Print this page Email this page | Users Online: 268
Home About us Editorial board Search Ahead of print Current issue Archives Submit article Instructions Subscribe Contacts Login 


 
 Table of Contents  
REVIEW ARTICLE
Year : 2014  |  Volume : 5  |  Issue : 1  |  Page : 31-35

Sjogren's syndrome: A review


Department of Oral Medicine and Radiology, Institute of Dental Sciences, Bareilly, Uttar Pradesh, India

Date of Web Publication19-Mar-2014

Correspondence Address:
Mallika Kishore
Department of Oral Medicine and Radiology, Institute of Dental Sciences, Bareilly, Uttar Pradesh
India
Login to access the Email id


DOI: 10.4103/0976-433X.129070

Rights and Permissions
  Abstract 

Sjogren's syndrome (SS) is a chronic autoimmune disease characterized by the lymphocytic infiltration of salivary and lacrimal glands leading to xerostomia and keratoconjunctivitis sicca. Prevalence of primary SS in the general population has been estimated to be around 1-3%. SS is an under-recognized disease in which most of the significant progress has been made in the past 25 years. The herald of newer diagnostic tools could help clinicians and thereby provide significant relief to patients through earlier treatments. The treatment of SS is limited to symptomatic management, and involves the use of solutions to replace salivary secretion and afford a measure of hydration. The purpose of present paper is to highlight the difficulties and complexities that are inherent in the diagnosis of SS and the important role that dental practitioners can play in the management of its oral manifestations.

Keywords: Diagnosis, oral, Sjogren′s syndrome


How to cite this article:
Kishore M, Panat SR, Aggarwal A, Agarwal N, Upadhyay N, Garg R. Sjogren's syndrome: A review. SRM J Res Dent Sci 2014;5:31-5

How to cite this URL:
Kishore M, Panat SR, Aggarwal A, Agarwal N, Upadhyay N, Garg R. Sjogren's syndrome: A review. SRM J Res Dent Sci [serial online] 2014 [cited 2021 Sep 27];5:31-5. Available from: https://www.srmjrds.in/text.asp?2014/5/1/31/129070


  Introduction Top


Sjogren's syndrome (SS) is a chronic autoimmune disease characterized by lymphocytic infiltration and subsequent destruction of the exocrine glands, including those found in the nose, ears, skin, vagina, respiratory and gastrointestinal systems. [1] It is among the group of diseases overseen by rheumatologists; however, its diagnosis and management require 3 areas of specialty practice: rheumatology, ophthalmology, and oral medicine. [2]

Therefore, this paper aims to review and critically address the recent advances on the aetiopathogenesis of the SS, taking into account the attained clinical features, with particular relevance given to the oral involvement.


  Epidemology Top


SS is estimated to affect 1-3% of the general population. [3] A cautious but realistic estimate from the studies presented so far will be that primary SS(pSS) is a disease with a prevalence not exceeding 0.6% of the general population (6/1000). [4] In an epidemiologic study, the calculated prevalence of SS in 705 randomly selected women aged ranges from 52-72 years was 2.7%. [5] SS, although a common disorder in Western countries with an estimated prevalence of 3 in 100 to 1 in 1000, has rarely been reported from India. [6] This report highlights the rarity of this disease in our geographic region.


  Etiology and Pathogenesis Top


Even if tremendous progress in the field of research has been made to unveil the different mechanistic processes underlying the development of SS, the initial triggering events of the disease have yet to be unearthed. Central to the pathophysiology of SS is chronic perpetual stimulation of the autoimmune system. Both B and T cells are implicated in the pathogenesis of the SS, even though the mechanisms underlying humoral and cellular abnormalities are not yet known. [7],[8]

It is probably the result of an environmental stimulus that promotes an autoimmune reaction in genetically susceptible persons. Infectious agents most commonly sialotropic viruses have been postulated to trigger the syndrome; however, associations with most of the potential viral candidates, including cytomegalovirus and Epstein-Barr virus, are weak. [9] The putative role of different viruses in SS can be viewed in the light that salivary glands are a site of latent viral infections. [10]

