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Rheumatic manifestations of hereditary hemochromatosis

John S Axford, DSc, MD, FRCP, FRCPCH
Section Editors
Peter H Schur, MD
Michael A Becker, MD
Deputy Editor
Paul L Romain, MD


Hereditary hemochromatosis (HH), also called genetic hemochromatosis, is a genetically determined disorder in which mutations in the HFE gene, or less frequently the transferrin receptor 2 (TFR2) gene or other genes, cause increased intestinal iron absorption [1-4]. Details of the interaction between the transferrin receptor and HFE gene product and of the role of the TFR2 gene are still uncertain [5-7]. (See "Genetics of hereditary hemochromatosis".)

The clinical manifestations of this disorder (and of other forms of iron overload) are related to iron deposition in tissues, such as the liver, pancreas, and heart. Approximately one-half of patients with HH, if untreated, eventually develop arthritis [8,9]. (See "Clinical manifestations and diagnosis of hereditary hemochromatosis".)

This topic review will focus on the major rheumatic manifestations of hemochromatosis: arthropathy and osteoporosis (OP). The major genetic, clinical, diagnostic, and therapeutic features of hereditary hemochromatosis are discussed separately. (See "Genetics of hereditary hemochromatosis" and "Clinical manifestations and diagnosis of hereditary hemochromatosis" and "Screening for hereditary hemochromatosis" and "Management of patients with hereditary hemochromatosis".)


The underlying cause of arthritis among patients with hereditary hemochromatosis (HH) is unknown. Iron deposition and defects in cartilage and in immunologic function have been implicated.

Iron deposition — Iron deposition within joints may trigger a number of pathologic events, such as free radical generation and crystal deposition. In some cases, the generation of free radicals may cause changes in immunoglobulin carbohydrate composition that promote immune complex formation and inflammation [10-14]. These alterations are superimposed upon the joint changes resulting from calcium pyrophosphate deposition.


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Literature review current through: Jan 2017. | This topic last updated: Thu Jan 19 00:00:00 GMT+00:00 2017.
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