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REVIEW ARTICLE
Year : 2008  |  Volume : 20  |  Issue : 3  |  Page : 85-89 Table of Contents   

Sjogren's syndrome


Department of Oral Medicine, Diagnosis and Radiology, KLE'S V.K. Institute of Dental Sciences, Belgaum, Karnataka, India

Date of Web Publication16-Jun-2009

Correspondence Address:
Ankur Jethlia
Department of Oral Medicine and Radiology, KLE'S V.K. Institute of Dental Sciences, Belgaum, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0972-1363.52772

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   Abstract 

Sjogren's syndrome (SS) is a chronic autoimmune disorder. It is characterized by dysfunction and destruction of exocrine glands associated with lymphocytic infiltrates and immunological hyperactivity. Salivary and lacrimal glands are the most affected, thus leading to mouth and eye dryness. The disorder can occur alone (it is then known as primary SS) or in association with another autoimmune disease (it is then known as secondary SS). The aim of this article is provide a complete overview of SS.

Keywords: Autoimmune disorder, salivary glands, Sjogren′s syndrome


How to cite this article:
Jethlia A, Keluskar V, Shetti A. Sjogren's syndrome. J Indian Acad Oral Med Radiol 2008;20:85-9

How to cite this URL:
Jethlia A, Keluskar V, Shetti A. Sjogren's syndrome. J Indian Acad Oral Med Radiol [serial online] 2008 [cited 2020 Sep 19];20:85-9. Available from: http://www.jiaomr.in/text.asp?2008/20/3/85/52772


   Introduction Top


Sjogren's syndrome (SS) is named after the Swedish ophthalmologist Henrik Sjogren who presented his doctoral thesis in 1933. [1] Sjogren's syndrome is a chronic autoimmune disorder which is characterized by dysfunction and destruction of the exocrine glands associated with lymphocytic infiltration and immunological hyper reactivity. Salivary and lacrimal glands are the most affected thus leading to dryness of mouth (xerostomia) and eye (xerophthalamia). The disorder can occur alone as Primary Sjogren's syndrome or Sicca syndrome and when it occurs in association with another autoimmune diseases such as Rheumatoid arthritis and Systemic lupus erythematosus, Polyarteritis nodosa, Scleroderma it is called as Secondary Sjogren's syndrome. [2]

It commonly affects women over 40 years of age, although children or young adults may be affected. [3],[4],[5] The female to male ratio is approximately 9:1. [4] This predominance of SS in women seems to be related to immunoregulatory properties of sex harmones. Prevalence of primary SS in the general population has been estimated to be around 1 to 3% whereas secondary SS has been observed in approximately 10-20% of patients with RA, SLE and Scleroderma. It is estimated that SS is the second most common rheumatologic disorder after only SLE. [2]


   Etiology Top


The etiology of Sjogren's syndrome remains largely obscure. A viral etiology has been suspected for the induction of Sjogren's syndrome. Some of the viruses that have been implicated in the development of Sjogren's syndrome are cytomegalovirus, Epstein-Barr virus, hepatitis C virus, human T-cell leukemia/lymphoma virus-1 and human immunodeficiency virus. However, no direct correlation has been established between viruses and Sjogren's syndrome.[1],[2]

Although genetic influences are thought to be responsible for pathogenesis, no such single factor has been identified. Studies from different countries and ethnic groups have revealed associations with various HLA-DR alleles (DRB1 genes), including DR3, DR5, DRw11 and DRw53.The association of primary Sjogren's syndrome with DQA1*0501, DQB1*0201 and DQB1*0301 alleles appears to cross ethnic barriers.

Sjogren's syndrome is considered an autoimmune disorder. There is up -regulation of the immune response, especially B-cell activation and elevated serum autoantibody levels suggests an autoimmune etiology for Sjogren's syndrome. One model for pathogenesis of Sjogren syndrome suggests a two phase process, non immune and immune. In the nonimmune phase, a genetically based abnormality or an infection would trigger glandular epithelial cell death via accelerated apoptosis. The byproducts of the dead cells would act as autoantigens, provoking an immune response. In the second phase, this immune mediated inflammatory process would damage the target glands or other organs.

