15 Questions - Lupus and Overlap Disease/Syndromes

(August 2012) Although lupus usually occurs alone, many people with lupus sometimes have symptoms characteristic of one or more of the other connective tissue diseases, like rheumatoid arthritis, scleroderma, Sjogren's syndrome, polymyositis-dermatomyositis, and various forms of vasculitis. In this circumstance, a physician may use the term "overlap" to describe the illness. This month, Dr. Wael Jarjour answered your questions about lupus and overlap diseases.

1. What defines an overlap disease? Is there a maximum of overlap diseases that an individual may develop? Bozeman, MT

If we apply the strictest definition, an overlap diagnosis can be made when a patient meets the official criteria for two autoimmune diseases. However, many times a patient is said to have an overlap in order to permit a degree of uncertainty regarding the exact diagnosis. This allows the patient to be observed very carefully to be certain that no additional problems are developing. As for the maximum number of diseases, there really is no limit regarding how many autoimmune diseases a patient may have, but practically it becomes very difficult to keep adding diagnoses.

2. How long after the diagnosis of one autoimmune disease is it most likely to develop additional diseases? Rowlett, TN

There is no time limit on when a second (or even third) autoimmune disease may develop, although it is more likely to happen early. Nevertheless, I have seen patients develop a second autoimmune disease more than ten years after the diagnosis of the first.

3. When you have overlap diseases, how do you (or your doctor) know which disease may be causing pain or symptoms on any given day?

In many situations, it is difficult to say with certainty which disease is causing a particular problem unless the problem is unique to a particular disease. In the case of joint pain, it is very difficult to differentiate pain associated with lupus arthritis from that associated with rheumatoid arthritis. However, from a treatment point of view, as long as a patient is experiencing an inflammatory type of joint pain the effective treatment is similar.

4. I have had SLE nephritis for over 20 years and as the years continue my doctors have diagnosed me with several other conditions, such as, pericarditis, arthritis, and most recently Sjögren’s syndrome. How do I know if these are overlapping diseases/syndromes or symptoms of my SLE?

That’s an extremely good question, and a difficult one. Autoimmune diseases are very complicated. For example, nephritis, pericarditis, arthritis and many others conditions such as anemia and skin rashes are all an integral part of lupus; but not all lupus patients have pericarditis or arthritis or anemia. To make the problem more challenging, not all pericarditis, for example, is related to lupus even in a patient with an established diagnosis of lupus. The pericarditis may be due to conditions that are not autoimmune.

You mentioned Sjögren’s syndrome.This is a disease that is characterized by infiltration of immune cells into glandular tissues causing reduced function. The most common glands affected are the salivary and lacrimal glands resulting in dry mouth and eyes, respectively. This syndrome is often a development in a lupus patient, particularly those who have had lupus for years. When this occurs it is referred to as secondary Sjögren’s. However, if there is no other autoimmune disease processes then Sjögren’s may be a primary process. The answer to your question is that as long as all the findings can be explained by lupus then no other diagnosis is likely. It is, however, always important to exclude non-autoimmune causes of a particular problem.

5. What are some of the more common disease/syndromes that overlap with lupus?

There are many diseases that overlap with lupus: anti-phospholipid syndrome, rheumatoid arthritis, polymyositis, dermatomyositis, scleroderma, and Sjögren’s syndrome. There are, however, many other less common autoimmune diseases that can affect lupus patients which it is important to recognize.

6. For purposes of treatment, should I favor one disease label over another or just call it overlap? Are there common treatments for overlap issues such as CREST/limited scleroderma, anti-phospholipid antibodies and SLE? Los Angeles, CA

Labels are not as important as defining the disease process that is active and that is causing the patient’s symptoms. However, for treatment purposes, it is critical to define as clearly as possible what is causing the patient’s symptoms because occasionally there are major differences in what treatment should be chosen. For example, prednisone is a drug that needs to be used with extreme care and at very low doses in CREST syndrome and anti-phospholipid syndrome requires treatment with blood thinners that are normally not indicated in rheumatoid arthritis.

7. I was initially told that I have SLE, and then the diagnosis was changed to fibromyalgia. Now I am told that I have both or possible Behçet's disease. I get treated for one issue then for another with no relief. How do you get a clear diagnosis and what tests should be run to get a clear understanding of what is going wrong? Donora, PA

I am sorry that you are not experiencing any improvement in your symptoms in spite of different treatments. Fibromyalgia syndrome can present as an isolated problem or in conjunction with another disease, such as lupus or a non-autoimmune disease like osteoarthritis. Making an accurate diagnosis of lupus is important and the way to do that is to see a doctor who specializes in lupus (usually a Rheumatologist). Sometimes patients are told that they have lupus on the basis of a positive blood test but if there are no other findings that support the diagnosis of lupus they may not, in fact, have this disease. Some diseases, like fibromyalgia, have no blood test to confirm the diagnosis and the decision must be made on the history and a physical exam. Certain lab results can, however, be helpful in excluding the presence of other diseases processes. Behçet’s is another disorder that has no diagnostic blood test but the diagnosis can be established based on history, physical exam, and supportive laboratory and imaging studies. The specific testing can only be determined by a physician who is an expert in evaluating these types of diseases and who has evaluated the patient.

8. My rheumatologist told me I have mixed connective tissue disease (MCTD). Is this related to my lupus or is it a separate disease? Fairless Hills, PA

MCTD is a disease that was described approximately 50 years ago. The term was used to describe patients with combinations of clinical findings similar to lupus, scleroderma, polymyositis and rheumatoid arthritis, and whose blood had a high level of an antibody to a certain protein called ribonucleoprotein antigen. If we use this definition, then MCTD is a separate disease. Practically speaking, however, the term has gradually come to be synonymous with overlap syndrome, discussed above.

