Sarcoidosis has paradoxical effects on inflammatory processes; it is characterized by increased macrophage and CD4 helper T-cell activation, resulting in accelerated inflammation, but immune response to antigen challenges such as tuberculin is suppressed. This paradoxic state of simultaneous hyper- and hypoactivity is suggestive of a state of anergy. The anergy may also be responsible for the increased risk of infections and cancer. The regulatory T-lymphocytes in the periphery of sarcoid granulomas appear to suppress IL-2 secretion, which is hypothesized to cause the state of anergy by preventing antigen-specific memory responses.While TNF is widely believed to play an important role in the formation of granulomas (this is further supported by the finding that in animal models of mycobacterial granuloma formation inhibition of either TNF or IFN-γ production inhibits granuloma formation), sarcoidosis can and does still develop in those being treated with TNF antagonists like etanercept. B cells also likely play a role in the pathophysiology of sarcoidosis. Serum levels of soluble human leukocyte antigen (HLA) class I antigens and angiotensin converting enzyme (ACE) are higher in people with sarcoidosis. Likewise the ratio of CD4/CD8 T cells in bronchoalveolar lavage is usually higher in people with pulmonary sarcoidosis (usually >3.5), although it can be normal or even abnormally low in some cases.
In 2000, Bratman, with David Knight, authored the book Health Food Junkies, which further expanded on the subject.Following the publication of the book, in 2004 a team of Italian researchers from La Sapienza University of Rome, published the first empirical study attempting to develop a tool to measure the prevalence of orthorexia, known as the ORTO-15.In 2015, responding to news articles in which the term orthorexia is applied to people who merely follow a non-mainstream theory of healthy eating, Bratman specified the following: "A theory may be conventional or unconventional, extreme or lax, sensible or totally wacky, but, regardless of the details, followers of the theory do not necessarily have orthorexia. They are simply adherents of a dietary theory. The term orthorexia only applies when an eating disorder develops around that theory." Bratman elsewhere clarifies that with a few exceptions, most common theories of healthy eating are followed safely by the majority of their adherents; however, "for some people, going down the path of a restrictive diet in search of health may escalate into dietary perfectionism." Karin Kratina, PhD, writing for the National Eating Disorders Association, summarizes this process as follows: "Eventually food choices become so restrictive, in both variety and calories, that health suffers – an ironic twist for a person so completely dedicated to healthy eating.