Sjögren’s syndrome

Sjögren’s syndrome is a chronic autoimmune disorder characterised by the body’s immune system mistakenly attacking the exocrine glands, particularly the salivary and lacrimal glands, leading to dryness of the mouth (xerostomia) and eyes (keratoconjunctivitis sicca). It can occur as an isolated condition (primary Sjögren’s syndrome) or in association with other autoimmune diseases such as rheumatoid arthritis or systemic lupus erythematosus (secondary Sjögren’s syndrome).
This syndrome primarily affects middle-aged women and has a gradual onset, often making diagnosis challenging. Although dryness is the hallmark feature, Sjögren’s syndrome can also involve multiple organ systems, including the skin, joints, lungs, kidneys, and nervous system.

Historical Background

The condition is named after Dr. Henrik Sjögren, a Swedish ophthalmologist who first described the disease in 1933 after studying women suffering from arthritis and chronic dryness of eyes and mouth. His observations led to the recognition of a distinct autoimmune disorder affecting the body’s secretory glands.

Aetiology and Pathogenesis

The exact cause of Sjögren’s syndrome remains unknown, but it is believed to arise from a combination of genetic, environmental, hormonal, and immune factors.
Key mechanisms involved include:

• Autoimmune Response: The immune system targets the body’s own glandular tissues, resulting in inflammation and gradual destruction of salivary and lacrimal glands.
• Genetic Predisposition: Certain HLA genotypes (e.g., HLA-DR3, HLA-B8) are associated with increased susceptibility.
• Environmental Triggers: Viral infections (such as Epstein–Barr virus, cytomegalovirus, or hepatitis C virus) may initiate the autoimmune process.
• Hormonal Influence: The predominance of the disease in females suggests that oestrogen deficiency may contribute to disease expression.

The autoimmune attack leads to lymphocytic infiltration (particularly by CD4+ T cells and B cells) within the glands, replacing normal tissue and reducing secretion.

Classification

1. Primary Sjögren’s Syndrome:
   • Occurs independently, without association with other autoimmune disorders.
   • Characterised mainly by dryness of eyes and mouth (sicca symptoms).
2. Secondary Sjögren’s Syndrome:
   • Occurs alongside other autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, or systemic sclerosis.
   • May present with additional systemic and joint manifestations.

Clinical Features

The symptoms of Sjögren’s syndrome can be divided into glandular (exocrine) and extra-glandular (systemic) manifestations.

1. Glandular Manifestations

• Ocular Symptoms (Dry Eyes):
  • Sensation of burning, grittiness, or foreign body in the eyes.
  • Redness, itching, and photophobia.
  • Blurred vision and corneal damage in severe cases.
• Oral Symptoms (Dry Mouth):
  • Difficulty in chewing, swallowing, and speaking.
  • Increased thirst and frequent need to sip water.
  • Cracked lips, sore tongue, and dental caries due to lack of saliva.
  • Recurrent salivary gland swelling, especially the parotid glands.
• Other Mucosal Surfaces:
  • Dryness of nasal passages, throat, trachea, and vagina.
  • Hoarseness, chronic cough, or vaginal discomfort.

2. Extra-glandular Manifestations

• Musculoskeletal: Arthralgia, arthritis, myalgia, and fatigue.
• Skin: Dryness (xerosis), vasculitic rashes, purpura.
• Respiratory System: Dry cough, interstitial lung disease.
• Renal: Tubulointerstitial nephritis, renal tubular acidosis.
• Neurological: Peripheral neuropathy, cognitive dysfunction.
• Hepatic: Autoimmune hepatitis or primary biliary cholangitis.
• Haematological: Anaemia, leukopenia, increased risk of non-Hodgkin’s lymphoma due to chronic B-cell activation.

