Risk of Several Autoimmune Diseases Increased in Childhood Cancer Survivors

Childhood cancer survivors are at heightened risk of a wide range of autoimmune diseases, revealed research published in the Annals of the Rheumatic Diseases (doi:10.1136/annrheumdis-2015-207659). Diabetes and Addison's disease, also referred to as adrenal insufficiency, make up almost half of the excess cases, according to the findings.

Over the past 40 years, the number of childhood cancer survivors has risen sharply, resulting in a 5-year survival rate of 80% among children who succumb to the disease. But mounting evidence suggests that these survivors are at heightened risk for various health problems as adults, which increase in number and severity as they get older.

The researchers looked at the risk of developing a wide range of autoimmune diseases among more than 20 000 adults who had had cancer before age 20 years, and survived for at least 1 year, and nearly 126 000 people, matched for age, gender, and country of birth, who had not had cancer as children.

They used national cancer registry data from Denmark, Iceland, and Sweden, dating back to the 1940s up until 2008, to identify those who had had cancer as a child. Also, they used hospital records to work out the difference between the expected and excess number of cases of autoimmune disease, expressed as a standardized hospitalization rate ratio (SHRR). The health of all the participants was tracked for an average of 15 to 19 years.

In all, 724 (3.6%) childhood cancer survivors had at least 1 episode of hospital treatment for any autoimmune condition, when 516 would have been expected ordinarily, amounting to a 40% increased risk. Or put another way, 7 extra cancer survivors were treated for every 1000 patients tracked over a decade.

The SHRRs were significantly higher for 11 of 33 autoimmune diseases investigated among the childhood cancer survivors, particularly for the rarer forms.

The analysis revealed that autoimmune hemolytic anaemia was 17 times more likely, Addison's disease 14 times more likely, and polyarteritis nodosa (inflammation of the small muscular arteries) 6 times more likely, among those who had had cancer as a child.

Similarly, childhood cancer survivors had significantly higher rates than expected of rheumatic heart disease, scleroderma (connective tissue disease), idiopathic thrombocytopenic purpura (tendency to bleed and bruise easily due to low clotting factor levels), Hashimoto's thyroiditis, pernicious anaemia, sarcoidosis (abnormal cell clumping), Sjögren syndrome (a tear duct and salivary gland disorder), and diabetes.

Those who had had leukemia, Hodgkin lymphoma, kidney cancer, and central nervous system tumors seemed to be at greatest risk of developing an autoimmune disorder in later life. They were up to 60% more likely to do so than those who had not had cancer in childhood.

The excess risk for all autoimmune diseases combined peaked during the first 5 years after a cancer diagnosis, which may be a consequence of closer medical monitoring, explained the researchers.

However, the excess persisted for up to 30 years later for most conditions, and up to 50 years later for some conditions.

One possible explanation for the findings is that "persistent immune abnormalities after treatment with chemotherapy predispose to the development of autoantibodies, which are central to the pathogenesis of many autoimmune diseases," they wrote.

"Cure is no longer a sufficient goal in childhood cancer care," they emphasized. "As the vast majority of these patients survive, attention must be paid to their long term quality of life and health challenges."

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