Guideline sources The following summarized guidelines for the evaluation and management of Sj gren s disease (SD) are prepared by our editorial team based on guidelines from the American College of Rheumatology (ACR 2023; 2021), the Brazilian Society of Rheumatology (BSR 2022), the European League Against Rheumatism (EULAR 2022; 2020), the European Respiratory Society (ERS 2022), the Royal College of Ophthalmologists (RCOphth 2020), and the Sj gren's Syndrome Foundation (SSF 2017). 1 2 3 4 5 6 7 8 9 10 11 12 13 Definition SD is an autoimmune disorder characterized by lymphocytic infiltration of exocrine glands, leading to glandular dysfunction, particularly of the salivary and lacrimal glands. 9 Epidemiology https://web.pathway.md/diseases/reck1kXBiSqjlSGxC 1/12 6/24/23, 3:06 PM Sj gren's disease Pathway SD is hypothesized to be triggered by environmental factors, such as viral infections (EBV, human herpes virus 6, human T cell lymphotropic virus 1, HCV) and smoking in genetically predisposed individuals (HLA class I, class II and class III genes). 11 Pathophysiology The estimated incidence of SD is 3.9 per 100,000 person-years in the United States. 10 Disease course The activation of mucosal epithelial cells secondary to lymphocytic infiltration leads to the activation of innate and acquired immune systems by secreting autoantibodies. These autoantibodies form immune complexes that maintain and amplify the production of interferon alpha, resulting in a cycle of immune system activation that ultimately causes tissue damage. The spectrum of associated end-organ disease includes exocrine glandular dysfunction, ILD, lymphoma, interstitial nephritis, cryoglobulinemia, arthralgias, cutaneous lupus, peripheral neuropathies, and cerebral vasculitis. 12 Prognosis and risk of recurrence Lymphoma, when it occurs in patients with SD, has a high mortality rate, with a disease-specific standardized mortality ratio of 7.89. 13 Calculator Calculator Pathway Diagnostic criteria for primary Sj EULAR Sj gren's Syndrome Dise Sj gren's Managemen Guidelines 1. Screening and diagnosis Screening in patients with lung disease: obtain clinical and serologic evaluation for SD in patients with uncharacterized ILD, diffuse cystic lung disease, or pulmonary lymphoma. A 2. Classification and risk stratification Severity assessment: As per BSR 2022 guidelines, use the ESSDAI as a measurement tool for diagnosing and evaluating the activity of systemic manifestations of SD. B As per EULAR 2020 guidelines, use the ESSDAI definitions to tailor treatment of systemic disease to organ-specific severity. B https://web.pathway.md/diseases/reck1kXBiSqjlSGxC 2/12 6/24/23, 3:06 PM Sj gren's disease Pathway 3. Diagnostic investigations 4. Diagnostic procedures Bronchoalveolar lavage: Do not perform routine bronchoscopy with BAL in patients with SD having respiratory symptoms. D Consider performing bronchoscopy with BAL in patients with SD having respiratory symptoms determined on a case-by-case basis and limited to special circumstances, such as the need to: rule out infectious etiologies, especially in patients on immune suppression rule out endobronchial abnormalities such as amyloidosis in patients with chronic cough not otherwise responsive to treatment distinguish between other etiologies of sicca symptoms such as sarcoidosis. B Lung biopsy: As per ERS 2022 guidelines: Consider performing transbronchial lung cryobiopsy in patients with undiagnosed ILD, whether deemed eligible or ineligible for surgical lung biopsy, if obtaining histopathological data is indicated. C Consider performing step-up surgical lung biopsy in patients with undiagnosed ILD and a non- informative transbronchial lung cryobiopsy, if obtaining histopathological data is indicated. C As per ACR 2021 guidelines, do not perform routine bronchoscopy with endobronchial or transbronchial lung biopsy in patients with SD having respiratory symptoms. D Show 3 more 5. Respiratory support Oxygen therapy: Initiate long-term oxygen therapy in patients with SD and suspected ILD and clinically significant resting hypoxemia (defined by resting oxygen saturation < 88%, PaO < 55 mmHg or < 60 mmHg with complication of chronic hypoxemia such as cor pulmonale). B Evaluate the need for supplemental oxygen in patients with SD-ILD considering air travel. B 6. Medical management 7. Nonpharmacologic interventions Exercise and self-care: provide education regarding self-care measures, including advice about exercise to reduce fatigue in patients with SD. A Smoking cessation: advise smoking cessation in all