Sjogren Syndrome 

  • Author: Anne V Miller, MD; Chief Editor: Herbert S Diamond, MD   more...
 
Updated: Oct 31, 2011
 

Background

Sjögren syndrome 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, which is seen in the image below. (See Presentation.)

Marked bilateral parotid gland enlargement in a paMarked bilateral parotid gland enlargement in a patient with primary Sjögren syndrome. Sicca syndrome is a common clinical finding.

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. About 50% of patients with Sjögren syndrome have cutaneous findings, such as dry skin (xeroderma), palpable and nonpalpable purpura, and/or urticaria.[1] (See Etiology, Presentation, and Workup.)

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. 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.

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). Treatment for Sjögren syndrome is largely based on symptoms, but patients must be monitored carefully for the potential development of lymphoma. (See DDx.)

American-European Consensus Group classification

A number of classification criteria for Sjögren syndrome were designed primarily for clinical research studies but are also often used to help guide clinical diagnoses. The American-European Consensus Group’s criteria for the classification of Sjögren syndrome are outlined below.[2, 3] These are the most currently accepted criteria for the diagnosis of Sjögren syndrome. These criteria allow a diagnosis of Sjögren syndrome in patients without sicca symptoms or who have not undergone a biopsy.

According to the American-European classification system (as modified by Tzioufas and Voulgarelis[4] ), 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:

  • Ocular symptoms - Dry eyes for more than 3 months, foreign-body sensation, use of tear substitutes more than 3 times daily
  • Oral symptoms - Feeling of dry mouth, recurrently swollen salivary glands, frequent use of liquids to aid swallowing
  • Ocular signs - Schirmer test performed without anesthesia (< 5 mm in 5 min), positive vital dye staining results
  • Oral signs - Abnormal salivary scintigraphy findings, abnormal parotid sialography findings, abnormal sialometry findings (unstimulated salivary flow < 1.5mL in 15min)
  • Positive minor salivary gland biopsy findings
  • 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 exist 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 is 97.2% and the sensitivity, 64.7%.[5]

Exclusion criteria include past head-and-neck irradiation, hepatitis C infection, acquired immunodeficiency syndrome (AIDS), prior lymphoma, sarcoidosis, graft versus host disease, and the use of anticholinergic drugs.

Complications

Complications related to Sjögren syndrome include the following (see Prognosis, Treatment, and Medication):

  • Emergence of disorders associated with Sjögren syndrome, such as SLE and RA
  • Infection of the parotid gland, typically staphylococcal, streptococcal, or pneumococcal - Clues include unilateral worsening of symptoms, along with tenderness, warmth, and erythema
  • Emergence of parotid tumors - Watch for unusually hard or unilateral parotid enlargement
  • Pregnant patients with antiRo/SS-A antidodies are at risk for fetal loss, complete heart block in the fetus ,and neonatal lupus syndrome in the newborn
  • Emergence of pseudolymphomas (pleomorphic cells that do not meet the criteria for malignancy) and non-Hodgkin B-cell lymphomas (see the image below)[4] Clinical photograph and photomicrograph of a 48-yeClinical 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.

Patient education

Educate patients with Sjögren syndrome on avoidance strategies and self-care issues for the treatment of dry mouth, eyes, skin, and vagina. Patient education pamphlets regarding the disease are available through the Arthritis Foundation. The Sjögren’s Syndrome Foundation, founded in 1983, is a good resource for patients. The foundation can be contacted at 6707 Democracy Blvd, Ste 325, Bethesda, MD, 20817; (800) 475-6473, (301) 530-4415 (fax).

For patient education information, see the Arthritis Center, as well as Sjögren’s Syndrome.

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Etiology

Sjögren syndrome can occur as a primary disease of exocrine gland dysfunction or in association with several other autoimmune diseases (eg, systemic lupus erythematosus [SLE], rheumatoid arthritis, scleroderma, systemic sclerosis, cryoglobulinemia, polyarteritis nodosa). These primary and secondary types occur with similar frequency, but the sicca complex seems to cause more severe symptoms in the primary form.

Virtually all organs may be involved. The disease commonly affects the eyes, mouth, parotid gland, lungs, kidneys, skin, and nervous system.

The etiology 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. In addition, the continuing presence of active interferon pathways in Sjögren syndrome suggests ongoing activation of the innate immune system.[6, 7] Together, these findings suggest an ongoing interaction between the innate and acquired immune systems in Sjögren syndrome.

Association with the human leukocyte antigen

The frequency of HLA-DR52 in patients with primary Sjögren syndrome is estimated to be 87%, but it is also significantly increased in secondary Sjögren syndrome that occurs with rheumatoid arthritis or systemic lupus erythematosus.

