Drug-induced lung disease: a brief update for radiologists

Abstract

Pulmonary adverse events and drug-induced lung disease (DILD) can occur when treating many conditions. The incidence of DILDs in clinical practice and the variety of radiological findings have increased, mainly due to the increased use of novel therapeutic agents. It is crucial to determine whether the newly emerging clinical and imaging findings in these patients are due to the progression of the underlying disease, infection, pulmonary edema, or drug use, as this will change the patient management. Although the diagnosis of DILD is usually obtained by excluding other possible causes, radiologists should be aware of the imaging findings of DILD. This article reviews the essential radiological results of DILD and summarizes the critical clinical and imaging findings with an emphasis on novel therapeutic agents.

Keywords: Computed tomography; immunotherapy; lung; pneumonitis; pulmonary toxicity; therapy.

Figure 1

Radiological findings of drug-induced lung disease during chest computed tomography.

Figure 2

Nivolumab-related organizing pneumonia (OP) pattern in a 49-year-old male with metastatic malignant melanoma. (a) Baseline chest X-ray and (b) 3 weeks after the initiation of pembrolizumab therapy shows newly onset nodular lung opacities (arrowheads). (c) Axial and (d) coronal chest computed tomography images show peripheral and peribronchovascular nodular opacities consistent with the OP pattern. A chest X-ray obtained 8 weeks later, after withholding nivolumab therapy and administering 1 mg/kg/day of prednisolone therapy, demonstrates the complete regression of lung opacities (not shown).

Figure 3

Pembrolizumab-related eosinophilic pneumonia in a 43-year-old female with metastatic malignant melanoma. (a) Baseline coronal chest computed tomography (CT) image shows the lungs before therapy and (b) three months after the initiation of pembrolizumab therapy, which demonstrates bilateral, peripheral ground-glass opacities with an upper lobe predominance (arrowheads). The patient had no respiratory symptoms, but laboratory analysis showed an elevated peripheral eosinophil count (857/mcL, normal range: <200/mcL) and bronchoalveolar lavage fluid (BALF) obtained from the left upper lobe bronchus revealed a high cell count (1.9 × 10⁵/mL) with significantly elevated eosinophils (59.3%). The bacterial/fungal culture was negative for BALF. Pembrolizumab was discontinued, and no treatment was introduced for her eosinophilic pneumonia. (c) The chest CT obtained two months later shows the complete regression of lung opacities with millimetric subpleural atelectasis.

Figure 4

Bleomycin-related non-specific interstitial pneumonia pattern in a 29-year-old male with a testicular germ-cell tumor. Baseline chest computed tomography (CT) was unremarkable (not shown). (a) Axial and (b) coronal chest CT images, which were obtained three months after the initiation of chemotherapy, show bilateral, patchy ground-glass opacity areas with a peripheral and basilar predominance (arrowheads). Note the immediate subpleural sparing and right pneumothorax (*). The bleomycin was discontinued, and the patient was followed up with hospitalization. A control chest CT obtained one year later demonstrates the complete regression of lung opacities (not shown).

Figure 5

Combined ipilimumab and nivolumab therapy-related non-specific interstitial pneumonia (NSIP) pattern in a 65-year-old male with metastatic malignant melanoma. (a) Baseline chest computed tomography (CT) image shows no interstitial abnormalities. (b) Axial chest CT image, which was obtained six months after the initiation of therapy, shows bilateral, patchy ground-glass opacities and subpleural reticulations with peripheral predominance (arrowheads), consistent with an NSIP pattern. Nivolumab and ipilimumab were discontinued, and 0.5 mg/kg/day of prednisone was started for three months. An axial chest CT image obtained six months later demonstrates the partial regression of interstitial lung opacities (not shown).

Figure 6

Nivolumab-related hypersensitivity pneumonitis pattern in a 59-year-old male with metastatic renal cell carcinoma. Baseline chest computed tomography (CT) was unremarkable (not shown). (a) Axial and (b) coronal chest CT images, which were obtained 3 months after the initiation of nivolumab, show patchy ground-glass opacity areas with air trapping, resulting in mosaic attenuation consistent with non-fibrotic hypersensitivity pneumonitis. Nivolumab was discontinued, and additional treatment was not given, because the patient’s symptoms were mild. (c) Axial chest CT image obtained 3 months later demonstrates the regression of lung opacities.

