Close
New

Medscape is available in 5 Language Editions – Choose your Edition here.

 

Sjogren Syndrome Workup

  • Author: Anne V Miller, MD; Chief Editor: Herbert S Diamond, MD  more...
 
Updated: Sep 25, 2015
 

Approach Considerations

Some laboratory tests can be used to assess salivary and lacrimal involvement in Sjögren syndrome. However, no single test is sufficiently sensitive or specific in the diagnosis of Sjögren syndrome. The condition is properly diagnosed only when the results of various tests are simultaneously positive and when subjective symptoms and serologic abnormalities are present.[59]

Laboratory test results may indicate the following:

  • Elevated erythrocyte sedimentation rate (ESR)
  • Anemia
  • Leukopenia
  • Eosinophilia
  • Hypergammaglobulinemia
  • Presence of antinuclear antibodies, especially anti-Ro and anti-La
  • Presence of RF
  • Presence of anti–alpha-fodrin antibody (reliable diagnostic marker of juvenile Sjögren syndrome)
  • Creatinine clearance may be diminished in up to 50% of patients

Multiple autoantibodies are associated with Sjögren syndrome.[60] In a study in which atypical autoantibodies were evaluated in 82 patients with primary Sjögren syndrome, an immunologic overlap (defined by the presence of autoantibodies typical of other systemic autoimmune diseases) was evident in 20% of the patients. The clinical significance of these atypical autoantibodies varied widely.[61]

Patients with primary Sjögren syndrome may have positive test results for lupus anticoagulant and/or anticardiolipin antibodies, and some patients develop clinical events (ie, fetal wastage, arterial and/or venous thrombosis) associated with antiphospholipid syndrome. Anti ̶ salivary duct antibodies are present in most cases of secondary Sjögren syndrome.

Type II cryoglobulins are noted, particularly in patients with palpable and nonpalpable vasculitic purpura. Hepatitis C should be sought in these patients.

In some studies, patients with Sjögren syndrome have an increased frequency of autoimmune thyroid disease with hypothyroidism (10-15%). Lymphocytic infiltration can be observed in the thyroid gland.

Elevations of serum immunoglobulin G4 (IgG4), found in IgG4-related plasmacytic disease (which can mimic the glandular infiltrations of Sjögren syndrome), are not seen in Sjögren syndrome.[62, 63]

Antibodies to carbonic anhydrase 11 can be seen in patients with Sjögren syndrome who have primary billiary cirrhosis.[56]

Schirmer test

The Schirmer test is probably the only test available in the emergency department (ED) that can be used to strongly support or refute suspicion of Sjögren syndrome. A test strip of number 41 Whatman filter paper is placed near the lower conjunctival sac to measure tear formation. Healthy persons wet 15mm or more after 5 minutes. A positive test occurs when less than 5mm are wet after 5 minutes. A Schirmer test is shown in the image below.

Photograph that demonstrates the Schirmer test, wh Photograph that demonstrates the Schirmer test, which is used to detect deficient tear production in patients with Sjögren syndrome. The filter paper strip is placed at the junction of the eyelid margins. After 5 minutes, 15 mm of paper should be moistened if tear production is normal, as shown here. Persons older than 40 years may moisten between 10 mm and 15 mm. Patients with Sjögren syndrome have less moistening. Sjögren syndrome is most common in patients with rheumatoid arthritis but may also occur without associated disease and in systemic lupus erythematosus, polyarteritis, systemic sclerosis, lymphoma, and sarcoidosis.

Rheumatoid factor

Rheumatoid factor is present in 52% of patients with primary Sjögren syndrome and in 98% of patients with the secondary disease, occurring even when RA is not present. Consider a diagnosis of RA if the patient has symmetrical polyarticular synovitis. Loss of a previously positive RF finding can be observed in some patients with Sjögren syndrome who develop lymphoma.

Antinuclear antibodies

ANAs are typically present in patients with Sjögren syndrome. Consider the diagnosis of SLE only if symptoms and signs typical of this disorder are present.

Serum protein electrophoresis

Patients with Sjögren syndrome often have a polyclonal gammopathy. Loss of a previously detected polyclonal gammopathy can be observed in some patients with Sjögren syndrome who develop lymphoma. Development of a monoclonal gammopathy can also signal the development of a lymphoma.

Staining

Rose bengal is an aniline dye that stains epithelial surfaces with diminished mucin protection or with exposed epithelial cell membranes. Conjunctival staining can be detected with the naked eye. Slit-lamp examination is performed after rose bengal staining to detect abnormal uptake in the cornea.

Lissamine green staining works similarly but is less irritating to the eye. Fluorescein staining can be used to detect corneal damage.

Salivary testing

Sialometry is a good measure of the degree of decreased salivary flow and helps to establish xerostomia, but the findings do not narrow the differential diagnoses.

Saliva from patients with Sjögren syndrome has elevated levels of sodium, chloride, lactoferrin, and IgA, but these findings are not specific.

Sedimentation rate

The erythrocyte sedimentation rate (ESR) is elevated in 80% of patients with Sjögren syndrome, but the finding is nonspecific.

