For Physicians

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. Definition Lupus 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.

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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.

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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, Sha
nker 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

Grand Rounds
Michael D. Lockshin

I want to give you both an overview of the antiphospholipid antibody syndrome and update the audience on things that happened at the recent meeting in Tours, France, which gave some of the most current and up-to-date information on the syndrome. I am also going to give you some speculations about the future.

The basic definition of the syndrome has been around for more than a decade now and has consisted of recurrent thromboses, venous or arterial, recurrent pregnancy losses (I will have more to say about that in just a few minutes), the presence of an antibody, a diagnostic antibody within a family of antibodies, not a single antibody, and some people will add another major component which is the catastrophic vascular occlusion syndrome. The clinical manifestations can be very dramatic and they happen in young people. This is one of the first patients I ever saw here at this hospital, probably 20 years ago, before we had a diagnosis of the antiphospholipid syndrome. This is a young lady, 21 years old at the time, who had multiple cerebral infarcts and a known lupus anticoagulant. I have used the term here now, which we did not have then, of antiphospholipid antibody syndrome or PAPS. This also is a MRI, one of the earliest versions of the MRI, demonstrating diffuse white matter disease and infarctive disease in a 33-year-old man whose presenting manifestations were dementia and occipital blindness. This is a more common manifestation; this is a lady whom I saw just about two weeks ago, a 42-year-old woman who had multiple UBOs (or just diffuse areas of hyperintensity) scattered throughout her brain-you can see them along here or in contrast along here-and forgetful episodes with some hints of dementia but very little else as a manifesting symptom. You can also see abrupt and severe vascular occlusion. This was a spontaneous event in the lady who ended up developing gangrene of three of her extremities before the catastrophic syndrome was stopped by plasmapheresis, and who survived this event despite the severity of what happened.

The way in which I got into studying this syndrome was with the pregnancies. This again, is a relatively old slide, demonstrating in a patient population with lupus and primary antiphospholipid antibody syndrome alone, the risk to pregnancy of having the antibody going from no antibody present (under 16 IgG antiphospholipid antibody units) to high titer on the first blood test drawn during the index pregnancy. In the green bars are women who have not been pregnant before. The yellow bars are women who have had prior losses, and you can see that in this group of patients the history of a prior fetal loss and a high titer antibody gave an over 80% probability of losing the current pregnancy. There was stepwise increment from negative titers but it was also true that the history of a prior loss even in women who had negative antibody titers also predicted loss at about a 2:1 ratio, that is, a prior loss plus the high titer antibody. Predicted losses in a woman who had never been pregnant but who had high titer antibody had about a 40% probability of losing that pregnancy. I guess it does not show well on this slide, but one of the characteristics also is livedo reticularis. This, in a better projection, shows rather striking livedo. It is characteristic of many patients and is distinct from a more hard livedo, as you see, here referred to as livedo racemosa, a point made by Jean-Charles Piette from France, that is different and that occurs in patients with vasculitis. There is a good paper by him in the recent Journal of Autoimmunity that describes the differences between the two types of livedo that occur, the one with antiphospholipid antibody and the one with vasculitis. This is one of the severe manifestations occurring in a young woman with the catastrophic syndrome. Those of you who recognize the histology will recognize this as myocardium. This is a coronary artery that has completely occluded and was the cause of her death. Again, I do not remember her precise age, but she was in her thirties. You will note the characteristic pathology, which is a totally bland thrombus like this, with no signs of inflammation, no vasculitis whatsoever within the coronary vessels. This is another patient, a young man who was well known to many of the physicians here. This is his aortic valve, along here, with this huge excrescence that led to severe aortic insufficiency and eventual valve replacement in this man, and also, mitral valve replacement. This is another manifestation of the syndrome that occurs in patients who have had the disease for some period of time. In the catastrophic syndrome, a relatively rare but dramatic event that can occur is the sudden onset of adrenal failure associated with hemorrhage around the adrenal glands. The hemorrhage occurs after infarction of the adrenal glands and is the cause for sudden hypotension, severe nausea, and back pain in patients with the antiphospholipid antibody syndrome; this slide given to me by Ware Branch shows extensive hemorrhage around both adrenal glands. …

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Michael D. Lockshin

Currently, the recommendation for asymptomatic patients who have antiphospholipid antibody (regardless of titer) is that they not be treated. One retrospective study, conducted here at HSS, looked at women who had been identified because of fetal loss and were/were not treated with aspirin; the results suggested that aspirin protects against future clotting events[1]. The primary author, Doruk Erkan, MD, is now engaged in a prospective study through the national registry (APSCORE) to verify the findings.

