Michael D. Lockshin, MD

Ask the Expert Michael D. Lockshin The answer to the question depends on what is meant by lupus, and what is meant by ANA. To start with the definition of lupus: systemic lupus erythematosus (SLE) is one of many similar illnesses that affect young women and that cause arthritis, rashes, low white blood cell counts, low platelet counts, and kidney disease. (I'll ignore, for this discussion, discoid [skin], drug-induced and neonatal lupus.) The features that unequivocally diagnose SLE are (1) high titer anti-double stranded DNA antibody, (2) anti-Sm (Smith) antibody, (3) biopsy-proven kidney disease, or (4) biopsy-proven skin disease. [The American College of Rheumatology criteria are used to group similar patients together for research and treatment trials. They are classification criteria and are not meant to be used to make a diagnosis.] The antibody tests must be accompanied by symptoms, since antibodies alone, with no symptoms, do not diagnose the disease. If a patient has symptoms plus diagnostic antibodies or biopsy proof of disease, the patient has SLE. If the patient lacks all four, the diagnosis is presumptive, even in the presence of illness. There is no real consensus among physicians how best to describe symptomatic patients who lack all four of the unequivocal features. This writer diagnoses "lupus-like" illness, "mixed connective tissue disease," "undifferentiated connective tissue disease," and "forme fruste (meaning incipient, or hidden form) lupus". Each has specific and separate meaning and describes different forms of illness. Most summaries report anti-DNA antibody in about half of patients, anti-Sm in about one-third, and ANA in 87-94% of patients with unequivocal SLE. Urowitz and Gladman cover this topic extensively in a textbook chapter[1]. In another textbook, Edworthy offers a complicated algorithm for diagnosis of lupus, using ANA titer, related antibodies, complement levels and symptoms to derive "diagnostic certainty"[2]. Still other text books discuss the uncertainties of serological testing without specifying frequencies of antibody negativity[3]. In this writer's practice, as many as one-quarter of patients referred for suspect SLE fall into the not-quite-lupus category, while persons who have any one of the four unequivocal features listed above have SLE[4]. Some but not all physicians diagnose lupus, even ANA-negative lupus, in cases in which, to this author, another term would be preferable. Because the medical community does not agree, whether to diagnose a patient as having lupus or lupus-like disease is not a question of the physician's being right or wrong; it is a question of a physician's style. In either case, treatment options are the same. Now, to the question of the meaning of ANA. The antinuclear antibody test is performed with different techniques in different laboratories; some techniques are more sensitive than others, such that one laboratory may find a (usually weak) positive test while another finds it negative. Some laboratories dilute 10-fold for screening (1:10), some as much as 100-fold (1:100), and some not at all. A commonly used method starts with a dilution of 1:10, then doubles with every successive dilution, so the next specimen tested is 1:20, then 1:40, 1:80, etc., the highest number positive being what the laboratory reports (for instance, 1:1280). Most lupus patients have sera that react at very high dilutions, essentially always more than 1:80, often more than 1:5120. Depending on the laboratory's reporting habits, a test that is positive at 1:10 or even 1:40 may be called either negative or weakly positive. Most laboratories count 1:80 and higher as clearly positive. The point is that ANA-negative does not always precisely mean completely negative. Another point is that speckled (as opposed to diffuse or peripheral) ANA patterns do not read well in automated immunofluorescence tests, so may be reported as lower titer or negative than they would be if they were hand read by an experienced technician[5]. There is a further complication. The ANA is used to screen for lupus, not to diagnose it. This means that, for practical purposes, if the ANA is negative, lupus does not exist and no further testing need be done; indeed, some laboratories will not further screen sera that are ANA negative. If the ANA is positive, that means only that lupus is possible and that tests for antibody to double-stranded DNA, Sm (Smith), Ro/SSA (Sjogren's syndrome A), La/SSB (Sjogren's syndrome B), and RNP (ribonucleoprotein) must be performed to determine whether lupus is or is not present. Because of a variety of technical factors, it is possible to have a negative ANA but a positive specific antibody test, though this is very uncommon; for diagnosis a positive test for a specific antibody is more important than is a negative ANA test. Thus an "ANA-negative" person with strongly positive antibody to Sm would unequivocally have lupus (the author has seen many such patients). Because of this possibility, this writer, evaluating a new patient for lupus, usually simultaneously (to save time) tests for ANA, anti-DNA, anti-Sm, anti-Ro/SSA, anti-La/SSB, and anti-RNP, as well as for other abnormalities relative to the patient's specific condition. That is, he does not completely discard the diagnosis if the ANA test is negative, though the diagnosis is much less likely. Now another complication: all of the above applies to the evaluation of new symptoms in an untreated patient at a specific time. In a lupus patient-or in a patient with suspect lupus-tests change over time, either improving or worsening. Furthermore, tests often revert to normal during treatment. If the question, "Can an ANA-negative person have SLE?" is asked of a patient with established or treated disease, it may be impossible to confirm or refute the diagnosis-on the basis of blood tests alone-made years earlier, or in a patient taking high doses of prednisone or immunosuppressive drugs. In our recent cross-sectional study of atherosclerosis in SLE studying treated patients with disease of variable duration, at the time of study, 42% had anti-DNA antibody and 10% anti-Sm[6]. We did not specifically tabulate frequency of ANA. The answer to the question, "Does ANA-negative lupus exist?" is technically "yes", with a large number of buts, and ifs, and whens. Another answer is that the question is not very important. It is never critical to say definitively that a given patient does or does not have lupus. What is important is to evaluate the current symptoms, to put the symptoms into an overall context that includes blood tests, duration of symptoms, other illnesses, and medications, and to develop a treatment plan based on the total information rather than on a blood test alone. See the complete article on the Hospital for Special Surgery's web site