The genetic associations in Sjögren syndrome vary among ethnic groups. In white persons, for instance, the condition is linked to human leukocyte antigen (HLA)–DR3, HLA-DQ2, and HLA-B8,[8] whereas the linkage is to HLA-DRB1*15 in Spanish persons[9] and to HLA-DR5 in Greek and Israeli persons.[10]

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.[11] These HLA associations appear restricted to individuals with Sjögren syndrome who have antibodies to the antigens SSA and SSB rather than to the disease manifestations themselves.[12]

Possible disease triggers

Viruses are viable candidates as environmental triggers, although proof of causation has remained elusive, and certainly no single virus has been implicated. Epstein-Barr virus (EBV), HTLV-1, human herpesvirus 6 (HHV-6), HIV, hepatitis C virus (HCV), and cytomegalovirus (CMV) may have a role. Sjögrenlike syndromes are seen in patients infected with HIV, HTLV-1, and hepatitis C.[13, 14, 15]

Damage and/or cell death due to viral infection or other causes may provide triggering antigens to Toll-like receptors in or on dendritic or epithelial cells, which, by recognizing pathogen-associated patterns, are activated and begin producing cytokines, chemokines, and adhesion molecules. As T and B lymphocytes migrate into the gland, they themselves become activated by dendritic and epithelial cells, thereafter acting as antigen-presenting cells.[16]

Expressed antigens include SSA/Ro, SSB/La, alpha-fodrin and beta-fodrin, and cholinergic muscarinic receptors.[12] Dendritic cell triggering by immune complexes formed from SSA ̶ anti-SSA (or other immune complexes) may propagate the ongoing innate and acquired immune activation.

Glandular pathology

The pathology of a typical involved salivary or lacrimal gland in Sjögren syndrome reveals aggregations of lymphocytes—periductal at first, then panlobular. These cells are primarily CD4 T cells (75%) and memory cells, with 10% B cells and immunoglobulin-secreting plasma cells. 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]

Studies suggest that the disease process of Sjögren syndrome has a neuroendocrine component. Proinflammatory cytokines released by epithelial cells and lymphocytes may impair neural release of acetylcholine. In addition, antibodies to acetylcholine (muscarinic) receptors may interfere with the neural stimulation of local glandular secretion,[18] perhaps by interfering with aquaporin.[19] Moreover, a study reports that M3 muscarinic receptor antibodies may cause autonomic dysfunction in patients with Sjögren syndrome.[20, 21]

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.[22]

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,[23] with evidence of immune activation of the conjunctival epithelium and local cytokine and metalloproteinase production. Damage to the corneal epithelium, already vulnerable due to inadequate tear film protection, ensues, with resultant epithelial erosions and surface irregularity.

Extraglandular involvement

Extraglandular involvement in Sjögren syndrome manifests in part as hypergammaglobulinemia and the production of multiple autoantibodies, especially ANA and RF. 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.[24]

Sex hormones

Sex hormones may influence the immunologic manifestations of primary Sjögren syndrome, because the disease is much more common in women than in men. The prevalence of serologic markers tends to be lower in male patients than in female patients. Although the role of sex hormones (eg, estrogens, androgens) in the pathogenesis of primary Sjögren syndrome remains unknown, adrenal and gonadal steroid hormone deficiency probably affects immune function.

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Epidemiology

Occurrence in the United States

Sjögren syndrome is estimated to be the second most common rheumatologic disorder, behind SLE. Sjögren syndrome affects 0.1-4% of the population. This wide range, in part, reflects the lack of uniform diagnostic criteria.[25]

International occurrence

Comparative studies between different ethnic groups have suggested that Sjögren syndrome is a homogeneous disease that occurs worldwide with similar prevalence and affects 1-2 million people.

Sex- and age-related demographics

The female-to-male ratio of Sjögren syndrome is 9:1. Sjögren syndrome can affect individuals of any age but is most common in elderly people. Onset typically occurs in the fourth to fifth decade of life.

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Prognosis

Sjögren syndrome carries a generally good prognosis. In patients who develop a disorder associated with Sjögren syndrome, the prognosis is more closely related to the associated disorder (eg, SLE, lymphoma).

Although salivary and lacrimal function generally stabilize, the presence of SSA and/or hypocomplementemia may predict a decline in function.[26]

Morbidity and mortality

Morbidity associated with Sjögren syndrome is mainly associated with the gradually decreased function of exocrine organs, which become infiltrated with lymphocytes. The increased mortality rate associated with the condition is primarily related to disorders commonly associated with Sjögren syndrome, such as SLE, RA, and primary biliary cirrhosis. Patients with primary Sjögren syndrome who do not develop a lymphoproliferative disorder have a normal life expectancy.[27]

Lymphoma

Among patients with Sjögren syndrome, the incidence of non-Hodgkin lymphoma is 4.3% (18.9 times higher than in the general population), with a median age at diagnosis of 58 years. The mean time to the development of non-Hodgkin lymphoma after the onset of Sjögren syndrome is 7.5 years.

The most common histologic subtype of non-Hodgkin lymphoma in Sjögren syndrome is mucosa-associated lymphoid tissue (MALT) lymphoma, which can develop in any nonlymphoid tissue infiltrated by periepithelial lymphoid tissue—most commonly the salivary glands, but also the stomach, nasopharynx, skin, liver, kidneys, and lungs. The progression of these infiltrates to lymphoma occurs slowly and in a stepwise fashion. Lymphoma is present at more than 1 site in 20% of patients at initial diagnosis.

