Sjogren's- Another  Look

“Another Look” provides a framework for understanding comprehensive Sjogren’s care.  Many clinicians remain unfamiliar with the systemic nature of Sjogren’s.  Rheumatologists often define how sick a patient is very differently from how patients experience the disease. This section describes four major categories of clinical concern.  Understanding these categories can facilitate patient-provider communication.  

Overview:  Sjogren's is much more than dryness

TIP:  Before reading this section, it may be helpful to review the SSF’s excellent description of core Sjogren’s features at https://www.sjogrens.org/home/about-sjogrens  

Sjogren’s can impact any organ system in the body.  Despite overwhelming evidence that Sjogren’s is a serious multi-systemic disease, many clinicians still think of it as mostly a nuisance sicca disease.  Even the American College of Rheumatology website, as of February 2019, perpetuates this incorrect understanding of Sjogren’s.   

Patients and doctors tend to think about diseases based on visible and measurable manifestations. This is partly why dryness (sicca) gets so much attention in Sjogren’s. Core features such as debilitating flu-like fatigue and neurologic complications may be overlooked (2, 3, 22, 24, 32).  Severe fatigue, widespread pain and malaise are sometimes called “benign” manifestations in the literature. This unfortunate term further perpetuates an already dismissive attitude toward Sjogren’s. 

The vast majority of patients have clear systemic features. Organ system involvement may precede sicca, particularly in the case of neurologic presentations. (22, 32, 36)  Serious and even life-threatening complications do occur.  Sjogren’s patients should be screened for organ involvement and predictive factors for lymphoma.  Monitoring and follow-up can be individualized based on a patient’s risk levels.    

It can feel overwhelming to consider all of the things that can go wrong with Sjogren’s.  Fortunately, most patients do not get most complications.  For some, Sjogren’s is a mild disease.  The goal of treatment, prevention and monitoring is to keep the disease as mild as possible.  This is more likely to happen when patients are diagnosed in a timely manner and have providers who understand the importance of proactive disease management.

Four Categories of Sjogren's Manifestations

Not everyone divides Sjogren’s manifestations as described below.  The terms “Systemic”and “Extraglandular Manifestations” (EGM) are not used consistently in the literature.  Most researchers use a very strict definition of EGM.  In contrast, some rheumatologists call all systemic features EGM. Therefore, it is important to define exactly what is meant when using these terms.

1. Glandular Features (Sicca)

Sicca / dryness is present in the vast majority of diagnosed patients. Even when sicca symptoms predominate, there is much more going on under the surface.

The actual prevalence of clinically apparent sicca is unclear because Sjogren’s is rarely diagnosed in the early stages of disease.

 

 

 Sicca:  The tip of the iceberg

Sicca manifestations deserve careful attention. Good treatment and preventive measures are essential to avoid bad outcomes such as severe dental decay and visual impairment.  Sicca is not limited to dry eyes and dry mouth.  Fluid secreting (exocrine) glands in the nose, throat, sinuses, airways, GI tract, pancreas, vagina or skin are often involved.

Sjogren’s is more than dryness, but even sicca symptoms are “more than dry.”  Local inflammation, neuropathic pain and changes in tear and saliva composition may all contribute to symptoms.   Many good treatments are available for eye and oral sicca manifestations.  All dental and eye providers should be familiar with the Clinical Practice Guidelines, available at the SSF website:

Dental: http://www.sjogrens.org/files/research/OralCPG.pdf

Eye:  http://www.sjogrens.org/files/research/OcularCPG.pdf

Sicca is often, but not always, the first sign of Sjogren's.  Because dryness tends to come on slowly, patients may not think that these symptoms are important.  Sometimes they don't notice the dryness, especially early on. Changes on dental and eye exam occur long after damage to the exocrine glands has started.  Even when dryness is clinically obvious, lack of awareness by eye and dental providers frequently results in missed opportunities for timely diagnosis.  Ophthalmologists treating dry eye disease often fail to consider Sjogren’s as a possible cause. (34, 35).

2A.  Extraglandular Manifestations (EGM)

EGM usually refers specifically to the 12 clinical domains laid out by the ESSDAI – the EULAR-SS disease activity index. (37)  The ESSDAI is the current tool used by researchers (and some rheumatologists) to measure Sjogren’s disease activity and prognosis. To avoid confusion about terminology, this website divides non-sicca Sjogren’s manifestations into EGM and General Systemic Features.  

The 12 "official" EGM categories:  A Brief Summary  (10, 37, 38)

  1. Constitutional-  Fever, night sweats and involuntary weight loss not thought to be due to other causes.
     

  2. Lymphadeneopathy and lymphoma- Lymph node swelling not thought to be due to infection or other cause.  Lymphoma, usually low grade, impacts 5-7% (2)
     

  3. Glandular- This does not mean sicca.  It refers to swelling of the salivary or tear glands, most commonly parotid gland enlargement. 
     

  4. Articular (joints)- Pain and stiffness of joints, especially of the hands, ankles, and feet, often accompanied by morning stiffness.  Inflammatory arthritis may occur, although without the joint erosions seen in rheumatoid arthritis (RA). (45)
     

  5. Cutaneous (skin)- Skin lesions including erythema multiforme, subcutaneous lupus and cutaneous vasculitis.
     

  6. Pulmonary (lungs)- Numerous manifestations, including small and large airway disease, interstitial lung disease, and more rarely, pulmonary hypertension. (39, 54)
     

  7. Renal (kidneys)- renal tubular acidosis (often mild), interstitial kidney disease, glomerulonephritis (rare).
     

  8. Muscular- Myositis may cause muscle weakness.   Muscle pain without weakness is included in EGM with a “low score” if tests are normal.
     