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[1] Urowitz MB, Gladman DD. Antinuclear antibody-negative systemic lupus erythematosus. In: Lahita, RG. Systemic Lupus Erythematosus, 3rd Edition. San Diego: Academic Press; 1999. p. 319-324. [2] Edworthy SM. Clinical manifestations of systemic lupus erythematosus. In: Ruddy S, Harris ED III, Sledge CB, editors. Kelley's Textbook of Rheumatology, 6th ed. Philadelphia: W.B. Saunders; 2001. p. 1105-1124. [3] Koopman WJ. Arthritis and Allied Conditions. Philadelphia: Lippincott Williams & Wilkins; Philadelphia. p 1445-1502. [4] Lahita RG, The clinical presentation of systemic lupus erythematosus. In: Lahita, RG. Systemic Lupus Erythematosus, 3rd ed. San Diego: Academic Press; 1999. p. 325-336. [5] Fritzler MJ. Immunofluorescent antinuclear antibody test. In: Rose NR, de Macario E, Fahey JL, Friedman H, Penn GM, editors. Manual of Clinical Laboratory Immunology. Washington: American Society for Microbiology; 1992. p. 724-729. [6] Roman MJ, Shanker B-A, Davis A, Lockshin MD, Sammaritano L, Simantov R, Crow MK, Schwartz JE, Paget SA, Devereux RB, Salmon JE. Prevalence and correlates of accelerated atherosclerosis in systemic lupus erythematosus: a case-control study. N Engl J Med;349:2399-2406

Ask the Expert Decision-making in such young women can be difficult and among the most agonizing - for both patient and physician. It usually requires a very prolonged conversation with the patient and her immediate family, whether parents or significant other. While such women clearly need treatment - and preservation of fertility is obviously desired - it is very difficult to know the best option. We use one of three options in these circumstances:

1. administer full-dose cyclophosphamide (with prednisone) and hope for the best; 2. administer prednisone and mycophenolate, although there is a little controversy as to whether this is as effective as cyclophosphamide; or 3. pretreat the patient with leuprolide acetate (Lupron) and administer prednisone and cyclophosphamide, although it makes young women pretty miserable and it must be continued for the full duration of treatment.

None of these options is ideal. The usual solution is number 2. Low-dose cyclophosphamide would not be helpful. The Europeans (English and French, in separate investigations) have published on "low-dose" cyclophosphamide in uncontrolled trials, but their definition of low-dose is 0.5 g per meter squared every two weeks, rather than the NIH protocol of 1.0 g per meter squared every month - so I don't get the point of it all. It seems to me the total cyclophosphamide dose is more or less the same, and they have provided no additional data regarding fertility or other critical information. See the complete article on the Hospital for Special Surgery's web site

Special Report Michael D. Lockshin, MD

1. ANA,FANA (Fluorescent)-Anti-Nuclear Antibody 2. Anti-DNA 3. anti-Sm antibody-_Antibody to the Smith antigen 4. anti RNP-Antibody to the Ribonucleoprotein 5. anti-Ro,(=anti-SSA(=anti-Ro)) 6. anti-La,(=anti-SSB) 7. Complement,CH50,C3,C4 8. aCL, aPL, lupus anticoagulant 9. BUN (Blood Urea Nitrogen) 10. Urinary protein, proteinuria, albuminuria 11. Platelets- blood cells that aid in clotting.

