Michael D. Lockshin, MD

S.L.E. Lupus Foundation “Get into the Loop”
NYC Hospital Tour, Public and Patient Education Department Program,
November 3, 2005
Michael D. Lockshin, MD

What is lupus?
Systemic lupus erythematosus (SLE), commonly called lupus, is a chronic autoimmune disorder that can affect virtually any organ of the body. In lupus, the body’s immune system, which normally functions to protect against foreign invaders, becomes hyperactive, forming antibodies that attack normal tissues and organs, including the skin, joints, kidneys, brain, heart, lungs, and blood. The disease is characterized by periods of illness, called flares, and periods of wellness, or remission.

Because its symptoms come and go and mimic those of other diseases, lupus can be difficult to diagnose. There is no single laboratory test that can definitively prove that a person has this complex illness. Thankfully, awareness of lupus is increasing and is therefore more readily identified.

Who gets lupus?
Lupus is estimated to affect nearly 1.5 million Americans. While it occurs in both sexes, 90 percent are women, and most are diagnosed during the childbearing years. African-American women are three times more likely to get the disease than Caucasian women, and they often suffer more severe disease. National Institutes of Health figures indicate that as many as one in every 250 African-American women has lupus. Lupus is also twice as prevalent in Asian-American and Hispanic women as it is among Caucasian women. Native American women are also disproportionately affected.

How is lupus treated?
While there is no cure for lupus, early diagnosis and appropriate treatment can help in managing the symptoms and lessening the chance of permanent damage to organs or tissues. Once a lupus diagnosis is established, an assessment is made of damage to major organs such as the brain, kidneys, heart, and lungs. Treatment strategies depend on the activity level and extent of the disease and can range from over-the-counter pain relievers and anti-inflammatory drugs to prescription medications, psychotherapy, healthy diet changes, and lifestyle revisions such as staying out of the sun and avoiding stress.

How serious a threat does lupus pose to heart health?
The cardiovascular system is a main target of lupus. It can directly weaken the heart by causing inflammation of the muscle itself (myocarditis) or its inner lining (endocarditis). But the most common heart involvement in people with lupus is inflammation in the sac around the heart (pericarditis), which causes shortness of breath and sharp chest pain. These complications are typically treated with powerful anti-inflammatory and immune system suppressants such as prednisone, a corticosteroid.

What about coronary artery disease?
More than a third of people with lupus are at risk for this complication, primarily because inflammation and various immune system abnormalities cause the coronary arteries to rapidly harden, narrow, and clog, a condition called atherosclerosis. In time, clots can form or bits of plaque can break off from artery linings, interfering with blood flow to the heart and brain. Less common causes of coronary artery problems in people with lupus include inflammation of the artery walls, actual spasms of the arteries, and blood clots. The potential for problems forms a chilling picture, with female lupus patients 50 times more likely than their peers to have chest pain or a heart attack. (Less is known about the increased risk among the 1 in 10 men with lupus.)

But I’m still young, and I take pretty good care of myself.
It appears that having lupus by itself means a person is more likely to develop coronary artery disease. Young women with lupus (under age 40) are nearly five times more likely to have this ailment than their same-age peers—regardless of whether they have other risk factors such as smoking, high blood pressure, diabetes, or excess weight. Over time, lessened blood and oxygen flow to the heart weaken the muscle. Bits of cholesterol can break off from artery linings, interfering with blood flow to the brain as well as the heart. Long-term use of corticosteroids can also cause harm.

What can I do to keep my heart healthy?
See your doctor regularly and always mention new or changing symptoms, including chest pain or shortness of breath. Ask about other warning signs of a heart attack or stroke and what to do if they develop. The goal is to detect and treat lupus flares as early as possible, limit corticosteroid use (in a smart way, with the doctor’s approval), take measures to stop other heart-damaging factors (smoking, high blood pressure, excess weight), get regular exercise (even a 30-minute daily walk helps), and follow a healthy diet. Also key: a close working relationship between you and the doctor, including heart specialists (cardiologists). Some doctors put lupus patients with coronary artery disease on cholesterol-lowering drugs called statins.

Are certain people with lupus at particularly high risk for heart problems?
Certain populations, such as black women, need to be particularly vigilant. Not only is heart disease the number one killer of all black women, but the death rate from heart disease is nearly 70 percent higher in women of color than it is in white women. Black women are also three times more likely than white women to have lupus—which in itself raises the risk for heart damage.

