Sections

DDx

Diagnostic Considerations

Sjögren syndrome is associated with a wide variety of other disorders, which may contribute to underdiagnosis or misdiagnosis. A careful review of systems is needed to detect problems such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), scleroderma, polymyositis, chronic active hepatitis, idiopathic pulmonary fibrosis, primary biliary cirrhosis,^[63]and autoimmune thyroid disease.^[64]

Xerophthalmia, xerostomia, and enlargement of the parotid glands can result from adverse effects of drugs and other diseases. HIV infection can result in diffuse infiltrative lymphocytosis syndrome (DILS), which is characterized by parotid enlargement; involvement of the renal, lung, and gastrointestinal systems; and a low frequency of autoantibody presence. Chronic graft versus host disease may mimic symptoms associated with idiopathic Sjögren syndrome.^[65]SLE might be considered, especially at onset of the disease.

Histologic findings of the following disorders can be consistent with Sjögren syndrome:

Sarcoidosis
Graft versus host disease
HIV infection
HTLV-1 infection
Hepatitis C virus (HCV) infection
Keratoconjunctivitis sicca

Sicca

Differential diagnoses to consider in patients with sicca include the following:

Medications (eg, antidepressants, anticholinergics, beta-blockers, diuretics, antihistamines, some antiarrhythmic and antiepileptic drugs)
Anxiety and depression
Viral infections (eg, mumps)
Complications from contact lenses
Dehydration
Hypervitaminosis A
Neurotropic keratitis
Mucous membrane pemphigoid
Environmental irritants
Mouth breathing
Chronic blepharitis
Chronic conjunctivitis
Rosacea
Therapeutic radiation or surgery to the head and neck
Age
Alzheimer disease
Parkinson disease
Bell palsy
Amyloidosis
Sarcoidosis
Lymphoma

Parotid enlargement

Differential diagnoses to consider in patients with parotid enlargement include the following:

Viral infection (eg, mumps, Epstein-Barr virus, cytomegalovirus, coxsackievirus A, influenza)
DILS associated with HIV disease
Granulomatous diseases (sarcoidosis, tuberculosis, leprosy)
Hyperlipoproteinemia
Hepatic cirrhosis
Hepatitis C
Bulimia
Recurrent parotiditis of childhood
Chronic pancreatitis
Acromegaly
Amyloidosis
Gonadal hypofunction
Diabetes mellitus
Salivary gland tumor (primarily unilateral)
Bacterial infection (primarily unilateral)
Chronic sialadenitis (primarily unilateral)
Lymphoma

Associated disorders

Importantly, evaluate the patient for disorders associated with Sjögren syndrome, including the following:

AIDS
Rheumatoid arthritis
Systemic lupus erythematosus (SLE)
Scleroderma
Polymyositis
Primary biliary cirrhosis
Thyroiditis
Chronic active hepatitis
Mixed cryoglobulinemia
Celiac sprue