  9. Peripheral nervous system (PNS)- Numerous.  Both large and small fiber neuropathies are fairly common.  The most common PNS feature, dysautonomia, is not included in the ESSDAI scoring system. See blog posts 1-15-19 and 4-11-19, and  https://www.hopkinssjogrens.org/disease-information/sjogrens-syndrome/neurologic-complications/ 
     

  10. Central nervous system (CNS)-  Less common than PNS. MS-like syndrome, cerebral vasculitis, transverse myelitis and others.  See link immediately above. 
     

  11.  Hematological-  Anemia (normocytic) not due to another cause, thrombocytopenia (low platelets), leucopenia (low wbcs), neutropenia (low neutrophils), autoimmune hemolytic  anemia.
     

  12. Biological- Low complement, hypergammaglobulinemia, high IgG or recent decrease of IgG level, cryoglobulinemia.

Most Sjogren’s patients do not have most EGMs!
However, the vast majority have at least one EGM as defined by this ESSDAI-based list. Multiple EGMs would be the norm if the missing features and vastly underdiagnosed neurologic complications (32, 33) were included in the official list.

“Applying the ESSDAI systemic definitions in nearly 1000 patients, we have confirmed that with only 18 % of patients being scored at diagnosis as having no systemic activity (ESSDAI=0), a percentage that fell to 8 % after a mean follow-up of 6 years. “
~ Ramos-Casals et al (
38)

2B. Ten notable EGM missing from the official list

  1. Dysautonomias are neurologic manifestations that impact the majority of Sjogren’s patients (33, also 49-53).  The ESSDAI guidelines (37) do not list them as a PNS feature.  These are often overlooked because many rheumatologists are not trained to recognize them. Cardiovascular dysautonomias such as POTS are a treatable contributor to fatigue. (33, 49, 50)
     

  2. Carpal tunnel syndrome is another common PNS complication that is not included in the ESSDAI scoring system.  
     

  3. Raynaud's is a systemic autoimmune feature that impacts a large subset of Sjogren’s patients.  
     

  4. Vasculitis of organs in addition to the skin and CNS. Thought to be uncommon but may affect peripheral nerves and multiple organs. (30, 46)
     

  5. GI manifestations are nearly ubiquitous. Difficulty swallowing, GERD, and chronic gastritis, gut dysmotility, and SIBO/dysbiosis frequently occur.  Autoimmune hepatitis, primary biliary cholangitis and pancreatitis are uncommon but serious organ system complications. (2, 13)
     

  6. Extraglandular eye manifestations such as scleritis, iritis and uveitis are uncommon but serious inflammatory complications of the eye.  Although these conditions impact the eyes, they are not related to sicca. (40)
     

  7. Severe headaches, including migraines, are as about as common in Sjogren’s as they are in systemic lupus erythematosus (SLE). (41)
     

  8. Pregnancy complications, including congenital fetal heart block and neonatal lupus.  Patients with antiphospholipid antibodies are at high risk of blood clots and miscarriage.
     

  9. Serositis, including periocarditis, pleuritis and abdominal serositis.  More common in SLE, but do occur.
     

  10. Interstitial cystitis, overactive bladder and frequent UTI.

3. General Systemic Features- THE GREAT UNMET NEED

 Life-changing symptoms such as disabling physical fatigue, flu-like malaise, widespread pain, and “brain fog” occur in the vast majority of patients. (2, 10, 26)  The burden of these disease features can be devastating.  The functional disability in Sjogren’s is as great as in SLE, and RA patients with active disease who fail TNF therapy.  (27, 43, 44)
 

Health-related quality of life (HRQOL) is more dependent on fatigue, pain and depression than on the severity of dryness symptoms. (27)  Yet little research has been done about these core features. They are often ignored by clinicians or dismissed as stress or anxiety.  It can be hard for clinicians (and family members) to “get it” that a patient who looks well and has relatively normal labs can feel so sick.
 

Rheumatologists and PCPs should be familiar with the SSF Clinical Practice Guidelines for systemic management, including pain and fatigue.
 

http://www.sjogrens.org/files/research/CPGSystemic.pdf  

4. Comorbidities

Other connective tissue diseases  (CTDs)
 

Most rheumatologists look for other CTDs such as RA or SLE that often coexist with Sjogren’s.  When this happens, the patient simply has several major diseases that each deserve specific management. The outdated term “Secondary Sjogren’s” is misleading and should not be used in this situation. See the following excellent explanation from the SSF of why this is the case:    https://tinyurl.com/y3bgc4kv

Other autoimmune conditions

Hashimoto’s thyroiditis and celiac disease occur at much higher rates in Sjogren’s patients than in the general population.  Anti-phospholipid antibodies (APA), more often seen in SLE, do occur in some Sjogren’s patients.  APA positive patients are at increased risk of developing blood clots, strokes, heart attacks and pregnancy complications.  Sjogren’s patients should be screened for all three diseases.

Diseases associated with systemic inflammation

As with other systemic inflammatory diseases, Sjogren’s patients are at elevated risk for serious infections, strokes, heart attacks and osteoporosis.  Infections and cardiovascular disease disease are a significant causes of premature mortality (early death) in Sjogren’s patients. (24, 42, 47).

Monitoring and prevention of all types of comorbidities is an important component of good Sjogren’s care.

Updated  4-23-19