Current research findings suggest that both neural and immune processes are involved in the pathogenesis of Sjogren syndrome. An immune-mediated neural pathogenesis for Sjogren syndrome is supported by the fact that normal salivary function depends on neural input to the gland. Cholinergic efferent nerves that release acetylcholine induce tearing and salivation by stimulating muscarinic M3 receptors of the lacrimal and salivary glands. Investigators have reported that immunoglobulin G from patients with primary Sjogren syndrome could bind and activate M3 receptors in lacrimal glands from rats. [6]


   Clinical Features Top


Chronic dryness of mouth (xerostomia) and or the eyes (keratoconjunctivitis Sicca) due to diminished secretion of the saliva and tears is characteristic of the disorder. Moistening glands in the nose, the pharynx the tracheobranchial tree, the skin and the stomach may also be affected. Patients experience difficulty in chewing, swallowing and speaking due to lack of salivation. They often have dry cracked lips and angular cheilitis, sore mouth, depapillation of tongue, unpleasant taste. Intraorally, the mucosa is pale and dry, minimal salivary pooling is noted and the saliva that is present tends to be thick and ropy. Mucocutaneous candidiasis infections are common in these patients. Decreased salivary flow results in increased incidence of dental caries and difficulty in wearing dentures. [3],[7]

Enlargement of major salivary glands occurs in 25-66% of primary SS, but is uncommon in patients with secondary SS. Bacterial infections or salivary gland tumors should always be suspected in unilateral salivary gland enlargement even in patients with established diagnosis of SS. Chronic eye dryness leads to persistent irritation and destruction of corneal and bulbar conjunctival epithelium (keratoconjunctivitis Sicca). Sandy or burning sensation is a complaint frequently reported. [1],[7]

More than half of the patients may develop an extraglandular manifestation during the evolution of the disease. Occasionally; systemic features may lead to diagnosis. The spectrum of the disease extends from an organ specific autoimmune disorders to a range of systemic manifestations (musculoskeletal, pulmonary, gastric, hematologic, dermatologic, renal, and nervous system involvement). Sjogren's syndrome may develop alone (primary) or in association with almost any of the autoimmune rheumatic diseases (secondary), the most frequent being rheumatoid arthritis and systemic lupus erythematosus.

Arthritis, Raynaud's phenomenon and leukocytoclastic vasculitis, in addition to focal myositis and lymphadenopathy are the most common extraglandular manifestations of primary Sjogren's syndrome. With regard to pulmonary involvement, diffuse interstitial pneumonitis has been documented. A wide range of neurological disorders has been reported, the peripheral nervous system being most frequently affected (neuropathy) but occasionally also CNS. Interstitial nephritis in a sub clinical form, and as a cause of renal tubular acidosis or nephritogenic diabetes insipidus, occurs in about 30% of the patients.

Lymphomas, almost exclusively of B cell lineage, are a characteristic but unusual feature of Sjogren's syndrome, occurring in about 5% of the patients this complication of Sjogren's syndrome is particularly found in patients with high levels of immunoglobulins, autoantibodies and cryoglobulins. When the lymphoma develops, the immunoglobulin levels often drop and the autoantibodies disappear.

Concerning secondary Sjogren's syndrome, rheumatoid arthritis patients with Sicca complex tend to have more severe disease, with frequent extra-articular manifestations including vasculitis presented as digital infarcts and/or cutaneous ulcers. In systemic lupus erythematosus, patients with concomitant Sjogren's syndrome have a lower frequency of glomerulonephritis and a relatively good prognosis. Primary biliary cirrhosis and scleroderma, although rare in general, are frequently complicated by Sjogren's syndrome. Other autoimmune diseases, which have been described in association with Sjogren's syndrome, include polymyositis, mixed connective tissue disease, chronic active hepatitis and Hashimoto's thyroiditis.[1]


   Diagnostic Criterias Top


The lack of adequate understanding of the underlying cause of SS and the broad spectrum of its clinical manifestations complicate a prompt diagnosis of the disease. Several sets of criteria have been proposed to facilitate the diagnosis of SS. Each set requires fulfillment of specific clinical and laboratory tests. Most of the published criteria place considerable emphasize on salivary gland biopsy for the diagnosis of SS. The European Community, or EC, criteria are among the most inclusive. The EC criteria requires evaluation of oral signs and symptoms, ocular signs and symptoms, histopathology (salivary gland biopsy) and serum autoantibodies such as rheumatoid factor y(RF); antinuclear antibody (ANA) antibodies to Ro(SSA)or La(SSB). ("European Community Criteria for the Diagnosis of Sjogren's Syndrome"). Using the EC criteria, the diagnosis of SS requires fulfillment of at least four out of the six criteria. A proposed modification would require, for the diagnosis of SS, the presence of either focal sialadenitis or salivary gland biopsy or antibody among the four criteria that are met. [2],[7]


   Diagnostic Tests for Sjogren's Syndrome Top


Laboratory investigations

Schirmer test: A standardized strip of filtering paper is applied over the margin of the lower lid. After 5 minutes with eyes lightly closed, the paper is removed and the length of the moistened part of the paper is measured [9] .In normal subjects there is great variation, but patients with SS invariably display very low reading. The internationally accepted cut-off value is now 5mm [Figure 1]. [8]

