Journal of Clinical Pharmacy and Therapeutics, 2014, 39, 691–694
doi: 10.1111/jcpt.12198
Case Report
Involvement of NLRP3 inflammasome in rituximab-induced interstitial lung disease: a case report H. Kong*1 MD PhD, Y. Wang*1 MD, X. Zeng* MD PhD, Q. Zhu† MD, W. Xie* MD PhD and S. Dai* MD *Department of Respiratory Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, and †Department of Cardiothoracic Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China
Received 4 July 2014, Accepted 16 July 2014
Keywords: inflammasome, interstitial lung disease, rituximab
erythematous (SLE) and autoimmune haemolytic anaemia (AHA).1 However, rituximab has been reported to induce a heterogeneous spectrum of lung disorders, particularly rituximabinduced interstitial lung disease (R-ILD).2 The mechanism underlying remains unclear by far. In this article, we report a case of rituximab-induced non-specific interstitial pneumonia (NSIP) with NLRP3 inflammasome activation in lung, which implied a link between inflammasome and R-ILD. This finding might provide a new insight into the understanding of R-ILD.
SUMMARY What is known and objective: Rituximab is a chimeric anti-CD20 IgG1 monoclonal antibody for the treatment of various forms of lymphoma and haematological autoimmune diseases. Interstitial lung disease is a rare but lethal pulmonary toxicity of rituximab. Nod-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome is a molecular platform activated upon signs of cellular ‘danger’ to trigger the maturation of pro-inflammatory cytokines. We report the first case of rituximab-induced interstitial lung disease (R-ILD) with NLRP3 inflammasome activation in the lung. Case summary: A 30-year-old male patient diagnosed with idiopathic thrombocytopenic purpura (ITP) was treated with four cycles of rituximab in one month. Three weeks after last rituximab administration, he developed progressive dyspnoea associated with respiratory failure, which was diagnosed as R-ILD. The patient showed a good response to steroid treatment, and lung biopsy was performed 5 days after the treatment. Immunohistopathological studies of lung specimens showed high expressions of inflammasome components NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) and caspase-1 in lung interstitium with a heavy infiltration of CD19-positive cells. The levels of inflammasome-related cytokines IL-1b and IL-18 in the serum were declined during the therapy. What is new and conclusions: This is the first report confirmed the role of NLRP3 inflammasome in pulmonary toxicity of rituximab. Inhibited activation of NLRP3 inflammasome in lung by steroid treatment could reverse R-ILD and block subsequent lung fibrosis. This result could open a new sight into the pathogenesis and provide a new target for the treatment of R-ILD.
DETAIL OF THE CASE A 30-year-old man was diagnosed with idiopathic thrombocytopenic purpura (ITP) in May 2013. He initially received high dose corticosteroids and mycophenolate mofetil treatment but with poor response. After four cycles infusion of low-dose rituximab (100 mg once weekly)3 in one month (last one 12th September 2013), complete response was achieved. However, 2 weeks after the last infusion, the patient developed dyspnoea, dry cough and fever. Despite a 5-day course of cefoxitin in the outpatient department, his cough persisted and he developed worsening shortness of breath. The patient was then hospitalized for further evaluation and therapy. He had no known drug allergies or environmental exposures and denied any tobacco, illicit drug or alcohol use. On examination, the patient’s pulse rate was 96 beats/min; BP, 110/70 mmHg; respiratory rate, 26 breaths/min. He was in moderate respiratory distress with respiratory failure (PaO2 = 48 mmHg) on room air. Crackles were audible in both lower lung fields. Chest computed tomography (CT) showed diffuse groundglass infiltration throughout both lungs with patchy consolidation of both lower lobes (Fig. 1a and a0 ). An empirical course of antibiotic, imipenem-cilastatin, was administered due to suspicion of immunocompromised host pneumonia, and methylprednisolone (1 mg/kg/day) infusion was initiated due to suspicion of R-ILD. During the hospitalization, consecutive sputum cultures for bacteria and fungi were negative. Tests for inflammation showed procalcitonin 005 ng/mL (
doi: 10.1111/jcpt.12198
Case Report
Involvement of NLRP3 inflammasome in rituximab-induced interstitial lung disease: a case report H. Kong*1 MD PhD, Y. Wang*1 MD, X. Zeng* MD PhD, Q. Zhu† MD, W. Xie* MD PhD and S. Dai* MD *Department of Respiratory Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, and †Department of Cardiothoracic Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China
Received 4 July 2014, Accepted 16 July 2014
Keywords: inflammasome, interstitial lung disease, rituximab
erythematous (SLE) and autoimmune haemolytic anaemia (AHA).1 However, rituximab has been reported to induce a heterogeneous spectrum of lung disorders, particularly rituximabinduced interstitial lung disease (R-ILD).2 The mechanism underlying remains unclear by far. In this article, we report a case of rituximab-induced non-specific interstitial pneumonia (NSIP) with NLRP3 inflammasome activation in lung, which implied a link between inflammasome and R-ILD. This finding might provide a new insight into the understanding of R-ILD.
