Sjögren's Syndrome

Overview

Sjögren's syndrome (pronounced "SHOW-grins") is a chronic autoimmune disorder in which the body's immune system mistakenly attacks its own moisture-producing glands. This primarily affects the salivary glands in the mouth and the lacrimal glands in the eyes, leading to the hallmark symptoms of dry mouth (xerostomia) and dry eyes (keratoconjunctivitis sicca). Named after Swedish ophthalmologist Henrik Sjögren who first described it in 1933, this condition affects millions of people worldwide, with women being nine times more likely to develop it than men.

The syndrome can occur alone (primary Sjögren's syndrome) or alongside other autoimmune conditions such as rheumatoid arthritis or lupus (secondary Sjögren's syndrome). While the most noticeable symptoms involve dryness of the eyes and mouth, Sjögren's syndrome is a systemic condition that can affect multiple organ systems throughout the body, including the joints, skin, lungs, kidneys, blood vessels, digestive system, and nervous system.

Although Sjögren's syndrome can develop at any age, most people are diagnosed after age 40, with the average age of diagnosis being in the late 40s to early 50s. The condition varies greatly in severity, from mild discomfort to significant impairment of quality of life. While there is no cure, various treatments can help manage symptoms and prevent complications, allowing most people with Sjögren's syndrome to lead active, productive lives.

Symptoms

The symptoms of Sjögren's syndrome can vary widely from person to person and may develop gradually over time. While dry eyes and dry mouth are the most characteristic features, the condition can affect many parts of the body, leading to a diverse range of symptoms that may fluctuate in severity.

Primary Symptoms

Systemic Symptoms

Additional Common Symptoms

• Oral symptoms: Swollen salivary glands, frequent thirst, cracked lips, oral thrush
• Skin manifestations: Dry skin, rashes, purple spots (purpura), Raynaud's phenomenon
• Respiratory symptoms: Persistent dry cough, shortness of breath, recurrent bronchitis
• Digestive issues: Acid reflux, difficulty eating dry foods, constipation
• Vaginal dryness: Discomfort, increased risk of infections, painful intercourse
• Neurological symptoms: Peripheral neuropathy, cognitive difficulties ("brain fog")
• Kidney involvement: Interstitial nephritis, kidney stones
• Blood vessel inflammation: Vasculitis causing rash or organ damage

Complications

• Dental decay and gum disease from reduced saliva
• Corneal damage and vision problems
• Oral and vaginal yeast infections
• Lymphoma (slightly increased risk)
• Pregnancy complications in some cases
• Peripheral neuropathy
• Kidney or liver problems

Causes

The exact cause of Sjögren's syndrome remains unknown, but research suggests it results from a complex interaction of genetic, environmental, and hormonal factors that trigger an abnormal immune response. In this autoimmune process, the body's immune system mistakenly identifies its own moisture-producing glands as foreign invaders and attacks them.

Autoimmune Process

In Sjögren's syndrome, the immune system produces autoantibodies and activates white blood cells (lymphocytes) that infiltrate and damage the exocrine glands, particularly:

• Salivary glands: Leading to reduced saliva production and dry mouth
• Lacrimal glands: Causing decreased tear production and dry eyes
• Other exocrine glands: Throughout the body, affecting various organs

Contributing Factors

• Genetic predisposition:
  • Certain HLA gene variants increase susceptibility
  • Family history of autoimmune diseases
  • Multiple genes likely involved
• Environmental triggers:
  • Viral infections (Epstein-Barr virus, hepatitis C, retroviruses)
  • Bacterial infections
  • Chronic inflammation
  • Stress or trauma
• Hormonal factors:
  • Female predominance suggests hormonal influence
  • Often develops during hormonal changes (menopause)
  • Estrogen may play a role in immune regulation

Pathophysiology

The disease process involves:

• T and B lymphocyte activation and infiltration of glands
• Production of autoantibodies (anti-SSA/Ro and anti-SSB/La)
• Inflammatory cytokine release
• Progressive destruction of glandular tissue
• Fibrosis and loss of secretory function
• Systemic inflammation affecting multiple organs

Risk Factors

Several factors increase the likelihood of developing Sjögren's syndrome:

Demographic Factors

• Gender: Women are 9-10 times more likely to develop Sjögren's syndrome
• Age: Most commonly diagnosed between ages 40-60, though can occur at any age
• Ethnicity: Slightly higher prevalence in Caucasians, though affects all ethnic groups

