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”