Lung transplantation for pulmonary fibrosis in dyskeratosis congenita: Case Report and systematic literature review

Abstract

Background: Dyskeratosis congenita (DC) is a progressive, multi-system, inherited disorder of telomere biology with high risks of morbidity and mortality from bone marrow failure, hematologic malignancy, solid tumors and pulmonary fibrosis. Hematopoietic stem cell transplantation (HSCT) can cure the bone marrow failure, but it does not eliminate the risks of other complications, for which life-long surveillance is required. Pulmonary fibrosis is a progressive and lethal complication of DC.

Case presentation: In this report, we describe a patient with DC who developed pulmonary fibrosis seven years after HSCT for severe aplastic anemia, and was successfully treated with bilateral lung transplantation. We also performed a systematic literature review to understand the burden of pulmonary disease in patients with DC who did or did not receive an HSCT. Including our patient, we identified 49 DC patients with pulmonary disease (12 after HSCT and 37 without HSCT), and 509 with no reported pulmonary complications.

Conclusion: Our current case and literature review indicate that pulmonary morbidity is one of the major contributors to poor quality of life and reduced long-term survival in DC. We suggest that lung transplantation be considered for patients with DC who develop pulmonary fibrosis with no concurrent evidence of multi-organ failure.

Figure 1

Chest computerized tomography of the patient at age 11 years, 7 years after hematopoietic stem cell transplantation and 17 months prior to lung transplantation. At the time of this evaluation, he had dyspnea on exertion, a chronic, non-productive cough, and a restrictive pattern on pulmonary function tests. Bilateral, diffuse areas of ground glass opacities and fibrosis of the lung parenchyma are shown.

Figure 2

Pulmonary histology at the time of lung transplantation. A: Representative microscopic field of explanted lung shows diffuse fibrosis, with both established collagen deposition (yellow-green hue) and fibroblastic proliferation (arrow, blue-green hue). There is prominent extension of smooth muscle into interstitium. Residual alveoli are lined by hyperplastic pneumocytes (200x, pentachrome stain). B: Bronchiolitis obliterans involving small airway shown by arrow (400x, pentachrome stain).

Figure 3

Age at pulmonary symptoms. Patients with DC reported in the literature who received a bone marrow transplant (red) had pulmonary symptoms younger than patients who did not have a BMT (green). Data are Kaplan-Meier survival plots, showing cumulative probability of being free of pulmonary symptoms. Shaded areas represent 95% confidence intervals.