What is Sjogren’s syndrome

Sjogren’s syndrome also known as Sjögren’s disease is a long-lasting (chronic) autoimmune disorder that happens when your immune system attacks the glands that make tears (lacrimal glands) in your eyes, salivary glands that make saliva in your mouth, and other parts of your body (multi-organ problems) ¹, ², ³, ⁴, ⁵, ⁶, ⁷, ⁸, ⁹. The main symptoms of Sjögren’s syndrome are dry eyes (xerophthalmia) and dry mouth (xerostomia), but other parts of your body may be affected as well, with many people reporting chronic fatigue, fever and joint and muscle pain ¹⁰. With Sjogren’s syndrome you may have dryness in other places that need moisture, such as your nose, throat, and skin. In addition, Sjögren’s syndrome can also damage other parts of your body including your lungs, kidneys, blood vessels, digestive organs, vagina and nervous system ¹¹. Most people with Sjogren’s syndrome are women, with women are 10 times more likely to have Sjogren’s syndrome than men ¹², ¹³, ¹⁴.

The first clinical description of Sjögren syndrome was by Mikulicz in 1892, who described a 42-year-old with bilateral parotid and lacrimal gland enlargement. In 1933, the Swedish Ophthalmologist Henrik Sjögren compiled a clinical and histopathologic description of a series of patients with the “sicca complex” of dry eyes and mouth.

Doctors have two categories for Sjogren’s syndrome ⁸, ¹, ¹⁵:

• Primary Sjogren’s syndrome: Occurs if you do not have other rheumatic diseases.
• Secondary Sjogren’s syndrome (Sjogren-overlap syndrome): Occurs if you already have another rheumatic disease, such as rheumatoid arthritis or systemic lupus erythematosus (SLE), scleroderma, or polymyositis.

The cause of Sjogren’s syndrome is unknown. Sjögren’s syndrome or Sjögren’s disease is an autoimmune disorder that happens when the immune system attacks and damages glands in your body that produce and control moisture. Normally, your immune system protects your body from infection and disease. Researchers theorize that Sjögren’s disease could be caused by complex interplay of genetic, hormonal, and environmental factors ¹. The leading “pathogenic model” suggests that environmental insults in genetically predisposed individuals injure the salivary gland epithelium. This epithelial damage initiates inflammation and triggers an abnormal immune response, driving the chronic autoimmune process that defines Sjögren’s disease ¹⁶. A genetic study identified a strong correlation between Sjögren syndrome and the HLA-DQB1 gene variants ¹⁷. These major histocompatibility complex variants (changes or mutations) appear to promote an abnormal immune response when combined with specific environmental triggers ¹⁷. Laboratory findings and indirect epidemiological data implicate viral infections, particularly Epstein-Barr virus (EBV), in Sjögren’s disease development ¹⁸, ¹⁹. Exposure to solvents and inorganic chemicals has also been associated with the development of Sjögren syndrome ²⁰.

Sjogren’s syndrome affects 400,000 to 4 million people (approximately 0.5% to 1.0% of the population) in the United States. Although Sjögren syndrome can develop at any age, symptoms most commonly begin between the ages of 45 and 55. Sjögren syndrome occurs globally in adults and less commonly in children across all racial and ethnic backgrounds. Approximately half of those diagnosed with Sjogren’s syndrome also have other autoimmune conditions such as rheumatoid arthritis or systemic lupus erythematosus (SLE) or Raynaud’s disease (Raynaud’s phenomenon). Most people with Sjogren’s syndrome are able to live normally, without any serious complications – especially if they take care to manage their symptoms.

The lack of an evidence-based, standardized screening tool to identify which dry eye patients require evaluation for Sjögren syndrome contributes to the underreferral of these individuals ¹. As a result, many cases of Sjögren syndrome remain undiagnosed, perpetuating a pattern of underrecognition and delayed diagnosis ²¹.

The 2 main symptoms of Sjogren’s syndrome are:

• Dry eyes. Your eyes may burn or itch or feel like they have sand in them. Sometimes, the dryness causes blurry vision or sensitivity to bright light. You may get irritated, itchy eyelids due to inflammation.
• Dry mouth. Your mouth may feel chalky, and you may have trouble swallowing, speaking, and tasting. Because you lack the protective effects of saliva, you may develop more dental decay (cavities) and mouth infections, such as candidiasis (also called thrush).

Most individuals with Sjögren syndrome present with sicca symptoms, such as xerophthalmia (dry eyes), xerostomia (dry mouth), and parotid gland enlargement ²².

In some people, the main problem is dry mouth, while for others it is dry eyes, and some people experience both problems equally. In some cases, Sjögren’s disease affects other tissues and organs and has more widespread effects on the body.

Some people with Sjogren’s syndrome also have one or more of the following:

• Fatigue
• Joint pain, swelling and stiffness
• Dry skin
• Skin rashes
• Dry gritty eyes
• Dry nasal passages and throat
• Dry cough
• Decreased sense of taste and smell
• Dry mouth with difficulty swallowing or talking
• Sore tongue or throat
• Muscle aches and pain
• Muscle weakness
• Stomach upset, irritable bowel
• Acid reflux.
• Vaginal dryness.
• Swelling of the glands around the face and neck.
• Swollen salivary glands — particularly the set located behind your jaw and in front of your ears (parotid glands)
• Trouble sleeping.
• Poor concentration and memory problems.
• Numbness, tingling, and weakness, especially in the hands or feet (peripheral neuropathy)
• Shortness of breath or trouble breathing.
• Recurrent bronchitis or pneumonia.

Sjögren’s disease may have different effects on the body, and the symptoms vary from person to person. In some people, Sjögren syndrome symptoms cycle between mild and severe. Sjögren syndrome symptoms can be severe, with some people reporting debilitating pain and fatigue.