The results of one study suggest that diagnostic labial salivary gland tissue biopsy can be used to detect germinal center ̶ like lesions, which can be a highly predictive and easily obtained marker for non-Hodgkin lymphoma in primary Sjögren syndrome patients.[28]

Patients at an increased risk of lymphoma include those with regional or generalized lymphadenopathy, hepatosplenomegaly, palpable purpura, leukopenia, renal insufficiency, loss of a previously positive polyclonal gammopathy or RF, development of a monoclonal gammopathy, or the development of a monoclonal cryoglobulinemia.

Neonatal lupus and congenital heart block

Children born to mothers with antibodies against SSA/Ro are at an increased risk of neonatal lupus and congenital heart block. If one such child develops congenital heart block, the risk for congenital heart block during a subsequent pregnancy is 15%.

Antiphospholipid syndrome

Patients with Sjögren syndrome who have antiphospholipid antibodies can develop the clinical features of antiphospholipid syndrome, which include increased fetal wastage and vascular thromboses.

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Contributor Information and Disclosures
Author

Anne V Miller, MD  Assistant Professor 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, and International Society for Clinical Densitometry

Disclosure: Nothing to disclose.

Coauthor(s)

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

Disclosure: Nothing to disclose.

Mark L Francis, MD  Consulting Staff, Arthritis and Osteoporosis Associates of New Mexico

Mark L Francis, MD is a member of the following medical societies: American College of Rheumatology, Illinois State Medical Society, and 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, and American Medical Association

Disclosure: Nothing to disclose.

Chief Editor

Herbert S Diamond, MD  Adjunct Professor of Medicine, Division of Rheumatology, University of Pittsburgh School of Medicine; 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, and Phi Beta Kappa

Disclosure: Merck Ownership interest Other; Smith Kline Ownership interest Other; Zimmer Ownership interest Other

Additional Contributors

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.

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. Jan-Feb 2011;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. Jun 2002;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. Jun 2007;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. Dec 2007;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. Sep 29 2008;[Medline].

  6. 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 of patients with Sjögren's syndrome. Arthritis Rheum. Oct 2002;46(10):2730-41.

  7. 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. Feb 21 2006;103(8):2770-5. [Medline].

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

  9. 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. Nov 2000;27(11):2611-6. [Medline].

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

  11. 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. Jun 1 1991;146(11):3871-6. [Medline].

  12. 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. Aug 2003;48(8):2240-5. [Medline].

  13. 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. Feb 8 1992;339(8789):321-3. [Medline].

  14. 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. Aug 1992;18(3):683-97. [Medline].

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

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

  17. 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. Nov 2005;112(11):2040-7. [Medline].

  18. 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. Jan 1998;39(1):151-6. [Medline].

  19. 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. Feb 2001;81(2):143-8. [Medline].

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

  21. 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. Apr 2006;54(4):1165-73. [Medline].

  22. 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. Jan 2003;48(1):174-85. [Medline].

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

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

  25. 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. Jan 2008;58(1):15-25. [Medline].

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

  27. 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. May-Jun 2005;23(3):351-6. [Medline].

  28. 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. Aug 2011;70(8):1363-8. [Medline]. [Full Text].

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

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

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

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

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

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

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

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

  37. 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). Sep 2007;86(5):299-315. [Medline].

  38. 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].

  39. 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). Sep 2004;83(5):280-91. [Medline].

  40. 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. Nov 2005;128:2518-34. [Medline].

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

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

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

  44. 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. Jul 2003;115(1):62-5. [Medline].

  45. 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. Dec 1998;114(3):448-54. [Medline].

  46. 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. Dec 15 2003;49(6):804-9. [Medline].

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

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

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

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

  51. 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). Jun 2009;48(6):704-6. [Medline].

  52. 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. Feb 2010;28(164):126-9. [Medline].

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

  54. 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. Apr 2007;24(4 Pt 1):535-51. [Medline].

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

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

  57. 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].

  58. 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. Mar 2008;246(3):845-53. [Medline].

  59. 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). Jul 2002;81(4):270-80. [Medline].

  60. 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. Apr 2006;35(5):312-21. [Medline].

  61. 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. Aug 13 2008;[Medline].

  62. 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. Mar 8 2001;344(10):732-8. [Medline].

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

  64. 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. Jul-Sep 2007;6(3):150-5. [Medline].

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

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

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

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

  69. 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. Apr 2010;20(2):123-9. [Medline].

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

  71. 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. Oct 2008;67(10):1437-43. [Medline].

  72. [Best Evidence] 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. Apr 2010;62(4):960-8. [Medline].

  73. 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].

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

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

  76. 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. Apr 2007;30(4):357-64. [Medline].

  77. 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. May 21 2010;[Medline].

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

  79. 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. Jul 2011;118(7):1242-52. [Medline].

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

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

  82. 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. Nov 2008;67(11):1541-4. [Medline].

  83. 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. Sep 2005;52(9):2740-50. [Medline].

  84. 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. Feb 2009;68(2):284-5. [Medline].

 
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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.
 
 
 
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