The hand arthropathy of hereditary hemochromatosis is strongly associated with iron overload.
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).


CONCLUSIONS
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.
Department of Internal Medicine, Medicina Interna IB, Universita' di Milano, Ospedale Policlinico Mangiagalli Regina Elena IRCCS, Milano, Italy.
Luca
L
Valenti
Anna Ludovica
AL
Fracanzani
Valeria
V
Rossi
Clementina
C
Rampini
Edoardo
E
Pulixi
Massimo
M
Varenna
Silvia
S
Fargion
Luigi
L
Sinigaglia
D000328:Adult; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D005260:Female; D005293:Ferritins / Q000097:blood; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006225:Hand / Q000473:pathology; D006432:Hemochromatosis / Q000150:complications* / Q000235:genetics / Q000503:physiopathology; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D019190:Iron Overload / Q000503:physiopathology*; D007592:Joint Diseases / Q000150:complications* / Q000235:genetics / Q000503:physiopathology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008662:Metacarpophalangeal Joint / Q000503:physiopathology*; D008875:Middle Aged; D016017:Odds Ratio
C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D005293:Ferritins