Increased Risk of Arthropathies and Joint Replacement Surgery in Patients With Genetic Hemochromatosis: A Study of 3,531 Patients and Their 11,794 First‐Degree Relatives

Abstract

Objective. Genetic hemochromatosis (GH) is an autosomal recessive disease in individuals of Northern and WesternEuropean descent. Heterozygosity for the C282Y mutation is common (6 -20%). Arthropathy is one of the few complications of GH suggested not to be associated with iron body stores; synovial iron deposition remains in iron-depleted patients. Previous studies suggest an elevated prevalence of clinical and radiographic signs of arthropathy in patients with GH, and 2 smaller studies suggest a possibly elevated risk of joint replacement surgery, but more mixed results are shown regarding risks with HFE genotype. We therefore assessed the risks of arthropathy and joint replacement surgery in patients with GH and in their first-degree relatives (FDRs). Methods. We performed a population-based cohort study of 3,531 patients with GH and of their 11,794 FDRs (assumed to be heterozygous for the C282Y mutation) using nationwide Swedish population-based health and census registers. Hazard ratios (HRs) of arthropathies and joint replacement surgeries among patients and their FDRs (versus the general population) were assessed using Cox regression. Results. Between 1997 and 2005, 406 of 3,531 patients were reported/hospitalized with any noninfectious arthropathies, including osteoarthritis, corresponding to an HR of 2.38 (95% confidence interval [95% CI] 2.14 -2.64). Patients were also at increased risk of hip replacement (HR 2.77, 95% CI 2.27-3.38) and knee replacement (HR 2.14, 95% CI 1.58 -2.88) surgery. Among the 11,794 FDRs (patients excluded), we found no increased risk of any of the joint morbidities. Conclusion. Patients with GH, but not their FDRs, are at increased risk of arthropathies, including the need for joint replacement surgery.

Age-dependent ferritin elevations and HFE C282Y mutation as risk factors for symptomatic knee osteoarthritis in males: a longitudinal cohort study

“…Among the H63D and C282Y HFE mutations and their compound heterozygotes, C282Y homozygosity in patients with SKOA resulted in significant increase in serum ferritin, confirming a previous report that C282Y mutation carriers are highly prevalent in hand OA involving metacarpophalangeal joints 2–5 and bilateral specified large joints [39]. Furthermore, a recent study has reported that patients with genetic hemochromatosis are at increased risk for arthropathies, including the need for joint replacement surgery [44]. …”

Treatment of Nongout Joint Deposition Diseases: An Update

“…Interleukin-1 receptor antagonist has been shown to be effective in some patients with refractory hemochromatosis-related arthritis of the hands [49] but these data remain very limited. Natural evolution can lead to joint replacement [50]. …”

Hämochromatose und Arthropathie

“…Bei einer Heterozygotie zeigt sich jedoch kein erhöhtes Auftreten einer Arthritis. Eine Studie von Elmberg et al [9] untersuchte hierzu 3531 HH-Patienten und 11 794 ihrer Verwandten 1. Grades, von denen angenommen wurde, dass sie heterozygot für die C282Y-Mutation sind.…”

“…Es zeigten die Patienten mit HH, nicht aber ihre Verwandten, ein erhöhtes Risiko für die Entwicklung einer Arthritis und die Notwendigkeit einer Gelenkersatzoperation [9]. Träger einer heterozygoten Mutation von C282Y zeigen auch ein insgesamt erhöhtes Risiko einer klinisch relevanten Eisenüberladung [1].…”