Revision of diagnostic guidelines for Kawasaki disease (the 5th revised edition)

Authors

  • Mamoru Ayusawa,

    1. Department of Pediatrics, Nihon University School of Medicine, Tokyo
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      Subcommittee for the Revision of Diagnostic Guideline (Chief, T. Sonobe) organized in Kawasaki Disease Research Committee sponsored by Japanese Ministry of Health Labor and Welfare (Chief, K. Harada).

  • Tomoyoshi Sonobe,

    1. Japan Red Cross Medical Center, Tokyo
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      Subcommittee for the Revision of Diagnostic Guideline (Chief, T. Sonobe) organized in Kawasaki Disease Research Committee sponsored by Japanese Ministry of Health Labor and Welfare (Chief, K. Harada).

  • Shigeru Uemura,

    1. Wakayama Prefectural Medical College, Wakayama
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      Subcommittee for the Revision of Diagnostic Guideline (Chief, T. Sonobe) organized in Kawasaki Disease Research Committee sponsored by Japanese Ministry of Health Labor and Welfare (Chief, K. Harada).

  • Shunnichi Ogawa,

    1. Nippon Medical School, Tokyo
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      Subcommittee for the Revision of Diagnostic Guideline (Chief, T. Sonobe) organized in Kawasaki Disease Research Committee sponsored by Japanese Ministry of Health Labor and Welfare (Chief, K. Harada).

  • Yoshikazu Nakamura,

    1. Department of Public Health, Jichi Medical College, Tochigi, Japan
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      Subcommittee for the Revision of Diagnostic Guideline (Chief, T. Sonobe) organized in Kawasaki Disease Research Committee sponsored by Japanese Ministry of Health Labor and Welfare (Chief, K. Harada).

  • Nobuyuki Kiyosawa,

    1. Kyoto Daini Red Cross Hospital, Kyoto
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      Subcommittee for the Revision of Diagnostic Guideline (Chief, T. Sonobe) organized in Kawasaki Disease Research Committee sponsored by Japanese Ministry of Health Labor and Welfare (Chief, K. Harada).

  • Masahiro Ishii,

    1. Kurume University School of Medicine, Kurume
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      Subcommittee for the Revision of Diagnostic Guideline (Chief, T. Sonobe) organized in Kawasaki Disease Research Committee sponsored by Japanese Ministry of Health Labor and Welfare (Chief, K. Harada).

  • Kensuke Harada

    1. Department of Pediatrics, Nihon University School of Medicine, Tokyo
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Mamoru Ayusawa, Department of Pediatrics, Nihon University School of Medicine, 30-1, Ooyaguchikamicho, Itabashi, Tokyo 173-8610, Japan. Email: maysw@med.nihon-u.ac.jp

Abstract

Abstract  Diagnostic guidelines for Kawasaki Disease was revised to meet the present situation in 2002. This issue intends to explain new guidelines and their backgrounds. Major alterations are interpretation of cases with 4 or fewer febrile days shortened by early intravenous immunoglobulin treatment, and the clinical importance of atypical (incomplete, or suspected) cases.

Diagnostic guidelines for Kawasaki Disease have not been revised in Japan since 1984. There have been several progressions during these 18 years concerning the management of Kawasaki Disease. A subcommittee for the revision of the diagnostic guidelines was organized through the Kawasaki Disease Research Committee to meet the present situation. A draft of new diagnostic guidelines was made in 2001, and the final revision was published in Japanese in 2002 (see Appendix 1 for English version). Major alterations to the new Diagnostic Guidelines are summarized as follows:

