Editor’s note: This article was originally published in Dutch in DIAGNED, the quarterly magazine of the Dutch Association of Diagnostics Manufacturers. DPC Nederland, a member of the Association, arranged for the writing and publication of the article, and provided the English translation below, with permission of DIAGNED.

Symptoms and prevalence
Systemic lupus erythematosus (SLE, LE), also known as lupus, is a rare, rheumatic autoimmune disease in which the patient produces antibodies that are directed against his own tissue. These autoantibodies can cause inflammation in any organ or area of the body, including skin, joints, kidneys, brain, heart and lungs. The disease comes and goes. The course and intensity is unpredictable and is not the same from one patient to another. Environmental factors such as infections, certain antibiotics and other drugs, ultraviolet light, extreme stress, and hormones (particularly estrogen) are known to play a key role in triggering the disease. A genetic predisposition also appears to be involved.

SLE occurs mainly in young people, aged between 20 and 40, and is nine to fifteen times more common in women than in men. People of African, American Indian, and Asian origin appear to have a higher incidence than Caucasians.

Dr. Hendrika Bootsma, rheumatologist at the university hospital in Groningen, The Netherlands, has been working on the disease for about ten years. SLE prevalence in that country is approximately 40 in 100,000. Patients come with a very wide range of complaints and may therefore see various specialists before they are referred to the rheumatology department. Dr. Bootsma reports chronic tiredness as the most frequent complaint. In addition, before the disease flares up, SLE patients often display flu-like symptoms, skin disorders and joint complaints. The general nature and variety of clinical symptoms makes diagnosis difficult. Sometimes patients suffer from complaints for years before finally receiving a diagnosis of SLE. Dr. Bootsma uses the eleven international criteria for diagnosis (Table 1); the identification of four of them leads to a diagnosis of SLE.

Table 1. Criteria for the diagnosis of lupus.²

Diagnosis
Although the diagnosis is established on clinical grounds, it is strongly supported by laboratory testing. The relevant laboratory tests seek to establish the presence of autoantibodies. Specificity and sensitivity are essential, but no single test offers 100 percent performance for either criterion. Dr. Bootsma usually uses a combination of two tests. The first is anti-nuclear antibody (ANA) testing in patient blood, to detect antibodies directed against elements of the cell nuclei. It is a simple and extremely sensitive test which is positive in over 95 percent of SLE patients. Lack of specificity for SLE—the test gives positive results for other autoimmune diseases such as rheumatoid arthritis or Sjögren’s syndrome—requires the use of a second test in the event of a positive ANA result. The anti-double-stranded DNA test (anti-DNA for short) is more specific for SLE and can provide a quantitative result.

Preventing disease flare-ups
If the patient remains under expert supervision, the prognosis in terms of life expectancy and quality of life is far more favorable than it was a few decades ago. The most worrisome times are the exacerbation or so-called flare-up periods, during which the disease strikes with its full intensity and serious functional disorders can occur in affected organs. One of the most serious manifestations, observed in 50 to 70 percent of patients, is nephritis. Although in many cases the organs recover again, permanent damage can also occur. Avoiding flare-ups means less patient distress and less chance of permanent, serious organ damage.

Desiring to improve her patients’ quality of life, Dr. Bootsma sought to predict flare-ups and offer preventive treatment. She and her colleagures found that the anti-DNA concentration appears to be a suitable indicator of an impending exacerbation. Conducting their research at the university hospitals in Groningen and Utrecht, they measured the blood anti-DNA concentration in 156 patients monthly. In 46 patients they found a significant increase at a certain moment. The striking thing was that at that time, these patients had no complaints at all, nor did they show any clinical symptoms. Twenty-four of the 46 patients received conventional treatment and 22 received preventive treatment with 30 mg of the anti-inflammatory prednisone. Of the 24 patients on conventional treatment, 20 of them suffered a flare-up; whereas of the 22 patients treated with prednisone, only two suffered a flare-up. (See Figure 1.) Dr. Bootsma and her colleagues have published papers and addressed international congresses on their findings. The university hospital in Groningen has implemented an extensive monitoring system to follow anti-DNA concentrations in the blood of SLE patients.

Figure 1. Effect of prednisone treatment on anti-DNA levels in SLE. A rising anti-DNA concentration in the blood often indicates an imminent flare-up of the disease. Treatment with the anti-inflammatory prednisone reduces anti-DNA antibody levels and is almost certain to prevent a flare-up.¹

Dr. Bootsma admits that this approach requires intense supervision and careful organization. The patient must be motivated enough to have a blood sample taken every month, and the laboratory must keep careful records. In addition, the doctor in attendance must be disciplined and follow the measurements up closely. Whenever Dr. Bootsma observes a significant increase, she alerts the patient to prepare for treatment, even in the absence of significant complaints.

A need for more research
Despite progress, a great deal of further research is required. It is desirable, for example, to find alternatives to drugs with unpleasant side effects. The causes and triggers of the disease remain to be fully elucidated. Although it is difficult to obtain funding for research into a rare disease such as SLE, Dr. Bootsma believes the rewards would far outweigh the costs. “Few people seem to realize the potential added return on SLE research. After all, this is research into the immune system and there are more and more indications that deficiencies in immune system function are also closely involved in the development of tumors.” Possible cost savings are also often overlooked. “Although an anti-DNA test and prednisone treatment are not cheap, these costs are still amply offset by the costs of admittance to hospital, treatment of possibly damaged organs, and the diminished quality of life.”

References
1. Spronk PE, Bootsma H, Kallenberg CG. Anti-DNA antibodies as early predictor for disease exacerbations in SLE. Guideline for treatment? Clin Rev Allergy Immunol 1998 Fall;16(3):211-8.
2. Tan EM, Cohen AS, Fries JF, Masi AT, McShane DJ, Rothfield NF, et al. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1982 Nov;25(11):1271-7.