SJOGREN'S AND MORTALITY

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Key Concepts

Sjogren’s is a serious disease with excess mortality, mainly related to the systemic involvement of the disease” (42)
 

The good news: most people with Sjogren’s do not die from the disease.

Both direct Sjogren’s manifestations and comorbidities contribute to Sjogren’s-related mortality.
 

Sjogren's is serious. Every Sjogren’s patient, regardless of antibody status, should be monitored over time for systemic involvement and comorbidities. Early detection is key to better outcomes.

Sjogren's-related mortality 

As a group, Sjogren’s patients experience at least a 50% higher than expected mortality. Direct disease manifestations and comorbidities both contribute to increased mortality. Researchers measure the burden of premature mortality (early death) associated with a disease by using a tool called the Standardized Mortality Ratio (SMR).

 What is the SMR for Sjogren’s?
The Standardized Mortality Ratio (SMR) is the ratio of the number of deaths in a study population (e.g., Sjogren’s patients) compared to the expected death rate in the general population, adjusted for age and sex. A SMR of 1.0 means that mortality is the same as the mortality in the general population. A SMR of 2.0 indicates that the group overall has twice the expected death rate as the general population.

Studies show that the SMR in Sjogren’s is elevated, ranging from 1.5-4.66 (42, 61,167).

Direct causes of premature mortality in Sjogren's 

Many patients are told that “Sjogren’s can’t kill you.” While most patients do not die from Sjogren’s, clinicians who perpetuate this myth are downplaying the serious nature of the disease. An estimated 10% of Sjogren’s patients die directly from their disease (24), most commonly from lymphoma and Sjogren’s lung (pulmonary) disease.

"Having a solid appreciation of the breadth and depth of extraglandular manifestations of SS is essential to making a timely diagnosis and preventing serious morbidity and mortality." (151, p. 109).

Potentially fatal direct Sjogren’s manifestations include

Pulmonary (lung) disease 

Sjogren’s lung disease is associated with a four-fold increase in mortality (79, 158). It is far more common (54, 102, 158) than previously recognized. Symptoms are not always apparent, especially early on, during the period when treatments are most likely to be effective (54, 79). Learn more about Sjogren’s lung disease here.

Lymphoma

Sjogren’s patients have a 5-10% lifetime risk (79) of developing lymphoma. Non-Hodgkins B cell lymphoma is a direct manifestation of Sjogren’s disease. It is often a non-aggressive type and patients usually do well (151, p.144).

“Lymphoma is not restricted to SS patients with anti-SSA/Ro antibodies although these antibodies do confer increased risk” (151, p.133)

Kidney disease leading to renal failure (61, 154)

Pulmonary arterial hypertension (sometimes listed with lung disease) (39, 159)

Cryoglobulinemic Vasculitis (47, 61)

Multiple myeloma (151, p.131)

Life-threatening Sjogren’s manifestations are not necessarily fatal.

Stable organ system disease and even low-grade lymphomas may not require aggressive treatment. However, they do require careful monitoring and management by a specialist. Much can be done to reduce the progression of severe systemic manifestations through early diagnosis and treatment (54, 155,151 p.131).

Individual Risk Profile
Multiple factors contribute to the risk profile for individual Sjogren’s patients. SS-A status alone is not adequate to define high-risk populations, other than for complications specific to SS-A positive pregnancies. Other measurements such as low complement, cryoglobulins, and the ESSDAI are stronger predictors for severe systemic involvement (119, 195).

Risk profile is a complicated and evolving topic that will not be addressed in detail on Sjogren’s Advocate. Patients should discuss their individual risk profile and  monitoring with their rheumatologist and other Sjogren’s clinicians

All Sjogren’s patients, including seronegative patients, have the potential to experience serious outcomes. Ongoing monitoring is essential, regardless of risk profile. Patients with a high-risk profile for severe disease require more frequent monitoring (119).

General comorbidities may cause premature death

Comorbidities are diseases and conditions associated with Sjogren’s but not considered to be direct manifestations. General comorbidities do not include immune-mediated comorbidities such as rheumatoid arthritis, celiac disease, or spondylitis. While these are important, they are excluded from this discussion because there are no clear data about their impact on Sjogren’s mortality

Potentially fatal comorbidities include

Cardiovascular diseases (CVD) such as strokes, heart attacks, and thromboembolism (103, 105) are a major cause of premature death in Sjogren’s patients (61, 153). People with Sjogren’s have an increased CVD risk even in the absence of other risk factors. Most primary care providers are well versed in CVD prevention and treatment. However, they may not be aware of the increased risk in Sjogren’s patients.

Severe infections, especially respiratory infections, urinary tract infections, and sepsis contribute to premature death in Sjogren’s (39, 61, 124.)  It is important for Sjogren’s patients to stay up to date on immunizations and protect themselves from unnecessary exposures to communicable diseases.

Non-hematologic cancers, including cancers of the thyroid, oral cavity, and stomach occur at higher rates in Sjogren’s patients (113).

The risk of cervical dysplasia and cervical cancer appears to be higher in Sjogren’s patients. This needs to be confirmed by further research.

A note about depression

Depression impacts about 30% of people with Sjogren’s (27). Severe depression may result in suicide. It is unclear how much of depression can be attributed to biologic factors vs. overwhelming loss. In addition to a high symptom burden, especially from fatigue, loss of social connections and employment are common (98). Sjogren’s is a serious disease that tends to be neglected, psychologized, and downplayed. The difficulty finding medical and social support for this life-altering disease is often devastating to patients (161).

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The Takeaway

While Sjogren’s patients overall experience higher than expected mortality, most can expect to live a normal lifespan. Ongoing monitoring and early intervention for systemic features improve outcomes. Where possible, preventive measures should be implemented, such as reducing cardiovascular risk factors, staying up to date on immunizations, and for women, cervical cancer screening.

Updated 01-17-2022