title: Refractory pulmonary sarcoidosis - proposal of a definition and recommendations for the diagnostic and therapeutic approach.
abstract: Patients with sarcoidosis undergo spontaneous remission or may be effectively controlled with glucocorticoids alone in many cases. Progressive and refractory pulmonary sarcoidoisis constitute more than 10% of patients seen at specialized centers. Pulmonary fibrosis and associated complications, such as infections and pulmonary hypertension are leading causes of mortality. No universal definition of refractoriness exists, we therefore propose classifying patients as having refractory disease when the following criteria are fulfilled: (1) progressive disease despite at least 10 mg of prednisolone or equivalent for at least three months and need for additional disease-modifying anti-sarcoid drugs due to lack of efficacy, drug toxicity or intolerability and (2) treatment started for significant impairment of life due to progressive pulmonary symptoms. Both criteria should be fulfilled. Treatment options in addition to or instead of glucocorticoids for these patients include second- (methotrexate, azathioprine, leflunomide) and third-line agents (infliximab, adalimumab). Other immunmodulating agents can be used, but the evidence is very limited. Newer agents with anti-fibrotic properties, such as pirfenidone or nintedanib, might hold promise also for the pulmonary fibrosis seen in sarcoidosis. Treating physicians have to actively look for potentially treatable complications, such as pulmonary hypertension, cardiac disease or infections before patients should be classified as treatment-refractory. Ultimately, lung transplantation has to be considered as treatment option for patients not responding to medical therapy. In this review, we aim to propose a new definition of refractoriness, describe the associated clinical features and suggest the therapeutic approach.
authors.affiliation: Department of Nephrology and Rheumatology, University Medical Center Göttingen, Göttingen, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Korsten
authors.affiliation: Deparment of Pulmonary Medicine, University of Illinois Hospital and Health Science System, Chicago, IL, USA.
authors.forename: Katharina
authors.initials: K
authors.lastname: Strohmayer
authors.affiliation: Department of Medicine, University of Cincinnati Medical Center, Cincinnati, OH, USA.
authors.forename: Robert P
authors.initials: RP
authors.lastname: Baughman
authors.affiliation: Department of Rheumatology and Department of Pulmonary Medicine, University of Illinois Hospital and Health Science System, Chicago, IL, USA.
authors.forename: Nadera J
authors.initials: NJ
authors.lastname: Sweiss
keywords: biological agents; corticosteroids; interstitial lung disease; pulmonary sarcoidosis