People with Sjögren syndrome have a higher chance of developing a type of cancer called lymphoma, but the risk of developing it is low.

To make a diagnosis, doctors may use a medical history, physical exam, certain eye and mouth tests, blood tests, and biopsies.

Sjogren’s syndrome is primarily managed by rheumatologists, in collaboration with ophthalmologists and oral medicine/pathology specialists.

There is no cure for Sjögren’s disease, but there are several ways to treat and manage the symptoms. Sjogren’s syndrome usually affects people differently so it is important to discuss treatment options with a health practitioner to decide on the best treatment plan.

Treatment can vary depending on the severity of your symptoms. Treatment is usually aimed at relieving your symptoms and preventing or minimizing complications and damage to tissues, such as the surface of the eye.

• Dry eyes can be treated with over-the-counter or prescription artificial tears, tear stimulants, and/or thicker eye lubricants. Sometimes plugs may be inserted into the drainage ducts in the eyes to help tears remain on the surface of the eyes.
• Dry mouth may be helped by frequent small drinks of water or sugarless chewing gum to stimulate saliva production, and mouth lubricants can be used as necessary. In some cases, medications that increase saliva production may be prescribed.
• Regular dental care and checkups are important as those affected are prone to cavities.
• Joint pain and other arthritis symptoms are treated with anti-inflammatory medicines, such as aspirin and other nonsteroidal anti-inflammaory drugs (NSAIDs).
• In some severe cases when internal organs of the body are affected, drugs that dampen the immune system (immunosuppressants) and steroids may be prescribed.

Figure 1. Sjogren’s syndrome rash (cutaneous vasculitis)

Figure 2. Sjogren’s syndrome parotid gland swelling

Sjogren’s syndrome causes

Sjogren’s syndrome is an autoimmune disorder. The immune system is supposed to fight disease by killing off harmful viruses and bacteria. But with autoimmune diseases, your immune system attacks parts of your own body by mistake.

In Sjogren’s syndrome, your immune system attacks the glands that make tears and saliva (spit). The damage keeps these glands from working right and causes dry eyes and dry mouth.

Scientists aren’t certain why some people develop Sjogren’s syndrome. Certain genes put people at higher risk of the disorder, but it appears that a triggering mechanism — such as infection with a particular virus or strain of bacteria — is also necessary ²⁴. For example, Epstein–Barr virus (EBV) was identified in saliva samples and in salivary and lacrimal gland biopsies of Sjogren’s syndrome patients with extraglandular manifestations, particularly with myopathies ²⁵. Furthermore, Epstein–Barr virus (EBV) has a well-established tropism for B cells, favoring the development of lymphoproliferative processes, the most severe extraglandular complication in Sjögren syndrome ²⁶. However, to date, no clear association with viral infections, such as human herpes virus-6 (HHV-6), hepatitis C or B viruses, human immunodeficiency virus (HIV), human T-lymphotropic virus type 1 (HTLV1), or Coxsackie A virus, have been reported in Sjögren’s syndrome ²⁷.

Genetic factors play an important role in Sjogren’s syndrome pathogenesis ²⁸. Associations between Human Leukocyte Antigen (HLA) alleles, such as DRB1*03:01, DQA1*05:01, DQB1*02:01, and Sjogren’s syndrome susceptibility, were identified by genomic studies ²⁹. Furthermore, six non-HLA regions were shown to be involved in Sjogren’s syndrome, including interferon regulatory factor 5 (IRF5), signal transducer and activator of transcription 4 (STAT4), BLK, interleukin (IL)-12A, TNFAIP3 interacting protein 1 (TNIP1), and C-X-C motif chemokine receptor 5 (CXCR5). The HLA-DQB1*0201 allele and the expression of IRF5 and STAT4 seem to have the strongest association with Sjogren’s syndrome ³⁰, ³¹. Based on genome-wide studies, key steps in Sjogren’s syndrome triggering were identified, such as aberrant activation of the innate immune response, through the IFN and NF-kB pathways, atypical recruitment to lymphoid sites, and T-cell activation with HLA susceptibility ascending ³².

In Sjogren’s syndrome, your immune system first targets the glands that make tears and saliva. But it can also damage other parts of your body, such as:

• Joints
• Thyroid
• Kidneys
• Liver
• Lungs
• Skin
• Nerves

Risk factors for Sjogren’s syndrome

Sjogren’s syndrome typically occurs in people with one or more known risk factors, including:

• Age. Sjogren’s syndrome is usually diagnosed in people older than 40.
• Sex. Women are much more likely to have Sjogren’s syndrome.
• Rheumatic disease. It’s common for people who have Sjogren’s syndrome to also have a rheumatic disease — such as rheumatoid arthritis or systemic lupus erythematosus (SLE).

Sjogren’s syndrome symptoms

The main symptoms of Sjogren’s syndrome are dry eyes and a dry mouth, but it can also cause several other problems.

Each person is affected differently. For some people Sjogren’s syndrome may just be a bit of a nuisance, while for others it can have a big impact on their everyday life.

There are many conditions that can cause similar symptoms. See your doctor if you have any symptoms you’re worried about.

