Medical Image of the Month: Bleomycin-Induced Pulmonary Fibrosis in a Patient with Lymphoma

Figure 1. Representative images from the thoracic CT in lung windows showing scattered bilateral ground glass opacities with areas of fibrosis consistent with multifocal pneumonia superimposed on pulmonary fibrosis.

Figure 2. Representative image from the thoracic CT in lung windows done just prior to lung transplantation.

Abstract

Interstitial pulmonary fibrosis is the most feared complication of bleomycin therapy and occurs in up to ten percent of patients that receive the drug. The risk of bleomycin-induced pulmonary fibrosis is related to the age of the patient, the dose of medication given, the patient’s kidney function, and whether the patient smokes cigarettes. Current screening guidelines for bleomycin-induced lung injury are limited, but most clinicians screen high risk and symptomatic patients with pulmonary function testing. This case report is of a patient with lymphoma who received bleomycin as a part of his chemotherapy regimen, and later developed pulmonary fibrosis complicated by bouts of eosinophilic multifocal pneumonia. The case highlights the importance of close monitoring of patients taking bleomycin for signs and symptoms of pulmonary fibrosis and the need for major medical societies to issue concrete screening guidelines.

Introduction 

Bleomycin’s labeled indications include treatment of squamous cell carcinomas of the head and neck, Hodgkin lymphoma, non-Hodgkin lymphoma, malignant pleural effusions, and testicular cancer (1). The most feared complication of bleomycin is interstitial pulmonary fibrosis (2). Pathogenesis is not fully clear but involves oxidative damage secondary to reactive oxygen species (2). Risk factors include age > 40, renal insufficiency (CrCl < 80 mL/min), bleomycin dose > 300 units, and cigarette smoking (2). Symptoms present within one to six months of starting the medication and often begin with dyspnea and auscultatory crackles on physical exam (2). Associated signs and symptoms include cough, chest pain, opacities on chest radiographs, or an asymptomatic decline in diffusing capacity for carbon monoxide (2,3).

Screening for pulmonary fibrosis in patients taking bleomycin is controversial and no clear guidelines exist. Most physicians agree that it is appropriate to get baseline pulmonary function tests (PFTs) in patients receiving bleomycin, and thereafter screen with PFTs intermittently throughout the course of treatment (3). FDG-PET has also been used as a screening tool, but the evidence for its efficacy is mixed (4).

This is a case of a 56-year-old man with a presumed diagnosis of multifocal eosinophilic pneumonia superimposed on pulmonary fibrosis who had to be admitted to the ICU for respiratory distress. The patient recovered and underwent a lung transplant.

Case Presentation 

A 56-year-old man with a history of lymphoma diagnosed 11 years prior and treated with chemotherapy, including bleomycin, presented to the emergency department with fever, chills, and productive cough. A CT of the chest with IV contrast was performed which revealed scattered bilateral ground glass opacities with areas of fibrosis (Figure 1). Next, the patient underwent a bronchoalveolar lavage (BAL) and shortly thereafter developed respiratory distress with respiratory failure that required non-invasive ventilation and admission to the ICU. In the ICU, the patient responded to ceftriaxone, azithromycin, prednisone, and fluconazole. The bronchoalveolar lavage was significant for elevated levels of eosinophils and neutrophils. There were also possible fungal elements on touch prep but no fungal growth. The presumed diagnosis on admission was multifocal pneumonia superimposed on pulmonary fibrosis.  

After recovering, the patient was discharged. Four months later, he underwent a bilateral lung transplant. At explant, the final pathology report confirmed a mixed pattern of fibrosing interstitial lung disease, clinically due to bleomycin. Figure 2 shows the patient’s pulmonary fibrosis just prior to transplant.

The patient’s lung transplantation was successful, and he is currently doing well.

