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Sjogren Syndrome Treatment & Management

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

Approach Considerations

No curative agents for Sjögren syndrome exist. The treatment of the disorder is essentially symptomatic.

In secondary Sjögren syndrome, treatment is based on the accompanying disease and its clinical features. Sjögren syndrome and associated SLE improve more than primary Sjögren syndrome. In Sjögren syndrome associated with polymyositis, monthly cyclophosphamide pulse therapy has been used successfully.

In annular erythema associated with Sjögren syndrome in Japanese patients, prednisolone (10-20 mg/d) is effective. No evidence-based strategies are available for the management of anular erythema in Western populations because it is rare. However, case reports have demonstrated that hydroxycloroquine can be effective in whites.[70]

The inhibition of protease activity in EBV-mediated apoptotic cells may be a potential therapeutic approach in the treatment of Sjögren syndrome.

Skin and vaginal dryness

Patients should use skin creams, such as Eucerin, or skin lotions, such as Lubriderm, to help with dry skin. Vaginal lubricants, such as Replens, can be used for vaginal dryness. Vaginal estrogen creams can be considered in postmenopausal women. Watch for and treat vaginal yeast infections.

Arthralgias and arthritis

Acetaminophen or nonsteroidal anti-inflammatory drugs (NSAIDs) can be taken for arthralgias. Consider hydroxychloroquine if NSAIDs are not sufficient for the synovitis occasionally associated with primary Sjögren syndrome. However, hydroxychloroquine does not relieve sicca symptoms. Patients with RA associated with Sjögren syndrome likely require other disease-modifying agents.

Additional treatment considerations

In patients with major organ involvement, such as lymphocytic interstitial lung disease, consider therapy with steroids and immunosuppressive agents, such as cyclophosphamide.

While cyclophosphamide and similar agents may be helpful for treating serious manifestations of Sjögren syndrome or disorders associated with Sjögren syndrome, clinicians should understand that these agents are also associated with the development of lymphomas.

Long-term anticoagulation may be needed in patients with vascular thrombosis related to antiphospholipid antibody syndrome.

In a small group of patients with primary Sjögren syndrome, mycophenolate sodium reduced subjective, but not objective, ocular dryness and significantly reduced hypergammaglobulinemia and RF.[71]

Among the biologic therapies, the greatest experience in primary Sjögren syndrome is with rituximab, an anti-CD20 (which is expressed on B-cell precursors) monoclonal antibody. Anti-B–cell strategies, particularly rituximab, have a promising effect in the treatment of patients with severe extraglandular manifestations of Sjögren syndrome.

Reports on the use of rituximab in patients with primary Sjögren syndrome have emerged in the literature.[72, 73, 74] In a double-blind, randomized, placebo-controlled trial, Meijer et al found that rituximab significantly improved saliva flow rate, lacrimal gland function, and other variables in patients with primary Sjögren syndrome.[75]

In an open-label clinical trial, modest improvements were noted in patient-reported symptoms of fatigue and oral dryness. However, no significant improvement in the objective measures of lacrimal and salivary gland function was noted, despite effective depletion of blood B cells.[76] In a randomized, placebo-controlled, parallel-group study of 120 patients with primary Sjögren syndrome, treatment with rituximab did not alleviate disease activity or symptoms at week 24, although it did alleviate some symptoms at weeks 6 and 16.[77]

Rituximab appears promising in the treatment of vasculitis and intravenous immunoglobulin (IVIG)–dependent ataxic neuropathy.[78, 79] Results from the AIR registry (French) indicated that rituximab appears to be effective in cryoglobulinemia or vasculitis-related peripheral nervous system involvement in primary Sjögren syndrome.[80]

In a prospective study of 78 patients with primary Sjögren syndrome treated with rituximab, significant improvement in extraglandular manifestations was reported, as measured by EULAR [European League Against Rheumatism] Sjögren Syndrome Disease Activity Index (ESSDAI) (disease activity score) and overall good tolerance reported.[81] Several smaller studies of rituximab revealed improvement of arthralgias, regression of parotid gland swelling,[82] and improvement of immune-related thrombocytopenia.[83]

Of the TNF inhibitors, both etanercept and infliximab have failed to demonstrate significant benefit in Sjögren syndrome.

