Is this Kawasaki Disease?

Patient Presentation
A 6-year-old male came to clinic with new rash and a 5 day history of recurrent fevers. The morning of day 1 he woke up with right eye conjunctivitis that was non-purulent. A family member was a healthcare provider and began him on antibiotic ophthalmic ointment. That evening his fevers began and were 103.5 degrees F axillary. They responded to acetaminophen and ibuprofen but recurred every 4 hours.
On day 2, he was seen in clinic because of the fever, sore throat, mild abdominal pain and a sibling who was being treated for strep throat. His lips were noted to be slightly dry but not cracked, the papillae of the tongue were slightly prominent. He also had shotty cervical adenopathy. The rapid strep test was negative, and he was diagnosed with a viral syndrome.
On day 3, his left eye also had non-purulent conjunctivitis and his fevers continued.
On day 4, his fevers continued as did his conjunctivitis and dry lips. On day 5 he broke out in a rash on his trunk, palms and soles.
The past medical history revealed him to be a healthy child.
The review of systems showed he had recently travelled within the U.S. and family members were sick with strep throat or bronchitis. He inconsistently complained of photophobia and also a sore foot. He had no other medications.
The pertinent physical exam showed him to be tired appearing with a fever to 39.5 degrees C. His eyes showed scleral and palpebral injection and increased tearing without exudate. His lips were dry without cracking or bleeding. Posterior pharynx was quite red, but without ulcers, petechiae or exudate present. Tongue papillae were prominent. Tympanic membranes were normal. He had general anterior cervical adenopathy and a 1 cm anterior cervical node on the left side. His skin showed a red, macular, blanching rash, that was slightly lacy appearing on his trunk, arms, legs, palms and soles.
His heart, lung, abdominal, genital and extremity examinations were normal.
His laboratory evaluation included a hemoglobin = 14.4 mg/dl, hematocrit = 38%, platelets = 188 x 1000/mm2, WBC = 7.4 x 1000/mm2 with 924 bands, C-reactive protein = 2.51mg/dl and ESR = 28 mm/hr.
The diagnosis of a febrile illness and possible Kawasaki Disease was made. The plan was to follow him clinically and consider beginning intravenous gamma globulin. His antibiotic ointment was also stopped.
The patient’s clinical course the following day (day 6), showed him to be having fevers around 102 degrees F axillary, his rash was also fading slightly. That night he had two drenching night sweats, but no fever was documented at that time. The plan was to continue to monitor him and treat
On day 7, his fevers were around 100-101 degrees F axillary. That night he also had another drenching night sweat.
On day 8 he returned to clinic, having had no fever for ~20 hours. On physical examination he was still tired appearing with bilateral conjunctivitis, a 1 cm anterior cervical node, dry lips, and prominent tongue papillae. The rash was gone.
A full work-up to decide if he needed intrvenous gamma globulin was made. Laboratory testing and consultation with cardiology and infectious disease specialists were obtained concurrently. The laboratory evaluation revealed hemoglobin = 13.9 mg/dl, hematocrit = 39%, platelets = 332 x 1000/mm2, WBC = 7.1 x 1000/mm2 with 144 bands, C-reactive protein = 1.1mg/dl and ESR = 30 mm/hr. Urinanalysis was normal. A chest radiograph and electrocardiogram were normal.
It was the opinion of the consultant specialists and the general pediatrician that this was unlikely to be Kawasaki Disease because the fevers were decreasing and the laboratory evaluation showed decreased markers of inflammation. Therefore, he was sent home with a diagnosis of an unknown viral syndrome to be monitored and again return if the symptoms worsened or returned.
His final viral culture for adenovirus, influenza virus, parainfluenza virus, respiratory syncytial virus as well as a blood and urine cultures. did not grow an organism. He remained fever free with resolution of his symptoms over the next 3 days. He did not have any later symptoms such as peeling fingers or toes.

Discussion
Kawasaki Disease (KD) is an acute, self-limited vasculitis of unknown etiology. It was first described in Japan in 1967 by Tomisaku Kawasaki. It occurs in children of all races and more commonly occur more in late winter and spring months. Boys have it more commonly than girls and ~75% are in children < 5 years old.
The etiology is unknown but data strongly suggests an infectious cause or trigger of the patient’s immune system.

