Sjögren Syndrome

Salivary, lacrimal, and other exocrine glands become infiltrated with CD4+ T cells and with some B cells. The T cells produce inflammatory cytokines (eg, IL-2, interferon-gamma). Salivary duct cells also produce cytokines, eventually damaging the secretory ducts. Atrophy of the secretory epithelium of the lacrimal glands causes desiccation of the cornea and conjunctiva (keratoconjunctivitis sicca Keratoconjunctivitis Sicca Keratoconjunctivitis sicca is chronic, bilateral desiccation of the conjunctiva and cornea due to an inadequate tear film. Symptoms include itching, burning, irritation, and photophobia. Diagnosis... read more ). Lymphocytic infiltration and intraductal cellular proliferation in the parotid gland cause luminal narrowing and in some cases formation of compact cellular structures termed myoepithelial islands; atrophy of the gland can result. Dryness and gastrointestinal mucosal or submucosal atrophy and diffuse infiltration by plasma cells and lymphocytes may cause symptoms (eg, dysphagia).

Sjögren syndrome should be suspected in patients with gritty or dry eyes or dry mouth, enlarged salivary glands, peripheral neuropathy, purpura, or unexplained renal tubular acidosis. Such patients should receive diagnostic tests that can include evaluation of the eyes and salivary glands and serologic tests.

Different criteria have been proposed for classification of primary Sjögren syndrome. Modifications to the American-European classification criteria for primary Sjögren syndrome were proposed in 2016 (see table ; 1 Diagnosis references Sjögren syndrome is a relatively common chronic, autoimmune, systemic, inflammatory disorder of unknown cause. It is characterized by dryness of the mouth, eyes, and other mucous membranes ... read more ). Not every patient who receives a clinical diagnosis of Sjögren syndrome fulfills the proposed criteria, but the criteria provide useful guidance for evaluation and are applied to patients who have at least 1 symptom of eye or oral dryness:

To fulfill the criteria, patients must have at least 1 symptom of eye or oral dryness, must also have a score of ≥ 4, and must not have any of the following exclusion criteria:

The most common causes of dry eyes and dry mouth (sicca symptoms) are aging and medications, but when parotid enlargement occurs in addition to sicca symptoms, diseases such as hepatitis C Hepatitis C, Chronic Hepatitis C is a common cause of chronic hepatitis. It is often asymptomatic until manifestations of chronic liver disease occur. Diagnosis is confirmed by finding positive anti-HCV and positive... read more , HIV Human Immunodeficiency Virus (HIV) Infection Human immunodeficiency virus (HIV) infection results from 1 of 2 similar retroviruses (HIV-1 and HIV-2) that destroy CD4+ lymphocytes and impair cell-mediated immunity, increasing risk of certain... read more , bulimia Bulimia Nervosa Bulimia nervosa is characterized by recurrent episodes of binge eating followed by some form of inappropriate compensatory behavior such as purging (self-induced vomiting, laxative or diuretic... read more , and sarcoidosis Sarcoidosis Sarcoidosis is an inflammatory disorder resulting in noncaseating granulomas in one or more organs and tissues; etiology is unknown. The lungs and lymphatic system are most often affected, but... read more should be differentiated from Sjögren syndrome. When submandibular glands are enlarged, particularly in patients with a history of pancreatitis, IgG4-related disease IgG4-Related Disease Immunoglobulin G4-related disease (IgG4-RD) is a chronic immune-mediated fibroinflammatory disorder that often manifests with tumor-like masses and/or painless enlargement of multiple organs... read more (characterized by lymphoplasmacytic infiltration and fibrosis of various organs) should be considered.

Eye signs should be evaluated with the Schirmer test, which measures the quantity of tears secreted in 5 minutes after irritation from a filter paper strip placed under each lower eyelid. A young person normally moistens 15 mm of each paper strip. Most people with Sjögren syndrome moisten < 5 mm, although about 15% of test results are false-positive and 15% are false-negative. Ocular staining with an eye drop of rose bengal or lissamine green solution is highly specific. The total ocular staining score (OSS) for each eye is recorded (2 Diagnosis references Sjögren syndrome is a relatively common chronic, autoimmune, systemic, inflammatory disorder of unknown cause. It is characterized by dryness of the mouth, eyes, and other mucous membranes ... read more ). Slit-lamp examination showing a fluorescein tear breakup in < 10 seconds is also suggestive.