A genetic predisposition to SS has been suggested because of multiple reports of two or more members of the same family developing the syndrome. Affected individuals of different ethnic origins carry different human leucocyte antigen susceptibilities. [4]

The high percentage of females with SS compared to males suggests that the immune regulatory properties of sex hormones are involved in its development. [11] Androgen deficiency, both locally and systemically, has also been pointed out to be a key factor prompting SS. Reduced plasmatic levels (up to 40 - 50%) of dehydroepiandrosterone sulfate, the precursor sex steroid hormone produced in the adrenal cortex, has been identified in SS-affected individuals, comparing to age and sex matched controls. [12]


  Clinical Features Top


Glandular manifestations

Xerostomia

The dry mouth is often manifest as the 'cream cracker' sign an inability to swallow dry dental caries is a common feature that may prompt a referral from a dentist. About half of the patients complain of recurrent parotid swelling, particularly relatively young patients in whom the inflammatory phase predominates. [13]

In advanced disease, the oral mucosa appears dry and glazed and tends to form fine wrinkles. Extreme dryness of the mouth, causing the tongue to stick to the palate, may lead to a "clicking" quality in the speech of patients with SS. In general, the surface of the tongue becomes red and lobulated, with partial or complete depapillation. [14]

Ocular manifestations

Diminished tear production due to lacrimal gland involvement leads to the destruction of both corneal and bulbar conjunctival epithelium and a constellation of clinical findings termed keratoconjunctivitis sicca (KCS). [15]

Symptoms of dry eye may include sensations of itching, grittiness, or soreness, even though the eyes' appearance is normal. Ocular complaints may include photosensitivity, erythema, eye fatigue, decreased visual acuity, a discharge in the eyes, and the sensation of a film across the visual field. [14]

In more severe disease, functional disability with visual impairment occurs. Complications of KCS include corneal ulcerations that can lead to perforations and iridocyclitis. [16]

Extraglandular manifestations

Musculoskeletal involvement

Joint disease associated with SS is commonly a polyarticular arthropathy which intermittently affects small joints. Evidence of joint deformity and erosion may be encountered in primary SS-affected individuals, as well as nonerosive arthritis. Arthralgias, myalgias and fibromyalgia-like features are also commonly found. [17]

Pulmonary involvement

Although common, pulmonary involvement is seldom clinically significant in patients with SS. [18] Interstitial lung disease is a classic feature of SS. The clinical manifestations include cough, dyspnea on exertion, bilateral pulmonary infiltrates on plain chest radiographs and other abnormalities on computer tomography scanner such as wall thickening at the segmental bronchi. With disease progression, fibrosis and neutrophilic alveolitis are present. [19]

Renal involvement

Kidney involvement is a frequent extraglandular manifestation of pSS. The renal involvement is rarely overt, and more often follows a subclinical course. In some cases, it may precede the onset of subjective sicca syndrome. [20] In SS patients who show evidence of glomerular lesions, hematuria, proteinuria, and renal insufficiency may be exhibited. Some patients may progress to nephrotic syndrome. [14]

Gastroenterologic involvement

The manifestations of gastrointestinal tract are not very specific and include esophageal dysmotility and gastro-intestinal reflux. Patients often complain of dysphagia, nausea and epigastric pain. Subclinical pancreatic involvement is present in approximately 25% of cases. There are no specific liver abnormalities, which can be attributed to SS, but autoimmune hepatitis and primary biliary cirrhosis can be associated diseases. [16],[21]

Neurologic involvement

Neurologic disease is one of the most common manifestations of SS, affecting cranial and peripheral nerves, and more rarely the central nervous system. The eclectic permutation of peripheral nervous system syndromes which occur in SS patients are among the most common and severe extraglandular complications. [22]

