Rapid Recurrence of Interstitial Fibrosis Following Lung Transplantation

Abstract

INTRODUCTION: Common causes of dyspnea in the first year following lung transplantation include infection, acute rejection, bronchiolitis obliterans and bronchial strictures. Recurrence of primary lung disease is uncommon and rarely clinically significant. We report a case of recurrence of fibrosing nonspecific interstitial pneumonitis in a transplanted lung. CASE PRESENTATION: A 42-year old female with fibrotic Nonspecific Interstitial Pneumonitis (NSIP) underwent bilateral lung transplantation. Post-operative course was complicated by grade 3 primary graft dysfunction, prolonged ventilator dependence with tracheostomy, heparin induced thrombocytopenia and deep vein thrombosis. She was discharged home after 5 weeks on prednisone, tacrolimus and azathioprine. Following discharge her exercise tolerance and allograft function improved. She was able to exercise on the treadmill without oxygen. Eight weeks after transplantation she underwent diagnostic bronchoscopy for new onset shortness of breath and was found to have acute rejection (A2B0). Histiocytic infiltrates were noted on biopsy at that time and were thought to be consistent with early post transplant findings. She was treated with methylprednisolone and azathioprine was switched to mycophenolate. Follow up biopsies 3 weeks later showed A1B0 rejection with increasing intraalveolar macrophages and evidence of early interstitial fibrosis. All cultures were negative. Fluorescence in situ hybridization confirmed recipient origin of the infiltrating macrophages. Over the next several months the patient developed exercise induced hypoxemia and six month surveillance biopsies showed features of mixed desquamative and non-specific interstitial pneumonitis, pathologically identical to her native lung disease. DISCUSSIONS: Recurrence of primary lung disease in a transplanted lung is rare complicating less than 1% of all lung transplants. While recurrence of systemic disease like sarcoidosis and lymphangiomyomatosis has been described, the course of disease after recurrence is usually indolent. Of the interstitial lung diseases, only two cases of recurrence of desquamative interstitial pneumonitis (DIP) and one of giant cell interstitial pneumonitis have been reported. The cause of recurrence is unknown. Possible etiologies include hypersensitivity, autoimmunity, viruses, induction therapy, recurrent aspiration, and smoking status of donor. In this case, pathologic accumulation of recipient macrophages was evident on transbronchial biopsies 2 months post transplant. This macrophage population continued to expand and subsequent biopsies revealed intraalveolar macrophage with concomitant interstitial fibrosis. CONCLUSION: Recurrence of clinically significant interstitial lung disease after lung transplant is rare. Recurrence of interstitial pneumonitis occurred after a double lung transplant. Host factors likely play a major role, evidenced by pathologic accumulation of recipient macrophages.