People with Sjogren’s syndrome can have:

• Dry eyes (xerophthalmia), including a painful burning, itchy or gritty feeling. Patients usually describe dry of gritty eyes. They may also feel a burning discomfort, notice decreased tear production, increased eye fatigue and sometimes intolerance of bright lights (photophobia). These symptoms may develop because of increased dryness of the eyes causing damage to the lining of the cornea at the front of the eyes.
  • Signs that you may have dry eyes include:
    • burning, stinging or itchy eyes
    • a feeling of grit or sand in your eyes
    • sore, red and swollen eyelids
    • discomfort when looking at lights
    • sticky eyelids when you wake up
    • blurred vision
  • These symptoms may be worse when the air is dry – for example, when you’re somewhere that’s windy, smoky or air conditioned.
  • Dry eyes can be caused by many conditions besides Sjogren’s syndrome

• Dry mouth (xerostomia), making it difficult to swallow, speak or eat dry foods. This may develop very gradually over a number of years. When first noticed it may only be the sensation of dryness of the mouth. As it progresses patients may notice difficulty swallowing dry food, difficulty speaking for long lengths of time, problems with dentures and sometimes increased tooth decay. Oral thrush is also more likely to develop.
  • Signs that you may have a dry mouth include:
    • feeling like food gets stuck in your mouth or throat – especially dry food like crackers
    • needing to drink water while eating to help you swallow food
    • your tongue sticking to the roof of your mouth
    • a hoarse voice
    • a smooth, red tongue
    • a change in how food tastes
    • dry, sore and cracked skin at the corners of your lips
    • problems such as tooth decay, gum disease, mouth ulcers, and oral thrush – a fungal infection that can cause a raw, red or white tongue
  • Other reasons for a dry mouth include things like diabetes or medicines.
• Swollen salivary glands — particularly the set located behind your jaw and in front of your ears

Eye and mouth dryness can also increase your risk for eye infections and dental problems.

Some people with Sjogren’s syndrome also get:

• Joint pain, swelling and stiffness
• Muscle pain
• Dry skin. The most common skin manifestation is dry or rough skin (xerosis), which is noted by more than half of patients. This may result in itch. Patients with Sjogren’s syndrome also sweat less than people without the disease. Although these symptoms are common, most patients with Sjogren’s syndrome are more bothered by the dry mouth and dry eyes.
• Vaginal dryness, which can make sex painful
• Persistent dry cough
• Prolonged fatigue or tiredness and exhaustion
• Difficulty concentrating, remembering and reasoning
• Rashes (especially after being out in the sun)
• Vasculitis (inflammation of blood vessels) is potentially more serious. This develops in about 10% of patients with primary Sjogren’s syndrome and affects the skin in half of them (cutaneous small vessel vasculitis). Skin lesions usually present as multiple purple or reddish brown spots. The color is due to bleeding from small inflamed vessels. Vasculitic skin lesions are most common and prominent on the legs but can develop anywhere. They may present as red flat patches, raised lumps, blisters, ulcers or a raised urticaria-like weals.

A few people will have their liver and kidneys affected. A few people will also develop lymphoma (cancer of the lymph nodes).

Some people have other conditions closely linked to Sjogren’s syndrome too, such as Raynaud’s phenomenon, a condition that affects the blood supply to the fingers and toes.

Gastrointestinal system

Rarely the gastrointestinal system may be affected in Sjogren’s syndrome. The resulting dryness may inflame the lining of the esophagus (esophagitis) and the stomach (atrophic gastritis).

Lungs

Although Sjogren’s syndrome may affect the lungs, and is rarely serious. The most common manifestation is a dry cough, due to dryness of the small airways.

Joints

Up to 60% of people with Sjogren’s syndrome will at some stage develop at least one episode of arthralgia (ache in joints) or arthritis (inflammation within the joint). The arthritis does not usually result in erosion of joint structures or in joint deformity.

Kidneys

Involvement of the kidneys is more common if Sjogren’s syndrome is present as part of an overlap syndrome with systemic lupus erythematosus. It can affect the kidneys in various ways including interstitial nephritis, kidney stones or glomerulonephritis.

Skin

The skin is affected in up to 72% of patients with Sjögren syndrome. Complications range from the more common, e.g, dry skin (xeroderma), eyelid dermatitis, and Raynaud phenomenon, to the less common, including cutaneous vasculitis (palpable purpura), cutaneous amyloidosis, and annular erythema ¹¹.

Vasculitis

Primary Sjogren’s syndrome vasculitis can damage kidneys, lungs, nerves and joints. Fevers and anaemia may also be present. Involvement of internal organs is more likely if the vasculitis is associated with cryoglobulins (a special form of protein that precipitates at cold temperatures). Some patients with Primary Sjogren’s syndrome and vasculitis have an underlying B-cell lymphoma (cancer of the lymphatic system).

Sjogren’s syndrome complications

Sjogren’s syndrome can sometimes lead to further problems or occur alongside other conditions. The most common complications of Sjogren’s syndrome involve your eyes and mouth.

• Dental cavities. Because saliva helps protect the teeth from the bacteria that cause cavities, you’re more prone to developing cavities if your mouth is dry.
• Yeast infections. People with Sjogren’s syndrome are much more likely to develop oral thrush, a yeast infection in the mouth.
• Vision problems. Dry eyes can lead to light sensitivity, blurred vision and corneal damage.

Eye problems

If you have very dry eyes and they’re not treated, there’s a risk the front layer of your eyes could become damaged over time (e.g., corneal erosions, vision loss).

If this isn’t spotted and treated, it could lead to permanent problems with your vision.

There are several treatments for dry eyes that can help reduce this risk. You should also have regular check-ups with an optician so any problems are picked up early on.

Contact your doctor as soon as possible if you have problems with your vision.

Musculoskeletal problems

Footnotes: This image shows a patient undergoing the Schirmer test. Wetting of the strips is measured in millimeters after 5 minutes. Some physicians measure for 1 minute and multiply by 3.

Figure 4. Sjögren’s syndrome Rose Bengal staining

Footnotes: In Sjögren’s syndrome, the Rose Bengal test involves staining the cornea and conjunctiva with a Rose Bengal dye to identify areas of cell damage or dryness caused by unshielded epithelial cells due to mucin deficiency. A high Rose Bengal score indicates significant ocular surface damage, a common feature of Sjögren’s disease, and contributes to the diagnosis of the condition. However, the dye can be irritating, so newer dyes like fluorescein and lissamine green are often preferred, though Rose Bengal remains a key component of diagnostic tools.

