Hemochromatosis? When Bloodletting Is Not the Cure

Reducing the Burden of False-Positive Tests: It Is Time to Optimize Diagnostic Testing for Undifferentiated Conditions

“…10 Her hyperferritinemia was due to alcohol abuse, not iron overload. 3 This diagnostic misadventure came at the expense of adverse events and a substantial delay in addressing her alcoholic liver disease. Shotgun testing fails when testing patients for rarer conditions in the context of high pretest probability for common conditions (eg, alcoholic liver disease), especially when using tests with low specificity (eg, those for Wilson disease or hemochromatosis), doubling the risk of false positives, exposing patients to needless harm and additional testing.…”

“…Costs may be measured in health care dollars, but may also be personal because shotgun testing increases false-positive results, 1 which in turn may cause a cascade of additional testing and patient or provider stress. 1,3,4 Although modern medical care strives toward precision and personalization, shotgun testing is imprecise and impersonal. Furthermore, shotgun testing inappropriately reduces the act of diagnosis to the ordering of test panels and such a practice may compromise the development of the diagnostic acumen of future physicians.…”

A Patient With Back Pain and Morning Stiffness

“…3 It is most commonly associated with homozygous C282Y variants in the HFE gene, which lead to downregulation of hepcidin, in turn increasing iron absorption, transferrin saturation, and parenchymal iron deposition. 4 This may manifest as cirrhosis, diabetes, and/or hyperpigmentation, although hereditary hemochromatosis also may lead to cardiomyopathy, hypogonadism, and susceptibility to certain infections. Arthritis occurs in more than 70% of patients, with more than 40% of cases involving the second and third MCP joints.…”

“…Hereditary hemochromatosis is most commonly seen in White populations, in whom the prevalence is as high as 1 in 150 . It is most commonly associated with homozygous C282Y variants in the HFE gene, which lead to downregulation of hepcidin, in turn increasing iron absorption, transferrin saturation, and parenchymal iron deposition . This may manifest as cirrhosis, diabetes, and/or hyperpigmentation, although hereditary hemochromatosis also may lead to cardiomyopathy, hypogonadism, and susceptibility to certain infections.…”