I don’t believe that anyone would treat asymptomatic patients with warfarin or heparin. Michelle Petri, MD, of Johns Hopkins Medical Center, advises hydroxychloroquine[2].

With regard to the INR, the best information comes from the a double-blind, prospective study by Crowther in The New England Journal of Medicine in 2003, which stated that, for uncomplicated antiphospholipid syndrome patients who have not previously failed anticoagulation, an INR of 2.5 is as effective as are higher INRs[5]. This paper reduces a recommendation previously made by Khamashta in 1995 for an INR of greater than 3[3],and a subsequent update raising (without justification, in this reviewer’s mind) the recommended INR to 3.5[4]. In the Crowther study, the recommendation applied equally to patients with venous and with arterial clots.

Many authorities also prescribe a baby aspirin as well.

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[1] Erkan D, Merrill JT, Yazici Y, Sammaritano L, Buyon JP, Lockshin MD. High thrombosis rate after fetal loss in antiphospholipid syndrome: effective prophylaxis with aspirin. Arthritis Rheum. 2001 Jun;44(6):1466-7.

[2] Petri M. Treatment of the antiphospholipid antibody syndrome: progress in the last five years? Curr Rheumatol Rep. 2000 Jun;2(3):256-61.

[3] Khamashta MA, Hughes GR. Antiphospholipid antibodies and antiphospholipid syndrome. Curr Opin Rheumatol. 1995 Sep;7(5):389-94. Review.

[4] Ruiz-Irastorza G, Khamashta MA, Hunt BJ, Escudero A, Cuadrado MJ, Hughes GR. Bleeding and recurrent thrombosis in definite antiphospholipid syndrome: analysis of a series of 66 patients treated with oral anticoagulation to a target international normalized ratio of 3.5. Arch Intern Med. 2002 May 27;162(10):1164-9.

[5] Crowther M A, Ginsberg J S, Julian J, Denburg J, Hirsh J, et al. A Comparison of Two Intensities of Warfarin for the Prevention of Recurrent Thrombosis in Patients with the Antiphospholipid Antibody Syndrome. New Engl J Med 2003 Sep 18; 349:1133-1138.

Special Report

Common questions about vaccinations for patients with rheumatic disease fall into four categories:

1. Does vaccination cause rheumatic disease?
2. Does vaccination worsen rheumatic disease?
3. Is vaccination effective in rheumatic disease?
4. Are vaccinations dangerous for someone with rheumatic disease?

Because there are many types of vaccinations (see Table below), many different vaccination schedules, and many differences among patients with rheumatic diseases, definitive answers are few. However, a number of specific studies permit general answers. In general, those answers are:

1. Vaccination does not cause rheumatic disease.

2. Vaccinations do not worsen rheumatic disease.

3. Vaccinations are generally effective in patients who are not taking high doses of prednisone or immunosuppressive drugs.

4. Vaccinations are not dangerous for persons with rheumatic disease, except: live-virus and bacterium vaccinations are dangerous for, and are contraindicated in, patients who take high doses of prednisone or immunosuppressive drugs, or who have very low white blood cell counts or are otherwise immunocompromised.

References to medical articles (below) can provide readers with information on specific rheumatic diseases. references to medical articles are attached. Detailed information about vaccinations, including immunization schedules and doses are available from the National Centers for Disease Control, Advisory Committee On Immunization Practices (CDC, ACID), which provides a comprehensive website. What follows are brief answers to questions patients with rheumatic disease may ask. …

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Michael D. Lockshin

The antiphospholipid syndrome (APS) causes excessive blood clotting, leading to strokes, heart attacks, and pulmonary emboli (clots in the lungs). It also causes pregnancies to fail, because of clots in the placenta.

