Statistics from Altmetric.com
A 65 year old white woman presented with a 5 year history of pain and intermittent swelling of the left ankle. There had been no preceding trauma to the ankle and the symptoms were initially gradual in onset with aching and stiffness but then evolved into a continuous pain, particularly nocturnally. Her previous medical history included a right total hip replacement aged 53, menopause aged 53, and essential hypertension. There was no family history of rheumatological illness and her mother died of a myocardial infarction aged 56 years.
Examination disclosed evidence of osteoarthritis in her hands and an unusual symmetrical bony swelling of her 1st and 2nd metacarpophalangeal joints. Her left ankle was swollen and warm to the touch (fig 1).
Investigations disclosed normal inflammatory markers and autoantibody screen, a mildly raised aspartate aminotransferase 35 U/l (normal 31 U/l) and alanine aminotransferase 42 U/l (normal 30 U/l), and a normal serum glucose. Radiographs of the ankle disclosed changes compatible with moderate to severe osteoarthritis, and those of the hands showed bilateral significant joint space narrowing, hooked osteophytes and sclerosis of the 2nd and 3rd metacarpophalangeal joints bilaterally, and chondrocalcinosis in the triangular ligament of the wrist. Her transferrin saturation index and ferritin were markedly raised at 98% (normal 20–40) and 4340 µg/l (normal 12–200), respectively. Genotyping was undertaken by polymerase chain reaction from genomic DNA. This showed the patient to be homozygous for the most common haemochromatosis mutation, cysteine to tyrosine (C282Y) on chromosome 6.1
After the description of haemochromatosis in 1935, Schumacher first described an associated arthropathy in 1964.2 The prevalence of arthralgia and arthritis in haemochromatosis varies between 28 and 81%. Characteristic radiological features have been reported in the hand, wrist, and hip. Involvement of the ankle joint seems to be rare and only four previous cases have been described, with only one presenting as ankle arthropathy3,4 (table 1).
The arthropathy of haemochromatosis is usually degenerative and non-inflammatory, first affecting the small joints of the hands and then larger joints such as hips, shoulders, knees, and ankles.5,6 The presentation of haemochromatosis may be confused with either rheumatoid arthritis or pseudogout. A polyarticular, symmetrical involvement, particularly of the 2nd and 3rd metacarpophalangeal joints, in association with other superficial bony swellings consistent with osteoarthritis should alert the clinician to the possibility of haemochromatosis. Acute attacks of synovitis in such patients can be secondary to calcium pyrophosphate dihydrate deposition. Despite treatment of haemochromatosis with phlebotomy, the arthropathy seldom improves.
To date, a number of theories have been reported to explain the relationship between haemochromatosis and arthropathy. Ferric salts are found to promote the formation and deposition of intra-articular calcium pyrophosphate crystals by inhibiting the activity of synovial pyrophosphatase, and hence can precipitate attacks of pseudogout in the joint. It has also been proposed that there is a metabolic abnormality independent of the primary iron absorption disorder which can disrupt the configuration of the cartilage matrix, leading to premature osteoarthritis.
This case report identifies only the second reported case of haemochromatosis presenting as an ankle arthropathy. This diagnosis should always be considered in the differential diagnosis of an arthropathy in unusual joint sites. Screening tests, such as measurements of iron metabolism, should be performed, followed by, if indicated, the diagnostic genomic DNA analysis for the mutations found in haemochromatosis. The importance of making a correct diagnosis is that effective treatment by phlebotomy can halt progression of the systemic effects of excess iron deposition and progression to resultant damage of internal organs. After a diagnosis of haemochromatosis is made, all close relatives (including parents, siblings, and all offspring) should be genetically tested for the presence of haemochromatosis mutations. Early diagnosis and treatment of family members with the disease is essential to prevent end-organ damage, which might include cardiomyopathy, diabetes, liver cirrhosis, and hepatocellular carcinoma.
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.