Hematologic/Oncologic involvement

Patients with SS frequently have leucopenia, thrombocytopenia, a high erythrocyte sedimentation rate and anti-nuclear antibodies. [13] Anemia of chronic disease and hypergammaglobulinemia are the most prevalent hematologic manifestations encountered at diagnosis and during the course of pSS. [23]

Thyroid Involvement

Hypothyroidism seems to be common in SS. [24] A study has shown that 45% of patients with SS also had associated thyroid dysfunction. This is further supported by a study suggesting that the prevalence of SS is 10 times higher in patients with autoimmune thyroiditis. [25]

Obstetrical and gynecological involvement

Dyspareunia secondary to impaired lubrication is verified in many premenopausal women with pSS. Other gynecological problems include vaginal dryness, endometriosis, episodes of amenorrhea and menorrhagia/metrorrhagia. [26]

Cardiac Involvement

Pericarditis and pulmonary hypertension can occur in SS. Cardiovascular tests suggestive of autonomic neuropathy, such as response of blood pressure to sustained hand grip, valsalva maneuver, heart-rate response to deep breathing, heart-rate and blood-pressure response to standing are abnormal in some patients with SS. [27]

Diagnosis

The diagnosis of SS is not straightforward as many of the symptoms are subjective and vague and can be dismissed initially as other conditions or effect of medications. [28] Although minor salivary gland biopsy has been traditionally considered "the gold standard" for the diagnosis of SS, newer criteria have emerged to assist on this disease identification.

The revised diagnostic criteria established in 2002 by the American-European Consensus Group are listed in [Table 1]. [4] Early recognition of SS may prevent complications such as dental caries, corneal ulceration, chronic oral infection, and sialadenitis, and it allows for clinical surveillance for the development of serious extraglandular systemic manifestations. [14]
Table 1: Diagnostic criteria of Sjögren's syndrome

Click here to view


Diagnostic Tests

Oral diagnostic tests

Sialometry

Patients with clinically overt SS have reduced flow rate.Measuring submandibular/sublingual flow rates may contribute to an early diagnosis of SS. In contrast, parotid flow rates are decreased in SS and Non-SS sicca patients. [29] The test should therefore be standardized; the unstimulated whole saliva collection test is performed for 15 min, and the test is considered positive when <1.5 ml whole saliva is collected. [4]

Sialography

The sialography typically shows sialectasias in contrast to the fine arborization seen in normal parotid ductules. Diagnosis is generally based on the classification given in [Table 2]. [30]
Table 2: Sialographic staging

Click here to view


Scintigraphy

In the scintigraphic test, 99mTc-pertechnate is given intravenously, and in SS patients the typical finding is decreased uptake in response to stimulation of the parotid and submandibular salivary glands. This test is a sensitive and valid method to measure abnormalities in salivary gland function in the hands of skilled personal. [31]

Sialochemistry

SS is a mixture of increased inflammatory proteins and decreased acinar proteins when compared with healthy controls. [32] Furthermore ionic changes were observed in SS-affected individuals, namely regarding the levels of chloride, potassium, calcium, sodium and magnesium. [29]

Magnetic Resonance (MR) and ultrasonography (US)

MR imaging (MRI), MR sialography and US are noninvasive methodologies that allow the imaging of salivary glands in their physiological state without artefacts induced by intraductal contrast media or biopsy procedures. MRI was shown to provide a reliable imaging procedure to evaluate glandular alterations. It allows multiplanar evaluation and processes a high contrast tissue resolution. Characteristically, in SS, MRI reveals an inhomogeneous internal pattern on both T1 and T2 sequences, with multiple hypo- and hyper-intense nodules of different sizes. [33]

Serologic tests

Serology is used to establish the presence of anti-SS-A/Ro and anti-SS-B/La auto-antibodies,based on (enzyme-linked immunosorbent assay). Anti-SS-A/Ro antibodies can also be detected in other autoimmune processes such as rheumatoid arthritis and systemic lupus erythematosus; for this reason, anti-SS-B/La antibodies are considered to be more specific of SS. Anti- SS-A/Ro can be isolated in 25-65% of cases, and anti- SS-B/La in 13-48%. [34]