Protein profiling

Protein profiling (tear proteomics) has revealed reproducible patterns in patients with primary Sjögren syndrome and appears to hold promise as a diagnostic test for this disorder.[64]

Additional test considerations

Other test results to consider are as follows:

  • High total protein level or a low albumin level - Should prompt the clinician to perform serum protein electrophoresis
  • High alkaline phosphatase level - Should prompt consideration of primary biliary cirrhosis
  • Elevated transaminase levels - Consider the possibility of chronic active hepatitis, which can be associated with sicca symptoms, or hepatitis C, which can cause mild salivary gland enlargement; however, mild (< 2-fold) increases in transaminase levels have been observed in 22% of patients with Sjögren syndrome [65]
  • Low bicarbonate level - Consider evaluating patients with a low bicarbonate level for type I (distal) renal tubular acidosis; less commonly, patients can also develop proximal renal tubular acidosis with Fanconi syndrome
  • Hypokalemia - This condition, which is occasionally severe enough to lead to periodic paralysis, can be observed in patients with type I renal tubular acidosis; however, it can also be observed in patients who have Sjögren syndrome without renal tubular acidosis [43]
Next

SSA and SSB

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). 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. Thus, the presence of antibody against SSA/Ro cannot by itself be used to establish a diagnosis of Sjögren syndrome.

Antibodies against SSB/La are present in 40-50% of patients with primary Sjögren syndrome and in 15% of patients with SLE. Finding antibodies against SSB/La in patients without antibodies against SSA/Ro is unusual, but this combination has occurred in patients with primary biliary cirrhosis and autoimmune hepatitis.

Titers of anti-SSA/Ro and anti-SSB/La antibodies do not reflect disease activity. Current enzyme-linked immunosorbent assay tests for these antibodies are more sensitive than previous tests. Thus, the specificity is lower.

Antibodies against SSA/Ro are also associated with the annular erythematous lesions of subacute cutaneous lupus. They are also found in the mothers of newborns with neonatal lupus syndromes and congenital heart block, and some of these mothers have or will develop Sjögren syndrome.

Previous
Next

CBC

In patients with Sjögren syndrome, the complete blood count (CBC) is most often within the reference range, but anemia of chronic disease may be present. Pernicious anemia may be associated with the atrophic gastritis.

An abnormal white blood cell (WBC) count, especially with an abnormal differential count, should prompt concerns for a lymphoreticular malignancy. In addition, although a low platelet or WBC count can occur in persons with primary Sjögren syndrome, the finding should also prompt consideration for coexisting SLE.

A mild, normochromic, normocytic anemia is present in 50% of patients. Leukopenia occurs in up to 42% of patients.

Previous
Next

Sialography and Scintigraphy

In sialography, radiopaque material is injected into the salivary glands. Sialography is useful to exclude the presence of obstructions or strictures, but the diffuse sialectasis of Sjögren syndrome is seen in various other diseases and is therefore not specific.

Oil-based contrast medium may not be adequately cleared in patients with Sjögren syndrome and, consequently, may damage adjacent tissues and lead to a chronic granulomatous reaction. Performing this procedure with oil-based contrast should be avoided, especially during episodes of acute swelling.

With salivary scintigraphy, the uptake and secretion of sodium pertechnetate technetium-99m (99m Tc) is a gauge of the salivary flow rates and can provide an objective measurement of salivary gland dysfunction. However, the finding of low flow rates is not specific to Sjögren syndrome.

Positive findings on either sialography or scintigraphy fulfill a criterion for objective evidence of Sjögren syndrome by the American-European Consensus Group.[2]

Previous
Next

Biopsy

Minor salivary gland biopsy[66] currently is the best single test to establish a diagnosis of Sjögren syndrome. In this procedure, an incision is made on the inner lip, and some minor salivary glands are removed for examination. In patients with a possible diagnosis of this disease but with severe extraglandular symptoms, a lip biopsy is often performed to firmly establish the diagnosis of Sjögren syndrome. Obtaining the biopsy sample from below normal-appearing mucosa is important in order to avoid false-positive results. At least 4 salivary gland lobules should be obtained for analysis.

While this is the most definitive test, performing it is not absolutely necessary from a clinical standpoint. Patients with Sjögren syndrome are essentially treated symptomatically and are observed for the development of other rheumatic disorders or lymphoma. This can be initiated without performing a biopsy. If, however, the diagnosis is in doubt or if a definitive diagnosis is needed, then this is the best test.

Salivary gland biopsy can also help to detect pseudolymphoma or lymphoma, as well as the noncaseating granulomas of sarcoidosis.

One study showed that not all patients undergoing lip biopsy derived diagnostic benefit from this procedure and that clinical symptoms and serology did not predict a positive lip biopsy.[67]

In another study, however, a significant correlation was found between positive findings in minor salivary gland biopsy and the Schirmer test, the rose bengal test, xerostomia, and parotid swelling. The investigators utilized biopsy specimens from the lower lip of 360 patients.[68]

Previous
Next

Histologic Findings

Although pathologists use different classification systems, the characteristic findings of minor salivary gland biopsy in a person with Sjögren syndrome include the following (see the image below)[69] :

  • The biopsy shows focal aggregates of at least 50 lymphocytes, and, to a lesser extent, plasma cells and macrophages
  • More than 1 focal aggregate is seen per 4 mm 2
  • T cells, predominantly CD4 + cells, are present, unlike the predominance of CD8 + T cells seen in the salivary gland biopsy samples from patients with DILS associated with HIV disease
  • Normal acini are replaced by lymphocytes
  • Focal aggregates are seen in almost all glands
  • Ten percent of the lymphocytes are CD5 + B cells that produce IgM and IgG antibodies, often with a monoclonal or oligoclonal pattern
  • 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
    Photomicrograph of a lip biopsy specimen showing t Photomicrograph of a lip biopsy specimen showing two lymphocytic foci adjacent to normal-appearing mucinous acini typical of minor salivary gland abnormalities in Sjögren syndrome.

