Elsevier

The Lancet

Volume 366, Issue 9482, 23–29 July 2005, Pages 321-331
The Lancet

Seminar
Sjögren's syndrome

https://doi.org/10.1016/S0140-6736(05)66990-5Get rights and content

Summary

Sjögren's syndrome is a chronic autoimmune disorder of the exocrine glands with associated lymphocytic infiltrates of the affected glands. Dryness of the mouth and eyes results from involvement of the salivary and lacrimal glands. The accessibility of these glands to biopsy enables study of the molecular biology of a tissue-specific autoimmune process. The exocrinopathy can be encountered alone (primary Sjögren's syndrome) or in the presence of another autoimmune disorder such as rheumatoid arthritis, systemic lupus erythematosus, or progressive systemic sclerosis. A new international consensus for diagnosis requires objective signs and symptoms of dryness including a characteristic appearance of a biopsy sample from a minor salivary gland or autoantibody such as anti-SS-A. Exclusions to the diagnosis include infections with HIV, human T-lymphotropic virus type I, or hepatitis C virus. Therapy includes topical agents to improve moisture and decrease inflammation. Systemic therapy includes steroidal and non-steroidal anti-inflammatory agents, disease-modifying agents, and cytotoxic agents to address the extraglandular manifestations involving skin, lung, heart, kidneys, and nervous system (peripheral and central) and haematological and lymphoproliferative disorders. The most difficult challenge in diagnosis and therapy is patients with symptoms of fibromyalgia (arthralgia, myalgia, fatigue) and oral and ocular dryness in the presence of circulating antinuclear antibodies.

Section snippets

Diagnosis: criteria and pitfalls

There is little disagreement among rheumatologists about the diagnosis of Sjögren's syndrome in a patient with obvious findings on physical examination of keratoconjunctivitis sicca, dry mouth, and the presence of ANA and antibodies to SS-A or SS-B. In these patients, the important issue is the extent of extraglandular disease and type of therapy needed.

In patients with milder sicca symptoms and less characteristic antibody profiles, diagnosis and therapy can be difficult. Although there is

Pathogenesis and relation to symptoms

Despite extensive study of the underlying cause of Sjögren's syndrome, the pathogenesis remains obscure. In broad terms, the pathogenesis is multifactorial; environmental factors are thought to trigger inflammation in individuals with a genetic predisposition to the disorder. In contrast to many other organ-specific autoimmune disorders, affected tissue can be obtained easily in Sjögren's syndrome by minor-salivary-gland biopsy; thus, researchers have an opportunity to study interaction between

Clinical features of the eyes

The characteristic ophthalmological finding in Sjögren's syndrome is keratoconjunctivitis sicca. In assessment of a patient complaining of dry eyes, the important aim is to find out whether the objective signs of dry eyes are commensurate with his or her symptoms. Methods to measure the integrity of the corneal surface and tear film include staining with Rose-Bengal, fluorescein, and lissamine green dye and the tear break-up time. A rheumatologist can rapidly and inexpensively assess the ocular

Oral symptoms and signs

Dryness of the mouth makes swallowing of food and even talking difficult, owing to dryness of the buccal mucosa. However, a dry mouth is not necessarily painful. The sudden development of pain in the mouth should stimulate a search for signs of angular cheilitis or erythematous petechial-type lesions on the palate (commonly under dentures); such findings suggest oral candidosis.45 Physicians46 generally do not appreciate the contribution of oral symptoms to quality of life. A series of tools

Extraglandular systemic manifestations

Systemic manifestations (table) are subdivided into non-visceral (skin, arthralgia, myalgia) and visceral (lung, heart, kidney, gastrointestinal, endocrine, central and peripheral nervous system). There is a close overlap in symptoms and signs between systemic lupus erythematosus and Sjögren's syndrome.9 We discuss the disorders more common in Sjögren's syndrome.

Skin manifestations of small vessels include palpable and non-palpable purpura in association with cryoglobulinaemia and

Pharmacological management

Non-visceral manifestations such as arthralgia and myalgia are generally treated with salicylates, non-steroidal agents, and hydroxychloroquine. As in systemic lupus erythematosus, corticosteroids are effective but limited by their usual side-effects including osteoporosis, diabetes, cardiovascular effects, and mood disruption. Patients with Sjögren's syndrome have greater problems with corticosteroids, including acceleration of periodontal disease and oral candidosis. Another difficulty is low

Search strategy and selection criteria

We searched MEDLINE (1977–2004) with the search terms “Sjögren's”, “Sjogren”, “keratoconjunctivitis sicca”, “xerostomia”, “salivary gland”, “lacrimal gland”, and “systemic lupus”, “systemic sclerosis” in association with ocular or oral manifestations. Several reviews and books were cited because they provide comprehensive overviews that are beyond the scope of this Seminar. The reference list was subsequently modified during the peer-review process on the basis of comments from the

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