Sjogren’s syndrome test

There is no single test that can definitively diagnose Sjogren’s syndrome. Usually a health practitioner will order laboratory tests and other types of tests, and the results are considered with other factors such as signs and symptoms and results of a physical exam to make a diagnosis.

Sjogren’s syndrome blood test to detect autoantibodies may include:

• Antinuclear antibodies (ANA) — a primary test for autoimmune disorders; this test is also positive in most cases of Sjogren’s syndrome.
• Antibodies specific to Sjogren’s syndrome — Anti-SS-A (also called Ro) and Anti-SS-B (also called La); the tests for these antibodies are often performed as part of an ENA panel and are frequently positive.
• Rheumatoid factor (RF) — may be positive
• Anti-dsDNA — also used to evaluate people for autoimmune diseases; this test is usually specific for lupus, but low levels may sometimes be seen with Sjogren’s syndrome.

Other general laboratory tests may include:

• Erythrocyte sedimentation rate (ESR) — detects inflammation and is often elevated in autoimmune diseases like Sjogren’s syndrome
• C-reactive protein (CRP) — another common test for inflammation, usually elevated
• Comprehensive metabolic panel (CMP) — evaluates the function of various organs, including the kidneys
• Complete blood count (CBC) — may be done to evaluate for anemia or low white blood count, which are sometimes seen in this disease

Non-laboratory tests:

• Mouth (salivary gland) biopsy — a few small salivary glands may be removed surgically from a lip and then examined under a microscope. This is done to look for inflammation (accumulation of white blood cells called lymphocytes) in the gland. This is characteristic of Sjogren’s syndrome.
• Schirmer test — to measure tear production
• Rose Bengal or lissamine green staining of eye (cornea or conjunctiva) — to evaluate the extent to which dryness has damaged the surface of the eye
• Salivary flow — measures the amount of saliva produced over a specific time period
• Sialogram. This special X-ray can detect dye that’s injected into the salivary glands in front of your ears. This procedure shows how much saliva flows into your mouth.
• Salivary scintigraphy. This nuclear medicine test involves the injection into a vein of a radioactive isotope, which is tracked over an hour to see how quickly it arrives in all your salivary glands.

Anti-SSA and Anti-SSB antibodies

Anti-SSA (anti-Ro) and Anti-SSB (anti-La) antibodies are found in approximately 50% of patients with Sjögren’s syndrome (75% of patients with primary Sjögren syndrome and 15% of patients with secondary Sjögren syndrome) ⁴⁴. Therefore, the absence of anti-SSA/Ro antibodies does not eliminate the diagnosis of primary or secondary Sjögren syndrome ⁴⁴.

Anti-SSA (anti-Ro) is a polyclonal antibody directed against nuclear and nucleolar RNA binding protein of 60KD or cytoplasmic protein of 52KD (E3 ubiquitin ligase). Patients can have a negative ANA and a positive Ro antibody (anti-SSA) test if they only have anti-Ro against cytoplasmic protein of 52KD ⁴⁴.

Anti-SSB (anti-La) is an oligoclonal antibody that is predominantly directed against nuclear 47KD RNA binding protein ⁴⁴.

Antibodies against SSA (Ro) are present in 50% of patients with systemic lupus erythematosus (SLE) and are sometimes found in healthy individuals. Therefore, the presence of antibody against SSA/Ro cannot by itself be used to establish a diagnosis of Sjögren syndrome ⁴⁴.

Antibodies against SSB (La) are present in 40% to 50% of patients with primary Sjögren syndrome and in 15% of patients with systemic lupus erythematosus (SLE) ⁴⁴. Finding antibodies against SSB (La) in patients without antibodies against SSA (Ro) is unusual, but this combination has occurred in patients with primary biliary cirrhosis and autoimmune hepatitis ⁴⁴.

Titers of anti-SSA/Ro and anti-SSB/La antibodies do not reflect disease activity. Current enzyme-linked immunosorbent assay (ELISA) tests for these antibodies are more sensitive than previous tests. Thus, the specificity is lower.

Antibodies against SSA/Ro are also associated with the annular erythematous lesions of subacute cutaneous lupus. They are also found in the mothers of newborns with neonatal lupus syndromes and congenital heart block, and some of these mothers have or will develop Sjögren syndrome.

Rheumatoid factor

Rheumatoid factor (RF) is present in 52% of patients with primary Sjögren syndrome and in 98% of patients with the secondary Sjögren syndrome, occurring even when rheumatoid arthritis is not present ⁴⁵. Consider a diagnosis of rheumatoid arthritis if the patient has symmetrical polyarticular synovitis.

The presence of rheumatoid factor (RF) has been independently associated with elevated risk for lymphoma in patients with primary Sjögren syndrome ⁴⁶. However, loss of a previously positive rheumatoid factor (RF) finding can be observed in some patients with Sjögren syndrome who develop lymphoma ⁴⁵.

Antinuclear antibodies

Antinuclear antibodies (ANAs) are typically present in patients with Sjögren syndrome ⁴⁵. Consider the diagnosis of systemic lupus erythematosus (SLE) in patients with antinuclear antibodies (ANAs) only if symptoms and signs typical of systemic lupus erythematosus (SLE) are present ⁴⁵.

Erythrocyte Sedimentation Rate (ESR)

Erythrocyte Sedimentation Rate (ESR) is elevated in 80% of patients with Sjögren syndrome, but the finding is nonspecific ⁴⁵.

Serum protein electrophoresis

Patients with Sjögren syndrome often have a polyclonal gammopathy ⁴⁵. Loss of a previously detected polyclonal gammopathy can be observed in some patients with Sjögren syndrome who develop lymphoma ⁴⁵. Development of a monoclonal gammopathy can also signal the development of a lymphoma ⁴⁵.

