Interstitial lung disease associated with Sjögren's syndrome: Clinical manifestations, evaluation, and diagnosis
- Carlos Roberto Ribeiro de Carvalho, MD, PhD
Carlos Roberto Ribeiro de Carvalho, MD, PhD
- Associate Professor of Pulmonology
- University of Sao Paulo
- Daniel Deheinzelin, MD, PhD
Daniel Deheinzelin, MD, PhD
- Assistant Professor of Medicine
- Advanced Center of Thoracic Diseases, Hospital Sirio e Libanes
- Ronaldo A Kairalla, MD, PhD
Ronaldo A Kairalla, MD, PhD
- Assistant Professor - Pulmonary Division
- University of São Paulo, Brazil
Sjögren's syndrome (SS) is a chronic inflammatory disorder characterized by diminished lacrimal and salivary gland function and associated with lymphocytic infiltration of exocrine glands, especially the lacrimal and salivary glands. In addition to causing dry eyes (keratoconjunctivitis sicca) and dry mouth (xerostomia), SS can affect extraglandular organ systems including the skin, lung, heart, kidney, neural, and hematopoietic systems.
Respiratory complications of SS include airway mucosal dryness (also known as xerotrachea), a variety of interstitial lung diseases (ILDs), non-Hodgkin lymphomas, pleural thickening or effusion, and, rarely, thromboembolic disease or pulmonary hypertension.
The clinical manifestations, evaluation, and diagnosis of interstitial lung disease in SS will be reviewed here. The clinical manifestations, classification, criteria for diagnosis, and pathogenesis of Sjögren's syndrome are presented separately. (See "Clinical manifestations of Sjögren's syndrome: Exocrine gland disease" and "Clinical manifestations of Sjögren's syndrome: Extraglandular disease" and "Diagnosis and classification of Sjögren's syndrome" and "Pathogenesis of Sjögren's syndrome".)
American-European criteria — The American-European criteria for the diagnosis of Sjögren's syndrome (SS) combine subjective symptoms of dry eye and dry mouth with objective signs of keratoconjunctivitis sicca and xerostomia (table 1). They were not developed for clinical practice and not every patient who receives a diagnosis of SS fulfills the proposed criteria. Diseases that can mimic SS and should be considered in the differential diagnosis of SS are included in the table (table 2). The diagnosis of SS is discussed separately. (See "Diagnosis and classification of Sjögren's syndrome", section on 'Classification criteria'.)
Primary Sjögren's syndrome — Primary Sjögren's syndrome (pSS) is diagnosed only when all other systemic rheumatic diseases are excluded; it predominantly affects women between 50 and 70 years of age. (See "Diagnosis and classification of Sjögren's syndrome".)
- Freemer MM, King TE Jr. Connective tissue disease. In: Interstitial Lung Disease, King TE Jr, Schwarz MI (Eds), BC Decker, Hamilton, Ontario 2003. p.535.
- Strimlan CV, Rosenow EC 3rd, Divertie MB, Harrison EG Jr. Pulmonary manifestations of Sjögren's syndrome. Chest 1976; 70:354.
- Vitali C, Tavoni A, Viegi G, et al. Lung involvement in Sjögren's syndrome: a comparison between patients with primary and with secondary syndrome. Ann Rheum Dis 1985; 44:455.
- Constantopoulos SH, Papadimitriou CS, Moutsopoulos HM. Respiratory manifestations in primary Sjögren's syndrome. A clinical, functional, and histologic study. Chest 1985; 88:226.
- Cain HC, Noble PW, Matthay RA. Pulmonary manifestations of Sjögren's syndrome. Clin Chest Med 1998; 19:687.
- Hunninghake GW, Fauci AS. Pulmonary involvement in the collagen vascular diseases. Am Rev Respir Dis 1979; 119:471.
- Papathanasiou MP, Constantopoulos SH, Tsampoulas C, et al. Reappraisal of respiratory abnormalities in primary and secondary Sjögren's syndrome. A controlled study. Chest 1986; 90:370.
