Clinical Characteristics of Antinuclear Antibody-Negative Systemic Lupus Erythematosus: A Systematic Review

Although antinuclear antibody (ANA) positivity on HEp-2 cells is a mandatory criterion for the classification of systemic lupus erythematosus (SLE), patients with ANA-negative SLE may still present with severe clinical manifestations. However, this subgroup of patients has been rarely studied, and the most relevant publications are limited to isolated case reports. This systematic review aimed to identify the clinical features and other potential markers (autoantibodies) that may aid in the identification of ANA-negative SLE. The review followed the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) guidelines. The PICOS criteria were as follows: population (patients diagnosed with SLE), intervention (ANA panel testing), comparison (ANA-positive vs. ANA-negative patients), outcome (clinical manifestations and other autoantibodies), and study design (prospective and retrospective primary studies, including case series and case reports). One hundred eighty-eight publications were initially identified. After screening, 21 studies (152 patients) were included in the final analysis. Cutaneous was the most common clinical manifestation observed in patients with ANA-negative SLE, followed by photosensitivity and joint complaints. The most commonly detected autoantibodies were anti-SSA/Ro and anti-dsDNA. To our knowledge, this is the first comprehensive systematic review of the clinical and laboratory characteristics of patients with ANA-negative SLE.