Sjogren syndrome: Pathology review

Definitions & Key takeaways

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Case Study0:00–0:36

On your rounds, you see a 55-year-old female named Patricia who presents with fatigue, dry skin, and red eyes. She mentions that she's had a recurrent sensation of sand in her eyes and dry mouth every day for the past three months.
She also mentioned that when it’s cold outside, the tips of her fingers turn white and hurt. On examination, there are signs of tooth decay and purpura on both lower extremities.
Sialometry was performed, which detected salivary hypofunction.Ok, so Patricia’s clinical picture is suggestive of Sjogren syndrome.

Pathology0:36–2:29

Now, Sjogren syndrome is an autoimmune disorder that mostly affects middle-aged females. The high yield concept here is that the immune system attacks various exocrine glands, especially salivary and lacrimal glands.
If Sjogren syndrome is primary or occurs alone, it’s called sicca syndrome. Alternatively, it can be secondary when it is accompanied by other autoimmune diseases like lupus, rheumatoid arthritis, and scleroderma.
Now, the exact cause of Sjogren syndrome is unknown, but both genetic and environmental factors are involved. In Sjogren syndrome, some helper T-cells perceive nuclear components that leak out of dead or damaged cells in the body as antigens.
These T-cells become active and proliferate and then activate B-cells which start producing anti-nuclear antibodies, or ANAs, against the nuclear antigens.
A high yield fact to remember is that the two types of ANA formed in Sjogren syndrome are anti-SSA/RO and anti-SSB/LA antibodies, which are formed against ribonucleoproteins SS-A and SS-B.
Next, both T-cells and antibodies enter the circulation and reach the exocrine glands, where activated T-cells secrete cytokines to recruit even more immune cells.
This results in a lymphocytic infiltration of the exocrine glands, which ends up damaging the exocrine gland tissue. Eventually, the secreted cytokines also activate fibroblasts, which produce fibrous tissue that replaces the damaged tissue.
The end result is a loss of secretory cells in the glands.The resulting symptoms of Sjogren syndrome can be divided into two main categories.

Symptoms2:29–6:03

First up are glandular manifestations, where involvement of the eyes or salivary glands occurs first and sometimes exclusively.
Lacrimal gland involvement results in decreased tear secretion, which leads to dryness of the eyes, blurry vision, irritation which is described as a sensation of sand in your eyes, redness and, ultimately, to keratoconjunctivitis, which is inflammation and ulceration of the cornea and conjunctiva.
Salivary gland involvement usually leads to diffuse fibrosis and painless enlargement of the gland, so remember that if you see nodules, think neoplasm instead.
The diffuse damage to the glands leads to xerostomia, or dry mouth, due to decreased saliva secretion. The lack of saliva causes mucosal atrophy and fissuring of the tongue.
It can also lead to decreased sensation of taste, problem swallowing and tooth decay. If it involves the parotid glands, fibrosis can lead to bilateral parotid enlargement, which can compress on the nearby nerves, causing pain.
In the nose and airways, Sjogren syndrome causes dryness that leads to ulceration and bleeding, and if this affects the larynx, it can lead to difficulty speaking.
And finally, some people can experience dryness of the skin and vagina, which might cause dyspareunia or painful intercourse.
Extraglandular manifestations occur when the syndrome affects organs beyond the exocrine glands, especially if it overlaps with another autoimmune disorder.
Systemic symptoms can include fever, fatigue, myalgia or muscle pain, unintentional weight loss, and lymphadenopathy. Joint involvement is typically manifested as arthralgia, or joint pain, with or without inflammatory arthritis, and it actually occurs in 50% of people with Sjogren syndrome.
There can also be vascular conditions like purpura, which occurs due to bleeding within the skin secondary to vasculitis, or Raynaud’s phenomenon, which is where arterial spasms reduce 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.
Lung problems include a chronic cough, as well as interstitial lung disease, which results in a restrictive pattern on pulmonary function tests.
Renal involvement can cause interstitial nephritis and defects in tubular function, causing creatinine levels to rise. The condition can be associated with autoimmune thyroiditis, hypergammaglobulinemia, monoclonal gammopathies, and cryoglobulinemia.
Finally, a really high-yield concept to know is that overtime, Sjogren syndrome can lead to lymphomas. One type is a non-Hodgkin lymphoma called mucosa-associated lymphoid tissue, or MALT, lymphoma, which is typically associated with chronic inflammation.
MALT lymphoma can present as nodular parotid enlargement instead of the diffuse enlargement normally seen in Sjogren syndrome, so keep that in mind!.
Since virtually any organ or gland can be affected, diagnosis is based on symptoms relating to salivary gland, mouth, and eye involvement, These symptoms must persist for more than three months and must occur daily.