While much is known about the syndrome, what actually triggers a clot at a specific time in an individual patient is unknown. Similarly, there are no definitive studies on the effect of herbals and other supplements on the initial occurrence of APS or on its worsening or improving when such supplements are taken. Indeed, with the large number of supplements available, the absence of standardization in their formulation and manufacture, and the differing doses with which they are used, the absence of such information is not very surprising.

Once a patient is diagnosed with APS, however, he or she is often prescribed warfarin (Coumadin) or a form of heparin (such as Lovenox or Fragmin) taken orally or injected daily to stop the abnormal clotting from recurring. In doses too high, the effect of these drugs is to cause hemorrhage. The body normally has redundant systems to prevent hemorrhage, so patients taking the appropriate dose of medicines that interfere with one type of clotting are still reasonably safe if, for example, they cut themselves because other ways to form clots are available. However, the dose must be constantly monitored to be certain that a patient is in a safe zone. That’s where taking herbal supplements may be dangerous.

According to a publicly available listing of drug interactions[1], the following is a minimum list of alternative medicines that interact with prescribed anticoagulants by increasing risk of bleeding: androgens, German chamomile, coQ10, danshen (red sage, saliva root), dong quai (Chinese angelica), evening primrose oil, fenugreek, feverfew, fish oils, flaxseed, garlic, ginger, ginko biloba, ginseng, grape seed, green tea, horse chestnut seed, milk thistle, quinine, red clover, red yeast, St. John’s wort, willow bark.

Other alternative therapies may increase the risk of clotting. Vitamin K counteracts Coumadin; vitamin preparations or diet supplements that include vitamin K increase the risk of clotting in patients taking Coumadin (but not in those using heparin or antiplatelet drugs like aspirin or Plavix).

Thus the major risk of herbals and other supplements to patients with antiphospholipid syndrome is interference with treatment rather than worsening the disease.

The same cannot be said for estrogen. Estrogen, in the form of postmenopausal treatment or oral contraception, including patches, increases a woman’s tendency to clot. Therefore, estrogen can provoke clotting in patients with APS, whether they are being treated with anticoagulants or not. Most specialists in the field advise against taking this hormone.

Progesterone, also used for contraception, amenorrhea, in some pregnancy situations, and in post-menopausal therapy, is probably safe for patients with APS. In fact, the literature on this topic is remarkably old and sparse[2], but information from the SELENA study of lupus patients may be available soon. Excessive clotting is a listed side-effect of drugs of the progesterone class.

Most experts in the field prefer that patients with APS use no estrogen or progesterone supplements until better information is available. In our small study of infertile women with APS undergoing artificial ovarian stimulation to achieve pregnancy, no APS-related complications of hormone treatment occurred[3].

Therefore, the take-home message is simple: both hormones and herbal and other dietary supplements may change one’s risk for clotting or, in some cases, bleeding. The best advice for APS patients is to use such products with extreme caution, if at all.

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[1] ePocrates RxPro, www.epocrates.com

[2] Comp PC, Zacur HA. Contraceptive choices in women with coagulation disorders. Am J Obstet Gynecol. 1993 Jun;168(6 Pt 2):1990-3.

[3] Guballa N, Sammaritano L, Schwartzman S, Buyon J, Lockshin MD. Ovulation induction and in vitro fertilization in systemic lupus erythematosus and antiphospholipid syndrome. Arthritis Rheum. 2000 Mar;43(3):550-6.|

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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.

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Several aspects of psoriatic arthritis make it hard to answer questions about its treatment succinctly.

First, there are at least three forms of psoriatic arthritis: in some patients it looks very much like rheumatoid arthritis, in others like ankylosing spondylitis, and in still others only the end joints of the fingers (and, usually, the fingernails) are involved. What may work for one type of psoriatic arthritis may not for another.

Second, although most doctors think all inflammatory rheumatic diseases are autoimmune, it has been very hard to identify specific problems with the immune system in patients with psoriasis or psoriatic arthritis. Since most treatments for autoimmune disease change the function of specific parts of the immune system, it is hard to know which function to identify as a potential target when you are not even certain that the immune system has gone awry.

Third, compared to rheumatoid arthritis, psoriatic arthritis is fairly uncommon. It is an ‘orphan’ disease, and most treatments that are tried have been borrowed from another disease rather than specifically developed for psoriatic arthritis.

