Pulmonary Sarcoidosis
Allen P. Burke, M.D.
Marie-Christine Aubry, M.D.
Seth Kligerman, M.D.
Definition
Sarcoidosis is a systemic disease characterized histologically by the presence of nonnecrotizing granulomas, with lung involvement occurring in up to 90% of patients. The etiology of sarcoidosis is thought to be multifactorial but ultimately remains unknown.1
Pathophysiology
The stimulus for granuloma formation involves antigen-presenting cells, human leukocyte antigen (HLA) class II molecules, and T-cell receptors.1 Several HLA-DR, DQ, and DP alleles have been shown to increase the risk of sarcoidosis in a race-dependent way.1 Mutations in non-HLA-related proteins have been shown to be associated with sarcoidosis, including butyrophilin-like 2 (BTNL2) in Caucasians.
The granuloma in sarcoidosis is composed of epithelioid histiocytes and giant cells derived from monocytes and CD4+ T lymphocytes. Experimental studies have shown important roles for interleukin-γ, interferon-α, and tumor necrosis factor (TNF) in the development of these granulomas. Bioinformatic studies have shown an involvement of the STAT1 pathway (signal transducer and activator of transcription 1). The identification of the inciting antigen has remained elusive, but recurrence in transplant patients indicates that host immunity and an exogenous factor are both necessary for the development of sarcoidosis. Candidates for the trigger of sarcoidosis include a variety of
proteins, especially those related to Mycobacterium tuberculosis, and other antigens based on ethnicity and geography.
proteins, especially those related to Mycobacterium tuberculosis, and other antigens based on ethnicity and geography.
Clinical Findings
Sarcoidosis is more prevalent in African American than in Caucasians and Asians. There is no sex predilection, and patients are usually young, between 20 and 50 years old. The clinical presentation of sarcoidosis varies according to the organ(s) of involvement. Most patients are asymptomatic at diagnosis. Symptoms are nonspecific. Systemic symptoms are common and include low-grade fever, night sweats, and fatigue. Pulmonary symptoms, when present, include dyspnea and cough. Occasionally, spontaneous pneumothorax may be the initial presentation.2,3 Pulmonary function tests may show restriction due to parenchymal lung involvement and/or obstruction. Obstruction may be caused by endobronchial disease, bronchial stenosis, distortion of airways, or increased airway reactivity.
Pulmonary hypertension occurs in 5% to 15% of asymptomatic patients, 50% of patients with symptomatic pulmonary sarcoidosis, and at higher frequencies in patients requiring transplant. The etiology of pulmonary hypertension in pulmonary sarcoidosis is multifactorial and includes vascular involvement and interstitial fibrosis.4,5,6,7
Radiologic Findings
Pulmonary sarcoid is staged by radiographic findings of mediastinal lymph nodes and lung fields (Table 22.1; Figs. 22.1 and 22.2). Reticulonodular densities correspond to granulomatous infiltrates. Stage 4 disease is characterized by cystic change, and traction bronchiectasis, corresponding to fibrosis. Lymph nodes are thought to regress in size with more advanced disease, secondary to scarring.
Gross Findings
At explant or autopsy, pulmonary sarcoidosis is typically bilateral and symmetric. Areas of granulomatous inflammation in the parenchyma resemble consolidation, typically centrally predominating over peripheral lesions. Scarring occurs in a lymphatic distribution (bronchovascular bundles, interlobular septa, and pleura), also with a central predominance. Scarring can cause secondary bronchiectasis and cystic change, but in contrast to idiopathic pulmonary fibrosis, subpleural cysts are uncommon (Fig. 22.3).
Tissue Sampling
The diagnosis is made either by finding of nonnecrotizing granulomas on bronchial biopsy or by biopsy of mediastinal lymph nodes. The latter can be accomplished by mediastinoscopy or by transbronchial needle aspiration (TBNA). The yield of TBNA is increased if there is endobronchial ultrasound (EBUS) guidance and as high as 90% in enlarged lymph nodes.1 The rate of positive bronchial biopsy is 40% (Fig. 22.4).8 The yield of finding granulomas in bronchial biopsies is high due to the common airway involvement by the granulomas in sarcoidosis.
TABLE 22.1 Clinical Stages of Pulmonary Sarcoidosis, by Chest Radiograph | ||||||||||||
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