Sjögren’s Syndrome (SS) is a chronic systemic autoimmune disorder primarily recognized for causing the dryness of the eyes and mouth (sicca symptoms) due to the immune system attacking exocrine glands. SS is a systemic disease that can impact major organs throughout the body, with the pulmonary system being a frequent and sometimes severe target. Understanding how SS affects the lungs is important, as pulmonary complications can significantly affect overall health.
The Autoimmune Mechanism Affecting the Lungs
The involvement of the lungs in Sjögren’s Syndrome stems from the same underlying pathology that affects the glands: chronic inflammation driven by immune cell infiltration. The immune system, specifically T and B lymphocytes, mistakenly targets non-glandular tissues, including the delicate structures of the lungs, leading to dense collections of immune cells within the lung tissue.
The histopathology often shows a predominance of mononuclear cell infiltration, largely composed of CD4+ T cells, within the submucosa of the airways and the lung parenchyma. This cellular attack activates an inflammatory cascade, damaging the epithelial lining of the airways and the tissue surrounding the air sacs. This continuous infiltration and resulting inflammation are the root cause for diverse pulmonary complications, setting the stage for both obstructive issues in the airways and restrictive diseases in the lung tissue.
Upper Airway and Bronchial Involvement
The conducting airways—the trachea and bronchi—are frequently involved in Sjögren’s Syndrome, often representing the most common pulmonary manifestation. This involvement is an extension of sicca symptoms, as the exocrine glands moistening the upper respiratory tract are affected. The resulting dryness of the airways, known as xerotrachea, can lead to a chronic, persistent dry cough.
The airways can also suffer from direct inflammatory attack, known as lymphocytic bronchiolitis or small airway disease (SAD). This involves the infiltration of lymphocytes into the walls of the small bronchioles, causing them to thicken and narrow, which leads to an obstructive pattern of lung disease.
Dryness and inflammation can predispose patients to complications, such as recurrent respiratory infections and bronchiectasis (permanent widening and damage of the airways). These issues result from the impaired function of the cilia, which normally clear mucus.
Interstitial Lung Disease and Pulmonary Parenchyma Damage
A more serious complication of Sjögren’s Syndrome is Interstitial Lung Disease (ILD), which involves inflammation and scarring of the lung tissue (parenchyma). ILD occurs when chronic autoimmune inflammation extends into the walls and spaces surrounding the air sacs, impairing oxygen exchange. This condition is a major concern as it can lead to progressive shortness of breath, particularly with exertion.
Several distinct patterns of ILD are observed in SS, with Non-Specific Interstitial Pneumonia (NSIP) being the most frequently identified subtype, accounting for approximately 45% of cases. NSIP is characterized by a uniform pattern of inflammation or fibrosis across the affected area and generally has a better prognosis than other patterns.
Another pattern is Lymphocytic Interstitial Pneumonia (LIP), which is relatively unique to SS among connective tissue diseases and is defined by a dense, benign lymphocytic infiltration of the lung tissue. The most concerning pattern is Usual Interstitial Pneumonia (UIP), characterized by a patchy distribution of lung injury, scarring, and the formation of honeycomb cysts. The UIP pattern is associated with a more progressive and severe course, similar to Idiopathic Pulmonary Fibrosis, and carries a worse prognosis. Sustained damage from ILD can ultimately lead to pulmonary fibrosis, causing the lung tissue to become stiff and scarred, resulting in a restrictive lung defect.
Clinical Evaluation and Treatment Approaches
The evaluation of Sjögren’s-related lung disease begins with a thorough clinical assessment, looking for symptoms like a persistent cough or progressive shortness of breath. To accurately diagnose and characterize the lung involvement, physicians rely on two primary diagnostic tools. High-Resolution Computed Tomography (HRCT) of the chest is considered the gold standard for imaging, as it can clearly identify the patterns of ILD, such as NSIP or UIP, and detect small airway changes.
Pulmonary Function Tests (PFTs) are performed to measure how well the lungs are working, including spirometry, lung volumes, and the diffusing capacity of the lung for carbon monoxide (DLCO). PFTs help determine if the patient has a restrictive defect, which suggests ILD, or an obstructive defect, which is more common with airway disease. Baseline PFTs are often recommended even in asymptomatic patients to detect early, subclinical disease.
The treatment strategy is highly dependent on the type and severity of the lung disease. For inflammatory patterns of ILD, such as NSIP and LIP, the mainstay of therapy is immunosuppression aimed at controlling the autoimmune attack. This typically involves corticosteroids, often in combination with steroid-sparing agents like mycophenolate mofetil, azathioprine, or cyclophosphamide.
Some severe cases require B-cell-targeting therapies like rituximab. For the more fibrotic and progressive UIP pattern, antifibrotic medications may be considered, particularly if the disease continues to progress despite immunosuppressive treatment.