FLUOROURACIL-INDUCED PULMONARY TOXICITY PRESENTING AS DIFFUSE ALVEOLAR HEMORRHAGE

Abstract

TOPIC: Diffuse Lung Disease TYPE: Fellow Case Reports INTRODUCTION: Fluorouracil (5-FU) is a chemotherapy medication often used alone or in combination with other agents (e.g., FOLFOX regimen) to treat gastrointestinal malignancies. Adverse effects of 5-FU include pancytopenia, alopecia, cardiotoxicity, and gastrointestinal symptoms. We describe a rare case of pulmonary toxicity associated with 5-FU. CASE PRESENTATION: The patient is a 78-year-old female with a history of unresectable metastatic cholangiocarcinoma on maintenance FOLFOX chemotherapy without Oxaliplatin (discontinued due to peripheral neuropathy and thrombocytopenia) presented with acute onset of dyspnea and pleuritic chest pain five days after a 5-FU and Leucovorin infusion. On initial evaluation, a chest radiograph showed pulmonary infiltrates for which she was treated with oral Levofloxacin as an outpatient. Despite this, she had progressive worsening of dyspnea, prompting further evaluation. Blood work revealed normal WBC and platelet counts, mild anemia with hemoglobin 9.4 g/dL, and normal BNP and troponin levels. ECHO showed normal systolic function. She was noted to be hypoxemic, requiring supplemental oxygen necessitating hospitalization. Repeat Chest radiograph showed worsening left upper lobe and lingular infiltrates. Her oxygen requirements rapidly increased from 3-4 L/min via nasal cannula to 12L/min via Oxymask. Despite treatment with broad-spectrum IV antibiotics, her dyspnea and hypoxia persisted. CTA chest was then performed, revealing extensive bilateral infiltrates and reactive enlarged mediastinal/hilar lymph nodes with no evidence of pulmonary embolism. She had a negative infectious workup, including a COVID-19 PCR. She underwent diagnostic bronchoscopy, which showed no endobronchial lesions or secretions. Bronchoalveolar lavage of the right middle lobe with three serial aliquots obtained progressively bloody returns diagnosing diffuse alveolar hemorrhage (DAH). The procedure was complicated by worsening hypoxia, and the patient required emergent intubation and transferred to the critical care unit, where she was treated with pulse dose steroids for three days. She was extubated to supplemental O2 via NC within 24 hours of treatment. Further lab evaluation showed negative ANA, ANCA, Anti GBM antibodies, Anti-dsDNA, and normal C3, C4 levels. Cytology of BAL was negative for malignancy. Given negative infectious and autoimmune workup, the diagnosis of DAH due to 5-FU was made. Steroid dose was reduced to Prednisone 1mg/kg with slow taper with improvement in clinical status and oxygen requirements. DISCUSSION: The diagnosis of 5-FU related pulmonary toxicity is based on clinical suspicion upon exclusion of infection, autoimmune disease, heart failure, and cancer progression. CONCLUSIONS: 5-FU induced pulmonary toxicity presenting as DAH is a rare entity. Prompt diagnosis can lead to early drug cessation and the use of high-dose steroids can improve patient outcomes. REFERENCE #1: Fernandez, L., Dominguez, A., Martinez, W., Sanabria, F., Leib, C. S., & Biomedical Research Group in Thorax. (2018). Pulmonary Toxicity Due to 5-Fluorouracil (5-FU) Manifested as Diffuse Alveolar Hemorrhage: Case Report. In D34. LUNG TRANSPLANT AND DRUG INDUCED LUNG DISEASE: CASE REPORTS (pp. A6577-A6577). American Thoracic Society. DISCLOSURES: No relevant relationships by Rajesh Kunadharaju, source=Web Response No relevant relationships by Puja Mehta, source=Web Response No relevant relationships by Ahmed Munir, source=Web Response No relevant relationships by Vandana Pai, source=Web Response No relevant relationships by Musa Saeed, source=Web Response