Fatal Rituximab-Induced Nonspecific Interstitial Pneumonia: Case Report and Review of the Literature

Case Report

Ann Hematol Oncol. 2016; 3(11): 1121.

Fatal Rituximab-Induced Nonspecific Interstitial Pneumonia: Case Report and Review of the Literature

Sato R1, Molligan J2 and Gaballa S3*

1Department of Internal Medicine, Thomas Jefferson University, USA

2Department of Pathology, Thomas Jefferson University, USA

3Department of Medical Oncology, Thomas Jefferson University, USA

*Corresponding author: Sameh R. Gaballa, Department of Medical Oncology, Thomas Jefferson University, 925 Chestnut Street Suite 420A, Philadelphia, PA 19107, USA

Received: September 16, 2016; Accepted: October 29, 2016; Published: November 01, 2016


Rituximab treatment can be associated with respiratory complications such as cough, bronchospasm, sinusitis, and rhinitis. Rarely, rituximab can cause fatal lung injury. We report the case of a patient on rituximab monotherapy who experienced shortness of breath and eventual respiratory failure despite steroid treatment. Limited biopsies of her bilateral lungs post-mortem revealed nonspecific interstitial pneumonia. We review the previous literature on rituximab-induced lung disease and use this case to highlight the need for close monitoring, early detection and treatment, especially for patients who have a previous history of lung disease.

Keywords: Interstitial lung disease; Nonspecific interstitial pneumonia; Rituximab


COPD: Chronic Obstructive Pulmonary Disease; CT: Computed Tomography; BiPAP: Bilevel Positive Airway Pressure; ICU: Intensive Care Unit; NSIP: Nonspecific Interstitial Pneumonia; RTXILD: Rituximab-Induced Lung Disease; DLCO: Diffusing Capacity of the Lungs for Carbon Monoxide; NLRP3: Nod-like receptor pyrin domain-containing protein 3


Rituximab is a chimeric anti-CD20 antibody that is used to treat some hematological malignancies such as B-cell lymphomas, and various autoimmune diseases including immune thrombocytopenic purpura, systemic lupus erythematous, rheumatoid arthritis, and autoimmune hemolytic anemia. Most common side effects include fever, chills, and rigors. Respiratory complications such as cough, bronchospasm, sinusitis, and rhinitis have also been reported in 30% of patients in clinical trials [1]. Rituximab-induced lung injury is a very rare but potentially fatal complication. The reported incidence ranges from 3.7 to 10%, and may even be higher as some cases may be regarded as lower respiratory tract infections. Of those with rituximab-induced lung injury it has been fatal in 18 to 30% of cases [2-5]. We report a case of fatal single agent rituximab-induced nonspecific interstitial pneumonia to increase awareness about this serious side effect and review the current literature.

Case Presentation

This case involves a 72-year-old female with stage IV marginalzone B-cell lymphoma who required therapy due to transfusiondependent anemia and was initiated on single agent rituximab (4 weekly doses at a dose of 375 mg/m2). She tolerated the first two infusions well, but started to feel short of breath after her third infusion. By the time she arrived to the infusion center for her fourth dose, she was short of breath at rest and was found to be hypoxic to 68% on room air. Of note the patient had COPD with a 30pack-year smoking history, quit 3 years ago, but had no oxygen requirements prior. She was admitted to the hospital where she was started on broad-spectrum antibiotics and placed on 5 liters of oxygen. A chest CT with contrast showed extensive bilateral ground-glass opacities with interlobular septal thickening (Figure 1A). On the second day of admission the patient became hypoxic to 70% on 6 liters but did not tolerate BiPAP so she was transferred to the medical ICU. Methylprednisolone 125 mg every 6 hours was started intravenously for possible rituximab-induced lung reaction on day 2. A repeat CT scan of the chest two weeks later revealed improvement in the bilateral airspace opacities (Figure 1B). However she clinically continued to deteriorate during this time and she eventually required intubation and mechanical ventilation. Bronchoscopy was performed which was negative for infection including any aerobic or anaerobic bacteria, acid-fast bacilli, fungus, or virus. The patient further decompensated with hypoxemic respiratory failure and expired on the third week of admission despite multiple rounds of resuscitation. The patient’s family agreed to an autopsy limited to a biopsy of her lungs. Two intercostal incisions measuring approximately 8cm in length were created bilaterally on the chest wall. The internal examination was limited due to the minimally invasive nature of the autopsy. On gross examination the pleural surface was smooth and glistening. There were no observable adhesions and the parenchyma was crepitant and firm. A limited biopsy of her bilateral lungs revealed a histologic pattern of nonspecific interstitial pneumonia with uniform thickening of the alveolar septa with a monotonous lymphoid infiltrate. There was spatial and temporal homogeneity seen (Figure 1C).

Citation:Sato R, Molligan J and Gaballa S. Fatal Rituximab-Induced Nonspecific Interstitial Pneumonia: Case Report and Review of the Literature. Ann Hematol Oncol. 2016; 3(11): 1121. ISSN : 2375-7965