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Arthritis and bone disease associated with hereditary hemochromatosis

Author
John S Axford, DSc, MD, FRCP, FRCPCH
Section Editor
Michael A Becker, MD
Deputy Editor
Paul L Romain, MD

INTRODUCTION

Arthritis is a common manifestation of hereditary hemochromatosis (HH), also called genetic hemochromatosis. HH 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. (See "Genetics of hereditary hemochromatosis".)

The resulting clinical manifestations of this disorder (and of other forms of iron overload) are related to the iron deposition in organs, such as the liver, pancreas, heart, and pituitary, and in the cartilage and synovial tissues of the joints. Other major clinical manifestations of iron accumulation include liver disease, skin pigmentation, diabetes mellitus, impotence in males, and cardiac enlargement with or without heart failure or conduction defects (table 1). (See "Clinical manifestations and diagnosis of hereditary hemochromatosis".)

The major rheumatic manifestations of hemochromatosis, including arthropathy and osteoporosis, and their pathogenesis, diagnosis, and management, will be reviewed here. Screening for HH and 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".)

PATHOGENESIS

Iron deposition and defects in cartilage and in immunologic function have been implicated as factors that contribute to the development of arthritis in hereditary hemochromatosis (HH). HFE gene analysis is useful in understanding the clinical manifestations of HH and patient management. However, the precise mechanisms underlying the arthritis among patients with HH are unknown. (See 'Iron deposition' below and 'Cartilage defect' below and 'Immunologic defects' below.)

HFE mutations were assessed in 31,192 persons of northern European ancestry who were followed for an average of 12 years [1]. C282Y is the HFE allele most commonly associated with HH. The proportion of HFE C282Y homozygotes with documented iron overload-related disease was 28.4 percent in men and 1.2 percent in women. Male C282Y homozygotes with a serum ferritin level of 1000 mg/L or more were more likely to report fatigue, use of arthritis medicines, and a history of liver disease.

                 
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Literature review current through: Sep 2017. | This topic last updated: Apr 17, 2017.
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