Fewer data are available with regard to the role of anti-CD22, anti-BAFF, anti-IL-1, type 1 interferon, and anti-T–cell agents in treatment of primary Sjögren syndrome, with further investigations ongoing. The overall paucity of evidence in therapeutic studies in primary Sjögren syndrome suggests that much larger trials of the most promising therapies are necessary.

Emergency department care

The diagnosis of Sjögren syndrome can be made from the ED if the index of suspicion is high. Patients may present with mild symptoms (eg, eye grittiness, eye dryness or discomfort, dry mouth, recurrent caries). Bilateral parotid gland swelling is also a common presentation.

Patients with known Sjögren syndrome should not be taken lightly for their complaint of dry eyes or dry mouth, as these chronic problems can be very distressing and obtrusive.

Inpatient care

Give attention to artificial lubricants and humidified oxygen for intubated and/or sedated patients with Sjögren syndrome.

Outpatient care

Encourage patients with Sjögren syndrome to be active. In addition, patients should be encouraged to avoid exacerbation of dryness symptoms (eg, through smoking or exposure to low-humidity environments). All patients with Sjögren syndrome should be monitored by an ophthalmologist and dentist, in addition to their rheumatologist. Certain patients may be candidates for punctal occlusion, which is usually performed by an ophthalmologist.

Monitoring

Most patients with Sjögren syndrome can be monitored at follow-up visits every 3 months and, if the patient is stable, up to every 6 months. Patients with active problems or in whom an emerging associated illness is a concern can be seen as often as monthly.

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Surgical Therapy

Occlusion of the lacrimal puncta can be corrected surgically. Electrocautery and other techniques can be used for permanent punctal occlusion.

During surgery, the anesthesiologist should administer as little anticholinergic medication as possible and use humidified oxygen to help avoid inspissation of pulmonary secretions. Good postoperative respiratory therapy should also be provided. Patients are at higher risk for corneal abrasions, so ocular lubricants should be considered.

Biopsies that may be performed in association with Sjögren syndrome include the following:

  • Minor salivary gland biopsy - For diagnostic purposes
  • Parotid gland biopsy - If malignancy is suggested
  • Biopsy on an enlarged lymph node - To help rule out pseudolymphoma or lymphoma
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Consultations

Sjögren syndrome and its associated disorders necessitate a total patient perspective that is often best provided by an internist. A rheumatologist with specific training and experience in Sjögren syndrome and its associated disorders is also essential to the management of the condition. In addition, good oral prophylaxis and therapy are necessary.

Involve ophthalmologists early in the care of patients, for rose bengal and fluorescein staining to help to establish the diagnosis and for assessment of the degree of eye damage.

Consultation with an otolaryngologist may be needed early to perform a minor or major salivary gland biopsy if this is deemed necessary to establish a diagnosis. The specialist may also need to perform a parotid biopsy if malignant transformation is suggested.

Depending on the problems, patients with Sjögren syndrome may need to be seen by other specialists, including the following:

  • Nephrologist - To help manage renal tubular acidosis
  • Pulmonologist - To help manage interstitial lung disease
  • Hematologist/oncologist - If pseudolymphoma or lymphoma develops
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Dry Eyes

The treatment of dry eyes depends on the severity of the dryness, which is best determined by an ophthalmologist and is graded according to the degree of symptoms, conjunctival injection and staining, corneal damage, tear quality, and lid involvement.[84, 85, 86, 87, 88, 89]

New therapeutic strategies designed to facilitate AQP5 trafficking to the apical plasma membrane may prove useful in the management of dry eyes in Sjögren syndrome. In addition, data on novel secretagogues and androgen therapies for dry eyes are promising.[78]

