Elsevier

The Lancet

Volume 361, Issue 9363, 29 March 2003, Pages 1111-1118
The Lancet

Seminar
Sarcoidosis

https://doi.org/10.1016/S0140-6736(03)12888-7Get rights and content

Summary

There have been several new insights into the cause and treatment of sarcoidosis. Studies of genetic variation have shown that specific genetic polymorphisms are associated with increased risk of disease or affect disease presentation. These polymorphisms include variation of MHC and cytokines such as tumour necrosis factor (TNF). Not all investigators have come to the same conclusion, suggesting an interaction of various factors, including the patient's ethnic origin. Treatment of sarcoidosis varies considerably. Patients with symptomatic disease for more than 2–5 years have been of particular interest. Corticosteroids remain the standard of care in such cases, but immunosuppressive drugs have proved steroid-sparing in many patients. New agents, including pentoxifylline, thalidomide, and infliximab have proved useful in selected cases. The effectiveness of these agents seems to lie in their ability to block TNF, especially in the treatment of chronic disease.

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

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.

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