Pulmonary Sarcoidosis

Background

• Pulmonary sarcoidosis refers to the pulmonary manifestations of a systemic disease of unknown cause resulting in the formation of immune granulomas.
• Genetic predisposition is likely, with first- and second-degree relatives at an increased risk of developing pulmonary sarcoidosis and known human leukocyte antigen (HLA) genotype associations.
• Possible environmental triggers include mycobacteria, propionibacteria, and particulate dust exposures.
• The majority of cases present in patients aged 25-45 years, with a second peak of incidence in women at age 50 years in Europe and Japan. It rarely presents at < 15 years old or at > 70 years old.
• About 50% of cases will spontaneously remit, usually within 5 years, but the disease has a variable and unpredictable course.
• Patients presenting with acute Lofgren syndrome have a particularly good prognosis.
• Pulmonary complications of interstitial lung disease and pulmonary hypertension are the most common causes of sarcoidosis-related mortality.

Evaluation

• Patients may be asymptomatic with radiographic presentation only or may present with dyspnea, cough, wheezing, chest pain, fatigue, or malaise.
• Physical exam is often normal but can present with erythema nodosum (in Lofgren syndrome), with parotid gland swelling, uveitis, and fevers (Heerfordt syndrome), as well as other possible skin manifestations such as lupus pernio.
• To diagnose sarcoidosis, obtain a biopsy of the most accessible organ involved (for example, skin, peripheral lymph nodes, lacrimal glands, or conjunctiva).
  • For suspected pulmonary sarcoidosis, endobronchial ultrasound-guided transbronchial needle aspiration is often the first procedure performed to prevent the need for mediastinoscopy.
  • Diagnosis is confirmed by the histological presence of noncaseating granuloma and with the exclusion of other causes.
  • Biopsy may not be needed in patients with Lofgren syndrome presentation.
• To assess pulmonary involvement
  • Obtain a set of posteroanterior and lateral chest x-rays. Chest x-ray classically shows bilateral hilar adenopathy with right paravertebral adenopathy and a variable degree of interstitial parenchymal inflammation or scarring.
  • Consider pulmonary function tests to assess the extent and severity of pulmonary function impairment.

Management

• Treatment may not be necessary as most patients are not disabled by sarcoidosis. Generally the decision to treat pulmonary sarcoidosis is guided by risk of severe disability, irreversible damage to major organs, or death; and/or presence of incapacitating symptoms.
• First-line treatment is oral corticosteroids, which should be initiated in patients with major pulmonary involvement and higher risk for mortality or morbidity, such as reduced forced vital or diffusing capacity, moderate-to-severe pulmonary fibrosis, or precapillary hypertension (Strong recommendation). Other factors that may indicate treatment include progressive disease, significant symptoms, or extrapulmonary disease.
• Consider a dosing of prednisolone or other steroid at 0.5 mg/kg/day for 4 weeks, then a lower level that controls symptoms and disease progression for a period of 6-24 months (Weak recommendation).
• Consider methotrexate or other immunosuppressive agents in patients when corticosteroids are not effective or not tolerable (Weak recommendation), though the use of immunosuppressants or cytotoxic agents may be limited by severe adverse effects.
• Consider infliximab as a third line agent in patients who have already been receiving corticosteroids or other immunosuppressants (such as methotrexate) but have continued disease (Weak recommendation).
• Consider lung transplantation in patients with end-stage disease (Weak recommendation).
• For patients with sarcoidosis-related fatigue, consider pulmonary rehabilitation and/or inspiratory muscle strength training for 6-12 weeks (Weak recommendation).