Impact of pSS-ILD

The risk of death quadruples in primary Sjögren’s syndrome (pSS) patients with interstitial lung disease (ILD) vs. those without ILD1



pSS patients with ILD have a significantly higher mortality rate vs. pSS patients without ILD (HR 4.328, 95% CI 1.040–17.532, p=0.010)1

Graph visualizing that pSS patients with ILD have a significantly higher mortality rate vs. pSS patients without ILD

The 5-year survival rate for all patients with pSS-ILD was 84%2

Graph visualizing 5-year survival rate for all patients with pSS-ILD

Survival time was calculated as the number of years from the initial visit for a respiratory consultation until death or time of censoring. 33 patients were censored if they were alive on April 30, 2003, or had died before that day from a cause unrelated to the disease.

Adapted from: Ito I, et al. Am J Respir Crit Care Med. 2005;171(6):632–638.

About 10%–16% of patients with pSS-ILD may die within 5 years of diagnosis1–5


Risk factors for mortality in pSS-ILD

  • Male1

HRCT pattern and extent
  • Higher number/extent of reticulations3

  • Increased extent of ground glass attenuation3

  • Honeycombing2

  • High disease extent6


Lung function impairment or decline(≤78% predicted at baseline5 and a threshold FVC of <60% predicted)6

  • KL-6 >800 U/mL5

Anterial blood gas sampling
  • Decreased PaO22

  • Higher level PaCO23


FVC and FEV1 <60% predicted are associated with early mortality in pSS patients with lung involvement.6 Patients with lower % FVC levels (≤78%) at baseline have a significantly higher mortality rate than those with higher % FVC levels (p=0.02).5

Survival was significantly shorter in patients with pSS-ILD with elevated serum KL-6 levels (>800 U/mL) at the time of initial diagnosis vs. to those with KL-6 levels ≤800 U/mL5

Elevated serum KL-6 levels (>800 U/mL) almost triples pSS-ILD patients’ risk of mortality (HR 2.93, 95% CI 1.04–8.10, p=0.04)5

Graph showing that pSS-ILD patient survival is significantly shorter in patients with elevated serum KL-6 levels  greater than 800 U / mL at time of initial diagnosis

Kaplan-Meier survival curve for 99 consecutive patients with pSS-ILD diagnosed between 1990 and 2017 in a Japanese retrospective study. The median patient age was 68 years, and 72 (73%) of the 99 patients were women. The median follow-up period was 5.97 years. 

Adapted from: Kamiya Y, et al. Respir Med. 2019;159:105811.

pSS patients with severe lung involvement (high HRCT scores of 13–18) had shorter median overall survival than those with mild or moderate lung involvement (HRCT scores of 0–12) (p<0.001)6

Graph presenting that pSS patients with severe lung involvement had shorter median overall survival than those with mild or moderate lung involvement

The severity of lung involvement was classified according to the HRCT, where HRCT scores of 0–6 was defined as mild, 7–12 was defined as moderate, and 13–18 was defined as severe.

Learn how to investigate pSS-ILD characteristics with HRCT

Acute exacerbation of ILD in pSS-ILD is rare but can be fatal3,5,7,8

  • During a study of 38-month follow-up of 18 pSS-ILD patients, 39% of patients died and 17% died from an acute exacerbation of ILD7

  • In a retrospective study of patients with pathologically-proven pSS-ILD, 3 (fibrotic NSIP, 2; UIP, 1) of 33 patients died of acute exacerbation of ILD (median follow-up, 110 months)3

  • In a Japanese retrospective study of 99 patients with pSS-ILD, 33% of deaths (7 of 21 patients) were attributed to acute exacerbations5

How can you identify, monitor and manage ILD in patients with pSS?


  • *HRCT changes were graded according to the Schurawitzki method. Lungs were divided in upper, middle and lower segments and each area of a segment was assigned a score of 0–3 according to the following scale: 0=no interstitial involvement, 1=minimal reticular pattern, 2=obvious reticular pattern, and 3=honeycombing. Scores obtained for the six lung segments were added to obtain an overall score, which ranged from 0 (normal scans) to a maximum score of 18 12
    CI, confidence interval; CTD-ILD, connective tissue disease-associated interstitial lung disease; FEV1, forced expiratory volume in 1 second; FVC, forced vital capacity; HR, hazard ratio; HRCT, high-resolution computed tomography; ILD, interstitial lung disease; KL-6, Krebs von den Lungen-6; NSIP, non-specific interstitial pneumonia; PaCO2, partial pressure of carbon monoxide; PaO2, partial pressure of oxygen; PFT, pulmonary function test; pSS, primary Sjögren's syndrome; pSS-ILD, primary Sjögren's syndrome-associated interstitial lung disease; UIP, usual interstitial pneumonia. 

  1. Yazisiz V, Göçer M, Erbasan F, et al. Survival analysis of patients with Sjögren’s syndrome in Turkey: a tertiary hospital-based study. Clin Rheumatol. 2020;39(1):233–241.

  2. Ito I, Nagai S, Kitaichi M, et al. Pulmonary manifestations of primary Sjögren’s syndrome: a clinical, radiologic, and pathologic study. Am J Respir Crit Care Med. 2005;171(6):632–638.

  3. Enomoto Y, Takemura T, Hagiwara E, et al. Prognostic factors in interstitial lung disease associated with primary Sjögren’s syndrome: a retrospective analysis of 33 pathologically-proven cases. PLoS One. 2013;8(9):e73774.

  4. Gao H, Zhang X-W, He J, et al. Prevalence, risk factors, and prognosis of interstitial lung disease in a large cohort of Chinese primary Sjögren syndrome patients: a case-control study. Medicine (Baltimore). 2018;97(24):e11003.

  5. Kamiya Y, Fujisawa T, Kono M, et al. Prognostic factors for primary Sjögren’s syndrome-associated interstitial lung diseases. Respir Med. 2019;159:105811.

  6. Chen M-H, Chiu H-P, Lai C-C, et al. Lung involvement in primary Sjögren’s syndrome: correlation between high-resolution computed tomography score and mortality. J Chin Med Assoc. 2014;77(2):75–82.

  7. Parambil JG, Myers JL, Lindell RM, et al. Interstitial lung disease in primary Sjögren syndrome. Chest. 2006;130(5):1489–1495.

  8. Suda T, Kaida Y, Nakamura Y, et al. Acute exacerbation of interstitial pneumonia associated with collagen vascular diseases. Respir Med. 2009;103(6):846–853.

  9. Lee AS, Scofield RH, Hammitt KM, et al. Consensus guidelines for evaluation and management of pulmonary disease in Sjögren’s. Chest. 2020 Oct 20. doi: 10.1016/j. chest.2020.10.011.

  10. Guisado-Vasco P, Silva M, Duarte-Millán M A, et al. Quantitative assessment of interstitial lung disease in Sjögren’s syndrome. PLoS One. 2019;14(11):e0224772.

  11. Li X, Xu B, Ma Y, et al. Clinical and laboratory profiles of primary Sjögren’s syndrome in a Chinese population: a retrospective analysis of 315 patients. Int J Rheum Dis. 2015;18(4):439–446.

  12. Schurawitzki H, et al. Interstitial lung disease in progressive systemic sclerosis: high-resolution CT versus radiography. Radiology. 1990;176(3):755-9.

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