A score of greater than 1 focus per 4 mm2 has a specificity of 83.5-95% and a sensitivity of 63-81.8% in the diagnosis of Sjögren syndrome. The focus score may be associated with keratoconjunctivitis sicca, the presence of autoantibodies, and, less commonly, xerostomia.

Lymphocytic infiltrates are also seen in other organs. Findings from a gastric mucosal biopsy may show lymphocytic infiltrates with atrophic gastritis. A kidney biopsy may show interstitial lymphocytic infiltration. Lung biopsy can reveal infiltrating CD4+ T cells of a lymphocytic interstitial pneumonitis. Salivary gland biopsy can help to detect pseudolymphoma or lymphoma, as well as the noncaseating granulomas of sarcoidosis.

Previous
 
 
Contributor Information and Disclosures
Author

Anne V Miller, MD Chief, Rheumatology Division; Assistant Professor of Internal Medicine, Department of Medicine, Division of Rheumatology, Southern Illinois University School of Medicine

Anne V Miller, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American College of Rheumatology, International Society for Clinical Densitometry

Disclosure: Nothing to disclose.

Coauthor(s)

Mark L Francis, MD Professor of Medical Education, Department of Medical Education, Paul L Foster School of Medicine, Texas Tech University Health Sciences Center

Mark L Francis, MD is a member of the following medical societies: American College of Physicians, Phi Beta Kappa

Disclosure: Nothing to disclose.

Kanchan Pema, MD Associate Professor of Rheumatology, Department of Internal Medicine, Texas Tech University Health Sciences Center

Kanchan Pema, MD is a member of the following medical societies: American College of Physicians, American College of Rheumatology, American Medical Association

Disclosure: Nothing to disclose.

Sriya K Ranatunga, MD, MPH Associate Professor of Clinical Medicine, Division of Rheumatology, Department of Internal Medicine, Southern Illinois University

Sriya K Ranatunga, MD, MPH is a member of the following medical societies: American College of Physicians, American College of Rheumatology, Association of American Medical Colleges

Disclosure: Nothing to disclose.

Anna Tumyan, MD Assistant Professor of Internal Medicine, Division of Rheumatology, Southern Illinois University School of Medicine

Disclosure: Nothing to disclose.

Chief Editor

Herbert S Diamond, MD Visiting Professor of Medicine, Division of Rheumatology, State University of New York Downstate Medical Center; Chairman Emeritus, Department of Internal Medicine, Western Pennsylvania Hospital

Herbert S Diamond, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American College of Rheumatology, American Medical Association, Phi Beta Kappa

Disclosure: Nothing to disclose.

Acknowledgements

Terry L Barrett, MD Clinical Professor of Dermatology and Pathology, University of Texas Southwestern School of Medicine; Director, ProPath Dermatopathology, Dallas, Texas

Terry L Barrett, MD is a member of the following medical societies: American Academy of Dermatology, American Dermatological Association, American Medical Association, American Society of Dermatopathology, College of American Pathologists, and United States and Canadian Academy of Pathology

Disclosure: Nothing to disclose.

David F Butler, MD Professor of Dermatology, Texas A&M University College of Medicine; Chair, Department of Dermatology, Director, Dermatology Residency Training Program, Scott and White Clinic, Northside Clinic

David F Butler, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, American Society for Dermatologic Surgery, American Society for MOHS Surgery, Association of Military Dermatologists, and Phi Beta Kappa

Disclosure: Nothing to disclose.

Daniel J Dire, MD, FACEP, FAAP, FAAEM Clinical Professor, Department of Emergency Medicine, University of Texas-Houston; Clinical Professor, Department of Pediatrics, University of Texas Health Sciences Center, San Antonio, Texas

Daniel J Dire, MD, FACEP, FAAP, FAAEM is a member of the following medical societies: American Academy of Clinical Toxicology, American Academy of Emergency Medicine, American Academy of Pediatrics, American College of Emergency Physicians, and Association of Military Surgeons of the US

Disclosure: Talecris Biotherapeutics Honoraria Speaking and teaching

Dirk M Elston, MD, Director, Ackerman Academy of Dermatopathology, New York

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Gino A Farina, MD, FACEP, FAAEM Associate Professor of Clinical Emergency Medicine, Albert Einstein College of Medicine; Program Director, Department of Emergency Medicine, Long Island Jewish Medical Center

Gino A Farina, MD, FACEP, FAAEM is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Elliot Goldberg, MD Dean of the Western Pennsylvania Clinical Campus, Professor, Department of Medicine, Temple University School of Medicine

Elliot Goldberg, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, and American College of Rheumatology

Disclosure: Nothing to disclose

Rick Kulkarni, MD Attending Physician, Department of Emergency Medicine, Cambridge Health Alliance, Division of Emergency Medicine, Harvard Medical School

Rick Kulkarni, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Emergency Medicine, American College of Emergency Physicians, American Medical Association, American Medical Informatics Association, Phi Beta Kappa, and Society for Academic Emergency Medicine

Disclosure: WebMD Salary Employment

Carlos J Lozada, MD Director of Rheumatology Fellowship Program, Professor, Department of Medicine, Division of Rheumatology and Immunology, University of Miami, Leonard M Miller School of Medicine

Carlos J Lozada, MD is a member of the following medical societies: American College of Physicians and American College of Rheumatology

Disclosure: Pfizer Honoraria Speaking and teaching; Amgen Honoraria Speaking and teaching

Jeffrey J Miller, MD Associate Professor of Dermatology, Pennsylvania State University College of Medicine; Staff Dermatologist, Pennsylvania State Milton S Hershey Medical Center

Jeffrey J Miller, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, Association of Professors of Dermatology, North American Hair Research Society, and Society for Investigative Dermatology

Disclosure: Nothing to disclose.

