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The European League Against Rheumatism (EULAR) Task Force of the European Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT) has issued new guidelines for the treatment of systemic lupus erythematosus (SLE) and published 12 key recommendations in the July 5 Online First issue of Annals of the Rheumatic Diseases. A panel of experts used the EULAR standard operating procedures to develop guidelines for management (diagnosis, treatment, monitoring) of SLE using a combination of research-based evidence and expert consensus.
"SLE is a complex disease with variable presentations, course and prognosis characterized by remissions and flares," write G. Bertsias, from the University of Crete School of Medicine in Heraklion, Greece, and colleagues from ESCISIT. "In the course of their disease, most patients present with arthritis, different types of rashes (sometimes scarring), serositis, cytopenias of various types, neurological symptoms, and nephritis. Because of the systemic nature of the disease, multiple medical specialties are involved in the care of these patients. To avoid fragmentation and optimize management there is a presently unmet need to establish an integrated approach based on widely accepted principles and evidence-based recommendations."
The EULAR Task Force on SLE consisted of 19 specialists, a clinical epidemiologist, and a research fellow. They compiled key questions for the management of SLE using the Delphi technique and performed a systematic search of PubMed and Cochrane Library Reports using McMaster/Hedges clinical queries' strategies for questions related to the diagnosis, prognosis, monitoring, and treatment of SLE. Other searches were conducted for neuropsychiatric, pregnancy, and antiphospholipid syndrome (APS) questions.
Based on sample size and type of design, the investigators categorized the evidence and identified the categories of available evidence for each recommendation. The strength of each recommendation was evaluated based on the category of available evidence, and agreement on the statements was measured across the 19 specialists.
The Task Force generated 12 questions concerning the prognosis, diagnosis, monitoring, and treatment of SLE, including neuropsychiatric SLE, pregnancy, APS, and lupus nephritis, and they evaluated and scored the evidence to support each proposition. After discussion and votes, the final recommendations were distilled into brief statements, with average agreement among experts being 8.8 of 10.
The 12 key recommendations are as follows:
- Prognostic information for general outcome and for involvement of major organs includes new clinical signs (rashes, arthritis, serositis, neurologic manifestations [seizures and psychosis]), routine laboratory analyses (complete blood cell count, serum creatinine, proteinuria, and urinary sediment), and immunologic tests (serum C3, anti–double-stranded DNA [anti-dsDNA], anti-Ro/SSA, anti-La/SSB, antiphospholipid, anti-RNP). These should be considered in evaluating patients with SLE. In selected patients, confirmation by imaging (brain magnetic resonance imaging), and pathology (renal biopsy) may be helpful.
- Parameters that are useful in monitoring lupus activity and flare-ups in patients with SLE include new clinical manifestations (number and type of skin lesions, arthritis, serositis, neurologic manifestations), laboratory tests (complete blood cell count), immunologic tests (serum C3/C4, anti-C1q, anti-dsDNA), and validated global activity indices.
- Comorbidities for which SLE patients are at increased risk, because of the disease process itself and/or its treatment, include infections (especially urinary tract infections), atherosclerosis, hypertension, dyslipidemias, diabetes, osteoporosis, avascular necrosis, and malignancies (especially non-Hodgkin's lymphoma). The panel recommends minimizing these risk factors, maintaining a high-index of suspicion, and performing timely evaluation and thorough follow-up.
- Antimalarials and/or glucocorticoids are helpful and may be used for treatment of SLE without major organ manifestations. In patients at low risk for complications from nonsteroidal anti-inflammatory drugs, these may be used judiciously for limited periods. Patients who are nonresponsive to these treatments or who cannot reduce steroids doses below those acceptable for long-term use may benefit from immunosuppressive agents such as azathioprine, mycophenolate mofetil, and methotrexate.
- Adjunct therapy may include photoprotection in patients with skin manifestations, lifestyle modifications (smoking cessation, weight control, exercise), and other agents (low-dose aspirin, calcium/vitamin D, bisphosphonates, statins, and antihypertensives including angiotensin-converting enzyme inhibitors). Although estrogens (oral contraceptives, hormonal replacement therapy) may be indicated in some patients, their risks should be considered.
- In patients with SLE and neuropsychiatric manifestations, diagnostic evaluation (clinical, laboratory, neuropsychological, and imaging tests) should resemble that in the general population presenting with the same neuropsychiatric manifestations.
- Patients with SLE and major neuropsychiatric manifestations thought to be of inflammatory origin, such as optic neuritis, acute confusional state or coma, cranial or peripheral neuropathy, psychosis, and/or transverse myelitis or myelopathy, may benefit from immunosuppressive treatment.
- Recommendations regarding pregnancy include consideration of both the mother and the offspring. Lupus patients have no significant difference in fertility. Although pregnancy may increase lupus disease activity, these flare-ups are usually mild. Patients with lupus nephritis and antiphospholipid antibodies are at greater risk for preeclampsia and should be monitored more diligently. History of lupus nephritis and antiphospholipid, anti-Ro, and/or anti-La antibodies are associated with increased risk for miscarriage, stillbirth, premature delivery, intrauterine growth restriction, and fetal heart block. Prednisolone, azathioprine, hydroxychloroquine, and low-dose aspirin may be used in pregnancies of women with lupus, but mycophenolate mofetil, cyclophosphamide, and methotrexate must be avoided.
- In patients with SLE and antiphospholipid antibodies, low-dose aspirin may be useful for primary prevention of thrombosis and pregnancy loss, and other risk factors for thrombosis should be evaluated, especially the use of estrogen-containing drugs. Long-term anticoagulation with oral anticoagulants is effective for secondary prevention of thrombosis in nonpregnant patients with SLE and APS-associated thrombosis. Unfractionated or low-molecular-weight heparin and aspirin may reduce pregnancy loss in patients with SLE and APS.
- Although renal biopsy, urine sediment analysis, and testing for proteinuria and kidney function may independently predict clinical outcome of lupus nephritis treatment, these should be interpreted together. Changes in immunologic tests (anti-dsDNA, serum C3) are limited in their ability to predict the response to treatment and should be used only as supplemental information.
- Glucocorticoids in combination with immunosuppressive agents are effective against progression to end-stage renal disease in patients with proliferative lupus nephritis. However, only cyclophosphamide-based regimens have proven long-term efficacy, and these drugs have significant adverse effects. Mycophenolate mofetil has been shown in short- and medium-term trials to be at least as effective as pulse cyclophosphamide, with a more favorable toxicity profile. Lack of treatment response by 6 months should instigate discussions for intensified therapy. Flare-ups following remission are fairly frequent, and patients who have them should be carefully followed up.
- In patients with SLE and end-stage renal disease, dialysis and transplantation have rates of long-term patient and graft survival similar to those observed in patients without diabetes and SLE. Transplantation is the method of choice.
"SLE is a challenging disease both for the patients and their families," the panel concludes. "The committee recognized the potential unnecessary anxiety that the historic name 'lupus' may evoke to patients and their families who tend to associate it with the worst forms of the disease. To this end, the committee reiterated the importance of education and psychological support to the patient and the family, and discussed the pros and cons to a potential change of the name to one that more accurately depicts the nature of the disease."
Ann Rheum Dis. Published online July 5, 2007.
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