Sjögren Syndrome-associated Interstitial Lung Disease Treated With Immunosuppression

Kimberly Showalter, MD, MS; Jessica K. Gordon, MD, MS; Bella Mehta, MBBS, MS


March 30, 2021

This article originally appeared on Hospital for Special Surgery's website.

Case Report

A 39-year-old woman with former tobacco use (4.5 pack-years) presented with rapidly progressive interstitial lung disease (ILD). Two years prior, the patient developed subacute exertional dyspnea and cough, for which she received antibiotics without improvement. One year later, she developed diffuse arthralgias (hands, wrists, knees, and ankles), xerophthalmia, xerostomia, and worsening dyspnea. CT of the chest revealed extensive peripheral honeycombing, traction bronchiectasis, and lower lobe–predominant ground-glass opacities (Figure).

Figure. Chest CT scan without contrast demonstrating extensive peripheral areas of honeycombing, areas of traction bronchiectasis, and scattered ground-glass opacities with a lower lobe predominance.

Laboratory testing was notable for positive antinuclear antibody (1:320, speckled) and Sjögren syndrome A (anti-SSA) autoantibody. Other laboratory results were unremarkable, including rheumatoid factor and serum antibodies to Sjögren syndrome B (anti-SSB), anti-Smith, anti-RNP, anti-double-stranded DNA, anti-topoisomerase, anticentromere, RNA polymerase III, myeloperoxidase, serine proteinase 3, anti–Jo-1 (and extended myositis panel), and cyclic citrullinated peptide. Evaluation for infectious etiologies (HIV, tuberculosis, and pulmonary bacterial, viral, and fungal pathogens) was also unremarkable.

Pulmonary function testing demonstrated restrictive lung disease, with reduced percent predicted FVC to 32% and normal FEV1/FVC ratio. There was no evidence of pulmonary hypertension on right-heart catheterization. A lung biopsy was obtained that demonstrated fibrosing and cellular interstitial pneumonitis with a usual interstitial pneumonia pattern. Prednisone (10 mg twice daily) and hydroxychloroquine were initiated without symptom improvement.

The patient left the country for 3 months, during which time her shortness of breath slowly worsened. Upon returning, she was hospitalized with acute hypoxemic respiratory failure with FVC decline to 29% predicted and an increasing exertional oxygen requirement (2 L/min to 4 L/min). Repeat infectious workup was unremarkable, and imaging revealed no pulmonary embolism. She was referred both for pulmonary transplantation and rheumatology evaluations.

Additional immunomodulatory medications were added: mycophenolate mofetil (MMF) (increased over 8 weeks to 3 g daily) and rituximab (1 g intravenously for 2 doses, 14 days apart). She also began pulmonary rehabilitation. Subsequently, her joint pain resolved, dyspnea improved, and exertional oxygen requirement decreased to 2 L/min. Her percent predicted FVC improved slightly: 30% and 32% after 6 and 12 months, respectively. Currently, lung transplantation is on hold owing to symptom improvement.


Approximately 10%-20% of individuals with Sjögren syndrome have clinically relevant pulmonary involvement, defined by respiratory symptoms with pulmonary function test and/or chest radiographic abnormalities. Common symptoms include dyspnea, cough, and sputum production. Histopathologic findings often include nonspecific interstitial pneumonitis, bronchiolitis, and usual interstitial pneumonia. Factors associated with increased risk for lung disease include male sex, older age, history of tobacco use, hypergammaglobulinemia, lymphopenia, and presence of rheumatoid factor, anti-SSA, or anti-SSB antibodies. Of note, the presence of ILD is associated with a fourfold increased risk for death at 10 years.

To date, no controlled trial has been conducted in Sjögren syndrome–associated ILD. Prednisone (1 mg/kg) is recommended as initial treatment, and MMF, azathioprine, rituximab, and cyclophosphamide have also been used. MMF was studied in 125 patients with connective tissue disease–associated ILD (five with Sjögren syndrome). Among individuals with usual interstitial pneumonia, MMF was associated with pulmonary function testing stability over a median of 2.5 years. Rituximab was evaluated in a retrospective cohort study of Sjögren syndrome–associated ILD (n = 10). There was no significant 6-month improvement in FVC; however, there was mild improvement in diffusing capacity for carbon monoxide (7% predicted) and significant improvements in patient-reported outcomes.

Lung transplantation is considered in patients with advanced pulmonary involvement. A retrospective study of 67,621 patients showed no difference in post-transplantation mortality between those with nonscleroderma connective tissue disease–associated ILD and idiopathic pulmonary fibrosis.

Acknowledgements: We acknowledge Fernando Martinez, MD (Pulmonary and Critical Care Medicine, Weill Cornell Medicine), for his contribution.


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