Herpes Zoster Infection Increases Risk of Sjögren’s Syndrome, Study Reports
Varicella can lead to B-cell activation, making herpes zoster possible disease trigger
People with a history of herpes zoster infection, mainly those with no other health conditions, are at an increased risk of developing Sjögren’s syndrome, according to a nationwide, population-based study in Taiwan.
Its researchers emphasized the importance of screening for Sjögren’s in patients with herpes zoster infection, particularly among those without other diseases.
The study, “Association between a History of herpes zoster and the risk of Sjögren’s syndrome: a nationwide, population-based, case-control study,” was published in BMJ Open.
The main feature of Sjögren’s syndrome, an autoimmune condition, is inflammation in the tear and salivary glands, leading to dry eyes and mouth.
While certain genes increase a person’s risk of developing it, other factors, such as viral or bacterial infections, are also thought to be involved. The activation of antibody-producing immune B-cells also plays a role in developing Sjögren’s.
Herpes zoster is caused by an infection from the varicella zoster virus that can also cause varicella, or chickenpox. Since varicella can lead to B-cell activation, herpes zoster has been pointed out as a potential candidate for triggering Sjögren’s. That association is still unclear, however, which is why a research team from Taiwan conducted a nationwide, population-based, case-control study of 5,751 Sjögren’s patients and 28,755 age- and sex-matched people without Sjögren’s as controls to investigate a connection.
Risk of Sjögren’s and comorbidities
Since other diseases (comorbidities) can be related to both herpes zoster and Sjögren’s, they were considered as potential confounding factors for an association. Researchers used the Charlson Comorbidity Index (CCI) to analyze the presence of such comorbidities. Each comorbidity category has an associated weight (from 1 to 6), based on the risk of death, with a score of zero signaling the absence of comorbidities.
The study showed a higher number of Sjögren’s patients had other health conditions when compared with people in the control group. These included blood circulation disorders (0.7% vs. 0.4%), chronic lung disease (7.2% vs. 3.7%), ulcer disease (11.8% vs. 5.1%), mild liver disease (6.5% vs. 2.2%), moderate or severe kidney disease (2.4% vs. 1.3%), and a history of herpes zoster infection (10.9% vs. 6.1%).
The study also showed a lower number of patients with Sjögren’s had diabetes mellitus (6.5% vs 8.7%), tumors (0.6% vs 2.8%), and metastatic solid tumors (0.1% vs 0.3%), compared with controls. Metastatic tumors are those that have become invasive and spread to other parts of the body.
Compared with the control group, more Sjögren’s patients received a herpes zoster diagnosis by a dermatologist (3.9% vs. 7.8%). A higher number of Sjögren’s patients also received treatment for herpes zoster that consisted of antiviral agents (1.8% vs. 3.5%), adjuvant therapies, (5.2% vs. 9.0%), or both (5.4% vs. 9.6%).
Those with a history of herpes zoster had a nearly twofold higher risk of developing Sjögren’s, statistical analyses showed. This risk remained significantly high (1.90-times higher) even when not taking into account other comorbidities’ effects.
This study “was the first to demonstrate a significant relationship between herpes zoster exposure and SS [Sjögren’s syndrome] risk,” the researchers wrote, who noted herpes zoster infection may have triggered a persistent activation of B-cells, leading to Sjögren’s in genetically-prone patients.
The association between herpes zoster and Sjögren’s risk dropped significantly in patients with diabetes. According to researchers, metformin, which is typically used to control blood sugar levels in diabetic patients, might have reduced the risk of Sjögren’s in patients with diabetes due to its anti-inflammatory effects.
The study also showed the risk of developing Sjögren’s was 3.09-times higher in those with less than three months between the time of their last visit for herpes zoster infection to their Sjögren’s diagnosis. The risk of developing Sjögren’s was nearly unchanged (3.13-times higher) when the effects of other comorbidities were removed.
Researchers also found the association between a history of herpes zoster and the risk of Sjögren’s was significantly higher in those without comorbidities compared with those who had a CCI score of 1 or higher. These findings remained significant when several classifications of herpes zoster were used. A differential classification of herpes zoster is established when a diagnosis is carried out by an experienced dermatologist, rather than by any other doctor.
The investigators said more studies are needed to explore the relationship between herpes zoster and Sjögren’s, as the molecular mechanism behind it remains unknown.
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