Joanna Narbutt, MD, PhD Senior Registrar, Lecturer, Department of Dermatology and Venereology, Medical University of Lodz, Poland

Disclosure: Nothing to disclose.

Darren Phelan, MD Medical Director, Department of Emergency Medicine, Sierra Nevada Memorial Hospital

Disclosure: Nothing to disclose.

Sriya K M Ranatunga, MD, MPH Associate Professor, Department of Clinical Medicine, Southern Illinois University School of Medicine

Disclosure: Nothing to disclose.

Robert A Schwartz, MD, MPH Professor and Head, Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, University of Medicine and Dentistry of New Jersey-New Jersey Medical School

Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American College of Physicians, and Sigma Xi

Disclosure: Nothing to disclose.

Anna Sysa-Jedrzejowska, MD, PhD Head, Professor, Department of Dermatology and Venereology, Medical University of Lodz, Poland

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Jolanta Dorota Torzecka, MD, PhD Consulting Staff, Department of Dermatology and Venereology, Medical University of Lodz, Poland

Disclosure: Nothing to disclose.

Anna Zalewska, MD, PhD Professor of Dermatology and Venereology, Psychodermatology Department, Chair of Clinical Immunology and Microbiology, Medical University of Lodz, Poland

Disclosure: Nothing to disclose.

References
  1. Kittridge A, Routhouska SB, Korman NJ. Dermatologic manifestations of Sjögren syndrome. J Cutan Med Surg. 2011 Jan-Feb. 15(1):8-14. [Medline].

  2. Vitali C, Bombardieri S, Jonsson R, Moutsopoulos HM, Alexander EL, Carsons SE, et al. Classification criteria for Sjögren's syndrome: a revised version of the European criteria proposed by the American-European Consensus Group. Ann Rheum Dis. 2002 Jun. 61(6):554-8. [Medline].

  3. Langegger C, Wenger M, Duftner C, Dejaco C, Baldissera I, Moncayo R, et al. Use of the European preliminary criteria, the Breiman-classification tree and the American-European criteria for diagnosis of primary Sjögren's Syndrome in daily practice: a retrospective analysis. Rheumatol Int. 2007 Jun. 27(8):699-702. [Medline].

  4. Tzioufas AG, Voulgarelis M. Update on Sjögren's syndrome autoimmune epithelitis: from classification to increased neoplasias. Best Pract Res Clin Rheumatol. 2007 Dec. 21(6):989-1010. [Medline].

  5. Gálvez J, Sáiz E, López P, Pina MA, Carrillo A, Nieto A, et al. Diagnostic evaluation and classification criteria in Sjögren's Syndrome. Joint Bone Spine. 2008 Sep 29. [Medline].

  6. Shiboski SC, Shiboski CH, Criswell L, Baer A, Challacombe S, Lanfranchi H, et al. 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 Apr. 64(4):475-87. [Medline]. [Full Text].

  7. Ogawa N, Ping L, Zhenjun L, Takada Y, Sugai S. Involvement of the interferon-gamma-induced T cell-attracting chemokines, interferon-gamma-inducible 10-kd protein (CXCL10) and monokine induced by interferon-gamma (CXCL9), in the salivary gland lesions o...

  8. Gottenberg JE, Cagnard N, Lucchesi C, Letourneur F, Mistou S, Lazure T, et al. Activation of IFN pathways and plasmacytoid dendritic cell recruitment in target organs of primary Sjögren's syndrome. Proc Natl Acad Sci U S A. 2006 Feb 21. 103(8):2770-5. [Medline].

  9. Price EJ, Venables PJ. The etiopathogenesis of Sjögren's syndrome. Semin Arthritis Rheum. 1995 Oct. 25(2):117-33. [Medline].

  10. Mattey DL, González-Gay MA, Hajeer AH, Dababneh A, Thomson W, García-Porrúa C, et al. Association between HLA-DRB1*15 and secondary Sjögren's syndrome in patients with rheumatoid arthritis. J Rheumatol. 2000 Nov. 27(11):2611-6. [Medline].

  11. Papasteriades CA, Skopouli FN, Drosos AA, Andonopoulos AP, Moutsopoulos HM. HLA-alloantigen associations in Greek patients with Sjögren's syndrome. J Autoimmun. 1988 Feb. 1(1):85-90. [Medline].

  12. Reveille JD, Macleod MJ, Whittington K, Arnett FC. Specific amino acid residues in the second hypervariable region of HLA-DQA1 and DQB1 chain genes promote the Ro (SS-A)/La (SS-B) autoantibody responses. J Immunol. 1991 Jun 1. 146(11):3871-6. [Medline].

  13. Gottenberg JE, Busson M, Loiseau P, Cohen-Solal J, Lepage V, Charron D, et al. In primary Sjögren's syndrome, HLA class II is associated exclusively with autoantibody production and spreading of the autoimmune response. Arthritis Rheum. 2003 Aug. 48(8):2240-5. [Medline].

