Two months ago I wrote a post on Multisystem Inflammatory Syndrome in Children (MIS-C), a rare condition associated with SARS-CoV-2 that causes severe inflammation throughout the body three to four weeks after an often-unrecognized infection. This week I diagnosed my first case of MIS-C, and when thinking through a differential for a patient presenting with persistent high fever, diffuse rash, and conjunctivitis was reminded of a case report I had come across a while ago and had tucked away for a possible future discussion. It’s bad. Real bad. I’m talking screaming at the computer monitor and then having to explain to my kids that everything is okay, Daddy is just upset at some doctors in China, kind of bad.
Published in the European Journal of Integrative Medicine last year, the report describes the treatment of a 17-month-old child suffering from Kawasaki disease (KD) with Chinese Herbal Medicine. Herbal therapy in this case was used instead of a science-based drug therapy proven to be safe and effective in preventing a deadly potential complication. The treatment strategy employed and ultimately recommended by the authors of the paper amounts to an abomination of disregard for the child’s well-being and is an egregious violation of ethical principles fundamental to the practice of medicine.
My patient with probable MIS-C reminded me of this case report on treating Kawasaki disease with quackery because KD and MIS-C share many features. In fact, KD is one of the most important conditions we consider when evaluating pediatric patients with prolonged fever and systemic inflammation because a delay in appropriate treatment can be catastrophic.
Allow me to explain in a bit more detail.
What is Kawasaki disease?
The most common cause of acquired heart disease in developed countries, KD is a febrile illness in children that is associated with inflammation of medium-sized arteries (vasculitis) throughout the body. Of particular concern is the possible involvement of the coronary arteries that deliver oxygenated blood to cardiac muscle. The underlying cause of KD is a mystery, and despite decades of study and refinement of our understanding of the clinical course, there is no established diagnostic test.
The diagnosis of KD is based on a set of criteria that any pediatrician or family doctor should know by heart. In addition to these historical and exam findings there are also a host of laboratory and imaging studies that can support a clinical suspicion. And while the diagnosis of so-called “classic” KD can be fairly straightforward, many cases are “incomplete” and clinical judgment must be relied upon. So, sadly, despite the fact that our diagnostic criteria are very purposefully designed to be a bit oversensitive in order to avoid the potential tragedy of delayed diagnosis, there are still children who suffer what are largely preventable sequelae.
KD is a self-limited condition that typically affects children less than 5 years of age, although it can rarely be seen in older children. This means that the unremitting fever, painful cracked lips and tongue, widespread rash, swollen and tender extremities, enlarged neck glands, and red eyes that make up the classic diagnostic clinical criteria will resolve without intervention, usually within 10 days of the first fever. Even the infamous extreme irritability seen in these patients, who are most often less than 3 years of age when hospitalized, will almost always just go away on its own. The potential problem, and it’s a big potential problem for these patients, is that even with appropriate treatment 3% to 5% of children with KD will have involvement of the coronary arteries. Without treatment, this occurs in a full quarter of patients.
Inflammation of the heart and coronary arteries can weaken the walls of these vital blood vessels. This weakening will result in mild dilation in most cases, but can also lead to giant aneurysms that put a child at particular risk for a host of acute and chronic cardiac problems. Death can occur months to years later when the coronary arteries become stiffened, thus decreasing blood flow to the cardiac muscle and resulting in myocardial infarction (“heart attack”), or during the acute phase of the illness when the function of the heart is impaired or there is an abnormal electrical rhythm.
The first description of KD came in 1967 from Japanese pediatrician Tomisaku Kawasaki, but it took several years before the link was made between the diagnosis and coronary artery involvement. It has since been seen in all geographic regions, however Japanese children are significantly more likely to be diagnosed than any other group. In the United States, around 1 in 5,000 children under the age of 5 years are hospitalized because of KD every year, but in Japan that rate is about thirteen times higher.
