Lung Involvement in Primary Sjögren's Syndrome—An Under-Diagnosed Entity

Abstract

Interstitial lung disease (ILD) represents a frequent extra-glandular manifestation of primary Sjögren's Syndrome (pSS). Limited published data regarding phenotyping and treatment exists. Advances in managing specific ILD phenotypes have not been comprehensively explored in patients with coexisting pSS. This retrospective study aimed to phenotype lung diseases occurring in a well-described pSS-ILD cohort and describe treatment course and outcomes. Between April 2018 and February 2020, all pSS patients attending our Outpatient clinic were screened for possible lung involvement. Clinical, laboratory and high-resolution computed tomography (HRCT) findings were analyzed. Patients were classified according to HRCT findings into five groups: usual interstitial pneumonia (UIP), non-specific interstitial pneumonia (NSIP), desquamative interstitial pneumonia (DIP), combined pulmonary fibrosis and emphysema (CPFE), and non-specific-ILD. Lung involvement was confirmed in 31/268 pSS patients (13%). One-third (10/31) of pSS-ILD patients were Ro/SSA antibody negative. ILD at pSS diagnosis was present in 19/31 (61%) patients. The commonest phenotype was UIP n = 13 (43%), followed by NSIP n = 9 (29%), DIP n = 2 (6 %), CPFE n = 2 (6 %), and non-specific-ILD n = 5 (16%). Forced vital capacity (FVC) and carbon monoxide diffusion capacity (D LCO) appeared lower in UIP and DIP, without reaching a significant difference. Treatment focused universally on intensified immunosuppression, with 13/31 patients (42%) receiving cyclophosphamide. No anti-fibrotic treatments were used. Median follow-up was 38.2 [12.4-119.6] months. Lung involvement in pSS is heterogeneous. Better phenotyping and tailored treatment may improve outcomes and requires further evaluation in larger prospective studies.

Clinical characteristics and outcomes in patients with primary Sjogren's syndrome-associated interstitial lung disease

“…Previous studies in pSS-ILD cohorts reported an average age at presentation ranging from 58 to 68 years, a female predominance, and a smoking history in 13%–31% of the patients, depending on the studied population. [ 2 3 4 6 7 8 10 23 24 ] In agreement with the cited studies, our cohort had a mean age at presentation of 60 years, 62% were women, and the majority were nonsmokers. Considerable variation among studies was noted regarding the prevalence of autoimmune symptoms and signs in pSS-ILD patients.…”

“…[ 2 3 4 7 8 9 10 23 ] However, recent studies reported a higher prevalence of the UIP pattern, ranging between 42% and 92%, implying that significant heterogeneity occurs among pSS patients and among studied populations. [ 6 24 ] In the present study, UIP was the most common pattern, followed by NSIP. Regarding the serological test results, we showed that autoantibodies against SSA and SSB were positive in only 22% and 5% of the patients, respectively.…”

“…In our cohort, the average percent predicted FVC during the initial evaluation was 57%, which is significantly lower than the values reported in any of the published studies on pSS-ILD, which ranged between 65% and 93%. [ 2 3 4 6 7 8 10 ] Such an advanced state of lung fibrosis at presentation is likely due to the significant delays in diagnosis and in referring these patients to specialized centers. For instance, dyspnea and cough are common complaints in ILD patients; thus, the misdiagnosis of these patients with more common conditions that have similar symptoms, such as asthma, chronic obstructive lung disease, heart failure and others, is quite common, resulting in a delay in diagnosis and the initiation of the appropriate treatment.…”

“…[ 1 ] The commonly reported radiological patterns in pSS-ILD are nonspecific interstitial pneumonia (NSIP), usual interstitial pneumonia (UIP), lymphocytic interstitial pneumonia, and organizing pneumonia. [ 2 3 4 5 6 7 8 ] While data on the survival rate in patients with pSS-ILD are limited, previous studies have shown that the 5-year survival rate ranges between 84% and 89.9%, depending on the studied population. [ 3 9 10 11 ] Among the reported risk factors independently associated with survival in patients with pSS-ILD are the partial pressure of oxygen, microscopic honeycombing, the partial pressure of carbon dioxide, the extent of reticular abnormality based on high-resolution computed tomography (HRCT), the severity of fibroblastic foci, the percent predicted forced vital capacity (FVC), and the serum Krebs von den Lungen-6 level.…”

Combined Pulmonary Fibrosis and Emphysema (CPFE) Clinical Features and Management

“…Case reports describing these treatments are limited. 37 Case reports on patients with CPFE show that they could possibly improve with lung volume reduction (LVR) in case of advanced emphysema, even without plethysmographic evidence of severe hyperinflation. 38 If LVR is not possible and after extensive exclusion of (lung) cancer, patients should be evaluated early for lung transplantation as the ultimate treatment modality of CPFE.…”