  14. Haddad J, Deny P, Munz-Gotheil C, Ambrosini JC, Trinchet JC, Pateron D, et al. Lymphocytic sialadenitis of Sjögren's syndrome associated with chronic hepatitis C virus liver disease. Lancet. 1992 Feb 8. 339(8789):321-3. [Medline].

  15. Itescu S, Winchester R. Diffuse infiltrative lymphocytosis syndrome: a disorder occurring in human immunodeficiency virus-1 infection that may present as a sicca syndrome. Rheum Dis Clin North Am. 1992 Aug. 18(3):683-97. [Medline].

  16. Fox RI. Epidemiology, pathogenesis, animal models, and treatment of Sjögren's syndrome. Curr Opin Rheumatol. 1994 Sep. 6(5):501-8. [Medline].

  17. Fox RI. Sjögren's syndrome. Lancet. 2005 Jul 23-29. 366(9482):321-31. [Medline].

  18. Parkin B, Chew JB, White VA, Garcia-Briones G, Chhanabhai M, Rootman J. Lymphocytic infiltration and enlargement of the lacrimal glands: a new subtype of primary Sjögren's syndrome?. Ophthalmology. 2005 Nov. 112(11):2040-7. [Medline].

  19. Bacman S, Perez Leiros C, Sterin-Borda L, Hubscher O, Arana R, Borda E. Autoantibodies against lacrimal gland M3 muscarinic acetylcholine receptors in patients with primary Sjögren's syndrome. Invest Ophthalmol Vis Sci. 1998 Jan. 39(1):151-6. [Medline].

  20. Steinfeld S, Cogan E, King LS, Agre P, Kiss R, Delporte C. Abnormal distribution of aquaporin-5 water channel protein in salivary glands from Sjögren's syndrome patients. Lab Invest. 2001 Feb. 81(2):143-8. [Medline].

  21. Waterman SA, Gordon TP, Rischmueller M. Inhibitory effects of muscarinic receptor autoantibodies on parasympathetic neurotransmission in Sjögren's syndrome. Arthritis Rheum. 2000 Jul. 43(7):1647-54. [Medline].

  22. Dawson LJ, Stanbury J, Venn N, Hasdimir B, Rogers SN, Smith PM. Antimuscarinic antibodies in primary Sjögren's syndrome reversibly inhibit the mechanism of fluid secretion by human submandibular salivary acinar cells. Arthritis Rheum. 2006 Apr. 54(4):1165-73. [Medline].

  23. Bolstad AI, Eiken HG, Rosenlund B, Alarcón-Riquelme ME, Jonsson R. Increased salivary gland tissue expression of Fas, Fas ligand, cytotoxic T lymphocyte-associated antigen 4, and programmed cell death 1 in primary Sjögren's syndrome. Arthritis Rheum. 2003 Jan. 48(1):174-85. [Medline].

  24. Pflugfelder SC. Antiinflammatory therapy for dry eye. Am J Ophthalmol. 2004 Feb. 137(2):337-42. [Medline].

  25. Ng KP, Isenberg DA. Sjögren's syndrome: diagnosis and therapeutic challenges in the elderly. Drugs Aging. 2008. 25(1):19-33. [Medline].

  26. Helmick CG, Felson DT, Lawrence RC, et al. Estimates of the prevalence of arthritis and other rheumatic conditions in the United States. Part I. Arthritis Rheum. 2008 Jan. 58(1):15-25. [Medline].

  27. Haldorsen K, Moen K, Jacobsen H, Jonsson R, Brun JG. Exocrine function in primary Sjögren syndrome: natural course and prognostic factors. Ann Rheum Dis. 2008 Jul. 67(7):949-54. [Medline].

  28. Belenguer R, Ramos-Casals M, Brito-Zerón P, et al. Influence of clinical and immunological parameters on the health-related quality of life of patients with primary Sjögren's syndrome. Clin Exp Rheumatol. 2005 May-Jun. 23(3):351-6. [Medline].

  29. Theander E, Vasaitis L, Baecklund E, et al. Lymphoid organisation in labial salivary gland biopsies is a possible predictor for the development of malignant lymphoma in primary Sjögren's syndrome. Ann Rheum Dis. 2011 Aug. 70(8):1363-8. [Medline]. [Full Text].

  30. Schein OD, Hochberg MC, Munoz B, et al. Dry eye and dry mouth in the elderly: a population-based assessment. Arch Intern Med. 1999 Jun 28. 159(12):1359-63. [Medline].

  31. Schaumberg DA, Buring JE, Sullivan DA, Dana MR. Hormone replacement therapy and dry eye syndrome. JAMA. 2001 Nov 7. 286(17):2114-9. [Medline].

  32. Soy M, Piskin S. Cutaneous findings in patients with primary Sjogren's syndrome. Clin Rheumatol. 2007 Aug. 26(8):1350-2. [Medline].

  33. Fox RI, Liu AY. Sjögren's syndrome in dermatology. Clin Dermatol. 2006 Sep-Oct. 24(5):393-413. [Medline].

  34. Constantopoulos SH, Tsianos EV, Moutsopoulos HM. Pulmonary and gastrointestinal manifestations of Sjögren's syndrome. Rheum Dis Clin North Am. 1992 Aug. 18(3):617-35. [Medline].

