occupy a place… much larger than that (so restricted) that belongs to them in space... in time.” Dr. Lockshin amends that statement to say, “Uncertainty is an inevitable part of our small place on the arrow of time. For my part, I now live comfortably with uncertainty. My job is to distinguish between what I know now and what I do not yet know. My job is to acknowledge, manage, and use that uncertainty, to make it work for and not against me, and to try always to improve.”

Summary by Gwyneth Kirkbride, Social Work Intern, Lupus Programs.


Headshot of Michael D. Lockshin, MD
Michael D. Lockshin, MD
Attending Rheumatologist, Hospital for Special Surgery
Director, Barbara Volcker Center for Women and Rheumatic Disease

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