Hard to diagnose with an unknown cause, Kawasaki disease has been puzzling doctors for 150 years. Jeremy Hsu explores what we know, and still don’t know, about this troubling childhood heart condition. His story first appeared on Mosaic and is republished here under a Creative Commons license.

A child’s death from scarlet fever wouldn’t have raised any eyebrows during the devastating epidemics that swept Europe and North America in the 1800s. But Samuel Gee, a highly regarded physician in England, found something very strange while cutting open the corpse of a seven-year-old boy in London in 1870. Gee’s autopsy findings, preserved in a single paragraph written in 1871, recorded signs of damage called aneurysms in the coronary arteries running across the surface of the boy’s heart. In the affected regions, the main blood vessels that supply blood to the heart had expanded like modeling balloons because of weakened vessel walls.

Gee described the case as follows:

“The peculiarity of the following case lies in the age of the patient. William Shrosbree, aet. 7, died in Mark on October 20, 1870, in consequence of scarlatinal dropsy with inter-current pneumonia and meningitis. The pericardium was natural. The heart natural in size, and the valves healthy. The coronary arteries were dilated into aneurysms at three places, namely, at the apex of the heart a small aneurysm the size of a pea; at the base of the right ventricle, close to the tip of the right auricular appendix, and near to the mouth of one of the coronary arteries, another aneurysm of the same size; and at the back of the heart, at the base of the ventricles, and in the sulcus between the ventricles, a third aneurysm the size of a horse bean. These aneurysms contained small recent clots, quite loose. The aorta near the valves, and the aortic cusp of the mitral valve, presented specks of atheroma.”

The case presented a puzzle to Gee. He commonly studied child patients while he worked at St Bartholomew’s, a London hospital founded in 1123 that’s often known simply as Barts. The boy’s medical history of having suffered a rash over his body would not have surprised Gee, as it was typical of scarlet fever. Still, heart disease in such a young child was simply baffling. Whatever the cause, it was beyond Gee’s Victorian-era medical knowledge.

Unable to solve the mystery, Gee did the next best thing: preserving the boy’s heart in formaldehyde and creating a medical curiosity for future generations in the process. The heart would float alone in its jar for more than 100 years before its significance was recognized—evidence of the earliest recorded case of Kawasaki disease in the world.

Alongside rheumatic heart disease, Kawasaki disease is the leading cause of acquired heart disease in young children in high-income countries. Modern medicine can treat most patients with Kawasaki if they are diagnosed early enough.

But progress has been limited, and we still do not know what causes it. There have been many theories since the disease was first medically recognized by Japanese physician Tomisaku Kawasaki in 1967. Some researchers have pointed to an unknown virus. Others say it’s a bacterial or fungal toxin. In the 1980s, the US Centers for Disease Control and Prevention suspected carpet-cleaning chemicals. Several groups have hypothesized that the disease is the result of many different agents that can trigger an overreaction of the patient’s immune system.

Nobody has a satisfactory answer.

Firsthand encounters

Kawasaki disease found me as a third-grader growing up in Cleveland, Ohio. An Asian-American boy with ancestral ties to Taiwan and China, I fit the typical patient profile. In the US, children of Asian descent have the highest rates of Kawasaki disease, followed by African-Americans, Hispanics, and whites. The disease is more common among boys than girls. But as an eight-year-old, I was somewhat older than the typical patient. Most are five or under, and the average age to have Kawasaki disease is two.

A month before I fell ill, I was watching a CNN news broadcast in awe as anti-aircraft fire lit up the night skies over Baghdad. It was the start of the US-led bombardment during Operation Desert Storm in January 1991. By the time US and coalition troops had begun their main ground assault on February 24, I no longer cared about the war half a world away. I was caught up in my own battle.

I developed the classic symptoms within a week. On Saturday, at the start of my illness, my parents took me to the doctor’s office to get a throat culture to test for a bacterial infection. It came back negative. I soon became feverish. The lymph nodes on the sides of my neck became swollen. My tongue took on a strawberry appearance and my lips grew dry and cracked. The skin on my fingers and toes began peeling. My eyes took on a reddish hue. I vomited. At one point, I felt too weak to walk upstairs to the first floor of my family home. I dropped to my hands and knees and crawled instead.

Such a cascade of symptoms helped me in one way: I was too preoccupied with my misery in the present to worry about the significance of my strange illness. Knowing better, my parents hid their anxiety from me at the time. My mom channeled her energy into tirelessly calling different pediatricians and friends in search of answers.

Five days after the start of my illness, pediatricians diagnosed me with Kawasaki disease. I was admitted to Rainbow Babies & Children’s Hospital on Thursday. By that time, I was complaining of aching joints and had developed a rash on my legs and ankles. My palms and feet were red and warm to the touch.

Still, I was lucky. My physicians had dramatically boosted my chances of full recovery by diagnosing me within the first seven to 10 days, a crucial window for treating Kawasaki disease. The hospital stuck an intravenous needle into my arm to deliver a single large dose of gamma globulin, a type of immunoglobulin, which contains antibodies derived from plasma from many blood donations.

This treatment has proved effective in preventing most patients from developing coronary artery aneurysms. This condition, where part of the coronary artery balloons, can lead to heart attacks and, very occasionally, premature death during childhood or adulthood. About 20 percent of children with untreated Kawasaki disease will develop coronary artery aneurysms.

While intravenous immunoglobulin is the main treatment for Kawasaki disease, a small group of unfortunate patients don’t respond to the standard treatment and remain at risk of developing coronary aneurysms. Other therapies have been tried but remain unproven: corticosteroids for intravenous immunoglobulin-resistant patients, tumor inhibitors such as etanercept or infliximab, or the immunosuppressant drug cyclosporin A.

Although aspirin is not normally given to under-16s, children with Kawasaki usually get aspirin to bring down the fever and ease joint pain. When I failed to swallow some aspirin tablets and spat them out into my cup of water, the nurse on the night shift was not amused. I ended up having to drink my medicine as a bitter dose of aspirin-flavored water. But my health was on the mend.

By Friday, I was eating frozen sherbet and feeling much better. Troops of medical residents stopped by my hospital room to hear about my unusual disease from an attending physician. By Saturday morning, I was allowed to go home. In the following months, echocardiogram tests showed that my coronary arteries had become only slightly enlarged as a result of the illness. They returned to normal size.

I survived my encounter with Kawasaki disease, but as I said, I was lucky. I fell ill at a time when more US physicians were recognizing and diagnosing the disease and when—just as importantly—they had learned from Japanese colleagues how to treat it.