Sjogren's Syndrome

 

Welcome to PT 635 Pathophysiology of Complex Patient Problems This is a wiki created by and for the students in the School of Physical Therapy at Bellarmine University in Louisville KY. Please do not edit unless you are involved in this project, but please come back in the near future to check out new information!!

Original Editors - Cassie Shay from Bellarmine University's Pathophysiology of Complex Patient Problems project.

Lead Editors - Your name will be added here if you are a lead editor on this page.  Read more.

Definition/Description

Sjogren's syndrome was first described by physician Henrik Sjogren in the early nineteen hundreds to explain the signs and symptoms of a group of women exhibiting chronic arthritis along with extremely dry eyes and dry mouth. It is now understood that Sjogren's syndrome is an autoimmune connective tissue disease in which the body's own immune system attacks moisture producing glands, causing inflammation in addition to reduction in both the quality and quantity of the glands' secretions. As observed by Dr. Sjogren, the glands responsible for producing saliva and tears, the salivary and lachrymal glands respectively, are the organs most notably impacted by the disease². However, Sjogren's syndrome is a systemic disorder in which many organs may be affected, including kidneys, gastrointestinal tract, blood vessels, respiratory tracts, liver, pancreas, and central nervous system³. Additionally, it is considered a rheumatic disease, like rheumatoid arthritis or lupus, and like these disease Sjogren's syndrome can cause inflammation in joints, muscles, skin, and other organs².

 

Prevalence

Sjogren's syndrome is the second most prevalent autoimmune rheumatic disease. In 2008, it was estimated that 1.3 million Americans were affected^2,3. Statistics from rheumotology clinics indicate that Sjogren's syndrome affects 0.5 - 1% of the general population, and approximately the same number of people have been diagnosed with Sjogren's syndrome and Systemic Lupus Erythematosus ⁴.

Although, it can affect individuals of all genders and ages, including children, symptoms usually occur in women between the ages of 45 and 55 years old¹. In fact, it is estimated that nine times as many women are affected when compared to men³. Among individuals with rheumatoid arthritis or systemic sclerosis, thirty percent have histological evidence of Sjogren's syndrome³.

Characteristics/Clinical Presentation

Patient's with Sjogren's syndrome can present with a number of complaints. However, the most common symptoms of this autoimmunue disease are dry mouth and dry eyes. Individuals with this condition may describe their symptoms as they relate to their eyes as an irritation, burning, or gritty feeling, as though they have sand in their eyes^1,3. The dryness in their mouth may make it difficult to speak, swallow,chew, or it may make foods taste differently³.

While these are the hallmark signs of Sjogren's syndrome, a patient may present with a number of other complaints including joint and muscle pain, fatigue, skin rashes or extremely dry skin, weakness, numbness, digestive problems, and Raynauld's phenomenon^1,2. Females diagnosed with Sjogren's may also experience vaginal dryness and pain with intercourse².

Associated Co-morbidities

Approximately half of patients who have been diagnosed with Sjogren's Syndrome have also been diagnosed with rheumatoid arthritis, lupus, or some other connective tissue disorder. Fewer people may also experience Sjogren's in association with lymphoma.  As more research is developed on the topic, more and more co-morbities are being associated with SS. Recent studies suggest that clinical depression is also common among individuals diagnosed with this disease.

Secondary Sjogren's is a form of the syndrome which develops after the presentation of a primary disease, usually another autoimmune connective tissue disease. Common primary diseases associated with Sjogren's Syndrome are listed in the table below.

Disease	Description
Polymyositis	Inflammation of muscles that cause pain, weaking, and difficulty moving. If the skin is involved too, it is called dermatomyositis.
Rheumatoid Arthritis	Severe inflammation of the joints caused by the bodies own immune system attacking the synovium located throughout the body.
Scleroderma	Accumulation of too much collagen, resulting in thick, tight skin, and possible damage to joints, muscles, and internal organs.
Systemic Lupus Erythematosus	An autoimmune disease in which the patient may experience joint pain, muscle pain, fatigue, weakness, skin rashes, and possibily even heart, lung, kidney, and nervous system issues.
Lymphoma	Although rare, there is a small percentage of individuals with Sjogren's whom also have lymphoma, which is cancer of the lymph system. This can affect salivary glands, lymph nodes, the gastrointestinal tract, and lungs.

