Sjogren syndrome: Clinical practice

Sjogren'ssyndrome is a common autoimmune disorder, that mostly occurs in females, where the immune system attacks various exocrine glands, which are glands that pour their secretions into a duct.

Most commonly the salivary glands and the lacrimal or tear glands are affected.

If Sjogren syndrome is primary or occurs alone - it’s called sicca syndrome, and that’s associated with anti-SSA/RO and anti-SSB/LA antibodies.

Alternatively it can be secondary, which means that it is accompanied by other autoimmune diseases like lupus, rheumatoid arthritis, and scleroderma.

Sjögren's syndrome causes dryness of various body surfaces.

Lacrimal gland involvement leads to dryness of the eyes, blurry vision, itching, redness and burning and ultimately to keratoconjunctivitis, which is the inflammation and ulceration of the cornea and conjunctiva.

Salivary gland involvement leads to xerostomia, or dry mouth, difficulty in tasting and swallowing, cracks and fissures in the mouth, and eventually tooth decay.

In the nose and airways, it causes ulceration and bleeding, and if this affects the larynx, it can lead to difficulty speaking.

In some people there may be dryness of the skin and vagina.

Finally the salivary and lacrimal glands can swell up and compress nearby structures like nerves, causing pain.

In addition, Sjögren's syndrome can also affect organs beyond the exocrine glands as well, and sometimes it can overlap into another autoimmune disorder.

Systemic symptoms include fever, fatigue, myalgia, unintentional weight loss, and lymphadenopathy.

There can be vascular conditions like palpable purpura, due to bleeding within the skin.

These purpura can develop into large ulcers that can get infected.

Another vascular condition is Raynaud’s phenomenon, which is where arterial spasm reduce the blood flow to the fingers for a few minutes at a time.

The fingers turn white and then blue, often with numbness or pain, and then as blood flow returns, the fingers turn red and burn.

Lung problems include a chronic cough, as well as interstitial lung disease.

Renal involvement can cause interstitial nephritis and defects in tubular function, causing creatinine levels to rise.

More rarely, it can cause glomerulonephritis, leading to hematuria and proteinuria.

Gastrointestinal problems include dysphagia, esophageal motility disorders, dyspepsia, gastritis, celiac disease, liver abnormalities like primary biliary cirrhosis or autoimmune hepatitis, and pancreatic diseases like autoimmune sclerosing pancreatitis.

Hematologic manifestations in Sjogren’s include mild anemia and leukopenia; as well as hypergammaglobulinemia; monoclonal gammopathies, cryoglobulinemia, and lymphoma.

Finally, some individuals with Sjogren’s may develop autoimmune thyroiditis.

Since virtually any organ or gland can be affected, there is a wide variety of diagnostic tests that can be done.

Starting from the eyes, there are three commonly used tests for dry eye.

First, is the Schirmer test, which measures reflex tear production.

A folded test strip of sterile filter paper, supplied in a standard kit, is placed over the margin of each lower eyelid at the junction of the middle and lateral thirds. The extent of wetting is measured over five minutes: wetting of less than 5 millimeters suggests aqueous tear deficiency.

Second, is ocular surface staining. That’s where dyes like rose bengal, fluorescein, or lissamine green, are used to stain areas of damaged tissue. The ocular surface is then examined with a slit lamp to assess the damage to the conjunctiva and cornea.

Third, there’s the tear break-up time.

Now, when we blink, a film of tears spreads over the eye, making the surface of the eye smooth and clear. Without this tear film, good vision would not be possible.

The tear break-up time is how long it takes for a dry spot to appear within this tear film - disrupting it.

The tear break-up time is determined by staining the tear film with one drop of fluorescein dye and measuring the time in seconds for a dry spot to develop. The tear film is observed with a slit lamp and cobalt blue light, and a tear break-up time of less than 10 seconds indicates a problem in the outermost mucus layer of the tear film.

Next up, are tests that help identify salivary gland hypofunction.

First, there’s quantitative salivary gland scintigraphy, also called technetium excretion radionuclide scanning, which shows how the major salivary glands are functioning based on their uptake of a radionuclide.

Second, there’s whole sialometry which measures the rate of saliva production.

The patient is asked to collect any saliva that accumulates in the floor of the mouth, and to spit it into a pre-weighed container. After 5 to 15 minutes, the collection vial is reweighed and the volume of saliva is measured. A collection of below 0.1 milliLiters per minute indicates salivary gland hypofunction.