- Lynch JP 3rd, Hunninghake GW. Pulmonary complications of collagen vascular disease. Annu Rev Med 1992; 43:17.
- Vitali C, Viegi G, Tassoni S, et al. Lung function abnormalities in different connective tissue diseases. Clin Rheumatol 1986; 5:181.
- Newball HH, Brahim SA. Chronic obstructive airway disease in patients with Sjögren's syndrome. Am Rev Respir Dis 1977; 115:295.
- Fairfax AJ, Haslam PL, Pavia D, et al. Pulmonary disorders associated with Sjögren's syndrome. Q J Med 1981; 50:279.
- Segal I, Fink G, Machtey I, et al. Pulmonary function abnormalities in Sjögren's syndrome and the sicca complex. Thorax 1981; 36:286.
- Ramos-Casals M, Brito-Zerón P, Seror R, et al. Characterization of systemic disease in primary Sjögren's syndrome: EULAR-SS Task Force recommendations for articular, cutaneous, pulmonary and renal involvements. Rheumatology (Oxford) 2015; 54:2230.
- Shi JH, Liu HR, Xu WB, et al. Pulmonary manifestations of Sjögren's syndrome. Respiration 2009; 78:377.
- Nannini C, Jebakumar AJ, Crowson CS, et al. Primary Sjogren's syndrome 1976-2005 and associated interstitial lung disease: a population-based study of incidence and mortality. BMJ Open 2013; 3:e003569.
- Kurumagawa T, Kobayashi H, Motoyoshi K. Potential involvement of subclinical Sjögren's syndrome in various lung diseases. Respirology 2005; 10:86.
- Watanabe M, Naniwa T, Hara M, et al. Pulmonary manifestations in Sjogren's syndrome: correlation analysis between chest computed tomographic findings and clinical subsets with poor prognosis in 80 patients. J Rheumatol 2010; 37:365.
- Kokosi M, Riemer EC, Highland KB. Pulmonary involvement in Sjögren syndrome. Clin Chest Med 2010; 31:489.
- Ito I, Nagai S, Kitaichi M, et al. Pulmonary manifestations of primary Sjogren's syndrome: a clinical, radiologic, and pathologic study. Am J Respir Crit Care Med 2005; 171:632.
- Parambil JG, Myers JL, Lindell RM, et al. Interstitial lung disease in primary Sjögren syndrome. Chest 2006; 130:1489.
- Baqir M, Kluka EM, Aubry MC, et al. Amyloid-associated cystic lung disease in primary Sjögren's syndrome. Respir Med 2013; 107:616.
- Deheinzelin D, Capelozzi VL, Kairalla RA, et al. Interstitial lung disease in primary Sjögren's syndrome. Clinical-pathological evaluation and response to treatment. Am J Respir Crit Care Med 1996; 154:794.
- Uffmann M, Kiener HP, Bankier AA, et al. Lung manifestation in asymptomatic patients with primary Sjögren syndrome: assessment with high resolution CT and pulmonary function tests. J Thorac Imaging 2001; 16:282.
- Davidson BK, Kelly CA, Griffiths ID. Ten year follow up of pulmonary function in patients with primary Sjögren's syndrome. Ann Rheum Dis 2000; 59:709.
- Constantopoulos SH, Drosos AA, Maddison PJ, Moutsopoulos HM. Xerotrachea and interstitial lung disease in primary Sjogren's syndrome. Respiration 1984; 46:310.
- Ramagopalan SV, Wotton CJ, Handel AE, et al. Risk of venous thromboembolism in people admitted to hospital with selected immune-mediated diseases: record-linkage study. BMC Med 2011; 9:1.
- Launay D, Hachulla E, Hatron PY, et al. Pulmonary arterial hypertension: a rare complication of primary Sjögren syndrome: report of 9 new cases and review of the literature. Medicine (Baltimore) 2007; 86:299.
