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Sjogren's Syndrome

last modified on: Sun, 04/12/2020 - 16:43

Return to: Salivary Swelling;  Parotid sialogram, ultrasound, and CT for Sjogrens syndrome ; Management of Xerostomia;  Sialograms and SialographySalivary Ultrasound

see also: Sjogrens Syndrome Foundation  https://www.sjogrens.org/

  1. Sjogren's Syndrome:
    1. Autoimmune disorder classically characterized by xerostomia and xerophtalmia (keratoconjunctivitis sicca - KCS)
      1. Variable clinical presentation
        1. Peripheral neuropathy
        2. Pulmonary insufficiency
        3. Joint pain
        4. Salivary gland enlargement
        5. Other: autoimmune thyroid disease (est in 50%); cough with dry larynx; primary biliary cirrhosis (Gutta 2008)
      2. Demographics
        1. occurs in 1% of general population
        2. occurs in 10-15% of patients with Rheumatoid arthritis
        3. 9:1 female:male ratio
        4. age of onset usually between age 40-60
      3. Pathologic mechanism for non-classic symptoms not well established.
      4. Primary Sjogren's syndrome: keratoconjunctivitis sicca and xerostomia
      5. Secondary Sjogrens syndrome: keratoconjunctivitis sicca, xerostomia, and an autoimmune disease, most commonly rheumatoid arthritis
    2. Diagnosis
      1. Discussion persists re: discriminating 'sicca syndrome' from Sjogrens syndrome. Classic criteria: (adapted from Viali et al 2002 and Gutta et al 2008) a.k.a. "European-American Criteria from 2002
        1. Primary Sjogren's: requires 4 of the 6 criteria below, including either positive antibodies or positive lip biopsy

Secondary Sjogren's requires diagnosis of connective tissue disease and one sicca symptom and 2 out of the 3 objective tests for either xeropthalmia (ocular) or xerostomia (oral) symptoms.
 

1.Positive antibodies

 anti-SSA

and/or SSB

 2.Lip Biopsy

3.Oral Symptoms

(1of3)

Dry mouth > 3 months

4.Oral Test

(1of3)

Unstim saliv flow <.1mL/min

5.Ocular Symptoms

(1of3)

Dry eyes > 3 months

6.Ocular Tests

(1of2)

 

positive

 

focus score >0.25 mm2

Swollen salivary glands

Abnormal parotid Sialography

Foreign body sensation in eye

+'ve slit lamp exam

 

see Lip biopsy

Need liquids to swallow

Abnormal salivary scintigraphy

Use of artificial tears >3 x per day

 +'ve Schirmer's test

 

 

