SJOGREN'S IS COMMON

IMMUNE SYSTEM COMORBIDITIES

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Key Concepts

Comorbidities are diseases or conditions that occur at higher rates in the Sjogren’s population than in the general population. Monitoring and managing comorbidities are an important part of Sjogren’s care.

 

By definition, comorbidities are not caused directly by the Sjogren’s disease process. Systemic Sjogren’s features such as lymphoma or neuropathy are direct manifestations, not comorbidities. Occasionally a researcher will refer to a systemic disease feature as a comorbidity. This is a holdover from the longstanding, disproven idea that Sjogren’s only attacks the exocrine glands.

 

Sjogren’s Advocate divides comorbidities into two large categories: immune system comorbidities and general comorbidities. This page reviews immune system comorbidities found in Sjogren’s. 
 

About half of patients have at least one immune-related comorbidity, but most do not have more than one or two. 

 

Rheumatologists should periodically monitor Sjogren’s patients for common immune system comorbidities. History and physical examination usually tip off rheumatologists that they should test for one of these conditions. 

 

The most common immune system comorbidities seen in Sjogren's:

  • Rheumatoid arthritis (RA)

  • Systemic lupus erythematosus (SLE)

  • Systemic sclerosis/scleroderma (SSc)

  • Axial spondylitis

  • Psoriatic arthritis

  • Primary biliary cholangitis

  • Hashimoto’s thyroiditis

  • Celiac disease (a single screening test is usually sufficient)

Four types of immune system comorbidities in Sjogren’s 

The diagnosis of Sjogren’s may precede or follow the diagnosis of these conditions:

  1. Autoimmune rheumatic diseases

  2. Autoinflammatory disease, the spondylitis family

  3. Organ & system-specific autoimmune diseases

  4. Other immune and rheumatologic conditions

Autoimmune rheumatic diseases (AIRDs)

Sjogren’s is one of the most prevalent AIRDs. AIRDs are systemic inflammatory disorders that are usually associated with autoantibodies found on blood tests. 30-50% of Sjogren’s patients do not test positive for SS-A, the primary autoantibody used to support a Sjogren’s diagnosis (6, 20, 139). Rheumatologists often use the term “Connective tissue disease” (CTD) when referring to an AIRD, but this is confusing because there are non-autoimmune diseases that impact connective tissue such as Marfan Syndrome and Ehlers Danlos Syndrome.


About half of Sjogren’s patients have a second AIRD such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), or systemic sclerosis (SSc) (214, p.205). When a patient has more than one AIRD, each disease should be considered during clinical management.   

Unfortunately, Sjogren’s is often ignored when it coexists with another AIRD. Some rheumatologists view Sjogren’s as “secondary” to another disease, a misleading idea that downplays the serious, systemic nature of the disease. Sjogren’s patients are far more likely than those with other AIRDs to develop lymphoma, dysautonomia, and many types of neuropathies. People with Sjogren’s have a worse quality of life, on average, than patients with RA or SLE (99).

Read this blog post to learn why Sjogren’s should not be referred to as “secondary Sjogren’s”. 

Autoimmune Rheumatic Diseases, with approximate prevalence in U.S./North American population 

Sjogren’s Disease 0.5-1%

Likely to be 1% plus because Sjogren’s associated with another AIRD is not included in estimates (1) , and Sjogren’s is largely undiagnosed and misdiagnosed. 
 

Sjogren's Resources:
For credible, up-to-date information, start with the Sjogren’s Foundation. Other than the Johns Hopkins Sjogren’s Center, most academic websites are out of date, ignore Sjogren's or downplay the systemic aspects of the disease.

Twitter:  @DrChadJohr  -Dr. Johr is a Sjogren’s expert who works closely with the Sjogren’s Foundation.
@SarahSchaferMD - Sjogren’s patient and creator of Sjogren’s Advocate.            

Rheumatoid Arthritis (RA) 0.85- 1% (1)
There has been a steady decline in RA diagnoses since the 1980s.  Sjogren’s patients with inflammatory arthritis are often misdiagnosed with RA (23).

RA Resources
Cleveland Clinic

Creaky Joints, RA page 
Creaky Joints has good information for most types of arthritis, except for Sjogren's. This is despite the fact that 70-80% of Sjogren's patients have joint involvement. 
 

Systemic lupus erythematosus (SLE) 0.05-0.3% (1)
SLE is a complex disease that often has serious kidney and other organ involvement. Sjogren’s patients with systemic presentations are often misdiagnosed with SLE or RA (23).
 

SLE Resources:
The Lupus Foundation of America
Website and blog by Dr. Donald Thomas, who also works with the Sjogren’s Foundation.
SLE diagnosis including the AVISE blood tests, musculoskeletal ultrasound (rhMSUS)

Scleroderma/ systemic sclerosis (SSc and a subtype called CREST) (.02-.15%) (1)
SSc Resources:

Johns Hopkins Scleroderma Center
National Scleroderma Foundation

The Scleroderma Education Project


Polymyositis- rare

Dermatomyositis-rare

Mixed connective tissue disease-contains features of multiple AIRDs, including Sjogren’s

 15-30% of people with RA, SLE, or SSc have or will develop Sjogren’s. 
Because rheumatoid arthritis (RA) is so prevalent, it is the most likely AIRD to be associated with Sjogren’s.  