Rose-bengal score dye test: 2.5 micro L 1% rose-bengal is installed in the eye, and it stains dying and desiccated epithelial cells without the protecting mucus layer. The amount of staining is expressed as a score, according to van Bijsterveld. The problem with this test is that the dye is rather toxic to the epithelium and the patients dislike it because of the intense stinging, burning sensation. As an alternative, lissamine-green can be used in same concentration to avoid problems associated with rose-bengal [Figure 2]. [9]

Break-up time: It is the measurement of the ability of the precorneal tear film to maintain its integrity. The test is performed by installing 2.5 micro L 1% fluorescein solution in the conjunctival sac. Fluorescein paper strips moistened with isotonic saline is used. After a few blinks, the patient is asked to look straight with eyes opened in a normal fashion. The tear film is observed in red free light through the slit-lamp and the time from opening of the lids until the first dry spot appears, is recorded. The cut-off value is 10 seconds. [10]

Sialometry: Salivary flow rate estimation is a sensitive indicator of salivary gland function. Parotid saliva makes the major contribution to total salivary flow and is the most consistently affected glands in patients with Sjogren's syndrome. Stimulated flow rate in symptomatic primary and secondary Sjogren's syndrome is usually below. 5 to 1.0 ml/minute (normal 1 to 1.5 ml/minute). [11]

Sialochemistry: Parotid saliva in Sjogren's syndrome contains twice as much total lipids and has elevated content of phospholipids and glycolipids than the normal saliva. The sodium chloride and phospholipids levels are higher in saliva of Sjogren's syndrome patient. [12]

Immunological: Routine autoantibody profile can usually be carried out. There is an elevated Rheumatoid Factor (RF) > 1:160 or elevated Antinuclear Antibody (ANA) > 1:160.Positive Anti-SS-A (RO) antibodies or positive Anti-SS-B (LA) antibodies are specific antinuclear antibodies common in patients of Sjogren's syndrome.

Salivary gland biopsy: The minor salivary gland biopsy specimen finding is considered to be the best sole diagnostic criterion for the salivary component of Sjogren's syndrome. A grading system exists for quantifying the salivary histological changes seen in the minor glands in Sjogren's syndrome, as follows (1) the number of infiltrating mononuclear cells are determined, with an aggregate of 50 or more cells being termed a focus, (2) the total number of foci and the surface area of the specimen are measured and (3) the number of foci per 4mm 2 is calculated. This constitutes the focus score. The range is from 0 to 12, with 12 denoting confluent infiltrates.A focus score of 1 is considered positive for Sjogren's syndrome in some criteria although others require the score to be >1. [3]


   Radiographic Features Top


  1. Sialography: The most typical finding in Sjogren's syndrome is that of Silaectasia, 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 cherry blossom appearance of the obstructed ductal system [Figure 3]. [6]
  2. Salivary Scintiscanning: Salivary scintiscanning with technetium pertechnetate may be useful in demonstrating impaired salivary function in patients with Sjogren's syndrome. The changes correlate with both salivary flow and labial glands abnormalities. [6]



   Differential Diagnosis Top


Various acute or chronic medical conditions may stimulate SS. These include adverse effects of drugs, metabolic disorders infection, tumor, and irradiation. In particular, sarcoidosis, lipoproteinemia (types-11,1V and V), chronic graft-versus host disease, lymphoma, amyloidosis and infection by hepatitis C virus (HCV) or human immunodeficiency virus (HIV) might be misdiagnosed as SS. In the elderly, mucosal dryness is frequently an age related process characterized by degeneration and liposis of the exocrine glands. [2]


   Management Top


At present, treatment for most patients is essentially symptomatic. The patient should regularly visit a rheumatologist as well as an ophthalmologist and dentist in order to prevent and treat the consequences of mucosal dryness, in addition to extraglandular manifestations and other associated complications. [1]

Artificial tears, ointments and soft contact lenses often alleviate the patient's ocular complaints, and are of importance in preventing corneal damage and conjunctivitis. Another treatment option for dry eye is 'punctal occlusion' by using a variety of 'plugs' to occlude the punctal openings at the inner aspects of the eyelids. Using this procedure, the instilled artificial tears will remain in the eye for longer time. [1],[3]

The management of dry mouth aims to prevent and treat infections, periodontal disease and dental caries. To reduce the risk of caries, it is necessary to maintain a good oral hygiene and use sugarless sweets and chewing gums to stimulate residual salivary flow. Artificial saliva products and special toothpaste may also be of benefit for certain patients, and fluoride supplementation is advocated. Eradication of oral candidiasis usually provides significant improvement of oral symptoms. [1],[3]

Oral pilocarpine has been shown to be a safe treatment and provides significant subjective and objective benefits for patients with Sjogren's syndrome, suffering from symptoms associated with xerostomia. Another potential therapy includes systemic use of interferon-alpha, which may be of benefit for the symptoms associated with xerostomia. Cemiveline, a novel quinuclidine derivative of acetylcholine exhibiting high affinity for the muscarinic M3 receptor, has long lasting sialogogic action and few side-effects.

