INTRODUCTION: We report a rare case of Rituximab-induced organizing pneumonia, proven by open lung biopsy.
CASE PRESENTATION: A 91-year-old male with recurrent grade 2 follicular lymphoma manifest as a left neck mass had been treated with four cyles of rituximab beginning 6 months prior to presentation. The tumor had completely subsided. He also had a history of type II diabetes and hypothyroidism. He presented in December 2007 after 2 weeks of progressive dyspnea. No fever or cough. Lung exam revealed coarse rhonchi. There was no JVD or cardiac gallops. 3+ edema of both LEs. Room air SpO2 84%. WBC 7610 mm3. BNP 187 pg/ml. Total protein 4.6, albumin 2.3. Initial chest CT (figure 1) showed diffuse ground glass opacities, bilateral pleural effusions and subsegmental pulmonary emboli in RLL. He was initially treated with broad spectrum antibiotics and anticoagulation. A bronchoscopy with BAL was negative for PCP, bacteria, fungi, AFB and atypical cells. He then underwent a right VATS procedure. Wedge biopsies from the RUL and RLL showed a temporally uniform pattern of organizing pneumonia with early fibroblastic organization within alveolar walls, as well as in bronchioles. There were few inflammatory cells, mostly lymphocytes. No granulomas or malignant cells. Special stains was negative for Pneumocystis, fungi, AFB and CMV. These histologic findings were consistent with a hypersensitivity of drug reaction. He was started on IV Solumedrol with gradual improvement in his respiratory status and clearing of pleural effusions and GGOs on chest imaging studies over the next three weeks. His hospital course was complicated by a retroperitoneal bleed while on anticoagulation that resulted in IVC filter placement; and SIADH that responded to water restriction. He was discharged from the hospital 27 days after admission on prednisone 5 mgm daily. He required no supplemental oxygen at discharge.
DISCUSSIONS: Rituzimab is a chimeric anti-CD20 antibody first approved in 1997 for treatment of CD20+ B-cell non-Hodgkin's lymphoma (NHL). It is also used for therapy of certain autoimmune disorders, such as ITP, SLE and autoimmune hemolytic anemias. Mild adverse respiratory effects are commonly seen, including rhinitis, sinusitis, cough, bronchospasm and dyspnea. However, severe lung toxicity is very rare. A recent review (1) of rituximab-induced interstitial lung disease summarized all 16 cases documented in the literature. 75% had a diagnosis of NHL and were elderly (average age 65). The average number of cycles of rituximab prior to presentation with ILD was four. The most common presenting symptoms of dyspnea and fever are non-specific. Only two of these cases had lung biopsies; the diagnosis was “clinical” in all others. HRCT in all cases demonstrated diffuse interstitial patterns with GGOs. 67% had full recovery after treatment with systemic corticosteroids. Our patient fits this clinical pattern and we believe that his organizing pneumonia, proven by biopsy, was induced by rituximab. The pathogenesis of interstitial pneumonia caused by rituximab is unknown. The drug acts by binding CD20+ B cells. Activation of complement and cytokine production may be responsible for severe lung injury in some patients.
CONCLUSION: Interstitial pneumonitis related to rituximab therapy is a very rare complication. Our case, which includes histologic information about the pattern of lung injury, responded dramatically to systemic corticosteroids, despite his advanced age.
DISCLOSURE: Hazem Ubaissi, No Financial Disclosure Information; No Product/Research Disclosure Information