Easily assessed clinical signs of joint and tendon involvement early in the course of systemic sclerosis (SSc) can help predict disease progression, a prospective European study found.
The presence of synovitis, as evidenced by the presence of any tender or swollen joints, was associated with overall worsening of SSc in a multivariate analysis (HR 1.26, 95% CI 1.01-1.59), according to , of Paris Descartes University, and colleagues.
Action Points
- Note that this cohort study of patients with scleroderma revealed that joint involvement was a strong early predictor of future systemic manifestations of the disease.
- Be aware that anti-topoisomerase antibodies also performed well prognostically.
Similarly, detection of tendon friction rubs -- a grating or rubbing sensation when tendons are palpated -- also predicted progression (HR 1.32, 95% CI 1.03-1.70), the researchers reported in the November
Systemic sclerosis, also known as scleroderma, remains a potentially devastating disease for which the mortality rate hasn't decreased over the past 4 decades.
"There are currently no validated predictors of disease evolution and this significantly limits patient risk-stratification and, consequently, the use of potentially innovative therapies in the earliest phase of the disease and/or for high-risk patients," Avouac and colleagues stated.
To address this and other needs, they and their collaborators from the European League Against Rheumatism (EULAR) Scleroderma Trials and Research group have established an international registry of SSc patients.
A previous cross-sectional analysis of a subgroup of EUSTAR patients suggested that articular involvement early in the disease course was associated with later severe internal organ involvement.
To further examine this, Avouac and colleagues obtained data from all enrollees, identifying 1,301 patients with disease duration less than 3 years who had no severe cardiac or vascular involvement at baseline.
The majority were women, mean age was 55, and mean disease duration was 2 years.
Joint synovitis was present in 18% and tendon friction rubs in 13%. Most of these patients with joint symptoms had the diffuse cutaneous, rather than limited cutaneous disease subset.
During a mean follow-up of 5 years, 45% of patients showed some form of progression, which could be cutaneous, pulmonary, or cardiovascular.
On a univariate analysis, factors associated with overall disease progression included synovitis, tendon friction rubs, diffuse cutaneous disease subset, modified Rodnan Skin Score (mRSS) above 14, anti-topoisomerase-I antibodies, elevated creatine kinase, muscle weakness, and forced vital capacity below 75% of predicted.
Factors other than synovitis and tendon friction rubs that remained significantly associated with disease progression on multivariate analysis were positive anti-topoisomerase-I antibodies (HR 1.25, 95% CI 1.02-1.53) and diffuse cutaneous subset (HR 1.30, 95% CI 1.05-1.61).
For worsening of skin involvement, multivariate analysis identified synovitis (HR 1.67, 95% CI 1.06-2.64), tendon friction rubs (HR 1.69, 95% CI 1.02-2.77), a history of digital ulcers (HR 1.50, 95% CI 1.01-2.23) and anti-topoisomerase-I antibodies (HR 1.72, 95% CI 1.09-2.62) as independent predictors.
Factors associated with the development of new digital ulcers on multivariate analysis were synovitis (HR 1.45, 95% CI 1.08-1.96), anti-topoisomerase-I antibodies (HR 1.76, 95% CI 1.30-2.40), and a past history of digital ulcers (HR 1.99, 95% CI 1.51-2.64).
For worsening of left ventricular ejection fraction, significant predictors were synovitis (HR 2.20, 95% CI 1.06-4.57), muscle weakness (HR 2.25, 95% CI 1.08-4.56), and pulmonary fibrosis (HR 2.21, 95% CI 1.09-4.47).
Significant predictors for scleroderma renal crisis were tendon friction rubs (HR 2.33, 95% CI 1.03-6.19), mRSS above 14 (HR 3.08, 95% CI 1.24-7.61), and anti-topoisomerase-I antibodies (HR 2.11, 95% CI 1.12-6.97).
Because of the consistent association of joint symptoms with various aspects of disease progression, "these clinical signs should be evaluated in all patients with SSc and early disease," the authors wrote.
The study findings "have important clinical implications because the detection of joint and tendon involvement may allow the identification of a subset of patients at risk of skin progression, which in turn, predicts internal organ involvement," they stated.
"This first report of the prospective follow-up of EUSTAR patients provides the first evidence of the value of synovitis and tendon friction rubs as predictive indicators of disease progression in patients with early SSc."
"The results were obtained from the largest database in the world, and argue for the use of these easily evaluated clinical signs for the risk stratification of patients with SSc," the researchers concluded.
A limitation was the exclusion of patients with kidney disease and heart failure at baseline.
Disclosures
The authors disclosed no financial conflicts.
Primary Source
Annals of the Rheumatic Diseases
Avouac J, et al "Joint and tendon involvement predict disease progression in systemic sclerosis: a EUSTAR prospective study" Ann Rheum Dis 2014; DOI: 10.1136/annrheumdis-2014-205295.