Characteristics of the arthropathy described in hereditary hemochromatosis

Abstract

Hereditary hemochromatosis (HH) is a common inherited metabolic disorder characterized by systemic iron over- load (1,2). HH affects approximately 1 in 200 people and is most common in persons of Northern European origin. Organ damage in the pancreas, liver, heart, endocrine glands, skin, and joints has been described in HH. There is evidence that the frequency and extent of organ damage may be changing with time, perhaps due to earlier diagnosis and treatment (3). In persons of Northern European origin, homozygosity for the C282Y mutation in the HFE gene found on chromosome 6 is present in more than 90% of patients with unequivocal HH (4), whereas in Southern Europe, as many as 30% of cases may be heterozygous or wild type for this mutation (5). The clinical manifestations of the disorder were first comprehensively reviewed by Sheldon in 1935, but interestingly, in his description, an arthropathy is not recorded (6). It was not until Schumacher described 2 cases and reported a peripheral arthritis in 5 of 23 hospital cases of idiopathic hemochromatosis in 1964 that arthropathy was identified in hemochromatosis (7). Subsequent studies have confirmed the presence of a clinically recognizable arthropathy (8–17). Although clinically and radiologically characteristic and highly suggestive of the joint disorder often found in HH, the arthropathy is not specific for hemochromatosis, since it cannot be differentiated from monarticular osteoarthritis (OA) in the same target joints or from the form of polyarticular OA provisionally classi- fied as the type 2 polyarticular OA phenotype, an example of which is depicted in Figure 1 (18,19). Moreover, differentiation from pyrophosphate deposition disease, diabetes mellitus with metacarpophalangeal (MCP) joint involvement, and even rheumatoid arthritis (RA) can sometimes be difficult (8,20).