Semin Respir Crit Care Med 2018; 39(04): 411-412
DOI: 10.1055/s-0038-1673370
Preface
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Pulmonary Vasculitis and Alveolar Hemorrhage

Loïc Guillevin
1   Department of Internal Medicine, Cochin Hospital, Referral Center for Rare Systemic and Autoimmune Diseases, University Paris Descartes, Paris, France
› Author Affiliations
Further Information

Publication History

Publication Date:
07 November 2018 (online)

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Loïc Guillevin, MD

Since the previous journal issue published on the same topic a decade ago, notable progress has been made in the classification, evaluation, and treatment of lung vasculitides and understanding their pathogenic mechanisms. This state-of-the-art report on lung vasculitides and alveolar hemorrhage gives the reader the opportunity to discover the most recent advances.

The revised 2012 version of the Chapel Hill Nomenclature classified the histological and clinical characteristics of vasculitides, and more precisely defined small-sized vessel vasculitides. Some of them were attributed to antineutrophil cytoplasm antibodies (ANCAs) or other autoantibodies. Goodpasture's syndrome (also known as antiglomerular basement membrane vasculitis) is now considered a small-sized vessel vasculitis. Alveolar hemorrhage is the consequence of capillaritis and its mechanism is common to most small-sized vessel vasculitides, suggesting that they should also be treated alike, that is, with corticosteroids, immunosuppressants or rituximab, and plasma exchanges.

Notably, the place of ANCA, as a diagnostic marker of vasculitis, a predictor of relapses and perhaps an indicator of treatment choice and duration, has been better elucidated. Also, ANCA-associated lung fibrosis has emerged as a new entity that is not systematically observed in all vasculitis patients. It is an autonomous disease implicating antimyeloperoxidase antibodies, which should be systematically sought in patients with interstitial pneumonia.

Targeted biotherapies, that is, monoclonal antibodies, represent the most remarkable advancement in therapeutic strategies. For granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA), rituximab, an anti-CD20 chimeric mouse–human monoclonal immunoglobulin G antibody, has been proven to be noninferior to cyclophosphamide to induce the remission of systemic disease. Although it is too early to switch all GPA and MPA patients from cyclophosphamide to rituximab, observations favoring rituximab as first-line treatment are increasing. However, efficacy alone cannot explain this treatment choice; its safety must also be taken into account. Over the long term, the frequency of side effects is comparable for patients treated with immunosuppressants or rituximab, but the latter has the highly desirable advantage of having no toxic effect on fertility and does not cause malignancies.

Regarding remission maintenance therapy, rituximab now holds a prominent position and its superiority to azathioprine will probably change treatment perspectives in a near future. It is also likely that maintenance therapy with azathioprine, and probably methotrexate or mycophenolate mofetil, which cannot be considered superior to azathioprine, is no longer relevant for patients initially treated with rituximab. Since rituximab has been used for remission induction, the need for maintenance has been questioned. Apparently, remission maintenance remains necessary. The relapse rate after stopping rituximab—without subsequent maintenance therapy—can be evaluated at around 50% at 2 years, especially for antiproteinase-3 ANCA-positive patients.

In contrast, among patients prescribed rituximab for maintenance, only 5% had relapsed at 28 months and 50% at 60 months after starting maintenance (28 and 72%, respectively, with azathioprine). Future therapeutic recommendations should probably include rituximab as a, if not, major agent of remission maintenance. In addition, based on prospective trial results, trying to prolong intervals between rituximab reinfusions is also suggested. At present, the optimal treatment duration is not known, but ongoing studies will hopefully answer this question soon.

In the update on eosinophilic GPA (EGPA), several major points are emphasized: (1) the phenotypic and genotypic heterogeneities of the disease; (2) the severity of some clinical manifestations, such as cardiomyopathy, which occurs more frequently in ANCA-negative patients; and (3) the therapeutic impact of residual asthma, which requires long-term steroids with their potentially severe adverse events. The beneficial role of rituximab in EGPA patient care has not yet been established and studies are ongoing. A recent prospective trial demonstrated the efficacy of mepolizumab, an anti-interleukin-5 monoclonal antibody, on corticosteroid-sparing and relapse prevention. Indeed, treatment strategies for EGPA could be dramatically modified in the near future based on the promising results obtained with these new targeted biotherapies.