Psoriasis may raise risk of Sjögren’s by 50%, large study finds
Risk, affected by age, sex and other factors, rose further with psoriatic arthritis
People with psoriasis, an autoimmune disorder marked by itchy, red patches of skin, appear to have a 50% increased risk of developing Sjögren’s syndrome, according to an analysis of medical records involving nearly 600,000 people.
The risk of developing Sjögren’s was even higher among people with psoriatic arthritis, and in those being treated with biological agents, therapies that target the immune system in specific ways.
In a gene activity analysis of affected tissue, molecular mechanisms shared by both autoimmune conditions were identified, including those related to cell proliferation and immune responses.
Further studies could “explore the molecular links between psoriasis and [Sjögren’s] to identify biomarkers and therapeutic targets for [Sjögren’s] management in psoriasis patients,” the researchers wrote.
Immune system dysregulation evident in psoriasis and Sjögren’s
The large-scale study, “Psoriasis increases the risk of Sjögren’s syndrome: evidence from a propensity score-matched cohort study and transcriptomic analysis,” was published in BMC Medicine.
Sjögren’s is a chronic autoimmune disorder that primarily affects the glands that produce saliva and tears. While hallmark disease symptoms are dry mouth and eyes, people with Sjögren’s also can experience fatigue, muscle pain, and problems with their lungs, kidneys, and nervous system.
In psoriasis, an overactive immune response triggers the buildup of skin cells, which develop into itchy, red, discolored, or scaly patches on the skin, most commonly found on the knees, elbows, trunk, and scalp. Psoriasis also is associated with several other conditions, including type 2 diabetes, cardiovascular diseases, and psoriatic arthritis, which is characterized by joint inflammation, pain, and stiffness.
“Despite the well-documented immune dysregulation in both psoriasis and [Sjögren’s], the specific link between these two autoimmune diseases has not been extensively explored,” the researchers wrote.
Scientists in China gathered de-identified electronic health records from the TriNetX database, a global health research network housing real-time electronic medical record data.
A total of 293,905 people with psoriasis were identified and matched to the same number of people without psoriasis. To ensure balance between the two groups, matching was based on age, sex, ethnicity, socioeconomic status, co-existing conditions (comorbidities), body mass index (body fat content), medical utilization, and medications. Then, the number of people who subsequently were diagnosed with Sjögren’s was compared.
Higher risk of Sjögren’s diagnosis with psoriatic arthritis, biological agents
During follow-up, Sjögren’s went on to be diagnosed in 3,339 people with psoriasis and 1,937 without psoriasis. Accordingly, psoriasis significantly associated with a 50% higher risk of developing Sjögren’s, which varied slightly according to age, sex, race, lifestyle habits, and comorbidities.
The risk of developing Sjögren’s among psoriasis patients with co-existing psoriatic arthritis was more than double that of people in whom psoriasis was limited to the skin. Likewise, psoriasis patients undergoing treatment with biological agents had a 66% higher risk of developing Sjögren’s.
Scientists then compared gene activity in affected skin and salivary gland tissues to explore shared molecular mechanisms between the two conditions.
Across both conditions, 320 genes were found to have higher activity and 170 to have lower activity. Those with higher activity mostly were involved in immune response pathways, while those with lower activity were associated with metabolic pathways and the development of exocrine glands, such as those that secrete saliva and tears.
A network analysis of these genetic changes identified three key gene groups underlying both psoriasis and Sjögren’s. One group was significantly enriched in genes linked to cell proliferation, while another contained genes involved in immune cell recruitment and the secretion of immune signaling proteins. The third was particularly enriched in genes associated with responses to viral infections involving the signaling protein interferon.
Researchers acknowledged several limitations in their analyses, including the study’s observational design, which does not allow causal relationships to be inferred between the two conditions. Also, because TriNetX data did not report on psoriasis severity or duration, the impact of disease progression over time could not be evaluated.
“Our study suggests that psoriasis is a risk factor for [Sjögren’s] and that the risk may vary slightly according to age, sex, race, lifestyle habits, and comorbidities,” the scientists wrote. “The overlapping immunological mechanisms may underlie the co-occurrence of psoriasis and [Sjögren’s].”
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