Immune Reconstitution Inflammatory Syndrome Presenting as Pneumocystis Pneumonia After Filgrastrim-Induced Neutrophil Recovery

Abstract

INTRODUCTION: Immune reconstitution inflammatory syndrome (IRIS) is a condition seen in immunosuppressed patients associated with immune system recovery and paradoxical worsening of a pre-existing opportunistic infection. IRIS is most commonly described in HIV patients following the initiation of highly active anti-retroviral therapy (HAART) as their CD4 counts increase. IRIS has also been reported in non-HIV-infected patients primarily in the setting of tuberculosis. We report a non-HIV-infected patient who developed acute respiratory distress syndrome(ARDS) after receiving filgrastim for methotrexate-induced neutropenia. CASE PRESENTATION: A 51 year old non-HIV-infected woman with a history of juvenile rheumatoid arthritis treated with methotrexate (20mg per week) and prednisone (5mg per day) for more than 15 years, presented with fever, fatigue and mouth sores for one week. The patient was neutropenic (absolute neutrophil count 50cells/mm3) with diffuse interstitial infiltrates on chest radiograph (CXR). Bone marrow biopsy showed a hypocellular marrow, and she was thought to have methotrexate-induced neutropenia. Initial treatment included broad-spectrum antibiotics for pneumonia associated with neutropenia. Filgrastim (Granulocyte Colony-stimulating factor) was begun and after 2 days the white blood count rose from 0.2k to 19.8k cells/mm3. During this time, she developed severe hypoxic respiratory failure requiring endotracheal intubation and mechanical ventilation. The CXR showed rapid progression of diffuse infiltrates and gas exchange showed poor oxygenation with a PaO2 89mmHg on 100% FiO2 (P/F ratio <100), consistent with acute respiratory distress syndrome. The patient was placed on lung-protective, low tidal volume mechanical ventilation. Broad spectrum antibiotics were continued and intravenous bactrim and steroids were started empirically. Bronchoscopy with BAL demonstrated pneumocystis carinii (P. jiroveci) on GMS staining. The patient responded to bactrim and steroids and was successfully extubated, weaned off oxygen and later discharged from the hospital. DISCUSSION: We report a case of PCP that became clinically evident after the initiation of filgrastrim therapy for methotrexate-induced neutropenia. A severe inflammatory response in the lung, ARDS, resulted from recovery of her neutrophil cell population, and unmasked the infection with pneumocystis. In particular, neutrophilic alveolitis, which is associated with greater severity of PCP, was elicited by filgrastim treatment. CONCLUSIONS: Our case illustrates yet another example of IRIS associated with recovery from severe neutropenia, and also identifies an additional potential cause of acute lung injury or ARDS.