Abstract: The Hand Arthropathy of Hereditary Hemochromatosis Is Strongly Associated with Iron Overload

The Hand Arthropathy of Hereditary Hemochromatosis Is Strongly Associated with Iron Overload

LUCA VALENTI, ANNA LUDOVICA FRACANZANI, VALERIA ROSSI, CLEMENTINA RAMPINI, EDOARDO PULIXI, MASSIMO VARENNA, SILVIA FARGION, and LUIGI SINIGAGLIA

ABSTRACT.

Objective. To analyze the clinical characteristics and genetic background associated with the presence of hand arthropathy, as determined by radiological findings, in Italian patients with hereditary hemochromatosis (HHC).

Methods. In 88 consecutive unselected patients with phenotypically expressed HHC, joint involvement was systematically evaluated in plain radiographs of hands, wrists, lumbar spine, pelvis, and knees. Risk factors considered were age, sex, body mass index, alcohol abuse, organ involvement at other sites, and indices of iron overload, including ferritin, transferrin saturation, and iron removed to reach depletion. HFE genotype was also considered. The independent role of risk factors was tested by logistic regression analysis.

Results. Thirty-two subjects (36%) showed signs of metacarpophalangeal (MCP) arthropathy. Intercarpal, radiocarpal, and chondrocalcinosis were less frequent and occurred in association with MCP arthropathy. At multivariate analysis MCP arthropathy was independently associated with older age [odds ratio (OR) 1.20, 95% confidence interval (CI) 1.1–1.33/yr; p = 0.0001], higher ferritin levels at diagnosis (OR 4.17, 95% CI 1.60–13.9 for values > 1000 ng/ml; p = 0.008), the presence of the C282Y +/+ and C282Y/H63D HFE genotypes (OR 2.69, 95% CI 1.09–7.87; p = 0.04), and higher percentage transferrin saturation (OR 1.05, 95% CI 1–1.1; p = 0.05). The severity of arthropathy was independently associated with older age (p = 0.03) and higher ferritin values (p = 0.05).

Conclusion. MCP arthropathy together with a typical pattern of joint involvement is observed in one-third of unselected patients with HHC, and is influenced by the duration and degree of the iron overload. (First Release Dec 1 2007; J Rheumatol 2008;35:153-8)

Key Indexing Terms:

HFE PROTEIN
HEMOCHROMATOSIS
IRON
OSTEOARTHRITIS

From the Department of Internal Medicine, Medicina Interna IB, Universita' di Milano, Ospedale Policlinico Mangiagalli Regina Elena IRCCS; Department of Rheumatology; and Department of Radiology, Gaetano Pini Institute, Milano, Italy.

Supported by COFIN 2004, FIRST 2004, FIRST 2005, Ricerca Corrente Ospedale Maggiore Policlinico Mangiagalli Regina Elena IRCCS 2004, 2005, 2006.

L. Valenti, MD; A.L. Fracanzani, MD; E. Pulixi, MD; S. Fargion, MD, Department of Internal Medicine, Medicina Interna IB, Universita' di Milano, Ospedale Policlinico Mangiagalli Regina Elena IRCCS; V. Rossi, MD; M. Varenna, MD; L. Sinigaglia, MD, Department of Rheumatology; C. Rampini, MD, Department of Radiology, Gaetano Pini Institute.

Address reprint requests to Prof. S. Fargion, Dipartimento di Medicina Interna, UO Medicina Interna IB, Padiglione Granelli, Universita' degli Studi di Milano, Ospedale Policlinico Mangialli e Regina Elena Fondazione IRCCS, Via F. Sforza 35, 20122 Milano (MI), Italy. E-mail: silvia.fargion@unimi.it

Accepted for publication September 10, 2007.