Abstract
Sjögren syndrome (SS) is a systemic autoimmune disease that presents with sicca symptomatology of the major mucosal surfaces. The clinical spectrum of this condition often extends to systemic involvement (extraglandular manifestations) and may be complicated by the development of lymphoma. SS is one of the most prevalent autoimmune diseases (with an estimated 0.5–3 million sufferers in the United States), and primarily affects perimenopausal women. When sicca symptoms appear in a previously healthy person, the syndrome is classified as primary SS. This chapter summarizes recent work focused on extending and characterizing the acute and/or complex clinical presentations of patients with primary SS, including a wide variety of symptoms and the involvement of internal organs. As a general rule, the management of extraglandular features in primary SS should be targeted to the specific organ involved. The mainstays of such treatment regimens remain glucocorticoids and immunosuppressive agents. Such therapies are more likely to affect favorably the extraglandular manifestations of SS, even though the patients’ most intense complaints often pertain to sicca features. Severe, life-threatening involvement has rarely been reported in primary SS. There are now substantially more data on the outcome of patients with primary SS, which indicate that patients with a predominantly extraepithelial expression (often associated with cryoglobulinemia) should be monitored and managed differently from patients with a predominantly periepithelial or sicca-limited disease.
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References
Sjögren H. Zur kenntnis der keratoconjunctivitis sicca (keratitis filiformis bei hypofunktion der tränendrüsen). Acta Ophthalmol. 1933;11(suppl 2):1-151.
Kassan SS, Moutsopoulos HM. Clinical manifestations and early diagnosis of Sjögren syndrome. Arch Intern Med. 2004;164:1275-1284.
Helmick CG, Felson DT, Lawrence RC, National Arthritis Data Workgroup, et al. Estimates of the prevalence of arthritis and other rheumatic conditions in the United States. Part I. Arthritis Rheum. 2008;58:15-25.
Ramos-Casals M, Tzioufas AG, Font J. Primary Sjögren’s syndrome: new clinical and therapeutic concepts. Ann Rheum Dis. 2005;64:347-354.
Ramos-Casals M, Font J. Primary Sjögren syndrome. In: Imboden J, Hellman D, Stone JH, eds. Current Diagnosis & Treatment in Rheumatology. New York: McGraw-Hill; 2007:237-245.
Ramos-Casals M, Daniels TE, Fox RI, et al. Sjögren’s syndrome. In: Stone JH, ed. A Clinician’s Pearls and Myths in Rheumatology. London: Springer; 2009:107-130.
Kamisawa T, Nakajima H, Egawa N, Funata N, Tsuruta K, Okamoto A. IgG4-related sclerosing disease incorporating sclerosing pancreatitis, cholangitis, sialadenitis and retroperitoneal fibrosis with lymphadenopathy. Pancreatology. 2006;6:132-137.
Ramos-Casals M, Anaya JM, García-Carrasco M, et al. Cutaneous vasculitis in primary Sjögren syndrome: classification and clinical significance of 52 patients. Medicine. 2004;83:96-106.
McCauliffe DP, Faircloth E, Wang L, Hashimoto T, Hoshino Y, Nishikawa T. Similar Ro/SS-A autoantibody epitope and titer responses in annular erythema of Sjögren’s syndrome and subacute cutaneous lupus erythematosus. Arch Dermatol. 1996;132:528-531.
García-Carrasco M, Sisó A, Ramos-Casals M, et al. Raynaud’s phenomenon in primary Sjögren’s syndrome. Prevalence and clinical characteristics in a series of 320 patients. J Rheumatol. 2002;29:726-730.
Nakamura H, Kawakami A, Hayashi T, et al. Anti-centromere antibody-seropositive Sjögren’s syndrome differs from conventional subgroup in clinical and pathological study. BMC Musculoskelet Disord. 2010;11:140.
Salliot C, Gottenberg JE, Bengoufa D, Desmoulins F, Miceli-Richard C, Mariette X. Anticentromere antibodies identify patients with Sjögren’s syndrome and autoimmune overlap syndrome. J Rheumatol. 2007;34:2253-2258.
Tsokos M, Lazarou SA, Moutsopoulos HM. Vasculitis in primary Sjögren’s syndrome. Histologic classification and clinical presentation. Am J Clin Pathol. 1987;88:26-31.
Molina R, Provost TT, Alexander EL. Two types of inflammatory vascular disease in Sjögren’s syndrome. Differential association with seroreactivity to rheumatoid factor and antibodies to Ro (SS-A) and with hypocomplementemia. Arthritis Rheum. 1985;28:1251-1258.
