What is the most likely diagnosis and appropriate evaluation and management for a patient with a restrictive pattern on pulmonary function tests, a rheumatoid factor of 90 IU/mL, and an elevated C‑reactive protein of 5.6 mg/L?

Rheumatoid Arthritis-Associated Interstitial Lung Disease (RA-ILD)

The most likely diagnosis is rheumatoid arthritis-associated interstitial lung disease (RA-ILD), given the restrictive lung pattern combined with elevated rheumatoid factor (90 IU/mL) and inflammatory markers (CRP 5.6 mg/L). 1

Diagnostic Evaluation

Immediate Confirmatory Testing

• High-resolution CT (HRCT) of the chest is mandatory to characterize the pattern of interstitial lung disease and assess severity, as restrictive physiology on pulmonary function tests requires imaging confirmation 1, 2
• Complete pulmonary function testing including total lung capacity via body plethysmography or washout technique to confirm true restriction (not just reduced FVC on spirometry), plus DLCO measurement to assess severity and differentiate parenchymal disease 2, 3
• Anti-CCP antibodies should be measured if not already done, as they are more specific for RA than rheumatoid factor alone 1

Additional Serologic Workup

• Antinuclear antibody (ANA) panel including anti-SSA/SSB, anti-Ro52, and anti-RNP to exclude overlap connective tissue diseases, as Sjögren syndrome and mixed connective tissue disease can present similarly with positive rheumatoid factor and ILD 1, 4
• ESR measurement provides additional prognostic information beyond CRP in rheumatoid disease 1
• Baseline chest radiograph to identify anatomic restriction patterns and chronic lung disease, though HRCT is superior 2

Important caveat: The rheumatoid factor of 90 IU/mL is significantly elevated and supports RA diagnosis, but rheumatoid factor can be positive in other conditions including Sjögren syndrome (which also causes ILD), so comprehensive autoantibody testing is essential 1.

Risk Stratification

High-Risk Features for Progressive RA-ILD

• Male sex, age ≥65 years, and smoking history are established risk factors for worse outcomes in connective tissue disease-associated ILD 1
• Elevated CRP (>5 mg/L) is associated with increased mortality risk in RA patients and predicts ongoing joint and potentially lung deterioration 1, 5, 6
• Persistently elevated CRP levels indicate patients at greater risk for continuing disease progression and need for aggressive treatment 5, 6

The CRP of 5.6 mg/L, while only mildly elevated, has prognostic significance—persistently elevated CRP in RA patients correlates with functional deterioration and increased mortality (RR 2.5,95% CI 1.2-5.1) 5, 7.

Management Approach

Initial Treatment Strategy

• Refer to pulmonology immediately for comprehensive ILD evaluation and management planning 1, 2
• Rheumatology consultation is essential for coordinated management of both articular and pulmonary manifestations 1
• Corticosteroids may be beneficial in inflammatory ILDs associated with connective tissue disease, though specific regimens depend on HRCT pattern and severity 2

Pattern-Specific Considerations

The HRCT will determine the specific ILD pattern, which guides prognosis and treatment:

• Nonspecific interstitial pneumonia (NSIP) pattern is most common in RA-ILD and typically responds better to immunosuppression than usual interstitial pneumonia (UIP) pattern 1
• UIP pattern in RA-ILD carries worse prognosis similar to idiopathic pulmonary fibrosis 1
• Organizing pneumonia pattern may respond dramatically to corticosteroids 1

Monitoring Protocol

• Pulmonary function tests (spirometry and DLCO) every 6 months initially for the first 3-4 years to detect progression early 1
• Serial CRP monitoring as normalization of CRP correlates with functional stabilization, while re-elevation predicts deterioration 5
• Repeat HRCT annually for first 3-4 years or sooner if PFTs decline or symptoms worsen 1

Critical pitfall: Do not assume stable disease based on symptoms alone—progression can occur asymptomatically, and waiting for symptoms may delay intervention during a potentially reversible phase 1.

Supportive Care

• Pneumococcal and influenza vaccinations are recommended for all patients with restrictive lung disease 2
• Smoking cessation is mandatory if applicable, as smoking worsens prognosis in ILD 1, 2
• Oxygen therapy and pulmonary rehabilitation should be initiated if hypoxemia or significant functional limitation develops 2

Prognostic Considerations

RA-ILD is associated with increased morbidity and mortality compared to RA without pulmonary involvement, with reported 5-year survival rates of approximately 85% in Sjögren syndrome-ILD (similar prognosis expected in RA-ILD) 1. The combination of elevated rheumatoid factor and inflammatory markers suggests active disease requiring aggressive management to prevent irreversible fibrosis 1, 5, 6.