Sjögren’s Syndrome

Epidemiology

Sjӧgren’s Syndrome is a systemic autoimmune disease, the second most common after rheumatoid arthritis. It is characterized by impairment of the exocrine glands (mainly lacrimal and salivary glands) due to lymphocytic in ltration, and also extraglandular, visceral involvement (Table 14.4) [40, 41]. It has a clear female predominance, and it occurs either as a primary disorder or in association with other CTDs as secondary SS. SS has a prevalence of 20–100/100,000 and an incidence of 3.9/100,000. The prevalence of lung involvement is between 10–20%, although up to 65% of asymptomatic patients may have abnormal lung imaging [42, 43].

Pathophysiology

SS pathophysiology involves a combination of environmental, genetic, and hormonal infuences, leading to autoimmune epithelitis, deregulated immune responses, and in ltration of B and T lymphocytes into affected tissues [44]. Triggered B-cells favor the secretion of anti-SSA and anti-SSB autoantibodies directed to small cytoplasmic RNP-bound peptides [45]. T-cells are also activated and involved in cytotoxic procedures. Lung involvement is associated with higher levels of circulating immune complexes and autoantibodies [46]. The main serum markers indicative of SS are anti-SSA and anti-SSB (Table 14.2). High levels of these antibodies, and also ANA, rheumatoid factor, hyper-γ-globulinaemia, as well as older age and smoking history, have been considered risk factors for pulmonary involvement [47, 48].

Table 14.4  American College of Rheumatology/European league against Rheumatism classi cation criteria for primary Sjögren’s syndrome (2016)

Individuals with signs and symptoms suggestive of Sjögren’s syndrome who have a total score ≥ 4 for the items above, meet the criteria for primary Sjögren’s syndrome

Reproduced and modi ed from [40]

Pulmonary Manifestations

Airway Disorders

Airway disorders are common manifestations of SS (Table 14.1). Apart from upper airway disorders due to mucosal dryness and impaired mucociliary clearance, bronchiolitis and bronchiectasis are also frequently described in patients with SS (more than 20%) (Fig. 14.3a, b) [49, 50]. SS should be included in the differential diagnosis in a patient presenting with airway disorder (chronic cough or small airway disease) or pulmonary lymphoproliferative disorder. However, clinicians should be careful as lymphoma and amyloidosis can present with a LIP pattern on HRCT, and so tissue biopsy should be discussed on a case-by-case base.

Lymphoproliferative Disease

Patients with SS display a high risk for both nonneoplastic (e.g., nodular lymphoid hyperplasia, follicular bronchiolitis,

lymphoid interstitial pneumonia), as well as neoplastic monoclonal lymphoproliferative disorders. The prevalence of lymphoma in SS ranges from 5% to 18% [51].

Approximately 6% of Sjögren-associated lymphomas involve the lungs and the most common types are the marginal zone B-cell lymphoma and mucosa-associated lymphoid tissue type [52, 53].

Such a lymphoproliferative involvement of the lungs in patients with SS can present as non-resolving consolidations, solitary or multiple nodules or masses, lymphadenopathy, and cystic lesions (Fig. 14.4). Given the increased risk for lymphoproliferative disorders, active clinical surveillance is recommended, especially for patients who are at high risk for lymphoma due to persistent salivary gland swelling, vasculitis and palpable purpura, lymphadenopathy, low C3 or C4 complement fraction, monoclonal gammopathy, cryoglobulins, anti-SSA and/or anti-SSB, rheumatoid factor, anemia, leukopenia, lymphopenia, neutropenia, thrombocytopenia, and elevated serum beta2-microglobulin [43, 54].

Lymphoma requires speci c hematological treatment, and a multidisciplinary approach is suggested for diagnosis and management [43].

Interstitial Lung Disease

ILD is mainly considered to be developed later in the course of Sjögren’s syndrome, with a prevalence of 47% in 15 years; however, in 10–51% of patients, ILD may occur before other SS manifestations [42]. NSIP seems to be the prominent ILD pattern (45%), while UIP (16%), LIP (15%), and OP (7%) are less common, although a combined pattern is frequently described [55, 56]. The UIP pattern is associated with a progressive phenotype (Fig. 14.5a, b) [57].

With regard to the management of pulmonary disease in Sjögren’s syndrome, recent consensus guidelines were

Fig. 14.4  Cystic lung disease in a patient with Sjögren’s syndrome

published­ shedding light on the optimal way of evaluation and treatment of these patients [43]. For patients presenting a mild disease with preserved lung function and minimal symptoms, a serial follow-up is recommended. In symptomatic or moderate-severe lung function impairment or/and HRCT ndings, the rst-line treatment including corticoste-