Since sarcoidosis is most often found in organs the directly interface to the environment (skin, eyes, lungs), it has been hypothesized that an environmental or toxic trigger would be found to cause the disease. Only beryllium salts (seen often at the author’s institution in Denver, Colorado where beryllium mining is common) have been noted to create granulomas similar in appearance to those of sarcoidosis [14]. Another environmental exposure has also recently been identified. In this report, exposure to high humidity workplaces or water damage in association with a genetic susceptibility with the HLA-DQB1 locus has been found to be potentially causative in sarcoidosis [15].

In the 1960s, Dr. Siltzbach and colleagues created the Kviem-Siltzbach antigen, a derivative from human sarcoidosis tissue samples, which when injected intra-dermally, was able to create granulomatous inflammation for 70 % of patients for about 6 weeks [16]. Further studies of this antigen did not demonstrate definitive causality of this agent (Table 2.2).

Much attention has been given to pathologic organisms such as viruses, bacteria, and mycobacterial diseases. For mycobacteria, a number of studies, including those using hybridization techniques and PCR, have found evidence of M. tuberculosis in sarcoidosis tissue. Unfortunately, as mycobacteria are notoriously difficult to culture, these results have not been easily reproduced [17]. One particularly important study demonstrated the growth of acid-fast cell wall-deficient forms of bacteria sources from blood samples of 19 of 20 patients with sarcoidosis, which did not grow in the 20 controls [18]. Further analysis of these isolated organisms stained positively with an antibody raised against M. tuberculosis. Unfortunately, it was not possible to determine if these organisms were causative. A large case-control study subsequently found no clear differences in the cell walls of organisms in the blood of sarcoidosis patients [19].

One more common organism, responsible for acne in many populations, propionibacterium, has been thought to be involved in sarcoidosis pathogenesis. This organism is now considered to possibly activate the immune system to create the environment to develop sarcoidosis [20].

Viruses have also been given some of the blame for the development of sarcoidosis. Most notably, human herpes virus 8 has been implicated, particularly in lung biopsies of afflicted patients [21]. Unfortunately, no other studies looking at this herpes etiology could confirm these findings [22].

An interesting pilot study from 2007 reported the empiric use of anti-fungal drugs combined with corticosteroids for up to 6 months in 18 patients resulted in improvement of clinical symptoms, chest X-ray imaging, and pulmonary function testing [23]. This is has not yet been replicated.

In short, much work has been completed into the etiologic search for sarcoidosis without any clear pathway to disease development. Ultimately, future immunogenetic research will likely yield more answers. Until then, continued screening, evaluation, and keeping sarcoidosis on the differential is critical to discovering those patients who have the disease but who may otherwise go unrecognized, with often dire consequences.

The clinical manifestations of sarcoidosis are dependent on both the development and location of granulomas. Cardiac sarcoidosis develops as noncaseating granulomas which may involve the left ventricular free wall, basal ventricular septum, right ventricle, papillary muscles, right atrium, and left atrium develop [24]. Histopathology of cardiac sarcoidosis suggests three successive stages: edema, granulomatous infiltration, and fibrosis and scar formation. Biopsy pathology demonstrates the presence of numerous lymphocytes in the border zones around the granulomas with a dense band of fibroblasts, collagen fibers, and proteoglycans which encircle an aggregate of inflammatory cells [24].

Cardiac involvement occurs in 20–27 % of sarcoidosis patients in the United States and may be as high as 58 % in Japan [25]. The prevalence of cardiac findings in cardiac sarcoidosis is variable and includes complete heart block, bundle branch block, ventricular tachycardia, congestive heart failure, and sudden cardiac death most commonly (12–75 % of the time) [2].