Gastrointestinal and genitourinary
Symptomatic gastrointestinal (GI)  involvement occurs in less than 1% of cases (if one excludes the liver), and most commonly the stomach is affected, although the small or large intestine may also be affected in a small portion of cases. Studies at autopsy have revealed GI involvement in less than 10% of people. These cases would likely mimic Crohns disease, which is a more commonly intestine-affecting granulomatous disease. About 1–3% of people have evidence of pancreatic involvement at autopsy. Symptomatic kidney involvement occurs in just 0.7% of cases, although evidence of kidney involvement at autopsy has been reported in up to 22% of people and occurs exclusively in cases of chronic disease. Symptomatic kidney involvement is usually nephrocalcinosis, although granulomatous interstitial nephritis that presents with reduced creatinine clearance and little proteinuria is a close second. Less commonly, the epididymis, testicles, prostate, ovaries, fallopian tubes, uterus, or the vulva may be affected, the latter may cause vulva itchiness. Testicular involvement has been reported in about 5% of people at autopsy. In males, sarcoidosis may lead to infertility.Around 70% of people have granulomas in their livers, although only in about 20–30% of cases, liver function test anomalies reflecting this fact are seen. About 5–15% of patients exhibit hepatomegaly. Only 5–30% of cases of liver involvement are symptomatic. Usually, these changes reflect a cholestatic pattern and include raised levels of alkaline phosphatase (which is the most common liver function test anomaly seen in those with sarcoidosis), while bilirubin and aminotransferases are only mildly elevated. Jaundice is rare.
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.