What are the primary areas of research in lupus—and is the cardiovascular system one of them?
With no major new treatment approved in more than 40 years, lupus needs a breakthrough. Researchers have made significant headway recently, however, reporting exciting findings in terms of how the disease works and what can be done to treat it. Among the discoveries are a deeper understanding of the genetic links to lupus and enhanced recognition of how lupus attacks the brain, kidneys, and skin. And several promising advances have also been made in figuring out lupus heart disease. Researchers have learned a lot more about immune system abnormalities that target this organ and have greater insight into biomarkers (predictors) of atherosclerosis. There are also improved techniques for early detection of heart disease, and more options for drug treatment.

Are companies developing new drugs to treat lupus?
Yes, finally. Several pharmaceutical companies are developing new medications. An online search will generate information on these companies and their drugs. You also can find websites that report new drug findings, such as

www.lupusny.org
www.lupusresearchinstitute.org.

How can I help advance research and drug development?
As a person with lupus, you can directly help in advancing lupus science—and simultaneously help yourself—by participating in a clinical trial. A clinical trial is a research project that evaluates the safety and effectiveness of medical treatments, drugs, or devices in human beings. The Food and Drug Administration (FDA) requires that such trials be performed before a product can be prescribed to patients. For information on clinical trials in lupus, try visiting the following websites:www.clinicaltrials.gov
www.lupusresearchinstitute.com
http://www.centerwatch.com/
 

What is the outlook for people with lupus?
There isn’t a cure yet, but every year now researchers are gaining promising new insights into this disease and uncovering promising treatments. Just twenty years ago, only 40 percent of people with lupus were expected to live more than three years following a lupus diagnosis. Now, with earlier diagnosis, refinements in treatments, and careful monitoring, most people with lupus can look forward to a normal lifespan. More than 80 percent of people diagnosed with lupus in 2005 will live for 10 years or more.

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

Summary of a presentation given at the SLE Workshop at Hospital for Special Surgery
Michael D. Lockshin, MD

• What is Clinical Research?
• Conducting Clinical Research: Safety and Confidentiality
• Treatment Trials
• Trial Phases
• Kinds of Drugs Observed in Clinical Trials
• Aims of Lupus Research
• Lupus Clinical Trial Consortium
• Tips for Patients/Participants
• The Good News
• The Bad News/Challenges
• Types of Studies at HSS

What is Clinical Research?
What is clinical research? “A whole doctor and a whole patient in a room at the same time.” This is very different than looking at tissues in a lab. There are several types of clinical research taking place here at Hospital For Special Surgery. These include:
• Treatment trials
• Observations to understand the course of disease
• Interventions to understand the course of disease
• Epidemiology studies that look at how much a population is affected and why
• Psychosocial studies
• Blood or tissue specimens or autopsies

Conducting Clinical Research: Safety and Confidentiality
In order to conduct a clinical research study, a series of regulations that is in the interest of patient safety and confidentiality must be followed. For example, a research project must meet Health Insurance Portability and Accountability Act (HIPAA) regulations that guarantee participants’ privacy. The Institutional Review Board (IRB), which is a hospital based entity, has to approve the process of the study as well as the risks and benefits involved and must grant permission to conduct the study in order to ensure the patient’s safety. This process can take about six months or so. In addition to several other regulatory bodies, an outside monitoring board that is not affiliated with the study must monitor the proceedings (Data and Safety Monitoring Board, DSMB). This board can put a stop to the study if they perceive that a participant’s safety and/or privacy are being compromised.

A substantial amount of time is invested to ensure that participants are safe throughout the research project and that their confidential health information is not compromised.

