Comment on Issaragrisil et al, page 1299
The largest and most comprehensive study on the epidemiology of aplastic anemia is reported by Issaragrisil and colleagues, which identifies new environmental risk factors for aplastic anemia in Thailand.
Despite advances in our understanding of the pathophysiology of aplastic anemia, the possible causes of aplastic anemia have proved more difficult to ascertain and most cases (70%-80%) are still considered to be idiopathic.1 Because aplastic anemia is a rare disease, only large national and international prospective studies will provide meaningful data on the etiology of this condition. The incidence in the West is about 1 to 2 per million per year, but it occurs more commonly in the Far East, with a 2- to 4-fold higher incidence. Reasons for this striking difference in incidence are unclear.
In this issue of Blood, Issaragrisil and colleagues report on a case control study that enrolled 541 patients with aplastic anemia and 2261 control subjects from urban and suburban regions of Bangkok and the rural areas of Khonkaen and Songklain Thailand. Previously reported risk factors for aplastic anemia were also observed in this study, such as exposure to benzene and other solvents and medical drugs, namely sulphonamides, thiazides, and mebendazole. For nonsteroidal anti-inflammatory drugs, the relative risk was increased but was not significant. There were too few exposures to chloramphenicol to exclude an increased risk. No association was found with household pesticides, although a previously reported study from the United Kingdom identified chemical treatment of houses, particularly for woodworm, as a significant risk factor.2
Farming practices in rural Thailand revealed important associations with aplastic anemia. Significant associations were observed with agricultural pesticides, namely organophosphates, DDT, and carbamates. Exposure of farmers to ducks and geese was also a significant risk factor. A borderline association was observed with animal fertilizer; in contrast, there was no association with chemical fertilizer.
Evaluation of sources of drinking water revealed differences between rural and urban areas of Thailand. In rural Khonkaen, where most cases and controls used water from nonbottled sources, there was a significant association with the use of drinking water from nonbottled sources, which was not observed in Bangkok. There was also a significant association with nonmedical needle exposure. Surprisingly, posthepatitic aplastic anemia occurred very infrequently, in a part of the world where viral hepatitis is endemic. In the West, posthepatitic aplastic anemia accounts for up to 10% of all cases.
On the basis of these new findings, the authors propose that an infectious agent may account for many cases of aplastic anemia in rural Thailand. Alternatively, chemical contamination of nonbottled water may be a factor. The low drug attributability of aplastic anemia is confirmed from their previously reported studies,3 and the current view is that the risk of aplastic anemia with chloramphenicol was probably previously overestimated. In contrast, the high etiologic fraction accounted for by these novel environmental factors should stimulate further research into identifying possible infectious agents and genetic factors, which may help to explain the difference in incidence and etiology of aplastic anemia in the Far East compared with the West. ▪