Ramos-Casals M, Loustaud-Ratti V, De Vita S, SS-HCV Study Group, et al. Sjögren syndrome associated with hepatitis C virus: a multicenter analysis of 137 cases. Medicine. 2005;84:81-89.
Ramos-Casals M, De Vita S, Tzioufas AG. Hepatitis C virus, Sjögren’s syndrome and B-cell lymphoma: linking infection, autoimmunity and cancer. Autoimmun Rev. 2005;4:8-15.
Ramos-Casals M, Sánchez-Tapias JM, Parés A, et al. Characterization and differentiation of autoimmune versus viral liver involvement in patients with Sjögren’s syndrome. J Rheumatol. 2006;33:1593-1599.
Lindgren S, Manthorpe R, Eriksson S. Autoimmune liver disease in patients with primary Sjögren’s syndrome. J Hepatol. 1994;20:354-358.
Skopouli FN, Barbatis C, Moutsopoulos HM. Liver involvement in primary Sjögren’s syndrome. Br J Rheumatol. 1994;33:745-748.
Prince MI, Chetwynd A, Craig WL, Metcalf JV, James OF. Asymptomatic primary biliary cirrhosis: clinical features, prognosis, and symptom progression in a large population based cohort. Gut. 2004;53:865-870.
Abraham S, Begum S, Isenberg D. Hepatic manifestations of autoimmune rheumatic diseases. Ann Rheum Dis. 2004;63:123-129.
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;35:312-321.
Beswick DR, Klatskin G, Boyer JL. Asymptomatic primary biliary cirrhosis. A progress report on long-term follow-up and natural history. Gastroenterology. 1985;89:267-271.
Goules A, Masouridi S, Tzioufas AG, Ioannidis JP, Skopouli FN, Moutsopoulos HM. Clinically significant and biopsy-documented renal involvement in primary Sjögren syndrome. Medicine. 2000;79:241-249.
Mellgren SI, Conn DL, Stevens JC, Dyck PJ. Peripheral neuropathy in primary Sjögren’s syndrome. Neurology. 1989;39:390-394.
Font J, Ramos-Casals M, de la Red G, et al. Pure sensory neuropathy in primary Sjögren’s syndrome. Longterm prospective followup and review of the literature. J Rheumatol. 2003;30:1552-1557.
Morozumi S, Kawagashira Y, Iijima M, et al. Intravenous immunoglobulin treatment for painful sensory neuropathy associated with Sjögren’s syndrome. J Neurol Sci. 2009;279:57-61.
Chen WH, Yeh JH, Chiu HC. Plasmapheresis in the treatment of ataxic sensory neuropathy associated with Sjögren’s syndrome. Eur Neurol. 2001;45:270-274.
Gorson KC, Natarajan N, Ropper AH, Weinstein R. Rituximab treatment in patients with IVIg-dependent immune polyneuropathy: a prospective pilot trial. Muscle Nerve. 2007;35:66-69.
Mori K, Iijima M, Sugiura M, et al. Sjögren’s syndrome associated painful sensory neuropathy without sensory ataxia. J Neurol Neurosurg Psychiatry. 2003;74:1320-1322.
Gorson KC, Ropper AH. Positive salivary gland biopsy, Sjögren syndrome, and neuropathy: clinical implications. Muscle Nerve. 2003;28:553-560.
Chai J, Herrmann DN, Stanton M, Barbano RL, Logigian EL. Painful small-fiber neuropathy in Sjögren syndrome. Neurology. 2005;65:925-927.
Gøransson LG, Herigstad A, Tjensvoll AB, Harboe E, Mellgren SI, Omdal R. Peripheral neuropathy in primary Sjögren syndrome: a population-based study. Arch Neurol. 2006;63:1612-1615.
de Seze J, Devos D, Castelnovo G, et al. The prevalence of Sjögren syndrome in patients with primary progressive multiple sclerosis. Neurology. 2001;57:1359-1363.
Miro J, Pena-Sagredo JL, Berciano J, Insua S, Leno C, Velarde R. Prevalence of primary Sjögren’s syndrome in patients with multiple sclerosis. Ann Neurol. 1990;27:582-584.
Montecucco C, Franciotta DM, Caporali R, DeGennaro F, Citterio A, Melzi d’Eril GV. Sicca syndrome and anti-SSA/Ro antibodies in patients with suspected or definite multiple sclerosis. Scand J Rheumatol. 1989;18:407-412.
Metz LM, Seland TP, Fritzler MJ. An analysis of the frequency of Sjögren’s syndrome in a population of multiple sclerosis patients. J Clin Lab Immunol. 1989;30:121-125.
Noseworthy JH, Bass BH, Vandervoort MK, et al. The prevalence of primary Sjögren’s syndrome in a multiple sclerosis population. Ann Neurol. 1989;25:95-98.
