Pulmonary sarcoidosis

More than a century after its discovery by Boeck, the cause of sarcoidosis remains unknown. However, recent research has revealed susceptibility genes on chromosome 5 and 6. The large US ACCESS study identified potential triggers that suggest infectious or other environmental agents play a role in the genesis of the disease. Diagnosis still depends on clinical evaluation, chest radiography, lung function testing, measurement of serum angiotensin-converting enzyme (ACE), tissue biopsy where indicated, and exclusion of other granulomatous disease. Treatment strategies have remained largely unchanged for two decades. No long-term systemic therapy is usually needed for the common presentation of Löfgren's syndrome (bilateral hilar lymphadenopathy (BHL), erythema nodosum (EN), transient iritis). Corticosteroids remain the drugs of first choice and are effective in suppressing tissue inflammation. They are indicated for all patients presenting with pulmonary infiltrates and impaired lung function, or for those with critical extrathoracic organ dysfunction or hypercalcaemia. However, in a number of cases, adverse effects are sufficient to prompt the introduction of corticosteroid-sparing immunosuppressive agents such as methotrexate and azathioprine, or hydroxychloroquine. Anti-tumour necrosis factor α agents, such as infliximab, have proved disappointing in pulmonary sarcoidosis but may have a useful niche role in some cases with refractory extrapulmonary disease as a supplement to other therapies. Methylphenidate may have a role in sarcoidosis-related fatigue. Pulmonary hypertension, with or without left ventricular dysfunction, may complicate advanced pulmonary sarcoidosis. This latter is associated with a higher mortality rate due to various forms of sarcoid-related pulmonary vasculopathy. Treatment options include epoprostenol, sildenafil or bosentan. Lung transplantation is successful in end-stage fibrotic disease, but sarcoid granulomas may reoccur in the allograft and fungal contamination of fibro-bullous cavities may confer increased post-operative risk of systemic infection.