Ocular Diagnostic tests

  1. Schirmer test
  2. Rose Bengal Staining
  3. Tear break up time (BUT)



  Histopathology Top


Salivary gland Biopsy

A positive biopsy is defined as at least one focus of dense, inflammatory infiltrate containing at least 50 lymphocytes/4 mm 2 . The lip biopsy may be useful in ambiguous cases or when therapy beyond symptom management is being considered. [35]

Differential Diagnosis

The differential diagnosis of SS includes conditions and medications that can produce KCS, xerostomia, and parotid gland enlargement [Table 3]. [14]
Table 3: Differential Diagnosis

Click here to view


Management

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 [Table 4]. [4],[36],[37],[38],[39]
Table 4: Management of SS

Click here to view



  Conclusion Top


People with SS may be more susceptible to drug allergies and care is needed to monitor their condition if medication is required. Like all chronic diseases it is important to have regular contact with your doctor and eye specialist to monitor your condition. Regular dental checkups are essential. Although SS is not life threatening, careful attention to the problems it causes can help minimize the "nuisance" aspect of this condition and assist in a more relaxed way.

 
  References Top

1.Bayetto K, Logan RM. Sjögren′s syndrome: a review of aetiology, pathogenesis, diagnosis and management. Aust Dent J 2010;55:39-47.  Back to cited text no. 1
    
2.Shiboski SC, Shiboski CH, Criswell L, Baer A, Challacombe S, et al; Sjögren′s International Collaborative Clinical Alliance (SICCA) Research Groups. American College of Rheumatology classification criteria for Sjögren′s syndrome: a data-driven, expert consensus approach in the Sjögren′s International Collaborative Clinical Alliance cohort. Arthritis Care Res (Hoboken) 2012;64:475-87.  Back to cited text no. 2
    
3.Hammi A, Al-Hashimi I, Nunn M, Zipp M. Assessment of SS-A and SS-B in parotid saliva of patients with Sjögren′s syndrome. J Oral Pathol Med 2005;34:198-203.  Back to cited text no. 3
    
4.Jonsson R, Moen K, Vesterheim D, Szodoray P. Current issues in Sjogren′s syndrome. Oral Dis 2002;8:130-40.  Back to cited text no. 4
    
5.Jacobsson L, Axell TE, Hansen BU, Henricsson VJ, Larsson A, Lieberkind K, et al. Dry eyes or mouth - an epidemiological study in Swedish adults with special reference to primary Sjogren′s syndrome. J Autoimmun 1989;2:521-7.  Back to cited text no. 5
    
6.Malaviya AN, Singh RR, Kapoor SK, Sharma A, Kumar A, Singh YN. Prevalence of rheumatic diseases in India. Results of a population survey. J Indian Rheum Assoc 1994;2:13-7.  Back to cited text no. 6
    
7.Delaleu N, Jonsson MV, Appel S, Jonsson R. New concepts in the pathogenesis of Sjögren′s syndrome. Rheum Dis Clin North Am 2008;34:833-45.  Back to cited text no. 7
    
8.Mariette X, Gottenberg JE. Pathogenesis of Sjögren′s syndrome and therapeutic consequences. Curr Opin Rheumatol 2010;22:471-7.  Back to cited text no. 8
    
9.Hansen A. James JA, Harley JB, Scofield RH. Role of viruses in systemic lupus erythematosus and Sjögren syndrome. Curr Opin Rheumatol 2001;13:370-6.  Back to cited text no. 9
    
10.Diss TC, Wotherspoon AC, Speight P, Pan L, Isaacson PG. B-cell monoclonality, Epstein Barr virus, and t(14;18) in myoepithelial sialadenitis and low-grade B-cell MALT lymphoma of the parotid gland. Am J Surg Pathol 1995;19:531-6 .  Back to cited text no. 10
    
