GENERAL COMORBIDITIES

Oriental%20Lotus_edited.png

Key Concepts

Comorbidities are diseases or conditions that occur at higher rates in people with Sjogren’s than in the general population. Rheumatologists and/or primary care providers (PCPs) should monitor Sjogren’s patients for comorbidities and offer preventive measures when possible.

 

Sjogren’s Advocate divides comorbidities into two large categories: immune system comorbidities and general comorbidities. This page reviews general comorbidities found in Sjogren’s. Primary care providers (PCPS) often take the lead on general comorbidities while rheumatologists usually focus on immune comorbidities, but there is overlap.

Comorbidities are not caused directly by Sjogren’s. Lymphoma, interstitial lung disease, and neuropathies are usually direct manifestations of Sjogren’s disease, but are sometimes inappropriately referred to as comorbidities. This is a holdover from the outdated idea that Sjogren's only impacts the exocrine glands. 

Systemic (non-dryness/sicca) features may be caused directly by Sjogren’s, by comorbidities, or by both. For example, small fiber neuropathy could be caused by Sjogren's and diabetes in a patient who has both diseases.

 

See the tips at the end of this page to learn more about choosing and sharing information with clinicians.   

Common general comorbidities seen in Sjogren's:

  • Cardiovascular disease*  

  • Infections*

  • Osteopenia, osteoporosis, and osteomalacia (see glossary)

  • Sarcopenia (muscle loss)

  • Nutritional deficiencies such as Vitamin D, B12, and iron

  • Anemia

  • Kidney stones (may be a direct feature caused by changes in kidney function)

  • Depression (See discussion below

  • Sleep disorders

  • Interstitial cystitis (IC)/ bladder pain syndrome 

    (*) indicates significant contributors to premature mortality.
     

General comorbidities in Sjogren’s may be caused by  

  • Immune system comorbidities

  • Other general comorbidities such as diabetes

  • Systemic inflammation

  • Gut malabsorption leading to nutritional deficiencies

  • Medication side effects

  • Immune dysfunction including the disruption of the mucosal lining of the respiratory tract.

General Comorbidities- The List (1-13)
This list is likely to change over time as the understanding of Sjogren’s evolves.

1. Cardiovascular disease and CVD risk factors  
CVD, a leading cause of premature mortality in Sjogren’s. This comorbidity is so important that it has a blog post dedicated to the topic. Read about Sjogren’s and CVD here.

Sjogren’s patients have higher rates of diabetes, hypertension, and elevated blood lipids. These are modifiable CVD risk factors.
 

2. Infections (47, 61) 

  • Oral and vaginal candidiasis (224)

  • Chronic/ recurrent sinusitis (214,Ch.25)

  • Shingles 

  • Pneumonia, sepsis, urinary tract infection and other severe infections cause increased hospitalization and contribute to early mortality in Sjogren’s (39, 225).  

  • COVID-19

It is unclear from current data whether Sjogren’s patients who are not  taking immune suppressants (e.g., prednisone, methotrexate, rituximab) are at increased risk of COVID-19. One study shows an elevated risk of developing long Covid. This is an evolving topic and may change as new variants arise. ​

Vaccines and Sjogren’s


Be sure to discuss vaccines with your PCP and/or rheumatologist.
  Consult with your rheumatologist if you are taking immune suppressing medications. Hydroxychloroquine is not an immune suppressant.

 
Do not forget the Tdap vaccine for preventing pertussis (whooping cough). Pertussis can be severe in people with dry airways or lung disease.

3. Osteopenia, osteoporosis, and osteomalacia (See Glossary for definitions)

Sjogren’s kidney involvement, inflammation, diet, medications, and low Vitamin D levels, and sarcopenia (low muscle mass) all contribute to bone thinning and weakening. Sjogren’s patients are more likely to develop fragility fractures at lower Fracture Risk Assessment Tool (FRAX) scores (226). Discuss screening and management with your PCP or endocrinologist. 

Vitamin D and Sjogren's


Vitamin D levels are often low in Sjogren’s and may require supplementation. These should be checked on an annual basis. Ideal levels range from 30-70 ng/ ml. Levels greater than 80 ng/ ml may lead to lower bone mineral density.
(personal communication with osteoporosis specialist).

4. Sarcopenia (muscle loss) (227)
It is normal to lose muscle mass with age, but this is even more of a problem with diseases such as rheumatoid arthritis and Sjogren’s, especially for patients who have been on long-term glucocorticoids (e.g., prednisone). Physical activity and resistance exercise (even mild) can prevent and improve this.

 

5. Nutritional deficiencies  

  • Vitamin D (241, Ch. 41) Often recommended to check blood levels annually.  

  • Vitamin B12 (228), especially with vegan diets.

  • Vitamin B9 (Folic acid). Few studies. Supplementation is usually recommended for patients taking methotrexate.  

  • Iron, including iron deficiency without anemia (IDWA) (229). IDWA can be a hidden cause of fatigue and is more common in systemic inflammation. It is detected by a blood test for ferritin which reflects iron stores in the brain and tissues. Note that IDWA may cause or worsen restless legs syndrome.


Discuss supplements with your clinician. Multivitamins are not always a good idea. Too much Vitamin B6 may contribute to neuropathy.

6. Anemia       
Anemia occurs when there are not enough red blood cells that function properly.  There are multiple types of anemia, not just low iron. Anemia can be a direct manifestation of Sjogren’s (a type of cytopenia), a comorbidity such as from a nutritional deficiency, or unrelated to Sjogren’s.
Do not take iron supplements unless they are recommended by your clinician. It can be dangerous to take iron if you have certain types of anemia or a hereditary condition called hemosiderosis.

