Sjogren's Syndrome

Written by: Dr Jeremy Steinberg – created: 16 December 2022; last modified: 12 March 2023

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Sjogren's Syndrome

Sjögren's syndrome (SS) is a chronic autoimmune disease that is characterised by reduced lacrimal and salivary gland function resulting in dry eyes and dry mouth. It can also result in skin disease, arthritis, nephritis, cytopaenia, pneumonitis, vasculitis, peripheral neuropathy, myelopathy, and cognitive dysfunction. The clinical features are divided into exocrine glandular features and extraglandular features.

Definitions

• Sjogren's disease - synonym for SS
• Sicca syndrome - synonym for SS
• Sicca complex - dryness of the eyes and mouth. Doesn't specify autoimmunity
• Keratoconjunctivitis sicca (KCS) - ocular findings of SS
• Dry eye syndrome (DES) - can be due to conditions such as SS and meibomian gland dysfunction. Only 10% of patients have SS.
• Mikulicz syndrome - parotid and lacrimal gland enlargement from any cause. Including SS or other conditions such as IgG4 related disease.

Epidemiology

SS is most common in women in their 50s and 60s. However it can affect young people as well as men. The overall prevalence is estimated at 43 per 100,000 people (0.043%). Dry eye and mouth occurs in up to 30% of older adults. This can be due to medication side effects and age-related atrophy of gland tissue.

Pathogenesis

Both genetic and non-genetic factors are thought to be involved. It is thought that SS occurs following an environmental trigger, likely viral (but no single virus has been implicated), in a genetically susceptible individual. The immune response involves both innate and adaptive immunity leading to autoimmunity and chronic inflammation. There is a cycle of mutual stimulation of the innate and acquired immune systems resulting in glandular injury.

The pathologic lesion is a lymphocytic infiltration of affected organs. The most frequently affected tissues are the lacrimal and salivary glands whereby there is focal aggregation of lymphocytes that start around the ducts and spread to the entire lobule. Infiltrates can also occur in extraglandular sites. Other mechanisms contribute to glandular dysfunction including antibodies to the muscarinic receptors that impair neural innervation of the gland as well as deleterious effects of cytokines on neurotransmitter release.

Specific autoantibodies are found in SS, particularly anti-Ro/SSA and anti-La/SSB in 60-80% of individuals. ANA antibodies are positive in around 90% of patients. High RF factor is also common. Autoantibodies can be found many years before the onset of SS. Autoantibodies alone are not sufficient for disease induction.

Clinical Presentation

SS occurs on a spectrum with a range of presentations.

On the mild to moderate side, patients have dry eyes and mouth along with fatigue, cognitive dysfunction, and myalgia. The diagnosis is confirmed by positive antibodies and/or gland biopsy. Without laboratory or histological studies the presentation may be identical to fibromyalgia or even patients with depression who have anticholinergic side effects from medication.

On the severe end patients may have frank salivary gland swelling and adenopathy. There may be cryoglobulinaemia, low complement, Hodgkin lymphoma, and extraglandular disease. Antibodies may again be positive.

In a minority of patients there is primary extraglandular involvement with limited eye or mouth symptoms. The diagnosis may be made, e.g. with positive antibodies, during workup of neuropathies, nephropathies, interstitial pneumonitis, or haematologic abnormalities.

Diagnosis

There is no single test. The diagnosis is made with having both objective clinical and laboratory features, following exclusion of other causes. The diagnosis can't be made with the presence of autoantibodies and no compatible symptoms.

Objective clinical findings of mouth or eye dryness: this includes one of abnormal Schirmer test of either eye, abnormal sialometry or Saxon test for the glands, or radiological evidence such as on MRI, CT, or US.

Serological or histological findings: Anti-Ro/SSA +/- Anti-La antibodies or positive labial salivary gland biopsy showing focal lymphocytic sialednitis. In the presence of isolated anti-La antibodies, biopsy is required to confirm the diagnosis. A diagnosis of secondary SS can be made without antibodies or biopsy in the presence of a well-established systemic rheumatological disease such as SLE or RA. Also acceptable are positive anticentromere antibodies without systemic sclerosis or findings of ANA greater or equal to 1:320 along with positive RF.

In individuals with isolated extraglandular disease, the diagnosis can be made with positive biopsy and anti-Ro antibodies.

Differential Diagnosis

Differential Diagnosis of SS

• Age-related Sicca Syndrome
• IgG4-related disease
• Eosinophilic sialodochitis
• Benign lymphoepithelial sialadenitis and dacryoadenitis
• Lymphona and other haematologic malignancy
• Sarcoidosis
• Hepatitis C
• HIV
• Graft-versus-host disease
• Sicca induced by immune checkpoint inhibitors
• Systemic vasculitis

Management

Management is similar for primary and secondary SS

General Measures

For mild SS without extraglandular disease systemic therapy is not usually required. Secretagogues plus local therapy for ocular and oral symptoms can be used such as artificial tears.

Smoking increases the risk of dental decay and other oral complications as well as reduces the efficacy of medications such as hydroxychloroquine. It also aggravates small airway disease. Medications that exacerbate drying side effects should be avoided.

Pregnancy counseling should be provided. The most serious adverse fetal outcome in SS is congenital heart block. Other complications are more common such as fetal loss, IUGR, and premature deliver.

Patietns are at increased risk of complications from surgery requiring general anaesthesia. Anticholinergic drugs and the low-humidity environment of the operating theatre predisposes to ocular surface, mucosal, and dental damage. There is increased risk of atelectasis.

Pharmacologic

Pilocarpine and cevimeline are examples of muscarinic agonists used as secretagogues.

For moderate to severe disease systemic therapy is usually used. The approach is similar to SLE and RA. Systemic therapy options include glucocorticoids, hydroxychloroquine, methotrexate, leflunomide, azathioprine, sulfasalazine, mycophenolate, cyclosporine, cyclophosphamide, and rituximab.

Literature Review

Literature Review

Reviews from the last 7 years: review articles, free review articles, systematic reviews, meta-analyses, NCBI Bookshelf

Articles from all years: PubMed search, Google Scholar search.

TRIP Database: clinical publications about evidence-based medicine.

Other Wikis: Radiopaedia, Wikipedia Search, Wikipedia I Feel Lucky, Orthobullets,