Antinuclear antibody-negative lupus as a distinct diagnostic entity--does it no longer exist?

Abstract

Systemic lupus erythematosus (SLE) is a multi-system autoimmune disorder with protean clinical presentations. Historically, Biett reported the first case of lupus erythematosus in 1833, and Kaposi later described the systemic form in 1872,1 but the varied presentation of this illness has made it a challenging diagnosis for clinicians. The difficulties in the diagnosis of SLE were considerably eased by the demonstration of antinuclear antibodies (ANA) as a marker of lupus, initially in the form of LE cells2 and later by indirect immunofluorescence.3 Since then, ANA positivity has become an important diagnostic criterion for the diagnosis of SLE and officially recognised as such by its inclusion in the American College of Rheumatology's criteria for the classification of this disorder.4,,5 The concept of ANA-negative lupus was first mooted by Koller et al. in 1976, with their description of five patients who were ANA-negative despite having clinical features consistent with SLE.6 Cutaneous features, particularly photosensitivity, appeared to be a predominant feature of this ANA negative group. A succession of reports over the next 10 years suggested that approximately 5% of patients with lupus were ANA-negative. Fessel7 corroborated that finding when he reported 10 cases of persistently ANA-negative SLE (as assessed on human granulocyte substrate) over a period of 10 years. More recently, in 1982 McHardy, Horne and Rennie,8 investigating a cohort of SLE patients in Aberdeenshire, suggested a prevalence of 8.9% for ANA-negative SLE. These findings were based on patients assessed by the modified American Rheumatism Association criteria (later known as the American College of Rheumatology or ACR criteria) for SLE, with ANA determinations performed on rat liver substrate. McHardy et al. justified the alteration of the ACR criteria on the basis that the criteria were conceived to allow comparison of patient groups in …