Advanced Practice Rheum: Systemic Lupus Erythematosus Save

Know-it-now:

• ANA positivity alone does not equal lupus. ANAs are found in up to 20 million Americans and are poorly specific. ‘Roughly, for every 90 positive ANA, only one will have SLE. Don’t order ANA tests unless two or more lupus features are present.
• ANA negative lupus is very rare! There is little/no value in ordering more specific autoantibodies (anti-dsDNA, anti-Sm) if the ANA is negative.
• Establish/confirm a lupus diagnosis using 1987 or 2019 ACR criteria. Remember to consider lymphopenia (<1500), leukopenia (<4000), proteinuria (3+ or > 0.5g/24 hr) and hypocomplementemia as criteria for diagnosis.
• Lupus nephritis and neuropsychiatric lupus are the highest-stakes manifestations.
• Antiphospholipid syndrome must be actively identified in lupus patients. Present in ~30% of lupus patients, APS requires both the antibody and clinical manifestations (thrombosis, recurrent pregnancy loss, or thrombocytopenia) and carries important treatment implications, including anticoagulation rather than immunosuppression.
• Hydroxychloroquine is the cornerstone of lupus management. Regardless of disease severity, all lupus patients should be on hydroxychloroquine, which has proven benefits including reduced flares, improved survival, decreased thrombotic risk, better glycemic control, and lower neonatal lupus complications.

(Slide deck available) Systemic lupus erythematosus (SLE) is the prototypic systemic autoimmune disorder, characterized by loss of self-tolerance, multi-organ involvement, and the production of pathogenic autoantibodies and immune complexes that facilitate diagnosis and mediate organ damage. SLE predominantly affects women of childbearing age at a 10:1 female-to-male ratio, with greater severity observed in African, Asian, Hispanic, and pediatric populations. Diagnosis remains clinical and criteria-based — either by the memorable 1987 ACR 4-of-11 criteria or the more complex 2018 EULAR/ACR (point-based) classification system. Diagnostic hallmark features include the malar rash (spares the nasolabial fold), painless oral ulcers, photosensitivity, serositis, cytopenias, and renal or CNS involvement. The ANA, while sensitive, is nonspecific and should only be ordered in the presence of two or more lupus features. Other lupus specific antibodies — anti-dsDNA, anti-Sm, and anti-SSA — carry greater diagnostic and prognostic weight. Disease severity guides treatment: mild cutaneous and musculoskeletal disease may be managed with NSAIDs, topical agents, and hydroxychloroquine, while nephritis, neuropsychiatric disease, and severe hematologic involvement require high-dose corticosteroids, immunosuppressants (mycophenolate, azathioprine, cyclophosphamide), and newer, targeted agents such as belimumab, anifrolumab, and voclosporin. Antiphospholipid syndrome, present in approximately 30% of lupus patients, requires both labs and clinical features to intervene with anticoagulation. Cardiovascular disease represents a major cause of late mortality, but infection remains the leading cause of death overall. Hydroxychloroquine stands as the universal cornerstone of lupus management, with demonstrated benefits across flare reduction, survival, thrombotic risk, glycemic control, and neonatal outcomes — and should be prescribed to every patient with chronic lupus regardless of disease severity.

Watch the full Advanced Practice Rheum video series, featuring Dr. Jack Cush. Topics include difficult-to-treat RA; methotrexate; evaluation of rheumatic complaints; steroids; antinuclear autoantibodies (ANA); and more.