Haemochromatosis and Arthropathies

Abstract

Arthropathy is the most common and often the earliest clinical manifestation of hereditary hemochromatosis (HH). It is difficult to treat and there is a high risk for early endoprosthetic joint replacement. Research done during the last decade shows that it is a joint disease in its own right. Clinically, there are degenerative articular changes with an atypical pattern of distribution, a crystal arthropathy (CPPD) with congenital joint swelling and synovitis like in RA. The X-ray image shows typical but not exclusive findings. In MRI, groundbreaking subchondral findings are found, especially in the large joints, and ultrasound shows inflammatory lesions in non-arthropathy patients as well. In animal experiments and pathomorphological studies of the synovial membrane, the arthropathy can be differentiated from osteoarthrits and RA. The pathophysiological significance of iron overload can be distinguished from immunohistochemical and cytogenetic investigations in chronic degenerative HH arthropathy and inflammatory-destructive arthropathy in hemophilia. By elucidating the pathophysiology, new therapeutic approaches can be formulated. In addition to colchicine, the IL-1 receptor antagonist anakinra is available for activation of the NLRP3 inflammasome by CPPD crystals and subsequent induction of IL-1β overproduction. Other manifestations include symptomatic pain therapy and intensive physiotherapy and occupational therapy. To promote further research into hemochromatosis arthropathy, the Hemochromatosis Arthropathy Research Initiative (HARI) was established in 2016.