Hemochromatosis is the most common inherited metabolic condition in Western populations. An estimated 10 percent of persons of northern European descent carry the autosomal recessive gene, and one person in 250 is affected by the disease. The basic disorder of iron metabolism results in excessive absorption of iron and deposition in the tissues. Traditionally, hemochromatosis has been suspected only when the classic triad of cirrhosis, diabetes and skin pigmentation indicate advanced disease and irreversible tissue damage. McCurdie and Perry review the various presentations of hemochromatosis, particularly the potential savings through prevention of morbidity and mortality that is associated with early diagnosis.
Arthropathy occurs in approximately 64 percent of patients with hemochromatosis. Although joint pain was originally thought to be a late symptom of hemochromatosis, it is reported by 45 percent of patients at the time of diagnosis and may be the presenting complaint or the most severe presenting symptom in a majority of new cases. The typical patient is male (male-to-female ratio: 9:1), 40 to 60 years of age and likely to have a family history of hemochromatosis, cirrhosis or diabetes. The disease presents insidiously with symptoms such as lethargy, weakness, sleep disturbance or sexual problems. Patients with joint symptoms report arthralgias for an average of three years before diagnosis. Although any joint may be affected, the second and third metacarpophalangeal joints are characteristically stiff, painful and tender. Radiographs show small cysts and hooked osteophytes at the metacarpal heads. Patients may also present with early onset of osteoarthritis, especially in the hips, or with episodes of pseudogout. Pseudogout results from deposition of calcium pyrophosphate, usually in the wrists, knees, hips and symphisis pubis, and may occur in up to 72 percent of cases.
The authors advocate wider screening using family history, clinical signs of liver disease and diabetes, serum ferritin concentration, liver function tests, serum glucose concentration and radiography of symptomatic joints. The single most useful value is serum ferritin, which exceeds 1,000 ng per mL (1,000 μg per L) in patients with hemochromatosis, compared with normal adult values of up to 330 ng per mL (330 μg per L) in men and 120 ng per mL (120 μg per L) in women. First-degree relatives of patients with confirmed hemochromatosis should also undergo screening.
The treatment of hemochromatosis is regular venisection to deplete body iron stores. Weekly venisection may be required initially, but most patients require maintenance veni-section only four to eight times per year. Once treatment is established, arthropathy improves in 30 percent of patients, worsens in 20 percent and is unchanged in the remainder. The development of diabetes and cirrhosis appears to be delayed or prevented, and the life expectancy of regularly treated patients is reported to be normal.
The authors report illustrative cases and urge consideration of hemochromatosis in the differential diagnosis of adults presenting with exercise-related or other joint pains. Early diagnosis can prevent the development of serious, irreversible complications.