Salivary testing

Sialometry is a good measure of the degree of decreased salivary flow and helps to establish xerostomia, but the findings do not narrow the differential diagnoses.

Saliva from patients with Sjögren syndrome has elevated levels of sodium, chloride, lactoferrin, and IgA, but these findings are not specific.

Other test results

Other test results to consider are as follows:

• High total protein level or a low albumin level – Should prompt the clinician to perform serum protein electrophoresis
• High alkaline phosphatase (ALP) level – Should prompt consideration of primary biliary cirrhosis
• Elevated transaminase levels – Consider the possibility of chronic active hepatitis, which can be associated with sicca symptoms, or hepatitis C, which can cause mild salivary gland enlargement; however, mild (< 2-fold) increases in transaminase levels have been observed in 22% of patients with Sjögren syndrome ⁴⁷
• Low bicarbonate level – Consider evaluating patients with a low bicarbonate level for type I (distal) renal tubular acidosis; less commonly, patients can also develop proximal renal tubular acidosis with Fanconi syndrome
• Hypokalemia – This condition, which is occasionally severe enough to lead to periodic paralysis, can be observed in patients with type I renal tubular acidosis; however, it can also be observed in patients who have Sjögren syndrome without renal tubular acidosis ⁴⁸

Patients with primary Sjögren syndrome may have positive test results for lupus anticoagulant and/or anticardiolipin antibodies, and some patients develop clinical events (ie, fetal wastage, arterial and/or venous thrombosis) associated with antiphospholipid syndrome ⁴⁵. Anti ̶ salivary duct antibodies are present in most cases of secondary Sjögren syndrome ⁴⁵.

Type II cryoglobulins are noted, particularly in patients with palpable and nonpalpable vasculitic purpura ⁴⁵. Hepatitis C should be sought in these patients.

In some studies, patients with Sjögren syndrome have an increased frequency of autoimmune thyroid disease with hypothyroidism (10-15%) ⁴⁵. Lymphocytic infiltration can be observed in the thyroid gland ⁴⁵.

Elevations of serum immunoglobulin G4 (IgG4), found in IgG4-related plasmacytic disease (which can mimic the glandular infiltrations of Sjögren syndrome), are not seen in Sjögren syndrome ⁴⁹, ⁵⁰.

Antibodies to carbonic anhydrase 11 can be seen in patients with Sjögren syndrome who have primary billiary cirrhosis ⁵¹.

American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) Sjögren’s syndrome Diagnostic Criteria

In 2016, a new set of Sjögren syndrome classification criteria was jointly endorsed by the American College of Rheumatology (ACR) and the European League against Rheumatism (EULAR) ⁷. These criteria have replaced two previous sets, those of the American-European Consensus Group 2002 ⁵² and the American College of Rheumatology 2012 classification criteria ⁵³. The new 2016 ACR-EULAR criteria incorporate elements of these previous sets and eliminate some that were outdated, but maintain the requirement that the diagnosis of Sjögren’s syndrome be only tenable if a patient has either anti-SSA antibodies or a “positive” minor salivary gland biopsy (focal lymphocytic sialadenitis with a focus score greater than or equal to 1).

• Labial salivary gland with focal lymphocytic sialadenitis and focus score ≥ 1. Score 3
• Anti-SSA (Ro) positive. Score 3
• Eye staining score ≥ 5 (or van Bijsterfeld score ≥ 4) on at least one eye. Score 1
• Schirmer test ≤ 5 mm/5 min on at least one eye. Score 1
• Unstimulated whole saliva flow rate ≤ 0.1 ml/min. Score 1

The classification of Sjogren’s syndrome applies to any individual who meets the inclusion criteria, does not have any condition listed as exclusion criteria, and who has a score ≥ 4 ⁷.

Inclusion criteria are criteria that are applicable to any patient with at least one symptom of eye or mouth dryness which is defined as a positive response to at least one of the following questions ⁷:

1. Have you had daily, persistent, troublesome dry eyes for more than 3 months?
2. Do you have a recurrent sensation of sand or gravel in the eyes?
3. Do you use tear substitutes more than 3 times a day?
4. Have you had a daily feeling of dry mouth for more than 3 months?
5. Do you frequently drink liquids to aid in swallowing dry food?); or suspicion of Sjogren’s syndrome from ESSDAI questionnaire (at least one domain with positive item)

Exclusion criteria: Prior diagnosis of any of the following conditions would exclude diagnosis of Sjogren’s syndrome because of overlapping clinical features or interference with criteria tests ⁷:

• History of head and neck radiation treatment
• Active Hepatitis C infection (with positive PCR)
• Acquired immunodeficiency syndrome
• Sarcoidosis
• Amyloidosis
• Graft versus host disease
• IgG4-related disease

Note: Patients who are normally taking anticholinergic drugs should be evaluated for objective signs of salivary hypofunction and ocular dryness after a sufficient interval off these medications for these components to be a valid measure of oral and ocular dryness.

Sjögren syndrome differential diagnosis

Differential diagnoses that should also be considered in the evaluation of Sjögren syndrome include ¹:

• Sarcoidosis
• Hashimoto thyroiditis
• Celiac disease
• Rosacea
• Mumps
• Dehydration
• Medications (eg, antidepressants and anticholinergics)
• Mouth breathing
• Lymphoma
• Advanced age with atrophy of exocrine tissues
• Sclerosing sialadenitis
• Parkinson disease
• Scleroderma
• Rheumatoid arthritis
• AIDS
• Lupus
• IgG4-related disease
• Sjögren syndrome/sicca syndrome associated with cancer immunotherapy

Sjogren’s syndrome treatment

There is no known cure for Sjogren’s syndrome nor is there a specific treatment to restore gland secretion. Sjogren’s syndrome treatment focuses on relieving symptoms. It can differ for each person; it depends on what parts of the body are affected. It may include artificial tears for dye eyes and sucking on sugar-free candy or drinking water often for a dry mouth. Medicines may help with severe symptoms. Moisture replacement therapies may ease the symptoms of dryness. Nonsteroidal anti-inflammatory drugs (NSAIDs) may be used to treat musculoskeletal symptoms. For individuals with severe complications, corticosteroids or immunosuppressive drugs that suppress the immune system may be prescribed.

