Systemic Sclerosis (SSc), commonly known as scleroderma, is an autoimmune disease characterized by the overproduction of collagen. This condition involves immune dysregulation and microvascular damage, causing structural changes throughout the body. Interstitial Lung Disease (ILD) is a frequent and serious complication of SSc, affecting a significant portion of patients. SSc-ILD is the specific diagnosis when this connective tissue disease involves the lungs, causing scarring and inflammation. Since pulmonary fibrosis is the leading cause of death for individuals with SSc, understanding SSc-ILD is important for early intervention.
What SSc-ILD Is
SSc-ILD is the manifestation of systemic sclerosis within the lung tissue, specifically the interstitium (the space between the air sacs and the blood vessels). The core pathology involves inflammation and fibrosis, resulting in the excessive deposition of extracellular matrix components like collagen. This scarring process begins with injury to the alveolar epithelial cells, triggering an abnormal repair response that activates fibroblasts into myofibroblasts, the primary cells generating fibrotic tissue.
The body’s dysregulated immune response makes the lungs vulnerable to chronic scarring. Immune activation involves the infiltration of monocytes and macrophages, along with the release of pro-inflammatory and pro-fibrotic signaling molecules. This sustained inflammatory environment perpetuates the fibrotic process, replacing normal, functional lung tissue with stiff, scarred tissue ineffective for gas exchange.
ILD is highly prevalent in SSc, affecting between 50% and 80% of all patients, though it only becomes clinically significant in about 25% to 30%. Risk factors for developing SSc-ILD include:
- Male sex
- African heritage
- The diffuse cutaneous form of SSc
- The presence of specific autoantibodies
The anti-topoisomerase I (Scl-70) antibody is strongly associated with a higher likelihood of developing progressive ILD.
Identifying the Condition Through Diagnosis
Diagnosing SSc-ILD starts with recognizing clinical symptoms, which are often non-specific early on. Patients typically experience progressive shortness of breath, especially with exertion, and a persistent, non-productive cough. A physical exam might reveal crackling sounds, known as bibasilar crackles, at the base of the lungs during auscultation.
The gold standard for identifying structural changes is High-Resolution Computed Tomography (HRCT) of the chest. HRCT scans visualize the extent and pattern of lung involvement, even in asymptomatic patients. The scan reveals characteristic findings such as ground-glass opacities, which indicate active inflammation, and reticulation, suggesting early fibrosis. Advanced scarring is identified by honeycombing, which refers to clustered cystic airspaces.
Pulmonary Function Tests (PFTs) measure the functional impact of the disease. The Forced Vital Capacity (FVC), measuring the maximum air exhaled, is a primary metric; a reduced FVC suggests a restrictive lung defect caused by stiff, scarred tissue. The Diffusing Capacity of the Lung for Carbon Monoxide (DLCO) measures how effectively oxygen moves into the bloodstream. A low DLCO is often the earliest physiological signal, reflecting damage to the gas-exchange surfaces.
Understanding Disease Progression and Monitoring
The clinical course of SSc-ILD is highly variable, ranging from stability to rapid, severe decline. Diagnosis is classified by the extent of disease on HRCT and the FVC value. Extensive disease carries a worse prognosis and is defined as greater than 20% lung involvement on HRCT, or 10% to 30% involvement combined with an FVC below 70% of the predicted value.
A significant concern is the development of Progressive Fibrosing ILD (PF-ILD), characterized by worsening fibrosis, declining lung function, and increased mortality. Progression is defined by a substantial drop in lung function over 6 to 12 months. This includes a relative decline in FVC of 10% or more, or a decline between 5% and 9% when coupled with a relative decline in DLCO of 15% or more.
Regular monitoring is necessary to detect progression early and inform treatment decisions. Patients are typically monitored with repeat PFTs (FVC and DLCO) at least every six months for the first three to five years after SSc onset. The pattern of fibrosis on HRCT also carries prognostic weight. The Non-Specific Interstitial Pneumonia (NSIP) pattern is most common and often responds better to treatment, while the Usual Interstitial Pneumonia (UIP) pattern is associated with worse outcomes.
Current Management and Treatment Strategies
Management aims to stabilize or slow fibrosis progression by suppressing autoimmune inflammation and inhibiting the fibrotic process. Immunosuppressive therapies are a cornerstone of management. Mycophenolate mofetil is a commonly recommended first-line agent, working by suppressing immune system activity to limit the inflammatory drive.
Cyclophosphamide is an alternative immunosuppressant, often used for severe or rapidly progressing cases. Other agents suggested for specific patients include rituximab, which targets B-cells involved in immune dysregulation, and tocilizumab, which blocks the interleukin-6 receptor linked to fibrosis. These therapies halt the immune-mediated injury fueling the scarring process.
Antifibrotic agents specifically target the scarring process. Nintedanib reduces the rate of FVC decline in SSc-ILD patients by inhibiting multiple tyrosine kinases involved in fibrosis signaling pathways. Supportive, non-pharmacological management includes pulmonary rehabilitation to improve exercise tolerance and oxygen therapy for low blood oxygen levels. Managing gastroesophageal reflux disease (GERD) is also important, as it is common in SSc and can potentially worsen lung disease.