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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
ABSTRACT
Introduction: In postmenopausal women, Palbociclib is a selective cyclin-dependent kinase CDK4 and CKD6 inhibitor to treat hormone receptor-positive metastatic breast cancer in combination with Letrozole (Aromatase Inhibitor). We describe a case presenting with the rare side effect of Palbociclib induced interstitial pneumonitis. Case report: A 70-year-old Caucasian female was admitted to the hospital with complaints of progressive dyspnea, dry cough, epistaxis, pleuritic chest pain over one month. Her past medical history was significant for stage IIIC (pT3N3) invasive ductal breast cancer (ER-positive/PR-negative/HER2-negative) status post left segmental mastectomy and axillary lymph node dissection 17 years ago. She received adjuvant chemotherapy, followed by Anastrozole, for five years. She had a metastatic recurrence to bones, liver, and lymph nodes, which was ER-positive/PR-negative/HER2-negative, and was started on Palbociclib and Letrozole by the oncology team four months before admission. Upon presentation, she was noted to have hypoxia requiring four liters of oxygen via nasal cannula. On examination, she was in severe respiratory distress and had bilateral crackles on lung auscultation. CT chest with contrast revealed no pulmonary embolism and bilateral patchy interstitial opacities. Her lab work showed neutropenia, lymphopenia, and anemia. She had a thorough evaluation for viral (including COVID-19), bacterial, and fungal infection, heart failure, and autoimmune disorders, which were negative. Although diagnostic bronchoscopy was offered, she declined the procedure. She continued to have worsening hypoxemia and required a high flow nasal cannula (FiO2 70% and 50 liters of flow) for moderate ARDS, which was presumed to be secondary to drug-induced pneumonitis. Given the pattern of lung injury on CT, the subacute nature of her symptoms, and initial non-invasive evaluation, it was felt that infectious pneumonia was unlikely. She was managed conservatively with discontinuation of Palbociclib, and IV steroids were initiated (20 mg dexamethasone daily). Over 14 days during the hospital stay, her hypoxemia largely resolved, and she was successfully discharged to a rehabilitation facility. On the day of discharge, she was discharged on PO Prednisone dose 0.5mg/kg for six weeks along with oral Bactrim full dose three times a week for PJP prophylaxis. Discussion: Palbociclib is commonly associated with neutropenia, anemia, thrombocytopenia, fatigue, infection, and gastrointestinal side effects. Rarely Palbociclib is associated with interstitial pneumonitis (incidence <1%) due to unknown mechanisms. The early identification of this side effect and treatment with immediate cessation of the drug and corticosteroids could be a life-saving measure, as is the case with our patient.