11.Talal N. What is Sjogren′s syndrome and why is it important? J Rheumatol 2000;61:1-3.  Back to cited text no. 11
    
12.Porola P, Laine M, Virkki L, Poduval P, Konttinen YT. The influence of sex steroids on Sjögren′s syndrome. Ann N Y Acad Sci. 2007;1108:426-32.   Back to cited text no. 12
    
13.Venables PJ. Sjögren′s syndrome. Best Pract Res Clin Rheumatol 2004;18:313-29.  Back to cited text no. 13
[PUBMED]    
14.Kassan S, Moutsopoulos H. Clinical manifestations and early diagnosis of Sjogren′s syndrome. Arch Intern Med 2004;164:1275-84.  Back to cited text no. 14
    
15.Manoussakis MN, Moutsopoulos HM. Sjögren′s syndrome: autoimmune epithelitis. Baillieres Best Pract Res Clin Rheumatol 2000;14:73-95.  Back to cited text no. 15
    
16.Fox RI. Sjögren′s syndrome. Lancet 2005;366:321-31.  Back to cited text no. 16
[PUBMED]    
17.Vitali C, Tavoni A, Neri R, Castrogiovanni P, Pasero G, Bombardieri S. Fibromyalgia features in patients with primary Sjögren′s syndrome. Evidence of a relationship with psychological depression. Scand J Rheumatol 1989;18:21-7.  Back to cited text no. 17
    
18.Papiris SA, Maniati M, Constantopoulos SH, Roussos C, Moutsopoulos HM, Skopouli FN. Lung involvement in primary Sjögren′s syndrome is mainly related to the small airway disease. Ann Rheum Dis 1999;58:61-4.  Back to cited text no. 18
    
19.Parambil JG, Myers JL, Ryu JH. Diffuse alveolar damage: Uncommon manifestation of pulmonary involvement in patients with connective tissue diseases. Chest 2006;130:553-8.  Back to cited text no. 19
    
20.Bossini N, Savoldi S, Franceschini F, Mombelloni S, Baronio M, Cavazzana I, et al. Clinical and morphological features of kidney involvement in primary Sjögren′s syndrome. Nephrol Dial Transplant 2001;16:2328-36.  Back to cited text no. 20
    
21.Mavragani CP, Moutsopoulos HM. The geoepidemiology of Sjögren′s syndrome. Autoimmun Rev 2010;9:A305-10.  Back to cited text no. 21
    
22.Sène D, Jallouli M, Lefaucheur J, Saadoun D, Costedoat-Chalumeau N, Maisonobe T, et al. Peripheral neuropathies associated with primary Sjögren syndrome: immunologic profiles of nonataxic sensory neuropathy and sensorimotor neuropathy. Medicine (Baltimore) 2011;90:133-8.  Back to cited text no. 22
    
23.Baimpa E, Dahabreh IJ, Voulgarelis M, Moutsopoulos HM. Hematologic manifestations and predictors of lymphoma development in primary Sjögren syndrome: Clinical and pathophysiologic aspects. Medicine (Baltimore) 2009;88:284-93.  Back to cited text no. 23
    
24.D′Arbonneau F, Ansart S, Le Berre R, Dueymes M, Youinou P, Pennec YL. Thyroid dysfunction in primary Sjögren′s syndrome: a long-term followup study. Arthritis Rheum 2003;49:804-9.  Back to cited text no. 24
    
25.Skopouli FN, Dafni U, Ioannidis JP, Moutsopoulos HM. Clinical evolution, and morbidity and mortality of primary Sjögren′s syndrome. Semin Arthritis Rheum 2000;29:296-304.  Back to cited text no. 25
    