Medical Risk Factors

• Other autoimmune diseases:
  • Rheumatoid arthritis
  • Systemic lupus erythematosus
  • Scleroderma
  • Autoimmune thyroid disease
  • Primary biliary cholangitis
• Family history: First-degree relatives with autoimmune diseases
• Previous infections: History of certain viral infections

Environmental and Lifestyle Factors

• Exposure to certain medications that can trigger sicca symptoms
• Occupational exposure to solvents or chemicals (under investigation)
• Chronic stress may trigger or exacerbate symptoms
• Smoking may worsen dry mouth and eye symptoms

Genetic Markers

• HLA-DR3 and HLA-DR2 gene variants
• Presence of certain autoantibody profiles
• Polymorphisms in immune system genes

Diagnosis

Diagnosing Sjögren's syndrome can be challenging because symptoms develop gradually and mimic other conditions. A comprehensive evaluation by a rheumatologist or specialist familiar with autoimmune diseases is often necessary. Diagnosis typically involves a combination of clinical assessment, laboratory tests, and specialized procedures.

Clinical Evaluation

• Medical history: Detailed symptom assessment, duration, severity
• Physical examination: Checking for dry eyes/mouth, swollen glands, joint involvement
• Review of medications: Many drugs can cause sicca symptoms
• Family history: Autoimmune diseases in relatives

Diagnostic Criteria

The 2016 ACR/EULAR classification criteria include:

• Labial salivary gland biopsy with focal lymphocytic sialadenitis
• Anti-SSA/Ro antibody positivity
• Ocular staining score ≥5
• Schirmer's test ≤5mm/5min
• Unstimulated whole saliva flow rate ≤0.1ml/min

Laboratory Tests

• Autoantibody tests:
  • Anti-SSA/Ro and anti-SSB/La antibodies (specific for Sjögren's)
  • Antinuclear antibodies (ANA)
  • Rheumatoid factor (RF)
  • Anti-mitochondrial antibodies
• Blood tests:
  • Complete blood count (may show anemia, low white cells)
  • Inflammatory markers (ESR, CRP)
  • Immunoglobulin levels (often elevated)
  • Kidney and liver function tests

Specialized Tests

• Eye tests:
  • Schirmer's test: Measures tear production
  • Rose bengal or lissamine green staining: Shows corneal damage
  • Tear break-up time: Assesses tear film stability
  • Ocular surface disease index questionnaire
• Salivary gland tests:
  • Unstimulated salivary flow test
  • Salivary gland ultrasound
  • Sialography (X-ray of salivary glands)
  • Salivary scintigraphy
• Lip biopsy: Minor salivary gland biopsy showing lymphocytic infiltration

Differential Diagnosis

Conditions that may mimic Sjögren's syndrome:

• Medication-induced dry mouth/eyes
• Dehydration
• Diabetes
• Hepatitis C
• Sarcoidosis
• IgG4-related disease
• Graft-versus-host disease
• Radiation therapy effects

Treatment Options

While there is no cure for Sjögren's syndrome, various treatments can effectively manage symptoms, prevent complications, and improve quality of life. Treatment is individualized based on symptom severity and organ involvement, ranging from topical therapies for dryness to systemic medications for more severe manifestations.

Management of Dry Eyes

• Artificial tears: Preservative-free drops used frequently throughout the day
• Lubricating ointments: Thicker formulations for nighttime use
• Cyclosporine eye drops: Restasis or Xiidra to increase tear production
• Punctal plugs: Tiny devices to block tear drainage
• Moisture chamber glasses: Special eyewear to retain moisture
• Warm compresses: For meibomian gland dysfunction
• Omega-3 supplements: May improve tear quality
• Environmental modifications: Humidifiers, avoiding wind and smoke

Management of Dry Mouth

• Saliva substitutes: Artificial saliva sprays and gels
• Secretagogues:
  • Pilocarpine (Salagen): Stimulates saliva production
  • Cevimeline (Evoxac): Specific for Sjögren's syndrome
• Sugar-free gum/candies: Stimulate natural saliva flow
• Frequent water sips: Keep mouth moist
• Fluoride treatments: Prevent dental decay
• Prescription toothpastes: High-fluoride formulations
• Avoid: Alcohol-based mouthwashes, caffeine, tobacco

