What is the appropriate management for an adult patient with a history of autoimmune or inflammatory diseases presenting with chest pain or dyspnea related to a rheumatological condition, such as rheumatoid arthritis (RA), lupus, or scleroderma?

Management of Rheumatological Conditions Causing Chest Pain or Dyspnea

For adults with autoimmune or inflammatory diseases presenting with chest pain or dyspnea, immediately screen for interstitial lung disease (ILD) with pulmonary function tests (PFTs) and high-resolution CT chest (HRCT), and evaluate for pericardial involvement with echocardiography, as these are the most common life-threatening cardiopulmonary manifestations requiring urgent multidisciplinary management. 1

Initial Diagnostic Approach

Pulmonary Evaluation for ILD

Screen all high-risk patients with both PFTs (including spirometry, lung volumes, and DLCO) and HRCT chest rather than relying on history and physical examination alone. 1

• High-risk features requiring immediate ILD screening include: 1

  • Systemic sclerosis: Anti-Scl-70 positivity, diffuse cutaneous subtype, male sex, African American race, early disease (first 5-7 years)
  • Rheumatoid arthritis: High-titer rheumatoid factor or anti-CCP, cigarette smoking, older age at onset, male sex
  • Inflammatory myopathies: Anti-synthetase antibodies (Jo-1, PL7, PL12), anti-MDA-5, mechanic's hands, arthritis
  • Mixed connective tissue disease: Dysphagia, Raynaud phenomenon, scleroderma features
  • Sjögren disease: Anti-Ro52 antibody, Raynaud phenomenon

• Do not rely on chest radiography for ILD screening—it is inadequate and conditionally recommended against. 1

• Seek specific symptoms: dry cough (15% sensitive but 89% specific) and dry "velcro" crackles on auscultation (69% sensitive, 66% specific), though their absence does not exclude ILD. 1

Cardiac Evaluation for Pericardial Disease

Pericardial involvement is common in systemic lupus erythematosus, Sjögren syndrome, rheumatoid arthritis, and scleroderma, occurring in 5-15% of patients with acute pericarditis. 1

• Typical features in rheumatological pericarditis include: 1

  • Lower rate of pleuritic chest pain (up to 30% asymptomatic in ESRD-related cases)
  • Absence of ECG abnormalities in many cases due to lack of myocardial inflammation
  • Pericardial effusion can be the initial presenting feature even without typical joint symptoms 2

• Perform echocardiography to assess for pericardial effusion and rule out tamponade physiology. 1, 2

• Rule out concomitant myocardial inflammatory involvement, which can complicate the presentation. 1

Immediate Multidisciplinary Referral

Pulmonology Referral

Refer immediately to pulmonology upon ILD diagnosis or suspicion based on screening tests, or when initiating any ILD-directed therapy. 3

• All patients with systemic autoimmune rheumatic disease-associated ILD (SARD-ILD) require co-management by both rheumatologists and pulmonologists from the time of diagnosis. 3

• Pulmonologists should perform definitive HRCT interpretation, conduct full PFTs, and participate in multidisciplinary discussion with rheumatologists, radiologists, and pathologists. 3

Urgent Evaluation for Rapidly Progressive ILD

For rapidly progressive ILD (RP-ILD)—defined as progression from stable disease to respiratory failure within days to weeks—immediately refer to pulmonology and consider early lung transplantation evaluation. 3

• RP-ILD requires upfront combination therapy rather than monotherapy: 1
  • For confirmed or suspected MDA-5 RP-ILD: Triple combination therapy (glucocorticoids plus two immunosuppressants)
  • For other RP-ILD: Double or triple combination therapy depending on severity

Disease-Specific Treatment Algorithms

Systemic Sclerosis-ILD (SSc-ILD)

First-line therapy: Mycophenolate is the preferred initial treatment. 1

• Additional first-line options include: tocilizumab, cyclophosphamide, rituximab, nintedanib 1

• Strongly avoid glucocorticoids in SSc-ILD due to high risk of scleroderma renal crisis (SRC), particularly at doses >15 mg/day prednisone. 1, 4

• If glucocorticoids are absolutely necessary, monitor blood pressure at least weekly to detect SRC early. 4

• For progressive disease despite first-line therapy: Consider switching to alternative first-line agent (rituximab, nintedanib, tocilizumab) or refer for lung transplantation evaluation rather than waiting for further progression. 1, 3

Inflammatory Myopathies-ILD (IIM-ILD)

First-line therapy: Mycophenolate is preferred, with azathioprine and JAK inhibitors as additional options. 1