Delalande S, de Seze J, Fauchais AL, et al. Neurologic manifestations in primary Sjögren syndrome: a study of 82 patients. Medicine. 2004;83:280-291.
Vrethem M, Ernerudh J, Lindström F, Skogh T. Immunoglobulins within the central nervous system in primary Sjögren’s syndrome. J Neurol Sci. 1990;100:186-192.
Saikali P, Cayrol R, Vincent T. Anti-aquaporin-4 auto-antibodies orchestrate the pathogenesis in neuromyelitis optica. Autoimmun Rev. 2009;9:132-135.
Nandhagopal R, Al-Asmi A, Gujjar AR. Neuromyelitis optica: an overview. Postgrad Med J. 2010;86:153-159.
Saiz A, Zuliani L, Blanco Y, et al. Revised diagnostic criteria for neuromyelitis optica (NMO). Application in a series of suspected patients. J Neurol. 2007;254:1233-1237.
Wingerchuck DM, Hogancamp WF, O’Brien PC, Weinshenker BG. The clinical course of neuromyelitis optica (Devic’s syndrome). Neurology. 1999;53:1107-1114.
Ramos-Casals M, Font J. Primary Sjögren’s syndrome: current and emergent aetiopathogenic concepts. Rheumatology. 2005;44:1354-1367.
Javed A, Balabanov R, Arnason BG, et al. Minor salivary gland inflammation in Devic’s disease and longitudinally extensive myelitis. Mult Scler. 2008;14:809-814.
Wandinger KP, Stangel M, Witte T, et al. Autoantibodies against aquaporin-4 in patients with neuropsychiatric systemic lupus erythematosus and primary Sjögren’s syndrome. Arthritis Rheum. 2010;62:1198-1200.
Pittock SJ, Lennon VA, de Seze J, et al. Neuromyeltis optica and non-organ-specific autoimmunity. Arch Neurol. 2008;65:78-83.
de Seze J, Delalande S, Fauchais AL, et al. Myelopathies secondary to Sjögren’s syndrome: treatment with monthly intravenous cyclophosphamide associated with corticosteroids. J Rheumatol. 2006;33:709-711.
Alexander EL, Craft C, Dorsch C, Moser RL, Provost TT, Alexander GE. Necrotizing arteritis and spinal subarachnoid hemorrhage in Sjögren syndrome. Ann Neurol. 1982;11:632-635.
Sá MJ. Acute transverse myelitis: a practical reappraisal. Autoimmun Rev. 2009;9:128-131.
Ramírez M, Ramos-Casals M, Graus F. Central nervous system involvement in primary Sjögren syndrome. Med Clín. 2009;133:349-359.
Shibata S, Ubara Y, Sawa N, et al. Severe interstitial cistitis associated with Sjögren’s syndrome. Intern Med. 2004;43:248-252.
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;115:62-65.
Tumiati B, Casoli P, Parmeggiani A. Hearing loss in the Sjögren’s syndrome. Ann Intern Med. 1997;126:450.
Ziavra N, Politi EN, Kastanioudakis I, Shevas A, Drosos AA. Hearing loss in Sjögren’s syndrome patients: a comparative study. Clin Exp Rheumatol. 2000;18:725-728.
Boki KA, Ioannidis JP, Segas JV, et al. How significant is sensorineural hearing loss in primary Sjögren’s syndrome? J Rheumatol. 2001;28:798-801.
Hatzopoulos S, Amoroso C, Aimoni C, Lo Monaco A, Govoni M, Martini A. Hearing loss evaluation of Sjogren’s syndrome using distortion product otoacoustic emissions. Acta Otolaryngol Suppl. 2002;54:20-25.
Brito-Zerón P, Soria N, Muñoz S, et al. Prevalence and clinical relevance of autoimmune neutropenia in patients with primary Sjögren’s syndrome. Semin Arthritis Rheum. 2009;38:389-395.
Coppo P, Sibilia J, Maloisel F, et al. Primary Sjögren’s syndrome associated agranulocytosis: a benign disorder? Ann Rheum Dis. 2003;62:476-478.
Friedman J, Klepfish A, Miller EB, Ognenovski V, Ike RW, Schattner A. Agranulocytosis in Sjogren’s syndrome: two case reports and analysis of 11 additional reported cases. Semin Arthritis Rheum. 2002;31:338-345.
Friedman J, Schattner A, Shvidel L, Berrebi A. Characterization of T-cell large granular lymphocyte leukemia associated with Sjogren’s syndrome – an important but under-recognized association. Semin Arthritis Rheum. 2006;35:306-311.
Maheshwari A, Christensen RD, Calhoun DA. Immune-mediated neutropenia in the neonate. Acta Pediatr Suppl. 2002;438:98-103.
