Diagnostic Considerations

When evaluating a patient with suspected hemochromatosis, alcoholic liver disease, ineffective erythropoiesis with marrow hyperplasia, iron overload associated with chronic anemia, multiple transfusions, and porphyria cutanea tarda should also be considered. In addition, patients may have susceptibility to certain bacterial infections, such as Yersinia enterocolitica liver abscess, Y pseudotuberculosis sepsis, Vibrio vulnificus sepsis, and Listeria monocytogenes meningitis.^[72]Also, take note of the increased risk of hepatoma in cirrhotic livers of patients with hemochromatosis.

Distinguishing hemochromatosis arthropathy from rheumatoid arthritis is important for several reasons. For example, patients with hereditary hemochromatosis do not require corticosteroid treatment. In addition, if a diagnosis of rheumatoid arthritis is made incorrectly, treatment with phlebotomy is not started early, and familial genetic counseling is not considered.^[73]

Alcoholic liver disease

Patients with alcoholic disease include those who are heavy drinkers, perhaps of iron-containing fortified wines, who have cirrhosis. Liver biopsy in these patients may show a modest increase in iron; however, contrary to patients with hemochromatosis, the hepatic iron levels are relatively normal and iron stores are less than 4 g.

Ineffective erythropoiesis with marrow hyperplasia

Patients with hyperplastic erythroid marrow absorb an increased amount of iron to the point where they may have clinical iron overload. Examples include the hereditary sideroblastic anemias, severe alpha and beta thalassemia, and the myelodysplastic syndrome variants, such as refractory anemia with ringed sideroblasts (RARS).

Iron overload associated with chronic anemia

Patients who have iron overload due to chronic anemia have increased effective erythropoiesis and increased iron absorption. Examples include hereditary spherocytosis and acquired sideroblastic anemia.

Multiple transfusions

Hypertransfusion is performed in patients with beta thalassemia major, sickle cell anemia, refractory aplastic anemia, and myelodysplastic syndrome. Such patients may receive as many as 100 units of red blood cells, which contain as much as 20-25 g of iron, similar to or more than the amount retained in many symptomatic patients with hereditary hemochromatosis.

Porphyria cutanea tarda

Porphyria cutanea tarda is primarily a skin and liver disease that occurs in familial and sporadic forms. The cause of liver siderosis in sporadic porphyria cutanea tarda has not been established, but it may be related to a mutation in the HFE gene in most patients.

Differential Diagnoses

Workup

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Media Gallery

Hemochromatosis. What is hemochromatosis? Hemochromatosis is a genetic disorder where the body isn’t able to regulate its iron absorption. Iron levels in the body build up over time and damage the liver as well as other organs, through the generation of free radicals. Courtesy of Osmosis.org (https://www.osmosis.org/).

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Author

Andrea Duchini, MD Associate Professor of Medicine and Surgery, Director of Hepatology, University of Texas Medical Branch School of Medicine; Medical Director of Liver Transplantation, Department of Surgery, University of Texas Medical Branch School of Medicine

Andrea Duchini, MD is a member of the following medical societies: American College of Physicians, International Liver Transplantation Society, American Gastroenterological Association, American Society for Gastrointestinal Endoscopy

Disclosure: Nothing to disclose.

Coauthor(s)

Hady E Sfeir, MD Clinical Assistant Professor of Medicine, Department of Internal Medicine, OSF St Francis Medical Center

Hady E Sfeir, MD is a member of the following medical societies: American Association of Clinical Endocrinologists, American Medical Association

Disclosure: Nothing to disclose.

David M Klachko, MD, MEd Professor Emeritus, Department of Internal Medicine, Division of Endocrinology, Diabetes, and Metabolism, University of Missouri-Columbia School of Medicine

David M Klachko, MD, MEd is a member of the following medical societies: Alpha Omega Alpha, Missouri State Medical Association, American College of Physicians-American Society of Internal Medicine, American Diabetes Association, American Federation for Medical Research, Endocrine Society, Sigma Xi, The Scientific Research Honor Society

Disclosure: Nothing to disclose.

Chief Editor

Praveen K Roy, MD, MSc Clinical Assistant Professor of Medicine, University of New Mexico School of Medicine

Praveen K Roy, MD, MSc is a member of the following medical societies: Alaska State Medical Association, American Gastroenterological Association

Disclosure: Nothing to disclose.

Acknowledgements

Vivek V Gumaste, MD Associate Professor of Medicine, Mount Sinai School of Medicine of New York University; Adjunct Clinical Assistant, Mount Sinai Hospital; Director, Division of Gastroenterology, City Hospital Center

Vivek V Gumaste, MD is a member of the following medical societies: American College of Gastroenterology and American Gastroenterological Association

Disclosure: Nothing to disclose.

Douglas M Heuman, MD, FACP, FACG, AGAF Chief of GI, Hepatology, and Nutrition at North Shore University Hospital/Long Island Jewish Medical Center; Professor, Department of Medicine, Hofstra North Shore-LIJ School of Medicine

Douglas M Heuman, MD, FACP, FACG, AGAF is a member of the following medical societies: American Association for the Study of Liver Diseases, American College of Physicians, and American Gastroenterological Association

Disclosure: Novartis Grant/research funds Other; Bayer Grant/research funds Other; Otsuka Grant/research funds None; Bristol Myers Squibb Grant/research funds Other; Scynexis None None; Salix Grant/research funds Other; MannKind Other

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment