Sjögren’s syndrome (SS) Case Report by Upul Cooray

Sjögren’s syndrome (SS) is a chronic inflammatory autoimmune disease mainly affecting the salivary and lacrimal glands, usually occurring in adults. Sjögren's syndrome can occur alone or in the presence of another connective tissue disease, respectively called primary and secondary Sjögren syndrome. When two of the three clinical hallmarks: keratoconjunctivitis sicca, xerostomia or connective tissue diseases are present, Sjögren's syndrome should be considered.[4]
Reported herein is a case of secondary Sjögren syndrome in a 46 year old female patient presented with dry mouth and bilateral facial swelling and pain during meal time for last two years and on medications for hypothyroidism, dry eyes and arthritis
Considering the history, clinical and radiographic demonstration of sialogram, the clinical diagnosis was made as Sjogren’s syndrome and the diagnosis was confirmed by labial gland biopsy. Currently patient is being managed symptomatically for her oral conditions with regular review and other medical problems are being managed by relevant specialties.
Sjögren’s syndrome (SS) was named after the Swedish ophthalmologist Henrik Sjögren who presented his doctoral
thesis in 1933.[8,9] Sjögren’s syndrome, also known as "Sicca syndrome", is a chronic, slowly progressive, inflammatory autoimmune disorder characterized by the infiltration of lymphocytes (T-cells in the majority of cases), monocytes, and plasma cells into the mainly parotid (salivary) glands and lacrimal (tear) glands leading to keratoconjunctivitis sicca (KCS) and xerostomia. Sjögren’s syndrome is a
worldwide disease, The overall prevalence of Sjogren's syndrome in the general population has been estimated to range from 0.5% to 3.0% and may occur in all ages.[4,8] However, the peak incidence is in the fourth and fifth decades of life with a
female/male ratio 9:1. It may develop alone (primary), or in association with an autoimmune diseases (secondary).[11]
Primary Sjogren's syndrome, defined as dry eye and dry mouth that occurs by itself and is not associated with another autoimmune disorder. Primary Sjogren's syndrome occurs in approximately 50% of cases (according to the Sjogren's
Foundation of America).[4,15] Secondary Sjogren's syndrome, characterized by dry eye and dry mouth that occurs in the presence of a major underlying autoimmune connective tissue disease such as rheumatoid arthritis, systemic lupus erythematosus, or scleroderma.
At presentation or during the course of the disease, almost one third of the primary-SS patients experience a more generalized disease, which does not usually evolve the failure of the
affected organ. The most important complication is a 44-fold increase in the risk of developing non-Hodgkin lymphoma, compared with the general population.[9,13,14] In addition, Sjogren's syndrome may cause skin, nose, and vaginal dryness, and may affect
other organs of the body, including the kidneys, blood vessels, lungs, liver, pancreas, peripheral nervous system
(distal axonal sensory motor neuropathy) and brain leading to diminished quality of life.
Case report

A 46 year old lady presented with dry mouth and bilateral facial swelling. She was referred from eye clinic of North Central Teaching Hospital to Oral and Maxillofacial unit of same hospital.
She has been experiencing dry mouth, pain and swelling during meal time for last two years, which became severe in last six months.
Patient was diagnosed to have rheumatoid arthritis in 2003 and hypothyroidism in 2009 since then she was on medications for those conditions. She is also being treated for dry eyes during last 2 years in eye clinic of North Central Teaching Hospital. No relevant positive family history regarding her medical conditions.
On extra oral examination swelling over parotid regions was not obvious but the areas over both parotid glands were tender. Submandibular and other cervical lymph nodes were not palpable. Intra oral examination revealed that her oral mucosa was dry, saliva pooling was not observed in the mouth and the milking of parotid glands revealed the reduced salivary flow. Patient is having periodontal disease with gingival recession and calculi deposits in the teeth and dentinal caries were observed in 43 , 51 .
Figure 1
Clinical differential diagnoses were made as, Sjogren’s syndrome and chronic sialadinitis. Several investigations were carried out to come to a definitive diagnosis.
Figure 2
Sialograme of right parotid gland
Figure 3
Sialograme of left parotid gland
Sialograme showed multiple punctuate glandular collections which are distributed throughout the gland this characteristic “snow storm” appearance was suggestive of SS.[4] Sialograme also revealed that there is no radiopaque calculi or filling defects in relation to both parotid ducts, no extravasations of contrast material and no evidence of parotid duct stenosis or stricture.
Considering the clinical features and findings of sialography the clinical diagnosis was made as Sjögren’s syndrome. To confirm the clinical diagnosis labial gland biopsies was taken and send for histopathological investigation to Pathology department of Peradeniya Teaching Dental Hospital.
Labial gland biopsy
Excisional biopsy of minor salivary glands of lower lip was done under local anesthesia.
Figure 4
Four soft tissues measuring 0.4x0.3x0.2cm was sent for histopathology.
Figure 5
H & E section of minor salivary glands of lower lip x10 magnification
Red arrow indicates the periductal lymphocytic infiltrate and the collection of macrophages were evident of in a single focus. These histopathological features are supportive of the clinical diagnosis of SJOGREN’S SYNDROME.
The patient was reviewed at the clinic to educate about the nature of the disease and oral problems which can occur due to reduced saliva. Then the patient was advised to take frequent sips of water to eliminate dry mouth and to maintain good oral hygiene. Currently patient is on regular review for any oral complication of the disease. Other systemic conditions are being managed by relevant specialties.
Sjögren syndrome (SS) is a systemic chronic inflammatory disorder characterized by lymphocytic infiltrates in exocrine organs. Most individuals with Sjögren syndrome present with sicca symptoms, such as xerophthalmia (dry eyes), xerostomia (dry mouth), and parotid gland enlargement.[4,12] In addition, numerous extraglandular features may develop, such as arthralgia, arthritis, Raynaud phenomenon, myalgia, pulmonary disease, gastrointestinal disease, leukopenia, anemia, lymphadenopathy, neuropathy, vasculitis, renal tubular acidosis, and lymphoma.[12,14]
Primary Sjögren syndrome occurs in the absence of another underlying rheumatic disorder, whereas secondary Sjögren syndrome is associated with another underlying rheumatic disease, such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), or scleroderma.[6,19] Given the overlap of Sjögren syndrome with many other rheumatic disorders, it is sometimes difficult to determine whether a clinical manifestation is solely a consequence of Sjögren syndrome or is due to one of its overlapping disorders.[11,14]
Importantly, classic clinical features of Sjögren syndrome may also be seen in viral infections with hepatitis C, human immunodeficiency virus (HIV), and human T-cell lymphotrophic virus (HTLV).[18] Treatment for Sjögren syndrome is largely based on symptoms, but patients must be monitored carefully for the potential development of lymphoma.
In the literature SS cases are reported with various glandular and extra glandular clinical presentations. Clinical presentation of the case discussed here is cs
Clinical presentations reported in literature
Clinical presentations reported in literature Case
Glandular manifestations
Sandy, or scratchy sensation under the lids Present
Loss of tearing Present
Red painful eyes No
Mild photophobia Present
Xerostomia related symptoms
Inability to eat dry food
Tongue sticking to the roof of the mouth
Difficulty speaking for long periods
Higher incidence of dental caries and
periodontal disease
Altered sense of taste Present
Difficulty wearing dentures Not a Denture wearer
Oral candidiasis with angular cheilitis No
Difficulty with dry skin No
Dyspareunia due to dry vagina No
Extraglandular manifestations
Athritis Present
SLE Scleroderma, polymyositis,
chronic active hepatitis
Idiopathic pulmonary fibrosis No
Autoimmune thyroid disease Present
Interstitial nephritis Neurologic symptoms Pericarditis and pulmonary hypertension Gastrointestinal symptoms history of recurrent miscarriages or stillbirths Lymphoproliferative disease No, pt is being reviewed for development of these conditions
The pathophysiology of Sjögren syndrome is not well understood. The presence of activated salivary gland epithelial cells expressing major histocompatibility complex (MHC) class II molecules and the identification of inherited susceptibility markers suggest that environmental or endogenous antigens trigger a self-perpetuating inflammatory response in susceptible individuals.[7,12] In addition, the continuing presence of active interferon pathways in Sjögren syndrome suggests ongoing activation of the innate immune system. Together, these findings suggest an ongoing interaction between the innate and acquired immune systems in Sjögren syndrome.
The genetic associations in Sjögren syndrome vary among ethnic groups. the condition is linked to human leukocyte antigen (HLA)–DR3, HLA-DQ2, and HLA-B8, HLA-DRB1*15, HLA-DR5. [13] Some evidence indicates that the true association of Sjögren syndrome may be with HLA-DQA1, which is in linkage disequilibrium with HLA-DR3 and HLA-DR5.[13] These HLA associations appear restricted to individuals with Sjögren syndrome who have antibodies to SSA and
SSB rather than to the disease manifestations themselves.[7,13]
The pathology of a typical involved salivary or lacrimal gland in Sjögren syndrome reveals aggregations of lymphocytes, periductal at first (figure 5), then panlobular. These cells are primarily CD4 T cells (75%) and memory cells, with 10% B cells and immunoglobulin-secreting plasma cells.[19] Although individual lobules can be destroyed, salivary gland biopsy samples from patients with Sjögren syndrome typically retain 40%-50% of their viable glandular structure. Therefore, inflammatory destruction of salivary and lacrimal glands may not fully account for the symptoms of Sjögren syndrome.[17]
Recent studies suggest that the disease process of Sjögren syndrome has a neuroendocrine component [7] which might explain the development of hypothyroidism in the patient or the hypothyroidism in this patient can be a completely overlapping disorder. Moreover recent study reports that M3 muscarinic receptor antibodies may cause autonomic dysfunction in patients with Sjögren syndrome.[2,13 ]
Current studies have also focused on the role of apoptotic mechanisms in the pathogenesis of primary Sjögren syndrome. A defect in Fas-mediated apoptosis, which is necessary for down-regulation of the immune response, can result in a chronic inflammatory destruction of the salivary gland, resembling Sjögren syndrome.[16 ]
Owing to these structural and functional changes in the lacrimal and salivary glands, their aqueous output is diminished. In the eye, tear hyperosmolarity results and is itself a proinflammatory stimulus, resulting in an inflammatory cascade on the ocular surface, with evidence of immune activation of the conjunctival epithelium and local cytokine and metalloproteinase production.[12,18 ] Damage to the corneal epithelium, already vulnerable due to inadequate tear film protection, ensues, with resultant epithelial erosions and surface irregularity. This explains the eye symptoms of the patient.[1]
Extraglandular involvement in Sjögren syndrome manifests in part as hypergammaglobulinemia and the production of multiple autoantibodies, especially antinuclear antibody (ANA) and rheumatoid factor (RF).[7,9,12] This may be due to polyclonal B-cell activation, but the cause of this expanded activation is not known. Involvement of other organs and tissues may result from effects of these antibodies, immune complexes, or lymphocytic infiltration and occurs in one third of patients with Sjögren syndrome. Prolonged hyperstimulation of B cells may lead to disturbances in their differentiation and maturation and may account for the greatly increased incidence of lymphoma in these patients.[15,17 ] The prevalence of non-Hodgkin’s lymphoma (NHL) in primary and secondary Sjögren syndrome is 4.3%,
representing a relative risk of 44-fold compared to age, sex, and race matched healthy individuals.[17]
Diagnosis of Sjögren syndrome is based on an internationally approved set of criteria. The sensitivity and specificity of the diagnostic criteria exhibited good discrimination between patients and controls.[8,17] Although labial gland biopsy for examination of minor salivary glands is the most common invasive diagnostic procedure for Sjögren syndrome, the diagnosis is usually a clinical one based onthe history and physical examination with support from laboratory data.Anti-Ro (SSA) and anti-La (SSB) antibodies are included as part of the diagnostic criteria for Sjögren’s syndrome and should be assessed in all patients considered for this diagnosis.[5] Antibodies against SSA/Ro are found in approximately 50% of patients with the disease (75% of patients with primary Sjögren syndrome and 15% of patients with secondary Sjögren syndrome).[5,17] Thus, the absence of anti-SSA/Ro antibodies does not eliminate the diagnosis of primary or secondary Sjögren syndrome. Antibodies against SSA/Ro are present in 50% of patients with SLE and are sometimes found in healthy individuals.[5,17] Thus, by itself, the presence of antibody against SSA/Ro cannot establish a diagnosis of Sjögren syndrome. In this patient serologic testing had not being performed. For many years, the labial salivary gland (LSG) biopsy has been considered an important consideration among other parameters to help confirm the SS diagnosis.[17] The LSG biopsy is performed on the lower lip following administration of local anesthesia. A 1.5- to 2.0-cm horizontal incision is made on clinically normal labial mucosa, parallel to the vermillion border and lateral to the midline (figure 4). Five or more accessory salivary glands are harvested, formalin fixed, and embedded in paraffin. Sections of 5 µm and examined histopathologically.
The characteristic findings of minor salivary gland biopsy in a person with Sjögren syndrome include the following:[17,19]
· The biopsy shows focal aggregates of at least 50 lymphocytes (predominantly CD4+ cells), and, to a lesser extent, plasma cells and macrophages [figure 5].
· More than 1 focal aggregate is seen per 4 mm2.
· Normal acini are replaced by lymphocytes.
· Focal aggregates are seen in almost all glands
· Large foci are present, possibly showing germinal centers.
· Epimyoepithelial islands are uncommon in the minor salivary gland but can be seen in the major salivary glands (in this case also Epimyoepithelial islands were not seen).
Direct measurement of salivary flow (sialometry), radiocontrast assessment of salivary ductal system (sialography), and functional evaluation of the rate and density of salivary gland uptake of 99Tcmpertechnetate (scintigraphic isotope scanning) are primarily used in clinical trials, rarely to confirm the diagnosis in routine clinical practice.[3,11] Schirmer’s Test is a strong indicator of diminished tearing.[1,17]
Sjögren’s syndrome
Chronic sialadenitis
Patchy, focal periductal or perivascular mononuclear infiltrates with >50 lymphocytes,plasma cells, and macrophages
Scattered and diffuse lymphocytic and plasmacytic infiltration
One or more foci per 4 mm2 of tissue adjacent to intact, normal- appearing mucous acini Foci are seen consistently throughout the lobules in the specimen[17]
Acinar atrophy
Lack of ductal dilatation
Ductal dilatation
Lack of fibrosis
Diffuse interstitial fibrosis
Histopathological findings
Characteristic histopathological features of Sjögren’s syndrome and chronic sialadinitis [table2]

According to the American-European Consensus criteria:
The diagnosis of primary Sjögren syndrome requires 4 of 6 of the below criteria; in addition, either criterion number 5 or criterion number 6 must be included. Sjögren syndrome can be diagnosed in patients who have no sicca symptoms if 3 of 4 objective criteria are fulfilled. The criteria are as follows:[8,9,17]

1. Ocular symptoms
· Dry eyes for more than 3 months
· Foreign-body sensation
· Use of tear substitutes more than 3 times per day
2. Oral symptoms
· Feeling of dry mouth
· Recurrently swollen salivary glands
· Frequent use of liquids to aid swallowing
3. Ocular signs
· Schirmer test performed without anesthesia (< 5 mm in 5 min)
· Positive vital dye staining results
4. Oral signs
· Abnormal salivary scintigraphy findings
· Abnormal parotid sialography findings
· Abnormal sialometry findings (unstimulated salivary flow < 1.5 ml in 15 minutes)
5. Positive minor salivary gland biopsy findings
6. Positive anti–SSA or anti–SSB antibody results
Secondary Sjögren syndrome is diagnosed when, in the presence of a connective-tissue disease, symptoms of oral or ocular dryness are present in addition to criterion 3, 4, or 5 above. Application of these criteria has yielded a sensitivity of 97.2% and a specificity of 48.6% for the diagnosis of primary Sjögren syndrome; for secondary Sjögren syndrome, the specificity was 97.2% and the sensitivity 64.7%.[9,17 ]according to this criteria case discussed herein can be considered as secondary Sjögren syndrome.