Surgery is an option for some people, to stop the eyes draining tears. A minor procedure to seal the tear ducts that drain tears from your eyes (punctal occlusion) might help relieve your dry eyes. Collagen or silicone plugs are inserted into the ducts to help preserve your tears.

It is important to see your doctor or rheumatologist (joint specialist) regularly to make sure the condition stays well-managed.

There are also ways to manage symptoms yourself:

• Dry eyes – use artificial tears or an eye lubricant; regular check-ups with an ophthalmologist (eye specialist), wear protective eye-wear to avoid exposure to the wind or sun
• Dry mouth – drink frequent sips of water; avoid drinking alcohol; use artificial saliva, mouth rinses, sugarless gum or lozenges; keep your mouth very clean, limit sugar, regular check-ups with a dentist
• Dry skin – avoid hot water when you bathe and shower. Pat your skin — don’t rub — with a towel, and apply moisturizer when your skin is still damp. Use rubber gloves when doing dishes or housecleaning. Vaginal moisturizers and lubricants help women who have vaginal dryness.
• General dryness – increase indoor humidity; use preservative-free moisturizer for skin; avoid drying conditions such as drafts from heaters and air conditioners, use a saline spray for a dry nose, avoid exposure to dusty or windy weather.

To help with dry mouth:

• Don’t smoke. Smoking can irritate and dry out your mouth.
• Increase your fluid intake. Take sips of fluids, particularly water, throughout the day. Avoid drinking coffee or alcohol since they can worsen dry mouth symptoms. Also avoid acidic beverages such as colas and some sports drinks because the acid can harm the enamel of your teeth.
• Stimulate saliva flow. Sugarless gum or citrus-flavored hard candies can boost saliva flow. Because Sjogren’s syndrome increases your risk of dental cavities, limit sweets, especially between meals.
• Try artificial saliva. Saliva replacement products often work better than plain water because they contain a lubricant that helps your mouth stay moist longer. These products come as a spray or lozenge.
• Use nasal saline spray. A nasal saline spray can help moisturize and clear nasal passages so that you can breathe freely through your nose. A dry, stuffy nose can increase mouth breathing.

Dry mouth increases your risk of dental cavities and tooth loss. To help prevent those types of problems:

• Brush your teeth and floss after every meal
• Schedule regular dental appointments, at least every six months
• Use daily topical fluoride treatments and antimicrobial mouthwashes

Some medicines can cause eye and mouth dryness. If you are taking one of the drugs listed below, talk to your doctor about adjusting the dose or finding a different medicine. Don’t stop taking any medicine without asking your doctor. These can include medicines that you take for:

• Allergies and colds (antihistamines and decongestants).
• Getting rid of extra fluids in your body (diuretics).
• Diarrhea.
• High blood pressure.

Some type of medicines that can cause dryness include:

• Antipsychotic medicines.
• Tranquilizers.
• Antidepressants.

Treatments for dry eyes

If you have dry eyes, it can help to:

• avoid dry, smoky or windy places – it may help to use a humidifier at home or work to keep the air moist
• avoid reading, watching TV or looking at screens for a long time – this can dry your eyes out
• wear wraparound sunglasses or glasses with sides that help stop wind drying out your eyes
• clean your eyelids regularly – read more about how to keep your eyelids clean
• have regular check-ups with an optician
• avoid medicines that can cause dry eyes – check the leaflet that comes with a medicine to see if dry eyes is listed as a side effect

Eye drops and ointments

You can also try eye drops and ointments that help keep your eyes wet, sometimes known as artificial tears.

There are several different types of drops that can be bought from pharmacies without a prescription. You may need to try a few types to find one that works for you.

If you use eye drops more than three times a day, avoid drops that contain preservatives as these can damage your eyes if used frequently.

If the surface of your eye is irritated (inflamed), your doctor may prescribe drops containing steroids to use for a short period.

Sometimes other anti-inflammatory drops, such as cyclosporin drops, may be prescribed by an eye specialist.

Treatments for a dry mouth

If you have a dry mouth, it can help to:

• practise good oral hygiene – including brushing your teeth with fluoride toothpaste twice a day
• avoid sugary food and drinks, and avoid snacking between meals
• use antibacterial mouthwash
• drink plenty of water
• regularly chew sugar-free chewing gum or suck on ice cubes
• use lip balm if your lips are dry and cracked
• avoid alcohol – read advice about cutting back on alcohol
• stop smoking if you smoke
• have a dental check-up at least every six months
• avoid medicines that can cause a dry mouth – check the leaflet that comes with a medicine to see if dry mouth is listed as a side effect

Saliva substitutes

There are also products you can buy from pharmacies that help keep the mouth moist – known as saliva substitutes.

There are several different types available, including sprays, lozenges (medicated sweets) and gels. You may need to try a few types to find one that works for you.

But these products don’t help prevent mouth infections in the same way that saliva does, so it’s still important to practise good oral hygiene.

Treatments for dry skin

If you have dry skin, it may help to use a moisturizing cream (emollient) every day. It’s also a good idea to avoid strong, perfumed soaps. Use emollient soap substitutes instead.

Emollients are moisturizing treatments applied directly to the skin to soothe and hydrate it. They cover the skin with a protective film to trap in moisture.

Emollients are often used to help manage dry, itchy or scaly skin conditions such as eczema, psoriasis and ichthyosis. They help prevent patches of inflammation and flare-ups of these conditions.

