We searched Medline and the Cochrane Library for reviews and original articles on sarcoidosis published in English from January 1, 2000, to January 1, 2013. We used the search term: “sarcoidosis [MeSH]” in combination with the following terms: “diagnosis [MeSH]”, “etiology [MeSH]”, “epidemiology [MeSH]”, “therapeutics [MeSH]”, or “therapy [Subheading]” or “drug therapy [MeSH]”, “follow-up studies [MeSH]”, or “treatment outcome [MeSH]”. We chose papers mainly from the past 5 years, although we
SeminarSarcoidosis
Introduction
Sarcoidosis was recognised more than 120 years ago, and it remains a confusing disease with many grey areas.1 The cause of sarcoidosis is not known and diagnosis can be difficult and delayed from the diverse, nonspecific, unusual, or initially misleading presentations. Many advances have been made since the previous seminar on sarcoidosis in The Lancet,2 and the publication of other reviews.3, 4 The indications for endobronchial ultrasound and for 18F-fluorodeoxyglucose (18F-FDG) PET have been elucidated further, and occurrence of persistent disabling symptoms such as fatigue, small-fibre neuropathy, and cognitive dysfunction have been investigated further. Recognition of health status and quality-of-life impairments has improved. These advances and efforts to accurately assess the development of disease have provided a more comprehensive and personalised care for patients. However, important steps are still needed, such as more accurate biomarkers, improving diagnosis of some extrapulmonary localisations, validated endpoints, and treatments that are efficient in refractory cases. The most important step is to provide evidence on the cause of sarcoidosis.
Section snippets
Epidemiology
Sarcoidosis is a global disease, with a prevalence of about 4·7–64 in 100 000, and an incidence of 1·0–35·5 in 100 000 per year. The highest rates are reported in northern European and African–American individuals, particularly in women, and lowest in Japan.5, 6 Differences in prevalence and incidence are linked to age, sex, ethnic origin, and geographical location. The disease can occur in both men and women, with 70% of patients aged 25–45 years; however, in Europe and Japan, a second peak of
Causes
The exact cause of sarcoidosis is still not known. Many studies suggest that genetic susceptibility and environmental factors contribute to disease development.2, 9, 14 Immunologically, sarcoidosis is an exaggerated immune response to so far unidentified antigens. Data for the clinical heterogeneity of sarcoidosis strongly suggest that pathogen-associated molecular patterns of microbial antigens can trigger or amplify inflammation. There is no evidence that sarcoidosis is an infectious disease;
Diagnosis
There have been several new insights in the diagnosis of sarcoidosis (figure 1 ). Endobronchial ultrasound-guided transbronchial needle aspiration is a highly effective investigation for mediastinal and hilar lymphadenopathy, and can prevent the need for 87% of mediastinoscopies.42 Moreover, rapid on-site assessment by well trained cytologists provides sufficient diagnostic information for the bronchoscopist about the need for additional lymph-node passes or transbronchial lung biopsy samples,43
Clinical course and prognosis
The clinical course for sarcoidosis varies (appendix p 3). In half of cases, disease resolves spontaneously within 2 years, and does so in many other cases within 5 years. After 5 years, remission is much less likely.1, 31, 94 These different outcomes have led to the classification of sarcoidosis into acute (≤2 years) and chronic (≥3–5 years) phenotypes.1, 31, 94 Refractory sarcoidosis refers to patients progressing despite treatment.3 The main concerns with chronic sarcoidosis are fibrosis
Treatment
There is no cure for sarcoidosis, and treatment only changes the granulomatous process and its clinical consequences. The mechanisms of action for drugs that are used in sarcoidosis are only partly understood (table 2). Most drugs target TNFα, which has a crucial role in the initiation and perpetuation of the granulomatous response. Debate exists about whether treatment can change the outcome of sarcoidosis, particularly fibrosis.1 No firm guidelines exist on whether, when, and how treatment
Conclusions
Sarcoidosis has many manifestations, its prognosis is difficult to predict, and its evolution and severity vary hugely from case to case. A personalised and multidisciplinary approach might be needed to address these challenges and prevent quality-of-life impairment and potential adverse effects of treatment.
Search strategy and selection criteria
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