Prevention and treatment of sicca and constitutional symptoms are among the primary objectives of management of Sjogren’s syndrome.[10,15,19] These objectives can generally be accomplished without rheumatology consultation, because Sjogren’s syndrome is a chronic disease with a broad clinical spectrum, patients should also be regularly followed for significant functional deterioration and evidence of disease complications such
as extra glandular involvement or lymphoma; if these occur, specialty consultation is appropriate. Thus this case should be closely monitored for progression of the disease while treating symptomatically and preventively.
1. Akpek EK, Lindsley KB, Adyanthaya RS, Swamy R, Baer AN,
McDonnell PJ. Treatment of Sjögren's Syndrome Associated Dry Eye an EvidenceBased Review.Ophthalmology. 2011 April 2.
2. Borchers AT, Naguwa SM, Keen CL, Gershwin ME. Immunopathogenesis of Sjögren's syndrome. Clin Rev Allergy Immunol. 2003 Aug ;25(1):89-104.
3. Claeys V, Wackens G. Rev Belge Med Dent (1984). 2006; 61 (3):161-72.Daniels TE, Benn DK. Is sialography effective in diagnosing the salivary component of Sjögren's syndrome?. Adv Dent Res. 1996 Apr;10(1):25-8.
4. Delaleu, N., Jonsson, R. and Koller, M. M. (2005), Sjögren's syndrome. European Journal of Oral Sciences, 113: 101–113.
5. Fox RI, Chan EK, Kang HI. Laboratory evaluation of patients with Sjögren's syndrome. Clin Biochem. 1992 Jun; 25(3):213-22.
6. Fox RI, Liu AY. Sjogren’s syndrome in dermatology. Clin Dermatol 2006; 24: 393413.
7. Fox RI, Stern M Sjögren's syndrome: mechanisms of pathogenesis involve interaction of immune and neurosecretory systems. Scand J Rheumatol Suppl. 2002 ;116:3-13.
8. Fox RI, Stern M, Michelson P. Update in Sjögren syndrome. Curr Opin Rheumatol. 2000 Sep ;12(5):391-8.
9. Fox RI, Törnwall J, Maruyama T, Stern M. Evolving concepts of diagnosis, pathogenesis, and therapy of Sjögren's syndrome. Curr Opin Rheumatol. 1998 Sep ;10(5):446-56.
10. Fox RI. Sjögren’s syndrome: current therapies remain inadequate for a common disease. Expert Opin Investig Drugs 2000; 9: 20072016.
11. Fox RI. Sjögren's syndrome. Controversies and progress. Clin Lab Med. 1997 Sep; 17 (3):431-44.
12. García-Carrasco M, Fuentes-Alexandro S, Escárcega RO, Salgado G, Riebeling C, Cervera R. Pathophysiology of Sjögren's syndrome. Arch Med Res. 2006 Nov ;37(8):921-32.
13. Jordan R, Diss TC, Lench NJ, Isaacson PG, Speight PM. Immunoglobulin gene rearrangements in lymphoplasmacytic infiltrates of labial salivary glands in Sjögren's syndrome. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1995 Jun ;79(6):723-9.
14. Kruize AA, Hené RJ, van der Heide A, Bodeutsch C, de Wilde PCM, van Bijsterveld OP, de Jong J, Feltkamp TEW, Kater L, Bijlsma JWJ: Long-term followup of patients with Sjögren's syndrome. Arthritis Rheum 39: 297303, 1996
15. Lavoie TN, Lee BH, Nguyen CQ. Current concepts: mouse models of Sjögren's syndrome.J Biomed Biotechnol. 2011;2011:549107. Epub 2010 Dec 30.
16. Manganelli P, Fietta P. Apoptosis and Sjögren syndrome.Semin Arthritis Rheum. 2003 Aug ;33(1):49-65.
17. Pesaramelli K, Anishetty R, Sravani K. sjogren’s syndrome: a review of clinical features, diagnosis and treatments available. Volume 5, Issue 1, November – December 2010; Article-014
18. Price EJ, Venables PJ. The etiopathogenesis of Sjögren's syndrome.Semin Arthritis Rheum. 1995 Oct; 25 (2):117-33.
19. Trenkić Božinović M, et al. Clinical, histopathological and immunohistological study of lymphoid disorders in the parotid gland of patients with Sjögren’s syndrome.Vojnosanit Pregl 2009; 66(12): 955–960.

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