Objective The Systemic Lupus Collaborating Clinics (SLICC) revised and validated the American College of Rheumatology (ACR) SLE classification criteria in order to improve clinical relevance, meet stringent methodology requirements and incorporate new knowledge in SLE immunology. Methods The classification criteria were derived from a set of 702 expert-rated patient scenarios. Recursive partitioning was used to derive an initial rule that was simplified and refined based on SLICC physician consensus. SLICC validated the classification criteria in a new validation sample of 690 SLE patients and controls. Results Seventeen criteria were identified. The SLICC criteria for SLE classification requires: 1) Fulfillment of at least four criteria, with at least one clinical criterion AND one immunologic criterion OR 2) Lupus nephritis as the sole clinical criterion in the presence of ANA or anti-dsDNA antibodies. In the derivation set, the SLICC classification criteria resulted in fewer misclassifications than the current ACR classification criteria (49 versus 70, p=0.0082), had greater sensitivity (94% versus 86%, p<0.0001) and equal specificity (92% versus 93%, p=0.39). In the validation set, the SLICC Classification criteria resulted in fewer misclassifications (62 versus 74, p=0.24), had greater sensitivity (97% versus 83%, p<0.0001) but less specificity (84% versus 96%, p<0.0001). Conclusions The new SLICC classification criteria performed well on a large set of patient scenarios rated by experts. They require that at least one clinical criterion and one immunologic criterion be present for a classification of SLE. Biopsy confirmed nephritis compatible with lupus (in the presence of SLE autoantibodies) is sufficient for classification.

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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.

Discoid lupus erythematosus (DLE) is the most common skin manifestation of lupus. Despite its high frequency in systemic lupus in addition to cases without extracutaneous manifestations, targeted treatments for DLE are lacking, likely due to a dearth of knowledge of the molecular landscape of DLE skin. Here, we profiled the transcriptome of DLE skin in order to identify signaling pathways and cellular signatures that may be targeted for treatment purposes. Further comparison of the DLE transcriptome to that of psoriasis, a useful reference given our extensive knowledge of molecular pathways in this disease, provided a framework to identify potential therapeutic targets. Although a growing body of data supports a role for IL-17 and Th17 cells in systemic lupus, we show a relative enrichment of IFN-γ-associated genes without that for IL-17-associated genes in DLE. Extraction of T cells from the skin of DLE patients identified a predominance of IFN-γ-producing Th1 cells and an absence of IL-17-producing Th17 cells, complementing the results from whole skin transcriptomic analyses. These data therefore support investigations into treatments for DLE that target Th1 cells or the IFN-γ signaling pathway.

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Objective Anti-C1q has been associated with systemic lupus erythematosus (SLE) and lupus nephritis in previous studies. We studied anti-C1q specificity for SLE (vs. rheumatic disease controls) and the association with SLE manifestations in an international multi-center study. Methods Information and blood samples were obtained in a cross-sectional study from patients with SLE (n=308) and other rheumatologic diseases (n=389) from 25 clinical sites (84% female, 68% Caucasian, 17% African descent, 8% Asian, 7% other). IgG anti-C1q against the collagen-like region was measured by ELISA. Results Prevalence of anti-C1q was 28% (86/308) in patients with SLE and 13% (49/389) in controls (OR=2.7, 95% CI: 1.8-4, p<0.001). Anti-C1q was associated with proteinuria (OR=3.0, 95% CI: 1.7-5.1, p<0.001), red cell casts (OR=2.6, 95% CI: 1.2-5.4, p=0.015), anti-dsDNA (OR=3.4, 95% CI: 1.9-6.1, p<0.001) and anti-Smith (OR=2.8, 95% CI: 1.5-5.0, p=0.01). Anti-C1q was independently associated with renal involvement after adjustment for demographics, ANA, anti-dsDNA and low complement (OR=2.3, 95% CI: 1.3-4.2, p<0.01). Simultaneously positive anti-C1q, anti-dsDNA and low complement was strongly associated with renal involvement (OR=14.9, 95% CI: 5.8-38.4, p<0.01). Conclusions Anti-C1q was more common in patients with SLE and those of Asian race/ethnicity. We confirmed a significant association of anti-C1q with renal involvement, independent of demographics and other serologies. Anti-C1q in combination with anti-dsDNA and low complement was the strongest serological association with renal involvement. These data support the usefulness of anti-C1q in SLE, especially in lupus nephritis.

The 1982 ACR classification criteria have become de facto diagnostic criteria for systemic lupus erythematosus (SLE), but a review of the criteria is necessary to include recent diagnostic tests. The criteria were not developed with the help of dermatologists, and assign too much weight to the skin as one expression of a multiorgan disease. Consequently, patients with skin diseases are classified as SLE based mostly on skin symptoms. We discuss specific problems with each dermatologic criterion, but changes must await a new study. We suggest the following guidelines for such a study, aimed at revision of the criteria. 1) The SLE patient group should be recruited in part by dermatologists. 2) The study should evaluate an appropriate international ethnic/racial mix, including late onset SLE as well as pediatric patients. 3) All patients should have current laboratory and clinical evaluations, as suggested in the paper, to assure the criteria can be up-to-date. This includes anti-SS-A and anti-SS-B antibodies and skin biopsies for suspected cutaneous lupus erythematosus except for nonscarring alopecia and oral ulcers. 4) The study should be based on a series of transparent power calculations. 5) The control groups should represent relevant differential diagnoses in numbers large enough to assess diagnostic problems that might be specific to these differential diagnoses. In order to demonstrate specificity of the criteria with a 95% confidence interval between 90 and 100%, each control group of the above should have at least 73 patients.

The incidence of alopecia areata in patients with lupus erythematosus is increased. Recognition of this form of alopecia allows for specific therapy with intralesional corticosteroids.