  35. Parambil JG, Myers JL, Lindell RM, Matteson EL, Ryu JH. Interstitial lung disease in primary Sjögren syndrome. Chest. 2006 Nov. 130(5):1489-95. [Medline].

  36. Wotherspoon AC. Gastric MALT lymphoma and Helicobacter pylori. Yale J Biol Med. 1996 Jan-Feb. 69(1):61-8. [Medline].

  37. Hammar O, Ohlsson B, Wollmer P, Mandl T. Impaired gastric emptying in primary Sjogren's syndrome. J Rheumatol. 2010 Nov. 37(11):2313-8. [Medline].

  38. Launay D, Hachulla E, Hatron PY, Jais X, Simonneau G, Humbert M. Pulmonary arterial hypertension: a rare complication of primary Sjögren syndrome: report of 9 new cases and review of the literature. Medicine (Baltimore). 2007 Sep. 86(5):299-315. [Medline].

  39. Cai FZ, Lester S, Lu T, Keen H, Boundy K, Proudman SM, et al. Mild autonomic dysfunction in primary Sjögren's syndrome: a controlled study. Arthritis Res Ther. 2008. 10(2):R31. [Medline].

  40. Delalande S, de Seze J, Fauchais AL, Hachulla E, Stojkovic T, Ferriby D, et al. Neurologic manifestations in primary Sjögren syndrome: a study of 82 patients. Medicine (Baltimore). 2004 Sep. 83(5):280-91. [Medline].

  41. Mori K, Iijima M, Koike H, Hattori N, Tanaka F, Watanabe H, et al. The wide spectrum of clinical manifestations in Sjögren's syndrome-associated neuropathy. Brain. 2005 Nov. 128:2518-34. [Medline].

  42. Gøransson LG, Herigstad A, Tjensvoll AB, Harboe E, Mellgren SI, Omdal R. Peripheral neuropathy in primary sjogren syndrome: a population-based study. Arch Neurol. 2006 Nov. 63(11):1612-5. [Medline].

  43. Ramachandiran N. Apparently persistent weakness after recurrent hypokalemic paralysis: a tale of two disorders. South Med J. 2008 Sep. 101(9):940-2. [Medline].

  44. van de Merwe JP. Interstitial cystitis and systemic autoimmune diseases. Nat Clin Pract Urol. 2007 Sep. 4(9):484-91. [Medline].

  45. Leppilahti M, Tammela TL, Huhtala H, Kiilholma P, Leppilahti K, Auvinen A. Interstitial cystitis-like urinary symptoms among patients with Sjögren's syndrome: a population-based study in Finland. Am J Med. 2003 Jul. 115(1):62-5. [Medline].

  46. Prajs K, Bobrowska-Snarska D, Skala M, Brzosko M. Polyarteritis nodosa and Sjögren's syndrome: overlap syndrome. Rheumatol Int. 2010 May 18. [Medline].

  47. Lemp MA. Advances in understanding and managing dry eye disease. Am J Ophthalmol. 2008 Sep. 146(3):350-356. [Medline].

  48. Versura P, Frigato M, Cellini M, Mulè R, Malavolta N, Campos EC. Diagnostic performance of tear function tests in Sjogren's syndrome patients. Eye. 2007 Feb. 21(2):229-37. [Medline].

  49. Antoniazzi RP, Miranda LA, Zanatta FB, et al. Periodontal conditions of individuals with Sjögren's syndrome. J Periodontol. 2009 Mar. 80(3):429-35. [Medline].

  50. Riccieri V, Sciarra I, Ceccarelli F, et al. Nailfold capillaroscopy abnormalities are associated with the presence of anti-endothelial cell antibodies in Sjogren's syndrome. Rheumatology (Oxford). 2009 Jun. 48(6):704-6. [Medline].

  51. Owczarek W, Kozera-Zywczyk A, Paluchowska E, Majewski S, Patera J. [Annular erythema as the skin manifestation of primary Sjögren's syndrome--case report]. Pol Merkur Lekarski. 2010 Feb. 28(164):126-9. [Medline].

  52. Bahous I. [Clinical experiences with tolectin in rheumatic diseases (author's transl)]. Schweiz Rundsch Med Prax. 1976 Aug 17. 65(33):1025-7. [Medline].

  53. Crestani B, Schneider S, Adle-Biassette H, Debray MP, Bonay M, Aubier M. [Respiratory manifestations during the course of Sjogren's syndrome]. Rev Mal Respir. 2007 Apr. 24(4 Pt 1):535-51. [Medline].

  54. Ren H, Wang WM, Chen XN, et al. Renal involvement and followup of 130 patients with primary Sjögren's syndrome. J Rheumatol. 2008 Feb. 35(2):278-84. [Medline].

  55. Lopate G, Pestronk A, Al-Lozi M, et al. Peripheral neuropathy in an outpatient cohort of patients with Sjögren's syndrome. Muscle Nerve. 2006 May. 33(5):672-6. [Medline].

  56. Invernizzi P, Battezzati PM, Crosignani A, Zermiani P, Bignotto M, Del Papa N, et al. Antibody to carbonic anhydrase II is present in primary biliary cirrhosis (PBC) irrespective of antimitochondrial antibody status. Clin Exp Immunol. 1998 Dec. 114(3):448-54. [Medline].

  57. 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 Dec 15. 49(6):804-9. [Medline].