Are you confused by the names of the blood tests doctors use to diagnose or monitor lupus? Do you know what the tests mean? If you are confused, perhaps the information below will help. In looking at the following information, remember: An antibody is a protein (such as gamma globulin and other globulins) that the body normally makes to defend itself against bacteria (germs), viruses, and other things that cause harm. In lupus, the body mistakenly makes antibodies against a person's normal tissue. An antibody is named according to the substance (antigen) which it is made to fight. Thus, an antibody induced by a polio vaccination is called anti-polio virus antibody. Because the basic abnormality of lupus is an immune system that is in overdrive, most of the tests measure the degree to which the immune system is active. Other tests measure the function of specific organs such as the kidneys. A lot of these tests and names are confusing. Don't worry about such designations as mg/dL (milligrams per deciliter). These are technical terms that refer to a specific way of measuring one or another substance. Some laboratories use international units (IUs); some laboratories report the results of chemical tests in mols instead of milligrams. I've given the measurements that are most often used. If your laboratory reports your results in a different way, ask your doctor to explain which units are used and what is normal for that laboratory. I have not given numbers for tests that are either reported as positive/negative, or in cases where there are too many ways of reporting to summarize briefly. Keep in mind that the statements above are just rough guides. There are always exceptions to every rule. I've listed the most common tests and the most common uses, but they may differ for you. If you are still confused, or you are in doubt, ask your doctor for an explanation. Test: ANA, FANA (Fluorescent) - Anti-Nuclear Antibody What test is for: An antibody against the nucleus, or central controlling part of each cell. All organs are made of cells and all cells have nuclei. ANAs have four basic patterns describing the way they look under the microscope. The patterns are "diffuse" (the whole nucleus lights up), "peripheral" or "rim" (only the ring around the nucleus does), "speckled" and "nucleolar" (two very specific spots light up). What a positive test means: Almost all patients with lupus have a strongly positive test (still positive even when diluted more than 100 times, commonly expressed 1:100). Many normal people also have positive tests, usually less strong (1:10-1:30). The "diffuse" and "speckled" patterns are common in lupus, but are also seen in other diseases and normal people. The "peripheral" pattern is relatively specific for lupus. The "nucleolar" does not often occur in lupus. A positive test means lupus is a possible diagnosis. What a negative test means: A negative test usually means that a patient does not have lupus, or that lupus is in remission. However, most patients in remission do not have negative ANAs. … See the complete article on the Hospital for Special Surgery’s web site

Ask the Expert Michael D. Lockshin The biggest problem in answering this is the definition of 'early' and 'late' lupus. Some patients have very minor symptoms that persist for years and need almost no treatment; others are very sick from the outset of their very first symptoms. Most people use the term 'early' to denote time, but in lupus the issue is probably one of severity. Clearly, the sooner the disease is recognized, and the sooner treatment is initiated, the less damage will occur. However, early treatment does not necessarily prevent later flares. Patients with SLE follow three types of courses: chronic active (accounting for about half of patient-years), relapsing-remitting, and long-remitting. There's also the concern about what sort of treatment is indicated. In some cases, that means corticosteroids; in others, immunosuppressives are needed, and in still others, anticoagulants. All have dangers associated with them, and it is a judgment call whether to use them or not in given circumstances. For example, even management of asymptomatic patients with anti-cardiolipin antibody is still controversial. There is, in fact, so much variability in the treatment of an individual lupus patient that I cannot provide a clear answer about early or late treatment. However, I do not know of any research suggesting that early treatment prevents later serious flares. (For further treatment information, see Dr. Lockshin's In-Depth Topic Review on SLE.) See the complete article on the Hospital for Special Surgery's web site