patients with SD. B https://web.pathway.md/diseases/reck1kXBiSqjlSGxC 3/12 6/24/23, 3:06 PM Sj gren's disease Pathway Air humidification: Consider advising humidification in patients with SD having dry, nonproductive cough after exclusion of other causes. C Consider advising humidification for improving positive airway pressure tolerance and compliance in patients with SD. C Pulmonary rehabilitation: refer symptomatic patients with SD and ILD having impaired pulmonary function for pulmonary rehabilitation. B Voice therapy: consider offering voice therapy before proceeding with surgical intervention in patients with SD and symptomatic vocal cord cystic lesions ("bamboo nodules"). C 8. Surgical interventions Vocal cord surgery: consider performing surgical resection in patients with SD and symptomatic vocal cord cystic lesions ("bamboo nodules") if initial less aggressive measures fail, with consultation by a laryngologist with experience in SD. C Lung transplantation: evaluate patients with SD and ILD for lung transplantation if the condition is advanced with resting hypoxia or lung function is rapidly deteriorating. B 9. Patient education Patient education: educate patients and caregivers/family about signs and symptoms of pneumothorax and instruct to seek immediate medical attention if they experience signs or symptoms because patients with SD and cystic lung disease might have an increased risk of pneumothorax. B Air travel: Do not discourage air travel in patients with SD and ILD unless the patient develops signs and symptoms of pneumothorax or new onset/unexplained chest pain or dyspnea before boarding. D Advise patients with SD and ILD considering air travel that the need for supplemental oxygen should be evaluated by a physician. B Medication-related adverse effects: Inform patients with SD and related connective tissue diseases about the following pulmonary complications associated with medications used, particularly when patients are progressive or refractory to therapies, and for which bronchoscopy, biopsy, and/or withdrawal of the medication may be required: infections malignancies bronchospasm drug-induced ILD. B Show 5 more https://web.pathway.md/diseases/reck1kXBiSqjlSGxC 4/12 6/24/23, 3:06 PM Sj gren's disease Pathway 10. Preventative measures Routine immunizations: As per ACR 2023 guidelines, consider offering high-dose or adjuvanted influenza vaccination, rather than regular-dose influenza vaccination, in 65 years old patients with rheumatic or musculoskeletal diseases and in 18-65 years old patients with rheumatic or musculoskeletal diseases on immunosuppressive medications. C Show 17 more As per ACR 2021 guidelines: Offer immunization against influenza and pneumococcal infection in all patients with SD in accordance with CDC guidelines. Avoid giving live vaccines with rituximab in patients with SD. D As per SSF 2017 guidelines, avoid giving live vaccines in patients receiving rituximab. D Prophylaxis for Pneumocystis jirovecii pneumonia: consider administering prophylaxis against P. jirovecii pneumonia in patients initiating high-dose corticosteroids, especially in combination with immunosuppressants and depending on the risk-benefit ratio. C 11. Follow-up and surveillance Monitoring of patients on rituximab: Monitor for the following adverse effects in patients receiving rituximab: infusion reactions tumor lysis syndrome in patients with non-Hodgkin lymphoma progressive multifocal leukoencephalopathy hepatitis B reactivation with possible fulminant hepatitis severe mucocutaneous reactions infections bowel obstruction and perforation cardiac arrhythmias and angina cytopenias serious bacterial, viral, or fungal infections. B Monitoring of patients on TNFi: Monitor for the following adverse reactions in patients receiving TNF inhibitors for rheumatoid arthritis or other related overlap conditions: lymphoma and other malignancies (recognize that patients with primary SD have an increased risk of non-Hodgkin lymphoma) serious infections, including tuberculosis invasive fungal infections hepatitis B reactivation hepatotoxicity https://web.pathway.md/diseases/reck1kXBiSqjlSGxC 5/12 6/24/23, 3:06 PM Sj gren's disease Pathway HF cytopenias hypersensitivity, serious infusion reactions demyelinating disease. A Monitoring of patients on hydroxychloroquine/chloroquine: obtain annual monitoring for retinopathy in all patients receiving hydroxychloroquine for > 5 years or chloroquine for > 1 year. B Show 17 more Monitoring for pulmonary function: As per BSR 2022 guidelines, obtain monitoring with high-resolution