 

7. Kidney stones   

These may be caused by distal renal tubular acidosis, a condition caused by Sjogren’s kidney disease. There are multiple types of kidney stones and multiple underlying causes. Be sure to discuss prevention and management with your clinician.

 

8. Depression
It is estimated that one third of people with Sjogren's disease are clinically depressed. It can be difficult to determine how much a person's depression is caused by biological factors such as systemic inflammation, or by other causes, such as social stress, loss of careers and roles, difficulty finding adequate care, and more. Depression must be identified for people to receive the care they need. Importantly, addressing physical disease symptoms is likely to improve both physical and mental health. 

People with Sjogren’s could seem depressed even though they are not. Depression is usually diagnosed based on a combination of somatic (physical) and mood symptoms. Clinicians sometimes default to a depression diagnosis to explain symptoms such as fatigue, difficulty concentrating, changes in appetite, and weight loss or weight gain. These are common physical manifestations of Sjogren’s. 
Learn more how depression may be over-diagnosed in patients with chronic invisible illnesses such as Sjogren’s (205).

9. Sleep disorders (230

  • Obstructive sleep apnea (222)

  • Restless legs syndrome (63) may be related to low ferritin levels.

  • Insomnia (230)

 

10. Interstitial cystitis/ bladder pain syndrome (170, 171) may also be direct feature (214, Ch. 35). Endometriosis is sometimes mistaken for painful bladder syndromes.

 

11. Endometriosis (214, Ch. 35)
 

12. Parkinsons (108), Alzheimer’s and other types of dementia (109) - weak data, few studies

13. Cancers

  • HPV- related cancer of the cervix (214, Ch. 35)

  • Non-melanoma skin cancers
    Increased in patients who take immune suppressing drugs such as methotrexate, glucocorticoids, and others.

  • Increased risk thyroid cancer, stomach cancer, lip/oral cavity cancers (113).
    These are not common cancers. The increased risk is measurable, but individual risk remains low. 

Sjogren's and Hematologic Cancers


Hematologic cancers, especially non-Hodgkin lymphoma (NHL), and to a lesser extent, multiple myeloma and Hodgkin lymphoma, are considered direct Sjogren’s manifestations, not comorbidities. 
 

NHL affects 5–10% of Sjogren's patients during the course of their lifespan and is the most prevalent cancer among them. The salivary glands are the site of the majority of Sjogren's lymphomas, which are slow-growing and typically not deadly. Lymphoma risk factors should be monitored in in every patient regardless of antibody status. High risk patients, including males, should be monitored more closely (113, 195, 214, Ch 37).

Possible General Comorbidities 
These conditions have not been adequately researched.  
These Conditions Are Often Called General Comorbidities 
They are not listed as general comorbidities for the reasons stated.  

1. Migraine and other severe headaches
Migraine and severe/ frequent headaches are found in up to 80% of Sjogren’s patients, a similar rate found in systemic lupus erythematosus (SLE) (206). In SLE, severe headaches are categorized as neurological manifestations. Headaches tend to be overlooked in Sjogren’s patients.
 

2. Asthma
Asthma is common in the general population. Sjogren’s patients may have asthma, but asthma-like symptoms may be caused by Sjogren’s lung disease. Sjogren’s patients with an asthma diagnosis should be evaluated for Sjogren’s lung disease.

 

3. Raynaud’s Phenomenon

 A systemic manifestation of Sjogren’s (79) that is sometimes called a comorbidity.
 

4. Myalgic encephalitis ((ME/CFS).
Sjogren’s patients may have ME/CFS features. It may be difficult to determine whether ME/CFS is a separate condition or part of Sjogren’s disease. See this blog post for a discussion about ME/CFS in Sjogren’s.


5. Fibromyalgia
Fibromyalgia is often diagnosed as a Sjogren’s comorbidity by rheumatologists. This is inaccurate because fibromyalgia features are direct manifestations of Sjogren’s and often respond to Sjogren’s treatments.  
See this blog post for more information.

6. Functional neurological disorder (FND) (aka conversion disorder)
FND is often the default diagnosis when a clinician is unfamiliar with a neurological manifestation such as non-length dependent neuropathy and autonomic disorders.  See this blog post for more information.


7. Irritable bowel syndrome (IBS)
IBS is a collection of symptoms, not a well-characterized disease like Sjogren’s disease. Most clinicians are not trained to investigate the underlying reasons for IBS symptoms in Sjogren’s. Sjogren’s patients often have gastritis, gastrointestinal reflux disorder (GERD) intestinal dysbiosis, and autonomic dysmotility contributing to “IBS” symptoms (112, 224).  Autonomic dysmotility may impact the esophagus, stomach (gastroparesis), and  the large and small intestines.

Endometriosis and autoimmune comorbidities that may cause IBS-like symptoms. Examples include celiac disease, autoimmune thyroid disease, or primary biliary cholangitis (224).

Talking With Your Clinician About Comorbidities

Clinicians may be unaware that Sjogren’s is associated with multiple immune and general comorbidities. Patients may find it helpful to share information about comorbidities with their clinician. Be sure to read the Clinician Handouts page to learn strategies for choosing and sharing educational material with clinicians. Please do not print out this page as a handout (see why here).

 
Oriental%20Lotus_edited.png

How To Use Citations


Sjogren’s Advocate is extensively researched and cited to provide you with powerful self-advocacy tools.
When the citation is underlined, this means that you can obtain the article, or at least an abstract of the article, by clicking on the number. When there is no underline, the source is a book. For example, citation 214 refers to The Sjogren’s Book, 5th edition. You can find the information about the book by looking for number "214" on the citations page.
Learn more about citations here.

Updated  11-02-2022