A Patient's Reference Michael D. Lockshin, MD 1. Definition 2. Pathogenesis 3. Clinical Presentation 4. Laboratory Findings 5. Differential Diagnosis 6. Initial Treatment 7. Long-term Management Issues 8. Prognosis 9. When to Seek Referral to a Specialist 10. Annotated Bibliography 1.  Definition Lupus is an autoimmune illness in which parts of the immune system, which normally protect you from outside invaders, run amok and attack parts of your body. Lupus has several forms: * systemic lupus erythematosus (SLE), which can affect the skin and other organs throughout the body, including abnormalities in the blood; * discoid lupus, which only affects the skin, causing a scarring rash (although subacute cutaneous lupus also primarily affects the skin); * subacute cutaneous lupus is a form of systemic lupus in which a characteristic rash predominates, indicators in the blood are strongly positive, but involvement of other organs is usually mild; * drug-induced lupus, which is relatively rare and disappears when the offending drug (such as hydralazine and procaine amide) is discontinued; * neonatal lupus, which occurs in infants of women with specific blood test abnormalities. (This article will focus primarily on SLE, with brief discussion of neonatal lupus in the section below on pregnancy.) Although SLE is a chronic disease that usually lasts a lifetime, many patients have periods of flare (when symptoms worsen) and remission (when symptoms lessen or disappear). SLE affects women nine times as often as men, blacks four times as often as whites, and is most likely to arise between the ages of 15 and 45. The reasons for this distribution are unknown. SLE affects women nine times as often as men, blacks four times as often as whites, and is most likely to arise between the ages of 15 and 45. The reasons for this distribution are unknown. Differential diagnosis and management of the various signs and symptoms differ depending on whether the patient is newly diagnosed and untreated or the patient has been treated for many years. (See Boumpas in bibliography below.) Two recent American textbooks for physicians present extensively referenced and detailed discussion of all aspects of these illnesses. (See Wallace and Lahita.) … See the complete article on the Hospital for Special Surgery's web site

Special Report
Michael D. Lockshin, MD

At this time of year, patients with lupus, rheumatoid arthritis, and other autoimmune diseases always ask, “Should I get a flu vaccination?” At this time in our history, many patients are also asking, “Should I get a smallpox vaccination?” These questions are really about three more general questions: 

1. Are patients with autoimmune diseases unusually susceptible to flu or smallpox?
2. Can patients with autoimmune diseases be adequately protected if they do receive a vaccination?
3. Is the vaccine safe, in the sense that it can either cause autoimmune disease to worsen or can cause complications by itself?

The brief answers, which are different depending on the disease and vaccine, are:

1. Patients taking immunosuppressive drugs, including prednisone or other corticosteroids, and those with lung and/or kidney disease, are unusually susceptible to flu.

Although little is known about susceptibility to smallpox, based on what happens with the related varicella virus (which causes chickenpox and shingles), patients on immunosuppressive drugs will likely be at high risk for severe disease if they are exposed to smallpox.

For both diseases, the increased risk includes patients taking: corticosteroids, such as prednisone and methylprednisolone (Medrol); immunosuppressive drugs, such as methotrexate (Rheumatrex, Trexall), azathioprine (Imuran), mycophenolate mofetil (CellCept), cyclophosphamide (Cytoxan), leflunomide (Arava), cyclosporine (Sandimmune, Neoral) and similar drugs; and biologics, such as the TNF-alpha inhibitors infliximab (Remicade) and etanercept (Enbrel) and the IL-1 inhibitor anakinra (Kineret).

2. Flu vaccine successfully protects patients with rheumatic disease, if they are not taking high doses of immunosuppressive drugs.
3. Flu vaccine does not worsen rheumatic disease and is generally well tolerated by rheumatic disease patients.

See the complete article on the Hospital for Special Surgery’s web site

Summary of a presentation at the Living with RA Workshop at HSS
Michael D. Lockshin, MD

The traditional answer to the question “Why are autoimmune diseases women’s diseases?” has been “It has to do with estrogen.” But that’s not a satisfactory answer because a lot of facts that don’t fit this theory. So the question has been researched with greater interest in recent years.

What is autoimmunity? Some define it by tests done in a laboratory that find antibodies (such as rheumatoid factor) to normal tissue (parts of the body). Others say it’s the kind of disease that cause arthritis and sometimes fevers, kidney disease and other problems. Others say any disease that causes arthritis is an autoimmune disease. Animal models are another way to define it because the autoimmune diseases that we recognize can be produced in animals by manipulating their immune systems. Because autoimmune diseases tend to run in families, we tend to use a positive family history as part of the definition. By and large, all the definitions require that an autoimmune disease not be an infectious disease, such as Lyme disease and some types of hepatitis, which would look like autoimmune disease if they were not clearly caused by an infection. (This suggests that diseases such as RA may also be infectious diseases but we just haven’t identified the cause of the infection.)

