Sjögren's syndrome

Sjögren's syndrome is a chronic inflammatory disease characterized by dryness of the eyes, mouth, and vagina that tends to occur along with certain disorders of the immune system. It was first described by Henrik Sjögren in 1933. It predominately affects middle aged and elderly women.

Etiology and Pathogenesis

• Immunological findings: The lesion in this syndrome is immunologically mediated inflammatory exocrinopathy. It begins with periductal infiltration of the tissue by mononuclear cells.
• Autoantibodies: The B cell hyperactivity may result from deficiency of suppressor T lymphocytes or B lymphocytes by producing autoantibodies against them. Antinuclear antibodies found in patients with Sjögren's syndrome are directed against many nuclear antigens, most commonly to DNA histone. Patients with secondary Sjögren's syndrome tend to develop antibodies against the EBV-associated nuclear antigen antibodies RANA (rheumatoid arthritis nuclear antigen).
• Polyclonal hyperglobulinemia: Serum immunoglobulin levels of IgG and IgM are also raised.
• B2 microglobulin: Serum salivary level of B2 microglobulin is raised in minority of patients and correlates with salivary lymphocyte infiltrate.
• Immune complex: circulating immune complexes are found in patients with primary and secondary Sjögren's syndrome.
• Cell mediated immune response: Delayed hypersensitivity response to skin testing is more depressed in patients with secondary Sjögren's syndrome than in patients with primary Sjögren’s syndrome. Lymphokine production in response to antigen present in normal salivary tissue, is increased in patients with Sjögren’s syndrome.
• Genetic aspect: Genetic effects of Sjögren’s syndrome depend on HLA-linked and non HLA-linked genes. Relatives of a patient with Sjögren's syndrome often show a high incidence of connective tissue diseases. Primary Sjögren's syndrome is associated with HGLAB8 and DR3 and secondary Sjögren's syndrome is

associated with HLA-B8 DR4 and BW44.

• Lympho-proliferative malignancy: Enlargement of salivary glands in patients with Sjögren’s syndrome is occasionally massive and associated with enlargement of regional lymph nodes, a condition known as 'pseudo lymphoma'. Malignant B cell lympho-proliferation has been shown to affect patients with Sjögren's syndrome.

Types

• Primary Sjögren's syndrome: It is also called as sicca syndrome and it consists of dry eyes (xerophthalmia) and dry mouth (xerostomia).
• Secondary Sjögren's syndrome: It consists of dry eyes, dry mouth and collagen disorders usually rheumatoid arthritis or systemic lupus erythematous.

Clinical Features

• Age and sex distribution: It is more commonly seen in middle age adults. It is most commonly found in females with 90% of cases are reported in them.
• Eyes: The effect on eye is called as keratoconjunctivitis sicca (dry). The patient usually complains of dry eyes or continuous irritation in the eyes. Severe lacrimal gland involvement may lead to corneal ulceration as well as conjunctivitis.
• Connective tissue disorders: In patients with secondary Sjögren’s syndrome, rheumatoid arthritis is typically long standing and clinically obvious feature. Patients may have small joint and ulnar deviation of fingers and rheumatoid nodules.
• Dryness of other organ: Dryness of pharynx, larynx and nose are noted by some patients. This is accompanied by lack of secretion in the upper respiratory tract, may lead to pneumonia. Vaginal dryness may be also complained by some females.