Diagnosis6:03–8:43

Next, tests that identify salivary gland hypofunction should be done. One option would be 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.
There’s also whole sialometry which measures the rate of saliva production by measuring the amount of saliva someone can producer over a timeframe.
In addition, imaging like ultrasound or MRI can be used to identify enlargement of the salivary glands. Finally, labial salivary gland biopsy can be done as a confirmatory test, and it typically shows focal lymphocytic sialadenitis.
That’s where there’s a focal collection of cells, especially CD4+ T- cells, plasma cells, and macrophages; and thickening of the inner duct wall.Eye involvement is tested by the Schirmer test, which measures reflex tear production and it typically shows aqueous tear deficiency.
Another test is ocular surface staining. That’s where a dye like fluorescein is used to stain areas of damaged tissue which is then observed under a slit lamp to look for signs of keratoconjunctivitis.
And a final test is the tear break-up time, which assesses how fast the film of tears that normally spreads over the eyes while blinking takes to dry.
In Sjogren syndrome, this occurs faster than normal. Finally, blood tests are also needed for diagnosis.
In Sjogren syndrome, there’s often a low white blood cell count, elevated globulins, and an elevated ESR, while CRP might be normal or only slightly elevated.
When it comes to autoantibodies, primary Sjogren syndrome is associated with anti-SSA/RO and anti-SSB/LA, while secondary disease can also present other antibodies like ANA and rheumatoid factor, depending on the associated autoimmune condition.
Other tests might be necessary, especially pulmonary function test to assess lung function since the lung involvement is highly common.

Treatment8:43–9:56

Okay, for treatment, Individuals with mild Sjogren syndrome without other organ involvement, can be treated with secretagogues.
This includes muscarinic agonists such as pilocarpine and cevimeline that can increase the production of saliva and tears.
Artificial tears for eye dryness can also help relieve symptoms. Individuals with moderate to severe Sjogren syndrome, with major salivary gland enlargement or involvement of other organs, generally require systemic medical therapy.
Major salivary glandular enlargement due to inflammation can be treated with glucocorticoids. 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 and methotrexate. By contrast, severe disease gets biological DMARDs, 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.
All right, as a quick recap, Sjogren syndrome causes the autoimmune destruction of the exocrine glands, most commonly the salivary and lacrimal glands.

Review9:56–11:57

It can be primary, when it’s called sicca syndrome, or it can be secondary, when it occurs alongside other autoimmune diseases.
The most common glandular symptoms include dryness and irritation of the eyes, blurry vision, redness, keratoconjunctivitis, xerostomia, difficulty in tasting and swallowing, tooth decay, bilateral parotid enlargement, and dryness of the vagina.
Extraglandular manifestations can include fever, fatigue, myalgia, purpura, Raynaud’s phenomenon, interstitial lung disease, joint pain, interstitial nephritis, and MALT lymphoma.
Diagnosis is based on clinical findings and on a series of tests like quantitative salivary gland scintigraphy and whole sialometry, which can detect salivary hypofunction; labial salivary gland biopsy which typically shows focal lymphocytic sialadenitis; the Schirmer test, which can show aqueous tear deficiency; ocular surface staining showing signs of keratoconjunctivitis; and the tear break-up time.
Blood tests might also reveal elevated levels of autoantibodies; primary Sjogren syndrome is associated with anti-SSA/RO and anti-SSB/LA, while secondary disease can also present other antibodies like ANA and rheumatoid factor.
Pulmonary function tests should also be performed to assess lung function Individuals with mild Sjogren syndrome, can be treated with secretagogues such as pilocarpine and cevimeline.
Moderate to severe Sjogren syndrome requires disease- modifying anti- rheumatic drugs or DMARDs.Now, back to our case. Patricia came in with symptoms of fatigue, dry skin, dry mouth, red eyes, and Raynaud’s phenomenon.

Summary11:57–12:42

These symptoms are highly suggestive of Sjogren syndrome, especially since they occurred for more than three months. Examination revealed signs of tooth decay, and purpura on both lower extremities which also fits the diagnosis.
Sialometry detected salivary hypofunction, and together with her symptoms, should be enough to diagnose Sjogren syndrome.
The next step would be blood work to look for anti-SSA/RO and anti-SSB/LA antibodies, and to check for signs of corneal ulceration as well as involvement of the lungs and
Sjogren syndrome: Pathology Review: Video, Causes | Osmosis