  58. Tuchocka-Piotrowska A, Puszczewicz M, Kolczewska A, Majewski D. [Graft-versus-host disease as the cause of symptoms mimicking Sjögren's syndrome]. Ann Acad Med Stetin. 2006. 52 Suppl 2:89-93. [Medline].

  59. Roberts C, Parker GJ, Rose CJ, et al. Glandular function in Sjögren syndrome: assessment with dynamic contrast-enhanced MR imaging and tracer kinetic modeling--initial experience. Radiology. 2008 Mar. 246(3):845-53. [Medline].

  60. García-Carrasco M, Ramos-Casals M, Rosas J, Pallarés L, Calvo-Alen J, Cervera R, et al. Primary Sjögren syndrome: clinical and immunologic disease patterns in a cohort of 400 patients. Medicine (Baltimore). 2002 Jul. 81(4):270-80. [Medline].

  61. Ramos-Casals M, Nardi N, Brito-Zerón P, et al. Atypical autoantibodies in patients with primary Sjögren syndrome: clinical characteristics and follow-up of 82 cases. Semin Arthritis Rheum. 2006 Apr. 35(5):312-21. [Medline].

  62. Masaki Y, Dong L, Kurose N, Kitagawa K, Morikawa Y, Yamamoto M, et al. Proposal for a new clinical entity, IgG4-positive multi-organ lymphoproliferative syndrome: Analysis of 64 cases of IgG4-related disorders. Ann Rheum Dis. 2008 Aug 13. [Medline].

  63. Hamano H, Kawa S, Horiuchi A, Unno H, Furuya N, Akamatsu T, et al. High serum IgG4 concentrations in patients with sclerosing pancreatitis. N Engl J Med. 2001 Mar 8. 344(10):732-8. [Medline].

  64. Tomosugi N, Kitagawa K, Takahashi N, Sugai S, Ishikawa I. Diagnostic potential of tear proteomic patterns in Sjögren's syndrome. J Proteome Res. 2005 May-Jun. 4(3):820-5. [Medline].

  65. Montaño-Loza AJ, Crispín-Acuña JC, Remes-Troche JM, Uribe M. Abnormal hepatic biochemistries and clinical liver disease in patients with primary Sjögren's syndrome. Ann Hepatol. 2007 Jul-Sep. 6(3):150-5. [Medline].

  66. Daniels TE. Labial salivary gland biopsy in Sjögren's syndrome. Assessment as a diagnostic criterion in 362 suspected cases. Arthritis Rheum. 1984 Feb. 27(2):147-56. [Medline].

  67. Langerman AJ, Blair EA, Sweiss NJ, Taxy JB. Utility of lip biopsy in the diagnosis and treatment of Sjogren's syndrome. Laryngoscope. 2007 Jun. 117(6):1004-8. [Medline].

  68. Giuca MR, Bonfigli D, Bartoli F, Pasini M. Sjögren's syndrome: correlation between histopathologic result and clinical and serologic parameters. Minerva Stomatol. 2010 Apr. 59(4):149-54, 154-7. [Medline].

  69. Ramos-Casals M, Font J. Primary Sjögren's syndrome: current and emergent aetiopathogenic concepts. Rheumatology (Oxford). 2005 Nov. 44(11):1354-67. [Medline].

  70. Katayama I, Kotobuki Y, Kiyohara E, Murota H. Annular erythema associated with Sjögren's syndrome: review of the literature on the management and clinical analysis of skin lesions. Mod Rheumatol. 2010 Apr. 20(2):123-9. [Medline].

  71. Willeke P, Schlüter B, Becker H, Schotte H, Domschke W, Gaubitz M. Mycophenolate sodium treatment in patients with primary Sjögren syndrome: a pilot trial. Arthritis Res Ther. 2007. 9(6):R115. [Medline].

  72. Dass S, Bowman SJ, Vital EM, et al. Reduction of fatigue in Sjögren syndrome with rituximab: results of a randomised, double-blind, placebo-controlled pilot study. Ann Rheum Dis. 2008 Nov. 67(11):1541-4. [Medline].

  73. Pijpe J, van Imhoff GW, Spijkervet FK, et al. Rituximab treatment in patients with primary Sjögren's syndrome: an open-label phase II study. Arthritis Rheum. 2005 Sep. 52(9):2740-50. [Medline].

  74. Meijer JM, Pijpe J, Vissink A, Kallenberg CG, Bootsma H. Treatment of primary Sjogren syndrome with rituximab: extended follow-up, safety and efficacy of retreatment. Ann Rheum Dis. 2009 Feb. 68(2):284-5. [Medline].

  75. Meijer JM, Meiners PM, Vissink A, Spijkervet FK, Abdulahad W, Kamminga N, et al. Effectiveness of rituximab treatment in primary Sjögren's syndrome: a randomized, double-blind, placebo-controlled trial. Arthritis Rheum. 2010 Apr. 62(4):960-8. [Medline].

  76. St Clair EW, Levesque MC, Luning Prak ET, Vivino FB, Alappatt CJ, Spychala ME, et al. Rituximab therapy for primary Sjögren's syndrome: An open-label clinical trial and mechanistic analysis. Arthritis Rheum. 2013 Jan 17. [Medline].

  77. Devauchelle-Pensec V, Mariette X, Jousse-Joulin S, Berthelot JM, Perdriger A, Puéchal X, et al. Treatment of primary Sjögren syndrome with rituximab: a randomized trial. Ann Intern Med. 2014 Feb 18. 160 (4):233-42. [Medline].

