Clinical and Serologic Features in Patients With Incomplete Lupus Classification Versus Systemic Lupus Erythematosus Patients and Controls

Abstract

Objective: Incomplete lupus erythematosus (ILE) involves clinical and/or serologic manifestations consistent with but insufficient for systemic lupus erythematosus (SLE) classification. Because the nature of ILE is poorly understood and no treatment recommendations exist, we examined the clinical manifestations, medication history, and immunologic features in a diverse collection of ILE and SLE patients.

Methods: Medical records of subjects enrolled in the Lupus Family Registry and Repository were reviewed for medication history and American College of Rheumatology (ACR) classification criteria to identify ILE patients (3 ACR criteria; n = 440) and SLE patients (≥4 ACR criteria; n = 3,397). Participants completed the Connective Tissue Disease Screening Questionnaire. Anticardiolipin and plasma B lymphocyte stimulator (BLyS) were measured by enzyme-linked immunosorbent assay, antinuclear antibodies (ANAs) by indirect immunofluorescence, and 13 autoantibodies by bead-based assays.

Results: On average, ILE patients were older than SLE patients (46.2 years versus 42.0 years; P < 0.0001), and fewer ILE patients were African American (23.9% versus 32.2%; P < 0.001). ILE patients exhibited fewer autoantibody specificities than SLE patients (1.3 versus 2.6; P < 0.0001) and were less likely to have ANA titers ≥1:1,080 (10.5% versus 19.5%; P < 0.0001). BLyS levels were intermediate in ILE patients (controls < ILE; P = 0.016; ILE < SLE; P = 0.008). Pericarditis, renal, or neurologic manifestations occurred in 12.5% of ILE patients and were associated with non-European American race/ethnicity (P = 0.012). Hydroxychloroquine use increased over time, but was less frequent in ILE than SLE patients (65.2% versus 83.1%; P < 0.0001).

Conclusion: Although usually characterized by milder symptoms, ILE manifestations may require immunomodulatory treatments. Longitudinal studies are necessary to understand how ILE affects organ damage and future SLE risk, and to delineate molecular pathways unique to ILE.

Figure 1. SLE classification criteria in ILE patients and SLE patients

Medical records of 440 ILE patients and 3,397 SLE patients were reviewed for the 1997 American College of Rheumatology (ACR) SLE classification criteria (A), including the major clinical sub-criteria of pericarditis, pleuritis, proteinuria, cellular casts, seizure, psychosis, hemolytic anemia, and thrombocytopenia (B). *P=0.027, ***P<0.001, ****P<0.0001

Figure 2. Use of anti-malarials, steroids, immunosuppressants, and major immunosuppressants in ILE patients and SLE patients

Medical records were reviewed for use of hydroxychloroquine (HCQ), steroids, immunosuppressants (IS; methotrexate, azathioprine, and sulfasalazine), and major IS (mycophenolate mofetil, cyclophosphamide). ILE and SLE patients were compared for the types (A) and numbers (B) of medications used. *P=0.034, ****P<0.0001.

Figure 3. BLyS levels are elevated in ILE patients, but remain lower than in SLE patients

Plasma BLyS concentrations (pg/mL) were analyzed by ELISA for a subset of 72 ILE patients, 100 SLE patients, and 124 healthy controls (HC). Medians and inter-quartile ranges are shown. *P=0.016, **P=0.008, ****P<0.0001 by Kruskal-Wallis with Dunn’s multiple comparisons test.