From the Guidelines
Patients with CREST syndrome are at high risk of developing interstitial lung disease (ILD), with an estimated prevalence of 40% to 80%, and treatment during the acute inflammatory phase is associated with a good prognosis. The most common radiological pattern is non-specific interstitial pneumonia (NSIP) 1. Lung associations in CREST syndrome include ILD and pulmonary arterial hypertension (PAH), with ILD being a major complication that can lead to deteriorating lung function and increased mortality if not treated promptly.
Key risk factors for ILD in CREST syndrome include esophageal dilatation and motor dysfunction, dysphagia, Raynaud phenomenon, anti-Smith or anti-Ro-52 antibodies, rheumatoid factor, and no history of arthritis 1. High anti-ribonucleoprotein antibody titers at baseline are a strong predictor of ILD progression. Treatment options for ILD in CREST syndrome focus on immunosuppressive therapy, with mycophenolate mofetil (1-1.5g twice daily) or cyclophosphamide (1-2mg/kg/day orally or monthly IV pulses) being commonly used. Nintedanib (150mg twice daily) may slow ILD progression.
Some important considerations for managing lung associations in CREST syndrome include:
- Regular pulmonary function tests with diffusion capacity measurements and echocardiography to monitor disease progression
- Oxygen therapy when hypoxemia is present
- Vasodilator therapies for PAH, including phosphodiesterase-5 inhibitors like sildenafil (20mg three times daily), endothelin receptor antagonists such as bosentan (62.5-125mg twice daily), and prostacyclin analogs like epoprostenol (initiated at 2ng/kg/min via continuous infusion)
- Early detection through screening is vital as pulmonary complications are leading causes of mortality in CREST syndrome
- Treatment should be individualized based on disease severity, with combination therapy often needed for PAH.
From the Research
Lung Associations in CREST Syndrome
- CREST syndrome is associated with various lung abnormalities, including interstitial lung disease (ILD) and pulmonary hypertension 2, 3.
- ILD is a group of pulmonary disorders characterized by inflammation and/or fibrosis of the lung parenchyma, which can lead to progressive dyspnea and respiratory failure 4.
- Pulmonary hypertension is a major cause of mortality in CREST syndrome, and it is often associated with severe pulmonary fibrosis 2.
Treatment Options for CREST Syndrome-Related Lung Disease
- Antifibrotic therapy with nintedanib or pirfenidone can slow the decline in forced vital capacity (FVC) in patients with ILD, including those with CREST syndrome 4.
- Immunomodulatory therapy, such as mycophenolate mofetil, may slow the decline in FVC or even improve it in patients with connective tissue disease-associated ILD, including CREST syndrome 4, 5, 6.
- Mycophenolate mofetil has been shown to be effective in treating scleroderma-related ILD, with significant improvements in lung function and a better tolerability profile compared to cyclophosphamide 5, 6.
- Lung transplant may be considered for patients with advanced ILD, including those with CREST syndrome, as it can improve symptoms and resolve respiratory failure 4.
- Oxygen therapy and structured exercise therapy can also improve symptoms and quality of life in patients with ILD, including those with CREST syndrome 4.