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H Ahmadzai, S Huang, C Steinfort, J Markos, RK Allen, D Wakefield, M Wilsher and PS Thomas
Abstract
Sarcoidosis is a systemic disease of unknown aetiology, characterised by non-caseating granulomatous inflammation. It most commonly manifests in the lungs and intrathoracic lymph nodes but can affect any organ. This summary of an educational resource provided by the Thoracic Society of Australia and New Zealand outlines the current understanding of sarcoidosis and highlights the need for further research. Our knowledge of the aetiology and immunopathogenesis of sarcoidosis remains incomplete. The enigma of sarcoidosis lies in its immunological paradox of type 1 T helper cell-dominated local inflammation co-existing with T regulatory-induced peripheral anergy. Although specific aetiological agents have not been identified, mounting evidence suggests that environmental and microbial antigens may trigger sarcoidosis. Genome-wide association studies have identified candidate genes conferring susceptibility and gene expression analyses have provided insights into cytokine dysregulation leading to inflammation. Sarcoidosis remains a diagnosis of exclusion based on histological evidence of non-caseating granulomas with compatible clinical and radiological findings. In recent years, endobronchial ultrasound-guided transbronchial needle aspiration of mediastinal lymph nodes has facilitated the diagnosis, and whole body positron emission tomography scanning has improved localisation of disease. No single biomarker is adequately sensitive and specific for detecting and monitoring disease activity. Most patients do not require treatment; when indicated, corticosteroids remain the initial standard of care, despite their adverse side effect profile. Other drugs with fewer side effects may be a better long term choice (eg, methotrexate, hydroxychloroquine, azathioprine, mycophenolate), while tumour necrosis factor-α inhibitors are a treatment option for patients with refractory disease.
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