Medications

There is no cure for Sjogren's syndrome, therefore its symptoms are managed through medications, both prescription and over the counter. A variety of  medications may be used to treat each of the associated symptoms.

Drug category	Signs/ Symptoms Treated	Examples of Brand Names
Nonsteroidal anti-inflammatory drugs	Joint and Muscle Pain	Ibuprofen
Corticosteriods	Inflammation of lungs, kidneys, blood vessels, or nervous system	Prednisone
Immune-modifying drugs	Overactivity of the immune system	Plaquenil (hydroxychloroquine), Rheumatrex (methotrexate), Cytoxan (cyclophosphamide)
Artificial Tears	Dry Eyes	Clear Eyes, Visine Tears, etc.
Ointments (for night use)		GenTeal, Systane
Hydroxypropyl methylcellulose		Ocucoat
Topical steroids		Restasis (cylcosporin A)
Saliva substitue	Dry Mouth	Oralube
Cholinergic Agonists		Salagen (pilocarpine), Evoxac (cevimeline)

This table was created using information from the National Institute of Arthritis and Musculoskeletal and Skin Diseases and PubMed Health, see references below.

Diagnostic Tests/Lab Tests/Lab Values 

Diagnosis of this disease is based on a medical history, a physical exam, and results from some clinical and laboratory tests. Due to the nature of disease in that the symptoms are similar to other diseases and they appear gradually over time, it may take years for Sjogren's to be properly diagnosed. Nonetheless, diagnostic testing may include the following:

File:Lip Biopsy.jpg

Histopathologic image of a lip biopsy demonstrating lymphoid infiltration in a minor salivary gland. H&E stain

• The Schirmer's test assesses the function of the lacrimal glands by measuring the amount of tears they are producing. This test involves putting a strip of paper under the lower eyelid, waiting five minutes, then measuring how much moisture was absorbed by the paper. An individual who tests positive for Sjogren's syndrome will typically produce too few tears to get more than 8 millimeters of the paper wet.
• During a slit lamp examination an ophthalmologist magnifies and examines the eye for severe dryness and inflammation. This test may be performed in conjunction with a vital dye applied to the eyes to determining the extent to which the eyes may have been damaged secondary to the dryness.
• A mouth examination may be performed to determine if signs of mouth dryness are present. These signs may include, sticky oral mucosa, tooth decay and cavities in certain locations, thick saliva, and redness inside the oral cavity. The physician may also be able to note inflamed or under-producing salivary glands during this examination. 
• A lip biopsy is a method used to determine if the dry mouth experienced by the patient is a symptom of Sjogren's syndrome. During this test, minor salivary glands are removed from the bottom lip and placed under a microscope. If the glands contain a certain arrangement of white blood cells, the test is positive for the salivary component of Sjogren's syndrome. 

Because dry eyes and dry mouth are common symptoms and side affects of a number of diseases and treatments, including radiation to the head and neck, the physician will commonly perform a battery of additional tests to confirm no other causes. These tests may include:

• Blood tests may be performed to determine the presence of antibodies and immunological substances often found in individuals positive for Sjogren's. Antibodies commonly present in affected individuals include immunoglobulins, antithyroid antibodies, rheumatoid factors, antinuclear antibodies (ANA), and Sjogren's antibodies.
  
• Chest X-Rays are a method used to examine for inflammation of the lungs, which may be present in Sjogren's syndrome.
• A urine analysis may also take place to determine if the kidneys are functioning properly.