SUMMARY What is known and objective: Rituximab is a chimeric anti-CD20 IgG1 monoclonal antibody for the treatment of various forms of lymphoma and haematological autoimmune diseases. Interstitial lung disease is a rare but lethal pulmonary toxicity of rituximab. Nod-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome is a molecular platform activated upon signs of cellular ‘danger’ to trigger the maturation of pro-inflammatory cytokines. We report the first case of rituximab-induced interstitial lung disease (R-ILD) with NLRP3 inflammasome activation in the lung. Case summary: A 30-year-old male patient diagnosed with idiopathic thrombocytopenic purpura (ITP) was treated with four cycles of rituximab in one month. Three weeks after last rituximab administration, he developed progressive dyspnoea associated with respiratory failure, which was diagnosed as R-ILD. The patient showed a good response to steroid treatment, and lung biopsy was performed 5 days after the treatment. Immunohistopathological studies of lung specimens showed high expressions of inflammasome components NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) and caspase-1 in lung interstitium with a heavy infiltration of CD19-positive cells. The levels of inflammasome-related cytokines IL-1b and IL-18 in the serum were declined during the therapy. What is new and conclusions: This is the first report confirmed the role of NLRP3 inflammasome in pulmonary toxicity of rituximab. Inhibited activation of NLRP3 inflammasome in lung by steroid treatment could reverse R-ILD and block subsequent lung fibrosis. This result could open a new sight into the pathogenesis and provide a new target for the treatment of R-ILD.
DETAIL OF THE CASE A 30-year-old man was diagnosed with idiopathic thrombocytopenic purpura (ITP) in May 2013. He initially received high dose corticosteroids and mycophenolate mofetil treatment but with poor response. After four cycles infusion of low-dose rituximab (100 mg once weekly)3 in one month (last one 12th September 2013), complete response was achieved. However, 2 weeks after the last infusion, the patient developed dyspnoea, dry cough and fever. Despite a 5-day course of cefoxitin in the outpatient department, his cough persisted and he developed worsening shortness of breath. The patient was then hospitalized for further evaluation and therapy. He had no known drug allergies or environmental exposures and denied any tobacco, illicit drug or alcohol use. On examination, the patient’s pulse rate was 96 beats/min; BP, 110/70 mmHg; respiratory rate, 26 breaths/min. He was in moderate respiratory distress with respiratory failure (PaO2 = 48 mmHg) on room air. Crackles were audible in both lower lung fields. Chest computed tomography (CT) showed diffuse groundglass infiltration throughout both lungs with patchy consolidation of both lower lobes (Fig. 1a and a0 ). An empirical course of antibiotic, imipenem-cilastatin, was administered due to suspicion of immunocompromised host pneumonia, and methylprednisolone (1 mg/kg/day) infusion was initiated due to suspicion of R-ILD. During the hospitalization, consecutive sputum cultures for bacteria and fungi were negative. Tests for inflammation showed procalcitonin 005 ng/mL (