Discussion

Pulmonary fibrosis is a dangerous and relatively common complication of bleomycin. The differential diagnosis includes pulmonary infection, cardiogenic pulmonary edema, radiation-induced pulmonary fibrosis, metastatic disease, and adverse reaction to other medications. Presented here is a case where a patient received bleomycin as a part of his chemotherapy regimen for lymphoma, and subsequently developed pulmonary fibrosis. When the patient presented 11 years after his lymphoma diagnosis, he had eosinophilic multifocal pneumonia superimposed on his already existing pulmonary fibrosis.

This case illustrates the difficulty of managing the pulmonary manifestations of bleomycin in patients taking the drug. There are currently no screening guidelines in place for patients that take the medication (3). Shippee et al. suggest patients undergo PFTs at baseline before starting treatment, followed by PFTs every 3 weeks during therapy (3). They suggest bleomycin should be discontinued in patients who have a linear decline in DLCO of 40-60% from baseline (3).

It is unclear if our patient had been screened for pulmonary fibrosis while he was receiving bleomycin. Regardless, it would be prudent and appropriate for a major medical society to issue clear guidelines regarding screening for pulmonary fibrosis. Standardizing screening protocols will lead to better patient outcomes.

Martin A. Dufwenberg, BS  

University of Arizona College of Medicine – Tucson

Tucson, AZ, USA

Acknowledgments

The author thanks Dr. Michael Larson, M.D., Ph.D., for mentorship, discussion, and help in making this case report become reality.

References

1. U.S. Food and Drug Administration. Blenoxane (bleomycin sulfate for injection, USP). Updated April 2010. Accessed June 8, 2021. https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/050443s036lbl.pdf
2. Sleijfer S. Bleomycin-induced pneumonitis. Chest. 2001 Aug;120(2):617-24. [CrossRef] [PubMed]
3. Shippee BM, Bates JS, Richards KL. The role of screening and monitoring for bleomycin pulmonary toxicity. J Oncol Pharm Pract. 2016 Apr;22(2):308-12. [CrossRef] [PubMed]
4. Groves AM, Win T, Screaton NJ, Berovic M, Endozo R, Booth H, Kayani I, Menezes LJ, Dickson JC, Ell PJ. Idiopathic pulmonary fibrosis and diffuse parenchymal lung disease: implications from initial experience with 18F-FDG PET/CT. J Nucl Med. 2009 Apr;50(4):538-45. [CrossRef] [PubMed]

Cite as: Dufwenberg MA. Medical image of the month: bleomycin-induced pulmonary fibrosis in a patient with lymphoma. Southwest J Pulm Crit Care. 2021;23(2):49-51. doi: https://doi.org/10.13175/swjpcc024-21 PDF 

Medical Image of the Week: Acute Pneumonitis Secondary to Boric Acid Exposure

Figure 1. Panel A: A normal baseline chest radiograph obtained a few months prior to the current presentation. Panel B: A chest radiograph obtained at the day of admission with respiratory distress post exposure to boric acid powder that shows diffuse hazy opacities of the lungs. Panel C: Representative image form thoracic computed tomography obtained on day of admission shows extensive diffuse central predominant ground glass opacification. Panel D: A chest radiograph obtained 3 days after large dose of systemic steroid given for a presumptive diagnosis of acute pneumonitis. Rapid improvement of the bilateral airspace disease is suggestive of resolving inflammation.

Figure 2. Video of thoracic computed tomorgraphy in lung windows obtained on the day of admission.

