Sjögren’s syndrome secondary to systemic lupus erythematosus (SLE) rises in frequency with age, affects around one-quarter of all people with systemic lupus, and, despite less internal organ involvement than in systemic lupus without Sjögren’s syndrome, is marked by a systemic inflammatory state with high levels of pro-inflammatory cytokines, say researchers writing in The Journal of Rheumatology this month.
The diagnosis Sjögren’s syndrome is based on the presence of dry eyes and mouth due to destructive inflammation in the exocrine glands, especially tear and salivary glands, and can exist as an isolated, primary disease or as a secondary condition, occurring together with other rheumatic diseases. A major difference according to the 2002 Revised American-European Consensus Criteria (AECC) is the classification where the serologic item (SSA/SSB antibodies) is included for primary Sjögren’s syndrome, but not for secondary Sjögren’s syndrome. In SLE, these autoantibodies are common, typically stable over time, and appear early, even several years before disease onset.
“Secondary Sjögren’s syndrome is an often-neglected subset of patients with SLE,” wrote the authors, led by Elisabet Svenungsson, M.D., Ph.D., of the Karolinska Institutet in Stockholm, Sweden.
Researchers evaluated 504 consecutive SLE patients and 319 controls from the general population. AECC was used to define SLE-secondary Sjögren’s syndrome and a thorough clinical investigation was completed on all patients, including analysis of autoantibodies and 20 selected cytokines. “To our knowledge this is the first study to investigate if systemic inflammation, as measured by cytokine levels, differs between SLE-secondary Sjögren’s syndrome and SLE without Sjögren’s syndrome,” the authors wrote.
SLE-secondary Sjögren’s syndrome occurred in 23 percent of the SLE patients. Compared with SLE patients who did not have secondary Sjögren’s syndrome, those with secondary Sjögren’s syndrome were an average of nine years older, more likely to be female, 96 percent versus 84 percent, and more likely to have leukopenia, 57 percent versus 45 percent, but less likely to have nephritis, 32 percent versus 43 percent, respectively.
Of the pro-inflammatory cytokines investigated, six (TNF-α, IL-6, MCP-4, MIP-1β, IL-12/IL23p40 and IP-10) were higher in participants with SLE-secondary Sjögren’s syndrome, as were IgG, anti-SSA/Ro52, anti-SSA/Ro60, anti-SSB/La antibodies and rheumatoid factor, IgM and IgA, (p<0.05 for all comparisons). But notably, 39 percent of SLE-secondary Sjögren's syndrome patients were negative for all three SSA/SSB antibodies.
“Thus, the presence of sicca symptoms is not exclusively related to SSA/SSB antibodies, but also to increasing age, rheumatoid factor, and possibly to other unidentified factors.”
“In clinical practice, it is often difficult to delineate primary Sjögren’s syndrome from SLE-secondary Sjögren’s syndrome. Organ manifestations commonly reported in primary Sjögren’s syndrome are fever, lymphadenopathy, parotid gland enlargement, Raynaud’s phenomenon, interstitial lung disease, peripheral neuropathy, and vasculitis. All these clinical features, except parotid gland enlargement, were investigated in the present study, but only peripheral neuropathy differed and was more frequent in SLE-secondary Sjögren’s syndrome than in SLE without Sjögren’s syndrome,” the authors wrote.
Guillermo Ruacho, Marika Kvarnström, Agneta Zickert, et al. “Sjögren’s syndrome in Systemic Lupus Erythematosus - a subset characterized by a systemic inflammatory state.” The Journal of Rheumatology. September 15, 2019. DOI: https://doi.org/10.3899/jrheum.190250