Pubmed was used to search for published material on sarcoidosis and related inflammatory processes. Emphasis was placed for those articles published since January, 2000. Additionally, we used our own files and stored bibliographies on articles related to sarcoidosis.
SeminarSarcoidosis
Section snippets
Epidemiology
Sarcoidosis is a granulomatous disorder of unknown cause, affecting multiple organs. The cells of the granuloma are organised spatially as immune granulomas, the hallmark of sarcoidosis, and the result of an immunological response to an antigenic trigger. Although precise epidemiological studies have not been undertaken, there are several reasons why we might infer that an infective agent or agents might be the trigger(s), including spatial, seasonal, and occupational clustering.
An
Genetic susceptibility
Sarcoidosis is genetically a complex disease whose genetic predisposition is determined by the varying effects of several genes. There are various lines of evidence that would support this idea. First, there is variable prevalence and incidence in severity of the disease in individuals of different races and ethnic backgrounds. Second, there is a higher likelihood of developing sarcoidosis if a first-degree or second-degree family member has sarcoidosis,18 and this relative risk ranges from 36
Other genetic loci of interest
The MHC class II region of the genome is the most likely target region for identification of disease susceptibility, not only because of the microsatellite marker studies of Schürmann and co-workers22, but also because the class II genes determine presentation of antigen to the T cell at the initiation of the response that results in immune granuloma formation.39, 40, 41, 42 In other words, there is a functional as well as a linkage relevance to investigation of these genes.
Similarly, there are
Immunological response
There are two aspects of the granulomatous response of sarcoidosis–the initial event leading to granuloma formation, and the evolution of the response as either resolution or chronic disease. Figure 1 summarises what is known or suggested about this inflammatory response. The exact point when sarcoidosis starts is usually unclear. An exception may be Löfgren's syndrome of erythema nodosum, hilar adenopathy, and associated uveitis.49 Patients are generally symptomatic from the erythema nodosum
Diagnosis
The pathological finding of sarcoidosis is a granuloma. These granulomas are usually non-necrotising, but occasionally necrosis is seen.60 The finding of a granuloma is not specific for sarcoidosis, since many other conditions can cause granulomas.60, 61 Among the conditions that can be confused with sarcoidosis are tuberculosis and deep-seated fungal infections, but these usually have frank necrosis. Malignant diseases can also cause a granulomatous reaction, including lymphoma62 as well as
Treatment
The most satisfying therapy for the patient and physician in sarcoidosis is no treatment at all. For many patients, systemic treatment is not necessary for the disease.76 Systemic therapy varies between treatment centres, with some groups treating only a third of their patients,77, 78 and others more than two-thirds.79 For patients needing systemic therapy, there is a subgroup with chronic disease in whom disease does not resolve after 2–5 years.80 These chronic patients often need long-term
Conclusion
New molecular methods have allowed us to ask why patients develop sarcoidosis and why it is such a divergent disease. Continuing familial and sporadic studies in Europe and the USA should provide insight into the various candidate genes. The treatment for chronic sarcoidosis has become a specific goal of the physician. Among the strategies being explored are drugs that affect macrophage function, including the release of TNF α.
Search strategy
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Familial sarcoidosis is linked to the major histocompatibility complex region
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Role of HLA-DR antigens in Japanese patients with sarcoidosis
Am Rev Respir Dis
T-cell receptor variable region gene usage by CD4+ and CD8+ T cells in bronchoalveolar lavage fluid and peripheral blood of sarcoidosis patients
Proc Natl Acad Sci USA
Analysis of restriction fragment length polymorphism for the HLA-DR gene in Japanese patients with sarcoidosis
Thorax
Genetic aspects of sarcoidosis. Class II histocompatibility antigens and a family study
Arch Intern Med
TNF-alpha and HLA-DR genotyping as potential prognostic markers in pulmonary sarcoidosis
Eur Cytokine Netw
HLA-DR predicts the prognosis in Scandinavian patients with pulmonary sarcoidosis
Am J Respir Crit Care Med
The sarcoidosis map
Am J Respir Crit Care Med
HLA-DRB1 position 11 residues are a common protective marker for sarcoidosis
Am J Respir Cell Mol Biol
Analysis of HLA-DPB1 polymorphisms in African-Americans with sarcoidosis
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Case-control association studies for the genetics of complex respiratory diseases
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Increased frequency of the uncommon tumor necrosis factor 857T allele in British and Dutch patients with sarcoidosis
Am J Respir Crit Care Med
Genetic polymorphisms of the TNFB and HSP70 genes located in the human major histocompatibility complex in sarcoidosis
Tissue Antigens
Genetic polymorphisms at the tumour necrosis factor loci (TNFA and TNFB) in cardiac sarcoidosis
Tissue Antigens
Welsh KI, du BR. Analysis of MHC encoded antigen-processing genes TAP1 and TAP2 polymorphisms in sarcoidosis
Am J Respir Crit Care Med
Deletion polymorphism in the angiotensin I converting enzyme (ACE) gene as a genetic risk factor for sarcoidosis
Thorax
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