KD is is defined as:

  • Fever of at least 5 days

  • Plus 4 or more of the following:
    • Polymorphous exantham

    • Bilateral bulbar conjunctival injection without exudate
    • Changes in lips and oral cavity – erythema, cracked lips, strawberry tongue, diffuse injection
    • Cervical lymphadenopathy – more than 1.5 cm, usually unilateral
  • Exclusion of other diseases with similar findings
    • Viral infections – especially adenovirus, entervirus, Epstein-Barr virus and measles

    • Scarlet fever
    • Staphylococcal scalded skin syndrome
    • Toxic Shock Syndrome
    • Bacterial cervical lymphadenitis
    • Drug hypersensitivity reactions
    • Stevens-Johnson syndrome
    • Juvenile rheumatoid arthritis
    • Rocky Mountain spotted fever
    • Leptospirosis
    • Mercury hypersensitivity reaction

Coronary artery aneurysm or ectasis occurs in 15-25% of untreated patients which can lead to ischemic heart disease, myocardial infarction, and possibly death.

As this constellation of symptoms is commonly seen, simple laboratory investigations are undertaken. Laboratory findings associated with KD include:

  • Leukocytosis with neutrophilia and immature forms

  • Elevated C-reactive protein
  • Elevated erythrocyte sedimentaiton rate
  • Thrombocytosis after week 1
  • Sterile pyuria

Treatment for KD involves giving intravenous gamma globulin and aspirin (or other anti-platelet medications) plus follow-up with echocardiograms.

Learning Point
Some patients do not fulfill the full criteria for KD and/or have unusual presentations of the findings. The American Heart Association states that patients with incomplete KD are those patients who “???lack sufficient clinical signs of the disease to fulfill the classic criteria; they do not demonstrate atypical clinical features.” They argue that ‘atypical KD’ should be “??? reserved for patients who have a problem, such as renal impairment, that generally is not seen in Kawasaki disease.” Suspected incomplete KD often makes healthcare providers and families very uncomfortable because one is balancing the risks of potentially serious cardiac morbidity and mortality against the risks of intravenous gamma globulin (i.e. potential anaphylaxis) that may not even be needed. In 2004 the American Heart Association released a scientific statement with an algorithm outlining the evaluation of suspected incomplete KD.
The algorithm outlines when to obtain laboraory tests, cardiac echocardiogram and subspecialty consults.

Algorithm for the Evaluation of Incomplete Kawasaki Disease is available from the American Heart Association.

The current patient’s symptoms were consistent with incomplete KD. He had the criteria for fever and exclusion of other diseases. He had the rash and conjunctivitis. But, he only had dry lips, and papillae on his tongue were prominent. Neither finding was described as classic for KD. He also did not have lymphadenopathy that was sufficiently large enough to meet criteria. He was followed closely and his work-up generally followed this algorithm. Luckily this patient did not have KD as the fevers decreased, the laboratory evaluation showed decreased inflamamtion markers and during follow-up he did not show other symptoms. The etiology of this patient’s symptoms was not identified.

Questions for Further Discussion
1. What other clinical findings are associated with KD?
2. What other laboratory findings are associated with KD?
3. What are the criteria for high dose or low dose aspirin therapy for patients with KD?

Related Cases

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Information prescriptions for patients can be found at Pediatric Common Questions, Quick Answers for this topic: Kawasaki Disease.

Newberger JW, Takahasi M, Gerber MA, et. al. Diagnosis, Treatment and Long-term Management of Kawasaki Disease. Circulation 2004;110:2747-2771. Available from the Internet at: Available from the Internet at: http://circ.ahajournals.org/cgi/content/full/110/17/2747 (cited 3/28/05).

Scheinfeld NS, Silverberg N, Jones EL. Kawasaki Disease. eMedicine.
Available from the Internet at http://www.emedicine.com/ped/topic1236.htm (rev. 6/6/03, cited 3/28/05).

Author
Donna M. D’Alessandro, MD
Associate Professor of Pediatrics, Children’s Hospital of Iowa

Date
April 11, 2005