The world's largest database on scleroderma, which now includes 5,500 patients from more than 100 centers on five continents, has begun to yield data that may more clearly delineate the evolution and variability of the disease and help assess risk for systemic organ involvement.
Currently, systemic sclerosis (SSc) is classified into diffuse cutaneous (dcSSc) and limited cutaneous (lcSSc) subsets according to degree and severity of skin involvement. This classification is inadequate, however, for predicting organ involvement, which is now crucial with the availability of targeted therapies that can alter outcomes, according to Dr. Ulrich A. Walker of the department of rheumatology, Basel University, Switzerland, and his colleagues.
With the goal of developing a more comprehensive disease classification system that better reflects the vascular, immunologic, and fibrotic processes that result in organ damage in SSc, the European League Against Rheumatism (EULAR) Scleroderma Trials and Research (EUSTAR) database was formed in 2004. The group has now published its initial report, analyzing the association of various demographic, clinical, and laboratory factors with systemic organ involvement (Ann. Rheum. Dis. 2007 Feb. 1 [Epub doi:10.1136/ard.2006.062901]).
At the data cutoff point for this first report in April 2006, 3,656 patients had been enrolled. A total of 1,349 (40%) were classified as dcSSc, with skin thickening extending proximal to the elbows and knees or with involvement of the trunk, and 2,101 (58%) as lcSSc, with skin involvement limited to the distal extremities and face.
The remaining 206 (6%) had scleroderma in combination with another connective tissue disease, according to the investigators. Among the SSc-associated autoantibodies detected were Scl70 autoantibodies in 1,330 patients and anticentromere autoantibodies (ACA) in 1,106, according to database findings reported by Dr. Walker and his associates.
Patients with dcSSc and those with lcSSc had the same mean age of onset of Raynaud's phenomenon, at 43 years, the investigators reported. The age of the first non-Raynaud's manifestation differed, however, being 45 years in dcSSc and 48 years in lcSSc. The mean modified Rodnan's skin score was 19 in the dcSSc group and 8.1 in the lcSSc group. Onset of disease was earlier in women, and early onset was associated with a decreased prevalence of severe organ involvement such as pulmonary fibrosis and pulmonary arterial hypertension, they noted.
Upon multivariate analysis, disease subset, antibody status, and age at onset of Raynaud's phenomenon all were independently associated with organ manifestations, but autoantibody status was associated with 15 organ manifestations and clinical subtype was associated with only 11 organ complications.
“The most important finding in this analysis was that antibody status is more predictive of individual disease presentation than is the disease subtype,” said Dr. Walker in an interview.
Other findings that emerged from the analysis included the observation that 88.7% of patients who were positive for ACA had lcSSc, as did 36.1% of those who were anti-Scl70 positive.
Although there was no difference in mean age of onset of Raynaud's phenomenon between patients who were ACA positive and those who were anti-Scl70 positive, those with ACA had a longer mean lag period of 6.5 years before the onset of non-Raynaud's manifestations than did those with antiScl70, whose mean lag period was 2.4 years.
The database does not yet contain information on treatment and outcomes. This will be included when the database goes online, which is expected in approximately 6 months, Dr. Walker said.
The majority of participating clinics are in Europe, but three centers in the United States have enrolled patients, he added.