Which diseases are autoimmune? Again, the answer is not totally clear. Most physicians would agree to this list: Hashimoto’s thyroiditis, primary biliary disease, chronic active hepatitis, Grave’s disease, lupus, scleroderma, rheumatoid arthritis, Sjogren’s syndrome, and most rheumatic diseases, including ankylosing spondylitis. But there are many other diseases that some doctors consider autoimmune and others do not. The American Autoimmune Association would include such diseases as multiple sclerosis, hemolytic anemia, pemphigus, pernicious anemia, type 1 diabetes, myasthenia gravis, Goodpasture disease, and many others - but there is no clear consensus. And there is considerable controversy about some neurologic, skin, and intestinal diseases that are accepted as autoimmune by some doctors and not others.

Are all autoimmune diseases women’s diseases? Not necessarily. While many are much more common in women, others are more common in men. For RA, women are affected about two and a half times more common in women compared to men.

This again raises the question of why so many autoimmune diseases are much more common in women. Two important efforts to explore the question were: a conference at Hospital for Special Surgery in 1999 exploring Gender, Biology and Human Disease; and a commission of the Institute of Medicine of the National Academy of Sciences, which last year published a book Exploring the Biological Contributions to Human Health - Does Sex Matter? - available for purchase or for free online. The NIH study looked at male/female differences in the following factors.

Environmental differences - Women may develop autoimmune diseases because they are more susceptible - or more exposed - to something in the environment. For example, scleroderma occurs spontaneously, primarily in women, but also in men who are gold and coal miners and in workers that manufacture plastics. Scleroderma-like diseases also are seen in those exposed to some toxins. Further, some drugs can cause lupus, which primarily occurs in men taking those drugs. However, no environmental culprit has been identified.

Genes - Due to genetics, women and women have some chemical reactions that are different. No genes have yet been proven to explain female predominance, but the field is just beginning to be explored.

Behavior - Some diseases are different in men and women due to behavioral differences. For example, you can develop osteoporosis based solely on personal habits because the amount of exercise you do and your body fat levels affect bone strength. Women who are intense athletes, such as marathoners, lose huge amounts of body fat, stop menstruating, and get severely osteoporotic. Girls who are anorectic and don’t eat also lose their body fat and get very thin bones. Other examples are venereal diseases, which are more common in men because of their relative level of promiscuity. And Reiter’s syndrome is a form of arthritis that is often triggered by venereal disease. So the theory is that women can predominate in a disease if men and women differ in basic personalities, but we don’t know what personality factors could lead to diseases like RA.

Whole Organism - Issues related to being a living person at given time, for example, might include age, and most autoimmune diseases start between the ages of 15 and 45. So there is something interesting about that age range. Many issues related to age might explain female predominance, such as a long period between encountering what causes these diseases and their eventual appearance. So it might be theorized that little girls do different things from little boys but it doesn’t show up as disease until 10 or 20 years later. The Army keeps blood samples of its recruits for many years; researchers have now looked at samples of this blood and found that blood tests are positive more than 10 years before the appearance of lupus and RA. So the disease has existed for more than 10 years before someone gets joint pains.

Hormones - Estrogen increases the immune response in humans and many animals. However, in some animal models we don’t see more frequent disease but more severe disease in females. That’s the opposite of what we see in humans; for example, the severity of RA and lupus are the same in men and women but the frequency is different. And the influence of hormones is inconsistent: during pregnancy, RA gets better but lupus may get worse or be unchanged. So there may be big differences in the way different autoimmune diseases appear when you get pregnant or take birth control pills or estrogen replacement. However, in two recent studies, it looks as if birth control pills and estrogen replacement have no effect on women with lupus. It’s possible that reaching a certain threshold of hormones or the cycling of hormones in menstruation could influence disease. But we still don’t know whether hormones cause disease.
Other possible differences in men and women that might relate to autoimmune disease include anatomy, pregnancy, differing physiologic responses to drugs and toxic substances, differing genitourinary tracts, influences on the baby before birth, and other factors.

Dr. Lockshin’s guess is that hormones are not the explanation for female predominance of autoimmune disease. Rather, he thinks the predominance relates to different exposures to something in the environment or differences in the way men and women’s bodies handle something, or some mixture of the various causes discussed above.

