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.