Differential Diagnoses

Workup

Kittridge A, Routhouska SB, Korman NJ. Dermatologic manifestations of Sjögren syndrome. J Cutan Med Surg. 2011 Jan-Feb. 15(1):8-14. [QxMD MEDLINE Link].
Shiboski CH, Shiboski SC, Seror R, Criswell LA, Labetoulle M, Lietman TM, et al. 2016 American College of Rheumatology/European League Against Rheumatism classification criteria for primary Sjögren's syndrome: A consensus and data-driven methodology involving three international patient cohorts. Ann Rheum Dis. 2017 Jan. 76 (1):9-16. [QxMD MEDLINE Link]. [Full Text].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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...
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. [QxMD MEDLINE Link].
Price EJ, Venables PJ. The etiopathogenesis of Sjögren's syndrome. Semin Arthritis Rheum. 1995 Oct. 25(2):117-33. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Fox RI. Epidemiology, pathogenesis, animal models, and treatment of Sjögren's syndrome. Curr Opin Rheumatol. 1994 Sep. 6(5):501-8. [QxMD MEDLINE Link].
Martelli Júnior H, Gueiros LA, de Lucena EG, Coletta RD. Increase in the number of Sjögren's syndrome cases in Brazil in the COVID-19 Era. Oral Dis. 2022 Nov. 28 Suppl 2:2588-2590. [QxMD MEDLINE Link]. [Full Text].
Fox RI. Sjögren's syndrome. Lancet. 2005 Jul 23-29. 366(9482):321-31. [QxMD MEDLINE Link].
Ma KS, Wang LT, Chong W, Lin CL, Li H, Chen A, et al. Exposure to environmental air pollutants as a risk factor for primary Sjögren's syndrome. Front Immunol. 2022. 13:1044462. [QxMD MEDLINE Link]. [Full Text].
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. [QxMD MEDLINE Link].
Brito-Zerón P, et al; Sjögren Big Data Consortium. Epidemiological profile and north-south gradient driving baseline systemic involvement of primary Sjögren's syndrome. Rheumatology (Oxford). 2019 Dec 24. [QxMD MEDLINE Link].
Rúa-Figueroa I, Fernández Castro M, Andreu JL, et al; Sjogrenser and Relesser Researchers and EAS-SER Group. Comorbidities in Patients With Primary Sjögren's Syndrome and Systemic Lupus Erythematosus: A Comparative Registries-Based Study. Arthritis Care Res (Hoboken). 2017 Jan. 69 (1):38-45. [QxMD MEDLINE Link]. [Full Text].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link]. [Full Text].
Vitali C, Minniti A, Pignataro F, Maglione W, Del Papa N. Management of Sjögren's Syndrome: Present Issues and Future Perspectives. Front Med (Lausanne). 2021. 8:676885. [QxMD MEDLINE Link]. [Full Text].
Gupta S, Gupta N. Sjögren Syndrome and Pregnancy: A Literature Review. Perm J. 2017. 21:[QxMD MEDLINE Link]. [Full Text].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Pflugfelder SC. Antiinflammatory therapy for dry eye. Am J Ophthalmol. 2004 Feb. 137(2):337-42. [QxMD MEDLINE Link].
Ng KP, Isenberg DA. Sjögren's syndrome: diagnosis and therapeutic challenges in the elderly. Drugs Aging. 2008. 25(1):19-33. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Schaumberg DA, Buring JE, Sullivan DA, Dana MR. Hormone replacement therapy and dry eye syndrome. JAMA. 2001 Nov 7. 286(17):2114-9. [QxMD MEDLINE Link].
Soy M, Piskin S. Cutaneous findings in patients with primary Sjogren's syndrome. Clin Rheumatol. 2007 Aug. 26(8):1350-2. [QxMD MEDLINE Link].
Fox RI, Liu AY. Sjögren's syndrome in dermatology. Clin Dermatol. 2006 Sep-Oct. 24(5):393-413. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Parambil JG, Myers JL, Lindell RM, Matteson EL, Ryu JH. Interstitial lung disease in primary Sjögren syndrome. Chest. 2006 Nov. 130(5):1489-95. [QxMD MEDLINE Link].
Wotherspoon AC. Gastric MALT lymphoma and Helicobacter pylori. Yale J Biol Med. 1996 Jan-Feb. 69(1):61-8. [QxMD MEDLINE Link].
Hammar O, Ohlsson B, Wollmer P, Mandl T. Impaired gastric emptying in primary Sjogren's syndrome. J Rheumatol. 2010 Nov. 37(11):2313-8. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Ramachandiran N. Apparently persistent weakness after recurrent hypokalemic paralysis: a tale of two disorders. South Med J. 2008 Sep. 101(9):940-2. [QxMD MEDLINE Link].
van de Merwe JP. Interstitial cystitis and systemic autoimmune diseases. Nat Clin Pract Urol. 2007 Sep. 4(9):484-91. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Choi BY, Oh HJ, Lee YJ, Song YW. Prevalence and clinical impact of fibromyalgia in patients with primary Sjögren's syndrome. Clin Exp Rheumatol. 2016 Mar-Apr. 34 (2 Suppl 96):S9-13. [QxMD MEDLINE Link].
Prajs K, Bobrowska-Snarska D, Skala M, Brzosko M. Polyarteritis nodosa and Sjögren's syndrome: overlap syndrome. Rheumatol Int. 2010 May 18. [QxMD MEDLINE Link].