- Hatron PY, Wallaert B, Gosset D, et al. Subclinical lung inflammation in primary Sjögren's syndrome. Relationship between bronchoalveolar lavage cellular analysis findings and characteristics of the disease. Arthritis Rheum 1987; 30:1226.
- Ramos-Casals M, Brito-Zerón P, García-Carrasco M, Font J. Sarcoidosis or Sjögren syndrome? Clues to defining mimicry or coexistence in 59 cases. Medicine (Baltimore) 2004; 83:85.
- Travis WD, Galvin JR. Non-neoplastic pulmonary lymphoid lesions. Thorax 2001; 56:964.
- Zen Y, Nakanuma Y. IgG4-related disease: a cross-sectional study of 114 cases. Am J Surg Pathol 2010; 34:1812.
- Kobayashi H, Shimokawaji T, Kanoh S, et al. IgG4-positive pulmonary disease. J Thorac Imaging 2007; 22:360.
- Dalavanga YA, Constantopoulos SH, Galanopoulou V, et al. Alveolitis correlates with clinical pulmonary involvement in primary Sjögren's syndrome. Chest 1991; 99:1394.
- Barranquero-Beltrán A, Meyer O, Haim T, et al. [Comparative profile of antinuclear antibodies in Gougerot-Sjögren syndrome with and without diffuse interstitial pulmonary fibrosis]. Rev Rhum Mal Osteoartic 1986; 53:615.
- Fischer A, Swigris JJ, du Bois RM, et al. Minor salivary gland biopsy to detect primary Sjogren syndrome in patients with interstitial lung disease. Chest 2009; 136:1072.
- Matsuyama N, Ashizawa K, Okimoto T, et al. Pulmonary lesions associated with Sjögren's syndrome: radiographic and CT findings. Br J Radiol 2003; 76:880.
- Sakamoto O, Saita N, Ando M, et al. Two cases of Sjögren's syndrome with multiple bullae. Intern Med 2002; 41:124.
- Gardiner P, Ward C, Allison A, et al. Pleuropulmonary abnormalities in primary Sjögren's syndrome. J Rheumatol 1993; 20:831.
- Franquet T, Giménez A, Monill JM, et al. Primary Sjögren's syndrome and associated lung disease: CT findings in 50 patients. AJR Am J Roentgenol 1997; 169:655.
- Koyama M, Johkoh T, Honda O, et al. Pulmonary involvement in primary Sjögren's syndrome: spectrum of pulmonary abnormalities and computed tomography findings in 60 patients. J Thorac Imaging 2001; 16:290.
- Kim EA, Lee KS, Johkoh T, et al. Interstitial lung diseases associated with collagen vascular diseases: radiologic and histopathologic findings. Radiographics 2002; 22 Spec No:S151.
- Taouli B, Brauner MW, Mourey I, et al. Thin-section chest CT findings of primary Sjögren's syndrome: correlation with pulmonary function. Eur Radiol 2002; 12:1504.
- Salaffi F, Manganelli P, Carotti M, et al. A longitudinal study of pulmonary involvement in primary Sjögren's syndrome: relationship between alveolitis and subsequent lung changes on high-resolution computed tomography. Br J Rheumatol 1998; 37:263.
- Papiris SA, Maniati M, Constantopoulos SH, et al. Lung involvement in primary Sjögren's syndrome is mainly related to the small airway disease. Ann Rheum Dis 1999; 58:61.
- Song MK, Seol YM, Park YE, et al. Pulmonary nodular lymphoid hyperplasia associated with Sjögren's syndrome. Korean J Intern Med 2007; 22:192.
- Rajagopala S, Singh N, Gupta K, Gupta D. Pulmonary amyloidosis in Sjogren's syndrome: a case report and systematic review of the literature. Respirology 2010; 15:860.
- Cohen C, Mekinian A, Uzunhan Y, et al. 18F-fluorodeoxyglucose positron emission tomography/computer tomography as an objective tool for assessing disease activity in Sjögren's syndrome. Autoimmun Rev 2013; 12:1109.