chest tomography and complete pulmonary function testing in patients with pulmonary involvement at least every 2 years or earlier, if necessary, according to the clinical judgment. A As per ACR 2021 guidelines, obtain serial monitoring by pulmonary function testing every 3-6 months to establish disease trajectory in patients with SD and ILD having asymptomatic lung disease or demonstrating minimal impairment on pulmonary function testing or HRCT. Initiate pharmacotherapy only if serial studies document a significant decline in lung function. B Monitoring for lymphoproliferative disorders: obtain clinical monitoring for signs and symptoms of pulmonary lymphoproliferative disorders, including lymphoma and amyloid, in all patients with SD. A Show 2 more References 1. Augustine S Lee, R Hal Scofield, Katherine Morland Hammitt et al. Consensus Guidelines for Evaluation and Management of Pulmonary Disease in Sj gren's. Chest. 2021 Feb;159 2 683 698. Open 2. Manuel Ramos-Casals, Pilar Brito-Zer n, Stefano Bombardieri et al. EULAR recommendations for the management of Sj gren's syndrome with topical and systemic therapies. Ann Rheum Dis. 2020 Jan;79 1 3 18. Open 3. Steven E Carsons, Frederick B Vivino, Ann Parke et al. Treatment Guidelines for Rheumatologic Manifestations of Sj gren's Syndrome: Use of Biologic Agents, Management of Fatigue, and Inflammatory Musculoskeletal Pain. Arthritis Care Res Hoboken). 2017 Apr;69 4 517 527. Open 4. Virginia Fernandes Mo a Trevisani, Alisson Pugliesi, Sandra Gofinet Pasoto et al. Recommendations for evaluation and diagnosis of extra-glandular manifestations of primary sjogren syndrome: results of an epidemiologic systematic review/meta-analysis and a consensus guideline from the Brazilian Society of Rheumatology (articular, pulmonary and renal). Adv Rheumatol. 2022 Jun 1;62 1 18. Open 5. The Royal College of Ophthalmologists. Hydroxychloroquine and Chloroquine Retinopathy: Recommendations on Monitoring. RCOphth. 2020 Dec. Open 6. Anne R Bass, Eliza Chakravarty, Elie A Akl et al. 2022 American College of Rheumatology Guideline for Vaccinations in Patients With Rheumatic and Musculoskeletal Diseases. Arthritis Rheumatol. 2023 Jan 4. Online ahead of print. Open https://web.pathway.md/diseases/reck1kXBiSqjlSGxC 6/12 6/24/23, 3:06 PM Sj gren's disease Pathway 7. George E Fragoulis, Elena Nikiphorou, Mrinalini Dey et al. 2022 EULAR recommendations for screening and prophylaxis of chronic and opportunistic infections in adults with autoimmune inflammatory rheumatic diseases. Ann Rheum Dis. 2022 Nov 3;ard-2022 223335. Open 8. Dani l A Korevaar, Sara Colella, Markus Fally et al. European Respiratory Society guidelines on transbronchial lung cryobiopsy in the diagnosis of interstitial lung diseases. Eur Respir J. 2022 Nov 10;60 5 2200425. Open 9. Nair JJ, Singh TP. Sjogren's syndrome: Review of the aetiology, Pathophysiology & Potential therapeutic interventions. J Clin Exp Dent. 2017 Apr 1;9 4):e584-e589. Open 10. Qin B, Wang J, Yang Z et al. Epidemiology of primary Sjogren's syndrome: a systematic review and meta-analysis. Ann Rheum Dis. 2015 Nov;74 11 1983 9. Open 11. Brito-Zeron P, Baldini C, Bootsma H et al. Sjogren syndrome. Nat Rev Dis Primers. 2016 Jul 7;2 16047. Open 12. Mariette X, Criswell LA. Primary Sjogren's Syndrome. N Engl J Med. 2018 Mar 8;378 10 931 939. Open 13. Both T, Dalm VA, van Hagen PM et al. Reviewing primary Sjogren's syndrome: beyond the dryness From pathophysiology to diagnosis and treatment. Int J Med Sci. 2017 Feb 23;14 3 191 200. Open 14. Vivino FB, Carsons SE, Foulks G et al. New Treatment Guidelines for Sj gren's Disease. Rheum Dis Clin North Am. 2016 Aug;42 3 531 51. Open 15. Rapha le Seror, Simon J Bowman, Pilar Brito-Zeron et al. EULAR Sj gren's syndrome disease activity index ESSDAI a user guide. RMD Open. 2015 Feb 20;1 1):e000022. Open 16. Expert Panel on Neurological Imaging, Vikas Agarwal, Lubdha M Shah et al. ACR Appropriateness Criteria Myelopathy: 2021 Update. J Am Coll Radiol. 2021 May;18 5S S73 S82. Open https://web.pathway.md/diseases/reck1kXBiSqjlSGxC 7/12 6/24/23, 3:06 PM Sj gren's disease Pathway https://web.pathway.md/diseases/reck1kXBiSqjlSGxC 8/12 6/24/23, 3:06 PM Sj gren's disease Pathway https://web.pathway.md/diseases/reck1kXBiSqjlSGxC 9/12 6/24/23, 3:06 PM Sj gren's disease Pathway https://web.pathway.md/diseases/reck1kXBiSqjlSGxC 10/12 6/24/23, 3:06 PM Sj gren's disease Pathway https://web.pathway.md/diseases/reck1kXBiSqjlSGxC 11/12 6/24/23, 3:06 PM Sj gren's disease Pathway https://web.pathway.md/diseases/reck1kXBiSqjlSGxC 12/12