Re: Common conditions associated with hereditary haemochromatosis genetic variants: cohort study in UK Biobank
As a founder member of the Haemochromatosis Arthropathy Research Initiative (HARI) I welcome these findings.
Patients with genetic haemochromatosis often report an excess of 5 years from first attributable symptoms to diagnosis (1) (and commencement of de-ironing) and our excellent patient society (Haemochromatosis UK) reports widespread frustration caused by the delay in recognition of this disease. As stated, fatigue and joint pain are the most prevalent symptoms at diagnosis (1).
The association of Genetic Haemochromatosis with a characteristic arthropathy is well described, resembling effectively 'accelerated osteoarthritis' whereby affected people develop the clinical characteristics of osteoarthritis (OA) in the absence of predisposing trauma, at an earlier than expected age (often less than 60 years), affecting typical joints (hips, knees, PIP, DIP, 1st CMC) and unusual joints for OA - especially 2nd and 3rd MCPs and ankles. Radiologically there are abundant OA features including osteophytes (termed 'hook like' at ther MCPs), early joint space narrowing and on MRI an excess of bone marrow lesions/subchondral cysts compared to controls (1, 2).
Earlier detection of patients with genetic haemochromatosis could be enhanced with greater primary care awareness that a patient presenting with what superficially looks like 'everyday OA' should be investigated if these unusual features are present - i.e. age less than 60, no predisposing trauma, rapidly progressive joint damage, involvement of the 2nd and 3rd MCPs or ankles. Transferrin saturation and ferritin are inexpensive first line screening tests, and if both are raised, indicating iron overload, then referral for HFE analysis is justified.
I am, however, concerned about the association reported with rheumatoid arthritis. This is a completely different arthropathy to OA, and having seen and examined in excess of 120 patients with genetic haemochromatosis and arthropathy in my specialist clinic, I have only seen 2 cases with co-existent rheumatoid arthritis (matching the expected population prevalence of ~1%) . I would therefore caution interpretation of these findings, and wonder whether diagnostic error, bias or confounding factors have spuriously produced this association? Indeed, I am unsure why rheumatoid arthritis was included in the 11 key outcomes 'implicated in the single shared underlying process of iron overload'. I would be concerned if patients concluded from this work that their homozygous C282Y state meant they were more likely to develop rheumatoid arthritis as well as the characterisitc arthropathy that resembles OA.
Nonetheless, there are many other conundrums associated with the aetiology of haemochromatosis arthropathy, yet scant research directed at unravelling them (3).
References
1. Richardson A, Prideaux A, Kiely PDW. Haemochromatosis: unexplained MCP or ankle arthropathy should prompt diagnostic tests; findings from two UK observational cohort studies. Scand J Rheumatol 2017; 46: 69-74. DOI: 10.3109/03009742.2016.1155645
2. Elstob A, Ejindu V, Heron C, Kiely PDW. Haemochromatosis arthropathy: MRI hindfoot characteristics; a case-control study. Clin Rad 2017 doi:10.1016/j.crad.2017.10.002
3. Kiely PDW. Haemochromatosis arthropathy – a conundrum of the celtic curse. J R Coll Physicians Edinb 2018; 48: 233-8. doi 10.4997/JRCPE.2018.307
Competing interests:
No competing interests
22 January 2019
Patrick KIELY
Consultant Rheumatologist
St George's University Hospitals NHS Foundation Trust
Rapid Response:
Re: Common conditions associated with hereditary haemochromatosis genetic variants: cohort study in UK Biobank
As a founder member of the Haemochromatosis Arthropathy Research Initiative (HARI) I welcome these findings.
Patients with genetic haemochromatosis often report an excess of 5 years from first attributable symptoms to diagnosis (1) (and commencement of de-ironing) and our excellent patient society (Haemochromatosis UK) reports widespread frustration caused by the delay in recognition of this disease. As stated, fatigue and joint pain are the most prevalent symptoms at diagnosis (1).
The association of Genetic Haemochromatosis with a characteristic arthropathy is well described, resembling effectively 'accelerated osteoarthritis' whereby affected people develop the clinical characteristics of osteoarthritis (OA) in the absence of predisposing trauma, at an earlier than expected age (often less than 60 years), affecting typical joints (hips, knees, PIP, DIP, 1st CMC) and unusual joints for OA - especially 2nd and 3rd MCPs and ankles. Radiologically there are abundant OA features including osteophytes (termed 'hook like' at ther MCPs), early joint space narrowing and on MRI an excess of bone marrow lesions/subchondral cysts compared to controls (1, 2).
Earlier detection of patients with genetic haemochromatosis could be enhanced with greater primary care awareness that a patient presenting with what superficially looks like 'everyday OA' should be investigated if these unusual features are present - i.e. age less than 60, no predisposing trauma, rapidly progressive joint damage, involvement of the 2nd and 3rd MCPs or ankles. Transferrin saturation and ferritin are inexpensive first line screening tests, and if both are raised, indicating iron overload, then referral for HFE analysis is justified.
I am, however, concerned about the association reported with rheumatoid arthritis. This is a completely different arthropathy to OA, and having seen and examined in excess of 120 patients with genetic haemochromatosis and arthropathy in my specialist clinic, I have only seen 2 cases with co-existent rheumatoid arthritis (matching the expected population prevalence of ~1%) . I would therefore caution interpretation of these findings, and wonder whether diagnostic error, bias or confounding factors have spuriously produced this association? Indeed, I am unsure why rheumatoid arthritis was included in the 11 key outcomes 'implicated in the single shared underlying process of iron overload'. I would be concerned if patients concluded from this work that their homozygous C282Y state meant they were more likely to develop rheumatoid arthritis as well as the characterisitc arthropathy that resembles OA.
Nonetheless, there are many other conundrums associated with the aetiology of haemochromatosis arthropathy, yet scant research directed at unravelling them (3).
References
1. Richardson A, Prideaux A, Kiely PDW. Haemochromatosis: unexplained MCP or ankle arthropathy should prompt diagnostic tests; findings from two UK observational cohort studies. Scand J Rheumatol 2017; 46: 69-74. DOI: 10.3109/03009742.2016.1155645
2. Elstob A, Ejindu V, Heron C, Kiely PDW. Haemochromatosis arthropathy: MRI hindfoot characteristics; a case-control study. Clin Rad 2017 doi:10.1016/j.crad.2017.10.002
3. Kiely PDW. Haemochromatosis arthropathy – a conundrum of the celtic curse. J R Coll Physicians Edinb 2018; 48: 233-8. doi 10.4997/JRCPE.2018.307
Competing interests: No competing interests