Clinical and laboratory features present at baseline among patients with Sjogren's syndrome can be used to predict mortality and determine whether intensive follow-up is needed, a large Spanish study suggested.
Patients were at increased risk of death if they had high disease activity in at least one disease domain or organ system (HR 2.14, 95% CI 1.19-3.86, P=0.011) or had a baseline disease activity score of 14 or higher (HR 1.85, 95% CI 1.04-3.30, P=0.037), according to , of Hospital Clinic in Barcelona, and colleagues.
In addition, the presence of more than one laboratory marker such as anti-La antibodies or low C4 also was associated with an elevated mortality risk (HR 2.82, 95% CI 1.73-4.58, P<0.001), the researchers reported online in
Sjogren's syndrome has typically been considered a nonlethal chronic disorder characterized by mucosal and ocular dryness. However, it's now recognized that in up to 80% of patients there is systemic involvement, most often affecting the skin, joints, lungs, and peripheral nerves, and the prognosis is largely dependent on these systemic components.
"The identification of baseline factors that confer an increased risk of death may be very useful in identifying, at diagnosis, patients who require a closer follow-up and treatment as early as possible," wrote Ramos-Casals and colleagues.
To identify these prognostic features, the researchers analyzed data from the Spanish Group of Autoimmune Diseases Sjogren's syndrome study group, which enrolled 1,045 patients with primary Sjogren's syndrome between 2005 and 2014.
More than 90% were women, and mean age at diagnosis was 54.
A total of 95% of patients had both dry eyes and mouth at baseline, 92% had abnormalities on ocular diagnostic testing such as Schirmer's test, 86% had abnormalities on parotid scintigraphy, and in 88%, there was focal lymphocytic infiltration on biopsy of the salivary gland.
High levels of antinuclear antibodies were present in 91%, anti-Ro/SS-A antibodies were present in 74%, rheumatoid factor in 53%, and anti-La/SS-B antibodies in 46%.
In addition, C4 was low in 12% and C3 in 10%, while cryoglobulinemia was detected in 11% and monoclonal gammopathy in 9%.
In just under 10 years, 11% of the patients died, at a mean age of 76. The adjusted standardized mortality ratio for the entire group was 4.66 (95% CI 3.85-5.60).
Survival rates at years 10, 20, and 30 were 90.5%, 80.9%, and 60.4%, the researchers reported. The most common causes of death were cardiovascular disease, infections, systemic Sjogren's, and hematologic malignancy.
In a regression analysis, baseline factors that were associated with mortality included male gender, levels of C4 below 0.11 g/L, C3 levels below 0.82 g/L, the presence of cryoglobulins, lymphopenia, anti-La antibodies, monoclonal gammopathy, and abnormalities on parotid scintigraphy.
On multivariate analysis, these factors were the most strongly associated with death after adjustment for age at diagnosis (P<0.05):
- Male gender, HR 2.98 (95% CI 1.69-5.25)
- Cryoglobulins, HR 2.58 (95% CI 1.59-4.16)
- Low C4, HR 2.06 (95% CI 1.14-3.71)
Systemic disease involvement was assessed on the European League Against Rheumatism Sjogren's syndrome Disease Activity Index , which includes 12 domains/organ systems, each of which is given a rating of zero (no activity) to three (high activity). The score is then calculated from the total of the individual domains.
The mean ESSDAI score for the overall cohort at baseline was 5.89.
The highest ESSDAI scores were for patients whose deaths were associated with infection, at 14.90, and systemic manifestations of Sjogren's syndrome, at 13.33.
Mean baseline ESSDAIs were 6.20 for those dying from hematologic malignancy, 4.06 from cardiovascular disease, and 4.90 from other causes.
The researchers also analyzed outcomes according to specific organ/domain involvement and found that lymphadenopathy and constitutional symptoms such as fever and weight loss were associated with a greater risk of systemic disease and lymphoma.
In addition, pulmonary involvement was associated with a two- to fourfold greater mortality risk. There also was a trend for worse survival among patients who had renal disease, especially when glomerular damage was associated with cryoglobulinemia.
The presence of cryoglobulins at baseline was considered particularly important, according to the authors, and for several reasons: "The most severe extraglandular manifestations of Sjogren's syndrome are often related to cryoglobulinemic disease; cryoglobulins are closely associated with other immunological prognostic markers (hypocomplementemia, monoclonal band), and patients with cryoglobulinemia are at a higher risk of developing B-cell lymphoma," they wrote.
Accordingly, patients with cryoglobulinemia at the time of diagnosis should be followed closely, they noted.
Other patients who should be seen frequently -- every 3 to 6 months -- include those with ESSDAI scores of 14 or higher and those who have multiple predictive immune markers.
In contrast, patients whose disease characteristics are limited to the mucosa may only need annual visits, they recommended.
Disclosures
The authors disclosed no financial conflicts.
Primary Source
Annals of the Rheumatic Diseases
Brito-Zeron P, et al "Systemic activity and mortality in primary Sjogren syndrome: predicting survival using the SULAR-SS Disease Activity Index (ESSDAI) in 1045 patients" Ann Rheum Dis 2014; DOI: 10.1136/annrheumdis-2014-206418.