In addition, imaging like ultrasound or MRI can be used to define structural abnormalities of the salivary glands.

Finally, a labial salivary gland biopsy is done as confirmatory test to examine the minor salivary glands, which typically show focal lymphocytic sialadenitis.

That’s where there’s a focal collection of one or more clumps of tightly aggregated lymphocytes, termed lymphocytic foci, which are typically adjacent to normal gland tissue and surrounding a duct. This lymphocyte infiltration progressively causes glandular dysfunction in the salivary and lacrimal glands, and is characteristic of Sjogren's syndrome.

In Sjogren’s, there’s often a low white blood cell count, elevated globulins, and an elevated ESR, while CRP might be normal or only slightly elevated.

Autoantibodies typically include anti-RO and anti-LA, but other antibodies can be present as well, especially if there’s an associated autoimmune condition.

If there’s interstitial nephritis, the urine may have proteinuria, and if there’s glomerulonephritis there may be hematuria as well.

Individuals with primary Sjogren’s syndrome have anti-RO, with or without anti-LA antibodies; or a labial salivary gland biopsy showing focal lymphocytic sialadenitis.

Some other conditions can also cause sicca symptoms.

For example, a history of head and neck radiation treatment, active hepatitis C infection, AIDS, sarcoidosis, amyloidosis, graft- versus- host disease, and IgG4- related disease - can all cause some of the same changes to the salivary glands.

Secondary Sjogren’s syndrome is associated with other autoimmune conditions.

Systemic lupus erythematosus, is associated with antinuclear antibodies, anti- double- stranded DNA, anti- Smith, and antiphospholipid antibodies; rheumatoid arthritis, is associated with rheumatoid factor and anti citrullinated peptide/protein antibodies; and scleroderma, is associated with anticentromere antibodies.

Individuals with mild Sjogren's syndrome, which includes those with sicca symptoms alone, without other organ involvement, can be treated with secretagogues.

These are substances that cause another substance to be secreted, and include muscarinic agonists such as pilocarpine and cevimeline which increase the production of saliva.

In addition, ocular dryness can be managed with artificial tears; and good dental care like fluoride treatment can help prevent cavities.

Individuals with moderate to severe Sjogren's syndrome, with major salivary gland enlargement or involvement of other organs, generally require systemic medical therapy.

Major salivary glandular enlargement, most often affecting the parotid glands and due to inflammatory sialadenitis, can be treated with short courses of glucocorticoids - so 20 milligrams per day of prednisone for one week, followed by a gradual taper to finish a two- week course.

Individuals with involvement of other organs are started on disease- modifying anti- rheumatic drugs or DMARDs.

Most individuals are started on non-biological DMARDs, like hydroxychloroquine, methotrexate, leflunomide, azathioprine, sulfasalazine, mycophenolic acid, and cyclosporine.

And individuals with severe disease get biological DMARDs, also called biologics, all of which suppress some part of the immune system, such as the alkylating agent cyclophosphamide and the anti-CD20 antibody rituximab, which targets B cells.

Summary

Alright, as a quick recap, Sjogren’s syndrome is an autoimmune disorder that targets the lacrimal gland which leads to keratoconjunctivitis.

The tests used include the Schirmer test, ocular surface staining, and tear break-up time.

It also targets the salivary gland which leads to xerostomia.

The tests done to quantify salivary hypofunction include quantitative salivary gland scintigraphy and whole sialometry.

There’s also swelling of the glands, which can compress nearby structures like nerves, and cause pain.

Laboratory testing may reveal a low white blood cell count, elevated globulins, and an elevated ESR and CRP.

Primary Sjogren’s syndrome -called sicca syndrome, is typically associated with anti-RO and anti-LA antibodies.

Alternatively, secondary Sjogren’s syndrome occurs along with other autoimmune diseases, such as lupus, rheumatoid arthritis, and scleroderma.

Finally, a lip biopsy is needed as confirmatory test to examine the minor salivary glands, which show focal lymphocytic sialadenitis.

For management, individuals with sicca symptoms alone get secretagogues, such as pilocarpine and cevimeline; in addition to local treatment for ocular dryness with artificial tears; as well as preventive dental treatment, such as at-home topical fluoride application.

Individuals with major salivary glandular enlargement can be managed with short courses of glucocorticoids, while individuals with involvement of other organs are started on DMARDs.