A 65-year-old man comes to the office due to shortness of breath, weakness, and cough for 1 week. He underwent bilateral lung transplantation for idiopathic pulmonary fibrosis 3 months ago. Temperature is 38.3 C (101 F), blood pressure is 130/80 mm Hg, pulse is 90/min, and respirations are 18/min. Chest x-ray shows perihilar opacities and interstitial edema. Transbronchial biopsies reveal moderate perivascular and peribronchiolar mononuclear infiltrate predominantly composed of lymphocytes. No viral inclusions are present. Which of the following is the most likely diagnosis?
Lung transplant rejection | |||
Type | Onset | Etiology | Pathophysiology |
Hyperacute | Minutes to hours | Preformed host antibodies to donor ABO or HLA | Neutrophilic infiltration with fibrinoid necrosis and thrombosis |
Acute | ≤6 months | Cell-mediated response to mismatched donor HLA | Perivascular (small lung vessels) & submucosal (bronchiole) lymphocytic infiltrates |
Chronic | Months or years | Chronic, low-grade, mixed cell-mediated and antibody response to HLA antigens | Submucosal inflammation → granulation, scarring & bronchiolitis obliterans |
HLA = human leukocyte antigen. | |||
This patient with dyspnea, cough, fever, and lung biopsy revealing lymphocytic infiltration several months after lung transplant likely has acute lung transplant rejection. Acute transplant rejection (ATR) is a cell-mediated response involving T-lymphocyte activation against donor antigens (eg, mismatched HLA types) and most commonly occurs within 6 months of transplant.
Patients with ATR may be asymptomatic (with rejection detected by surveillance biopsy) or can present with low-grade fever, dyspnea, cough, and/or fatigue. Chest x-ray may reveal hilar lymphatic enlargement and edematous interstitial thickening. Lung biopsy reveals perivascular and peribronchiolar mononuclear infiltrate primarily composed of lymphocytes. The absence of viral inclusions in epithelial cells helps rule out cytomegalovirus, a common infection in lung transplant recipients that can present similarly to acute rejection.
The risk of ATR markedly increases with poor adherence to immunosuppression medications (eg, tacrolimus, mycophenolate), but it can affect all transplant recipients, regardless of medication adherence. Episodes of ATR are usually reversible with increased immunosuppression (eg, high-dose steroids); however, patients with frequent episodes of ATR are at greater risk of developing chronic transplant rejection, which is typically irreversible.
(Choice A) Left ventricular dysfunction can cause pulmonary edema with similar appearance to ATR on chest x-ray. However, fever is not expected, and lung biopsy typically reveals hemosiderin-laden macrophages with no evidence of inflammatory lymphocytic infiltrate.
(Choice B) Lung transplant recipients are at increased risk of bacterial (eg, Pneumococcal) pneumonia; however, chest x-ray is more likely to reveal focal alveolar consolidation, and neutrophil predominance is expected on lung biopsy.
(Choice C) Polyarteritis nodosa is a medium vessel vasculitis that typically demonstrates lymphocytic infiltrate with vascular wall necrosis on biopsy. It can affect multiple organs, including the liver, kidneys, intestines, and skin; however, it characteristically spares the lungs.
(Choice D) Eventual recurrence of primary lung disease following lung transplantation is possible for many diseases (eg, interstitial lung disease, bronchiectasis) but is unlikely within only several months.
Educational objective:
Acute lung transplant rejection is a cell-mediated response involving T-lymphocyte activation against donor antigens and typically occurs within 6 months of transplant. Affected patients can have shortness of breath, cough, and low-grade fever. Lung biopsy reveals perivascular and peribronchiolar lymphocytic infiltrate and absence of epithelial cell viral inclusions (ruling out cytomegalovirus).