Treatment Trials
When most people think of clinical research, they usually think of treatment trials. In placebo-controlled studies, treatment is compared to no treatment, and researchers just look to see what happens. These studies usually produce the cleanest and clearest answers. However, an undesirable consequence of this kind of study is that some patients come to realize that they may not receive the treatment under question. More commonly used as a comparison is the standard-therapy controlled approach. In this type of study, a new drug is compared to standard therapy. Although very common and informative, this type of comparison requires more patients to participate than does a placebo-controlled trial because all patients are expected to improve. Lastly, treatment can be compared to how patients did in the past when compared to the new treatment; these comparisons are called historical controls. This involves looking at the history of the treatment of a person over a number of years. This method is not very reliable, however, because the period of time under observation can be influenced by the introduction of other medications in the system, such as antibiotics or blood pressure medications that may also influence a patient’s outcome. …

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

Summary by Jillian Rose, MSW

Ask the Expert
Michael D. Lockshin, MD

If you look in current texts, or even on this web site, you do not easily find answers to these very basic questions. The reasons clear answers are hard to come by reflect the great diversity of clinical manifestations of lupus, its proclivity to flare and remit unpredictably, and the long follow-up times necessary to demonstrate superiority of treatment protocols. The only credible studies that have addressed the issue of duration of treatment are the long-term studies initiated at the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) at the National Institutes of Health (NIH) decades ago. In these studies, which have been periodically updated, intravenous cyclophosphamide given with prednisone monthly for 6 months followed by 2 additional years of infusions given every 3 months, or azathioprine continued for 2 years, resulted in fewer renal flares and better long-term (10 year) renal outcome than did monthly intravenous cyclophosphamide and daily oral cyclophosphamide or azathioprine for 6 months[1],[2],[3].

vasculitis and in lupus, several recent studies from England and from continental Europe now suggest that a short, 3 month, induction course of cyclophosphamide followed by azathioprine or mycophenolate mofetil (for unspecified times) result in durable remissions. These studies do not address the length of oral treatment nor very long-term outcomes; indeed, most look at outcomes at no more than 1 or 2 years. Although the vasculitis studies may have implications for non-renal SLE, no duration of immunosuppressive therapy studies exist for other non-renal manifestations of disease, for instance brain or spinal cord lupus, thrombocytopenia, or hemolytic anemia. Protocol studies with experimental agents usually treat for induction only, then await recurrence before retreating.

That said, a reasonable rule for the clinician to follow might be: in the treatment of renal lupus, immunosuppression can be withdrawn after 2 years in those patients who are clinically (and serologically?) inactive. For treatment of non-renal lupus, one can consider withdrawal of azathioprine or mycophenolate mofetil after a full year of clinical quiescence. In patients who remain clinically active with either renal or non-renal lupus, it is common practice to continue azathioprine or mycophenolate mofetil indefinitely. The cumulative toxicity of cyclophosphamide (especially marrow fibrosis, hemorrhagic cystitis, and bladder cancer) prohibits its continued use after 2 years. In the event of recurrent flare, re-treatment with any of the immunosuppressive medications is possible; multiple recurrent flares require ad hoc treatment decisions highly tailored to the specific circumstances of the patient.

See the complete article on the Hospital for Special Surgery’s web site
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[1] Illei GG, Takada K, Parkin D, Austin HA, Crane M, Yarboro CH, Vaughan EM, Kuroiwa T, Danning CL, Pando J, Steinberg AD, Gourley MF, Klippel JH, Balow JE, Boumpas DT. Renal flares are common in patients with severe proliferative lupus nephritis treated with pulse immunosuppressive therapy: long-term followup of a cohort of 145 patients participating in randomized controlled studies. Arthritis Rheum. 2002 Apr;46(4):995-1002.

[2] Illei GG, Austin HA, Crane M, Collins L, Gourley MF, Yarboro CH, Vaughan EM, Kuroiwa T, Danning CL, Steinberg AD, Klippel JH, Balow JE, Boumpas DT. Combination therapy with pulse cyclophosphamide plus pulse methylprednisolone improves long-term renal outcome without adding toxicity in patients with lupus nephritis. Ann Intern Med. 2001 Aug 21;135(4):248-57.

[3] Gourley MF, Austin HA 3rd, Scott D, Yarboro CH, Vaughan EM, Muir J, Boumpas DT, Klippel JH, Balow JE, Steinberg AD. Methylprednisolone and cyclophosphamide, alone or in combination, in patients with lupus nephritis. A randomized, controlled trial. Ann Intern Med. 1996 Oct 1;125(7):549-57.

For Physicians
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 Refer

1. DefinitionLupus is both an acute and a chronic autoimmune, multisystem illness. Lupus has several forms: systemic (SLE), discoid (DLE, scarring rash only), drug-induced (DILE), and neonatal (NLE). For purposes of brevity, drug-induced lupus,[1] which is relatively rare, and discoid lupus are not discussed in this chapter.

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

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

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