Oral Manifestation

• Symptoms: Xerostomia is a major complaint in most of the patients. But many patients do not complain of dry mouth, but rather of an unpleasant taste, difficulty in eating dry food, soreness or difficulty in controlling dentures.
• Signs: Pus may be emitted from the duct. Angular stomatitis and denture stomatitis also occur.
• Salivary gland enlargement: Dry mouth may be accompanied by unilateral or bilateral enlargement of parotid gland, which occurs in about one-third of the patients and may be intermittent. Enlargement of submandibular gland may also occur.
• Saliva: Clinically, the mouth may appear moist in early stages of Sjögren’s syndrome but later, there may be lack of the usual pooling of saliva in the floor of the mouth and frothy saliva may form along the lines of contact with oral soft tissue.
• Mucosa: In advanced cases, the mucosa is glazed, dry and tends to form fine wrinkles. Soreness and redness of mucosa is usually the result of candidial infection.
• Speech: In some patients, there may be 'clicking' quality of their speech, caused by sticking of the tongue to the palate.
• Tongue: The tongue typically develops a characteristic lobulated, usually red surface with partial or complete depapillation. There is also decrease in number of taste buds, which leads to an abnormal and impaired sense of taste.
• Dental caries: Dental caries is severe and gross accumulation of plaque may be obvious.
• Periodontal disease: periodontal disease can also occur.
• Acute bacterial sialadenitis: Sjögren's syndrome is the most common underlying cause of acute bacterial sialadenitis in ambulated patients. Such infections are usually either staphylococcal or pneumoccocal and usually cause swelling of the salivary gland. The overlying skin is red, tender and shiny.
• Lymph nodes: The regional lymph nodes may be enlarged and tender.

Radiological Features

• Sialography: If the salivary flow rate is equivocal, sialography can be used to detect the damage. The most typical finding in Sjögren's syndrome is that of sialectasia, which typically produces a snowstorm appearance as a result of leakage of contrast medium. Atrophy of ductal tree may also be seen; emptying of the duct is also typically delayed. In some cases it will show cheery blossom or fruit laden branchless tree appearance of the obstructed ductal system.
• Salivary scintiscanning: salivary scinti scanning with technetium pertechnetate may be useful in demonstrating impaired salivary function in patients with Sjögren's syndrome. The changes correlate with both salivary flow rate and labial gland abnormalities.

Diagnosis

• Clinical diagnosis: xerostomia, keratoconjunctivitis sicca with parotid enlargement may aid in diagnosis of Sjögren's syndrome
• Sialography: snowstorm and branchless fruit laden tree appearance.
• Rose Bengal staining test: Keratoconjunctivitis sicca is characterized by corneal keratotic lesion, which stains pink when ‘rose Bengal’ dye is used.
• Schirmer test: The reduced lacrimal flow rate is measured by this test. A strip of filter paper is placed in between the eye and the eyelid to determine the degree of tears which should be measured in millimeter. When the flow is reduced to less than 5 mm in a 5 minute sample, patient should be considered positive for Sjögren's syndrome.
• Sialometry: salivary flow rate estimation is a sensitive indicator of salivary gland function. Parotid glands make the major contribution to total salivary flow and are the most consistently affected glands in patients with Sjögren's syndrome. Stimulated flow rate in symptomatic primary and secondary Sjögren's syndrome is usually below 0.5 to 1.0 ml/minute (normal 1 to 1.5 ml/minute).
• Sialochemistry: parotid saliva in Sjögren’s syndrome contains twice as much total lipid and has elevated content of phospholipids and glycolipids than the normal saliva. The sodium chloride and phospholipids levels are higher in saliva of Sjögren's syndrome patient.
• Immunologic: A routine autoantibody profile can usually be carried out with the particular aim of detecting rheumatoid and antinuclear factors.
• Hematological investigations: It is necessary, particularly to exclude anemia. ESR or plasma viscosity, leucopenia occasionally may also be found.
• Microbiological investigations: A swab from oral mucosa should be taken to confirm candidiasis, if there is soreness and erythema. Examination of pus is also of course essential as a guide to antimicrobial treatment, if acute sialadenitis develops.
• Salivary gland biopsy: The changes in minor glands of lower lip show close correlation with those in the major salivary glands and provide a safe and convenient source of material.

Management

• Ocular lubricant: Keratoconjunctivitis is treated by instillation of ocular lubricants, such as artificial tears coating methylcellulose and xerostomia is treated by saliva substitutes.
• Oral hygiene maintenance: scrupulous oral hygiene and frequent fluoride application is indicated to reduce these problems.
• Salivary stimulant: Bromhexine, pilocarpine and cevimeline can be used to stimulate salivary flow.
• Surgery: Surgery for enlargement of salivary gland is only recommended when the enlargement is casing discomfort to the patient.

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Source: Data courtesy of the U.S. National Library of Medicine. Since the data might have changed, please query MeSH on Sjögren's syndrome for any updates.

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