Hydroxychloroquine, azathioprine, cyclosporin-A and cyclophosphamide may be useful as immunomodulating agents reducing immune activation and lymphoproliferation and sometimes are employed in patients with Sjogren's syndrome with extraglandular symptoms. Administration of NSAIDs and systemic steroids have been suggested to improve the signs and symptoms of Sjogren's syndrome but are mainly used for treatment of severe extra glandular complications such as arthritis, vasculitis, pulmonary and renal involvement [1]


   Conclusion Top


Sjogren's syndrome is a common and under diagnosed inflammatory disease of the exocrine glands with a significant impact on oral health. Dental practitioners are likely to be the first health care providers to encounter the early signs of SS. Therefore, they should be familiar with the manifestations of the disease and be prepared to take an active role in the diagnosis, management and treatment of the oral complications of SS.[Table 1][16]

 
   References Top

1.Jonsson R, Moen K, Vestrheim D, Szodoray P. Current issues in Sjogren's syndrome. Oral Dis 2002;8:130-40.  Back to cited text no. 1  [PUBMED]  [FULLTEXT]
2.Doctor MN. Manoussakis. Sjogren's syndrome. Orphanet encyclopedia. Available from: http:/www.orpha.net/data/patho/GB/uk-sjogren.pdf. [cited in Nov 2001].  Back to cited text no. 2    
3.Greenberg MS, Glick M. Burkets oral medicine diagnosis and Treatment, 10th ed. Hamilton: BC Decker Inc; 2003. p. 261.  Back to cited text no. 3    
4.Shafer WG, Hine MK, Levy BM. A textbook of oral pathology, 4 th ed. Philadelphia, PA: Saunders; 1983. p. 238.  Back to cited text no. 4    
5.Neville BW, Damm DD, Allen CM. Oral and maxillofacial pathology. Philadelphia, PA: Saunders; 1995. p. 343.  Back to cited text no. 5    
6.AL-Hashimi I. The management of Sjogren's syndrome in dental practice. J Am Dent Assoc 2001;132:1409-17.  Back to cited text no. 6  [PUBMED]  [FULLTEXT]
7.Rankow, Polayes. Diseases of the salivary glands. Philadelphia: W.B Saunders; 1976. p. 215.  Back to cited text no. 7    
8.Bjerrum KB. Tests and symptoms in keratoconjunctivitis Sicca and their correlation. Arch ophthalmol scand 1996;74:436-41.  Back to cited text no. 8    
9.Bijsterveld OP. Diagnostic tests in the Sicca syndrome. Arch Ophthalmol 1969;82:10-4.  Back to cited text no. 9  [PUBMED]  [FULLTEXT]
10.Lee JH, Kee CW. The significance of tear film break up- time in the diagnosis of dry eye syndrome. Korean J Ophthalmol 1988;2:69-71.  Back to cited text no. 10  [PUBMED]  [FULLTEXT]
11.Tenovno JO, Odont D. Human saliva. Clinical chemistry and microbiology Vol.1, Florida: 1989.  Back to cited text no. 11    
12.Tenovno JO, Odont D. Human saliva: Clinical chemistry and microbiology Vol.2, Florida: 1989.  Back to cited text no. 12    
13.Prause JU, Kriegbaum NJ, Manthorpe R, Oxholm P. Rose Bengal score: A possible key parameter when evaluating disease level and progression in primary Sjogren's syndrome. Autoimmune 1989;2:501-712.  Back to cited text no. 13    
14.Ellis, Douglas A. Surgical Pathology of the salivary glands. Philadelphia: W.B Saunders; 1991.  Back to cited text no. 14    
15.Daniels TE. Sjogren's syndrome: Clinical spectrum and current diagnostic controversies. Adv Dent Res 1996;10:3-8.  Back to cited text no. 15  [PUBMED]  [FULLTEXT]
16.Hamburger J. Sjorgen's syndrome-managing oral and systemic symptoms via a multi-disciplinary approach. Oral Dis 2002;10:306-9.  Back to cited text no. 16    


    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1]



 

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  In this article
    Abstract
    Introduction
    Etiology
    Clinical Features
    Diagnostic Criterias
    Diagnostic Tests...
    Radiographic Fea...
    Differential Dia...
    Management
    Conclusion
    References
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