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Other meanings of Sjögren syndrome

Autoimmune Diseases

Sjögren syndrome

Sjögren syndrome is a chronic autoimmune disorder characterized by lymphocytic infiltration of exocrine glands, leading to dryness of the eyes and mouth, and often accompanied by systemic symptoms such as fatigue and joint pain. It can occur alone (primary Sjögren syndrome) or in association with other autoimmune diseases like rheumatoid arthritis or systemic lupus erythematosus (secondary Sjögren syndrome). The condition affects approximately 0.1–4% of the population, with a strong female predominance (9:1 ratio) and typical onset in the fourth to sixth decades of life.1

0.1–4%
Prevalence in general population
Estimated prevalence varies by diagnostic criteria and population
9:1
Female-to-male ratio
Strong female predominance
40–60
Typical age of onset (years)
Most commonly diagnosed in middle age
5–10%
Risk of lymphoma
Lifetime risk of non-Hodgkin lymphoma in primary Sjögren syndrome
1

Clinical features and diagnosis

The hallmark symptoms are keratoconjunctivitis sicca (dry eyes) and xerostomia (dry mouth), resulting from immune-mediated destruction of lacrimal and salivary glands. Patients often report a gritty sensation in the eyes, difficulty swallowing dry food, and a need to sip water frequently. Systemic manifestations include fatigue, arthralgia, Raynaud phenomenon, and interstitial lung disease. Diagnosis relies on the 2016 ACR/EULAR classification criteria, which combine objective tests such as Schirmer test, ocular surface staining, salivary flow measurement, and the presence of anti-SSA/Ro antibodies or a positive minor salivary gland biopsy showing focal lymphocytic sialadenitis.1 The differential diagnosis includes drug-induced dryness, hepatitis C, and IgG4-related disease.

2

Pathophysiology and genetics

The pathogenesis involves an interplay of genetic susceptibility, environmental triggers, and dysregulated immune responses. Genome-wide association studies have identified risk loci in the HLA region (particularly HLA-DRB1*03) and in genes such as IRF5, STAT4, and BLK, implicating type I interferon signaling and B-cell activation.2 Viral infections, notably Epstein-Barr virus and coxsackievirus, have been proposed as triggers, though no definitive causative agent is established. The autoimmune process is characterized by infiltration of CD4+ T cells, B cells, and plasma cells into exocrine glands, leading to glandular destruction and dysfunction. Aberrant activation of the type I interferon pathway is a central feature, with elevated expression of interferon-stimulated genes in peripheral blood and salivary gland tissue.

3

Management and complications

Treatment is symptomatic and multidisciplinary, focusing on relieving dryness and managing systemic manifestations. Artificial tears, saliva substitutes, and muscarinic agonists such as pilocarpine or cevimeline are first-line therapies. For systemic symptoms, hydroxychloroquine is commonly used, though evidence for its efficacy is limited; more severe cases may require corticosteroids or immunosuppressants like methotrexate or rituximab.3 The most serious complication is the development of non-Hodgkin lymphoma, particularly mucosa-associated lymphoid tissue (MALT) lymphoma, which occurs in 5–10% of patients, especially those with persistent parotid gland swelling, lymphadenopathy, and low complement levels. Regular monitoring for lymphoma is recommended.

4

Lesser-known aspects

Beyond the classic sicca symptoms, Sjögren syndrome can affect the nervous system, causing peripheral neuropathy, autonomic dysfunction, and even cognitive impairment (often termed 'brain fog').4 A rare but severe subtype is primary Sjögren syndrome with renal involvement, leading to distal renal tubular acidosis and nephrogenic diabetes insipidus. The disease also has a significant impact on oral health, with increased risk of dental caries and oral candidiasis. Notably, the syndrome was first described in 1933 by Swedish ophthalmologist Henrik Sjögren, but a similar condition was reported earlier by Mikulicz in 1892, and the term 'sicca syndrome' is sometimes used interchangeably. In addition, the presence of anti-centromere antibodies in a subset of patients defines a distinct clinical phenotype with more severe Raynaud phenomenon and pulmonary hypertension.

Glossary

Keratoconjunctivitis sicca
Dryness of the conjunctiva and cornea due to reduced tear production.
Xerostomia
Dry mouth caused by reduced salivary flow.
Anti-SSA/Ro antibodies
Autoantibodies against Ro/SSA ribonucleoproteins, a hallmark of Sjögren syndrome.
MALT lymphoma
A type of non-Hodgkin lymphoma arising from mucosa-associated lymphoid tissue.
Schirmer test
A test measuring tear production using filter paper strips.

The term 'Sjögren syndrome' is sometimes used interchangeably with 'sicca syndrome', but the latter is a broader term that includes dryness from non-autoimmune causes.