26.Marchesoni D, Mozzanega B, De Sandre P, Romagnolo C, Gambari PF, Maggino T. Gynaecological aspects of primary Sjogren′s syndrome. Eur J Obstet Gynecol Reprod Biol 1995;63:49-53.  Back to cited text no. 26
    
27.Gyöngyösi M, Pokorny G, Jambrik Z, Kovács L, Kovács A, Makula E, et al. Cardiac manifestations in primary Sjögren′s syndrome. Ann Rheum Dis 1996;55:450-4.  Back to cited text no. 27
    
28.Von Bültzingslöwen I, Sollecito TP, Fox PC, Daniels T, Jonsson R, Lockhart PB, et al.ary dysfunction associated with systemic diseases: systematic review and clinical management recommendations. Oral Surg Oral Med Oral Pathol Oral Radiol Endod.2007;103 Suppl:S57.e1-15.   Back to cited text no. 28
    
29.Kalk WW, Vissink A, Stegenga B, Bootsma H, Nieuw Amerongen AV, Kallenberg CG. Sialometry and sialochemistry: a non-invasive approach for diagnosing Sjögren′s syndrome. Ann Rheum Dis 2002;61:137-44.  Back to cited text no. 29
    
30.Rubin P, Holt J. Secretory sialography in diseases of the major salivary glands. Am J Roentgenol Radium Ther Nucl Med 1957;77:575-98.  Back to cited text no. 30
    
31.Håkansson U, Jacobsson L, Lilja B, Manthorpe R, Henriksson V. Salivary gland scintigraphy in subjects with and without symptoms of dry mouth and/or eyes, and in patients with primary Sjögren′s syndrome. Scand J Rheumatol 1994;23:326-33.  Back to cited text no. 31
    
32.Hu S, Wang J, Meijer J, Ieong S, Xie Y, Yu T, et al. Salivary proteomic and genomic biomarkers for primary Sjögren′s syndrome. Arthritis Rheum 2007;56:3588-600.  Back to cited text no. 32
    
33.Niemelä RK, Takalo R, Pääkkö E, Suramo I, Päivänsalo M, Salo T, et al. Ultrasonography of salivary glands in primary Sjogren′s syndrome. A comparison with magnetic resonance imaging and magnetic resonance sialography of parotid glands. Rheumatology (Oxford) 2004;43:875-9.  Back to cited text no. 33
    
34.Nakamura H, Kawakami A, Eguchi K. Mechanisms of autoantibody production and the relationship between autoantibodies and the clinical manifestations in Sjögren′s syndrome. Transl Res 2006;148:281-8.  Back to cited text no. 34
    
35.Daniels TE. Salivary histopathology in diagnosis of Sjögren′s syndrome. Scand J Rheumatol Suppl 1986;61:36-43.  Back to cited text no. 35
[PUBMED]    
36.Fox RI. Treatment of the patient with Sjogren′s syndrome. Rheum Dis Clin North Am 1992;18:699-709.  Back to cited text no. 36
[PUBMED]    
37.Tsifetaki N, Kitsos G, Paschides CA, Alamanos Y, Eftaxias V, Voulgari PV, et al. Oral pilocarpine for the treatment of ocular symptoms in patients with Sjögren′s syndrome: A randomised 12 week controlled study. Ann Rheum Dis 2003;62:1204-7.  Back to cited text no. 37
    
38.Whitcher JP. The treatment of dry eyes. Br J Ophthalmol 2004;88:603-4.  Back to cited text no. 38
[PUBMED]    
39.Burt BA. The use of sorbitol- and xylitol-sweetened chewing gum in caries control. J Am Dent Assoc 2006;137:190.  Back to cited text no. 39
[PUBMED]    



 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

Top
 
 
  Search
 
Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

 
  In this article
Abstract
Introduction
Epidemology
Etiology and Pat...
Clinical Features
Histopathology
Conclusion
References
Article Tables

 Article Access Statistics
    Viewed2864    
    Printed47    
    Emailed0    
    PDF Downloaded378    
    Comments [Add]    

Recommend this journal