Diagnostic Criteria

Diagnosis of Sjögren’s syndrome is based on a combination of clinical symptoms, serological tests, and histopathological findings.
Key diagnostic tools include:

1. Schirmer’s Test:
   • Measures tear production using filter paper placed under the lower eyelid.
   • Wetting of less than 5 mm in 5 minutes indicates reduced tear secretion.
2. Rose Bengal or Lissamine Green Staining:
   • Detects damage to the conjunctiva and cornea due to dryness.
3. Sialometry:
   • Measures the flow rate of saliva. Reduced flow confirms salivary gland dysfunction.
4. Salivary Gland Scintigraphy or Sialography:
   • Imaging tests used to evaluate salivary gland structure and function.
5. Minor Salivary Gland Biopsy (Lip Biopsy):
   • Demonstrates lymphocytic infiltration and destruction of glandular tissue.
6. Serological Tests:
   • Anti-SSA (Ro) and Anti-SSB (La) antibodies: Highly specific markers.
   • Rheumatoid factor (RF) and antinuclear antibodies (ANA): Frequently positive.
   • Elevated ESR and hypergammaglobulinaemia indicate chronic inflammation.

According to the American-European Consensus Group Criteria (AECG) and the ACR–EULAR Classification Criteria (2016), diagnosis requires both objective evidence of dryness and serological or histological confirmation.

Differential Diagnosis

Sjögren’s syndrome must be distinguished from other causes of dryness or glandular dysfunction, including:

• Dehydration or ageing.
• Medication side effects (antihistamines, antidepressants, diuretics).
• Sarcoidosis.
• Chronic viral infections (Hepatitis C, HIV).
• Radiation therapy to head and neck.

Management and Treatment

There is no definitive cure for Sjögren’s syndrome; treatment focuses on symptom relief, prevention of complications, and control of systemic involvement.
1. Management of Glandular Symptoms:

• Artificial Tears and Lubricating Eye Drops: To relieve ocular dryness.
• Punctal Occlusion: Blocking tear drainage ducts to retain moisture.
• Artificial Saliva or Sugar-free Lozenges: To alleviate dry mouth.
• Good Oral Hygiene: Prevents dental caries and oral infections.
• Pilocarpine or Cevimeline: Muscarinic agonists that stimulate saliva and tear secretion.

2. Management of Systemic Symptoms:

• Non-steroidal Anti-inflammatory Drugs (NSAIDs): For arthralgia or mild arthritis.
• Corticosteroids and Immunosuppressants: Such as hydroxychloroquine, methotrexate, or azathioprine, used for severe systemic involvement.
• Biologic Agents (Investigational): Rituximab and other monoclonal antibodies targeting B-cells have shown promise in selected cases.

3. Lifestyle and Supportive Measures:

• Adequate hydration.
• Avoidance of caffeine, alcohol, and tobacco.
• Use of humidifiers indoors.
• Regular ophthalmic and dental check-ups.

Complications

If untreated or poorly managed, Sjögren’s syndrome can lead to:

• Corneal ulceration or vision loss due to severe dryness.
• Extensive dental decay and oral infections.
• Difficulty swallowing or chronic hoarseness.
• Systemic organ involvement (lungs, kidneys, nerves).
• Increased risk of non-Hodgkin’s lymphoma, particularly mucosa-associated lymphoid tissue (MALT) lymphoma.

Prognosis

The prognosis of Sjögren’s syndrome is generally favourable for most patients with mild glandular symptoms. However, those with systemic manifestations or lymphoma risk require long-term monitoring. The disease is chronic and progressive, but early diagnosis and appropriate management can greatly improve quality of life and prevent severe complications.

Summary of Key Features

Conclusion

Sjögren’s syndrome is a complex autoimmune disorder characterised by dryness, fatigue, and systemic inflammation. While its hallmark features involve the eyes and mouth, the condition can affect multiple organs and significantly impact quality of life. Early recognition and multidisciplinary management—combining symptomatic relief, immune modulation, and lifestyle adjustments—are essential for preventing complications and ensuring long-term stability. It remains an area of active research, particularly in understanding immune mechanisms and developing targeted biological therapies.