  78. Thanou-Stavraki A, James JA. Primary Sjogren's syndrome: current and prospective therapies. Semin Arthritis Rheum. 2008 Apr. 37(5):273-92. [Medline].

  79. Moutsopoulos NM, Katsifis GE, Angelov N, Leakan RA, Sankar V, Pillemer S, et al. Lack of efficacy of etanercept in Sjögren syndrome correlates with failed suppression of tumour necrosis factor alpha and systemic immune activation. Ann Rheum Dis. 2008 Oct. 67(10):1437-43. [Medline].

  80. Mekinian A, Ravaud P, Hatron PY, Larroche C, Leone J, Gombert B, et al. Efficacy of rituximab in primary Sjogren's syndrome with peripheral nervous system involvement: results from the AIR registry. Ann Rheum Dis. 2012 Jan. 71(1):84-7. [Medline].

  81. Gottenberg JE, Cinquetti G, Larroche C, Combe B, Hachulla E, Meyer O, et al. Efficacy of rituximab in systemic manifestations of primary Sjogren's syndrome: results in 78 patients of the AutoImmune and Rituximab registry. Ann Rheum Dis. 2012 Dec 21. [Medline].

  82. Gottenberg JE, Guillevin L, Lambotte O, Combe B, Allanore Y, Cantagrel A, et al. Tolerance and short term efficacy of rituximab in 43 patients with systemic autoimmune diseases. Ann Rheum Dis. 2005 Jun. 64(6):913-20. [Medline]. [Full Text].

  83. Brah S, Chiche L, Fanciullino R, Bornet C, Mancini J, Schleinitz N, et al. Efficacy of rituximab in immune thrombocytopenic purpura: a retrospective survey. Ann Hematol. 2012 Feb. 91(2):279-85. [Medline].

  84. Management and therapy of dry eye disease: report of the Management and Therapy Subcommittee of the International Dry Eye WorkShop (2007). Ocul Surf. 2007 Apr. 5(2):163-78. [Medline].

  85. Behrens A, Doyle JJ, Stern L, Chuck RS, McDonnell PJ, Azar DT, et al. Dysfunctional tear syndrome: a Delphi approach to treatment recommendations. Cornea. 2006 Sep. 25(8):900-7. [Medline].

  86. Spiteri A, Mitra M, Menon G, et al. Tear lipid layer thickness and ocular comfort with a novel device in dry eye patients with and without Sjögren's syndrome. J Fr Ophtalmol. 2007 Apr. 30(4):357-64. [Medline].

  87. Egrilmez S, Aslan F, Karabulut G, Kabasakal Y, Yagci A. Clinical efficacy of the smartplug in the treatment of primary Sjogren's syndrome with keratoconjunctivitis SICCA: one-year follow-up study. Rheumatol Int. 2010 May 21. [Medline].

  88. [Guideline] American Academy of Ophthalmology. American Academy of Ophthalmology Cornea/External Disease Panel, Preferred Practice Patterns Committee. Dry eye syndrome. National Guidelines Clearinghouse. 2008.

  89. Akpek EK, Lindsley KB, Adyanthaya RS, Swamy R, Baer AN, McDonnell PJ. Treatment of Sjögren's syndrome-associated dry eye an evidence-based review. Ophthalmology. 2011 Jul. 118(7):1242-52. [Medline].

  90. [Guideline] Foulks GN, Forstot SL, Donshik PC, Forstot JZ, Goldstein MH, Lemp MA, et al. Clinical guidelines for management of dry eye associated with Sjögren disease. Ocul Surf. 2015 Apr. 13 (2):118-32. [Medline].

  91. Jain AK, Sukhija J, Dwedi S, Sood A. Effect of topical cyclosporine on tear functions in tear-deficient dry eyes. Ann Ophthalmol (Skokie). 2007 Spring. 39(1):19-25. [Medline].

  92. Daniels TE, Fox PC. Salivary and oral components of Sjögren's syndrome. Rheum Dis Clin North Am. 1992 Aug. 18(3):571-89. [Medline].

 
Previous
Next
 
Marked bilateral parotid gland enlargement in a patient with primary Sjögren syndrome. Sicca syndrome is a common clinical finding.
Clinical photograph and photomicrograph of a 48-year-old man with Sjögren syndrome with a large left parotid mass. On biopsy, B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type was identified. Microscopic section of parotid biopsy, stained with immunoperoxidase for kappa light chains (brown-stained cells), showed monoclonal population of B cells, confirming the diagnosis.
Photograph that demonstrates the Schirmer test, which is used to detect deficient tear production in patients with Sjögren syndrome. The filter paper strip is placed at the junction of the eyelid margins. After 5 minutes, 15 mm of paper should be moistened if tear production is normal, as shown here. Persons older than 40 years may moisten between 10 mm and 15 mm. Patients with Sjögren syndrome have less moistening. Sjögren syndrome is most common in patients with rheumatoid arthritis but may also occur without associated disease and in systemic lupus erythematosus, polyarteritis, systemic sclerosis, lymphoma, and sarcoidosis.
Dryness of the mouth and tongue due to lack of salivary secretion is characteristic of xerostomia associated with Sjögren syndrome. Mouth dryness may produce a deep red tongue, as shown here, and dental caries are common.
Photomicrograph of a lip biopsy specimen showing two lymphocytic foci adjacent to normal-appearing mucinous acini typical of minor salivary gland abnormalities in Sjögren syndrome.
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.