Etiology/Causes 

The primary symptoms of Sjogren's syndrome, including the dry

File:Acinar cells.JPG

Digital camera shot of human acinar cells through a microscope.

eyes and dry mouths, are a result of the destruction of the exocrine (lacrimal and salivary) glands by focal T-lymphocytic infiltrates. T-cells and B-cells are components of the immune system and usually work together to detroy foreign structures in the body, such as viruses and bacterias. However, in autoimmune diseases, such as Sjogren's syndrome, these cells interfere with the function and structure of organs within the body. In the case of Sjogren's, these cells interfere with glandular function.

Regulation of the salivary glands by the nervous system is impaired, and the secretory acinar apparatus displays structural abnormalities. The acinus is the terminal end of the exocrine gland where the secretions are produced. The membrane of this structure lacks the laminin alpha-1 chain, which may explain this organ's inability to induce differentiation of the stem cells into acinar cells.

Evidence in the pattern of cases suggest that the cause of Sjogren's syndrome has a genetic component. Recent research has found that the same gene variant commonly present in individuals with other connective tissue diseases, such as RA and lupus is also associated with Sjogren's syndrome. The discovery of the STAT4 gene variant in association with autoimmune diseases could lead to a number of cutting edge treatments, including the possiblitly of gene replacement therapy to combat these incurable conditions.

As with other autoimmune diseases, scientist believe that Sjogren's may be triggered by an infection in individuals with a genetic predisposition. This infection jump starts the the immune system. However instead of calming down when the infection is eraticated, the immune system continues to remain on high alert, and starts to destroy the body's own cells.

Systemic Involvement

Individuals with Sjogren's syndrome are prone to a number of problems such as inflammation and infection throughout the body. These issues may include:

Pulmonary Problems

• bronchitis
• tracheobronchitis
• lymphocytic interstitial pneumonitis
• pleurisy

Kidney Problems

• interstitial nephritis
• glomerulonephritis (rarely)
• renal tubular acidosis
• hypokalemia

Nervous System Problems

• peripheral neuropathy
• cranial neuropathy

Liver Problems

• hepatitis
• cirrhosis

Thyroid Problems

• Grave's disease
• Hashimoto's thyroiditis

Vascular Problems:

• vasculitis
• Raynaud's phenomenon 

Medical Management (current best evidence)

add text here

Physical Therapy Management (current best evidence)

Individuals with Sjogren's syndrome have reduced physical capacity and tend to fatigue very easily. While research on the effects of exercise on individuals diagnosed with Sjogren's is limited, the available studies suggest these patients benefit from moderateto high-intensity levels of exercise³. This type of activity has a positive influence on aerobic capacity, fatigue, physical function, and mood.

Alternative/Holistic Management (current best evidence)

add text here

Differential Diagnosis

There are several diseases that present with symptoms similar to Sjogren's syndrome, including the dry eyes and dry mouth³. Some differential diagnoses include:

• Systemic Lupus Erythematosus
  
• Vasculitis
• Thyroid disease
• Scleroderma
• Medication side-effects

Case Reports/ Case Studies

add links to case studies here (case studies should be added on new pages using the case study template)

Szturmowicz M, Wilinska E, Paczek A, et al. Primary Sjogren's syndrome with two extraglandular sites involvement-case report. Pneumonol. Alergol. Pol. 2010:78;445-450.

Resources

National Institute of Arthritis and Musculoskeletal and Skin Disease

American College of Rheumatology

Sjogren's Syndrome Foundation

National Eye Institute

American Academy of Ophthalmology

American Autoimmune-Related Diseases Associated, Inc. (AARDA)

Arthritis Foundation

National Organization for Rare Disorders (NORD)

Recent Related Research (from Pubmed)

Failed to load RSS feed from http://eutils.ncbi.nlm.nih.gov/entrez/eutils/erss.cgi?rss_guid=1jeAVjyuKpXiEUVu0BHJQBuRC5NMeqm6NxzqGzoerHIyvWUYT0|charset=UTF-8|short|max=15: Error parsing XML for RSS

References

see adding references tutorial.