A consensus clinical guideline for the management of dry eyes associated with Sjögren syndrome recommends the following[90] :

  • Patient evaluation should include symptoms of both discomfort and visual disturbance along with evaluation of the relative contribution of aqueous production deficiency and evaporative loss of tear volume
  • Objective parameters of tear film stability, tear osmolarity, degree of lid margin disease, and ocular surface damage should be used to stage disease severity and assist in guiding treatment
  • Successful management requires patient education on the nature of the problem, aggravating factors, and treatment goals

Treatment options are used according to the severity and character of dry eye disease and include the following[90] :

  • Tear supplementation and stabilization
  • Control of inflammation of the lacrimal glands and ocular surface
  • Possible stimulation of tear production

Level 1 - Mild symptoms, no corneal signs

Artificial tears should be applied liberally. Patients may need to apply artificial tears more often if they enter a low-humidity environment (ie, air conditioning, airplanes). Artificial tears with hydroxymethylcellulose or dextran are more viscous and can last longer before reapplication is needed. Encourage patients to try various preparations to determine what works best for them.

If artificial tears burn when they are instilled, the preservative in the artificial tears is likely irritating the eye. If artificial tears are used more often than every 4 hours, patients should use a preservative-free preparation to avoid eye irritation from the preservatives.

The use of humidifiers may help. If the patient is living in an area with hard water, he or she should use distilled water. Patients should avoid medications with anticholinergic and antihistamine effects.

Level 2 - Moderate or severe symptoms with tear film signs or visual signs, or mild corneal/conjunctival staining

Patients should use unpreserved tears or gels or nighttime ointments. Patients who wake up in the morning with severe matting in the eyes should use a more viscous preparation (eg, Lacri-Lube) at night. While the more viscous preparations can be applied less often, they can make patients' vision filmy. Therefore, they are best used at night. The more viscous preparations occasionally lead to blepharitis, which can exacerbate sicca symptoms.

The following agents may also be indicated:

  • Topical steroids
  • Secretagogues
  • Cyclosporine A [91]
  • Nutritional supplements

Level 3 - Severe symptoms with marked corneal changes or filamentary keratitis

The following treatments may be indicated:

  • Tetracyclines
  • Autologous serum tears
  • Temporary plugging of the lacrimal puncta to increase the amount of tears that remain in the eyes

Level 4 - Extremely severe symptoms with altered lifestyle, or severe corneal staining, erosions, or conjunctival scarring

The following therapies may be indicated:

  • Systemic anti-inflammatory therapy, including acetylcysteine
  • Topical vitamin A
  • Electrocautery and other techniques for permanent punctal occlusion
  • Glasses fitted with moisture shields to decrease evaporation
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Dry Mouth

Patients with dry mouth can liberally drink sips of water and take bottled water with them on trips. They can also place a glass of water at their bedside for nighttime use, as needed.[92] Sugar-free lemon drops can also be used as needed to stimulate salivary secretion. Artificial saliva can be used as needed, although patient tolerance varies. Preparations include Salivart, Saliment, Saliva Substitute, MouthKote, and Xero-Lube. Patients should avoid medications with anticholinergic and antihistamine effects.

The use of humidifiers may help. Distilled water is best in patients living in an area with hard water.

Patients should be seen regularly by a dentist, who may advise fluoride treatments. Toothpaste without detergents can reduce mouth irritation in patients with Sjögren syndrome. Brands include Biotene toothpaste, Biotene mouth rinse, Dental Care toothpaste, and Oral Balance gel.

Watch for oral candidiasis and angular cheilitis and treat them with topical antifungal agents, such as nystatin troches. Oral fluconazole may occasionally be needed. Patients also need to be sure to disinfect their dentures.

Sinusitis and sinus blockade should be treated because these problems may contribute to mouth breathing. Emphasize the use of isotonic sodium chloride solution nasal sprays to avoid antihistamine use.

Pilocarpine or cevimeline tablets are options. Some small studies suggest that interferon alfa may be a useful therapy in the future.

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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].

 
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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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