Is it Kawasaki disease? Diagnosing challenging cases

Is it Kawasaki disease?A young child presents in your office with a fever of several days, erythema of the palms and soles of the feet, a rash on the trunk and a bright red tongue. For most pediatricians, this classic presentation of Kawasaki disease is fairly straightforward to diagnose.

“A majority of pediatricians have seen at least one case of Kawasaki in training,” says David Fulton, MD, chief emeritus of the Division of Cardiology Outpatient Services at Boston Children’s Hospital. “And most know how to make a diagnosis when all the clinical signs are present. But it’s important to understand the features of this disease that can make diagnosis more challenging.”

An accurate, prompt diagnosis is imperative, as Kawasaki disease leads to coronary artery aneurysms in about 25 percent of untreated cases. It is the number one cause of acquired heart disease in children in the United States. However, when treated with intravenous immune globulin (IVIG) within 10 days of onset, the frequency of coronary abnormality drops to between 2 and 4 percent.

Notes sat down with Fulton to discuss some critical points to keep in mind when diagnosing Kawasaki disease and new approaches to treatment.

What are the biggest challenges pediatricians face in diagnosing Kawasaki disease?

One big challenge is that children in certain age categories sometimes don’t present with the usual findings that would fit a classical picture of Kawasaki disease.

We’re most concerned about infants under 6 months, because those cases are often very challenging. These kids may have fever and no other real signs except a nondescript rash.

This means pediatricians need to start thinking about the possibility of Kawasaki in infants who have a fever for more than five days, even in the absence of other symptoms. Assessment when you lack full clinical signs should include laboratory testing and possibly an early echocardiogram, because these kids can present with early changes in their coronary arteries. And the earlier we intervene, the more likely we are to prevent long-term damage.

The longer you wait, the greater chance there is for coronary artery damage to have occurred.

Another group that can be a challenge to diagnose are children over age 5. These kids often present with lymphadenitis and generally have a fever, so the pediatrician may assume an infection in the lymph glands. These kids are then often started on oral antibiotics, and when they don’t respond, may be given intravenous antibiotics. At this point, 10 to 14 days has passed, and they may have already evolved to coronary artery changes.

What advice would you give pediatricians for diagnosing these challenging cases?

I would say the most important advice is to keep thinking broadly, and to have Kawasaki on your radar screen. We see about 5,000 cases a year in U.S., so many pediatricians will see a reasonable number in their practice.

We’ve found that pediatricians are getting better at spotting incomplete cases of Kawasaki, but we still see a couple of cases each year that get missed and come to us late. The American Heart Association released updated guidelines earlier this year to provide clinicians with evidence-based guidance for diagnosis of Kawasaki disease.

What happens when you miss that 10-day treatment window?

Treatment with IVIG within 10 days of fever is the gold standard for Kawasaki disease. But that doesn’t mean you shouldn’t treat at day 12 or day 14, it just means that the response is less identifiable. The longer you wait, the greater chance there is for coronary artery damage to have occurred.

How do you handle incomplete or uncertain cases of Kawasaki disease?

Sometimes it’s even challenging for us to diagnose incomplete Kawasaki. We often see kids who have a couple of the signs and have had a fever for five or six days. If they don’t meet the diagnostic criteria at that point, we may follow them for a few days to see if they evolve with more signs that may help with a diagnosis. If we reach day seven or eight with no more symptoms, we may look for laboratory abnormalities or use an echocardiogram to decide whether to treat. Finally, there are some kids that we’re just never going to be 100 percent sure about, but decide to treat them before they go past that 10-day window.

Is there any harm in treating kids for Kawasaki who may not have it?

There’s always a risk with any type of treatment. The risk for transmission of infectious disease through IVIG is very small, but children can have adverse reactions to treatment, such as fever, rash, low blood pressure and shaking chills. It’s also expensive, so we try to be mindful of that. But we generally err towards treating as we approach that 10-day window. Without a doubt, the benefits of treating outweigh the risk.

What’s new on the treatment front?

About 10 to 20 percent of kids are resistant to IVIG and may require multiple doses and adjunctive therapy to suppress the immune response. We’re continually evaluating new therapeutic modalities to see what works best.

We’re also looking at ways to identify people who might not respond early so we can start adjunctive therapy as soon as possible. In the future, we will likely move toward more aggressive therapeutic approach earlier in the cycle for these people to see if it makes a difference with outcomes. But the sooner these kids get referred to us, the better likelihood we have of selecting the best therapeutic approach for them.

 

David R. Fulton, MD, is chief emeritus of the Division of Cardiology Outpatient Services at Boston Children’s Hospital, associate professor of Pediatrics and Tommy Kaplan Chair in Cardiovascular Studies at Harvard Medical School.