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Refractory Kawasaki disease

Robert Sundel, MD
Section Editors
Marisa Klein-Gitelman, MD, MPH
Sheldon L Kaplan, MD
Deputy Editor
Elizabeth TePas, MD, MS


Kawasaki disease (KD), also called mucocutaneous lymph node syndrome, is one of the most common vasculitides of childhood [1]. It is typically a self-limited condition with fever and manifestations of acute inflammation lasting for an average of 12 days without therapy. However, cardiovascular complications, such as coronary artery (CA) aneurysms leading to potential occlusion and cardiac ischemia, occur in a sizeable percentage of untreated children. The major sequelae of KD are dramatically decreased as a result of therapy with intravenous immune globulin (IVIG). Nonetheless, the duration of fever correlates with risk of developing CA aneurysms. Therefore, additional therapy is advised in patients with persistent fever after initial IVIG therapy.

The treatment of refractory KD is discussed in this review. The initial treatment of KD, diagnosis, clinical manifestations, and cardiovascular sequelae are reviewed elsewhere. (See "Kawasaki disease: Initial treatment and prognosis" and "Kawasaki disease: Clinical features and diagnosis" and "Cardiovascular sequelae of Kawasaki disease: Clinical features and evaluation".)


Persistent or recurrent fever of any magnitude between 36 hours to approximately two weeks after the start of treatment in patients with KD is generally assumed to be the result of failure to abort the disease process. Patients who have persistent or recurrent fever more than 24 hours after completion of the initial treatment should also be assessed for intercurrent infection, and the diagnosis of KD should be reevaluated. However, these patients should be retreated for presumed recrudescence of KD, unless there is clear evidence of another explanation for fever, since numerous studies have confirmed an association between prolonged fever and development of coronary artery (CA) abnormalities. Fever within 36 hours of the start of intravenous immune globulin (IVIG) therapy does not warrant retreatment, because it may represent a reaction to the medication or a slow response to therapy. (See "Kawasaki disease: Initial treatment and prognosis", section on 'Follow-up'.)

It is important for the clinician to remain alert to mild temperature elevations in children treated for KD. In one study of 378 patients, those who remained febrile had an almost ninefold increased risk of developing CA abnormalities compared with those who responded to initial IVIG (12.2 versus 1.4 percent) [1]. Accurate core temperature measurements are important for optimal management of KD patients in view of the strong association between elevated temperatures and CA abnormalities. Temperatures should be taken orally or rectally [2]. Inaccurate temperature measurement may explain the rare reports of development of CA abnormalities after children apparently became afebrile based upon axillary temperature measurement [3]. Thus, the most prudent approach to a child recovering from KD is regular follow-up during the convalescent period regardless of whether there are any signs of smoldering vasculitis. (See "Kawasaki disease: Initial treatment and prognosis".)

Incidence — Fever persists or returns within 48 hours in approximately 10 to 15 percent of patients with KD who are initially treated with IVIG and aspirin [1,4-6]. For unclear reasons, however, this fraction can vary significantly. In 2006, the incidence of refractory KD in Boston was 8 percent. In contrast, the likelihood of having KD refractory to initial IVIG therapy in San Diego increased to 38 percent in 2006 from a range of 10 to 20 percent between 1998 and 2005 [7]. This increase was not associated with any changes in the formulations of IVIG used. In addition, the same IVIG brands and lots administered in San Diego to treat patients with KD were also used in Boston.

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Literature review current through: Sep 2017. | This topic last updated: Sep 26, 2017.
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