Shastri KA, Logue GL. Autoimmune neutropenia. Blood. 1993;81:1984-1995.
Bux J, Behrens G, Jaeger G, Welte K. Diagnosis and clinical course of autoimmune neutropenia in infancy: analysis of 240 cases. Blood. 1998;91:181-186.
Vivancos J, Vila M, Serra A, Loscos J, Anguita A. Failure of G-CSF therapy in neutropenia associated with Sjögren’s syndrome. Rheumatology. 2002;41:471-473.
Ramos-Casals M, Font J, Garcia-Carrasco M, et al. Primary Sjögren syndrome: hematologic patterns of disease expression. Medicine. 2002;81:281-292.
Kyle RA, Rajkumar SV. Monoclonal gammopathies of undetermined significance. Rev Clin Exp Hematol. 2002;6:225-252.
Zandecki M, Genevieve F, Jego P, Grosbois B. Monoclonal gammopathies of undetermined significance. Rev Méd Interne. 2000;21:1060-1074.
Sugai S, Shimizu S, Konda S. Lymphoproliferative disorders in Japanese patients with Sjögren’s syndrome. Scand J Rheumatol Suppl. 1986;61:118-122.
Walters MT, Stevenson FK, Herbert A, Cawley MI, Smith JL. Lymphoma in Sjögren’s syndrome: urinary monoclonal free light chains as a diagnostic aid and a means of tumour monitoring. Scand J Rheumatol Suppl. 1986;61:114-117.
Brito-Zerón P, Ramos-Casals M, Nardi N, et al. Circulating monoclonal immunoglobulins in Sjögren syndrome: prevalence and clinical significance in 237 patients. Medicine. 2005;84:90-97.
Moutsopoulos HM, Steinberg AD, Fauci AS, Lane HC, Papadopoulos NM. High incidence of free monoclonal lambda light chains in the sera of patients with Sjögren’s syndrome. J Immunol. 1983;130:2663-2665.
Sibilia J, Cohen-Solal J. Prevalence of monoclonal gammopathy and myeloma in a cohort of primary Sjögren’s syndrome. Arthritis Rheum. 1999;42(suppl 9):S140.
Zintzaras E, Voulgarelis M, Moutsopoulos HM. The risk of lymphoma development in autoimmune diseases: a meta-analysis. Arch Intern Med. 2005;165:2337-2344.
García-Carrasco M, Ramos-Casals M, Cervera R, Font J. Primary Sjögren’s syndrome and lymphatic proliferation. Med Clín. 2000;114:740-746.
Hansen LA, Prakash UB, Colby TV. Pulmonary lymphoma in Sjögren’s syndrome. Mayo Clin Proc. 1989;64:920-931.
Gentric A, Hervé JP, Cledes J, Pennec Y, Leroy JP. Renal insufficiency as a manifestation of lymphoma with acquired hypocomplementemia and Gougerot-Sjögren syndrome. Apropos of a case. Ann Méd Interne. 1987;138:668-669.
Voulgarelis M, Dafni UG, Isenberg DA, Moutsopoulos HM. Malignant lymphoma in primary Sjögren’s syndrome: a multicenter, retrospective, clinical study by the European Concerted Action on Sjögren’s syndrome. Arthritis Rheum. 1999;42:1765-1772.
Ramos-Casals M, Brito-Zerón P. Emerging biological therapies in primary Sjögren’s syndrome. Rheumatology. 2007;46:1389-1396.
Ioannidis JP, Vassiliou VA, Moutsopoulos HM. Long-term risk of mortality and lymphoproliferative disease and predictive classification of primary Sjögren’s syndrome. Arthritis Rheum. 2002;46:741-747.
Theander E, Manthorpe R, Jacobsson LT. Mortality and causes of death in primary Sjögren’s syndrome: a prospective cohort study. Arthritis Rheum. 2004;50:1262-1269.
Brito-Zerón P, Ramos-Casals M, Bove A, Sentis J, Font J. Predicting adverse outcomes in primary Sjögren’s syndrome: identification of prognostic factors. Rheumatology. 2007;46:1359-1362.
Ramos-Casals M, Tzioufas AG, Stone JH, Sisó A, Bosch X. Treatment of primary Sjögren syndrome: a systematic review. JAMA. 2010;304:452-460.
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Ramos-Casals, M., Brito-Zerón, P., Boada, A.B., Sisó-Almirall, A. (2011). Sjögren’s Syndrome: Beyond Sicca Involvement. In: Khamashta, M., Ramos-Casals, M. (eds) Autoimmune Diseases. Springer, London. https://doi.org/10.1007/978-0-85729-358-9_5
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