- Kelly C, Gardiner P, Pal B, Griffiths I. Lung function in primary Sjögren's syndrome: a cross sectional and longitudinal study. Thorax 1991; 46:180.
- Brune, J, Emonot, A, Wiesendanger, T, et al. Syndrome de Gougerot-Sjögren et fibrose pariéto-alvéolare diffuse. A propos de cinq observations. Rev Fr Mal Resp 1976; 4:560.
- Ziza JM, Kaplan G, Salomon C, Kahn MF. [Severe pulmonary fibrosis disclosing primary Gougerot-Sjögren syndrome. Apropos of 5 cases, 2 of which were fatal]. Ann Med Interne (Paris) 1986; 137:46.
- Dalavanga YA, Voulgari PV, Georgiadis AN, et al. Lymphocytic alveolitis: A surprising index of poor prognosis in patients with primary Sjogren's syndrome. Rheumatol Int 2006; 26:799.
- Yamadori I, Fujita J, Bandoh S, et al. Nonspecific interstitial pneumonia as pulmonary involvement of primary Sjögren's syndrome. Rheumatol Int 2002; 22:89.
- Ioannou S, Toya SP, Tomos P, Tzelepis GE. Cryptogenic organizing pneumonia associated with primary Sjogren's syndrome. Rheumatol Int 2008; 28:1053.
- Matteson EL, Ike RW. Bronchiolitis obliterans organizing pneumonia and Sjögren's syndrome. J Rheumatol 1990; 17:676.
- Tonami H, Matoba M, Yokota H, et al. CT and MR findings of bilateral lacrimal gland enlargement in Sjögren syndrome. Clin Imaging 2002; 26:392.
- Horiuchi Y, Hakugawa J, Shimizu K, et al. Massive cutaneous follicular lymphoid hyperplasia in a patient with the Sjögren syndrome: 7-year follow-up and immunohistochemical study. Rheumatol Int 2006; 26:1044.
- Ooms V, Decupere M, Lerut E, et al. Secondary renal amyloidosis due to long-standing tubulointerstitial nephritis in a patient with Sjögren syndrome. Am J Kidney Dis 2005; 46:e75.
- Hansen LA, Prakash UB, Colby TV. Pulmonary lymphoma in Sjögren's syndrome. Mayo Clin Proc 1989; 64:920.
- Jeong YJ, Lee KS, Chung MP, et al. Amyloidosis and lymphoproliferative disease in Sjögren syndrome: thin-section computed tomography findings and histopathologic comparisons. J Comput Assist Tomogr 2004; 28:776.
- Perlat A, Decaux O, Gervais R, et al. Systemic light chain amyloidosis and Sjogren syndrome: an uncommon association. Amyloid 2009; 16:181.
- Nakamura N, Yamada G, Itoh T, et al. Pulmonary MALT lymphoma with amyloid production in a patient with primary Sjögren's syndrome. Intern Med 2002; 41:309.
- American-European criteria
- - Primary Sjögren's syndrome
- - Secondary Sjögren's syndrome
- ACR classification criteria for SS
- CLINICAL FEATURES
- DIFFERENTIAL DIAGNOSIS
- Pulmonary vascular disease
- Sjögren's syndrome and sarcoidosis
- IgG4-related systemic disease
- Other causes of diffuse parenchymal lung disease
- EVALUATION AND DIAGNOSIS
- Chest imaging
- - Chest radiograph
- - High resolution computed tomography
- Pulmonary function tests
- Minor salivary gland biopsy
- Bronchoalveolar lavage
- Lung biopsy
- - Nonspecific interstitial pneumonia
- - Lymphocytic interstitial pneumonia
- - Usual interstitial pneumonia
- - Organizing pneumonia
- - Follicular bronchiolitis
- - Nodular lymphoid hyperplasia (pseudolymphoma)
- - Lymphoma
- - Pulmonary nodular amyloidosis
- SUMMARY AND RECOMMENDATIONS