A DUAL DIAGNOSIS: CYCLOPHOSPHAMIDE TOXICITY AND DIFFUSE ALVEOLAR-SEPTAL AMYLOIDOSIS CAUSING HYPOXEMIA

Abstract

TOPIC: Diffuse Lung Disease TYPE: Fellow Case Reports INTRODUCTION: Patients with cardiac amyloidosis have multiple possible causes of hypoxia including pulmonary edema, infection, drug toxicity, and pulmonary involvement of amyloidosis. Treatment varies significantly for these different etiologies. This broad differential can make diagnosis challenging and bronchoscopy is often needed to establish a definitive diagnosis. CASE PRESENTATION: A 72 yo male with cardiac AL amyloidosis presented with fever and hypoxic respiratory failure. He completed 4 cycles of cyclophosphamide, bortezomib, and dexamethasone 2 weeks prior to presentation. Right heart catheterization (RHC) demonstrated normal pressures. CT chest showed diffuse ground glass opacities (GGO) and basilar predominant interlobular septal thickening. He was diuresed but continued to require supplemental oxygen. Bronchoscopy with BAL and transbronchial biopsy was performed. BAL WBC was 121 with 48% lymphocytes and 48% macrophages. Infectious evaluation returned negative. Transbronchial biopsy returned with lambda-predominant plasma cell infiltrate and amyloid deposition. He was started on prednisone with improvement in symptoms and liberation from supplemental oxygen after 3 weeks of therapy. PFTs obtained at follow-up showed mild obstruction and moderately reduced DLCO. DISCUSSION: Pulmonary toxicity is a known complication of cyclophosphamide therapy that results in pneumonitis, typically occurring weeks after administration. CT imaging shows scattered or diffuse GGOs. Pathology demonstrates diffuse alveolar damage. Case series have shown improvement with drug cessation and steroids. Diffuse alveolar-septal amyloidosis (DASA) is 1 of several patterns of pulmonary amyloidosis. DASA is associated with AL amyloidosis. DASA is a common pathologic finding but is rarely symptomatic unless severe enough to impair gas exchange. CT imaging shows interlobular septal thickening, reticular opacities, and GGOs. Pathology reveals amyloid deposition within the alveolar septum and vessel walls and a plasma cell infiltrate. Treatment is systemic therapy for amyloidosis. This patient with cardiac amyloidosis and cyclophosphamide use was a diagnostic challenge. Given his fever, normal RHC, and failure to improve with diuresis, there was concern for infection vs cyclophosphamide toxicity. Infectious evaluation with BAL was negative and he was started on steroids with improvement in symptoms. However, pathology returned with findings consistent with DASA.His clinical presentation and rapid improvement with prednisone indicate a component of cyclophosphamide toxicity causing hypoxemia. His pathology findings and persistent reduction in DLCO suggest DASA also contributed to his hypoxemia. CONCLUSIONS: DASA and cyclophosphamide toxicity are uncommon causes of respiratory failure and have nonspecific findings on CT imaging. Distinguishing these etiologies can be challenging without bronchoscopy and histological samples. REFERENCE #1: Khoor A, Colby TV. Amyloidosis of the Lung. Arch Pathol Lab Med. 2017 Feb;141(2):247-254. doi: 10.5858/arpa.2016-0102-RA. PMID: 28134587. REFERENCE #2: Malik SW, Myers JL, DeRemee RA, Specks U. Lung toxicity associated with cyclophosphamide use. Two distinct patterns. Am J Respir Crit Care Med. 1996 Dec;154(6 Pt 1):1851-6. doi: 10.1164/ajrccm.154.6.8970380. PMID: 8970380. REFERENCE #3: Rossi SE, Erasmus JJ, McAdams HP, Sporn TA, Goodman PC. Pulmonary drug toxicity: radiologic and pathologic manifestations. Radiographics. 2000 Sep-Oct;20(5):1245-59. doi: 10.1148/radiographics.20.5.g00se081245. PMID: 10992015. DISCLOSURES: No relevant relationships by David Dennis, source=Web Response No relevant relationships by David Zaas, source=Web Response