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The Lupus Foundation of America (LFA) convened an international working group to obtain a consensus definition of disease flare in lupus. With help from the Paediatric Rheumatology International Trials Organization (PRINTO), two web-based Delphi surveys of physicians were conducted. Subsequently, the LFA held a second consensus conference followed by a third Delphi survey to reach a community-wide agreement for flare definition. Sixty-nine of the 120 (57.5%) polled physicians responded to the first survey. Fifty-nine of the responses were available to draft 12 preliminary statements, which were circulated in the second survey. Eighty-seven of 118 (74%) physicians completed the second survey, with an agreement of 70% for 9/12 (75%) statements. During the second conference, three alternative flare definitions were consolidated and sent back to the international community. One hundred and sixteen of 146 (79.5%) responded, with agreement by 71/116 (61%) for the following definition: “A flare is a measurable increase in disease activity in one or more organ systems involving new or worse clinical signs and symptoms and/or laboratory measurements. It must be considered clinically significant by the assessor and usually there would be at least consideration of a change or an increase in treatment.” The LFA proposes this definition for lupus flare on the basis of its high face validity.

Although cumulative evidence suggests that a genetic predisposition plays a major role in the development of systemic lupus erythematosus (SLE), the susceptibility genes are mostly unknown. The difficulty in identifying susceptibility genes is due in part to the inherent nature of this polygenic complex disease and the diverse genetic backgrounds of human populations. Murine SLE models that have homogenous genetic backgrounds are less complex for genetic dissection. Genome-wide linkage studies of murine SLE have mapped the position of a number of susceptibility loci. Recently, several of these major murine loci have been shown to link to different clinical and laboratory features of lupus-like phenotypes. In addition, evidence for additional genetic contributions via interaction between murine loci has been reported. In human SLE, many polymorphic genes (which have potential roles in SLE, as suggested by their known functions) have been associated with SLE or SLE subsets by population-based case-control or within-case studies. Because more compelling genetic evidence includes linkage analysis, our group has used the identified murine susceptibility loci as a guide and conducted linkage analysis of genetic markers located within a specific, possibly syntenic human chromosomal region. Evidence for linkage of a chromosome 1q41-42 region was observed in SLE-affected sibling pairs from multiple ethnic groups. This article summarizes recent developments and outlines possible future directions in delineating the genetic basis of SLE.

To compare the relative safety and efficacy of hydroxychloroquine (HCQ) and placebo (Pl) in the treatment of the articular complaints of systemic lupus erythematosus (SLE).Seventy-one patients with mild SLE requiringor = 10 mg of prednisone or equivalent daily and with arthritis or arthralgias were entered into a 48-week prospective, controlled, double blind multicenter trial and randomly assigned to either HCQ or Pl.Both HCQ and Pl were well tolerated in the 48-week trial. There were no remissions. With the exception of the patient assessment of joint pain, all other joint measures were similar between the groups. Twenty-nine patients withdrew before the end of the trial although only 2 patients withdrew for adverse drug effects.Our study found subjective pain relief as the only statistically significant difference in joint count variables from HCQ in the treatment of the articular manifestations of SLE.

Maternal lupus anticoagulants and anticardiolipin antibodies are associated with a syndrome of recurrent pregnancy loss or preterm birth in live-borns, fetal growth retardation, and placental infarction. Fourteen women with one or more abnormal pregnancy outcomes (total 28 losses, one severely growth-retarded premature live-born) and no normal outcomes were treated with full-dose, subcutaneous, twice-daily heparin therapy in subsequent pregnancies. Treatment was started at an estimated gestational age of 10.3 +/- 4.0 (mean +/- SD) weeks (range 6-18), in a mean total daily dosage of 24,700 +/- 7400 units (range 10,000-36,000). Fourteen of 15 pregnancies resulted in live births at 36.1 +/- 1.7 weeks (range 33-39). The mean birth weight percentile was 57 +/- 21 (range 10-90), and Apgar scores were good to excellent. The number of placental infarcts was fewer in treated cases than in previous deliveries. Five fetuses had third-trimester or perinatal problems with no sequelae, four discovered by close maternal-fetal monitoring. There was an increased rate of preterm and cesarean deliveries. Maternal complications of treatment were few and minor, with no hypertension, preeclampsia, or serious drug-related complications. Heparin appears suitable for further investigation in the treatment of this obstetric syndrome.

A mechanism for sustained production of pathogenic autoantibody subsets in patients and mice with systemic lupus erythematosus may be centered on selective up-regulation of B cells bearing certain idiotypes. Public idiotypes are characteristic of some autoantibodies, including anti-DNA. Evidence is reviewed that suggests that immunoglobulins bearing certain public idiotypes, such as IdGN2, contain autoantibody subsets that are nephritogenic in human systemic lupus erythematosus and in New Zealand black/New Zealand white F1 mice. Up-regulation of such cells could promote development of nephritis. Work from several laboratories has shown that production of immunoglobulin G antibodies to DNA depends upon T cell help. In New Zealand black/New Zealand white F1 mice, cloned T cells are dominated by autoreactive cells that produce B cell growth factors. We suggest that this sustained release of B cell growth factors combined with selection by T helper cells for B cells bearing IdGN2 are a major mechanism for sustained up-regulation of nephritogenic subsets of autoantibodies.

Ischemic necrosis of bone, a frequent complication of glucocorticoid therapy, can result in disability due to bone collapse and destruction. Some investigators have suggested that core decompression of involved marrow benefits patients with early disease. As radiographs are normal in early disease, identification of patients has been dependent on nonspecific radionuclide imaging or more specific but invasive hemodynamic studies. In order to define a sensitive, noninvasive diagnostic tool, we compared magnetic resonance imaging (MRI) to 99mtechnetium diphosphonate and 99mtechnetium sulfur colloid scintigraphy in 10 consecutive glucocorticoid treated patients with suspected femoral head ischemic necrosis of bone but normal roentgenograms. MRI identified the ischemic necrosis (defined by characteristic radiographic progression or histology) in 13/13 femoral heads. Both scans together identified only 5/13 of the cases. Only 1/20 osteoarthritic femoral heads had MRI patterns similar to those seen in ischemic necrosis of bone. We conclude that MRI is a sensitive and relatively specific method to detect early femoral head ischemic necrosis of bone.