Ahmed, N.

Abstract Introduction: Eosinophilic Granulomatosis with Polyangiitis (EGPA) is an ANCA-associated vasculitis (AAV) that causes eosinophil-rich granulomatous vasculitis affecting small vessels. While pulmonary manifestations of EGPA are diverse, development of pulmonary fibrosis is rare. We present two cases of EGPA with pulmonary fibrosis.Case 1: A 31-year-old female with refractory asthma, chronic rhinosinusitis, recurrent ear infections, presented with productive cough, dyspnea, wheeze with relief from antibiotics and steroids. Labs noted peripheral eosinophilia, elevated IgE, P-ANCA positivity with equivocally positive PR3 antibody. CT chest revealed bilateral lower lobe predominate honeycombing, traction bronchiectasis, subpleural reticulations indeterminate for UIP. Pulmonary function tests (PFTs) noted complex restriction with mildly reduced diffusion capacity of carbon monoxide (DLCO). Exhaled nitric oxide (ENO) was elevated at 132 parts per billion (ppb) (normal <39 bbp). Bronchoalveolar lavage (BAL) demonstrated eosinophilia. CT of the sinuses, infectious workup, anti-cyclic citrullinated peptide antibody (CCP), and genetic testing for hypereosinophilia were negative. Treatment with prednisone and Mepolizumab months led to significant improvement of respiratory symptoms.Case 2: A 69-year-old man with refractory allergic rhinitis and chronic sinusitis, gastroesophageal reflux (GERD) presented with eight years of chronic productive cough, dyspnea on exertion, weight loss, dysphagia. Labs noted peripheral eosinophilia, elevated IgE, isolated P-ANCA positivity. CT chest noted peripheral predominant reticulations, traction bronchiectasis, and ground-glass opacities indeterminate for UIP. PFTs noted severe restrictive pattern with reduced DLCO. ENO was elevated at 54 ppb (normal <30 ppb). CT of sinuses noted bilateral mucosal thickening and polyps. BAL and biopsies were unable to be performed prior to prednisone initiation given severity of symptoms and hypoxemia. Prednisone led to dramatic symptom improvement. Mepolizumab initially added but discontinued due to side effects and he denied Mycophenolate due to concern for side effects.Discussion: While pulmonary fibrosis in patients with P-ANCA and MPO positive microscopic polyangiitis (MPA) has been well described, it is rare in EGPA. In cases of ILD associated with EGPA, usual interstitial pneumonia (UIP) is the most common imaging finding, with nonspecific interstitial pneumonia (NSIP) and unclassified interstitial lung disease (ILD) also reported. Fibrosis develops either secondary to eosinophilic release of profibrotic and inflammatory cytokines and deficiency of anti-inflammatory neutrophil extracellular traps (NET), as described with idiopathic eosinophilic pneumonia, or due to overlap with MPA. Similar to MPA, fibrosis in our cases preceded development of systemic vasculitis, although many cases of AAV with pulmonary fibrosis report concomitant systemic vasculitis. Despite adequate initial treatment, fibrosis may progress, requiring antifibrotics.