  1. The 2012 American College of Rheumatology Criteria (2012 Shiboski et al) narrowed the inclusion criteria for Sjogren's syndrome to:
    1. Eliminate the distinction between primary and secondary forms of Sjogren's Syndrome
    2. Employ only three inclusion criteria for the classification as SS established in individuals with signs/symptoms suggestive of SS and at least two of the three objective features:
      1. Keratoconjunctivitis sicca with ocular staining score >= 3 (excluding pts who have had corneal or eyelid surgery in 5 yrs and individuals using daily eye drops for glaucoma)
      2. Labial salivary gland biopsy exhibiting focal lymphocytic sialadenitis with a focus score >= 1 focus/4 mm2
      3. Positive serum anti-SSA/Ro and/or anti-SSB/La or (positive rheumatoid factor and Ana titer >=1:320)
    3. A critical comparison of this ACR (American College of Rheumatology) Criteria with the established AECG (American-European Consensus Group) concluded that neither system is clearly superior to the other when classifying a patient with SS - and that the AECG criteria may be applicable to broader use (2013 Rasmussen et al)
  2. Clinical presentation
  3.  Blood - anti-SSA, anti-SSB, rheumatoid factor (see Simard and Holmqvist 2012) and antinuclear antibody (ANA)
    1. Rheumatoid factor has been reported by Ingegnoli et al (20130 to be elevated with rheumatoid arthritis (70-90%) and primary Sjogren's syndrome (75-95%) and to a lesser extent among multiple other diseases including infectious processes and cirrhosis with the highest percentage of patients with elevated RF occurring in those with 'mixed cryoglobulinemia type II (100%)
  4.  Lip Biopsy -useful for selected cases but 'noted inconsistency and unreliability with the lip biopsy' (ref Bamba et al)
    1. False negative biopsy:
      1. common when on immunosuppressive medication (including corticosteroids)
      2. False negative in the face of chronic Sjogren's syndrome with atrophy and fibrosis of salivary glands (long standing Sjogren's may not benefit)
      3. Cigarette smoking (Manthorpe 2000)
      4. Sialography felt to be diagnostically more sensitive but less specific than labial salivary gland biopsy (Daniels et al 1996)
    2. False positive
      1. Aging, trauma, hepatitis C, lymphoma, graft v host disease, sarcoidosis (Huo et al 2010)
    3. Not useful in the face of elevated anti-SSA or anti-SSB antibodies (reliably predict positive results of a lip biopsy)
          4.   Useful in selected cases of suspected Sjogren's in the face of negative ANA, RF, anti-SSA or anti-SSB antibodies.
          5.   Suggested by Huo et al that 'lip biopsy be reserved only for patients whose serological tests for ANA, RF, anti-SS-A and anti-SS-B are all negative" (Huo et al 2010)
          6    Technique: Lip biopsy for minor salivary gland (biopsy for Sjogren's syndrome)
  5. Imaging - see Sjogren Syndrome Rads and Sialogram Left Parotid Sjogrens Syndrome
  6. Pathology - see Sjogren Syndrome Pathology
  7. Medical Management:
    1. Symptom control, that is, treating dental caries, fungal infections, stimulating salivary gland production, and supplementing salivary production (Daniels 1992).  In addition, systemic steroids, cytokines and disease modifying agents have been tried with mixed results (von Bültzingslöwen 2007). 
  8. Surgical Management:
    1. Corticosteroid irrigation of the parotid gland significantly increased the salivary flow rate in patients with Sjögren’s syndrome. (Izumi et al 1998)
    2. More recently (Shacham et al 2011) a group from Israel reported relief of chronic recurrent sialadenitis associated with Sjogren's and SLE with 100 mg hydrocortisone instilled into ducts at the time of sialendoscopy with duct dilation
    3. Our experience (U of Iowa) is similar to Shacham in relief of pain and swelling following instillation of steroid (usually 3 cc of kenalog 10) for patients with sialadenitis due to irradiation (I131), Sjogren's syndrome, and sialosis.  In the absence of defined stricture (identified through sialography / sialendoscopy), instillations are commonly done in the clinic under topical anesthesia (Diggelmann 2015)
      1. See: Parotid duct dilation and steroid insufflation in clinic
    4. Resection of salivary glands
  9. Useful Resources:
    1. The New Sjogren's Syndrome Handbook  ed Wallace, DJ Oxford University Press   New York  2005
    2. Sjogren's Syndrome Foundation (educational site):  http://www.sjogrens.org/home/about-sjogrens-syndrome
  10. SUGGESTED READING
    1. Bamba R, Sweiss NJ, Langerman AJ, Taxy JB and Blair EA: The Minor Salivary Gland Biopsy as a Diagnostic Tool for Sjorgren Syndrome.  Laryngoscope, 119:1922-1926, 2009
    2. Izumi M, Eguchi K, Nakamura H, Takagi Y, Kawabe Y, Nakamura T.  Corticosteroid irrigation of parotid gland for treatment of xerostomia in patients with Sjögren’s syndrome.  Ann Rheum Dis 1998 ;57:464-469
    3. von Bulzingslowen, et. all.  Salivary 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
    4. Daniels TE, Fox PE.  Salivary and oral components of Sjögren’s syndrome.  Rheum Dis Clin North Am. 1992;18(3):571-89
    5. Manthorpe R et al (2000) Lower frequency of focal lip sialadneitis (focus score) in smoiking patients...  Ann Rheum Dis 59,54-60
    6. Huo A-P, Lin K-C and Chou C-T: Predictive and prognostic value of antinuclear antibodies and rheumatoid factor in primary Sjogren's syndrome. Int. J o fRheumatic Diseases 2010;13:39-47 
    7. Gutta R, McLain L and McGuff SH: Sjorgren Syndrome: A Review for the Maxillofacial Surgeon. Oral Maxillofacial Surg Clin N Am 20 (2008)567-575
    8. Vitali C, Bombardieri S, Moutsopoulos HM et al (2002) Classification criteria for Sjogrens syndrome: a revised version of the European criteria proposed by the American-European Consnesus Group. Ann Rheum Dis 61, 554-8
    9. Shacham R, Puterman MB, Ohana N, and Nablieli O: Endoscopic Treatment of Salivary Glands Affected by Autoimmune Diseases  J Oral Maxillofc Surg 69:476-481, 2011
    10. Daniels TE and Benn DK: Is sialography effective in diagnosing the salivary component of Sjogren's syndrome? Adv Dent Res  1996 Apr;10(1):25-8
    11. Rasmussen A, Ice JA, Li H, et al: Comparison of the American-European Consensus Group Sjogren's syndrome classification criteria to newly proposed American College of Rheumatology criteria in a large, carefully characterised SICCA cohort. Ann Rheum Dis Published Online First accessed 09-23-2013; doi:10.1136/annrheumdis-2013-203845
    12. Simard JF and Holmquist: Rheumatoid factor positivity in the general population BMJ 2012, 345
    13. Ingegnoli f, Castelli R, and Gualtierotti R: Rheumatoid factors: clinical applications. Dis Markers. 2013;35(6):727-34
    14. Diggelmann HR, Hoffman HT.: Intraductal infusion of steroids in patients with Sjögren syndrome to treat painful salivary swelling: Report of 2 cases.Ear Nose Throat J. 2015 Jun;94(6):238-9.

    15. Elizabeth J Price Alan N Baer: How to treat Sjögren’s syndrome Rheumatology, key363, https://doi.org/10.1093/rheumatology/key363 Published: 15 February 2019Jousse-Joulin s, D’agostino Ma, nicolas C, et al.Video clip assessment of a salivary gland ultrasound scoring system in Sjögren's syndrome using consensual definitions: an OMERACT ultrasound working group reliability exercise. Ann Rheum Dis 2019;78:967–973.

    16. Foggia MJ, Peterson J, Maley J, Policeni B, Hoffman HT. Sialographic analysis of parotid ductal abnormalities associated with Sjogren's syndrome.Oral Dis. 2020 Feb 7. doi: 10.1111/odi.13298. [Epub ahead of print]PMID:32031309

      Jousse-Joulin S, Gatineau F, Baldini C,et al Weight of salivary gland ultrasonography compared to other items of the 2016 ACR/EULAR classification criteria for Primary Sjögren's syndrome.J Intern Med. 2020 Feb;287(2):180-188. doi: 10.1111/joim.12992. Epub 2019 Nov 12.