Connective Tissue Disease-Associated Interstitial Lung Disease - Causes, Diagnosis, and Management

Introduction

Connective tissue disease-associated interstitial lung disease (CTD-ILD) is a lung disorder that occurs in individuals affected with connective tissue diseases. It causes inflammation and fibrosis of the lungs. Various connective tissue diseases can impact the lungs in different ways. It prevents oxygen absorption in the lungs and results in shortness of breath, cough, and fatigue.

What Is Connective Tissue Disease?

Connective tissue is the tissue with an extracellular matrix that supports and protects various organs of the body. Connective tissue diseases are a group of diseases that affect the connective tissues of the organs. It results in organ damage. These diseases are usually autoimmune of blood vessels and cause chronic inflammation of blood vessels and connective tissues. Connective tissue disease causes pulmonary complications like bronchitis, bronchiolitis, bronchiectasis, pleuritis, and pulmonary hypertension.

What Is Interstitial Lung Disease?

Interstitial lung diseases are a group of diseases that affect alveolar epithelial cells, basement membranes, pulmonary capillary endothelial cells, and perivascular and lymphoid tissues. It is a heterogeneous group of noncancerous diseases that belong to the category of diffuse parenchymal lung diseases. It causes inflammation and fibrosis. It can be caused by chronic exposure to hazardous materials or autoimmune diseases. It causes irreversible scarring of the lung tissues that impairs oxygen availability. Interstitial lung disease is subdivided into idiopathic interstitial pneumonia and idiopathic pulmonary fibrosis.

What Is Connective Tissue Disease-Associated Interstitial Lung Disease (CTD-ILD)?

Interstitial lung disease is associated with connective tissue disorders because they share a common autoimmune nature. Interstitial lung disease is associated with various connective tissue diseases like systemic sclerosis, rheumatoid arthritis, Sjogren’s syndrome, polymyositis, dermatomyositis, systemic lupus erythematosus, and undifferentiated and mixed connective tissue diseases. Various pulmonary components can be involved depending on the underlying connective tissue disease. It affects the airways, vessels, pleura, lung parenchyma, and respiratory muscles.

What Are the Causes of Connective Tissue Disease-Associated Interstitial Lung Disease?

Connective tissue disease-associated interstitial lung disease is caused by various factors like genetic changes, epigenetic changes, and dysregulated immunity that interact and result in diseases under various ill-defined environmental trigger factors. The exact cause is unknown. Interstitial lung disease can occur secondary to inflammation, alveolar injury, dysregulated tissue repair, and fibroproliferation in connective tissue diseases.

How Does Connective Tissue Disease-Associated Interstitial Lung Disease Occur?

Interstitial lung disease is caused by epithelial injury. The epithelial injury occurs secondary to multiple causes, including microaspiration. Endothelial or epithelial injury precedes inflammation and fibrosis. Autoimmunity, inflammation, and vascular injury are responsible for the development of interstitial lung disease in connective tissue disorders. The pattern of occurrence of interstitial lung disease in various connective tissue diseases includes the following:

• Systemic Sclerosis - Systemic sclerosis is a disorder caused by excessive collagen deposition. It is associated with the development of pulmonary hypertension and interstitial lung disease. It causes fibrosis and scarring of the lung tissues. Autoantibody expression causes lung involvement.

• Rheumatoid Arthritis - Rheumatoid arthritis is an inflammatory disease that affects the joints and causes pain and inflammation. The inflammation and damage to epithelial and endothelial cells promote the development of pulmonary fibrosis and interstitial pneumonia. Rheumatoid arthritis causes pulmonary abnormalities like bronchial wall thickening, bronchial dilation, micronodules, and opacities with pleural effusions.

• Polymyositis and Dermatomyositis - Dermatomyositis and polymyositis cause inflammation of the skeletal muscles, skin, and lungs. The initiation and maintenance of autoantibodies predispose the individual to interstitial lung disease.

• Sjogren Syndrome - Sjogren syndrome is a chronic autoimmune disease that destroys the exocrine glands and causes mucosal dryness due to lymphocytic infiltration. The impaired mucosal defense and glandular dysfunction within the lungs predispose the development of parenchymal fibrosis and pulmonary inflammation.

• Systemic Lupus Erythematosus - Systemic lupus erythematosus affects the pleura, pulmonary vasculature, and lung parenchyma. It causes pleuritic pain and pulmonary hemorrhage. Diffuse interstitial lung disease or chronic pneumonitis is seen in individuals with systemic lupus erythematosus.

• Undifferentiated Connective Tissue Disease - Interstitial lung disease precedes or occurs along with rheumatic symptoms of the undifferentiated connective disease.

• Mixed Connective Tissue Disease - Mixed connective tissue disease affects the diffusing capacity of carbon monoxide and also causes restrictive abnormalities in pulmonary function tests.

What Are the Symptoms of Connective Tissue Disease-Associated Interstitial Lung Disease?

The pulmonary symptoms associated with connective tissue disease include the following:

• Shortness of breath.

• Breathing difficulty.

• Chronic cough.

• Weakness and fatigue.

• Nosebleeding.

• Bloody phlegm.

• Anemia.

• Oral ulcers.

• Rashes.

How Is Connective Tissue Disease-Associated Interstitial Lung Disease Diagnosed?

The diagnosis is based on physical examination, laboratory studies, radiographic imaging, and assessment of other manifestations.

• Antibody Testing is performed to detect the presence of autoantibodies in connective tissue diseases.

• Radiographic Images are taken to diagnose the presence of focal or diffuse pulmonary abnormalities associated with connective tissue disease.

• Chest X-Ray is taken to diagnose the presence of ground-glass opacities, reticulations, pleural effusions, pulmonary nodules, bronchiectasis, prominent pulmonary vessels, and volume loss.

• Pulmonary Function Tests like spirometry, lung volumes, diffusion capacity for carbon monoxide, and arterial blood gas measurements are performed to identify the restrictive lung disease pattern in connective tissue disease.

• Histopathological Examination - Histopathological examination reveals the presence of inflammation, fibrosis, and inflammatory infiltration.

How Is Connective Tissue Disease-Associated Interstitial Lung Disease Treated?

• Individuals with connective tissue associated-interstitial lung diseases are managed with immunosuppressants like corticosteroids and corticosteroid-sparing medications like Azathioprine, Cyclosporine, Cyclophosphamide, and Methotrexate.

• Adjunctive therapy with supplemental oxygen, pulmonary rehabilitation, yearly influenza vaccine, and periodic vaccination against pneumococcal pneumonia is given to patients with connective tissue disease-associated interstitial lung disease.

• Refractory diseases with progressive fibrosis in connective tissue associated-interstitial lung disease are treated with lung transplantation. Lung transplantation is the major treatment option for patients with end-stage lung disease.

Complications of Connective Tissue Disease-Associated Interstitial Lung Disease

Pulmonary complications associated with connective tissue disease include the following:

• Lung infections.

• Drug-induced pulmonary disease.

• Pulmonary hypertension.

• Bronchiolitis.

• Pleuritis.

• Bronchiectasis.

• Acute respiratory distress syndrome (ARDS).

• Pneumothorax.

• Cor pulmonale.

• Diffuse alveolar hemorrhage.

Conclusion

Interstitial lung disease is a common complication of connective tissue disorder. Connective tissue disease-associated interstitial lung disease is a progressive disease in which both diseases may progress independently or concurrently. Each type presents unique clinical characteristics, therapeutic response, and prognosis. Advancements in understanding the pathogenesis of this disease are essential for managing patients with connective tissue disease-associated interstitial lung disease.