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Th17-polarized effector T cells have been detected in sarcoidosis granulomas, blood, and bronchoalveolar lavage fluids from patients with pulmonary sarcoidosis, and the Th17 effector response (including the production of interferon-γ) may influence the course and severity of sarcoidosis.
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21 T helper cells produce IL-2 and interferon gamma, which increase immune cell proliferation and cytotoxicity, respectively. Along with other inflammatory cytokines, activated macrophages avidly express tumor necrosis factor (TNF)-α, which, through stimulating naive CD4 + T cells, appears critical for the formation and maintenance of sarcoid granulomas. 20 Granulomas are composed of epithelioid macrophages and CD4 + T helper cells surrounded by a ring of fibroblasts with scattered B cells and CD8 + cytotoxic T cells at the periphery. The accumulation of granulomas that disrupt normal tissue microarchitecture and cause organ dysfunction is a central feature of sarcoidosis. Mechanisms of Inflammation and Granuloma Formation In this review, we discuss the pathophysiology, diagnosis, and treatment of NS, emphasizing clinically relevant updates. 7, -, 9 Over the last several years, there have been important advances in diagnosis and treatment for sarcoidosis and NS. 5 Although sarcoidosis is classically considered a multisystem disease, including by American Thoracic Society sarcoidosis diagnostic criteria, 6 approximately 10%–20% of patients with NS do not have identifiable systemic sarcoidosis (termed isolated NS). 4 Neurologic manifestations are the presenting syndrome in 50%–70% of patients with NS, and a meta-analysis of 1,088 patients with NS found that only 31% had systemic disease at presentation, whereas 84% eventually developed systemic manifestations. Clinically occult NS is identified at autopsy in 15%–25% of patients, and a 2017 study identified NS in 234/290 (34%) of patients with systemic sarcoidosis. NS was historically reported to occur in 5%–10% of all patients with sarcoidosis, although this number could reflect sampling bias from pulmonary sarcoidosis-focused cohorts. Neurologic involvement of sarcoidosis (neurosarcoidosis, NS) can involve the CNS or peripheral nervous system (PNS) or both and can cause substantial morbidity. 1 Compact, well-formed, coalescent non- or minimally necrotizing epithelioid granulomas with scattered lymphocytes are pathologic hallmarks of the disease. Sarcoidosis is an immune-mediated disorder characterized by granulomatous inflammation of affected organs.
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