A CASE OF AUTOIMMUNE PULMONARY ALVEOLAR PROTEINOSIS WITH UNDERLYING MONOCLONAL B-CELL LYMPHOCYTOSIS

Abstract

SESSION TITLE: Fellows Diffuse Lung Disease Posters SESSION TYPE: Fellow Case Report Posters PRESENTED ON: October 18-21, 2020 INTRODUCTION: We describe a rare case of autoimmune pulmonary alveolar proteinosis (PAP) with a concurrent low-grade lymphoproliferative disorder. CASE PRESENTATION: A 47-year-old male nonsmoker with obesity, hypertension and type 2 diabetes with nephropathy was admitted to the ICU with fever, cough and dyspnea leading to acute hypoxemic respiratory failure requiring intubation. He had been hospitalized for “heart failure” 6 months prior to presentation, and his dyspnea had slowly progressed since then. He worked as a butcher. Three of his 1st-degree relatives had died from presumed heart failure between ages 44-54. Additional features of his presentation included Raynaud’s phenomenon, high CRP of 254 mg/L and no clinical signs of heart failure. Chest x-ray (CXR) demonstrated nonspecific patchy bilateral opacities. The CXR from 6 months ago showed similarly distributed, albeit less prominent, opacities (Fig 1). Chest CT revealed diffuse, bilateral ground-glass opacities (GGOs) with interlobular septal thickening (crazy-paving pattern), consolidation and mediastinal lymphadenopathy (Fig 2). TTE showed normal biventricular function. Rheumatologic workup was negative. BAL microbiology showed S. pneumoniae, which was treated. Periodic acid-Schiff (PAS) staining from BAL showed bright globular material consistent with PAP (Fig 3). Serum anti-GM-CSF antibody was positive. Bone marrow biopsy revealed monoclonal B-cell lymphocytosis involving 20% of the marrow with positive peripheral blood flow cytometry, mutated IGH-V, and negative TP53 mutation. The patient required bilateral whole lung lavage (WLL) on two occasions, one month apart. He was started on inhaled GM-CSF after the first WLL and rituximab was added subsequently. His course was complicated by massive pulmonary embolism requiring VA-ECMO support, acute kidney injury requiring dialysis, and critical illness myoneuropathy. He was discharged home after 84 days. DISCUSSION: PAP is classified into 3 groups: primary (autoimmune and hereditary), secondary, and congenital (1). PAP is diagnosed with positive PAS stain on BAL fluid or lung biopsy in combination with typical features on CT, including bilateral GGOs with interlobular septal thickening. The hallmark of primary, or autoimmune, PAP includes presence of autoantibodies to GM-CSF, which are not present in secondary PAP (2). Common etiologies of secondary PAP are hematologic malignancies, most commonly myeloid (3). Ascertaining the etiology of PAP is important, and guides the choice of therapy. For autoimmune PAP, treatment includes WLL and inhaled GM-CSF. For secondary PAP, treatment is directed at the underlying cause. CONCLUSIONS: This is one of the first reported cases of autoimmune PAP with a concurrent low-grade lymphoproliferative disorder. The patient improved with WLL, inhaled GM-CSF and rituximab. Reference #1: Trapnell BC, Nakata K, Bonella F, et al. Pulmonary alveolar proteinosis. Nat Rev Dis Primers. 2019 March 7;5(1):16. Reference #2: Kumar A, Abdelmalak B, Inoue Y, Culver DA. Pulmonary alveolar proteinosis in adults: pathophysiology and clinical approach. Lance Respir Med. 2018 Jul;6(7):554-565. Reference #3: Chaulagain CP, Pilichowska M, Brinckerhoff L, Tabba M, Erban JK. Secondary pulmonary alveolar proteinosis in hematologic malignancies. Hematol Oncol Stem Cell Ther. 2014 Dec; 7(4):127-35. DISCLOSURES: No relevant relationships by Simone Barreto Siqueira Parrilha T, source=Admin input No relevant relationships by Brittany Blass, source=Web Response No relevant relationships by Melanie Bois, source=Web Response No relevant relationships by Sumedh Hoskote, source=Web Response no disclosure on file for Mark Norton