• Short-term glucocorticoids (≤3 months) can be used, unlike in SSc-ILD. 1

• For anti-MDA-5 positive rapidly progressive disease: Triple combination therapy (pulse IV methylprednisolone plus two immunosuppressants such as mycophenolate and calcineurin inhibitor). 1

• Monitor with PFTs every 3-6 months for the first year, then less frequently once stable. 1

Rheumatoid Arthritis-ILD (RA-ILD)

First-line therapy: Mycophenolate is preferred, with azathioprine, cyclophosphamide, rituximab, and tocilizumab as additional options. 1

• Short-term glucocorticoids (≤3 months) can be used. 1

• Avoid or use with extreme caution: 1

  • Methotrexate: Can rarely cause idiosyncratic pneumonitis; may continue for extrapulmonary manifestations if ILD is stable, but stop if ILD develops or worsens on methotrexate
  • Leflunomide: Associated with development or worsening of ILD in rare cases
  • TNF inhibitors: No beneficial effect on ILD and observational data suggest potential harm; can be used for extrapulmonary manifestations but consider stopping if ILD develops

• For patients requiring DMARDs or biologics, refer to chest physician for assessment before starting treatment, especially if bronchiectasis is present. 1

• Monitor with PFTs every 3-12 months for the first year, then less frequently once stable. 1

Mixed Connective Tissue Disease-ILD (MCTD-ILD) and Sjögren Disease-ILD (SjD-ILD)

First-line therapy: Mycophenolate is preferred, with azathioprine, cyclophosphamide, rituximab, and tocilizumab (for MCTD) as additional options. 1

• Short-term glucocorticoids (≤3 months) can be used, but use cautiously in MCTD patients with scleroderma phenotype due to SRC risk. 1

• Monitor with PFTs every 3-12 months for the first year, then less frequently once stable. 1

Monitoring Strategy for Established SARD-ILD

Pulmonary Function Testing

Monitor with PFTs (spirometry, lung volumes, DLCO) to provide objective data for assessing disease stability or progression. 1

• Frequency: 1

  • IIM-ILD and SSc-ILD: Every 3-6 months for the first year, then less frequently once stable
  • RA-ILD, SjD-ILD, MCTD-ILD: Every 3-12 months for the first year, then less frequently once stable

• Patients with SSc may have difficulty achieving adequate oral seal; use pediatric mouthpiece if needed. 1

High-Resolution CT Chest

Monitor with HRCT chest to assess extent and pattern of parenchymal involvement. 1

• Perform HRCT when clinically indicated rather than on a fixed schedule. 1

• HRCT provides assessment of disease progression that complements PFT data. 1

Ambulatory Desaturation Testing

Monitor with ambulatory desaturation testing every 3-12 months. 1

• Can be performed during routine office visit or as part of 6-minute walk testing. 1

• In SSc patients with poor finger perfusion, use ear or forehead oxygen saturation monitor. 1

Tests to Avoid for Routine Monitoring

Do not use the following for routine ILD monitoring: 1

• Chest radiography
• 6-minute walk test distance alone
• Bronchoscopy (reserve for ruling out infection, sarcoidosis, lymphoma, or alveolar hemorrhage)
• Surgical lung biopsy (reserve for ruling out malignancy)

Management of Pericardial Disease

Treatment is targeted at control of the underlying systemic disease. 1

• Pericardial involvement reflects the degree of activity of the underlying autoimmune disease. 1

• Pericarditis in RA is most common in patients with rheumatic nodules and positive serum rheumatoid factor. 5, 2

• Consider NSAIDs, corticosteroids, or colchicine for symptomatic pericarditis, following standard pericarditis management principles. 1

• Monitor for development of chronic pericardial effusion or constrictive pericarditis, though these are less common. 1

Critical Pitfalls to Avoid

Do not delay pulmonology referral until symptoms become severe—early multidisciplinary management improves outcomes. 3

Do not wait for disease progression before considering lung transplantation referral in appropriate candidates with progressive ILD despite first-line therapy. 3

Do not manage SSc-ILD with rheumatology alone—co-management with pulmonology is essential. 3

Do not use biologics preferentially over traditional DMARDs in RA patients with bronchiectasis, as biologics carry higher infection risk (OR 8.7). 1

Do not ignore the possibility of pericardial effusion as an initial presenting feature of RA, even in the absence of typical joint symptoms. 2

Do not use high-dose glucocorticoids (>15 mg/day prednisone) in SSc patients without intensive blood pressure monitoring due to SRC risk. 4