Types of emollients

Emollients are available as:

• Lotions – good for hairy or damaged areas of skin (such as weeping eczema) as they’re thin and spread easily, but aren’t very moisturizing
• Sprays – good for hard-to-reach areas and sore or infected skin that shouldn’t be touched, and are absorbed quickly
• Creams – good for daytime use as they’re not very greasy and are absorbed quickly
• Ointments – good for very dry, thickened skin and night-time use as they’re greasy, thick and very moisturizing; they’re usually free of preservatives so are suitable for sensitive skin, but shouldn’t be used on weeping eczema
• Bath oils and shower products
• Soap substitutes

They can be bought over the counter from a pharmacy. If the skin condition is more severe, talk to a doctor, nurse or health visitor, as you may need a stronger treatment.

If you or your children need to use an emollient regularly, it’s a good idea to keep some in small pots or tubes at home, school or work.

Although aqueous cream is often prescribed, it’s not always the best option. Some people may have a reaction to an ingredient in aqueous cream, and it’s thinner and less effective than other products as a leave-on emollient.

Leave-on products

There are lots of different types of leave-on emollient that can be put directly on the skin. Some create a protective barrier over the skin to lock in moisture. Some have added ingredients to reduce itching or prevent infection.

Your doctor or pharmacist will talk to you about which type of emollient will work best for your skin condition. You may have to try a few different emollients to find the best one for your or your child’s skin. Many of these leave-on products can also be used to wash with.

Soap substitutes (emollient wash products)

Everyday soaps, shampoos and shower gels usually dry out the skin and can make skin conditions like eczema worse.

Using an emollient soap substitute instead of normal soap for handwashing and bathing can help improve your skin.

How to use emollients

• Leave-on emollients: Emollient lotions, sprays, creams and ointments should be applied directly to the skin. They should be smoothed, not rubbed, into the skin gently in the same direction that your hair grows. This helps prevent hair follicles getting blocked. They can be used to replace lost moisture whenever your skin feels dry or tight. They’re very safe and you can’t overuse them. You may need to experiment with different emollients or try a combination. For example, you may decide to use a cream during the day and an ointment at night.

• Soap substitutes (emollient wash products): Mix a small amount (around teaspoonful) of soap substitute in the palm of your hand with a little warm water and spread it over damp or dry skin. Rinse and pat the skin dry, being careful not to rub it. You can use soap substitutes for handwashing, showering or in the bath. They don’t foam like normal soap, but are just as effective at cleaning the skin. If your skin stings after using an emollient wash product and doesn’t settle after rinsing, ask a pharmacist to recommend a different soap substitute.

• Bath additives: Emollient bath additives often come as a bath oil. Add this to warm or lukewarm bath water and soak in it for at least 10 minutes. Once out of the bath, pat your skin dry with a towel. You can also apply bath oil directly to the skin in the shower, but this isn’t as effective as soaking in the bath. Using a bath additive leaves a protective film of oil over the skin that helps it stop losing moisture. Some bath oils contain an antiseptic, which can help prevent infections. But these products should only be used occasionally, unless the infection covers a large area of your skin or comes back. Talk to your doctor, nurse or pharmacist if you have questions about this. Never use more than the recommended amount of bath additive, as high concentrations may cause skin irritation.

Using emollients with other skin treatments

If you’re using a steroid cream or another treatment for your skin condition, wait at least 30 minutes after putting on your emollient before applying it.

This avoids diluting the effect of the treatment and spreading it to areas of skin that don’t need it.

When to apply emollients

Emollients can be applied as often as you like to keep the skin well moisturised and in good condition. Ideally, this should be done at least 3 or 4 times a day.

It’s especially important to regularly apply an emollient to your hands and face, as they’re exposed to the elements more than any other part of your body.

Certain activities, such as swimming or gardening, can irritate the skin. It may help to apply an emollient before doing these.

It’s a good idea to protect babies’ hands and cheeks with an emollient before meal times to stop them getting sore from food and drink.

Emollients are best applied after washing your hands, taking a bath or showering because this is when the skin most needs moisture.

The emollient should be applied as soon as you have patted your skin dry to make sure it’s properly absorbed.

Skin reactions

Emollients can sometimes cause a skin reaction, such as:

• an overheating, burning sensation or stinging that doesn’t settle after a few days of treatment – usually caused by a reaction to a certain ingredient contained in the emollient
• blocked or inflamed hair follicles (folliculitis) that may cause boils
• rashes on the face that can aggravate acne

If you experience any of these symptoms, talk to your doctor, nurse or pharmacist.

Safety advice when using emollients

Follow this general safety advice when using emollients:

• Keep away from fire, flames and cigarettes when using paraffin-based emollients. Dressings and clothing soaked with the ointment can be easily ignited.
• Use a clean spoon or spatula to remove emollients from a pot or tub. This reduces the risk of infections from contaminated pots.
• Take care of slipping when using emollients in a bath or shower, or on a tiled floor. Protect the floor with a non-slip mat, towel or sheet. Wearing protective gloves, wash your bath or shower after with hot water and washing up liquid, then dry with a kitchen towel.
• Never use more than the recommended amount of bath additive. It may cause skin irritation if the concentration is too high, particularly when used with antiseptic bath oils.
• Be careful of using aqueous cream. It can cause burning, stinging, itching and redness for some people, especially children with atopic eczema.

Treatments for vaginal dryness

Treatments for vaginal dryness include:

• water based lubricants – liquids or gels that you apply to your vagina just before having sex for immediate relief from dryness
• moisturizers – creams that you apply inside your vagina to keep it moist for a few days
• hormone treatments – such as estrogen medication you place in your vagina, or hormone replacement therapy (HRT)

Lubricants

Lubricants are liquids or gels that you apply to your vulva, vagina or your partner’s penis just before having sex to keep your vagina moist. They offer immediate but short-term relief from vaginal dryness.