Systemic Medications

• NSAIDs: For joint pain and inflammation
• Hydroxychloroquine: May help fatigue, joint pain, and rashes
• Corticosteroids: For severe flares or organ involvement
• Immunosuppressants:
  • Methotrexate for arthritis
  • Azathioprine for systemic involvement
  • Mycophenolate for kidney disease
• Biologics:
  • Rituximab for severe systemic disease
  • Other biologics under investigation

Symptom-Specific Treatments

• Vaginal dryness: Lubricants, moisturizers, estrogen cream
• Joint pain: Physical therapy, gentle exercise
• Fatigue: Energy conservation, graded exercise, treat underlying causes
• Neuropathy: Gabapentin, pregabalin, or duloxetine
• Acid reflux: Proton pump inhibitors
• Skin dryness: Moisturizers, mild soaps

Lifestyle Modifications

• Regular dental care (cleanings every 3-4 months)
• Good oral hygiene with electric toothbrush
• Humidify living and working spaces
• Wear sunglasses outdoors
• Stay well-hydrated
• Manage stress through relaxation techniques
• Regular gentle exercise
• Balanced, anti-inflammatory diet

Prevention

Since the exact cause of Sjögren's syndrome is unknown, primary prevention is not currently possible. However, early recognition and management can prevent or minimize complications. For those diagnosed with the condition, secondary prevention focuses on maintaining gland function and preventing organ damage.

Complication Prevention

• Dental health:
  • Regular dental check-ups every 3-4 months
  • Daily fluoride treatments
  • Minimize sugar intake
  • Treat dry mouth aggressively
• Eye health:
  • Regular ophthalmology exams
  • Consistent use of lubricating drops
  • Protect eyes from wind and irritants
  • Monitor for corneal damage
• Infection prevention:
  • Good hygiene practices
  • Prompt treatment of infections
  • Vaccinations as recommended
  • Avoid sick contacts when possible

Monitoring and Screening

• Regular rheumatology follow-ups
• Annual blood work to monitor organ function
• Screening for lymphoma (slightly increased risk)
• Monitor for development of other autoimmune conditions
• Pregnancy planning and monitoring if applicable

Lifestyle Measures

• Maintain good overall health
• Avoid medications that worsen dryness when possible
• Stop smoking and limit alcohol
• Manage stress effectively
• Stay current with vaccinations

When to See a Doctor

Early diagnosis and treatment of Sjögren's syndrome can help prevent complications and improve quality of life. Certain symptoms warrant medical evaluation:

Seek Medical Attention For:

• Persistent dry eyes or mouth lasting more than 3 months
• Recurrent swelling of salivary glands
• Unexplained dental decay despite good oral hygiene
• Persistent joint pain or swelling
• Unexplained fatigue affecting daily activities
• Recurrent eye infections or vision changes
• Difficulty swallowing or speaking due to dryness
• Skin rashes or purple spots
• Numbness or tingling in hands or feet

Urgent Symptoms Requiring Immediate Care:

• Severe eye pain or sudden vision loss
• Signs of serious infection (fever, chills, confusion)
• Severe abdominal pain (possible pancreas involvement)
• Difficulty breathing or chest pain
• Signs of kidney problems (blood in urine, swelling)
• Severe headache or neurological symptoms

Regular Monitoring

If diagnosed with Sjögren's syndrome, maintain regular appointments with:

• Rheumatologist for overall disease management
• Ophthalmologist for eye care
• Dentist for oral health
• Other specialists as needed based on organ involvement

Related Conditions

References

1. Mariette X, Criswell LA. Primary Sjögren's Syndrome. New England Journal of Medicine. 2018;378:931-939.
2. Shiboski CH, et al. 2016 American College of Rheumatology/European League Against Rheumatism Classification Criteria for Primary Sjögren's Syndrome. Arthritis & Rheumatology. 2017.
3. Vivino FB, et al. Sjögren's syndrome: Clinical aspects. Clinical Immunology. 2017;182:48-54.
4. Sjögren's Syndrome Foundation. Clinical Practice Guidelines. 2023.
5. Ramos-Casals M, et al. Primary Sjögren syndrome. British Medical Journal. 2022.
6. National Institute of Arthritis and Musculoskeletal and Skin Diseases. Sjögren's Syndrome. 2023.