Figure 7

Pembrolizumab-related diffuse alveolar damage (DAD) pattern in a 52-year-old male with metastatic non-small cell lung carcinoma. (a) Baseline axial chest computed tomography (CT) image shows a left hilar mass with perilesional fibrosis due to radiotherapy (arrowheads). (b) Axial and (c) coronal chest CT images, which were obtained two weeks after the initiation of pembrolizumab, show diffuse ground-glass opacity areas that affect most lung areas consistent with a DAD pattern. The pembrolizumab was discontinued, the patient was hospitalized, and 1 mg/kg/day of prednisone therapy was started. (d) Two months later, a chest X-ray shows the regression of lung opacities.

Figure 8

Erlotinib-related diffuse alveolar damage (DAD) pattern in a 42-year-old male with metastatic non-small cell lung cancer. (a) Baseline axial chest computed tomography (CT) image at the left main pulmonary artery level shows no parenchymal abnormality. (b) Axial chest CT image, which was obtained three weeks after the initiation of erlotinib therapy, shows bilateral, patchy consolidation and ground-glass opacity areas with peripheral predominance (arrowheads) consistent with an organizing pneumonia pattern. Bronchoalveolar lavage fluid (BALF) was obtained, but the BALF results were unremarkable, and the bacterial/fungal culture was negative. Erlotinib was discontinued, but the patient’s general condition worsened, and he was intubated five days after CT. During the second day of intubation, pneumothorax and pneumomediastinum were detected, and chest tube replacement was performed. (c) Axial chest CT image obtained three days after intubation demonstrates diffuse ground-glass opacity areas that affect the entirety of the lung areas, consistent with a DAD pattern. Note the chest tube on the right side (arrow). The patient died on the eighth day of intubation.

Figure 9

Bleomycin-related diffuse alveolar damage pattern in a 20-year-old female patient with Hodgkin’s lymphoma. The baseline chest computed tomography (CT) was unremarkable (not shown). (a) Axial and (b) coronal chest CT scans obtained 3.5 months after the initiation of bleomycin therapy show bilateral, diffuse ground-glass opacities and centrilobular ground-glass nodules. The patient had no clinical or laboratory findings consistent with infectious pneumonia. The viral panel was negative, including for Cytomegalovirus, and a bronchoalveolar lavage fluid culture was negative for Pneumocystis jirovecii. Bleomycin was discontinued, 0.5 mg/kg/day of prednisone was started, and the patient’s clinical and imaging findings were resolved.

Figure 10

Osimertinib-related simple pulmonary eosinophilia pattern in a 40-year-old male with lung adenocarcinoma. (a) Axial chest computed tomography (CT) image at the level of the proximal left upper lobe bronchi shows multifocal ground-glass nodules (red rectangle) during osimertinib therapy. The patient was completely asymptomatic, and laboratory findings were within normal limits. Osimertinib therapy was continued. (b) Axial chest CT image, which was obtained 10 weeks later, shows that pulmonary opacities had disappeared entirely without any additional therapy.

Figure 11

Ipilimumab-related sarcoid-like granulomatosis in an asymptomatic 41-year-old female patient with metastatic malignant melanoma. (a) The baseline contrast-enhanced axial chest computed tomography (CT) image at the left atrium levels shows no lymphadenopathies. (b) Contrast-enhanced axial chest CT scan obtained six months after the initiation of ipilimumab therapy shows new bilateral symmetric hilar (arrows) lymphadenopathies resembling sarcoidosis. A lymph node biopsy was performed for suspicion of metastasis, and a non-caseating granulomatous reaction was found histopathologically.

Figure 12

Nivolumab-related pneumonitis flare in a 44-year-old symptomatic female patient with metastatic urothelial carcinoma. Baseline chest computed tomography (CT) was unremarkable (not shown). (a) Axial chest CT scan obtained 2 months after the initiation of nivolumab therapy shows the bilateral, multifocal, peripheral, and peribronchovascular distribution of ground-glass opacity nodules compatible with an organizing pneumonia pattern (arrowheads). The patient had no clinical or laboratory findings consistent with infection. Nivolumab was discontinued, 1 mg/kg/day of oral prednisone was started, and the patient’s clinical findings were resolved. (b) Axial chest CT scan obtained 3 months later shows mild residual ground-glass opacity areas (red rectangles) and pulmonary opacities that had regressed almost completely. Corticosteroid treatment was discontinued. (c) Chest CT obtained 1 month after the discontinuation of corticosteroid therapy shows newly emerged patchy ground-glass opacities and nodules in both lungs (red rectangles). The patient was treated with anti-TNF-α (infliximab) and 1 mg/kg/ day of oral prednisone, and the patient’s clinical and imaging findings were resolved.