Several different brands of lubricant are available to buy from shops and pharmacies without a prescription. You may need to experiment with a few different types to find one that works best for you.

Vaginal moisturizers

Vaginal moisturizers are creams that you apply inside your vagina to keep it moist.

They may be better than lubricants if the dryness isn’t just causing problems during sex, as they tend to have a longer-lasting effect. They usually need to be applied every few days.

As with lubricants, several different brands are available to buy. You may need to experiment with a few different types to find one that works best for you.

Water-based moisturizers are generally best, as oil or petroleum-based products can damage latex condoms and sometimes irritate the vagina.

Treatments for muscle and joint pain or stiffness

If you have pain or stiffness in your joints or muscles, it can help to:

• exercise regularly – a mixture of aerobic exercises (such as cycling)and strength and flexibility exercisesmay be helpful; a physiotherapist can recommend a suitable exercise plan
• take anti-inflammatory painkillers, such as ibuprofen – your doctor may prescribe stronger painkillers if these don’t work
• lose weight if you’re overweight

Sjogren’s syndrome medications

Depending on your symptoms, your doctor might suggest medications that:

• Decrease eye inflammation. Prescription eyedrops such as cyclosporine (Restasis) or lifitegrast (Xiidra) may be recommended by your eye doctor if you have moderate to severe dry eyes.
• Increase production of saliva. Drugs such as pilocarpine (Salagen) and cevimeline (Evoxac) can increase the production of saliva, and sometimes tears. Side effects can include sweating, abdominal pain, flushing and increased urination.
• Address specific complications. If you develop arthritis symptoms, you might benefit from nonsteroidal anti-inflammatory drugs (NSAIDs) or other arthritis medications. Yeast infections in the mouth should be treated with antifungal medications.
• Treat systemwide symptoms. Hydroxychloroquine (Plaquenil), a drug designed to treat malaria, is often helpful in treating Sjogren’s syndrome. Drugs that suppress the immune system, such as methotrexate (Trexall), also might be prescribed.

Medicines and procedures for dry eyes

If self-help measures and eye drops aren’t helping, your doctor may recommend:

• The medicine pilocarpine can be used to treat a dry mouth and eyes. It comes as tablets that help the body produce more saliva and tears.
• a procedure to block the tear ducts with tiny man-made plugs to stop tears draining away – this can help keep your eyes covered with a layer of tears, so they don’t feel as dry

Medicines for dry mouth

The medicine pilocarpine can be used to treat a dry mouth and eyes. It comes as tablets that help the body produce more saliva and tears.

But pilocarpine isn’t suitable for everyone and can cause some side effects, such as sweating, headaches, and needing to pee more often than normal.

If your doctor recommends pilocarpine, talk to them about the benefits and risks of taking it.

Medicines for for muscle and joint pain or stiffness

A medication called hydroxychloroquine is sometimes recommended by Sjogren’s syndrome specialists as a treatment for joint pain or stiffness if other methods haven’t helped.

But it isn’t suitable for everyone and can take several months to work. It can also cause side effects such as tummy pain and feeling sick.

Surgery

A minor procedure to seal the tear ducts that drain tears from your eyes (punctal occlusion) might help relieve your dry eyes. Collagen or silicone plugs are inserted into the ducts to help preserve your tears.

Sjogren’s syndrome prognosis

Sjogren’s syndrome can damage vital organs of your body with symptoms that may remain stable, worsen, or go into remission. Some people may experience only the mild symptoms of dry eyes and mouth, while others go through cycles of good health followed by severe disease. Mild Sjögren syndrome generally carries a favorable prognosis, while moderate to severe disease often results in diminished quality of life. Persistent symptoms such as dry mouth and dry eyes commonly lead to chronic pain, dental decay, and tooth loss.

Many patients are able to treat problems symptomatically. Others are forced to cope with blurred vision, constant eye discomfort, recurrent mouth infections, swollen parotid glands, hoarseness, and difficulty in swallowing and eating. Debilitating fatigue and joint pain can seriously impair quality of life.

In long term studies, the reduced glandular function in Sjogren’s syndrome has not been observed to improve. If arthritis, Raynaud phenomenon or interstitial nephritis are present early in the course of the illness they can resolve with treatment and time. Worse prognostic factors are the presence of glomerulonephritis, decreased blood levels of C4 complement, vasculitis and cryoglobulinemia.

Among patients with seropositive disease (positive SSA or SSB antibodies), approximately 7% developed ANA-associated rheumatologic conditions, e.g, systemic lupus erythematosus (SLE), polymyositis, and scleroderma (systemic sclerosis), over a follow-up period of 5 to 6 years ⁵⁴. Systemic diseases, skin abnormalities, kidney abnormalities, and hematological findings occur more frequently in patients with positive ANA or SSA serologies ⁶.

Ongoing long-term studies aim to identify which Sjögren syndrome patients face the greatest risk of complications. A recent French study revealed three distinct clinical subsets based on Sjögren syndrome disease activity scores (ESSDAI), patient-reported symptom burden (ESSPRI), and markers of B-cell activation ⁵⁵. One group consists of younger individuals with low systemic disease activity but a high symptom burden, typically including fatigue, dryness, and pain. These patients often exhibit increased B-cell activation, eg, hypergammaglobulinemia, reduced C4 levels, and higher seropositivity for SSA or SSB antibodies ⁵⁵. A second group presents with both high systemic disease activity and a high symptom burden. These individuals frequently possess additional autoantibodies, including anti-RNP or anti-centromere antibodies ⁵⁵. The third subset includes patients with a high symptom burden but low systemic disease activity. This cohort demonstrated minimal disease progression over a 5-year period and no lymphoma development during a 15-year follow-up. Patients with both high symptom burden and high systemic disease activity demonstrated the greatest risk for developing lymphoma ⁵⁵.

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