Pulmonary Fibrosis in Antineutrophil Cytoplasmic Antibodies (ANCA)-Associated Vasculitis

Pulmonary fibrosis (PF) is an uncommon manifestation observed in patients with antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV), particularly microscopic polyangiitis (MPA). While patients with PF associated with AAV seem to e Brun, MD, Philip D, avid Saadoun, MD, PhD patients with PF associated with AAV, fulfilling the American College of Rheumatology criteria and/or Chapel Hill definitions. Forty-nine patients (30 men [61%]; median age at diagnosis of AAV, 68 [interquartile range, 58–73] years) with PF associated with AAV were identified. Forty (81.6%) patients had MPA and 9 (18.4%) had granulomatosis with polyangiitis. The diagnosis of PF preceded the onset of vasculitis in 22 (45%) patients. Usual interstitial pneumonia was the main radiologic pattern (n1⁄4 18, 43%). ANCA were mostly of antimyeloperoxidase specificity (88%). All patients were treated with glucocorticoids as induction therapy, combined with cyclophosphamide (CYC) (n1⁄4 36, 73.5%) or rituximab (RTX) (n1⁄4 1, 2%). Factors associated with mortality included occurrence of chronic respiratory insufficiency (hazard ratio [HR], 7.44; 95% confidence interval [CI], 1.6–34.5; p1⁄4 0.003), induction therapy with glucocorticoids alone (HR, 2.94; CI, 1.05–8.33; p1⁄4 0.04), and initial weigh loss (HR, 2.83; CI, 1.05–7.65; p1⁄4 0.041). The 3-year survival rate in patients treated with glucocorticoids alone or combined with an immunosuppressant (CYC or RTX) as induction therapy was 64% (95% CI, 41–99) and 94% (95% CI, 86– 100), respectively (p1⁄4 0.03). After a median follow-up of 48 months [interquartile range, 14–88 mo], 18 (37%) patients died, including 11 related to respiratory insufficiency. PF is a rare manifestation of AAV with a very poor prognosis. Induction therapy with CYC might improve the outcome. (Medicine 2014;93: 340–349) Abbreviations: ANCA = antineutrophil cytoplasmic antibodies, AAV = antineutrophil cytoplasmic antibodies-associated vasculitides, BAL = bronchoalveolar lavage, CI = confidence interval, CPFE = combined pulmonary fibrosis-emphysema, CYC = cyclophosphamide, EGPA = eosinophilic granulomatosis with polyangiitis, GPA = granulomatosis with polyangiitis, HR = hazard ratio, HRCT = high-resolution computed tomography, IQR = interquartile range, MPA = microscopic polyangiitis, MPO = myeloperoxidase, NSIP = nonspecific interstitial pneumonia, PF = pulmonary fibrosis, RA = rheumatoid arthritis, RTX = rituximab, UIP = usual interstitial pneumonia. INTRODUCTION NCA-associated vasculitides (AAV) are a type of systemic itis affecting smalland medium-sized ssociated with the presence of antiantibody (ANCA). AAV represent a olume 93, Number 24, November 2014 heterogeneous group of diseases including microscopic polyangiitis (MPA), granulomatosis with polyangiitis (GPA, formerly Wegener’s), and eosinophilic granulomatosis with polyangiitis (EGPA, formerly Churg-Strauss syndrome). The specific clinical phenotypes of these 3 distinct AAV are often distinguished based on initial presentation and ANCA specificity. Because of therapeutic considerations involving the use of glucocorticoids alone or combined with cyclophosphamide (CYC) or rituximab (RTX), the identification of characteristics at AAV diagnosis as prognostic factors is a major concern for clinicians. Conventional treatment of AAV includes a strategy of remission induction using glucocorticoids alone or combined with CYC or RTX, depending on characteristics at AAV diagnosis and the severity of initial manifestations that are not consensually defined, followed by maintenance therapy using azathioprine or methotrexate. Pulmonary fibrosis (PF) occurs in variable frequency in connective tissue diseases such as systemic sclerosis, rheumatoid arthritis (RA), polymyositis/dermatomyositis, and mixed connective tissue disease, and is often associated with a poor prognosis. PF is an uncommon manifestation also observed in patients with AAV, particularly microscopic polyangiitis. Patients with PF and AAV have been reported only in different small retrospective case series but tend to share characteristics such as male predominance, older age, the presence of myeloperoxidase (MPO)-ANCA, usual interstitial pneumonia (UIP) pattern, and poor prognosis. However, the pathogenesis of PF in AAV, the outcome and the possible link between PF, ANCA positivity and specificity, and vasculitis remain unclear. Moreover, the impact of therapeutic strategies on outcome of patients with PF and AAV has been analyzed only sporadically. We conducted the current study to describe the main features and the long-term outcome of PF in AAV in a cohort of 49 patients.