Can baseline features predict progression to defined connective tissue disease? Insights from a minimum 5-year...

Undifferentiated connective tissue disease (UCTD) represents a systemic autoimmune condition characterized by clinical and serological features suggestive of defined connective tissue diseases (CTDs), yet it is insufficient to fulfil existing classification criteria. Despite increasing interest, long-term outcomes - particularly progression to defined CTDs - remain incompletely understood. This study aimed to evaluate the clinical outcomes of a UCTD cohort followed for at least 5 years and to identify baseline clinical and serological factors associated with an increased risk of evolution to a defined CTD.

A total of 658 patients were screened for this retrospective cohort study. After applying predefined eligibility criteria, 504 patients who met established UCTD definitions were included. Baseline clinical, laboratory, and serological characteristics were analysed. Two patient outcome groups were defined at a 5-year follow-up: those who evolved to a defined CTD and those who remained stable. Given the limited number of cases evolving to defined CTDs, group comparisons were performed using Student's t-test or the Mann-Whitney U test rather than logistic regression. Autoantibodies were assessed using indirect immunofluorescence for antinuclear antibodies and validated immunoassays for anti-dsDNA, anti-Sm, anti-Ro/SS-A, anti-La/SS-B, anti-Scl-70, anticentromere, anti-U1RNP, anti-Jo1, rheumatoid factor, anticyclic citrullinated peptide antibodies, antiphospholipid antibodies (anti-β2 glycoprotein I IgM/IgG and anticardiolipin IgM/IgG), and lupus anticoagulant.

After a mean follow-up of 82 months, 102 of the 504 UCTD patients (20.2%) developed a defined CTD (37 with Sjögren's disease, 35 with systemic lupus erythematosus, 12 with systemic sclerosis, 14 with rheumatoid arthritis, and 4 with mixed CTDs) within a follow-up period of at least 5 years. The most common clinical manifestations of UCTD included arthralgia, sicca symptoms, photosensitivity, oral aphthae, and Raynaud's phenomenon. Differentiation was significantly associated with features, such as a Schirmer test ≤5 mm (P = .007), anti-dsDNA (P = .001), anti-Ro/SS-A (P < .001), and hypocomplementemia (P = .004). Multivariate analysis identified several disease-specific predictors, including anti-Ro/SS-A for Sjögren's disease and anti-dsDNA and hypocomplementemia for systemic lupus erythematosus.

Approximately one-fifth of UCTD patients progressed to a defined CTD during long-term follow-up, most frequently to Sjögren's disease or systemic lupus erythematosus. Anti-Ro/SS-A, anti-dsDNA, and a Schirmer test ≤5 mm were significant predictors of progression.