What is the diagnostic approach for a patient with suspected scleroderma-associated Interstitial Lung Disease (ILD)?

Diagnostic Approach for Scleroderma-Associated Interstitial Lung Disease

All patients with systemic sclerosis should undergo high-resolution computed tomography (HRCT) screening for ILD at diagnosis, regardless of symptoms, as HRCT is the primary diagnostic tool and pulmonary function tests alone miss significant disease in up to 62.5% of cases. 1, 2

Initial Screening at Diagnosis

Mandatory Baseline Testing for All SSc Patients

• HRCT of the chest is the gold standard and must be performed even in asymptomatic patients, as SSc-ILD is the leading cause of death and has highest prevalence in the first 5 years of disease 1
• Pulmonary function tests including spirometry (FVC) and diffusion capacity (DLCO) provide baseline parameters but should NOT be the sole screening tool 1
• 6-minute walk distance test with pulse oximetry to assess exercise capacity and oxygen desaturation 1, 3
• Clinical assessment for respiratory symptoms (dyspnea, cough), though these may be absent in early disease 1
• Auscultation for fine inspiratory crackles (Velcro-crackles), though sensitivity is only moderate 1

Critical Pitfall: The False-Negative Rate of PFTs

Do not rely on pulmonary function tests alone for screening. A landmark study demonstrated that 40 of 64 patients (62.5%) with significant ILD on HRCT had normal FVC values, and 5 patients had severe fibrosis despite normal FVC 2. Additionally, 90% of patients with confirmed RA-ILD on HRCT had no dyspnea or cough 1. This underscores why HRCT screening is mandatory regardless of symptoms or PFT results.

Risk Stratification After Initial Assessment

High-Risk Features for Progressive ILD

• Diffuse cutaneous SSc (rather than limited cutaneous subtype) 4
• Anti-Scl-70/anti-topoisomerase I antibody positivity 4, 2
• Absence of anti-centromere antibody 4, 2
• Male gender 1
• Early disease (first 3-5 years after SSc diagnosis carries greatest risk) 1, 4
• Baseline FVC <80% predicted or DLCO impairment 3
• Extensive fibrosis on HRCT 4

Ongoing Monitoring Strategy

For High-Risk Patients

• PFTs (spirometry and DLCO) every 6 months 1
• Annual HRCT for the first 3-4 years of SSc diagnosis 1
• Echocardiography annually to screen for pulmonary hypertension, especially with isolated low DLCO 1
• 6-minute walk test at regular intervals 1

For Lower-Risk Patients

• Annual PFTs 1
• HRCT if symptoms develop or respiratory function worsens 1

Defining Progressive Disease

Progressive pulmonary fibrosis requires at least two of three criteria within the past year: 1, 3

• Worsening respiratory symptoms
• Physiological progression on PFTs (declining FVC or DLCO)
• Radiological progression on chest CT

Multidisciplinary Evaluation

Integrate pulmonology, rheumatology, and radiology expertise for diagnosis and severity assessment, as this multidisciplinary approach is considered the method of choice 1, 3. Radiological interpretation becomes more meaningful when clinical context is incorporated, requiring consultation between radiologist and clinician 1.

HRCT Pattern Recognition

• Non-specific interstitial pneumonia (NSIP) is the most common pattern in SSc-ILD, showing ground glass opacities with or without reticulations 1
• Usual interstitial pneumonia (UIP) pattern shows reticulation, traction bronchiectasis, and honeycombing, associated with poorer prognosis 1
• HRCT can detect subclinical abnormalities that may not progress to clinically significant ILD 1

Additional Diagnostic Considerations

Tests NOT Routinely Recommended

• Bronchoscopy, surgical lung biopsy, or cryobiopsy are not recommended for CTD-ILD diagnosis according to expert consensus and ACR guidelines 1
• Chest radiography alone has low added value; up to 10% of ILD patients have normal chest X-rays 3
• Ultrasound is not recommended for diagnostic or screening purposes as it is operator-dependent, poorly reproducible, and supported by limited data 1

When to Consider Additional Testing

• Bronchoalveolar lavage may provide diagnostic clues when HRCT and clinical findings are insufficient, such as lymphocyte count >25% suggesting alternative diagnoses 3
• Cardiac evaluation including ECG, troponin, NT-proBNP, and cardiac MRI should be performed to assess for myocardial involvement in SSc 5
• Right heart catheterization is mandatory for definitive diagnosis if pulmonary hypertension is suspected 5

Key Clinical Pearls

Symptoms are unreliable for early detection. Patients frequently adapt their lifestyles to their condition or lead sedentary lives, making it difficult to elicit a history of dyspnea on exertion 1. The median survival with SSc-ILD is only 5-8 years, emphasizing the critical importance of early detection through systematic HRCT screening 1, 6.