Fatigue in Sjogren's: A Paradoxical Response


Factors that were associated with high levels of fatigue among patients with Sjogren's syndrome included pain, depression, and -- unexpectedly -- low levels of two proinflammatory cytokines, a U.K. study found.

In a logistic regression model, pain, depression, and low levels of interferon (IFN)-γ and IFN-γ-induced protein-10 (IP-10) predicted fatigue in 67% of cases, according to Wan-Fai Ng, PhD, of the Institute of Cellular Medicine at Newcastle University in Newcastle-upon-Tyne in England, and colleagues. However, clinical disease activity did not appear to correlate with fatigue, the researchers reported online in RMD Open: Rheumatic & Musculoskeletal Diseases.

Inflammation has been postulated to have a central role in fatigue associated with chronic autoimmune disease as part of a phenomenon termed sickness behavior.

Previous research has found that inflammatory burden does not necessarily correlate with fatigue scores in diseases such as Sjogren's syndrome, rheumatoid arthritis, and lupus, "suggesting that there may be a complex range of positive and negative feedback loops contributing to fatigue in autoimmune conditions," they wrote.

Sjogren's syndrome is a suitable disease model for investigating fatigue because of its straightforward diagnostic criteria and the fact that patients generally are not receiving potent immunosuppressive drugs that could influence fatigue, according to the authors. There also is a wide variability in the degree of fatigue that patients with this condition report.

Therefore, to explore the potential relationship between inflammation, fatigue, and other disease characteristics, the researchers selected 159 women and 28 healthy controls from the U.K. Primary Sjogren's Syndrome Registry. Physical fatigue was rated as minimal, mild, moderate, and severe on a 0-7 scale, while depression and anxiety were assessed with the Hospital Anxiety and Depression Score. Clinical assessments included the European League Against Rheumatism Sjogren's Syndrome Disease Activity Index and Patient Reported Index, along with measures of salivary gland function and sicca scores.

The research suggests that measures of disease activity in primary Sjogren's syndrome appear to be less important than cytokines, depression, and pain in accurately predicting fatigue levels," the researchers observed.