Chest
Volume 139, Issue 1, January 2011, Pages 174-182
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Recent Advances in Chest Medicine
Recent Advances in Sarcoidosis

https://doi.org/10.1378/chest.10-0188Get rights and content

Sarcoidosis, a systemic granulomatous disease of undetermined etiology, is characterized by a variable clinical presentation and course. During the past decade, advances have been made in the study of sarcoidosis. The multicenter ACCESS (A Case Control Etiologic Study of Sarcoidosis) trial recruited > 700 subjects with newly diagnosed sarcoidosis and matched control subjects. Investigators were unable to identify a single cause of sarcoidosis, but ACCESS paved the way for subsequent etiologic studies. The Mycobacterium tuberculosis catalase-peroxidase protein has been identified as a potential sarcoidosis antigen. Genetic aspects of the disease have been elucidated further. Genome-wide scans have identified candidate genes. Gene expression analyses have defined cytokine dysregulation in sarcoidosis more clearly. Although the criteria for diagnosis have not changed, sarcoidosis remains a diagnosis of exclusion best supported by a tissue biopsy specimen that demonstrates noncaseating granulomas in a patient with compatible clinical and radiologic features of the disease. Endobronchial ultrasound-guided transbronchial needle aspiration of mediastinal lymph nodes has facilitated diagnosis, often eliminating the need for more invasive procedures, such as mediastinoscopy. PET scanning has proven valuable in locating occult sites of active disease. Currently, no reliable prognostic biomarkers have been identified. The tumor necrosis factor inhibitors, a relatively new class of agents, have been used in patients with refractory disease. It is unclear whether phosphodiesterase-5 inhibitors, prostaglandin analogs, or endothelin antagonists should be used for the treatment of sarcoidosis-associated pulmonary hypertension.

Section snippets

Etiology

Progress has been made in elucidating the cause of sarcoidosis. The ACCESS trial collected data on 704 patients with newly diagnosed, biopsy specimen-proven sarcoidosis and control subjects matched by age, sex, race, and geographic area.4 The study identified several environmental exposures modestly associated with sarcoidosis risk (OR, ∼ 1.5).8 The associated exposures included agricultural employment, mold or mildew, musty odors at work, and pesticide-using industries. Tobacco use was

Genetics

Genetic and host factors are involved in the pathogenesis of sarcoidosis (Fig 1).12 Twin studies indicate that monozygotic twins are more often concordant for disease than dizygotic twins.14 In the United States, blacks are more frequently affected by sarcoidosis than other ethnic groups and generally have chronic and more severe disease.12 Familial clustering of sarcoidosis cases has been observed worldwide.15 In ACCESS, subjects were five times more likely than control subjects to report a

Biomarkers of Disease Activity

Investigators continue to search for potential biomarkers of disease activity in sarcoidosis. Chitotriosidase, an enzyme involved in the degradation of chitin, is expressed by activated macrophages. Bargagli and colleagues53 found elevated levels of chitotriosidase in the serum of patients with sarcoidosis compared with control subjects, with > 90% exhibiting increased levels of the marker. Significantly higher levels were observed in patients with active sarcoidosis than in those with inactive

Diagnosis

BAL can be used as an adjunctive measure to support the diagnosis of sarcoidosis by demonstrating a reduced number of CD8 cells and an elevated CD4/CD8 ratio. But the diagnosis of sarcoidosis is best supported by obtaining tissue specimens that show noncaseating granulomas. EBUS-TBNA allows real-time ultrasound localization and aspiration of hilar and mediastinal lymph nodes. Tremblay and colleagues55 compared the diagnostic yield of TBNA using a 19-gauge needle vs EBUS-TNBA in 50 patients with

Cardiac Sarcoidosis

Cardiac sarcoidosis is a potentially sudden and life-threatening manifestation of sarcoidosis. Current studies likely underestimate the true prevalence of disease. Cardiac sarcoidosis is difficult to diagnose. Most patients have minimal or no symptoms, and no gold standard for diagnosis exists. Results from endomyocardial biopsy specimens, which may be difficult to obtain, are positive in < 10% of patients.56 Occasionally, echocardiogram or nuclear stress testing will reveal findings consistent

Therapy

Patients with chronic sarcoidosis often require prolonged treatment. Sustained treatment with even modest doses of systemic corticosteroids may result in disabling side effects. Steroid-sparing agents often are administered to minimize the long-term side effects of systemic corticosteroids.

TNF inhibitors have been investigated for the treatment of sarcoidosis. Utz and colleagues61 assessed the efficacy of etanercept in a preliminary clinical trial of patients with progressive pulmonary

Conclusion

Although the etiology of sarcoidosis remains uncertain, recent studies suggest that mKatG is a pathogenic antigen in sarcoidosis. Much has been learned about the genetic aspects of the disease. HLA gene loci and polymorphisms in transforming growth factor-β and TNF-α strongly influence individual susceptibility to sarcoidosis and clinical phenotype. Novel genes that determine the immunologic features of sarcoidosis have been identified. Reduced numbers of NKT cells may promote an exaggerated

Acknowledgments

Financial/nonfinancial disclosures: The authors have reported to CHEST the following conflict of interest: Dr Morgenthau owns stock in Johnson & Johnson. Dr Iannuzzi has reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

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