Critical Care Medicine-Pulmonary Disorders>>>>>Lung Transplantation, Complications, and VV ECMO
Question 4#

Three months after bilateral lung transplantation, a 50-year-old female patient is admitted to the ICU with complaints of worsening shortness of breath, low grade fever, and cough. She is compliant with her drug regimen consisting of prednisone, tacrolimus, azathioprine, valganciclovir, and trimethoprim-sulfamethoxazole. Examination reveals bilateral crackles and decreased breath sounds over the left lower chest wall. She has:

She is started on oxygen therapy, and a chest CT is obtained, which reveals bilateral ground glass opacities with a leftsided pleural effusion. Laboratory testing is unremarkable except for slight eosinophilia. Bronchioalveolar lavage reveals lymphocytic predominance and transbronchial biopsy is significant for dense perivascular and bronchial mononuclear infiltrates with a negative C4d staining.

Which of the following is the best next step in management?

A. Intravenous methyl prednisone
B. Intravenous ganciclovir and piperacillin-tazobactam
C. Intravenous immunoglobulins (IvIg) and rituximab
D. Therapeutic plasma exchange

Correct Answer is A


Correct Answer: A

Patient seems to be undergoing acute cellular rejection and will need to be treated with intravenous corticosteroids such as methylprednisone (A). Spirometry typically shows a decrease in FEV1 in acute rejection. CT scan findings in acute rejection include ground-glass opacities, interlobular septal thickening, pleural effusions, and lung volume loss. The gold standard test to diagnose rejection is flexible bronchoscopy with bronchoscopic alveolar lavage and transbronchial biopsy. Two main histopathological components used for grading are the severities of lymphocytic bronchiolitis and perivascular mononuclear cell infiltrates. Intravenous high-dose corticosteroids are the mainstay of treatment for symptomatic or high-grade acute cellular rejection. Other treatment options that have been used for acute cellular rejection include antithymocyte globulin, extracorporeal photopheresis, and alternative immunosuppressive agents such as alemtuzumab and sirolimus or everolimus. Acute rejection episodes are important risk factors for the development of chronic lung allograft dysfunction. Therefore, prevention and treatment of acute rejection by appropriate immunosuppressive regimen is essential. CMV pneumonitis is unlikely in a patient who is already on valganciclovir prophylaxis. Therefore, intravenous ganciclovir in this patient is not warranted (B). 

The main differential diagnoses of acute cellular rejection include humoral rejection and infections. Humoral rejection can be hyperacute rejection or acute antibody-mediated rejection. Hyperacute rejection presents in the first 24 hours following transplantation and is due to preformed donor-specific antibodies (DSA). Acute antibody-mediated rejection presents later and is due to DSA that developed or increased in titers after transplantation. The diagnoses require demonstration of DSA along with ruling out other conditions. The histopathological hallmark of acute antibody-mediated rejection is subendothelial deposition of C4d demonstrated by immunohistochemistry but is not essential for diagnosis. Specific treatment options for humoral rejection include intravenous immunoglobulins (IvIg), therapeutic plasma exchange (D), rituximab (C), and bortezomib.


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