Autoinflammatory rheumatic diseases, the spondylitis family

Rheumatologists are often not aware that Sjogren’s patients are at increased risk for spondylitis, and vice versa. Like Sjogren’s, diseases in the spondylitis family are underdiagnosed, especially in women, even though they impact about 1% of the U.S. population. Sjogren’s Patients with inflammatory back pain that started before age 45 should discuss the possibility of spondylitis with their rheumatologist.
Click here to take the inflammatory back pain quiz.

About 10% of Sjogren’s patients will have one of these types of spondylitis (209, 210):

  1. Radiographic axial spondylitis (aka ankylosing spondylitis)

  2. Non-radiographic axial spondylitis

  3. Psoriatic arthritis

 

Spondylitis Resources
Axial spondylitis, radiographic and non-radiographic
Spondylitis Association of America

Psoriatic arthritis

Johns Hopkins
https://www.hopkinsmedicine.org/health/conditions-and-diseases/arthritis/psoriatic-arthritis


Printable article about spondylitis and Sjogren’s.  

Autoinflammatory vs. Autoimmune

Autoinflammatory diseases are often loosely referred to as “autoimmune”. This is technically incorrect because no autoantibodies have been associated with these diseases. See the Glossary for the definitions of autoimmune, autoinflammatory, and immune-mediated diseases.

 

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Organ & system - specific autoimmune diseases.  

Hashimoto’s thyroiditis impacts about 30% of Sjogren’s patients. Graves disease is a less frequent Sjogren's comorbidity. 

Every Sjogren’s patient should be routinely screened for Hashimoto’s thyroiditis because it may arise at any time (88, 110). Primary care clinicians may take the lead on this. 
 

Thyroid disease resources:

The American Thyroid Association

Cleveland Clinic

Celiac disease impacts 6-7% of Sjogren’s patients (vs. 1% of the general population) (208).
Celiac disease should be ruled out in every Sjogren’s patient, regardless of symptoms. One-time screening is usually adequate, Patients must be eating gluten for the screening test to be valid.
 
Primary biliary cholangitis (PBC) impacts about 5% of Sjogren’s patients.  

Autoimmune Hepatitis (AIH) impacts 1-2% of Sjogren's patients

The Liver and Sjogren’s

The following is based on Dr. Chadwick Johr's presentation at the Sjogren’s Foundation’s April 2022 National Patient Conference about autoimmune (PBC, AIH) and other causes of liver disease in Sjogren’s.

 

Because symptoms usually occur long after damage has started, it is important to routinely screen for liver function using tests such as  AST and ALT. The frequency of screening depends on risk factors, medications and previous test results.

Other tests may be indicated, such as serum bilirubin, alkaline phosphatase or liver ultrasound. Every patient should be screened at least once for Hepatitis C virus.

 

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Antiphospholipid syndrome (APS)
More common in SLE but may occur in Sjogren’s (212).
Any Sjogren’s patient with a history of blood clots, stroke, or recurrent miscarriage should be assessed for this condition.
APS Resources:
Cleveland Clinic

Pernicious anemia

An autoimmune condition that causes Vitamin B-12 deficiency. B12 deficiency is common in Sjogren’s, but usually not caused by pernicious anemia.
Pernicious Anemia Resources
Cleveland Clinic

Genetic Lifehacks

Immune thrombocytopenic purpura (ITP) (146)

May cause bruising and bleeding from low platelet count
ITP Resources
Mayo Clinic

 

Neurological comorbidities (rare)
Multiple sclerosis (MS)
MS is an immune-mediated demyelinating disorder of the central nervous system. Sjogren's impacting the central nervous system is sometimes mistaken for MS. Patients may have both MS and Sjogren's. It is important to know if you have one or both because treatments differ.

Neuromyelitis optica (NMO)
demyelinating disease that mainly effects the optic nerves and spinal cord
 

 Myasthenia gravis 
An autoimmune disease that causes muscle weakness and fatigue.

CIDP (Chronic inflammatory demyelinating polyradiculopathy)
A rare demyelinating disease of the peripheral nervous system. It causes gradual weakening of the arms and legs, as well as sensory changes. It is unclear whether this is a comorbidity or direct feature of Sjogren's. 

What About Vasculitis? 
 

This condition, especially cryoglobulinemic vasculitis is usually considered to be a direct systemic manifestation of Sjogren’s, although it may have other causes.  

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Other immune and rheumatologic comorbidities

Polymyalgia rheumatica (PMR)- Impacts about 3% of Sjogren’s patients, vs. 0.75% of the general population (213).  PMR almost always occurs after age 50. It is usually diagnosed and treated by rheumatologists.
 

Amyloidosis
A rare disease that may attack multiple areas of the body. A comprehensive pulmonary evaluation will look for this condition in the lungs.  

 

Immune deficiency, including CVID (chronic variable immune deficiency) 

 

Mast cell activation syndrome (MCAS)
Mast cells are a key part of the innate immune system. The understanding of this condition and its role in Sjogren’s disease is just starting to be studied.

What About Fibromyalgia?
 

Fibromyalgia is commonly diagnosed in Sjogren’s patients. While more is being learned about fibromyalgia, nearly every fibromyalgia symptom is a common, direct feature of Sjogren’s disease, not a comorbidity.

Sjogren’s is a well-characterized AIRD. Once Sjogren’s is diagnosed, the label “fibromyalgia” (a syndrome) should usually be dropped, and treated according to the Sjogren’s Clinical Practice Guidelines, Systemic.
 

            See this blog post to learn more about Sjogren’s and fibromyalgia.

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Reminder: Sjogren's Advocate is for educational purposes only, and is not intended to be used as a substitute for medical advice. 
See this page for tips about sharing information with clinicians. 

Updated  09-28-2022