HFE variants were linked to haemochromatosis-pattern arthritis even without iron overload

Design

Comparison across inception cohorts

Population

373 participants: HFE genotypes with and without iron overload, and controls

Primary outcome

Fulfilment of EULAR haemochromatosis arthropathy classification criteria

Effect

43% other HFE genotypes and 22% C282Y without overload vs 7% controls

This study drew on EULAR haemochromatosis arthropathy inception cohorts: 154 C282Y homozygotes with iron overload, 27 without, 72 people with other HFE genotypes irrespective of iron status, and 120 controls with osteoarthritis or calcium pyrophosphate disease without iron overload.

Arthropathy meeting the EULAR classification criteria was present in 71% of iron-loaded C282Y homozygotes, 22% of those without overload, 43% of other HFE genotypes including H63D, and 7% of controls. Within the non-haemochromatosis groups, ferritin and transferrin saturation did not predict the arthropathy.

The authors propose 'HFE-associated arthropathy without genetic haemochromatosis' for metacarpophalangeal or ankle disease in any HFE genotype. The non-haemochromatosis groups were selected from patients with unexplained joint pain, so prevalence here overstates what would be found in the general population.

• Consider HFE genotyping in unexplained second and third MCP or ankle arthropathy
• Do not exclude an HFE-related cause because ferritin and transferrin saturation are normal
• Look for chondrocalcinosis and hook-like osteophytes on hand radiographs
• Manage iron overload when present; the joint disease may persist regardless

Why it matters

Separates the joint disease from the iron, which changes who gets tested.

Don't overread it

Patients were selected for joint pain; this does not give the arthropathy risk for all HFE carriers.

The statistics, in plain English

The odds ratios of about 1.0 for ferritin and transferrin saturation mean iron levels made no measurable difference to whether arthropathy was present. Because patients in the HFE groups were selected for joint symptoms, the prevalence figures are higher than in unselected carriers.

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