That said, much has happened in the last few years. For at least the past two decades, the standard treatment for psoriatic arthritis has included nonsteroidal anti-inflammatory drugs, sulfasalazine and, in more severe cases, methotrexate or cyclosporin. Corticosteroid drugs such as prednisone have not been very effective. Methotrexate, the most effective, has the added advantage that it treats the skin condition as well as the joints, but even with it many patients failed to respond well. Drugs useful in treating the skin disease, such as acitretin (Soriatane), sometimes work in refractory cases but are often toxic.

About 5 years ago the dramatic success in rheumatoid arthritis of the new class of drugs called biologics, specifically inhibitors of a small chemical called tumor necrosis factor alpha led to trials of these drugs in psoriatic arthritis. In brief, TNF alpha inhibitors — etanercept (Enbrel) and infliximab (Remicade) – work extremely well in many patients with psoriatic arthritis of all three types[1],[2],[3]. Adalimumab (Humira) is a very recently released similar drug that may be expected to work as well. These drugs may work by inhibiting TNF alpha or by breaking the inflammatory cycle in a different way. TNF alpha inhibitors also appear to protect bone from being eaten away[4]. In clinical trials, these drugs reduce inflammation and prevent deterioration over several years, and they improve skin disease as well.

As a result of success with TNF alpha inhibitors, other biologics, which have different effects on the immune system, are now under trial[5],[6],[7]. The down side is that all of these drugs are extremely expensive, that they are injectable rather than available in pill form, and that their major side effect is that they make recipients susceptible to certain kinds of infections. Otherwise they are not particularly difficult to take. Specific information about these drugs can be found elsewhere on this website.

The details of how these biologics affect the immune system is less important than the fact that they do work in psoriatic arthritis. In doing so, they teach us that the immune system is abnormal in psoriatic arthritis, that very specific abnormalities can be corrected, and that the development of treatments based on an immunological theory of this disease is valid. Thus, in the next several years, we can expect to see many more immunologically active drugs – largely biologics – developed for and tried in psoriatic arthritis. With luck, one or more of the new drugs will be inexpensive, orally administered, side-effect free, and possibly even curative.

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[1] Braun J, Sieper J. Role of novel biological therapies in psoriatic arthritis : effects on joints and skin. BioDrugs. 2003;17(3):187-99.

[2] Anandarajah AP, Ritchlin CT. Etanercept in psoriatic arthritis. Expert Opin Biol Ther. 2003 Feb;3(1):169-77.

[3] Yazici Y, Erkan D, Lockshin MD. Etanercept in the treatment of severe, resistant psoriatic arthritis: continued efficacy and changing patterns of use after two years.Clin Exp Rheumatol. 2002 Jan-Feb;20(1):115.

[4] Ritchlin CT, Haas-Smith SA, Li P, Hicks DG, Schwarz EM. J Clin Invest 2003 Mar;111(6):821-31. Mechanisms of TNF-alpha- and RANKL-mediated osteoclastogenesis and bone resorption in psoriatic arthritis. J Clin Invest. 2003 Mar;111(6):821-31.

[5] Kraan MC, van Kuijk AW, Dinant HJ, Goedkoop AY, Smeets TJ, de Rie MA, Dijkmans BA, Vaishnaw AK, Bos JD, Tak PP. Alefacept treatment in psoriatic arthritis: reduction of the effector T cell population in peripheral blood and synovial tissue is associated with improvement of clinical signs of arthritis. Arthritis Rheum. 2002 Oct;46(10):2776-84.

[6] Utset TO, Auger JA, Peace D, Zivin RA, Xu D, Jolliffe L, Alegre ML, Bluestone JA, Clark MR. Modified anti-CD3 therapy in psoriatic arthritis: a phase I/II clinical trial.J Rheumatol. 2002 Sep;29(9):1907-13.

[7] McInnes IB, Illei GG, Danning CL, Yarboro CH, Crane M, Kuroiwa T, Schlimgen R, Lee E, Foster B, Flemming D, Prussin C, Fleisher TA, Boumpas DT. IL-10 improves skin disease and modulates endothelial activation and leukocyte effector function in patients with psoriatic arthritis. J Immunol. 2001 Oct 1;167(7):4075-82.

Ask the Expert 

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 Blog – Comment In-Depth Topic Review on SLE.)

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