Undifferentiated connective tissue disease: predictors of evolution into definite disease

The natural evolution of undifferentiated connective tissue diseases (UCTD) has not yet been established. The aim of our study was to analyse the clinical outcomes of a cohort of UCTD patients followed in a routine outpatient setting and to establish which clinical, serological or capillaroscopy features are associated with an increased risk of evolution to definite connective tissue disease (CTD).

Data for this study were collected by a retrospective review of 758 patients referred to our hospital, between 1999 and 2008, with suspected CTD. After selection criteria, 98 patients were considered eligible and their records, laboratory findings and nailfold-capillaroscopy pattern (NCP) were analysed until clinical outcome. Three groups of patient outcomes were established: remission, UCTD, and definite CTD. Logistic regression analysis was performed to study the association of baseline clinical features, including NCP progression during monitoring, with clinical outcomes.

After a mean follow-up of 11±3 years, 62% of the patients continued to suffer from UCTD, 24% regressed to a remission state and 14% developed definite CTD. Cytopenias (p=0.030), positivity for antibody specificities (ENA) (p=0.008), anti-Ro (p=0.036) and antiphospholipid antibodies (p=0.032), and the presence of an altered NCP (p=0.026) at baseline proved different between groups and were more frequently encountered in the group that evolved to definite CTD when compared with the others two groups. Specifically, cytopenias (odds ratio -OR- 4.20 [1.30-13.56] p=0.016), the presence of an antinuclear antibody (ANA) titre ≥1/640 (OR 7.00 [1.99-24.66], p=0.002) and anti-centromere positivity (OR 3.77 [1.03-13.79], p=0.045) at baseline and NCP progression (OR 6.63 [1.70-25.87], p=0.007) were associated with the future presence of definite CTD.

Most patients with UCTD remain in an undifferentiated state after routine outpatient clinic follow-up. High ANA titres or the presence of cytopenias at baseline, as well as progression of NCP during follow-up, are the leading factors associated with evolution to definite CTD.