Dissecting Kawasaki Disease, Part 1: Misdiagnosis is Mandatory

According to the latest numbers available, Kawasaki Disease (KD) is still technically defined as a rare disease in most countries around the world.  We know that more and more children are being diagnosed with KD each year, but we don't know how many children are still going misdiagnosed.  The reasons for the misdiagnosing, while not always talked about, are clear.  The answer for this problem is simple; we need a diagnostic test for Kawasaki Disease.

Is Kawasaki Disease a rare disease?

While the definition of rare disease varies by country (US, EU, Canada, Japan all have their own definitions) the latest number of diagnosed cases of Kawasaki Disease still defines it as a rare disease.  In America, about 20 in 100,000 kids will be diagnosed each year.  According to this article in The Permanente Journal, 5,500 cases were estimated in the United States in 2009.  This 2012 article reported an incident rate in Japan of over 230 in 100,000 children under 4-years-old.

KD may still technically be rare, but numbers are rising all over the world. This 2009 article in the Journal of the American College of Cardiology described KD as "commonplace all around the world" and estimated there may have been as many as 1,000,000 cases of diagnosed and undiagnosed KD since it was first defined in 1967, with many more people affected before 1967.  Dr. Burns' Kawasaki Disease Lab goes even further by stating, "Kawasaki Disease is not a rare illness and the exact number of cases which occur in the United States has not been determined."

How do we know there are cases going misdiagnosed?

Many classic cases of KD start out as multiple misdiagnoses.  DSK's Kawasaki Disease Resource List enumerates many of these personal stories, like Cooper's story, Maya's story, Isaiah's journey, or Julian's saga.  My own daughter was misdiagnosed multiple times with both her bouts of KD. 

The numbers seem to show what these KD families have experienced.  This study, published in Pediatrics in 2005, found many children had to be seen by a doctor at least four times before a diagnosis of KD was made.  Even though over half of patients saw a doctor within the first 2 days of symptoms, only 5 of 106 children were given a diagnosis of KD at the initial visit.

In addition, we are now seeing adult patients who are experiencing coronary complications that presumably stem from an undiagnosed case of Kawasaki Disease they had sometime as a child.  An article in The Permanente Journal states, “many cases of fatal and nonfatal MIs in young adults have been attributed to 'missed' KD in childhood."  A January, 2013 article in Internal Medicine describes the case of a 72-year-old man who had giant coronary aneurysms, even though he had never been diagnosed with KD and was not symptomatic.  The authors conclude, "The present case suggests that there may be a substantial number of patients who have attained middle to old age with undiagnosed KD."

WHY does KD get misdiagnosed so frequently?

In the absence of a diagnostic test, KD is diagnosed by taking a thorough history and physical, and ruling out other illnesses.  In order to be diagnosed with KD, a child must run a fever for at least 5 days and have at least 4 of these accompanying symptoms: 1) rash; 2) swollen neck lymph nodes; 3) swollen hands and feet, red palms and soles; 4) bloodshot eyes; and 5) red, chapped lips and strawberry tongue.  Sounds pretty simple, right? Wrong.  Here are four reasons why it's more complicated.

1. The symptoms might not show up all at once.

Coronary artery complications (the most serious complication of KD) are greatly reduced when the treatment of intravenous immunoglobulin (IVIG) is given within the first 10 days of fever onset.  Unfortunately, sometimes it takes all ten of those days (or longer) for enough of the classic KD symptoms to show up.  Some symptoms may already be gone by the time others show up.  Sarah Chalke has mentioned that all of her son’s classic KD symptoms had started to dissipate by the time they saw a specialist on day 10.  If she hadn’t taken pictures of her son while he had the symptoms, the doctor may not have been able to diagnose KD. 

A 2007 article from Taiwan concluded that wide dispersement of the classic symptoms leads to more delayed-diagnoses beyond day 10, which leads to a higher incidence of coronary artery aneurysms (CAAs).  This excerpt from the American Heart Association statement on KD shows just how a misdiagnosis from delayed onset of symptoms can happen: "Children may present with only fever and a unilateral enlarged cervical lymph node. The rash and mucosal changes that follow often are mistaken for a reaction to antibiotics that are administered for presumed bacterial lymphadenitis." 

Many people like to talk about the peeling skin on the fingers and/or toes as a definitive symptom of KD.  Even though a majority of KD children do experience this desquamation, it usually occurs in the sub-acute or convalescent phase of the disease, after the 10-day window for effective IVIG treatment.  This article mentions that it is during this second phase of the illness that heart complications are likely to occur, so it is very important to diagnose KD before the fingers or toes start peeling. 