Salivary gland involvement can be confirmed by abnormally low saliva production (≤ 0.1 mL/minute) as measured by salivary flow, sialography, or salivary scintiscanning, although these tests are used infrequently. Saliva production can be qualitatively evaluated by several methods (3 Diagnosis references Sjögren syndrome is a relatively common chronic, autoimmune, systemic, inflammatory disorder of unknown cause. It is characterized by dryness of the mouth, eyes, and other mucous membranes ... read more ), including looking for normal pooling of saliva under the tongue. Alternatively, a tongue blade can be held against the buccal mucosa for 10 seconds. If the tongue blade falls off immediately when released, salivary flow is considered normal. The more difficulty encountered removing the tongue blade, the more severe the dryness. In women, the lipstick sign, where lipstick adheres to the front teeth, may be a useful indicator of dry mouth.

Autoantibodies have limited sensitivity and particularly low specificity. They include antibodies to Ro (SSA autoantibodies—see Systemic Lupus Erythematosus (SLE) Systemic Lupus Erythematosus (SLE) Systemic lupus erythematosus is a chronic, multisystem, inflammatory disorder of autoimmune etiology, occurring predominantly in young women. Common manifestations may include arthralgias and... read more ) or to nuclear antigens (termed La or SSB autoantibodies), antinuclear antibodies, or an elevated level of antibodies against gamma-globulin. Rheumatoid factor is present in > 70% of patients. Erythrocyte sedimentation rate (ESR) is elevated in 70%, 33% have anemia, and up to 25% have leukopenia. However, only SSA autoantibodies are included as part of the new classification criteria.

Histopathology is assessed by biopsy of minor salivary glands in the buccal mucosa. Salivary gland biopsy is usually reserved for patients in whom the diagnosis cannot be established by autoantibody testing or when a major organ is involved. Histopathologic involvement is confirmed if labial minor salivary glands show multiple large foci of lymphocytes with atrophy of acinar tissue. Biopsy can be complicated by protracted dysesthesias.

Sjögren syndrome is chronic. Overall health and life expectancy are mainly unaffected in patients whose only symptoms are dry eyes and mouth. However, prognosis is less favorable in those with systemic organ involvement. In those with severe disease, death may occasionally result from pulmonary infection and, rarely, from renal failure or lymphoma. Associated systemic autoimmune disorders may dictate prognosis.

Sjögren syndrome should be initially managed by topical therapy of dry eyes and dry mouth. Other systemic manifestations of the disease should be treated depending on the severity and the involved organ. Recognition of therapies for other conditions that can exacerbate dryness complaints is crucial. Oral hydroxychloroquine 5 mg/kg of body weight once a day is often given to halt the progression of the disease and for the treatment of arthralgias, but supportive trial data are limited. Oral methotrexate 15 to 20 mg once a week can be given for musculoskeletal manifestations.

Dry eyes should be treated with lubricating eye preparations (initially drops such as hypromellose or methylcellulose and an over-the-counter ointment at bedtime). Other treatments include drainage (punctal) duct closure and topical cyclosporine. Skin and vaginal dryness can be treated with lubricants.

Mouth dryness may be avoided by sipping fluids throughout the day, chewing sugarless gum, and using a saliva substitute containing carboxymethylcellulose as a mouthwash. Drugs that decrease salivary secretion (eg, antihistamines, antidepressants, other anticholinergics) should be avoided. Fastidious oral hygiene and regular dental visits are essential. Stones must be promptly removed, preserving viable salivary tissue. The pain of suddenly enlarged salivary glands is generally best treated with warm compresses and analgesics. Oral pilocarpine 5 mg 3 times a day or oral cevimeline hydrochloride 30 mg 3 times a day can stimulate salivary production but should be avoided in patients with bronchospasm and closed-angle glaucoma.

Aggressive systemic treatment is occasionally indicated; it is usually reserved for patients with associated diseases (eg, severe vasculitis, optic neuritis, or visceral involvement). Corticosteroids (eg, oral prednisone 1 mg/kg once a day), or rituximab may be needed in severe disease with cryoglobulinemic vasculitis, peripheral neuropathy/multiple mononeuropathy, severe parotid swelling, severe lung involvement, or inflammatory arthritis that does not respond to non-biologic therapy. (See also treatment guidelines for rheumatologic manifestations of Sjögren syndrome.)

Fatigue has no clearly effective treatment.

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