Kawasaki disease is a condition that can affect many parts of a child’s body, including the mucous membranes (lining of the mouth and breathing passages), skin, eyes, and lymph nodes, which are part of the immune system. The disease is the leading cause of acquired heart disease in children in the U.S, and it can affect the coronary arteries, which supply blood to the heart. This can lead, in rare cases, to heart attack and death.
What causes Kawasaki disease?
There are lots of theories about what causes Kawasaki disease. Researchers have thought that it might be linked to genetics or even the wind, of all things. Patients tend to be diagnosed with the condition more frequently from winter through spring, which suggests a possible environmental trigger. Some investigators have even theorized that carpet mites could be carrying a pathogen that causes the disease. “People had their carpets cleaned and, soon after, their children were diagnosed with Kawasaki disease,” said Michael Portman, MD, of Seattle Children’s Research Institute.
Dr. Portman has a new theory, that the soy you eat could perhaps be an important factor in Kawasaki disease. His paper, “Kawasaki disease and soy: Potential role for isoflavone interaction with FcGamma receptors,” was recently published online in Pediatric Research Dr. Portman is a pediatric cardiologist at Seattle Children’s, professor of pediatrics at the University of Washington, and an expert on Kawasaki disease from both the research and clinical perspectives.
Kawasaki disease prevalence, soy consumption
Kawasaki disease is common in Japan—up to 20,000 new cases are diagnosed each year. In the U.S., clinicians diagnose 5,000 cases of Kawasaki disease each year.
Dr. Portman’s theory began with a look at differences in diet. “Soy consumption in Asian cultures is considerably higher than in the U.S.,” said Dr. Portman. Soybeans and soy products are the richest sources of isoflavones, a plant hormone that resembles human estrogen in chemical structure. The earliest significant dietary exposure to isoflavones in children comes through either breast milk or soy-based infant formulas. “Up to 25 percent of infant formula used in the U.S. is soy-based,” he said. Breastfeeding is not as popular in Japan, so use of soy formula may be similar or greater than in the U.S.
Differences in diet between Asians and Westerners are touted as reasons for certain ethnic-related discrepancies in susceptibility for cardiovascular disease and cancer in adults. “Surprisingly, these cultural dietary differences have not been previously considered as the source of the discrepancy in Kawasaki disease incidence among these ethnic populations,” said Dr. Portman.
The science: Could soy play a role in Kawasaki disease susceptibility?
The primary treatment for Kawasaki disease is a high dose infusion of Immunoglobulin (IVIG). IVIG is also used for treatment of inflammatory diseases in adults and children. Although researchers do not completely understand how IVIG works, it appears to bind to receptors termed FcGamma receptors on inflammatory cells. Data from studies conducted by Dr. Portman and others support the hypothesis that modifications in FcGamma receptors impact Kawasaki disease susceptibility and, in some cases, response to treatment. The FcGamma receptors regulate certain immune responses and these receptors are in turn regulated by enzymes called protein tyrosine kinases.
Soy contains genistein, which is one type of a naturally-occurring estrogen compound. Genistein and other isoflavones in soy are enzyme inhibitors that block the action of the tyrosine protein kinases. Dr. Portman’s hypothesis is that genistein in soy affects function of the FcGamma receptors leading to increased susceptibility for Kawasaki disease.
Dr. Portman analyzed data from the Multiethnic Cohort, Hawaii component study, which includes reported daily soy consumption in thousands of Caucasians, Native Hawaiian and Japanese subjects. He compared this data with the incidence for Kawasaki disease in these Hawaiian populations. “The data suggests an association between soy consumption and Kawasaki disease incidence for all children less than 18 years old,” said Dr. Portman.
New study in the works
Soy consumption in children by ethnic groups in the greater U.S. has not yet been studied. Dr. Portman and his team are moving ahead with a case-controlled study to capture that data.
Clinicians at Seattle Children’s diagnose, on average, 40 new patients each year with Kawasaki disease, and follow the cases of up to 1,000 patients.
The American Academy of Pediatrics in 2008 made recommendations to restrict the use of soy formula for infant feeding. Dr. Portman said he believes that many clinicians do not follow the AAP guidelines.