Is lung transplantation a viable treatment option for a patient with Scl-70 positive systemic sclerosis and significant interstitial lung disease (ILD) who has failed other treatments, including immunosuppressive therapy and anti-fibrotic medications such as mycophenolate mofetil, nintedanib, and pirfenidone?

Lung Transplantation in Scleroderma-Associated Interstitial Lung Disease

Lung transplantation should be considered for patients with Scl-70 positive systemic sclerosis and end-stage ILD who have failed immunosuppressive therapy (mycophenolate mofetil) and anti-fibrotic medications (nintedanib, pirfenidone), as it is the only treatment that can improve long-term outcomes in end-stage lung fibrosis. 1

When to Refer for Lung Transplantation

Refer patients with progressive SSc-ILD to a lung transplantation center early—specifically when disease progresses despite first-line treatment—rather than waiting for further deterioration. 2

Specific Triggers for Transplant Referral:

• Progressive disease despite optimal medical management (immunosuppressive therapy plus anti-fibrotics) 3, 2
• Need for high-flow oxygen supplementation 2
• FVC decline ≥10% predicted, OR FVC decline 5-10% predicted plus worsening respiratory symptoms or increased fibrosis on HRCT—all within 24 months 4
• Development of end-stage respiratory failure 1

Critical timing consideration: Pre-transplantation evaluation takes considerable time, making early referral essential to avoid missing the transplant window. 2

Survival Outcomes

Lung transplantation provides meaningful survival benefit in carefully selected SSc-ILD patients:

• 1-year survival: 81% 1
• 5-year survival: 66% 1
• Median survival post-transplant: 5.2-6.7 years compared to less than 2 years in advanced ILD patients who do not undergo transplant 5

Cohort studies demonstrate that outcomes after lung transplantation in SSc are comparable to those in other chronic lung diseases in age- and sex-matched patients. 1

Patient Selection Criteria

Ideal Candidates:

• End-stage lung fibrosis with limited extrapulmonary systemic disease 6
• Severe disease or poor prognosis despite maximal medical therapy 1
• Carefully selected patients without significant extrapulmonary systemic disease experience similar survival compared to non-SSc ILD patients 6

Key Comorbidity Considerations:

Gastroesophageal reflux disease (GERD) is a particular concern because it can predispose to post-transplantation bronchiolitis. 1 However, this should not be an absolute contraindication:

• Aggressive GERD management is essential: high-dose proton pump inhibitors, promotility agents, sleeping with head elevated, avoiding eating after dinner 1, 3
• Consider fundoplication surgery for severe reflux before or at time of transplantation 1
• Early aggressive surgical treatment of GERD decreases bronchiolitis rates and improves survival in lung transplant patients 6
• Studies show GERD was not a limitation for lung transplantation in SSc when symptoms were under control 7

Other Considerations:

• Renal function must be adequate 6
• Skin fibrosis severity should be assessed but is not an absolute contraindication 6
• Donor availability remains a limiting factor 1

Single vs. Bilateral Lung Transplantation

Given the scarcity of donor lungs, single lung transplantation has become commonplace for most SSc patients without severe pulmonary hypertension. 6

• Bilateral lung transplantation is preferred when severe pulmonary hypertension is present 6
• In one cohort, 73% of SSc patients underwent bilateral lung transplantation 7

Post-Transplant Complications

Acute cellular rejection and infections are the most frequent complications post-transplantation in SSc patients. 7

• Chronic rejection rates in SSc patients are similar to those transplanted for non-connective tissue disease-related ILD 6
• SSc-specific complications are relatively scarce post-transplant 7
• No patients developed pulmonary hypertension after lung transplantation in one cohort study 7

Multidisciplinary Co-Management

All patients with SSc-ILD should be co-managed by both rheumatologists and pulmonologists from the time of ILD diagnosis or treatment initiation. 2

The optimal management team includes:

• Rheumatologist 2
• Pulmonologist 2
• Radiologist 2
• Pathologist 2
• Transplant surgery team (when appropriate) 2

Critical Pitfalls to Avoid

Do not delay transplant referral until symptoms become severe—refer early when disease progresses despite first-line therapy. 2

Do not wait for further disease progression before considering lung transplantation in appropriate candidates, as pre-transplant evaluation is time-intensive. 2

Do not allow poorly controlled GERD to be an absolute contraindication—aggressive medical and surgical management can mitigate this risk. 1, 6, 7

Alternative: Autologous Hematopoietic Stem Cell Transplantation

For patients with rapidly progressive early diffuse cutaneous SSc at high risk of organ failure and mortality, autologous hematopoietic stem cell transplantation (AHSCT) should be considered as an alternative, but only in experienced centers with documented expertise and positive outcomes. 3, 2