Value of ultrasound in hemochromatosis associated arthropathy

Hereditary hemochromatosis (HH) is an autosomal-recessive inherited iron overload disease caused by a mutation of the HFE gene. Patients may present with hepatomegaly, hypogonadism, skin hyperpigmentation and/or diabetes. Arthropathy occurs in two thirds of HH patients and has a significant impact on quality of life. HH arthropathy usually resembles osteoarthritis (OA), however, joint symptoms manifest earlier and are characterized by intermittent arthritis of metacarpophalangeal joints (MCP), wrists, hips, knee and/or ankle. Regular phlebotomy does not improve joint symptoms and the value of anti-inflammatory agents to modify pain and/or the disease course is elusive so far. Histological studies demonstrated inflammatory synovitis in a proportion of patients and imaging methods might be useful to identify these HH patients with inflammatory joint disease. Musculoskeletal ultrasound is well established in rheumatoid arthritis, chondrocalcinosis, OA and other rheumatic diseases; however, in HH arthropathy no study has been performed to investigate the value of this technique to detect structural and inflammatory lesions so far. The primary hypothesis of this study is that joint inflammation is detected more frequently by ultrasound [defined as synovial hypertrophy and/or effusion (SH/E) by B-mode and/or hypervascularisation by Power Doppler (PD)] than by clinical examination (defined as synovial swelling). Secondary objectives are the correlation between ultrasound and clinical findings, the comparison of structural lesions identified by sonography and by x-ray as well as the comparison of ultrasound findings between HH arthropathy and hand OA. The results of this study could guide future treatment decisions in HH arthropathy regarding the use of anti-inflammatory agents (that might be more effective in cases with verified synovitis) and might reveal HH arthropathy specific ultrasound findings improving the diagnostic work-up of the disorder in the future. According to the power analysis we plan to recruit 35 patients with HH arthropathy, 35 HH patients without arthropathy and 35 hand OA patients. Patients undergo structured history and clinical examination, routine blood tests as well as x-rays of hands, hips, knees and ankles. In addition ultrasound examination of 36 joints [bilateral wrists, MCP, proximal (PIP), distal interphalangeal joints (DIP), hip, knee and ankle joints] is performed to address inflammatory and structural changes. Taken together, this study investigates the value of musculoskeletal sonography to assess inflammatory and structural lesions in patients with HH arthropathy.

In the present study, we demonstrated that joint inflammation is common in patients with hereditary hemochromatosis associated arthropathy (HH-A), although this disease has long been considered as a non-inflammatory disorder. In addition, we observed that cartilage damage at finger joints was more prominent in patients with HH-A than in patients with hand osteoarthritis (HOA). Subclinical joint inflammation was present in the majority of patients with hemochromatosis without clinically evident arthropathy (HH-WA). Our results indicate that inflammation and cartilage damage play an important role in the pathogenesis of joint disease in patients with hereditary hemochromatosis. For this study we included 24 patients with HH-WA, 26 patients with HH-A and 37 patient with HOA. Patients were recruited at the Medical University of Graz, the Hanusch hospital Vienna and the general hospital Oberndorf (all Austria). All patients underwent a full clinical assessment, standard x-rays and ultrasound examination of 36 joints at hands, hips, knees and ankles. Apart from the results described above, we also observed that inflammation and structural alterations were most prominent at the metacarophalangeal joints, which are those joints connecting the carpus with fingers. Ultrasound verified inflammatory and cartilage abnormalities correlated well with structural damage as verified by x-ray. However, pain, global assessment of disease activity and measures of hand functions were unrelated to ultrasound findings of inflammation. In summary, we demonstrated that patients with HH-A reveal ultrasound verified inflammatory findings and cartilage damage at joints. The majority of patients with HH-WA suffer from subclinical joint inflammation.