9. I have been diagnosed with SLE & Sjögren’s there is a constant confusion with my rheumatologist which is primary. For a long time she would state SLE is primary now she recently stated that Sjögren’s is primary. Why is it so difficult to determine which is primary or does it matter at all? Poughkeepsie, NY

Sjögren’s syndrome and SLE have many things in common but, as a matter of definition, primary and secondary only apply to Sjögren’s syndrome. Sjögren’s can exist as a primary process when there is no other connective tissue disease that can be identified. Secondary Sjögren’s can develop in patients with many autoimmune diseases, but most commonly in those with rheumatoid arthritis or lupus. But if a patient develops symptoms and findings diagnostic of Sjögren’s first and later develops symptoms and findings diagnostic of lupus, the distinction between primary and secondary Sjögren’s would be obsolete.

When considering treatment, it is most important to identify all the different processes present and to address each of them specifically. Labeling the Sjögren’s as primary or secondary is less important. But it is critical to establish the diagnosis of Sjögren’s because it requires certain therapeutic interventions that are not normally prescribed for lupus patients.

10. I was diagnosed six years ago with SLE/Sjögren’s overlap. Over the past two years, I have also developed Rheumatoid-like arthritis. How does having Rheumatoid-like arthritis as part of SLE differ from having RA/SLE overlap? Does it still carry the other health risks associated with RA? Nicholasville, KY

As discussed in the previous question, the diagnosis of SLE and Sjögren’s together is common and in this case Sjögren’s would be considered a secondary process. Sometimes rheumatoid arthritis is also seen in patients with lupus. Rheumatoid arthritis is diagnosed when certain changes in the bones (erosions) are seen, as well as certain laboratory findings. Some Rheumatologists use the term Rupus to describe this presentation. The differentiation between someone who has rheumatoid-like arthritis and lupus vs. someone who has rheumatoid arthritis/SLE overlap is either an issue of severity of the findings or more likely a matter of semantics with no significant clinical difference. The health risk difference between these two descriptors is probably very minimal.

11. Is irritable bowel syndrome common with SLE patients? Damascus, MD

Irritable bowel syndrome (IBS) is a common gastrointestinal (GI) disorder but is not related to lupus. However, GI symptoms such as oral ulcers, trouble swallowing, abdominal pain, diarrhea, and blood in the stool can all be symptoms associated with GI involvement with lupus. Therefore, it is important that an evaluation be done by a Gastroenterologist to be certain that the IBS diagnosis is well established.

12. Is there more than one kind of vasculitis or is there only one kind and all over your body? Garden Grove, CA

There are many kinds of vasculitis and many different classification systems for vasculitis. Vasculitis is inflammation involving a blood vessel that can result in occlusion or narrowing of that blood vessel. It can affect practically any part of the body and it produces symptoms that depend on the size of the blood vessel affected and its location. The most common kind of vasculitis in lupus is small vessel type which usually affects the skin.

13. I was diagnosed with lupus and overlapping disease of primary biliary cirrhosis, but the doctor says it hasn't hit my liver yet. Can you explain what this means and will controlling my lupus help with any possible liver involvement? Bridgeport, WV

Primary biliary cirrhosis (PBC) is an autoimmune disease that is characterized by attacks on the cells that line the duct that transports the bile (a substance that is made by the liver to help with digestion). Early on in the disease process there is little liver damage, but without treatment liver failure (cirrhosis) may occur. This disease coexists with Sjögren’s syndrome in about half of patients. There are several symptoms and findings that can be shared by lupus and PBC, such as fatigue and positive anti-nuclear antibodies. However, the treatments for lupus and for PBC are somewhat different since the main treatment for lupus is suppressing or modulating the immune system while the main treatment of PBC is using drugs that protect the liver from the negative effects of the bile salts. However, there are several investigational treatment regimens that use immunosuppression in PBC. Therefore it is difficult to say with certainty whether treating the lupus will help the PBC.

14. I was diagnosed with polymyositis and later SLE and scleroderma. My question is, my lab work has not indicated flare ups although I continue to have the same symptoms I have had when labs indicated flare ups. Does this mean I no longer have SLE and was possibly misdiagnosed with SLE? Orangeburg, SC

The correlation between lupus flares and laboratory findings is very difficult. There is intense research under way to identify markers that can predict lupus flares reliably. Prediction is further complicated by the fact that many of the symptoms that are experienced by patients with one systemic autoimmune disease can be also be seen in other diseases. For example, joint pain can be a symptom in polymyositis, lupus, or scleroderma. Additionally, it is possible for a lupus patient to go into remission and no longer have symptoms; but that does not mean they never had lupus. During remission we say that the lupus is inactive. Finally, many symptoms that may be seen during a flare of lupus could be multifactorial in origin. For example, patients may have fatigue associated with active lupus or rheumatoid arthritis but fatigue can also be related to depression and sleep disturbance.

15. Is Undifferentiated Connective Tissue Disease (UCTD) a blend of multiple diseases or is it one disease by itself? How is it related to lupus?

This term, UCTD, was introduced about 30 years ago and in the strictest use describes a patient who has symptoms and findings suggestive of connective tissue disease but does not meet the official criteria for any one specific disease such as rheumatoid arthritis or lupus. Some patients with UCTD eventually develop lupus.