Supplemental Figure S1

Nivolumab-related organizing pneumonia (OP) pattern in a 24-year-old male with Hodgkin’s lymphoma. (a) Baseline axial chest computed tomography (CT) image at the middle lobe level shows centrilobular nodules and consolidation area (arrowheads) in the middle lobe compatible with radiation pneumonitis. (b) Automatic lung segmentation map of the baseline CT image. (c) Three-dimensional reconstruction CT image with rainbow colors according to CT attenuation values. In the baseline CT, healthy lung volume [(HLV), attenuation values between −950 and −800 HU] were calculated as 4.384 c c, and the mean lung attenuation as −878 HU. (d) In the axial chest CT image obtained 1 week after the initiation of nivolumab treatment, ground-glass opacities and consolidation areas (arrows) were observed in both lungs and were consistent with an OP pattern. (e) The automatic lung segmentation map of the control CT image shows lung opacities (arrowheads) and interval lung volume loss compatible with OP. (f) Three-dimensional reconstruction CT image with rainbow colors according to CT attenuation values. In the control CT, the HLV was calculated as 3.975 c c, and the mean lung attenuation was −856 HU.

Supplemental Figure S2

Organizing pneumonia (OP) pattern in a 51-year-old female during FOLFIRINOX (5-fluorouracil/leucovorin, irinotecan, oxaliplatin) therapy for metastatic pancreas adenocarcinoma. (a) Baseline axial chest computed tomography (CT) image at the inferior pulmonary vein level shows the lungs before chemotherapy was initiated. (b) Axial chest CT image obtained three months later, after FOLFIRINOX therapy, shows peripheral consolidation (arrow) and airspace opacities with reverse halo sign (arrowheads) consistent with an OP pattern of pneumonitis. (c) Axial chest CT image obtained four weeks later, after withholding FOLFIRINOX therapy and administering 0.5 mg/kg/day of prednisolone therapy, demonstrates that the residual ground-glass opacities and lung opacities had significantly improved (red rectangles).

Supplemental Figure S3

Amiodarone-related alveolar pattern in a 64-year-old male patient with arrhythmia and heart failure. (a) Axial unenhanced chest computed tomography (CT) image shows right pleural effusion, peripheral consolidation areas with high attenuation (arrows), and a pacemaker catheter (arrowhead). (b) Axial CT image with lung window settings shows peripheral consolidation areas with high attenuation (arrows) and centrilobular ground-glass nodules in both lower lobes (red rectangles). (c) Axial unenhanced CT images at the adrenal gland levels show the increased attenuation of the liver with 108 HU. Bronchoalveolar lavage fluid was obtained, and lipid-laden macrophages were detected. Additionally, amiodarone-induced corneal toxicity was found, and amiodarone was discontinued.

Supplemental Figure S4

Transfusion-related acute lung injury in a 31-year-old female with known acute myeloid leukemia who developed dyspnea shortly after transfusion. (a) Pretransfusion axial chest computed tomography (CT) image shows clear lungs. (b) Post-transfusion axial chest CT image obtained approximately six hours after transfusion shows developing alveolar opacities with perihilar predominance in the bilateral lung zones.

Supplemental Figure S5

All-trans retinoic acid (ATRA)-related alveolar pattern in a 24-year-old male with acute promyelocytic leukemia. (a) Pre-treatment axial unenhanced chest computed tomography (CT) image shows clear lungs except for linear atelectasis and a small area of ground-glass opacity in the right middle lobe. (b) The patient developed respiratory distress 12 hours after the initiation of therapy, and an axial CT image shows bilateral patchy ground-glass opacities, interstitial thickening, and bilateral mild pleural effusion. The ATRA was discontinued, and intravenous systemic corticosteroid therapy (dexamethasone 8 mg/m²) was initiated. The patient’s clinical condition improved rapidly. (c) Axial chest CT image obtained one month later shows mild residual ground-glass opacities (red rectangles) and linear atelectasis (red arrows).