There is a clear genetic predisposition to developing KD, but there have also been seasonal peaks as well as increased incidence in localized areas, which points towards a possible viral etiology. There have also been various bacterial toxins proposed as candidate triggers. There may in fact be several agents that trigger a common final pathway in genetically-susceptible children. To date, however, there is no proven cause.
The standard treatment for KD is intravenous immune globulin, or IVIG, ideally given within 10 days of the onset of fever. It’s safety and efficacy is well established even if the exact mechanism of action in treating KD isn’t clear. It appears to have a general anti-inflammatory effect but it may also bind toxins or modulate the adaptive and innate immune response in a variety of ways. Regardless, it almost always stops the fever and other signs of inflammation within 24 hours of dosing, and it significantly reduces the risk of coronary artery complications. It’s an expensive drug, but it is very cost effective considering the savings of preventing things like heart transplants in toddlers.
One more interesting tidbit on Kawasaki disease. It is one of the very few conditions for which we actually recommend aspirin in young children, primarily for its anti-thrombotic (clot prevention) properties. There isn’t any evidence that it prevents coronary artery lesions or hastens recovery, however. It is just a thing that we do because it’s a thing that we have always done.
If a child doesn’t have evidence of coronary artery involvement at the 6-week check after treatment, aspirin is typically discontinued. Aspirin use has been linked to a rapidly progressive encephalopathy associated with liver dysfunction (Reye syndrome) in pre-pubertal children. Although the occurrence of Reye syndrome in the setting of treating KD with aspirin is incredibly rare, I can’t help but be a bit apprehensive every time I prescribe it.
Chinese herbal medicine for Kawasaki disease?
In the case report, an irritable and febrile 17-month-old child was appropriately diagnosed with KD by a “Western medical physician” based on clinical diagnostic criteria. This isn’t one of those cases where maybe it was actually something else. He had 5 days of fever, red eyes without discharge, swollen hands and feet, inflamed lips and tongue, a diffuse rash, and swollen neck glands. This diagnosis was also supported by elevated inflammatory markers in his blood. Hospitalization was recommended but the family refused and opted for outpatient herbal treatment by an affiliated traditional Chinese medicine clinic.
He was prescribed a number of herbal remedies and followed closely by the clinic. The signs and symptoms of his KD improved over the following several days, resolving completely by the eleventh day of illness. Two days later the skin around his fingernails and toenails began to peel, a finding that is alone almost diagnostic of KD when it occurs 2-3 weeks after a febrile illness. He had two ultrasounds of the heart several weeks after his diagnosis that did not find any involvement of the coronary arteries. 12 months after his diagnosis he was healthy and thriving, likely unaware of just how lucky he was.
The authors of the paper, some of which having had the medical training to know better, explain Kawasaki disease in the language of TCM. There is a lot of nonsense about pathogenic heat and toxin battling positive Qi, coagulated meridians, and something called a phlegm nucleus. When attempting to reconcile the particular herbal remedies they chose with a more scientific understanding of the condition, they don’t have much to go on. It’s essentially just rat models and other preclinical research. Certainly there isn’t anything that would remotely justify taking the risk that they did, and there is no mention of providing proper informed consent to the child’s parents. They conclude the paper by declaring that their approach is safe and effective as an alternative to IVIG.
Conclusion: Stick to science-based treatment of Kawasaki disease
The child at the center of this case report was extremely lucky. While the odds were in his favor because of its self-limited nature, he still faced a 25% chance of injury to his coronary arteries and all the potential subsequent adverse outcomes of untreated Kawasaki disease. There is simply no evidence to support the use of any herbal remedy as a treatment for such a serious condition.
Standard of care management of KD that is safe and effective was available to this child, it just wasn’t given. Also, it wasn’t clear that the family, who was essentially thrown under the bus in this report, was even made aware of the risk of not treating their child with IVIG, thus violating fundamental ethical principles in the practice of medicine. This simply should not have been allowed to happen and the European Journal of Integrative Medicine had no business publishing this report.