Reduced survival in microscopic polyangiitis patients with pulmonary fibrosis in a respiratory referral centre

Abstract

We read with interest the article by Fernández-Casares et al. [1]. Pulmonary fibrosis (PF) seems to be a growing complication arising during the long-term evolution of microscopic polyangiitis (MPA). It seems, though, as when compared to idiopathic pulmonary fibrosis, it holds still a better prognosis than the latter [2].We want to share our observations regarding survival and differences in patients with MPA who developed PF or not. As in the case of the above-cited report, our patients attend a respiratory centre. Since November 2013 and until December 2014, 40 patients (mean age 54.2 years) have been diagnosed with MPA (according to the 2012 Chapel Hill Nomenclature Consensus) [3] at our institution. Ninety percent were MPO-ANCA, 5 % PR3-ANCA and 2.5 % double positive by indirect immunofluorescence. At the time of last follow-up since first symptoms of disease (median 43 months, range 11-213), 17 (42.5 %, nine males and eight females) have developed PF (two were histologically proven, and the rest was clinically and tomographically compatible with usual interstitial pneumonia [4]), with 14 developing PF prior to other MPA manifestations. Main clinical differences were as follows: gender (18 females without PF and 8 with PF; p=0.04), a higher frequency of myalgias (9 vs 3; p=0.008), nasal crusting and peripheral neuropathy (3 vs 0 for both findings; p=0.02), a lower frequency of diffuse alveolar haemorrhage (6 vs 15; p= 0.04), acute respiratory failure (1 vs 8; p=0.02), haematuria (6 vs 13; p=0.003) and lymphopaenia (0 vs 5; p=0.01) in those with PF. The latter also had higher Hb at presentation (mean 12.1 vs 10.6 g/dL; p=0.047), lower ESR (mean 18.8 vs 30.8; p=0.02) and higher damage as measured by the Vasculitis Damage Index [5] (mean 4.6 vs 2.6; p=0.008). At diagnosis, activity (BVAS score) [6] did not differ.By means of Kaplan-Meier analysis, we found that survival is decreased in those who develop PF by almost half. As shown in the figure, considering either the time of first MPA symptom (Fig. 1a) or the time from diagnostic confirmation (Fig. 1b), those with PF have shorter life expectancy than those without. Median survival of the whole group was 98 months, 104 for those with PF and 212 for those without. There were nine deaths, seven with PF and two without PF.These observations are in accordance with previous reports from different parts of the world, including the recent one from Latin America [1,7,8], in which it has also been observed that an important percentage of patients may present with PF before other disease characteristics appear [7]. The influence of ethnics on such outcome seems minimal, although a larger number of patients and longer follow-up is needed to conclusively state this. It is interesting that those without PF were predominantly females. Gender was independent from others not found to be distinct (laboural, tobaccoism) which may predispose males to develop PF more frequently. In trying to establish factors leading to MPA development in PF patients, eosinophils in BAL and low att...

Interstital lung disease in ANCA vasculitis

“…Pulmonary manifestations include progressive breathlessness (30–100%), alveolar hemorrhage (21–49%) and chronic cough (23–84%) [15,17,18, 20,48,51]. Of note, when comparing MPA patients with and without PF, some authors have reported that the first usually exhibited less severe systemic inflammatory response, manifested as lower ESR, higher levels of hemoglobin and importantly, reduced frequency of clinical evident diffuse alveolar hemorrhage, peripheral nerve and kidney involvement [19,20]. …”

“…Most of the series that compare MPA patients with and without PF reported that ILD was associated with poor prognosis and reduced survival [13,15,17,26,96]. In two recent publications, mortality was 2 to 4 times higher in MPA patients with PF [7,19]; although this has not been confirmed by others [18]. …”

“…Mean time from presentation to death was 3.5–6 years [13,17,18,58]. In addition, 5-year survival was only 29–60% [13,18,19,55]. Primary causes of death include acute exacerbations, sepsis and progressive lung involvement with end stage respiratory failure [15,17,18,51,58].…”

The Respiratory System in Autoimmune Vascular Diseases

“…Pulmonary fibrosis may precede other disease manifestations by a range of 5-108 months, but would not occur after the diagnosis of MPA [65,67]. The prognosis of MPA with pulmonary fibrosis is worse than that of MPA without pulmonary fibrosis and seems to be better than that of patients with idiopathic pulmonary fibrosis [65,67,68].…”

Diagnosis and treatment of ANCA-associated interstitial lung disease

“…Легочные симптомы включают в себя прогрессирующую одышку (30-100%), кровохарканье (21-49%) и кашель (23-84%) [29,38,39]. Следует отметить, что у пациентов с МПА-ИЗЛ реже выявляют признаки системного воспаления, что выражается в более низком уровне СОЭ, более высоком уровне гемоглобина, и, что важно, в меньшей частоте таких проявлений васкулита, как ДАК, поражение периферической нервной системы и почек [29,40].…”