Table Appendix 1.    Diagnostic Guidelines for Kawasaki Disease. (MCLS: Infantile Acute Febrile Mucocutaneous Lymph Node Syndrome; The 5th Revised Edition, February 2002)
This is a disease of unknown etiology affecting most frequently infants and young children under 5 years of age. The symptoms can be classified into two categories, principal symptoms and other significant symptoms or findings.
Principal symptoms
1Fever persisting 5 days or more (inclusive of cases in whom the fever has subsided before the fifth day in response to therapy);
2Bilateral conjunctival congestion;
3Changes of lips and oral cavity: reddening of lips, strawberry tongue, diffuse injection of oral and pharyngeal mucosa;
4Polymorphous exanthema;
5Changes of peripheral extremities: (Initial stage) reddening of palms and soles, indurative edema; (Convalescent stage) membranous desquamation from fingertips;
6Acute non-purulent cervical lymphadenopathy.
At least five items of 1–6 should be satisfied for diagnosis of Kawasaki Disease. However, patients with four items of the principal symptoms can be diagnosed with Kawasaki Disease when coronary aneurysm or dilatation is recognized by 2-D echocardiography or coronary angiography.
Other significant symptoms or findings
The following symptoms and findings should be considered in the clinical evaluation of suspected patients:
1Cardiovascular: auscultation (heart murmur, gallop rhythm, distant heart sounds), electrocardiogram changes (prolonged PR/QT intervals, abnormal Q wave, low-voltage QRS complexes, ST-T changes, arrhythmias), chest X-ray findings (cardiomegaly), 2-D echo findings (pericardial effusion, coronary aneurysms), aneurysm of peripheral arteries other than coronary (axillary etc.), angina pectoris or myocardial infarction;
2Gastrointestinal tract: diarrhea, vomiting, abdominal pain, hydrops of gall bladder, paralytic ileus, mild jaundice, slight increase of serum transaminase;
3Blood: leukocytosis with shift to the left, thrombocytosis, increased erythrocyte sedimentation ratio, positive C-reactive peptide, hypoalbuminemia, increased α2-globulin, slight decrease in erythrocyte and hemoglobin levels;
4Urine: proteinuria, increase of leukocytes in urine sediment;
5Skin: redness and crust at the site of Bacille Calmette-Guèrin inoculation, small pustules, transverse furrows of the finger nails;
6Respiratory: cough, rhinorrhea, abdominal shadow on chest X-ray;
7Joint: pain, swelling; and
8Neurological: cerebrospinal fluid pleocytosis, convulsion, unconsciousness, facial palsy, paralysis of the extremities.
Remarks
1For item 5 under principal symptoms, the convalescent stage is considered important.
2Non-purulent cervical lymphadenopathy is less frequently encountered (approximately 65%) than other principal symptoms during the acute phase.
3Male:Female ratio, 1.3–1.5:1; patients under 5 years of age, 80–85%; fatality rate, 0.1%.
4Recurrence rate, 2–3%; proportion of siblings cases, 1–2%.
5Approximately 10% of the total cases do not fulfil five of the six principal symptoms, in which other diseases can be excluded and Kawasaki Disease is suspected. In some of these patients, coronary artery aneurysms (including so-called coronary artery ectasia) have been confirmed.
  • 1Cases with 4 or less febrile days shortened by early intravenous immunoglobulin (IVIG) treatment were proposed to be equivalent to cases with 5 or more febrile days in the previous criteria1,2. The reason being, that many experienced pediatricians have made a diagnosis of Kawasaki Disease even before the fifth febrile day when there were other principal symptoms of Kawasaki Disease. The 16th and latest Japanese nationwide surveillance has shown that approximately 30% of patients started to receive IVIG treatment on or before the fourth day, including approximately 10% of them being started on or before the third day of illness. Also, some cases became afebrile before the fifth day when a single high dose of IVIG was given2.
  • 2The clinical importance of atypical (incomplete, or suspected) cases which do not meet the criteria of Kawasaki Disease is emphasized in the new diagnostic guidelines, since they often develop coronary artery abnormalities1,3.
  • 3The order of six principal symptoms of Kawasaki Disease was rearranged (except for fever and cervical lymphadenopathy) so as to be remembered easily: (i) fever; (ii) conjunctival congestion; (iii) changes of lips and oral cavity; (iv) rash; (v) changes of extremities; and (vi) cervical lymphadenopathy.

Criteria for duration of fever

The policy of alteration 1 is based on the data from the 16th nationwide surveillance for Kawasaki Disease in 1999 and 2000. A total of 1741 (66.5%) hospitals among 2657 hospitals with pediatric departments in Japan answered the questionnaire. Figure 1 shows the number of days of illness at IVIG initiation. A total of 15 314 patients were reported and of these, 13 167 patients (86.0%) received IVIG treatment. From 12 829 patients whose initial day of IVIG treatment was reported, 3916 patients (30.5%) received IVIG from the fourth or earlier day of illness, while 8913 patients received treatment from the fifth day or later2. Experienced pediatricians currently make diagnosis of Kawasaki Disease before the fifth febrile day for cases where there are some other principal symptoms and laboratory data compatible with Kawasaki Disease. This situation helps fever to be subsided earlier than it was previously when criteria needed duration of fever to persist for 5 or more days.

Figure 1.

Day of illness at intravenous immunoglobulin initiation.

Remark of the incidence of cervical lymphadenopathy

Physicians, residents or medical students who refer to these guidelines for diagnosis of Kawasaki Disease are occasionally misunderstanding that more than five principle symptoms must appear on the same day. Since the committee is worrying that their decisions are too strict to suspect this disease at the first examination of the patient, delay of diagnosis has a possibility of a higher incidence of coronary artery complication. Non-purulent cervical lymphadenopathy appears with the prevalence of approximately 65%, while other principal symptoms do with higher prevalence during the acute phase.

Concept for atypical cases

The clinical importance of atypical (incomplete or suspected) cases is emphasized in the new diagnostic guidelines since they often develop coronary artery abnormalities.

On the basis of results from the 16th nationwide surveillance in Japan, the prevalence of atypical (incomplete or suspected) patients was 13.8%. Approximately 10% of the total cases did not fulfil the criteria of a typical case, in which other diseases can be excluded and Kawasaki Disease is suspected3. In some of these patients, coronary artery aneurysms (including so-called coronary artery ectasia) have been confirmed.

The prevalence of coronary artery abnormalities among those ‘atypical’ patients was 5.5%. This prevalence is less than that of typical cases, however, with some cases complicated with a giant coronary artery aneurysm. Therefore, the committee proposed to add a new sentence concerning atypical cases as a remark.

The order of principle symptoms

In the view of education for medical students, general physicians or patients and their family, the order of symptoms other than fever are rearranged, except for cervical lymphadenopathy which occur with the least frequency of around 60–70%.

Acknowledgment

The authors deeply appreciate Professor Masato Takahashi, Childrens Hospital Los Angeles, for his cooperation with translating and polishing the new Japanese guideline into this English version.

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