Send to

Choose Destination
Immunobiology. 2017 Apr;222(4):672-675. doi: 10.1016/j.imbio.2016.12.005. Epub 2017 Jan 6.

Anomalies in the dominant sarcoidosis paradigm justify its displacement.

Author information

Thoracic Oncology Program, Earle A. Chiles Research Institute, Portland, OR, United States. Electronic address:


The prevailing paradigm defines sarcoidosis as a disease of unknown etiology characterized by a systemic noncaseating epithelioid granulomatous response (SGR). This formulation fails to account for the elusiveness of the etiological agent, the nature of the Kveim response, the paradox of cutaneous delayed type hypersensitivity anergy in a setting of intense immune response and the appearance of SGR, indistinguishable from sarcoidosis, in persons with lymphohematogenous and solid neoplasms and a variety of cellular immune deficiencies. Displacing this formulation with an evidence-based alternative in which the SGR is viewed as an etiologically diverse, primitive immunological fallback due to inefficient cellular immune processing eliminates these shortcomings, providing a unifying accounting for the puzzles and violations of expectations associated with the prevailing paradigm. Its clinical import resides in the reported annual three-percent increase in sarcoidosis mortality in the past two decades (Swigris et al., 2011), which may be attributable, in part, to unneeded suppressive treatment.


Dendritic cell; Granulomatous response; Immune paradox; Immunodeficiency; Kveim; Sarcoidosis

[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center