2. Many symptoms may not show up at all (Incomplete KD).

Incomplete Kawasaki Disease can be diagnosed in children who present with a fever and only 2 or more of the classic KD symptoms.  When so few classic KD symptoms show up, it should be no surprise that diagnosing incomplete KD is even harder than diagnosing complete KD.  Children with incomplete KD still have a risk for cardiovascular complications, including CALs, aneurysms, and heart failure. Children with incomplete KD have a higher risk of delayed diagnosis and were less likely to be treated with IVIG. Many studies (like this one and this one) have found an increased risk of cardiovascular complications, which is probably related to the other risk factors associated with incomplete KD.

3. Classic KD symptoms may look like other illnesses.

Many of the classic KD symptoms are also normal symptoms of other, less rare diseases.  My daughter was first diagnosed with a double ear infection, then strep, then scarlet fever, and they also thought the rash may be due to an allergic reaction to antibiotics.  I've heard other parents tell this tale of misdiagnosis so many times, it almost sounds like a mandatory step in diagnosing Kawasaki Disease. 

According to this site, "the rash may mimic common infections like measles, rubella, parvovirus and scarlet fever and may also resemble erythema multiforme.”  This 2005 Pediatrics article found instances of ultimate Kawasaki Syndrome first being diagnosed as “cervical adenitis, meningitis, pneumonia, appendicitis, or pyelonephritis."

4.  There may be additional symptoms that further complicate the KD diagnosis. 


My daughter had the worst cough she's ever experienced, both times she had Kawasaki Disease.  She would also have bouts with abdominal pain, vomiting, diarrhea, joint pain, lethargy, and extreme irritability.  Her personality literally changed during her illness and she reacted to things completely differently than she would normally.  These are all common symptoms for KD, and about a million other illnesses.

This 2013 article records a long list of "nonspecific clinical features," that may accompany the classic KD symptoms.  Some of these symptoms include irritability, uveitis, aseptic meningitis, cough, vomiting, diarrhea, abdominal pain, gallbladder hydrops, urethritis, arthritis.  Additional symptoms could be lethargy and myalgia.  Other symptoms (many very rare) reported by the American Heart Association include more irritability than with other febrile illnesses, facial nerve palsy, sensorineural hearing loss, hepatic enlargement and jaundice, testicular swelling, and pulmonary nodules.

Many of these symptoms can most definitely be mistaken for other more common diseases like, "influenza, upper respiratory infection, strep throat, or food poisoning."  Right Diagnosis points out that "Kawasaki disease is usually diagnosed by eliminating other disease possibilities, such as scarlet fever, cytomegalovirus infection and toxic shock syndrome”

Closer to a Diagnostic Test for Kawasaki Disease

It’s been a big year for Kawasaki Disease, but this hasn’t always been the case.  KD has been a pretty steady bench warmer on the team of rare diseases.  Every once in a while, we’re called in to pinch hit.  We bat a marathon here, a House episode there.  But all jokes aside, Kawasaki Disease is just not very well known.  I’ve had nurses ask me what it is when giving them my daughter’s history.

According to Seattle Children’s Hospital, doctors in America diagnose approximately 4,000 cases of KD each year.  And this, of course, doesn’t consider the countless cases that go misdiagnosed.  The Kawasaki Disease Lab at UCSD tells parents as much by stating, “Kawasaki Disease is not a rare illness and the exact number of cases which occur in the United States has not been determined,” They estimate that 10 out of every 100,000 children will be affected and have observed KD occurring in “clusters or localized outbreaks - usually in the winter and spring.”  I’ve seen other statistics as high as 19 or 20 out of every 100,000. 

The only time I’d ever heard of this illness before 2008 was in an episode of the TV show ER.  Then my 22 month old started displaying the classic symptoms of Kawasaki Disease and I got very familiar very quickly.  If that wasn’t enough, I became even more intimately involved when she was diagnosed again at 6 years old with Recurrent Kawasaki Disease.

From a medical standpoint, KD is defined as a pediatric self-limited vasculitis that is the leading cause of acquired heart disease in children.  The complication that raises the most concern is inflammation in the coronary arteries of the heart.  If left untreated, KD can lead to coronary artery aneurysms in up to 25% of reported cases.  When treated with Intravenous Immunoglobulin (IVIG) within the first 10 days after symptoms start, chances of heart complications are reduced. The primary symptom of KD is a fever that lasts more than five days.  The other symptoms are visually alarming and include red and swollen feet and hands, red eyes, red/chapped/cracked lips, strawberry tongue, rash, and swollen lymph nodes in the neck.

From a kid engulfed in its blaze standpoint, KD is defined as pain - an awful, burning pain.  My daughter has a hard time describing it.  She will talk about how much it hurt, but can’t tell me where.  It’s like it hurt everywhere at the same time, and then it hurt worse because someone was always “doing something to me.”

