Development of SLE among “potential SLE” patients seen in consultation: long-term follow-up

Abstract

Objective To identify factors associated with development of systemic lupus erythematosus (SLE) among patients evaluated at a tertiary care Lupus Center for potential SLE Methods We identified patients first seen at the Brigham and Women's Hospital Lupus Center between January 1, 1992 and December 31, 2012 and thought to have potential SLE by a board certified rheumatologist. All had 1-3 SLE ACR criteria at initial visit and >2 follow-up visits ≥ 3 months apart. We reviewed medical records through May 15, 2013 for: SLE signs and symptoms, autoimmune serologies, prescriptions, and diagnoses by board certified rheumatologists. Bivariable analyses and multivariable logistic regression models were used to identify independent predictors of developing SLE. Results 264 patients met inclusion criteria. At initial visit, mean age was 39.2 (SD 12.4) years, 94% were female and 67% white. Mean number of SLE ACR criteria was 2.7 (SD 1.0) and 88% were antinuclear antibody (ANA) positive at initial consultation. Mean follow-up time was 6.3 (SD 4.3) years and 67% were prescribed hydroxychloroquine in follow-up. At most recent visit, 56 (21%) had been diagnosed with SLE; 47 (18%) were thought not to have SLE; and 161 (61%) were still considered to have potential SLE. In multivariable regression models, oral ulcers (OR 2.40, 95%CI 1.03-5.58), anti-dsDNA (OR 2.59, 95% CI 1.25-5.35) and baseline proteinuria or cellular casts (OR 16.20, 95%CI 1.63-161.02) were independent predictors of developing SLE. The most common other final diagnoses included fibromyalgia, Sjögren's syndrome, mixed connective tissue disease and cutaneous lupus. Conclusion Among patients with potential SLE at initial consultation, 21% were diagnosed with definite SLE within 6.3 years. Oral ulcers, anti-dsDNA and proteinuria or cellular casts were independent predictors of developing definite SLE. A better means of accurately identifying those who will develop SLE among those presenting with potential disease is necessary.

Clinical and Immunologic Profiles in Incomplete Lupus Erythematosus and Improvement with Hydroxychloroquine Treatment

“…One change in the 2012 criteria is the loss of photosensitivity as a separately scored point. Photosensitivity is a frequent feature of patients with unclassifiable lupus-like syndromes, present in more than 20% of these patients [17], but the loss of this as a separate criterion did not appear to have a great impact on the ILE scores in the present study. Another change in the 2012 criteria is the addition of low complement as scored item.…”

“…In clinical care, repeated and inconclusive evaluations may go on for many years. In one cohort, 56% of patients identified as “potential” SLE remained in that category after a mean of 6.3 years of followup [17]. This long period of diagnostic uncertainty may explain the somewhat surprising finding of the self-assessment responses in the ILE group reported here, showing that these patients thought that they were actually worse than they had been a year previously, even though a diagnosis of a more serious illness, SLE, had not been made.…”

“…This observation is consistent with the association of anti-C1q with nephritis, which is not present in ILE [14], and suggests that the presence of an elevated anti-C1q in a patient with ILE might raise concerns for SLE or more specifically, nephritis. Few ILE patients in this study had significant levels of C1q, so sensitivity for detection of impending nephritis may be low, and it remains undetermined whether anti-C1q is, like anti-dsDNA, a demonstrated predictor of SLE risk [17]. …”

We Need Better Classification and Terminology for “People at High Risk of or in the Process of Developing Lupus”

“…The term "undifferentiated connective tissue disease" (UCTD) has been used to refer to individuals presenting with clinical symptoms suggestive of some autoimmune CTD (SLE, Sj€ ogren's syndrome, scleroderma, mixed CTD, or RA), but not clearly meeting ACR classification criteria for any of these diseases, a common clinical scenario. Followup studies of UCTD patients have revealed the rates of progressing to SLE are very similar to those in incomplete lupus cohorts, approximately 20% (9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19). Additionally, those patients who have a prolonged clinical onset of their SLE tend to have a mild disease course without severe organ involvement (10).…”

Clinical Significance of a Positive Antinuclear Antibody Test

“…In patients suspected of having SLE but not fulfilling ACR classification criteria, the presence of oral ulcers, renal disease (defined by as persistent proteinuria, cellular casts, or both), and anti-doublestranded DNA antibodies were predictors of evolution to definite SLE. 9 Although not everyone with a positive ANA requires evaluation by a rheumatologist, in cases of uncertainty, it may be helpful to refer patients to a rheumatologist for evaluation. Testing all patients with a positive ANA for thyroid-specific antibodies is unnecessary and should be at the discretion of the evaluating physician.…”