Rituximab-induced Lung Disease Research Articles

RITUXIMAB INDUCED LUNG DISEASE IN A MANTLE CELL LYMPHOMA PATIENT RECEIVING MAINTENANCE: CASE PRESENTATION

Rituximab-induced lung disease (R-ILD) is a rare entity that should be considered in patients treated with rituximab who present with dyspnea, fever, and cough but no clear evidence of infection. We describe the clinical presentation, management, and response to rechallenge in one mantle cell lymphoma patient who developed R-ILD during maintenance rituximab. Case report 66 years old male with history of mantle cell lymphoma (MCL), who had been treated with RCHOP and underwent autologous stem cell transplantation (ASCT), was diagnosed with relapse 5 years after ASCT. Six courses of rituximab-bendamustine resulted in 2nd complete response and 2-monthly rituximab maintenance was initiated.10 days after 3rd rituximab , he presented with a 1 week history of progressive exertional dyspnea and cough. He was tachypneic and hypoxemic. Thorax HRCT showed peripheral bilateral patchy ground glass opacities and nodular opacities. Bronchoalveolar lavage identified no bacterial,viral or fungal pathogen. With presumptive diagnosis of late R-ILD, methylprednisolone(MP) 1 mg/kg/day was started. In absence of rapidly progressing respiratory failure and fever, the patient was evaulated as non severe R-ILD. Thus, rechallenge with rituximab is being considered due to the risk of relapse of MCL. Discussion: Reported rate of possible R-ILD is <0.03% in over 540,000 patients. Pulmonary complications of rituximab are hypersensitivity pneumonitis, ARDS, interstitial pneumonitis, organizing pneumonia, pulmonary fibrosis, and alveolar haemorrhage. Symptoms of R-ILD are dyspnea, fever, and hypoxemia and HRCT findings include focal alveolar densities, ground glass opacities and alveolar opacification. Time to symptom onset ranges from 1 day to several weeks after 1st infusion with mean mean duration of 3 months. Our patient had received rituximab prior to relapse and developed R-ILD after 9 doses of rituximab for relapse, which is a rare finding. All other causes of potential lung injury had to be meticulously excluded. ILD is a rare but potentially fatal pulmonary toxicity due to rituximab. As the symptoms at presentation are nonspecific, physicians must maintain a high index of suspicion to recognize it early and initiate treatment to avoid severe morbidity and mortality.

Rituximab Induced Interstitial Lung Disease in Patients with Non-Hodgkin’s Lymphoma: A Clinical Study of Six Cases and Review of the Literature

Background. Rituximab-induced lung disease (R-ILD) is a rare entity that should be considered in patients treated with rituximab who present with dyspnea, fever, and cough but no clear evidence of infection. Aim. The aim of this prospective longitudinal study is to describe the clinical presentation, management, and response to rechallenge in patients diagnosed with rituximab induced ILD over a period of one year. Results. Out of sixteen patients with CD20 positive non-Hodgkin’s lymphoma who received rituximab along with standard chemotherapy, six patients developed features suggestive of R-ILD. Four (66.6%) of these patients had diffuse large B cell lymphoma. The median time of presentation of R-ILD was after the 3rd cycle of chemotherapy. Three patients (50%) presented with acute onset of high fever, dyspnea, and dry cough while the remaining three presented with insidious onset of dyspnea and dry cough. An infectious etiology for the respiratory illness was ruled out in all patients with an exhaustive work-up. Four patients (66.6%) responded to corticosteroid treatment and supplemental oxygen. One patient required mechanical ventilation and succumbed to ILD while another required prolonged supplemental oxygen. Two (33.3%) of patients were successfully rechallenged with rituximab under cover of corticosteroids. Conclusions. Rituximab induced lung disease is a rare but potentially fatal pulmonary toxicity which requires a high index of suspicion for early diagnosis and treatment.

Rituximab-Induced Bronchiolitis Obliterans Organizing Pneumonia

Rituximab-induced lung disease (R-ILD) is a rare entity that should be considered in patients treated with rituximab who present with dyspnea, fever, and cough, but no clear evidence of infection. A variety of pathologic findings have been described in this setting. Bronchiolitis obliterans organizing pneumonia (BOOP) is the most common clinicopathologic diagnosis, followed by interstitial pneumonitis, acute respiratory distress syndrome (ARDS), and hypersensitivity pneumonitis. Prompt diagnosis and treatment with corticosteroids are essential as discussed by Wagner et al. (2007). Here we present a case of an 82-year-old man who was treated with rituximab for recurrent marginal zone lymphoma. After the first infusion of rituximab, he reported fever, chills, and dyspnea. On computed tomography imaging, he was found to have bilateral patchy infiltrates, consistent with BOOP on biopsy. In our patient, BOOP was caused by single-agent rituximab, in the first week after the first infusion of rituximab. We reviewed the relevant literature to clarify the different presentations and characteristics of R-ILD and raise awareness of this relatively overlooked entity.

Rituximab-induced lung disease: a systematic literature review

The anti-CD20 antibody rituximab has been reported to induce a heterogeneous spectrum of lung disorders. The aim of the present study was to critically review data on the clinical presentations, causality assessments and management strategies of lung diseases possibly related to rituximab. A systematic literature review was performed on English-language reports in PubMed until September 2008. Cases of lung diseases ascribed to rituximab (n = 45) were identified, with three time-to-onset patterns. The most common presentation was acute/subacute hypoxaemic organising pneumonia (n = 37), starting 2 weeks after the last infusion (often around the fourth cycle) and resolving, in most cases, provided glucocorticoid therapy was given early. Acute respiratory distress syndrome occurred in five patients, within a few hours and usually after the first infusion. In the remaining three patients, macronodular organising pneumonia developed insidiously long after rituximab therapy and responded to steroids. Eight patients died. Based on time to onset, symptoms, and responses to discontinuation and rechallenge with rituximab and other drugs, 13 cases were highly compatible and 32 compatible with rituximab-induced lung disease. Knowledge of these presentations of rituximab-induced lung disease should prove helpful for diagnosis and causality assessment purposes. Time-to-onset data, suggesting different pathogenic mechanisms, support closer clinical and perhaps radiological monitoring between infusions, particularly in patients with a history of reversible respiratory symptoms.