What is benign granulomatous disease of the lungs, also known as Sarcoidosis?

From the Guidelines

Benign granulomatous disease of the lungs, also known as Sarcoidosis, is a chronic, multisystem, granulomatous disease of unknown cause, most commonly seen in young and middle-aged adults, with pulmonary manifestations dominating the presentation in over 90% of cases. This condition is characterized by the formation of granulomas (small clusters of immune cells) in lung tissue that are non-cancerous and non-infectious in nature 1. The most common example is sarcoidosis, though the term also encompasses other conditions like hypersensitivity pneumonitis and berylliosis.

Key Characteristics

• The disease has protean clinical manifestations, although presentation with abnormalities of the lymphatic, pulmonary, ophthalmologic, or dermatologic systems are most common 1.
• Pulmonary manifestations generally dominate the presentation with > 90% of all patients with sarcoidosis having identifiable lung involvement 1.
• Symptoms may include shortness of breath, dry cough, chest pain, fatigue, and sometimes fever or weight loss.
• Diagnosis usually requires chest imaging (X-ray or CT scan), pulmonary function tests, and often a biopsy to confirm the presence of granulomas while ruling out infection or malignancy.

Treatment and Prognosis

• Treatment depends on symptom severity, with mild cases only needing monitoring, while more severe cases typically require corticosteroids like prednisone (starting at 20-40mg daily and gradually tapering) 1.
• Other immunosuppressants like methotrexate or azathioprine may be added for steroid-sparing effects in chronic cases.
• The prognosis is generally favorable, with many cases resolving spontaneously, though some patients develop chronic disease requiring long-term management 1.
• Recent studies have identified features associated with increased risk for death from pulmonary disease, including pulmonary hypertension, reduced lung function, and pulmonary fibrosis 1.

Recent Guidelines

• The European Respiratory Society (ERS) has developed new guidelines for treating sarcoidosis, which emphasize the importance of treating patients with symptomatic disease to prevent progression to irreversible disease 1.
• The guidelines also highlight the need to prioritize treatment for patients with troublesome fatigue and small-fibre neuropathy-associated symptoms 1.

From the FDA Drug Label

7 Respiratory Diseases Symptomatic sarcoidosis Sarcoidosis is a condition where the disease is symptomatic, as indicated in the drug label for prednisone, but the label does not provide a definition of the disease itself.

• The label only mentions sarcoidosis as one of the conditions for which prednisone is indicated, specifically for symptomatic cases. 2

From the Research

Definition and Prevalence of Sarcoidosis

• Sarcoidosis is a sterile non-necrotizing granulomatous disease without known causes that can involve multiple organs with a predilection for the lung and thoracic lymph nodes 3.
• It is estimated to affect 2-160/100,000 people worldwide 3, 4.
• The disease can involve virtually any organ, but it predominantly affects the lungs 4, 5.

Clinical Manifestations and Stages

• Pulmonary sarcoidosis can present with constitutional symptoms and computed tomographic scan findings of bilateral, symmetric micronodules in a peribronchovascular distribution with upper and middle lung zone predominance accompanied by bilateral, symmetric hilar lymphadenopathy 6.
• The Scadding stages for pulmonary sarcoidosis associate with clinical outcomes, with stages I and II having radiographic remission in approximately 30%-80% of cases 3.
• Stage III has a 10%-40% chance of resolution, while stage IV has no chance of resolution 3.
• Up to 40% of pulmonary sarcoidosis patients progress to stage IV disease with lung parenchyma fibroplasia, bronchiectasis with hilar retraction, and fibrocystic disease 3.

Treatment and Management

• First-line treatment for patients who are symptomatic with parenchymal infiltrates and abnormal pulmonary function testing is oral glucocorticoids, such as prednisone 3, 4.
• Prednisone can be tapered over 6-18 months if symptoms, spirometry, pulmonary function tests, and radiographs improve 3, 4.
• Prolonged use of oral glucocorticoids may be required to control symptoms and stabilize disease 3, 4.
• Second and third-line treatments include immunosuppressive agents, such as methotrexate and azathioprine, and anti-tumor necrosis factor medication 3, 7.

Complications and Mortality

• The mortality rate for sarcoidosis is approximately 7% within a 5-year follow-up period 3, 4.
• More than 60% of deaths from sarcoidosis are due to pulmonary involvement, although in Japan, more than 70% of deaths are due to cardiac involvement 3, 4.
• Up to 70% of patients with advanced pulmonary sarcoidosis develop precapillary pulmonary hypertension, which is associated with a 5-year mortality rate of approximately 40% 3, 4.