A 33-year-old man presented with acute severe dyspnea and pleuretic chest pain one day after accidental inhalational exposure to boric acid powder. The patient was spraying boric acid in his apartment to kill bugs and he got trapped in a poorly ventilated area with a cloud of the dusted boric acid for more than a minute. He did not feel any significant symptoms initially. Overnight he started to develop shortness of breath and chest tightness. The patient visited an urgent care where he was reassured due to normal chest radiograph and was given a course of oseltamivir empirically due to a widespread influenza epidemic. After a few hours the patient’s symptoms got much worse and he presented to the emergency department with severe pleuretic chest pain and respiratory distress. The patient required 5 liters of oxygen to keep his saturation above 90%. His chest images showed extensive bilateral airspace disease suggestive of either pulmonary edema, multifocal pneumonia or inflammatory pneumonitis. His microbiologic work up was negative including influenza PCR. Echocardiogram was normal. With his recent exposure to boric acid inhalation an acute chemical pneumonitis was suspected. The patient received systemic high dose prednisone for 3 days and he improved significantly clinically and on imaging. His oxygen saturation was 97% on room air 4 days post admission.

Boric acid is an odorless partially water-soluble antiseptic, insecticide, flame retardant, neutron absorber, and a precursor to other chemical compounds (1,2). The material safety data sheet for boric acid suggests that it may be also toxic to kidneys, cardiovascular system, central nervous system (CNS) (2). Repeated or prolonged exposure to the substance can produce target organ damage (1,2)

Huthayfa Ateeli, MBBS¹, Laila Abu Zaid, MD², Sachin Chaudhary, MD¹

¹Pulmonary and Critical Care Division, Department of Medicine, University of Arizona, Tucson, AZ USA

²Department of Medicine, University of Arizona, Tucson, AZ USA

References

1. Agency for Toxic Substances & Disease Registry. Toxicological profile of boron. November 2010. Available at: https://www.atsdr.cdc.gov/toxprofiles/tp26.pdf (accessed 2/27/18).
2. ScienceLab.com. Material Safety Data Sheet: Boric acid MSDS. October 10, 2005. May 21, 2013. Available at: http://www.sciencelab.com/msds.php?msdsId=9927105 (accessed 2/27/18).

Cite as: Ateeli H, Zaid LA, Chaudhary A. Medical image of the week: acute pneumonitis secondary to boric acid exposure. Southwest J Pulm Crit Care. 2018;16(2):108-9. doi: https://doi.org/10.13175/swjpcc025-18 PDF 

Medical Image of the Week: Typical Pulmonary CT Findings Following Radiotherapy

Figure 1. Panel A: CT chest, lung windows, demonstrating a spiculated nodule, biopsy proven adenocarcinoma in the right lower lobe (arrow). Panel B: Eight months post stereotactic radiation therapy, there has been development of focal consolidation, with air bronchograms, involving the right middle and lower lobes. Notice the volumetric appearance. The primary malignancy is no longer identified as such. Panel C: Thirteen months later the consolidation has evolved into an area of volume loss, containing bronchiectasis, and sharp contours as a result of organized fibrosis.

Radiation-induced lung disease (RILD) commonly develops in patients treated with radiation for intrathoracic and chest wall malignancies.

There are two distinct radiographic patterns:

1. Radiation pneumonitis which occurs within 4-12 weeks after completion of therapy, and is characterized by development ground-glass opacities and/or consolidation in and around the treated lesion. A somewhat nodular or patchy appearance may occur. Typically, the affected tissue conforms to the radiation ports and may cross fissures/lobes. There may be milder similar changes in the contralateral lung.
2. A chronic phase, known as radiation fibrosis, is noticeable about 6-12 months post treatment and may progress up to 2 years, after which the findings tend to stabilize. In this stage, the areas of consolidation undergo volume loss, architectural distortion and may contain traction bronchiectasis. Linear and band scarring may also be seen. In this phase, sharper demarcation between normal and irradiated lung parenchyma is commonly seen.

Special attention to the typical radiological characteristics and timeline, in most cases allows to distinguish RILD from potential superimposed infection, subacute inflammatory diseases, locally recurrent neoplasm and radiation-induced neoplasms.