Lemp MA. Advances in understanding and managing dry eye disease. Am J Ophthalmol. 2008 Sep. 146(3):350-356. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Antoniazzi RP, Miranda LA, Zanatta FB, et al. Periodontal conditions of individuals with Sjögren's syndrome. J Periodontol. 2009 Mar. 80(3):429-35. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Bahous I. [Clinical experiences with tolectin in rheumatic diseases (author's transl)]. Schweiz Rundsch Med Prax. 1976 Aug 17. 65(33):1025-7. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Nocturne G, Virone A, Ng WF, Le Guern V, Hachulla E, Cornec D, et al. Rheumatoid Factor and Disease Activity Are Independent Predictors of Lymphoma in Primary Sjögren's Syndrome. Arthritis Rheumatol. 2016 Apr. 68 (4):977-85. [QxMD MEDLINE Link]. [Full Text].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Ramos-Casals M, Font J. Primary Sjögren's syndrome: current and emergent aetiopathogenic concepts. Rheumatology (Oxford). 2005 Nov. 44(11):1354-67. [QxMD MEDLINE Link].
Saraux A, Pers JO, Devauchelle-Pensec V. Treatment of primary Sjögren syndrome. Nat Rev Rheumatol. 2016 Aug. 12 (8):456-71. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Thanou-Stavraki A, James JA. Primary Sjogren's syndrome: current and prospective therapies. Semin Arthritis Rheum. 2008 Apr. 37(5):273-92. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link]. [Full Text].
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. [QxMD MEDLINE Link].
Greb E. Leflunomide-hydroxychloroquine combination for Sjögren’s shows potential. MD Edge Rheumatology. Available at https://www.mdedge.com/rheumatology/article/219916/lupus-connective-tissue-diseases/leflunomide-hydroxychloroquine. March 31, 2020; Accessed: March 19, 2023.
van der Heijden EHM, Blokland SLM, Hillen MR, et al. Leflunomide–hydroxychloroquine combination therapy in patients with primary Sjögren's syndrome (RepurpSS-I): a placebo-controlled, double-blinded, randomised clinical trial. Lancet Rheumatol. March 26, 2020. [Full Text].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
[Guideline] Akpek EK, Amescua G, Farid M, Garcia-Ferrer FJ, Lin A, Rhee MK, et al. Dry Eye Syndrome Preferred Practice Pattern®. Ophthalmology. 2019 Jan. 126 (1):P286-P334. [QxMD MEDLINE Link]. [Full Text].
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. [QxMD MEDLINE Link].
[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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Daniels TE, Fox PC. Salivary and oral components of Sjögren's syndrome. Rheum Dis Clin North Am. 1992 Aug. 18(3):571-89. [QxMD MEDLINE Link].
[Guideline] Ramos-Casals M, Brito-Zerón P, Bombardieri S, et al, EULAR-Sjögren Syndrome Task Force Group. EULAR recommendations for the management of Sjögren's syndrome with topical and systemic therapies. Ann Rheum Dis. 2020 Jan. 79 (1):3-18. [QxMD MEDLINE Link]. [Full Text].
[Guideline] Vivino FB, Carsons SE, Foulks G, Daniels TE, Parke A, Brennan MT, et al. New Treatment Guidelines for Sjögren's Disease. Rheum Dis Clin North Am. 2016 Aug. 42 (3):531-51. [QxMD MEDLINE Link]. [Full Text].
[Guideline] Lee AS, Scofield RH, Hammitt KM, Gupta N, Thomas DE, Moua T, et al. Consensus Guidelines for Evaluation and Management of Pulmonary Disease in Sjögren's. Chest. 2021 Feb. 159 (2):683-698. [QxMD MEDLINE Link]. [Full Text].

Media Gallery

Marked bilateral parotid gland enlargement in a patient with primary Sjögren syndrome. Sicca syndrome is a common clinical finding. (C) 1972-2004 American College of Rheumatology Clinical Slide Collection. Used with permission.
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. (C) 1972-2004 American College of Rheumatology Clinical Slide Collection. Used with permission.
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. (C) 1972-2004 American College of Rheumatology Clinical Slide Collection. Used with permission.
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. (C) 1972-2004 American College of Rheumatology Clinical Slide Collection. Used with permission.
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. (C) 1972-2004 American College of Rheumatology Clinical Slide Collection. Used with permission.

of 5

Author

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

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.

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.

Additional Contributors

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.

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.

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.

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

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.