The differences in the male to female ratio of autoimmune diseases is the single most bizarre clinical fact about these diseases. It has not received a great deal of research attention so far, but finding the answer will teach us a great deal about these diseases.

See the complete article on the Hospital for Special Surgery’s web site
Summary prepared by Diana Benzaia.

About the Living with RA Workshop at Hospital for Special Surgery

Adapted from a talk at The SLE Workshop at Hospital for Special Surgery Michael D. Lockshin, MD

Warning About Misuse of the Term What is Vasculitis? What Vasculitis is Not When Does Vasculitis Occur in Rheumatic Disease? When is Vasculitis an Important Complication of an Autoimmune Disease? Diseases in Which Vasculitis is the Specific Illness Vasculitis by the Size of the Vessel Small Vessel Vasculitis Medium Vessel Vasculitis Large Vessel Vasculitis Summary

Vasculitis means inflammation of the blood vessels. (Vasc refers to blood vessels and itis means inflamation). Vasculitis is a problem that can arise independently of other illness, or it may co-exist with lupus or other autoimmune diseases. When it exists in lupus, it may simply confirm the diagnosis, causing no problems, or it may represent a change in the course of the lupus, with vasculitis as a serious complication. Thus, vasculitis may mean many things. If a doctor says you have vasculitis, ask what that really means - what disease process is going on and what it means for you. Warning About Misuse of the Term "Vasculitis" Vasculitis should not be confused with vasculopathy, which simply means something is wrong with the blood vessels, although it's usually not vasculitis. Some people use these words interchangeably, which is wrong. Some people, even physicians and especially on the Internet, use the term "vasculitis" very loosely. So you may see statistics about vasculitis on the Internet that are very frightening, but they don't provide any information on your situation. The term vasculitis is used ten times as often as it should be by people who are not really referring to this disease. Unfortunately, even some doctors often use the term vasculitis to mean "person with autoimmune disease and blood vessel abnormality that I don't understand." If your doctor says you have vasculitis, ask specifically what he/she means before you go to the Internet! What is Vasculitis? Vasculitis is blood vessel inflammation that causes fever, pain, local tenderness, and other evidence of blocked blood vessels. When a blood vessel becomes inflamed and narrowed, blood supply to that area can become partially or completely blocked. Complete blockage is called occlusion; it causes the vessel wall to swell and makes things stick to the wall — so a clot forms. When vasculitis interferes with circulation in any part of the body, it causes local tenderness and pain. If the blood vessels are close to the skin, characteristic rashes occur. Depending on where the blockage occurs, almost any organ in the body can be affected. (Note: Vasculopathy can also block blood vessels, but it does not cause the fever, pain, and local tenderness associated with vasculitis.) While vasculitis may involve arteries (the thick muscular vessel that carries blood away from the heart) and veins (the thinner, less muscled vessels that carry blood toward the heart), it is rare for both arteries and veins to be involved at the same time. What Vasculitis is Not Many problems that block blood vessels looks like vasculitis, and doctors often jump the gun and call them vasculitis, but greater care is needed to find out what's really going on. Among the diseases involving blocked blood vessels that are not vasculitis: Atherosclerosis (hardening of the arteries); Growths on the heart valves that break off, especially those due to infection; Excessive blood clotting (antiphospholipid syndrome); Vessel spasm, especially due to drugs (legal and illegal). When Does Vasculitis Occur in Rheumatic Disease? All of the rheumatic diseases involve some level of underlying vasculitis. That includes lupus, rheumatoid arthritis, scleroderma, and dermatomyositis. If you biopsy a swollen joint in RA, you routinely find vasculitis. That finding is used to confirm the diagnosis, but it doesn't mean anything important is happening. It just suggests that one of these autoimmune diseases is present. So vasculitis is a common finding in these diseases, important in diagnosis, but it doesn't necessarily mean anything more. It may never be a problem! When is Vasculitis an Important Complication of an Autoimmune Disease? There are times in lupus and RA when the disease takes a different course in the presence of vasculitis. You start getting sicker and develop fever - clues to the physician that there has been a change in the course of illness. Now we say "This is lupus complicated by vasculitis" or "This is rheumatoid arthritis complicated by vasculitis." The disease has changed its character and usually needs more vigorous treatment. See the complete article on the Hospital for Special Surgery's website