From a parent sitting helplessly at the foot of the bed standpoint, KD is defined as watching my child burning from the inside, out.  Think about the last time you had a sunburn and how much that hurt.  Now imagine having a sunburn on the inside of your body.  It’s like every cell in her body was on fire, and nothing could quench it.  You want desperately to soothe your baby, and your baby wants so desperately to be soothed.  But there is no soothing.  There is no comforting.  There is only burning. 

And the hits just keep on comin’.  No one knows what causes KD.  There is no diagnostic test for KD and no test to show it’s “cured.”  No one knows how to prevent Kawasaki Disease and many cases of a-typical or incomplete KD are never diagnosed.  Many other cases of KD aren’t diagnosed within the 10 day window, which often leads to further complications. 

But, I don’t mean to be quite so dire.  Even though there are still many confusing questions, the quest for answers has never been more fervent than in the past few years.  In November of 2011, a group of Singapore scientists published a study in Nature Genetics that identifies a specific gene (a protein called FCGR2A) associated with an increased risk of KD.  That same month, a group of doctors, including Dr. Burns, published a study that suggested the environmental trigger for KD could be wind-borne. 

Many more hospitals are now focusing in on Kawasaki Disease.  Seattle Children’s Hospital’s Portman Research Group Kawasaki Disease Program is currently trying to understand and improve the treatments for KD and is also pursuing a hypothesis that soy consumption may be associated with KD risk.  Rady’s Children’s Hospital’s Kawasaki Disease Clinic follows the status of 1,200 KD patients in San Diego and treats 80 to 90 cases every year. Dr. Burn’s Kawasaki Disease Lab at UCSD has information about 12 separate studies on their website.  Many of the research studies conducted by these groups are still accepting participants. 

There have also been media sightings of a slightly flashier nature.  In April of 2011, chef Nate Appleman chose the Kawasaki Disease Foundation as his charity when he won the Food Network’s Chopped All-Star competition because his son had been affected.  After his own son recovered from KD, Gary Busey joined the campaign and started The Busey Foundation.  Busey went on (and was fired from) the latest season of Donald Trump’s Celebrity Apprentice, in the hopes of winning money for KD. 

The biggest spotlight yet came on March 8, 2013, when Sarah Chalke guest starred as the mom of a little boy sick with Kawasaki Disease on an episode of Grey’s Anatomy.  The prominent storyline not only mentioned the classic symptoms of KD, but also illustrated the kind of cat-scratch fighting a parent often has to endure when Kawasaki Disease invades their child and how important it is to listen to your intuition when it comes to the health of your child. 

The wonderfully hilarious actress got serious when she opened up a small window into her private life and told the world that her own son was a Kawasaki Disease survivor.  Ms. Chalke explained that after meeting other KD survivors and their parents, she felt compelled to join the KD awareness campaign.  She approached Grey’s creator, Shonda Rhimes, with the KD storyline idea and made the round of popular talk and news shows, giving millions of people their first glimpse at this unusual disease. 

Promising research and a larger public spotlight have now collided into the most hopeful KD news yet. We may soon have a diagnostic test for Kawasaki Disease! The combined efforts of Dr. Burns' team, The Kawasaki Disease Foundation, and Sarah Chalke have culminated into the Kawasaki Disease Challenge Fundraiser on CrowdRise.com.  On the fundraiser’s website, Sarah Chalke writes:

When my son had Kawasaki Disease and was misdiagnosed for ten days, I can’t tell you how many times I said, “I just wish there was a test. A test that could tell us if this is KD.”

And now there might be.  A team of doctors at Stanford University and UCSD have devised a prototype for a diagnostic test. This is a huge deal. This test could be 95% accurate but it needs to be tested for two years before it can be used. We NEED this test because of the ticking clock to get treatment to prevent heart damage that can lead to a heart attack.

The disease that didn’t even get its name until 1967 may yet be considered a rare childhood disease to some and many have still never even heard of it, but once Kawasaki Disease enters your life, you never forget it.  So many moms, just like myself, have gone through this nightmare and felt compelled to reach out and make sure other parents have indeed heard of Kawasaki Disease.  Sarah Chalke is one of these moms.  We want the misdiagnosing to stop.  The best way to do that is with a diagnostic test.  We’re now closer than we’ve ever been before.  Please go to Sarah Chalke’s Kawasaki Disease Challenge today.  It has already raised over $5,000 in its first 2 days, and the Gordon and Marilyn Macklin Foundation will match dollar for dollar up to $100,000! Let's raise $200,000 for a Kawasaki Disease diagnostic test.  Donate.  Share.  Tell your coworker over coffee.  Mention it to your neighbor over the fence.  Save a heart.  Save a life.


 

For an organized list of all the links in this article and many more, please check out my KD Resource List.