Andrew Erickson MS IV¹, Berndt Schmidt MD², Veronica Arteaga MD², Diana Palacio MD²

¹Midwestern University – Arizona College of Osteopathic Medicine

²Division of Thoracic Radiology, Department of Medical Imaging. University of Arizona, Tucson (AZ)

Reference

1. Choi YW, Munden RF, Erasmus JJ, Joo Park K, Chung WK, Jeon SC, Park CK. Effects of radiation therapy on the lung: radiologic appearances and differential diagnosis. Radiographics. 2004 Jul;24(4):985-97. [CrossRef] [PubMed]

Cite as: Erickson A, Schmidt B, Arteaga V, Palacio D. Medical image of the week: typical pulmonary CT findings following radiotherapy. Southwest J Pulm Crit Care. 2017;15(3):120-1. doi: https://doi.org/10.13175/swjpcc112-17 PDF

Medical Image of the Week: Pembrolizumab-induced Pneumonitis

Figure 1. Thoracic CT showing multifocal, bilateral extensive lung opacities consistent with consolidation with a striking peribronchovascular distribution. Note the opacities are primarily distributed along the airways. Peripheral lung opacity, both ground-glass opacity and consolidation, is also present.

Figure 2. Axial thoracic CT performed several months after Figure 1 following discontinuation of the pembrolizumab and initiation, and subsequent tapering, of corticosteroid therapy, shows significant regression in the previously noted extensive peribronchovascular consolidation. Residual areas of consolidation and ground-glass opacity associated with architectural distortion are consistent with scarring.

A 76-year-old man with metastatic melanoma, undergoing treatment with pembrolizumab, an antibody against programmed cell death 1 (PD-1), beginning 8 months ago developed low-grade fever, non-productive cough, and shortness of breath. A thoracic CT scan showed multifocal, bilateral extensive lung opacities (Figure 1). The patient underwent bronchoscopy with bronchoalveolar lavage which showed non-specific inflammatory changes associated with foci of organizing pneumonia. Microbiologic studies, including Coccioides antibody enzyme immunoassay and Aspergillus antigen, were negative.

The patient was begun on corticosteroid therapy for presumed medication-induced pulmonary injury, manifestation as an organizing pneumonia pattern, due to pembrolizumab. Over the ensuing months, his symptoms abated and his CT scan abnormalities regressed (Figure 2).

Organizing pneumonia may occur as an idiopathic, primary pulmonary process, often referred to as “cryptogenic organizing pneumonia,” or may occur in the context of a number of systemic conditions, a situation often referred to as secondary organizing pneumonia. Among the various etiologies of secondary organizing pneumonia, medication-induced pulmonary injury is fairly common and when imaging features of organizing pneumonia are seen, careful correlation regarding the possibility of a medication-induced etiology should be undertaken. Recently, three cases of pembrolizumab-induced pneumonitis were described, two being consistent with organizing pneumonia (1).

The thoracic CT findings of organizing pneumonia include peripheral and peribronchovascular consolidation and ground-glass opacity, areas of consolidation surrounding ground-glass opacity (often referred to as the “atoll” or reverse ground-glass halo” sign- see Medical Image of the Week: The Atoll Sign in Cryptogenic Organizing Pneumonia), single and multiple nodules, and perilobular consolidation. The case illustrates a dramatically peribronchovascular distribution of pulmonary consolidation as a manifestation of medication-induced organizing pneumonia.

Michael B. Gotway, MD

Department of Radiology

Mayo Clinic Arizona

Scottsdale, AZ USA

Reference

1. Leroy V, Templier C, Faivre JB, Scherpereel A, Fournier C, Mortier L, Wemeau-Stervinou L. Pembrolizumab-induced pneumonitis. ERJ Open Res. 2017 May 2;3(2). pii: 00081-2016. [CrossRef] [PubMed]

Cite as: Gotway MB. Medical image of the week: pembrolizumab-induced pneumonitis. Southwest J Pulm Crit Care. 2017;15(3):118-9. doi: https://doi.org/10.13175/swjpcc110-17 PDF